Organic Chemistry All

CHEM 345 Organic Chemistry I
Fall 2016
Instructors:
Dr. Greg Crouch, Fulmer 414 gcrouch@wsu.edu
Dr. Rock Mancini, Fulmer 170 rmancini@wsu.edu
Stockroom Manager:
Andrea Kirchner Loewus, Fulmer 435A
andreakl@wsu.edu
Prerequisite: A letter grade of C or better in Chem 102 or 106 or the equivalent course transfer.
Contacting Instructors and TAs: Please do not call. Rather, all instructor and TA email addresses are listed on the
Blackboad course website. Please put chem 345 in the subject field of the email.
Office Hours:
Dr. Crouch: M/W/F 10:00-11:00 am and by email appointment.
Dr. Mancini: M/W/F 2:00-3:00 pm and by email appointment.
TAs office hours are held in Fulmer 401 as well as CUE tutoring center. A schedule will be posted on the course
website as well as on the door to Fulmer 401 no later than the first week of class.
Class Meeting:
Section 1 MWF 11:10-12:00 Fulmer 226
Section 2 MWF 13:10-14:00 Heald G3
Prelab meeting times depend on section. All labs meet in Fulmer 438 beginning the week of September 7th.
Course Website: All course material is on our website at:
http://learn.wsu.edu
In addition, we have a course Facebook group page at: http://www.facebook.com/groups/chem.345
Required Course Materials: Two choices
1. There is a bundle in the bookstore for $225 that contains Fundamentals of Organic Chemistry by McMurry (7th
edition) in addition to the online homework system called OWL.
2. You may opt to buy access to OWL directly at:
http://www.cengagebrain.com/micro/wsuchme1016
This option costs $129. If you chose this route, you can find a used copy of Fundamentals of Organic Chemistry by
McMurry for as little as $10 from amazon or abebooks.com. An older (5th or 6th edition) of this text will work fine.
IMPORTANT: Make sure you only purchase the text with the exact name Fundamentals of Organic Chemistry. This
author has written many books so make sure you get the correct version. Here are the covers from the last three
editions:
7th edition
6th edition
5th edition
For either option above, you will also need to purchase access to Learning Catalytics at a cost of $12 for six months of
access:
http://learningcatalytics.com
IMPORTANT: When registering for Learning Catalyics you must enter your student ID and make sure your name is
spelled correctly. At the end of the term, your scores from the Learning Catalytics gradebook will be imported to
Blackboard based on Student ID. If your ID is missing or incorrect, you will miss points.
Finally, a model kit is required. While there is a kit at the Bookie for $26, you may also purchase one for $15 from:
http://www.darlingmodels.com/Individual-Orders-Molecular-Model-Kits/KIT-3-ISBN-978-09648837-4-1-MOLECULARVISIONS-Organic-Kit/prod_7.html
Model kits can also be purchased on eBay or Amazon for a reasonable price. It is essential you have a model kit before
the first exam.
In summary the cheapest option is $129 + $10 (approximate used book) + $12 (Learning Catalytics) + $15 (model kit)
$166. For those students going to Chem 348, you will not be required to purchase any additional materials.
For lab, you will need googles and a lab coat. These are sold by the Chemistry Club at the beginning of the semester.
You will not need to buy a lab book or a lab notebook.
Course Objectives and Description: Students completing Chem 345 will be able to
1) Rationalize molecular reactivity based on functional groups,
2) Master the foundational knowledge necessary for success in Chem 348,
3) Master simple laboratory methods dealing with compound separation, identification, and synthesis, and
4) Safely manipulate chemical compounds and understand chemical hazards in the laboratory.
Lecture Course Description: The Chem 345 curriculum is based on the survey of functional groups approach to
teaching organic reactions and mechanisms. Each week we will be exploring a different type of organic compound.
Please consult the lecture topic outline section of the course web site and keep up with reading and homework.
Lab Course Description: Chem 345 has a laboratory component that meets once per week for 3 hours. In order to pass
the course, you must complete and pass all of the labs. You are not required to purchase any lab manuals as all printed
materials are freely available on the course website. You are required to purchase a lab coat as well as goggles.
You must complete and turn in all of the labs in order to pass this course. In other words, failure to turn in a lab report
at the end of the term will result in an automatic failing grade. Lab attendance is mandatory. If you miss a lab, there will
be a make-up session at the end of the semester; you may make up a maximum of two labs. If you miss more than two
labs during the semester without an excellent reason, you will automatically fail the course. If you cannot attend lab,
you must email your TA and Andrea Kirchner-Loewus (andreakl@wsu.edu) before the scheduled lab time.
All labs must be turned in directly to your TA the week following their completion or to the Organic Stockroom Fulmer
435 (Manager, Andrea Kirchner-Loewus). Your TA will sign the report acknowledging receipt and Andrea or the Organic
Stockroom staff will date-stamp them.
Early Policy: You will receive 0.25 points EXTRA CREDIT for each day you turn in your lab prior to the due date
(maximum of 1 point per lab). If you wish to turn in a lab early, give it to your TA directly or Andrea/Organic Stockroom
staff in 435 from 10-4 pm, Monday-Thursday (closed Fridays).
Late Policy: There is none. It has been superseded by the Early Policy. Labs turned in after the due date will be scored
as a 0 (zero) and counted as a completed lab and thus cannot be made up at the end of the semester. If no stockroom
personnel are present to accept your lab, you may drop it through the mail slot on the door to Fulmer 435A.
Student Learning Outcomes:

1. Use chemical acid/base reactivity to predict chemical equilibrium.
2. Describe chemical reactivity in terms of organic functional group chemistry, including functional group
transformation.
3. Interpret structural changes within a chemical framework considering bond making and bond breaking.
4. Propose reasonable mechanisms that convert starting materials to product
5. Interpret stereochemical data that informs a mechanistic hypothesis.
6. Plan an organic synthesis using a retrosynthetic approach based on known chemical reactions.
7. Develop skill in safe chemical handling, measurements, experimental technique, and simple synthesis.
8. Plan simple compound separation schemes using solubility characteristics.
Assignments & Grading Policy: This course will be graded on the basis of homework, two midterm exams, a
comprehensive final exam, lecture participation, and lab.
Homework: We will be using Mastering Chemistry for online homework this term. All assignments will be accessible
through Blackboard Learn and count at 10% of your grade.
Midterm exams: Two hourly exams will be administered to assess subject mastery. These exams are not multiple
choice. Prior semester exams are provided on the course website. The second midterm exam (as well as the final) are
comprehensive. Each midterm exam is 20% of your grade. If you miss a midterm exam, your final will count at 45%
Final exam: A two-hour mandatory final exam will be administered at the end of the course. The final exam is worth
25% of your grade.
Lecture participation: Learning Catalytics will be used to assess lecture participation. Lecture participation is worth 5%
of your grade.
Lab: Completing all 12 labs is required to pass this course and will count at 20% of your grade.
Assessment: Student Learning Outcomes 1 through 7 will be assessed using hand-graded exams, homework, and inclass participation. We do not use multiple choice exams so we can assign partial credit for reasonable answers. Any
chemical separations theory necessary to Student Learning Outcome 8 will also be assessed using exams. The remainder
of outcomes 7 and 8 will be assessed by graded lab reports.
Grade Scale: This course will use the following grade scale. Please note this scale may change slightly from year-toyear.
A
92-100
B
83-85
C
72-76
D
61-64
A89-91
B80-82
C69-71
F
<60
B+
86-88
C+
77-79
D+
65-68
Grade Summary: The breakdown for each of graded component is show below, along with their weight in percentage.
A sample calculation is also provided.
graded components weight score

homework
10%
70
test 1
20%
67
test 2
20%
62
lecture participation
5%
88
final
25%
77
lab
20%
90
100%
sample calculation
weight weighted score
x 0.1 =
7
x 0.2 =
13.4
x 0.2 =
12.4
x 0.05 =
4.4
x 0.25 =
19.25
x 0.2 =
18
sum
74.45
In the sample calculation above, the composite score of 74.45 would round to 74 and correspond to a letter grade of C
according to the grade scale. However, since the final exam is comprehensive, we also consider that score alone and if it
is better than the composite score, that will be the grade awarded. For example, the final exam score above is 77%,
which corresponds to a letter grade of C+, so that is the grade awarded for the class.
composite score
final exam
best score
best letter grade
74
77
77
C+
We do not give make-up exams. If you miss one hourly exam, the final exam will increase to 45% of your course grade.
To pass this course, you must complete all of the labs. If you miss a lab, there will be make-up times available.
Test Schedule: All tests and exams are evening exams. If you off campus due to a university sponsored event, you may
arrange for an academic counselor to proctor the exam. You must make these arrangements within the first two weeks
of the semester. If you miss an hourly exam, the final exam will count at 45%.
Test 1, Thursday September 29th from 8:00 to 10:00 pm in Todd 116 & Fulmer 226
Test 2, Thursday November 10th from 8:00 to 10:00 pm in Todd 116 & Fulmer 226
Final Exam, Thursday December 15th from 7:00 to 10:00 pm, locations TBD
Tests 1 and 2 are written for a standard one-hour time frame so it is permissible to start Test 1 or Test 2 up to 9:00 pm
and still have time to complete the exam. The Final Exam is written for an average student to complete in 90 minutes.
Officially approved and scheduled night examinations have priority everything except officially scheduled lectures and
labs. If you have a conflict with another evening academic activity such as a biology or physics lab course, you must
arrange for an alternate test time at least two weeks prior to the exam. There is no penalty for missing an hourly exam
as it simply increases the weight of the final exam. Do not make travel plans before the final exam. Your travel cannot
be accommodated.
Test Policy and Regrades: In advance of exams, you will be provided with a notecard that you may bring to the exam.
In addition to this notecard, bring only your student ID, a model kit, and pencils to the exams. You will be provided
scratch paper. You may not bring any electronic or internet connected device to the exam. Do not bring or leave visible
any notes other than on your card. If you are observed using any electronic device, reading off fellow students tests, or
having notes other than allowed, you will fail the exam and be asked to leave the testing room. interpreted as a breach
of academic integrity and will be reported. Once exams have been graded, you may pick them up from the stockroom.
Look over the exam carefully and make sure the points have been added correctly. If you find an error or have a
question about the grading of the exam, return it to the stockroom attendant with a regrade request form attached (you
can get these from the stockroom or on the course website) we will not re-grade an exam once you remove it from the
stockroom. Be very clear when completing the regrade form. For example, there is an error in my total points or on
question 2, I drew the correct intermediate structure. Avoid requests that include I feel as if I deserve more points.
Lecture Schedule
Week
Week 1
Week 2
Week 3
Week 4
Week 5
Week 6
Week 7
Week 8
Week 9
Week 10
Week 11
Week 12
Week 13
Week 14
Week 15
Starting
August 22
August 29
September 5
September 12
September 19
September 26
October 3
October 10
October 17
October 24
October 31
November 7
November 14
November 21
November 28
December 5
Finals
December 12
Monday
Lecture 1
Lecture 4
Labor Day
Lecture 9
Lecture 12
Lecture 15
Lecture 16
Lecture 19
Lecture 22
Lecture 25
Lecture 28
Lecture 31
Lecture 32
Lecture 35
Review
Tuesday
Wednesday
Thursday
Lecture 2
Lecture 5
Lecture 7
Lecture 10
Lecture 13
Review
Test 1
Lecture 17
Lecture 20
Lecture 23
Lecture 26
Lecture 29
Review
Test 2
Lecture 33
Thanksgiving Vacation
Lecture 36
Review
Final Exam
7-10 pm
Friday
Lecture 3
Lecture 6
Lecture 8
Lecture 11
Lecture 14
No lecture
Lecture 18
Lecture 21
Lecture 24
Lecture 27
Lecture 30
Veterans Day
Lecture 34
Lecture 37
Review
Lecture Topics:
We will cover chapters 1 through 12 in the text. Slides will be provided in advance of class. Typically Chapters 1-5 are
covered on Test 1, Chapters 6-10 on Test 2, and all 12 chapters on the final exam.
Students with Disabilities: Reasonable accommodations are available for students with a documented disability. If you
have a disability and need accommodations to fully participate in this class, please either visit or call the Access Center
(Washington Building 217; 509-335-3417) to schedule an appointment with an Access Advisor. All accommodations
MUST be approved through the Access Center. For more information, contact a Disability Specialist
Academic Integrity: You are encouraged you to work with classmates on assignments, however, each student must turn
in original work. No copying will be accepted. Falsified lab data is also a violation of academic integrity. Students who
violate WSU's Standards of Conduct for Students will receive an F as a final grade in this course, will not have the option
to withdraw from the course, and will be reported to the Office Student Standards and Accountability. Cheating is
defined in the Standards for Student Conduct WAC 504-26-010 (3). It is strongly suggested that you read and understand
these definitions. In addition, if during an exam you use an internet connected or other electronic devices, you will fail
the exam and be reported as described above.
Safety Statement: Washington State University is committed to enhancing the safety of the students, faculty, staff, and
visitors. It is highly recommended that you review the Campus Safety Plan (http://safetyplan.wsu.edu/) and visit the
Office of Emergency Management web site (http://oem.wsu.edu/) for a comprehensive listing of university policies,
procedures, statistics, and information related to campus safety, emergency management, and the health and welfare
of the campus community.
Chapter 1 Outline
This first slide presentation will include
review from general chemistry therefore it
will cover more information that in the
textbook.
Periodic table & trends
Ionic & covalent bonding
Atomic structure, orbitals and isotopes
Molecular orbitals and hybridization
Acids/base chemistry
s-block (metals), p-block (non-metals)
An ionic bond is formed between metals

and non-metals
Covalent Bonds are Formed by

Sharing Electrons Between Non-Metals
Nonpolar covalent bond = bonded atoms are the same

No difference in electronegativity between atoms
Polar covalent bond = bonded atoms differ in electronegativity
How Many Bonds Does

an Atom Form?
Lewis Structures
Bond Polarity Depends on

the Difference in Electronegativity
Polar Covalent Bonds
Formal Charge
For example, consider oxygen in methanol shown

below.
Oxygen is in group 16, which means a valence
number of 6.
Oxygen has two lone pairs and shares an
electron in each of the two covalent bonds so
FC = 6 4 (4) = 0
Formal Charge
Methyl oxonium ion (the acidic form of methanol) is shown below.

In this structure, oxygen has used one of its lone pair to form a covalent bond
with a proton so the formal charge for oxygen is
FC = 6 2 (6) = +1
Neutral Carbon Forms Four Bonds
if carbon does not form four bonds, it has a charge

(or it is a radical)
A Hydrogen Atom Can Lose or

Gain an Electron
Neutral Nitrogen Forms Three Bonds
Nitrogen has one lone pair.

If nitrogen does not form three bonds, it is charged.
Neutral Oxygen Forms Two Bonds
Oxygen has two lone pairs.

If oxygen does not form two bonds, it is charged.
Hydrogen and the Halogens

Form One Bond
A halogen has three lone pairs.

if hydrogen or halogen does not form one bond, it has a charge
(or it is a radical)
Lewis Structures
In organic chemistry it is common to use lines to represent covalent bonds.

A single line between atoms represents one bond, two lines represents a double
bond, and three lines represents a triple bond.
Drawing Conventions in Organic Chemistry

butane
H H H H
H C C C C H
H H H H
CH3CH2CH2CH3
OH
terminal line implies -CH3
butanol
H H H H
H C C C C OH
H H H H
CH3CH2CH2CH2OH
OH
Learn to use line/bond drawing convention for Lewis structures

Simplifies drawing task
bent line implies -CH2-
Atomic & Molecular Orbitals
The Structure of an Atom

Protons are positively charged.
Neutrons have no charge.
Electrons are negatively charged.
Atomic number = # of protons
Atomic number of carbon = 6
Neutral carbon has six protons
and six electrons.
Isotopes
Isotopes are atoms that have the same atomic number (number
of protons) but differ in mass (differing number of neutrons)
Isotopes may be stable or unstable (radioactive).
Isotopes are widely used to understand chemical mechanism and
as radiotracers
stable
Unstable
(beta emitter)
The Distribution of Electrons in an Atom
The first shell is closest to the nucleus.

The closer the atomic orbital is to the nucleus,
the lower its energy.
Within the same shell, s < p.
-Aufbau principle: An electron goes into the atomic orbital with

the lowest energy.
-Pauli exclusion principle: No more than two electrons can be
in an atomic orbital.
-Hunds rule: An electron goes into an empty degenerate
orbital rather than pairing up.
increasing energy
Reorder such that energy becomes the y-axis
Electrons may be excited from lower to higher energy

orbitals creating excited electronic states
What is an Atomic Orbital?
The Lobes of a p Orbital Have

Opposite Phases
The Three p Orbitals
Molecular Orbitals - Diatomic

Hydrogen
Hydrogen is one of the seven elements that form
diatomic molecules. In order for H2 to form, atomic
hydrogen must come together to form a covalent
bond.
Orbital overlap
1s
+
1s
atomic hydrogen
molecular hydrogen
Atomic Orbitals Combine

to Form Molecular Orbitals
Side-to-Side Overlap of In-Phase

p Orbitals Forms a Bond
Molecular Geometry & Hybridization
The Bonding in Methane
increasing energy
In Order to Form Four Bonds,

Carbon Must Promote an Electron
Four Orbitals are Mixed to Form

Four Hybrid Orbitals
An sp3 orbital has a large lobe and a small lobe.
The Carbon in Methane is sp3
4 sp3 orbitals = tetrahedron

.
The Carbon Hydrogen Bond

When the four sp3 hybrid orbitals of carbon
overlap with four 1s orbitals of hydrogen,
tetrahedral geometry arises
carbon sp3 - hydrogen 1s =
bond
The Bonding in Ethane

H
this line represents a carbon sp3 to hydrogen 1s
bond
this line represents a carbon sp3 to carbon sp3
bond
Graphically, the molecular orbitals of ethane can be represented as:
Bonding in Ethene
Molecular Orbitals in Ethene

one of these lines represents a carbon sp2 to carbon sp2
the other line represents a carbon to carbon bond
H
H
C
bond
this line represents a carbon sp2 to hydrogen 1s bond
sp2
sp2
2p
2p
sp2
sp2
sp2
sp2
C-C
1s
1s
sp hybridized
carbon atom
2 hydrogen atoms
1s
sp2 hybridized
carbon atom
2 hydrogen atoms
C sp2 - C sp2
C sp2 - H 1s
1s
C sp2 - H 1s
An sp2 Carbon Has Three sp2 Orbitals

and One p Orbital
The Carbons in Ethene are sp2
Bonding in Ethyne
2s
2py
2pz
atomic orbitals
ground state
2px
2s
2p
2p
atomic orbitals
excited state
2p
2p
2p
sp
sp
two sp hybrid orbitals

2 unhybridized 2p orbitals
Molecular Orbitals in Ethyne

one of these lines represents a carbon sp to carbon sp bond
the other two lines represents two carbon to carbon bonds
H
this line represents a carbon sp to hydrogen 1s bond
2p
sp
2p
2p
sp
sp
C-C
1s
sp
C-C
1s
sp hybridized
carbon atom
sp hybridized
carbon atom
hydrogen atom
2p
hydrogen atom
C sp - C sp
C sp - H 1s
C sp - H 1s
The Two sp Orbitals Point in Opposite Directions

The Two p Orbitals are Perpendicular
The Carbons in Ethyne are sp
Methyl Cation and Methyl Radical are sp2
Methyl Anion is sp3
Nitrogen Has Three Unpaired Valence Electrons

and Forms Three Bonds in NH3
Nitrogen does not have to promote an electron.
The Bonds in Ammonia (NH3)
The Ammonium Ion (+NH4)
Oxygen Has Two Unpaired Valence

Electrons and Forms Two Bonds in H2O
Oxygen does not have to promote an electron.
The Bonds in Water (H2O)
Overlap of an s Orbital with an sp3 Orbital
The Length and Strength of a

Hydrogen Halide Bond
Summary of Hybridization
orbitals used in bond formation determine the bond angle
Single Bond: 1 Double bond: 1 + 1

Triple Bond: 1 + 2
Hybridization of C, N, and O
Bond Strength and Bond Length
The shorter the bond, the stronger it is.
s Character
The More s Character in the Orbital,

the Shorter and Stronger the Bond
The more s character, the shorter and stronger the bond.
The More s Character in the Orbital,

the Greater the Bond Angle
The more s character, the greater the bond angle.
Hybridization, Bond Angle,

Bond Length, Bond Strength
Summary
The greater the electron density in the region of orbital
overlap, the stronger the bond.
The more s character, the shorter and stronger the bond.
The more s character, the larger the bond angle.
A Bond is Weaker Than a Bond
Dipole Moments of Molecules
Dipole Moments of Molecules
Acids and Bases Reactions in Equilibrium
Two acid base theories will be explored:

Bronsted Lowery acid base theory: loss and
gain of a proton
Lewis acid base theory: donation or
acceptance of a pair of electrons
B.L. AcidBase Reactions in Equilibrium
Equilibrium arrows indicate the if the products or

reactants are favored
An Acid Loses a Proton

A Base Gains a Proton
When an acid loses a proton, it forms its conjugate base.

When a base gains a proton, it forms its conjugate acid.
An Acid and its Conjugate Base

A Base and its Conjugate Acid
The stronger the acid, the weaker its conjugate base.
Acids Have Different Strengths
The stronger the acid, the weaker its conjugate base.
Acid Strength
The stronger the acid, the larger the Ka.

The stronger the acid, the smaller the pKa.
See Simple pKa Chart on course

web for a complete list. You must
know pKa values for exams.
Water & Alcohols Can Act as

Either Acid or Base
Alkoxide
anion
Alcohol
Oxonium
cation
An Amine Can Behave

as an Acid and as a Base
A curved arrow points from the electron donor to the electron acceptor.
An Amine Can Behave

as an Acid and as a Base
Amide
anion
ammonia
Ammonium
cation
Other Amine Acid/Base Chemistry
The Position of Equilibrium

Take Home Concept:
The equilibrium favors formation of the weaker acid.
Determine Position of Equilibrium
First Label the acids
acid
acid

Second, approximate the pKas
Acid
35
Acid
15

Second, approximate the pKas
Acid
35
Acid
15

Second, approximate the pKa value
Equilibrium always favors the weaker acid
(larger pKa value)
The Stronger the Acid,

the Weaker Its Conjugate Base
stable bases are weak bases
Why are Alcohols Stronger Acids Than Amines?
Oxygen is more electronegative than nitrogen.
Why Are Protonated Alcohols Stronger Acids

Than Protonated Amines?
Oxygen is more electronegative than nitrogen.
Substituents Affect the

Strength of the Acid
inductive electron withdrawal
HX vs Substituted Acetic Acid Trends

For substituted carboxylic acids, consider the conjugate base forms.
The area circled in red has a lot of excess electron density. Groups near
this electron density can help stabilize it if they are electronegative.
Since Cl is more electronegative than Br, the conjugate base form of 2chloroacetic acid is more stable - therefore the acid is stronger

Another way to think about it is bond dipoles. Because the singly
bonded oxygen of the carboxylate is negatively charged, that forces the
carbon next to it to be positively charged, which in turn forces the next
carbon to be negatively charged. The more electronegative atom will
stabilize carbon #2 better
pKa 2.81
pKa 2.86
Smaller pKa = stronger acid

Chlorine more electronegative than bromine
pKa ~0
A Substituents Effect on pKa

Depends on Distance

Comparing acids such as HCl to HI, you can think
about the bond strength. The weaker the bond, the
easier to break.
The Length and Strength of a

Hydrogen Halide Bond
Acid
strength
Base
Base strength
pKa
form
3.14
F-
-7
Cl-
-8
Br-
-9
I-
Why is a Carboxylic Acid a Stronger Acid

Than an Alcohol?
delocalized electrons (resonance)
Lab #1 How ionization impacts solubility

like dissolves like
O
O
+ NaOH (aq)
OH
benzoic acid
neutral form
not soluble in water
O Na
sodium benzoate
ionized form
soluble in water
pKa = ?
pKa = ?
O
O
H3C
+ H2O
OH
+ NaOH (aq)
acetic acid
neutral form
soluble in water
H3C
O Na
+ H2O
sodium acetate
ionized form
soluble in water
Red is a greasy hydrocarbon (not soluble in water) Blue is the carboxylic

acid functional group (neutral) and Carboxylate (charged)
Can be used to separate compounds

using extraction techniquies
O
OH
dissolve in Et2O
extract with NaOH (aq)
separate
ether
water
neutralize with HCl (aq)

vacuum flter
The HendersonHasselbalch Equation

Lab the week of Sept 7th. In summary, when the pKa of an acid is equal to the
pH of the solution, then there will be 50:50 distribution between ionized and
unionized forms.
Benzoic Acid has a pKa of 4.20
O
O
50
OH
50
pH = 4.20
Amine-based Drugs are often Salts

acid form
OH
H2N
H2N
Desoxyn
NH3
Adderall
basic form OH
HN
Ephedrine
HN
Methamphetamine
A carboxylic acid is neutral in its acidic form and charged in its basic form.
An amine is charged in its acidic form and neutral in its basic form.
Hybridization Affects Acidity
Mores
character most
electronegative
Lesss
character less
electronegative
The weakest acid has the

strongest conjugate base.
Hybridization Affects Acidity

Electronpairin
sporbital(more
stable)
Electronpairin
sp3orbital(less
stable)
Lewis Acids and Bases

Lewis definitions:
acid: a species that accepts a share in an electron pair
base: a species that donates a share in an electron pair
All Brnsted acids (proton donor) are Lewis acids.

All Brnsted bases (proton acceptor) are Lewis bases.
Lewis Acids and Bases
Chapter3
FunctionalGroups Alkanes
Hydrocarbons
Alkanes,alkenes,alkynes,benzene
cyclic
H H
C C
H H
C
C
C
C
C
C
C C
C
C
C
C
C
C
FunctionalGroups
AlkylHalides,amines,alcohols,ethers
FunctionalGroups
CarbonylCompounds
Aldehydesandketones
Carboxylicacidsandderivatives
FunctionalGroups
Aromatics
OtherAromatics
OH
NH2
H
N
FunctionalGroups
AlkanesandCycloalkanes
Nomenclature/structure acyclic
alkanes with 1-3 carbons
condensed
methane
CH4
ethane
line-bond
one carbon
two carbons
CH3CH3
propane
CH3CH2CH3
three carbons
Nomenclature/structure of acyclic
alkanes with 4-5 carbons
Alkyl Substituents
Replace ane of alkane with yl.
Common Names
Propyl and Isopropyl

CH3CH2CH3
propane
If X = Cl
X
CH3CH2CH2
X
CH3CHCH3
a propyl substituent
a 2-propyl substituent
commonly called isopropyl
Cl
CH3CH2CH2
Cl
CH3CHCH3
1-chloropropane
2-chloropropane
or isopropyl chloride
functional group = alkyl halide
Butyl, isobutyl, sec-butyl, tert-butyl
Primary, Secondary, and Tertiary Carbons

A primary carbon is bonded to one carbon.
A
. secondary carbon is bonded to two carbons.
A tertiary carbon is bonded to three carbons.
A quaternary carbon in bonded to four carbons
Alkanes Systematic Nomenclature
First identify the longest continuous chain

(the parent hydrocarbon).
Add the Name of the Substituent
Number the chain in the direction that gives the

substituent as low a number as possible.
List Substituents in Alphabetical Order
The correct name is the one that contains the

lowest of the possible numbers (5+3 < 4+6)
Multiple Substituents
Chain is numbered in the direction that puts the lowest number in the name.
Start numbering from the end that has the earliest branch point
Substituents are listed in alphabetical order (di- and tri- are not alphabetized).
Cycloalkanes
Skeletal structures do not show Cs and Hs bonded to Cs.
Bond angles in cyclic alkanes
Not 108o
Not 120o
We will revisit this when discussing bond rotations

and eclipssed vs staggered conformations
Angle Strain in cylcoalkanes
Angle strain results from poor orbitalorbital overlap because

bonds have to deviate from the ideal (109.5) bond angle.
Mono-Substituted Cycloalkanes
A number is not needed.
Di-Substituted Cycloalkanes
Substituents are stated in alphabetical order.

Lowest possible sum of substituent numbering
#1 goes to first-listed substituent.
Nomenclature of Alkyl Halides
Nomenclature of Ethers
Common
aprotic solvent
used in
chemical
synthesis
The substituents are listed in alphabetical order.
Nomenclature of Alcohols
1-propanol
2-propanol
2-butanol
Classification of Alcohols
Primary alcohol = OH is on a primary carbon.

Secondary alcohol = OH is on a secondary carbon.
Tertiary alcohol = OH is on a tertiary carbon.
Diols
OH
HO
ethane-1,2-diol
common name = ethylenediol
moderately toxic
HO
OH
propane-1,2-diol
common name = propylenediol
far less toxic
OH
HO
O
glycolic acid
O
OH
HO
O
oxyalic acid
toxic
pyruvic
acid
acetic
acid
lactic
acid
propionaldehyde
Boxed structures are metabolites
Propylene diol used extensively
Systematic Names of Alcohols
Pay attention to the number of the substituent

only if you get the same number for the
functional group in both directions.
Begin numbering from the end of the chain with the earliest branch point
A Substituent is a Prefix
A Functional Group is a Suffix
Classification of Amines
The classification depends on how many groups are bonded to N.
Primary amine
= one group bonded to N
Secondary amine = two groups bonded N
Tertiary amine
= three groups bonded N
Common Names of Amines

NH3
CH3NH2
N
H
CH3NHCH2CH2CH3
ammonia
(CH3CH2)3N
(CH3CH2)4N+
methylamine
methylpropylamine
triethylamine
tetraethylamine
a 1o amine
a 2o amine
a 3o amine
a 4o amine
R NH2
N
H
N
R
Substituents are in alphabetical order followed

by amine.
They are all written as one word.
R
R
N
R
Dont forget acid/base properties

of amines
NH3
ammonia
CH3NH2
methylamine
N
H
methylpropylamine
HCl
triethylamine
ammonia, 1o, 2o and 3o amines are bases
Cl
NH4 Cl
ammonium
chloride
N
H2
methylammonium methylpropylammonium
chloride
chloride
CH3NH3 Cl
Cl
H
N
pKa = 10
triethylammonium
chloride
Some special amines
NH2
HN
N
pyridine
NH
aniline
NH3
imidazole
HN
NH
pyridinium ion
anilinium ion
imidazolium ion
pKa = 5
Summary of Nomenclature
The Structure of an Alkyl Halide
The CX bond of an alkyl halide becomes longer and weaker

as the size of the halogen increases.
The Structure of an Alcohol

Resembles the Structure of Water
An alcohol is structurally like water with one H replaced by an R.
The Structure of an Ether

Resembles the Structure of an Alcohol
An ether is structurally like water with both Hs replaced by Rs.
Boiling Points
The greater the attractive forces between molecules,
the higher the boiling point.
attractive forces
van der Waals forces
dipoledipole interactions
hydrogen bonds
Boiling Points
Methane -167.7 C
Ethane
-88.6 C
Propane -42.1 C
Butane
-0.5 C
Pentane
36.1 C
Hexane
68.7 C
Heptane
98.4 C
Octane
125.7 C
induced dipole-induced dipole

interactions
van der Waals forces
The greater the surface area of the molecule, the higher the bp.
Branching Lowers the Boiling Point
cigar
tennis ball
DipoleDipole Interactions
Dipoledipole interactions are

stronger than van der Waals forces.
Diethylether
35 = oC
Hydrogen Bonds in H2O and NH3
CH4 167.7 C
no hydrogen bonds
H2O 100 C
hydrogen bonds
Hydrogen bonds are stronger than

other dipoledipole interactions.
Compounds with Similar Shapes and Properties

Often Have Similar Physiological Activities
Drugs bind to their receptors by van der Waals interactions,

dipole-dipole interactions, and hydrogen bonding.
Solubility
like dissolves like
Polar compounds dissolve in polar solvents (H2O).

Nonpolar compounds dissolve in nonpolar solvents (hexane).
Solvation
Solvation is the interaction between solute molecules and solvent molecules.
Competing effects with increasing

carbon count
Competing effects with increasing

carbon count
O
O
+ NaOH (aq)
OH
benzoic acid
neutral form
O Na
sodium benzoate
ionized form
soluble in water
O
H3C
+ H2O
OH
+ NaOH (aq)
acetic acid
neutral form
soluble in water
H3C
O Na
sodium acetate
ionized form
soluble in water
+ H2O
Conformational Analysis of
alkane and cycloalkanes
Rotation Occurs About

Single ()Bonds
Staggered and Eclipsed Conformers

of Ethane
Rotation Can Occur About the

Three CarbonCarbon Bonds in Butane
Rotation About C-2C-3 in Butane
butane.mov
Steric strain is repulsion between the electron clouds of atoms or groups.
Cyclopropane
Cyclobutane
Molecules twist out of a planar arrangement

to minimize angle strain and the number of eclipsed hydrogens.
Cyclopentane
Molecules twist out of a planar arrangement to

minimize angle strain and the number of eclipsed hydrogens.
Chair Conformer of Cyclohexane
The chair conformer of cyclohexane is completely free of strain.

All bond angles are 111 and all adjacent bonds are staggered.
Axial and Equatorial Bonds
Ring Flip
Cyclohexane interconverts between two stable chair conformers.
Ring Flip
Cyclohexane interconverts between two stable chair conformers.
Conformers of Cyclohexane
Ring flip we will only talk about the two chair conformations
Conformers of Monosubstituted
Cyclohexanes
1,3-Diaxial Interactions
Cis and Trans Isomers
Conformers of Disubstituted
Cyclohexanes
cis
trans
1,2
1,3
1,4
1,4-dimethylcyclohexane
trans
cis
CH3
H3C
C1
C4
H
CH3
CH3
?
H
C4
C1
H
CH3
C1
C4
CH3
?
H
H3C
C4
C1
H
CH3
Each Isomer Has

Two Chair Conformers
cis
trans
CH3
CH3
CH3
C3
H
C1
?
H
H3C
C3
C1
CH3
C3
H3C
C1
?
H
C3
C1
CH3
CH3
cis-1-tert-butyl-3-methylcyclohexane
trans-1-tert-butyl-3-methylcyclohexane
Chapter 3
Alkenes&Alkynes
Structure,Nomenclature,andanintroductiontoReactivity
andMechanism
Saturated and
Unsaturated Hydrocarbons
Saturated hydrocarbons have no double bonds.
Unsaturated hydrocarbons have one or more double bonds.
Nomenclature of Alkenes
Replace ane of alkane with ene.
The functional group gets the lowest possible number.
Stereoisomers May Be Named Using

a cis or trans Prefix
Nomenclature of Dienes
two double bonds = diene
Number in the direction so that the functional group

gets the lowest number.
Substituents are stated in alphabetical order.
Nomenclature of Cyclic Alkenes
A number is not needed to denote the position of the C=C functional group;
it is always between C1 and C2.
Vinylic and Allylic Common Names
Double Bonds Have

Restricted Rotation
The six carbon

atoms are in the
same plane
Rotation about a double bond breaks the bond.
Alkenes May Have cistrans Isomers
Cis: The hydrogens are on the same side of the ring.

Trans: The hydrogens are on opposite sides of the ring.
They have different configurations; they can be separated.
Sometimes cis and trans do not work
The E,Z System of Nomenclature
Z = Zusammen (together)
E = Entgegen (opposite)
Relative Priorities
The relative priorities of the two groups depends on the

atomic numbers of the atoms attached to the sp2 carbon.
The E and Z Isomers
(E) 1-chloro-3-(chloromethyl)-4-ethyl-5-methylhex-3-ene
Double Bonds
lower
higher
Break multiple bonds into

equivalent single bonds
Isotopes
Reactions of Organic Compounds
Electrophilic Addition (general)

Hydrohalogenation (more specific, could be HCl, HBr, or HI
Hydrobromination (specific for HBr)
Electrophiles
An electrophile is a Lewis acid and has:

a positive charge or
a partial positive charge or
an incomplete octet.
Nucleophiles
A nucleophile is a Lewis base and has:

a lone pair of electrons and/or
a negative charge
Reactive Intermediates
During the course of a reaction, a reactive
intermediate may be involved. We will limit our
study to the carbocation intermediate.
sp2, trigonal
planar
Empty p orbital
Increasing stability
Carbocation Stability
Alkyl groups:
decrease the concentration of positive charge on the carbon and
increase the stability of the carbocation.
Hyperconjugation Stabilizes a Carbocation
Bond Making and Bond Breaking

Reaction Mechanism
Arrows denote the flow of electrons from the Lewis base

to the Lewis acid
Functional Group Transformation
hydrohalogenation
(transformation)
Learn to recognize
the functional group
transformation.
In this case it is an
alkene going to an
alkyl chloride
Draw Notecards for each reaction

you are expected to learn (see course
handouts)
Me
Cl
HCl (g)
ether
Type: hydrohalogenation
Me
Reaction Mechanism
hydrohalogenation
(mechanism)
The curved arrow

notation is used to
describe bond
making and bond
breaking in a
mechanism
Draw Notecards for each reaction

mechanism you are expected to
learn (see course handouts)
How to Draw Curved Arrows
Exothermic and Endothermic Reactions

Transition
state
Eact
Ignore entropy G H
Reaction coordinate diagram
Bond Enthalpy
Endothermic or Exothermic
Bond
DH (kcal/mol)
Breaking
-bond
62
H-Br
88
COST
150
Bond Making
C-H
C-Br
GAIN
DH (kcal/mol)
101
71
172
150 kcal/mol 172 kcal/mol=22kcal/molorexothermic
Reaction Coordinate Diagrams for Fast and Slow

Exothermic and Endothermic Reactions
Reactions in Chapter 4
name
1. Hydrohalogenation
2. Hydration
class
electrophilic
addition
electrophilic
addition
3. Halogenation
electrophilic
addition
4. Hydrogenation
electrophilic
addition
5. cis Di-hydroxylation oxidation
6. Oxidative cleavage oxidation
7. Epoxidation
oxidation
mechanism
subclass
hydrochlorination, yes
hydrobromination
, hydroiodination
yes
bromination,
chlorination
reduction
yes
no
no
no
no
Refer to the course map in the syllabus when studying the remainder
of the material in this course as we will not cover every reaction in the
textbook. Always refer to the 345 reactions summary in the course
materials folder in Blackboard. If the reaction has a yes under the
mechanism column, you are expected to learn the mechanism that
goes along with the reaction.
Chapter 4
TheReactionsof
Alkenes/Alkynes
TheStereochemistryof
AdditionReactions
AlkeneReactionsinChapter4
name
1.Hydrohalogenation
class
electrophilic
addition
2.Hydration
electrophilic
addition
electrophilic
addition
electrophilic
addition
oxidation
oxidation
oxidation
3.Halogenation
4.Hydrogenation
5.cis Dihydroxylation
6.Oxidativecleavage
7.Epoxidation
subclass
mechanism
hydrochlorination, yes
hydrobromination,
hydroiodination
yes
bromination,
chlorination
reduction
yes
no
no
no
no
Refer to the course map in the syllabus when studying the remainder
of the material in this course as we will not cover every reaction in the
textbook. Always refer to the 345 reactions summary in the course
materials folder in Blackboard. If the reaction has a yes under the
mechanism column, you are expected to learn the mechanism that
goes along with the reaction.
AlkeneSubstitutionPatterns
H
mono
di
tri
tetra
Addition of Hydrogen Halides
Et2O
Et2O
Et2O = diethyl ether = solvent only
Which sp2 Carbon Gets the H+?
Et2O
The Mechanism
Carbocation formation is the rate-limiting step.
Why the Difference in Rate?
The more stable carbocation is formed more rapidly.
The Difference in Carbocation Stability

Determines the Products
Et2O
What Product Will Be Formed?
Formation of a Racemic Mixture

H Br
H
H3C
C C
H
CH3
Carbocation Stability and Product

Distributions
All carbocations are reactive intermediates
Secondary carbocations are less stable than
tertiary carbocations but can form during the
course of a reaction
Products cannot be derived from methyl and
primary carbocations
Methyl carbocations only form under special
circumstances
If a primary carbocation forms, it will quickly
rearrange to a more stable form.
Alkene Hydration: Alcohol Synthesis
Mechanism for the Acid-Catalyzed

Hydration
H2SO4 +
R C
H
CH2
H
O
H
O
H2O
H3O+
H OH2
H
C H
H
R C
H
H
R C
H
H
C H
H
O
R C
H
H
C H
H
O
R C
H
H
O
R C
H
HSO4-
H2O
Step 1 - endothermic
formation of carbocation
H
C H
H
H
C H
H
Step 2 - exothermic
formation of protonated alcohol
H3O+
Step 3, often not shown, regenerates

hydronium and is why the reaction is
catalytic
Formation of an Ether
A Variation of Hydration
Halogenation: Addition of Br2 or Cl2
CCl4
CCl4
Product is a 1,2 dihalide (vicinyl dihalide)
Carbon tetrachloride (CCl4) is the reaction solvent and
does not participate in the reaction
The Mechanism for

the Addition of a Halogen
CCl4
The intermediate is a cyclic bromonium ion.
The Mechanism for

the Addition of a Halogen
Bromonium ion
C
C
H
C
C
C
H
Bromonium ion in 3-D
Addition of a Halogen is an Anti Addition
Formation of a Bromohydrin
A Variation on Halogenation
In this reaction, the solvent is water not CCl4. Since water

is a nucleophile it can ring open the bromonium ion.
Water is in much higher concentration than bromide anion.
Hydrogenation Addition of H2 across

a double bond
catalytic hydrogenation
a reduction reaction
Mechanism for Hydrogen Addition
catalytic hydrogenation
Hydrogenation Undergoes Syn Addition
Cis Dihydroxylation (pg 509-510)

Mechanism proceeds through a osmate
ester. You are responsible for knowing
only the functional group transformation
not the mechanism
H
H
Syn addition
H
a) OsO4 / H2O
OH
OH
b) NaHSO3
H
O
O
Os
O
O
metal ester
OH
OH
H
Cis Dihydroxylation
Draw eclipsed
H
H
H
H
OsO4
H2O
H
OH
OH
H
(2R,3S)-butane-2,3-diol
OH
H
OsO4
H2O
H
HO
(2R,3R)-butane-2,3-diol
Drawn staggered
HO H
HH
Me
Me
OH
OH
H OH
Optically active?
Oxidative Cleavage
Like hydrogenation, products depend on the substitution of the
starting alkene. Note that the intermediate aldehydes cannot be
isolated under these strongly oxidative conditions. Instead, they
are further oxidized to carboxylic acids.
(CO2)
Oxidative Cleavage
Mechanism proceeds through a manganate ester. You
are responsible for knowing only the functional group
transformation not the mechanism
Oxidative Cleavage
Products depend on the substitution of the starting
alkene sp2 to 1s bonds are fully oxidized
H
H
mono
H
H
KMnO4
OH
H3O+
OH
O
tri
KMnO4
CH3
OH
tetra
CH3
KMnO4
KMnO4
H3O+
CH3
H3O+
H3O+
OH
OH
di
CH3
O
O
CH3
O
CH3
OH
Expoxidation
Epoxides are strained three-member cyclic ethers
Like bromonium ions, nucleophiles may ring open
expoxides
MCPBA is a Commonly Used Peroxyacid
CH2Cl2
Precipitates out of
solution as epoxide
is formed
Mechanism for Epoxidation

You are not responsible for knowing this mechanism
the mechanism is similar to that for the addition of Br2
Syn Addition to a cis Isomer

Forms Only the cis Stereoisomers
Syn Addition to a trans Isomer

Forms Only the trans Stereoisomers
Strained Epoxides Ring Open

Recall the formation of a bromohydrin from the ring opening of a
bromonium ion
Nucleophiles can also ring open epoxides with the same

stereochemical result
Formation of cis and trans Diols

Consider the complementary reactions below
2
3
With the chemistry you now have, both products are available to
you.
Nomenclature of Epoxides
Alkynes
Nomenclature
Structure
Reduction
Acid/basechemistry
Carboncarbonbondforming
reactions
Nomenclature of Alkynes
An alkyne is a hydrocarbon that contains a carboncarbon triple bond.
General formula: CnH2n2 (acyclic)
CnH2n4 (cyclic)
The Structure of Alkynes
The triple bond is composed of a sigma bond and two bonds.
Alkynes Are Less Stable and

Less Reactive Than Alkenes
Addition of Hydrogen Forms an Alkane
Stopping at the Alkene
Lindlar Catalyst
Syn Addition
Why Cis?
The catalyst delivers the hydrogens to one side of the triple bond.
Relative Electronegativities of Carbon

Remember from chapter 2:
sp hybridized carbons have 50% s character and 50% p character
sp2 hybridized carbons have 33% s character and 66% p character
sp3 hybridized carbons have 25% s character and 75% p character
A Hydrogen Attached to an sp Carbon

is the Most Acidic
Remember from Chapter 2, the more s character, the closer the electrons are
to the offsetting nuclear charge and that results in the pKa values of alkynes,
alkenes, and alkanes
Amide ion the conjugate base of ammonia

Used to deprotonate acids with pKa values outside of water
pKa = 25
pKa = 35
HO is Not Strong Enough
pKa = 25
pKa = 15
Forming a New CarbonCarbon Bond
Mechanism for Formation of the

CarbonCarbon Bond
Two Steps
Designing a Synthesis
all reactions covered
in chapter 3
?
Me
Et
Me
H 2, Linlar
NaNH 2/NH3
Me
EtBr
Et
Me
Chapter5
DelocalizedElectronsandTheirEffect
onStability,pKa,andtheProductsofa
Reaction
Conceptsanddrawingresonance
structures
AromaticChemistry
ElectrophilicAromaticSubstitution(4
reactions),reduction.andsidechain
oxidation
Curvedarrowsdenoteelectronflow
Bothpositiveandnegativechargemaybedelocalized
DelocalizedElectronsAffect
pKa Values
Delocalizationinacids
Phenolsversus Alcohols
WhyPhenolsareMoreAcidic
AllylicandBenzylic
ResonanceContributorsfor
anAllylicCation
Allylic notaprimarycarbocation
aBenzylicCation
aBenzylicCation
DelocalizationEnergy
Thedelocalizationenergyistheextrastabilityacompoundhas
asaresultofhavingdelocalizedelectrons.
Electrondelocalizationisalsocalledresonance.
Delocalizationenergyisalsocalledresonanceenergy.
Theresonancehybridismorestablethananyofits
resonancecontributorsispredictedtobe.
Benzene extremedelocalization
Heatsofhydrogenation
Thedelocalizationenergyofbenzeneis36kcal/mol.
Benzene anaromatic molecule
CriteriaforaCompoundtoBeAromatic
Mustbecyclic
All atomsmustbesp2 hybridized flat
Musthave2,6,10... electrons(Huckelnumber)
PolycyclicAromaticHydrocarbons
e
2
6
10
14
18
etc.
10e
14e
ExamplesofCompounds
ThatareNotAromatic
e
2
6
10
14
18
etc.
CyclobutadienedoesnthaveaHuckelnumber ofelectrons.
Cyclooctatetraeneisnotplanar.
Aromaticions
e
2
6
10
14
18
etc.
cyclopentadiene
cyclopentadienylanion
Anionisaromatic
HeterocyclicAromaticCompounds
e
2
6
10
14
18
etc.
pyrimidine
purine
caffeine
nicotine
LSD
OrbitalStructureofPyridine
OrbitalStructureofPyrroleandFuran
Pyrrolesimilartocyclpentadienylanioninstructure
ProtonatedAnilinesversus
ProtonatedAmines
NitrogenContainingHeteroaromatics
H+
pKa = 5
N
N
H
pyridine - a base
lone pair not part of the aromatic system - able to form a bond to a proton
H+
N
N
pKa = 2
N
H
pyrimidine a base
lone pair not part of the aromatic system - able to form a bond to a proton
e
2
6
10
14
18
etc.
CombiningConcepts:
WithdrawingElectronsbyResonance
WithdrawingElectronsbyResonance
Combiningconcepts hydrohalogenation
andresonancedelocalization
WhytheDifferenceinRate?
Localizedvs.delocalized
ReactionsofBenzene
ElectrophilicAromaticSubstitution(EAS)
1. Halogenation
2. Nitration
3. Acylation
4. Alkylation
Redoxreactionsofsubstitutedbenzenes
6. Sidechainoxidation
7. Reductionofnitrobenzene
TheNomenclatureofSubstituted
Benzenes
somemonosubstitutedbenzenesarenamed
justbyaddingthenameofthesubstituenttobenzene
TheNomenclatureofSubstituted
Benzenes
Mostaromaticcompoundsarecommonlynamed.
ElectrophilicAromaticSubstitution
Aromaticcompoundssuchasbenzeneundergoelectrophilic
aromaticsubstitutionreactions(EAS).
OfthefourEASreactionsthatwillbediscussed,allproceedwith
themechanismshownabove onlydifferingintheidentityof
theelectrophile
NobelPrizeinChemistry2016
JeanPierreSauvage
J.FraserStoddart
BernardL.Feringa
NobelPrizeinChemistry2016
JeanPierreSauvage
J.FraserStoddart
BernardL.Feringa
Substitution not addition
The electronsarenucleophilic(likeelectrophilicaddition)
Aromaticityisrestoredintheproductfromelectrophilicsubstitution.
CommonEASmechanism
1.Halogenation ofBenzene
Bromination orchlorination ofbenzenerequiresaLewisacidcatalystbecause

benzenesaromaticitycausesittobelessreactivethananalkene.
Iron(III)oraluminiumchloridesorbromidesarethetypicalLewisacidcatalysts.
EASmechanism halogenation
M=metal=aluminumoriron(III)
Br+ orCl+ istheelectrophile
(e.g.,FeCl3 orFeBr3)
H
+
Br
H
Br
Base
Br
2.NitrationofBenzene
EASmechanism nitration
Sulfuricacidprotonatesnitricacid.
Protonatednitricacidloseswater
toformtheelectrophile(thenitroniumion).
3.EASAcylation
An acid (acyl) chloride is the source of the acyl group

Acid chlorides are easy to make with thionyl chloride
EASmechanism acylation
Theacylium ionistheelectrophile.
EASacylation intramolecular
Cycliccompoundsareformedfromintramolecularreactions.
Formationoffive andsixmemberedringsarefavored.
4.EASAlkylation
Analkyhalideisthesourceofthealkylgroup.
ALewisacid(AlCl3)isrequired.
EASmechanism alkylation
Acarbocationistheelectrophile.
Thisreactionislimitedtoalkylhalidesthatcanformcarbocations
5.Sidechainoxidation no mechanism
functionalgrouptransformation=alkylbenzenetobenzoicacid
Alkylbenzenemusthaveatleastonebenzylichydrogen
Multiplesidechainscanbeoxidized
orKMnO4
orKMnO4
6.Nitrobenzenereduction no
mechanism
Nitrobenzenereduction functionalgrouptransformation
Nitrobenzenetoaniline
NomenclatureofDisubstitutedBenzenes
Therelativepositionsoftwosubstituentscanbeindicated
bynumbersorbytheprefixesortho (1,2),meta (1,3)orpara (1,4)
TheEffectofSubstituentsonReactivity
EASrequiresthe electronsinringtoattackelectrophile
ElectronDonatingGroups(EDG)donateelectrondensitytothebenzeneringincreasing
benzenesnucleophilicityandstabilizingthecarbocationintermediate.
ElectronWithdrawingGroups(EWG) withdrawelectrondensitytothebenzenering
decreasingbenzenesnucleophilicityanddestabilizingthecarbocationintermediate.
ElectronDonatingGroups(EDG)
Themethoxygroupiselectrondonating.
Sameargumentastowhyphenolisastrongeracidthancyclohexanol
electrondelocalization
O
ElectronWithdrawingGroups(EWG)
Thenitrogroupiselectronwithdrawing
Anatomdirectlyattachedtotheringthatisdoublyortriplybondedtoan
electronegativeatomwithdrawselectronsbyresonance.
Comparedwithbenzene
Electrondonatinggroups
EDGdonateelectrondensitytothebenzeneringincreasingbenzenes
nucleophilicityandactivating towardsEAS.
Electronwithdrawinggroups
EWGwithdrawelectrondensitytothebenzeneringdecreasingbenzenes
nucleophilicityanddeactivating towardsEAS
Electroniceffects
EWG:Substituentsthatwithdrawelectrondensityhaveafullorpartial
positivechargenexttothearomaticring
EDG:Substituentsthatdonateelectrondensityhaveaalkylgroupora
heteroatom(lonepair)nexttothearomaticringandactivatethecompound
towardsadditionalEAS
O
CH3
CH3
same concept
Remember that alkyl groups can donate electron density

this was used to explain the order of carbocation stability
Synthesisofdisubstituted
aromatics directingeffect
Allactivatingsubstituentsareorthoparadirectors.
Activation meansthattoluenewillbebrominatedfaster comparedwith

benzene
MetaDirectors
Alldeactivatingsubstituentsaremetadirectors.
Deactivationmeansthatnitrobenzenewillbebrominatedslower compared
withbenzene
Halogensareunique
Halogens withdraw electron density (more electronegative than carbon)
but have lone pair electrons so they are deactivating but ortho/para
directors. This is the only exception
Nitrationofphenol
OH
OH
ortho
OH
H
NO2
H
NO2
OH
OH
H
NO2
OH
OH
H
NO2
OH
NO2
ortho
OH
OH
meta
H
NO2
H
NO2
H
NO2
OH
OH
OH
O2N H
O2N H
O2N H
NO2
OH
para
OH
O2N H
NO2
para
Brominationofnitrobenzene
O
O
H
NO
Br 2
NO2
ortho
NO2
NO2
H
Br
NO2
H
Br
NO2
NO2
NO2
Br
Br
NO2
NO2
meta
H
Br
H
Br
NO2
NO2
H
Br
NO2
Br
NO2
para
Br H
Br H
O2Br
N H
Br H
Br
meta
Positivecharge(+)alwaysisortho andpara
tosp3 carbonofintermediate
Positivecharge(+)alwaysisortho and
para tosp3carbonofintermediate
EWG
H
(+)
(+) (+)
H
(+)
(+) (+)
(+)
(+) (+)
EWG
ortho
EWG
para
very destabilizing
meta
less destabilization
TheOrderoftheReactionsisImportant
starting from toluene, draw a synthesis of 4-chlorobenzoic acid
CO2H
CHR2
KMnO4
Cl
Cl2, AlCl3
toolkit
side chain oxidation
EAS chlorination
CO2H
CO2H
CH3
CH3
CH3
Cl
CO2H
Cl
Cl
CO2H
Cl
Cl
TheOrderoftheReactionsisImportant
starting from toluene, draw a synthesis of 4-chlorobenzoic acid
CO2H
CHR2
KMnO4
Cl
Cl2, AlCl3
toolkit
side chain oxidation
EAS chlorination
CO2H
CO2H
CH3
CH3
CH3
Cl
CO2H
Cl
Cl
CO2H
Cl
Cl
RecognizeEWGandEDG andextendto
othersystems
ExplainthetrendofpKavalues
Chapter 6 - Stereochemisty
Why You Care

Frances Oldham Kelsey
1914-2015
Thalidomide
Pioneering Work
Tartaric acid salts
Louis Pasteur
1822-1895
Concept of isomerism
Carvone - Different Smells
spearmint
Caraway seed
Carvone - Different Smells
Isomers
Compounds that have the
same molecular formula but
different structures.
Constitutional Isomers
Constitutional isomers differ in the way the atoms are connected.
CisTrans Isomers in Rings

Cistrans isomers result from restricted rotation.
Cyclic structures restrict rotation.
Cis: The substituents are on the same side of the ring.

Trans: The substituents are on opposite sides of the ring.
CisTrans Isomers in Alkenes

Double bonds restrict rotation.
Cis: The hydrogens are on the same side of the double bond.
Trans: The hydrogens are on opposite sides of the double bond.
Stereochemistry, Odd Terminology but

Easy Concepts
Chiral, chirality, chiral center, achiral
Plane of symmetry
Asymmetric center
Enantiomer, diastereomer, meso compound
Absolute configuration
Fischer projections
Optical activity, plane polarized light
Racemic
Stereoisomers: Chiral and Achiral

Objects
Chiral objects
Achiral objects
Chiral Molecules
A chiral center is an atom that is attached to four different groups.
Finding a Chiral Center
4-octanol
Look for a carbon bound to 4 different groups
Enantiomers
Enantiomers are different compounds but can be difficult to separate.

Enantiomers have the same physical and chemical properties.
Enantiomers
Plane-Polarized Light
A Chiral Compound is Optically Active
A chiral compound rotates

the plane of polarization of plane-polarized light.
If it rotates the plane clockwise = (+)
If it rotates the place counterclockwise = ()
Chiral and Achiral Molecules
Chiral compounds have nonsuperimposable mirror images.

Achiral compounds have superimposable mirror images
(there is a plane of symmetry).
Chiral and Achiral Molecules
achiral
achiral
chiral
Tetrahedral carbon with 4 different groups is just a

shortcut to thinking about symmetry.
Chiral compounds lack a plane of symmetry
Achiral compounds possess a plane of
symmetry
How to Draw Enantiomers

Wedge and Dash
Fischer projections
Fischer projections are just another way of showing a tetrahedral center
Naming Enantiomers
Assign relative priorities to the four groups.

1 = highest priority; 4 = lowest priority
Naming Enantiomers
Prioritize Groups
1 = highest priority
4 = lowest priority
Identify chiral carbon, assign priorities 1 and 4 first. Evaluate connections for
assigning priorities 2 and 3.
Naming Enantiomers
clockwise = R
and
counterclockwise = S
Naming Enantiomers
draw an arrow from 1 to 2 to 3
if the lowest priority group is on a hatched wedge, then

clockwise = R
and
counterclockwise = S
Naming Enantiomers
(S)
(R)
Swapping two groups (but only two groups) will give the
opposite enatiomer.
Sometimes it is easier to draw the R enantiomer and
convert to S.
R and S Versus (+) and ()

Some R enantiomers are (+) and some are ().
Some S enantiomers are (+) and some are ().
Compounds with Two Asymmetric Centers

maximum # of stereoisomers = 2n
(n = # of asymmetric centers)
1 and 2 are enantiomers.
Diastereomers
Diastereomers are stereoisomers that are not enantiomers.

1 and 3 are diastereomers.
Diastereomers have different physical and chemical properties.
Chirality in Rings
Two Asymmetric Centers,

Four Stereoisomers
The cis stereoisomers are a pair of enantiomers.

The trans stereoisomers are a pair of enantiomers.
Identifying an Asymmetric Center
An asymmetric center is attached to four different groups.
two asymmetric centers, four stereoisomers
No Asymmetric Centers
There are only two stereoisomers: cis and trans.
Two Asymmetric Centers: Three Stereoisomers

(a meso compound and a pair of enantiomers for
symmetrically substituted compounds)
A Meso Compound Has a

Superimposable Mirror Image
Meso compounds are optically inactive even though they have asymmetric centers.
A Meso Compound Has a

Plane of Symmetry
A Meso Compound
A compound with two asymmetric centers that have the same four groups
bonded to each asymmetric center will have three stereoisomers:
a meso compound and a pair of enantiomers.
Naming Stereoisomers
Naming Stereoisomers
Physical Properties of Stereoisomers
Stereochemistry Presents Challenges to Synthetic Chemistry

In the 90s, over 30 teams worked to achieve a total synthesis
C
D
Paclitaxel was harvested from

the pacific yew, a species that
is near threatened
The pacific yew
Stereochemistry Presents Challenges to Synthetic Chemistry

In the 90s, over 30 teams worked to achieve a total synthesis
C
D
Annual sales reached US$1.6

billion in 2000; Paclitaxel is now
available in generic form.
K. C. Nicolaou
R. H. Holton
Contrave weight-loss formulation FDA approved 9/10/14
Bupropion Wellbutrin
Antidepressant/smoking cessation
HO
N
CH3
H
HO
Naltrexone an
opioid antagonist:
binds opioid receptor
with higher affinity
than the agonist
without activating the
receptor
Morphine an opioid
agonist: binds opioid
receptor with
activation
Controlling Stereochemistry is Critical in Drug Manufacture.

Top 5 Drugs in 2013
Chapter 7
Substitution&EliminationReactionsof
AlkylHalides
We will start considering alkyl halides with X being Cl, Br, or I
Alkyl halides can undergo subsitition and

elimination
Substitution reactionthe electronegative group is replaced by another group.
Elimination reactionthe electronegative group is eliminated along with a hydrogen.
More precisely called a nucleophilic substitution reaction

because the atom replacing the halogen is a nucleophile.
Leaving Group
Nucleophile
A Substitution Reaction
Relative Rates of an SN2 Reaction
Does not
undergo
SN2
Tertiary alkyl halides do not undergo SN2 substitution.
If the halogen is bonded to an chiral sp3 cabron,

the product will have the inverted configuration.
Leaving Group
Nucleophile
Inverted Configuration
Summary of the Experimental Evidence

for the Mechanism of an SN2 Reaction
1. The rate of the reaction is dependent on the concentration
of both the alkyl halide and the nucleophile.
2. The relative rate of the reaction is
methyl > primary > secondary
tertiary alkyl halides do not undergo SN2 reactions.
3. If the starting alkyl halide is chiral at the halogen, the

configuration of the product will be inverted.
The Mechanism
back-side attack
Inversion!
Why Bimolecular?
Why Do Methyl Halides React the Fastest

and Tertiary Halides are Unreactive?
steric hindrance
Why the Configuration of the Product

is Inverted
The Weakest Base is the Best Leaving Group
The Rate of an SN2 Reaction

is Affected by the Leaving Group
Steric Hindrance Decreases Nucleophilicity
Even though the tert-butoxide ion is a

stronger base, it is a poorer nucleophile
because
nucleophilic
attack
is
more
sterically hindered than proton removal.
SN2 Reactions Can Be Used to Make

a Variety of Compounds
The reactions are irreversible because a strong base displaces a weak base.
Tertiary Alkyl Halides & SN1
A tertiary alkyl halide will not undergo SN2 but

will react by an alternate mechanism called SN1
The Product is a Pair of Enantiomers

No inversion (unlike SN2)
Racemization (loss of control over stereochemistry) in SN1
If a halogen is bonded to a chiral center,

the product will be a pair of enantiomers.
Summary of the Experimental Evidence

for the Mechanism of an SN1 Reaction
1. The rate of the reaction depends only on the
concentration of the alkyl halide.
2. Tertiary alkyl halides react the fastest.
3. If the halogen is attached to an asymmetric center

the product will be a pair of enantiomers.
The Mechanism
The leaving group departs before the nucleophile approaches.
Rate-Determining Step
Most SN1 reactions are solvolysis

reactions; the nucleophile is the solvent.
The Rate of an SN1 Depends Only on the

Concentration of the Alkyl Halide
Rate-Determining Step
The Slow Step is Formation of the Carbocation
Tertiary alkyl halides react the fastest

they form the most stable carbocations.
Primary alkyl halides do not undergo SN1 reactions
they form the most unstable carbocations.
Why a Pair of Enantiomers?
The Weakest Base is the Best Leaving Group
pKa
HF
3
HCl -7
HBr -9
HI
-11 Most acidic (most stable X)
Benzylic and Allylic Halides

Undergo SN2 Reactionsbut

Can Also Undergo SN1 Reactions
The SN1 Reaction of Allylic Halides

Can Form Two Products
Vinylic and Aryl Halides

Cannot Undergo SN2 Reactions
Vinylic and Aryl Halides

Cannot Undergo SN1 Reactions
Summary of Alkyl Halide Reactivity
Substrate
Substitution Mechanism
methyl and 1o
SN2 only
allylic, benzylic, and 2o
Both SN2 and SN1
3o
SN1 only
vinylic and aryl halides
Neither SN2 or SN1
Intermolecular versus Intramolecular

SN2 Reactions
The Intramolecular Reaction is Favored When

a Five- or Six-Membered Ring Can Be Formed
3-Membered and 4-Membered Rings

are Less Stable
Three-membered rings are generally formed faster than 4-membered rings.
EliminationReactionsofAlkylHalides
CompetitionBetweenSubstitutionandElimination
Alkyl Halides Undergo

Substitution and Elimination Reactions
In an elimination reaction, a halogen is removed from one carbon
and a hydrogen is removed from an adjacent carbon.

A double bond is formed between the two carbons
from which the atoms were removed.
An E2 Reaction
The Halogen Comes off the Alpha Carbon;

the Hydrogen Comes off the Beta Carbon
All elimination reactions are elimination. The double

bond always forms between the and carbons
Stereochemistry
180o
Leaving group and hydrogen must have a

dihedral angle of 180o also called antiperiplanar
Energy
Anti Elimination is Preferred
Like SN2, an E2 is a one-step reaction.

The base and the substrate must come together to form the transition state
thus giving the kinetic profile
Anti Elimination
The alkene with the bulkiest groups on opposite sides

of the double bond will be formed in greater yield,
because it is the more stable alkene.
An E2 Reaction is Regioselective
A disubstituted alkene
A monosubstituted alkene
The major product is the most highly substituted alkene.
RecallAlkeneSubstitutionPatterns
H
mono
di
tri
tetra
More E2 Reactions
-Identify all carbons

-All possible products will have a bond between the and carbons
-Major product will be the most highly substituted alkene
Conjugation is preferred
The conjugated alkene is the more stable alkene.
An E1 Reaction
Recall the Stabilities of Carbocations
doesnt
form
The Mechanism for an E1 Reaction
An E1 Reaction is Regioselective
The major product is the more substituted alkene.

Undergo E2 & E1 Reactions
Conjugated Dienes

Undergo E2 & E1 Reactions
Both E2 and E1
Compare these elimination reactions
E2 and E1 Reactions are Regioselective

E2
E1
All elimination reactions are eliminations and

the most substituted alkene is preferred
trans is preferred to cis
E2 Elimination from Six-Membered Rings
Both groups being eliminated must be in axial positions.
H and Cl Must Both Be Axial

-Lowestenergychair
-E2notpossibleinthisringconforma on
H
C
-Highestenergychair
-E2possibleinthisringconforma on
-Two hydrogensat180o toleavinggroup
H
C
C
H
Cl
C
H
E2
Cl
Neomenthyl Chloride is Faster

CH(CH3)2
C
Cl
CH3
C
H
CH
C
CH3
Cl
Cl
H3C
disubs tuted
minor
trisubs tuted
major
C
CH
CH3
Menthyl Chloride is Slower

CH(CH3)2
Cl
C
H
Cl
CH3
CH
Cl
CH3
H
C
H
CH
H 3C
disubs tuted
onlyproduct
CH3
SN2 and E2 can compete
2o undergo both E2 and SN2
Under SN2/E2 Conditions

Primary Alkyl Halide = Primarily Substitution
Steric Hindrance Favors Elimination

Secondary Alkyl Halide = Substitution and Elimination
Substitution is favored by a weak base.

Elimination is favored by a strong base.

Tertiary Alkyl Halide = Only Elimination
Under SN1/E1 Conditions Tertiary Alkyl Halides

Undergo Substitution and Elimination
Tertiary (SN1/E1): Substitution is Favored

Tertiary (SN2/E2): Only Elimination
Weak base
Strong base
William Ether Synthesis:

an SN2 Reaction
Forming an Alkoxide Ion
Synthesizing Butyl Propyl Ether
Synthesizing Ethyl Isopropyl Ether

synthesizeethylisopropyletherusingaWilliamsonethersynthesis:
Firstbreakapartintonucleophile(alkoxide)andelectrophile(alkylhalide)
Therearetwopossible"disconnects"
O
O
Br
Br
O
analysis: SN2islimitedbystericsinthetransi onstatesothebestrouteisusingthe1o alkyl

halidebromoethaneandisopropoxide
Synthesizing an Alkene
The more hindered group should be provided by the alkyl halide.
Hydration of an alkene/dehydration of
an alcohol
Dilute vs. concentrated acid

Lots of water
Not very much water
Same mechanism run in reverse
Converting an Alkene to an Alkyne

A special case
Br
Br NaNH2/NH3
Br2
3 eq
NaNH2
NaNH2
Br
NaNH2
Driving force is deprotonation of alkyne
Chapter 8
ReactionsofAlcohols,Ethers,
Epoxides,andThiols
Manyreactionsinthischapterare
extensionsfromchapter7.
Strongly Basic Leaving Groups

Cannot Be Displaced
alcohols
Acid Converts the Poor Leaving Group

into a Good Leaving Group
Alcohols have to be protonated or converted into good leaving groups

SN2 chemistry
alcohols
The Reactions of Secondary and Tertiary Alcohols

with Hydrogen Halides are SN1 Reactions
alcohols
The Reactions of Primary Alcohols

with Hydrogen Halides are SN2 Reactions
alcohols
Why is It Important to Be Able

to Convert Alcohols to Alkyl Halides?
All SN2 reactions

alcohols
Other Methods to Convert

Alcohols into Alkyl Halides
NEW REACTIONS!
phosphorus tribromide & thionyl chloride
You do not need to know the mechanism of these reactions
alcohols
Sulfonate Esters in SN2 reactions

o
alcohols
A Sulfonate Ester is a good leaving group
alcohols
Stereochemical Considerations
2 inversions
1 inversion
alcohols
Two SN2 Reactions or

One SN2 Reaction?
inversion
inversion
inversion
Stereochemistry is important here.
alcohols
Dehydration of an Alcohol
Dehydration of an alcohol either E1 or E2

depending on the substitution of the alcohol
alcohols
Dehydration is a Reversible Reaction
The difference between concentrated and dilute acids
alcohols
Dehydration of Secondary and Tertiary

Alcohols are E1 Reactions
alcohols
Dehydration (E1) is a Regioselective

Reaction
The major product is the more stable alkene.

alcohols
Dehydration of a Primary Alcohol

is an E2 Reaction
alcohols
Dehydration is Stereoselective
The major product is the stereoisomer with the

largest groups on opposite sides of the double bond.
alcohols
A better way to eliminate an alcohol
Non-acidic conditions
alcohols
Ethers are alkylated alcohols
ethers
Ethers react with hydrogen halides
ethers
Ethers Are Common Solvents

Because They React Only with Hydrogen Halides
Common solvents
ethers
Devise a mechanism that accounts for the

following reaction
THF is a common organic solvent that is stable under many reaction
conditions except those including HCl, HBr, and HI. Under these strongly
acidic conditions, THF undergoes the following reaction. Draw a mechanism
that accounts for the formation of product using the curved arrow notation to
show all bond making and bond breaking.
ethers
Devise a mechanism that accounts for the

following reaction
Under these strongly acidic conditions (1 equivalent of HI), What would
happen with 2 equivalents of HI?
What mechanism is shown above?
ethers
Tert-butyl ethers are often used to reversibly

protect the hydroxyl group
When isobutylene gas is reacted with a compound containing a hydroxyl
group in the presence of a non-aqueous acid, a tert-butyl ether may be
formed as shown below. Devise a mechanism that accounts for the formation
of this product.
ethers

Start by remembering electrophilic addition of the proton to the alkene to
give the tert-butyl cation. The cation is attacked by the hydroyl group to give
the ether.
ethers

This reaction is reversible depending on conditions.
H+
(TFA)
ethers
Recall synthesis of an epoxide

from a per-acid
Naming epoxides: add oxide to the end of the alkene name.

For example, cyclohexene is converted to cyclohexene oxide when
reacted with m-chloroperbenzoic acid (mCPBA) in dichloromethane.
epoxides
Synthesis of an Epoxide from a

halohydrin intramolecular SN2
chlorohydrin
epoxides
Epoxides can be easily ring opened

with SN2 or SN1 type chemistry
because of ring strain
When the epoxide isnt symmetric
epoxides
The Acid-Catalyzed Mechanism

SN1-like
epoxides
If the Epoxide is Not Symmetrical,

Which Carbon Does the Nucleophile Attack?
The nucleophile attacks the more substituted epoxide carbon.

epoxides
Under Acidic Conditions the Nucleophile Attacks

the More Substituted Ring Carbon
epoxides
Under Neutral or Basic Conditions the

Nucleophile Attacks the Less Substituted Carbon
SN2-like
epoxides
Using Epoxides in Synthesis
P.T.
P.T. = proton transfer

epoxides
Forming a trans-1,2-Diol
enantiomers
1,2-diols
Forming a cis-1,2-Diol
: :
: :
Sulfur containing compounds
Nomenclature of Thiols
Chemistry of thiols
Acid/base & SN2
Thiols have pKa values of about 10.

The conjugate base form (thiolates) are excellent nucleophiles and less
prone to elimination chemistry
Chemistry of thiols
Redox
O
HS
O
OH
OH
NH2
NH2
cysteine
methionine
Chemistry of sulfides
Redox
Polar aprotic solvents

SN2
Sulfonate esters are good leaving

groups
O
S Cl
O
Me
OH
OTs
NaN3
N3
TsCl
O
O S
O
Me
O
Me
O S
O
stable conjugate base
O
HO S
O
Me
pKa <0
good leaving group

which means
which means
Secondary Alcohols can be

oxidized to ketones
Redox chemistry
Primary alcohols can be oxidized

to acids and aldehydes
aldehyde
Redox chemistry
Tertiary Alcohols Cannot Be Oxidized

to a Carbonyl Compound
Redox chemistry
Carbonyl Chemistry
Chapter9 ReactionsofAldehydesand
Ketones
Reactionsof,UnsaturatedCarbonylCompounds
Lookingforward,Chapter10coverscarboxylicacidsand
derivativesandChapter11coversenolandenolate
chemistry
Carbonyl Overview
Three areas:
aldehyde & ketone chemistry
carboxylic acids & derivatives
enol/enolate chemistry
Note that Y is not a leaving group in this chapter
common nomenclature
3
3
3
3
synthesis via oxidation of alcohols

1o and 2o alcohols may be oxidized using chromic
acid, chromate salts, dichromate salts, or
permanganate. Note that primary alcohols do not stop
at the aldehyde but rather oxidize to the carboxylic
acid.
No Mechanism Required
synthesis via oxidation of alcohols

To oxidize a primary alcohol to an aldehyde without
over oxidizing to the carboxylic acid, PCC is used.
PCC may also be used to oxidize secondary alcohols
to ketones.
No Mechanism Required
O
O Cr Cl pyridinium chlorochromate = PCC
O
N
H
OH
OH
PCC
CH2Cl2
PCC
CH2Cl2
CHO
Aldehydes and ketones are

attacked by nucleophiles
The partial positive charge on the carbonyl carbon causes it to be
attacked by nucleophiles:
nucleophilic attack on the carbonyl
carbon
O
C
Nu
Nu
chapter 10: carboxylic acids and

derivatives: Y = Leaving Group
O
C Y
R
Nu
O
C
common tetrahedral
intermediate
OH
C Y
R
Nu
chapter 9: aldehydes and ketones
irreversible
alcohol syntheses
Grignard, hydride reduction
reversible reactions
imines and acetals
Grignard Chemistry
Grignard reagents have inverted polarity at the carbon bound to

magnesium thereby making that carbon nucleophilic.
Grignard reagents are formed by reacting the alkyl (or other) halide
with magnesium metal in the aprotic solvent ether
Nomenclature
Name the organic group, then the metal.
MgBr
phenylmagnesium bromide
ethylmagnesium chloride
MgCl
vinylmagnesium bromide
MgBr
allylmagnesium chloride
benzylmagnesium bromide
MgCl
MgBr
Grignard reagents react as if they were

carbanions
Grignard reagents are strong bases. If

Grignard reagents are exposed to water,
they are destroyed
Grignard reagents are nucleophiles

SN2 chemistry
Carbonyl addition chemistry
Girgnard and formaldehyde, aldehyde, ketone, and epoxide a

synthesizing alcohols
Girgnard reagents combined with formaldehyde,

aldehydes, ketones, and epoxides are all ways
of synthesizing alcohols
Aldehydes and ketones may be reduced to

alcohols using nucleophilic hydride
Sodium Borohydride NaBH4
H
H
B
H
H
Na
O
HO
+
H3O
Hydrogen is added in two steps:

first hydride then proton
Different flavors of hydride

NaBH4 and LiAlH4 are both sources of nucleophilic hydride.
LiAlH4 is a more powerful reducing reagent able to reduce
carboxylic acids and derivatives such as esters to alcohols.
These reactions will be discussed in the next chapter
OH
O
no reaction
NaBH4
MeOH
Me
a. LAH, ether
b. H3O+
NaH, sodium hydride is only used as a strong base.
HO
Me
Both Grignard reactions and hydride

reduction are irreversible reactions
A
When the Eact reverse is

too great the reaction is
considered irreversible
Eact fwd
Eact rev
Eact rev
Grignard reactions and

hydride reductions of
aldehydes and ketones are
irreversible
Irreversible Reactions
Grignard reagents react with aldehydes & ketones to give alcohols
Hydride reduction
Reversible reactions of aldehydes and

ketones
We will cover two reversible reactions:

Imine bond formation
Acetal formation
You are required to demonstrate knowledge of the
mechanism of each of these reactions.
aldehydes and ketones give imines

with 1o amines
Imine bond formation is reversible
Mechanism for Imine Formation
Imine formation is reversible

imine hydrolysis
Imines are like carbonyl compounds

and can be reduced
When formation and reduction are coupled:
The reactions of alcohols with aldehydes

and ketones - formation of acetals
Formation remove water

Hydrolysis add water
The reactions of alcohols with aldehydes

and ketones - formation of acetals
P.T.
H3C
HO
H3C
CH3
P.T.
H
O OH
P.T.
H3C
O OH
P.T.
H3C
H
O O H
Hemiacetal
("half-acetal")
CH3
H3C
H3C
O O H
H3C
acetal
H3C
OH
Removing water drives formation
-H2O
H3C
resonance stablilized
cation
The reactions of diols with aldehydes and

ketones - formation of cyclic acetals
The attack of the second hydroxyl oxygen in

intramolecular
Like imines, acetals can be hydrolyzed
Dilute acid drives hydrolysis
Only cyclic hemiacetals are stable
Sugar Units in Carbohydrates

are Held Together by Acetal Groups
Cyclic Acetals are Protecting Groups
Using Protecting Groups in Synthesis
LiAlH4 will reduce the ester to an alcohol, but the keto group will also be reduced.
The keto group is protected as a ketal in the following synthesis:
,-Unsaturated Aldehydes and Ketones

Have Two Electrophilic Sites
Direct Addition to ,-Unsaturated

Aldehydes and Ketones
1,2-addition
Y: = RMgBr, H:
Conjugate Addition to ,-Unsaturated

Aldehydes and Ketones
1,4-addition
Weak Bases Form

Conjugate Addition Products
In a Chemoselective Reaction,
One Functional Group Reacts Preferentially
4
3
Retrosynthetic analysis
Starting from propene, draw a synthesis of 4-methylpentan-2-ol. Hint:
Grignard chemistry is a key step
When assigned such a problem, the key is to determine where to
disconnect so that you can work backwards towards the starting material.
Only practice will help with this analysis. For the purpose of this lecture, the
disconnection is shown with the wavy red line.
Each disconnect is a heterolytic bond cleavage (one partner takes the
electrons in the covalent bond) therefore there are always two possibilities of
electrophile/nucleophile pair
Here are those two possibilities with the given product
At this point, you should realize that these anion/cation pairs likely
cant be formed, but we can use synthetic equivalents. You have
seen this with alkyl halide chemistry using SN2
O
O
base
C2H2
not possible
While we cant form the primary carbocation, we can use a alkyl halide
that is synthetically equivalent to the cation. This was the basis of alkyl
halides in SN2 chemistry.
The best disconnect is boxed below
Synthesis:
mcpba
CH2Cl2
HBr
ether
key bond
O
Br
O
Mg
ether
BrMg
H3O+
product
Sometimes these type problems are presented as road maps that tether
your analysis
Roadmap problems are in turn, linked functional group transformations. The
key it to recognize the transform use notecards and study in groups.
Roadmap problems are in turn, linked functional group transformations. The
key it to recognize the transform.
Chapter 10
ReactionsofCarboxylicAcidsand
CarboxylicAcidDerivatives
Carbonyl Overview
The next three chapters cover the chemistry of the carbonyl group
that are focused on:
carboxylic acid & derivative chemistry
aldehyde & ketone chemistry
enol/enolate chemistry
chapter 18
OH
C
enol
Y
enolate
Nomenclature of carboxylic acids
Carboxylic acids
Nomenclature of Carboxylate Ions
Carboxylic acids
Two basic reactions of carbonyl compounds
Nucleophilic acyl substitution
Carboxylic acids and

Derivatives
R
OH
carboxylic acid
carboxylate
O
R
thioester
O R
O
acyl phosphate
amide R
ester
O
O P
Cl
acyl chloride
acid anhydride
The structure of a carbonyl compound
The carbonyl carbon is electrophilic
For carboxylic acids and derivatives, Y is a leaving group
Carbonyl resonance contributors
A Nucleophilic acyl substitution reaction
Y = Leaving Group
Z = nucleophile
The relative reactivities towards nucleophilic acyl

substitution depend on the Leaving Group
Acid/Base and properties

pKa values, solubility - review
Carboxylic acids
Synthesis of acids
Oxidative cleavage (review)
Oxidation of primary alcohol (review)
Grignard with CO2 (new reaction)
Hydrolysis of derivatives (new reaction,
covered throughout the chapter)
Carboxylic acids
New synthesis of a carboxylic acid
Add to your Grignard notecards:

Grignard + formaldehyde = primary alcohol
Grignard + epoxide = primary alcohol
Grignard + aldehyde = secondary alcohol
Grignard + ketone = tertiary alcohol
Grignard + CO2 = acid
Carboxylic acids
Closer look at
Carboxylic acid derivatives
Carboxylic acids can be converted into the
following derivatives
carboxylic acid chlorides
carboxylic acid anhydrides
esters
amides
anhydrides
nitriles
All carboxylic acid derivatives can be

hydrolyzed back to carboxylic acids
Synthesis & Reactions of acid chlorides

Carboxylic acid chlorides are easily synthesized from
carboxylic acids upon reaction with thionyl chloride (SOCl2).
Acid chlorides can themselves be used to synthesize:
acid anhydrides, esters, & amides
O
C
O
SOCl2
C
OH pyridine R
Cl
hydrolysis
HNR'2 (2 eqivalents)
R'OH
O
C
O2CR'
OR'
O
C
O
C
O
C
NR'2
Acid chlorides
Nomenclature of acid chlorides
Acid chlorides
Ester synthesis via acid chloride

R
O
C
O
C
Cl
Nu
O
C
R
Cl
Nu
O
C
Nu
Cl
O
O
HCl
C
C
H 3C
H 3C
Cl
H3C
OEt
O
H
Et
sythesis of ethyl acetate from acetyl chloride
H
Et
Cl O
Esterification Lab
H3C
O
C
O
Cl
acetyl chloride
OH
isopentyl alcohol
O
isopentyl acetate
"banana ester"
Acid chlorides
Amide synthesis via acid chloride
Acid chlorides
Amides cannot be synthesized by

combining an acid and amine directly
A carboxylic acid is an acid and an amine is a base,

so an acid-base reaction occurs.
Anhydride synthesis via acid chloride
Acid chlorides
Nomenclature of acid anhydrides
Acid anhydrides
Acid Anhydrides are Less Reactive than Acyl Chlorides

but More Reactive Than Esters
Acid anhydrides
Reactions of Acid Anhydrides
As you will see, acid anhydrides are for the

most part, interchangeable with acid chlorides
Acid anhydrides
The Mechanism
Acid anhydrides
Esters can be prepared using a concentrated

acid-catalyst
O
OH
CH3OH
conc'n acid
(H+,
OCH3
e.g., H2SO4)
P.T.
P.T.
OH
Ph
OH
Ph
OH
H
H
H2O
OH
CH3
P.T.
OH
Ph
H P.T.
O
O H
OH
OCH3
CH3
CH3
This ester synthesis is called Fischer esterification and complements

your prior synthesis via an acid chloride
Nomenclature of Esters named as

carboxylates
cyclic esters are called lactones

O
Cyclic ester = lactone

O
tetrahydro-2H-pyran-2-one
-valerolactone
esters
The Reaction of an Ester with Water
esters
The Carbonyl Oxygen is the Oxygen That is Protonated
+ H3O+ ClProtonation of the carbonyl carbon increases the electrophilic character of the carbon
Less electrophilic
Resonance forms
+
More electrophilic
Resonance forms
esters
The Mechanism for the

Acid-Catalyzed Hydrolysis of an Ester
Proton Transfer
P.T.
esters
Protonation Makes the Leaving Group

a Better Leaving Group
esters
Use Excess Water

to Drive the Reaction to the Right
esters
The Mechanism for Hydroxide-Ion Promoted

Hydrolysis of an Ester
esters
The Reaction of an Ester with an Alcohol
important in biochemistry and biodiesel fuel production

esters
The Reaction of an Ester with a Grignard

From chapter 12
Esters react with two equivalents of Grignard to give tertiary alcohols via a
ketone intermediate
LG at tetrahedral intermediate
first equivalent
EtO O
Ph OH
MgBr EtO
O
MgBr
ketone more
electrophilic than
starting ester
second tetrahedral
intermediate
esters
Summary of Grignard Reactions

for 345
For final exam
Grignard + formaldehyde = primary alcohol
Grignard + epoxide = primary alcohol
Grignard + aldehyde = secondary alcohol
Grignard + ketone = tertiary alcohol
Grignard + CO2 = acid
2 equivalents of Grignard + ester = tertiary alcohol
Nomenclature of Amides
Cyclic amide = lactam

amides
Nomenclature of Amides
The substituent attached to the nitrogen is stated first.
Amide bonds are peptide bonds
amides
The Mechanism for the

Acid-Catalyzed Hydrolysis of an Amide
amides
Amide Hydrolysis Can Be Promoted

by Hydroxide Ion
Draw a mechanism. Which do you think is more resistant to basic

hydrolysis, an ester or an amide?
amides
Nomenclature of Nitriles
Nitriles dont look like other carboxylic acid derivatives but

they can be considered a dehydrated amide
nitriles
Acid-Catalyzed Hydrolysis of a Nitrile
Amide tautomer
nitriles
Another synthesis of a carboxylic acid
Compare to Grignard and CO2
nitriles
Reduction of carbonyl systems
Chainsaw
reduction
Reduction of carbonyl systems
LAH is strong enough to reduce all common carbonyl systems

LAH is strongly basic and must be used under anhydrous conditions like
Grignard reagents
LAH transfers two hydride atoms per carbonyl group
reduction
Fats and Oils are Formed by

Esterifying Glycerol with Fatty Acids
Fats/soaps
Fats/soaps
2014 Pearson Education, Inc.
Hydrolysis of Fat or Oil in a

Basic Solution Forms a Soap
A soap is a sodium or potassium salt of a fatty acid.

The reaction is called saponification and you
will run this reaction in lab.
Fats/soaps
A Micelle
Long-chain carboxylate ions form micelles.
Fats/soaps
Summary
Lots of substitution and hydrolysis reactions all the same mechanism
All carboxylic acid derivatives can be made from the acid chloride by choosing
the appropriate nucleophile
All carboxylic acids can be hydrolyzed with the nucleophile is water (aq acid
conditions) or hydroxide (aq base conditions)
Summary
Nitriles can be installed via SN2 chemistry and although they do not
look like other carbonyl compounds, they react the same.
Nitriles can be considered dehydrated amides
2
2
You have two methods of synthesizing esters: via the acid chloride
and an alcohol and by using Fischer esterification
Lithium aluminum hydride LiAlH4 is a source of nucleophilic hydride
and can reduce all carboxylic acids and derivatives. LiAlH4 must be
used under anhydrous conditions.
Chapter 11
Reactionsatthe
CarbonofCarbonylCompounds
Whatisan carbon?
enolateandenolconsiderations
carbon reactivity
a base can remove a proton from an carbon to form an

enolate ion
KEY POINT = electron delocalization is possible with
enolates
KEY POINT = enolate ions are nucleophiles
A Hydrogen Attached to an sp3 Carbon adjacent to a

Carbonyl Carbon have pKa values from 16-25
You can approximate the pKa value of any -hydrogen

to be 20
A hydrogen attached to an sp3 carbon adjacent to TWO

carbonyl carbon have pKa values of about 10
More electron delocalization

More stable conjugate base
Electron delocalization
3
Why?
Electron delocalization
in both compounds, the non-bonding electron can be

delocalized onto an electronegative atom
Enol equilibrium - tautomers
Tautomers differ in the location of a double bond and a hydrogen
Tautomers are in equilibrium
Tautomers are not resonance structures
Acid catalysis promotes enol formation
Enolates are nucleophiles
NaNH2
this method can be used to alkylate the -carbon of

ketones, esters, and nitriles
5 reactions from Chapter 11

halogenation
-acidic conditions
-basic conditions
2. aldol condensation
3. Claisen condensation
4. malonic ester synthesis
5. acetoacetic ester synthesis
6. Michael reaction (not new)
-you have already seen this reaction in chapter 9
Halogenation
only one -hydrogen is replaced by Br
Mechanism for
Acid-Catalyzed Halogenation
The halogen of the -carbon of an aldehyde

or ketone can undergo SN2
strong bases cannot be used for this reaction otherwise

E2 would predominate
-halogenation products can also eliminate to

give conjugated double bonds
Pyridine is a non-nucleophilic base
Methyl ketones the Haloform reaction

-halogenation under basic conditions
Each successive enolate is more stable

Final step is simple hydrolysis
Aldol reaction
aldehydes and ketones undergo aldol addition reactions

one molecule of the carbonyl carbon is an electrophile
and the other is a nucleophile
Aldol addition reactions
the product has twice as many carbons as the reactant
Aldol mechanism
recall
Same mechanism enolate is nucleophile
-hydroxyaldehydes and ketones can

undergo elimination
Crossed/Mixed Aldol additions

can give a mess
the crossed/mixed aldol addition forms 4 possible products
Some crossed/mixed aldols

will form 1 major product
the carbonyl compound with -hydrogens is added slowly

to a solution of the carbonyl compound without -hydrogens
and a base
Some crossed/mixed aldols

will form 1 major product
Your lab
A Claisen Condensation
a condensation reaction of two molecules of an ester
Mechanism for the Claisen Condensation

O
H
O
H
R'O
OR'
H H
O
H
H
form enolate
formation of new enolate

drives reaction
H H
O
R'O
OR'
H
O
OR'
OR'
OR'
OR'
H
H
H H
tetrahedral intermediate
loss of alkoxide, reform
carbonyl center
H
H
H
O
O
H
OR'
generate -keto ester,

pKa about 10
1,3-dicarbonyl
hydrogen
A Crossed Claisen Condensation

to a solution of the carbonyl compound without -hydrogens
and a base
A Crossed Condensation Between

a Ketone and Diethyl Carbonate

to a solution of the carbonyl compound without -hydrogens and a
base
Intramolecular Claisen condensations
1,3-dicarbonyl
Intramolecular Claisen condensations
Same mechanism
O
OCH3
Intramolecular Aldol Additions
No!
Followed
by
Dehydration
2 different enolate ions can be formed

formation of a 5-membered ring is favored over formation of
a 3-membered ring

No!
2 different enolate ions can be formed
Followed
by
Dehydration
formation of a 5-membered ring is favored over formation of

a 7-membered ring
Followed
by
Dehydration
Followed
by
Dehydration
3-Oxocarboxylic Acids Can be

Decarboxylated
Mechanism decarboxylation
You will not be tested on the mechanism for decarboxylation.

But know that 3-oxocarboxylic acids will decarboxylate when heated
structure of a 3-oxocarboxylic acid
O
Y 3
can be a 1,3-diacid
O
2
1 OH
HO
-CO2
OH
HO
can be a 1,3-ketoacid
O
R'
OH
R
-CO2
R'
The Malonic Ester Synthesis
a malonic ester synthesis forms a carboxylic acid

with two more carbons than the alkyl halide used in the synthesis
The Steps in the

Malonic Ester Synthesis
Malonic ester forming rings

O
EtO
NaOEt/EtOH
EtO
OEt
Br
Br
OEt
Sn2
H H
diethylmalonate
pKa = 10
O
EtO
OEt
H
Br
O
O
O
NaOH (aq)
saponification
EtO
EtO
HO
diester
HO
diacid
OEt
Br
second enolate
intramolecular Sn2
OH
OH
decarboxylation
OEt
HCl (aq)
bond tautomers
OH
The Acetoacetic Ester Synthesis
an acetoacetic ester synthesis forms a methyl ketone with three

more carbons than the alkyl halide used in the synthesis
The Steps in the Acetoacetic

Ester Synthesis
Same mechanism as
O
NaOEt/EtOH
Br
Br
OEt
OEt
Sn2
H H
acetoacetic ester
pKa = 10
OEt
H
Br
O
O
O
OEt
NaOH (aq)
OEt
saponification
diester
second enolate
intramolecular Sn2
HCl (aq)
Br
OH
OH
decarboxylation
bond tautomers
diacid
Acid/base chemistry to enolate, Sn2 (or two), saponification, decarboxylation
,-unsaturated aldehydes and ketones

undergo direct addition and conjugate addition
From Chapter 9
1,2 addition
1,4 addition
REVIEW ALERT FROM CHAPTER 9:

Weak Bases Form
Conjugate Addition Products
Michael Reactions
Look for the
1,5-dicarbonyl
substructure
when the nucleophile is an enolate ion,

the reaction is called a Michael Reaction
The Mechanism for a Michael Reaction
Robinson Annulation a Michael

reaction followed by an aldol
condenations
a Robinson annulation forms a product with a

fused 2-cyclohexenone ring
retrosynthetic analysis
O
O
OH
O
O
O
C
H3C
C
OH
HO
AceticAcid
OH
CarbonicAcid
Na O
OH
SodiumBicarbonate
SodiumCarbonate
oxalicacid
palmiticacid
O
C
H
Formaldehyde
Formamide
C
H3C
C
H
H3C
Acetaldehyde
CH3
Acetone
OH
HO
OH
Ethyleneglycol
glycerin
THF(tetrahydrofuran)
Furan
NH
Pyridine
H
Pyrrole
H
Ethylene
Acetylene
O
C
H
Benzaldehyde
Acetonitrile
O
C
OH
benzoicacid
Acetophenone
Phenol
Toluene
NH2
Aniline
Napthalene
vinyl
Hydroquinone
Allyl*
Isopropyl*
npropyl*
tbutyl*
Isobutyl*
nbutyl*
Phenyl*
Benzyl*
*Note:Thesearesubstituentgroups,meaningthatthereisabondtosomethingatthewavyline.
Short Summary of IUPAC Nomenclature of Organic Compounds

Introduction
The purpose of the IUPAC system of nomenclature is to establish an international standard of
naming compounds to facilitate communication. The goal of the system is to give each structure
a unique and unambiguous name, and to correlate each name with a unique and unambiguous
structure.
I. Fundamental Principle
IUPAC nomenclature is based on naming a molecules longest chain of carbons connected by
single bonds, whether in a continuous chain or in a ring. All deviations, either multiple bonds or
atoms other than carbon and hydrogen, are indicated by prefixes or suffixes according to a
specific set of priorities.
II. Alkanes and Cycloalkanes
Alkanes are the family of saturated hydrocarbons, that is, molecules containing carbon and
hydrogen connected by single bonds only. These molecules can be in continuous chains (called
linear or acyclic), or in rings (called cyclic or alicyclic). The names of alkanes and cycloalkanes
are the root names of organic compounds. Beginning with the five-carbon alkane, the number of
carbons in the chain is indicated by the Greek or Latin prefix. Rings are designated by the prefix
cyclo. (In the geometrical symbols for rings, each apex represents a carbon with the number of
hydrogens required to fill its valence.)
CH4
CH3CH3
CH3CH2CH3
CH3[CH2]2CH3
CH3[CH2]3CH3
CH3[CH2]4CH3
CH3[CH2]5CH3
CH3[CH2]6CH3
CH3[CH2]7CH3
CH3[CH2]8CH3
CH3[CH2]9CH3
methane
ethane
propane
butane
pentane
hexane
heptane
octane
nonane
decane
undecane
H
CH3[CH2]10CH3
CH3[CH2]11CH3
CH3[CH2]12CH3
CH3[CH2]18CH3
CH3[CH2]19CH3
CH3[CH2]20CH3
CH3[CH2]21CH3
CH3[CH2]28CH3
CH3[CH2]29CH3
CH3[CH2]38CH3
CH3[CH2]48CH3
dodecane
tridecane
tetradecane
icosane
henicosane
docosane
tricosane
triacontane
hentriacontane
tetracontane
pentacontane
H
C
H
cyclopropane
cyclohexane
C
H
C
H
cyclobutane
cycloheptane
cyclopentane
cyclooctane
Short Summary of IUPAC Nomenclature, p. 2

III. Nomenclature of Molecules Containing Substituents and Functional Groups
A. Priorities of Substituents and Functional Groups
LISTED HERE FROM HIGHEST TO LOWEST PRIORITY, except that the substituents within
Group C have equivalent priority.
Group AFunctional Groups Indicated By Prefix Or Suffix
Family of Compound
Structure
O
Prefix
Suffix
Carboxylic Acid
C OH
O
carboxy-
-oic acid
(-carboxylic acid)
Aldehyde
C H
O
oxo(formyl)
-al
(carbaldehyde)
Ketone
C R
oxo-
-one
Alcohol
R O H
hydroxy-
-ol
Amine
R N
amino-
-amine
Group BFunctional Groups Indicated By Suffix Only

Family of Compound
Structure
Prefix
Suffix
Alkene
C C
--------
-ene
Alkyne
C C
--------
-yne
Group CSubstituents Indicated by Prefix Only

Substituent
Structure
Prefix
Suffix
Alkyl (see list below)
alkyl-
----------
Alkoxy
R O
alkoxy-
----------
Halogen
F
Cl
Br
I
fluorochlorobromoiodo-
-------------------------------------
Group C continued on next page

Group CSubstituents, continued
Miscellaneous substituents and their prefixes
NO2
nitro
CH CH2
vinyl
CH2CH
allyl
CH2
phenyl
Common alkyl groupsreplace ane ending of alkane name with yl. Alternate names for
complex substituents are given in brackets.
CH3
methyl
CH3
CH
CH3
CH
CH2CH3
ethyl
CH3
isopropyl
[1-methylethyl]
CH2CH3
sec-butyl
[1-methylpropyl]
CH2CH2CH3
propyl (n-propyl)
CH2CH2CH2CH3
butyl (n-butyl)
CH2
CH3
CH
CH3
isobutyl
[2-methylpropyl]
CH3
C CH3
CH3
tert-butyl or t-butyl
[1,1-dimethylethyl]
B. Naming Substituted Alkanes and CycloalkanesGroup C Substituents Only

1. Organic compounds containing substituents from Group C are named following this sequence
of steps, as indicated on the examples below:
Step 1. Find the longest continuous carbon chain. Determine the root name for this
parent chain. In cyclic compounds, the ring is usually considered the parent chain, unless it is
attached to a longer chain of carbons; indicate a ring with the prefix cyclo before the root
name. (When there are two longest chains of equal length, use the chain with the greater number
of substituents.)
Step 2. Number the chain in the direction such that the position number of the first
substituent is the smaller number. If the first substituents from either end have the same number,
then number so that the second substituent has the smaller number, etc.
Step 3. Determine the name and position number of each substituent. (A substituent on
a nitrogen is designated with an N instead of a number; see Section III.D.1. below.)
Step 4. Indicate the number of identical groups by the prefixes di, tri, tetra, etc.
Step 5. Place the position numbers and names of the substituent groups, in alphabetical
order, before the root name. In alphabetizing, ignore prefixes like sec-, tert-, di, tri, etc., but
include iso and cyclo. Always include a position number for each substituent, regardless of
redundancies.

Examples
6
1
CH3
CH
CH
CH3 CH2CH2CH3
C
4
CH
5
CH2CH2CH3
CH2CH3
Cl
Br
CH3
3-bromo-2-chloro-5-ethyl-4,4-dimethyloctane
CH3
CH
CH
CH
2 CHCH3
CH3
F
CH3
3-fluoro-4-isopropyl-2-methylheptane
H3C CHCH2CH3
1
1-sec-butyl-3-nitrocyclohexane
(numbering determined by the
alphabetical order of substituents)
6
5
3
4
NO2
C. Naming Molecules Containing Functional Groups from Group BSuffix Only

1. AlkenesFollow the same steps as for alkanes, except:
a. Number the chain of carbons that includes the C=C so that the C =C has the lower
position number, since it has a higher priority than any substituents;
b. Change ane to ene and assign a position number to the first carbon of the C =C;
c. Designate geometrical isomers with a cis,trans or E,Z prefix.
CH3
F
F
5
CH
CH CH
CH2
CH3
4,4-difluoro-3-methylbut-1-ene
CH
CH2
CH3
1,1-difluoro-2-methylbuta-1,3-diene
4
2
5-methylcyclopenta1,3-diene
Special case: When the chain cannot include the C=C, a substituent name is used.
CH
CH2
3-vinylcyclohex-1-ene
2. AlkynesFollow the same steps as for alkanes, except:

a. Number the chain of carbons that includes the CtC so that the functional group has the
lower position number;
b. Change ane to yne and assign a position number to the first carbon of the CtC.
Note: The Group B functional groups (alkene and alkyne) are considered to have equal priority:
in a molecule with both a double and a triple bond, whichever is closer to the end of the chain
determines the direction of numbering. In the case where each would have the same position
number, the double bond takes the lower number. In the name, ene comes before yne
because of alphabetization. See examples on next page.

H
F
1
CH
CH
CH
HC
F
CH3
4,4-difluoro-3-methylbut-1-yne
C C CHCH3 HC C CH2 CH CH2

pent-3-en-1-yne
pent-1-en-4-yne
("yne" closer to end ("ene" and "yne" have equal
of chain)
priority unless they have the
same position number, when
"ene" takes the lower number)
(Notes: 1. An e is dropped if the letter following it is a vowel: pent-3-en-1-yne , not 3pent-3-ene-1-yne. 2. An a is added if inclusion of di, tri, etc., would put two consonants
consecutively: buta-1,3-diene, not but-1,3-diene.)
D. Naming Molecules Containing Functional Groups from Group APrefix or Suffix
In naming molecules containing one or more of the functional groups in Group A, the group of
highest priority is indicated by suffix; the others are indicated by prefix, with priority equivalent
to any other substituents. The table in Section III.A. defines the priorities; they are discussed
below in order of increasing priority.
Now that the functional groups and substituents from Groups A, B, and C have been described, a
modified set of steps for naming organic compounds can be applied to all simple structures:
Step 1. Find the highest priority functional group. Determine and name the longest
continuous carbon chain that includes this group.
Step 2. Number the chain so that the highest priority functional group is assigned the
lower number.
Step 3. If the carbon chain includes multiple bonds (Group B), replace ane with ene
for an alkene or yne for an alkyne. Designate the position of the multiple bond with the
number of the first carbon of the multiple bond.
Step 4. If the molecule includes Group A functional groups, replace the last e with the
suffix of the highest priority functional group, and include its position number.
Step 5. Indicate all Group C substituents, and Group A functional groups of lower
priority, with a prefix. Place the prefixes, with appropriate position numbers, in alphabetical
order before the root name.
1. Amines: prefix: amino-; suffix: -aminesubstituents on nitrogen denoted by N
CH3O
CH3CH2CH2
NH2
NH2
propan-1-amine
CH3CH2
CH2
3-methoxycyclohexan-1-amine
("1" is optional in this case)
CH
CH2CH3
CHCH3
N,N-diethylbut-3-en-2-amine

2. Alcohols: prefix: hydroxy-; suffix: -ol
OH
OH
CH3CH2
OH
H3C
ethanol
CH
CH CH2
but-3-en-2-ol
NH2
2-aminocyclobutan-1-ol
3. Ketones: prefix: oxo-; suffix: -one

O
O
CH3
CH C
CH3
OH
3-hydroxybutan-2-one
CH3
H3C
CH3
CH2 C
CH2
4-(N,N-dimethylamino)pent-4-en-2-one
cyclohex-3-en-1-one
4. Aldehydes: prefix: oxo-, or formyl- (O=CH-); suffix: -al (abbreviation: CHO).

An aldehyde can only be on carbon 1, so the 1 is generally omitted from the name.
O
HCH
CH3
OH
CH
CH2 CH
CH
CH
CH3CCH2CH2
CH
methanal;
ethanal;
4-hydroxybut-2-enal
4-oxopentanal
formaldehyde acetaldehyde
Special case: When the chain cannot include the carbon of the CHO, the suffix carbaldehyde
is used:
O
CH
cyclohexanecarbaldehyde
5. Carboxylic Acids: prefix: carboxy-; suffix: -oic acid (abbreviation: COOH).

A carboxylic acid can only be on carbon 1, so the 1 is generally omitted from the name.
O
HC OH
CH3C OH
methanoic acid; ethanoic acid;
acetic acid
formic acid
O
CH2 CH COH
CH3
HC
COOH
NH2
CH3
2-amino-3-phenylpropanoic acid 2,2-dimethyl-3,4dioxobutanoic acid
(Note: Chemists traditionally use, and IUPAC accepts, the names formic acid and acetic
acid in place of methanoic acid and ethanoic acid.)
Special case: When the chain numbering cannot include the carbon of the COOH, the suffix
carboxylic acid is used. See example on next page.

CHO
2
1
4
COOH
2-formyl-4-oxocyclohexanecarboxylic acid
("formyl" is used to indicate an aldehyde as
a substituent when its carbon cannot be in
the chain numbering)
E. Naming Carboxylic Acid Derivatives

The six common groups derived from carboxylic acids are salts, anhydrides, esters, acyl halides,
amides, and nitriles. Salts and esters are most important.
1. Salts of Carboxylic Acids
Salts are named with cation first, followed by the anion name of the carboxylic acid, where ic
acid is replaced by ate :
acetic acid
butanoic acid
cyclohexanecarboxylic acid
becomes
becomes
becomes
acetate
butanoate
cyclohexanecarboxylate
2. Esters
Esters are named as organic salts that is, the alkyl name comes first, followed by the name of
the carboxylate anion. (common abbreviation: COOR)
carboxylate
alkyl
CH3 O
CH3
R C O
R
H3C C O CH2CH3 H3C C
C O CHCH3
"alkanoate" "alkyl"
ethyl acetate
CH3
"alkyl alkanoate"
isopropyl 2,2-dimethylpropanoate
O
CH2
CH C O CH
vinyl prop-2-enoate
CH2
HO
CH2COO
O
C
OCH3
cyclohexyl 2-phenylacetate
methyl 3-hydroxycyclopentanecarboxylate
IV. Nomenclature of Aromatic Compounds

Aromatic compounds are those derived from benzene and similar ring systems. As with
aliphatic nomenclature described above, the process is: determining the root name of the parent
ring; determining priority, name, and position number of substituents; and assembling the name
in alphabetical order. Functional group priorities are the same in aliphatic and aromatic
nomenclature.

A. Common Parent Ring Systems
8
1
2
or
6
5
benzene
3
5
naphthalene
10
anthracene
B. Monosubstituted Benzenes
1. Most substituents keep their designation, followed by the word benzene:
Cl
NO2
CH2CH3
chlorobenzene
nitrobenzene
ethylbenzene
2. Some common substituents change the root name of the ring. IUPAC accepts these as root
names, listed here in decreasing priority:
COOH
benzoic
acid
SO3H
CHO
benzenebenzaldehyde
sulfonic acid
OH
NH2
phenol
aniline
OCH3
anisole
C. Disubstituted Benzenes
1. Designation of substitutiononly three possibilities:
X
X
CH3
toluene
Y
Y
common:
IUPAC:
ortho1,2-
Y
para1,4-
meta1,3-
2. Naming disubstituted benzenesPriorities determine root name and substituents

Br
COOH
HO
NH2
OCH3
Br
CHO
3-aminobenzoic acid
1,4-dibromobenzene
2-methoxybenzaldehyde
CH3
3-methylphenol

D. Polysubstituted Benzenes
CH3
Cl
HN
CH3
O2N
COOCH2CH3
NO2
Cl
OH
NO2
3,4-dichloro-N-methylaniline
NH2
2,4,6-trinitrotoluene ethyl 4-amino-3-hydroxybenzoate

(TNT)
E. Aromatic Ketones
A special group of aromatic compounds are ketones where the carbonyl is attached to at least one
benzene ring. Such compounds are named as phenones, the prefix depending on the size and
nature of the group on the other side of the carbonyl. These are the common examples:
O
O
C CH3
C CH2CH3
acetophenone
O
C CH2CH2CH3
butyrophenone
propiophenone
O
C
benzophenone
Courtesy of Dr. Jan Simek, California Polytechnic State University at San Luis Obispo
Ketone -carbons
Aldehyde -carbons
Thioester -carbons
Ester -carbons
Acetonitrile -carbons
Sulfone -carbons
Thioester sulfide carbon
Amide -carbons
MajorReaction
Subreaction
Hydrohalogenation
Alkene
StartingMaterial
Hydration
Alkene
Halogenation
Alkene
ElectrophilicAddition
Bromohydrinformation
Alkene
CatalyticHydrogenation
Alkene
CisHydroxylation
Alkene
Oxidativecleavage
Alkene
Epoxideformation
Alkene
REDOX
Substitution
Alkynes
Alkynes
Deprotonationofterminalalkyne
Alkynes
Sn1
2oor3oalkylhalide
Elimination
Sn2
methyl,1 or2 alkylhalide
E1
o
o
2 or3 alcohol
E2
Reduction
alkylhalide
Aldehydes
Ketones
Carboxylicacids&derivatives
reactionsofalcohols
oxidation
1Alcohol
oxidation
2Alcohol
oxidation
1Alcohol
ethersynthesis
alkoxideandalkylhalide
reactionsofethers
tbutylethersynthesis
1 or2 alcohol
E1,dehydration
o
o
2 or3 alkylhalideoralcohol
ethercleavage
ether
tbutylether
Conversionofalcoholtoalkylhalideortosylate
Synthesisofalkylbromides
Alcohols
Synthesisofalkylchlorides
Alcohols
Synthesisoftosylates
Alcohols
Reversibleadditionstoaldehydesandketones
Synthesisofamines
hemiacetals/acetalsformation
AldehydeorKetone
imineformation
AldehydeorKetone
Imines
AlcoholSynthesis
Grignard
EthyleneOxide
Grignard
Aldehydes
Grignard
Formaldehyde
Reactionsofcarboxylicacids
Grignard
Ketones
Grignard
CO2
formationofacidchloride
CarboxylicAcid
formationofanhydride
AcidChloride
esterification
CarboxylicAcidandalcohol
hydrolysis
Amide
reactionsofacidchloride(anhydrides)
hydrolysis
hydrolysis
esterification
formationofamide
AcidChloride
Anhydride
acidchloride
AcidChloride
reactionsofesters
Hydrolysis
synthesisofalcohols
synthesisofalcohols
ester
ester
ester
reactionsofamides
Hydrolysis
Reduction
amide
amide
Synthesisofnitriles
SN2
methyl,1oor2oalkylhalide
Reactionsofnitriles
hydrolysis
reduction
nitrile
nitrile
Haloform
Ketoneoraldehyde
methylketone
Halogenation
synthesisofcarboxylicacids
Reactionsattheapositionofcarbonyls
Aldol
Claisen
AcetoaceticEsterSynth.
MalonicEsterSynth.
Michaelreaction
aldehydesandketones
esters
ketoester
diester
,unsaturatedcompound&nucleophile
RobinsonAnnulation
Acid/basechemistry
formationofenolate
formationofenols
carbonylcompoundwithahydrogen
carbonylcompoundwithahydrogen
oxidationchemistry
ElectrophilicAromaticSubstitution
formationoftransdiols
Halogenation
Nitration
Sulfonation
Alkylation
Acylation
Sidechainoxidation
reductionofnitroaromatics
alkene
Aromatics
Aromatics
Aromatics
Aromatics
Aromatics
Aromaticsw/atleast1benzylichydrogen
nitroaromatics
REDOX
HX,ether
Reagent
Alkylhalides
Product
acidic
Conditions
Mechanism
yes
H3O+
Alcohols
acidic
yes
Br2/CH2Cl2orCCl4
trans1,2dibromides
neutral
yes
Br2/water
trans1,2bromohydrins
neutral
yes
H2,Pd/C
Alkanes
neutral
no
OsO4
cis1,2diols
basic
no
KMnO4,H3O+
ketonesoracids
acidic
no
mcpba
epoxides
neutral
no
H2,Pd/C
alkanes
neutral
no
H2,Lindlarcatalyst
cisalkenes
neutral
no
NaNH2
Acetylideanion
basic
yes
weaknucleophile(maybesolvent)
Racemicmixtureifsubstrateischiral
neutraloracidic
yes
goodnucleohile
InversionofConfiguration
neutralorbasic
yes
weakbases
Alkene@mostsubstitutedC
neutraloracidic
yes
Strongbase(bulkybasesarebetter)
Alkene/Alkyne@mostsubstitutedC
neutralorbasic
yes
a.NaBH4/MeOHora.LAHb.H3O+
1Alcohol
no
a.NaBH4/MeOHora.LAHb.H3O+
2Alcohol
no
+
a.LAHb.H30
1Alcohol
no
PCC
Aldehydes
no
PCCorCrO3
Ketone
no
KMnO4orCrO3
CarboxylicAcid
no
ethers
basic
yes
isobutylenegas,acidcatalyst
tbutylether
acidic
yes
H2SO4orH3PO4
alkene
acidic
yes
HBrorHI(conc)
alkylbromideoriodide/alcohol
acidic
yes
CF3CO2H
alcohols
acidic
yes
PBr3
AlkylBromides
no
SOCl2
AlkylChlorides
no
tosylchloride
tosylates
no
hemiacetaloracetal
yes
o
+
1 amine,H
imine
yes
H2andPd/CORNaBH4
Amines
no
Alcohol,H
a.RMgBr/etherb.H30
1Alcoholw/2C's
basic
yes
a.RMgBr/etherb.H30
2Alcohol
basic
yes
1Alcoholw/1C
basic
yes
+
a.RMgBr/etherb.H30
a.RMgBr/etherb.H30
3Alcohol
basic
yes
a.RMgBr/etherb.H30
CarboxylicAcid
basic
yes
SOCl2
AcidChloride
no
CarboxylateAnion
Anhydride
acidcatalyst
ester
yes
acidic
yes
Hydrolysis
CarboxylicAcid/Amine
acidicorbasic
H2O
H2O
Alcohol
Amine
CarboxylicAcid
CarboxylicAcid
ester
Amide
yes
yes
yes
yes
acidorbase
a.LAHb.H30+
a.RMgBr/etherb.H30+
CarboxylicAcid&Alcohol
1Alcohol
3Alcohol
yes
no
yes
acidorbase
+
a.LAHb.H30
Carboxylicacid&amine
amine
yes
no
NaCN
Nitrile
yes
acidorbase
a.LAHb.H30+
carboxylicacids
Amines
yes
no
X2/HX
I2,NaOH
Halogenatedaldehydeorketone
CarboxylateAnion
Acidic
Basic
yes
no
no
a.NaOH(cat)EtOHb.neutralize
a.ROb.H30+
a.NaOEt,EtOH;RX,c.H30+,Heat
a.NaOEt,EtOH;RX,c.H30+,Heat
depends
,unsaturatedcompound(enoneorenal)
ketoester
SubstitutedKetones
SubstitutedAcids
newbondatcarbon
yes
yes
yes
yes
yes
base
acid
enolate
enol
basic
acidic
yes
yes
a.mcpba,b.aqueousacidorbase
X2,FeX3ORAlX3
HNO3/H2SO4
H2SO4/SO3
3oalkylhalide,FeX3
RCOCl,FeCl3ORAlCl3
KMnO4
H2,Pd/CORironandtinreagents
transdiol
halogenatedaromatic
nitratedaromatic
sulfonatedaromatic
alkylatedaromatic
acylatedaromatic
benzoicacids
Anilines
either
acidic
acidic
acidic
acidic
acidic
neutral
yes
yes
yes
yes
yes
no
no
Notes
Unimolecular;twostepwhereRDSisformationofcarbocation;substratemustbeabletoformcation(2 or3 )
Bimolecular;onestep;1 or2 substrates
o
o
Unimolecular;twostepwhereRDSisformationofcarbocation;substratemustbeabletoformcation(2 or3 )
Bimolecular;onestep
selectiveoxidation
aSN2reactionwherethenucleophileisanalkoxide
areversiblereactionthatcanserveto"protectanalcohol"
aspecificE1reaction
ethersaresusceptabletostrongacids
awayof"deprotecting"atertbutylethertoreviealanalcohol
convertingapoorleavinggroupintoagoodleavinggroup
Watermustberemovedduringthereaction;onlycyclichemiacetalsarestable.
Watermustberemoved;canbereducedtoamine
anothersynthesisofamines
epoxideringopening
willnottolerateacidicfunctionalgroupsorsolvents
susceptibletohydrolysis
susceptibletohydrolysis
Fisheresterification
mustusetwoequivalentofamine
underbasicconditions,reactioniscalledsaponificationandresultsinacarboxylate
Grignardreagentwilladdtwiceontocarbonylcenterofanester
nitrilescanbeinstalledusingSN2chemistryandhydrolyzedtoacids
canbesubstrateforSN2oreliminatedtogivea,bunsaturatedcompound
limitedinscope,butgoodtoknowinordertounderstandpKa/equilibrium
Intermediateishydroxyaldehydeorhydroxyketonethatdehydrates;canbeselformixedcondensations
canbeselformixedcondensations
canbeinterorintramolecular;secondstepisSN2andsubstratecan'tbehindered
canbeinterorintramolecular;secondstepisSN2andsubstratecan'tbehindered
nucleophilesareenolate,thiol,oramine;alsocalled1,4conjugateaddition
aMichaelreactionfollowedbyanaldol
enolatescanbenucleophilic
enolsinequilibriumwiththeirketoform
epoxideringopening
onlyalkylhalidesthatformstablecarbocationsmaybeused
mayoxidizemultiplesidechains
Chem. 345 Hour Examination I

Name
Tuesday, October 1, 2013
WSU ID #______________________
1. Consider the reaction AH + H2O D A:() + H3O(+) For the following named acids: 1) draw the structure of
the acid, 2) give the approximate pKa of the acid in units of 5, and 3) draw the structure of the conjugate base.
Draw structures clearly and include all lone pair electrons and indicate formal charge where appropriate. (24
points possible)
tert-Butyl ammonium ion
(C4H12N)
pKa 10
Phenyl acetylene (C8H6)

pKa 25
Isopropyl oxonium ion

(C3H9O)
pKa <0
Benzoic acid (C7H6O2)

pKa 5
Nitric acid (HNO3)

pKa <0
Anilinium ion (C6H8N)

pKa 5
Cyclopentadiene (C5H6)
pKa 15
acid
conjugate base
acid
Phenol (C6H6O)
pKa 10
conjugate base
OH
O
O
2. The compound called lynestrenol, an active ingredient in some oral

contraceptives, is shown below. Circle and label a single example of
each of the following types of bonds or atoms shown to the right. The
first is given as an example of how to complete this question. (4 points
possible)
a.
b.
c.
d.
e.
a highly polarized covalent bond

an sp-hybridized carbon atom
an sp2-hybridized carbon atom
an sp3-hybridized carbon atom
a bond between atoms of different
hybridization
3. Some commercial headache remedies contain aspirin as well as caffeine, salicylamide and/or
acetaminophen. All of these components may be separated using liquid/liquid extraction.
3a. Complete the flow chart below using acid/base chemistry you learned in the first three labs. The acidic and
basic atoms are shown in bold. Hint: sodium bicarbonate is the conjugate base of carbonic acid, pKa = 6, 10.
(8 points possible)
3b. Why does the separation scheme shown above depend on the use of aqueous sodium bicarbonate? In other
words, briefly explain why only the caffeine would be separable if aqueous sodium hydroxide were used. (4
points possible)
4. Starting from benzene, draw a synthesis of 3-acetylbenzoic acid. You may use any necessary organic or
inorganic reagents in your proposed synthesis. (8 points)
5. The figure below is from your textbook.
5a. Consider the following series of monosubstituted benzene molecules. Using the figure above, complete the
table by stating if X is an o/p director or a m-director, activating or deactivating, and how you would expect the
molecules to rank in order of a typical EAS reaction. (9 points possible)
directing ability
(o/p or m)
X = CHO
X = OCH3
X = Br
meta
ortho / para
ortho / para
activating or deactivating
deactivating
activating
deactivating
relative rate (1=fastest, 3=slowest)

3
1
2
5b. Consider hydrohalogenation of styrene using HCl (g) and diethyl ether as solvent. Which group X (from the
table above) would you expect to give the fastest rates? Show the reaction and justify your answer with a few
pictures and words. (5 points possible)
Styrene
The intermediate carbocation is delocalized through ring with both the OCH3 and Br substituents able to
stabilize but according to the figure above, the methoxy is a stronger activator than bromine and would be
expected to a faster rate.
6. Consider cis-1,2-dimethylcyclohexane and trans-1,2-dimethylcyclohexane. Complete the chair templates

below as indicated. Which isomer (cis-1,2 or trans-1,2) would exist in equivalent energy chair conformations.
Briefly explain your reasoning. (8 points possible)
For the cis isomer, one methyl group will always be in the higher energy axial position therefore both chairs are
equivalent in energy. For the trans, one chair allows both methyl groups to either be di-axial or di-equatorial.
7. Complete the following: (Stereochemistry and regiochemistry are important). (30 points possible)
OH
OH
OsO 4, H2 O
a)
type cis hydroxylation
b)
HBr
ether
H 3CO
type
N
H
type acid/base chemistry
CO 2H
HO 2C
type side chain oxidation
H
N
i)
N
H
H 3 CO
NH 2
H 2 , Pd/C
NO 2
H 3CO
type reduction
O
e)
KMnO4 , H 3O +
h)
type epoxide formation
d)
OH
bromohydrin f ormation, ring opening of
type bromonium ion by water
CH 2 Cl2
HCl(aq)
Br
Br 2, H2 O
g)
H 3 CO
mcpba
reduction
Br
type hydrohalogenation
c)
H 2, Lindlar cat
f)
OEt
HNO3 /H 2 SO 4 O 2N
type E.A.S nitration
OEt
j)
KMnO4 , H 3O +
type oxidative cleavage
O
2 eq
OH

Name
Thursday, September 26, 2011
WSU ID # ______________________
1) Consider the reaction AH + H2O A:(-) + H3O(+) For the following named acids: 1) draw the structure of the
acid, 2) give the approximate pKa of the acid in units of 5, and 3) draw the structure of the conjugate base.
Draw structures as clearly as you can and include all lone pair electrons and indicate formal charge where
appropriate. (24 points possible)
Sulfuric acid
pKa
Isopropyl oxonium ion

pKa
Anilinium ion
pKa
Pent-1-en-4-yne
CHCCH2CHCH2
pKa
Cyclopentadiene
pKa
Nitric acid
pKa
Benzoic acid
pKa
conjugate base
acid
conjugate base
acid
Acetic acid
pKa
2. For the indicated bonds below, use the empty boxes to describe their composition in terms of orbital
overlap. As an example, a tetrahedral carbon-hydrogen is shown as sp31s. (6 points possible)
sp31s
3) Complete the flow chart below by drawing the expected structure in the boxes below for the separation of 4chloroaniline, benzoic acid, and naphthalene using acid/base chemistry used in the first three labs. (16 points
possible)
4. Cyclohexene reacts with m-chloroperbenzoic acid (mcpba) in dichloromethane (CH2Cl2) solvent to give the
epoxide cyclohexene oxide, which is reacted in a second step with aqueous sodium hydroxide and neutralized to
give a trans-1,2-diol with the molecular formula C6H12O2.
4a. Draw the reaction of cyclohexene with mcpba in CH2Cl2. (5 points possible)
4b. Draw the reaction of cyclohexene oxide with aqueous sodium hydroxide. (5 points possible)
4c. Draw a mechanism that accounts for the formation of diol only. In other words, do not draw a mechanism
for the formation of the expoxide. Use curved arrows to show bond making and bond breaking and draw any
reactive intermediates, if formed. For full credit, your mechanism must account for the observed
stereochemistry. (5 points possible)
5. Draw the lowest energy Newman projection by sighting along C3C4 bond of 2,5-dimethylhexane. (5
points possible)
7. Complete the following by drawing the lowest energy chair conformation of

cis-1-(tert-butyl)-2-methylcyclohexane. (8 points possible)
Sign Below
I pledge on my honor that this exam was completed by me, that I received no unauthorized help, and that I have
not violated the academic conduct code of Washington State University.
Please sign your name

Name
WSU ID #______________________
1. Consider the reaction AH + H2O A:() + H3O(+) For the following named acids: 1) draw the structure of
points possible)
Nitric acid (HNO3)
pKa
Diisopropyl ammonium
ion (C6H16N)
pKa

pKa
But-1-yne (C4H6)
pKa
pKa
Methyl oxonium ion

(CH5O)
pKa
Cyclohexanol (C6H12O)
pKa
conjugate base
acid
conjugate base
acid
Butanoic acid (C4H8O2)

pKa
2. For the indicated atoms below, write their hybridization (sp, sp2, or sp3) in the empty boxes. (5 points
possible)
3. You have been provided with an aqueous mixture of sodium benzoate and diphenyl ammonium chloride.
You have available 3M HCl and 3M NaOH, and all necessary lab equipment and solvents. Complete the flow
chart below the steps you would use to isolate pure benozic acid and pure diphenyl amine by writing reagents
and procedures next to the bold numbers. Write the products that would be formed from your procedures. For
ease of grading, please start Step 1 by using the acid. Please be aware there is more than one way to accomplish
this separation. You may not need all the boxes depending on your separation scheme. (10 points possible)
NH3 Cl
O Na
4. Starting from benzene, draw a synthesis of 3-aminobenzoic acid. You may use any necessary organic or
5. 3,4-dihydro-2H-pyran (shown below) reacts with acidic methanol to give a single regioisomer shown below.
5a. Draw a mechanism that accounts for the formation of observed product. For full credit you must use the
curved arrow notation to show all bond making and bond breaking events. You must also draw all reactive
intermediates and relevant resonance structures to account for the formation of this regioisomer (5 points
possible)
5b. Draw a mechanism that would result in the formation of product that is not observed. Use curved arrow
notation to show all bond making and bond breaking events. Draw all reactive intermediates and relevant
resonance structures to account for the formation of this regioisomer. Briefly explain why this isomer is not
observed. (5 points possible)
6. Electrophilic addition of bromine to acenaphthylene in carbon tetrachloride gives the unexpected cis-1,2dibromide along with the expected trans-dibromide. As you learned in lecture, some of the trans product is the
result of anti attack by the bromide anion on a bromonium ion, but this cannot explain the formation of the cis
product. Draw a mechanism that accounts for the formation of a mixture containing both cis and trans products.
For full credit you must show all intermediates and relevant resonance structures. (10 points possible).

trans-1-fluoro-3-methylcyclohexane. (5 points possible)
Sign Below

Name
WSU ID #______________________
points possible)
Butanoic acid (C4H8O2)
pKa 5
Diisopropyl ammonium
ion (C6H16N)
pKa 10
Nitric acid (HNO3)

pKa <0

pKa 5
NH3
conjugate base
acid
N
H H
NH2
pKa 15
Methyl oxonium ion

(CH5O)
pKa <0
pKa 15
conjugate base
acid
But-1-yne (C4H6)
pKa 25
2. For the indicated atoms below, write their hybridization (sp, sp2, or sp3) in the empty boxes. (5 points
possible)
sp
sp3
H
O
sp2
sp
sp3
3. You have been provided with an aqueous mixture of sodium benzoate and diphenyl ammonium chloride.
You have available 3M HCl and 3M NaOH, and all necessary lab equipment and solvents. Complete the flow
chart below the steps you would use to isolate pure benozic acid and pure diphenyl amine by writing reagents
and procedures next to the bold numbers. Write the products that would be formed from your procedures. For
ease of grading, please start Step 1 by using the acid. Please be aware there is more than one way to accomplish
this separation. You may not need all the boxes depending on your separation scheme. (10 points possible)
- add 3M HCl
-filter
-add 3M NaOH
-filter
NH2
Ph
PhCO2H
Ph
There are several ways to do this, the one shown above is the most simple starting with acid.
4. Starting from benzene, draw a synthesis of 3-aminobenzoic acid. You may use any necessary organic or
Two ways
5. 3,4-dihydro-2H-pyran (shown below) reacts with acidic methanol to give a single regioisomer shown below.
5a. Draw a mechanism that accounts for the formation of observed product. For full credit you must use the
curved arrow notation to show all bond making and bond breaking events. You must also draw all reactive
intermediates and relevant resonance structures to account for the formation of this regioisomer (5 points
possible)
5b. Draw a mechanism that would result in the formation of product that is not observed. Use curved arrow
notation to show all bond making and bond breaking events. Draw all reactive intermediates and relevant
resonance structures to account for the formation of this regioisomer. Briefly explain why this isomer is not
observed. (5 points possible)
6. Electrophilic addition of bromine to acenaphthylene in carbon tetrachloride gives the unexpected cis-1,2dibromide along with the expected trans-dibromide. As you learned in lecture, some of the trans product is the
result of anti attack by the bromide anion on a bromonium ion, but this cannot explain the formation of the cis
product. Draw a mechanism that accounts for the formation of a mixture containing both cis and trans products.
For full credit you must show all intermediates and relevant resonance structures. (10 points possible).

trans-1-fluoro-3-methylcyclohexane. (5 points possible)
F
C5
C6
C4
C3
C1
C2
CH3
trans-1,3 forces one of the substituents to be axial. In cases such as this, the small substituent takes the axial
allowing the larger to take the equatorial
HO
OH
OsO4, H2O
a)
H2, Lindlar cat
f)
type cis hydroxylation
type
reduction
Br
HBr
ether
b)
H3CO
Br
g)
H3CO
type hydrohalogenation
OH
+
c)
H3O
OH
h)
NaNH2/NH3
i)
H2, Pd/C
NO2
NH2
type reduction

O
O
e)
OH
bromohydrin formation, ring opening of
type bromonium ion by water
O
CH3COCl
AlCl3
CH
type E.A.S Acylation
type epoxide ring opening
d)
Br2, H2O
CH3
Br2, FeBr3
type E.A.S Halogenation
Br
CH3
j)
CH2
KMnO4, H3O+
type oxidative cleavage
Chem.345HourExaminationII
Name
WSUID#
Tuesday,November5,2013
1a)ConsiderthereactionAH(+)+H2OA:()+H3O(+).Forthefollowingnamedacids:a)draw
thestructureoftheacid,b)givetheapproximatepKaoftheacid,andc)drawthestructureofthe
conjugatebase.(12pointspossible)
Benzaldehydeoxoniumion
(C7H7O)
pKa
pKa
Phenol(C6H6O)
pKa
Butanoicacid(C4H8O2)
pKa
conjugatebase
acid
tertButanoloxoniumion
(C4H11O)
1b)ConsiderthereactionB:()+H3O+BH(+)+H2O.Forthefollowingnamedbases:a)draw
thestructureofthebase,b)drawthestructureoftheconjugateacid,andc)givetheapproximate
pKaoftheconjugateacid.(12points)
Allylamine
Acetone
ethyn1ide
(C3H8S)
pKa
(C3H8N)
pKa
(C3H7O)
pKa
(C2H2)
pKa
conjugateacid
base
Isopropylthiolateanion
___/24 Page 1
2)Completethefollowingmultistepsynthesisproblembydrawingproductsintheemptyboxesbelow.
(9points)
OH
PCC
CH2 Cl2
OH
HO
+
H , -H2 O
Br2 , AlBr3
a. Mg o, Et2 O
b. CO2
c. HCl (aq)
CHO
CO 2H
___/9
3)Astudenttriedtoreact4hydroxybenzaldehydewithoneequivalentofbutylGrignard(preparedfrom1
bromobutaneandmagnesiummetal)inordertosynthesize4(1hydroxypentyl)phenol.Attheendofthe
reactionandfollowingneutralization,thestudentrecoveredthestartingaldehydeandbutane.Writethis
reaction(2points)anddeterminewhatwentwrong(2points).Usingthesamestartingmaterialsandany
otherreagentsneeded,modifythesynthesissoitwillwork(6points).
___/10
___/19 Page 2
4)Completethefollowing:(Stereochemistryandregiochemistrymaybeimportant).(27points)
O
Br
OH
a)
heat
H 3O +
f)
type intramolecular SN1
type
H
N
H+
g)
b)
N
H
OH
type formation of tert-butyl ether
type acid/base chem
c)
h)
HBr
N3 H
type
SN2
type
OH
NaBH4
OH
i)
d)
MeOH
type f ormation of an alkykl bromide
O
e)
H2 N
type
H +, -H 2O
type
j)
O
H
type EAS - bromination
___/13
___/14
5)Startingfromtheappropriate2butene,deviseasynthesisofmeso2,3butane2,3diol.(10points)
___/10
___/37 Page 3
6)SN2chemistrycanbeusedtosynthesizeethersfromalkylhalidesandalkoxides(Williamsonether
synthesis).Makeuseofthisreactionbydrawingasynthesisofdiisopropylether(C6H14O)usingonly
isopropanolasyouronlyorganicstartingmaterial.Youmayuseanyotherinorganicreagentsasnecessarybut
allthecarboninyourproductmustcomefromisopropanol.(10points)
___/10
7)Fisheresterificationisamethodofsynthesizingestersfromacarboxylicacidandalcoholusinganacid
catalyst.Drawthemechanismthataccountsfortheformationofisopentylacetatestartingfromaceticacid
andisopentanol(3methylbutan1ol).Forfullcredit,yourmechanismmustusethecurvedarrownotationto
showallbondmakingandbondbreakingandanyintermediates,ifformed.(10points)
isopentyl acetate
O
O
___/10
___/20 Page 4
SignBelow
Ipledgeonmyhonorthatthisexamwascompletedbyme,thatIreceivednounauthorizedhelp,andthatI
havenotviolatedtheacademicconductcodeofWashingtonStateUniversity.
Chem. 345 Hour Examination II

Name
Tuesday, November 6, 2012
WSU ID #______________________
points)
pKa
(R)-but-3-en-2-thiol (C4H8S)
pKa
Allyl ammonium cation

(C3H8N+)
pKa
Benzoate anion
Aniline
2-Methylphenoxide anion
tert-Butoxide anion
(C7H6O2)
pKa
(C6H8N+)
pKa
(C7H8O)
pKa
(C4H10O)
pKa
conjugate acid
base
conjugate base
acid
Phenol (C6H6O)
pKa
2. Road map question (8 points)
3a. Circle all the chiral carbon atoms in the chemical structure below. (3 points)
3b. Assign R or S configuration to the circled atoms of the following molecules. (6 points)
4. Write a synthesis to transform benzoic acid to benzyl ethyl sulfide. You may use any
reagent/reactants you wish as long as your synthesis begins with benzoic acid. (10 points)
S
benzyl ethyl sulfide
5. Write a synthesis to transform cyclopentene to dicyclopentylmethanone. You may

use any reagent/reactants you wish as long as your synthesis begins with cyclopentene.
(10 points)
6. The following lactone (cyclic ester) when reacted with hydrogen chlorine in methanol give the hydroxyester
product shown below. Draw a mechanism for this reaction using the curved arrow notation to show all bond
making and breaking. For full credit, you must show all intermediates. (10 points)
O
a)
NaOH (aq)
NH
f)
type
type
O
O
Cl
b)
type Formation of acid chloride
Me
N
Me
N
g)
O N
Me
type
h)
c)
Br
OH
HCl (aq)
tBuOK
tBuOH
type
type
OH
d)
H3O+
H Br
i)
NaCN
H
type
type
O
NaBH4
e)
H3CO OCH3
k)
methanol
type
type
HO
l)
H2SO4 (cat)
OH
type FIsher esterification

cat = catalyst, only a catalytic (submolar) amount
is needed
tBuOK =
K O

Name
Tuesday, November 6, 2012
WSU ID #______________________
points)
pKa 25
(R)-but-3-en-2-thiol (C4H8S)
pKa 10
Allyl ammonium cation

(C3H8N+)
pKa 10
Aniline
2-Methylphenoxide anion
tert-Butoxide anion
conjugate base
acid
Phenol (C6H6O)
pKa 10
Benzoate anion
NH2
base
CH3
(C6H8N+)
pKa 5
conjugate acid
(C7H6O2)
pKa 5
(C4H10O)
pKa 15
(C7H8O)
pKa 10
OH
NH3
CH3
2. Road map question (8 points)

O
NaBH4
AlCl3
Cl
CH3OH
OH
H2SO4
H3O+
mcpba
OH
OH
CH2Cl2
3a. Circle all the chiral carbon atoms in the chemical structure below. (3 points)
3b. Assign R or S configuration to the circled atoms of the following molecules. (6 points)
4. Write a synthesis to transform benzoic acid to benzyl ethyl sulfide. You may use any
reagent/reactants you wish as long as your synthesis begins with benzoic acid. (10 points)
S
benzyl ethyl sulfide
5. Write a synthesis to transform cyclopentene to dicyclopentylmethanone. You may

use any reagent/reactants you wish as long as your synthesis begins with cyclopentene.
(10 points)
6. The following lactone (cyclic ester) when reacted with hydrogen chlorine in methanol give the hydroxyester
product shown below. Draw a mechanism for this reaction using the curved arrow notation to show all bond
making and breaking. For full credit, you must show all intermediates. (10 points)
CH3
O
CH3
HCl, CH3OH
HO
OCH3
CH3
CH3
OH
H
O
CH3
P.T.
H
OCH3
OH
CH3
OH
OCH3
OH
CH3
HO
OH
OCH3
O
a)
O
NaOH (aq)
NH
type amide hydrolysis

O
OH
b)
f)
O
NH2
O
SOCl2
Cl
type Formation of acid chloride

H+
type imine hydrolysis

O
O
Me
Me
Me
N
N
HCl (aq)
N
g)
O N
N
O N
Me
Me acid/base chemistry
type
h)
PCC
CH2Cl2
H Br
i)
e)
N
H
tBuOK
tBuOH
NaCN
NC H
type oxidation of 1 alcohol

O
NaBH4
Me
N
type E2 elimination
type tert-Butyl ether synthesis

OH
Br
OH
CHO H2N
c)
d)
H3O+
type
Sn2
OH
CH3OH, H+
O
k)
-H2O
methanol
H3CO OCH3
type formation of acetal
type reduction
O
HO
l)
H2SO4 (cat)
OH
type FIsher esterification
cat = catalyst, only a catalytic (submolar) amount

is needed
tBuOK =
K O
Chem.345HourExaminationII
Name
WSUID#
Tuesday,November5,2013
thestructureoftheacid,b)givetheapproximatepKaoftheacid,andc)drawthestructureofthe
conjugatebase.(12pointspossible)
(C4H11O)
Benzyaldehydeoxoniumion
(C7H7O)
pKa<0
pKa<0
Phenol(C6H6O)
pKa10
OH
OH
OH 2
Butanoicacid(C4H8O2)
pKa5
O
OH
acid
conjugatebase
OH
thestructureofthebase,b)drawthestructureoftheconjugateacid,andc)givetheapproximate
pKaoftheconjugateacid.(12points)
Isopropylthiolateanion
Acetone
Allylamine
NH 2
base
conjugateacid
ethyn1ide
(C3H8N)
pKa10
(C3H8S)
pKa10
(C3H7O)
pKa<0
(C2H2)
pKa25
OH
NH 3
SH
___/24 Page 1
(9points)
___/9
3)Astudenttriedtoreact4hydroxybenzaldehydewithoneequivalentofbutylGrignard(preparedfrom1
bromobutaneandmagnesiummetal)inordertosynthesize4(1hydroxypentyl)phenol.Attheendofthe
reactionandfollowingneutralization,thestudentrecoveredthestartingaldehydeandbutane.Writethis
reaction(2points)anddeterminewhatwentwrong(2points).Usingthesamestartingmaterialsandany
otherreagentsneeded,modifythesynthesissoitwillwork(6points).
___/10
Analysis:thestudentforgottotakeintoaccountthatGrignardreagentsarestrongbasesandwould
deprotonatethephenolicproton.Protectingthephenolasatertbutyletherwillallowformationofproduct.
___/19 Page 2
___/13
___/14
5)Startingfromtheappropriate2butene,deviseasynthesisofmeso2,3butane2,3diol.(10points)
___/10
Analysis:Eithercisortranswillworkdependingonconditions.Thetransalkenewillgivethemesodiolviaa
epoxideformationandringopening.Thecisdienecanbeconvertedtothemesoalcoholinonestepusing
OsO4.
___/37 Page 3
6)SN2chemistrycanbeusedtosynthesizeethersfromalkylhalidesandalkoxides(Williamsonether
synthesis).Makeuseofthisreactionbydrawingasynthesisofdiisopropylether(C6H14O)usingonly
isopropanolasasyouronlyorganicstartingmaterial.Youmayuseanyotherinorganicreagentsasnecessary
butallthecarboninyourproductmustcomefromisopropanol.(10points)
___/10
OH
NaH or other base
PBr 3 OR SOCl2
OH
Br (Cl)
SN2
7)Fisheresterificationisamethodofsynthesizingestersfromacarboxylicacidandalcoholusinganacid
catalyst.Drawthemechanismthataccountsfortheformationofisopentylacetatestartingfromaceticacid
andisopentanol(3methylbutan1ol).Forfullcredit,yourmechanismmustusethecurvedarrownotationto
showallbondmakingandbondbreakingandanyintermediates,ifformed.(10points)
___/10
___/20 Page 4
SignBelow
Chem.345FinalExamination
Name
WSUID#
Monday,December10,2012
1)ConsiderthereactionAH+H2OA:()+H3O(+)Forthefollowingnamedacids:a)drawthestructureofthe
acid,b)givetheapproximatepKaoftheacidinunitsof5,andc)drawthestructureoftheconjugatebase.
Drawstructuresasclearlyasyoucanandincludealllonepairelectronsandindicateformalchargewhere
appropriate.(2pteachstructure,1ptpKavalue,40ptspossible)
acid
Isopropanol(C3H8O)
pKa
Pent1yne(C5H8)
pKa
conjugatebase
Dimethylamine(C2H7N)
pKa
Phenoxideanion(C6H5O)
Pyridine(C5H5N)
AllylmagnesiumBromide
(C3H5BrMg)
tertButylthiolate
pKa
pKa
pKa
pKa
base
conjugateacid
Pentan3one(C5H10O)
pKa
2)Startingfromphenol,drawasynthesisofthecompoundshown.Youmayuseanyrequiredreagentsto
accomplishthissynthesis(12points)
O
3)Fillintheblanks.(12points)
NH2
H+
+
H3O
PCC
CH2Cl2
-H2O
O
NaBH4
CH3OH
Cl
a. LiAlH4
b. H3O+
Et3N
4)Wastevegetablefats(triestersortriacylglycerides)arethefeedstockusedtomakebiodieselfuel.The
processinvolvesreactingtriacylglycerideswithsodiumhydroxideinanhydrousmethanoltogivemethylesters
andglycerolasshownbelow.Thefinalstepsintheproductionofbiodieselareallpurification,primarilyto
isolatethemethylesters,whicharethecombustiblecomponentsofthefuel.
Usingethylacetateasasimplemonoestermodel,drawamechanismthatillustratestheformationofa
methylesterundertheseconditions.Toreceivefullcredit,youmustusethecurvedarrownotationtoshow
allbondmakingandbondbreakingstepsinyourmechanismaswellasshowingallintermediatesformed
duringthereaction.
5) The unsaturated product shown on the right was made via a Robinson annulation
reaction (a Michael reaction followed by an aldol/dehydration.) Using retrosynthesis,
determinethetwostartingproductsthatundergoRobinsonannulation.(15pts)
6)Startingfrom4bromobenzaldehyde,drawasynthesisof4
propionylbenzaldehyde.Hint:Aprotectinggroupisrequired.(12points)
7)UnderE2conditions,trans1bromo2methylcyclohexanegivesthelesssubstituted3methylcyclohex1
eneratherthanthemoresubstituted1methylcyclohex1ene.
7a)Drawthisreaction(6points)
7b)Usingmorepicturesthanwords,drawamechanismthataccountsforthisreaction.Forfullcredityou
mustdistinguishwhyonlyoneregioisomerisformed.Templatechairstructuresareprovidedforyouranswer.
(6points)
C4
C3 C2
C5 C6
C1
C5
C3 C
4
C2
C1 C6
8)Considertheaminoacidhistidine,whichhasthreeacidicgroupswith
pKavaluesof1.82(carboxylicacid),6.04(pyrroleNH),and9.17
(ammonium).AtpH=1,allgroupswouldbeprotonatedasshownhere:
8a)CompletetheLewisstructuresbelow(byincludingrelevantprotonson
oxygenandnitrogenatoms)toaccuratelyrepresentthestructuresfor
histidineatthegivenpHvalues(9points)
8b)Determinetheabsoluteconfigurationofthechiralcarbon(3points).
9)Completethefollowing(2ptsstructure,1ptreagents,1pttype,48pointspossible)
OH
COCH3
a. CH3MgBr (2 eq)
b. H3O+
a)
PBr3
i)
type
type
O
OH
PCC
b)
j)
a. LAH, Et2O
NH2
b. H2O
CH2Cl2
type
type
OH
H+
a) NaOH (aq)
k)
c)
b)
Ph
OH
Br
type
type
O
Br
d)
a)
H CH3
NaCN
DMSO
l)
O
type
type
H
N
NH2
e)
CH3
type
O
n)
type
HO
KOtBu/tBuOH
OH
o)
type
type
a) NaOEt/EtOH
b)
Br
Br
OEt c) NaOH (aq); H3O+
type
H
type
a. OsO4
b. NaHSO3
NaOH (cat)
EtOH
O
OEt
b. H3O+
h)
CH3OH
type
a. NaOEt/EtOH
g)
NaBH4
m)
f)
b) H3O+
O
Br
pyridine
p)
type
Sign Below
Name
WSUID#
Wednesday,December11,2013
1a)ConsiderthereactionAH(+)+H2OA:()+H3O(+).Forthefollowingnamedacids:a)drawthe
structureoftheacid,b)givetheapproximatepKaoftheacid,andc)drawthestructureoftheconjugatebase.
(12pointspossible)
Benzenesulfonicacid
pKa
<0
Phenol
pKa
10
Cyclopentadiene
pKa
15
conjugatebase
acid
Phenylacetylene
pKa
25
1b)ConsiderthereactionB:()+H3O+BH(+)+H2O.Forthefollowingnamedbases:a)drawthe
structureofthebase,b)drawthestructureoftheconjugateacid,andc)givetheapproximatepKaofthe
conjugateacid.(12points)
tertButoxideanion
Ethylacetateenolateanion
Pyridine
pKa
10
pKa
1518
pKa
2025
pKa
5
conjugateacid
base
Isopropylamine
NH3
OH
N
H
___/24 Page 1
(9points)
___/9
3)Thecompoundshownbelow,4(4hydroxyphenyl)butan2one),aketonefoundinraspberry,canbe
synthesizedinatwostepprocesswithoutusingprotectinggroupsfrom4hydroxybenzaldehydeandalarge
excessofacetone.
3a)Drawasynthesisofthisraspberryketonestartingfromacetoneand4hydroxybenzaldehydeandany
othernecessaryreagents.Hint:rememberthatcatalyticreductionusinghydrogengasandpalladiumwill
cleanlyreducethedoublebondofanunsaturatedsystemwhileleavingthecarbonylfunctionintact.(10
points)
___/10
___/19 Page 2
3b)Intheinitialcondensationreaction,acetonemustbeusedinexcessorthefollowingbyproductis
observed.Usingthecurvedarrownotationtoshowbondmakingandbondbreaking,drawamechanismthat
showshowthisbyproductisformed.(10points)
Dont need to show mechanism of

elimination for full credit
___/10
4)Drawasynthesisof2(4(tertbutyl)phenyl)propanoicacidstartingfrombenzeneandusinganyother
necessaryorganicreagentsthatcontain4orfewercarbonatoms.(10points)
O
OH
AlCl3, AcCl
Cl
NaBH4
AlCl3,
EtOH
CO2H
a) Mg, Et2O
Br
b) CO2
PBr3 OR
HBr
c) neutralize
2-(4-(tert-butyl)phenyl)propanoic acid
NaCN
CN
H3O+, heat
___/10
___/20 Page 3
H Br
NaCN
a)
CHO
NC H
h)
type SN2
type alpha halogenation
j)
either regioisomer
k)
a. LiAlH4, Et2O
Br
NH
m)
type Reduction
type
O
CO2Et
a) NaOEt/EtOH
CO2Et
b) neutralize
type Claisen condensation
___/21
n)
CO2H
Grignard or formation of acid
O
OEt
a. Mg, Et2O
b. CO2
c. H3O+
b. neutralize
g)
O
other acetals ok (acetal) hydrolysis
type
t-butyl ether formation
NH
H3O+
O
f)
Cl
formation of acid chloride

O
l)
type
SOCl2
CO2H
e)
NEt2
amide formation
type
type
H+
Et2NH, pyridine
Cl
E1
OH
-1 if acid O
H2SO4 (conc'n)
d)
CO2
saponification
type
OH
CH3
ok if neutral
OH
Br
b. neutralize
SN2 or Grignard
NaOH (aq)
i)
a. CH3MgBr, Et2O
O
type
aldol
O
Br2, HOAc
b)
type
OH
CHO
Ph
ok if -hydroxy
aldehyde
EtOH cat NaOH

then heat
type
c)
CH3CHO
Ph
type
NaBH4
Ph
MeOH
OH
Ph
Ph
reduction
___/21
___/42 Page 4
6)Considertheelectrophilicadditionreaction(hydrochlorination)ofthemoleculeshownbelow.Drawthe
expectedproduct.(5points)
3pointsifwrongregioisomer
___/5
7)ConsiderthetwoenantiomersofglyceraldehydeshownasaFischerprojectionbelow.First,addpriority
numberstotheemptyboxes.Second,assignabsoluteconfigurationbycirclingRorSforeachenantiomer.(5
points)
___/5
___/10 Page 5
8)Robinsonannulationmaybeusedtosynthesizecyclohex2enonestartingfromacetoneandthe
unsaturatedaldehydeprop2enal(C3H4O).Drawthesynthesisandmechanismofthisreaction.Forfull
credit,youmustusethecurvedarrownotationtoshowallbondmakingandbondbreakingandincludeall
intermediatestructures.Youdonotneedtodrawthemechanismofeliminationleadingtotheformationof
thedoublebond.(10points)
___/10
4pointsiftheydrawthereaction
9)Rememberthatunsaturatedaldehydesandketonesmayalsobesynthesizedbyeliminationusing
pyridine(orothertertiaryamine)fromanhaloaldehydeorketone.Usingthischemistry,drawanalternate
synthesisofcyclohex2enonestartingfromcyclohexene.Drawingthemechanismisnotnecessaryforfull
credit,butbecompletewithshowingfunctionalgrouptransformations.
___/10
___/20 Page 6
Name
Wednesday,December17,2014
WSUID#
thestructureoftheacid(1point),b)givetheapproximatepKaoftheacid(1point),andc)drawthe
structureoftheconjugatebase(1point).(12pointspossible)
(C4H11O)
Benzenesulfonicacid
(C6H6O3S)
pKa<0
pKa<0
Phenol(C6H6O)
pKa10
Cyclopentadiene(C5H6)
pKa15
OH
acid
OH 2
conjugatebase
SO3
OH
thestructureofthebase(1point),b)drawthestructureoftheconjugateacid(1point),andc)give
theapproximatepKaoftheconjugateacid(1point).(12pointspossible)
tertButylthiolateanion
Pyridine
Allylamine
1butynide
NH 2
S
conjugateacid
base
(C4H10S)
pKa10
(C3H8N)
pKa10
(C5H6N)
pKa5
(C4H6)
pKa25
NH 3
___/24 Page 1
(9points)
___/9
3)Whenthediketoneproductinquestion2issubjectedtosodiumhydroxideinethanol,anew
unsaturatedcompoundisproduced(showntotheright).Usingthecurvedarrownotationtodenote O
bondmakingandbondbreaking,drawamechanismthataccountsforthisproductformation.For
fullcredityoumustshowallintermediates.(10points)
O
O
O
O
NaOH/EtOH
OH
OH
___/10
___/19 Page 2
4a)Inthelabthisterm,younitratedmethylbenzoatebyreactingwithnitricandsulfuricacids.Drawthis
reaction.(5points)
4b)Usingthecurvedarrownotation,showthemechanismofthisreactionandincludeabriefexplanation
(morepicturesthanwords)onthedirectingeffectsofmethylbenzoate.(5points)
HNO3 + H2SO4
NO2
H2O
HSO4
O
O
HNO3 / H2SO4
OCH3
OCH3
N
NO2
___/10
OCH3
H
base
H NO2
5)Startingfromanalkylhalidecontainingnomorethan4carbons,drawasynthesisof2methylpentan2ol.
Youmayuseanyadditionalorganicorinorganicreagentsyourequiretocompletethesynthesis.(10points)
___/10
___/20 Page 3
O
O
Base
HCl
OH
a)
h)
Cl
CHO
Br2, HOAc
b)
i)
Ph
H3O
Ph
Br
OH
b. neutralize
Et2NH, pyridine
j)
o
type Grignard synthesis of 1 alcohol
OH
NEt2
Cl
amide formation
type
H2SO4 (conc'n)
d)
a.
MgBr
NH2
type imine hydrolysis
halogenation
c)
type SN2
O
type
k)
SOCl2
Et3N
CO2H
Cl
O
E1
type
type
formation of acid chloride

O
e)
Ph
OH
CF3CO2H
(g)
OH
l)
H+
OH
type
deprotection of a t-butyl ether
formation of acetal
type
O
f)
NH
a. LiAlH4, Et2O
Br
NH
m)
g)
type
H2, Lindlar cat.

Ph
type reduction, formation of cis alkene
CO2H
Grignard or formation of acid

NaBH4
n)
O
Ph
___/21
a. Mg, Et2O
b. CO2
c. H3O+
b. neutralize
type Reduction
type
MeOH
OH
reduction
___/21
___/42 Page 4
7)rankthefollowingsubstitutedanilinesinorderofincreasingbasestrength(strongestbaseonthefarleft,
weakestbaseonthefarright).(10points)
___/10
8)Startingfromacetylene(ethyne),drawasynthesisofthefollowingracemicdiol.Youmayuseany
reagentsnecessary.(10points)
HO H
S
R
HO H
From test 2, fall 2014
C2H2
a) NaNH2
a) NaNH2
b) BnBr
b) BnBr
H2
Lindlar Cat.
3 pts
3 pts
HO H
OsO4
H2O
___/10
HO H
3 pts
___/20 Page 5
9)Whenthefollowingisotopicallylabeledbenzylbromideisreactedwithmethanol,amethyletheris H D
producedbutallopticalactivityislost.
Br
9a)Drawthisreactionanddefinethetermracemic.(5points)
9b)Accountforthelossofopticalactivityintheproduct.Forfullcredit,youmustdescribealikely
mechanism.(5points)
___/10
___/10 Page 6
ScoreSummary
PageNumber
Page1
Page2
Page3
Page4
Page5
Page6
TOTAL
PossiblePoints
24
19
20
42
20
10
135pointspossible
PointsAwarded
SignBelow
Name
KEY
WSUID#
acid
Monday,December10,2012
1)ConsiderthereactionAH+H2OA:()+H3O(+)Forthefollowingnamedacids:a)drawthestructureofthe
acid,b)givetheapproximatepKaoftheacidinunitsof5,andc)drawthestructureoftheconjugatebase.
Drawstructuresasclearlyasyoucanandincludealllonepairelectronsandindicateformalchargewhere
appropriate.(2pteachstructure,1ptpKavalue,40ptspossible)
Isopropanol(C3H8O)
pKa15
Pentan3one(C5H10O)
pKa20
Pent1yne(C5H8)
pKa25
Dimethylamine(C2H7N)
pKa3035
CH3
HN
CH3
OH
conjugatebase
base
Phenoxideanion(C6H5O)
Pyridine(C5H5N)
AllylmagnesiumBromide
(C3H5BrMg)
tertButylthiolate
conjugateacid
pKa10
pKa5
pKa4050
pKa10
NH
2)Startingfromphenol,drawasynthesisofthecompoundshown.Youmayuseanyrequiredreagentsto
accomplishthissynthesis(12points)
ThereareatleasttworeasonableroutesbutthekeytoeitherisaSN2reactionbetweenthephenolicoxygen
andacarbonandanEAStoclosethering.
O
OH
a base capable of
removing a proton with
a pKa value of 10
O
LG
EAS
O
SN2
H+
non acqueous
acid
3)Fillintheblanks.(12points)
4)Wastevegetablefats(triestersortriacylglycerides)arethefeedstockusedtomakebiodieselfuel.The
processinvolvesreactingtriacylglycerideswithsodiumhydroxideinanhydrousmethanoltogivemethylesters
andglycerolasshownbelow.Thefinalstepsintheproductionofbiodieselareallpurification,primarilyto
isolatethemethylesters,whicharethecombustiblecomponentsofthefuel.
Usingethylacetateasasimplemonoestermodel,drawamechanismthatillustratestheformationofa
methylesterundertheseconditions.Toreceivefullcredit,youmustusethecurvedarrownotationtoshow
allbondmakingandbondbreakingstepsinyourmechanismaswellasshowingallintermediatesformed
duringthereaction.
Thisissimpliedversiontakenfromquestion6ontest2.Thisquestiondiffersintheesterandisalsorununderbasic
conditionsratherthanacidic.Formechanismcredit,youmustshowthetetrahedralinermediate.
5)The unsaturated product shown on the right was made via a Robinson annulation
reaction (a Michael reaction followed by an aldol/dehydration.) Using retrosynthesis,
determinethetwostartingproductsthatundergoRobinsonannulation.(15pts)
6)Startingfrom4bromobenzaldehyde,drawasynthesisof4
propionylbenzaldehyde.Hint:Aprotectinggroupisrequired.(12points)
Thereareacoupleofwaysofdoingthisreaction.Thecommonthemeisthatyoumustprotectthealdehyde.
7)UnderE2conditions,trans1bromo2methylcyclohexanegivesthelesssubstituted3methylcyclohex1
eneratherthanthemoresubstituted1methylcyclohex1ene.
7a)Drawthisreaction(6points)
7b)Usingmorepicturesthanwords,drawamechanismthataccountsforthisreaction.Forfullcredityou
mustdistinguishwhyonlyoneregioisomerisformed.Templatechairstructuresareprovidedforyouranswer.
(6points)
KOtBu/tBuOH
Br
Me
Me
Me
less substituted
more substituted not obtained
H
Br
Br
C4
C5
C6
C3 C
C5
C
H
5
4
H
H
C
C
Br
H
2
1
H
C
C
3
6
C2
C1
C2
H
H
H3C
H
H
CH3
dihedral angle of 180 can be

achieved only between the
halogen on C1 and a proton
on
C6
8)Considertheaminoacidhistidine,whichhasthreeacidicgroupswith
pKavaluesof1.82(carboxylicacid),6.04(pyrroleNH),and9.17
(ammonium).AtpH=1,allgroupswouldbeprotonatedasshownhere:
8a)CompletetheLewisstructuresbelow(byincludingrelevantprotonson
oxygenandnitrogenatoms)toaccuratelyrepresentthestructuresfor
histidineatthegivenpHvalues(9points)
H
N
N
O
N
O
NH3
pH = 4
O
O
NH3
pH = 8
(S)
NH2
O
NH2
pH = 11
8b)Determinetheabsoluteconfigurationofthechiralcarbon(3points).
OH
9)Completethefollowing(2ptsstructure,1ptreagents,1pttype,48pointspossible)
OH
OH
COCH3
a. CH3MgBr (2 eq)
b. H3O+
a)
type
PBr3
i)
formation of alkyl bromide (conversion to

type good leaving group)
Grignard synthesis of alcohol
OH
O
PCC
b)
Br
j)
a. LAH, Et2O
NH2
type
oxidation
OH
type
a) NaOH (aq)
b)
reduction
H+
O
k)
c)
Ph
OH
Br
NaCN
DMSO
H CN
l)
O
type
H
N
Cl
Et3N
O
OEt
O
n)
type Claisen condensation
g)
type
h)
reduction
NaOH (cat)
EtOH
CHO
aldol condensation
LG
HO
KOtBu/tBuOH
OH
o)
cis hydroxylation
type
a) NaOEt/EtOH
b)
Br
Br
OEt c) NaOH (aq); H3O
acetoacetic ester synthesis
E2
O
O
+
type
HN
H
type
a. OsO4
b. NaHSO3
NaBH4
O
OEt
b. H3O+
CH3OH
type
a. NaOEt/EtOH
Michael reaction
m)
b) H3O+
CH3
type amide bond formation
f)
a)
type SN2
e)
CH3
NH2
Ph
formation of ether (test 1 question 5)
type
O
H CH3
Br
type acid/base; SN2
d)
NH2
b. H2O
CH2Cl2
Br
pyridine
p)
type
elimination

Wednesday, October 6th, 2010
Name
WSU ID # ______________________
1) Consider the reaction AH + H2O ' A:(-) + H3O(+) For the following named acids: a) draw the structure of
the acid, b) give the approximate pKa of the acid in units of 5, and c) draw the structure of the conjugate base.
Draw structures as clearly as you can and include all lone pair electrons and indicate formal charge where
appropriate. (1 pt each structure, 1 pt pKa value, 24 pts possible)
Anilinium cation (C6H8N)
pKa

pKa
Diethyl ether (C4H10O)

pKa
Acetic acid (C2H4O2)

pKa
Phenol (C6H6O)
pKa
Hydronium cation (H3O)

pKa
Benzenesulfonic acid
(C6H6SO3)
pKa
conjugate base
acid
conjugate base
acid
Nitric acid (HNO3)

pKa
2) Complete the following drawing of a disubstituted cyclohexane by filling in all the hydrogens and other
substituent to give the lowest energy chair conformation of cis-1-tert-Butyl-4-methylcylcohexane (6 points)
C4
C3
C6
C5
C2
C1
3) Complete the flow chart below by drawing the expected structure in the boxes below for the separation of 4aminobiphenyl, phenol, and 9-florenone using aqueous extraction techniques learned in lab. (12 points possible)
OH
H2N
dissolve in ether, extract with 2M HCl
ether layer
water layer
extract with 2 M NaOH
neutralize with 2M NaOHl

f ilter and isolate crystals
ether layer
water layer
evaporate
ether
neutralize with
2M HCl, f ilter and
isolate crystals
4a) Complete the Newman projections shown below for the two staggered conformations of 2-methylbutane
sighting along the C2-C3 bond. (2 pts each part, 6 pts possible)
4b) Circle the lower energy staggered conformation
4c) Briefly explain your answer to 4b)
5) A student was given the task of preparing trans-1,2-dibromocyclohexane from cyclohexene. Because the
student had been texting during lecture on the day that bromination of alkenes had been discussed, he missed
the point about the importance of the solvent in this reaction. So rather than use carbon tetrachloride as the
solvent, he used methanol. Upon workup he discovered that he had not made the trans dibromide but rather an
unknown compound with the formula C7H13BrO. Help this student out by using words and pictures to explain
where he went wrong and show him the structure of his unknown. To receive full credit, you must show a
mechanism that accounts for the formation of product using the curved arrow notation to show bond-making
and bond-breaking and also draw any reactive intermediates, if formed. (12 points)
6) Complete the following: (Stereochemistry and regiochemistry may be important). (2 pts structure, 1 pt
reagents, 1 pt type, 28 points possible)
7) Starting from toluene (C7H8), draw a synthesis of 4-aminobenzoic acid (C7H7NO2). You do not need to
draw a mechanism but must draw reagents and products for each synthetic step. (12 points)
Sign Below
I pledge on my honor that this exam was completed by me, that I received no unauthorized help,
and that I have not violated the honor code of the University.

Wednesday, December 1st, 2010
Name
WSU ID # ______________________
1) Consider the reaction AH + H2O ' A:(-) + H3O(+) For the following named acids: 1) draw the
structure of the acid, 2) give the approximate pKa of the acid in units of 5, and 3) draw the structure of
the conjugate base. Draw structures as clearly as you can and include all lone pair electrons and
indicate formal charge where appropriate. (24 points total)
Ethyl propanoate (C5H10O2)
pKa
Acetaldehyde (C2H4O)
pKa
N-Methyl anilinium cation

(C7H10N+)
pKa
Benzyl oxonium cation

(C7H9O+)
pKa
2,4-Pentanedione (C5H8O2)
pKa

pKa
pKa
conjugate base
acid
conjugate base
acid
Isopropanol (C3H8O)
pKa
2) Determine the products for each of the reaction steps show below (2 pts each, 8 pts total).
3) Complete the following: (Stereochemistry and regiochemistry may be important, 28 point total).
O
a)
a) NaOEt, EtOH
OEt
type
f)
b) neutralization
Claisen condensation
CF3CO2H
a)
g)
OtBu
deprotection of an alcohol
a)
b)
c)
type
O a) CH3MgBr, ether
b) H3O+
h)
Acetoacetic Ester Synthesis
type
i)
b) neutralization
type
type
O
EtNH2
type
a) NaOH (aq)
Br
e)
KOtBu
d) HO
CO2H b)
c)
type
aldol condensation
type
b)
type
CHO
H+
remove water
H+
j)
OH
type
formation of a cyclic hemiacetal
4. When the -chloroester ethyl 2-chloroacetate reacts with potassium tert-butoxide in the presence of
acetone, an epoxy ester is formed. Although you havent seen this particular condensation reaction
before, it is very similar to an aldol. Devise a mechanism that accounts for the reaction shown below.
Use the curved arrow notation to specify all bond making and bond breaking events. (13 points total).
5) You have been assigned to synthesize the hemiacetal 2-methyltetrahydrofuran-2-ol starting from
keto ester ethyl 4-oxopentanoate. Remembering hemiacetal chemistry, you know that you must first
convert the keto ester to a keto alcohol, which can then be cyclized to the target hemiacetal. 5a) First,
deduce the structure of the intermediate keto alcohol. 5b), Second, devise a synthesis of this keto
alcohol from the starting keto ester (5a = 6 pts, 5b =7 pts, total 13 points possible)
6) Draw a synthesis of 1-cyclohexyl-3-methylbutan-2-one starting from

cyclohexanol. Use any necessary reagents, however you are limited to
compounds containing three or fewer carbon atoms. (13 points).
O
1-cyclohexyl-3-methylbutan-2-one
7) We learned many reactions this semester but there are many more organic chemistry reactions that
we did not discuss. A reaction we did not discuss this semester (and specifically based on our
discussion Friday November 20, 2010) is which of the following? (1 pt)
a) Aldol condensation
b) Berkman rearrangement
c) Crouch condensation
d) Diekmann condensation (intramolecular Claisen condensation)
I pledge on my honor that this exam was completed by me, that I received no unauthorized help,
and that I have not violated the honor code of the University.
Chem. 345 Hour Examination III

Wednesday, December 15th, 2010
Name
WSU ID # ______________________
1) Consider the reaction AH + H2O ' A:(-) + H3O(+) For the following named acids: 1) draw the
structure of the acid, 2) give the approximate pKa of the acid in units of 5, and 3) draw the structure of
the conjugate base. Draw structures as clearly as you can and include all lone pair electrons and
indicate formal charge where appropriate. As a reminder, deuterium (D or 2H) is a heavy isotope of
hydrogen. (24 points total)
Phenyl butanoate (C10H12O2)
pKa
Acetophenone (C8H8O)
pKa
Allyl oxonium cation

(C3H7O+)
pKa
Benzyl ammonium cation

(C7H10N+)
pKa
Diethyl malonate (C7H12O4)

pKa
1-Butyne (C4H6)
pKa
p-Toluenesulfonic acid
(C7H8O3S)
pKa
conjugate base
acid
conjugate base
acid
pKa
2) Determine the products for each of the reaction steps show below (2 pts each, 8 pts total).
O
EtO
a) NaOEt/EtOH
SOCl2
AlCl3
OEt b) PhCH2Br
c) NaOH; H3O+, heat
HN
CH3NH2, H+
remove water
NaBH4
CH3OH
3) Complete the following: (Stereochemistry and regiochemistry may be important, 36 point total).
O
O
a)
a) NaOH, EtOH
H
g)
b) neutralization
type
type
H2SO4, conc'n
OH
b)
type
CO2Me
OH
h)
a)
b)
O
OH
c)
a. NaNH2, NH3
d)
mCPBA, CH2Cl2
i)
type
CHO
type formation of a cyclic hemiacetal
dehydration
c)
Claisen condensation
type
CO2H
j)
a) SOCl2
b) 2 eq Et2NH
b. EtBr, THF
type
type
OH
Br2
PBr3
e)
k)
CH3OH
type
type
O
OH
f)
OH
type
NaCN
H+
remove water
Br
l)
H3C H H D
DMSO
type
4. When 4-(dimethylamino)benzaldehyde reacts with nitromethane in triethylamine and is heated,

N,N-dimethyl-4-(2-nitrovinyl)aniline is formed. Although you havent seen this particular
condensation reaction before, it is very similar to an aldol. Devise a mechanism that accounts for the
reaction shown below. Use the curved arrow notation to specify all bond making and bond breaking
events. (10 points total).
5) You have been assigned to synthesize the lactone dihydrofuran-2(3H)-one starting from aldo ester
methyl 4-oxobutanoate. Remembering ester chemistry, you know that you must first convert the aldo
ester to a hydroxyl acid, which can then be cyclized to the target hemiacetal. 5a) First, deduce the
structure of the intermediate hydroxyl acid. 5b), Second, devise a synthesis of this hydroxyl acid from
the starting aldo ester (5a = 6 pts, 5b =7 pts, total 10 points possible)
6) Draw a synthesis of propyl cyclopentanecarboxylate starting

from cyclopentanol. Use any necessary reagents, however you are
limited to compounds containing three or fewer carbon atoms. (10
points).
7) In the banks below, assign R or S configuration to the circled atoms of the following molecules. (8
pts)
_____________
_____________
8) Provide simple example reactions for the following (mechanisms not required, 5 points each, 20 pts
total):
8a) a deprotection step
8b) a reduction
8c) a reaction that results in inversion of stereochemical configuration
8d) a saponification reaction
9) Based on the table of strain energies below, circle the more stable conformational isomer (a or
b). You should also need to know that steric strain also exists between two staggered alkyl groups
when viewed in a Newman projection; this is also known as a gauche interaction. (4 pts.)
Y
CH3
C(CH3)3
CH3CH3
(gauche)
Steric strain of one Y-H

1,3-diaxial interaction
(kcal/mol)
1
5
Other strains (kcal/mol)
1
This is a worksheet lab there is no prelab write up required

Lab #1
Acid and Base Calculations; Solubility and Permeability of Organic Compounds
Review acid/base chemistry using class notes, your text, and Organic acid-base chemistry from Kahn
academy. There is a math help sheet also linked on the lab calendar page.
Turn in the last two pages of this workbook.
Acid/base equilibrium reactions. In this lab, you will explore Brnsted-Lowry acid/base theory
introduced in general chemistry. This theory defines an acid as a proton donor and a base as a proton
acceptor. Simply put, Brnsted theory is a way of thinking about an acid/base reaction in terms of
proton transfer equilibria. A generic example is given below where HA is any acid reacting with
water:
H-A
+
+
H2O
K eeqq
+
+
H 3O
Equation 1
The reaction shown above uses a special kind of double arrow that infers a relationship between the
reactants and products. This double arrow (
) denotes that the reactants are in equilibrium with the
products where the position of equilibrium is governed by the constant Keq which is unique to each
acid/base reaction. The value of Keq is given by the equation
Keq =
[H 3 O + ][ A ]
[HA ][H 2 O]
Equation 2
where the square brackets indicate the concentration of the substance involved. Since the
concentration of water remains essentially constant at 55.5M, equation 2 can be rearranged to give:
Keq [H 2O] =
[H 3O + ][ A ]
[HA]
Equation 3
The acid equilibrium constant K a for the acid HA is defined as

[H 3O + ][ A ]
Keq [H 2 O] = K a =
[HA ]
Equation 4
Example 1. The acid hydrogen chloride HCl is reacted with the base water to give hydronium ion and
chloride ion:
H
H
Cl
O
H
Cll

Note the use of the convention to draw unequal equilibrium arrows where the longer arrow points to
the side favored at equilibrium. For this particular reaction, you should not be surprised that the
products are favored at equilibrium since you know HCl is defined as a strong acid (an acid that
almost completely dissociates to ions in water.) The value of K a for HCl is approximately 1 10 6 .
Example 2. Acetic acid is reacted with water to give hydronium ion and acetate ion:
H3C
H 3C
H
O
O
O
H
In this example, the double arrows indicate that equilibrium favors the reactant acid (the un-ionized
form.) Again, this should not be a surprise since you know acetic acid is a weak acid (an acid that does
not appreciably dissociate in water.) This means that when acetic acid and water are combined, very
little ionization occurs and equilibrium lies toward the reactants (on the left-hand side of the arrows.)
The value of K a for acetic acid is approximately 1.8 10 5 .
Many chemical reactions that are governed by equilibrium use this double arrow convention to indicate
whether equilibrium favors products, as in example 1, or reactants, as in example 2. For whatever acid
base reaction being evaluated, the acid dissociation constants Ka indicate the position of equilibrium
that is whether the equilibrium favors reactants or products. Look again at HCl reacting with water.
Since HCl nearly completely dissociates in water, concentrations of hydronium ion and chloride ion
(the products of dissociation) are much greater than the concentration of undissociated HCl.
Therefore, the K a of HCl will be greater than 1 since the numerator of the fraction that defines K a
will be much larger than the denominator. In contrast, for acetic acid where equilibrium favors nondissociated acid in water, the concentration of undissociated acid will be much higher and so the
denominator of the fraction that defines K a will be greater than the numerator. Thus, the K a for
acetic acid will be less than 1. While K a values are easily accessible, they tend to be unwieldy in
everyday use. A quick comparison of our examples shows this: The K a of HCl is about 1 10 6 while
the K a of acetic acid is about 1.8 10 5 . Since acid dissociation equilibria are so central to
understanding reactivity, chemists have developed a shorthand notation called pKa where the lowercase p denotes the negative logarithm. Logarithms are used to make the quantities much more
manageable. These pKa values are readily available in table form (see the course website) and provide
the same information as Ka. Such tables would show that the pKa of HCl is 6 and the pKa of acetic
acid is 4.76. Recall that log x determines the power to which 10 must be raised to arrive at x. Thus for
HCl, we would have log(1106) = 6, and so
pKa = log(1 10 6 ) = 6 .
For acetic acid, we would have log(1.8105) = 4.76, and so
pKa = log(1.810-5) = 4.76.

When comparing the strengths of acids, remember the lower the pKa, the stronger the acid. For our
examples, HCls pKa of 6 is lower than acetic acids pKa of 4.76, so HCl is a stronger acid than acetic
acid.
Predicting the Position of Equilibrium in an Acid Base Reaction
We can use pKa values to determine the position of equilibrium in many acid/base systems. For
example, consider the acetic acid/ ammonia system below. Will equilibrium favor reactants or
products (acetate anion and ammonium cation)?
H3 C
H3 C
N
H
H
H
Consulting your pKa table, you will find that the acid (acetic acid) has a pKa of about 5 whereas the
conjugate acid (ammonium ion) has a pKa of about 10. In any acid/base reaction, the position of
equilibrium always favors reaction of the stronger acid (acetic acid) and stronger base to form the
weaker acid (ammonium cation) and weaker base. So in this example, the products will be favored at
equilibrium. When considering base strength, remember that the stronger acid always give the weaker
conjugate base).
pH and pKa. When we measure the pH of an aqueous solution, we are measuring the concentration of
hydronium ion (protonated water, a molecule made up of neutral water bonded to a proton.) Because
strong acids almost completely dissociate in water, they will increase the presence of protons in
solution (as H3O+.) While free protons (H+) do not exist in water, it has become tradition to use
protons and hydronium ion interchangeably in equilibrium expressions. Thus, the symbol pH is
used instead of p[H3O+].
Recall from equation 4 the definition of Ka:
[H 3O + ][ A ]
Ka =
[HA]
If we rearrange equation 4 to isolate [H3O+], we have

[ H 3O + ] = K a
[HA]
[A ]
If we take the base-ten logarithm of both sides, we have
log [H 3O + ] = log K a + log( [HA] /[ A ] )

Multiplying both sides by 1 gives us
log [H 3O + ] = log K a log( [HA] /[ A ] )

or by using the fact that log( y / x) = log( x / y ) ,
log [H 3O + ] = log K a + log( [ A ] /[HA] )

Finally, since p is used for log, we obtain
pH = pKa + log( [ A ] /[HA] )
Equation 5
Equation 5 is known as the Henderson-Hasselback equation; this equation tells us that it is enough to
know the pH of a solution and pKa of the acid in order to determine the relative concentrations of the
acid HA and the ion A in solution at equilibrium. A quick rearrangement of equation 5 gives us
[A ]
= 10 ( pHpK a )
[HA ]
Equation 6
Suppose, for instance, that the pH equals the pKa. Then the right-hand side of equation 6 becomes
10 0 = 1 . This means that [A] = [HA] and so the concentrations of the acid and ion are equal. We can
conclude that 50% of the acid HA has disassociated.
The following table illustrates the amount of dissociation of an acid HA with a pKa = 4 in solutions of
various pH values:
pH
2
3
4
5
6
pKa
4
4
4
4
4
Ratio [A]/[HA]
0.01
0.1
1
10
100
Percentage of HA Dissociated
1%
9%
50%
91%
99%
So, for instance, at a pH of 3, very little of the acid dissociates (there are only 1/10 as many A ions as
there are HA molecules) while at a pH of 5, most of the acid dissociates (there are ten times as many
A ions as there are HA molecules.)
Biological pH and Acid Dissociation. Given that physiological pH is 7.3, we can use the Henderson
Hasselbalch equation to determine exact ratios ([A] / [HA]) of an acid in a cellular system. For
example, determine [A] / [HA] for a 0.0010 M solution of p-nitrophenol (pKa 7.2) at pH = 7.3.
Recall that
[A ]
[A ]
= 10 ( 7.37.2 ) = 1.26
= 10 ( pH pK a ) so
[HA]
[HA]
Rearranging gives [A] = (1.26) [HA] and substituting into [A] + [HA] = 0.0010M and solving two
simultaneous equations gives [A] = 0.00056M and [HA] = 0.00044 M

Solvent Polarity. We need to think about how polarity affects a compounds solubility in aqueous and
organic solvents. First, an organic solvent is understood to be any liquid that is not water. Next, we
need to understand the distinctions between non-polar, protic, and polar aprotic solvents in addition to
the terms miscible and immiscible. We approach these terms by means of specific examples. Hexane,
an example of a non-polar solvent, is a liquid at room temperature with the molecular formula C6H14.
The experimentally determined density of hexane is 0.672 g/mL (less dense than water). Hexane is
immiscible with water; when vigorously mixed with water it will form an emulsion that quickly
separates into two layers, with hexane as the top layer (think of oil and vinegar salad dressing). Note
that hexane (a hydrocarbon) has only carbon-hydrogen covalent bonds. Further, the electronegativity
difference between carbon and hydrogen is slight, giving rise to non-polar covalent bonds. In terms of
solvents, hydrocarbons such as hexane are always considered to be non-polar.
Next, ethanol (CH3CH2OH), considered a protic solvent, is a short chained alcohol that is completely
miscible with water. This means that a mixture of ethanol and water does not separate into layers the
way a hexane-water mixture does. If you consult a table of pKa values, you will note that ethanol has a
pKa of about 16 whereas hydronium cation has a pKa of <0. That is to say,
H3C
CH2
O
base
CH2
O
H
H
H
O
H
H3C
acid
pKa = 16
conjugate acid
pKa -1.74
O
conjugate base
While a pKa of 16 is weak compared with a pKa of <0, alcohols are sufficiently acidic to be considered
protic solvents solvents able to act as Bronsted acids under sufficiently basic conditions. Certainly
ethanol is polar or it would not be miscible with water. Other protic solvents include water, amines,
acetic acid, formic acid, etc.
Finally, consider diethyl ether (CH3CH2OCH2CH3), considered a polar aprotic solvent. This
compound has a density of 0.807 g/mL, is immiscible with water, is a less polar solvent than ethanol,
but more polar solvent than hexane. Why is ether more polar than hexane? Consider the Lewis
structure of each. While hexane is composed of non-polar covalent bonds, diethyl ether on the other
hand has two carbon-oxygen covalent bonds. Since oxygen is more electronegative than carbon, these
will be polar covalent bonds so the molecule overall will be polar. However, ether does not contain an
acidic proton, hence it is classed as aprotic. Most non-polar solvents will be immiscible with water,
most protic solvents will (at least to some extent) be miscible with water, polar aprotic solvents may or
may not be miscible with water.
Solubility as a function of pKa. Solvent polarity and acid/base characteristics come together in the
phrase like dissolves in like. Here, this means less polar substances dissolve in less polar solvents
while more polar substances dissolve in more polar solvents. You will use this principle in your first
lab experiment to move a compound from a less polar organic solvent to more polar water. For
example, benzoic acid in its neutral (un-ionized) form is less polar than in its more polar charged form
called benzoate ion. Therefore, neutral benzoic acid will be more soluble in less polar organic solvents
(diethyl ether) than in water, whereas benzoate ion will be more soluble in the more polar solvent
water than in less polar organic solvents. Another way of thinking about this is when you ionize a
neutral acid to a charged base the charged base will look like water since it will then be very polar.
benzoic acid
neutral f orm
sodium benzoate
ionized f orm
soluble in water
OH
stronger acid
water
+ NaOH
stronger base
pKa = 4.2
less polar
all covalent bonds
weaker conjugate base

more polar
ionic bond
Na
+ H2O
weaker conjugate
acid
pKa 15.7
From before, we found that if we take a compound HA with a pKa of 4 and add it to an aqueous
solution at pH 6, most of it (at a 100/1 ratio) will be in the conjugate base (ionized) form A .
Furthermore, from our guiding principle of like dissolves like, A will dissolve in water. On the other
hand, if we put our compound with a pKa of 4 into an aqueous solution at pH 2, most of it will remain
as neutral HA and it will not dissolve. However, if we now add a non-miscible polar aprotic solvent to
generate a two phase system (aqueous/organic), HA will be soluble in the less polar organic solvent.
Again, for this to work, the organic solvent must not be miscible with water so to provide two phases
a more polar aqueous phase and a less polar organic phase. This is the principle you will use in lab
to separate mixtures of compounds with different pKas. This is illustrated in the next figure for an acid
with a pKa of 4.
Organic
Water
HA HA HA
HA
HA
HA HA
HA
HA
HA
pH = 3
HA
A A
A A A
A
A
A
A
A
pH = 5
Notice that when the pH of the aqueous phase is equal to 3, the acid dissociates only slightly (there is
10 times as much HA as there is A-.) and much more HA will be in the organic phase. Conversely,
when the pH of the aqueous phase is equal to 5, the acid dissociates readily (the concentration of A- is
10 times as much as that of HA.) The ionized form of the acid (A-) will be soluble in water but not in
the organic solvent.

This same principle holds true for transport of chemicals across biological
membranes. Drugs are more likely to be absorbed into the body if they are neutral
since cell membranes are made mostly of organic compounds called lipids.
Not all compounds become charged when deprotonated. An example is an amine such as
diethylamine. Diethylamine is charged at low pH and neutral at a higher pH.
CH 2CH 3
CH 2 CH 3
CH 2CH 3
CH 2 CH 3
N
N
H
H
Diethyl ammonium ion form

predominates at lower pH
Diethyl amine neutral form

predominates at higher pH
The pKa of diethylammonium ion (protonated diethylamine) is 10.8. Most aliphatic amines have pKas
between 9 and 11, while aromatic amines such as aniline have much lower pKas of around 3 to 5.
Protonated aniline has a pKa of around 5.

Acid and Base Calculations
Section #______
Name__________________
Date__________
TA __________________
Homework questionsinclude lone pairs on all heteroatoms (S, O and N) in your answers.
1.
Draw the structure of protonated aniline (anilinium ion) and its conjugate base aniline.
2.
Calculate the percentage of ionized and unionized forms present in the following solutions. Assume that
the given concentrations start completely unionized and then ionize to some ratio at the given pH. Show
your calculations:
a. 0.0010 M glycolic acid (pKa = 3.83) at pH = 4.50
b. 0.0020 M propanoic acid (pKa = 4.87) at pH = 5.30
Page 1

3.
Complete the following three tasks below.

a. Find the approximate pKa value (you can estimate to the nearest 5) for each compound in the
table below and draw the structure of each compound and its conjugate base.
b. Circle the form (the acid or the base) that predominates at a pH of 7.
c. Write whether the predominate form would be more water soluble or more organically soluble.
(You do not need to show any calculations for this question)
Butyl Ammonium
pKa = ____
Octanol
pKa = ____
Carbonic Acid
pKa (1) = ____
pKa (2) = ____
acid
Decanoic Acid
pKa = ____
conjugate base
Conj. Base #1
Conj. Base #2
Phenol
pKa = ____
Pentane thiol
pKa = ____
conjugate base
acid
tertButanol
pKa = ____
Page 2
3-Hydroxypropanoic Acid
pKa = ____
Aldol Condensation
Pre-Lab Assignment: Complete the pre-lab cover page and develop a procedure. Draw the mechanism
of acetone reacting with 2 equivalents of benzaldehyde. Use the arrow drawing convention to show all
bond making and bond breaking steps in the reaction.
Learning Goals:
Learn the mechanism of an self and crossed aldol condensations
Learn the technique of recrystallization as a method of purification
Introduction:
The aldol reaction is a carbonyl condensation reaction between two aldehydes or two ketones giving a
-hydroxy aldehyde or ketone, which under basic conditions dehydrates to give ,-unstaurated
compounds as shown below for acetophenone.
OH
EtOH
CH3
acetophenone
CH3
CH3
NaOH (cat)
C
Ph
Ph
C
H2
Ph
a -hydroxy ketone
Ph
C
H
Ph
an
-unsaturated compound
also called an enone
The mechanism of an aldol reaction followed by dehydration is shown below and in Section C of Chapter
16.
An aldol condensation reaction can take place between two of the same aldehydes or ketones (known as
self condensation) or between two unique aldehydes or ketones (known as crossed aldol condensations).
A crossed aldol condensation between acetophenone and pivalaldehyde is shown below. Notice that
acetophenone has only one alpha carbon (three acidic hydrogen atoms) whereas pivalaldehyde has no
protons on the alpha carbon and can only act as an electrophile in this crossed aldol.
In this lab, you will run a crossed aldol reaction using benzaldehyde and acetone. Because acetone has
two alpha carbons, it will condense with two molecules of benzaldehyde (one condensation per side),
depending on reaction conditions.
Recrytallization:
Recrystallization is a purification technique that works well for some compounds that are solids at room
temperature. The trick to recrystallization is finding a solvent (or solvent mixture) in which the product
you are attempting to purify has enhanced solubility when warm and diminished solubility when cold.
This allows you to dissolve your compound in warm solvent and upon cooling, your product slowly
crystallizes. Purification results because, at least in theory, the impurities remain in solution. When
collecting your recrystallized products using vacuum filtration, it is important to rinse the crystals with a
minimum amount of cold solvent, in this case cold ethanol, to remove any remaining contamination. You
must use a minimum of solvent so as not to dissolve too much of your product, which would result in
reduced yields.
Procedure:
Assemble an ice bath. Combine 12 mL of absolute ethanol with 5 mL of 10% aqueous NaOH solution in
a 50 mL Erlenmeyer flask equipped with a stir bar. Place this flask on the stir plate and engage the stir
motor. In a short disposable test tube, using a dispensing pipette, combine 500 L of benzaldehyde with
200 L of regent grade acetone. Using a pasture pipette, transfer the benzaldehyde/acetone mixture to the
Erlenmeyer flask containing the stirring solution of ethanol and aqueous sodium hydroxide solution at a
fast drop rate (this transfer should take about 1 minute). As the reaction progresses, a product will
precipitate out of the solution. If after 5 minutes you do not see product beginning to precipitate, turn the
hot plate control to its lowest setting for two to three minutes only. After 30 minutes place the
Erlenmeyer in the ice bath for an additional 10 minutes. Following this, collect your product by vacuum
filtration using a Hirsch funnel with a side-arm vacuum flask.
Remember to clamp your securely clamp your vacuum flask and to pre-wet your filter
paper with a small about of ethanol.
Wash the product with no more than 2 mL of ice cold ethanol. Allow the vacuum to pull across your
crude product for a few minutes in order to aid drying. Weigh your crude sample and calculate yield,
note the color of the crystals. Carefully transfer the crystals from the filter paper into a 50 mL
Erlenmeyer flask, reserving a tiny amount of your crude product in a labeled sample vial. Place this crude
sample vial in your drawer to completely dry. Collect a melting point when your crude crystals are
thoroughly dry. You will now recrystalize your remaining product in order to obtain a purified sample.
Recrystallization:
Add 3 mL of absolute ethanol to the 50 mL Erlenmeyer containing your crude crystals and a boiling stick
and carefully warm your solution on the hotplate at a low setting. Continue adding ethanol drop-wise to
the warm solution until all of the solid product dissolves. If you add too much ethanol, gently boil-off the
excess
Adding too much solvent will result in reduced yields.
When your product is in solution, remove the flask from the bath and allow it to cool to room
temperature. Do not rush this stage of crystallization. Watch your product carefully and make good
observations. Your product may begin to crystallize. After your product has come to room temperature,
place the flask into an ice bath for 4-5 minutes to complete crystallization. Isolate your product by
vacuum filtration using a Hirsch funnel using a minimum of ice cold ethanol to wash the crystals. Again,
allow the vacuum to pull across the crystals to aid drying. Transfer the purified product to a second
labeled sample vial and allow to dry overnight. Note the color of your crystals, calculate percent yield,
and determine a melting point. You will determine and compare both your crude and pure samples sideby-side.
Post-Lab:
Determine the percent yield for your reaction. This will require you to do limiting reactant calculations
for each of your reagents. Show your work in the calculations section of your lab report.
Answer the following questions separate from your conclusions.
1.
2.
3.
4.
Draw the structure of your product?

What information does the melting point give you about purity?
What a possible side products from this reaction (Draw at least 2)?
Why doesnt benzaldehyde undergo a self aldol condensation?
Esterification
Pre Lab Assignment: Complete the pre-lab cover page and develop a procedure. Draw the
mechanism of the reaction you will complete in lab. Use the proper arrow drawing convention
to show all bond making and bond breaking steps in the reaction. Include all intermediates,
including resonance structures.
Learning Goals:
Understand the mechanism of esterification and how it relates to ester hydrolysis.
Understand how column chromatography can be used to separate compounds of
different polarity.
Relate column chromatography to TLC separation
Introduction:
An ester is a functional group where a carbonyl carbon is bonded to an alkoxyl group. These
compounds are commonly found in nature.
O
OCR 1R 2R 3
Generic Ester
methyl butyrate
ethyl 2-methylpropionate
The portion of the molecule in red is the ester f unctionality
Many esters have strong and pleasant odors. The fragrances and odors of flowers and fruits are
usually due to a complex mixture of several different chemicals, including esters, where one
ester typically predominates over the rest. The dominant ester in pineapples is ethyl butyrate,
while methyl butyrate is the predominating ester in apples. Esters are commonly used as
artificial flavors in the food and beverage industry.
Despite pleasant flavors and smells, esters are rarely used in perfumes or other scents designed to
be applied to skin due to their tendency to hydrolyze to the alcohol and acid. Ester hydrolysis,
resulting from the water in perspiration, gives medium chain length fatty acids that smell terrible
(think rancid butter or milk!), defeating the purpose of a perfume.
In this lab you will synthesize isopentyl acetate using isopentyl alcohol and acetyl chloride to
make isopentyl acetate.
OH
Cl
For humans, isopentyl acetate has a characteristic smell that is associated with bananas (hence
the banana oil nickname for isopentyl acetate). Isopentyl acetate is also one of the components
of the honeybee alarm pheromone. Pheromones are compounds secreted by organisms that
affect the behavior of members of the same species. The honeybee alarm pheromone is released,
along with venom, when a honeybee stings an intruder, and signals to other bees to attack the
intruder.
Procedure:
Obtain a hotplate from the stockroom. Prepare your drying tube (see the picture below) by
inserting a piece of cotton up to the bend in the tube using a spatula. Next fill the remaining tube
volume with calcium chloride to 1cm from the end. What is the function of the calcium chloride
in this set up? Place another piece of cotton into the end to keep the calcium chloride from
falling out.
Cotton
CaCl2
Cotton
Combine 200 L of isopentyl alcohol and

800uL of acetyl chloride in your 5mL
conical vial equipped with a conical spin
vane. Assemble the conical vial, a water
condenser and the drying tube and clamp
securely to your hood support bar (As
shown in the picture below).
Stir your reaction mixture for 15 minutes.

Disassemble your condenser and drying tube, being
careful not to spill your reaction. Using forceps,
remove the spin vane from the vial. Add
approximately 1mL of 5% sodium bicarbonate
solution with a Pasteur pipette (caution: bubbling!
What are the bubbles?). Cap the vial and gently mix
without inversion. Re-clamp the vial and wait for the
aqueous and organic phases to separate. Carefully
remove the bottom layer (what is it?) using a Pasteur
pipette and discard. Repeat this procedure three
additional times using 1mL of 5 % sodium bicarbonate
for each wash.
Next, prepare a small silica column by packing a small
piece of cotton into a 5 Pasteur pipette using the tip
of a 9 Pasteur pipette. Once the cotton plug is in
place, add silica gel to a level of 2 cm from the
plugged end of the pipette. Tap the pipette gently on
the bench to pack the silica. Next, add the same amount of anhydrous sodium sulfate (Na2SO4)
(what does this do?) to the top of the silica bed and clamp the pipette to the bench support. Add
one boiling stone to a product vial and weigh (including the cap) the container.
Place this vial under the pipette so the end of the pipette is just below the rim of the vial. Wet
(wet: to add pure solvent to a solid prior to addition of a solution of a compound) the column
with approximately 1 mL of methylene chloride. Next, transfer the crude product solution from
the reaction vial into the column using a pipette. When all the solution has been transferred to
the column, rinse the reaction vial with 500 L of methylene chloride and add this to the column.
When the solvent level in the column has reached the level of the Na2SO4 add another 1 mL of
methylene chloride to the column to make sure all of the product is eluted from the column.
How is this column aiding in the purification process?
Evaporate the solvent from the product vial by heating at 75C until the vial comes to a constant
weight. Youll know if your reaction was successful based on the smell. Transfer to and label a
product vial and place in the glassware container above your fume hood.
Post Lab:
Include what is required in the Lab Expectations handout.
Calculate percent yield for your reaction (this will require you to determine which
reactant is limiting).
1. Draw the mechanism of an esterification using an acid chloride and alcohol.
2. Could acetic acid be used in the esterification, instead of acetyl chloride? Why or why
not?
3. Could acetic anhydride be used?
4. Instead of getting your desired product, what would happen if your glassware was wet
before you started the reaction?
5. What is the relationship between TLC and Column Chromatography?
6. What is the limiting reagent in the reaction that you ran? Prove your answer with
limiting reagent calculations in the calculation section of the post-lab.
Extraction of a Three Component Mixture

Pre-Lab Assignment:
Complete the pre-lab cover page of the Lab-template Handout.
o Transcribe your own procedure using the procedure written below (Note:
You cannot have our copy of the procedure on your bench during lab; you
must create and work from your own written procedure. This is to ensure
youve read the lab and have a fair idea of what youre supposed to do!)
Create a detailed Flowchart mapping out the extractions separations.
Learning Goals:
Learn how acid/base chemistry is related to solubility
Learn liquid/liquid extraction techniques as a way of separating and purifying
organic compounds.
Learn how to construct a separations flowchart
Learn how to calculate percent recovery
Introduction:
Understanding how a molecule will react based on its properties is the core of organic
chemistry. One of the most easily understood structure-activity relations is acid/base
chemistry. In addition, the chemistry and thinking process in acid/base chemistry can be
extended to be the basis for many of the reactions that you will learn about in this class.
This lab will take advantage of acid/base properties in order to separate compounds using
liquid/liquid extraction techniques. The following compounds are present in the sample
that you will be given and need to be separated into their pure components.
O
O
OH
H2N
Benzoic Acid
Ethyl-4-aminobenzoate
9-Fluorenone
Note: Be kind to the environment and do not put organic waste down the sink.
Safety Issues:
1. Diethyl ether is flammable and intoxicating: do not use around an open flame and
do keep it inside your desk hood.
2. The aqueous sodium hydroxide solution is caustic (basic). If you get it on your
skin, it will dissolve the skin and/ or remove hair. If you or your clothes make
contact with either solution, immediately wash with tap water and advise your TA
that you got some on yourself.
3. The aqueous hydrochloric acid is acidic. If you get it on your skin it may cause
local irritation. If you or your clothes make contact with either solution,
immediately wash with tap water and advise your TA that you got some on
yourself.
Gen Chem Reminder: 3M HCl is not pure HCl. It is 3 moles of HCl(g) dissolved in 1 liter
of water. The water layers referenced throughout this lab are referring to these molar
solutions of acid or base.
Procedure:
In the main hood you will find a powdered mixture of containing 250mg of each of the
three compounds, Benzoic Acid, Ethyl-4-Amino Benzoate, and 9-Fluorenone. Add this
mixture to a clean separatory funnel (be sure the stopcock and closed before you add
anything to your funnel!) and then add ~20ml of diethyl ether (often called simply
ether.) Seal the funnel and shake briefly to fully dissolve the compound mixture.
Once dissolved, add ~20ml of 3M HCl (pH <0), seal the sep funnel, invert it (keeping
your fingers on the cap), briefly shake the mixture, and then open the stopcock to vent
pressure build up in the funnel. Note: Ether is extremely volatile and will easily build up
gaseous pressure from the heat of reaction. If you do not vent your stopcock every
few shakes, it may cause the lid to shoot off. Continue to shake vigorously and vent
periodically for ~30 seconds. After shaking, allow the two immiscible layers to fully
separate and then drain the bottom layer (water layer) into a 50ml Erlenmeyer flask and
label it acid extract. Note: If the lid is on your sep funnel when you try to drain it, it
may drain slowly or suck air bubbles up through the stopcock. With the top layer (ether
layer) still in the sep funnel, repeat the same process using 3M NaOH (pH >14), again
draining the bottom layer into a flask and label it base extract. Once both acid and base
extractions are finished, drain the remaining ether layer into a third flask (pre-weigh this
flask and write down the weight) labeled neutral extract.
Take your acid extract flask and slowly add to it
~8ml of 6M NaOH, then continue to add dropwise
additions of 6M NaOH until litmus paper shows a
shift from red to yellow/blue. Repeat the same with
your base extract using 6M HCl to neutralize it
until your litmus turns from blue to yellow/red.
Line a Hirsch funnel with a small filter paper (preweigh your filter paper!) that just covers the holes
on the bottom of the funnel. Dampen your filter
paper with a few drops of water and, hooked to a
vacuum as shown in the picture, slowly poor your
acid extract into the funnel and filter the precipitant
from your neutralized acid (what does your flow
chart say this precipitant should be?) Remove the
filter paper (precipitant and all) and set it aside.
Repeat the process for your base extract on a new
piece of pre-weighed filter paper.
Vacuum filtration setup using a 25mL Erlenmeyer Flask

and Hirsch Funnel. Remember to clamp your funnel.
Once you have isolated your two compounds, carefully transfer them (little filter paper
and all) to two larger pieces of pre-weighed filter paper and place them in your drawer to
dry. You can place your neutral extract with the ether in it directly in your drawer.
Note: Due to ethers volatility, no boiling is necessary and it will have evaporated
overnight. Do not put samples in a closed vial. They must be exposed to the air to
dry. You must allow at least 24 hours before weighing your compounds in order to let
them dry. If your compound appears wet, do not weigh it. Allow more drying time.
Once weighed, determine percent recovery. Put all solid wastes into the solids waste
container.
Post Lab:
1. What is the pKa of each of the three compounds used in this experiment?
2. Given that aqueous conditions have a pH range of 0-14, why is a pKa of
30 not of interest in extractions using aqueous conditions? (remember that
pKa refers only to acidity of a molecule)
3. How did the pKa of each component play a role in this experiment?
4. How did changes in pH alter the polarity of ethyl-4-aminobenzoate?
5. Why is the pKa of fluorenone different than that of most ketone
compounds?
6. Give an example how the principles illustrated in this lab apply to
everyday life.
Include the appropriate material that was indicated in the Lab Report Expectations
handout available in the lab folder of the course webpage.
Isolation of Caffeine from Soda

Pre-Lab Assignment:
Complete the pre-lab cover page and develop a procedure.
Develop an in-depth separations flowchart detailing the procedure in your pre-lab.
Learning Goals:
Understand the concepts and applications of natural product isolation
Reinforce liquid/liquid extraction techniques
Understand the pH dependent equilibrium of caffeine
Introduction:
Caffeine belongs to a family of heteroaromatic compounds known as xanthines. Other common
compounds found in this group are theophylline and theobromine. Theophylline is used in the
treatment of asthma and theobromine is found in chocolate. Xanthine, caffeine, and theobromine
are shown below. Note that the ring system and position of the nitrogen atoms are the same in
all three molecules.
O
H
H
N
H3C
N
H
Xanthine
CH3
CH3
N
N
CH3
Caffeine
CH3
Theobromine
A single cup of coffee can contain up to 200 mg of caffeine. Commercially, coffee is

decaffeinated by removing 97% or more of the naturally existing caffeine from the green beans
before roasting. Three methods for extracting caffeine from coffee are:
Direct Contact Method. After softening the beans by steam, the green beans are extracted
with methylene chloride, which dissolves the caffeine. The beans are steamed a second
time, heated and blown dry to remove almost all of the methylene chloride (US laws
allows no more than 10 ppm- 0.001% wt/wt- residual methylene chloride.).
Indirect Contact Method. The green beans are soaked in hot water, which extracts the
caffeine. The water is separated from the beans and extracted with either methylene
chloride or ethyl acetate. The extracted water, which is now caffeine-free, is put back
with the beans to restore some of the natural oils and flavor.
Water Filtration Method. After the beans soak for several hours in water, the water is
removed and passed through charcoal filters to remove the caffeine. The water, still
containing other flavor elements, is added back to the beans. This is often called the
"Swiss Water Process
In this lab you will isolate the caffeine found in common soft drinks, using extraction techniques
learned in earlier labs. Soft drinks are mainly carbonated water containing phosphoric acid,
caffeine, citric acid and other flavorings. Caffeine is an organic compound that in its neutral
state is weakly polar. Caffeine is also an organic base that when reacted with an aqueous acid
will become protonated to give an acid with a pKa of 3.6. Protonated caffeine is ionic and thus
polar, making it water soluble. Caffeines acid/base equilibrium is exploited in this lab to enable
separation from a complex mixture. The soft drinks used in this lab have been allowed to de-gas
over several days to facilitate handling. You will be provided with one can of de-gassed soft
drink that must be a shared with two other students. Do not forget to consider the starting pH
state of the soda, which will affect the initial protonation state of the caffeine.
Procedure:
Obtain a 250 mL separatory funnel and a hotplate from the stockroom. Once your separatory
funnel is secured in the iron ring (making sure the valve is closed), use a graduated cylinder to
add 125 mL of soda to the funnel. Using tweezers, add one pellet of sodium hydroxide (be
careful as sodium hydroxide is very basic: wash skin with water if contact is made with skin). Do
not pull out more than 1 or 2 pellets at a time, as they will absorb moisture from the air and you
wont be able to put them back. Cap and shake the funnel with frequent venting to dissolve the
sodium hydroxide. Remember to vent in your hood. Tilt the separation funnel upside down and
slowly open the drain valve to release any gas pressure.
Using litmus paper, determine the pH of your solution. Continue adding sodium hydroxide, one
pellet at a time, until the target pH of 8 is obtained. Why is a pH of 8 desired? Next, add 20 mL
of methylene chloride to the separatory funnel and shake vigorously, remembering to vent the
funnel into the hood frequently. Replace your separatory funnel in the ring, remove the cap and
allow the phases to separate (which layer is the methylene chloride?). You will notice a foam
layer between the organic and aqueous phases, this is called an emulsion. Carefully drain the
organic and the emulsion layer into a beaker. Add another 20 mL of methylene chloride and
repeat the extraction. Again, drain the organic layer into the same beaker. Pour your aqueous
layer into the sink while the cold water is running. Thoroughly clean your separatory funnel and
secure in the ring. Add the organic solution (your methylene chloride solution in the beaker)
back into the separatory funnel (again, making sure the valve is closed). Use an additional 10
mL of methylene chloride to rinse your beaker and add this rinse to the separatory funnel. To
this solution, add approximately 20 mL of saturated aqueous sodium chloride (brine), being
careful not to transfer any of the solids. Shake vigorously with venting, place back into the iron
ring and allow the phases to separate. (Brine makes the water layer more polar, decreases
emulsions, and helps remove polar compounds that are slightly soluble in methylene chloride.)
When the phases have separated, carefully drain the methylene chloride solution into a dry tared
125 mL Erlenmeyer flask.
Carefully boil off the methylene chloride using your heating plate and a boiling stick. At what
temperature does methylene chloride boil? Be careful to not pass this temperature by more than
20 degrees, to make sure the caffeine is not burned or sublimed. Why is a boiling stick used in
place of a boiling stone in this experiment? When all the solvent has evaporated, you will see an
off-white solid on the bottom of the flask: impure caffeine. After the flask cools, weigh the flask
and determine the amount of crude caffeine obtained.
Place a small amount of your crude caffeine into a disposable culture tube and obtain a small
sample of pure caffeine in a second tube. Add 1 mL of methylene chloride to each tube and
using disposable spotting pipets spot a TLC plate with your solutions (crude, pure, and co-spot).
What is the function of the co-spot? Develop the plate using ethyl acetate with 5% acetic acid as
the developing solution. Examine your plate under the UV light and mark the location of the
solvent front along with any spots that you see.
Post Lab:
Tape a properly labeled TLC plate to the observations section of your lab report, and
describe what it illustrates.
1. Draw the equilibrium mechanism between caffeine and aqueous acid.
2. Using resonance structures, explain why one nitrogen is more basic than the others.
(Hint: Only one nitrogen can resonate a positive charge around the ring once protonated.)
3. Determine the total amount of crude caffeine in one can of soda pop using your
experimental yield in milligrams.
4. What does your TLC plate tell you about the purity of the crude caffeine you extracted?
5. Sublimation is a technique that can be used to purify your crude caffeine. What is
sublimation and how would it purify a compound?
Nitration of Methyl Benzoate

to show all bond making and bond breaking steps in the reaction. Include all intermediates,
including resonance structures.
Learning Goals:
Introduce electrophilic aromatic substitution
Understand how substituent groups affect aromatic substitution
Introduction:
When an aromatic compound such as benzene reacts with an electrophile (E+), it undergoes an
electrophilic aromatic substitution reaction. The mechanism is shown below.
The electrophile accepts an electron from the pi system of the aromatic ring to form a resonance
stabilized carbocation.
Base
Resonance Stabilized Intermediates
When the electrophile is added to benzene, it can substitute onto any carbon in the ring. If a
substituent group is already present on the ring (a mono substituted aromatic system), it will
direct substitution to a specific carbon depending on whether the substituent is electron donating
or withdrawing. (Brown and Poon Pages 258-259)
In this experiment, you will be nitrating an aromatic ester. In most cases a Lewis acid catalyst
must be added to form an electrophile that is strong enough to undergo substitution. The
nitronium ion (NO2+) is the electrophile and it is generated by reacting nitric acid with sulfuric
acid (the catalyst) according to the following equilibrium reaction.
O
N
O
OH
S
O
O
OH
H2 O
N
OH2
N
O
HSO4
Because nitric acid alone does not provide a concentration of the ions that is sufficient for the
reaction to proceed at a significant rate, sulfuric acid is used as a proton source to generate a
higher concentration of nitronium ions at equilibrium.
The reaction between nitric acid and sulfuric acid is reversible, so adding water will reduce the
amount of nitronium ion, according to Le Chtliers principle. This will terminate the reaction.
Procedure:
Caution: Sulfuric and nitric acids are strong acids and can cause severe burns to skin on
contact. Nitric acid is a strong oxidant. It can rapidly oxidize organic materials: do not
put in contact with flammable materials. Nitric acid will also react with proteins (read:
skin) to stain the skin yellow: do not get nitric acid on skin. Wear gloves and avoid contact
with eyes, skin clothing, and other flammable materials. In case of contact with either
sulfuric or nitric acid, quickly wash the exposed surface with large amounts of water and
then report the issue to your TA.
Materials and supplies:
Stir plate
250 mL beaker containing ice and containing:
a 5 mL conical vial containing 560 L of sulfuric acid and spin vane,
a disposable test tube containing 240 L of nitric acid and 240 L of sulfuric acid,
a disposable test tube containing 200 L of methyl benzoate,
a disposable test tube containing 3 mL of deionized water, and
a disposable test tube containing 2 mL 1:1 methanol and water.
Obtain a stir plate from the stockroom and fill your beaker with crushed ice. Add 560 L of
sulfuric acid to a 5 mL conical vial containing a conical (triangular) spin vane and place in the
ice bath (beaker of crushed ice) for five minutes to cool. In a small disposable test tube, combine
240 L of nitric acid and 240 L of sulfuric acid and place this in your ice bath. Finally, add 3
mL of deionized water to a disposable test tube and place in the ice bath.
Remove your conical vial containing the sulfuric acid from the ice bath and clamp it above your
stir plate. While the acid solution is gently stirring, transfer the 200 L of methyl benzoate to the
conical vial dropwise using a Pasture pipette. After the addition of the methyl benzoate is
complete, add the cold nitric acid/sulfuric acid mixture to the conical vial again, dropwise. Let
the solution stir at room temperature for 15 minutes. After 15 minutes stop the reaction by
adding approximately 2 mL of de-ionized ice water. Using tweezers, carefully remove the spin
vane, and rinse the spin vane with the final 1 mL of cold water. Place the reaction solution in
your ice bath for 10 minutes. Stir the solution several times with a glass rod. You should see a
white precipitate (crystals!) forming once the solution cools. If the precipitate does not form,
wait a little longer and/ or get your TA.
Collect the precipitate using a Hirsch funnel (remember to clamp your funnel to the hood
structure and dont forget the filter paper!). Scrape any remaining product in the reaction vial
into your Hirsch funnel. Dissolve the remaining material in your reaction vial with
dichloromethane (~ 1 mL) for use in your TLC
With the crystals in the Hirsch funnel, rinse the crystals with 2 mL of a cold 1:1 methanol and
water solution and continue to pull a vacuum over the crystals for 5 minutes (this will remove the
excess methanol). Carefully place the filter paper containing your product in a beaker in your
drawer and allow to air dry for at least 24 hours. Dispose of all
liquid solutions in the sink with cold water.
Spot the known samples of methyl p-nitrobenzoate, mnitrobenzoate, and o-nitrobenzoate along side your reaction
sample (the material in the reaction vial that was dissolved in
dichloromethane) on a TLC plate and elute with 20 % ethyl
acetate/ 80% hexane. Which isomer, ortho, meta or para, do
you expect your product to be? Visualize the samples with UV
light and tape your TLC plate onto your report. If you cannot
unambiguously identify your product(s), run a co-spotted TLC
( lane 1: your reaction, lane 2: your reaction plus one of the
isomers, and lane 3: the isomer used in lane 2).
Temperature
Gauge
Come into the lab after 24 hrs have passed and weigh a vial.
Carefully scrape the product into the vial and re-weigh the vial.
The difference in weights is the weight of your product. After
you have weighed your product, calculate the percent yield and
determine the melting point of your product as was
demonstrated by your TA.
Post Lab:
Calculate your percent yield and determine the melting point. Put these calculations in
the calculations section of your report.
Address the following questions separately from your conclusion.
1. Is the ester group of your starting material electron donating or withdrawing?
Support your conclusion with resonance drawings.
2. Draw the mechanism of the nitronium ion reacting with the methylbenzoate.
3. Why does water stop the reaction?
4. According to your TLC plate, how many products did your reaction produce and
which isomers are produced?
Capillary tube
with product
Viewport
Temperature
Control
Nucleophilic Substitution
to show all bond making and bond breaking steps in the reaction.
Learning Goals:
Understand nucleophilic substitution reactions
Introduction:
A substitution reaction takes place when a nucleophile (Nu:) forms a bond with a carbon atom,
displacing a leaving group (L).
H
Nu
Nu
H
H
Sn2
Leaving groups are typically weak Bronsted bases that are stable as anions (often halide anions).
The precise timing of when the leaving group leaves depends on the structure of the substrate
the molecule bearing the leaving group. Methyl and primary alkyl halides tend to undergo SN2
type reactions. In this type of reaction, the nucleophile attacks the carbon from the side opposite
the leaving group and the nucleophile-carbon bond is made simultaneous with the carbon-leaving
group bond breaking. SN2 reactions are one-step and there is an inversion of stereochemistry at
Mechanism for Sn2
Me
HO
Me
HO
Et
H
Me
Br
Br
Et
HO
Br
Et
Sn2 Transition State
Note: Inversion of
stereochemistry
the carbon bonded to the nucleophile.

See also:
(Brown & Poon: Pages 175-176 and http://www.bluffton.edu/~bergerd/classes/CEM221/sne/SN2-1.html)
Additional notes to augment chapter 7, in the handouts section of the course website.
Sn1
If the carbon undergoing substitution is sterically hindered (as is the case with tertiary alkyl
systems) or the intermediate carbocation is relatively stable (tertiary alkyl or resonance stabilized
systems), SN1 reactions are prevalent. In this case, the nucleophile cannot approach the carbon
bearing the leaving group as it would in an SN2 reaction or the carbocation is fairly stable, and
the leaving group leaves first, forming a planar carbocation with a formal positive charge on the
carbon. Once the carbocation is formed, it is attacked by the nucleophile forming a new bond.
Reactivity, in terms of SN1 substitutions, is based on the stability of the carbocation intermediate
formed. SN1 reactions are two step reactions where the first step involves the formation of the
carbocation and the second step involves the attack of the nucleophile. Because of the achiral
nature of the carbocation intermediate, if the carbon bearing the leaving group is chiral, then
stereochemistry is lost in an SN1 reaction. (Brown & Poon: Page 177.)

The reaction you will be carrying out in lab will convert 9-fluorenol to 9-methoxy fluorene using
a nucleophilic substitution reaction.
OH
OCH 3
H 2SO 4
MeOH
Procedure:
Obtain a hotplate, 10 mL round-bottom flask, and heat transfer block from the stockroom. Set
up a reflux apparatus using a 10 mL round-bottom flask and a water condenser (which can be
found in the red kit on your bench).
Before attaching the round bottom flask, add your spin bar and 200 mg of 9fluorenol (pre-weighed) to this flask and place it in your cork ring for safe
holding. Measure out approximately 6 mL of methanol into your graduated
cylinder. In the hood, slowly add 1.5 mL of concentrated sulfuric acid to the
methanol with a transfer pipette (CAUTION: concentrated sulfuric acid is a
strong acid. In case of contact with ANY organic material, immediately
wash with cold water. Do not leave drops of sulfuric acid on the table.
Dispose of the transfer pipette in the container in the back of the hood.). The
solution will become hot as the sulfuric acid is added (Why?). Return to
your bench and pour the H2SO4/MeOH mixture into your flask and reassemble your reflux
apparatus. Rinse the graduated cylinder with cold water. Start circulating the water in the water
condenser. The water flow should be a slow steady stream and should enter from the bottom of
the condenser (as shown in the picture above).
Set the reaction flask in the largest hole in the aluminum block and set the thermometer in the
smallest hole of the aluminum block using the thermometer clamp. Heat the reaction mixture to
about 100C while stirring. The solution should boil gently. Heat the solution for a total of 20
minutes, beginning from the time the reaction flask is put on heat. Remove the reaction flask
from heat, i.e. unplug and move your hot plate, and allow it to cool to approximately room
temperature, but do not detach the flask from the condenser yet. Be careful not to shake the flask
when removing it from the heating block because it may start to boil violently.
During this time obtain two spotting pipettes. Put a small amount of 9-fluorenol in a disposable
culture tube and add enough dichloromethane to dissolve the sample.
Once your reaction has cooled, prepare a TLC plate and spot it with 9-fluorenol and your
reaction mixture. Develop the TLC plate in methylene chloride. Visualize your plate using UV
light and trace around the spots. Pour your reaction mixture into the waste bottle provided in the
hood.
Post Lab:
Tape a properly labeled TLC plate to the observations section of your lab report, and
describe what it illustrates.
1. Is this reaction more likely to proceed via an SN1 or SN2 reaction? Explain.
2. Did the reaction favor products or reactants? How can you tell?
3. Whyisconcentratedsulfuricacidusedinthisreactionandnotaqueousacid?
Hint:Whatisthebigdifferencebetweenconcentratedandaqueousacids,and
whatrolewouldthatdifferenceplayinthereaction?(Explainanddrawthe
reactionandshowtheequilibriumthatisdependentontheacid.)
4. Why is Benzyl Bromide, which appears to be a primary halide, able to undergo SN2
and SN1 reactions? Support your answer with drawings.
Reduction of a Ketone
to show all bond making and bond breaking steps in the reaction. Include all intermediates and
appropriate resonance structures.
Learning Goals:
Understand both the conceptual and technical sides of reducing a ketone using a
metal hydride
Understand the concept of oxidation states with respect to alcohols and ketones
Application of thin layer chromatography to monitor reaction progress
Introduction:
The reduction of carbonyl compounds to alcohols using metal hydride reagents is a common
reaction. Two of the most common metal hydride reducing agents are sodium borohydride
(NaBH4) and lithium aluminum hydride (LiAlH4). Sodium borohydride is the less reactive and
more selective of the two compounds. It will readily reduce aldehydes and ketones to primary
and secondary alcohols (respectively), reduce esters only under select conditions, and is
unreactive towards carboxylic acids and amides. Lithium aluminum hydride is much more
reactive and less selective. It readily reduces aldehydes, ketones, esters, and carboxylic acids to
alcohols (1o, 2o, 1o, and 1o respectively) and reduces amides to the corresponding amine. An
approximate mechanism for metal hydride reduction is shown below.
Reduction of a ketone:
MH3
O
OH
O
H2O
H
H
MH3
Reduction of an ester:
MH3
MH3
O
O CH 3
H
O
H 2O
H
H
MH3
OH
MH3
H
H
In this lab you will use sodium borohydride to reduce 9-fluorenone to 9-fluorenol and monitor
the reaction at several time intervals by TLC.
O
HO
H
NaBH4
MeOH
9-Fluorenol
Fluorenone
Procedure:
Bring a watch, a metric ruler, and a pencil to lab. Obtain a hotplate and a heat transfer block
from the storeroom. Place the magnetic spin vane into your 5 mL conical reaction vial with the
point down. Add 200 mg of 9-fluorenone and ~4 mL of anhydrous methanol into the vial. Put
the vial into the heat transfer block (sitting on the hotplate/stirrer) and stir until all of the 9fluorenone has dissolved.
Mark the two TLC plates in pencil as shown below.
1 = f luorenone
2 = f luorenol
3 = t0s
4 = t30s
5 = t60s
6 = t120s
7 = t240s
8 = t600s
1
Label two 12x75 culture tubes as fluorenone and fluorenol and add a few crystals (~ 1 mg) of
fluorenone (starting material) and fluorenol (reduction product) to the appropriate tube. Add
~500 L of acetone to each tube to make a solution of the known samples and use two spotting
capillaries to spot lanes 1 and 2 as shown above.
In a separate 12x75 culture tube, obtain ~20 mg of NaBH4 (do not add this to the reaction
mixture yet). As the reaction progresses you will take samples of the solution at times 0, 30, 60,
120, 240, and 600 seconds. Timing is important in this experiment, so make sure you understand
the procedure and have supplies prepared before you begin the reaction.
Using a spotting capillary, spot a sample of the reaction solution (before addition of the sodium
borohydride) in lane 3 designated t0s (time zero).
Using your watch, monitor the time and transfer the sodium borohydride to the reaction vial. At
times =30s, 60s, 120s, 240s, and 600s spot lanes 4 through 8, respectively. After the last spot,
develop your two TLC plates using methylene chloride as the developing solvent. Use UV light
to visualize the plates. Trace, with pencil, any spots visualized.
After you have developed and marked your TLC plates, isolate the 9-fluorenol from the reaction
mixture by transferring the reaction solution to a 10 mL Erlenmeyer flask and adding
approximately 2 mL of water. What affect does adding water have on the product solution and
why? Heat the mixture (no higher than 100 C) on your hotplate until the solid dissolves
completely in solution. When your solid is dissolved, remove the flask from the hotplate.
Remove the Erlenmeyer flask from the hotplate and let it cool to room temperature. Once it has
cooled to room temperature, carefully place it in an ice bath to complete the crystallization of the
9-fluorenol. In general, why is re-crystallization of a product performed?
Collect the product using vacuum filtration with a Hirsch funnel fitted with a 1.5cm diameter
filter paper wetted with water. Remember to securely clamp your vacuum flask before use.
Using ~1 mL of ice-cold water, rinse the Erlenmeyer flask and pour this through the filter.
Continue pulling vacuum on the filter for 5 minutes in order to dry sufficiently. Transfer the
crystals to a tared piece of filter paper and place this on a watch glass in your drawer to dry for
24 hours. After the product has dried, weigh the product, and determine percent yield and
melting point of the product. What is the expected melting point of 9-fluorenol? How does this
compare with your experimental melting point range?
Post Lab:
Include the material required in the Lab Syllabus handout.
Tape the properly labeled TLC plates to the observations section of your lab report.
1. What is the significant difference between 9-fluorenone and 9-fluorenol that allows
reaction progress to be monitored by TLC?
2. Draw the reaction that would transform 3-methylbutan-1-ol to 3-methylbutanal.
3. Draw the reaction that would transform 3-methylbutan-1-ol to 3-methylbutanoic acid.
4. Draw the reaction that would transform benzaldehyde to benzyl alcohol.
5. Sodium borodeuteride is a commercially available reducing reagent that can convert
aldehydes and ketones to the corresponding alcohols along with an isotopic label. Draw
the reaction between benzaldehyde and sodium borodeuteride showing the position of
isotopic labeling.
Saponification soap making

Learning Goals:
Understand the concept of ester hydrolysis
Understand how the structure of a salt of a fatty acid helps a soap function
Illustrate how an ester carbonyl group acts as an electrophile
Introduction:
In this experiment you will make soap by hydrolyzing coconut oil. Fats and oils are composed
of a complex mixture of esters. One family of these esters is called triglycerides. Triglycerides
are composed of the esters of the three carbon triol (three hydroxyl groups) called glycerol and a
variety of long chain carboxylic acids containing between 8 and 24 carbons. These ester bonds
can be hydrolyzed under basic conditions to give salts of the carboxylic acids and glycerol.
O
R1 CO 2
R1
Na
Na
Na
HO
NaOH
R 2CO2
H2O
R 3 CO 2
R2
HO
HO
R3
Vegetable oils such as coconut oil contain mixtures of triglycerides that when hydrolyzed will
give many different fatty acids. These mixtures of fatty acids, which vary in the length of the R
group and number of double bonds, give soap its characteristics (water solubility, ability to
lather, etc.) Coconut oil contains triglycerides that when hydrolyzed give mainly lauric acid
(C12H24O2), a water soluble fatty acid that easily lathers and has little smell. Dyes, scents, and
other additives give soaps their unique color and smell.
Fatty acid soaps have two domains that are important to their function of cleaning things. The
first domain is the carboxylate, which is an ion and therefore very soluble in water (hydrophilic).
The second domain is the long chain hydrocarbon tail of the fatty acid, which is insoluble in
water (hydrophobic) but very soluble (lipophilic) in oils. As a result
Na
Na
Na
Na
of
long chain
fatty acid salts
dirt
micelle (in water)

charge and sodium ions not shown
these two
opposite domains, long chain fatty acid salts form complexes called micelles in which the
carboxylate group is on the outside (next to the water) and the hydrocarbon tails are on the inside
(next to each other).
Objects are dirty usually because dirt has become trapped in oil that is absorbed to the object.
The soap micelles dissolve this oil. The water soluble micelle-oil complexes and dirt are then
removed with water and the object is clean.
On the web:
http://www.alcasoft.com/soapfact/history.html
http://chemistry.about.com/library/weekly/aa081301a.htm
Procedure:
Obtain a hotplate from the stockroom. Attach your thermometer to a heat block and heat to 110
C. Add about 15 g of coconut oil to a 50 mL beaker and heat. Once the oil has melted, begin
stirring with a glass rod. Meanwhile, under the hood, combine 5 mL of water and 2.2 g of
sodium hydroxide in a 10mL Erlenmeyer flask (Caution: 1. sodium hydroxide is very basic: if
spilled, wash with water immediately; 2. dissolving sodium hydroxide in water is an exothermic
process (HOT) and produces aerosolized sodium hydroxide). Swirl the flask until the sodium
hydroxide has completely dissolved. Slowly add the solution of sodium hydroxide to the melted
oil. Stir this mixture on for 10 minutes while maintaining a temperature of 110 C. The mixture
should slowly turn cloudy. Turn off the heat to the hotplate and continue to stir for an additional
10 minutes. If you choose, add color or scent at this time. When the solution cools to room
temperature, place the beaker in an ice bath until the solution begins to thicken. If your solution
does not thicken, you have not completely hydrolyzed your esters (reheat for 10 minutes more).
Pour the thickened solution into the plastic cup and place it in your drawer. It may take up to
two weeks for your soap to cure (non-technical word which means to assume its final form- ie
to become rigid).
Post Lab:
Include what is required in the Lab Expectations handout
In your post lab address the following questions:
1. Draw the mechanism for saponification.
2. What is the nucleophile in this reaction?
3. Why doesnt sodium acetate act as soap?
4. Detergents contain compounds that have a sulfonate group instead of a carboxylate.
Why do detergents work better than soaps at all pH ranges?
5. Why wouldnt you want to put your banana oil (isopentyl acetate) from last weeks
lab into this reaction?
Solubility and Extraction

Pre-Lab Assignment:
Complete the pre-lab cover page of the Lab-template Handout (available on the course website).
Draw a flow chart to represent which layer (organic or water) the benzoic acid goes into during
each phase of the procedure.
Learning goals:
Understand aqueous and organic solubility principles
Become acquainted with extraction techniques & use of separatory funnel
Understand how pH, pKa, and charge affect solubility.
Introduction:
This lab is designed to teach acid and base chemistry using liquid/liquid extraction. From
earlier chemistry classes you may have heard the saying like dissolves like, which refers to
polar compounds dissolving better in polar solvents and non-polar compounds dissolving better
in non-polar solvents. In this experiment you will dissolve benzoic acid in diethyl ether and
extract using water solutions of varying pH.
OH
OH
Ether
Dissolved
Benzoic acid
Solid
Benzoic acid
In ether, a relatively non-polar solvent, benzoic acid is soluble and therefore will be mostly
dissolved into solution.
O
OH
OH
H2O
Dissolved
Benzoic acid
Solid
Benzoic acid
In water, a polar solvent, benzoic acid is not soluble and therefore will remain mostly as a solid
in the solution.
Procedure:
You will be provided with a 250mL separatory funnel on your bench. Attach an iron ring to the
support bar on the hood and place the 250 mL separatory funnel in it (as shown in the picture
below).
Obtain the pre-weighed 250mg of benzoic acid from the hood.
Remove the cap from the separatory funnel and, making sure the
stopcock is closed (blue rod is perpendicular to the axis of the funnel),
combine the benzoic acid and 20 mL of diethyl ether in the separatory
funnel. Does the benzoic acid dissolve in this solvent? Why or why
not?
Place your fingers over the cap to secure it and invert the separatory
funnel. While holding the separatory funnel under the fume hood upside down, carefully open the drain valve to release pressure in the
funnel (see picture). Close the valve and gently shake the separatory
funnel for a few seconds. Using the same technique as before, release
the pressure on the separatory funnel. Repeat this process until the
benzoic acid has completely dissolved.
Warning: Liquid/liquid extraction using a separatory funnel produces
pressure when shaking. If you fail to vent the funnel during an
extraction, the pressure may build to a point that the cap is expelled
and the contents of the extraction lost.
Add 20 mL of 3M HCl to the separatory funnel and replace the cap.
Repeat the shaking/venting technique described above, five times.
Reminder: molar solutions are moles of solute in a liter of solvent.
For example, 3M HCl is 3 moles of HCl in 1 L of water.
After several shaking/venting cycles, replace the funnel in the iron
ring, remove the cap and allow the aqueous and organic (diethyl ether)
layers to separate. Why do these two layers separate from each other?
When the layers have separated you will be able to see a mirror-like
surface between the two layers. Label an Erlenmeyer flask acid
extract and drain the aqueous layer (caution: which layer is the
aqueous layer? Hint: water has a density of 1.00g/mL, and diethyl
ether has a density of 0.706g/mL. ) into it and set it aside.
Make sure you vent your

separation funnel away from you
and into the hood.
Add 20 ml of 3M NaOH to the remaining organic phase in the separatory funnel and repeat the
extraction procedure. Drain the aqueous layer into an Erlenmeyer flask labeled base extract
and set it aside. What does the NaOH do to the benzoic acid?
Carefully pour the diethyl ether into a beaker labeled neutral extract and place it in your hood.
Pour 10mL of ether from the beaker onto a watch glass and place in the back of the hood
Using a pipet and litmus paper, neutralize the acid extract by adding 6M NaOH dropwise
(caution: do not get this on your skin or clothes. If you get it on yourself, thoroughly wash it off
with water) until the solution is slightly basic. How is the NaOH neutralizing the solution?
Next, neutralize the base extract with 6M HCl until the solution is slightly acidic (see caution
above). One solution should have a relatively heavy white precipitate, while the other should
have no precipitate, why?
Observe your watch glass with the material from the flask labeled neutral extract. Most of the
ether should have evaporated. Is there any solid? Document which aqueous fraction has the
most precipitate.
Pour any residual ether into the waste bottle marked organic and your benzoic acid- water
mixtures into the bottle marked for benzoic acid disposal.
Post Lab:
Answer the following questions separate from your conclusion:
1. Which is the more polar solvent, water or diethyl ether?
2. When the pH of the solution is altered from neutral to basic, how is the solubility of
benzoic acid in the water layer affected? Why?
3. What is the function of a separatory funnel?
4. How many grams of sodium hydroxide are required to make 1 liter of a 3M solution
of NaOH? (show calculation)
Remember to include the required information that is described in the Lab Expectations
handout.
Conclusions/Discussion: The key to a good conclusion/discussion is answering why something
happened. Why did the reaction happen, why did you see a color change, and why was adding base
important etc.? Then answer how your reaction took place, including the chemistry, mechanisms, and
techniques involved.
Explanation of Data what does your data mean?
Chemistry, Mechanism, and Techniques explain the techniques used in lab. Examples: For extraction,
why were acids and bases used? For TLC, what is the importance of taking a TLC, how is solubility
involved? If your experiment did not work, you should explain how it should have worked!
Address Question asked in the Procedure Throughout the procedure questions regarding the
techniques are being asked. Make sure to address these questions completely and accurately to get full
points for your conclusion.
Stereochemistry Worksheet Lab

Section #
TA Name
Student Name
Student ID
1. Label (by circling or marking with an asterisk) all the stereoisomers on the following molecules. Note: you
cannot label absolute configuration (R or S) on the given structures since there is no wedge/dash scheme.
HN
B.
A.
H
N
F3C
Cl
Fluoxetine
Cl
HO
Setraline
C.
O
HO
O
F
O
Triamcinolone acetonide
2. Label the following compounds as having R or S configuration around the stereocenter(s).

HO H
1 2
Br
1
H
AcO H
H OH
1
H
H
Br
Br
OH
OTs
2
OH
F
Cl H
3. Give an example of:

a. A compound with two or more stereocenters that is superimposable on its mirror image.
b. A pair of compounds that are chiral but are non-superimposable and non-mirror images.
c. A pair of compounds with 2 or more stereocenters that are non-superimposable and mirror
images.
4. Draw the following compounds

a. (2S,5R)-5-chloro-2-ethylhexanoic acid
b. (1R,2R,4R)-4-ethylcyclohexane-1,2-diol
c. (2S,3R)-3-amino-2-phenylbutanal
d. (1S,2S,3R)-2-fluoro-3-propylcyclobutanol
e. (2E, 7Z)-5-bromo-2,7-nonadiene
5. For the following reactions:

a. Complete the reactions with both possible chiral products.
b. Determine and label the absolute configuration (R or S) of all stereocenters.
c. Label the reaction type and the stereochemical relationship (meso, enantiomer, diastereomer, or
none).
Starting
material
Reagents
Products
type
OsO4
H 2O
D2, Pd/C
MeOH
H 3O
Ph
HCl
Ether
OH
heat
Cl
Br2
CH2Cl
2
d. For reactions 5c through 5f, draw the reaction mechanism showing lone pairs, arrows, bond
making/breaking, etc. for each reaction.
3
Thin Layer Chromatography

Pre-Lab Assignment:
Complete the pre-lab cover page of the Lab-template Handout. Develop your own procedure.
Learning Goals:
Understand the principles and applications of thin layer chromatography.

You will be using TLC throughout the semester. It is important that you thoroughly
understand the concepts of TLC.
Introduction:
Thin layer chromatography (TLC) is a separation technique commonly used to monitor reaction
progress, develop large-scale separation schemes, and identify unknown compounds. TLC plates
consist of a glass, plastic, or metal sheet coated with a thin layer of porous silica gel (SiO2) onto
which a compound is applied (spotted). TLC plates are developed by partially immersing in a
chamber containing a solvent mixture. As the solvent is pulled up the plate by capillary action,
compounds are carried along (migrate or elute) - desorbing and absorbing to the silica gel at
different rates to afford separation. In general polar compounds migrate the least and non-polar
compounds migrate the most in this type of chromatography. Varying the elution solvent polarity
will increase or decrease the degree of compound migration. A more polar solvent will interact
more strongly with polar portions of dissolved molecules, decreasing their availability. This
decreased availability of the polar regions of the molecules decreases the amount of interaction
the molecules can have with the polar silica gel on the TLC plate itself. The result is that polar
solvents tend to make molecules travel further up the plate by decreasing the amount of
interaction (and thus resistance) the plate has with the molecules. The opposite is true of less
polar solvents, which dont interact with the polar portions of molecules, allowing greater
interaction between the molecule and the TLC plate. The compounds separated on the TLC
plates can be made visible by a variety of means including using UV light. Several excellent
websites that give information on TLC are given below:
General theory:
http://en.wikipedia.org/wiki/Chromatography
Specific TLC techniques:
http://orgchem.colorado.edu/hndbksupport/TLC/TLCprocedure.html
http://www.usm.maine.edu/~newton/TANES/TLC.HTML
Journals:
Thin-layer chromatography: The "eyes" of the organic chemist
Hamilton Dickson, Kevin W Kittredge, Arlyne M Sarquis. Journal of Chemical Education.
Easton: Jul 2004. Vol. 81, Iss. 7; p. 1023
What factors affect the separation of substances using thin-layer chromatography?
John J Nash, Jeanne A Meyer, Barbara Everson. Journal of Chemical Education. Easton: Mar
2001. Vol. 78, Iss. 3; p. 364
In this lab you will be given a mixture containing two of the following three compounds.
O
Fluorene
OH
9-Fluorenone
9-Flourenol
You will use TLC to determine your unknowns. An example is shown below:
Before Developing
1 = known compound 1
4 = unknown mixuture
After Developing
unknown is a mixture
of compounds 2 & 3
solvent front
To accomplish this, you will first spot your compounds on to the TLC plate. This technique is
probably the most difficult part of this lab too much product will streak when the plates are
developed and too little will be difficult to visualize. To spot your compounds, you will use
special disposable pipets that dispense between 1 and 5 Ls. After the compounds are spotted
you must allow a few minutes for the spotting solvent to evaporate prior to developing (allowing
the solvent to migrate up the plate) the plates and visualize using UV light. The TLC plates used
in this lab contain a material that fluoresces when exposed to short wave UV light (green).
When a compound that also absorbs UV light at this wavelength is applied to the TLC plate, it
absorbs the light and quenches the background fluorescence, causing it to appear as a dark spot.
You will use hand held UV lights to visualize your TLC plates. You will also determine the
retention factor (Rf) of each known compound by dividing the distance from the origin to each
spot (in millimeters) by the distance from the origin to the solvent front. An example is shown
below
Determining Retention Factor
Note: A properly
labeled TLC Plate has
the solvent front, the
origin, and the dots
labeled. You must
properly label and
tape your TLC plate in
the observations
section of your lab
report for full credit.
solvent f ront
= 60 mm
50 mm =
origin
1
Rf =
distance from origin to red spot = 50 mm

distance from origin to solvent front = 60 mm
= 0.83
Procedure:
Be sure to bring a pencil and metric ruler to lab. Prepare a developing chamber by lining the
inside of a 4 ounce vial with filter paper. What is the purpose of the filter paper? Next, add
enough methylene chloride (the elution solvent) to the vial so that the top of the liquid is about
0.5 cm from the bottom of the vial. Obtain a TLC plate from the hood and, using a pencil, gently
draw a line at about 1 cm from the bottom of the TLC plate (dotted line in the figure above).
Next, divide the line that you have drawn with short perpendicular lines to indicate where
compounds are to be spotted.
Refer to http://orgchem.colorado.edu/hndbksupport/TLC/TLCprocedure.html for pictures of
TLC plates before, during and after development
It is important that the line on the TLC plate is above the solvent surface when it is placed into
the developing chamber.
Label (1-3) three 12x75 disposable test tubes and put them into the test tube rack. To each tube,
add a few crystals of each compound according to the table below. Tube 4, your unknown will
be provided to you and can be found in the hood. Add about 0.5 mL of methylene chloride to
each tube and shake gently to dissolve
Tube 1
fluorene
Tube 2
9-fluorenone
Tube 3
9-fluorenol
Tube 4
unknown
Using the micro pipet, spot the TLC plate with the solutions in the tubes making sure to keep the
numbering correct. Your TA will demonstrate proper spotting technique.
Use a new spotting pipette for each compound to avoid cross contamination. After spotting is
complete, allow the TLC plate to dry completely. How might the results of the TLC plate be
altered if the spots are not dry? Transfer the TLC plate to the developing chamber using forceps.
Make sure that the line on your plate is parallel to the surface of the developing liquid and
leaning against the side of the chamber. Replace the lid on the chamber, but do not tighten it.
Remove the plate when the liquid is 1cm from the top of the plate and mark the solvent front
with a pencil. Once the plate is dry, use the UV light to visualize it. CAUTION: Do not look
into the UV light, because it can damage your eyes. The spots will appear as dark dots and the
plate will glow green. Hold the light over your plate and trace the spots using a pencil.
Generally speaking, which compound, more polar or less polar, travels the furthest up the TLC
plate? Why? Measure the Rf values for each spot, using the method described above.
Post Lab:
Include the material required in the Lab Expectations handout.

Tape a properly labeled TLC plate to the observations section of your lab report.
Determine and list the Rf values for known compounds 1 through 3.
Determine and list the Rf values for your unknown sample: Identify the components of
the unknown mixture.

1. Contrast liquid/liquid extraction and TLC.
2. What are the non-polar and polar phases in TLC?
3. Suppose you were visualizing a TLC plate and all the spots were at the solvent
front. How could you remedy this problem?
4. How could TLC be used to analyze the progress of a chemical reaction?
5. Name and explain two other types of analytical techniques used in organic
chemistry.

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CHEM 345 Organic Chemistry I

Student Learning Outcomes:

graded components weight score

s-block (metals), p-block (non-metals)

An ionic bond is formed between metals

Covalent Bonds are Formed by

Nonpolar covalent bond = bonded atoms are the same

Polar covalent bond = bonded atoms differ in electronegativity

How Many Bonds Does

Bond Polarity Depends on

Polar Covalent Bonds

For example, consider oxygen in methanol shown

Methyl oxonium ion (the acidic form of methanol) is shown below.

Neutral Carbon Forms Four Bonds

if carbon does not form four bonds, it has a charge

A Hydrogen Atom Can Lose or

Neutral Nitrogen Forms Three Bonds

Nitrogen has one lone pair.

Neutral Oxygen Forms Two Bonds

Oxygen has two lone pairs.

Hydrogen and the Halogens

A halogen has three lone pairs.

In organic chemistry it is common to use lines to represent covalent bonds.

Drawing Conventions in Organic Chemistry

Learn to use line/bond drawing convention for Lewis structures

bent line implies -CH2-

Atomic & Molecular Orbitals

The Structure of an Atom

The Distribution of Electrons in an Atom

The first shell is closest to the nucleus.

-Aufbau principle: An electron goes into the atomic orbital with

Reorder such that energy becomes the y-axis

Electrons may be excited from lower to higher energy

What is an Atomic Orbital?

The Lobes of a p Orbital Have

The Three p Orbitals

Molecular Orbitals - Diatomic

Atomic Orbitals Combine

Side-to-Side Overlap of In-Phase

Molecular Geometry & Hybridization

The Bonding in Methane

In Order to Form Four Bonds,

Four Orbitals are Mixed to Form

An sp3 orbital has a large lobe and a small lobe.

The Carbon in Methane is sp3

4 sp3 orbitals = tetrahedron

The Carbon Hydrogen Bond

The Bonding in Ethane

The Bonding in Ethane

this line represents a carbon sp3 to hydrogen 1s

this line represents a carbon sp3 to carbon sp3

Graphically, the molecular orbitals of ethane can be represented as:

The Bonding in Ethane

Molecular Orbitals in Ethene

this line represents a carbon sp2 to hydrogen 1s bond

An sp2 Carbon Has Three sp2 Orbitals

The Carbons in Ethene are sp2

two sp hybrid orbitals

Molecular Orbitals in Ethyne

this line represents a carbon sp to hydrogen 1s bond

The Two sp Orbitals Point in Opposite Directions

The Carbons in Ethyne are sp

Methyl Cation and Methyl Radical are sp2

Methyl Anion is sp3