Note For All 202L Sections - Spring2014

Chem
202L Laboratory Notes
Spring 2014

NOTES and OUTLINES for
ORGANIC CHEMISTRY LABORATORY 202L SECTIONS
Prepared by:
Professor Steven C. Welch

Revised by:
Dr. Lenuta Gonzales
Department of Chemistry and Biochemistry CSUSM

Email: lgonzale@csusm.edu
1
Chem 202L Laboratory Notes
Spring 2014
Table of Contents:
Page
Experiments Schedule
Laboratory Outlines
Laboratory Notebook
Exp. 1
Mass Spectroscopy: Identification of unknown organic

compounds.
12
Exp. 2
Infrared Spectrometry: Identification of unknown organic

compounds.
21
Exp. 3
H-NMR & 13C-NMR Spectrometry: Identification of

unknown organic compounds.
38
Exp. 4
Electrophilic Aromatic Substitution (EAS) - Directing

Effects.
48
Exp. 5
EAS - Friedel-Crafts Alkylation: Synthesis of 1,4-di-tbutyl-2,5-dimethoxy-benzene.
57
Exp. 6
Nucleophilic Addition (NA): Reduction of 4-tbutylcyclohexanone to cis- & trans-4-t-butylcyclohexanol.
63
Exp. 7
NA - Grignard reaction: Synthesis of triphenylmethanol.
66
Exp. 8
Oxidation Reaction: Synthesis of 9-fluorenone.
69
Exp. 9
Substitution Nucleophilic (SN-2) - Williamson Synthesis:

Synthesis of propyl para-tolyl ether
73
Exp. 10
Acyl Nucleophilic Substitution (ANS) - Esterification:

Synthesis of 4-t-butylcyclohexyl acetate
75
Exp. 11
Acyl Nucleophilic Substitution(ANS): Rate of Base-Induced

Hydrolysis of Cyclohexyl Acetate
77
Exp. 12
NA - Aldol Condensation: Synthesis of dibenzylacetone
80
Check out procedure
82
Spring 2014
Experiments Schedule:
Week
of
Experiment
Pre-Lab Reading Assignment

Pages
(Microsc.
Org.Lab, 5e)
1-43
Pages
(Microsc.
Org.Lab, 4e)
Pages
(Lecture:
McMurry 7e)
1-32
Pages
(Lecture:
McMurry 8e)
-
Jan.
27
Check-in, Chapter 1: Introduction,

Chapter 2: Safety, Chapter 3:
Introduction to Microscale Org. Lab.,
Equipment and
Feb. 3
Unknowns: Mass Spectra, Rule 13,

Molecular Formula
Unknowns: IR Spectra
618-628
608 - 617
Ch12
Ch12
539-560
532-553
Ch12
Ch12
Unknowns: 13C- and 1H-NMR Spectra
561-593
554 -584
Ch13
Ch13
Directing Effects in Electrophilic

Aromatic Substitution (EAS), Quiz 1
EAS: Friedel-Crafts: 1,4-di-t-butyl-2,5dimethoxy-benzene, Quiz 2
NA: Reduction: 4-t-butylcyclohexanone
630-631
cis&
trans-4-t-butylcyclohexanol
(NaBH4), Quiz 3
NA: Grignard: triphenylmethanol, Quiz 4
Handout
Handout
580-591
560-571
Handout
Handout
575-580
554-59
Handout &
152-153,
158-163
Handout &
133-135,
139-144
630-631
609-610
Handout &
275-283
Handout &
401-403
Handout &
246-253
Handout &
359-361
355-56; 634638, 734-735

645-647
345-346;
613-617;
623 -625
SN-2: Williamson Ether Synthesis: propyl

para-tolyl ether, Quiz 6
ANS: Esterification: Synthesis of 4-tbutylcyclohexyl acetate, Quiz 7
ANS: Rate of the Base-Induced
Hydrolysis of Cyclohexylacetate, Quiz 8
Handout &
321-326
Handout &
196 - 209
Handout
Handout &
290-295
Handout &
173 - 183
Handout
678-679
655
644, 824-826
837-840,
1036
623; 795 797

809 811;
1064
NA: Aldol Condensation: Synthesis of

dibenzylacetone, Quiz 9
Cleaning & Check out
Handout &
309-317
Handout &
279-286
904-910
877 - 883
Feb.
10
Feb.
17
Feb.
24
Mar. 3
Mar.
10
Mar.
17
Mar
24
Mar.
31
Apr. 7
Apr.
14
Apr.
21
Apr.
28
May.
5
Oxidation (H2CrO4 / acetone): Synthesis

of 9-fluorenone, Quiz 5
Spring break
Spring 2014
Laboratory Outlines
Safety Lecture
Read How to Survive Chemistry Lab (professor and students), the CSUSM Student Safety Training
(students) handout and Chapter 2 Safety (students) in the textbook Microscale Organic Laboratory 5th
Ed. by D. W. Mayo, R. M. Pike & D. C. Forbes.
Pay particular attention to the Reduction of Risks on page 8.
It is not recommended that pregnant women take OChem laboratory.
Study the experiment before you come to lab. Make sure that you understand the chemistry, chemical &
physical properties and well as the MSDS data for all chemicals and solvents to be used.
Policy on Supplies
In order to minimize student laboratory fees the Department of Chemistry requests that you conserve
and recycle certain disposable supplies such as:
1. Pasteur and calibrated pipettes - these can be reused the next lab period if they are only
contaminated with DI water or volatile organic solvent or if they can be readily rinsed with DI
water and a squirt of acetone. If the pipettes are stained or used as filter or chromatography
columns, then just dispose of them in the broken glass receptacle.*
2. Save the IR-cards, corks, rubber stoppers, Al-foil, Al-dishes, rubber tubing, septa, culture tubes
that are clean and in good condition.
*The Broken Glass receptacle is for glass only. No paper or trash is permitted in this container.
Analytical Balances
The Analytical Balances are precision instruments. They are calibrated and leveled. DO NOT MOVE
or DISTURB.
Press ON/OFF to turn the balance on or off. These balances are set for a room with rapid air flow and
vibration; therefore, they are slow to display the weight.
Turn the balance on to weigh an object. After the balance reads 0.0000 g, open the door and place the
object to be weighed on the pan. Close the door and wait until the balance reads the weight (x.xxxx g)
count 5 seconds then read and record the weight.
To tare a container follow the above instructions. When the weight is displayed (x.xxxx g) simply push
the TARE to zero. Remove the container. Insert a substance in to the container then place the filled
container back on the pan. Close the door and read the weight as above. Always weigh samples to 4
places past the decimal (.xxxx).
Automatic Pipettes
If you do not know how to use the pipette then practice loading and then unloading into a graduated
cylinder. Check to see if the correct amount was transferred.
Generalguidelines:
a. Keep automatic pipettes vertical at all times to avoid damage.
b. Do not change the volume of the automatic pipettes.
Spring 2014
c. Tips are designed for single use. They should not be cleaned for reuse as their metrological
characteristics will no longer be reliable. Avoid turning the pipette on its side when there is
liquid in the tip. Liquid might go to the interior of the pipette and contaminate the pipette.
d. Avoid contamination to or from fingers by using the tip ejector and gloves. Pushing the ejector
button all the way down to the second level ejects the disposable tip.
e. Store pipettes in an upright position when not in use. Pipette stands are ideal for this purpose.
Pipettingtechnique:
1. Press the plunger to the first stop.
2. Dip the tip into the solution to a depth of 1 cm, and slowly release the plunger. Wait 1-2 seconds
and withdraw the tip from the liquid, touching against the edge of the reservoir to remove excess
liquid.
1. Dispense the liquid into the receiving vessel by gently pressing the plunger to the first stop and
then press the operating button to the second stop. This action will empty the tip.
2. Remove the tip from the vessel, sliding it up the wall of the vessel.
Ready position
First stop
Second stop
Requirements for Being a Scientist

1. One must be a careful observer. Record all your observations in the laboratory notebook in
ink during an experiment. (White-out is not permitted.)
2. One must make careful and accurate measurements of data. Make careful and accurate
measurements of data and record them in your notebook.
a. The analytical, balances are accurate to 4 places past the decimal (x.xxxx),
b. mps & bps are accurate to 2-3 significant figures (sig figs),
c. Percent yields are accurate to 3 sig figs
d. TLC Rfs are accurate to 2-3 significant figures (sig figs),
e. GC Rts are accurate to 3 sig figs,
f. IR bands are accurate to 3-4 sig figs.
3. One must draw conclusions based upon your observations and data using inductive and
deductive reasoning skills:
a. One must read the reading assignment(s) in the syllabus for the experiment before
coming to lab.
b. You must prepare a complete Data Table in your notebook before coming to lab. You
will not be allowed into the lab without a complete Data Table in your notebook.
c. You must have the assigned homework problems where applicable done before the lab.
Spring 2014
How to Survive Chemistry Lab

1. Always wear safety glasses. YOU MUST HAVE YOUR OWN PAIR.
2. Wearing shorts or dresses are not allowed in the laboratory. Suitable shoes must be worn in the
laboratory at all times. (SANDALS AND OTHER OPEN-TOED SHOES ARE NOT
ALLOWED.)
3. NO EATING, SMOKING, OR DRINKING IN LABORATORIES.
4. Become thoroughly acquainted with the location and use of exits, eye wash/shower station, the sinks
and fire extinguishers. Draw a floor plan of the lab and where these item are on the back inner leaf
of your notebook.
5. All lab equipment must be checked in during the very first lab period. If a student drops the lab,
he/she must check out of the lab with the instructor or Stockroom Personnel immediately. At the end
of the semester each student must check-out of the laboratory. Any glassware broken or lost,
including the key, must be paid for at the Cashiers Office by the end of the semester or transcript
referral and registration/graduation stops will be instituted.
6. If you injure yourself (minor cut or burn) you must notify the instructor immediately. A first aid kit
is at the west end of SCI2-351. The safety shower is operated by pulling the lever. If you get an
irritating substance in your eye go immediately to the eye wash station and wash your eye (s)
thoroughly for 15 minutes and have someone notify your instructor immediately.
7. Once chemicals have been measured DO NOT pour excess chemical back into the original bottles.
Always keep the automatic pipettes vertical. Do not change the volume of an automatic pipet.
Never pipet by mouth, use suction bulbs.
8. Dispose of any chemicals in the proper containers provided by the Stockroom Personnel. Chemical
spills must be cleaned up immediately. A 10% penalty will be accessed for any chemical spill not
cleaned immediately. (Mops, sponges, brooms, etc.... are available in the stockroom for any
mishaps. Please feel free to ask for them.)
9. Perform all flammable/toxic liquid transfers and handle all toxic substances in the fume hood.
10. Broken glassware & dirty pipettes must be disposed of ONLY in the container marked for glass
disposal. Recycle clean Pasteur pipettes by rinsing with DI water then a few drops acetone. Clean
syringes and syringe needles with DI water followed by acetone immediately after use.
11. Material Safety Data Sheets (MSDS) for all chemicals are on the book shelf in SCI 351.
12. The sinks are not to be used as trash cans. PLEASE dispose of all trash properly. DO NOT put
paper trash in the Glass Disposal container.
13. Do not hesitate to comment to a neighbor engaging in an unsafe practice or operation, this includes
not cleaning chemical spills. If necessary, inform your instructor.
14. Do not try to stop a centrifuge with your hand.
15. You must have a complete Data Table and knowledge of the experiment before coming to the lab.
16. There are no dumb questions only dumb mistakes. Please ask for assistance.
Laboratory Grading
The grades for this course are based on an absolute point scale, they are NOT curved. See your syllabus
for details on grading in this class. Your grade will be assigned based upon the grading scheme outlined
below:
-A/A (90%); -B/B/+B (75%); -C/C/+C (60%); D (60%);
F < 50% or cheating, fabrication of data or plagiarism (See the General Catalog)
Please note that to get a C in this class your score has to be more than 65%.
Spring 2014
Glassware kit
Spring 2014
Laboratory Notebook
Tape the following three pages at the very beginning of your notebook
The entrances in the notebook: (Tape this on the first page of the notebook)
1. Date, should appear on the first line in the upper right corner of the first page of each experiment.
2. Experiment #: Title should appear on the second line on the first page of the experimental write-up.
3. Purpose (Write 2-3 sentences on what you are trying to accomplish and how, how the compounds will be
purified, how the identity and purity of the product will be determined. Do not begin a Purpose with the
phrase The purpose of this lab is to. ..).
4. Chemical equation and the reaction mechanism.
5. Procedure (tape the experimental procedure from your handout). Include any modifications to procedure if
different from handout.
6. Data Table of all reagents, solvents and products prepared in Word or Excel according to the example
presented in the first lab class. (see the ex. on next page)
(Prepare the data table using one of the following sites: http://hazard.com/msds/,
http://www.chemexper.com/, http://www.sigmaaldrich.com/united-states.html.
7. Calculation of the theoretical yield, place it just under the Data Table and add the theoretical yield in the
right place in Data Table.
8. Health Hazard Data & Spill and Disposal Procedure
9. Homework/answers All the above sections will be filled before coming in the lab.(Prelab)
10. Draw of the experimental set-up or the flow chart of procedures.

11. Observations, Calculations & Result Summary: this section will be filled during the experiment. All your
data should be recorded permanently when they are collected. Remember if it is not written down, it was not
done. Record and briefly list your data (What you measured: analytical amounts, bp, mp, spectral data,
yields, etc), calculations (Rfs, Rts, %yields, etc) and observations (What you see during the experimental
procedure: reaction changes, color, appearance, estimated relative size of TLC spots, IR data, etc.). Show
your calculations of yields and Rfs. Tape your annotated and interpreted TLC plates, GC traces and IR
spectra (with the interpretations written on the spectra) in the notebook. Report the results in a Table.
12. Discussion & Conclusions: this section will be prepared in WORD after the lab. Write a brief (1 page or
less) summary using complete sentences in scientific style. Include a written description of the results of the
experiment (What you measure: analytical amounts, bp, mp, spectral data, yields, etc.), calculations (Rfs,
Rts, %yields, etc) and observations (What you saw during the experimental procedure: reaction changes,
color, appearance, estimated relative size of the TLC spots, IR, etc.) and interpretation of the data. The
purpose of the Discussion is to analyze the observed facts shown by the Results. The Discussion section
compares your results to literature values or to the results that might be expected from theoretical models. Do
not use personal pronouns. Take your time and put some thought into your discussions and conclusions.
13. References: (the references are presented in the used order and please follow the given example to post them.
a) Mayo, D.W., Pike, R.M., Forbes, D.C., Microscale Organic Laboratory, 5th Ed., John Wiley & Sons, Inc.,
2011, pg. 71-77, 148.
b) Welch, S., L. Gonzales Notes and Outlines for Organic Chemistry Laboratory 202L; CSUSM, 2013.
c) www.sigmaaldrich.com,
d) www.chemexper.com
Spring 2014
Example of Data Table (Tape this on the second page of the notebook)
Compound
MF
MW
mg/mol
Amount
mmol
1-octene
EtOH
water
0.2M chloroplatinic acid
1.0M sodium
borohydride
6M hydrochloric acid
pentane
Sodium sulfate
C8H16
C2H6O
H2O
H2PtCl6
112.2
46.
0.770
517.9
120 L
1.25 mL
1.0 mL
50.0 L
NaBH4
37.8
1.25 L
HCl
C5H12
Na2SO 4
36.5
1.00 L
0.720
1.00
m.p.
0
C
121
78.5
100
0.626
0.55 g
500 mg
10%silver nitrate/ silica AgNO3/

gel
SiO2
C8H18
Octane
yield)
d
b.p.
0
mg/L C
114.2
(theoretical
0.770
0.700
125.7
87.9 mg =
126 L
Theoretical yield goes here!
Example of Calculation of Theoretical and Percent Yield

CH3(CH2)5CH
CH2
H2PtCl6 / NaBH4/ H3O
CH3(CH2)5CH2CH3
C8H16
C8H18
MW = 112.2 mg/mmol
MW = 114.2 mg/mmol
mmols octane = mmols octene
120 L x 0.72 mg/L = 86.4 mg octane;

86.4 mg / 112.2 mg/mmol = 0.770 mmol octane
theoretical yield = 0.770 mmol x 114.2 mg/mmol x = 87.9 mg octane
theoretical volume (for liquids only) = 87.9 mg/0.700 mg / L = 126 L octane
% yield
measured mass ( mg )
x 100
87 .9 mg
9
Spring 2014
Example of a Typical Experimental Summary and Conclusions

(Tape this on the third page of the note book)
In this lab, the purpose was to synthesize n- octane through the use of a catalytic hydrogenation reaction involving 1octene. Bubbles of H2 gas were observed as the 6M NaBH4 solution (amount here) was added to H2PtCl6
/ EtOH (amount here) with rapid stirring. The initial solution in the vial was a black-ink color but as the
reaction progressed the balloon slowly inflated with H2 as the clear solution turned gray-black suspension. The
reaction was conducted at ~ 50 0C for 45 minutes. Afterwards, pentene was added into the solution to allow the collection and
separation of the organic layer from the water. .During the extraction process the upper pentane layer was clear
and colorless and the bottom aqueous layer was a gray-black suspension. After carefully concentrating
the dried pentane layer ~ 125 L, 80.2 mg (91.2% yield) of clear colorless octane was obtained. The
purity of the product (1-octane) was analyzed by b.p. and GC and the structure by IR. The b.p. of octane
had to be repeated 3 times on the same sample to achieve a b.p. of 124 o C. Comparison with the b.p.
found in the literature (see data table) the value measured is lower with ~ 1. 7oC. The GC analysis shows
a small peak for 1-octene at 2.48 min (~ 5.5%) and a large peak for octane at 5.10min (94.5%), that
proves that the product was not completely pure. 1-Octene appears first on the GC chromatogram since
its boiling point is lower than 1-octane. The IR spectrum for octane displayed bands at 2820 2960 cm 1
(sp 3 C H stretch), 1450 cm -1 (CH2 bending) and 1380 cm -1 (CH3bending). The characteristic peak
for C=C bond was practically missing, this being an indication of the fact that the double bond from 1octene was successfully hydrogenated. The overall yield for the performed experiment was high, but
some errors were possibly due to measurement in automatic pipettes or syringes. This can be avoided in
further lab experiments with careful measurements of reagents.
(* This section could be written for the experiment: Synthesis of octane from 1-octene)
The following were applicable in writing the above section:

NO experimental procedure included.
NO personal pronouns, like for ex.: I extract, I obtained etc...
NO equations or calculations.
NO sentence started with a number.
Use short sentences to report the observations and results.
Observations during the experiment: reaction changes, gas evolution, color changes, precipitate, loss
of solvent, spillage, color of the liquid or solid product, accidental loss of reactant or product, etc.
Record and report the measured: b.p., m.p., Rfs or TLC spots, relative size of TLC spots, GC peak
tRs in minutes (area).
Describe the IR spectrum that was recorded in detail giving the band positions in cm-1 (and
functional group interpretation)
Reported results have to be calculated values to 3 significant figures. Ex.: report the yield or percent
recovery in the following way: XX.X mg (ZZ.Z%), report the IR data in the following way: 3080
-1
cm (sp2 C-H).
Your interpretation of the data and observations.
10
Spring 2014
Identification of Unknown Structures by Combined

Spectroscopic Techniques
Week 1:
a) Mass spectra including accurate M+1 & M+2 data for 2 unknowns provided.
b) The molecular formulas and degrees of unsaturation for each unknown are to be
calculated using the "Rule of 13".
c) Most of the fragmentation bands for each unknown are to be interpreted using the Tables
provided. The "Rule 13" calculation results and the interpretation of the fragmentation
bands for each unknown are submitted for grading.
d) Reference: read Lecture Chapter 12 & pag. 618-628 in the lab textbook (20pts)
Week 2:
a) Each student receives IR spectra of the 2 unknowns.
b) Using the molecular formula determined by MS and the IR absorption bands table
identify the functional groups contained by each unknown. Remember to note functional
groups that are absent (especially the C=O). Remember to account for degree of unsaturation
if possible. You can often begin making simple substructures at this point (for example, C=O,
COH, etc.). The IR interpretations for each unknown are submitted for grading.
c) Reference: read Lecture: Chapter 12 & pag. 546-560 in the lab textbook . (20pts)
Week 3:
a) 13CNMR and 1HNMR for 2 unknown compounds are provided.
b) [Off-resonance decoupling or proton decoupling] allows the identification of different types
of carbons based on chemical environments around carbons. This may or may not add up to
the number of carbons since some carbons may be chemically identical. Spin coupling or
DEPT C-NMR allows to determine # of Hs on each carbon.
c) Identify types of Hs based on chemical environments. Coupling gives information about
connections. This may be where you begin piecing together substructures into the full
structure.
a) Interpretation of the 13CNMR and 1HNMR data for each unknown along with a proposed
structure of each are submitted for grading.
b) Reference: read Lecture Chapter 13 & pag. 561-593 in the lab textbook . (20pts)
c) Turn in all recorded data and interpretations on the data sheets provided as well as the
solutions to the structures. (20pts)
Please do not write on the spectra. Turn in the spectra with your data sheets.
11
Spring 2014
Lab.#1:
Structure Determination: Mass Spectroscopy

Review:
Mass Spectra (MS) M.+ = MW
Base peak = most prevalent and stable radical-cation or carbocation fragment
Hydrocarbons usually fragment to give the largest radical R
Rule of 13: M.+ /13 = n + r MF = CnH(n+r)
Rule of 13 substitutions (C=12H, O=CH4, N=CH2, etc.)
Nitrogen rule: M.+ is odd for an odd number of Ns
Fragmentations
Mass Spectroscopy
Bond cleavage:
R R'
eionization
organic
compound
2e-
Molecular ion:
[ R R']
radical cation
(molecular ion)
e-
molecule
bonding or
nonbonding
electrons
fragmentation
larger alkyl radical

(fragment lost)
R'
most prevalent or
most stable
carbocation will be
the base peak
2e -
molecular ion
(radical cation)
m/z = molecular weight (MW )
M + , usually gives the
molecular weight (MW )
very accurately. It appears
as the peak at highest mass
at the extreme right.
12
Spring 2014
Exam ple M S :
100
Relative abundance (%)
base peak
(BP)
M
500 am u
(atom ic m ass units)
Atom ic w eight (m / z)
M
M + 1
M +2
M + 1 & M + 2 are from the

naturally occuring isotopes
High resolution m ass spectrom etry can
give the m olecular form ula from the M +1/M
ratio of intensities and the exact m ass to 6
to 7 significant figures.
Fragmentation Rules for Mass Spectroscopy

1. Cleavage is favored at alkyl-substituted carbons; the more substituted, the more likely is the
cleavage. This results from the stability of carbocations: 3o > 2o ~ allyl ~ benzyl > 1o > CH3+ .
Generally, the largest alkyl group (R) at a branch is eliminated most readily as a radical:
H 3C
CH 3
H 3C
e-
C
H 3C
CH 3
CH 3
2. Double and triple bonds favor allylic (or propargylic) cleavage and give resonance-stabilized allylic
(or propargylic) carbocations:
e-
R CH2 HC CH2
HC HC CH2
m/z = 41 allylic or 39 propargylic
3. Alkyl-substituted aromatic compounds undergo cleavage to form resonance-stabilized benzyl cations

which rearrange to tropylium ions:
13
Spring 2014
CH
CH2
CH2 R
rearrange
-R
m/z = 91
4. Carbon-carbon bonds next to a heteroatom undergo alpha cleavage:
R'
CH 2 X
- R'
CH 2 X
X = N, O or S
CH 2NH 2 m/z = 30
m/z = 31
CH 2OH
CH 2OCH 3 m/z = 45
m/z = 47
CH 2SH
CH 2SCH 3 m/z=61
O
R'
- R'
R
R
R
R
R
C
=
=
=
=
H
CH 3
NH 2
C6H 5
m/z = 29
m/z = 43
m/z = 44
m/z = 105
5. Carbonyl compounds with a g-hydrogen atom fragment by the McLafferty Rearrangement:
H
O
H 2C
X=H
X = CH3
X = OH
X = OCH3
X = NH2
X
m/z = 43
m/z = 58
m/z = 60
m/z = 74
m/z = 59
14
Spring 2014
Protocol for Interpreting the Spectra

A. Read the molecular ion peak , M+, the experimental values for M+1 and M+2 on the MS spectrum
provided for each unknown. List M+, M+1 & M+2 values on the chart provided.
B. Determine the molecular: apply Rule of 13 and appropriate substitution in order to much the M+1
and M+2 calculated values with the experimental values of M+1 and M+2 you list on the chart.
C. Calculate degree of unsaturation (U) for the molecular formula of the unknown you have found.
Consider the general molecular formula: CaHbOcNdXe :
Degree of Unsaturati on (U )
[( 2a 2) (b d e)]
2
(Formula 1)
D. Calculate the four decimal digits for the molecular mass and recorded on the chart
E. Identify the Base peak (BP) and some of the representative fragments on the mass spectrum and
propose a structure for each fragment using the tables provided below.
F. To do so, subtract the mass of each of the major intensity fragment observed (R+) to the left of the
M + from the M + mass to determine the mass of the common fragments lost (R.).
G. Determine the mass of the lost fragments (R) to form the observed fragments (R+)you analyzed and
propose structures for each of the lost fragments using the tables below .
1) an odd numbered M+ = MW = an odd number of N atoms
2) for compounds containing 1 Cl, the M+2 = 1/3 M +
3) for compounds containing 1 Br, the M+2 = 0.98 M +
M+ - M
M+ -1
M+ - 15
M+ - 17
M+ - 18
M+ - 26
M+ - 28
M+ - 29
M+ - 30
M+ - 31
M+ - 32
M+ - 33
M+ - 35
M+ - 41
M+ - 42
Fragment lost
-H
-CH3
-OH
-H2O or NH4
C2H2 or -CN
-CO or CH2=CH2
-C2H5 or -CHO
-CH2O or -CH2NH2
-OCH3 or -CH2OH or CH3NH2
-CH2O
-CH3 and H2O
-Cl
-C3H5 or CH2=CHCH2-CH2=C=O or -C3H6
M+ - M
M+ - 43
M+ - 44
M+ - 45
M+ - 46
M+ - 54
M+ - 57
M+ - 58
M+ - 59
M+ - 69
M+ - 70
M+ - 71
M+ - 73
M+ - 77
M+ - 79
Common Fragments lost

-C3H7 or -CH3C=O
-CO2 or C2H4O or C3H8
-C2H5 O or -CO2H or C2H7N or C4H7
-C2H5 OH
-CH2=CHCH=CH2
-C4H9 or -C3H5O
-C4H10 or -C3H6O
-C3H7O or C2H3O2
-C5H9
-C5H10
-C3H5O2
-CH3CH2OC=O or -C4H9O
-C6H5
-Br
15

m/z
Spring 2014
Common Fragments Observed
m/z
Common Fragments Observed
107
C6H5CH2O
61
105
93
C6H5C=O+, CH3C7H6+ (tropylium)

C7H9+ (terpenes)
60
59
94
91
88
85
84
C6H5OH+
C6H5CH2+
CH2CO2C2H5/H+ (ethyl ester)
C5H9O+
C5H8O+
58
57
55
53
47
79
Br+, C5H3O+, C5H7+ (from C6H5CH2+)
45
77
74
C6H5+
CH2CO2CH3/H+ (methyl ester)
44
43
71
70
69
67
C5H11+ , C4H7O+
C5H10O+
CH3CH=CHC=O or C5H9+
C5H7+ or C4H3O+
41
39
35
31
66
C5H6+ (cyclopentadiene from benzene

disintegration)
C5H5+
30
CH3CO2H2+ (acetate ester),

CH3SCH2+, CH3CH2S+
CH2CO2H2+ (carboxylic acid)
CO2CH3+ (methyl ester), CH2OC2H5+
(ethyl ester), CH2CONH2+ (primary
amide)
CH3COCH2/H+ (methyl ketone)
C4H9+,CH3CH2C=O+ (ethyl ketone)
C4H7+, C3H3O+
C4H5+ = CH3C3H2+
CH2SH+ (primary thiol),
SCH3+(methyl sulfide)
CO2H+ (carboxylic acid), CH3OCH2+
(methyl ester), CH3CH=OH+ (ethyl
ether)
CH2=CHOH+ (aldehyde), CO2
C3H7+,CH3C=O+ (methyl ketone or
acetate group), CH2=CHO+ (aldehyde)
C3H5+,CH2CHCH2+ (alkene),
C3H3+
Cl+
CH2OH+ (primary alcohol), OCH3 +
(methyl ether)
CH2NH2+ (primary amine)
29
CHO+, CH3CH2+
65
16
Spring 2014
Unk # _______
MW =
%M+1
%M+2 Mx10-3
Experimental
MW/13 =
n+r
n=
CnHn+r
r=
U (from
formula 1)
U=
%M+1 = 1.1n %M + 1 =
%M+2 = 0.006n2 + 0.2 (#O) + 4.4 (#S) + 32.5 (#Cl) + 98 (#Br)

M = (n + r) (7.825 x 10-3)
M =
%M+2 =
Accurate Mass = MW + M
MW + M =
Element
C
H12
N
O
S
F
Cl
Br(79)
C/H
equiv
H12
C
CH2
CH4
C2H8
CH7
C2H11
C6H7
(-) %(M+1)
(-) (M)x10-3
-1.1
1.1
0.7
1.1
1.4
1.1
2.2
6.6
93.90
-93.90
12.58
36.38
90.25
56.37
117.22
136.45
17
Spring 2014
Unk # _______
MW =
%M+1
%M+2 Mx10-3
Experimental
MW/13 =
n+r
n=
CnHn+r
r=
U from
formula 1
U=
%M + 1 =
%M+1 = 1.1n
%M+2 = 0.006n2 + 0.2 (#O) + 4.4 (#S) + 32.5 (#Cl) + 98 (#Br)

M = (n + r) (7.825 x 10-3)
M =
%M+2 =
Accurate Mass = MW + M
MW + M =
Element
C/H equiv
C
H12
N
O
S
F
Cl
Br(79)
H12
C
CH2
CH4
C2H8
CH7
C2H11
C6H7
(-) %(M+1)
-1.1
1.1
0.7
1.1
1.4
1.1
2.2
6.6
(-) (M)x10-3
93.90
-93.90
12.58
36.38
90.25
56.37
117.22
136.45
18
Spring 2014
Unk # _______
Name__________________________________
Mass Spectral Interpretation

Mass (M)
M+-M
(mass of
LF)
(Indicate which peak is the base peak (BP))
Possible structure or
formula of lost
fragment (LF)
_____M+
formula of observed
fragment (OF)
______________________
1._____
_______
_______
______________________
2._____
_______
_______
______________________
3.____
_______
_______
______________________
4._____
_______
_______
______________________
5._____
_______
_______
______________________
6._____
_______
_______
______________________
7.____
_______
_______
______________________
8._____
_______
_______
______________________
IR Interpretation
Absorption wavelength
1. _________
Functional group or
structural characteristic
_______________________
2. _________
_______________________
3. _________
_______________________
4. _________
_______________________
5. _________
_______________________
6. _________
_______________________
7. _________
_______________________
8. _________
_______________________
19
Spring 2014
Unk # _______
Name__________________________________
Mass Spectral Interpretation

Mass (M)
M+-M
(mass of
LF)
(Indicate the base peak (BP))
formula of lost
fragment (LF)
_____M+
formula of observed
fragment (OF)
______________________
1._____
_______
_______
______________________
2._____
_______
_______
______________________
3.____
_______
_______
______________________
4._____
_______
_______
______________________
5._____
_______
_______
______________________
6._____
_______
_______
______________________
7.____
_______
_______
______________________
8._____
_______
_______
______________________
IR Interpretation
Absorption wavelength
1. _________
Functional group or
structural characteristic
_______________________
2. _________
_______________________
3. _________
_______________________
4. _________
_______________________
5. _________
_______________________
6. _________
_______________________
7. _________
_______________________
8. _________
_______________________
20
Spring 2014
Lab#2:
Infrared Spectroscopy
Review:
IR = functional groups analysis
1. H-stretch: 4000 2500 cm-1: O-H, N-H, C-H, S-H
2. Triple bond stretch: 2400 2100 cm-1: C C, C N
3. Double bond stretch: 1850 1470 cm-1: C=O, C=N, C=C
4. Finger print:
a. 1470-650 cm-1
b. C-C, C-N, C-O stretch
c. C-H, O-H bend
IR radiation (4000-650 cm-1) when absorbed by an organic molecule, causes specific movements of the
atoms in a molecule (molecular vibrations), such as stretching and bending of bonds between groups of
atoms.
Some of these vibrational bands are functional group specific.
Infrared spectroscopy is a method of functional group analysis.
Most functional groups absorb at about the same energy and intensity, independent of the
molecule they are in.
Characteristic higher energy IR absorptions (1500 to 4000 cm-1) can be used to confirm the
presence of a functional group in a molecule.
An infrared spectrum can be divided into four regions:
1. Hydrogen stretching: 4000 2500 cm-1: O-H, N-H, C-H, S-H
2. Triple bond stretching: 2400 2100 cm-1: CC, C N
3. Double bond stretching: 1850 1470 cm-1: C=O, C=N, C=C
4. Finger print region: 1470-650 cm-1
C-H, O-H bending
C-C, C-N, C-O stretching
Vibrations in this region are often complex and hard to assign to a specific functional group
of the molecule.
a given molecule has a DISTINCT pattern in this region (therefore reason for being called
fingerprint region) due to the vibrational motion of the whole molecule.
21
Spring 2014
InfraredAbsorptionBands(5cm1)(Tapethese2pagesattheendofyournotebook)
1
FunctionalGroup
Bandcm
Alkanes
2960 (stretch), 1380 (bend)
(C-H) from CH3-
2850 (stretch), 1470 (bend)
(C-H) from -CH2-
1380 (d)
(CH3)2CH- or (CH3)3C
Alkenes
3080 (stretch)
=CH2 ; (Csp2 H terminal)
3020 (stretch)
1645, 990 & 910
=CHR-CH=CH2 ; (C=C terminal monosubstituted)
1655, 890
R2C=CH2
1660, 675-730 variable

1675, 970
1670, 790-840 variable
R-CH=CH-R ; (C=C cis)

R-CH=CH-R; (C=C trans)
R2C=CHR (C=C terminal tri-substituted)
Alkynes & Other Triple Bonds

3300
Acetylene, -CC-H (terminal alkyne)
Terminal position: 2100-2140
-CC-H
Internal: 2190-2260
RCC-R
2210-2260
Nitrile, RCN or ArCN
2349.3
Carbon dioxide, O=C=O
Aromatics
3030
Ar-H (Csp2-H from aromatic)
1580-1600
Ar-ring C=C
1450-1500
Ar-ring C=C
750 & 700 (2 strong bands)
Mono-substituted phenyl ring
740 (1 band)
Ortho-di-substituted ring
860, 775 & 700 (3 strong bands)
Meta-di-substituted ring
810-840 1 band
Para-di-substituted ring
Alcohols & Phenols
1050-1085
p-OH (C-O)
11085-1125
s-OH (C-O)
1125-1205
t-OH (C-O)
1200
Ar-OH
3200-3400
O-H hydrogen bonded
Ethers
1050-1150
Ethers, aliphatic and ring C-O-C
1200-1275
Aromatic and vinyl =C-O-C
Nitro Groups
Ar-NO2
1527, 1348
22
Spring 2014
Amines
~3500, & 3400 2 bands
p-amine R-NH2; ArNH2
3310-3350
3450
1030-1230 (bend)
s-amine RNHR
ArNHR
R-NH2
250-1360 (bend)
1180-1280 (bend)
ArNHR
ArN-R2
1180
1240
Carbonyl Groups
RCOR, ketone C=O
CCOC
C=CCOR
ArCOR ; C=O
ArCOR
Cyclopropyl-COR
Cycloheptanone and larger ring
cyclohexanone
cyclopentanone
Aldehyde C-H
-HC=O
C=CH-C=O
ArCH=O
RCO2H O-H
C=O (monomer)
C=O (dimer)
C=CCOOH and
ArCOOH
RCOOR, ester C=O
RCOOR
RCOOR
RCOOR
HCOOR C-O
CH3COOR C-O
1190
1165
RCOOR C-O
RCOCCH3 C-O
1720
1720
3500, 3400 2 bands
C=CCOOR
ArCOOR aromatic ester
CONH2 amide, primary N-H
1650
CONH2 amide, primary (N-H)
3300
1640-1680
CONHR N-H amide, secondary (N-H)

CONHR secondary & tertiary amides
1715
1100-1230 1-2 bands
1675
1690
1200-1300 1-2 bands
1695
1705
1715
1745
2720-2820
1725
1685
1700
2500-3200
1760
1710
1720 (monomer)
1690 (dimer)
1735
1165-1300 1 band
1050-1150 1 band
1100-1230 1 band
23
Spring 2014
Example of Interpreted IR Spectra

1. Alkane and alkanes
24
Spring 2014
2. Alkenes
25
Spring 2014
3. Alkynes and Nitriles
26
Spring 2014
4. Aromatics
27
Spring 2014
28
Spring 2014
5. Alcohols and Phenols
29
Spring 2014
6. Ethers
30
Spring 2014
7. Aldehyde and Ketones
31
Spring 2014
32
Spring 2014
8. Carboxylic Acids
33
Spring 2014
9. Esters
34
Spring 2014
10. Amides
35
Spring 2014
11. Amines
36
Spring 2014
12. Nitro-compounds

37
Spring 2014
Lab.#3:
Structure Determination: 13C - & 1H NMR
Review:
13
CNMR Carbon-13 Nuclear Magnetic Resonance
= ppm chemical shift in ppm
downfield from TMS
off-resonance spectra
a. singlet, (C)
b. doublet, d (CH)
c. triplet, t (CH2)
d. quartet, q (CH3)
Decoupled spectra all are singlets for all nonequivalent Cs
DEPT-90 spectrum shows only CH carbons.
DEPT-135 spectrum shows CH and CH3 carbons as positive signals and CH2 carbons as
negative signals.
HNMR - Proton Nuclear Magnetic Resonance = ppm chemical shift in ppm downfield from tMS
Integration of NMR peaks: Area = number of protons
Spin-Spin Splitting: J = coupling constant
N+1 Rule: s, d, t, q

13C Nuclear Magnetic Resonance
13
C spectra are usually collected with the 1H-13C coupling turned off (broad band decoupled). In the
proton decoupled spectrum all the nonequivalent 13C resonances appear as singlets (single sharp
resonance lines). The number of NMR absorptions (lines) gives the number of nonequivalent carbon
atoms.
Spin Coupling and DEPT 13C-NMR (Distortionless Enhancement by Polarization Transfer) is a
modern 13C-NMR technique that allows you to determine the number of hydrogens attached to each
carbon.
1H-13C Spin Coupling 13C-NMR allow you to tell how many hydrogens are attached to each 13C
nuclei, since 13C nuclei are split only by the protons attached directly to them (1H-13C spin-spin
coupling) according to (N + 1) Rule: a carbon with N number of protons gives a signal with (N + 1)
peaks, where N = number of protons attached to the carbon atom. DEPT 13C-NMR tells what type
of carbons you have in a molecule (i.e., primary, secondary tertiary, or quaternary carbon)
s = C (small peak in the decoupled 13C-NMR)
d = CH (DEPT-90 they appear by themselves as (+) signals & DEPT-135 appear along CH3 as
(+) signals )
t = CH2 (DEPT-135 () signals)
q = CH3 (DEPT-135 (+) signals)
38
Spring 2014
ra tio
s in g le t
m e t h in e
CH
d o u b le t
m e t h y le n e
CH
m e th y l
CH
q u a te rn a ry
13
1 :1
1 :2 :1
t r ip le t
1 :3 :3 :1
d o u b le t
C NMR Chemical Shifts Correlation

sp
sp
sp
C H
-C H
-C H =C
C =O
200ppm
13
100
0 .0 p p m
C h e m ic a l S h if t t e lls u s a b o u t t h e t y p e o f b o n d s .
C NMR Chemical Shifts Data
8-30
-CH3
15-55
-CH220-60
CH
30-65
C-N
40-80
C-O
65-85
CC
100-150
C=C
140-170
C=C-C=O
120-135
C=C-C=O
100-160
115-125
150-220
150-175
160-175
165-185
195-220
77.5
128.5
Ar-ring (C)
RCN
C=O
RCONH2
RCO2R
RCO2H
RCHO or RCOR
CHCl3
C6H6
Number of non-equivalent carbon atoms in disubstituted benzene rings:

X
Y
Y
X
3
39
Spring 2014
Proton Nuclear Magnetic Resonance: 1HNMR

Information provided:
A. Functionality
chemical shift
tells the type of hydrogen
Via position on x-axis
B. Presence of symmetry
via the # signals
C. Number of protons of each type per signal
Integration
D. Number of neighboring protons per signal
via the splitting patterns
N+1 rule, where N= number of protons on neighboring carbons
Peaks Integration
Not only does each different type of hydrogen give adistinct peak in the NMR spectrum, but we can also
tell the relative numbers of each type of hydrogen by a process called integration.
Integration = determination of the area under a peak.
The area under a peak is proportional to the number of hydrogens that generated the peak. This
information is used to deduce the structure.
For narrow peaks, the heights are the same as the areas and can be measured with a ruler.
40
Spring 2014
A r e a In te r p r e ta tio n :
(3 H )
C H 3-
m e th y l g ro u p
(6 H )
(C H 3 )2 -
2 m e th y l g ro u p s b o n d e d to th e s a m e c a rb o n
(2 H )
-C H 2 -
m e t h y le n e g r o u p o r 2 e q u i v a l e n t C H m e t h i n e g r o u p s
(1 H )
CH
m e th in e g ro u p o r a n O H g ro u p
(9 H )
(C H 3 )3 C -
t-b u ty l g ro u p
(5 H )
C 6H 5- o r P h
p h e n y l g ro u p
(4 H )
1 , 4 - s u b s t i t u t e d b e n z e n e r in g
Spin-Spin Splitting in 1H NMR Spectra: (N+1) Rule

The signal of a proton or group of equivalent protons can split into multiple peaks called a multiplet. In
general, protons signals are only split by neighbors (adjacent atoms), not by roommates (same
atom), unless the roommate is VERY different. (i.e. examine CH3-CH=CH2)
Spin-spin splitting (coupling) of NMR signals, has a coupling constant, Jab, tells u about the environment
of those protons with respect to protons on adjacent carbon atoms. This is called the (N+1) Rule:
Hb
Ha
C
C
Hb
N = num ber of
e q u iv a le n t (H b )
h yd ro g e n s o n
a d ja c e n t
c a r b o n a to m s
0
1
2
3
(N + 1 ) ,
n u m b e r o f p e a k s fo r
N M R s ig n a l H a
ra tio
1 ( s in g le t)
2 (d o u b le t)
1 :1
3 ( trip le t)
1 :2 :1
4 ( q u rte t)
1 :3 :3 :1
41
Spring 2014
In alcohols (R-CH2-OH) coupling between the O-H hydrogen and those on adjacent carbon atoms is
usually not seen. In alcohols coupling between the O-H hydrogen and those on adjacent carbon atoms is
usually not seen. The exchange happens so quickly that the C-H group sees many different hydrogens
on the O-H during the time the spectrum is being determined (average spin = 0).
In ultrapure alcohols, however, coupling will sometimes be seen.

42
Spring 2014
Proton nuclear magnetic resonance: 1H-NMR

1.5 -CH1. -CH 2 0. CH 3 -
up field (shielded)
RC
OH
RC=O
chemical
shift
RCH=O
9.5
10 ppm
Ar-H
7.2
C CH
5.1
CH
2
0.0ppm
All H-NMR spectrum can be solved with this table
TM S
Me4Si
internal
standard
RCH 2 Cl 3.4
RCH 2 Br 3.
RCH 2 Cl 3.
43
Spring 2014
Coupling of Nuclear Magnetic Resonance Signals

Decoupled 13C-NMR (N+1) Rule (DEPT)
s = C (small peaks in the decoupled 13C-NMR)

d = CH (DEPT-90 & 135, + signals)
t = CH2 (DEPT-135, signals)
q = CH3 (DEPT-135, + signals)
H-NMR (N+1) Rule
s, CH3-C (no adjacent protons)

d, CH3-CH
t, CH3-CH2
q, CH2-CH3
h = heptet, CH(CH3)2
The 1H-NMR data in the Chemical Shift Tables are generally 0.2
A
Negative charge at o, p-positions

causes 1H & 13C absorptions to
move:
O
Positive charge at o, p-positions
causes 1H & 13 C absorptions to
move:
CH
C O
CH 2 C
C O
Positive charge at the -position

causes 1H & 13 C absorptions to
move:
H NMR Chemical Shifts Data

Methyl
Methylene
Methine
0.9
CH3-C
1.3
-C-CH2-C
1.5
C-CH-C
1.1
C H3-C-C=C
1.5
cyclic
2.2
(bridgehead)
1.4
C H3-C-O
1.7
-C-C H2-C-C=C
2.0
-C-CH-C-O
1.6
C H3-C=C
1.9
-C-C H2-C-O
3.0
-CH-Ar
2.3
C H3-Ar
2.3
-C-C H2-C=C
2.7
-C-CH-CO-R
2.2
C H3-CO-R
2.7
-C-C H2-Ar
3.7
-C-CH-O-R
2.6
C H3-CO-Ar
2.4
-C-C H2-CO-R
3.9
-C-CH-O-H
44
Spring 2014
2.0
C H3-CO-O-R
2.2
-C-C H2-CO-O-R
4.8
-C-CH-O-CO-R
2.4
C H3-CO-O-Ar
3.4
-C-C H2-O-R
2.8
-C-CH-N
2.0
C H3-CO-N-R
3.6
-C-C H2-O-H
0.7
(-CHCH2CH2)
3.3
C H3-O-R
4.3
-C-C H2-O-Ar
3.1
(CHCH2O)
3.8
C H3-O-Ar
4.1
-C-C H2-O-CO-R
5.1
-C=CH
3.7
C H3-O-CO-R
2.5
-C-C H2-N
5.9
-C=CHC=O
2.3
C H3-N
2.4
-C-C H2-S
6.8
-CH=CC=O
3.3
C H3-N+
2.4
-C-C H2-C=C-CO
7-9
Ar-H
2.1
C H3-S
2.4
-C=C(C H2)-CO
2.6
R-CCH
2.0
C H3-C=C-CO
0.3
(C H2)3
5.3
C-CHCl2
1.8
-C=C(C H3)-CO
2.6
(OC H2CH2)
7.27
CHCl3
2.34
C H3-Ph toluene
2.5-4.0
C-C H2X; X = Cl, Br
11-12
-COOH
2.4
-C=C(C H3)-CO
5.3
-C=C H2
2.5-5
R-OH variable, pH & conc
4.6
exocyclic C=C H2
3-8
Ar-OH
1.44
C6H12 cyclohexane
9.3-9.9
R-CHO
9.3-10
Ar-CHO
Spin-spin coupling constants, J

Group
J (Hz)
CH-CH
CH2 (sp3)
CH-C-CH (W)
=CH2 (sp2)
CH=CH cis
CH=CH trans
C=CHCH
CH=C-CH
-C=CH-CH=CCH-CHO
CH-CC-H
Ar-H ortho
Ar-H meta
Ar-H para
-CH2CH3
CH-(CH3) 2
2-9
12 -15
0-1
0 3.5
6-12
12-18
4 - 10
0.5-2
10 13
1-3
2-3
6 - 10
1-3
0-1
6.7-7.2
5.7-6.8
45
Spring 2014
1H NMR Interpretation
ppm
# of H Multiplicity
Structural characteristic
1. _____
_____
_____
_____
____________________________________
2. _____
_____
_____
_____
____________________________________
3. _____
_____
_____
_____
____________________________________
4. _____
_____
_____
_____
____________________________________
5. _____
_____
_____
_____
____________________________________
6. _____
_____
_____
_____
____________________________________
7. _____
_____
_____
_____
____________________________________
8. _____
_____
_____
_____
____________________________________
9. _____
_____
_____
_____
____________________________________
10._____
_____
_____
_____
____________________________________
13C NMR Interpretation
ppm
Multiplicity
1. _____
_____
___________________________________________
2. _____
_____
___________________________________________
3. _____
_____
___________________________________________
4. _____
_____
___________________________________________
5. _____
_____
___________________________________________
6. _____
_____
___________________________________________
7. _____
_____
___________________________________________
8. _____
_____
___________________________________________
9. _____
_____
___________________________________________
46
Spring 2014
1H NMR Interpretation
ppm
# of H Multiplicity
1. _____
_____
_____
_____
____________________________________
2. _____
_____
_____
_____
____________________________________
3. _____
_____
_____
_____
____________________________________
4. _____
_____
_____
_____
____________________________________
5. _____
_____
_____
_____
____________________________________
6. _____
_____
_____
_____
____________________________________
7. _____
_____
_____
_____
____________________________________
8. _____
_____
_____
_____
____________________________________
9. _____
_____
_____
_____
____________________________________
10._____
_____
_____
_____
____________________________________
13C NMR Interpretation
ppm
Multiplicity
1. _____
_____
___________________________________________
2. _____
_____
___________________________________________
3. _____
_____
___________________________________________
4. _____
_____
___________________________________________
5. _____
_____
___________________________________________
6. _____
_____
___________________________________________
7. _____
_____
___________________________________________
8. _____
_____
___________________________________________
9. _____
_____
___________________________________________
10._____
_____
___________________________________________
47
Spring 2014
Lab#4:
Directing Effects in Electrophilic Aromatic Substitution
Introduction:
One class of important reactions of aromatic compounds is electrophilic substitution. The mechanism
for this type of substitution is thought to take place in two steps. The first step is the attack by the
aromatic ring containing the -electrons (nucleophile) on the electrophile. This leads to the formation of
+
a positive benzenium ion. The second step is the elimination of an H yielding the substituted aromatic.
This process is shown below for benzene.
H
H
+E
- H+
Since all the carbon positions on the benzene ring are equivalent, they present identical chemical
environments for the nucleophile. However, a substituted benzene does not possess carbon atoms that
are all equivalent. In this case, there will be different preferences for the nucleophilic attack by the
carbon atoms ortho, meta, and para to the substituent. The preferred site of reaction will be the position
that leads to the most energetically stable benzenium ion. This will lead to an unequal distribution of
ortho, meta, and para products as a result of the reaction. In actuality, the substituents on the aromatic
ring usually fall into two basic groups that either favor substitution at the ortho- and para-positions or at
the meta-position. In this exercise, we will study the effect of substituents on the products of the
reaction of substituted aromatic rings with a nitro group. We will calculate the relative stability of
various substituted benzenium cations to see at which site the positive ion is most stabilized. This will
be used to predict whether a particular substituent will favor ortho/para or meta substitution of the
aromatic ring. The calculations will be done using the computational software called Spartan for
Windows. With this software, we will use an approximate quantum mechanical method to solve the
wave equation for the electrons in the various cations and from this, calculate the relative stability of the
various cations for a number of different substituents.
Before going on to the exact experimental procedure, a little explanation as to what you will be doing is
necessary. This computational experiment will have a procedure consisting of 3 steps. These are:
1. Building a basic molecular structure (an unsubstituted nitro-benzenium ion)
2. Running the quantum mechanical calculation and finding the distribution of electrons in the
molecule as well as a stable set of bond lengths and angles.
3. Tabulating the resultant energy of the various substituted nitro-benzenium ions and comparing
their energies. (Note: It is only appropriate to compare energies of species with the same
substituents).
Step 1 in the list above is necessary to input into the computer program the approximate positions of the
atoms in the system. For the simple systems in this experiment, you will do this by using some basic
ideas of covalent bonding to connect atoms so they have the appropriate number of bonds. You will
need to recall the Lewis structures for the molecules that you build. (Note: Even though we build the
48
Spring 2014
molecules with explicit bonds, the solution to the quantum mechanical wave equation will tell us
where the electrons in the molecule will go).
Step 2 will be the most mysterious step. It involves the mathematical solution of the quantum
mechanical equations that describe the behavior of electrons in order to get the wave equation for the
electrons. Luckily, you do not have to understand the details of the calculations to be able to run them
and to gain useful information from them. For this experiment we will use an approximate quantum
mechanical method called the PM3 method. (PM actually stands for Parameterized Model, a semiempirical method for the quantum calculation of molecular electronic structure in computational
chemistry). During this step, the most stable arrangement of electrons and the corresponding positions
of the nuclei will be calculated. Depending on how far away your initial input structure is from the final
structure, you should see a small change in the overall structure of the system when the calculation is
completed. This portion of the computation is often called energy minimization or geometry
optimization.
Step 3 uses the quantum mechanically calculated energy to get relative stabilities. Since the stabilities
are relative, it is convenient to pick one general structure (for each substituent) for a reference. Here we
will use the substituted ion with the lowest energy as a reference. In this case, the relative energy of
substituted ion with the lowest energy will always be 0.0kcal/mol, while the other substituted ions can
be calculated from:
Relative Energy highest/medium = E highest/medium - E lowest

The larger the relative energy is the less stable that isomer will be. An example of this is shown
below in the following table:
Isomer
Calculated Energy Relative Energy
(in kJ/mol)
(in kJ/mol)
ortho (medium)
515.7
7.5
meta (highest)
581.4
73.2
para (lowest)
508.2
0.0
This result would indicate that the substituent is an ortho/para-director, since these ions are more stable
than the meta substituted ion.
Computational Instructions
For each of the molecules, you will follow the same basic set of steps to run the calculations. Below are
some general instructions for using the software program for this experiment.
To access Spartan Student program:
1. link on: https://cougarapps.csusm.edu,
2. log on with your campus user ID and password.
3. From Applications, click on Chemistry and chose Spartan Student.
4. Create a New Folder on the Desktop with your name.
5. Save all your structures in this folder.
6. At the end of this lab put this Folder in the Trash.
Building the molecule
Make structures in Inorganic only. To build a new molecule, select New from the File menu. A tool
palette should appear on the screen. On the palette select Inorganic if it has not already been selected.
49
Spring 2014
At this point a number of standard bonding arrangements for some common elements should appear.
Click on the atom you wish to select from the periodic table and the connectivity (i.e. the number and
types of bonds you think the atom will make) you want. After these have been selected, click on the
screen. The atom should appear with unfilled valences (i.e. unpaired electrons) appearing as dashes. To
fill the unfilled valences, click on the appropriate atom and type in the palette and then click on an open
valence on the screen where you wish to make a connection. Build up your molecule in this way. Be
sure all the valences you want filled are bonded to other atoms. When you have done this, select Save
As from the File menu, type in a name for your molecular ion and click Save. Be sure to save your files
in the Spartan File Folder on the desktop.
Some Helpful Hints:
The molecule can be rotated by clicking and holding the left mouse button and then using the
mouse to position the molecule in the desired orientation.
The molecule can be translated by holding down the right mouse button and dragging the
molecule to a new position.
An atom can be deleted by choosing the * next to the + in the list of symbols across the top of
the screen and clicking on the atom to be deleted.
Setting up the calculation
Each time you build a molecule, select Calculations from the Setup menu. Next to the word
Calculate: select Equilibrium Geometry with Semi-empirical PM3 from the list of choices. Now,
select Cation from the Total Charge menu then click OK.
Running the calculation
To run the calculation you have just set up select Submit from the Setup menu. A box will appear
asking you for a name of the file in which to save your calculation, if you havent named and saved it
already. If necessary, type in the appropriate file name and then click on Save. Be sure to save your files
in your folder on the desktop.
A message should appear telling you that the calculation has started. Click OK. A few seconds later,
another message should appear telling you the calculation has successfully completed. If this does not
appear within one minute, or if a different message appears, check your calculation setup and then
resubmit. If it still does not complete successfully, then see your instructor.
Displaying the Energy
The easiest way to obtain the calculated energy of the system is to select Properties under the Display
menu. Click on the molecule of interest and one of two types of displays will be shown. If the Atom
Properties display is shown, click on the molecule again and the Molecule Properties box will be
displayed. In the upper left hand side of this box will appear the energy for the system. Although it will
be shown to many decimal digits, you need only record the energy to the nearest kJ/mol. Click the x
in the upper right hand corner of the Molecule Properties box to close it.
Selecting a Molecule
50
Spring 2014
If you have multiple molecules displayed on the screen at once, you can select any of them by simply
left-clicking on it. The name of the molecule you have selected will appear on the top of the window.
Clearing the Screen
If at any time you want to stop displaying one of the molecules that you have worked with, follow these
instructions. Click on the molecule you wish to stop displaying, then select Close from the File menu.
Click Save if the program asks you if you want to save the changes.
Exercises
All data and responses to questions should be written in the appropriate spots on the data sheets.
A. Build the unsubstituted nitro-benzenium cation.
Hint: When building this structure:
Be sure to have selected the build palette marked Inorganic if it has not already been selected.
Select carbon from the periodic table and then select the trigonal icon for the carbon atom (three
planar bonds). After these have been selected, click on the screen. Connect five such trigonal
atoms (carbon 1-5 in the above figure).
Select the tetrahedral icon for the six carbon atom and bond it to carbon one or five.
Close the ring by selecting Make Bond from the building template and click on an open valence
of adjacent trigonal planar and tetrahedral carbons.
NO2
H
H
1
2
Hint: You may want to change the model display to get a better view of the open valences. Do this by
selecting Ball and Wire from under the Model menu. If you prefer the other structural model, you can
go back to it by selecting Ball and Spoke from under the Model menu.
Add the NO2 group on the tetrahedral carbon by selecting Nitro from the Groups submenu
(underneath the bonding template) and clicking on an open valence of the tetrahedral carbon
atom.
Finally, select the singly bonded atom from the bonding template and hydrogen from the
periodic table and add the H atoms to the appropriate position on the ring carbons.
The structure should now be complete.
You should use this structure as a model for building all the other substituted nitro
benzeniumions.Youcandothisbysimplyaddinganddeletingthesubstituentgroupsatthe
various positions. You should not make any modifications to the nitro group on the
tetrahedralcarbonatom.
B. Run the PM3 calculation on the nitro-benzenium ion as discussed above under Setting up the
calculation and Running the calculation. We do not need any energy from this calculation. We only
need the final structure that has been generated from this calculation.
51
Spring 2014
C. We are now ready to start calculating relative energies for substituted nitro-benzenium cations. Use
the structure generated in parts A and B as a starting point for all future calculations.
Click on the + symbol on the icon bar at the top of the screen. This puts you in the mode where
you can modify structures by adding and deleting groups.
Click on the Inorganic tab at the top of the build menu. You will see a much simplified bonding
template. We can use this template from now on to make changes.
Add an OH group to the nitro-benzenium ion to make the ortho, then the meta, and then the paraisomers. Be sure to save each of these into separate files with names that you can easily remember.
Hint: Once you modify a structure and save it, it replaces the previous structure. One easy way to
minimize your work is to recall from disk the structure of the nitro-benzenium cation that you
generated in parts A and B. You can do this by selecting Open from the File menu and then
selecting the name you gave for the nitro-benzenium ion in parts A and B. As long as you keep
saving your new structures to different names, the original nitro-benzenium ion structure will always
be intact.
After you have built these structures, set up the PM3 calculations and run them.
Record the energies of each of the ortho, meta, and para-isomers in the data table. Convert these
energies to relative energies and record these in the data table.
From these data, explain whether you think that the OH group is an ortho/para or meta-director.
D. Follow the instructions in Part C to build the structures and calculate the relative energies of
benzenium ions substituted with a methylcarboxylate group (-COOMe) group.
Record the energies of each of the ortho, meta, and para-isomers in the data table. Convert these
From these data, explain whether you think that the CO2Me group is an ortho/para or metadirector.
E. Follow the instructions in Part C to build the structures and calculate the relative energies of nitrobenzenium ions substituted with a C6H5 group.
Record the energies of each of the ortho, meta, and para isomers in the data table. Convert these
From these data, explain whether you think that the C6H5 group is an ortho/para or meta-director.
F. Follow the instructions in Part C to build the structures and calculate the relative energies of nitrobenzenium ions substituted with a CF3 group.
Record the energies of each of the ortho, meta, and para isomers in the data table. Convert these
From these data, explain whether you think that the CF3 group is an ortho/para or meta-director.
G. Based on your relative energies, classify each of the four substituents as one of the following:
(strong ortho/para-director, weak ortho/para-director, strong meta- director, weak meta-director).
H. Now we will investigate what occurs when an aromatic ring starts out with more than one substituent
before the electrophilic substitution. Here, we will have these initial substituents oriented para to
each other. The tetrahedral carbon with the nitro- group will then be either ortho or meta to these
substituents. We will start out with the two reactants pictured below.
Build the structures for the nitro-benzenium ions for both ortho and meta- substitution for each of
these two systems. (Recall that you can start with the unsubstituted nitro-benzenium ion from parts
A and B).
52
Spring 2014
Perform the PM3 calculations as you have done previously. Tabulate the calculated energies and
relative energies for each of these isomers in the data table.
What do your results tell you about which product will be favored in each case?
OCH3
C6H5
NO2
NO2
OH
H3C
I. The experimentally observed distributions for the nitro substitution in the systems above are: 100%
meta (to C6H5 group) in para-methyl phenol and 100 % ortho (to the OCH3 group). Explain these
results. Are they consistent with your calculations in Part H?
53
Spring 2014
Name:
Data Sheet for Directing Effect in Electrophilic Aromatic

Substitution
C. OH substituent
PM3 Energy (kJ/mol)
Relative Energy (kJ/mol)
ortho
___
meta
___
para
___
Is OH an ortho/para or meta-director? Explain.
D. COOCH3 substituent
PM3 Energy (kJ/mol)
ortho
meta
para
Is COOCH3 an ortho/para or meta-director? Explain.
54
Spring 2014
E. C6H5 substituent
PM3 Energy (kJ/mol)
ortho
meta
para
Is C6H5 an ortho/para or meta-director? Explain.
F. CF3 substituent
PM3 Energy (kJ/mol)
ortho
meta
para
Is CF3 an ortho/para or meta-director? Explain.
G. Groups classified as: strong ortho/para director, weak ortho/para-director, strong meta-director, weak
meta-director.
-OH
-CO2CH3
55
Spring 2014
- C6H5
-CF3
H. para-phenyl phenol: draw the 2 benzenium ions (with respect to the C6H5 group)
here:
PM3 Energy (kJ/mol)

ortho
meta
Energy difference (kJ/mol) ___

Which product will be favored?
para-methoxy acetophenone :draw the 2 benzenium ions (with respect to the OCH3 group)
here:
PM3 Energy (kJ/mol)
ortho
meta
Energy difference (kJ/mol) __
Which product will be favored?
I. Are your calculations and results from Part H consistent with the experimental product distribution?
See page 53. Explain, why or why not.
56
Spring 2014
Lab#5:
Friedel - Crafts Alkylation (EAS) - Synthesis of 1, 4-di-t-butyl-2, 5dimethoxybenzene
OCH3
OCH3
t-B u
C H 3 )3 C O H / H O A c / H 2 S O 4
t-B u
OCH3
p -d im e th o x y b e n z e n e
OCH3
1 ,4 -d i-t-b u ty l-2 ,5 -d im e th o x y b e n z e n e
Readings: pages 575-580 in lecture textbook 8e.

This reaction is an example of electrophilic aromatic substitution (EAS), Friedel-Crafts
alkylation, on an activated aromatic ring. The methoxy ether groups direct the alkylation to the
ortho- / para-positions.

Procedure:
1. Weigh 1,4-dimethoxybenzene (100 mg) in a 10mL Erlenmeyer flask.
2. Add tert-butyl alcohol (170 L) using a 1-mL
syringe.
3. Add glacial acetic acid (HOAc, 340L) using
an automatic pipet. Caution: keep the automatic
pipet vertical at all times.
4. Warm on the hot plate until the 1,4dimethoxybenzene dissolves.
5. Clamp the Erlenmeyer flask in an ice bath
(crystallizing dish).
6. Using a 1.0-mL calibrated pipet transfer
concentrated H2SO4 (0.67 mL) into a glass 12
mL-centrifuge tube. Chill the tube in the ice
bath (crystallizing dish). Caution: sulfuric acid
is extremely dangerous. Do not get any on your
skin.
7. While stirring the mixture in the Erlenmeyer
flask carefully with a glass rod, add the H2SO4
drop wise with a Pasteur pipet over a period of 1
min.
8. Let the reaction flask to stand at room
temperature for 10 min.
9. Clamp and cool the flask in the ice bath and
while stirring the contents with the glass rod,
slowly and carefully add 5 mL of iced-water.
10. Add diethyl ether (2.0 mL) and transfer the

contents to a 12-mL centrifuge tube using a
Pasteur pipet.
11. Rinse the Erlenmeyer flask with another portion
of diethyl ether (2.0 mL) and transfer the
ethereal rinse to the 12-mL centrifuge tube.
12. Remove the aqueous layer with a Pasteur pipet
and place it into a 50-mL beaker containing 30mL of water. Save the ether layer.
13. Extract the ether solution with water (2 mL) and
then with sat NaHCO3 solution (2 mL), and
again with water (1 mL). Save the ethereal
layer. Carefully add the aqueous extracts to the
50-mL water in the beaker then dispose of the
contents down the drain.
14. Add anhydrous Na2SO4 (0.5 g) to the ether layer.
15. Transfer the dried ether solution to a clean, dry
weighed 12-mL centrifuge tube using a Pasteur
pipet. Do not transfer any solid Na2SO4.
16. Evaporate the ether with a gentle flow of N2.
17. Weigh the 12-mL centrifuge and calculate the %
yield.
18. To proceed with the recrystallization you should
first analyze the % yield. If your % yield is low
than you should decrease the amount of solvent
advised to add for recrystallization (consult with
the instructor).
57
Spring 2014
19. Add methanol (1.5 mL) and the boiling stick and
heat in a warm water bath (~ 70 C) to boiling in
order to completely dissolve the crude product.
Caution: Methanol is very toxic. Do not
breathe.
20. Concentrate the solution by boiling (warm water
bath, (~70 C) until the solution becomes
cloudy, remove the boiling stick and cool to
room temperature, then cool in an ice-bath to
crystallize the crude product.
21. Centrifuge the crystals to the bottom of the tube
and then remove as much of the solvent as can
be removed using a Pasteur pipet. Dry the
crystals with a gentle stream of N2 and a warm
water bath (~45 C) then under vacuum for 10
minutes.
22. Determine the mp. Tape the mp tube in your
notebook. Show your crystals to your professor.
23. Place ~2 mg (tip of the curved end of the
spatula) of the product in a clean dry 6 x 50 mm
culture tube. Add 10 drops of Et2O and
carefully stir with a spatula until solution results.
Keep the rest of this solution to perform the
TLC. If no solution rest add one drop of ether.
24. Using a 9" Pasteur pipet place 1 drop of this
solution onto your IR card, after you have run
the Background of the card. Allow the solvent

to evaporate for ~ 2-3 minutes. Run the Sample
spectrum and Print the spectrum. Draw the
structure of the product and indicate on the
spectrum the bands attributed to the ether groups
and the aromatic ring. Tape the spectrum in your
notebook.
25. Clean your IR card on a clean paper towel with
the drop wise addition of Et2O and blotting with
a clean part of the paper towel. Repeat 3 times.
Do not rub.
26. Check the purity of your product by TLC. Spot a
TLC plate with a solution of 1,4dimethoxybenzene in Et2O (prepared in a clean
dry 6 x 50 mm culture tube) on the left lane of
the plate labeled R, and with the solution of your
product in Et2O on the right lane labeled P.
Develop the plate with hexanes (6 mL).
Visualize the plate with the UV lamp, circle the
visible spots and calculate the Rf of the starting
material and your product. Tape the TLC plate
in your notebook.
Electrophilic Aromatic Substitution (EAS) _ General Mechanism:

Electron releasing groups (ERG = A:) activate the aromatic ring towards EAS and direct subsequent
substitutions to the ortho- , para-positions:
A
A:
E+
.. -
.. E+
Electron withdrawing groups (EWG = A=O or AN) deactivate the aromatic ring towards EAS and
direct subsequent substitutions to the meta-position:
E
A =O
A -O :
A -O :
A =O
A =O
H +
H
E
E+
58
Spring 2014
Mechanism of the Friedel-Crafts Alkylation:

1. Step 1: Formation of the carbocation (electrophile)
30 - stable
H-HSO4
..
(CH3)3COH
..
(CH3)3C
(CH3)3COH
.. 2
- H2 O
t-butyl carbocation
2. Step 2: Atack of the nucleophile (substrat) on the electrophile with the formation of benzeniu ion
..
: OCH3
..
OCH3
C(CH3)3
OCH3
..
OCH3
..
OCH3
..
OCH3
C(CH3)3
C(CH3)3
C(CH3)3
OCH3
benzenium ion
C(CH3)3
C(CH3)3
OCH3
OCH3
OCH3
OCH3
..
OCH3
stabilized by conjugation
3. Step 3: Proton Elimination and formation of the reaction product containing one radical
..
OCH3
OCH3
t-Bu
repeat
C(CH3)3
OCH3
benzenium ion
- H+
OCH3
t-butyl-2,5-dimethoxy benzene
OCH3
t-Bu
t-Bu
OCH3
1,4-di-t-butyl-2,5-dimethoxybenzene
(alkylation product
containing two alkyl groups)
59
Spring 2014
Orientation in Electrophilic Aromatic Substitution

An aromatic ring which contains electron donating groups (EDG) is considered electron-rich relative to
benzene and is said to be activated toward electrophilic aromatic substitution. This ring is more reactive
towards EAS than benzene.
An aromatic ring which contains electron withdrawing groups (EWG) is considered electron-deficient
relative to benzene and is said to be deactivated toward electrophilic aromatic substitution. This ring is
less reactive towards EAS than benzene.
Based on the type of substituent, EDG or EWG, they can be classified in:
1. Ortho-, para-directors direct subsequent substitutions to the o-, p-positions, by increasing
electron density on these positions.
2. Meta-directors direct subsequent substitutions to the m-positions, by decreasing the electron
density on o- and p-positions.
Substituent Group
NH2
NHR
NR2
OH
NHCOR
OR
OCOR
Ar
R
Name of Group
amino
alkylamino
dialkylamino
hydroxyl
acylamino
alkoxy
acyloxy
aryl
alkyl
-X
halogen
CH2X
CHO
COR
CO2H
CO2R
C(=O)Cl
CN
SO3H
NO2
CF3
NR3+
halomethyl
formyl
acyl
carboxylic acid
ester
acyl chloride
cyano
sulfonic acid
nitro
trifluoromethyl
trialkylamino
Substituent effect on the benzene ring

electron releaser by resonance
electron releaser by induction
electron releasers by resonance &
electron withdrawers by induction
which deactivates the ring relative to
benzene
electron withdrawer by resonance
electron withdrawer by induction
electron withdrawer by induction
Directing Effect
ortho, para
ortho, para
ortho, para
ortho, para
ortho, para
ortho, para
ortho, para
ortho, para
ortho, para
ortho, para
ortho, para
meta
meta
meta
meta
meta
meta
meta
meta
meta
meta
60
Spring 2014
Micro-Scale Extraction (Tape this page in your notebook for reference)

1. After mixing the organic and water layers in a stopered V-shaped vessel (vial, flask, or 12-mL
centrifuge tube) always remove the lower (more dense, See your data table.) layer and
transfer it to a second vessel.
2. Use another V-shaped vessel as the second vessel if the lower layer is to be extracted another
time or use a beaker or Erlenmeyer flask if the lower layer is to be neutralized or disposed.
3. Extract the aqueous layer a second time, again removing the lower layer and transferring it to an
appropriate vessel.
4. Repeat step 3 for a total of 3 extractions.
5. Always combine the organic extracts in one vessel.
Extraction of a product from an aqueous solution with a solvent less dense than water:
61
Spring 2014
Micro-Scale Recrystallization Procedure (Tape in your notebook for reference)

1. Place the solid in a clean, dry and weighed 12-mL centrifuge tube. Insert a boiling stick and the
recommended volume of solvent.
2. Completely dissolve the solid contained in the 12-mL centrifuge tube in a minimum of boiling solvent
(Et2O, CH2Cl2, MeOH, or EtOH, etc) by heating in a warm to hot water bath (50-mL beaker).
3. Concentrate the volume of the solution by boiling until the solution is saturated or as soon as the crystals
begin to develop (~ 0.5-0.75 the original volume). Immediately remove the tube from the water bath then
remove the boiling stick.
4. Allow the solution to cool to room temperature slowly, and then place the tube in an ice-bath
(crystallizing dish).
5. Centrifuge the 12-mL centrifuge tube, and carefully remove as much solvent as possible using a Pasteur
pipet without removing the crystals.
6. Clamp the centrifuge tube and a N2 pipet and carefully dry the crystals with a gentle flow of N2 and a
warm water bath occasionally stirring the crystals with a clean spatula.
7. Weigh the 12-mL centrifuge tube containing the dried crystals.
8. Calculate the % recovery or % yield.
filter
xx
xx
xy xyxyx
xxyxxyyxx
yx xyyxx
x yx
use round
filter paper
apply vacuum
carefully!
cool
(slowly)
dissolve in
hot solvent
crude solid clump

x = "good stuff"
y = impurities
xx
xx
clamp filter
flask!
x x y
x
x x x
y x
xy y x x
molecules free
in solution
x
xx y xx y
xx x xx y
purer solid precipitates

impurities stay in sol'n.
y
x
x
y
..
Buchner
filtration
62
Spring 2014
Lab#6:
Ketone Reduction (NA): Synthesis of cis- & trans-4-t-butylcyclohexanol
O
H
H
N aBH 4 / C H 3 O H
OH
C H 3 O - Na +
OH
+
H
H
4-t-butylcyclohexanone
cis-4-t-butylcyclohexanol
trans-
Readings: pages151-153, 158-163 in lab textbook 5e & pages 630-631 in lecture textbook 8e.
Homework problems: 6-28, 6-30 & 6-33 in 5e (pag. 162) OR 4e (pag. 144)
The present experiment is a typical sodium borohydride (NaBH4) reduction. These same conditions and
isolation procedures could be applied to hundreds of other ketones and aldehydes. Sodium borohydride was
discovered in 1943 by H. I. Schlesinger and H. C. Brown.
Unlike lithium aluminum hydride (LiAlH4), sodium borohydride is a mild and selective reducing reagent
being insoluble in ether but soluble in methanol and ethanol. In methanol solution it reduces aldehydes and
ketones rapidly at room temperature, esters very slowly, and is inert toward functional groups that are readily
reduced by lithium aluminum hydride: carboxylic acids, epoxides, lactones, nitro-groups, nitriles, azides, amides,
and acid chlorides. To check that the NaBH4 is good, place a small amount in a few drops of methanol and
heating gently. Remove from heat, and if H2 gas bubbles are vigorously forming on the NaBH4, the material is
still good.
Procedure:
1. Prepare a set-up similar to the one presented on
page 158, but substitute the air condenser with a
Multi-Purpose adapter with a septum and a N2
line.
2. Weigh 50 mg (0.324 mmol) of 4-tbutylcyclohexanone in the 3.0-mL conical vial.
Place a spin vane in the vial.
3. Add 50 L of MeOH using the syringe
provided. Place a cap on the vial and gently stir
to dissolve the ketone.
4. Add 120 L of NaBH4 solution using the
automatic pipet provided. Caution: keep the
automatic pipet vertical at all times. Attach the
Multi-purpose adapter with a septum and N2
line.
5. Allow the solution to gently stir at room
temperature for 10 minutes.
6. Carefully drop wise add 1.0 mL of cold dilute
HCl using a graduated pipet.
7. Extract the solution 3 times with 0.5 mL of
CH2Cl2 and separate the phases using Vortex
8.
9.
10.
11.
12.
13.
mixing. The combined 3 CH2Cl2 extracts are

collected in a small flask.
Prepare a column from a 6" Pasteur pipet filled
with a cotton plug and 250 mg of anhydrous
Na2SO4. Pass 1.0 mL of CH2Cl2, through the
column and dispose it.
Pass the CH2Cl2 extracts through the column
into a clean weighed 5.0-mL conical vial. Rinse
the column with another 0.5 mL of CH2Cl2 and
collect into the 5.0 mL conical vial.
Check the purity of your product by GC. Inject 1
L of the CH2Cl2 solution in the analytical GC.
Record the Rt's and ratio of the 2 products in
your notebook. Tape the GC trace in your
notebook.
Carefully evaporate the CH2Cl2 at 40-50 0C
(Al-Block) using a gentle flow of N2.
Weigh the dried product and calculate the %
yield. Show your product to your professor.
Place ~2 mg (tip of the curved end of the
spatula) of the product in a clean 6 x 50 mm
63
Spring 2014
culture tube. Add 3 drops of Et2O and carefully

shake until a solution results.
14. Using a Pasteur pipet place 1-2 drops of this
solution onto your IR card after you have run the
Background of the card. Allow the solvent to
evaporate for ~ 2-3 minutes. Run the Sample
structures of the products on the spectrum and
indicate on the spectrum the position of the
bands attributed to the alcohol, the t-butyl group
and the C-O bonds. Tape the spectrum in your

notebook.
the drop-wise addition of Et2O and blotting with
Do not rub.
16. IMPORTANT: For the experiment next week
place a 3.0-, 5.0-mL conical vials, 3-mL heavy
vial, a clean spin vane, and the Multi-Purpose
adapter in a dry 50x100 mm crystallizing dish
(with your name or station number on)
Reduction Reaction Mechanism

Step 2: The oxygen anion eventually
removes a proton from methanol.
H
OH
OCH3
H
H
Step 1. NaBH4 transfers a hydride ion

to the carbonyl carbon through
an exo- or endo-attack..
H
trans-product (80%)
- BH3
OCH3
O
H
- BH3
H
OH
H
H
cis-product (20%)
Due to the large size of the t-butyl group, the molecule 4-t-butylcyclohexanone exists almost exclusively
in one chair conformation: the one in which the t-butyl group is in the equatorial position. As a result of
this conformational immobility of the molecule, the sodium borohydride reduction of 4-tbutylcyclohexanone from one side of the molecule gives trans-4-t-butylcyclohexanol as the major
64
Spring 2014
product, whereas reduction from the other side of the molecule gives cis-4-t-butylcyclohexanol as the
minor product. Since 4-t-butylcyclohexanol is an unhindered compound the product stability will decide
which one will be the major product of the reduction reaction. The two products are diastereomers and
the identity and percent of each stereoisomer present in the product mixture are established easily by
GC. If the starting material is a hindered compound then the major product will be the one resulted from
the less hindered attack (steric controlled), as seen below:
u n h in d e re d : p ro d u c t d e v e lo p m e n t c o n tro l
OH
O
B H 4-
OH
80%
20%
h in d e re d : s te ric a p p ro a c h c o n tro l
e xo -atta ck
B H 4-
OH
O
en do -a ttack
OH
14%
86%
cam phor
en d o -p ro d u ct
ex o -p ro d u ct
Calculation of Percent Yield
NaBH4 / CH3OH
C10H18O
CH3O Na
C10H20O
4-t-butylcyclohexanone
4-t-butylcyclohexanol
MW = 154.3 mg/mmol
MW = 156.3 mg/mmol
50.0 mg/154.3 mg/mmol = 0.324 mmol 4-t-butylcyclohexanone

0.324 mmol
x 156.3 mg/mmol = 50.6 mg 4-t-butylcyclohexanol
theoretical yield (TY)

TY = XX.X mg x MW mg/mmol (product) / MW mg/mmol (starting material)
65
Spring 2014
Lab#7:
Grignard Reaction (NA): Synthesis of triphenylmethanol
O
OH
1) C 6H 5MgBr / Et2 O
2) H 3O +
benzophenone
triphenylmethanol
Readings: pages 275-283 in lab textbook 5e & pages 355-356 in lecture textbook in 8e.
Homework problems: 6-109, 6-110 & 6-111 in 5e (pag. 283) OR in 4e (pag 253)
In 1912, Victor Grignard received the Nobel prize in chemistry for his discovery of a new series of reactions that
result in the formation of a carbon-carbon bond. This Grignard reaction is an example of nucleophilic addition
(NA) to a ketone (benzophenone) by the organic metallic reagent phenylmagnesium bromide (C6H5MgBr).
Anhydrous diethyl ether is the solvent of choice for carrying out a Grignard synthesis. Vapors of ether help to
prevent oxygen from reaching the reaction solution and the ether molecules actually coordinate the Grignard
reagent and stabilize it. You must finish this lab by 5:45 PM, so be prepared.
Procedure:
1. Carefully take your equipment out of the oven
and immediately assemble on the magnetic
stirrer the dry 3.0-mL conical vial with a spin
vane, Multi-purpose adapter fitted with a
septum. Use forceps to handle the spin vane.
Attach the N2 line. Allow the apparatus to cool
to room temperature under N2.
2. Carefully remove the Multi-purpose adaptor and
place 50.0 mg (0.274 mmol) of benzophenone in
the 3.0-mL conical vial. Then replace the
Multi-adaptor and continue blowing nitrogen.
3. While stirring slowly, transfer phenyl
magnesium Grignard reagent (3.0 M, 0.50 mL,
1.50 mmol) using a 1.0-mL syringe.
4. After stirring for 10 minutes, remove the MultiPurpose adapter and place the 3.0-mL reaction
vial in a 25-mL beaker ice-bath.
5. Using a Pasteur pipet carefully add drop-wise 3
M HCl (0.5 mL) followed by DI H2O (0.5 mL).
Add Et2O (1.0 mL) then cap the vial and
carefully shake.
6. Remove the spin vane with your forceps with

rinsing into the 3.0-mL reaction vial with 0.25
mL of Et2O.
7. Cap the vial, shake and carefully vent.
8. Using a Pasteur pipet transfer the H2O layer to a
clean 5.0-mL vial. Save the Et2O layer.
9. Add another 0.5 mL of Et2O into the water
layer, vortex the mixture and extract the H2O
layer into another clean vial. Transfer the ether
layer into to the Et2O layer from step 8, saved in
the 3.0mL vial.
10. Repeat 9 one more time with the water layer.
Note: Be aware that you do an ether extraction.
Think where the product is!
11. The combined Et2O layers are extracted with
0.5 mL of iced H2O. Now discard the H2O
layer.
12. Add 300 mg of anhydrous Na2SO4 to the
combined washed Et2O layer.
13. Stir the Na2SO4 with a glass rod until the Et2O
solution is clear (~10 minutes). If some ether
evaporates add some more.
66

14. Using a clean 9" Pasteur pipet, transfer the
solution (liquid only) to a weighed centrifuge
tube. Wash the 3.0-mL vial/Na2SO4 with an
additional 0.5 mL of Et2O and transfer to the
centrifuge tube. Evaporate all the Et2O with a
gentle stream of N2 in the hood.
15. Add 0.5 mL of ice-cold hexane to the centrifuge
tube and stir with a glass rod.
16. Centrifuge the tube and separate the mother
liquor (biphenyl/hexane) in a 10-mL Erlenmeyer
flask and the crystals (triphenylmethanol) in the
centrifuge tube.
17. Repeat steps 14 and 16 on the contents of the
centrifuge tube again adding
the mother
liquor to the 10-mL Erlenmeyer flask.
18. Discard the biphenyl/hexane in the 10-mL
Erlenmeyer flask in the waste container
provided.
19. Dry the crystals of triphenylmethanol in the
centrifuge tube by gentle warming at ~70 C
(water bath) on the hotplate with a gentle flow
of N2. Be careful not to overheat.
20. Cool and weigh the triphenylmethanol product
and determine the % yield.
21. Place ~2 mg the triphenylmethanol product in a
clean dry 6 x 50 mm culture tube. Using a 9"
Pasteur pipet, add 4 drops of Et2O and stir by
Spring 2014
22.
23.
24.
25.
swirling. Make up a similar sample of

benzophenone.
Perform a TLC analysis on the product by
spotting 2 L of the Et2O solution on a TLC
plate in the right lane and a similar sample of
benzophenone in the left lane. Develop the plate
with CH2Cl2. Visualize the plate by UV light
and mark the spots with a pencil. Calculate the
Rf's of the spots. Tape the TLC plate in your
notebook.
Using a Pasteur pipet place 1-2 drops of the
product Et2O solution onto your IR card after
you have run the Background of the card.
Allow the solvent to evaporate for ~ 5 minutes.
Run the Sample spectrum and Print the
spectrum. Draw the structure of the product
and identify the position of the bands attributed
to the alcohol and aromatic ring groups on your
IR spectrum. Tape the spectrum in your
notebook.
Clean your IR card on a clean paper towel with
Clean the 1.0 mL syringe by rinsing with DI
H2O then with acetone. Blow-dry the needle
with N2. Leave the syringe in your drawer
unassembled.
67
Spring 2014
Grignard Mechanism:
Br
..
:Mg / Et2 O
..
+ .Mg + + :Br:..
OEt2
OEt2
.. ++
Mg
:Br:
..
..
.. ++
:Br:
Mg
..
..
O:
C
Ph
OEt2
Ph
Ph
:O:
C
Ph
Nucleophilic Addition
(NA)
..
.. - Mg ++ :Br:..
:O:
Ph
OH
H 3 O:+
Ph
Ph
Ph
Ph
Ph
radical
.
coupling
biphenyl (side
product)
68
Spring 2014
Lab#8:
Oxidation Reaction: Synthesis of 9-fluorenone
H
OH
H2CrO4/ acetone
9-fluorenol
9-fluorenone
Readings: pages 401-403 in lab textbook 5e & pages 645-647 in lecture textbook 8e.
Homework problems:
a) 6-209, 6-210, 6-211 & 6-213 in 5e (pag. 402) OR in 4e (pag 361)
b) Balance the following reaction equations using the half-reaction method:
1. RCH2OH + H2CrO4
RCO2H
2.
RCHO +
Ag2O
HO- / H2O
RCO2(-)
This is an example of oxidation of a secondary alcohol (9-fluorenol) to a ketone (9-fluorenone)

with Jones reagent H2CrO4 / acetone.
Procedure
1. Weigh 50 mg (0.274mmol) of 9-fluorenol in a 5mL conical vial.
2. Add a spin vane into the vial.
3. Using the graduated pipet add 1.5 mL of acetone
and stir until all of the 9-fluorenol is
completely dissolved.
4. While stirring carefully add 4-5 drops of Jones
reagent H2CrO4 until the solution remains light
orange with a green precipitate. Caution: Jones
reagent can cause severe burns. Do not get it on
your skin.
5. After stirring the light orange solution for 10
minutes add 3-4 drops of 2-propanol using a
Pasteur pipet until the color changes to green.
6. Using a graduated pipet add1.0 mL of H2O and
50 mg of NaCl, stir for 1-2 minutes. Remove the
spin vane with the forceps while rinsing it with
1.0 mL of Et2O into the reaction vial. Cap the
vial, vortex mix, and remove the water layer into
a 3-mL conical vial. Extract the water layer 2
7.
8.
9.
10.
more times with Et2O and add these extracts to

the original ether layer.
Add 250 mg of anhydrous Na2SO4 to the
combined ethereal extracts and stir with a glass
rod.
Filter the ether through a filter pipet containing
100 mg anhydrous Na2SO4 into a weighed 12mL centrifuge tube. Add a boiling stick.
Carefully remove a small drop from the tube with
a clean 9-pipet and load a 2 L-microcap, than
spot a TLC plate in the right lane. Make a
sample of the starting material in Et2O in a
culture tube and using a 2 L-microcap spot the
starting material in the left lane. Develop the
plate with 30% acetone/hexane. Visualize the
plate by UV light and mark the spots with a
pencil. Calculate the Rf's of the spots. Tape the
TLC plate in your notebook.
Remove the solvent by heating the centrifuge
tube in a 50-mL beaker-water bath at ~40 C with
a gentle stream of N2.
69
Spring 2014
16. Determine the mp. Tape the mp tube in your
notebook.
17. Dissolve ~ 2 mg of the product in 3-4 drops of
Et2O in a clean dry 6 x 50 mm culture tube.
Using a Pasteur pipet place 1-2 drops of this
evaporate for ~ 2-3 minutes. Run the Sample
structure of the product and identify the position
of the bands attributed to the ketone and aromatic
ring groups on your IR spectrum. Tape the
spectrum in your notebook.
the drop-wise addition of Et2O and blotting with
11. Cool to room temperature.

12. Determine the weight and % yield of the 9fluorenone.
13. Recrystallize the 9-fluorenone from 0.5 mL of
hexane in the weighed centrifuge tube containing
a boiling stick.
14. Heat the solution to dissolve the solid and
continue heating to concentrate the solution from
0.5 mL to ~ 0.3 mL by boiling. Remove the
boiling stick, then cool to room temperature (10
minutes), and then cool in an ice bath for an
additional 15 minutes.
15. Centrifuge the tube, carefully remove the hexane
with a Pasteur pipet, and dry the crystals with a
gentle flow of N2.

Oxidation Mechanism:
Step 1: Nucleophilic attack of alcohol to the Cr=O bond to form a chromate ester:
O
R
OH
Cr
OH
fast
R
HO
Cr
OH
OH
alcohol
R chromate ester
(an organomethalic ester)
chromic acid
Step 2: An elimination reaction occurs by removal of a hydrogen atom from the alcohol carbon
and departure of the chromium group with a pair of electrons that formerly belonged to the
alcohol; the alcohol is thereby oxidized and chromium reduced:
OH
OH
Cr
OH
O
O
R
C
R
slow
rate determining step
OH
C
R
+
R
ketone
Cr
OH
several
OH
steps
OH
chromium group
Cr3+
70
Spring 2014
Balancing Oxidation-Reduction Equations:

1. Determine the species that are involved in the redox process (the one that change their oxidation
number) by listing the oxidation states of each atom in each compound .To determine the
oxidation state of a given carbon, any attached carbons are treated as 0 and the other elements
are assigned their normal oxidation states in their combined form.
2. Write and balance two half reactions for the redox equation (no. of electrons donated has to be
equal to no. of electron accepted).For each half reaction:
a. Balance charges by adding, as needed, H+ (in acidic solution) or OH- (in basic solution)
b. Balance O by adding H2O as needed
c. Balance H by adding H (neutral H atoms). The number of Hs for oxidation must equal
the number of Hs for reduction.
d. Balance atoms other than O and H in each half reaction by inspection
3. Combine the two half-reactions and balance charge and atoms.
Example 1:
Overall
reaction: CH3CH2OH
H+
CH3COH
K2Cr2O7
Cr+3
1. Determine the elements that are involved in the redox process

-3
-1
CH3CH2OH +
-3
+6
+1
CH3COH
K2Cr2O7
Cr+3
2. Write and balance two half reactions for the redox equation.
-1
(oxidation): CH3CH2OH
- 2 e-
+1
CH3CHO
+ 2H+
C atoms: balanced
charges: add 2e- to right or
(-2 e-) on the arrow
O atoms: balanced
H atoms: add 2H to right
Cr atoms: add 2Cr+3 to right
+6
(reduction): (Cr2O7)-2
+ 6 e-
+ 14H+
+3
2Cr
charges: add 6e- to left or (+6e-)

+ 7H2O
on the arrow
O atoms: add 7H2O to right
H atoms: add 14H to left
3. Multiply each half-reaction by the smallest whole number that is required to equalize the number of
electrons gained by reduction with the number of electrons produced by oxidation.
3
-1
CH 3 CH 2 O H
+6
(Cr 2 O 7 ) -2
-2 e -
14H +
+1
CH 3 COH
+ 6 e-
2Cr +3
2H +
7H 2 O
71
Spring 2014
4. Combine the two half-reaction equations:
3CH3COH + Cr+3 + 7H2O
K2Cr2O7 + 8H+
3CH3CH2OH +
+ 2K+
Example 2:
H 3C
H 3C
O v e r a ll
r e a c t io n :
H 2C rO
CH
OH
a c e to n e
H 3C
H 3C
1. Determine the elements that are involved in the redox process
H3C
H3C
+6
H2CrO4
CH OH +
-2
H3C
Cr+3
H3C
2. Write and balance two half reactions for the redox equation.
H3C
0
CH
(oxidation):
C atoms: balanced
H3C
OH
+2
C
- 2 e-
H3C
charges: add 2e to right or

(-2 e-) on the arrow
+ 2H+
O atoms: balanced
H atoms: add 2H to right
H3C
Cr atoms: balanced
+6
(reduction): H2CrO4
+ 3 e-
+ 6H+
charges: add 3e- to left or (+3e-)
+3
+ 4H2O
Cr
on the arrow
O atoms: add 4H2O to right
H atoms: add 6H to left
3. Multiply each half-reaction by the smallest whole number that is required to equalize the number of
electrons gained by reduction with the number of electrons produced by oxidation.
H 3C
H 3C
0
CH
OH
-2 e
+2
C
H 3C
+6
H 2 C rO 4
2H +
H 3C
6H +
4. Combine the two half-reaction equations:

H3C
+
3
CH OH + 2 H2CrO4 + 6 H
H3C
+ 3 e-
C r +3
4H 2 O
H3C
3
+3
O + 2 Cr + 8 H2O
H3C
72
Spring 2014
Lab#9:
Williamson Ether Synthesis (SN-2): Synthesis of propyl p-tolyl ether
OH
O C H 2C H 2C H 3
C H 3C H 2C H 2
N aO H / H 2 O / n-B u 4 N + B r -
CH3
CH3
p ro pyl p-to lyl eth er
p -cresol
Readings: pages 321-326 in lab textbook 5e & page 678-679 in lecture textbook 8e.
Homework problems: 6-144, 6-145, 6-148, 6-150 & 6-151 (assign all the 1HNMR and 13CNMR
peaks on the spectra on pages 325 &326) in 5e pag. 337 OR in 4e, pag. 300/301
This is an example of a Williamson ether synthesis that involves a substitution nucleophilic bimolecular
(SN-2) reaction mechanism between a phenoxide anion (nucleophile) and 1-iodopropane (electrophile).
The phase transfer catalyst (n-Bu4N+ Br -) makes the phenoxide anion more soluble in the organic phase
(1-iodopropane).
Procedure:
1. Place a spin vane in a 3.0-mL conical vial and
using the respective automatic pipets provided
add 160 L (163 mg, 1.51 mmol) of p-cresol (d
= 1.02) and 260 L of 25% NaOH/H2O.
Caution: keep the automatic pipets vertical. Do
not mix the pipets.
2. Thoroughly mix the resulting solution by stirring
magnetically.
3. Add 18 mg of n-Bu4N+ Br -.
4. Perform the following transfer in the hood. Add
150 L (263 mg, 1.54 mmol) of propyl iodide
using the automatic pipet provided. Caution:
nPr-I is toxic.
5. Attach the condenser (H2O).
6. Attach a water condenser (water in at the bottom
and out at the top) to the conical vial and
vigorously stir the reaction mixture at 110-115
C (Al-block) for 60 minutes.
7. Cool the reaction vial to room temperature with
an ice bath.
8. Using forceps remove and rinse the spin vane
with 12 drops of H2O and 1 mL of Et2O (into
9.
10.
11.
12.
13.
the 3.0-mL conical reaction vial) then vortex

mix.
Using a 9" Pasteur pipet transfer the H2O layer
to a 3.0-mL conical flask supported in a 25-mL
beaker.
Add 1 mL of Et2O and cap the 3.0-mL conical
flask from 9, Vortex mix, and remove the H2O
layer.
Transfer the Et2O layer to the 3.0-mL conical
reaction vial from 8.
Extract the combined Et2O layers in the 3.0-mL
conical reaction vial with 0.40 mL of 5%
NaOH/H2O using the automatic pipet provided.
Discard the H2O layer.
Wash the product in the conical reaction vial
with 0.20 mL of H2O using a graduated pipet.
Discard the H2O layer. Be sure to completely
remove the lower aqueous layer.
Note: If the ether layer is getting small due to
evaporation make sure to add more ether at any
time.
73
Spring 2014
18. Carefully evaporate the solvent at 55-60 C (Alblock) using a gentle flow of N2 until you
observe ~ 0.25 mL (propyl p-tolyl ether, MW =
150.3, d = 0.950) remaining in the vial.
19. Cool to room temperature, weigh the product
and calculate the % yield.
20. Using a 9" Pasteur pipet add 1 drop of the
product onto your IR card after you have run the
evaporate for ~ 1 minute. Run the Sample
spectrum and Print the spectrum. Identify the
bands attributed to the nPr-O, Ar-O, and
aromatic ring groups on your IR spectrum. Tape
the spectrum in your notebook.
a clean part of the paper towel. Repeat 3 time.
14. To a 6" Pasteur pipet add a small cotton plug, 50

mg of sand, 500 mg of SiO2, and 50 mg of
anhydrous Na2SO4.
15. Add 0.25 mL of CH2Cl2 to the organic layer
from 13 and carefully transfer the resulting
solution to the chromatography column from
14and collect into a weighed 5.0-mL conical vial
containing a small boiling stick.
16. Elute the column with 2.0 mL of CH2Cl2 into
the same vial.
17. Check the purity of the product by GC. Using a
Pasteur pipet place 1 drop of this solution in a
6x50 mm culture tube. Add 3 drops of CH2Cl2
then mix and stopper for the GC analysis. Inject
1L of this solution on the GC. Note the purity
and the Rt of your product. Tape the GC trace in
your notebook.
Williamson Ether Synthesis Mechanism:

O-H
..
:O-H
..
CH3
p-cresol / n-Pr-I layer
NaOH / H2O layer

..
:O:
..
:O:
Na +
+ N(n-Bu)4
O-CH2CH2CH3
CH3 CH2CH2-I
n-Bu 4NBr
SN-2
CH3
CH3
CH3
p-cresol anion
rate = k [n-Pr-I] [p-cresol anion]
water soluble
organic & water soluble
74
Spring 2014
Lab#10:
Esterification Reaction (ANS / Acid Catalyzed)
OH
OCOCH3
(C H 3 C O ) 2 O / C H 3 C O C l
4 -t-b u t y lc y c lo h e x a n o l
4 -t -b u ty lc y c lo h e x y l a c e ta te
Readings: pages 196-209 in lab textbook 5 & page 644 & 824-826 in lecture textbook 8 .
Homework problems: 6-53 & 6-54 (pag. 209) in 5e OR in 4e (pag. 183)
Procedure:
1. Weigh 80 mg (0.512 mmol) of 4-t-butyl
cyclohexanol in a 3.0-mL conical vial.
2. Perform the following in the hood. Add 100 L
(1.06 mmol) of Ac2O and 60 L (0.85 mmol) of
AcCl. Caution: AcCl can cause burns.
Fig.1:Microscalerefluxwithstirringunder
anhydrousconditions:
3. Immediately place a spin vane in the flask,

attach a water condenser with a CaCl2 drying
tube. Start the condenser H2O (see Figure 1)
4. Heat the reaction with stirring at 120-130C for
1 hr.
5. Cool the reaction to room temperature with an
ice bath.
6. Add 0.5 mL of Et2O and 0.2 mL of 5%
NaHCO3 solution to the reaction vial using 1.0mL graduated pipets.
7. Cap the vial and extract with Vortex mixing.
Carefully loosen the cap to vent the 2 phase
mixture.
8. Remove and discard (hood drain) the H2O layer
using a Pasteur pipet.
9. The organic layer is extracted with 3 x 0.25 mL
of NaHCO3 solution using Vortex mixing.
10. Fill a 6" Pasteur pipet with a small cotton plug,
50 mg sand, 500 mg SiO2, and 500 mg
anhydrous Na2SO4.
11. Wet the column with 0.5 mL CH2Cl2 and
discard in a waste container.
12. Use a weighed 5.0-mL conical vial containing a
boiling stone to collect the pure product.
13. Using a 9" Pasteur pipet transfer the reaction
solution to the chromatography column.
14. Using the same 9" Pasteur pipet, rinse the
reaction vial with 2 x 0.5 mL of CH2Cl2 and
transfer to the chromatography column.
15. An additional 2.0 mL of CH2Cl2 is used to
finish the elution of the column.
75
Spring 2014
16. Check the purity of your product by GC. Inject 1

L of the CH2Cl2 solution in the analytical GC.
Record the Rt's and ratio of the 2 products in
your notebook. Tape the GC trace in your
notebook.
17. The CH2Cl2 is removed on the hotplate set at 50
C using a gentle stream of N2.
18. Weigh the ester and calculate the % yield.
19. Using a 9" Pasteur pipet add 1 drop of the
product onto your IR card after you have run the
evaporate for ~ 1 minute. Run the Sample

spectrum and Plot the spectrum. Identify the
bands attributed to the two C-O and carbonyl
groups (C=O) on your IR spectrum. Tape the
spectrum in your notebook.
21. Indicate on your spectrum the bands attributed to
the ester functional group. Tape the IR spectrum
in your notebook.
ANS-Esterification Mechanism
.. _
:O :
:O :
sp2
C
Cl
CH3
sp3
Cl
CH3
a c e ty l c h lo rid e
..
R -O :
R O H = 4 -t-b u ty lc y c lh e x a n o l
..
: O -H
:O :
sp
sp3
C
O -R
CH3
Cl
CH3
e s te r
R
:O :
:O :
CH3
+ H
:O :
:O
H -C l
C
O
CH3
CH3
C
O
CH3
a c e t y l a n h y d r id e
..
: OH
R
.. H
:O
CH3
.. +
O -H
.. H
:O :
:O
C
O
CH3
CH3
C
+:O
O
..
:O
CH3
C
O
CH3
+
O -R
C H 3 C O 2 H /H +
e s te r
76
Spring 2014
Lab#11:
Acyl Nucleophilic Substitution (ANS): Rate of Base-Induced Hydrolysis
of Cyclohexyl Acetate
O
O
OH
CH3
NaOH / H2O / ethanol
O
+
NaO
CH3
cyclohexyl acetate (RCO2R')
cyclohexanol
Readings: pages 837-840 in lecture textbook 8e.

Base-induced hydrolysis (saponification) of esters is an example of acyl nucleophilic substitution (ANS)
where the nucleophile, hydroxide, attacks the electrophilic carbonyl carbon atom in a two step reaction
mechanism to produce an alcohol and a carboxylate anion. This is an example of a bimolecular reaction,
meaning the rate of the reaction is proportional to the concentration of two species the hydroxide ion [OH] and the ester [RCO2R]. The rate equation for the above reaction is:
rate = -d [RCO2R]/dt = k [-OH] [RCO2R]
where k is the rate constant for the reaction. In this experiment the [-OH] = [RCO2R] so the above
equation simplifies to:
-d [RCO2R]/dt = k [RCO2R] 2
Integration of this differential rate equation produces:
1/[RCO2R]t = kt + 1/[RCO2R]0
where [RCO2R]t is the concentration of the ester after t seconds.
The rate constant k, in M-1 sec-1, is obtained from the slope of a straight line plot of 1/[RCO2R] vs t.
The following experiment is to be performed in two teams of 2 students. One student does the gc injections
and records the data, and the other does the calculations, and graphing. The first 2 teams will begin as soon
as possible and a subsequent team will begin when one team notifies them that a GC is available. Calculate
and measure all data to 3 significant figures.
Procedure:
1. Weigh cyclohexyl acetate (71.1 mg, 0.500
mmol) into the bottom of a clean, dry tared 5mL conical flask. The person who did the
weighing should have the weight data in his/her
notebook.
2. Place the magnetic stir vane into the flask and
carefully transfer 95% ethanol (3.00 mL) into
the flask using an automatic pipet held in an upright position. Attach the screw cap to prevent
loss of solvent. Stir at room temperature for
about 10 minutes to dissolve the ester. The
person who measured this volume should have
this information in his/her notebook.
3. After stirring for 10 minutes carefully add 1.00

M NaOH solution (0.500 mL) rapidly using an
automatic pipet. Note the time of the addition (t
= 0) by pushing Start, then Stop on the gc
intergrator. Continue stirring the reaction. The
person who measured this volume should have
this information in his/her notebook. Note:
[RCO2R]0 = 0.50 mmol/3.50 mL = 0.143 M and
0 = time 0
4. The concentration of the ester [RCO2R]t with
time is obtained from the gc percentage of the
ester vs the alcohol product: [RCO2R]t = gc %
of RCO2R x [RCO2R]0 = gc% [0.143 M]
77
Spring 2014
5. Perform the GC analyses (1-L injection of the

reaction solution) at approximately 480, 960,
1440, etc. second intervals. The time, t , will be
recorded on the gc when you push Start at each
injection.
6. List your initial t0 and each t in hrs/min/sec vs
the gc% of [RCO2R] in your notebook. Enter
the data, t in hrs/min/sec and gc% as a decimal,
in the Excel document Reaction Rate on the
computers in the lab. Print and tape the
Reaction Rate data/graph in your notebook.
Measure and calculate the slope, k, for all the
data points on the graph using a trend line.
7. Circle the data points on the graph that resulted
from your teams injections.
8. Report the GC column temperature and the He

flow rate. Report the experimental times,
retention times and area % of cyclohexyl acetate
for your team's injections.
9. Measure and report that value for k with the
correct units. Calculate and report the rate of the
reaction at t0 with the correct units. R2, provided
by the instructor, is the least squares fit of your
data on the trend line.
10. Describe what you did, what you observed, and
explain your results including your R2, k, rate at
t0. Account for any errors, unusual observations,
data point(s) off the trend line, or results.
Saponification (ANS) Mechanism

Step 1: formation of tetrahedral intermediate by nucleophilic addition of HO- to C=O bond
O
O
O
OH
sp 3
CH3
CH3
HO
Step 2: dissociation of tetrahedral intermediate by elimination of alkoxide & deprotonation of carboxylic

acid
O
3
O
HO
sp
OH
2
sp2
sp
CH3
HO
O
CH3
CH3
78
Spring 2014
Rate of Base-Induced Hydrolysis of Cyclohexyl Acetate
79
Spring 2014
Lab#12:
Aldol Condensation: Synthesis of dibenzalacetone
O
CHO
CH
C
CH
CH
CH
CH3
H 3C
NaOH / EtOH/ H2O
benzaldehyde
dibenzalacetone
Readings: pages 309-317 in lab textbook 5e & pages 904-910 in lecture textbook in 8e.
Homework problems: 6-132, 6-133 & 134b in 5e ( pag. 316/317) OR in 4e (pag. 285/286)
This is an example of a mixed aldol condensation (Claisen-Schmidt reaction) between a ketone
(acetone) with -protons and an aldehyde (benzaldehyde) with no -protons.
Procedure:
1. Place a spin vane in a 3.0-mL conical flask and
using the automatic pipet provided add 80.0 L
(84.0 mg, 0.792 mmol) of benzaldehyde.
Caution: keep the automatic pipet vertical.
2. Attach a septum cap to the vial.
3. Add 29.0 L (22.8 mg, 0.393 mmol) of acetone
using an automated pipet.
4. Open the flask and add 1.0 mL of
NaOH/H2O/EtOH solution using a calibrated
automatic pipet, then replace the cap.
5. The reaction mixture is stirred at room
temperature for 30 minutes. During this time a
yellow solid precipitates from solution.
6. Remove the spin vane with forceps and transfer
the contents of the 3.0-mL flask into a weighed
12-mL centrifuge tube using a 6-Pasteur pipet.
Then carefully centrifuge, separate, and discard
the aqueous layer using a 6-Pasteur pipet.
7. Wash the remaining product in the 3.0-mL
reaction flask with 1.0 mL of H2O by vortex
mixing and transfer it to the 12-mL centrifuge
tube.
8. Carefully centrifuge, separate, and discard the
aqueous layer using a 6-Pasteur pipet.
9. Repeat steps 7 and 8 at least 8-12 times until the
aqueous layer is neutral to pH paper (pH = 7).
Test with the pH paper on a clean surface (paper
towel).
10. Dry the product using a warm water-bath (60-70

C) on the hotplate with a gentle stream of N2.
11. Cool to room temperature. Insert a boiling stick.
12. Dissolve the product in a minimum amount
(~1.0 mL) of 95% EtOH, stirring with the
boiling stick, and using a hot water-bath (80-90
C) on the hotplate.
13. Concentrate the solution to ~0.75 mL by boiling,
remove the stick and cool to room temperature
slowly, and then cool in an ice bath for 15
minutes.
14. Centrifuge and carefully remove the liquid layer
with a 9" Pasteur pipet.
15. Dry the crystals using a warm water-bath (60-70
C) on the hotplate with a gentle stream of N2
followed by vacuum drying.
16. Weigh the product and calculate the % yield.
17. Place ~2 mg the product in a clean dry a clean
dry 6 x 50 mm culture tube. Using a 9" Pasteur
pipet, add 3 drops of Et2O and mix by swirling.
18. Perform a TLC analysis on the product by
spotting 2 L on a TLC plate and developing the
plate with EtOAc. Visualize the plate by UV
light and mark the spots with a pencil. Calculate
the Rf's of the spots. Tape the TLC plate in your
notebook.
80
Spring 2014
21. Perform the 2,4-dinitrophenylhydrazine (2,4DNP) test described on page 630. Dissolve ~ 5
mg of product in 5 drops of 95% EtOH and add
7-8 drops of the 2,4-DNP reagent. Use a 6x50
mm culture tube in place of a spot plate.
What did you observe?
19. Using a Pasteur pipet place 1-2 drops of this

evaporate for ~ 5 minutes. Run the Sample
spectrum and Print the spectrum. Identify the
bands attributed to the alkene, ketone and
aromatic ring groups on your IR spectrum. Tape
the spectrum in your notebook.

Aldol Condensation Mechanism:
S tep 1: F o rm ation of en olate from aceto n e

O
H
C
CH3
..
:O
.. H
..C
CH3
C
H
CH3
en o late ion stab ilize d b y reso n an ce

Step 2: Nucleophilic attack of the enolate on the carbonyl of benzaldehyde and formation of a -Hydroxy
ketone.
O
C
H3C
OH
OH
:O:
H3C
CH2
H3C
H
electrophile
nucleophile
aldol
Step 3: Elimination of water and formation of alpha-beta unsaturated ketone

OH
H3C
OH
H3C
H3C
H
- H2 O
- H2 O
HO
Repeat on the
O
right side.
81
Spring 2014
Check out procedure

1. On second to last lab.
a. Students check glassware on their drawer before leaving.
b. The instructor will issue debt notice to all students who have lost or broken glassware.
Debt is to be paid before check-out.
c. Dirty glassware will be soaked in KOH/ Ethanol mix.
2. Last Lab
a. Each student to clean glassware and drawer.
b. The glassware paid at the cashier will be replaced.
c. If any more missing glassware is discovered, students are to go to cashier and pay before
being checked out.
d. Disposables can be replaced for free (Pasteur pipettes, etc).
e. Once students are ready will checkout and sign up on the original sign in sheet.
f. Place a department lock on the drawer.
82

Note For All 202L Sections - Spring2014

Hochgeladen von

Dokumentinformationen

Originalbeschreibung:

Originaltitel

Copyright

Verfügbare Formate

Dieses Dokument teilen

Dokument teilen oder einbetten

Freigabeoptionen

Stufen Sie dieses Dokument als nützlich ein?

Sind diese Inhalte unangemessen?

Copyright:

Verfügbare Formate

Note For All 202L Sections - Spring2014

Hochgeladen von

Copyright:

Verfügbare Formate

Chem

202L Laboratory Notes

Professor Steven C. Welch

Dr. Lenuta Gonzales

Department of Chemistry and Biochemistry CSUSM

Chem 202L Laboratory Notes

Mass Spectroscopy: Identification of unknown organic

Infrared Spectrometry: Identification of unknown organic

H-NMR & 13C-NMR Spectrometry: Identification of

Electrophilic Aromatic Substitution (EAS) - Directing

EAS - Friedel-Crafts Alkylation: Synthesis of 1,4-di-tbutyl-2,5-dimethoxy-benzene.

Nucleophilic Addition (NA): Reduction of 4-tbutylcyclohexanone to cis- & trans-4-t-butylcyclohexanol.

NA - Grignard reaction: Synthesis of triphenylmethanol.

Oxidation Reaction: Synthesis of 9-fluorenone.

Substitution Nucleophilic (SN-2) - Williamson Synthesis:

Acyl Nucleophilic Substitution (ANS) - Esterification:

Acyl Nucleophilic Substitution(ANS): Rate of Base-Induced

NA - Aldol Condensation: Synthesis of dibenzylacetone

Check out procedure

Chem 202L Laboratory Notes

Pre-Lab Reading Assignment

Check-in, Chapter 1: Introduction,

Unknowns: Mass Spectra, Rule 13,

Unknowns: 13C- and 1H-NMR Spectra

Directing Effects in Electrophilic

355-56; 634638, 734-735

SN-2: Williamson Ether Synthesis: propyl

623; 795 797

NA: Aldol Condensation: Synthesis of

Oxidation (H2CrO4 / acetone): Synthesis

Chem 202L Laboratory Notes

Chem 202L Laboratory Notes

Requirements for Being a Scientist

Chem 202L Laboratory Notes

How to Survive Chemistry Lab

Chem 202L Laboratory Notes

Chem 202L Laboratory Notes

10. Draw of the experimental set-up or the flow chart of procedures.

Chem 202L Laboratory Notes

10%silver nitrate/ silica AgNO3/

Theoretical yield goes here!

Example of Calculation of Theoretical and Percent Yield

H2PtCl6 / NaBH4/ H3O

120 L x 0.72 mg/L = 86.4 mg octane;

Chem 202L Laboratory Notes

Example of a Typical Experimental Summary and Conclusions

The following were applicable in writing the above section:

Chem 202L Laboratory Notes

Identification of Unknown Structures by Combined

Chem 202L Laboratory Notes

Base peak = most prevalent and stable radical-cation or carbocation fragment

Hydrocarbons usually fragment to give the largest radical R

Rule of 13: M.+ /13 = n + r MF = CnH(n+r)

Rule of 13 substitutions (C=12H, O=CH4, N=CH2, etc.)

Nitrogen rule: M.+ is odd for an odd number of Ns

larger alkyl radical

Chem 202L Laboratory Notes

M + 1 & M + 2 are from the

Fragmentation Rules for Mass Spectroscopy

3. Alkyl-substituted aromatic compounds undergo cleavage to form resonance-stabilized benzyl cations

Chem 202L Laboratory Notes

5. Carbonyl compounds with a g-hydrogen atom fragment by the McLafferty Rearrangement: