Organic Chemistry Lab Manual, Chem221 - Fall2012 - LabManual

Chemistry 221:
Organic Chemistry I

2012 Lab Manual

Chemistry 221:
Organic Chemistry I

2011 Lab Manual

Chem 221: General Laboratory Instructions

Welcome to lab!

The laboratory period starts promptly (M 3:00 pm, Tu and Th 8:00 am, Tu and Th 2:30 pm, W
2:00 pm) with a pre-lab lecture in Merrill 430. We will then move to the organic lab, Room 421.
You must come on your assigned day unless you make other arrangements in advance with your
lab instructor.

You are expected to wear safety glasses at all times when working in the laboratory, except
when explicitly told otherwise. We will issue a pair to you at the beginning of the semester,
which should be returned at the end of the semester. You may wear contact lenses in the
laboratory; we also have safety glasses that will fit over your prescription glasses. Open-toed
shoese.g., sandalsand shorts are not permitted in the lab, nor are exposed midriffs! So
as to avoid dangerous entanglements, long hair should be securely tied back. Finally, no
food (including chewing gum) or drink (including water) is permitted in the lab.

A good laboratory notebook is an indispensable part of your work in the lab. For use in this
course, we ask that you obtain an Organic Chemistry Laboratory Notebook from the stockroom.
On page ii, you will find guidelines for keeping a good notebook. Follow them! Please write
neatly and concisely. A feature of this notebook is that a carbonless copy of all of your entries
is generatedwe will collect these copies when you have completed your work for the day.
Some weeks, you will be completely finished with the experiment when you submit these copies;
for the other weeks, you will also be required to write a more formal lab report.

A crucial part of your preparation for an experiment is an understanding of what you will be
doing. This knowledge will save you time in the lab and will prevent you from making mistakes.
Before coming to lab, therefore, you should read the lab handout and the supplementary reading,
if any. Furthermore, we will usually ask that you write a pre-lab reportrequirements
for which will be explained in each individual experimentin your laboratory notebook.
The pre-lab report for a given experiment will be turned in to your T.A. before the pre-lab
lecture.

Be considerate of your fellow students and of yourself. Keep your desktop neat, and clean up
your work areas at the end of the afternoon. After weighing out any material, tidy up the balance
and surrounding environs. Wash your dishes! Wet glassware hung on your rack and placed in
your bench will be dry by the following week.

All work submitted in the laboratory, as in the rest of this course, should be your own. You
may, of course, talk with your classmates prior, during, and after the labswe encourage
you to do soand you will be working with a lab partner. Nonetheless, your pre-lab
reports, lab notebook, and lab write-upsthat is, the work you submitmust not be copied
from another student or be the product of a joint effort. Occasionally, you will need to
use data that was acquired by your partner or another lab group. In such cases, the
source(s) of the data must be clearly acknowledged in your write-up.

Chem 221: Schedule of Laboratory Experiments

Week Experiment

09/03 0. Check-in

09/10 1. Distillation

09/17 2. A Reaction of Cyclohexene

09/24 3. Extraction & Acid-Base Chemistry

10/01 4. (More Extraction and) Thin-Layer Chromatography

10/08 FALL BREAK (M, Tu)
5. Molecular Modeling Extravaganza! (W, Th)

10/15 5. Molecular Modeling Extravaganza! (M, Tu)

10/22 6. S
N
1, S
N
2

10/29 7. Determination of the Rate of a Chemical ReactionKinetics of the Solvolysis
of t-Butyl Chloride

11/05 8. Recrystallization

11/12 9. Qualitative Analysis

11/19 THANKSGIVING VACATION

11/26 10. Infrared Spectroscopy

12/03 11. Spectroscopy Dry Lab

Experiment 1:
Distillation and Gas Chromatography

Week of September 10

Chemistry 221 Fall 2012
1
Experiment 1: Distillation and Gas Chromatography
Pre-lab Preparation
Before coming to lab, read Jones, sections 15.1 and 15.2. Also, please download and read the
supplementary material for this experiment (from Fieser and Williamson, Chapter 5,
Distillation, and from Fessenden, Fessenden, and Feist, Technique 13, Gas
Chromatography).
Additionally, please answer the following pre-lab questions:
Pre-lab Q1: In your notebook, write a short paragraph summarizing what you will be doing in
this experiment and what you hope to learn about the efficiencies of the distillation techniques.
Pre-lab Q2: Look up the structures and relevant physical data for the two compounds you will be
using. What data are relevant? Read the procedure, think about the data analysis, and decide
what you need.
Background
While crystallization is the most commonly performed operation in the organic chemistry
laboratory, distillation is number two. It is also harder to do properly, as you will see this
afternoon. Moreover, distillation underlies the technique of gas-liquid chromatography (GLC)
often shortened to gas chromatography or simply GCwhich is one of the most frequently and
most readily performed of the common instrumental methods.
Procedure
You will perform two distillations, the first simple, the second fractional. Please work with a
lab partner.
1. Perform a simple distillation using the apparatus pictured on the next page. Note the
following:
Experiment 1 Fall 2012
2
Before beginning, familiarize yourself with the assembly of the apparatusa little
advance planning will minimize the possibility of a spill. Be sure that the rubber tubing is
securely attached to your condenser and that a rubber band is positioned over both the
condenser inlet and outletas shown, these rubber bands will securely hold the
condenser in place once everything is fully assembled. The direction of the water flow
will be through the lower end of the condenser and out the upper.
Begin by setting the infrared (IR) lampthe heat source for the distillationinto place.
Well show you a neat way to support the lamp (discovered after the picture below was
drawn!).
Clamp the round-bottom flask (use the 100 mL size) to the monkey bars. This clamp
provides most of the supportmake sure that it is securely attached to the monkey bars
and is finger-tight around the flask. Center the round bottom directly above the lamp with
the screen and round bottom gently touching. (As you see, flask is typically dropped
from round-bottom flaskjust like the period in Dr Pepper.) Using a graduated
cylinder, add 50 mL of the 40:60 (v/v) mixture of cyclohexane and toluene provided in
the laboratory to the round bottom; to promote smooth boiling, also add a few boiling
stones.
Chemistry 221:
Organic Chemistry I

2011 Lab Manual

The apparatus for a simple distillation.
3
Now lightly grease the ground-glass joints of the remaining pieces of glasswarea little
dabl do ya. Wipe off any excess grease with a Kimwipe
lab tissue. Assemble the rest

of the apparatus, remembering to employ the rubber bands as shown in the diagram.
While the clamp holding the condenser should, of course, be well secured to the monkey
bars, it should not be tightened around the condenser itself (otherwise, undue stress will
be placed on the ground-glass joints).
Use a mercury thermometer (available in the lab, as are the brick-red rubber adapters
needed to secure the thermometer to the still head) and position it as shownthat is, with
the top of the bulb just below the side arm of the still head. Use a 100 mL graduated
cylinder to collect the distillate (you may need to use a few wooden blocks or a clamp to
position the graduated cylinder directly underneath the end of the distillation apparatus).
2. After assembling everything, gently turn on the cooling water. The flow should be a slow
streamtoo much pressure may pop a rubber tube, resulting in a flash flood for you and your
neighbors! Again, water goes in the lower end of the condenser and out the upper. Before
proceeding, have your lab instructor or T.A. check your set-up. Once you have received the
okay, review the instructions below and then turn on your lamp and distill away!
As the distillation proceeds, you should:
Record the temperature at the still head for each 2 mL of distillate collected.
Nota bene: The rate of distillation should be such that you get drops of distillate at a steady
ratesay 30 drops a minute. A steady stream of distillate is much too fastif necessary, you
should slow the rate by moving the IR lamp an inch or two farther away from the round bottom.
At three points during the distillation, collect samples comprising three or four drops of
distillate in a small test tube for subsequent GC analysissimply shift the graduated
cylinder to the side and directly collect the drops in the test tube; then immediately
reposition the graduated cylinder and stopper the test tube with a cork. Collect the three
samples at different still-head temperatures: Ideally, you should collect the first and last
few drops of distillate, as well as a sample in the middle. Label the corks of your samples
with both your initials and an S1, S2, or S3 (for simple distillation, fractions 1-3).
As soon as possible, rush each sample to your T.A. for instant GC analysis.
4
Continue the distillation until you have collected 36 mL of distillate. Do not leave your
apparatus unattended and do not let the cyclohexane/toluene mixture distill to dryness
(you will have a 14 mL cushionstill, pay attention!).
4
with both your initials and an S1, S2, or S3 (for simple distillation, fractions 1-3).
As soon as possible, rush each sample to your T.A. for instant GC analysis.
Continue the distillation until you have collected 36 mL of distillate. Do not leave your
apparatus unattended and do not let the cyclohexane/toluene mixture distill to dryness
(you will have a 14 mL cushionstill, pay attention!).

3. Once you have collected the 36 mL of distillate, turn off the IR lamp. Allow the glassware to
cool for a few minutes and then pour the distillate back into the round bottom. Add a few fresh
boiling stones. Mentally prepare for the fractional distillation by studying the diagram on the
next page.
Before you assemble this apparatus, obtain a dry condenser, still head, and distillation
adapter from the partner whose glassware was not used for the first distillation (this will
ensure that the first drop of fractional distillate collected for GC analysis isnt contaminated with
the last drops from the simple distillation). Then, pack your distilling (i.e., fractionating) column
with the ceramic saddles provided in the laboratory. (Note that these saddles are expensive.
When you are finished with the experiment, please return them whence they came. Do not, under
penalty of a severe frown, discard them into the drain, wastebasket, etc.) As shown in the
diagram, the packed column should be inserted between the round bottom and the still head.
Once you have reassembled the distillation apparatus (dont forget the fresh boiling stones), you
should wrap the fractionating column and still head in aluminum foil to ensure efficient heating.

3. Once you have collected the 36 mL of distillate, turn off the IR lamp. Allow the glassware to
cool for a few minutes and then pour the distillate back into the round bottom. Add a few fresh
boiling stones. Mentally prepare for the fractional distillation by studying the diagram on the
next page.
Before you assemble this apparatus, obtain a dry condenser, still head, and distillation
adapter from the partner whose glassware was not used for the first distillation (this will
ensure that the first drop of fractional distillate collected for GC analysis isnt contaminated with
the last drops from the simple distillation). Then, pack your distilling (i.e., fractionating) column
with the ceramic saddles provided in the laboratory. (Note that these saddles are expensive.
When you are finished with the experiment, please return them whence they came. Do not, under
penalty of a severe frown, discard them into the drain, wastebasket, etc.) As shown in the
diagram, the packed column should be inserted between the round bottom and the still head.
Once you have reassembled the distillation apparatus (dont forget the fresh boiling stones), you
should wrap the fractionating column and still head in aluminum foil to ensure efficient heating.
To further ensure efficient heating, carefully center the IR lamp directly below the round
bottom with the screen and round bottom gently touching.
5
When all is again ready, switch on the IR lamp and begin the distillation. If the first drops of
distillate dont appear after a few minutes, seek assistance from your instructor or T.A. Proceed
as above, collecting 36 mL of distillate and recording the temperature data. Again, sequester
three samples for GC analysislabel each with your initials and an F1, F2, or F3 (for
fractional distillation, fractions 1-3). When you are finished with this distillation, you should
pour the pot residue and distillate into the waste bottle located in the hood.
5
To further ensure efficient heating, carefully center the IR lamp directly below the round
bottom with the screen and round bottom gently touching.
When all is again ready, switch on the IR lamp and begin the distillation. If the first drops of
distillate dont appear after a few minutes, seek assistance from your instructor or T.A. Proceed
as above, collecting 36 mL of distillate and recording the temperature data. Again, sequester
three samples for GC analysislabel each with your initials and an F1, F2, or F3 (for
fractional distillation, fractions 1-3). When you are finished with this distillation, you should
pour the pot residue and distillate into the waste bottle located in the hood.

The apparatus for a fractional distillation.

The apparatus for a fractional distillation.
6
Topics for Report
For your lab report, you need only answer the questions belowthat is, you need NOT write an
introduction, summary of the experiment, etc.! (As noted below, we will also ask you to hand in
the carbonless copies of your notebook pages for this experiment.)
1. Make a plot of still-head temperature vs. volume of distillate for both the simple and
fractional distillation. What do your plots tell you about the efficiencies of the two kinds of
distillation? Hint: The plot for a perfect fractional distillation would look like this:

2. Do the GC analyses of the samples you collected at three points during each distillation
(S1, S2, S3 and F1, F2, F3) corroborate your answers to Question 1? Explain.
3. GC was invented around 1960. Imagine you were doing a Ph.D. thesis in 1950. You have a
mixture of cyclohexane and toluene, the composition of which you have to determine before
you can start writing your thesis. How could you readily accomplish this task? (The answer
wait ten years is unacceptable!) Hint: In 1950, you would have had at your disposal the
data plotted in Fig. 2 on p. 60 of the supplementary reading from Fieser and Williamson!
4. Suppose you met someone who had never seen a gas chromatograph. You want to give the
person a sense of how GC works. What would you say? (Hints: What are the principles
underlying fractional distillation? Why is there a positive pressure of helium gas passing
through the GC column?)
7
This lab report is due in your regular lab period next week. In addition to your answers to the
above questions, you should hand in the carbonless copies of your lab notebook pages for this
experiment.

Experiment 2:
A Reaction of Cyclohexene


1
Experiment 2: A Reaction of Cyclohexene
Pre-lab Preparation
Before coming to lab, please read Jones, section 15.4.
Additionally, answer the following pre-lab questions:
Pre-lab Q1: Look up the relevant physical data for cyclohexene and draw its structure. (What
data are relevant? Consider the experiment. For example, are you going to boil it, freeze it, or set
fire to it? Do you need the boiling point, the melting point, or the flash point?)
Pre-lab Q2: Refer to the data table on page 4 of this handout, and determine what IR absorptions
you should see in your spectrum of cyclohexene.
Background
Today you will be given the opportunity to investigate an intriguing chemical transformation
the reaction of cyclohexene with palladium-on-charcoal catalystand we shall not tell you either
the products or the mechanism of this reaction. It will be your task to run the reaction, to analyze
the products using gas chromatography (GC) and infrared (IR) spectroscopy, and to generate a
plausible explanation for your observations.

2
As you know from last week, GC readily allows the components of a mixture of liquids to be
separated and quantified. IR spectroscopy is also an invaluable tool for analyzing chemical
reactions: Functional groups that have disappeared from the reactant or that have appeared in the
product can typically be identified.
Procedure
Work with a partner. Into your 50 mL round bottom flask, which must be dry (it does not have
to be sparkling clean), add 3 mL cyclohexene and approximately 0.10 g palladium-on-charcoal
catalyst (you can eyeball thisthis amount is about the size of half an aspirin tablet). Also add a
few boiling stones. Clamp the flask to the monkey bars above an IR lampwe will use the lamp
to heat the reaction, rather than the steam pot shown in the figure below.

Apparatus for Reflux
3
Make sure the top finger on the clamp is just below the lip on your round bottom. Attach a
reflux condenser, first using a tiny bit of vacuum grease to lubricate the ground-glass joint
(really, just a tiny bit of grease is enough!), and gently turn on the cooling water. The water
flows in the bottom of the condenser, out the top, and not too rapidly (simulating a fire hose is
not the idea here!). When you have finished assembling your apparatus, heat the contents under
reflux for one hour. Once the reaction has fully come to a boil, you should raise the reflux
apparatus so that the round bottom is about 5 inches above the lampto use a cooking analogy,
you want to allow your reaction to simmer, not boil uncontrollably.
Note: Reflux, the most commonly performed operation in organic chemistry, literally means a
flowing back.
When the hour has elapsed, turn off the IR lamp, and allow the reaction to cool for a minute or
two. Add one drop of water to coagulate the catalyst, add three or four pieces of calcium chloride
(CaCl
2
) to remove excess water, and then, using a piece of fluted filter paper in a stemmed, glass
funnel, filter the suspension into the clean, dry test tube provided.
Analysis
First, be sure to keep your filtered product tightly stoppered so that its composition doesnt
change!
GC
Obtain a gas chromatogram of the mixture. Assume that molar response ratios for all
components are unity, i.e., Area A/Area B = [A]/[B]. Calculate the relative concentrations of the
components in your mixture. You will be told the retention time of cyclohexene. Consideration
of these relative concentrations is the first step in determining the fate of cyclohexene in the
presence of the palladium-on-charcoal catalyst.
NOTE: If your gas chromatogram contains three peaks, make sure you talk to your instructor.
4
IR
Next, obtain an infrared spectrum of the mixture as a neat sample. You will be provided with the
IR spectrum of cyclohexene. The second key to solving todays riddle will be an analysis of key
carbon-hydrogen and carbon-carbon absorptions in the samplethe table below should be of
great utility.
Bond type
Typical ! range
Intensity
C
sp
H stretch
3310 - 3320 cm
1

Strong
C
sp
2
H stretch
3000 - 3100 cm
1

Moderate
C
sp
3
H stretch
2850 - 2950 cm
1

Moderate
C"C stretch
2100 - 2200 cm
1

Weak-Moderate
C=C=C stretch
1900 - 2000 cm
1

Moderate
C=C stretch
1640 - 1670 cm
1

Weak-Moderate
C=C stretch
(conjugated)
1600 - 1630 cm
1

Moderate
CC combo stretch
(aromatic ring)
1450 - 1500 cm
1
Moderate
CH
2
bend
1420 - 1480 cm
1

Strong
=CH bend 650 - 1000 cm
1
Weak-Moderate
=CH bend
(aromatic ring)
700 - 800 cm
1

Moderate-Strong
Characteristic IR Absorptions
Topics for Report
Answer the questions below and on the following page.
1. What are the products of the cyclohexene/Pd reaction? Which data proved most useful in
your analysis? Explain, noting clearly what conclusions you could draw from each of your
data sources.
5
2. Write a balanced chemical equation for the reaction that has occurred. Please be sure that it
accounts for the ratio of the products observed.
3. Provide a quantitativei.e., using actual numbers!explanation for why the reaction
goes. You must use enthalpies of hydrogenation in your analysis. We will assume that in
this instance #H ! #G. Remember, the palladium catalyst is just thata catalyst. (Hint:
Use Hesss Law.)
In addition to your carbonless copies, please attach your spectra, chromatograms, etc. to your lab
report. Its due in your regular lab period next week.

Experiment 3:
Extraction & Acid-Base Chemistry


1
Experiment 3: Extraction and Acid-Base Chemistry

Pre-Lab Preparation
(1) Please read the supplementary material for this experiment, which you can download from
our course site: Fessenden, Fessenden, and Feist, Technique 3, Extraction, Sections 3-3.4.
(Note that the relevance of this reading will become apparent when you reach Section 3.4,
Chemically Active Extraction.) (2) For benzoic acid, 2-napthol, and 1-aminoadamantane write
out acid-base equilibrium expressions (akin to the one for In-OH on the next page). In each
equilibrium expression, draw out complete structures for the organic molecules participating in
the acid-base chemistry and show all (non-zero) formal charges. Circle the organic structures that
you predict to be water-soluble. (3) Answer the following two pre-lab questions:

Pre-lab Q1: Organic chemists often talk about the aqueous and organic layers of extractions
as if all organic solutions were the same; of course, theyre not. In your extractions for todays
lab, you will use diethyl ether as the organic solvent, but a number of other organic solvents
could be used to effect similar separations. Imagine you used dichloromethane (a.k.a. methylene
chloride) instead of diethyl ether. What would be different about your experimental protocols in
todays lab?

Pre-lab Q2: In todays lab, you will regularly use solutions of the strong acid HCl. Yet, we never
even bother to give you the pK
a
of HCl in the list of essential pK
a
values (Part 2, Question 9).
Why not?
2

Background

Your previous experience with acids, bases, pH, pK
a
s, etc., may have left you somewhat
confused. We hope, however, that this afternoons simple experiments will prove to be most
illuminatingplease work with a partner and thoroughly discuss all of your observations.
Procedure
Part 1: In the first part of this experiment, we will use an indicator, 2,6-dichloroindophenol (In
OH), to learn how protonation and deprotonation can be used to move a compound between
organic and aqueous layers. 2,6-dichloroindophenol (InOH) itself is red, but its conjugate base
(InO
) is bluethese different colors will literally let you see whats going on.

3
In the lab, you will find a deep blue, basic solution of InO

Na
+
(this solution contains 25 mg
of InO

Na
+
in 50 mL of 0.02 M NaOH). Using a Pasteur pipette, add two drops of this
solution to a 15 mL falcon tube. Then use a fresh clean Pasteur pipette to add approximately 3
mL (two squirts from the pipette) of water to the falcon tube.
NOTE: Pasteur pipette bulbs are reusablei.e., discard the pipette after every
measurement but not the bulb!!
Using yet another fresh pipette (OK, you get the idea), add approximately 3 mL of diethyl ether
to the tube. Seal the falcon tube tightly with a cap and mix by inverting several times.

1. What is the structure of diethyl ether? (Note, diethyl ether is commonly referred to
simply as ethyl ether or even more simply as ether.)

2. How many phases are there in the falcon tube? That is, are ethyl ether and water
miscible?

3. Which solvent is on top, and which is on the bottom? How could you readily (and
quickly) tell for sure?

4. Which layer contains the indicator (the ether or the water)? Based on its color, is
the indicator in its neutral (InOH) or anionic (InO
Na
+
) form? Thinking now in
terms of structure and polarity (of both the indicator and the two solvents), explain
briefly why the indicator is where it is. In other words, why is it dissolved in one
solvent and not the other?

Now add 2 drops of 0.05 M aqueous HCl to the falcon tube. Note the appearance of the mixture
before shaking. Cap and mix.

5. How did shaking the falcon tube change in the appearance of the mixture? In
chemical terms, explain what just happened.

4
6. After shaking, which layer contains the indicator? Based on its color, what is the
form of the indicator (i.e., InOH or InO
Na
+
)? Thinking again in terms of
structure and polarity, explain briefly why the indicator is where it is.

Now add 2 drops of 0.1 M aqueous NaOH to the falcon tube. Cap and mix.

7. Which layer contains the indicator? Based on its color, what is the form of the
indicator (i.e., InOH or InO
)? As you will see, we have now returned to where we

begandoes this all make sense to you?

Part 2: In the second part of this experiment, we will work with standard colorless organic
compoundsi.e., from this point on, we wont have the red and blue colors to help us! In
particular, we will study benzoic acid, 2-naphthol (used in place of the simpler benzene
derivative phenol, C
6
H
5
OH, which has a similar pK
a
but which is smelly and corrosive) and 1-
aminoadamantane (one of the first antiviral compounds in clinical use):
O OH
Benzoic acid
pK
a
= 4
2-naphthol
pK
a
= 10
1-aminoadamantane
pK
a
= 10
(for NH
3
+
)
OH
NH
2

NOTE: While organic compounds are usually drawn as neutral molecules (and are typically
commercially available as such), pK
a
values always pertain to the conjugate acid (as explicitly
noted for the 1-aminoadamantane above).
A. Place 50 mg of benzoic acid into each of four falcon tubes. (You should weigh out the 50
mgwhich equals how many grams?for the first tube and then just eyeball the amount for the
remaining three.) Use a Pasteur pipette to add approximately 3 mL (again, two squirts from the
pipette) of 1 M aqueous HCl to the first tube, 3 mL of distilled water to the second, 3 mL of 1 M
5
aqueous NaHCO
3
to the third, and 3 mL of 1 M aqueous NaOH to the fourth. Seal each tube
tightly with a cap and mix by inverting several times.

8. In which falcon tube(s) does the benzoic acid dissolve?

9. Explain why the benzoic acid has dissolved in some of the tubes but not others by
writing out the relevant acid-base reactions. Here is information that will be essential
as you consider this question: the pK
a
of H
3
O
+
(hydronium ion) = 1.7; the pK
a
of H
2
O

= 15.7; and the pK
a
of H
2
CO
3
(carbonic acid) = 6.4.

B. Take one of the solutions into which the benzoic acid has dissolved. Add the appropriate
solution to neutralize it (e.g., an acid to a base) and to change its pH to the opposite end of the
range. (Warning: Rapid addition of acid to a bicarbonate solution leads to much fizzing!)

10. What do you observe? Write out an acid-base reaction that describes what has
happened.

C. Now, add diethyl ether (3 mL) to the tube from part B, seal tightly with a cap and mix by
inverting several times.

11. Where is the benzoic acid now?

12. How might you recover it in pure formthat is, free from any acid or base or
salt? (Hint: Ether has a very low boiling point and thus evaporates quickly at room
temperature.)

D. First check your answer to question 12 with your instructor and then attempt actually to
recover the benzoic acid.

E. Repeat parts A and B using 2-naphthol in place of benzoic acid (you can imagine how parts C
and D would go!). Be sure to make use of the pK
a
s above in Question 9!

6
F. Now, repeat Parts A and B using 1-aminoadamantane in place of benzoic acid. Again, be sure
to make use of the pK
a
s above in Question 9!

13. Given all of your results above (in both Parts 1 and 2), summarize your
conclusions regarding the solubility of organic compounds as neutral molecules and
as salts in both organic (e.g., ether) and aqueous solvents?

Note: You are now done with the experimental portion of the lab. If your head is swimming,
and you cant fathom thinking about more acid/base chemistry right now, you may show
your instructor your results and (with his or her approval) leave the lab, leaving parts G and
H to be completed on your own time for next week. Alternatively, it might be helpful to try
to complete G and H nowthat is, when your instructor and T.A. are around to answer
questions. If you choose the latter option, you wont have to write up a lab report this week.

G. Imagine you have a mixture of benzoic acid, 2-naphthol, and 1-aminoadamantane dissolved
in ether. You must obtain the three separate components in pure formi.e. as the neutral organic
compound with all solvents and salts removed.
14. Begin by summarizing your observations so far. Copy the table below into your
notebook, and write either soluble or insoluble in each box.
benzoic acid 2-naphthol 1-aminoadamantane
1 M NaHCO
3

1 M NaOH
1 M HCl
Now draw a flow chartakin to the one shown on p. 58 of the supplementary
readingsummarizing the series of steps you would perform to achieve your goal.

H. To finish, answer the two final questions below which pertain to the difunctional (as
distinct from dysfunctional) compound salicylic acid:
7
O OH
Salicylic acid
pK
a
= 3 and 10
OH

15. For salicylic acid, which pK
a
do you think corresponds to which functionality?
Explain your reasoning.

16. Using only the solutions we employed above (1 M aqueous HCl, 1 M aqueous
NaHCO
3
, and 1 M aqueous NaOH), could you separate an ethereal solution of
benzoic acid and salicylic acid? If so, provide a flow chart indicating how; if not,
explain why.

Topics for Report
Your answers to all the questions posed above will constitute your lab report. If you
finish parts G and H today, you may simply hand in the carbonless copies from your
laboratory notebook to your instructor before you leave. Otherwise, turn in the report
at the beginning of next weeks lab period.

Experiment 4:
(More Extraction and) Thin-Layer Chromatography
Week of October 1

1
Experiment 4: (More Extraction and)
Thin-Layer Chromatography
Pre-lab preparation
(1) Back to acid-base chemistry: Write a flow chart for the separation and isolation (as ethereal
solutions) of benzoic acid, benzocaine, and fluorenone from a mixture of the three. Include
structures of the compounds at every step. Your available solvents are Et
2
O, water, 1 M aqueous
HCl and 1 M aqueous NaOH.
Note 1: Youll actually be doing this separation today, so prepare this flowchart carefully!
Note 2: Less benevolent instructors would make you look up the structures and pK
a
values of
benzoic acid, benzocaine, and fluorenone, but since were such big softies
O OH
O O
NH
2
O
Benzoic acid
pK
a
= 4.0
Benzocaine
pK
a
(conjugate acid) = 2.5
Fluorenone
pK
a
~ 4.0 (?, hard to measure)

(2) On to TLC: Read this handout in its entirety, as well as the short introduction to TLC that can
be found at www.chemguide.co.uk/analysis/chromatography/thinlayer.html (external link on
course website).
(3) Answer the following pre-lab question:
Pre-lab Q: Sketch a prediction for what an (informative) TLC plate that was spotted with a
benzoic acid/benzocaine/fluorenone mixture might look like after development with a suitable
mobile phase. To do this, you will need to make predictions about the relative R
f
values of the
compounds. Remember that this is a predictionits OK to be wrong! Briefly explain your
predictions. (Do not worry about how each compound could be visualized; assume the spots can
be readily seen in your experiment.
2
Introduction
Thin-layer chromatography (TLC) is an extremely valuable analytical technique in the organic
lab. It provides a rapid separation of compounds, and thereby gives an indication of the number
and nature of the components of a mixture. TLC can also be used to identify compounds by
comparison with known samples, to check the purity of a compound, or to monitor the progress
of a reaction or a purification procedure.

This experiment will introduce you to the mechanics of TLC and the chemical principles behind
it. In the first part, you will separate three compounds using the extraction techniques that you
mastered last week; in the second, you will use TLC to analyze the identity and purity of the
compounds you separate.

Principles of TLC
TLC is normally done on a small glass or plastic plate coated with a thin layer of a solid the
most common are silica (SiO
2
) or alumina (Al
2
O
3
). This is the stationary phase. The mobile
phase is an organic solvent or solvent mixture. The sample mixture is applied near the bottom of
the plate as a small spot, then placed in a jar containing a few mL of solvent. The solvent climbs
up the plate by capillary action, carrying the sample mixture along with it. Each compound in the
mixture moves at a different rate, depending on its solubility in the mobile phase and the strength
of its adsorption to the stationary phase. When the solvent gets near the top of the plate, it is
allowed to evaporate, leaving behind the components of the mixture at various distances from the
point of origin. The ratio of the distance a compound moves to the distance the solvent moves is
the R
f
value (retention factor). This value is characteristic of the compound, the solvent, and the
stationary phase.

Silica and alumina are relatively polar stationary phases. Both have OH groups on their surfaces
that interact strongly with polar compounds. Such compounds are adsorbed strongly and
therefore move along the plate slowly, while non-polar compounds are adsorbed only weakly
and are therefore carried along the plate more quickly. Of course, solvent polarity also affects
how fast compounds travel. Polar compounds are carried along quickly by polar solvents, but
3
move slowly or not at all with non-polar solvents. Because non-polar compounds don't adsorb
strongly to the silica, they tend to move more quickly in most solvents. The table below lists
several common chromatographic solvents in order of increasing dielectric constant (!), which is
a measure of bulk polarity. Since a solvent's chromatographic eluting power (ability to move
compounds) is roughly related to its polarity, this is an approximate eluotropic series.
Eluotropic series
Solvent ! " Solvent ! "
alkanes 2 isopropyl alcohol 18.3
benzene 2.3 acetone 20.7
diethyl ether 4.3 ethanol 24.3
chloroform 4.7 methanol 32.6
ethyl acetate 6.0 acetonitrile 37.0
dichloromethane 8.9 water 78.5
* dielectric constant (debyes)
(Data from JA Landgrebe Theory and Practice in the Organic Laboratory, 4th ed, p. 68 and AJ
Gordon, RA Ford The Chemist's Companion, pp 3"14.)

Part A. Separation of three compounds
While we could have you do TLC experiments on already pure compounds right out of the
Aldrich bottle, its more fun and informative to analyze something that youve actually attempted
to purifyyou get to see how well you did! And, since youve recently learned about the power
of acidic and basic extractions to facilitate organic separations, it seems natural to have you use
extraction to purify some compounds for TLC analysis this week. So heres the purification that
will get you to your TLC experiments:
Over the summer, an accident in the stockroom caused the benzoic
acid, benzocaine (ethyl p-aminobenzoate), and fluorenone to get
mixed together. Your mission is to purify them by extraction into
separate ether solutions that can be analyzed by TLC. This will be
done on a larger scale than the extractions you did in experiment 3,
so you'll need to use a separatory (sep) funnel.

4
All three compounds are nearly insoluble in water. But one of them should dissolve in aqueous
acid, and the other in aqueous basethis is not a surprise because you already figured this out in
the flowchart you prepared for your pre-lab report. right? Have your lab instructor or T.A.
check your flow chart before you attempt the actual separation, and (if it checks out) refer to it
liberally during the actual separation process.

Note: The use of the sep funnel is one technical difference from the small-scale (test-tube)
extractions you performed last week. Your instructor will give the class a brief demo on how to
useand how not to usea sep funnel before you begin your own separations. Heres the text
version: Always keep a finger tightly over the sep funnels stopper when shaking. Shake, vent,
shake, vent, shake, vent... make sure you don't point the sep funnel at anyone including
yourself when you vent it. Shake means really shake it vigorously. Your goal is to get good
contact between the liquid phases so that the solute molecules have a chance to sample both
solvents and decide which one they prefer.
Extraction Procedure
(a) You will start by dissolving 1.0 g of the benzoic acid/benzocaine/fluorenone (1:1:1 by mass)
mixture in about 30 mL of Et
2
O. (Save approximately 1 mL of this solution in a set-aside test
tube as a no-purification control in your later TLC analysis.)

(b) If you want to extract with aqueous acid or base, use two 10-mL portions of the 1 M aq. HCl
or NaOH. Do you agree that this should be more than enough based on the amount of each solid?
(1 M = 1 mol/liter = 1 mmol/mL, so 10 mL contains how much H
+
or OH
?)

(c) Notice the beauty of the sep funnel: unlike last week you can easily remove the bottom layer
from your extraction. Once you have isolated a compound in either acidic or basic aqueous
solutions, the best way to recover pure (neutral) compound is to neutralize the solution by slow,
careful addition of 1 M HCl or 1 M NaOH. Some acid-base reactions are quite exothermic. Have
ice ready just in case things get out of hand. Actually, we're going to go a bit past neutral. Add
HCl to the basic solution until it is acidic; add NaOH to the acidic solution until it's basic. Use
pH paper to check. (Transfer a drop to the pH paper; don't dip the paper into the solution!)

5
(d) After neutralizing, you might have a heterogeneous suspension. What are you going to do to
get a nice, clear ethereal solution that you can spot on a TLC plate? (Remember last week and
consult your pre-lab flow chart.)

(e) So, do you now have three clear solutions that (putatively) contain one organic solute each? If
so, proceed to part B. If youre confused, ask your instructor or T.A. for help before moving on
to Part B.

Some Technical Hints for the Extraction
1. Diethyl ether is quite volatile, so all operations with Et
2
O need to be done in a fume hood. If
too much ether evaporates during the procedure, you may need to add a little more to keep the
volume from getting too low.

2. You'll need to remove one layer or another in each step of the extraction don't throw
anything away until you're done! You may think you have a solution that contains nothing of
value, but you could be mistaken. Chemists more experienced than you have accidentally tossed
valuable really valuable compounds into the waste. Save all the solutions, then if
something goes awry you should still be able to locate and rescue the goodies.

3. Keep an Erlenmeyer flask under the sep funnel as you fill it in case the stopcock leaks or your
partner (not you!) forgets to close it.

4. Be sure that all your flasks are labeled so you don't lose track of what's what.

Part B. TLC analysis of compounds from the Part A extraction
How well did you do with your separation? Did you get three nice, pure solutions, which could
easily yield three nice, pure solids after evaporation of ether? Or, are your products contaminated
with the other components of the mixtureor with other unknown junk? TLC is an easy way to
find out. Your instructor will perform a nice demo with organic dyes that shows the technique
and analysis of a basic TLC experiment. For your experiments
6

1. Plastic-backed silica TLC plates (roughly 3 x 6 cm) will be provided. Be sure you handle these
by the edges, preferably with tweezers. Draw a light pencil line about 0.75 cm from the bottom
of one plate. Estimate, don't measure all you're doing is marking the starting point it just
has to be high enough that your sample mixture is above the solvent level! You're going to use a
capillary micropipet to make four separate spotsremember the control solution you saved?
along the pencil line, so make four evenly spaced tick marks with the pencil to indicate where
you will place these spots. (Before you spot a real TLC plate, practice on a piece of filter paper
try to make as small a spot as possible.) Now that you're proficient, go ahead and spot the
TLC plate. TLC is an extremely sensitive technique, so make the spots as small as possible (1
mm in diameter or lessbut make sure that some small amount of solution did actually go down
onto the plate!).

2. Now for the development: A mobile phase of ether and hexane (40:60 v/v) will be provided.
This is a case where speed is more important than precision. Just pipet about 2 ml of the mobile
phase into one of the small screw-cap bottles provided, then cap and gently swirl to get the air
inside saturated with solvent vapor. Use forceps to carefully insert the spotted TLC plate, cap the
bottle, and allow the solvent to rise until it gets close to the top of the plate. Be careful not to
disturb the bottle. Remove the plate with forceps, mark the position of the solvent front with a
pencil, and allow the solvent to evaporate. (Why doesn't it matter exactly how close the solvent
gets to the top? Why does it matter that you mark exactly where the solvent front ended up
immediately after you remove the plate?)

3. In contrast to the dyes used in the demo, you now need to find the spots. To do so, expose the
plate to 254-nm UV light by using one of the hand-held UV lamps. Caution: UV light is
harmful to your eyes. (1) Keep your goggles on they will absorb UV, and (2) Do not look
directly at the light. The silica TLC plates contain a fluorescent indicator that will glow green
when exposed to 254-nm light. Many compounds will quench (decrease the intensity of) this
fluorescence and appear as dark spots against the bright background. In addition, some spots may
fluoresce and appear bright on exposure to UV light. Mark all the spots that show up, noting
whether the compounds are fluorescent (bright) or fluorescence quenchers (dark) , and sketch the
7
plate in your notebook. Dispose of your used TLC plates in the waste bottle provided, not in the
trash!

4. Now for the fun part: analysis. Is it obvious which spot corresponds to which compound? (If
your purification went swimmingly, it may be. If your lanes contain multiple spots, however, it
might be tricky.) If correct spot assignments are not obvious, meekly shuffle toward your
instructor and notify him or her that you would like to request bona fide solutions of the pure
compounds in ether. If he or she is feeling particularly benevolent today, the solutions will be
provided. Your job will then be to figure out how to utilize these solutions to clear up any
ambiguities that exist in your data.

Lab Report
For your lab report, which will be due at the beginning of your next lab period, provide
thoughtful, thorough answers to the following questions:

1. You may organize your TLC data however you like, but your report should contain an easily
navigable Part B results section that provides clear descriptions of all TLC experiments,
including a record of what you spotted in each lane, sketches of the developed plates, and a list
of R
f
values and corresponding descriptions (fluorescent or quenchers, big spot or small) for all
significant spots.

Note: Be sure to explain how you arrived at the identity of each compound. For example, if you
spotted benzoic acid in Lane 1, how did you know it was benzoic acid?

2. Assign an R
f
value to each of the three compounds benzoic acid, benzocaine, and fluorenone.
If these were assignable from data on your purified compounds, briefly describe why. If you
needed to request authentic samples to be sure, describe how you used data from the pure
solutions to clear up the confusion.

8
3. Use your TLC data to qualitatively assess the success (or lack thereof) of your purification
that is, how did the extraction go? If your group's TLC results indicate that one or more of the
compounds were less than completely pure, what can you say about the impurities? Were they
random (Aldrich isnt perfect, you know), or were the only impurities easily identifiable as the
other constituent(s) of the original mixture? If your separation did not go as planned, what could
have gone wrong?

4. In light of your data, re-assess the relative R
f
predictions that you made in your pre-lab report.
Were you right? If not, what did you get wrong? Do your experimental R
f
valuesthat is, the
correct onesmake sense in terms of the structures of the compounds? Explain.

5. You may not have even noticed at the time, but as your TLC mobile phase, we provided you
with a mixture of ether and hexane. Why? What do you think you would have observed with
pure hexane as the mobile phase? With pure ether? Explain.

Experiment 5:
Molecular Modeling Extravaganza!
Weeks of October 8 (W, Th) and October 15 (M, Tu)

1
Experiment 5: Molecular Modeling Extravaganza!
Please bring your model kit to lab! Todays lab will be a bit different than normal in that your
lab session will be broken up into two parts: (i.) doing model-kit work in the normal organic lab,
where theres plenty of room to play with your toys, and (ii.) doing computer-based modeling in
the computer lab, affectionately known as the Chem Cave (Merrill 411). After your lab group
has completed Part 1: Configurational Stereochemistry, proceed to the Cave to complete the
days work. Your instructor and T.A. will get their exercise for the day by moving frequently
between the two rooms to answer all questions.
There is no pre-lab report required for this experiment, nor is there any supplementary reading.
But before coming to lab, please read this entire (admittedly long) handout. Also, please print out
this lab protocol from the course website. For your lab report, you will write all of your answers
directly on the printout. (Alternatively, you may write your answers directly in your lab manual
and photocopy the relevant pages to turn in before you leave lab.)

2

Part I: Configurational Stereochemistry
Background
The purpose of this portion of this laboratory is to provide a guided introduction to the field of
configurational stereochemistry. The list of definitions on the final page of this handout will be
of great assistance as you work through the problems. Dont hesitate to ask questions as you
proceed!
Tetrahedral Asymmetric Stereocenters
a. Guided by the structure drawings below, assemble two models of compound I and two models
of compound II. (Why two of each? Patience, patience. All will become clear in due time.) This
is readily done if you remember the code: CH
3
= C = black atom; R = red atom; B = blue atom;
H = small white sphere. (Well get to G = gray atom at the end of this section.). Be sure you
recognize the connection between 3-dimensional models and 2-dimensional
representationswedges point at you; hatched lines away.
R B
H
CH
3
B R
H
CH
3
I II

b. Your answers to Parts c., d., e., and g. should be selected from the following options:
identical, enantiomers, diastereomers, racemate.

c. Complete the following sentences by selecting the correct word from Part b. above:
1. I and II are ______________________.
2. An equimolar mixture of I and II is termed a _____________________.
3
d. What now follows will work if you assembled I and II correctly. Join one I and one II by
removing the hydrogen atoms (and, of course, one stick) and making a new C-C bond between
the models. The offspring is a new molecule we shall represent as (I + II), which contains two
tetrahedral asymmetric stereocenters. Construct the mirror image of (I + II), designated (I +
II), from the pool of loose atoms.
1. What word from Part b. describes the relationship between (I + II) and (I + II)?
_________________________. Note: To see the relationship between (I + II) and
(I + II)and between the other pairs of molecules that follow in this section
its best to align the carbon-red atoms bonds on the two central carbons:
R R

2. Is (I + II) chiral or achiral? _________________________.
In fact, (I + II) is a meso compound. Look up this term on your list of definitions.
e. Separate (I + II) into I and II, but save (I + II). Assemble (I + I), and (II + II) in the manner
of Part d. Analyze the stereochemical relationships among (I + I), (II + II) and (I + II). Again,
use the possible answers in Part b. above to define the relationships below.
1. (I + I) and (II + II) are ____________________________.
2. (I + I) and (I + II) are _____________________________.
3. (II + II) and (I + II) are _____________________________.

f. How can we understand the results of Parts d. and e.i.e. why are (I + I), (I + II), etc. chiral
or achiral (whichever you found previously)? The best way to analyze the problem is to relate
the properties of a given combination to the stereochemical properties of the two constituents
e.g. that of (I + II) to those of the separate components I and II. To pursue this analysis,
4
collaborate with another student and pool your hands. Your four hands provide a precise
analogy to the molecules. If you combine your left hand and right hand, palm-to-palm or
thumb-to-thumb side-by-side, is that combination chiral or achiral (see by using your lab
partners hands as a mirror image)?__________ Which combination in Parts d. and e. is
analogous? ____________ So? What if you combine your left hand with your partners left
hand? Do you get it? If you are confused, talk this over with your lab instructor or T.A. before
proceeding onward. Briefly explain what you get about the whole hands thing in the space
below:

g. Just to be sure you understand: Is the molecule below, which does not contain a plane of
symmetry, chiral or achiral? Briefly explain your answer.
H
H
H
H
Cl
Br
Cl
Br

h. At last to G = gray atom! Once again construct (I + II) and its (identical) mirror image (I +
II). Now replace one of the blue atoms on (I + II), as well as the mirror-image blue atom on (I +
II), with gray atoms. Well designate the resulting molecules (I + II)
B!G
and (I + II)
B!G
.
1. What word from Part b. describes the relationship between (I + II)
B!G
and (I +
II)
B!G
? _________________________.
5
2. Are (I + II)
B!G
and (I + II)
B!G
chiral or achiral? ________________________.
i. How can we understand why your answers to Parts d. and h. differ? Now you should think
about combining both your hands and feet (at least as a thought experiment)! That is, if (I +
II)
B!G
corresponds to your right hand joined to your left foot, then (I + II)
B!G
corresponds
to...?____________________________________
Allenes
Using your model kits, make models for compounds III and IVto build the double bonds, use
your sp
3
-hybridized carbons and two of the curved light-blue bonds (yes, use the sp
3
-hybridized
carbons even though none of the allene carbons is in fact sp
3
-hybridizedas youll see, it all
works out in the end!) Is molecule III chiral?___________ Is molecule IV
chiral?_______________ Try to understand what features in III and IV give them their
stereochemical properties and explain briefly in the space below.
Br
2
C C CH
2
BrHC C CHBr
III IV

After youve discussed your part I answers with your instructor, you may proceed to the
computer lab for part II.
6
Part II: Conformational Analysis using HyperChem

Background
HyperChem is a computer program that calculates the three-dimensional structures of molecules
and displays beautiful images of the results. From these images, which can be readily
manipulated, one can precisely measure bond lengths, bond angles, and inter-atomic distances.
(Although such data may sometimes also be determined using actual modelsfor example, of
the ball and stick varietythe values obtained are only approximate.)
Today you will use HyperChems three-dimensional modeling and energy minimizing
capabilities to explore alternative conformations of simple organic molecules. Doing so, you
enter the field of study called Computational Chemistry, which is of major scientific importance.
7
In order to use the program, you must know the following: what the program can do, how it
performs its calculations, and how to make the computer do what you want. This introduction
contains only enough information to enable you to do the exercises that follow and to learn
something from them. You may learn much more about the full capabilities of HyperChem by
perusing the manuals.
There are two different approaches to calculating the energy of a molecule. The first involves
pure quantum mechanics, and is termed ab initio calculation. The equations associated with this
methodoriginating with the Schrdinger Equationare complex and time-consuming to solve,
and we shall consider this method no further. The second approach, which relies on empirical
data and employs many mathematical approximations, comes in two guises: semi-empirical
quantum mechanics and molecular mechanics. Semi-empirical quantum mechanical calculations
use quantum equations, coupled with experimentally measured parameters. Like the ab initio
methods, semi-empirical quantum mechanical calculations are better suited for obtaining
molecular orbitals. We will employ molecular mechanics, as it has been developed to answer
precisely the type of question we will be addressing today.
Molecular mechanics uses the equations of classical mechanics to describe potential energy
surfaces and physical properties of molecules. A molecular mechanics calculation relies on a set
of equationsknown as the force fieldthat approximate the potential energy of various
intramolecular interactions. For example, one component of the force field is the energy arising
from compression and stretching of a bond. This component is often approximated as a harmonic
oscillator and can be calculated using Hookes law. The value of the force constants in each
calculation depends upon the elements involved in the calculation and their bonding
arrangements. Not only does the program recognize that the force constants for bonds to carbon
and to oxygen differ, but it also assigns different parameters to different bonding arrangements
of the same atom. Thus, the atomic force constants differ for an oxygen atom in for example,
formaldehyde (H
2
C=O), ethanol (CH
3
CH
2
OH), and water (H
2
O). Each force field has its own
equations and sets of atomic parameters.
HyperChem can utilize atomic parameters for four different force fields. Three of these (BIO+,
OPAL, and AMBER) were designed for use on large biological molecules such as proteins and
8
DNA. The fourth, which you will use for these exercises, is MM+, a force field designed by N.L.
Allinger et al. to reproduce experimental physical data for small organic molecules. The
parameters of MM+ are manipulated by seven equations that approximate the following
interactions: bond stretching (the electrostatic energy associated with the distance between the
nuclei), bond dipoles (the energy of charge separation due to differing electron density), angle
bending (energy associated with changing the angle between two atoms attached to a central
atom), linked angle bending and bond stretching (the two often occur at the same time), out-of-
plane bending (energy associated with loss of planarity in sp
2
hybridized atoms), torsional
bending (energy of the interaction of dihedral angles), and van der Waals interactions (long-
range attraction and short range repulsion of non-bonded atoms).
HyperChem energy calculations are of two types. On the simple side, the program can assign an
energy to a geometry. Much more sophisticated is HyperChems ability to bring the molecule to
an optimal, low-energy stateto minimize the structure. This is done by computationally
searching the mathematical surface represented by the potential energy function, each point of
which corresponds a different molecular geometry. The essential idea is that the computer
explores conformational space and finds an energy minimum by calculating what sort of changes
in geometrybond lengths, dihedral (a.k.a. torsion) angles, etc.will lead to a more favorable
structure. Those changes are incorporated, and the program then calculates what modifications of
the new geometry will decrease the energy once again. When the computer cannot calculate a
change that will further lower the energy, a minimumi.e., an optimized geometryhas been
reached. (For the curious, more details of this energy minimization procedure are given below.)
Nota bene: It is critical to appreciate that the conformation obtained after minimization may be,
and typically is, one of a myriad of local minima, rather than the true global minimum. The
reason for this is that the energy-minimization algorithms search, in each step of the calculation,
for a similar structure of lower energy. When no such lower-energy structure can be found, an
energy minimum has been reached, and the calculation ends. Thus, if a molecule must first
increase in energy to then find a lower-energy conformationi.e., by passing through a
transition statethis lower-energy structure will not be found.
9
The Energy Minimization Procedure
The computer finds a minimum energy by generating an N-dimensional surface. A three
dimensional surface is like the surface of the ocean at a given point in time, where every point is
described by three coordinates (x, y, z, or latitude, longitude, height above sea level). A point on
an N-dimensional surface is described by N coordinates. For a molecule of A atoms, the energy
can be described by a system of 3A Cartesian coordinates. The direction of greatest change in the
energy is employed to narrow in on the minimum of the surface. This is calculated using a
mathematical entity called the gradient. On a two-dimensional surface (for instance, a parabola:
y = x
2
+ 2), the gradient is simply the derivative of the equation for the curve (dy/dx = 2x). With
three dimensions or more, partial derivatives are taken and these become mathematically very
ugly. So you have the computer to do it for you.
There are four energy-minimization methods available on HyperChem, which are, in order of
increasing sophistication: Steepest Descent, Fletcher-Reeves, Polak Ribiere, and Block-Diagonal
Newton-Raphson. Today, we will use the Block-Diagonal Newton-Raphson algorithm, which
gives superb results. (Note that all four methods give essentially the same resultshappily!but
differ in the precise algorithm used to calculate the molecular geometry with the lowest energy.)
Before You Start
HyperChem is a very flexible program, and can be customized to the users taste and
requirements. You must check to make sure that the format you are using is the same as the
format of the instructions. Choose Preferences... under the File menu. Set the Window to
Black. Set the Bond Color to By element. Set the Selection Color to Green. Click on OK.
Open the Build menu, and make sure that there are no checks by any of the options. Under the
Select menu there should be checks by Atoms and Multiple Selections only. Make sure the
Display menu has a check by Show Hydrogens and Show Multiple Bonds. Choose Element
Color... from the Display menu. When the dialog box opens, set Hydrogen as White, Carbon
as Cyan (which beautifully complements the black background), Nitrogen as Blue, Oxygen
as Red, and Bromine as Yellow. Click on OK. Then choose Rendering... from the Display
menu and select Sticks on the Rendering Method dialog box and click OK. Finally, choose
10
Molecular Mechanics... from the Setup menu. When the dialog box opens, choose MM+ as
the force field. Click OK, and now you are ready to begin the experiment.
The Tools
NOTE: In the following instructions, if neither right- nor left-click is specified, use left-click.
The Draw Tool
This vital tool has several functions. Double-clicking on the draw tool icon brings up a periodic
table, from which the desired atom can be selected. Left-click then places these atoms in the
work spacei.e., begins to build the molecule. Left-drag places bonds in the workspace.
Right-click deletes whatever is under the cursor.
NOTE: If you switch your element choice on the periodic table and then click on an atom
already on screen, it will change to the new type.
The Selection Tool
Anything you left-click on will become highlighted and be the subject of any subsequent action
(geometry optimization, for instance). To select more than one item, left-click on each of your
choices in succession. Left-click on the background selects everything in the workspace.
If one atom is selected, its type is displayed on the line at the bottom of the screen. If one bond is
selected, the bond length is displayed. Selection of two non-connected atoms gives the distance
between them. Selection of three connected atoms gives the relevant bond angle, while selection
of four connected atoms gives the torsion angle (note: torsion angle is synonymous with dihedral
angle, the term used in our textbook).
Right-clicking removes from selection whatever is underneath the cursor. Right-clicking on the
empty workspace deselects the entire selection.
Double-clicking on the selection tool icon in the tool bar on the top of the screen converts any
two-dimensional sketches in the workspace (made with the draw tool) to three-dimensional
11
models. When you go from 2D to 3D, the program automatically fills the unoccupied valence of
any atoms on the screen with hydrogens, so you need not draw them out. HyperChem assumes
standard geometries and average bond lengths in creating the models, so it does not matter how
crudely you draw the 2D sketch. Once a 2D drawing has been converted to a 3D model, you may
further alter it, adding 2D sketches and rebuilding until you have your end product. Note that
building a model does not necessarily give the lowest energy conformation, but rather a good
guess as to what the geometry may resemble.
The Rotate out-of-plane Tool
This tool is very useful for changing the view of the molecule. Left-drag rotates the molecule
around the x and y axes (which together define the plane of the screen). Dragging horizontally
controls the y-axis, and vertically, the x. Use this tool whenever you need to change the view and
bring different parts of the molecule clearly into perspective. This is the best tool to have chosen
prior to a geometry optimization, as it continues to function while the computer calculates. This
allows you to align molecules so that the interesting changes in their geometries during the
optimization are visible.
The Translate and Rotate in-plane Tools
These two tools also change the view of the molecule. The first moves the molecule in the plane
of the screen, the second rotates it in the plane of the screen (i.e., around the z axis).
The Magnify/Shrink Tool
Left-dragging with this tool increases and decreases the magnification of a molecule.
Space Bar
The space bar centers and fills the screen with the selection (or the whole molecule if there is no
selection). It is useful for getting a good look at things.
12
Other Tools
The other tools on the screen are also for zooming and are of little use for small molecules. Play
with them if you likeif your molecule disappears, you can always hit the space bar to retrieve it.
Two Important Reminders
1. Before manipulating any newly drawn structure (whether whole or partial), you must
first model build it by double-clicking on the selection tool.
2. Before performing an energy minimization or calculating a single-point energy, all
atoms must be deselected.
Introductory Experiments
Building Methane
(This part of the experiment will introduce you to the tools described above. Please share a PC
with a partner as you work through this lab.)
1. Double-click on the draw tool icon in the tool bar at the top of the screen and choose carbon
from the periodic table.
2. Click OK.
3. Left-click once on the workspace. A carbon atom (cyan circle) should appear.
4. Add the four hydrogens by double-clicking on the selection tool icon in the tool bar at the top
of the screen. A three-dimensional representation of methane should appear on the screen. This
process is known as model building. (You will likely need to rotate your methane to see all four
hydrogens!)
5. Now, start an energy optimization by choosing Geometry Optimization... from the Compute
menu. Set the RMS gradient to 0.1 kcal/( mol), thereby telling the computer (which does not
understand zero) at what point the energy changes calculated are not worth pursuing. Choose
Block-Diagonal Newton-Raphson as the method of minimization. Enter 1 for the Screen
refresh period, and then click OK.
13
6. Choose the rotate out-of-plane tool, and spin the molecule by left-dragging the mouse.
7. Choose Rendering... from the Display menu. Choose the Overlapping Spheres on the
Rendering Method dialog box to change the image to a space-filling representation and click
OK.
8. Move the methane around, moving the mouse fairly slowly to keep the image smooth.
9. Use the Rendering Method dialog box to return the image to Sticks. (Note: Many students
prefer the Balls and Cylinders representationfeel free to use it as you proceed. Note, as well,
that you can customize the appearance of your representations with the other menus in the
Rendering Options box.)
Conformations of Ethane
(This part of the experiment introduces you to the calculations and more complex tools of
HyperChem.)
1. First, under the File menu, click on New (do NOT save your methane file), then build
ethane by left-clicking and dragging with the draw tool to create two carbons bonded to each
other. (They will simply appear as a line.)
2. Finish building ethane by double-clicking on the selection tool (a process that will add the
requisite hydrogens and convert the structure to three-dimensionality).
3. Optimize the geometry (just as you did in Part 5. above with methane).
4. Use the rotate out-of-plane tool to position the molecule so that you are looking down the C-C
bond. You should see ethane in the staggered conformation.
5. Choose the selection tool. Left-click on any two C-H bonds that are adjacent as you look down
the C-C axis (these two C-H bonds will in fact be connected to the two different carbons). The
display bar on the bottom of the screen should read a torsion angle (again, synonymous with
dihedral angle) of 60 degrees or -60 degrees if you have selected the proper bonds. (Note: Dont
concern yourself with all of those decimal places!)
14
6. Now create the eclipsed conformation of ethane. To do so, choose Set Bond Torsion from the
Edit menu, making sure that the atoms forming the dihedral angle from Part 5 are still selected.
Enter 0 (zero) degrees when the dialog box comes up, and click OK. Eclipsed ethane should
appear on the screen.
7. Deselect the selected atoms by right-clicking on a blank part of the workspace.
8. To find the energy of eclipsed ethane, select Geometry Optimization... from the Compute
menu. Make sure the RMS gradient is still set to 0.1 kcal/( mol) and that Block-Diagonal
Newton-Raphson as the method of minimization. Then click OK. Record the energy (all
energies are in kcal/mol) from the display bar at the bottom of the screen here: ___________
(Note: Throughout the afternoon, record all energies to just two decimal places.)
Reminder: Whenever you do an energy calculation, all atoms must be deselected, just as
above.
9. Choose the selection tool, and measure the distances between hydrogen atoms attached to
different carbon atoms. Do any of these hydrogens impinge upon each otheri.e., is any
distance less than 2.35 , which is twice the van der Waals radius of hydrogen? ___________
Record the minimum distance you find here: ___________
10. Again, use the rotate out-of-plane tool to position the molecule so that you are looking down
the C-C bond. You should see ethane in the eclipsed conformation.
11. Does eclipsed ethane truly represent a minimum energy conformation? Find out. Optimize
the geometry again by choosing Geometry Optimization... from the Compute menu. This time,
set the RMS gradient to 0.0001 kcal/( mol) and click OK. As HyperChem optimizes the
geometry, continue to view the molecule by looking down the C-C bond. Whats happening?
_____________________________________________________________________________
_____________________________________________________________________________
12. Record the final energy (from the display bar on the bottom of the screen) here:
___________ (Again, record all energies to just two decimal places.)
15
13. Choosing any one of the carbon-hydrogen bonds, select and record the torsion angle with
respect to each of the three carbon-hydrogen bonds on the other carbon: ___________
______________________ (Record all torsion angles as whole numbers.)
14. Recall that the energies you recorded in Parts 8. and 12. are in kcal/mol. HyperChem
calculates that the eclipsed and staggered conformations of ethane differ by how much? Which is
the more stable? Based upon your answers in Part 9., is this energy difference due to a steric (van
der Waals) contact? _____________________________________________________________
_____________________________________________________________________________
_____________________________________________________________________________
_____________________________________________________________________________
More advanced analyses
Conformational Analysis of Butane
1. First, under the File menu, click on New (do NOT save your ethane file), then build butane
(the usual drill: repeatedly left-click and drag using the draw tool to create the four-carbon chain,
then double-click with the selection tool to add the hydrogens and convert to three-
dimensionality).
2. Choose Geometry Optimize from the Compute menu, set the RMS gradient back to 0.1
kcal/( mol) and click OK.
3. Record the final energy from the display bar here: ___________
The butane molecule is in the so-called anti conformation.
4. Choose the selection tool, and measure the distances between hydrogen atoms attached to
different carbon atoms. Do any of these hydrogens impinge upon each otheri.e., is any
distance less than 2.35 , which, again, is twice the van der Waals radius of hydrogen?
___________ Record the minimum distance you find here: ___________
16
5. Deselect the previous selection by right-clicking on an empty part of the workspace, and select
and measure the torsion angle between the C1-C2 and C3-C4 bondsin other words, between
the two anti methyl groups. Record the torsion angle here: ___________
6. Now change the selected torsion angle to 60 degrees in the Set Bond Torsion dialog box from
the Edit menu. The conformation displayed is unoptimized gauche butane.
7. Measure the methyl-methyl torsion angle (again, the torsion angle between bonds C1-C2 and
C3-C4) to check that it is indeed 60 degrees. Record the angle here: ___________
8. Measure the distances between hydrogen atoms attached to different carbons. Now is there
any impingement (again, any distance less that 2.35 )? ___________ Record the minimum
distance you find here: ___________
9. Deselect the torsion angle, optimize the geometry, and record the final energy here:
___________ The conformation now displayed is true gauche butane.
10. Measure the final methyl-methyl torsion angle (again, the torsion angle between bonds C1-
C2 and C3-C4) for gauche butane. Record the angle here: ___________
11. Measure the distances between hydrogen atoms attached to different carbons. Now is there
any impingement (again, any distance less that 2.35 )? ___________ Record the minimum
distance you find here: ___________
12. What is your conclusion from Parts 6.-11.?________________________________________
_____________________________________________________________________________
_____________________________________________________________________________
_____________________________________________________________________________
_____________________________________________________________________________
_____________________________________________________________________________
13. Based upon your answers to Parts 3. and 9., which conformation, anti or gauche, is
preferred? ___________
17
14. Is your answer to Part 13. sensible given your answers to Part 4. and Parts 6.-12.? _____
_____________________________________________________________________________
_____________________________________________________________________________
_____________________________________________________________________________

Conformations of Cyclohexane Derivatives
1. First, under the File menu, click on New (do NOT save your butane file), then build
cyclohexane by repeatedly left-clicking and dragging with the draw tool to create a ring of six
carbons. Finish building your cyclohexane by double-clicking on the selection tool. Use the
rotate out-of-plane tool to convince yourself that it is indeed the chair conformation of
cyclohexane that youve built. (All of the subsequent steps below will involve the chair
conformation.)
2. Make axial methyl cyclohexane by left-clicking with the draw tool on one of the axial
hydrogens and then double-click on the selection tool to model build.
3. Optimize its geometry, and record the energy here: ___________
4. Measure the torsion angle between the methyl group and an adjacent equatorial hydrogen:
___________
5. Choose the selection tool, and measure the distances between hydrogen atoms on the axial
methyl group and hydrogens on the cyclohexane ring. Is any distance less than the now familiar
2.35 ? Record the minimum distance you find here: ___________
6. Delete the axial methyl group by right-clicking with the draw tool on the carbon at the center
of the methyl. Model build the cyclohexane, then add an equatorial carbon by overwriting one of
the equatorial hydrogens with the draw tool. Model build again.
7. Optimize the geometry, and record the energy here: ___________
8. Measure the torsion angle between the methyl group and an adjacent equatorial hydrogen:
___________
18
9. Choose the selection tool, and measure the distances between hydrogen atoms on the
equatorial methyl group and hydrogens on the cyclohexane ring. Is any distance less than 2.35
? Record the minimum distance you find here: ___________
10. What is the energy difference between anti and gauche butane? ___________ Between
equatorial and axial methylcyclohexane? ___________ That these differences are related by a
factor of 2 is not merely a coincidence. To see why, build all four molecules with your model kit
and compare their structures (i.e., here, use of tactile three-dimensional models is the best way to
see the point). Review your conclusions with your lab instructor or T.A. Draw a sketch of your
conclusions here:

Conformations of 1,2-Dimethylcyclohexane
1. Build 1,2-trans-diequatorial-dimethylcyclohexane. Note that 1,2-diequatorial is perforce
trans.
2. Optimize its geometry, record the energy, and measure the torsion angle between the two
methyl groups. Record these values here:
1,2-diequatorial-dimethylcyclohexane energy: __________
Me-Me torsion angle: ___________
3. Choose the selection tool, and measure the distances between hydrogen atoms on the two
equatorial methyl groups. Is any distance less than 2.35 ? Record the minimum distance you
find here: ___________
4. Delete the two methyl groups, and rebuild the model of cyclohexane (i.e., by double-clicking
on the selection tool).

19
5. Convert it to 1,2-trans-diaxial-dimethylcyclohexane (again, note that 1,2-diaxial is perforce
trans) and again model build. Optimize its geometry, record the energy, and measure the torsion
angle between the two methyls.
1,2-diaxial-dimethylcyclohexane energy: ___________
6. Choose the selection tool, and measure the distances between hydrogen atoms on either of the
axial methyl groups and hydrogens on the cyclohexane ring. Is any distance less than 2.35 ?
Record the minimum distance you find here: ___________
7. What is the preferred conformation of trans-1,2-dimethyl-cyclohexane?_________________
8. Delete one of the methyl groups, rebuild axial methylcyclohexane, then make 1,2-cis-
equatorial,axial-dimethylcyclohexane (once again, 1,2-equatorial, axial is perforce cis). Optimize
its geometry, record the energy, and measure the torsion angle between the two methyl groups.
1,2-equatorial,axial-dimethylcyclohexane energy: __________
9. Compare the three 1,2-dimethyl isomers. Which has the lowest energy? ___________ Are the
energy differences among them consistent with your analysis of the conformations of
methylcyclohexane? Be as quantitative as possible. ____________________________________
_____________________________________________________________________________
_____________________________________________________________________________
_____________________________________________________________________________
_____________________________________________________________________________
_____________________________________________________________________________
10. Before you leave, discuss your findings with your instructor to make sure that your
conclusions are valid. Getting the right answers on this handout is, with respect to your
Chemistry 221 grade, not of huge importancebut understanding the concepts of
conformational analysis is critical for the rest of your organic-chemistry career!
20
Topics for Report
Your answers to all the questions posed above will constitute your lab reportjust hand in the
sheet youve been writing on. (If youd like to keep a copy of these answers as a study aid for the
first Evening Examyou may have noticed that the material is quite related to what might be
covered!you are welcome to photocopy the relevant pages to turn in and keep your original.)

21
Definitions of Terms Employed in Stereochemistry
Stereochemistry - Chemistry in three dimensions.
Constitutional Isomers - Species of the same molecular formula that differ in the connectivity
of their atoms. For example, CH
3
CH
2
CH
2
CH
3
and (CH
3
)
3
CH are constitutional isomers.
Stereoisomers - Species of the same molecular formula and with the same connectivity of
atoms, but differing in the arrangement of their atoms in three-dimensional space. For example,
cis- and trans-2-butene are stereoisomers.
Configurational Stereoisomers - Stereoisomers that cannot be interconverted by rotations about
single bonds. As such, configurational stereoisomers do not normally interconvert readily at
room temperature. Often, configurational stereoisomers are simply called stereoisomers (a
convention that sometimes can lead to confusion).
Conformational Stereoisomers (Conformers) - Stereoisomers that can be interconverted by
rotations about single bonds. As such, conformational stereoisomers normally interconvert
readily at room temperature (but certainly the rate of interconversion will depend on the
experimental conditions).
Chiral - Describes an object, such as a molecule, not superimposable on its mirror image. A
chiral object therefore has a handedness.
Enantiomers - Stereoisomers that are non-superimposable mirror images (and hence are chiral).
An enantiomer is one molecule of the pair, and may be either a configurational or conformational
stereoisomer of its mirror image.
Commentary: When used without further specification, chiral universally refers to a
configurational enantiomer. That is, a chiral molecule is one that cannot be interconverted with
its enantiomer simply by rotations about single bonds. Similarly, a molecule simply termed
achiral is superimposable upon its mirror image, even if rotations about single bonds are
required to achieve the superposition. A chiral conformation however is one that is not
superimposable on its mirror image (even if superposition can be achieved after rotations about
single bonds).
22
Diastereomers - Stereoisomers that are not enantiomers.
Commentary: The terms enantiomers and diastereomers define the relationship between two
stereoisomers, while configurational and conformational specify the process required to
interconvert them.
Stereocenter (or Stereogenic Center) - An atom for which the interchange of any two groups
will afford a configurational stereoisomer.
Tetrahedral Asymmetric Stereocenter - An sp
3
-hybridized atom that has four different groups
attached (and for which, therefore, the interchange of any two will afford a configurational
stereoisomer).
Racemic Mixture or Racemate - A mixture containing an equal amount of both enantiomers.
Meso Compound - An achiral compound containing two or more tetrahedral asymmetric
stereocenters.
Optically Active Compound - A compound that rotates the plane of polarized light (and which,
therefore, is chiral).
Optically Pure Compound - A pure chiral compound uncontaminated with any of its
enantiomer.
Dextrorotatory, (+), d - Rotating the plane of polarized light clockwise.
Levorotatory, (-), l - Rotating the plane of polarized light counterclockwise.
Specific Rotation, ["] - A quantification of the direction and extent by which a chiral molecule
rotates the plane of polarized light; ["] = "/cl, where " is the observed rotation, c is the
concentration of the sample in g/mL, and l is the length of the sample tube in decimeters, a unit
chosen because the standard polarimeter sample tube has a length of 1 dm.

Experiment 6: S
N
1, S
N
2
Week of October 22

1
Experiment 6: S
N
1, S
N
2
Pre-lab Preparation
Answer the following pre-lab questions:
Pre-lab Q1: Write the S
N
2 reaction of 1-bromobutane with NaI. Illustrate the electron flow with
curved arrows. Since this is a one-step reaction, you've just written the mechanism.
Pre-lab Q2: Write a balanced equation representing the S
N
1 solvolysis of tert-butyl bromide in
ethanol. The product is t-BuOEt. Write the reaction mechanism. (Refer to the introduction
below or the text if we haven't gotten to this mechanism in class before your lab.)
Pre-lab Q3: Draw the structures of all the organo-halides you will be using in this lab.
Pre-lab Q4: Predict the relative reactivities of the reactions that you will run in this lab today;
that is, fill in the Predicted Order columns of the tables on pages 3 and 4 as part of the pre-lab
report that you will submit.
Procedure
In the laboratory you will find dropping bottles containing the following halides: 1-bromobutane,
2-bromobutane, t-butyl bromide, allyl bromide, allyl chloride, benzyl chloride, and
bromobenzene. Note that the allyl and benzyl halides are powerful lachrymators and should be
tested in the hoods only. You will also find bottles containing the following alcohols to be used
in Part 3: 1-butanol, 2-butanol and t-butyl alcohol.
We begin with the surmise that the reaction between nucleophiles (Nuc) and alkyl or aryl halides
can occur only by one of two mechanisms:
R
+
+ X
-
R-Nuc
slow fast
+ Nuc
-
R-X + Nuc
-
slow
R-Nuc + X
-
S
N
1
S
N
2
R-X

(Note: S
N
1 reactions are typically run as solvolysis reactions, in which the nucleophile is the
solvent rather than the charged Nuc
above.)
2
Begin by answering the three questions below. If you dont understand whats up, ask.
State: 1. The rate law for S
N
1 and the rate law for S
N
2.
2. Which mechanism will be favored by:
a. high concentration of a good nucleophile?
b. a very polar solvent?
c. a highly accessible carbon bearing the leaving group?
We wish to test the effect of structure upon reactivity in these two mechanisms. The two reagents
we shall use are NaI in acetone and AgNO
3
in ethanol.
3. Which reagent for which mechanism? Why? Note that iodide ion is a good nucleophile
and nitrate is not, and that ethanol is a moderately ionizing solvent (far more so than is acetone).
Do not start until you have understood the answers to Questions 1-3 above. For all of your
experiments below, please make sure that all of the test tubes that you use are clean and
dry!

3
Part 1: NaI Reagent.
Perform the NaI test in a 3-inch test tube. To 1 mL of the NaI reagent (a Pasteur pipettes worth
will suffice), add 2 drops of the halide, stopper the test tube and shake it, and then measure the
time required for the appearance of a precipitate of insoluble NaBr or NaCl. (Note: If the
sample merely turns yellow, that is not a positive result.) If no precipitate has formed after
three minutes, put the reaction tube into a beaker of warm water (40-50 C, but no hotter) and
record the time needed to produce a precipitate; if no reaction occurs after ten minutes, you may
classify the alkyl halide as unreactive. If NaBr or NaCl appears instantaneously at room
temperature in two or more of the reactions, repeat the test with just these samples at a lower
temperaturein an ice bath, for exampleso that you can derive a complete order of reactivity.

A. Begin by testing the following four halides with the NaI reagent (following the procedure
outlined on the previous page). You have already predicted the relative reactivities
(remember your pre-lab?); now do the experiment. Run the four experiments concurrently
(again, use one Pasteur pipette full of reagent as the 1 mL and do your best to ensure that
each tube has an equal amount). Ask questions if your expectation and observation disagree!
RX Predicted Order Observed Precipitate (Time)
1-bromobutane
2-bromobutane
t-butyl bromide
bromobenzene

B. Now test allyl bromide, allyl chloride, and benzyl chloride with the NaI reagent. Remember,
these compounds are powerful lachrymators and should be tested in the hoods. Be sure
you know the structures of these materials! As a reference point, also retest 1-bromobutane.
When you do your pre-lab predictionsyou should just consider 1-bromobutane vs. allyl
bromide, allyl bromide vs. allyl chloride, and allyl chloride vs. benzyl chloride, pairs of
molecules that differ only by a single structural feature. As always, it is best to run all
4
samples concurrently. As before, make sure you understand what is going on if expectation
and observation disagree.
1-bromobutane
allyl bromide
allyl chloride
benzyl chloride

The key questions: Are allyl and benzyl derivatives unexpectedly reactive or unreactive under
these test conditions? Why do allyl bromide and allyl chloride react at different rates?
Part 2: AgNO
3
in Ethanol.
The procedure for this reagent is analogous to that above. To 1 mL of AgNO
3
reagent, simply
add 2 drops of the halide, stopper and shake. The appearance of a precipitate of AgCl or AgBr
signifies that a reaction is complete.
A. Test the following four halides with the reagent (as always, running the tests
concurrently). As before, predict, test, explain, ask.
1-bromobutane
2-bromobutane
t-butyl bromide
bromobenzene

B. Now test allyl bromide with the AgNO
3
/ethanol reagent. Your conclusions?? No need to test
allyl chloride and benzyl chloride, but can you predict the relative rate of reaction of allyl
bromide vs. allyl chloride and of allyl chloride vs. benzyl chloride (again, pairs of molecules
that differ only by a single structural feature)?
5
Part 3: Lucas Reagent for ROH Reactivity.
Now we turn things on their head. Your final task for today is to determine whether the Lucas
reagent promotes S
N
1 or S
N
2 reactions. Specifically, the Lucas reagent consists of a solution of
ZnCl
2
in concentrated HCl that converts alcohols (ROH) to alkyl chlorides (RCl). A test with the
reagent is performed by adding 2 mL of it to 4-5 drops of ROH in a test tube, stoppering the tube
and shaking. If a nucleophilic substitution reaction occurs and alkyl chloride product is formed, it
will either separate as a distinct phase or will generate an opaque emulsion.
A. So, with the Lucas reagent, do alcohols display S
N
1 or S
N
2-like reactivity? Design and
perform an experiment, employing the alcohols provided (i.e., 1-butanol, 2-butanol, and t-
butyl alcohol) to find out. Based on your results, propose an arrow-pushing mechanism for
the Lucas reaction with the alcohol that you found to be most reactive in your experiment
(this will be included in your lab report). Be sure that your mechanism accounts for the
presence of HCl in Lucas reagent. (Dont worry about the role of the Zn
2+
, but certainly
indicate how the strong acid HCl facilitates the reaction. Hint: Which is a better leaving
group, OH
or H
2
O?)
Topics for Report
Your report, due in lab next week, should consist of your answers to the initial Questions 1-3 and
your data tables. Additionally, write a brief discussion of your experimental results making sure
to address the following points:
For Part 1 (experiments with the NaI reagent): (a) What was the effect of substitution at the
carbon undergoing nucleophilic attack, in particular, 1 vs 2 vs 3 alkyl? (b) Do the allylic and
benzylic halides fit this pattern? If not, suggest an explanation. (c) Can the relative reactivity of
bromobenzene be explained in terms of the principles established by the series of other
compounds, or is some other factor important here? (d) What was the effect (if any) of changing
the leaving group? How do you account for that?
For Part 2 (experiments with AgNO
3
in Ethanol): When answering the following questions,
be sure to draw out all the relevant carbocation/resonance structures. (a) What was the effect of
substitution at the carbon undergoing nucleophilic attack, in particular, 1 vs 2 vs 3 alkyl? (b)
6
Did the allylic halide fit this pattern? If not, suggest an explanation. (c) Can the relative
reactivity of bromobenzene be explained in terms of the principles established by the series of
other compounds, or is some other factor important here?
For Part 3 (experiments with Lucas Reagent): Include the arrow-pushing mechanism for the
Lucas reaction with the alcohol that you found to be most reactive in your experiment.
This report is due in your regular lab period next week.

Experiment 7:
Determination of the Rate of a Chemical Reaction
Kinetics of the Solvolysis of t-Butyl Chloride
Week of October 29

1
Experiment 7: Determination of the Rate of a Chemical
ReactionKinetics of the Solvolysis of t-Butyl Chloride
Pre-lab Preparation
Please read Sections 15.4 and 15.8 in Zumdahl (6
th
Edition) before coming to lab (if you need
one, copies of Zumdahl are on reserve in the Science Library).
Also, answer the following pre-lab questions:
Pre-lab Q1: Write the complete mechanism for S
N
1 reaction of tBuCl with EtOH.
Pre-lab Q2: Calculate the total quantity of 0.01 M aq NaOH needed to neutralize the HCl
produced by complete solvolysis of the tBuCl in 0.5 ml of 0.2 M tBuCl in acetone.
Background
To measure the rate of a chemical reaction, one needs an analytical method for quantitative
determination of the concentration of starting material or of product as a function of time. Some
analytical procedures give a direct measure of one of these concentrations, while others monitor
another property of the system (e.g., absorbance) that can be readily converted into the necessary
concentration data. Today you will employ perhaps the simplest assay there is: direct
measurement of the production of acid.
The rates of chemical processes are dependent on many variables. In particular, the reaction
temperature, the purity and composition of the solvent, and the concentration of the starting
material(s) can significantly affect the rates of reactions. Today, in fact, you will systematically
vary these three parameters to determine their effect on the rate of (and the rate constant for) the
solvolysis of t-butyl chloride.
Solvolysis of t-Butyl Chloride
In the experiment below, t-butyl chloride is solvolyzed in aqueous ethanol. All three of the
reactions observed give one molecule of hydrogen chloride for each molecule of t-butyl chloride
consumed (see below). You will titrate with NaOH to determine how much acid has been
produced as a function of time; from these titration data, the concentration of t-butyl chloride as
a function of time can then be calculated.
2
solvolysis by water (S
N
1): (CH
3
)
3
CCl + H
2
O ! (CH
3
)
3
COH + HCl
solvolysis by ethanol (S
N
1): (CH
3
)
3
CCl + C
2
H
5
OH ! (CH
3
)
3
COC
2
H
5
+ HCl
elimination (E1): (CH
3
)
3
CCl ! CH
2
=C(CH
3
)
2
+ HCl
Procedure
The detailed planning of the experiment is left to you, but here is a general procedure that should
yield accurate kinetic data.
Please work in pairs. Prepare 500 mL of a 55:45 (v/v) mixture of distilled H
2
O and 95% EtOH
(i.e., mix 275 mL of distilled H
2
O and 225 mL of 95% EtOH). Add 100 mL of this solution to a
250 mL Erlenmeyer flask, followed by three-four drops of bromthymol blue (BTB) indicator.
Bromthymol blue is yellow at acidic pH and blue at basic pH. (You will find that placing a piece
of white paper under your flask greatly aids in visualization of the color.) Typically, this initial
solution will be a bit acidic, and thus you should carefully pretitrate it with NaOH until the
indicator JUST BARELY CHANGES color from yellow to blue. Only a DROP OR TWO of
NaOH may be needed here, although sometimes more is required. Be sure to swirl the solution
after adding each drop of NaOH solution. Note: Once the solution has turned blue, the color may
change back to yellow after a few moments due to the absorption from the atmosphere of carbon
dioxide, which then forms carbonic acid in solutionthis is perfectly fine; dont pretitrate again!
2
solvolysis by water (S
N
1): (CH
3
)
3
CCl + H
2
O ! (CH
3
)
3
COH + HCl
solvolysis by ethanol (S
N
1): (CH
3
)
3
CCl + C
2
H
5
OH ! (CH
3
)
3
COC
2
H
5
+ HCl
elimination (E1): (CH
3
)
3
CCl ! CH
2
=C(CH
3
)
2
+ HCl
Procedure
The detailed planning of the experiment is left to you, but here is a general procedure that should
yield accurate kinetic data.
Please work in pairs. Prepare 500 mL of a 55:45 (v/v) mixture of distilled H
2
O and 95% EtOH
(i.e., mix 275 mL of distilled H
2
O and 225 mL of 95% EtOH). Add 100 mL of this solution to a
250 mL Erlenmeyer flask, followed by three-four drops of bromthymol blue (BTB) indicator.
Bromthymol blue is yellow at acidic pH and blue at basic pH. (You will find that placing a piece
of white paper under your flask greatly aids in visualization of the color.) Typically, this initial
solution will be a bit acidic, and thus you should carefully pretitrate it with NaOH until the
indicator JUST BARELY CHANGES color from yellow to blue. Only a DROP OR TWO of
NaOH may be needed here, although sometimes more is required. Be sure to swirl the solution
after adding each drop of NaOH solution. Note: Once the solution has turned blue, the color may
change back to yellow after a few moments due to the absorption from the atmosphere of carbon
dioxide, which then forms carbonic acid in solutionthis is perfectly fine; dont pretitrate again!

3
Now the kinetics may begin! You should record your data as total volume of NaOH neutralized
as a function of total time elapsed. Your first data point will therefore be: 0 mL NaOH
neutralized at time = 0.
Add 0.5 mL of 0.01 M NaOH solution from a full burette (dont forget also to read the burette
before adding the NaOH)the indicator should turn decidedly blue. At t = 0, add 0.5 mL of the
stock 0.2 M t-butyl chloride solution (which, incidentally, has been prepared in acetone solvent)
and swirl the flask thoroughly. Carefully observe and note the exact time that the indicator
changes color back to yellow (acid). This is your second data pointi.e., 0.5 mL base
neutralized at the time you just measured. Immediately, add an additional 0.5 mL increment of
NaOH so the BTB again assumes its blue (alkaline) color and swirl thoroughly. Watch and note
the time at which the solution again turns yellow (acid). This is your third data pointi.e., 1.0
mL total base neutralized at the total time elapsed since t = 0.
Nota bene: The t-butyl chloride will continue to react regardless of whether NaOH has been
added! Thus, as noted above, you must add the next aliquot of NaOH solution immediately after
the indicator changes color back to yellowi.e., time and kinetics wait for no person.
Repeat the above process several timesremembering to swirl after each addition of NaOH
solution!collecting data for an additional five or six time points.
When you have collected all of your data points, do not immediately add more NaOH. Rather,
drive the reaction to completion by heating the solution on a steam bath for approximately 5-10
minutes. After cooling the solution to room temperature (use an ice bath), then do a final NaOH
titration, recording the volume required to just neutralize the solution. Since the pH indicator
doesnt work at high temperature, it really is essential that you cool the reaction flask in an
ice bath before you perform the final titration. You will now have all of the data needed for
the analysis of this reaction. Note: The total volume of NaOH solution added in the
experimenti.e., that required for all of the time points plus the final titrationis proportional
to the total amount of t-BuCl with which you began.
Do one or two trial experiments. When you are confident of your techniquei.e., a plot of your
data on semi-log paper (see Topics for Report, Question 4.) gives a straight line with negative
slopestart the serious work (see next page). Read the remainder of this section before
beginning, and organize with neighboring groups to ensure that you can collect all the kinetic
data with maximum efficiency.
Every pair should perform this first experiment:
4
Duplicate runs with 0.5 mL t-butyl chloride solution at room temperature (standard
conditions)one of these runs may be a successful trial experiment from above.
In addition, each of the three groups should perform ONE of the following pair of experiments
(as determined within your confederation of neighboring groups):
Single runs with 0.75 mL and with 0.25 mL of t-butyl chloride at room temperature;
Single runs at temperatures above and below room temperaturethermostat the flask
by immersing it in a large volume of cool or warm water in one of the plastic wash tubs;
let the flask thermally equilibrate for at least ten minutes before proceeding with the run;
Single runs with 65 mL H
2
O/35 mL 95% EtOH and with 45 mL H
2
O/55 mL 95% EtOH
at room temperature.
(Note: For all of the above experiments, you should jot down what temperature room
temperature actually is!)
The design of these experiments is left to you. Hint: You may vary the initial amount of t-butyl
chloride solution employed for the warm and cool runs, and for the runs that test the effect of
solvent composition (under what circumstances should you use more of t-butyl chloride solution,
should you use less??). You need NOT add 0.5 mL aliquots of NaOH solution for each time
pointincrease or decrease the amount (of course, measuring the precise amount with your
burette) as necessary. Finally, to ensure that the warm and cool reactions are neither too fast nor
too slow, we recommend temperatures of approximately 40 C for the warm and 10 C for the
cool.
When you have completed the experiment, please clean your burette with distilled water by
rinsing the inside out and clamping it, with the stopcock open, upside down in the holder to dry.

5
Topics for Report
For your lab report, answer the questions below. Be sure to hand in the carbonless copies of
your lab notebook pages for this experiment and include ALL plots. Please show all work for
your calculations.
1. Even though acid is continually produced by the solvolysis of t-BuCl, why for each data point
does the indicator change color only after a discrete interval of time?
2. S
N
1 and E1 reactions are both first-order in alkyl halide. Hence:
[ ]
[ ] RX k
dt
RX d
rate
1
= ! =
where k
1
is first order rate constant for the reaction (the minus sign indicates that alkyl halide
concentrationt-BuCl, of course, in this experimentis decreasing as the reaction progresses).
The rate is also known as the reaction velocity. Integrate the expression between the limits t = 0
and t = t to show the relationship between t and [RX]. (See Zumdahl, Section 15.4 for a detailed
discussion.) What are the units of k
1
? Remember, in your equation [RX]
t
will refer to the
concentration of unreacted RX at time t, and [RX]
0
will refer to the concentration of RX at t = 0.
3. Assume that the reaction you have studied is truly first-order, as defined in Question 2.
Explain, for the four room-temperature experiments performed in 55 mL H
2
O/45 mL 95% EtOH
(duplicate runs with 0.5 mL t-BuCl, individual runs with 0.25 and 0.75 mL), why in principle:
a. The values for the k
1
s should/shouldnt be the same. Hint: k
1
= Ae
-Ea/RT
, as youll
further analyze in Question 6that is, k
1
depends on both E
a
and T (you may ignore
the pre-exponential factor A).
b. The values for the initial reaction rates should/shouldnt be the same. Hint: initial
reaction rate = k
1
[t-BuCl
initial
]; the stock solution of the t-butyl chloride has a
concentration of 0.2 Mfor each run, you added either 0.25, 0.5, or 0.75 mL of this
stock solution (or perhaps a different volume if you adjusted the conditions) to 100
mL of ethanol/water solution.
Explain, for the two runs above and below room temperature, why in principle:
c. The values for the k
1
s should/shouldnt be the same.
d. The values for the initial reaction rates should/shouldnt be the same.
6
Explain, for the runs in 65 mL H
2
O/35 mL 95% EtOH and in with 45 mL H
2
O/55 mL 95%
EtOH, why in principle:
e. The values for the k
1
s should/shouldnt be the same.
f. The values for the initial reaction rates should/shouldnt be the same.
4. We now wish to determine k
1
for the eight experiments performed. As you consider the
experimental procedure, you will realize that you have effectively measured the amount of acid
produced as a function of time, but the integration performed in Question 2 demands a
concentration of [RX] remaining at each time point. Your first inclination will be to convert all
these acid quantities to concentrations, but that is pretty tedious and, youll be happy to know,
unnecessary. For first-order reactions of the type you have performed, a plot of ln{volume NaOH
(infinity) - volume NaOH (time)} (y-axis) vs. time (x-axis) has a slope equal to -k
1
. Thats pretty
amazing. If you know how to use semi-log paper, it is still easier, if you recall that for a first-
order reaction k
1
= ln2/t
!
= 0.693/t
!
(note: you cannot measure a slope off of semi-log paper!). If
you do not know how to use semi-log paper, askor, if you insist, you may use a computer.
When semi-log paper is properly utilized, it allows one to obtain the rate constant for an
experiment in about 30 seconds. Include all graphs with your report.
Determine and tabulate the rate constants for the eight experiments performed. Beside each k
1
,
put your calculated value for V
i
, the initial reaction rate for the run. Be sure your units for k
1
and
V
i
are correct.
5. Analyze the accuracy of your experimental technique, as revealed by a comparison of your
predictions (Question 3.) to reality (Question 4.) for the eight runs.
6. The Arrhenius equation can be written in the form: k = Ae
-Ea/RT
. By taking the natural
logarithm of both sides and plotting ln(k) vs. (1/T), calculate E
a
for the solvolysis of t-BuCl in the
55% H
2
O/45% EtOH. (See Zumdahl, Section 15.8 for a detailed discussion.) Note: The
temperature values must be in units of Kelvin! Organic chemists believe reactions that proceed at
a reasonable pace at room temperature have an E
a
! 20 kcal/mole. Does your value of E
a
support
this belief?
This report is due in your regular lab period next week.

Experiment 8:
Recrystallization
Week of November 05

1

Experiment 8: Recrystallization
Pre-lab Preparation
Before coming to lab, please download and read the supplementary material for this
experiment: Fessenden, Fessenden, and Feist, Techniques 1, Crystallization, and 14.2,
Heating Reaction Mixtures. (The two readings are combined in a single PDF.)

Also, answer the following pre-lab questions:
Pre-lab Q1: You will be using two different recrystallization solvents in todays experiment:
water for recrystallizing salicylic acid and hexane for recrystallizing fluorenone. Why? What do
you think would happen if you accidentally switched the recrystallization solvents for the two
experiments?

Pre-lab Q2: Weve used diethyl ether several times this semester, but not today. In fact, its not a
very popular solvent for recrystallization. Why? (Hint: It might work alright if you were
recrystallizing your favorite compound in Antarctica.)

Pre-lab Q3: Calculate how much 1 M H
2
SO
4
you expect to use to neutralize your hydrolysis
reaction after it is complete (see pages 2 and 3). (Hint: Although chemical reactions will have
occurred, the total moles of base present in your reaction mixture will simply equal that in the
initial 50 mL of 20% NaOH; a second hint: H
2
SO
4
is a diprotic acid.)

Background
Purification of an impure substance by recrystallization is one of the most commonly performed
operations in the organic laboratory. In this experiment you will perform two recrystallization
experiments: one as part of the work-up of a reaction that youll run today, and a second to
further purify a compound that you isolated by extraction many moons ago.

2
For your first lesson in recrystallization, you will saponify (i.e., hydrolyze under alkaline
conditions) methyl salicylate and isolate the product salicylic acid by precipitation with acid,
followed by filtration. You will then recrystallize your salicylic acid to obtain a fabulously pure
sample. The chemical reactions involved, some of which will be unfamiliar to you at this point,
are shown below.
O OCH
3
OH
NaOH/H
2
O
O O
O
H
2
SO
4
/H
2
O
O OH
OH
Methyl Salicylate
Salicylic Acid

The second recrystallization will be performed on fluorenone, a compound that you purified by
acid-base chemistryor, more precisely, by its lack thereofway back in Experiment 4. Can
you purify it further by recrystallization? Well find out soon enough.

Procedure
Part A: Saponification of Methyl Salicylate and Recrystallization of Salicylic Acid

The equipment for the saponification of methyl salicylate is illustrated in the diagram on the next
page, although you will use a Bunsen burner, rather than the steam pot shown, to heat the
reaction flask as the reaction solvent today is water (rather than a more commonly encountered
flammable organic solvent).

Using a Pasteur pipette, weigh out 5.0 g of methyl salicylate directly into a 500-mL round-
bottom flask. Add 50 mL of the 20% NaOH (i.e., 20 g NaOH per 100 mL of solution) provided
and a few (4!6) boiling chips. Note what happens immediately upon mixing of the NaOH and
methyl salicylate.

a. What is the explanation for what you just observed? That is, give the formula for
the species to which methyl salicylate has been converted. (Hint #1: The reaction you
just witnessed occurred very rapidly. Hint #2: Despite comprising ions, organic salts
can be quite hydrophobic and not freely soluble in water.)
3

Clamp your round bottom to the monkey bars, making sure that the clamp is around the
ground-glass joint of the round bottomsee the figure below. Place a reflux condenser into
the round bottom. (If the ground-glass joints appear to be bone dry, you may smear them with a
tiny bit of vacuum grease to create a more snug fitreally, just a tiny bit of grease is enough!)
The water flows in the bottom of the condenser, out the top, and not too rapidly.

Gently reflux the solution for 20 minutes. Turn off the flame and let the reaction apparatus cool
for a few minutes (obviously, the round bottom will be very hot!); then cool it to room
temperature in an ice-water bath. (Simply remove the reflux condenser, and then detach the
clamp with the round bottom still attached from the monkey barsuse the clamp as a handle to
place the round bottom in your ice bath. As youll see, the clamp will keep the round bottom
from tipping over.)

b. Has the appearance of the solution changed since your observation in part a? Give
the structural formula of the substance that you believe is now present, and, if there
has been a change of appearance, explain.

While the round bottom is still in the ice bath, acidify the mixture with 1 M H
2
SO
4
. (Remember
that you calculated how much 1 M H
2
SO
4
to use in your pre-lab, but before you start adding it
4
you may want to check your calculation with your instructor or T.A.) Add 10 mL of the H
2
SO
4

solution at a time, swirl well, place the flask back into the ice bath, and then repeat. After youve
added the requisite amount of 1 M H
2
SO
4
, check the pH of the solution by putting a drop on to a
small piece of pH paperif the paper isnt red, acidify the mixture with a bit more 1 M H
2
SO
4

(10 mL at a time) until it is.

c. Has the appearance of the mixture changed since your observation in part b? Give
the structural formula of the substance that you believe is now present, and, if there
has been a change of appearance, explain.

When the acidification is complete, cool the solution in an ice bath and collect your crude
product on your large Bchner funnel fitted with the proper-size, flat filter paperi.e., a piece
that lies flush on the bottom of the Bchner funnel (see the picture on the next page, which youll
note instead shows a small Bchner funnel; again, use the large one today).

This is a vacuum filtrationthe standard method for recovering a valuable precipitate. Please
remember how to do it, as you will need this technique in the future. Use the house vacuum
hereas you add your crude product to the Bchner funnel, press down gently on the funnel to
be sure that the vacuum takes. Be careful that your vacuum flask does not fill and overflow into
the trap. If it is about to overflow, stop the filtration, empty out the filtrate into the waste
container, and then continue. Wash your crude product several times with ice-cold water after the
filtration is complete (ice-cold water is used so as not to redissolve any of the salicylic acid).

Remove a small portion of this crude material and let it dry on a small watch glass until the next
period. Your melting point analysis of the crude material will provide a baseline for
determination of whether or not your recrystallization actually umm, how do we put this did
anything useful.

5

Your sample must now be recrystallized from water. Recrystallization theory and procedures are
described in the supplementary reading, but let us note some particulars for today:
a. Transfer your crystals into a 250 mL Erlenmeyer flask
b. Add about 50 mL of distilled water and a few fresh boiling chips to your crude material.
c. Use a hot plate to heat the solution!watch it carefully and be sure that the solution doesnt
boil out of the flask.
d. Once the water is boiling, add small portions (5!10 mL) of distilled water and bring the
solution to a boil again (pre-heating the extra water and/or keeping it in an Erlenmeyer on the hot
plate will help expedite the process).
e. Repeat step d until all of the solid has dissolved. Watch how much solid dissolves each time
this will give you an idea of how much water you'll need to add to dissolve it all.
[f. Remove, only if necessary, insoluble impurities from the hot solution via gravity filtration
using fluted filter paper in a stemless funneltoday, you should NOT need to do a hot filtration.]
g. Let the solution cool sllloooooooowwwwly to room temperature on your bench top. Slow
crystallization is the key to getting high-purity product. Plunging the hot solution into ice may
6
cause tiny crystallites to crash out of solution, and impurities will end up trapped in the crystal
lattice. So don't do that. But do say Ooooh and Aaaaaah when the crystals begin to form.
Note: Do you feel like youre just waiting around for your solution to cool? It might be a good
time to start part B.
h. After the suspension of crystals has come to room temperature, cool the flask in an ice-water
bath for 5 minutes. Isolate the final product via vacuum filtration (as shown above), concluding
by washing your crystals, while theyre still in the Bchner funnel and with the vacuum on, with
ice-cold water.

i. Let your purified sample air dry until next week by simply placing your Bchner funnel, moist
crystals and all, into a large beaker; then place the beaker/Bchner funnel/crystals into your
bench. Next week, you will weigh your dry crystals and determine the melting-point ranges of
your crystals and of your crude precipitate.

Note the general rule: If you wish to remove insoluble impurities, gravity filter using fluted
filter paper; if you wish to collect a solid (which typically is your product), vacuum filter using a
Bchner funnel.

Part B: Recrystallization of Student-Extracted Fluorenone
You didnt know this at the time, but way back in experiment 4, when you used extraction to
purify three organic compounds, we saved all of your ethereal solutions of fluorenone. Later, we
pooled them and evaporated the ether, yielding a big pile of student-extracted fluorenone. With
your new skills, you can now attempt to purify the fluorenone further. All were going to tell you
is the following: use 0.5 g of fluorenone and use hexane as your recrystallization solvent.

OK, we lied. Were going to tell you one more thing: notice the difference in scale between your
salicylic-acid recrystallization and your soon-to-be-performed fluorenone recrystallization. Do
you think you should start with 50 mL of the recrystallization solvent again? Do you think you
should use the same size Erlenmeyer? Should you use the same-size Bchner funnel to collect
your crystals?

7
After your fluorenone-from-hexane recrystallization is complete, let your purified fluorenone
crystals air dry until next week by simply placing your Bchner funnel, moist crystals and all,
into a beaker; then place the beaker/Bchner funnel/crystals into your bench. Next week, you
will weigh your dry fluorenone and determine its melting-point range. (Dont worry about saving
a little bit of crude fluorenone for comparison. Everybody will be using the same fluorenone
starting material for their recrystallization, so well measure the melting-point range of the pile
and provide the data to you.)

Topics for Report
Part A
1. Be sure to answer Questions a, b, and c that are interspersed in the part A text.

2. Calculate your percent yield of salicylic acid. If it is, below 90%, briefly comment on what
could have caused the loss of material. Show all work.

3. Did your salicylic-acid recrystallization go as planned? If not, what would you change if you
had the chance to repeat the experiment?

4. Based on the melting points of your crude and recrystallized salicylic acid, did your
recrystallization effect an actual purification of the material? Note that salicylic acid has a
melting point of 158161 Cmelting points are often reported as a range from the temperature
at which melting first begins to the temperature at which the sample is fully melted. The higher
and narrower your temperature range iswith 158161 C being the standard of excellencethe
purer your material.

5. Provide an alternative name for methyl salicylate (what were looking for here is oil of...),
as well as the structure and an alternative name for acetylsalicylic acidwe dont need to tell
you that Google is a good place to find the answers to these two questions!

Part B
6. Did your fluorenone recrystallization go as planned? If not, what would you change if you had
the chance to repeat the experiment?
8

7. Based on the melting points of the crude (provided for you) and recrystallized fluorenone, did
your recrystallization effect an actual purification of the material? Note that pure fluorenone has
a melting-point range of 80!83 C.

Your lab report is due at the beginning of lab the week after Thanksgiving. (Yes, that is a
really long time from now.) The reason for this delay is that you will still be collecting and
analyzing data from this experiment during next weeks lab period.

Experiment 9:
Qualitative Analysis
Week of November 12

1
Experiment 9: Qualitative Analysis
Pre-lab Preparation
Answer the following pre-lab questions:
Pre-lab Q1: Find and carefully record in your notebook the structure of each of the eight
unknown compounds you will be working with. If you can't find the data in Wikipedia, try
ChemSpider or another source. Also find and draw the structures of the five compounds to be
used as controls in the DNP, chromic acid and permanganate tests. Note any information that
you happen to find regarding physical appearance (at room temperature)this may help you
identify the compounds.
Pre-lab Q2: Based on its functional group, to which class does each compound belong?
Pre-lab Q3: Read through the chemical tests that you will be running, as described below. Based
on these tests, write a flow chart for the sequence of tests that you will use. This will serve as a
guide that you will be able to follow as you work. At each stage, indicate which compounds give
positive and which give negative tests, and what positive and negative results look like. The
order of the tests and a sample flow chartshowing tests irrelevant to todays experimentsis
included below on page 3.
Background
Chemists frequently use qualitative patterns of reactivity to identify the functional groups of
unknown compounds. This technique, called qualitative analysis, was an especially important
tool for structure determination in the early days of organic chemistry. An alkene, for example,
can be identified by its reaction with Br
2
disappearance of the red-brown color of the bromine
provides clear visual evidence that a reaction has occurred. Similarly, upon treatment with
chromic acid, certain functional groups are oxidized, and this is accompanied by reduction of the
orange Cr(VI) to the blue-green Cr(III) an obvious change.
Since the development of powerful spectroscopic methods for structure determination, including
infrared (IR), and especially nuclear magnetic resonance (NMR, which we will study this
semester), most of these qualitative chemical tests have become less important than they once
2
were. However, these tests are quick and easy, and they are still useful for identifying functional
groups or confirming the presence of functional groups identified spectroscopically. Perhaps
more important for our purposes, these tests will familiarize us with the chemical behavior of a
variety of different compounds, they'll give us a chance to learn some new chemistry, and
gosh darn it they're just plain old fashioned fun.
In this lab you will use a combination of physical and chemical tests to identify eight
compounds. Each of these tests should give an easily visible result. The different tests are
explained in detail and the procedures are described below. The eight compounds that you will
be testing have been placed in plain brown bottles labeled "A" - "H" to protect their identities.
Fortunately, you will not have to determine the entire structure of each compound (you couldn't
do that at this point in the course even if you wanted to). The compounds are 1-butylamine,
butanone, 1-butanol, butanal, propanoic acid, 1-chloropropane, pentane, and 2-pentene (a
mixture of cis and trans). Since each compound has a different functional group (or lack
thereof), you will be able to determine which compound is in which bottle by determining what
functional group is present.
Caution: Most of the unknown liquids are flammable, and their vapors may be harmful.
Some can cause irritation on contact with eyes or skin. Keep them away from open flames
and avoid unnecessary contact or inhalation of vapors.
Procedure
Please work with a partner on this experiment, but do not split the taskseach partner should
participate in each part of this experiment and independently record observations in his or her
notebook.
You will run the following qualitative analyses today: litmus test (here there are three options,
of course neutral, acidic, or basic), DNP test, H
2
CrO
4
test, KMnO
4
test, and Beilstein flame
test. You already have your flow chart that shows which compounds should give positive and
negative results for each of the tests (organized in the sequence described above). Once you have
positively identified a compound, you can set that aside don't continue running tests. For
example, if one compound tests acidic with litmus, you know which one that is, right? Don't
3
bother running the other tests on that one. As an example, a flow chart for a completely different
series of compounds and tests is shown below.
unknowns:
OH
OH
O
Ceric nitrate test for alcohols
((NH
4
)
2
Ce(NO
3
)
6
, H
2
O, HNO
3
)
positive
(red complex)
negative
OH
OH
O
Lucas test
(ZnCl
2
, aq HCl)
positive
(cloudy soln
within 10 min
with 2 ROH)
Sample flow chart
negative
(No or very
slow rxn
with 1 ROH)
OH
OH

Your flow chart is the most important part of your pre-lab write-up. You must do this carefully
and thoughtfully before you can start the experiment. Your TA will check the flow charts early
in the lab so potential points of confusion can be identified before anyone gets completely off
track.
I. Litmus tests. Because the molecules in our set of eight are relatively small, a polar functional
group will probably make the compound miscible with, or at least soluble in, water. Based on
their structures, which compounds do you expect to be water-soluble and which insoluble?
Procedure. To get an idea of the water solubility of each compound, add about two mL of water
to 10-drops of compound in a test tube, stopper the tube and shake it vigorously. If a
homogeneous solution results, the compound is soluble in water. If the compound dissolves,
we'll call it soluble; if not, we'll call it insoluble.
Test the pH of all the homogeneous solutions by placing a drop on pH paper (don't dip the paper
into the solution). One of the compounds in the set should test acidic; one should test basic.
Which ones? Note that it's not necessary for a compound to be completely protonated or
4
deprotonated by water to alter the pH (think gen-chem pH calculations here). Now, for the
compounds that didn't dissolve at all, it's pointless to test the pH of the water, so don't do that.
Discard these solutions and mixtures when you're finished the remaining tests must be done
starting with the pure compounds.
II. DNP test. Ketones and aldehydes react with hydrazines to form compounds called
hydrazones. For example, the reaction of 2,4-dinitrophenylhydrazine ("2,4-DNPH") with a
generic ketone is shown below.
O
2
N
NO
2
Ar =
O
R
R
+
H
2
N
NH
Ar
H
+
N
R
R
NH Ar
+ H
2
O
a 2,4-dinitrophenylhydrazone
("2,4-DNP")

Although this is a reaction you haven't seen before, you can write the mechanism. There are two
steps and some "proton shuffling". The N attached to the aromatic ring is not nucleophilic
because its lone pair is delocalized by resonance; the "end" nitrogen is the nucleophilic one. This
N attacks the carbonyl C, displacing the !-electrons onto O that's step 1 formation of the
CN bond. Next, the negative O is protonated and the positive N is deprotonated (H
+
is
transferred to the solvent). The resulting "carbinolamine" then undergoes an acid-catalyzed
dehydration (you already know that mech!) to form the CN !-bond of the product O is
protonated, then water is lost (that's "step 2" cleavage of the CO bond), the resonance-
stabilized cation spits out a proton and... congratulations, you've just made a hydrazone!
2,4-Dinitrophenylhydrazones ("2,4-DNPs") are typically yellow or orange crystalline solids.
The hydrazones derived from simple aldehydes and ketones are usually yellow; those derived
from conjugated carbonyl compounds are usually orange or red-orange. Hydrazones of simple
aldehydes and ketones normally form quite easily. (Complications are sometimes encountered
as a result of impurities, formation of colored complexes with certain compounds, and side-
reactions that can give false positive tests, but these complications should not be a major concern
5
for us. However, this is why we also need to run control experiments so we can see what
authentic positive and negative results look like!)
Procedure. Dissolve 1 drop of compound in about 1 mL of 95% aq ethanol, and add 2 mL of the
2,4-DNPH reagent (this is a solution of the hydrazine (about 2%) in EtOH (50%), H
3
PO
4
(40%),
and H
2
O (10%) Caution: this solution is toxic and corrosive.) Gently shake the mixture and
let it stand. Also run three controls: cyclohexanone, benzaldehyde, and 1-pentanol so that you
can see what authentic positive and negative results look like.
III. Chromic acid test. Certain alcohols, aldehydes, and a few other types of compounds can be
oxidized with aqueous chromic acid, H
2
CrO
4
. Oxidation of the organic compound is
accompanied by reduction of the chromium from the soluble orange Cr(VI) reagent to an
insoluble blue-green Cr(III) product.
Most oxidations of organic compounds involve loss of hydrogens and/or gain of oxygens or gain
of bonds to oxygen. For example, a primary alcohol one whose OH group is attached to a
primary C can be oxidized by Cr(VI) (as well as other reagents) to an aldehyde; most
oxidants, including aqueous chromic acid, will further oxidize the aldehyde to a carboxylic acid.
At this stage the C has no more Hs, so that's the end of the road carboxylic acids cannot
(easily) be oxidized further. Note the exchange of CH bonds for CO bonds in each step. (To
recognize oxidations and reductions, you need to focus on what's happening to the C not the O!)
C
O
R
H
C
OH
R
H
H
[ox]
[red]
[ox]
[red]
C
O
R
OH

Secondary alcohols are oxidizable (to ketones), but tertiary alcohols are not. Draw these and
you'll see why the key is whether the C bearing the hydroxyl group has an H or not if not,
that C is not oxidizable. To take this idea one step further, unlike all other carboxylic acids,
formic acid, HCO
2
H can be oxidized to CO
2
(or to the "hydrate" of CO
2
, H
2
CO
3
). Formic acid
is the only oxidizable carboxylic acid because it's the only one with an H on the carboxyl C!
Alcohols are normally oxidized rapidly with chromic acid, H
2
CrO
4
; aldehydes are oxidized a bit
more slowly, possibly because their oxidation occurs via an intermediate hydrate (RCH(OH)
2
,
6
formed by addition of water to the CO !-bond). In addition, chromic acid will oxidize phenols
and may also oxidize amine nitrogens and even alkenes, alkynes, and certain ketones under more
extreme conditions. The amine should be out of the picture by the time you get to this test, but
you should run controls on the other functional groups.
Procedure. Dissolve 1 drop of compound in about 1 mL of reagent grade acetone. Add one
drop of the chromic acid reagent (this was made by combining 20 g of Na
2
Cr
2
O
7
, 14 mL of
H
2
SO
4
, and 100 mL of H
2
O Caution: this solution is toxic and corrosive. Chromic acid is a
suspected carcinogen). Gently swirl the mixture and let it stand. Note the time required for
reaction. A positive result should be visible within a few minutes. Run the same three controls
that you did for the DNP test, plus tert-butyl alcohol and cyclohexene.
IV. Permanganate test. In basic solution at room temperature KMnO
4
will hydroxylate an
alkene (i.e. add two OH groups to the !-bond); in neutral or acidic solution, it will chop an
alkene into two pieces by cleaving both !- and "-bonds. Both of these reactions are oxidations
of the organic compound; the manganese is reduced from Mn(VII) to Mn(IV) in the process.
This reduction changes the purple permanganate solution to a brown precipitate of MnO
2
.
Under the relatively mild conditions of our test (dilute, neutral permanganate solution), only
alkenes and alkynes should react. However other oxidizable compounds may react as well, e.g.
amines, phenols, aldehydes, and alcohols (surprisingly, most alcohols are not oxidized under
these conditions). Also, be aware that a tiny amount of oxidizable impurity might cause a false
positive with the first drop of permanganate added. Again, these are the reasons that we run
controls so we can see what authentic positive and negative test results look like.
Procedure. Dissolve 1 drop of the pure compound in 2 mL of 95% aq EtOH, and add 5 drops of
0.1 M aqueous KMnO
4
solution. (Caution: this is likely corrosive.) Remember, decolorization of
just the first drop may be due to an oxidizable contaminant rather than the compound of interest.
If a reaction does not take place immediately, shake the mixture and let it stand for 5 min. This
should be sufficient time for even the most stubborn alkene to decide to react; anything that
happens after this time is probably due to oxidation of a less reactive functional group. Even
alcohols tend not to react within 5 min under these conditions (strange, but true). Also run
7
cyclohexene, 1-pentanol, and tert-butyl alcohol as controls (we'll find out if alcohols really fail to
react!).
V. Beilstein test. This is a classic test for halogenated compounds. When red-hot Cu is placed
in contact with an organo-halide, some CuX is formed. Cuprous halides are volatile enough that
placing them in a flame will generate a green color in the flame from the vaporized CuX. The
green color is characteristic of the copper atoms.
Procedure. Get about 10 cm of copper wire and make a small loop at the end. Heat the loop in a
flame, in the fume hood, until it's glowing red. Plunge the red-hot Cu loop into about 0.5 mL of
the compound to be tested (seriously), then return it to the flame and watch carefully. Note that
Bunsen burners have an air intake that may need to be adjusted a yellow flame (too much gas,
not enough air) is too cool and too bright; you need a blue flame for this experiment. Caution:
Be careful not to set fire to the compounds, your notebook, paper towels, yourself, your
partner, the instructors, or anything else. No controls this time; at this point you should be
down to two compounds, one that creates fireworks and one that doesn't.

Your report for this experiment is due at the end of the period. A reminder before you go: be
sure to finish up the remainder of the lab work for Experiment 8!

Topics for Report
For your report, please include everything you did and observed, and the compound
assignments you were able to make at every step of the process. Be sure to carefully note any
unclear or anomalous results (there are bound to be some things that are less than clear in these
tests). Provide a final summary of the compound structures that correspond to your section's
unknowns A."H.

Have a Happy Thanksgiving!

Experiment 10:
Infrared Spectroscopy
Week of November 26

1
Experiment 10: Infrared Spectroscopy
Pre-Lab Preparation
Please read Jones, section 15.4. (Are you getting a feeling of dj vu? Yes, we did indeed ask
you to do the very same thing months ago during your preparation for Experiment 2. But we
havent returned to the concepts of IR spectroscopy since then, so a refresher might not be a bad
idea.) Note that although IR spectroscopy will be an important part of the structure-
determination problems that you encounter in the next couple weeksoh yeah, and maybe also
on the final examthere will be little coverage of IR concepts in lecture. So your preparation for
and attention to todays lab are very important! One more thing: after you re-read Jones, section
15.4, make sure that you bring Jones, which includes handy tables of characteristic IR
absorption bands on pages 710 and 711, to lab. Now the good news: there is no pre-lab report
required for this experiment.
Procedure
Today, with the help of the computer program IR Tutor, we will explore the remarkable world of
infrared spectroscopy. As you work through the tutorial, write the answers to the questions posed
below in your lab notebook. When you have finished with the program, you should be an expert
in infrared spectroscopy!before leaving today, please test your newly acquired knowledge by
also doing the problems at the end of this handout. For your lab write-up, simply hand in all of
your answers when you are finished.
Preliminaries
Open IR Tutoryoull find it in the bottom Course-related folder under All Programs. Then
set the screen resolution on your computer to 800 by 600 or 1024 by 768 pixels (whichever
looks better to you) by going to Control Panel " Display " Settings. Begin with the
Theory of Infrared Spectroscopy section of IR Tutorfirst click on Classical Model of a
Molecule and then use the arrow buttons on the bottom right to move forward (and backward, if
youd like to review any text). As you work through this section of the program, please be sure
that you understand and write down in your lab notebook what a fundamental and
overtone are, and also the factor that determines the intensity of an IR absorption. (Note that if
2

you find yourself looking at an IR spectrum of hexane, youve moved on to the next part of this
handout.)

We know that weve asked you to read Jones, Section 15.4 two times already, but everything
today will make much more sense if you begin by taking just a few minutes to re-re-read the IR
spectroscopy overview by Jones, which is reprinted for your convenience on the next page:
3

4

Spectral Interpretation
Now move on to Interpretation of Spectra (also entitled Spectral Interpretation). Click on
Hexane to view its IR spectrum. Click on the right-arrow button. First, you will be given some
general information about the spectrum. Continue to click on the right-arrow button. You will
soon see the molecular vibration giving rise to each infrared absorption in the spectrum. Chat
approvingly with your lab partner. Make use of the Expand option to obtain a better view of
those portions of the spectrum with numerous absorptions. Continue clicking the right-arrow
button until you see summaries of the absorptions due to the presence of the methyl (CH
3
) and
methylene (CH
2
) groups.
Another nice feature of IR Tutor is the overlay function, which allows direct comparison of two
spectra. To see how this works, open the Overlay menu and click on 2,3-Dimethylbutane. You
should now see the spectrum of 2,3-dimethylbutane superimposed on that of hexane, and youll
notice that the spectrum of 2,3-dimethylbutane contains no methylene absorptions (hmmm can
you figure out why?). Use of the Expand feature will be of help in seeing this clearly. As always,
you can use the right-arrow button to view each of the molecular vibrations. Now use the
Overlay menu to superimpose the spectrum of cyclohexane onto that of hexane, and youll see
that the spectrum of cyclohexane contains no methyl absorptions (another shocker).
5

Practical Spectral Interpretation: Functional Groups
While the above is interesting, the most useful information to be gleaned from an IR
spectrum pertains to the functional groups presenti.e., structural features that are not
merely methyl or methylene groups. Joness division of the IR spectrum into regions see the
text above is an extremely helpful place to begin thinking about where particular absorptions
appear in an IR spectrum. Open your text to Joness Table 15.3 of characteristic absorptions (pp.
710711), which youll need to use as you work through the rest of this lab. Once you start to
work lots (and lots) of structure-determination problems on your own, youll find that youll
naturally learn many of these characteristic absorptions, and you wont need to consult this table
so frequently.
Now lets use IR Tutor to examine the characteristic absorptions of a number of common
functional groups. As you view each one, draw the structure of the example compound in
your notebook, note the relevant characteristic functional-group absorption(s), and answer
any related questions that are posed in the text of this protocol. In addition, for each
functional group, attempt to corroborate the typical ranges given in Joness Table 15.3
with the experimental data in IR Tutor. That is, note the relevant range given in Jones and
state whether or not the specific example in IR Tutor is consistent.
Open the Spectra menu and click on Hexene (which, more accurately, is 1-hexene). What are
the absorptions characteristic of a terminal alkene?
Now, view the spectrum of Heptyne (which, more accurately, is 1-heptyne). What are the
absorptions characteristic of a terminal alkyne? Write down the answer in your lab notebook.
All right, you get the idea. As you view the spectra indicated on the next page, make liberal use
of the overlay function and continue to draw the structures and note the pertinent absorptions in
your notebook. Use of the arrow keys will give you bond summaries.
To determine the absorptions characteristic...
Of a cyano group, view the spectrum of heptyl cyanide
6

Of an aromatic ring, view the spectrum of toluene
Of a hydroxyl group, view the spectrum of hexanol
Of a primary amine group, view the spectrum of hexyl amine
Of an aldehyde, view the spectrum of heptaldehyde
Of a ketone, view the spectrum of heptanone
Of a carboxylic acid, view the spectrum of heptanoic acid!note the extremely broad O-H
stretch
Of an ester, view the spectrum of ethyl acetate
Of an anhydride, view the spectrum of butyric anhydride
You just viewed the IR spectra of five different carbonyl (C=O) containing functional groups
(aldehyde, ketone, carboxylic acid, ester, anhydride). Lets think about the annotation at the top
of Joness carbonyl section: subtract 20-30 cm
-1
for a conjugated carbonyl. Why does
conjugation shift the C=O stretch to a lower wave number? Hint: Resonance structures of
carbonyl compounds in which the pi-bond simply goes away are much more important
contributors than the analogous structures of alkenes. Write down the answer in your lab
notebook.
With the information you have just mastered, you are now ready to do the spectroscopy problems
given on the following pages. Write your answers in your lab notebook.
7

Question 1 (IR theory): Below are a figure, a scheme, and some accompanying text from the
article, In situ infrared spectroscopic studies of the Friedel-Crafts acetylation of benzene in
ionic liquids using AlCl
3
and FeCl
3
(Csihony et al., Green Chemistry 2001, 3, 307-309).

Note that all of the bands shown in Fig. 2 and discussed in the text arise from the stretch of the
carbon-oxygen bond in each molecule discussed. First, focus on bands D (2300 cm
-1
) and B
(1644 cm
-1
). Why does band D, assigned by the authors to the acetylium ion CH
3
CO
+
(AlCl
4
-
serves as the counter ion) appear at a higher energy than that for acetyl chloride (A) itself? Why
does band B, assigned by the authors to the acetyl chloride-AlCl
3
complex appear at a lower
energy than that for acetyl chloride itself?
Hint: You can think of MCl
3
as being analogous to a proton. Also, think about resonance
structures.
8

Additional questions (spectral interpretation):
Question 2: Each of the three IR spectra below is of one of the following difunctional
compounds: an alkene, carboxylic acid; an amino nitrile; or an aromatic aldehyde. Which
spectrum is which?

9

Question 3: Identify the functional groups in each compound from the following infrared spectra.
Note that the spectra in parts (f) and (g) were obtained using a different instrument than that used
for the spectra in parts (b)(e). This is a common situation. Although the spectra obtained with
the two instruments have a different appearance, the characteristic absorptions are independent
of the spectrometer used.
Note: With the exception of (e), each unknown contains only one functional group.
Note further: Alkenes and alkynes count as functional groups, and a heteroatom is any atom
except carbon and hydrogen.
Experiment 10 Chemistry 21
9

10

Experiment 11:
Spectroscopy Dry Lab
Week of December 03

Experiment 11: Spectroscopy Dry Lab
Pre-lab Preparation
Please read Jones, Sections 15.5!15.6, and make sure that you bring the text to lab, it
contains handy tables of characteristic IR absorptions (pages 710 and 711) and
1
H-NMR
chemical shifts (p. 720). An additional chemical shift table and as well as a table of J values are
also provided at the end of this handout.
For your pre-lab report, please answer the following question:
Pre-lab Q: Students who are new to organic-chemistry research are often horrified to find large
impurity peaks in the their NMR spectra, only to be reassured by more senior chemists that the
impurity is really just residual solvent left over from incomplete drying after the work-up
procedure. After feeling a bit silly, the new researcher is pleased to learn that the solvent can be
easily removed with more thorough drying. To help ensure that you will never make the same
mistake, sketch predictions of
1
H-NMR spectra for the common lab solvents ethyl acetate,
diethyl ether, isopropanol, methylene chloride, and tetrahydrofuran. You, of course, will not be
able to predict exact chemical shifts, but proper use of the table at the end of this handout will
yield some pretty good guesses. And, please dont spend time wondering, How do I draw a 7
Hz splitting to scale on a spectrum from a 400 MHz machine? All were after here are rough
schematic sketches that show approximate chemical shifts and the predicted splitting patterns
(singlet, doublet, etc.).
Experimental Objective
To deduce the structure of eight unknowns, given only the molecular formula and the
1
H-NMR
and IR spectra of each. Note that both the
1
H-NMR and the IR spectra given were recorded on a
variety of instruments"in all instances, you should first carefully examine the ppm and cm
-1

scales. You are not required to turn in your answers, but you must complete an exit
interview before you leave the lab today. That is, you must discuss your answersand the
thought process by which you arrived at themwith your instructor and get his or her OK
before you go!

Approximate chemical shifts of hydrogens on
1
H NMR Spectra

Proton Spin-Coupling Constants:

Organic Chemistry Lab Manual, Chem221 - Fall2012 - LabManual

Hochgeladen von

Dokumentinformationen

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

Organic Chemistry Lab Manual, Chem221 - Fall2012 - LabManual

Hochgeladen von

Copyright:

Verfügbare Formate

Chemistry 221:

lab tissue. Assemble the rest

)? As you will see, we have now returned to where we

Das könnte Ihnen auch gefallen