Organic Chemistry, Chem 231 Lab Manual S2013

Chemistry 231:
Organic Chemistry II

2013 Lab Manual

Chemistry 231
Spring 2013

Chemistry 231: General Laboratory Directions

Welcome to lab!

The laboratory period starts promptly (Monday 3:00 pm, Tuesday 8:00 am and 2:30 pm,
Wednesday 2:00 pm, Thursday 8:00 am and 2:30 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
(you may continue to use your notebook from Chemistry 221 if space remains). 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 into 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. 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.
Chemistry 231
Spring 2013

Schedule of Laboratory Experiments

Week Experiment

01/24 No Lab

01/28 No Lab

02/04 1. Synthesis of 1,4-Di-tert-Butyl-2,5-Dimethoxybenzene by Friedel-Crafts
Alkylation

02/11 2. Carbonyl Dry Lab

02/18 3. Synthesis of Nylon

02/25 4. Grignard Synthesis of Triphenylmethanol

03/04 5. Enolate chemistry, Part I

03/11 6. Aldol Reactions (i.e., Enolate chemistry, Part II)

03/18 Spring Break

03/25 No Lab: Week of First Evening Exam

04/01 7. Acetylation of Anthranilic Acid

04/08 8. Diels Alder Extravaganza, Week 1

04/15 8. Diels Alder Extravaganza, Week 2

04/22 No Lab: Week of Second Evening Exam

04/29 Check Out

Experiment 1:
Synthesis of 1,4-Di-tert-Butyl-2,5-Dimethoxybenzene
by Friedel-Crafts Alkylation

Week of February 4

Chemistry 231 Spring 2013
1
Experiment 1: Synthesis of 1,4-Di-tert-Butyl-
2,5-Dimethoxybenzene by Friedel-Crafts Alkylation
[Adapted from Organic Experiments, 7th Edition, L.F. Fieser and K.L. Williamson; D.C. Heath,
Lexington 1992; Experiment 37: Friedel-Crafts Alkylation of Dimethoxybenzene, pp. 359362.]
Pre-Lab Preparation
Before coming to lab, please review Section 14.5 in Jones (Carbon-Carbon Bond Formation:
Friedel-Crafts Alkylation). In that section Jones writes, the gross outcome of the [Friedel-
Crafts alkylation] reaction depends on the structure of the [alkyl group] R. For example, during
the Friedel-Crafts alkylation of benzene with 1-chloropropane, a rearrangement of hydride
generatesa cation in which a secondary carbon bears the positive chargeThese
rearrangements are very common, and are encountered whenever a hydride or alkyl shift will
generate a more stable cation For your pre-lab report, please answer the following question:
Do we need to worry about carbocation rearrangements in todays reaction? Why or why not?
Obviously, you will need to provide some mechanistic details of todays reaction to answer this
question.
Background
This experiment illustrates the Friedel-Crafts alkylation of an activated benzene molecule with a
tertiary alcohol in the presence of sulfuric acid (rather than AlCl
3
) as the acid catalyst. The
electrophilic aromatic substitution (EAS) reaction involves two attacks by 1,4-dimethoxybenzene
on the electrophilic tert-butyl carbocation.
OCH
3
H
3
CO
OH
OCH
3
H
3
CO
+ 2
H
2
SO
4
1,4-dimethoxybenzene
1,4-di-t-butyl-2,5-dimethoxybenzene

Experiment 1 Chemistry 231
2
2
Experimental Procedure
Note: Please measure out all liquid reagents in the fumehood.
Weigh out 6.0 g of 1,4-dimethoxybenzene into a 125 mL Erlenmeyer flask (simply tare the flask
and directly add the 1,4-dimethoxybenzene); add 10 mL of tert-butyl alcohol and 20 mL of
acetic acid. Place the flask, properly supportedi.e., clamped to your monkey barsin an
ice-water bath to cool. Meanwhile, carefully pour 30 mL of concentrated sulfuric acid (H
2
SO
4
)
directly into a separate 125 mL Erlenmeyer flask. Again, place this flask in a small ice-water
bath to cool and secure it with a clamp. (Note: for good thermal contact, your ice-water baths
should indeed contain water.) Be sure to label the flasks so that they you know which is which.
CAUTION: Concentrated sulfuric acid is highly corrosive to human tissue and reacts violently
with water. Plastic disposable aprons with long sleeves and special gloves will be provided by
your instructor before you start the experiment.

3
3
Take the 125 mL flask containing the tert-butyl alcohol and acetic acid and insert a thermometer.
Swirl in the ice-water bath until the temperature in the flask is in the range 58 C. Note: Do not
use the thermometer as a stirring rod! (Any solid that remains after chilling will dissolve
later.) Remove the thermometer and clamp a small separatory funnel in position to deliver into
the flask that contains the tert-butyl alcohol/acetic acid mixture, which must remain in the
ice-water bath. (See the diagram on the previous page.) Wipe dry the other flask that contains
sulfuric acid and pour the chilled sulfuric acid solution into the separatory funnel. While gently
swirling the flask in the ice bath (to facilitate swirling, feel free to remove the clamp at this
point), slowly add the sulfuric acid dropwise over the course of 510 min.
By this time considerable solid reaction product should have separated. Cool the flask in ice until
the temperature is 15 C or below. Once the flask is well chilled, carefully add 1520 pieces of
crushed ice directly to the mixture to dilute the sulfuric acid; then add distilled water to nearly
fill the flask. Continue to cool the reaction mixture and stir with a glass rod; when it is at room
temperature (heat will have evolved from the dilution of sulfuric acid), collect the product in
your large Bchner funnel with suction. Rather than the standard filter paper, use the glass fiber
filter circles youll find in the labthey are quite resistant to the strongly acidic filtrate and
wont dissolve during the filtration! Since youll have a large amount of filtrate, use your 250 or
500 mL filter flask. Once the filtration is complete, press the filter cake down with a spatula and
leave the vacuum on for an additional minute or two. Meanwhile, cool a 30 mL portion of
methanol for washing your crystals (the methanol wash will remove a yellow impurity). Release
the suction from your large Bchner funnel. Cover the filter cake with 10 mL of the chilled
methanol and then reapply the suction. Release the suction and wash your crystals with a second
10 mL of cold methanol, again reapplying the suction after a moment or two; follow with a third
and final wash with 10 mL of cold methanol.
Since air-drying of the crude reaction product takes time, the following short procedure is
suggested. Carefully scrape the moist crude product from the Bchner funnel directly onto a
large piece of weighing paper; then transfer the crystals into a clean, dry 125 mL Erlenmeyer
flask. Take this flask over to the hood and add 15 mL of dichloromethane, CH
2
Cl
2
, which is also
known as methylene chloride, to dissolve your crude product. You will likely note the
appearance of aqueous droplets. Add enough anhydrous sodium sulfate (or anhydrous
4
4
magnesium sulfate) to the flask so that the drying agent no longer clumps together. Let the
solution dry for an additional 2 min and then remove the drying agent by gravity filtration (use a
glass stemmed funnel and fluted filter paper) into another clean, dry 125 mL Erlenmeyer flask.
You will now perform a mixed-solvent recrystallization. Remove the funnel from your flask
and add 30 mL of methanol to the filtered solution. Insert a boiling stick into the flask and begin
boiling off the solvent using a steam pot in the hood. Note that the boiling point of methanol is
65 C, while that of dichloromethane is only 40 C; the recrystallization solution thus enriches in
methanol as the solvent boils off. And since the final product is far less soluble in methanol than
in dichloromethane, it will become less and less soluble as more solvent is boiled away
eventually the product will crystallize. When the volume has been reduced to ~25 mL (or the
first crystals actually begin to appear), remove your flask from the steam pot and allow the
solution to cool slowlyafter a few minutes, large crystal plates of product should have formed.
Once the crystallizing solution has cooled to room temperature, place your flask in an ice bath
for a few minutes to maximize the yield of your crystals. Collect your product via vacuum
filtration again using a large (clean!) Bchner funnel. Wash your crystals with 15 mL of ice-cold
methanol, maintaining the vacuum for a few minutes after the final filtration to help dry them.
Let the crystals air-dry until your next lab period when you will weigh them to determine the
percent yield (see Topics for Report).
Cleaning Up
To remove the residual droplets of sulfuric acid, thoroughly rinse out your separatory funnel with
tap water. All waste solutions should be place into the hazardous liquid-waste container. The
sodium sulfate (or magnesium sulfate) used as the drying agent, along with the fluted filter
paper, should be placed into the hazardous solid-waste container.
5
5
Antics of Growing Crystals
R. D. Stolow of Tufts University has reported
1
that growing crystals of 1,4-di-tert-butyl-2,5-
dimethoxybenzene change shape in a dramatic mannerthin plates curl and roll up and then
uncurl so suddenly that they propel themselves a distance of several centimeters. You may or
may not be able to observe these anticsthe solvent mixture recommended by the Tufts workers
is different from the one we are usingbut keep your eyes open!
Topics for Report
For your report, which is due in your lab section next week, please answer the questions below.
(Set up all the calculations for Question 1 ahead of time, so that you can simply plug in the mass
of your crystals, once it has been measured.)
1. Calculate the theoretical yield of 1,4-di-tert-butyl-2,5-dimethoxybenzene. (Which of the
starting materials is the limiting reagent? To answer this question, it will help to know that the
density of tert-butyl alcohol is 0.775 g/mL.) From this theoretical yield, calculate the actual
percentage yield that you have obtained. SHOW ALL WORK.
2. Draw a detailed mechanism for the formation of 1,4-di-tert-butyl-2,5-dimethoxybenzene.
3. Why is the 1,4 isomer (i.e., 1,4-di-tert-butyl-2,5-dimethoxybenzene) the major product in the
alkylation of dimethoxybenzene? Would you expect either of the other possible isomeric
products (i.e., 1,3-di-tert-butyl-2,5-dimethoxybenzene and 1,4-dimethoxy-2,3-di-tert-butyl-
benzene) to be formed as side products? Why or why not? Be sure that your answer includes all
relevant resonance forms for each of the relevant arenium ions. Note that a tert-butyl group can
participate in hyperconjugation. Certainly consider steric effects as well.

1
R. D. Stolow and J. W. Larsen, Chemistry and Industry, 449 (1963). See also, J. Blatchly and N. H. Hartshorne,
Transactions of the Faraday Society, 62, 513 (1966).

Experiment 2:
Carbonyl Dry Lab

Week of February 11

1
Experiment 2: Carbonyl Dry Lab

Pre-Lab Preparation
Your goal today is to master the principles covered in lecture by working the problems below.
You need NOT prepare a pre-lab report, and there is no additional background reading. Please
bring your copy of Jones to the lab, as well as your carbonyl chemistry lecture notes. You will
wish to consult these as you proceed.
The Problems
1. Consider an aldehyde, ketone, ester, amide, and acid chloride. When undergoing nucleophilic
attack at the electrophilic carbonyl carbon, what is the relative order of reactivity of these five
carbonyl derivatives? Explain, considering both resonance (including hyperconjugation) and
inductive effects. Hint: As always when considering the stability of carbonyl derivatives, it is
best to focus on the charge-separated carbonyl resonance form.
2. Now, lets return to electrophilic aromatic substitution (EAS) chemistry for a moment:
a. Write the mechanism for an EAS reaction between benzene and a general electrophile
E
+
.
b. For the benzene derivatives corresponding to the five carbonyl derivatives discussed in
Question 1, the relative order of EAS reactivity is: NH
2
> OR > R > H (i.e., benzene
itself) > Cl. In light of your answer to Question 1., account for this order of reactivity.
Explain, making sure that you fully understand why, for example (to give part of the answer
away), an acid chloride is the most reactive of the five carbonyl derivatives, whereas in an
EAS reaction, chlorobenzene is the least reactive of the five benzene derivatives.
3. Acetals hydrolyze in aqueous acid (H
3
O
+
/H
2
O) but are stable in base (including aqueous base,
OH
/H
2
O). Explain. Begin by writing out the complete mechanism for the acid-catalyzed
hydrolysis reaction of an acetal.

2
4. Amides hydrolyze in water to yield, of course, the corresponding carboxylic acid and amine
(note that in the equation below, all that is shown is the overall stoichiometry!below, you will
be asked to consider whether this equation needs to be modified a bit when an acid or base
catalyst is present):
R NHR'
O
+ H
2
O
R OH
O
+ R'NH
2

The following pK
a
information will be of use in answering many of the questions below:
pK
a
of H
2
O (going to HO
) = 16 pK
a
of H
3
O
+
(going to H
2
O) = 2
pK
a
of ROH (going to RO
) = 16 pK
a
of ROH
2
+
(going to ROH) = 2
pK
a
of RNH
2
(going to RNH
) = 35 pK
a
of RNH
3
+
(going to RNH
2
) = 10
pK
a
of RCO
2
H

(going to RCO
2
) = 4

First, consider the hydrolysis of an amide in aqueous base (OH
/H
2
O).
a. Write out the step-by-step mechanism for the hydrolysis of an amide in aqueous base. Be
sure to indicate all proton transfers.
b. Do you predict this hydrolysis reaction to be base-catalyzed or base-induced? Explain.
Now, consider the hydrolysis of an amide in aqueous acid (H
3
O
+
/H
2
O).
c. Write out the step-by-step mechanism for the hydrolysis of an amide in aqueous acid. Be
sure to indicate all proton transfers.
d. Do you predict this hydrolysis reaction to be acid-catalyzed or acid-induced? Explain.
5. Given your answers to parts b. and d. of Question 4. above, explain why an amide cannot be
synthesized from a carboxylic acid and an excess of amine under either acidic or basic
conditions. For that matter, why can an ester be synthesized from a carboxylic acid and an
alcohol under acidic conditions, but not basic conditions? In the ester synthesis, why is an excess
of one of the reagents (the alcohol or the carboxylic acid) required (hint: what are the relative
stabilities of the carbonyl functionality in a carboxylic acid and ester)? Why does treatment of an

3
acid chloride with just one equivalent of alcohol yield an ester in high yield (hint: now, consider
the relative stabilities of an acid chloride and an ester)? Why must a weak base, such as pyridine,
be added to this reaction? Similarly, why does treatment of an acid chloride with an amine yield
an amide in high yield? Why are two equivalents of the amine typically employed in this reaction
(hint: each equivalent of amine plays an entirely different role)?
6. Aldehydes and ketones react with two equivalents of alcohols under strongly acidic conditions
to give acetals:
(R' can equal H)
R R'
O
+ 2 R"OH
R R'
+ H
2
O
OR" "RO
H
+

However, aldehydes or ketones react with only one equivalent of amine to yield an imine;
moreover, the maximum rate of this reaction occurs at pH = 4-6:
(R' can equal H)
R R'
O
+ R"NH
2
R R'
+ H
2
O
N
R"
pH = 4-6

Why dont these two reactions yield comparable products? Hint: What species is analogous to an
imine upon reaction of an aldehyde or ketone with just one equivalent of alcohol? Why does this
species react further (to add the second equivalent of alcohol), but the imine does not? Why do
the two reactions have different pH dependences? Of course, drawing out the step-by-step
mechanism for acetal and for imine formation is an excellent place to begin.
7. When an aldehyde or ketone is dissolved in H
2
18
O under acidic conditions, an exchange
reaction takes place to yield the
18
O-labeled carbonyl derivative (in the diagram below, just plain
O is, of course,
16
O):

4
(R' can equal H)
R R'
O
+ H
2
18
O
R R'
+ H
2
O
18
O
H
+

As you may recognize, the above reaction is akin to that for the formation of an imine, but with
an oxygen nucleophile. Why does this reaction occur, when the analogous reaction with an
alcohol does not (as you saw in Question 6. above)?
Topics for Report
Simply submit your answers to the above seven questions.

Experiment 3:
The Synthesis of Nylon

Week of February 18

1
Experiment 3: The Synthesis of Nylon:
A Fun and Easy Carbonyl Chemistry Lab
Pre-Lab Preparation
1. Read the attached supplementary info: Polymers from Organic Experiments, Seventh
Edition 1992, L.F. Fieser and K.L. Williamson, D.C. Heath and Company (Lexington, MA), pp.
545!551. Also read sections 17.7b and 17.7c of Jones.
2. For your pre-lab report: (a) Write the mechanism and draw the product for a reaction
between a generalized acyl chloride, RCOCl, and a generalized primary amine, R"NH
2
. (b) Do
the following problem: Nylon 6,10 is quite rigid and is used in applications such as bristles.
Show the monomers that are used to prepare this polymer.
C(CH
2
)
8
CNH(CH
2
)
6
NH
O O
n
Nylon 6,10

2
Part I: Preparation of a sebacoyl chloride/hexanes solution

Weigh out 1.0 g of sebacic acid on a piece of glassine weighing paper and carefully transfer the
compound to a large test tube (25 # 200 mm). Place the test tube in a 400 mL beaker to keep it
from tipping over. From this point on, WORK IN THE HOOD. Add 1.0 mL of thionyl
chloride (SOCl
2
) to the test tube of sebacic acid. Then, with a Pasteur pipette, add 3 drops of
dimethylformamide (DMF). Add about 250 mL of hot tap water to a 800 mL beaker. Put this
beaker onto a steam pot in the hood and gently turn on the steam. Heat the water until the
temperature reaches approximately 70 C. Turn off the steam and place your large test tube into
this beaker and let the reaction heat for 15 minutes, making sure that the temperature of the water
stays between 60 and 70 C.

After the 15 minutes have elapsed, remove the test tube from the steam pot and place it into the
original 400 mL beaker and let it cool to room temperature. Measure out 50 mL of hexanes in a
small beaker and add it to the large test tube to yield a cloudy solution of sebacoyl chloride. Pour
this solution back into the small beakerit is now ready to carefully layer onto a solution of
hexane-1,6-diamine. (The hexane-1,6-diamine solution has been prepared for you ahead of time;
FYI, it contains 1.0 g of sodium hydroxide and 3.75 mL of hexane-1,6-diamine per 50 mL of
solution.)
Part II: Time to make nylon!
Place 50 mL of the pre-made hexane-1,6-diamine solution into a 250 mL beaker. Gingerly layer
your sebacoyl chloride/hexanes solution onto the top of the aqueous hexane-1,6-diamine solution
(in the 250 mL beaker). Do NOT shake, swirl, stir, jiggle, or jostle the two-phase mixture. Nylon
will form at the interface between the two solutions! Make a small hook at the end of a piece
of copper wire and use this hook to remove the nylon rope from the interface. Pull straight up
out of the beaker and carefully keep pulling! As you pull up, the polymerization will continue,
and you will form a long strand of nylon. You can wind this around a glass stirring rod, or see
how long a strand you can create. (There are tales of strands extending down the halls to the
Chem Cave; well see if theyre true.)
After you get tired of playing with the nylon strands, you can stir the remainder of the mixture
for more potential ooohs and aaahs. Discard the polymer and remaining solutions in the waste
container. If you tell your instructor at least three times how fun/awesome/impressive/exciting/
cool/neat-o this lab was, there will not be a lab write-up required.
From WILLIAMSON. Organic Experiments, 7E. 1992 Brooks/Cole, a part of Cengage
Learning, Inc. Reproduced by permission. www.cengage.com/permissions

Supplementary Reading for
The Synthesis of Nylon

Louis F. Fieser and Kenneth L. Williamson, Organic Experiments, Seventh Edition (1992), pp.
545!551 (D.C. Heath and Company).

Experiment 4:
Grignard Synthesis of Triphenylmethanol

Week of February 25

1
Experiment 4:
Pre-Lab Preparation
1. Read the attached supplementary info from Organic Experiments, Seventh Edition 1992, L.F.
Fieser and K.L. Williamson, D.C. Heath and Company (Lexington, MA), pp. 319!323. Also
read section 18.8 of Jones and, of course, this entire protocol.
2. For your pre-lab report: (a) Show the products of the following reactions:
O
OCH
3
1. PhMgBr (2 equiv)
2. NH
4
Cl, H
2
O
(i)
(ii)
(iii)
OCH
3
O 1. CH
3
Li (2 equiv)
2. NH
4
Cl, H
2
O
H OCH
3
O 1.
2. NH
4
Cl, H
2
O
MgBr
(2 equiv)

(b) Sketch the apparatus youll be using and explain how the apparatus satisfies the five criteria
(a!e) listed in the first paragraph of Part I of the experimental procedure. (Note: Although they
depict somewhat different setups from the ones that we will use, taking a look at Figures 1 and 2
on pages 5 and 6 of this protocol will be very helpful for this question.)
Background
Developed by the French chemist Victor Grignard in the early 1900s, organomagnesium halides,
RMgX, quickly became some of the most important reagents in the synthetic organic chemist's
repertoire. Grignard was awarded the 1912 chemistry Nobel prize for the development of these
versatile reagents and exploration of their reactions.
Grignard reagents are prepared by the reaction of organo halides and magnesium metal. The
reaction happens on the surface of the Mg and involves single-electron transfers, radical ions,
surface-bound species, and possibly free radicals as well. The result is an overall insertion of Mg
into the CX bond. Because the divalent Mg is electron-deficient, solvation by electron-donating
2
ethers is normally required to stabilize these reagents during their formation, storage, and
reactions.
Their polar carbon-metal covalent bond causes Grignard reagents to behave as carbanion
equivalents. They are extremely strong bases as well as excellent nucleophiles. Because these
compounds are such strong bases, they must be prepared and handled in environments free of
water and other proton sources like alcohols and amines. Dry solvents and glassware are
essential to the success of any reaction that involves a Grignard reagent.
In this experiment, you will allow two equivalents of phenylmagnesium bromide, PhMgBr, to
react with methyl benzoate, PhCO
2
Me, to produce triphenylmethanol, Ph
3
COH.
DO NOT WASH ANY GLASSWARE BEFORE USEDRYNESS IS ESSENTIAL FOR
THE GRIGNARD REACTION!
Part I: Setup
This reaction will require (a) the controlled addition of bromobenzene to a stirred mixture of Mg
metal in dry diethyl ether and then a similar controlled addition of methyl benzoate. We may
need to (b) cool the mixture if the reaction becomes too vigorous, or we may need to warm it to
keep it going and to ensure that it has gone to completion. At the same time as the additions,
well need to be able to (c) condense the vapor of the boiling ether, and (d) stir the reaction
mixture. And all this needs to happen with (e) everything protected from atmospheric moisture.
This means that we cant very well use an Erlenmeyer flask with a stirring rod, nor can we keep
switching flask accessoriesremember, we need to condense ether, stir, and add reagents all at
once, in a dry environment.
A solution that meets all these requirements well enough for our purposes is a 3-necked flask
with ground-glass joints. On the center neck will be a stoppered addition funnel. On one side
neck will be a condenser topped with a drying tubea calcium chloride-filled tube that is open
to the outside. This allows the reaction to breathe but any air that it inhales gets dried by the
CaCl
2
. On the other side neck will be a stopper.
As you go, record in your notebook what you actually did and what you observed in
enough detail that someone else can follow this and repeat the procedure.
Put several small and medium sized graduated cylinders (10!50 mL) in the oven to dry them.
The plastic bases on some of the cylinders will melt in the oven, so be sure to remove these.
3
Assemble the glassware as described above, leaving the condenser and drying tube aside (we
dont want to flame-dry the rubber tubing on the condenser). Place the magnesium turnings (2.0
g, 0.082 mol) and a magnetic stir bar in the flask. Remember that heating anything in a closed
system could lead to disaster, so check carefully that your apparatus has no sealed spaces
think about itif you heat a particular part of the apparatus, where will the hot air go? If there's
no vent, the pressure increase will blow the apparatus apart if you're lucky it will fail at a joint
and the airborne glassware will break when it lands on the benchtop or floor. Unlucky is what
happens when no joints can come apart and the pressure causes the glass itself to failviolently.
Check your set-up with the lab instructor or TA, then flame-dry the apparatus. Be careful not to
roast the Mg; you only need to heat the glassware enough to drive off the moisture on the inside
surface. You'll see the water vapor recondensing on nearby cooler surfaces as you go. Work from
the bottom of the flask, chasing moisture up the necks and out the top of the addition funnel.
(Well have to live with the bit of moisture on the inner tube of the condenser.) If you now leave
the set-up open as it cools, moisture will reenter the apparatus. Don't do that. But if you stopper
everything, cooling will create a vacuum, and moist air will rush in as soon as you remove a
stopper. So don't do that either. The apparatus and Mg will appreciate being able to inhale nice
dry air as they cool. So, once youve extinguished your flame, immediately place the condenser
and drying tube on the available neck of the flask and allow the entire apparatus to cool to room
temperature.
Now would be a good time to retrieve your dry graduated cylinders. Cover the opening with
aluminum foil to restrict air circulation, and let them cool to room temperature. You'll need to
use these at several stages of the procedure, so keep them covered with foil to minimize the
amount of moisture that gets in.
Because diethyl ether is so volatile and flammable, this will be kept in an undisclosed location
until everyone is finished flame-drying their set-ups. When all flames are out and all burners
have been put away, the instructor or TA will fetch the ether. Please keep in mind that anhydrous
ether is expensive and that the air in the room is not anhydrousin other words, always replace
the cap on the ether bottle!
Part II: Synthesis of phenylmagnesium bromide (phenyl Grignard reagent)
Get 15 mL of diethyl ether. Add about half of the ether to the Mg turnings and pour the other
half into the addition funnel. (Is the stopcock closed?) Then add bromobenzene (9.1 mL, 13.5 g,
0.086 mol) to the addition funnel. Start the magnetic stirrer, and then add about 1/4 of the
bromobenzene solution from the addition funnel. The reaction will probably begin on its own
within 5 to 10 min; the solution may become slightly cloudy, and the ether will begin boiling.
Once it gets going, you can add the remainder of the bromobenzene solution, in portions, so that
the reaction maintains a nice reflux rate. (Have an ice bath ready, but do not cool the reaction
4
mixture unless the reaction becomes too vigorous. This will be obvious from the rate of reflux.)
Once all the bromobenzene is in and the reaction is still going, add another 25 mL of ether, a few
mL at a time, via the addition funnel. This dilution will help keep the reaction under control.
Your job now is to ensure that it keeps going, in a controlled manner, until the Mg is consumed.
Again, cool with ice only if necessary.
If your reaction doesn't get going, don't despair because this is a common problem with making
Grignard reagents. Organic chemistry lore includes the following possible remedies: (a) Warm
the flask with your hands (were not joking). (b) Carefully crush the Mg with a glass stirring rod
(don't break the flask or the stirring rod). (c) Add a tiny crystal of I
2
. (d) Add a little (1/4 mL) of
the PhMgBr solution from someone nearby whose reaction worked. Once it's started, follow the
procedure described in the previous paragraph.
Part III: Synthesis of triphenylmethanol
Once there are no more than a few tiny specks of Mg left, youre ready for the next step. If you
lost a lot of ether, add a little more to bring the volume up to what it should be, then figure out
how you lost so much ether. (Is your condenser water flowing? Is there a loose joint?) In one of
your dried graduated cylinders, make a solution of methyl benzoate (4.60 mL, 5.0 g, 0.037 mol)
in about 15 mL of diethyl ether. Add this solution to the addition funnel (You didn't forget to
close the stopcock, did you?)
Cool the flask briefly in an ice bath, then add the methyl benzoate solution dropwise. You may
see a white precipitate during the addition. (What do you think that is?) You should be able to do
this addition at a moderately rapid rate; go slow at first, and keep an eye on the reflux rate this
will give you an indication of how much heat is being generated. After the addition is complete,
rinse the addition funnel with a few mL of dry ether. To ensure completion of the reaction, heat
the reaction mixture to a gentle reflux with a warm water bath for 30 min.
In an Erlenmeyer flask, combine about 50 mL of ice and 50 mL of 10% sulfuric acid, and
carefully pour your reaction mixture into the ice/acid slurry. Swirl the mixture for a few minutes.
(What is the purpose of this step?) Note that any remaining bits of Mg metal will be destroyed by
the acid. Use a separatory funnel to separate the layers. Be sure to vent this frequently your
hand will warm the ether and increase its vapor pressure, and any acid-base reactions that occur
in the funnel will also increase the temperature. Keep track of where your product is, and dont
discard anything until you're sure you have it. Wash the ether layer first with 25 mL of water,
then with 10 ml of saturated NaCl (brine), and then dry it over MgSO
4
. After a few minutes,
remove the drying agent by gravity filtration through fluted filter paper into an Erlenmeyer flask.
To encourage the product to crystallize, add 25 mL of alkane solvent (this could be hexanes,
ligroin, or petroleum ether all of which are mixtures of alkanes), and heat on a steam bath,
5
with a boiling stick, to drive off the ether. Once crystals of product begin to appear, cool and
isolate the solid via vacuum filtration. Which solvent should you use to rinse the crystals?
Let the crystals air-dry until your next lab period when you will weigh them to determine the
yield.

Topics for Report
For your report, which is due in your lab section next week, please answer the questions
below. (Set up all the calculations for Question 3 ahead of time, so that you can simply plug in
the mass of your crystals, once it has been measured.)
1. Write complete mechanisms for reactions 1, 3, 5, 6, 7, and 9 on p. 321 of the supplementary
reading. In reaction 9, O=C(OC
2
H
5
)
2
is diethyl carbonate:
CH
3
CH
2
O OCH
2
CH
3
O

Note: As stated in the text, each of these reactions is followed by (an implicit) acidic work-up to
give the products shown.
2. If the methyl benzoate used to prepare triphenylmethanol is wet, what (undesirable) by-
product is formed in the Grignard reaction? (Hint: youve already answered this in the question
above!)
3. Calculate your percent yield of triphenylmethanol. As always, do not ignore stoichiometry.
SHOW ALL WORK.
Figure 1: Calcium chloride drying tube fitted with a rubber stopper.

6
Figure 2: Old Grignard setup. The biggest difference for us is that we will be using a magnetic
stir bar (not the mechanical stirrer shown), allowing us to place our addition funnel in the center
neck of the 3-necked flask. Also, you need not setup your reaction over a steam pot; a warm
water bath will do just fine when needed.

From WILLIAMSON. Organic Experiments, 7E. 1992 Brooks/Cole, a part of
Cengage Learning, Inc. Reproduced by permission.
www.cengage.com/permissions


Experiment 5:
Enolate Chemistry I

Week of March 4

1
Experiment 5: Enolate Chemistry I
Pre-Lab Preparation
Todays reaction is a puzzlethat is, were not going to tell you what the product is. But, to push
you in the right direction, we highly recommend that you carefully read sections 19.2, 19.4, and
19.5 of Jones before coming to lab. Note: Even though you are using a ketone and iodine, you are
not performing the haloform reaction (described on pp. 948-949 of Jones) today. You will note
that the haloform reaction requires a methyl ketone as a reagent, and the ketone you are using today
(see below) is not a methyl ketone. Before coming to lab, please read this handout, and your pre-lab
report couldnt be simpler: just predict the structure of the product in todays reaction. This is
only a predictiongo ahead and take a wild guess!

2
Experimental Objective
To deduce the actual structure of the product obtained from the reaction of 1,5-diphenyl-1,5-
pentanedione with sodium hydroxide and iodine in methanol. You will use the
1
H-NMR and
13
C-
NMR spectra of the productwhich, as you will see, are quite remarkableto do so.
O O
+ I
2
+ 2 NaOH
MeOH
C
17
H
14
O
2
Structure???

Place a magnetic stir bar in a 50 mL round-bottom flask. Weigh out 1.0 g of 1,5-diphenyl-1,5-
pentanedione into the flask. Add 12 mL of a 0.67 M solution of sodium hydroxide in methanol
(pre-made for you) directly to the flask. Affix the flask to the monkey bars of your lab bench.
Place a water bath on a hot plate (also a stir plate) under your flask and warm the bath to 40-50
C. Stir the solution until all of the solids have dissolved. Once you have a homogenous
solution, insert a ground-glass-jointed separatory funnel into the top of your flask. After you
have made sure that the stopcock is closed, pour 6.0 mL of 0.67 M iodine in methanol (also
pre-made for you) into the separatory funnel. Begin dropwise addition of the iodine solution
wait until the color from one drop has disappeared before adding another drop. After the addition
is complete, stir for 45 minutes, maintaining the water-bath temperature between 40 and 50 C.
Once the 45 minutes have elapsed, dismantle the reaction apparatus, cool the flask to room
temperature, and then cool it further in an ice-water bath. At this point there are a few possible
scenarios:
Scenario #1: If your cooled reaction mixture contains a solid precipitate, you are one of the
lucky (good?) chemists! (If not, hang your head in shame. No, no, just kiddingsimply move on
to Scenario #2.) Collect the product by filtration in a Bchner funnel. Wash the product in the
funnel twice with 10 mL portions of ice-cold water. Recrystallize your crude product in a small
amount of methanol, starting with ~10 mL of methanol. (Remember how to do this?) Collect
your crystals by vacuum filtration, wash them with ice-cold methanol, and dry them over
3
vacuum for a few minutes. Move the (still moist) crystals to a large watch glass and dry them in
a 70 C oven for 15 minutes. Record the mass of your crystals.
Scenario #2: If you have no precipitate, add three pieces of ice directly into the reaction mixture
and continue cooling in the ice-water batha precipitate should soon form! If it does, collect the
product by filtration in a Bchner funnel and recrystallize/wash/dry as described in Scenario #1.
(If you still have no precipitate, hang your head in shame. No, no, just kiddingmove on to
Scenario #3.)
Scenario #3: If your cooled reaction mixture still does not contain a solid precipitate, you of
course cannot filter out the desired product. (Dont be discouraged, as this is a common
phenomenon in the organic-chemistry lab.) Obtain a separatory funnel (without a ground-glass
joint) from your instructor and extract your organic product into an organic solvent (in this case,
diethyl ether). After you have made sure that the stopcock is closed, add your aqueous
solution to the separatory funnel, followed by 50 mL of ether. Close the separatory funnel with a
stopper and shake vigorously with your finger tightly over the stopper. Place the separatory
funnel on a metal ring that has been attached to the monkey bars, remove the stopper, and allow
the aqueous and organic phases to separate. Carefully collect the bottom (aqueous layer) in an
Erlenmeyer flask, leaving the ether layer in the separatory funnel. Dab the last drops of water
from the stem of the separatory funnel, and collect the ether layer in a clean and dry Erlenmeyer
flask. Add enough drying agent (either anhydrous sodium sulfate or anhydrous magnesium
sulfate) to the ether solution so that the drying agent no longer clumps together. Let the solution
dry for an additional 5 min and then remove the drying agent by gravity filtration (use a glass
stemmed funnel and fluted filter paper) into a clean, dry, and tared 250-mL round-bottom flask.
Remove the ether solvent using a rotary evaporator (you will, of course, need to ask your
instructor how to do this). After evaporation of ether is complete, re-weigh your flask to get the
mass of your product. Chances are, your extracted product wont be quite as pure as
recrystallized product.
4
Topics for Report
For your report, which is due in lab next week, please answer the questions below.
1. Calculate the percent yield for your reaction. Note that you wont need to know the products
structure to do thisyou are given the products molecular formula in this handout. SHOW
ALL WORK.

2. Before lab this week, we took
1
H and
13
C NMR spectra of a representative sample of your
unknown product; these will be distributed electronically. Propose a structure for your mystery
product. If your proposed product has multiple stereoisomers, be sure to SPECIFY
STEREOCHEMISTRY in your answer. Describe how you arrived at your conclusion,
explaining in detail how your structure is consistent with the
1
H-NMR and
13
C-NMR data.
Critical hint: As indicated by the signals at 1.8 and 3.4 ppm in the in the
1
H-NMR spectrum,
there are only two kinds of aliphatic (i.e., non-aromatic) protons. However, these apparent
triplets are deceptively simple (hence the term apparent). Referring to the table of coupling
constants on the next page, provide an explanation as to why each of the signals is an apparent
triplet (rather than, as might have been expected, a more complex multiplet).

3. Propose an arrow-pushing mechanism for the formation of your product from 1,5-diphenyl-
1,5-pentanedione. Note that the reaction used two equivalents of NaOH and one equivalent of I
2
;
also note that methanol was present only as a solvent.

4. Given your mechanism from question 3, why were you asked to add the I
2
solution so slowly?
Why not dump it all in at once?

5

Table of Coupling Constants:

Experiment 6: Aldol Reactions
An Illustration of Combinatorial Chemistry

Week of March 11

1
Experiment 6:
Aldol Reactions: An Illustration of Combinatorial Chemistry

Pre-Lab Preparation
Please (re)read Jones, Section 19.6 before coming to lab.
Your pre-lab report: Using the reaction on the bottom of this page as a guide, draw out the 16
possible aldol products (dont worry about stereochemistry) that could be formed from the 4
aldehydes and 4 ketones that will be used in this lab. We know this sounds tedious, buttrust
usit will be very helpful to have these structures in front of you when you are attempting to
deduce the structure of your particular aldol product.
This experiment will illustrate the combinatorial approach to making large numbers of
compounds. You will prepare, in collaboration with your labmates, a library of (up to) 16 !,"-
unsaturated ketones. In the spirit of many combinatorial experiments, you will deduce the
structure of your groups product after it is prepared. If this were a real combinatorial
experiment, your structure-deducing detective work would be performed on the high-activity
(hit) compound from a large combinatorial library. In todays experiment, each group will
figure out the structure of their own unique product. The !,"-unsaturated ketones will be
synthesized via aldol-condensation/dehydration chemistry, using hydroxide ion as the catalyst:
R R
O
R' H
O
+ 2
NaOH
EtOH/H
2
O
R R
O R' R'

2
Background
What is combinatorial chemistry? Although there are numerous sets of reaction conditions that
have been described as combinatorial, they all share a common goal: the straightforward
production and analysis of a relatively large number of diverse, but related compounds. Why
make a large number of related compounds? This is often necessary in the screening process for
the discovery of new pharmaceutical agents. A vast number of compounds can be made and their
biological activity measured (using a high-throughput assay) in the search for a new drug. Unlike
traditional synthetic methods, combinatorial reaction conditions are optimized for general
effectiveness, not for a specific product. Similarly, no attempt is made to identify and
characterize every compound made; this effort is expended only upon those products that show
the desired activity. By using reliable chemistry (and omitting characterization), many more
compounds may be prepared and screened than is possible using more traditional approaches.
Not only have combinatorial methods provided a radically new paradigm for the synthesis,
screening, and discovery of new pharmaceutical agents, the underlying concepts have been
extended to other aspects of organic chemistry, such as the discovery of asymmetric catalysts.
Often in combinatorial chemistry, the libraries of compounds are synthesized attached to small,
inert, plastic beads. With a clever experimental design, thousands of beads, each holding a
single, unique compound, can be analyzed simultaneously. A conceptually simpler approach is
called parallel synthesis, in which numerous products are made at the same time, in separate
flasks. In a research laboratory, parallel synthesis is commonly automated, and a single robotic
machine runs all of the reactions and screens the products for the desired activity.
In this experiment, you will carry out a non-automated, parallel synthesis of !,"-unsaturated
ketones#that is, we will substitute your entire lab section for the robot.
During the pre-lab lecture, each lab group will be assigned an unknown aldehyde and ketone
(unknown is in quotes because there are only four options for eachmultiple choice might be a
better term).
The four possible aldehydes are: benzaldehyde, 4-methylbenzaldehyde, 4-methoxybenzaldehyde,
and E-3-phenylprop-2-enal (trivial name: cinnamaldehyde).
The four possible ketones are: acetone, cyclopentanone, cyclohexanone, and 4-methylcyclo-
hexanone.
3
Caution: Rare allergic reactions to some aldehydes are known to exist. Please wear gloves
throughout this experiment. Lab coats are also available in the lab; let your instructor know if
you would like to wear one.
Once you have your aldehyde and ketone assignments, place a magnetic stir bar in a 50 mL
Erlenmeyer flask. Add 0.8 g of your unknown aldehyde to the flaskbe sure to note the
numbers of both of your unknowns in your lab notebook and lab report. Add 0.2 g of your
unknown ketone to the flask. Add 4 mL of 95% ethanol and 3 mL of 2 M sodium hydroxide to
the Erlenmeyer. Stir the solution with a magnetic stirrer for 15 minutes. If after 15 minutes at
room temperature precipitate is still forming, or very little precipitate has formed (i.e., the
solution is only cloudy), heat the reaction over a steam pot for an additional 15 minutes.
Note: During the reaction time, you may want to chill (in an ice-water bath) 10 mL of 95%
ethanol and 5 mL of 4% acetic acid in 95% ethanol; these chilled solvents will be necessary for
washing your filtered aldol products.
When precipitation of your product is complete, cool the flask in an ice-water bath for 10
minutes, and collect the product by vacuum filtration using a small Bchner funnel. Successively
wash the collected product with your pre-chilled solvents in the following order: ~5 mL 95%
ethanol; 5 mL 4% acetic acid in 95% ethanol; ~5 mL 95% ethanol.
To purify your crude product, you will want to recrystallize it; to do this, you will need to
identify a suitable solvent for your particular product. (Remember: you and your neighbors have
made different compounds!) Test both 95% ethanol and toluene as potential recrystallization
solvents. Place small samples (~0.025 g) of your crude product in two separate clean, dry test
tubes. Add ~0.25 mL (a quarter squirt with a Pasteur pipette) of either 95% ethanol or toluene to
the tubes. If your product dissolves immediately, it is too soluble in the solvent for
recrystallization to be effective. If your product does not dissolve at room temperature, place the
test tube in a hot-water bath on a steam pot. If the compound dissolves, cool the test tube on your
bench top. If crystals form within 10$20 minutes, you have found a good recrystallization
solvent. (If neither 95% ethanol nor toluene appears to work well, try a 9:1 mixture of 95%
ethanol/acetone.)
4
Once you have identified a good recrystallization solvent, use it! In other words, scale up the test
recrystallization you just did with your entire batch of crude product, adding just enough hot
solvent to completely dissolve your aldol product. After dissolution, allow the flask to cool on
your bench top. Once your recrystallization flask has cooled to room temperature, chill it for a
few minutes in an ice-water bath, collect the crystals in a Bchner funnel, and wash the crystals
with a little bit of cold recrystallization solvent. Press them between two pieces of dry filter
paper to draw off most of the residual solvent, then spread them out on a large watch glass and
pop them into the oven (100C) for 15 min to drive off the remaining traces of solvent. Obtain a
mass and melting point for your dried crystals.
Note that
1
H-NMR spectra of representative samples of the various aldol products were taken by
your instructors; these will be distributed electronically.
Topics for Report
For your report, which is due in lab the week of April 1, please answer the questions below.
1. Propose a structure for your mystery product. You should also reveal the identity of the
unknown aldehyde and ketone that you were assigned (which, of course, goes hand-in-hand with
the mystery structure). Carefully explain how your proposed structure is consistent with
ALL of your data and assign as many peaks as you can in your
1
H-NMR spectrum. Are
your
1
H-NMR and melting-point data (see reference table, below) consistent with one another? If
you encounter any ambiguity, discuss it.

NOTE that even if you can deduce the identity of your product using only melting point, you
MUST explain how your proposed structure is consistent with the NMR.

Table 1: Melting points of aldol-dehydration products
ketone

aldehyde
acetone cyclopentanone cyclohexanone 4-methylcyclohexanone
benzaldehyde
113 C 189 C 118 C 98 C
4-methylbenzaldehyde
175 C 235 C 170 C 134 C
4-methoxybenzaldehyde
129 C 212 C 159 C 141 C
cinnamaldehyde
144 C 225 C 180 C 163 C

5
As you interpret your
1
H-NMR spectrum, please note the following:
Real-world integrals arent perfect and often errors of up to 20% are seen (e.g., a ratio of
integrals of 1.8:1 is really 2:1);
You may well see a signal at ~1.5 ppm for the small amount of water that can dissolve in the
deuterochloroform solvent (CDCl
3
), as well as a signal at ~7.3 ppm for the residual chloroform
(CHCl
3
) in the deuterochloroform solvent;
Due to the fact that the all of the starting aldehydes are aromatic and all of the products are !,"-
unsaturated ketones, the signals for the alkene protons are shifted downfield to ~6.58.0 ppm
(rather than appearing in the standard 5.06.5 ppm range); you must therefore be on your toes,
since aromatic protons, of course, typically appear in this same range;
A good place to begin your analysis is with any singlets that might be present in your spectrum:
After brief consideration, you will see that only a subset of the possible products will yield NMR
spectra containing a singlet; moreover, the chemical shifts of these possible singlets will vary;
Finally, remember that cycloalkane derivatives can yield complex multiplets since their
geminal protons can be diastereomeric and their cis- and trans-protons typically split each other
with different coupling constants.

2. Propose an arrow-pushing mechanism for the formation of your product.

3. Calculate the theoretical and percent yield for your aldol reaction. As always for this question,
dont ignore stoichiometry. Note that every group used fixed masses of aldehyde and ketone;
since the unknown starting materials have varying molecular weights, theoretical yields will vary
from group to group. SHOW ALL WORK.

Experiment 7: Acetylation of Anthranilic Acid
Triboluminescent Crystals from the Microwave Oven

Week of April 01

1
Experiment 7: Acetylation of Anthranilic Acid:
Triboluminescent Crystals from the Microwave Oven
[Adapted from B.W. Baldwin and D.M. Wilhite, Journal of Chemical Education 2002, 79, 1344.]
Pre-Lab Preparation
Before coming to lab, please read this handout and the brief Nature News Feature on the use of
microwave ovens for heating chemical reactions that can be accessed as an External Link on our
Chemistry 231 Moodle site. (If youre a dinosaur who would prefer to read it on paper in the
Science Library, the citation is: Nature 2003, 421, 571-572.) For your pre-lab report, please
answer the following question: What are two explanations that have been put forth to explain the
basis of microwave action?
To deduce the structure of the product obtained from the reaction of anthranilic acid with acetic
anhydride (is it the O-acetyl or N-acetyl derivative?) and to observe the triboluminescence of this
product. The acetylation reaction will be run in a microwave oven with a total heating time of a
minute or less. In other words, you will use an unconventional heating method, irradiation in a
microwave oven, to produce a compound with an unusual energy-release mechanism,
triboluminescence; moreover, you will then deduce the precise structure of this compound (using
conventional spectroscopic methods).
O OH
NH
2
O
O O
O O
NH
2
O OH
H
N
O
O
+
anthranilic acid acetic anhydride
O-acetylanthranilic acid N-acetylanthranilic acid
??

2
Background
In our discussion of IR and NMR spectroscopy, we focused on the absorption of light by a
molecule. Today you will observe the complementary phenomenon of the emission of light by a
molecule. While light can be emitted via a variety of processes (e.g., incandescence,
chemiluminescence, and phosphorescence), we will experience the least-well understood today:
triboluminescence, the phenomenon of crystals sparking when they are crushed. The word
luminescence means to glow, and tribo comes from the Greek word tribien, which means to rub.
Many people have observed that wintergreen lifesavers exhibit this effect while crunching the
candies in a darkened room. It is thought that the lifesaver sparking is due to triboluminescence
of the sugar and wintergreen flavoring in the candy. Other compounds give even brighter
sparks when crushed one of these, acetylanthranilic acid, is the subject of this laboratory
synthesis.
Although the triboluminescent effect was first observed by Francis Bacon in the early 1600s, the
cause of the effect is still debated. Many ways of generating the sparks have been observed,
including quickly lowering the temperature of crystals, running mercury across the crystal
surface, quickly forming the crystals by immersion in liquid nitrogen, or grinding the crystals. X-
ray diffraction analysis of a variety of triboluminescent crystals has not yet indicated specific,
common molecular orientations that predispose a crystal to exhibit this property. At present, it is
thought that when triboluminescent crystals are crushed, the freshly prepared surfaces of the
fractured crystals are highly charged. When the electrons rearrange to neutralize these charges,
sparks are formed. However, the underlying cause of triboluminescence is still being studied.
Regardless of the mechanism, triboluminescence has, in a few instances, been put to practical
use. A 1981 article in the Japanese journal, Chemistry Letters, provides one such application.
What if a molecule could be made that would spark when crushed and then undergo
polymerization initiated by the sparks? The Japanese researchers synthesized such a molecule, 9-
ethyl-3-vinylcarbozole (see the figure on the next page). When crystals of this compound are
crushed, a polymer similar to high-strength plastic is formed. One possible application is to
include these compounds in lubricants for bearingsas the bearings moved, the crystals would
be ground and sparks would initiate the polymerization, producing a tough plastic film directly
3
on the grinding surfaces. Thus the lubricant would form hard coatings on the bearing surfaces,
prolonging the life of moving parts!
N

9-ethyl-3-vinylcarbozole: triboluminescent and polymerizable
Finally, another clever (if frivolous) use for triboluminescent compounds was described in a
2002 patent application:
Manufacture of triboluminescent materials in paper products for wrapping
or gift papers. Geddes, Norman James; Sage, Ian Charles; Rozelaar, Christopher
Frank; Mason, Ian Robert; Bourhill, Grant Hannah. (Qinetiq Limited, UK). PCT
Int. Appl. (2002), 20 pp.
A method of making paper that emits light when torn and/or pressed and/or
gripped and/or folded comprises the steps of coating and/or impregnating the
paper with triboluminescent material. The coating and/or impregnation is applied
in one or more of the following ways: (I) in an adhesive compn., (II) in a solvent
followed by solvent evapn., (III) by melting the triboluminescent material such
that it soaks into the paper, or (IV) by incorporating the triboluminescent material
together with pulp and/or fiber during manuf. of the paper. Thus, a gift wrapping
paper was manufd. by impregnating in 18.947 g of chloroform contg. 0.813g of
menthyl 9-anthracene carboxylate (triboluminescent material).

Weigh out 2.6 g of anthranilic acid into a 125 mL Erlenmeyer flask (simply tare the flask and
directly add the anthranilic acid). Then IN THE HOOD, add 8.0 mL of acetic anhydride directly
to the flask. To measure out the 8 mL, use a DRY 10 mL graduated cylinder use a Pasteur
pipette to transfer the acetic anhydride from the reagent bottle to your graduated cylinder, and
then simply pour the acetic anhydride into the Erlenmeyer flask containing the anthranilic acid.
(Note that the density of acetic anhydride is 1.08 g/mL, a number youll need later for the
limiting reagent calculation in the Topics for Report.) Finally, add three boiling chips to the
4
reaction flask and youre set to go. (Notice that no solvent, other than the acetic anhydride itself,
is used.)
Place the Erlenmeyer on the turntable in the microwave oven (1,000 watts) and irradiate at full
power. Watch your reaction carefully the microwave oven should be turned off as soon as the
crystals dissolve and the mixture begins to boil. The boiling should begin after as little as 20
seconds, but it may take a bit more or less time. Carefully remove the hot flask from the
microwave oven and allow it to cool in the hood until it can be handled without discomfort.
You will now crystallize your product acetylanthranilic acid directly from this initial reaction
mixture. Add 20 mL of distilled water to your Erlenmeyer flask, and again use the microwave
oven to heat the solution until all of your crude product dissolves and the mixture just boils. This
process may take as little as 15 seconds watch your flask carefully through the oven door as it
is irradiated! Carefully remove the hot flask from the microwave oven and allow it to cool slowly
to room temperature in the hood. Once the crystallizing solution has cooled to room
temperature, place your flask in an ice bath for a few minutes to maximize the yield of your
crystals. Back at your bench, collect your plate-like crystals via vacuum filtration using a large
Bchner funnel. Wash your crystals with 15 mL of ice-cold distilled water, followed by 10 mL
of ice-cold methanol.
Now you should recrystallize your crystals from 15 mL of 90% methanol/10% water. Scrape
them (avoiding the boiling chips) into a clean 125 mL Erlenmeyer flask. Insert a boiling stick
and use a steam bath, not the microwave oven to heat the solution. Once the crystals have all
completely dissolved, remove the flask from the steam bath, take out the boiling stick, and allow
the hot flask to cool, undisturbed, slowly to room temperature. (It is critical to avoid agitating
the solution while it is cooling as the crystals may crash out of solution prematurely.) Once the
crystallizing solution has cooled to room temperature, again place your flask in an ice bath for a
few minutes to maximize the yield of your crystals. Do a final vacuum filtration using your large
Bchner funnel, wash the crystals with 15 mL of ice-cold 90% methanol/10% water, and then
scrape your crystals into a small beaker. Place your beaker of crystals in an 80 C oven for 15
minutes this will dry the crystals, which will enhance the triboluminescent effect.
After your crystals are dried, weigh them and record their mass. Now youre ready to examine
them in the dark back room under UV light. The crystals should fluoresce yellow or yellow-
5
green. To observe their triboluminescencebright blue sparksgrind the crystals between
two watch glasses: Place your crystals on a larger one and use a smaller one to grind. You can
also carefully drop the smaller watch glass directly onto the larger crystal-containing one from a
height of about 2 inches. The crystals should emit bright blue sparksmurmur approvingly
and youre done!

Topics for Report
For your write-up, which is due in lab the week of April 8, please answer the questions
below.
1. Calculate the theoretical yield of acetylanthranilic acid note that the answer will be the same
regardless of whether you have the O- or N-acetyl derivative. (Which of the starting materials is
the limiting reagent?) From this theoretical yield, calculate the actual percentage yield that you
have obtained. SHOW ALL WORK.
2. Now the time has come to determine whether you have made the O- or N-acetyl derivative. On
pages 6 and 7 are simulated
1
H-NMR spectra for both the actual product obtained and for the
product not formed (ahhh, the beauty of simulation!). Which isomer is which? Which features of
the spectra are key to making the assignment?
3. You will notice that the four aromatic signals for the isomer not formed are all upfield from
the corresponding signals in the isomer obtained. Why? Hint: Think resonance.
4. On the last page of the handout is the IR spectrum of the isomer formed. Does it corroborate
your answer to Question 2. above? Explain. How would the IR spectrum of the isomer not
formed differ from this spectrum?
5. Why is the isomer actually obtained favored over the one that isnt?
6. Provide an arrow-pushing mechanism for the formation of the obtained, triboluminescent
product.

6
A simulated 200 MHz
1
H-NMR spectrum of the actual product:
13 12 11 10 9 8 7 6 5 4 3 2 1 0
0.00
0.10
0.20
0.30
0.40
0.50
0.60
0.70
0.80
0.90
1.00
1.10
1.20
1.30
1.40
1.50
1.60
1.70
1.80
1.90
2.00
2.10
2.20
9.0 8.5 8.0 7.5 7.0
0.00
0.10
0.20
3H
1H 1H
1H 1H
1H 1H

7
A simulated 200 MHz
1
H-NMR spectrum of the product not formed:
9 8 7 6 5 4 3 2 1 0
0.00
0.10
0.20
0.30
0.40
0.50
0.60
0.70
0.80
0.90
1.00
1.10
1.20
1.30
1.40
1.50
1.60
1.70
1.80
1.90
2.00
2.10
2.20
8.0 7.5 7.0 6.5
0.00
0.10
0.20
3H
2H
1H
1H 1H
1H

8
And an actual IR spectrum of the actual product:

Experiment 8:
Two-Week Diels-Alder Extravaganza!

Weeks of April 8 and April 15

1
Experiment 8: Two-Week Diels-Alder Extravaganza!

+
O
O O
anthracene maleic anhydride
xylenes
(reux)
????
+
O
O O
"eucalyptus oil"
maleic anhydride
diethyl ether
(reux)
????

Pre-Lab Preparation
Week 1: Before coming to lab, please read this handout, sections 12.12 and 20.4 of Jones, and
the attached supplementary reading, Identification of a Conjugated Diene from Eucalyptus Oil.
Remarkably, no written pre-lab report is required for this experiment. (Youre welcome.)

Week 2: Please bring your model kits to lab.

Background
During the first week of the experiment, you will perform the Diels-Alder reaction, one of the
most synthetically important reactions in all of organic chemistryTWICE! We hope that the
excitement of this will make up for the lack of entertaining drawings in this lab handout. In week
two, you will determine, with the aid of
1
H-NMR spectroscopy, the structures of the products in
the two reactions pictured above (and in the process, the structure of the predominant diene in
eucalyptus oil) and will answer a number of other questions too.
Because organic molecules are made primarily of carbon chains, reactions that give rise to new
carbon-carbon bonds are highly prized. The Diels-Alder reaction is doubly prized because it is
carbon-carbon bond forming and it is used to generate new ring systems. Much of modern
synthetic chemistry focuses on the total synthesis of highly complex natural molecules, which
often contain many rings. Thus, the 80-plus-year-old Diels-Alder reaction continues to be an
invaluable tool in the synthetic organic chemists toolbox.
2
Safety
Maleic anhydride and its Diels-Alder adducts are intense skin irritants. Please wear gloves when
you are weighing out the maleic anhydride and be careful not to get any compounds you
synthesize on your skin.

Procedure
Each pair of lab partners will run two separate reactions: One partner should focus on the
anthracene reaction, the other on the eucalyptus oil reaction. Follow the procedures directly
below (i.e., for the eucalyptus oil reaction, not the procedure in the supplementary reading).

DIELS-ALDER REACTION OF ANTHRACENE AND MALEIC ANHYDRIDE
Week 1:
1. Place 1.0 g of anthracene and 0.5 g of maleic anhydride in a DRY 50 mL round-bottom
flask. Record the precise mass of each reactant in your notebook.
2. Add 12 mL of xylenes and a couple of boiling chips to the flask. Ask your instructor or
TA about the structure of xylenes. Why is it called xylenes instead of xylene?
3. Place a reflux condenser on the flask (with water flowing through the appropriate tubing)
and heat the flask over an IR lamp. The boiling point of xylenes is (are?) quite high (137-144
!
C), so make sure that the lamp is as close as possible to your round-bottom flask.
4. Reflux the anthracene/maleic anhydride reaction mixture for 30 minutes.
5. After the 30 minutes have elapsed, remove the IR lamp and allow the refluxing reaction
mixture to cool to room temperature. Cool the flask in an ice bath for 10 minutes to complete
crystallization of the product.
6. Collect the anthracene/maleic anhydride adduct crystals by vacuum filtration using your
small Bchner funnel. Wash the crystals with a small amount of ice-cold xylenes and set
them aside in your bench (simply place the funnelfilter paper, crystals, and allinto a
beaker) to air dry until next week.

Week 2:
7. Now that your anthracene/maleic anhydride adduct has dried, obtain its mass (i.e., weigh
it!). A proton-NMR spectrum of the adduct will be provided to you in lab.
3
DIELS-ALDER REACTION OF EUCALYPTUS OIL AND MALEIC ANHYDRIDE
Week 1:
1. Place 2.0 g of eucalyptus oil and 0.73 g of maleic anhydride in a DRY 50 mL round-
bottom flask. Record the precise mass of each reactant in your notebook.
2. Add 5 mL of diethyl ether and a couple of boiling chips to the flask.
3. Place a reflux condenser on the flask (with water flowing through the appropriate tubing)
and heat the flask gently in a warm water bath. The boiling point of ether is quite low (only
35
!
C!).
4. Reflux the eucalyptus oil/maleic anhydride reaction mixture for 45 minutes.
5. After the 45 minutes have elapsed, remove the reaction mixture from the warm water
bath and allow to cool to room temperature. Cool the flask in an ice bath for 10 minutes to
complete crystallization of the product.
6. Collect the eucalyptus oil/maleic anhydride adduct crystals by vacuum filtration using
your small Bchner funnel. Wash the crystals with a small amount of ice-cold petroleum
ether (which is NOT diethyl ether!) and set them aside in your bench (simply place the
funnelfilter paper, crystals, and allinto a beaker) to air dry until next week. Note:
Petroleum ether is in fact not an ether at all; it is instead a mixture of pentanes and hexanes
with a boiling range that begins at about 35
!
Ci.e., the boiling point of real ether.

Week 2:
7. Obtain the mass of your eucalyptus oil/maleic anhydride adduct. A proton-NMR
spectrum of the adduct will be provided to you in lab.

Topics for Report (Anthracene reaction)
1. Imagine you were named Supreme Ruler of the Universe and were given the power to rid the
world of all maddening trivial compound names. Propose a more systematic name for m-
xylene. Oh, and while were on the topic, why did we use xylenes anywaythat is, whats
the advantage of using xylenes as opposed to, say, cyclohexane or benzene?

2. What was the limiting reagent of the anthracene reaction? Calculate the theoretical yield and
the percent yield of your reaction. SHOW ALL WORK.

3. Use the arrow-pushing formalism to show the Diels-Alder reactions between anthracene and
maleic anhydride that lead to the four possible isomeric products. Please also draw out the
structures of these four isomeric products. (Note: your four products should be good ol
structural isomers of one anotherwell save stereochemistry for the eucalyptus oil
reaction.) Hints: 1. Note that anthracene is quite symmetric and thus reaction on the left
4
side can give the same product as reaction on the right, and ditto for up vs. down and
top vs. bottom. 2. Consider the resonance forms of anthracene as you look for reactive
diene sites:

4. Now consider the HOMO of anthracene and the LUMO of maleic anhydride (due to the
extensive conjugation in both of these molecules, these orbitals are clearly rather
complicated):
HOMO of anthracene
O
O O
LUMO of maleic anhydride

Are all four of the possible isomeric products allowed by the tenets of HOMO-LUMO
(frontier-orbital) theory? Explain. For the product(s) that are allowed, draw the HOMO-
LUMO interactions.

5. In fact, only one product is formed from the reaction of anthracene with maleic anhydride,
and now its time to decide which it is. Given the
1
H-NMR spectrum of the actual product
(which we will distribute to you), which of the possible products remaining after your answer
to Question 4 is in fact the one formed? Explain, making reference to all of your answers
from Question 3 that werent ruled out in your answer to Question 4.
5
6. The product obtained in this reaction is in fact the most stable (i.e., in this reaction, the
thermodynamically most stable product is also formed the most quickly). Explain why. To
decipher this riddle, you will need to use the following information:

Compound Active in standard Diels-
Alder reactions?
Resonance stabilization
energy (kcal/mol)
benzene NO 36
naphthalene NO 60
anthracene YES 84

7. Finally, given the data in the table above, suggest a reason why the activation barriers for
Diels-Alder reaction of benzene and naphthalene are much higher than that for anthracene.

Topics for Report (Eucalyptus oil reaction)
8. Presuming that the eucalyptus oil is 50% diene or triene, what was the limiting reagent of this
reaction? (Note that all seven of the structures shown on page 247 of the supplementary
reading are isomeric and thus have the same molecular weight. Note further that if one of the
trienes is the predominant species in eucalyptus oil, then only two of the three double bonds
will participate in the Diels-Alder reaction.) Calculate the theoretical yield and the percent
yield of your reaction. SHOW ALL WORK.

9. Now consider the four dienes (!-phellandrene, "-phellandrene, !-terpinene, and limonene)
and three trienes ("-myrcene, "-ocimene, and allo-ocimene) shown on page 247 of the
supplementary reading. Which two of these seven isomers are, simply by virtue of their
structures, unreactive in a Diels-Alder reaction? Explain.

10. Draw out structures for the remaining six possible Diels-Alder cycloadducts. (Hmmmmm
why are there six possible cycloadducts when there are only five remaining possibilities for
the diene/triene structure?)

6
11. Given the
1
H-NMR spectrum of the adduct formed upon reaction with maleic anhydride and
given your answers to Questions 9 and 10, what must be the structure of the predominant
species in eucalyptus oil? Justify your answeri.e., the NMR spectrum is consistent with the
Diels-Alder adduct for only one of the remaining six possible isomers. Note: A complete
assignment of the NMR spectrum is not required to make this determination, but you must
clearly state what features of the spectrum make it consistent with your proposed structure
and inconsistent with the other possible isomers.

12. Now, lets deduce the precise stereochemistry of the adduct, which in fact has five tetrahedral
asymmetric stereoisomers. Thus, in principle, 32 possible stereoisomers existin principle
because many of the 32 are too strained to actually exist. Analogously, note as well that the
alkene functionality in the product must be cis rather than trans, since it is part of a six-
membered ringotherwise there would be 64 possible stereoisomers overall.
Remarkably, only one stereoisomer is actually formed in this reaction. (No wonder the Diels-
Alder reaction is so prized!) Which one is it? Alas, the
1
H-NMR spectrum wont help you
here, since all of the possible stereoisomers are predicted to give roughly the same spectra.
So, to answer this question, note the following: One, the tetrahedral asymmetric stereocenter
in the predominant diene in eucalyptus oil is of the R absolute configuration; two, as noted on
page 248 of the supplementary reading, Diels-Alder reactions typically give the endo adduct,
and this one is no exception; and three, also as noted on page 248, Sometimes more than
one endo adduct is possible; in that event, the dienophile will tend to approach the diene from
its [i.e., the dienes] less hindered side to give the more stable adduct. The use of your
model kit at this point is strongly advised!

13. Finally, provide a HOMO-LUMO analysis of the eucalyptus-oil reaction to demonstrate that
it is a thermally allowed process (which of course it is!).

Your lab report will consist of the answers to all of the above questionshappily, we will spend
much of the second week of the lab discussing these questions. Your report will be due in lab
the week of April 29 (during check out).

Although this is the last experiment you must come next week to check out.
Two-Week Diels-Alder
Extravaganza

Organic Chemistry, Chem 231 Lab Manual S2013

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