LABORATORY MANUAL
ORGANIC CHEMISTRY 241
4th Edition
Dr. Steven Fawl
1
LABORATORY MANUAL
ORGANIC CHEMISTRY 241
FOURTH EDITION
Dr. Steven Fawl
Mathematics and Science Division
Napa Valley College
Napa, California
2
NAPA VALLEY COLLEGE
COURSE: Chemistry 241
INSTRUCTOR: Dr. Steven Fawl, Room 1843, 253-3195
LECTURES: MW
LABS:
MT
OFFICE HRS: MTW
9:30 to 10:50
2:00 to 4:50
12:20 to 1:20 Room 1843
EXAM DATES:
The following are tentative dates for your exams and the material each exam will cover.
Exam #1 - Wednesday, February 22nd - Spectroscopy
Exam #2 - Wednesday, March 28th - Aromatics, Diels-Alder, MO Theory
Exam #3 - Wednesday, May 9th - Carbonyl Chemistry
Final Exam - Comprehensive - Monday, May 21st, 8:00-10:00
DESCRIPTION: A continuation of CHEM 240. Introduction to NMR, IR, and Mass Spectroscopy.
Chemical reactions and syntheses of aromatic, carbonyl, and amine compounds. Special topics in
carbohydrate, amino acid, and lipid chemistry. Lab work includes simple and multi-step synthesis
and spectral identification.
COURSE CONTENT:
1. Spectroscopy
Nuclear Magnetic Resonance
Infrared Spectroscopy
Mass Spectrometry
2. Aromatics I: Aromaticity
Reactions of benzene, Kekules structure, stability, and modern theories of the structure for
benzene.
Huckel's Rule and other aromatics.
Nomenclature of benzene derivatives.
Heterocyclic aromatics and aromatics in biochemistry.
3. Aromatics II: Reactions with Electrophiles
Electrophilic aromatic substitutions and their mechanisms.
Halogenation, nitration, sulfonation and alkylation of benzene.
Effects of substituents-reactivity and directing influences.
Alkyl and alkenyl benzenes and their reactions.
Carbenes.
3
4. Aldehydes and Ketones
Structure, nomenclature and physical properties.
Reactions of carbonyls - acetals, hemi-acetals, ammonia derivatives, and Schiff base reactons.
Keto-enol tautomerism, and the Cannizzaro Reaction.
5. Carboxylic Acids and their Derivatives
Nomenclature and physical properties.
Preparation and reactions at acyl carbon.
Synthesis and reactions of acyl halides, acid anhydrides, esters and amides.
Hell-Volhard-Zelinski and decarboxylation reactions.
Claisen, Michael, and Aldol reactions and synthetic pathways.
6. Amines
Nomenclature, physical properties and their basicities.
Some biologically important amines.
Preparation and reactions of amines with nitrous acid, diazonium salts.
Analysis of amines.
7. Carbohydrates
Monosaccharides, mutarotation and glycoside formation.
Oxidation and reduction, osazone formation.
Synthesis and degradation of monosaccharides.
The D-family of aldoses.
Methylation of monosaccharides.
Di- and poly- saccharides.
Nitrogen containing sugars.
8. Lipids
Fatty acids and Triacylglycerols.
Steroids and prostaglandins.
Phospholipids, waxes and terpenes.
9. Amino Acids and Proteins
Important amino acids.
Laboratory synthesis and analysis of amino acids.
Amino acid sequence of proteins and polypeptides.
Primary structure of polypeptides and their synthesis.
Secondary and tertiary structure of proteins.
COURSE OBJECTIVES
1.
2.
3.
4.
Solve complex reaction mechanisms.
Synthesize compounds starting with simple ingredients.
Determine the structure of organic compounds from spectrographic data.
Name organic compounds based on their structure.
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STUDENT LEARNING OUTCOMES
1.
Communicate chemical and physical processes at the molecular level and how they relate to the
macroscopic environment.
2.
Solve synthetic reaction pathways and mechanisms while demonstrating the reasoning clearly
and completely.
3.
Implement laboratory techniques correctly using appropriate safety procedures and express them
clearly in written laboratory reports.
STUDENT ACCOMMODATION IN THE COLLEGE LEARNING ENVIRONMENT
Any student who feels s/he may need accommodation based on the impact of a learning disability
should contact Learning Services in the Library and Learning Resource Center (LLRC), room 1766,
phone (707) 256-7442. A Learning Disability Specialist will review your needs and determine
appropriate accommodations.
If you need accommodations for physical or other types of disabilities, schedule an appointment with
DSPS Counselor, Sheryl Fernandez, in the Counseling Department located on the top floor of the 800
building, phone (707) 253-3040 for appointment.
All information and documentation is confidential.
Please feel encouraged to make an appointment with me privately to discuss your specific learning
needs in my class.
GRADING POLICY: Three exams and a final, quizzes, plus laboratory scores will count toward the
final grade according to the following schedule,
3 Exams = 300pts (100pts each)
Final = 200pts
Quizes = 50pts (5 @ 10pts each)
Lab
= 80pts
Total = 630pts
Grading is based on the class average = B-. The approximate breakdown of grades is,
100-85% A / 84-70% B / 69-60% C / 59-50% D / <50% F
It is the policy of this class that the final exam will automatically replace the score of your lowest
exam. In essence, this means that you can drop one exam and replace it with your final. There is one
exception – if you are caught cheating on an exam, you will receive a zero on the exam and the final
exam WILL NOT replace this grade.
LABS ARE CONSIDERED LATE IF THEY ARE TURNED IN ANY TIME AFTER THE
FRIDAY THAT THEY ARE DUE. LABS THAT ARE TWO WEEKS LATE WILL RECEIVE NO
CREDIT. Special arrangements must be made if a lab must be missed!
5
SAFETY AND TECHNIQUE RULES
Safety in the laboratory is extremely important. It is expected that you know laboratory safety rules.
It is important that if you feel uncomfortable with your knowledge of these rules that you take the
time to learn them. The following list is NOT complete. The Media Center, room 1028, there is a
video tape available in which a Napa Valley College instructor explains in detail safety and technique
rules. There is NO excuse for not following safety rules.
1)
Be attentive to instructions and follow them carefully. Read the board at the back of the class
room when you first come to class, any changes in procedure will be written there.
2)
If you ever have any questions about the procedure, apparatus, or chemicals it is important that
you ask the Instructor or Instructional assistant.
3)
Do not perform any unauthorized experiments. Anyone found doing so faces permanent
expulsion from class.
4)
Do not handle chemicals or materials not assigned to you or not called for in the experiment.
5)
Learn the location and proper use of the fire extinguisher, safety shower, eye and face wash.
Keep the first aide sink area clear at all times
6)
Coats, books, etc, should be kept in the space provided for them at the back of the lab. Many of
the chemicals used in the lab can ruin or stain paper and clothing.
7)
Never taste chemicals, nor pipet by mouth. Always use pipet bulbs or wheels.
8)
Smell chemicals by fanning a little vapor towards you.
9)
Experiments in which dangerous or obnoxious fumes are produced must be done in the fume
hood. Be sure to stop these reactions as soon as possible.
10) No eating, drinking or smoking in the lab.
11) Never point test tubes at yourself or others.
12) In the event of any injury, spill or glass breakage inform the Instructor immediately.
13) Goggles must be worn at all times when in the lab.
14) Chemicals may not be taken out of the lab (not even to the I.A.'s desk.)
15) Chemicals may not be stored in lockers.
16) Avoid unnecessary contact with ALL chemicals.
17) Do not leave lit burners unattended.
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18) Every time you use a chemical read it's label carefully. If any discrepancies inform the IA or
instructor immediately.
19) All containers which contain a chemical or in which a reaction occurs must be labeled.
20) When labeling a storage container include name and/or formula of chemical, any appropriate
warnings, concentration, date and your name.
21) NEVER place anything inside a reagent bottle, no spatulas, droppers, nor pipets. If the reagent
is a clumpy solid inform the IA. Proper technique is to "roll" containers from side to side to
remove solids and to pour liquids into smaller containers (such as a beaker) first.
22) NEVER return unused chemical (liquids or solids) back to the original container - offer excess
to another student or dispose of it appropriately.
23) Be conservative of reagents, place only the amount you need into a labeled container (such as a
beaker). Do not take the reagent bottles to your work area - leave them where every one can
find them.
24) Use tap water to wash glassware - you should rinse with DI water - please be conservative.
25) To dilute acids and bases, Add the Acid (or Base) to the Water.
26) Dispose of liquids and solids appropriately, read the board, or your experimental procedure for
special instructions, otherwise dispose of liquids and soluble solids down the sink with lots of
water, insoluble materials (such as paper towels) should be put in the waste basket. KEEP THE
SINKS CLEAN
27) It is very important to keep the lab clean. Before you leave each time be sure to:
a) return equipment to its proper place
b) clean up your workspace with the sponge
c) put away your labware
d) lock your locker
There is NO reason for a messy lab. Everything you need to keep your lab neat and clean is
available. Dirty counters, paper towels left in the sink or troughs, labware left out, messes left
under the fume hood, chemical spills left on the balance, are BAD technique and as such will
not be tolerated.
28) You may not be in the laboratory at any time other than your scheduled laboratory period unless
you have the permission of the instructor in charge as well as your course instructor. Do not
visit friends during their lab time and do not invite your friends or family to visit you.
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TABLE OF CONTENTS
EXPERIMENT 1
Synthesis of p-Nitroacetanilide
10
WORKSHEET
14
EXPERIMENT 2
Synthesis of Aspirin - Ester Formation
16
WORKSHEET
19
EXPERIMENT 3
Reactions of Aromatic Aldehydes - Cannizaro Reaction
WORKSHEET
21
25
EXPERIMENT 4
Synthesis of 9,10-Dihyroanthracene-9,10-endo-α,β-succinic Anhydride:
A Diels-Alder Reaction
WORKSHEET
26
27
EXPERIMENT 5
sec-Butylbenzene - Friedel Craft Alkylation
WORKSHEET
28
29
EXPERIMENT 6
Sodium Borohydride Reduction of Acetophenone
WORKSHEET
30
33
EXPERIMENT 7
Synthesis of 2-Methyl-2-Hexanol: A Grignard Reaction
34
EXPERIMENT 8
Biodiesel Synthesis
42
8
EXPERIMENT ONE


SYNTHESIS OF P-NITROACETANILIDE
O
H
C
O
CH3
H
N
C
CH3
N
HNO3
H2SO4
Discussion:
NO2
The aromatic nitration of acetanilide
is an exothermic reaction ; the temperature must be carefully controlled by chilling, stirring, and the
slow addition of reagents. Acetanilide is first dissolved in the solvent, glacial acetic acid, by warming.
Glacial acetic acid is used because it is a polar solvent capable of dissolving acetanilide and the
acetate ion is a poor nucleophile so no substitution is possible. After the solution is cooled, sulfuric
acid is added; however, even with cooling, the temperature of the solution rises almost 40̊. Both the
acetanilide solution and the nitrating solution (a mixture of HNO3, and H2SO4) must be chilled to
about 10̊C before the reaction is begun.
To prevent dinitration of the acetanilide, the nitrating mixture is added in small portions to the
acetanilide solution (and not vice versa) so that the concentration of HNO3, is kept at a minimum.
After all the HNO3, H2SO4 solution has been added, the reaction mixture is allowed to warm slowly
to room temperature. If the reaction mixture has been kept excessively cold during the addition, there
will be a relatively large amount of unreacted HNO3, present, which may cause the temperature to
rise above room temperature. If this should happen, the mixture must be rechilled.
The work-up procedure consists of removal of the acids and crystallization of the product. Every trace
of acid must be removed because hydrogen ions catalyze the hydrolysis of the amide to p-nitroaniline
or its protonated cation. Most of the acid is removed by pouring the reaction mixture onto ice and
water, then filtering the flocculent yellow precipitate of p-nitroacetanilide. The last traces of acetic
acid are removed by neutralization. Because bases also catalyze the hydrolysis of amides, the
neutralizing agent used is disodium hydrogen phosphate (Na2HPO4). This reagent reacts with acids to
yield NaH2PO4. The result is a buffered solution with a pH near neutral.
The crude product is air-dried before crystallization. If all of the acid was removed, the product will
be light yellow. A deep yellow to yellow-orange product is indicative of the presence of pnitroaniline from hydrolysis. Unfortunately, p-nitroaniline is difficult to remove from pnitroacetanilide by crystallization.
Equipment
250-mL beaker
dropper or disposable pipet
9
two 50-mL and one 125-mL Erlenmeyer flasks
10-mL graduated cylinder
hot plate
ice bath
spatula
stirring rod
thermometer
vacuum filtration assembly
watch glass
acetanilide, 6.5 g
disodium hydrogen phosphate, 15 g
95% ethanol, 60 mL
glacial acetic acid, 10 mL
conc. nitric acid, 3.5 mL
conc. sulfuric acid, 15 mL
Time Required: about two hours to crude product; 15-20 minutes for crystallization; two overnight
dryings; 15 minutes for melting-point determination
STOPPING POINTS: during either of the two drying periods or while the product is crystallizing
from ethanol
>>>>SAFETY NOTE 1: A mixture of concentrated nitric and sulfuric acids is used as the nitrating
mixture. Use extreme caution when preparing and using this mixture.
>>>>SAFETY NOTE 2: Nitro compounds are toxic and can be absorbed through the skin. You may
wish to wear disposable plastic gloves during portions of this experiment.
PROCEDURE
Place 6.5 g of acetanilide in a 125-mL Erlenmeyer flask, add 10 mL of glacial acetic acid
(CAUTION: strong irritant), and warm the flask on a hot plate in a fume hood until the acetanilide
dissolves. Cool the flask in an ice bath to about 20̊; then add 10 mL of cold, conc. sulfuric acid. The
temperature of the mixture will rise to about 60̊. Chill the solution to about 10̊ in an ice bath. (The
solution will become very viscous.)
Mix 3.5 mL of conc. nitric acid and 5 mL of conc. sulfuric acid in a 50-mL flask, and chill the flask
in an ice bath. When both solutions are cold, slowly add the HNO3, H2SO4 solution, 1 mL at a time,
to the acetanilide solution. Keep the reaction flask in an ice bath so that the temperature of the
reaction mixture is maintained between 10-20̊. Stir the reaction mixture carefully after each addition.
The entire addition requires about 15 minutes.
After the addition is completed, allow the reaction flask to stand at room temperature for 30 minutes.
Monitor the temperature; if it rises above 25̊, chill the flask in an ice bath. Should the rechilling be
necessary, allow the flask to stand for 30 minutes or more at room temperature after the rechilling.
Pour the reaction mixture into a 250-mL beaker containing 100 mL of water and 25 g of cracked ice.
Using a large Buchner funnel, filter the heavy lemon-yellow precipitate with vacuum. Press out as
10
much aqueous acid from the filter cake as possible with a spatula or clean cork while suction is being
applied (CAUTION: see Safety Note 2). The precipitate is voluminous; use care in transferring it to
the Buchner funnel or a substantial amount of product will be lost.
Transfer the filter cake to a clean 250-mL beaker, and add 100 mL of 15% aqueous disodium
hydrogen phosphate. Stir the mixture to a paste-like consistency and refilter using vacuum. Wash the
beaker with two 30-mL portions of cold water. Finally, wash the filter cake with an additional 50 mL
of cold water. Press the filter cake with a spatula or clean cork to remove as much water as possible,
then dry the solid overnight on a watch glass. Determine the yield and melting point.
The crude product can be purified by crystallization from 30-60 mL of 95% ethanol. (The crude
product dissolves very slowly, even with heating; avoid using an excess of solvent.)
11
NAME
DATE ________________
SYNTHESIS OF P-NITROACETANILIDE WORKSHEET
Mass of Product
Melting Point
CRC Melting
Point
Theoretical
Yield (grams)
Actual Yield
(Percent)
Problems
1. List at least two reasons for the choice of glacial acetic acid as the solvent for the nitration of
acetanilide.
2. What would be the effects of each of the following changes of reaction conditions in this
experiment, assuming that all other conditions are held constant? Some of these are simple dilutions
while others are addition of extra reactants. Explain your answers.
(a)
increasing the amount of glacial acetic acid from 10 mL to 20 mL
(b)
increasing the amount of nitric acid from 3.5 mL to 7.0 mL
(c)
decreasing the amount of sulfuric acid from 15 mL to 5 mL
3. Write equations for the hydrolysis of p-nitroacetanilide in (a) aqueous acid; (b) aqueous hydroxide.
The products of the reation should be p-nitroaniline and acetic acid (or acetate ion in base).
4. Predict what would happen during the crystallization of p-nitroacetanilide from 95% ethanol if all
the acidic material had not been neutralized previously? Use an equation in your answer. You should
ask yourself, “What is the other 5% and what will it do to this reaction?”
12
EXPERIMENT TWO


SYNTHESIS OF ASPIRIN: ESTER FORMATION
O
OH
O
C
OH
O
O
CH 3 C O C CH 3
OH
C
O
O
C
CH3
H2SO4
Salicylic Acid
Aspirin
Discussion
Salicylic acid is found in the bark of willow trees (trees of the genus Salix, from whence salicylic acid
derives its name). Today all aspirin sold is synthesized from phenol, which, in turn, is obtained from
petroleum. The last step of the commercial synthesis is the conversion of salicylic acid to aspirin
using the Fisher ester synthesis. The conversion of salicylic acid to aspirin is not required in order for
aspirin to work but the conversion to aspirin does make it more easily tolerated by the stomach.
The reaction of salicylic acid with acetic anhydride occurs rapidly. The reactants and a sulfuric acid
catalyst are mixed, then warmed in a hot water bath. Solid salicylic acid is insoluble in acetic
anhydride. Aspirin is soluble in a hot mixture of acetic anhydride and acetic acid, which is formed as
the reaction proceeds. Thus, the course of the reaction can be followed by the disappearance of the
solid salicylic acid. The reaction is essentially complete when all the salicylic acid has dissolved.
Aspirin is only slightly soluble in a cold mixture of acetic anhydride and acetic acid. Therefore, as the
mixture is cooled to room temperature, the aspirin precipitates.
At the end of the reaction period, the mixture contains aspirin, acetic anhydride, and acetic acid.
Acetic acid is miscible with water, and acetic anhydride reacts fairly rapidly with water to yield acetic
acid. By adding water to the reaction mixture and allowing the aqueous mixture to stand at room
temperature for a few minutes, we can achieve a reasonable separation-the contaminants dissolve in
the water, and the aspirin precipitates. Because of the presence of acetic acid and because aspirin is
slightly soluble in water, about 10% of the aspirin remains in solution. Therefore, the mixture is
thoroughly chilled before filtration and crystallization.
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An additional small amount of aspirin can be recovered from the mother liquor if it is allowed to
stand overnight. Despite this fact, it is not good practice to leave the bulk of the aspirin in acidic
solution for an extended period of time because it will undergo a slow hydrolysis to yield salicylic
acid and acetic acid, a typical acid-catalyzed ester hydrolysis.
EQUIPMENT
400-mL beaker (for hot water bath) dropper
two 125-mL Erlenmeyer flasks
10-mL and 100-mL graduated cylinders spatula
thermometer
vacuum filtration assembly
two watch glasses
CHEMICALS
acetic anhydride, 5.0 mL
salicylic acid, 2.8 g
conc. sulfuric acid, 3-4 drops
TIME REQUIRED: 1 hour plus overnight drying and time for a melting-point determination
STOPPING POINTS: after the initial vacuum filtration; while the product is crystallizing from
water; while the final product is being air-dried
>> SAFETY NOTE: Acetic anhydride is volatile and is a strong irritant.
PROCEDURE
Place 2.8 g of salicylic acid in a dry 125-mL Erlenmeyer flask, then add 5.0 mL acetic anhydride and
3-4 drops concentrated sulfuric acid. Mix the resultant white slurry thoroughly with a spatula, and
place the flask in a warm water bath (45-50̊C) for 5-7 min. Swirl or stir the mixture occasionally to
dissolve all the solid material. Because the reaction is slightly exothermic, a small temperature rise
can be detected.
Allow the flask to cool. The aspirin begins to precipitate when the temperature of the solution is
about 35-40̊C, and the mixture becomes semisolid. When this occurs, add 50 mL water and break up
any lumps with a spatula. Allow the mixture to stand for an additional 5 minutes, then chill the flask
in an ice bath and remove the crystals by vacuum filtration.
Crystallize the crude aspirin from 25 mL of warm water not exceeding 80̊C (see Experimental Note).
Allowing the mother liquor to sit overnight may produce a second crop of crystals. Air-dry the
crystals and determine the percent yield and melting point.
14
EXPERIMENTAL NOTE
At temperatures exceeding 80̊C, aspirin forms an oil that dissolves organic impurities from the water;
in this case, it may be difficult to redissolve the aspirin in water. If the solid does not dissolve in 25
mL of water, add more water from a dropper. Let the mixture warm 2-4 minutes between additions to
allow the solid to dissolve.
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NAME
DATE ________________
SYNTHESIS OF ASPIRIN WORKSHEET
Mass of
Product
Melting Point
CRC Melting
Point
Theoretical
Yield (grams)
Actual Yield
(Percent)
PROBLEMS
1) Write an equation for the synthesis of aspirin from salicylic acid with an acid chloride instead of
acetic anhydride.
2) The following compounds all have antipyretic and analgesic properties similar to aspirin. Suggest a
synthesis for each from salicylic acid.
(a) sodium salicylate
(b) methyl salicylate
(c) salicylamide
(d) phenyl salicylate
(e) 2-0-acetyl-5-bromosalicylic acid
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3a) Commercial aspirin sometimes has a distinct acetic acid odor. Why?
3b) Would ingestion of such aspirin be harmful? Explain.
17
EXPERIMENT THREE
THE CANNIZARO REACTION: THE
DISPROPORTIONATION OF BENZALDEHYDE
H
H
O
HO
C
DISCUSSION
O
H
C
OH
C
KOH
+
2x
In planning the laboratory schedule, it should be observed that this experiment requires materials to
be mixed and allowed to stand for 24 hr or longer.
In the presence of strong alkalis, benzaldehyde (like formaldehyde) undergoes disproportionation to
form the corresponding primary alcohol and a salt of the carboxylic acid : the Cannizzaro reaction.
The process involves addition of hydroxyl ion to the carbonyl group of one molecule and transfer of
hydride anion from the adduct to a second molecule of benzaldehyde, accompanied by proton
interchange to form the benzoate anion and benzyl alcohol. If the reaction is effected under anhydrous
conditions with the sodium derivative of benzyl alcohol as catalyst, the product is the ester, benzyl
benzoate.
EQUIPMENT
18 g KOH
20 mL Benzaldehyde
125 mL Erlenmeyer/stopper
100 mL methylene chloride
Steam bath
125 mL separatory funnel
10 mL 20% sodium bisulfite
4 g anhydrous magnesium sulfate
100 mL round bottom flask
Thermometer (0-250̊C)
Bunsen burner
40 mL conc. HCl
Chipped ice
Blue litmus paper
Side arm flask
Buchner funnel
EXPERIMENT: In a small beaker dissolve 0.27 mole (18 g of 85% pure solid) of solid potassium
hydroxide in 18 mL of water and cool the solution to about 25̊C. Place 0.2 mole (21 g, 20 mL) of
benzaldehyde in a 125-mL Erlenmeyer flask (or narrow-mouth bottle) and to it add the potassium
hydroxide solution. Cork the flask firmly and shake the mixture thoroughly until an emulsion is
formed. Allow the mixture to stand for 24 hr or longer. At the end of this period, the odor of
benzaldehyde should no longer be detectable.
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Isolation of Benzyl Alcohol
To the mixture add just enough distilled water to dissolve the precipitate of potassium benzoate.
Shake the mixture thoroughly to facilitate solution of the precipitate. Extract the alkaline solution
with three or four 20-mL portions of methylene chloride to remove the benzyl alcohol and traces of
any unconverted benzaldehyde. Combine the methylene chloride extracts for isolation of benzyl
alcohol and reserve the aqueous solution to obtain the benzoic acid.
Concentrate the methylene chloride solution of benzyl alcohol by distillation on a steam bath using a
water-cooled condenser, until the volume of the residual liquid has been reduced to 15-20 mL. A
steam bath is just a beaker of boiling water into which the distillation flask is emersed. Cool the
remaining liquid, transfer it to a small separatory funnel (using 2-3 mL of methylene chloride to rinse
the distilling flask), and shake it thoroughly with two 5-mL portions of 20% aqueous sodium bisulfite
to remove any benzaldehyde. Wash the methylene chloride solution finally with two 10-mL portions
of water and dry it with 3-4 g of anhydrous magnesium sulfate. Filter the solution into a small dry
distilling flask and carefully distill off the methylene chloride. Attach a short air-cooled condenser
and distill the benzyl alcohol, by heating the flask directly with a luminous flame kept in motion.
Collect the material boiling at 200-206̊C. The yield is 4-5 g.
Isolation of Benzoic Acid
To free the acid, pour the aqueous solution of potassium benzoate (from which the benzyl alcohol has
been extracted) into a vigorously stirred mixture of 40 mL of concentrated hydrochloric acid, 40 mL
of water, and 40-50 g of chipped ice. Test the mixture with indicator paper to make sure that it is
strongly acidic. Collect the benzoic acid with suction and wash it once with cold water. Crystallize
the product from hot water, collect the crystals, and allow them to dry thoroughly. The yield is about
8g.
I.R. SPECTROSCOPY
Setup Instructions
1. Remove the cover from the machine.
2. The "ON" switch is located to the rear on the right side of the machine. Switch the machine on.
The spectrometer will take about a minute to warm-up. When it is ready for use it will beep twice.
3. Running the machine involves several simple steps. The machine can scan at two rates, a three
minute and a twelve minute scan. A three minute scan will give you all of the major spectroscopic
peaks, but none of the details. The twelve minute scan will give you the details that the three minute
scan missed. Set the machine to a three minute scan.
19
4. There are several kinds of chart paper that can be used for plotting the output. We use the shortest
sheets. Set the machine for short paper output.
5. Before a plot can be made a pen must be placed into the slide bar located near the center of the
machine. The pens are located on a shelf next to the spectrometer (several colors are available).
Slide one of the pens (any color) into the pen holder on the slide bar.
6. Occasionally the edge of the chart paper becomes misaligned with the pen position. The chart can
be moved by pressing the Chart button (either the UP or the DOWN button) to move the chart into
the proper position.
The spectrometer is now ready to accept a sample.
Sample Preparation
Infrared spectroscopy can be done on either liquid or solid samples. The preparation of these samples
differ dramatically. Follow these general guidelines.
Liquid Samples
Liquid samples are loaded into "cells". What this means is that the liquid will be sandwiched
between two plates. Each plate has a shallow indentation in it's surface that holds a small amount of
sample. When the plates are put together the sample is trapped in this indentation producing a thin
film of sample which can be analyzed by the spectrophotometer.
The process is very simple. Locate the cell and it's holder. It should be found in a small white box on
a shelf adjacent to the machine. The cell holder is a round piece of white plastic with a hole in the
center and should be found together with small piece of protective cloth which contains the cells
themselves. The cells are small round disks of what appear to be plastic but they are really made of
solid AgCl so be careful with them.
You will notice that the cell holder unscrews. Unscrew the cell holder and inside you will see a black
rubber "O" ring. Take one of the two cells and place it, shallow side up, on top of the "O" ring. Place
two or three drops of sample onto the cell surface and quick place the other half cell and place it on
top (shallow side down). Now screw the top of the cell holder back onto the cell. The cell should be
snug but not overly tight. Overtightening can warp or even break the AgCl cells. Please be careful.
Now that the sample is in the cell you are ready to mount the cell into the spectrometer and take a
spectrum of the sample.
Solid Samples
Solid samples can be prepared by mixing (actually grinding) the solid together with KBr. You will
do this using an agate morter and pestle. It is usually wise to use about two to three times more KBr
than the amount of solid sample (eye-ball it). Use very small amounts of each, 1 gram of KBr and 0.3
grams of solid are more than enough (usually). After the sample has been well mixed place a small
20
amount in the KBr wafer press and make a thin, nearly transparent wafer of this mixture. Small
cracks in the sample are alright. Mount the pellet in the IR and run the sample.
Problem
Write equations for the preparation of benzaldehyde from
(a) benzene
(b) toluene
(c) benzoic acid
21
NAME
DATE ________________
REACTIONS OF AROMATIC ALDEHYDES WORKSHEET
Results: Benzyl Alcohol
Mass of
Benzyl Alcohol
Ref. Index of
Benzyl Alcohol
Boiling Point
of Benzyl
Alcohol
Theoretical
Yield (grams)
Actual Yield
(Percent)
Results: Benzoic Acid
Mass of
Benzoic Acid
Melting Point
of Benzoid Acid
Theoretical
Yield (grams)
Actual Yield
(Percent)
Attach your spectra to this sheet and locate the following peaks by circling and labeling them.
Benzyl Alcohol
OH stretch
CH stretch
Benzene C=C stretch
C-O stretch
Benzoic Acid
OH stretch
CH stretch
Benzene C=C stretch
C-O stretch
C=O stretch
22
EXPERIMENT FOUR

Synthesis of 9,10-Dihyroanthracene-9,10-endo-α,β-succinic Anhydride
A Diels-Alder Reaction
O
O
O
+
O
O
O
EQUIPMENT
2.0 g Anthracene
50 mL round bottom flask
55 mL mixed xylenes
1.0 g maleic anhydride
Reflux condenser
Ice bath
Buchner funnel
Side-arm flask
10 mL iced xylene
Watch glass
Parafilm
EXPERMENT
Place 2.0 g of anthracene in a 50 mL round bottom flask and add 25 mL of mixed xylenes. Add 1.0 g
of well ground maleic anhydride, fit the flask with a reflux condenser, and heat the mixture at reflux
for 30 minutes. Allow the flask to cool to room temperature, then chill it in an ice bath. The product
if fairly insoluble in xylene. Once crystallization begins, it cannot be reversed by heating the
solution. Filter the solid using a Buchner funnel and wash the product with 10 mL of of ice-cold
mixed xylene. Dry the solid on a watch glass next to a small beaker of paraffin wax, both covered by
a larger beaker. A typical yield is 2.5 g of colorless product mp 262-264̊C. If the sample is tinged
with yellow and has a depressed melting point, recrystallize the product from xylene (20 mL per gram
of product).
23
NAME
DATE ________________
Synthesis of 9,10-Dihyroanthracene-9,10-endo-α,β-succinic Anhydride
A Diels-Alder Reaction Worksheet
Mass of
Product
Melting Point
CRC Melting
Point
Theoretical
Yield (grams)
Actual Yield
(Percent)
Problems
1) Predict the products of hydrolysis (cleavage by water) of the following anhydrides.
O
CH3
CH2
O
C
O
C
CH3
O
O
O
2) What products would be obtained from a Diels-Alder reaction of anthracene with following
dienophiles?
A. CH3
C
H
O
C
C
O
C6 H 5
H
O
B.
C.
H
C
C
C
O
CH3
O
24
EXPERIMENT FIVE


Friedel Craft Alkylation: Formation of sec-Butylbenzene
H3 C
C
C
CH3
C-C-C-C-Br
DISCUSSION
AlCl3
The reaction between
bromobutane and benzene in the presence of AlCl3 is a classic Friedel-Craft alkylation reaction. The
reaction begins with the removal of the bromine by the AlCl3 to produce a bromobutane carbocation.
This cation rearranges to place the positive charge on the secondary carbon of butane. Thus, when
benzene attacks the butane carbocation the attachment is on the secondary rather than the primary
carbon. The only product formed in this reaction is sec-butylbenzene. No butylbenzene is formed.
EQUIPMENT
250 mL round bottom flask
condenser
7.8 mL n-butyl bromide
50 mL benzene
3.25 g Anhydrous Aluminum chloride
6 mL conc. HCl
40 g ice
steam bath
250 mL separatory funnel
3-4 g CaCl2
thermometer (0-200̊C)
EXPERIMENT
In a dry 250 mL round-bottomed flask fitted with an upright condenser, place 11g (7.8 mL) of n-butyl
bromide and 50 mL of benzene. To provide for the acid vapors evolved during the reaction do the
experiment in the hood.
Add 0.025 mole (3.25g) of pulverized anhydrous aluminum chloride and allow the reaction to
proceed in the cold, shaking the flask occasionally on a steam bath, and finally reflux the mixture on
a steam bath for about an hour. Cool the reaction mixture and pour it with stirring into a mixture of
40 g ice, 25 g water, and 6 mL of concentrated HCl. Stir thoroughly to dissolve the excess aluminum
compounds and transfer the mixture to a large separatory funnel. Separate the benzene layer and dry
it with 3-4 g anhydrous calcium chloride, and decant the dried liquid into a 250 mL round bottom
flask. Fit the flask with a fractionating column and distill the mixture. Distill very slowly but at a
regular rate. Save all the sample that distills above 130̊C and put this into a 50 mL round bottom
flask and refractionate, keeping the ethylbenzene fraction which boils from 173-178̊C.
25
NAME
DATE ________________
sec-Butyl Benzene Worksheet
Mass of
Product
Boiling Point
CRC Boiling
Point
Theoretical
Yield (grams)
Actual Yield
(Percent)
Questions
1) Why is such a large excess of benzene used in this experiment?
2) What products would be formed by the reaction of the following alkenes with benzene, in the
presence of aluminum chloride: ethylene? isobutylene? cyclohexene?
3) Explain why n-propyl bromide reacts with benzene in the presence of aluminum chloride to form
mainly isopropylbenzene. How could you make propylbenzene?
4) Write the reactions for the formation of;
diphenylmethane
triphenylmethane
p-chloroethylbenzene
26
EXPERIMENT SIX


SODIUM BOROHYDRIDE REDUCTION OF ACETOPHENONE
O
CH3
HO
CH3
NaBH4
DISCUSSION
The reduction of an aldehyde or ketone with sodium borohydride is straight forward and usually
affords a high yield of the alcohol. The usual procedure (and the one employed in this experiment)
involves dissolving the borohydride in 95% ethanol and adding the carbonyl compound to this
solution. To ensure complete reaction, an excess of sodium borohydride is used.
The reaction between sodium borohydride and acetophenone is exothermic. Therefore, it is important
to add the acetophenone drop-wise and to control the reaction temperature with an ice bath. After the
reaction has been completed, the excess borohydride and the ethoxyborohydrides are destroyed with
aqueous acid. Because hydrogen gas is evolved, this treatment with acid must be carried out in a fume
hood or a very well-ventilated room.
Because ethanol, the reaction solvent, is water-soluble, a clean separation of organic and inorganic
products cannot be achieved by a simple extraction with water and diethyl ether at this point. (Too
much product would be lost in the aqueous ethanol layer.) To circumvent this problem, the first step
in the work-up is to boil off much of the ethanol. In a larger-scale reaction, the ethanol would be
distilled and collected. In a small-scale reaction such as in this experiment, the ethanol can be boiled
away in the fume hood. When most of the ethanol has been removed, the product 1-phenylethanol
oils out.
Water and diethyl ether are then added to the residue for the extraction of the organic compounds
from the inorganic salts. The ether extract is dried with either sodium sulfate or magnesium sulfate.
The crude product is obtained by distilling the ether.
Because of its high boiling point, 1-phenylethanol cannot be distilled at atmospheric pressure.
Although it could be vacuum-distilled, distillation could not separate it from unreacted starting
material (if any) because the two compounds have boiling points only 1̊ apart. (An infrared spectrum
can be used to determine if any ketone is present in the product.)
27
EQUIPMENT
150-mL beaker
distillation apparatus
dropper
three 50-mL Erlenmeyer flasks
10-mL and 50-mL graduated cylinders
hot plate or steam bath with magnetic stirrer (optional)
ice bath
two 50-mL round-bottom flasks
125-mL separatory funnel
thermometer
CHEMICALS
acetophenone, 12.0 g
anhydrous magnesium sulfate (or Na2SO4) (1 g)
diethyl ether, 40 mL
95% ethanol, 30 mL
3M hydrochloric acid, 10 mL
sodium borohydride, 1.5 g
TIME REQUIRED: about 4 hours
STOPPING POINTS: after the acetophenone has been added; after
the excess ethanol has been boiled off ; while the ether solution is drying
>>>> SAFETY NOTE: Sodium borohydride is caustic. Do not let it come into contact with your
skin. If accidental contact should occur, wash immediately and thoroughly.
PROCEDURE:
Place 1.5 g of sodium borohydride (see Safety Note) in a 150-mL beaker. Add 30 mL of 95% ethanol
and stir until the solid is dissolved (see Experimental Note). Weigh 12.0 g of acetophenone into a 50mL Erlenmeyer flask, and prepare an ice bath.
Add the acetophenone dropwise to the borohydride solution while stirring the mixture continuously,
preferably with a magnetic stirrer. Keep the temperature of the reaction mixture between 30-50̊C by
controlling the rate of addition and by cooling the beaker in the ice bath as necessary. As the
acetophenone is added, a white precipitate forms. The addition should take about 45 minutes. After
the addition is complete, allow the reaction mixture to stand at room temperature for 15 minutes with
occasional stirring (or continuous stirring if you are using a magnetic stirrer).
(Stopping Point)
In the fume hood, add about 10 mL of 3M HCl to the reaction mixture. After the reaction has
subsided, heat the mixture to boiling on a hot plate or steam bath in the fume hood until the mixture
separates into two layers.
28
(Stopping Point)
Cool the reaction mixture in an ice bath, then transfer it to a separatory funnel. Wash the residual
material in the beaker into the separatory funnel with 20 mL of diethyl ether (flammable). If the
inorganic salts precipitate, add 20-40 mL of water, as necessary, to dissolve them. Extract the
aqueous layer with this ether, then with a second 20-mL portion of ether; combine the ether extracts;
wash them with an equal volume of water; and dry them with anhydrous magnesium sulfate or
sodium sulfate.
(Stopping Point)
Decant or filter the dried solution into a tared flask, and distil the ether slowly, using a heating mantle
or steam bath and an efficient condenser. Do not overheat the flask. You are not keeping the ether that
is being removed, keep what is left in the tared flask. A typical crude yield is 10 g (82%). Measure
the refractive index, and run the infrared spectrum (thin film). From these two pieces of data, estimate
the purity of the crude product.
EXPERIMENTAL NOTE
Fresh sodium borohydride dissolves in 95% ethanol, but partially hydrolyzed sodium borohydride
will not all dissolve. This should not affect the experiment because an excess of borohydride is used.
(If your borohydride is extremely poor quality, your instructor may suggest that you use a greater
excess than is called for.)
29
Name
DATE ________________
SODIUM BOROHYDRIDE REDUCTION WORKSHEET
Mass of
Product
Ref. Index
CRC Ref.
Index
Theoretical
Yield (grams)
Actual Yield
(Percent)
Attach the I.R. Spectrum of the Product
Locate the position of the following peaks in your spectrum;
-OH peak
-phenyl peak (benzene stretch)
-CH stretch
-C-OH stretch
PROBLEMS
1) Write an equation for the hydrolysis of NaBH4. The products should be NaH2BO3 and H2 gas.
2) Under what circumstances would you expect to find unreacted acetophenone in the product in this
experiment?
3) Which compound would you expect to undergo borohydride reduction more rapidly? Explain.
(a) CH3CH2CHO or (b) CH3CH2COCH2CH3
30
EXPERIMENT SEVEN
SYNTHESIS OF 2-METHYL-2-HEXANOL:
A GRIGNARD REACTION
DISCUSSION
A standard Grignard synthesis is carried out in three steps: (1) preparation of RMgX; (2) the reaction
of RMgX with the carbonyl compound or other reactant; and (3) the acidic hydrolysis. The first two
steps (and often all three steps) are generally carried out in the same reaction vessel. The intermediate
products (the Grignard reagent,and the alkoxide) are rarely isolated.
PREPARATION OF THE GRIGNARD REAGENT (STEP 1)
In this experiment, the Grignard reagent is prepared by slowly adding a solution of 1-bromobutane in
anhydrous diethyl ether (not solvent ether, which is wet) to Mg turnings. Unfortunately, the reaction
leading to the formation of a Grignard reagent is often difficult to initiate. Difficulties can usually be
traced to contaminants, primarily water. Therefore, scrupulous care must be taken to dry all glassware
and to use only dry reagents and solvents. The techniques used to start the reaction are discussed in
Experimental Note 3.
Once started, the formation of a Grignard reagent is
exothermic; therefore, excess 1-bromobutane should not
be added to initiate the reaction. If a large excess of 1bromobutane is present in the reaction vessel, the reaction
may be difficult to control. Once the reaction has begun,
the 1-bromobutane is added at a rate that will maintain a
gentle reflux of the ether in the reaction flask.
At the end of the reaction, some of the magnesium may
remain unconsumed. The reason for this is that some 1bromobutane is destroyed by undergoing a coupling
reaction with the Grignard reagent to yield octane. Other
than providing a mechanical inconvenience in the
extraction steps, the residual magnesium metal does not
interfere with the remainder of the experiment.
An ether solution of a Grignard reagent has a translucent
gray-to-black tint. The color arises from impurities in the
magnesium metal, rather than from the Grignard reagent
itself. Once formed, the Grignard reagent must be carried
on to Step 2 (the reaction with acetone) immediately. It
cannot be saved until the next laboratory period because it
reacts with oxygen and moisture from the air.
1: Grignard apparatus
31
REACTION WITH ACETONE (STEP 2)
The reaction of n-butylmagnesium bromide with acetone is extremely vigorous. The acetone must be
added very slowly; otherwise, the reaction mixture will boil over. The product is a magnesium
alkoxide of an alcohol and thus insoluble in diethyl ether. This alkoxide sometimes forms a crusty
precipitate that must be broken up by swirling the flask so that the unreacted acetone can become
mixed with the Grignard reagent.
After the reaction of acetone and the Grignard reagent is completed, it is no longer necessary to
protect the reaction mixture from air or moisture. This mixture can be stored until the next laboratory
period.
HYDROLYSIS OF THE ALKOXIDE (STEP 3)
The alkoxide product of the Grignard reaction is converted to 2-methyl-2-hexanol by treatment with
aqueous NH4Cl instead of with a dilute mineral acid. The reason is that the final product is a tertiary
alcohol (R3COH) and is easily dehydrated to an alkene by a strong acid. When the magnesium
alkoxide is poured into aqueous NH4Cl, the alkoxide ion (a strong base) reacts with water or NH4+ to
extract a proton. Water alone is not used as a hydrolyzing agent for two reasons. First, the product
hydroxide ion is only a slightly weaker base than the alkoxide ion. The addition of an acid results in a
more favorable equilibrium.
Second, in alkaline solution, the magnesium ions are converted to a gelatinous precipitate of
Mg(OH)2, which is difficult to remove from the product. In a neutral or acidic medium, the
magnesium ions remain in solution. The product alcohol is extracted from the aqueous layer with
diethyl ether (solvent grade). The aqueous layer, which contains the magnesium salts, is discarded.
The ether solution is washed with sodium carbonate solution to ensure alkalinity prior to distillation.
(Any acid remaining in the ether layer would cause dehydration of the alcohol during the distillation.)
Because diethyl ether can dissolve a considerable amount of water (1.2 g H2O in 100 g of ether), the
ether extract is partially dried by extraction with saturated NaCl solution before an inorganic drying
agent is used. The final drying is accomplished by allowing the ether solution to stand over anhydrous
MgSO4. The bulk of the ether is removed by simple distillation. Before the alcohol is distilled, the
residue is transferred to a smaller distillation flask; otherwise, a considerable amount of product
would be lost as vapor filling the large flask.
EQUIPMENT:
400-mL beaker
calcium chloride drying tube
Claisen head
condenser
disposable pipet
25-mL or 50-mL tared distillation receiving flask
125-mL dropping funnel
50-mL, 125-mL, and two 250-mL Erlenmeyer flasks
heating mantle and rheostat (or steam bath)
ice bath
50-mL (or 100-mL) and 250-mL round-bottom flasks
32
250-mL or 400-mL separatory funnel
simple distillation apparatus
stirring rod
warm water bath
CHEMICALS:
ammonium chloride, 25 g
anhydrous acetone, 5.8 g
anhydrous diethyl ether, 50 mL
anhydrous magnesium sulfate or potassium carbonate, 5 g
10% aqueous sodium carbonate, 25 mL
1-bromobutane, 13.7 g
diethyl ether (for extraction), about 75 mL
magnesium turnings, 2.4 g
saturated aqueous NaC1, 25 mL
TIME REQUIRED: 3½ hours, plus 1½ hours for the distillation. The Grignard reagent must be used
immediately after its formation. Therefore, enough time should be allotted to carry out Steps 1 and 2
(about 1 hour each) in a single laboratory period. IMPORTANT: If anhydrous acetone is not
available, then reagent acetone must be dried with anhydrous MgSO4 (5 g for each 50 mL) for at least
24 hours prior to the Grignard reaction (see Experimental Note 4).
STOPPING POINTS: after the acetone has been added to the Grignard reagent (and reaction has
subsided); when the ether extracts are drying
>>SAFETY NOTE I Diethyl ether (bp 34.6̊) is used as a reaction solvent and as an extraction
solvent. It is very volatile and extremely flammable. There must be no flames in the laboratory. An
efficient condenser must be used for both the reaction and the distillation. The distillation should be
carried out slowly to minimize ether vapors escaping into the room.
>> SAFETY NOTE 2 Because the formation of a Grignard reagent and a Grignard reaction are both
exothermic, there is the danger of a runaway reaction. Keep an ice bath handy at all times in case the
reaction flask needs rapid cooling.
>>SAFETY NOTE 3 The heavy caked precipitate that sometimes forms makes thorough mixing of
acetone and the Grignard reagent difficult and can allow unreacted acetone to accumulate in one spot.
When this acetone eventually contacts the Grignard reagent, the reaction may become impossible to
control. Therefore, swirl the reaction flask gently, but frequently and thoroughly.
PROCEDURE
Step 1, Preparation of n-Butylmagnesium Bromide. Heat a 250-mL round-bottom flask, a Claisen
head, a condenser, and a dropping funnel in a drying oven until they are hot to the hand. Then
assemble them as shown in Figure 10. Fit the reflux condenser with a drying tube containing
anhydrous calcium chloride (see Experimental Note 1). To prevent atmospheric moisture from
condensing inside the condenser, do not turn on the condenser water until the reaction is initiated.
33
Place 2.4 g of oven-dried magnesium turnings in the round-bottom flask. To the dropping funnel, add
a well-mixed solution of 13.7 g of 1-bromobutane and 50 mL of anhydrous diethyl ether.
(CAUTION: flammable! See Safety Note 1; see also Experimental Note 2.)
To initiate the reaction, add 10-15 mL of the ether solution from the dropping funnel to the reaction
flask. Loosen the clamp holding the round-bottom flask and gently swirl the flask to mix the contents.
When the Grignard reagent begins to form, the ether solution will become cloudy and then begin to
boil. Turn on the condenser water at this time. If your Grignard reagent does not start to form within
5-10 minutes, follow the procedure outlined in Experimental Note 3. Because the reaction is
exothermic once initiated, do not add an excessive amount of 1-bromobutane to the magnesium at
any one time (see Safety Note 2).
After the reaction has been initiated, add the remaining ether solution dropwise at a rate that
maintains a gentle reflux. After all the solution has been added, close the stopcock of the dropping
funnel and heat the mixture at a gentle reflux for 15 minutes in a warm (50̊C) water bath. As the
magnesium is consumed, the mixture will become darker colored. At the end of the reflux period,
proceed immediately to Step 2.
Step 2, Reaction of n-Butylmagnesium Bromide with Acetone. Chill the flask containing the
Grignard reagent with an ice bath. Pour 5.8 g of anhydrous acetone (not ordinary reagent grade) in the
dropping funnel, and add it a few drops at a time to the reaction mixture. After each addition, loosen
the clamps to the reaction assembly and gently swirl the reaction flask. (CAUTION: See Safety Note
3.)
When the addition of the acetone is completed, allow the reaction mixture to stand at room
temperature for 30 minutes or longer before going on to the hydrolysis step. If the mixture will be
standing for more than an hour, stopper the reaction flask with a glass stopper or a cork (not a rubber
stopper) to prevent the solvent from evaporating.
Step 3, Hydrolysis and Purification. Prepare 100 mL of 25% aqueous ammonium chloride. Mix 75
mL of this solution with 50 g of crushed ice in a 400-mL beaker. Transfer the remaining 25 mL of the
ammonium chloride solution to a 50-mL Erlenmeyer flask, and chill it in an ice bath. Slowly pour the
Grignard reaction mixture into the ice mixture in the beaker, stirring vigorously (see Experimental
Note 4). Rinse the reaction vessel into the ice mixture, first with the 25 mL of chilled NH4C1
solution, then with 25 mL of solvent ether. Transfer the contents of the beaker to a 400-mL
separatory funnel. (If a 250-mL separatory funnel must be used, divide the mixture into two batches
and process each separately.) Add solvent ether to bring the volume of the upper ether layer to about
50 mL, shake the funnel, and allow the layers to separate. Drain the lower aqueous layer into a 250mL Erlenmeyer flask or a second separatory funnel and drain the ether layer into a separate
Erlenmeyer flask. (Draining instead of pouring minimizes evaporation of the ether.) Return the
aqueous layer to the separatory funnel, add 25 mL of fresh solvent ether, and shake the mixture again.
Drain and discard the lower, aqueous layer.
Add the first 50-mL ether extract to the second extract in the separatory funnel. Rinse the flask that
contained the original extract into the separatory funnel with a few mL of ether. Wash the combined
ether extracts by shaking them with 25 mL of water, then with 25 mL of 10% sodium carbonate
solution. Finally, wash the ether solution with 20-25 mL of saturated sodium chloride solution.
34
Pour the ether solution into a clean, dry 250-mL Edenmeyer flask, add 5 g of anhydrous magnesium
sulfate or potassium carbonate, cork the flask tightly, and allow it to stand for at least one hour
(overnight is better).
Carefully decant (or filter through a small plug of glass wool) the dried solution into a 250-mL roundbottom flask for distillation of the ether. Add a few boiling chips and slowly distil the bulk of the
ether (bp 34.6̊C), using a steam bath or heating mantle and an efficient condenser. Stop the distillation
when there is about 25 mL remaining in the distillation flask. Cool the flask and, using a disposable
pipet, transfer the residue to a 50-mL round-bottom flask for distillation of the product. Wash the last
traces of crude product from the 250-mL flask into the 50-mL flask with a few mL of anhydrous
diethyl ether.
Add fresh boiling chips and distil the product, collecting the fraction boiling at 135-143̊C in a tared
receiver. A typical yield is 5.0 g (43%). (The yield may vary considerably, depending on the degree
of dryness of the anhydrous ether used in Step 1.) Determine the refractive index of the product. Place
the distilled product in a correctly labeled vial, and hand it in to your instructor.
EXPERIMENTAL NOTES
1) The purpose of the drying tube is to prevent atmospheric moisture from entering the reaction
vessel via the condenser and yet allow the reaction vessel to be open to the atmosphere so that gas
pressure does not build up. There are two types of drying tubes: curved (better) and straight (less
expensive). A straight drying tube must not be connected directly to the top of the condenser because
the dessicant can liquefy and drain into the condenser. Connect the straight tube to the condenser by a
short length of heavy-walled rubber tubing, as shown in Figure 10. In either type of drying tube, the
dessicant is held in place with loose plugs of glass wool. A one-hole rubber stopper may be used as a
secondary plug at the wide end of the drying tube.
2) Solvent ether contains an appreciable amount of water (up to 1-2%) and is totally unsuitable as a
Grignard solvent. Anesthesia ether contains ethanol, which makes it also unsuitable. Commercial
anhydrous ether is adequate only if a freshly opened can is used. Anhydrous ether must not be left
open to the air because it absorbs both oxygen and moisture. (Oxygen and ethers yield peroxides,
which can explode if the ether is distilled. Absorbed moisture will ruin a Grignard reagent.) Your
instructor will probably provide anhydrous ether for this experiment. In many laboratories, storeroom
personnel prepare anhydrous ether by passing solvent ether through a column containing molecular
sieves, which are adsorbents with pores that trap molecules of a certain size (in this case, H2O
molecules). Another procedure for the preparation of anhydrous ether from solvent ether and a
procedure for the testing of peroxides in anhydrous ether follow. If you find it necessary to prepare
your own anhydrous ether, allot an additional laboratory period.
Preparation of Anhydrous Diethyl Ether. With cooling, mix a 2:1 ratio of solvent ether and
conc. H2SO4 in a large round-bottom flask, and distill about two-thirds of the ether. (Do not
distill all the ether.) Any water and ethanol contaminating the ether will remain with the
sulfuric acid. To discard the residue, pour it onto cracked ice, allow the residual ether to
evaporate in the hood, then dilute the aqueous acid with water and pour it down the hood
drain with additional water. Add freshly prepared sodium wire or ribbon to the distilled ether,
then allow the ether to stand at least overnight in the fume hood with the fan on. Stopper the
container with a very loose-fitting cork or drying tube to allow the hydrogen gas to escape.
35
Sodium wire or ribbon is prepared by pressing sodium metal through a die, using a press. If a
sodium press is not available, the ether can be dried with finely diced sodium; however, diced
sodium is inferior to wire or ribbon. Another method is to add a few grams of CaCl2 to the
ether and allow the mixture to stand until hydrogen has ceased to be evolved. The dried ether
can then be decanted or (better) pipetted, using a rubber bulb, as needed. Commercial
anhydrous ether can be further dried with sodium wire without the sulfuric acid purification
step.
Peroxide Test. Shake 5 mL of ether with a solution of 1 mg of sodium dichromate and one
drop of dilute H2SO4 in 1 mL of water in a corked test tube. If the ether layer turns blue (from
perchromate ion), peroxides are present and must be removed.
Peroxide Removal. Shake the peroxide-contaminated ether with 5% aqueous ferrous sulfate
(FeSO4) solution acidified with H2SO4. The iron(II) ions are oxidized with concurrent
reduction of the peroxide. Aqueous sodium sulfite (Na2SO3) can be substituted for the ferrous
sulfate solution.
3) The most common cause of failure of initiation of the reaction leading to the Grignard reagent is
moisture (in the apparatus, in the ether, or on the magnesium turnings). In addition, in a humid
atmosphere, water will collect on the sides of a cold condenser. If the initial cloudiness becomes a
white precipitate, then the Mg is being converted to Mg(OH)2 by the water, and not to RMgX. If
excessive moisture is present, it is best to begin anew with dry equipment and reagents.
Sometimes, Grignard reagents are reluctant to form because of a magnesium oxide coating on the
metal turnings. The following procedure can often overcome this difficulty. First, warm the reaction
flask with a pan of warm water (about 50-60̊C). This warming will cause the ether to boil (not a sign
of initiation, in this case). Remove the warm water bath and watch for the signs of initiation
(spontaneous boiling of the ether). This warming may be repeated if initiation does not occur.
If repeated warming does not initiate Grignard-reagent formation, add an additional 5 mL of the 1bromobutane solution from the dropping funnel and warm the flask again.
As a last resort, another reagent may be added to activate the surface of the magnesium and/or
indirectly complex with any water present. A number of reagents are useful: a crystal of I2, a few
drops of Br2, 1.0 mL of iodomethane (methyl iodide) or dibromomethane (methylene bromide). (Only
one, not all, of these should be added.) Add the reagent directly to the reaction mixture without
swirling, then warm the flask in the water bath.
The two inorganic halogen compounds function by reacting with the magnesium to yield an
anhydrous magnesium halide, which complexes with any water present. Iodomethane and
dibromomethane are reactive organohalogen compounds that react with the magnesium in slightly
different ways. For example, iodomethane first forms a Grignard reagent (even when a less reactive
alkyl halide does not react), which then reacts with any water present and thus removes it from
solution.
36
4) The reaction mixture may contain small pieces of unreacted magnesium metal. If possible, avoid
transferring these bits of metal to the ice mixture. However, a tiny piece of magnesium that cannot be
removed easily from the ice mixture will do no harm.
37
Name
DATE ________________
SYNTHESIS OF 2-METHYL-2-HEXANOL:
A GRIGNARD REACTION: WORKSHEET
Mass of
Product
Ref. Index
CRC Ref.
Index
Theoretical
Yield (grams)
Actual Yield
(Percent)
Attach the I.R. Spectrum of the Product
Locate the position of the following peaks in your spectrum;
-OH peak
-CH stretch
-C-OH stretch
PROBLEMS
1) Write equations for the three standard steps in a Grignard synthesis in which the principal reactants
are cyclohexanone and ethylmagnesium bromide.
2) A student oven-dries the glassware needed for a Grignard reaction, then stores them in a locker
until the next laboratory period. Will the glassware still be dry when the Grignard reaction is begun?
Explain.
3) Suggest a reason for using magnesium turnings instead of magnesium powder or chunks in a
Grignard reaction.
38
4) In which of the following steps in a Grignard synthesis is anhydrous ether (instead of solvent
ether) necessary? Explain.
(a) Preparation of the Grignard reagent.
(b) Addition of an ether solution of a ketone (instead of pure ketone, as in this experiment).
(c) Extracting the product from the hydrolysis mixture.
(d) Washing the dried product into a distillation flask.
5) Are diethyl ether vapors lighter or heavier than air? What are the safety implications of your
answer?
6) As an alternative to drying tubes to protect a Grignard reaction, some chemists carry out these
reactions under a dry nitrogen atmosphere. Which of the following techniques could also be used to
keep a Grignard reagent dry? Explain.
(a) a dry argon atmosphere
(b) a dry carbon dioxide atmosphere
(c) a gentle stream of dried air passed over the surface of the mixture.
39
EXPERIMENT 8
Biodiesel Synthesis
This experiment demonstrates the use of vegetable oil as an alternative, renewable fuel. The reaction
incorporates NaOH as a catalyst in order to achieve high yield and minimize waste. In addition, the
glycerol by-product can be reused in order to make glycerine soap.
INTRODUCTION
The United States is the largest single consumer of fossil fuels in the world. Each year, the U.S.
consumes 125 billion gallons of gasoline and 60 billion gallons of diesel fuel. With current energy
consumption, the desire to find alternative fuels for our energy needs is increasing. One such
alternative fuel is vegetable oil. Vegetable oil offers the benefits of a greener synthetic route for
obtaining diesel fuel. This fuel source is commonly known as biodiesel, and can be synthesized on an
individual level or on an industrial scale.
The methods behind biodiesel synthesis have been known for quite a while. In recent years, however,
there has been significant interest in the production of biodiesel from the waste oils of the food
industry. Every year, fast food restaurants in the U.S. produce over 3 billion gallons of used cooking
oil. Since many gallons of this used oil inevitably end up in landfills and sewers, the production of
biodiesel from waste oil has the potential to significantly reduce environmental impact.
In this experiment you will synthesize diesel fuel from a triester of glycerol (a triacylglycerol or
triglyceride). This reaction is known as a transesterification reaction. Transesterification is the process
of transforming one type of ester into another type of ester. This reaction incorporates the use of the
strong base sodium methoxide in a base- catalysed nucleophilic addition/elimination reaction at the
carbonyl carbon of the triglyceride. This experiment is not entirely “Green.” The methanol used in
this experiment is derived from petroleum sources. Ethanol, derived from vegetable sources like
corn, could have been used but the product is less volatile and more difficult to make than the methyl
ester.
The overall mechanism is catalyzed by the presence of NaOH. In the first step of the reaction, NaOH
reacts with methanol in an acid-base reaction. The product of this reaction is the very strong base
sodium methoxide and water. In the second step, the sodium methoxide acts as a nucleophile and
attacks the three carbonyl carbons of the vegetable oil. This produces a tetrahedral intermediate that is
highly unstable. The overall result is the "cracking" of the triglyceride. The elimination of the
glycerol backbone leads to the formation of the three methyl esters (the biodiesel) and glycerol. The
NaOH is reproduced as a product in the reaction. If the biodiesel is removed from the mixture,
glycerol and unreacted NaOH and methanol remain. The glycerol can be converted to soap through a
saponification reaction if excess NaOH is used. Care must be exercised when using excess NaOH,
because using too much will produce a jelly like mix of glycerol and soap.
40
EXPERIMENTAL PROCEDURE
Note: The following procedure is for synthesizing a biodiesel mini-batch from 100% pure
unused vegetable oil. This method can easily be modified for using recycled, used vegetable oil
or fats like bacon grease.
1. Add 0.35 g of finely ground anhydrous NaOH into 20 mL of pure (99% or higher purity) methanol
in a 250 mL Erlenmeyer flask containing a magnetic stir bar. Put the flask on a magnetic stir plate,
and stir vigorously until all of the NaOH is dissolved. This flask now contains sodium methoxide.
Note: Sodium methoxide is an extremely strong base and should be handled with care.
2. Warm up 100 mL of vegetable oil or grease to about 40°C in a 250 mL beaker. Warming the oil up
is not necessary, but increases the reaction rate.
3. When all of the NaOH is dissolved, pour the 100 mL of oil into the methoxide solution while
continually stirring. At first the mixture will become cloudy, but should soon separate into two layers.
Stir for 15-30 minutes on high. (Stop here if experiment is being done over 2 weeks.)
4. Transfer the contents of the flask into a 250 mL separatory funnel. The mixture will separate into
two different layers. The glycerol will fall to the bottom, and the methyl ester (biodiesel) will float to
the top. Since about 75% of the separation occurs within the first hour, you will be able to see
immediate progress. Allow the experiment to sit for about an hour.
5. Open the stopcock of the separatory funnel and allow the glycerol to drain into a small beaker.
Make sure not to get any biodiesel in the glycerol or glycerol in the biodiesel.
6. Use the IR spectrometer to identify your products. Print out the spectras and compare with known
spectra. The biodiesel may be hard to compare, since most oils are comprised of different length
carbon chains. Comparing to known spectra can easily identify the glycerol. The presence of glycerol
indicates a successful reaction.
EXPERIMENT REPORT
For this experiment I would like you to create a summary report. The report should be a typed one or
two page narrative and should include:
 A brief summary of your experiment and results
 Analyze the quality and error of your experiment.
 Evaluate this experiment in terms of its greenness.
 What recommendations do you have to improve the green character of this reaction?
 Attach a copy of your IR (another copy should be taped in your notebook).
41
In addition, you should answer the following questions and make them a part of your report.
1. What is the reaction that is occurring that produces biodiesel?
2. Most oils and fats contain palmitic and stearic acid as building blocks. Give the structure for both
these compounds.
3. Describe the role of sodium hydroxide in this reaction.
4. How “Green” is this experiment? Please answer the following,
a) Where did you get your oil/fat you used in this experiment and what would have happened to it
had you not converted it to biodiesel?
b) What was the source of your methanol? Is methanol made from natural sources or is it a product
of the oil industry? Is methanol “Green”?
c) What was in the waste product and what did you with it?
42
Exam I
NMR
IR
MS
Diels-Alder
43
Chem 241
Exam #1
Name___________________
February 28, 2001
CLOSED BOOK EXAM - No books or notes allowed. All work must be shown for full credit. You
may use a calculator.
Question
1(20)
Credit
2(20)
3(15)
4(10)
5(15)
6(20)
TOTAL
1) Please draw the product of a 6 + 2 reaction. Draw the MO diagram indicating the orbital
symmetry, the HOMO and LUMO, and whether the reaction occurs thermally or photochemically.
2) The cyclopropenyl cation is a completely conjugated ring system. Please draw the cyclopropenyl
cation and its MO diagram below
44
3a) Please draw the product of each of the following Diels-Alder reactions.
O
O
+
+
C
O
C
O
Cl
O
+
3b) One of the two dienes below can be used in a Diels-Alder reaction and the other one cannot.
Which one CANNOT be used and why?
A.
B.
4) Please draw the MO diagram for each of the following compounds. Circle the aromatic
compounds (if any).
H
5) Please explain the endo rule and give an example
45
N
Chem 241
Exam #1
Name___________________
February 28, 2001
CLOSED BOOK EXAM - No books or notes allowed. All work must be shown for full credit. You
may use a calculator.
Question
1(20)
Credit
2(20)
3(15)
4(10)
5(15)
6(20)
TOTAL
1) Please draw the product of a 6 + 2 reaction. Draw the MO diagram indicating the orbital
symmetry, the HOMO and LUMO, and whether the reaction occurs thermally or photochemically.
+-+-+-
The HOMO of the 2 matches
the LUMO of the 6 only if
an electron is photochemically
moved.
+ - ++ - +
-
+
-
Thefore the reaction
occurs photochemically
+--++-
+
Zero of Energy
-
+
+
HOMO
+-
LUMO
++--++
-
++
+++---
++++++
2) The cyclopropenyl cation is a completely conjugated ring system. Please draw the cyclopropenyl
cation and its MO diagram below
H
H
H-
46
3a) Please draw the product of each of the following Diels-Alder reactions.
O
O
O
O
+
Cl
+
C
C
Cl
O
O
O
O
O
+
O
3b) One of the two dienes below can be used in a Diels-Alder reaction and the other one cannot.
Which one CANNOT be used and why?
Rotate
A.
These groups hinder one another
so the molecule does not want to
take this shape.
Rotate
B.
These groups do not hinder one
another so the molecule can take
this shape and do a Diels Alder.
4) Please draw the MO diagram for each of the following compounds. Circle the aromatic
compounds (if any).
H
N
5) Please explain the endo rule and give an example
Cl
The endo rule says that the electron
withdrawing group on the dienophile must
overlap with the double bond from the
diene (toward the interior of the molecule)
+
47
C
C
Cl
Chem 241
Practice Exam #1 – NMR/IR/MS/MO Theory
Name___________________
February 28, 2001
CLOSED BOOK EXAM - No books or notes allowed. All work must be shown for full credit. You
may use a calculator.
Question
1(20)
Credit
2(20)
3(15)
4(10)
5(15)
6(20)
TOTAL
1a) Using drawings, please show how a triplet is formed in NMR spectroscopy.
1b) What are the relative peak heights in a heptet? Show them as a ratio, ie. 1:2:1 etc.
1c) Please draw the complex NMR splitting diagram for the following molecule. JAB = 11, JBC = 9.
Along with your diagram indicate where the signal would be found in the spectrum.
H
Cl
A
C
H
H
B
C
H
H
C
C
H
H
48
1d) Look at the complex splitting pattern shown below
10
2
8
2 2
6
2 2
8
2
10
What is the value of JAB and JBC?
JAB =
JBC =
JAB is a singlet, doublet, triplet, quartet (circle one)
JBC is a singlet, doublet, triplet, quartet (circle one)
2a) Please explain why alkenes are found at 5-6 in an NMR but alkynes are found around 2.5.
2b) In NMR an alcohol and an acid OH differ in position by 8ppm. Please give two reasons why the
acid OH is so much farther downfield.
3) Please draw the product of a 4 + 4 reaction. Draw the MO diagram indicating the orbital
symmetry, the HOMO and LUMO, and if the reaction occurs thermally or photochemically.
4a) In Mass Spectrometry what are the approximate relative peak heights (in percent) for the
following halogens,
35
Cl =
79
Br =
37
Cl =
81
Br =
49
4b) In IR the C-Cl bond is found at 754 cm-1 and the C-Br stretch is found at 548 cm-1. Which of
these has the stronger force constant and by how much? C = 12g/mol, Cl = 35.45g/mol, Br = 79.9
g/mole
5) Please explain the endo rule and give an example.
6) Please draw the product of the following Diels-Alder reactions.
C
C
O
O
C
C
C
+
CH3
+
Cl
C
C
50
Chem 241
Practice Exam #1 – NMR/IR/MS/MO Theory
Name___________________
February 28, 2001
CLOSED BOOK EXAM - No books or notes allowed. All work must be shown for full credit. You
may use a calculator.
Question
1(20)
Credit
2(20)
3(15)
4(10)
5(15)
6(20)
TOTAL
1a) Using drawings, please show how a triplet is formed in NMR spectroscopy.
1:2:1
1b) What are the relative peak heights in a heptet? Show them as a ratio, ie. 1:2:1 etc.
Singlet
1
Doublet
1
1
Triplet
1
2
1
Quartet
1
3
3
1
Pentet
1 4
6
4 1
Hextet
1 5 10 10 5 1
Heptet 1 6 15 20 15 6 1
1c) Please draw the complex NMR splitting diagram for the following molecule. JAB = 11, JBC = 9.
Along with your diagram indicate where the signal would be found in the spectrum.
~ 2.0
H
Cl
A
C
H
H
B
C
H
H
C
C
H
11
H
9
4
5
51
4
11
4 1 4
4
5
4
9
1d) Look at the complex splitting pattern shown below
10
2
8
2 2
6
2 2
8
2
10
What is the value of JAB and JBC?
JAB = 12
JBC = 10
JAB is a singlet, doublet, triplet, quartet (circle one)
JBC is a singlet, doublet, triplet, quartet (circle one)
2a) Please explain why alkenes are found at 5-6 in an NMR but alkynes are found around 2.5.
H
H
C
H
C
H C
C H
H
Since the ring current in an alkene pulls electrons away from the hydrogens they are pulled
downfield as compared to an alkyne whose circulating electrons help shield its hydrogens.
2b) In NMR an alcohol and an acid OH differ in position by 8ppm. Please give two reasons why the
acid OH is so much farther downfield.
a) The extra oxygen on an acid pulls more electron density out of the OH bond forcing it
further downfield.
b) An acid group has a C=O which sets up ring currents that pull electrons out of the atoms to
which they are attached and this pulls the OH group farther downfield.
52
3) Please draw the product of a 4 + 4 reaction. Draw the MO diagram indicating the orbital
symmetry, the HOMO and LUMO, and if the reaction occurs thermally or photochemically.
+-++
LUMO
+
-
+-+Symmetry
match +
+--+
-
HOMO
--+
Photochemically
induced promotion
Zero of Energy
-
+
++ --
++ --
+
++++
++++
If an electron is photochemically moved to the next
highest orbit, the symmetry of the new HOMO
matches the LUMO of its reacting partner.
4a) In Mass Spectrometry what are the approximate relative peak heights (in percent) for the
following halogens,
35
37
79
81
Cl = 75%
Br = 50%
Cl = 25%
Br = 50%
4b) In IR the C-Cl bond is found at 754 cm-1 and the C-Br stretch is found at 548 cm-1. Which of
these has the stronger force constant and by how much? C = 12g/mol, Cl = 35.45g/mol, Br = 79.9
g/mole
 12  79.9 
k Cl 

v1
k
k
754
12  79.9 

 1 2

 Cl  1.626
v2
k2 1
548
k Br
 12  35.45 
k Br 

 12  35.45 
Therefore, the Cl force constant is 1.626 times larger than the Br.
5) Please explain the endo rule and give an example.
The endo rule says that we should place the
electron-withdrawing
group
on
the
dienophile in such a way that it is stabilized
by the p-orbital overlap on the diene. The
essentially places the electron withdrawing to
the “inside of the diene.
Cl
Cl
H3C
H3C
This way is endo.
The Cl is not stabilized
This way is endo.
The Cl is stabilized.
6) Please draw the product of the following Diels-Alder reactions.
C
C
C
C
O
O
O
C
+
O
Cl
C
C
CH3
+
Cl
C
C
CH3
53
Chem 241
Practice Exam #1
Name___________________
February 28, 2000
CLOSED BOOK EXAM - No books or notes allowed. All work must be shown for full credit. You
may use a calculator.
Question
1(12 )
Credit
2(24)
3(24)
4(10)
5(15)
6(15)
TOTAL
1a) What is the possible explanation for the differences in the postion of the aromatic protons in the
following compounds?
Benzene = 7.37
Toluene = 7.17
p Xylene = 7.05
1b) Please draw the complex splitting diagram for carbon B in the following compound.
Where will the signal be centered? Jab = 11 Hz and Jbc = 9 Hz
Br
C
C
C
C
A
B
C
Cl
54
2) Approximately where would you expect to find a C=S bond in an I.R. spectrum? Show your work
and state your assumptions. C= 12, S=32, O=16
3) Please draw the MO diagram for a 6+2 reaction showing the symmetry of all energy levels, where
the electrons go, and label the HOMO and LUMO for each. Will the reaction occur photochemically
or thermally?
4) Choose any two of the NMR/IR/MS spectras on the next page and determine the structure of the
compound. Draw the compounds here.
55
5a) Please explain the difference between the position of a double bond versus a triple bond in NMR.
5b) I am sure that you know that the hydrogens on C=C are not as far down field as those on C=O,
which are not as far downfield as those found on an acid group, COOH. Please explain this
observation. Give at least two separate and unrelated reasons why this is so.
6) Please draw the product of the following Diels-Alder reactions;
O
O
O
O
2x
56
Chem 241
Practice Exam #1
Name___________________
February 28, 2000
CLOSED BOOK EXAM - No books or notes allowed. All work must be shown for full credit. You
may use a calculator.
Question
1(12 )
Credit
2(24)
3(24)
4(10)
5(15)
6(15)
TOTAL
1a) What is the possible explanation for the differences in the postion of the aromatic protons in the
following compounds?
Benzene = 7.37
Toluene has one methyl group, Xylene has two methyl
groups and Benzene has none. Methyl groups push
electrons into the ring and these electrons help shield the
ring from the effects of the externally applied magnetic field
and this pushes the signal upfield -->
Toluene = 7.17
p Xylene = 7.05
1b) Please draw the complex splitting diagram for carbon B in the following compound.
Where will the signal be centered? Jab = 11 Hz and Jbc = 9 Hz
Br
C
~2.0
C
C
C
A
B
C
Cl
11
9
7
2
57
2
9
2) Approximately where would you expect to find a C=S bond in an I.R. spectrum? Show your work
and state your assumptions. C= 12, S=32, O=16
Since both of them have double bonds, assume k1 = k2 which means that they will cancel, so
the only difference is the mass effect (). Since C=O is at 1710 cm-1 use it as 1.
v1

v2
 12  32 


1710
12  32 
 
 v2  1516cm 1
v2
 12 16 


 12  16 
k1 2
k2 1
3) Please draw the MO diagram for a 6+2 reaction showing the symmetry of all energy levels, where
the electrons go, and label the HOMO and LUMO for each. Will the reaction occur photochemically
or thermally?
+-+-++-++-+
HOMO
++--++++--++
LUMO
Photon
+
++
+++--++++++
The reaction occurs photochemically
4) Choose any two of the NMR/IR/MS spectras on the next page and determine the structure of the
compound. Draw the compounds here.
58
5a) Please explain the difference between the position of a double bond versus a triple bond in NMR.
H
H
C
C
H
H C
C H
H
Since the ring current in an alkene pulls electrons away from the hydrogens they are pulled
downfield as compared to an alkyne whose circulating electrons help shield its hydrogens.
5b) I am sure that you know that the hydrogens on C=C are not as far down field as those on C=O,
which are not as far downfield as those found on an acid group, COOH. Please explain this
observation. Give at least two separate and unrelated reasons why this is so.
a) The ring current in the double bond push all of them down field.
b) The electron withdrawing effect of the C=O pushes the hydrogens on this carbon farther
down field.
c) Since the hydrogen in an acid group is directly attached to the electron withdrawing
oxygen and there is a nearby C=O that causes a shift downfield, the acids hydrogen is pushed
farthest downfield of the three.
6) Please draw the product of the following Diels-Alder reactions;
O
O
O
O
O
O
O
O
2x
59
Chem 241
Practice Exam #1
Name___________________
February 25, 1994
Closed Book Exam - No books or notes allowed. All work must be shown for full credit. You may
use a calculator.
Question
1(16 )
Credit
2(40)
3(16)
4(12)
5(16)
TOTAL
1) One of the proton environments in an organic compound produces the following complex splitting
pattern. What is the value for Jab and Jac for this compound? Show how this pattern arises and label
the splitting diagram.
2) Please draw the MO diagram each of the following compounds,
O
60
3) Choose any one of the following NMR / IR’s and draw the compound.
4a) Cyclopentadiene is not aromatic because it is not completely conjugated and it is not flat. There
are three forms of the molecule that are completely conjugated and one of them is aromatic. Please
draw all three forms and indicate which one is aromatic.
4b) Please draw the MO diagram for each of the molecules you drew above.
61
Chem 241
Practice Exam #1
Name___________________
February 25, 1994
Closed Book Exam - No books or notes allowed. All work must be shown for full credit. You may
use a calculator.
Question
1(16 )
Credit
2(40)
3(16)
4(12)
5(16)
TOTAL
1) One of the proton environments in an organic compound produces the following complex splitting
pattern. What is the value for Jab and Jac for this compound? Show how this pattern arises and label
the splitting diagram.
Jab = 10
Jac = 14
2) Please draw the MO diagram each of the following compounds,
O
62
3) Choose any one of the following NMR / IR’s and draw the compound.
4a) Cyclopentadiene is not aromatic because it is not completely conjugated and it is not flat. There
are three forms of the molecule that are completely conjugated and one of them is aromatic. Please
draw all three forms and indicate which one is aromatic.
Remove H+
Remove H
Remove H-
Aromatic
4b) Please draw the MO diagram for each of the molecules you drew above.
See above
63
Exam II
Aromatics
Electrophilic Substitution
MO Theory
Hückel Reaction
64
Activators and Deactivators on Benzene
O/P Activators by Induction
O/P Activators by Resonance
CH3
OH
C2H5
NH2
C(CH3)3
NHR
CH(CH3)2
NR2
OCH3
O
O/P Deactivators w/ Resonance
O
C
CH3
Meta Deactivators by Induction
F
NO2
Cl
HSO3
Br
COOH
I
CN
CHO
NH3+
Note: There is no such this as a meta activator
65
Resonance forms of O/P Activators by Resonance
+O
H
E
A
OH
OH
OH
OH
A
E+
Ortho
E
+
E
E
B
B
+
OH
+
OH
OH
E+
OH
+
+
Meta
E
+
OH
E
OH
E
OH
OH
A
E+
+
Para
B
B
+
+
E
E
E
A
+O
H
E
66
Resonance forms of O/P Deactivators - Halogens
+ Cl
E
A
Cl
Cl
Cl
Cl
A
E+
Ortho
E
+
E
E
B
B
+
Cl
+
Cl
Cl
E+
Cl
+
+
Meta
E
+
Cl
E
Cl
E
Cl
Cl
A
E+
+
Para
B
B
+
+
E
E
E
A
+ Cl
E
67
Resonance forms of O/P Activators by Induction – Alkyl Groups
CH3
CH3
E+
CH3
E
+
CH3
E
E
Ortho
+
CH3
CH3
+
CH3
E+
CH3
+
+
Meta
E
+
CH3
E
CH3
E
CH3
E+
CH3
+
Para
+
+
E
E
E
Resonance forms of Meta Deactivators by Induction
NO2
NO2
E+
NO2
E
+
NO2
E
E
Ortho
+
NO2
NO2
+
NO2
E+
NO2
+
+
Meta
E
+
NO2
NO2
E
E
NO2
E+
NO2
+
Para
+
+
E
E
68
E
Reactions of Benzene – Electrophilic Substitution
Cl 2,FeCl 3
X = Cl
X
Br2, FeBr3
Cl 2O, CF 3COOH
I2, CuCl 2
X = Br
X = Cl
X=I
NO2
HNO 3, H2SO4
Nitration
SO3H
Fuming H2SO4
Sulfonation
OH
H2O2, HSO3F
Hydroxylation
C2H5
C2H5Cl, AlCl 3
+ HCl
Friedel Crafts Alkylation
O
C
CH3
CH 3COCl , AlCl 3
+ HCl
69
Friedel Crafts Acylation
Benzene Side Group Reactions
O
R
R
C
H2C
Zn(Hg)
Dilute HCl
NH2
NO2
KMnO4, H2O
Heat
NO2
NH2
Will not reduce other
reducible side groups
like aldehydes and acids.
1. SnCl2, HCl
2. NaOH, H2O
CH3
CH2Br
NBS
HSO3
OH
Conc. NaOH
Heat
COOH
CH2OH
1. LiAlH4, THF
2. H+
Cl
OH
1. NaOH, Heat
2. H2O, H+
70
Chem 241
Exam #2
Name___________________
April 3, 2000
CLOSED BOOK EXAM - No books or notes allowed. All work must be shown for full credit. You
may use a calculator.
Question
1(12)
Credit
2(12)
3(12)
4(10)
5(10)
6(16)
7(28)
TOTAL
1) Please name each of the following compounds.
NH2
Cl
CH3
HO
COOH
H3C
O
O
O
O
Cl
71
2) For each of the following compounds label them as either an activator or deactivator, and as an
ortho, para, or meta director.
HC
O
NH2
Cl
Act/Deact
________
________
________
Director
________
________
________
3a) Please draw all of the resonance structures for ortho attack of chlorobenzene with an electrophile
(E+).
3b Please draw all of the resonance structures for ortho attack of phenol with the chloronium cation.
Circle the most stable strcture.
4) Please draw the MO diagram each of the following compounds,
O
72
5) Please draw the complete mechanism for the Friedel-Craft alkylation of benzene using
bromobutane as the alkylating agent.
6a) Please synthesize both of the compounds given below. You may start with benzene, an alcohol,
alkyl halide, or alkane. Neither of these compounds require more than five steps to synthesize.
C C C
NH2
6a) Please name three criteria that determines whether a molecule is aromatic.
6b) Cyclopropene is not aromatic but it can be made aromatic. Please draw the aromatic form of
cyclopropene.
6c) Can 1,3-cyclobutadiene be made aromatic? Why or why not? Use examples.
73
7) Please complete the following reactions. If there is no reaction, write “No Reaction.”
CH3
KMnO 4, H2SO4, Heat
NHCH2CH3
AlCl3, C-C-Cl
1. CO, HCl, AlCl3
2. HNO3, H2SO4
O
C C C
H2SO4, HO-C- C-OH
OH
C C C
1. PCC
2. C-C-MgCl
3. H2O
O
C C C
N2H4, NaOH, H 2O
C
C C C O
C
KOH, H 2O
74
Chem 241
Exam #2
Name___________________
April 3, 2000
CLOSED BOOK EXAM - No books or notes allowed. All work must be shown for full credit. You
may use a calculator.
Question
1(12)
Credit
2(12)
3(12)
4(10)
5(10)
6(16)
7(28)
TOTAL
1) Please name each of the following compounds.
NH2
Cl
CH3
HO
COOH
H3C
Aniline
m-methyltoluene
(m-xylene)
2-chloro-3-hydroxybenzoic acid
O
O
O
O
Cl
Phenanthrene
1,3-cyclobutadione
75
3-chloro-6-oxo-2-hexanone
4-chloro-5-oxohexanal
2) For each of the following compounds label them as either an activator or deactivator, and as an
ortho, para, or meta director.
HC
O
NH2
Cl
Act/Deact
_Deact__
__Act___
_Deact__
Director
___m___
__o/p___
__o/p___
3a) Please draw all of the resonance structures for ortho attack of chlorobenzene with an electrophile
+ Cl
(E+).
E
A
Cl
Cl
Cl
Cl
A
E+
E
+
E
E
B
B
+
+
3b Please draw all of the resonance structures for ortho attack of phenol with the chloronium cation.
Circle the most stable strcture.
+O
H
Cl
Most Stable
A
OH
OH
OH
OH
A
+
Cl
Cl
Cl
B
B
+
+
4) Please draw the MO diagram each of the following compounds,
O
76
5) Please draw the complete mechanism for the Friedel-Craft alkylation of benzene using
bromobutane as the alkylating agent.
Br
C
C
C
C
Br
AlBr3
C
C
C
C
Al
Br
Br
Br
H
C
C
C
CH3
Hydride
Shift
C
C
H
C
C
C
C
H
C
Br
CH2
+
Al
Br
H
C
C
C
Br
Br
C
+ H+
6a) Please synthesize both of the compounds given below. You may start with benzene, an alcohol,
alkyl halide, or alkane. Neither of these compounds require more than five steps to synthesize.
C
C C C
C
C
1. Propanoyl Chloride, AlCl3
2. H2SO4, HNO3
3. Zn(Hg), HCl
NH2
NH2
O
O
1. Br C C C Br
2. Zn(Hg), HCl
AlBr3
6a) Please name three criteria that determines whether a molecule is aromatic.
i)
ii)
iii)
The molecule must be completely conjugated.
The molecule must be flat
The molecule must have 4n+2 electrons in the ring.
6b) Cyclopropene is not aromatic but it can be made aromatic. Please draw the aromatic form of
cyclopropene.
H
H
H + H-
Remove the H
with its electrons
Produces an
empty p orbital
cyclopropenyl cation
6c) Can 1,3-cyclobutadiene be made aromatic? Why or why not? Use examples.
No. Regardless of the number of electrons in the ring, some of the electrons will be on the zero of
energy.
Zero of Energy
77
7) Please complete the following reactions. If there is no reaction, write “No Reaction.”
CH3
COOH
KMnO 4, H2SO4, Heat
NHCH2CH3
AlCl3, C-C-Cl
No Reaction
H
C O
1. CO, HCl, AlCl3
2. HNO3, H2SO4
NO2
O
C C C
H2SO4, HO-C-C-OH
OH
C C C
1. PCC
2. C-C-MgCl
3. H2O
O
C C C
N2H4, NaOH, H 2O
C
C C C O
C
O
O
OH
C C C
C
C
C C C
KOH, H2O
C
C OH
C C C O and C C C OH
C
C
78
Chem 241
Exam #2
Name___________________
March 29, 2006
CLOSED BOOK EXAM - No books or notes allowed. All work must be shown for full credit. You
may use a calculator.
Question
1(12)
Credit
2(12)
3(12)
4(10)
5(16)
6(14)
7(24)
TOTAL
1) Please name each of the following compounds.
NH2
O
O2N
C
Cl
OH
Cl
Cl
N
N
79
2) For each of the following compounds label them as either an activator or deactivator, and as an
ortho, para, or meta director.
H
OCH 3
S
C
Act/Deact
________
________
________
Director
________
________
________
3) Please draw all of the resonance structures for para attack of chlorobenzene with the nitronium
cation (NO2+). Circle the most stable structure.
4) Please draw the complete mechanism for hydroxylation of toluene.
80
5a) Please name three criteria that determines whether a molecule is aromatic.
1)
2)
3)
5b) Pyrrole is an aromatic compound. Please draw the compound and explain why it is aromatic.
5c) Please draw the aromatic form of 1,3,5 cycloheptatriene.
5d) The following compound is not currently aromatic. Can it be made aromatic? If so, draw the
aromatic form of the molecule. If not, explain why not.
N
81
6) Please synthesize two of the three following compounds. You can start with benzene, alkyl
halides or alcohols.
OH
OH
m catechol
Naphthalene
O
O
O
C
CH3
C
HO
Aspirin
82
7) Please complete the following reactions. If there is no reaction write “No Reaction.”
H
C
O
AlCl3
CH3Cl
HSO3
1. FeCl3, Cl2
2. NH3, NaNH2
1, CO, HCl, AlCl3
2. H2SO4, HNO3
3. LiAlH4
NO2
Fuming H2SO4
CH3
C-C-C-Cl
AlCl3
C
C
C
KMnO 4, H+, H2O, 
Cl2, 1000 psi, 300oC
NH2
FeCl3
Cl 2
83
Chem 241
Exam #2
Name___________________
March 29, 2006
CLOSED BOOK EXAM - No books or notes allowed. All work must be shown for full credit. You
may use a calculator.
Question
1(12)
Credit
2(12)
3(12)
4(10)
5(16)
6(14)
7(24)
TOTAL
1) Please name each of the following compounds.
NH2
O
O2N
Aniline
C
m-nitrobenzoic acid
OH
Cl
Cl
1,2,3-trichlorobenzene
N
N
Anthracene
Cl
pyrrole
pyridine
84
2) For each of the following compounds label them as either an activator or deactivator, and as an
ortho, para, or meta director.
H
OCH3
S
C
Act/Deact
__Act___
__Act___
__Deact_
Director
__o/p__
__m____
___o/p__
3) Please draw all of the resonance structures for para attack of chlorobenzene with the nitronium
cation (NO2+). Circle the most stable structure.
Cl
Cl
Cl
Cl
A
+
B
B
+
+
NO2
NO2
NO2
A
+ Cl
Most Stable
NO2
4) Please draw the complete mechanism for hydroxylation of toluene.
H
O
O
H
HSO3F
H
H+
O
+
O
HO+
H
H
CH3
CH3
CH3
HO+
+ H+
+
HO
H
OH
85
+ H2O
5a) Please name three criteria that determines whether a molecule is aromatic.
1) Completely conjugated ring
2) 4n + 2 electrons
3) No non-bonding orbitals
5b) Pyrrole is an aromatic compound. Please draw the compound and explain why it is aromatic.
Normally, the nitrogen would be sp3 hybridized, but in pyrrole, it is sp2 hybridized so that the
electrons can be in a p orbital and completely conjugate the ring giving it 6 electrons as
required by Huckel’s Rule
H
N
N
N
H
H
Normal sp3
hybridized nitrogen
pyrrole
Rehybrized nitrogen
to sp2
5c) Please draw the aromatic form of 1,3,5 cycloheptatriene.
Leaves
as
H-
H
H
1,3,5-cycloheptatriene
showing the electrons
in one of the bonds to
hydrogen
Empty
p orbital
H
+
H
Remove the hydrogen
with the electrons so that
you don't add any more
electrons to the ring.
Six total electrons
in the ring.
Aromatic cation
5d) The following compound is not currently aromatic. Can it be made aromatic? If so, draw the
aromatic form of the molecule. If not, explain why not.
N
This molecule cannot be made aromatic because, no matter what you do, its MO diagram will
have orbitals on the zero of energy (non-bonding orbitals).
86
6) Please synthesize two of the three following compounds. You can start with benzene, alkyl halides
or alcohols.
OH
OH
m catechol
Naphthalene
O
O
O
C
CH3
C
HO
Aspirin
HSO3
Fuming
H2SO4
HSO3
OH
conc. NaO H
Heat
H2O2, HSO3F
Heat
OH
O
OH
OH
O
Cl
1. KMnO4, H+ H2O, heat
2. SOCl2
1, LiAlH4
2. SOCl2 x 2
3. tButO-, tButOH
AlCl3
Cl
OH
O
O
O
O
1. CH3Cl, AlCl3
HO
2. H2O2, HSO3F, Heat
3. KMnO4, H+, H2O, Heat
OH
C
O
C
Acetic Anhydride
H2SO4, H2O, Heat HO
87
O
C
CH3
7) Please complete the following reactions. If there is no reaction write “No Reaction.”
H
C
O
AlCl3
No Reaction - the ring is deactivated
CH3Cl
HSO3
NH2
1. FeCl3, Cl2
2. NH3, NaNH2
NH2
CH3
1, CO, HCl, AlCl3
2. H2SO4, HNO3
3. LiAlH4
NH2
NO2
NO2
Fuming H2SO4
CH3
HO3S
CH3
C
C
C
C-C-C-Cl
AlCl3
C
C
C
COOH
KMnO 4, H+, H2O, 
Cl2, 1000 psi, 300oC
Cl
H
H
Cl H
Cl
H
Cl
H Cl
NH2
NH2
Cl
H
FeCl3
Cl 2
Cl
88
Lindane - a pesticide
Exam III
Carbonyl Chemistry
Acids, Esters, Aldehydes,
Ketones, Amides, Nitriles
The chemistry of carbonyls is broken down into four main
groups;
1. Substitution - Aldehyde and Ketone Chemistry
2. Addition – Acid and Acid Derivative Chemistry
3. Conjugate Addition - Acid Derivatives, Ketones, & Aldehyde
4. Alpha Substution – Acid Derivatives
Each of these four types of reactions are shown on the next page.
We will study them one at a time. In each case we will learn how
to make the compounds in which we are interested and then apply
one of these four reactions to them.
89
Carbonyl Chemistry
Four Main Reaction Types
1. Addition – Aldehydes and Ketones
O-
O
H3C
C
CH3
OH
H2O
Nuc-
H3C
C
CH3
H3C
C
Nuc
CH3
+
OH-
Nuc
2. Substitution – Acid & Derivatives
O-
O
H3C
C
Cl
Nuc-
H3C
O
C
H3C
Cl
+ Cl-
C
Nuc
Nuc
3. Conjugate Addition – All Carbonyls
O
C
C
C
OCH3
Nuc-
C
C
O
OH
C
CH3
H2O
Nuc
C
C
C
CH3
keto-enol
C
C
Nuc
Nuc
4. Alpha Substitution – All Carbonyls
O
O
Base-
H3C
C
CH3
H3C
O
CH2-
C
CH 3Br
H3C
-
(Nuc )
90
C
C
CH3
+
Br-
C
CH3
How to make Aldehydes and Ketones
C
C
OH
PCC
CH2Cl2
C
C
C
C
PCC
CH2Cl2
C
CH
C
KMnO 4, H+, H2O
C
C
C
C
O
OH
C
C
O
OH
C
O
O
OH
C
C
C
K2Cr2O7,
H2SO4, Heat
C
C
C
O
O3, (CH 3)2S
C
C
O
C
C
O
O
C
C
+ C
C
C
O
C
C
C
C
OH
DIBAH, -70C
C
BH3, H2O2,
NaOH, H 2O
C
H2SO4, HgSO4,
H2O
C
O
C
C
C
C2H5MgBr
C
C
O
O
C
C
Cl
C
C
C2H5
C
C
O
O
C
C
Cl
Li(t-ButO)3AlH
HC O
CO, HCl, AlCl3
Gatterman-Koch Rxn
R
RCOCl , AlCl 3
C
O
Friedel-Craft Acylation
91
1. Nucleophilic Addition Reactions on Aldehydes and Ketones
General Mechanism
-
O
C
O
-
C
Nuc
C
C
C
OH
H2O
C
C
C
Nuc
Nuc
Reactions
O
C
C
OH
C
HCN
C
C
C Cyanohydrin
CN
OCH3
OH
CH 3OH
H+, H2O
C
C
C
CH 2OH
H+, H2O
Acetal
Hemiacetal
OH
C
C
C
Gemdiol
OH
OH
1. C2H5MgBr
2. H2O, H+
C
C
C
C2H5
OH
LiAlH4, H2O
C
C
C
OH
NaBH4, H2O
C
C
C
OH
H2/Pd/BaSO 4/S
Rosenmund Catalyst
C
C
C
C
OCH3
OCH3
OH-, H2O
C
C
92
C
Aldehyde / Ketone Amine Reactions
O
C
C
NH
C
NH 3
NH2
N
N2H4
C
C
C
Imine
C
C
C
Hydrozone
Hydrazine
OH
N
NH 2OH
C
C
C
Oxime
Hydroxylamine
R
N
NH 2R
C
C
C
Imine "Schiff Base"
Amine
NHPh
N
PhNHNH 2
C
C
C
Phenylhydrozone
Phenylhydrazine
NHCONH2
N
NH 2CON 2H4
C
C
C
Semicarbazone
Semicarbizide
Aldehyde/Ketone Name Reactions
O
C
C
C
Zn(Hg), HCl
C
C
C
Clemmenson Reduction
C
C
C
Wolff-Kishner Reduction
O
C
C
H
C
N2H4, KOH
HO
O
O
H
C
C
KOH, H 2O
+
93
CH
OH
Cannizaro Reaction
How to make Acids
C
C
C
KMnO 4, Heat
OH
C
C
O
K2Cr2O7, H2SO4
C
C
C
KMnO 4, Heat
C
C
N
O
C
OH
O
C
C
1, I2, NaOH
2. H+
C
H3C
C
H+, H2O, Heat
1. Mg, Ether
2. CO2
3. H+
Br
2. Nucleophilic Substitution Reactions on Acids
General Mechanism
O-
O
H3C
C
X
Nuc-
H3C
C
O
H3C
X
Nuc
Nuc
Formation of Acid Halides
SOCl 2
O
O
POCl 3
CH3 C
CH3 C
OH
PCl3
Cl or Br
PBr3
Formation of Anhydrides
O
CH3
C
O
C CH3
HO
O
O
Cl
O
O
CH3
C
O
C CH3
HO
CH3 C
OH
+ X-
C
H2SO4
94
C
H3C
Formation of Esters
O
CH3 C
C2H5OH
O
Cl
CH3 C
O
CH2
CH3
N
CH2
CH3
O
C2H5OH, H2SO4
CH3 C
OH
Formation of Amides
O
CH3 C
C2H5NH 2
O
Cl
CH3 C
O
H
C2H5NH 2
CH3 C
OH
Formation of Nitriles
O
CH3
C
NH2
POCl 3 or
P2O5
CH3
H3C
Br
NH2
C
N
HCN
1. NaNO2, HCl
2. CuCN
CN
95
Sandmeyer Reaction
3. Conjugate Addition Using Esters, Diones, and Enones
General Michael Reaction
Enone
C
C
Nucleophile
O
C
Nuc-
R
OC
C
C
O
OH
R
H2O
Nuc
C
C
C
keto-enol
R
C
Nucleophiles
R =
 diester
 dione
Keto-ester
O
-CH3 Ketone
-O-R Ester
-H
Aldehyde
-NH2 Amide
Lewis Acceptors (acids)
C
R
Nuc
Nuc
Enones
C
H3C
O
O
C
H3C
CH 2
H3C
O
H3C
C
CH 2
H3C

diester
O
CH 2
H3C
O
Lewis Donors (bases)
O
C
O
O

dione
ketoester
Therefore, if R = CH3 and Nuc- = Keto-ester, the product would be;
O
O
H3C
O
H3C
O
C
CH2 + C
C
C
O
O
C
C
CH3
C
C
C
CH3
H3C
H3C
O
O
If the ester is hydrolyzed then you get a spontaneous decarboxylation of a β keto acid;
O
O
H3C
O
CH3OH + HO
O
C
C
H3C
C
C
C
CH3
C
C
H+, H2O
H+ + O
O
C
H3C
C
C
C
O
CH3
C
H3C
O
O
The mechanism of the decarboxylation is in your notes.
96
O
O
C
C
C
CH3
4. Alpha Substitutions - Claisen Reactions
Classic Claisen Reaction - between two of the same esters
O
H3C
O
C
O
NaNH 2
CH3
H3C
O
C
O-
O
CH2-
H3C
O
C
H3C
CH3
H3C
O
O
C
CH3
CH2
C
O
O
O
O
CO2 + H+ +
C
CH3
CH3O +
C
spontaneous
decarboxylation
CH3
-
CH3OH + HO
C
CH3
CH2
H+, H2O
H3C
Heat
O
C
CH3
CH2
C
O
O
 keto acid
Acetone
Crossed Claisen – between two different esters
O
H3C
O
C
O
NaNH 2
CH3
H3C
O
C
O-
O
CH2-
H3C
O
C
CH2
CH3
H3C
H3C
O
O
C
CH2
CH3
CH2
C
O
O
O
O
CO2 + H+ +
C
CH2
CH3
CH3O + C
C
spontaneous
decarboxylation
CH3
-
CH3OH + HO
C
CH2 CH3
H+, H2O
Heat
CH2
H3C
O
C
CH2 CH3
CH2
O
O
Methyl ethyl ketone
( 2 propanone)
 keto acid
Dieckmann Reaction – A Claisen cyclization
O
O
O
O
H
O
O
EtO C C C C C C OEt
OEt
NaEtO
-
OEt
OEt
OEt
OEt
OEt
O
O
OEt
-
O
O
+ EtO-
cyclic  keto ester
97
Other Claisen Type Reactions –
There are three types of compounds that can do Claisen type reactions. They are shown below. The
main difference between classic Claisen reaction and the ones shown here is the molecule that the
Claisen nucleophile attacks. In the classic Claisen reaction the nucleophile attacks another ester, in
these reactions the nucleophile attacks something other than an ester. Typically, in these reactions,
the nucleophile will attack an alkyl halide like ethylbromide, but it could also attack a ketone or
aldehyde.
The nucleophiles are made using one of the following compounds.
O
C2H5
O
O
C
C2H5
O
CH2
C2H5
O
C
H3C
C
CH2
O
CH2
H3C
O
H3C
O
O

dione
Acetoacetic Ester
Malonic Ester
Malonic Ester Synthesis – makes substituted acetic acids (the acid is circled)
O
C2H5
O
CH2
C2H5
O
O
O
C
NaNH 2
C
C2H5
O
C
CH-
C2H5
O
C-C-Cl
O
2 C2H5OH + CO2
C
+
CH C
( SN2 )
C2H5
C
O
C2H5
O
H , H2O, Heat
H2C
C spont. decarbox.
HO
C
C
C
C
O
O
O
C
C
Acetoacetic Ester Synthesis – makes substituted acetones (the acetone is circled)
O
C2H5
O
C
CH2
H3C
O
O
NaNH 2
C
C2H5
O
C
CH-
H3C
C-C-Cl
C2H5
C2H5OH + CO2
C
+
CH C
( SN2 )
H3C
C
O
O
H , H2O, Heat
H3C
C
C
O
O
O
H2C
C spont. decarbox.
 Dione
O
H3C
CH2
H3C
C
NaNH 2
H3C
C
CH-
H3C
O
O
O
C
C-C-Cl
H3C
CH C
( SN2 )
H3C
C
C
C
O
O
98
C
H+, H2O, Heat
No Reaction - the product
is not a  keto acid.
Aldol Reactions Between two Aldehyde/Ketones
Classic Aldol – two of the same aldehydes or ketones
O
C
O
H
C
C
H
1/2 eq. NaNH2
or ButLi, or NaEtO
C
C
_
C
C
H
C
_
H +
H
H
O
C
O
C
C
C
C
C
H
C
O
H
C
C
C
C
H
C
H2O
O
C
OH
Aldol
Crossed Aldol – two different aldehydes or ketones
O
C
O
H
C
1 eq. NaNH2
H or ButLi, or NaEtO
C
C
C
C
_
C
H
C
_
H +
C
H
H
O
O
C
C
C
C
C
H
C
C
O
H
C
C
C
C
H
C
H2O
O
C
C
OH
C
Aldol Cyclization
O
H3C
C
O
C
C
C
O
CH3
CH2-
O
O
O NaNH
2
C
O-
O
O
H2O
If you have excess base present then all of these aldol products can undergo dehydration by the
following mechanism;
C
O
H
C
C
C
C
H
C
O
OH
C
C
_
C
C
C
H
C
O
OH
C
C
C
C
H
Base
H
O
H
H
OH
O
H
_
OH
99
O
C
C
OH
Exam 3 – Practice Synthesis Problems
Please synthesize each of the following compounds given the starting reactant shown. You may use
any other carbon compounds or inorganic reagents you need to accomplish the synthesis.
O
C
C
C
Br
C
C
C
O
C
O
C
C
O
C
C
C
C
C
C
N
C
C
H
O
C
C
O
C
O
O
C
C
C
C
C
C
C
OCH3
CH2CH2NH2
CH3Br
O
O
H3C
O
O
C
OH
O
O
C
OH
CH3
Aspirin
O
C
O
O
C
C
O
O
C
C
C
100
C
C
C
Exam 3 – Practice Synthesis Answers
C
C
C
O
C
C
O
1. HCN
2. H+, H2O, Heat
3. SOCl2
4. Acetic Acid
Br
1. NH2-C2H5
2. LiAlH4
C
C
C
C
C
C
C
C
O
O
N
C
C
C
C
H
C
C
C
C
O
O
O
C
O
1. Br2, light
2. tButO3. NBS
4. KCN
5. BH3, H2O2,
NaOH, Water
6. H+, Water, heat
C
OCH3
1. NaNH2
2. Ethyl Acetate
3. H2O, H+, Heat
C
C
C
C
CH2CH2NH2
CH3Br
1. KCN
2. LiAlH4
O
O
H3C
1. Br2, PBr3
2. KOH, Ether
3. K2Cr2O7, H2SO4
4. HO-C-C-OH, H2SO4
C
OH
O
O
O
O
C
1. CH3Cl, AlCl3
2. HSO3F, H2O2
3. KMnO4, H+, H2O, 
HAc, H2SO4
OH
CH3
O
C
Aspirin
O
O
O
1. NaNH2
C
C
O
C
C
C
O
2. C C C C
3. H+, Water, Heat
101
C
C
C
Chem 241
Exam #3 – Aldehydes/Ketones
Name___________________
Closed Book Exam - No books or notes allowed. All work must be shown for full credit.
Question
1(18 )
Credit
2(32)
3(16)
4(14)
5(20)
TOTAL
1) Please name the structure of the following compounds.
H
O
C
O
C
C
O
C
C
C
H
O
O
C
C
C
O
H3C
102
O
O
C
C
CH3
2) Please provide the product of each of the following reactions;
O
C
C
C
HOCH 2CH 2OH, H+
O
C
C
C
1. HCN
2. H+, H2O, Heat
O
C
C
C
NaBH4, H2O
O
C
C
C
N2H4
O
C
C
H
1. Ag(NH3)2+, KOH
2. H+, H2O
O
C
C
C
Br2, NaOH
O
C
C
H
CrO3, H2SO4
C
C
O3, (CH 3)2S
C
C
C
C
C
C
O
KOH, H2O
C
H
O
C
C
Cl
1. C-C-MgBr
2. H2O, H+
103
3) Please show the complete mechanism of the formation of a Schiff base using acetone (propanone)
and ethyl amine (ethanamine).
4) Please show the complete mechanism of the formation of an acetal using acetone and ethanol.
5a) Please describe why aldehydes are generally more reactive than ketones.
5b) Please describe why aldehydes and ketones go through nucleophilic addition reactions and acids
tend to go through nucleophilic acyl substitions.
104
6) Using benzene or alkyl halides that are two carbons or less, synthesize each of the following
compounds. Note: CO2, and CO are not organic compounds and may also be used.
H
O
C
O
C
C
C
H
O
O
O
O
C
C
OH
C
C
C
105
Chem 241
Exam #3 – Aldehydes/Ketones
Name___Answer Key ____
Closed Book Exam - No books or notes allowed. All work must be shown for full credit.
Question
1(18 )
Credit
2(32)
3(16)
4(14)
5(20)
TOTAL
1) Please name the structure of the following compounds.
H
O
C
O
C
C
O
C
C
C
H
Benzaldehyde
4-oxo-pentanal
O
O
C
C
C
Acetone
benzophenone or diphenylmethanal
O
H3C
Cyclopentanone
O
O
C
C
CH3
2,3-butadione
106
2) Please provide the product of each of the following reactions;
O
C
O
C
C
HOCH 2CH 2OH, H+
O
O
C
C
C
C
1. HCN
2. H+, H2O, Heat
HO
C
COOH
C
O
C
OH
C
C
NaBH4, H2O
C
C
C
NH2
O
C
N
C
C
N2H4
C
C
O
O
C
C
H
Ag(NH3)2+,
1.
2. H+, H2O
KOH
C
C
O
C
C
Br2, NaOH
C
C
O
H
CrO3, H2SO4
C
O3, (CH 3)2S
C
C
C
C
C
C
O
C
O
C
C
KOH, H2O
C
H
C
C
Cl
C
C
O
and
C
OH
O
O
C
OH
H
O
C
C
H
C
C
OH
O
C
C
OH
O
C
C
C
1. C-C-MgBr
2. H2O, H+
C
107
C
C
C
C
C
H
C
C
C
H
OH
3) Please show the complete mechanism of the formation of a Schiff base using acetone (propanone)
and ethyl amine (ethanamine).
O
O
H
H
O
+
C
C
H
C
C
C
C
C
C
C
H2N-C- C
O
H
C
C
C
H
N
C
C
H
H
C
H2O +
C
C
N
C
C
C
H
C
O
H
C
C
N
C
H+ + C
C
H
C
C
N
C
O
H
C
C
N
C
C
H
C
4) Please show the complete mechanism of the formation of an acetal using acetone and ethanol.
O
O
H
H
O
+
C
C
H
C
C
C
C
C
H
H2O +
C
C
C
O
C
O
H
C
C
C
H
O
C
O
H
C
C
O
C
HO-C-C
C
C
C
O
H
C
C
O
C
C
H+ + C
C
C
C
HO-C-C
H
C
O
C
C
C
O
C
C
C
C
O
C
C
C
O
C
C
+ H+
C
5a) Please describe why aldehydes are generally more reactive than ketones.
Aldehydes are more reactive than ketones because they have only one methyl group pushing
electrons into them rather than two. Ketones have more methyl groups and this reduces the
partial charge on the carbonyl carbon making them less reactive than aldehydes.
5b) Please describe why aldehydes and ketones go through nucleophilic addition reactions and acids
tend to go through nucleophilic acyl substitutions.
Aldehydes and ketones do not have good leaving groups therefore they undergo addition
reactions that break the double bonded oxygen. Acids have good leaving groups. This allows
them to undergo substitution and preserve the carbonyl carbon (the double bonded oxygen).
108
6) Using benzene or alkyl halides that are two carbons or less, synthesize each of the following
compounds. Note: CO2, and CO are not organic compounds and may also be used.
H
H
O
C
O
C
1. CH3Cl, AlCl3
2. NBS
3. KOH, Ether
4. PCC
O
C
C
C
C
C
Br
1. Mg, dry ether
2. CO
C
3. H+, H2O
O
C
H
C
H
O
O
1. Br2, AlBr3
2. Mg, dry ether
3. CO2
4. H+, H2O
5. SOCl2
6. Benzene, AlCl3
O
O
Br
O
C
C
OH
C
C
C
C
Br
C
C
C
1. KOH, ether x 2
2. CO, H+, heat
Br
1. Mg, Dry Ether
2. CO
3. Zn(Hg), HCl
4. Br2, h
C
5. KOH, ether
6. PCC
O
O
C
C
O
C
C
Br
1. KOH
2. PCC
C
C
H
109
1. 1 eq NaNH2
2. C-C=O
3. H+, H2O
C
C
OH
C
C
C
Chem 241
Exam #3 – Acids/Derivatives
Name___________________
April 26,1999
Closed Book Exam - No books or notes allowed. All work must be shown for full credit.
Question
1(18 )
Credit
2(32)
3(16)
4(14)
5(20)
TOTAL
1) Please name the structure of the following compounds.
O
N
C
O
C
C
N
C
C
O
O
O
C
H
O
C
C
C
N
C
C
C
O
C
Cl
Br
C
C
C
O
O
C
C
OH
110
C
OH
O
2) Please give the product of each of the following reactions. If the given reaction does not occur,
write No Rxn.
O
C
C
C
C2H5NH 2
OH
O
C
C
C
OH
Cl
1) PBr3, Br2
2) H2O, H+
1) HCN
2) H+, H2O, Heat
3) C2H5OH, H2SO4, H2O
O
C
C
H2SO4, Heat
C
OH
O
C
C
C
P 2O 5
NH2
O
C
C
1. Ag(NH3)2+, KOH
2. H+, H2O
C
H
O
HO
C
C
C
C
H2SO4, Heat
C
OH
Br
C
C
C
H3C
C
1. Mg, Ether
2. CO2
3. H+, H2O
CH2
KMnO 4, H+
H2O, Heat
111
3a) Please draw the mechanism of the Hell-Volhardt-Zelinsky reaction using propanoic acid.
3b) Please draw the mechanism of the hydrolysis of a nitrile into an acid in base.
4a) Please explain why we almost always do nucleophilic substitutions on acid chlorides, anhydrides,
and esters, but rarely on acids or amides. This is not “a better leaving group” question!
4b) Please rank the following acids in order of increasing acidity (1 is lowest). Please explain your
reasoning.
O
C
C
C
C
CH3
C
OH
C
C
Br
O
C
C
OH
C
C
C
C
OH
112
Br
O
C
O
C
C
OH
5) Starting with benzene or alkyl halides of two carbons or less synthesize each of the following
compounds.
COOH
N
O
O
O
O
O
C
C
O
C
O
C
H
O
C
C
C
C
N
113
Chem 241
Exam #3 – Acids/Derivatives
Name___________________
April 26,1999
Closed Book Exam - No books or notes allowed. All work must be shown for full credit.
Question
1(18 )
Credit
2(32)
3(16)
4(14)
5(20)
TOTAL
1) Please name the structure of the following compounds.
O
N
O
5-aminopentoic acid lactam
C
C
C
N
C
C
O
O
O
C
H
cyclobutyl methanoate
butadioic anhydride
O
C
3-methylbutanitrile
C
C
N
C
C
C
N-propylpropanamide
O
C
Cl
Br
C
C
C
O
O
C
C
OH
benzoyl chloride
O
2-bromobutanoic acid
114
C
OH
acetic acid
2) Please give the product of each of the following reactions. If the given reaction does not occur,
write No Rxn.
O
C
C
C
O
C2H5NH 2
C
C
C
OH
N
C
C
H
O
C
C
C
OH
Cl
Br
1) PBr3, Br2
C
O
C
C
2) H2O, H+
OH
O
C
1) HCN
2) H+, H2O, Heat
O
C
C
3) C2H5OH, H2SO4, H2O
O
O
C
C
H2SO4, Heat
C
C
O
C
C
C
OH
O
O
C
C
C
P2O5
C
NH2
C
C
O
O
C
C
Ag(NH3)2+,
1.
2. H+, H2O
C
N
KOH
C
C
C
OH
H
O
O
HO
C
C
C
C
H2SO4, Heat
C
O
OH
Br
C
C
COOH
C
H3C
C
1. Mg, Ether
2. CO2
3. H+, H2O
C
C
C
COOH
CH2
KMnO 4, H+
H2O, Heat
115
C
C
C
3a) Please draw the mechanism of the Hell-Volhardt-Zelinsky reaction using propanoic acid.
O
O
C
C
C
PBr3
OH
C
C
C
O
P
H
Br
OH
C
C
C
O
Br
C
Br
C
Br
O
+ Br-
P
Br
H
OH
Br2
C
Br
O
Br
keto-enol
C
(Br+ + Br-)
C
C
Br
C
C
C
Br
O
P
Br
H
O
OH
C
C
C
C
Br
C
Br
+
C
H
O
Br
C
Br
C
C
Br
+ H+
Br
3b) Please draw the mechanism of the hydrolysis of a nitrile into an acid in base.
OH
C
C
OH-
N
C
OH
H2O
N
C
C
C
H
N
OH
OH-
C
H
C
N
OH
H2O
O
O
NH2- +
C
H2O + C
C OH
C
H
OH-
C
N
C
H
OH
H2O
OH
H
N
H
OH
NH3 + OH-
4a) Please explain why we almost always do nucleophilic substitutions on acid chlorides, anhydrides,
and esters, but rarely on acids or amides. This is not “a better leaving group” question!
Acids and amides have OH and NH2 groups that will react with and neutralize any incoming
nucleophile. The other compounds mentioned do not have any OH’s or NH’s so they do not
suffer from this problem
4b) Please rank the following acids in order of increasing acidity (1 is lowest). Please explain your
reasoning.
O
C
C
C
C
CH3
C
C
C
OH

Br
O
C
C
C
C
OH
Br
O
C
C
C
O
C
OH


C
OH

Methyl groups push in electrons making acids weaker so #1 is the weakest. The acid with no groups
is next, and then as the halogen gets closer to the acid group, the acid gets stronger.
116
5) Starting with benzene or alkyl halides of two carbons or less synthesize each of the following
compounds.
O
COOH
Br
N
C
O
O
C
O
Br
C
C
C
OH
KMnO 4, H+
H2O, Heat
N
O
1. tButO-, tButOH
2. NBS
Br
3. NaCN, THF
4. HBr, PBA
C
O
C
1. KOH, Ether
2. KMnO4, H+, H2O, Heat
3. SOCl2
4. Benzene, AlCl3
CH3CH3Br
O
CH3
C
1. tButO-, tButOH
2. NBS
3. NaCN, THF NC
4. HBr, PBA
5. NaCN, THF
C C C CN
1. NH3(liq)
2. H+, H2O, Heat
3. Heat
C C C CN
1. H+, H2O, Heat
2. H2SO4, Heat
O
O
O
O
C C C Br
O
C
C
C
O
O
C
H
1. KOH, Ether
2. KMnO4, H+,
H2O, Heat
C
C
O
C
O OH
1. KOH, Ether
CH3Br 2. PCC
HO
C
H2SO4,
Heat
C
C
C
O
O
C
H
H
3. Tollens Reagent
Br O
O
C
C
C
C C C Br
C
N
1. NaCN, THF
2. H+, H2O, Heat
3. HVZ
4. NH3
C
C
C
O
NH2
1. KOH, Ether
2. PCC
3. P2O5
C C C C N
Note: I used Tollens reagent on the 4th synthesis because most oxidations will take formaldehyde and
convert it all the way to CO2. Tollens will only take the oxidation to the acid, not CO2.
117
Final Exam
118
Protein Sequencing Problems
1) A small peptide was completely hydrolyzed to yield the following set of amino acids;
Ala + Arg + Gly + 2 Met + Lys + Ser + Val
In addition the peptide was subject to the following tests with the results given.
Sanger Reagent - DNP Gly and ,-DNP Lys
Carboxypeptidase A - a) Ser
b) All the rest
Cyanobromide -
a) Ala + Gly + Lys + Met
b) Met + Val
c) Arg + Ser
Chymotrypsin - Nothing Released
Trypsin -
a) Ala + Gly + Lys
b) Arg + 2 Met + Val
c) Ser
What is the order of amino acids in the peptide chain?
2) A small protein was completely hydrolyzed and found the contain Arg + Cys + 2 Lys
+ Met + Thr + Val. Based on the observations below, reconstruct the protein sequence.
FDNB - DNP-Arg released
Carboxypeptidase A a) Val
b) All the rest
Carboxypeptidase B Nothing released
Cyanobromide -
a) Lys-Cys-Met-Arg
b) Thr-Val-Lys
Trypsin -
a) Arg-Lys
b) Cys-Thr- Lys-Met
c) Val
Are there any unresolved amino acids? Which are they?
119
Answer Key
Problem #1
Sanger – Gly must have been the AA on the far left side (amino side) of the protein
sequence. Lys has an NH2 on its side chain. That is why FDNB attacked it.
Chain = Gly ~
Carb A – Carb A attacks the AA on the other end of the protein (the carboxylic acid
side). Since Ser was released, it must have been the last AA in the chain.
Chain = Gly ~~~~~~~~~~~~~~~~~~~~~~~~~~Ser
Cyanobromide – This cleaves on the carboxyl side of Met. This means that anything
attached to the NH2 side of Met remains attached. There from each piece we deduce,
a) Gly is the first AA in the chain - Gly~(Ala~Lys)~ Met or Gly~( Lys~Ala)~ Met
b) Val~Met in this order because Val is attached to Met’s NH2
c) Ser is the last AA so must be Arg~Ser
Chain = Gly ~(Ala~Lys)~Met~Val~Met~Arg~Ser or
Gly ~(Lys~Ala)~Met~Val~Met~Arg~Ser
Trypsin – All we need to do is to resolve the position of Ala with respect to Lys. The
first piece cleaved off does this for us. If the order had been Gly~Lys~Ala~ then trypsin
would have cleaved between Lys and Ala and you would have gotten a piece containing
just Gly+Lys, but you didn’t, you got Gly+Lys+Ala which means that the order must
have been Gly~Ala~Lys. So the order of the protein must have been,
Final Chain = Gly~Ala~Lys~Met~Val~Met~Arg~Ser
120
Problem #2
Moving a little faster this time,
Sanger/CarbA&B – Gives us the following information
Chain = Arg~~~~~~~~~~~~~~Val
Cyano – Cleaves Met on the right, so
a) Arg~(Lys~Cys)~Met or Arg~(Cys~Lys)~Met
b) (Thr~Lys)~Val or (Lys~Thr)~Val
Chain = Arg~(Lys~Cys)~Met~(Thr~Lys)~Val
Trypsin – Cleaves Lys and Arg on the right, so
a) Arg~Lys was released, but since we also know Arg~(Lys~Cys)~Met from above, then the
order must be Arg~Lys~Cys~Met
b&c) Since Val was released separately, Lys must have been attached to it, therefore since we
knew from Cyano (b) (Thr~Lys)~Val or (Lys~Thr)~Val, the order must have been
Thr~Lys~Val.
Final Chain = Arg~Lys~Cys~Met~Thr~Lys~Val
There are no unresolved amino acids
121
Carbohydrate Problem Set
1) Galactose is the C4 epimer of glucose. Please draw lactose, which is a disaccharide, made by
bonding galactose to glucose using a  1,4’ link. Both sugars must be cyclic.
2) Please draw the ring structure of the C2 epimer of galactose.
3) Please draw the C3 epimer of glucose.
4) Please draw the ring structure of Talose.
5) Please draw the ring structure of Fructose.
6) What is a reducing sugar? Why is it reducing?
7) How do we determine whether a structure is D or L? Is R 3-hydroxybutanoic acid, D or L?
8) Draw lactose. It is galactose––1,4’ glucose.
9) Draw gentiobiose. It is glucose--1,6’ glucose
10) Show the complete mechanism for the base conversion of fructose into glucose.
11) Show the complete mechanism for the acid conversion of fructose into glucose.
122
Carbohydrate Problem Set
1) Galactose is the C4 epimer of glucose. Please draw lactose, which is a disaccharide, made by
bonding galactose to glucose using a  1,4’ link. Both sugars must be cyclic.
H
O
H
O
OH
HO
CH2OH
CH2OH
C
O
OH
H
H
OH
H
OH
O
OH
OH
OH
OH
OH
Glucose
CH2OH
Galactose
Glucose
2) Please draw the ring structure of the C2 epimer of galactose.
CH2OH
HO
CH2OH
HO
O
OH
O
OH OH
OH
OH
OH
Galactose
Gulose
3) Please draw the C3 epimer of glucose.
CH2OH
CH2OH
O OH
O OH
OH
HO
OH
OH
 Glucose
OH OH
 Allose
4) Please draw the ring structure of Talose.
CH2OH
HO
O OH
OH OH
 Talose
123
5) Please draw the ring structure of Fructose.
HOH2C
O
HO
CH2OH
OH
OH
6) What is a reducing sugar? Why is it reducing?
A reducing sugar causes the reduction of other things by becoming oxidized. This occurs
aldehyde end of the sugar. Aldoses are reducing, ketoses are not. When oxidized, aldoses
become acids.
7) How do we determine whether a structure is D or L? Is R 3-hydroxybutanoic acid, D or L?
When drawn in a Fisher projection, a D molecule has the second to last OH group on the
right side of the molecule. An L molecule has the second to last OH on the left.
HO
O
H
C
H
C
This is R 3-hydroxybutanoic acid. The arrow indicates the rotation. You will note that
the arrow is going counter-clockwise, but because the low priority hydrogen is on the
H
right, we are seeing the rotation backwards so the actual rotation is clockwise (R). Since
OH the second to last carbon has the OH on the right, this molecule is D.
H
C
H
C
H
8) Draw lactose. It is galactose––1,4’ glucose.
CH2OH
HO
O OH
O OH
OH
CH2OH
CH2OH
HO
O OH
O
OH
OH
CH2OH
OH
O
OH
OH
Galactose
OH
OH
 Glucose
OH
Galactose 1,4'- glucose
9) Draw gentiobiose. It is glucose--1,6’ glucose
CH2OH
CH2OH
O OH
OH
O OH
OH
OH
OH
O
O
CH2
OH
OH
 Glucose
CH2OH
O OH
OH
OH
OH
 Glucose
OH
OH
Glucose  1,6' glucose
124
OH
10) Show the complete mechanism for the base conversion of fructose into glucose.
H
H
_
C
HO
H
OH
C
O
C
H
C
OH
H
C
OH
H
C
OH
C
OH
C
H
_
OH-
HO
C
O
C
H
HO
C
O
C
H
H2O
HO
OH-
H
H
C
OH- +
O
H
C
OH
HO
C
H
H2O
_
HO
C
O
C
OH
C
H
H
HO
C
O-
C
OH
C
H
11) Show the complete mechanism for the acid conversion of fructose into glucose.
H
H
C
C
H
OH
H+
H
O
C
C
H
OH
+
O
C
OH
C
OH
HO
C
H
HO
C
H
HO
C
H
_
+ H+
H
HO
H
H+ +
C
O
H
C
OH
HO
C
H
125
H
H
C
O+
C
OH
C
H
H
H
C
O+
H
C
OH
HO
C
H
Chem 241
Final Exam
Name___________________
May 27, 2000
CLOSED BOOK EXAM - No books or notes allowed. ALL work must be shown for full credit. You
may use a calculator.
Question
1(10)
2(10)
3(8)
4(16)
5(15)
6(20)
Total
Credit
Question
7(15)
8(12)
9(12)
10(42)
11(10)
12(30)
Total
Credit
1a) Please draw the complex splitting diagram for carbon B in the following compound.
Where will the signal be centered? Jab = 11 Hz and Jbc = 9 Hz
Br
C
C
C
C
A
B
C
Cl
1b) What is the possible explanation for the differences in the postion of the aromatic protons in the
following compounds?
Benzene = 7.37
Toluene = 7.17
p Xylene = 7.05
126
2) Approximately where would you expect to find a C=S bond in an I.R. spectrum? Show your work
and state your assumptions. C= 12, S=32, O=16. Your answer should be somewhere between 1000
and 3000. I want and exact anwser. Show your math.
3) Please explain why we almost always do nucleophilic substitutions on acid chlorides, anhydrides,
and esters, but rarely on acids nor amides. This is not “a better leaving group” question!
4a) One of the products below was made using a Michael reaction and the other was made using a
Claisen reaction. Which is which?
C
C
C
O
C
C
C
C
O
C
C
C
C
O
O
4b) For the Michael product given above, show the Michael reaction that made it. Just show the two
(or more) reactants and the product(s). Do not give a mechanism.
127
5a) Please draw all of the resonance structures for ortho attack of aniline with the nitro cation (NO2+).
You do not have to make the nitro cation.
5b) Please draw the complete mechanism for the Friedel-Craft alkylation of benzene using
bromobutane as the alkylating agent.
5c) Please give the complete mechanism for the base hydrolysis of phthalic anhydride.
O
O NaOH H2O
O
6) Please interpret and draw any two of the three compounds given on the back pages based on their
IR and NMR spectra.
128
7a) Please draw glycine (R = H) dissolved in a neutral solution.
7b) What are the four levels of protein structure? Describe each of them.
a)
b)
c)
d)
8) Galactose is the C4 epimer of glucose. Please draw lactose, which is a disaccharide, made by
bonding galactose to glucose using a  1,4’ link. Both sugars must be cyclic.
9) Please circle the terpene units found in the following compound.
CH3
CH3
CH3
CH3
129
10) Please give the product for each of the following reactions.
Cl
HNO 3, H2SO4
C
NH2
O
KOH, H 2O
O
NO2
AlCl3,
C
C
C
Cl
O
CH3
C
CH3
1/2 eq. NaEtO
Water
O
CH3
C
NH2
P2O5
O
O
1. NaEtO
O
Et
2. H+, H2O, 
O
NH2
H2SO4, 
OH
O
O
O
O
1. 2x NaEtO
2. Br-C-C-C-C-Br
3. H+, H2O, 
130
10 cont’d)
1. C-C-C-Cl, AlCl3
2. NBS
3. KCN
4. H+, H2O, 
NH2
C
COOH
1. LiAlH4
2. H2SO4
O
O
O
O
O
NaEtO,
1. C-C-MgBr
2. Water
O
O
HO-C-C- OH, H2SO4
O
C
C
1. PBr3, Br2
C
OH
2. H2O, H2SO4
11) Synthesize one of the compounds given below starting with alcohols, alkyl halides or alkanes of
three carbons or less. You cannnot start with benzene.
O
N
H2N
O
CH C
OH
O
CH OH
O
CH3
NH2
131
12a) Please draw the product of the following Diels-Alder reactions;
O
O
O
O
2x
12b) Please draw the product and the MO diagram for a 6+4 reaction. Show the HOMO, LUMO,
and state whether the reaction occurs thermally or photochemically.
12c) What are the rules of aromaticity?
12d) What is the “endo” rule?
132
Chem 241
Final Exam
Name_Answer Key________
May 27, 2000
CLOSED BOOK EXAM - No books or notes allowed. ALL work must be shown for full credit. You
may use a calculator.
Question
1(10)
2(10)
3(8)
4(16)
5(15)
6(20)
Total
Credit
Question
7(15)
8(12)
9(12)
10(42)
11(10)
12(30)
Total
Credit
1a) Please draw the complex splitting diagram for carbon B in the following compound.
Where will the signal be centered? Jab = 11 Hz and Jbc = 9 Hz
2.3
Br
C
C
C
C
A
B
C
Cl
1b) What is the possible explanation for the differences in the postion of the aromatic protons in the
following compounds?
Benzene = 7.37
Toluene = 7.17
p Xylene = 7.05
Methyl groups push electrons into the things to which they
are attached. Pushing electrons into a benzene ring causes
the benzene’s hydrogens to become shielded and less
downfield that benzene alone. The more methyls you have,
the more shielded benzene become and the less downfield
are the benzenes hydrogens.
133
2) Approximately where would you expect to find a C=S bond in an I.R. spectrum? Show your work
and state your assumptions. C= 12, S=32, O=16. Your answer should be somewhere between 1000
and 3000. I want an exact anwser. Show your math.
Since both of them have double bonds, assume k1 = k2 which means that they will cancel, so
the only difference is the mass effect (). Since C=O is at 1710 cm-1 use it as 1.
 12  32 


1710
12  32 


 v2  1516cm 1
12

16
v2




 12  16 
k1 2
k2 1
v1

v2
3) Please explain why we almost always do nucleophilic substitutions on acid chlorides, anhydrides,
and esters, but rarely on acids nor amides. This is not “a better leaving group” question!
Both acids and amides have H’s available because of the hydrogen bonding of the OH and NH2.
These acidic protons interfere with nucleophilic substitutions by neutralizing the nucleophile. That is
why acid derivatives other than acids and amides are used in most syntheses requiring acids.
4a) One of the products below was made using a Michael reaction and the other was made using a
Claisen reaction. Which is which?
C
C
C
O
C
C
C
C
O
Michael
C
C
C
C
O
O
Claisen
4b) For the Michael product given above, show the Michael reaction that made it. Just show the two
(or more) reactants and the product(s). Do not give a mechanism.
O
Et
1, NaNH2
2. C=C-C=O
3. H+, H2O, 
O
O
O
O
134
5a) Please draw all of the resonance structures for ortho attack of aniline with the nitro cation (NO2+).
You do not have to make the nitro cation.
+ NH2
NO2
A
NH2
NH2
NH2
NH2
A
NO2+
+
NO2
NO2
NO2
B
B
+
+
5b) Please draw the complete mechanism for the Friedel-Craft alkylation of benzene using
bromobutane as the alkylating agent.
Br
+
AlBr3
H
-
Br AlBr3
+ + AlBr4Hydride
Shift
H
+
+
+ H+
5c) Please give the complete mechanism for the base hydrolysis of phthalic anhydride.
O
O-
O
OH
O
O
OH -
OH
O
O-
O
H2O
O
O
OH
+ OH-
OH
O
6) Please interpret and draw any two of the three compounds given on the back pages based on their
IR and NMR spectra.
135
7a) Please draw glycine (R = H) dissolved in a neutral solution.
H
+
H3N
O
C
C
O-
H
7b) What are the four levels of protein structure? Describe each of them.
a) Primary – the simple sequence of proteins
b) Secondary – folded into helix or sheets
c) Tertiary – Helix or sheets folded into globular structures
d) Quaternary – Two or more globular structures bonded together
8) Galactose is the C4 epimer of glucose. Please draw lactose, which is a disaccharide, made by
bonding galactose to glucose using a  1,4’ link. Both sugars must be cyclic.
H
O
C
H
OHOH
OH
HO
H
H
OH
H
OH
H OH
H O
H
HO
H
H
H O
O
OH
H
CH2OH
HO
H
H
Glucose
9) Please circle the terpene units found in the following compound.
CH3
CH3
CH3
CH3
136
H
OH
OH
10) Please give the product for each of the following reactions.
Cl
Cl
HNO 3, H2SO4
NO2
C
NH2
O
OH
C O
KOH, H 2O
C OH
O
NO2
AlCl3,
C
C
C
Cl
No Reaction - The ring is
deactivated
O
O
CH3
C
CH3
CH3
1/2 eq. NaEtO
CH3
Water
C
C
CH3
O
CH3
C
C
NH2
P2O5
CH3
C
N
O
O
O
1. NaEtO
O
Et
2. H+, H2O, 
O
O
NH2
O
H2SO4, 
N
OH
O
O
H
O
O
1. 2x NaEtO
2. Br-C-C-C-C-Br
3. H+, H2O, 
O
HO
137
OH
10 cont’d)
COOH
1. C-C-C-Cl, AlCl3
H3C C CH3
2. NBS
3. KCN
4. H+, H2O, 
NH2
C
COOH
NH2
C
C
OH
1. LiAlH4
2. H2SO4
O
O
O
O
O
NaEtO,
O
O
O
O
1. C-C-MgBr
2. Water
O
O
HO-C-C- OH, H2SO4
O
Br
O
C
C
1. PBr3, Br2
C
OH
O
C
O
C
C
2. H2O, H2SO4
OH
11) Synthesize one of the compounds given below starting with alcohols, alkyl halides or alkanes of
three carbons or less. You cannnot start with benzene.
O
N
H2N
O
CH C
OH
O
CH OH
O
CH3
NH2
See last page
138
12a) Please draw the product of the following Diels-Alder reactions;
O
O
O
O
O
O
O
O
2x
12b) Please draw the product and the MO diagram for a 6+4 reaction. Show the HOMO, LUMO,
and state whether the reaction occurs thermally or photochemically.
+
h
LUMO
+
-
+
+
+
-
+
-
+
+
Zero of Ene rgy
Reaction occurs photochemically
HOMO
+
+
+
-
+
-
+
+
+
+
12c) What are the rules of aromaticity?
1. Completely conjugated ring
2. Flat
3. No orbitals on zero of energy
12d) What is the “endo” rule?
A molecule is endo with the dienophile is oriented in such a way so that the electron withdrawing
groups is able to interact with the p orbitals of the diene.
139
Answers to syntheses question Br
C
C
O
1. t-ButO-, tButOH
2. NBS
Br
3. CN4. HBr, PBA
C
C
C
C
CN
1. NH3
2. H+, H2O, 
H2N
C
C
C
C
OH
O
H
H2SO4,
Heat
N
OH
C
PCC
C
OH
O
C
C
1. 1/2 eq. NaNH2
2. H2O
C
C
C
1. SOCl2
2. KMnO4, H+
H2O, Heat
C
O
H2N
CH C
OH
OH Br
NH 3
C
CH OH
C
C
Cl
O
OH
O
PBr3, Br2
C
C
C
C
H
C
H
H
Br
C
C
C
1. t-ButO-, tButOH
2. NBS
3. Mg, dry ether
H
C
C
O
HO-C-C-C-OH
H2SO4, Heat
C
C
C
1. NBS x 2
2. t-ButOt-ButOH
KOH,
Ether
C
C
C
C
C
OH
H2SO4
Heat (E1)
C
Br
C
O
C
C
C
NH2
NO2
OH
O
1. CH3OH, PCC
2. H2SO4
MgBr
C
1. C-C-COCl
2. AlCl3
3. con. H2SO4
con. HNO3
C
OH
O
H
C
C
CH3
PCC
C
O
OH
OH
C
O
Zn(Hg), HCl
O
140
Cl
C
t-ButOt-ButOH
1. KMnO4,
H+, H2O, Heat
C
2. SOCl2
C
C
C
C
OH
Chem 241
Final Exam
Name________________________
May 23, 2005
Closed Book Exam - No books or notes allowed. All work must be shown for full credit. You may
use a calculator.
Question
1(21)
2(20)
3(24)
4(20)
5(15)
Total
Credit
Question
6(20)
7(30)
8(15)
9(15)
10(20)
Total
Credit
1) Please name the following compounds.
O
O
O
C
C
NH2
H
C
N
H
HO
Cl
C
C
C
C
N
C
HO
C
OH
O
O
C
141
C
C
C
N
2a) Please draw the mechanism of the acid cleavage of acetic anhydride using H2SO4 and water.
2b) Please draw the mechanism of the Hell-Volhardt-Zelinsky reaction using butanoic acid, PBr3,
and Br2
2c) Please draw the mechanism for the Claisen reaction that occurs when ethyl acetate reacts with
half an equivalent of NaNH2.
2d) Please draw the mechanism for the formation of an enone using acetone, a strong base, and water
(if necessary).
142
3a) Please draw all of the resonance structures for ortho attack of aniline with a chloronium ion (Cl+).
3b) Please draw the complete mechanism for the hydroxylation of benzaldehyde.
3c) For each of the following compounds label them as either an activator or deactivator, and as an
ortho, para, or meta director.
NHCH3
CN
H3C
C
Act/Deact
_______
________
________
Director
_______
________
________
143
CH3
4a) Using drawings and words, please show how a quartet is formed in NMR spectroscopy.
4b) What is the relative height of each peak in a hextet?
4c) If Jab = 8 and Jbc = 7, what is the complex splitting diagram for the following molecule?.
H
H
a
C
O
b
H
c
C
C
H
H
Cl
5) Please draw the MO diagram for a 6 +2 reaction. Label the HOMO, LUMO, the orbital symmetry
and state how the reaction occurs.
6) Please interpret and draw any two of the three compounds given on the back pages based on their
IR and NMR spectra.
144
7) Please give the product for each of the following reactions.
1. HCN
C
C
C
Cl
2. LiAlH4
O
C
C
C
O
C
O
C
C
C2H5NH2
1. NaNH2
C
CH3
2. Benzaldehyde
3. H2O
O
1. C-C-C-C-Br
N
2. N2H4, Heat
O
O
C
O
C
C
C
1. NaNH2
C
O
C
C
C
C
NH2
2. H2O
Heat
HO
H
C
O
AlCl3, CH3Cl
O
N2H4, OH-,heat
Cl
OH
1. PCC
2. C2H5MgBr
3.Water, H+
145
8a) Draw a phospholipid and a fat. Label each of them. You can use squiggly lines for long chains.
8b) What is a soap and how do they work? Please draw a picture as part of your answer.
8c) Most candles are made from a compound that, though called a wax, is not really a wax. What is
it and how does it differ from a true wax?
146
9a) What are Hückel’s Rules?
9b) An OH peak in NMR is usually a singlet, why? And when would you expect it to be a triplet?
9c) What are the restrictions on Friedel Craft Alkylation?
10) Starting with alkanes, alcohols, benzene, or cyclopentane, synthesize two of the following
compounds.
COOH
N
H
C
O
NH2
147
O
Chem 241
Final Exam
Name__Answer Key______
May 23, 2005
Closed Book Exam - No books or notes allowed. All work must be shown for full credit. You may
use a calculator.
Question
1(21)
2(20)
3(24)
4(20)
5(15)
Total
Credit
Question
6(20)
7(30)
8(15)
9(15)
10(20)
Total
Credit
I want to drop my lowest exam _____________________.
Signature
1) Please name the following compounds.
O
O
O
C
C
NH2
H
C
N
H
HO
methanal
(formaldehyde)
2-aminoacetic acid
5-aminopentanioic acid lactam
Cl
C
C
C
C
N
C
HO
C
OH
N,N,N-triethylamine
4-chloro-2-hydroxyphenol
O
O
C
C
C
C
N
diphenylmethanone
(benzophenone)
N,N-diphenylbutanimide
148
2a) Please draw the mechanism of the acid cleavage of acetic anhydride using H2SO4 and water.
O
O
O
+
+O
H
C
C
O
O
H
C
C
H
C
C
O
C
C
C
O
C
C
O
+
C
C
O
O
H
O
C
C
H
O
H
O
H
O+
C
OH + HO
C
C
H+
C
C
O
O
H
C
C
O
H
C
O
+
O
C
C
HO
O
O
H
C
C
+O
H
H
O
C
H2O
C
+ H+
C
2b) Please draw the mechanism of the Hell-Volhardt-Zelinsky reaction using butanoic acid, PBr3,
and Br2
Br
O
O
O
C
C
C
PBr3
C
C
C
C
+
C
OH
-
O
P
H
Br
C
Br
C
C
+
C
O
P
H
Br
Br
-
Br
OH
C
C
C
C
Br
O
O
keto-enol
C
-
C
C
C
C
Br
C
C
+
C
O
P
Br H
Br
Br
+ H+
Br
Br+
OH
C
C
C
C
Br
C
C
+O
H
C
Br
C
Br
+
O
C
C
Br
C
C
Br
2c) Please draw the mechanism for the Claisen reaction that occurs when ethyl acetate reacts with
half an equivalent of NaNH2.
O
C
C
O
C
CH3
NaNH 2
O
C
C
+ C
O
O
O
C
C
O-
C
C
O
CH2- + C
C
O
C
C
C
O
CH3
C
C
O
C
O
C
CH3
OH2
C C O
C
C
CH3
2d) Please draw the mechanism for the formation of an enone using acetone, a strong base, and water
(if necessary).
O
H3C
O
H3C C CH3
O
C
CH3
NaNH 2
H3C
C
-
O
H3C
CH2
C
CH3
C
C
O-
CH3
H2O
O
H3C
C
+ OH-
O
CH3
C
H
H3C
C
CH3
C
-
CH3
C
C
H
CH3
149
OH
NaNH 2
H3C
O
H
CH3
C
C
C
H
CH3
OH
+ OH-
3a) Please draw all of the resonance structures for ortho attack of aniline with a chloronium ion (Cl+).
+ NH2
Cl
A
NH2
NH2
NH2
NH2
A
Cl
+
Cl+
Cl
Cl
B
B
+
+
3b) Please draw the complete mechanism for the hydroxylation of benzaldehyde.
H
H
H
O
O
H
HSO3F
H
H
O
O
O
+
OH+
H
H
O
+ H2O
O
OH+
+ H+
OH
+
OH
H
3c) For each of the following compounds label them as either an activator or deactivator, and as an
ortho, para, or meta director.
NHCH3
CN
H3C
C
Act/Deact
__Act___
_Deact_
__Act___
Director
__o/p___
__m_____
___o/p__
150
CH3
4a) Using drawings and words, please show how a quartet is formed in NMR spectroscopy.
CH
If a hydrogen or set of hydrogens is sitting next to a CH3
group, those hydrogens are split by the combination of
spins set up by the methyl group. The hydrogens on the
methyl group can have four possible sets of orientations
that cause the attached hydrogens to be split into a
quartet.
CH3
A CH looking at a CH3 will get
split into a quartet by the
combination of spins produced
by the methyl group.
4b) What is the relative height of each peak in a hextet?
1:5:10:10:5:1:
4c) If Jab = 8 and Jbc = 7, what is the complex splitting diagram for the following molecule?.
H
H
a
C
O
b
2.5
H
c
C
C
H
H
Cl
5) Please draw the MO diagram for a 6 +2 reaction. Label the HOMO, LUMO, the orbital symmetry
and state how the reaction occurs.
+-+-+LUMO
+
+-++-+
++-+--
+-
++--++
++
Zero
of
Energy
HOMO
Reaction occurs Photochemically
---+++
h
++++++
6) Please interpret and draw any two of the three compounds given on the back pages based on their
IR and NMR spectra.
151
7) Please give the product for each of the following reactions.
1. HCN
C
C
C
C
Cl
C
C
NH 2
2. LiAlH4
O
O
C
C
C
O
C
O
C
C
C2H5NH2
C
C
C
H
N
HO
CH3
2. Benzaldehyde
3. H2O
O
1. C-C-C-C-Br
N
C
C
C
C
1. NaNH2
C
2. H2O
OH
O
O
C
C
C
C
NH 2
O
O
C
C
2. N2H4, Heat
O
O
C
NH2
Heat
N
H
HO
H
C
O
AlCl3, CH3Cl
No Reaction
O
N2H4, OH-,heat
Cl
Cl
OH
HO
1. PCC
2. C2H5MgBr
3.Water, H+
152
C
O
C
1. NaNH2
C
C
C
C
C
C
8a) Draw a phospholipid and a fat. Label each of them. You can use squiggly lines for long chains.
O
O
C
O
C
O
C
O
C
O
C
O
C
C
O
P
C
O
O
C
C
O
O
C
O
Fat (Triglyceride)
O
O
P
O
O
O
P
O-
O
Phospholipid
8b) What is a soap and how do they work? Please draw a picture as part of your answer.
Soaps are nothing more than the salts of long chain
fatty acids. Their tails dissolve into oils and grease
which leaves their hydrophilic “heads” poking out into
the water. This has the affect of making the surface of
the oil look hydrophilic which allows the oil to
emulsify in water, which is how soaps remove oils and
other dirt from clothing.
Fat, oil
or dirt
Hydrophobic
hydrocarbon
Hydrophilic
acid (head)
8c) Most candles are made from a compound that, though called a wax, is not really a wax. What is
it and how does it differ from a true wax?
Most candles are made of paraffin which is really just a very long alkane. A true wax, like
bees wax, is an ester made from very long fatty acids (~24 carbons) and very long alcohols
(~24 carbons). Common waxes are bees wax and carnuba wax, which is the wax used to wax
a car.
153
9a) What are Hückel’s Rules?
i
Completely conjugate ring
ii
Must be flat
iii
No orbitals on the zero of energy
9b) An OH peak in NMR is usually a singlet, why? And when would you expect it to be a triplet?
The OH in an NMR is a singlet because hydrogen bonding allows the hydrogen to move on
and off the oxygen more rapidly that the NMR can “see” it. The hydrogen is not on the
oxygen long enough to cause splitting.
An OH would be a triplet if the alcohol were in the gas phase. As a gas, the hydrogen is not
allowed to leave the oxygen and would therefore be split by neighboring hydrogens.
9c) What are the restrictions on Friedel Craft Alkylation?
i
The ring cannot be more deactivated that caused by a halogen
ii
There cannot be any OH or NH2’s on the ring since they will react with the AlCl3
10) Starting with alkanes, alcohols, benzene, or cyclopentane, synthesize two of the following
compounds.
COOH
N
H
C
O
NH2
See next page
154
O
1. Br2, h
t-ButO-, t-ButOH
3. NBS
4. t-ButO-, t-ButOH
Br
C
C
C
1. t-ButO-, t-ButOH
2. NBS
3. KOH, Ether
C
4. PCC
1. HBr
2. EtO-, EtOH
H
C
C
H
C
O
O
C
Cl
COOH
1. CN2. H+, H2O, Heat
1. FeCl3, Cl2
2. con H2SO4, con HNO3
3. Zn(Hg), HCl
NH2
Br
C
C
C
1. t-ButO-, tButOH
2. NBS
Br
3. CN4. HBr, PBA
O
NH2
O
C
C
C
CN
1. NH3
2. H+, H2O, 
H2N
C
C
C
C
OH
O
H
N
155
H2SO4,
Heat