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LABORATORY MANUAL

ORGANIC CHEMISTRY 241

THIRD EDITION

4th Edition

Dr. Steven Fawl

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LABORATORY MANUAL

ORGANIC CHEMISTRY 241

FOURTH EDITION

Dr. Steven Fawl

Mathematics and Science Division

Napa Valley College

Napa, California

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N A P A V A L L E Y C O L L E G E

COURSE: Chemistry 241

INSTRUCTOR: Dr. Steven Fawl, Room 1843, 253-3195

LECTURES: MW 9:30 to 10:50

LABS: MT 2:00 to 4:50

OFFICE HRS: MTW 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.

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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. Solve complex reaction mechanisms.

2. Synthesize compounds starting with simple ingredients.

3. Determine the structure of organic compounds from spectrographic data.

4. 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!

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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 21

WORKSHEET 25

EXPERIMENT 4 Synthesis of 9,10-Dihyroanthracene-9,10-endo-α,β-succinic Anhydride:

A Diels-Alder Reaction 26

WORKSHEET 27

EXPERIMENT 5 sec-Butylbenzene - Friedel Craft Alkylation 28

WORKSHEET 29

EXPERIMENT 6 Sodium Borohydride Reduction of Acetophenone 30

WORKSHEET 33

EXPERIMENT 7 Synthesis of 2-Methyl-2-Hexanol: A Grignard Reaction 34

EXPERIMENT 8 Biodiesel Synthesis 42

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EXPERIMENT ONE

SYNTHESIS OF P-NITROACETANILIDE

Discussion:

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 o

acetanilide solution and the nitrating solution (a mixture of HNO3, and H2SO4

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 p-

nitroaniline from hydrolysis. Unfortunately, p-nitroaniline is difficult to remove from p-

nitroacetanilide by crystallization.

Equipment

250-mL beaker

dropper or disposable pipet

N

C

O

CH3H

HNO3

H2SO4

N

C

O

CH3H

NO2

10

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 a

I ,

,

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 , ,

-

The entire addition requires about 15 minutes.

,

,

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

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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.)

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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

, “W % ?”

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EXPERIMENT TWO

SYNTHESIS OF ASPIRIN: ESTER FORMATION

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.

C

O OH

OHCH3 C

O

O C CH3

O

H2SO4

C

O OH

O C CH3

O

AspirinSalicylic Acid

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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 ,

- -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.

- , W ,

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.

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.

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EXPERIMENTAL NOTE

,

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.

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EXPERIMENT THREE THE CANNIZARO REACTION: THE

DISPROPORTIONATION OF BENZALDEHYDE

DISCUSSION

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

-

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 t ,

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.

COH

COHH

COHO

H

KOH

2x +

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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 mater - -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.

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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

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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

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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

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O

O

O

O

O

O+

EXPERIMENT FOUR

Synthesis of 9,10-Dihyroanthracene-9,10-endo-α,β-succinic Anhydride

A Diels-Alder Reaction

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 ,

- I

with yellow and has a depressed melting point, recrystallize the product from xylene (20 mL per gram

of product).

24

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.

2) What products would be obtained from a Diels-Alder reaction of anthracene with following

dienophiles?

O

O

O

CH3 CH2 C O

O

C

O

CH3

CH3 C C C O

H

H O

C6H5

C C C O

O

CH3H

O

A.

B.

C.

25

EXPERIMENT FIVE

Friedel Craft Alkylation: Formation of sec-Butylbenzene

DISCUSSION

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

-

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 m

, -

CH3C C

CH3

C-C-C-C-Br

AlCl3

26

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

27

EXPERIMENT SIX

SODIUM BOROHYDRIDE REDUCTION OF ACETOPHENONE

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 hig , -

- ,

An infrared spectrum

can be used to determine if any ketone is present in the product.)

CH3O

NaBH4

CH3HO

28

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 50-

mL 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 reac -

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.

29

(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.)

30

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

31

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 1-

bromobutane 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 1-

bromobutane 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

32

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

33

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 34.6 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.

34

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 mi

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 250-

mL 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.

35

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 round-

bottom flask for distillation of the ether. Add a few boiling chips and slowly

,

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.

, -

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.

36

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

,

- e 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 1-

bromobutane 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.

37

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.

38

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.

39

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.

40

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

“G ”

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.

41

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).

42

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.

H “G ” ent? 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

? I “G ”?

c) What was in the waste product and what did you with it?

43

Exam I

NMR

IR

MS

Diels-Alder

44

Chem 241 Name___________________

Exam #1 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 Credit

1(20)

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

45

NH

3a) Please draw the product of each of the following Diels-Alder reactions.

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?

4) Please draw the MO diagram for each of the following compounds. Circle the aromatic

compounds (if any).

5) Please explain the endo rule and give an example

A.

B.

O

O

+

C C Cl+

O OO

+

46

Chem 241 Name___________________

Exam #1 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 Credit

1(20)

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

2) The cyclopropenyl cation is a completely conjugated ring system. Please draw the cyclopropenyl

cation and its MO diagram below

+ + + + + +

+ + + - - -

+ + - - + +

+ - - + + -

+ - ++ - +

+ - + - + -

Zero of Energy

+ +

+ -+

+

+

-

-

-

+

-

HOMO

LUMO

H HH

-

47

NH

3a) Please draw the product of each of the following Diels-Alder reactions.

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?

4) Please draw the MO diagram for each of the following compounds. Circle the aromatic

compounds (if any).

5) Please explain the endo rule and give an example

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)

A.

B.

These groups hinder one anotherso the molecule does not want totake this shape.

These groups do not hinder oneanother so the molecule can takethis shape and do a Diels Alder.

Rotate

Rotate

O

O

+

C C Cl+

O OO

+

Cl

O

O

O

O

O

C C Cl+

Cl

48

Chem 241 Name___________________

Practice Exam #1 – NMR/IR/MS/MO Theory 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 Credit

1(20)

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.

C C C H

H

H

Cl

H

H

H

H

A B C

49

1d) Look at the complex splitting pattern shown below

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 = 37

Cl =

79

Br = 81

Br =

10 2 8 2 2 6 2 102 8 2

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

5) Please explain the endo rule and give an example.

6) Please draw the product of the following Diels-Alder reactions.

C C C C

C OO

CH3

C C

Cl

+

+

51

Chem 241 Name___________________

Practice Exam #1 – NMR/IR/MS/MO Theory 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 Credit

1(20)

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.

C C C H

H

H

Cl

H

H

H

H

A B C

11 1

1 2 11 3 3 1

1 4 6 4 11 5 10 10 5 1

1 6 15 20 15 6 1

SingletDoubletTripletQuartetPentetHextetHeptet

11 11

99 4 5 4 4 4 4 5 41

~ 2.0

1:2:1

52

1d) Look at the complex splitting pattern shown below

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.

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.

10 2 8 2 2 6 2 102 8 2

C C

H

H

H

H

C CH H

53

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 = 75% 37

Cl = 25% 79

Br = 50% 81

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

Therefore, the Cl force constant is 1.626 times larger than the Br.

5) Please explain the endo rule and give an example.

6) Please draw the product of the following Diels-Alder reactions.

626.1

45.3512

45.3512

9.7912

9.7912

548

754

Br

Cl

Br

Cl

k

k

k

k

12

21

2

1

k

k

v

v

C C C C

C OO

CH3

C C

Cl

+

+

O

O

C

CCl

CH3

Cl

H3C

This way is endo.The Cl is stabilized.

H3C

This way is endo.The Cl is not stabilized

ClThe 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

“

+ + + +

+ + - -

+ - - +

+ - + -

Zero of Energy

+ + + +

+ + - -

+ - - +

+ - + -

HOMOLUMO

If an electron is photochemically moved to the next highest orbit, the symmetry of the new HOMO matches the LUMO of its reacting partner.

Photochemicallyinduced promotion

Symmetrymatch

+

+

-

-

+

+

-

-

54

Chem 241 Name___________________

Practice Exam #1 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 Credit

1(12 )

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

C C C C Cl

Br

A B C

C C C C Cl

55

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.

56

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;

OO

O

O

2x

57

Chem 241 Name___________________

Practice Exam #1 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 Credit

1(12 )

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

C C C C Cl

Br

A B C

C C C C Cl

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 -->

11

9 2 7 2 9

~2.0

58

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.

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?

++++++

+++---

++--++

+--++-

+-++-+

+-+-+-

++

+-

Photon +HOMO

LUMO

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.

1

2

2

1516

1612

1612

3212

3212

1710

cmvv12

21

2

1

k

k

v

v

59

5a) Please explain the difference between the position of a double bond versus a triple bond in NMR.

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;

OO

O

O

2x

O

O

O

O

C C

H

H

H

H

C CH H

60

Chem 241 Name___________________

Practice Exam #1 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 Credit

1(16 )

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

61

R / IR’

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.

62

Chem 241 Name___________________

Practice Exam #1 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 Credit

1(16 )

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

Jab = 10

Jac = 14

63

R / IR’

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.

See above

Remove H+

Remove H Remove H-

Aromatic

64

Exam II

Aromatics

Electrophilic Substitution

MO Theory

Hückel Reaction

65

Activators and Deactivators on Benzene

Note: There is no such this as a meta activator

O/P Activators by Induction

CH3

CH(CH3)2

C(CH3)3

C2H5

O/P Activators by Resonance

OH

NR2

NHR

NH2

OCH3

O C CH3

O

O/P Deactivators w/ Resonance

F

I

Br

Cl

Meta Deactivators by Induction

NO2

CN

COOH

HSO3

CHO

NH3+

66

Resonance forms of O/P Activators by Resonance

OH

E+

OH OH OH

E E E

++

+

OH

E+

OH OH OH

E E E

++

+

OH

E+

OH OH OH

E E E

+

+

+

O

E

H+

O H+

E

A

B

A

A

B

B

B

A

Ortho

Meta

Para

67

Resonance forms of O/P Deactivators - Halogens

Cl

E+

Cl Cl Cl

E E E

++

+

Cl

E+

Cl Cl Cl

E E E

++

+

Cl

E+

Cl Cl Cl

E E E

+

+

+

Cl

E

+

Cl+

E

A

B

A

A

B

B

B

A

Ortho

Meta

Para

68

Resonance forms of O/P Activators by Induction – Alkyl Groups

Resonance forms of Meta Deactivators by Induction

CH3

E+

CH3 CH3 CH3

E E E

++

+

CH3

E+

CH3 CH3 CH3

E E E

++

+

CH3

E+

CH3 CH3 CH3

E E E

+

+

+

Ortho

Meta

Para

NO2

E+

NO2 NO2 NO2

E E E

++

+

NO2

E+

NO2 NO2 NO2

E E E

++

+

NO2

E+

NO2 NO2 NO2

E E E

+

+

+

Ortho

Meta

Para

69

Reactions of Benzene – Electrophilic Substitution

X

NO2

SO3H

OH

C2H5

C

Cl2,FeCl3

HNO3, H2SO4

Fuming H2SO4

H2O2, HSO3F

C2H5Cl, AlCl3

CH3COCl, AlCl3

CH3

O

+ HCl

+ HCl

Nitration

Sulfonation

Hydroxylation

Friedel Crafts Alkylation

Friedel Crafts Acylation

Br2, FeBr3

Cl2O, CF3COOH

I2, CuCl2

X = Cl

X = Br

X = Cl

X = I

70

Benzene Side Group Reactions

CO R

NH2

NO2

CH3

HSO3

Zn(Hg)Dilute HCl

NBS

H2CR

NO2

NH2

CH2Br

Conc. NaOHHeat

OH

KMnO4, H2OHeat

COOH CH2OH

1. SnCl2, HCl2. NaOH, H2O

Will not reduce otherreducible side groupslike aldehydes and acids.

1. LiAlH4, THF2. H+

Cl OH

1. NaOH, Heat2. H2O, H+

71

Chem 241 Name___________________

Exam #2 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 Credit

1(12)

2(12)

3(12)

4(10)

5(10)

6(16)

7(28)

TOTAL

1) Please name each of the following compounds.

NH2Cl

CH3

H3C

HO COOH

O

O

O

O

Cl

72

2) For each of the following compounds label them as either an activator or deactivator, and as an

ortho, para, or meta director.

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

HCO

NH2 Cl

73

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.

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.

C C C

NH2

74

7) Please complete th I , “ R ”

CH3

KMnO4, H2SO4, Heat

NHCH2CH3

AlCl3, C-C-Cl

1. CO, HCl, AlCl32. HNO3, H2SO4

C C C

OH2SO4, HO-C-C-OH

C C C

OH 1. PCC2. C-C-MgCl3. H2O

C C C

O N2H4, NaOH, H2O

C C C O

C

C

KOH, H2O

75

NH2Cl

CH3

H3C

HO COOH

O

O

O

O

Cl

Chem 241 Name___________________

Exam #2 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 Credit

1(12)

2(12)

3(12)

4(10)

5(10)

6(16)

7(28)

TOTAL

1) Please name each of the following compounds.

Aniline m-methyltoluene 2-chloro-3-hydroxybenzoic acid

(m-xylene)

Phenanthrene 1,3-cyclobutadione 3-chloro-6-oxo-2-hexanone

4-chloro-5-oxohexanal

76

2) For each of the following compounds label them as either an activator or deactivator, and as an

ortho, para, or meta director.

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

(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

HCO

NH2 Cl

Cl

E+

Cl Cl Cl

E E E

++

+

Cl

E

+

A

B

A

B

OH OH OH OH

Cl Cl Cl

++

+

O

Cl

H+

A

B

A

B

Most Stable

77

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.

6a) Please name three criteria that determines whether a molecule is aromatic.

i) The molecule must be completely conjugated.

ii) The molecule must be flat

iii) 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.

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.

C C C

NH2

C C C C BrAlBr3

C C C C Br Al

Br

Br

Br

C C C CH2Al

Br

Br

Br

Br

H

H

+HydrideShiftC C C CH3

H

CCC CH

CCC C

+ H+

H H

H + H-

Remove the Hwith its electrons

Produces anempty p orbital

cyclopropenyl cation

Zero of Energy

1. Propanoyl Chloride, AlCl32. H2SO4, HNO3

3. Zn(Hg), HCl

CC C

NH2

1. AlBr3

2. Zn(Hg), HClC C C

O O

BrBr

78

I , “ R ”

CH3

KMnO4, H2SO4, Heat

NHCH2CH3

AlCl3, C-C-Cl

1. CO, HCl, AlCl32. HNO3, H2SO4

C C C

OH2SO4, HO-C-C-OH

C C C

OH 1. PCC2. C-C-MgCl3. H2O

C C C

O N2H4, NaOH, H2O

C C C O

C

C

KOH, H2O

COOH

No Reaction

C OH

NO2

O O

C C C

OH

C

C

C C C

C C C O

C

C

C C C OH

C

C

OH

and

79

Chem 241 Name___________________

Exam #2 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 Credit

1(12)

2(12)

3(12)

4(10)

5(16)

6(14)

7(24)

TOTAL

1) Please name each of the following compounds.

NH2

CO2N

Cl

ClCl

N

O

OH

N

80

2) For each of the following compounds label them as either an activator or deactivator, and as an

ortho, para, or meta director.

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.

81

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.

82

6) Please synthesize two of the three following compounds. You can start with benzene, alkyl

halides or alcohols.

83

I “ R ”

84

Chem 241 Name___________________

Exam #2 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 Credit

1(12)

2(12)

3(12)

4(10)

5(16)

6(14)

7(24)

TOTAL

1) Please name each of the following compounds.

NH2

CO2N

Cl

ClCl

N

O

OH

N

Aniline m-nitrobenzoic acid 1,2,3-trichlorobenzene

Anthracene pyrrole pyridine

85

2) For each of the following compounds label them as either an activator or deactivator, and as an

ortho, para, or meta director.

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.

4) Please draw the complete mechanism for hydroxylation of toluene.

OCH3 CSH

86

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

N

HNormal sp3hybridized nitrogen

N H

Rehybrized nitrogento sp2

N

H

pyrrole

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.

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).

87

6) Please synthesize two of the three following compounds. You can start with benzene, alkyl halides

or alcohols.

OH

OH

O C

O

CH3

C

O

HO

Aspirin

m catechol

Naphthalene

FumingH2SO4

HSO3

H2O2, HSO3F

Heat

HSO3

OH

OH

OH

conc. NaOHHeat

OH

OH

1. KMnO4, H+ H2O, heat2. SOCl2

O

O

Cl

ClAlCl3

O

O

1, LiAlH42. SOCl2 x 23. tButO-, tButOH

1. CH3Cl, AlCl32. H2O2, HSO3F, Heat

3. KMnO4, H+, H2O, Heat

C

OHO

HO Acetic AnhydrideH2SO4, H2O, Heat

O C

O

CH3

C

O

HO

88

I “ R ”

89

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.

90

Carbonyl Chemistry

Four Main Reaction Types

1. Addition – Aldehydes and Ketones

2. Substitution – Acid & Derivatives

3. Conjugate Addition – All Carbonyls

4. Alpha Substitution – All Carbonyls

H3C C CH3

O

Nuc-H3C C CH3

O-

Nuc

H2O

H3C C CH3

OH

Nuc

+ OH-

H3C C Cl

O

Nuc- H3C C Cl

O-

Nuc

H3C C

O

Nuc

+ Cl-

C C CH3

O

CNuc-

C C CH3

O-

C

Nuc

H2OC C CH3

OH

C

Nuc

keto-enolC C CH3

O

C

Nuc

H3C C CH3

O

H3C C CH2-

O

H3C C C

OBase

-

(Nuc-)

CH3Br

CH3 + Br-

91

How to make Aldehydes and Ketones

PCCCH2Cl2

PCCCH2Cl2

C C O

C C C

OH

C C C

O

C C C

OH

C CH

OH

KMnO4, H+, H2O

K2Cr2O7, H2SO4, Heat

O3, (CH3)2S

C C OH

O

DIBAH, -70C

C

C C OH

C C C

O

C C C

O

C C C

O

C C O

C C O

C C C BH3, H2O2,

NaOH, H2O C C CO

C C CH2SO4, HgSO4,H2O C C C

O

C C Cl

OC2H5MgBr

C C C2H5

O

+

CO, HCl, AlCl3

HC O

RCOCl, AlCl3

COR

Gatterman-Koch Rxn

Friedel-Craft Acylation

C C Cl

OLi(t-ButO)3AlH

C C O

92

1. Nucleophilic Addition Reactions on Aldehydes and Ketones

General Mechanism

Reactions

C C C

O

Nuc-

C C C

O-

Nuc

H2OC C C

OH

Nuc

C C C

O

HCN

CH3OH

H+, H2O

CH2OH

H+, H2O

OH-, H2O

1. C2H5MgBr

2. H2O, H+

LiAlH4, H2O

NaBH4, H2O

C C C

OH

CN

C C C

OH

OCH3

C C C

OCH3

OCH3

C C C

OH

OH

C C C

OH

C2H5

C C C

OH

C C C

OH

Hemiacetal Acetal

Gemdiol

Cyanohydrin

H2/Pd/BaSO4/S

C C C

OH

Rosenmund Catalyst

93

Aldehyde / Ketone Amine Reactions

Aldehyde/Ketone Name Reactions

C C C

O

C C C

NHNH3

N2H4

NH2OH

NH2R

PhNHNH2

NH2CON2H4

C C C

N

C C C

N

C C C

N

C C C

N

C C C

N

NH2

OH

R

NHPh

NHCONH2

Imine

Hydrozone

Oxime

Imine "Schiff Base"

Phenylhydrozone

Semicarbazone

Hydrazine

Hydroxylamine

Amine

Phenylhydrazine

Semicarbizide

C C C

O

C C CZn(Hg), HCl

Clemmenson Reduction

C C C

O

C C CN2H4, KOH

Wolff-Kishner Reduction

COH

COHO

CHOHH

+ Cannizaro Reaction

KOH, H2O

94

How to make Acids

2. Nucleophilic Substitution Reactions on Acids

General Mechanism

Formation of Acid Halides

Formation of Anhydrides

C C OHKMnO4, Heat

K2Cr2O7, H2SO4C C O

C C C C KMnO4, Heat

C C

OH

O

C C NH+, H2O, Heat

H3C Br1. Mg, Ether

2. CO2

3. H+

C C C

1, I2, NaOH

2. H+

O

CH3 C

OH

O

SOCl2

POCl3

PCl3

PBr3

CH3 C

Cl or Br

O

CH3 C

Cl

O

CH3 C

O

CH3C

HO

O

H3CCO

O

CH3 C

OH

O CH3C

HO

O

H2SO4

H3C C X

O

Nuc- H3C C X

O-

Nuc

H3C C

O

Nuc

+ X-

95

Formation of Esters

Formation of Amides

Formation of Nitriles

CH3 C

Cl

O

CH3 C

O

CH3CH2O

CH3 C

OH

O

C2H5OH

C2H5OH, H2SO4

CH3 C

Cl

O

CH3 C

O

CH3CH2N

CH3 C

OH

O

C2H5NH2

C2H5NH2 H

CH3 C

O

NH2

POCl3 or

P2O5

CH3 C N

H3C BrHCN

NH2

1. NaNO2, HCl2. CuCN CN Sandmeyer Reaction

96

3. Conjugate Addition Using Esters, Diones, and Enones

General Michael Reaction

Enones Nucleophiles

R = -CH3 Ketone diester

-O-R Ester dione

-H Aldehyde Keto-ester

-NH2 Amide

Lewis Acceptors (acids) Lewis Donors (bases)

Therefore, if R = CH3 and Nuc- = Keto-ester, the product would be;

I β

The mechanism of the decarboxylation is in your notes.

C C R

O

CNuc-

C C R

O-

C

Nuc

H2OC C R

OH

C

Nuc

keto-enolC C R

O

C

Nuc

Enone Nucleophile

H3C O C

CH2

O

OH3C

O

H3C C

CH2

O

H3C

O

H3C O C

CH2

O

H3C

O

diester dione ketoester

H3C O C

C

O

H3C

O

C C CH3

O

C

H3C O C

CH2

O

H3C

O

C C CH3

O

C+

H3C O C

C

O

H3C

O

C C CH3

O

CH+, H2O

CH3OH C

C

O

H3C

O

C C CH3

O

C

HOC

C

O

H3C

O

C C CH3

O

C

OH+

++

97

4. Alpha Substitutions - Claisen Reactions

Classic Claisen Reaction - between two of the same esters

Crossed Claisen – between two different esters

Dieckmann Reaction – A Claisen cyclization

H3C O C CH3

O

NaNH2H3C O C CH2

-

O

H3C O C CH3

O

H3C O C CH3

O-

CH2COH3C

O

C CH3

O

CH2COH3C

O

CH3O- +

H+, H2OHeat

C CH3

O

CH2CHO

O

CH3OH +

spontaneousdecarboxylationC CH3

O

CH3

CO2 + H+

+

keto acidAcetone

H3C O C CH3

O

NaNH2H3C O C CH2

-

O

H3C O C CH2

O

H3C O C CH2

O-

CH2COH3C

O

C CH2

O

CH2COH3C

O

CH3O- +

H+, H2OHeat

C CH2

O

CH2CHO

O

CH3OH +

spontaneousdecarboxylationC CH2

O

CH3

CO2 + H+

+

keto acidMethyl ethyl ketone

( 2 propanone)

CH3 CH3

CH3

CH3CH3

EtO C C C C C C OEt

OO OEt

OEt

O

O

NaEtOOEt

OEt

O

O

-

H

OEt

OEt

O-

O

OEt

O

O

+ EtO-

cyclic keto ester

98

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.

Malonic Ester Synthesis – makes substituted acetic acids (the acid is circled)

Acetoacetic Ester Synthesis – makes substituted acetones (the acetone is circled)

Dione

C2H5 O C

CH2

O

OC2H5

O

H3C C

CH2

O

H3C

O

C2H5 O C

CH2

O

H3C

O

Malonic Ester dioneAcetoacetic Ester

C2H5 O C

CH2

O

COC2H5

O

NaNH2

C2H5 O C

CH-

O

COC2H5

O

C-C-Cl

( SN2 )

C2H5 O C

CH

O

COC2H5

O

C CH

+, H2O, Heat

spont. decarbox.H2C

CHO

O

C C

2 C2H5OH + CO2

C2H5 O C

CH2

O

CH3C

O

NaNH2

C2H5 O C

CH-

O

CH3C

O

C-C-Cl

( SN2 )

C2H5 O C

CH

O

CH3C

O

C CH

+, H2O, Heat

spont. decarbox.H2C

CH3C

O

C C

C2H5OH + CO2

H3C C

CH2

O

CH3C

O

NaNH2

H3C C

CH-

O

CH3C

O

C-C-Cl

( SN2 )

H3C C

CH

O

CH3C

O

C CH

+, H2O, Heat No Reaction - the product

is not a keto acid.

99

Aldol Reactions Between two Aldehyde/Ketones

Classic Aldol – two of the same aldehydes or ketones

Crossed Aldol – two different aldehydes or ketones

Aldol Cyclization

If you have excess base present then all of these aldol products can undergo dehydration by the

following mechanism;

C C C

O

1/2 eq. NaNH2

or ButLi, or NaEtO C C C

OH

H

H

H

H

_C

C

C

O+ C C C

O H

H

C

C

C

O_ H2O

C C C

O H

H

C

C

C

OH

Aldol

C C C

O

1 eq. NaNH2

or ButLi, or NaEtO C C C

OH

H

H

H

H

_C

C

C

O+ C C C

O H

H

C

C

C

O_ H2O

C C C

O H

H

C

C

C

OH

C C C

H3C C C

O

C C C

OCH3O

O NaNH2

CH2-

O

O

O O-

H2O

O OH

C C C

O H

H

C

C

C

OH

O OH

H H

Base

C C C

O

H

C

C

C

OH

O OH

H

_

_

C C C

O

H

C

O

C

C

H

100

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.

C C C Br

C C C

O

H

C C C

O

C O C C

O

C C NC C C

O

O

C C C

C C C

O

OCH3

C C C C

O

CH3BrCH2CH2NH2

O

O

O

O

H3C C

O

OH

C

O

O

C

OH

O

CH3

Aspirin

C C O

O

C C C C C C

O

101

Exam 3 – Practice Synthesis Answers

C C C Br

1. HCN2. H+, H2O, Heat3. SOCl24. Acetic Acid

C C C

O

H

1. NH2-C2H5

2. LiAlH4

C C C

O

C O C C

O

C C NC C C

O

O

C C C

1. Br2, light

2. tButO-

3. NBS

4. KCN

5. BH3, H2O2,

NaOH, Water

6. H+, Water, heat

C C C

O

OCH3

1. NaNH2

2. Ethyl Acetate3. H2O, H+, Heat

CCCC

O

CH3BrCH2CH2NH2

O

O

O

O

H3C C

O

OH

1. KCN2. LiAlH4

1. Br2, PBr32. KOH, Ether

3. K2Cr2O7, H2SO4

4. HO-C-C-OH, H2SO4

C

O

O

C

OH

O

CH3

Aspirin

C C O

O

C C C C C C

O

1. CH3Cl, AlCl32. HSO3F, H2O2

3. KMnO4, H+, H2O,

HAc, H2SO4

1. NaNH2

2.

3. H+, Water, Heat

C C C C

O

102

Chem 241 Name___________________

Exam #3 – Aldehydes/Ketones

Closed Book Exam - No books or notes allowed. All work must be shown for full credit.

Question Credit

1(18 )

2(32)

3(16)

4(14)

5(20)

TOTAL

1) Please name the structure of the following compounds.

CH O

C C C

O

C C C C C

O

H

O

O

O

H3C C C CH3

O O

103

2) Please provide the product of each of the following reactions;

C C C

OHOCH2CH2OH, H+

C C C

O

1. HCN2. H+, H2O, Heat

C C C

O

NaBH4, H2O

C C C

O

N2H4

C C H

O

1. Ag(NH3)2+, KOH

2. H+, H2O

C C C

O

Br2, NaOH

C C H

O

CrO3, H2SO4

C C

C

CO3, (CH3)2S

C C

C

C

C

H

OKOH, H2O

C C Cl

O

1. C-C-MgBr2. H2O, H+

104

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.

105

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.

CH O

C C C

O

OO

O

H

C C C C C

O OH

106

CH O

C C C

O

C C C C C

O

H

O

O

O

H3C C C CH3

O O

Chem 241 Name___Answer Key ____

Exam #3 – Aldehydes/Ketones

Closed Book Exam - No books or notes allowed. All work must be shown for full credit.

Question Credit

1(18 )

2(32)

3(16)

4(14)

5(20)

TOTAL

1) Please name the structure of the following compounds.

Benzaldehyde 4-oxo-pentanal

Acetone benzophenone or diphenylmethanal

Cyclopentanone 2,3-butadione

107

2) Please provide the product of each of the following reactions;

C C C

OHOCH2CH2OH, H+

C C C

O

1. HCN2. H+, H2O, Heat

C C C

O

NaBH4, H2O

C C C

O

N2H4

C C H

O

1. Ag(NH3)2+, KOH

2. H+, H2O

C C C

O

Br2, NaOH

C C H

O

CrO3, H2SO4

C C

C

CO3, (CH3)2S

C C

C

C

C

H

OKOH, H2O

C C Cl

O

1. C-C-MgBr2. H2O, H+

O

O

C

C

C

HO COOH

C C C

OH

C C C

N

NH2

C C OH

O

C C OH

O

C C OH

O

C C C

O

C

H

H

O

C C

C

C

C

OH

O

C C

C

C

C

H

OH

H

and

C C C

O

C

108

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.

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).

C C C

O

H+

C C C

OH

C C C

O H

H2N-C-CC C C

O H

N C CH

H

C C C

O H

N C C

H

H+ +C C C

O H

N C C

H

H

C C C

N C C

H

H2O +

C C C

N C C

C C C

O

H+

C C C

OH

C C C

O H

HO-C-CC C C

O H

O C CH

C C C

O H

O C C

H+ +C C C

O H

O C C

H

C C C

O C C

H2O +

HO-C-C

C C C

O C C

O C C

H

C C C

O C C

O C C

+ H+

109

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.

C

H O

C C C

O

OO

O

H

C C C C C

O OH

1. CH3Cl, AlCl32. NBS

3. KOH, Ether

4. PCC

CH O

C C Br

1. Mg, dry ether

2. CO

3. H+, H2O

C C C

O

H

1. Br2, AlBr32. Mg, dry ether

3. CO2

4. H+, H2O

5. SOCl26. Benzene, AlCl3

O

Br C C Br1. KOH, ether x 22. CO, H+, heat

C C Br

1. Mg, Dry Ether2. CO3. Zn(Hg), HCl4. Br2, h5. KOH, ether6. PCC

C C C

O

1. KOH2. PCC C C

O

H

1. 1 eq NaNH2

2. C-C=O

3. H+, H2O

C C Br

C C C C C

O OH

110

Chem 241 Name___________________

Exam #3 – Acids/Derivatives April 26,1999

Closed Book Exam - No books or notes allowed. All work must be shown for full credit.

Question Credit

1(18 )

2(32)

3(16)

4(14)

5(20)

TOTAL

1) Please name the structure of the following compounds.

N

O

O C

O

H

CCCC

C N

O OO

NCCC C C C

O

C

O

Cl

CCCC

O

OH

Br

C C

OH

O

111

2) Please give the product of each of the following reactions. If the given reaction does not occur,

write No Rxn.

C C C

O

OH

C2H5NH2

C C C

O

OH

C C C

O

NH2

C C C

O

OH

H2SO4, Heat

P2O5

Cl1) HCN

2) H+, H2O, Heat

3) C2H5OH, H2SO4, H2O

1) PBr3, Br2

2) H2O, H+

C C C

O

H

1. Ag(NH3)2+, KOH

2. H+, H2O

C C C C C

O

OH

HOH2SO4, Heat

C C C C

Br

1. Mg, Ether

2. CO2

3. H+, H2O

CH2

H3C

KMnO4, H+

H2O, Heat

112

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,

, “ ” q !

4b) Please rank the following acids in order of increasing acidity (1 is lowest). Please explain your

reasoning.

C C C C

O

OH

C C C C

O

OH

C C C C

O

OH

C C C C

O

OH

CH3 Br Br

113

5) Starting with benzene or alkyl halides of two carbons or less synthesize each of the following

compounds.

COOH

NO

O OO

C C C O

O

C H

O

C C C C

O

N

114

N

O

O C

O

H

CCCC

C N

O OO

NCCC C C C

O

C

O

Cl

CCCC

O

OH

Br

C C

OH

O

Chem 241 Name___________________

Exam #3 – Acids/Derivatives April 26,1999

Closed Book Exam - No books or notes allowed. All work must be shown for full credit.

Question Credit

1(18 )

2(32)

3(16)

4(14)

5(20)

TOTAL

1) Please name the structure of the following compounds.

5-aminopentoic acid lactam cyclobutyl methanoate butadioic anhydride

3-methylbutanitrile N-propylpropanamide

benzoyl chloride 2-bromobutanoic acid acetic acid

115

2) Please give the product of each of the following reactions. If the given reaction does not occur,

write No Rxn.

C C C

O

OH

C2H5NH2

C C C

O

OH

C C C

O

NH2

C C C

O

OH

H2SO4, Heat

P2O5

Cl1) HCN

2) H+, H2O, Heat

3) C2H5OH, H2SO4, H2O

1) PBr3, Br2

2) H2O, H+

C C C

O

H

1. Ag(NH3)2+, KOH

2. H+, H2O

C C C C C

O

OH

HOH2SO4, Heat

C C C C

Br

1. Mg, Ether

2. CO2

3. H+, H2O

CH2

H3C

KMnO4, H+

H2O, Heat

C

O

O C C

CC

C CC

CO

O O

C C C N

C C C

O

OH

O

O

C C C C

COOH

COOH

C C C

O

N C C

H

C C C

O

OH

Br

116

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 rare “ ” q !

Acids and amides have OH and NH2 groups that will react with and neutralize any incoming

H’ H’

suffer from this problem

4b) Please rank the following acids in order of increasing acidity (1 is lowest). Please explain your

reasoning.

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.

C C C C

O

OH

C C C C

O

OH

C C C C

O

OH

C C C C

O

OH

CH3 Br Br

C C C

O

OHPBr3

C C C

O

O

H

P

Br

Br

Br

C C C

O

O

H

P

Br

Br

+ Br-

C C C

O

O

H

P

Br

Br

Brketo-enol

C C C

OH

BrBr2

C C C

OH

Br(Br

+ + Br

-)

C C C

OH

Br

Br+

C C C

O

Br

H

Br

C C C

O

Br

Br

+ H+

C C NOH

-

C C N

OH

H2OC C N

OHH

OH-

C C N

OHH

OH

H2O

C C N

OHH

OHH

OH-

C C N

OH

OHH

H2O +C C

O

OHNH2- +

H2O

NH3 + OH-

117

5) Starting with benzene or alkyl halides of two carbons or less synthesize each of the following

compounds.

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.

COOH

NO

O OO

C C C O

O

C H

O

C C C C

O

N

CH3CH3Br

1. KOH, Ether

2. KMnO4, H+, H2O, Heat

3. SOCl24. Benzene, AlCl3

CCH3O

KMnO4, H+H2O, Heat

COHO

C C C

Br 1. tButO-, tButOH2. NBS3. NaCN, THF4. HBr, PBA

C C CBr CN

1. NH3(liq)2. H+, H2O, Heat3. Heat

NO

C C C

Br 1. tButO-, tButOH2. NBS3. NaCN, THF4. HBr, PBA5. NaCN, THF

C C CNC CN1. H+, H2O, Heat2. H2SO4, Heat

O OO

1. KOH, Ether2. KMnO4, H+, H2O, Heat

C C C

OH

O

CH3Br1. KOH, Ether2. PCC3. Tollens Reagent

HO C H

O

H2SO4,Heat

CC

CO

O

CH

O

C C C Br1. NaCN, THF2. H+, H2O, Heat3. HVZ4. NH3

C C C NH2

OBr

1. KOH, Ether

2. PCC

3. P2O5

C C C C

O

N

C C C Br

118

Final Exam

119

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?

120

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

V ~ V ’ H

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

j G + , ’ , G + +

have been Gly~Ala~Lys. So the order of the protein must have been,

Final Chain = Gly~Ala~Lys~Met~Val~Met~Arg~Ser

121

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

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 , ’

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–– , ’

9) Draw gentiobiose. It is 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.

123

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 , ’

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.

H

C

OH

HHO

OHH

OHH

CH2OH

Glucose

OH

O

OH

OH

OH

CH2OH

O

OH

OH

OH

CH2OH

Glucose Galactose

O

O

OH

OH

OH

CH2OH

Galactose

HO O

OH

OH

CH2OH

Gulose

HO

OH

O OH

OH

OH

OH

CH2OH

Glucose

O OH

OH

HO

CH2OH

Allose

OH

O OH

OH

HO

CH2OH

Talose

OH

124

5) Please draw the ring structure of Fructose.

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.

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

right, we are seeing the rotation backwards so the actual rotation is clockwise (R). Since

the second to last carbon has the OH on the right, this molecule is D.

8) Draw lactose. It is galactose–– , ’

9) Draw gentiobiose. It is glucose-- , ’

OCH2OHHOH2C

HO

OH

OH

C

C HH

C OHH

C HH

H

OHO

O OH

OH

OH

CH2OH

Galactose

HO O OH

OH

OH

OH

CH2OH

Glucose

O

OH

OH

CH2OH

Galactose 1,4'- glucose

HO O OH

OH

OH

CH2OH

O

O OH

OH

OH

OH

CH2OH

Glucose

O OH

OH

OH

OH

CH2OH

Glucose

O

OH

OH

OH

CH2OH

Glucose 1,6' glucose

O OH

OH

OH

OH

CH2O

125

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.

C

C O

C HHO

H

H OH

OH-

C

C O

C HHO

H OH

_

C

C O

C HHO

H OH_

H2O

C

C OH

C HHO

H OH

C

C OH

C HHO

H O-

C

C OH

C HHO

H

O

OH-

_H2O

C

C OH

C HHO

H

O

HOH- +

C

C O

C HHO

H

H OHH

+C

C O

C HHO

H

H OH

H

+

C

C OH

C HHO

H

OH

+ H+

C

C OH

C HHO

H

O

_

C

C OH

C HHO

H

O

H

H

+

H

+C

C OH

C HHO

H

O

HH+ +

126

Chem 241 Name___________________

Final Exam 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 Credit Question Credit

1(10) 7(15)

2(10) 8(12)

3(8) 9(12)

4(16) 10(42)

5(15) 11(10)

6(20) 12(30)

Total Total

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

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

C C C C Cl

Br

A B C

C C C C Cl

127

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,

, “ ” q !

4a) One of the products below was made using a Michael reaction and the other was made using a

Claisen reaction. Which is which?

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.

CC

CC

CC

O

O CC

CC

C

O O

128

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.

6) Please interpret and draw any two of the three compounds given on the back pages based on their

IR and NMR spectra.

O

O

O

NaOH H2O

129

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 , ’ must be cyclic.

9) Please circle the terpene units found in the following compound.

CH3

CH3

CH3

CH3

130

10) Please give the product for each of the following reactions.

Cl

HNO3, H2SO4

C OKOH, H2O

NH2 NO2 AlCl3, C C C

O

Cl

CH3 C CH3

O

1/2 eq. NaEtO

Water

CH3 C NH2

O

P2O5

O

O

O Et

1. NaEtO

2. H+, H2O,

NH2O

OHH2SO4,

O O

O O

1. 2x NaEtO2. Br-C-C-C-C-Br

3. H+, H2O,

131

’

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.

H2N CH C

CH

OH

O

OH

CH3

1. C-C-C-Cl, AlCl3

2. NBS

3. KCN

4. H+, H2O,

C COOHNH2

1. LiAlH4

2. H2SO4

O

O O NaEtO,

O

O O1. C-C-MgBr

2. Water

O

HO-C-C-OH, H2SO4

C C C

O

OH

1. PBr3, Br2

2. H2O, H2SO4

NO

O

O

NH2

132

12a) Please draw the product of the following Diels-Alder reactions;

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?

W “ ” ?

OO

O

O

2x

133

Chem 241 Name_Answer Key________

Final Exam 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 Credit Question Credit

1(10) 7(15)

2(10) 8(12)

3(8) 9(12)

4(16) 10(42)

5(15) 11(10)

6(20) 12(30)

Total Total

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

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

C C C C Cl

Br

A B C

C C C C Cl

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.

2.3

134

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.

3) Please explain why we almost always do nucleophilic substitutions on acid chlorides, anhydrides,

, “ ” q !

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?

Michael 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

O

O

Et1, NaNH2

2. C=C-C=O3. H+, H2O,

O

O

CC

CC

CC

O

O CC

CC

C

O O

1

2

2

1516

1612

1612

3212

3212

1710

cmvv12

21

2

1

k

k

v

v

135

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.

6) Please interpret and draw any two of the three compounds given on the back pages based on their

IR and NMR spectra.

NH2 NH2 NH2 NH2

NO2 NO2 NO2

++

+

NH2

NO2

+

A

B

A

BNO2+

Br AlBr3 Br AlBr3

+ -+ + AlBr4

-

H

HydrideShift

+H

++ H

+

O

O

O

OH-

O

O-

O

OH

O-

O

O

OH

H2O

OH

O

O

OH+ OH

-

136

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) 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 , ’

9) Please circle the terpene units found in the following compound.

H

C

OH

HHO

OHH

OHH

CH2OH

Glucose

OH

H3N+

C C

O

O-

H

H

CH3

CH3

CH3

CH3

HO

OH

H

HO

H

H

OHHO

OH

O

H

H

HO

H

OH

OHHH

OH

137

10) Please give the product for each of the following reactions.

Cl

HNO3, H2SO4

C OKOH, H2O

NH2 NO2 AlCl3, C C C

O

Cl

CH3 C CH3

O

1/2 eq. NaEtO

Water

CH3 C NH2

O

P2O5

O

O

O Et

1. NaEtO

2. H+, H2O,

NH2O

OHH2SO4,

O O

O O

1. 2x NaEtO2. Br-C-C-C-C-Br

3. H+, H2O,

Cl

NO2

C O

OH

C OH

No Reaction - The ring is deactivated

CH3 C C

O

C

CH3

CH3

OH

CH3 C N

O

O

N

O

H

O

HO

138

’

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.

See last page

H2N CH C

CH

OH

O

OH

CH3

1. C-C-C-Cl, AlCl3

2. NBS

3. KCN

4. H+, H2O,

C COOHNH2

1. LiAlH4

2. H2SO4

O

O O NaEtO,

O

O O1. C-C-MgBr

2. Water

O

HO-C-C-OH, H2SO4

C C C

O

OH

1. PBr3, Br2

2. H2O, H2SO4

CH3C CH3

COOH

C CNH2 OH

O

O

O

O

OO

C C C

O

OH

Br

NO

O

O

NH2

139

12a) Please draw the product of the following Diels-Alder reactions;

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.

Reaction occurs photochemically

12c) What are the rules of aromaticity?

1. Completely conjugated ring

2. Flat

3. No orbitals on zero of energy

W “ ” ?

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.

OO

O

O

2x

O

O

O

O

+

Zero of Energy

HOMO

LUMO

+ +

+ -

+ +

+ -

+ +

+ -

+ +

+ -

+ +

+ -h

140

Answers to syntheses question -

C C C

Br 1. t-ButO-, tButOH2. NBS3. CN-4. HBr, PBA

C C C CNBr1. NH32. H+, H2O, C C C CH2N

O

OH

H2SO4,Heat

N

O

H

C

OH

H H

H

PCC

C

O

H H

HO-C-C-C-OHH2SO4, Heat

O O

C C C

Br1. t-ButO-, tButOH2. NBS3. Mg, dry ether

C C C MgBr 1. CH3OH, PCC

2. H2SO4C C C C OH

H2SO4

Heat (E1)C C C C

C C

Br

t-ButO-t-ButOHC C

1. NBS x 22. t-ButO- t-ButOH

C C C OH

1. KMnO4, H+, H2O, Heat2. SOCl2

C C C

O

Cl

1. C-C-COCl

2. AlCl33. con. H2SO4

con. HNO3

NO2

Zn(Hg), HCl

NH2

O

C C

OH

PCCC C

O

1. 1/2 eq. NaNH2

2. H2O C C C C

OOH

1. SOCl22. KMnO4, H+ H2O, Heat

C C C C

OCl

OH

KOH,Ether

C C C C

OOH

OH

PBr3, Br2C C C C

OOH

OH

Br

NH3

H2N CH C

CH

OH

O

OH

CH3

141

Chem 241 Name________________________

Final Exam 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 Credit Question Credit

1(21) 6(20)

2(20) 7(30)

3(24) 8(15)

4(20) 9(15)

5(15) 10(20)

Total Total

1) Please name the following compounds.

142

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).

143

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.

Act/Deact _______ ________ ________

Director _______ ________ ________

NHCH3 CN C CH3H3C

144

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?.

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.

145

7) Please give the product for each of the following reactions.

146

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?

147

9 W Hü ’ R ?

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.

148

Chem 241 Name__Answer Key______

Final Exam 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 Credit Question Credit

1(21) 6(20)

2(20) 7(30)

3(24) 8(15)

4(20) 9(15)

5(15) 10(20)

Total Total

I want to drop my lowest exam _____________________.

Signature

1) Please name the following compounds.

149

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).

150

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.

Act/Deact __Act___ _Deact_ __Act___

Director __o/p___ __m_____ ___o/p__

NHCH3 CN C CH3H3C

151

4a) Using drawings and words, please show how a quartet is formed in NMR spectroscopy.

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.

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?.

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.

152

7) Please give the product for each of the following reactions.

153

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.

Soaps are nothing more than the salts of long chain

fatty acids. Their tails dissolve into oils and grease

“ ”

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.

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.

154

9 W Hü ’ R ?

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.

See next page

155