laboratory manual organic chemistry 241 - … 241... · laboratory manual organic chemistry 241...
TRANSCRIPT
Chem 241 - Organic Chemistry 2
LABORATORY MANUAL
ORGANIC CHEMISTRY 241
FIFTH EDITION
Dr. Steven Fawl
Mathematics and Science Division
Napa Valley College
Napa, California
Chem 241 - Organic Chemistry 3
PREFACE
Chemistry is an experimental science. Thus, it is important that students of chemistry do experiments
in the laboratory to more fully understand applications of the theories they study in lecture and how to
critically evaluate experimental data. The laboratory can also aid the student in the study of the
science by clearly illustrating the principles and concepts involved. Finally, laboratory
experimentation allows students the opportunity to develop techniques and other manipulative skills
that students of science must master.
The faculty of the Napa Valley College clearly understands the importance of laboratory work in the
study of chemistry. The Department is committed to this component of your education and hopes that
you will take full advantage of this opportunity to explore the science of chemistry.
A unique aspect of this laboratory program is that a concerted effort has been made to use
environmentally less toxic or non-toxic materials in these experiments. This was not only done to
protect students but also to lessen the impact of this program upon the environment. This
commitment to the environment has presented an enormous challenge, as many traditional
experiments could not be used due to the negative impact of the chemicals involved. Some
experiments are completely environmentally safe and in these the products can be disposed of by
placing solids in the wastebasket and solutions down the drain. Others contain a very limited amount
of hazardous waste and in these cases the waste must be collected in the proper container for
treatment and disposal. The Department is committed to the further development of environmentally
safe experiments which still clearly illustrate the important principles and techniques.
The sequence of experiments in this Laboratory Manual is designed to follow the lecture curriculum.
However, instructors will sometimes vary the order of material covered in lecture and thus certain
experiments may come before the concepts illustrated are covered in lecture or after the material has
been covered. Some instructors strongly feel that the lecture should lead the laboratory while other
instructors just as strongly believe that the laboratory experiments should lead the lecture, and still a
third group feel that they should be done concurrently. While there is no "best" way, it is important
that you carefully prepare for each experiment by reading the related text material before coming to
the laboratory. In this way you can maximize the laboratory experience.
In conclusion, we view this manual as one of continual modification and improvement. Over the past
few years many improvements have come from student comments and criticisms. We encourage you
to discuss ideas for improvements or suggestions for new experiments with your instructor. Finally,
we hope you find this laboratory manual helpful in your study of chemistry.
Chem 241 - Organic Chemistry 4
LABORATORY SAFETY RULES
Your participation in this laboratory requires that you follow safe laboratory practices. You are required to adhere to the
safety guidelines listed below, as well as any other safety procedures given by your instructor(s) in charge of the course.
You will be asked to sign this form certifying that you were informed of the safety guidelines and emergency procedures
for this laboratory. Violations of these rules are grounds for expulsion from the laboratory.
Note: You have the right to ask questions regarding your safety in this laboratory, either directly or anonymously, without
fear of reprisal.
Goggles must be worn at all times while in lab. You must purchase a pair of goggle for yourself and you may
store them in your locker. You will be advised of the appropriate goggles to be purchased.
Locate the emergency evacuation plan posted by the door. Know your exit routes!
Locate emergency shower, eyewash station, fire extinguisher, fire alarm, and fire blanket.
Dispose of all broken glassware in the proper receptacle. Never put broken glass in the trashcan.
Notify you instructor immediately if you are injured in the laboratory; no matter how slight.
Never pipette fluids by mouth. Check odors cautiously (i.e. wafting). Never taste a chemical.
Shoes must be worn in the laboratory. These shoes must fully enclose your foot.
Long hair must be tied up in a bun during lab work. Loose long sleeves should be avoided in the lab.
Children and pets are not allowed in the laboratory.
Eating or drinking in the lab is prohibited. Do not drink from the laboratory taps.
Wash your hands before and after working in the lab.
Turn off the Bunsen burner when you are not using it.
If any reagents are spilled, notify your instructor at once.
Follow the instructor’s directions for disposal of chemicals.
Only perform the assigned experiment. No unauthorized experiments are allowed.
Every chemical in a laboratory must be properly labeled. If a label is unclear, notify your instructor.
Use the proper instrument (eye-dropper, scoopula, etc.) to remove reagents from bottles. Never return unused
chemicals to the original container. Do not cross contaminate reagents by using the same instrument for 2
different reagents. (e.g. don’t use the mustard knife in the mayonnaise jar)
Material Safety Data Sheets (MSDS) are available for your reference. These contain all known health hazards of
the chemicals used in this course. In addition, there is information concerning protocols for accidental exposure
to the chemical. You are advised to inspect this binder.
Chem 241 - Organic Chemistry 5
TABLE OF CONTENTS
EXPERIMENT 1
Introduction to NMR and IR Spectroscopy 6
WORKSHEET 9
EXPERIMENT 2 Synthesis of p-Nitroacetanilide 11
WORKSHEET 14
EXPERIMENT 3 Synthesis of Aspirin - Ester Formation 16
WORKSHEET 19
EXPERIMENT 4 Reactions of Aromatic Aldehydes - Cannizaro Reaction 21
WORKSHEET 23
EXPERIMENT 5 Synthesis of 9,10-Dihyroanthracene-9,10-endo-α,β-succinic Anhydride:
A Diels-Alder Reaction 24
WORKSHEET 25
EXPERIMENT 6 sec-Butylbenzene - Friedel Craft Alkylation 26
WORKSHEET 28
EXPERIMENT 7 Sodium Borohydride Reduction of Acetophenone 29
WORKSHEET 32
EXPERIMENT 8 Synthesis of 2-Methyl-2-Hexanol: A Grignard Reaction 33
WORKSHEET 40
EXPERIMENT 9 Unknown Reaction – Using NMR/IR to Determine Reactants and Products 42
WORKSHEET 43
EXPERIMENT 10 Biodiesel Synthesis 44
Exam I 47
Exam II 68
Exam III 93
Final Exam 122
Chem 241 - Organic Chemistry 6
EXPERIMENT ONE Introduction to NMR and IR Spectroscopy
Identifying Unknown Liquids
INTRODUCTION
The purpose of this laboratory experiment is for students to learn how to use a Thermo Scientific™
picoSpin™ 80 MHz NMR spectrometer and the Nicolet FT-IR and use the 1H NMR and IR
spectrums to determine the structure of two or more unknown organic liquids chosen from a variety
of compounds representing multiple functional groups.
Using the picoSpin 80 NMR
The general procedure for sample analysis using a picoSpin NMR spectrometer is as follows:
Shimming: Shimming is the procedure that prepares the NMR for use and takes about an hour. Your
instructor will have shimmed NMR prior to lab and made it ready for use.
Pre-sample preparation
Displace the shim fluid (water) from the picoSpin capillary cartridge with air.
Flush the cartridge with 0.1 mL of chloroform, and then displace the solvent with an air push.
A small signal in your sample spectrum may appear at 7.24 ppm due to residual chloroform, it
can be used to shift reference the spectrum.
Set up the onePulse script according to parameters listed in the Pulse Script table.
Pulse Script: onePulse
Parameter Value
tx frequency (tx) proton Larmor frequency (MHz)
scans (ns) 16
pulse length (p1) Instrument specific 90° pulse length
acquisition time (aq) 750 ms
rx recovery delay (r1) 500 μs
T1 recycle delay (d1) 6 s
bandwidth (bw) 4 kHz
post-filter atten. (pfa) 10 (11)a
phase correction (ph) 0 degrees (or any value)
exp. filter (LB) 0 Hz
max plot points 400
max time to plot 250 ms
min freq. to plot -200 Hz
max freq. to plot +1000 Hz
zero filling (zf) 8192
align-avg. data
live plot
JCAMP avg.
JCAMP ind. Unchecked
Chem 241 - Organic Chemistry 7
Injection
Using a 1 mL disposable polypropylene syringe fitted with a 1.5” long, 22 gauge blunt-tip
needle, withdraw a 0.2 mL aliquot of sample.
Inject about half the sample. Ensure all air bubbles have been displaced from the cartridge by
examining the drain tube.
Cap both the inlet and outlet ports with PEEK plugs.
Acquire
Execute the onePulse script according to the values in the table of parameters provided
Once the onePulse script has finished, prepare the cartridge for the next user by displacing the
sample from the cartridge according to the following protocol: air, solvent, air.
Acquisition parameters apply to both the picoSpin 45 and picoSpin 80 spectrometers. Use the tx
frequency (tx) and pulse length (p1) appropriate for each system.
Download the experimental JCAMP spectra files and open them by importing into Mnova. The free
induction decay (FID) will undergo automatic Fourier transformation and a spectrum will be
displayed. To each spectrum, apply the following processing steps using the given settings
MNOVA Processing Parameters
Function Value
Zero-filling (zf) & Linear Predict (LP) 16 k
Forward predict (FP) From aq → 16 k
Backward predict (BP) From -2 → 0
Phase Correction (PH) PH0: Manually adjust
PH1: 0
Apodization
Exponential (LB) 0 Hz
First Point 0.5
Shift reference (CS) Manually reference
Peak Picking (pp) Manually Select Peaks
Integration (I) Automatic Selection
Multiplet Analysis (J) -
EXPERIMENTAL
Students will work in groups and run the 1H NMR spectrum of two or more unknown organic liquids
chosen from those listed below. All of the compounds are liquids and the unknown samples will be
spiked with TMS (tetramethylsilane) at approximately 10% (v/v). The TMS signal should be easily
observed and will be used to normalize the spectrum of your unknown.
Chem 241 - Organic Chemistry 8
POSSIBLE UNKNOWNS Ethyl acetate 2-butanone
Ethyl benzene 4-methoxybenzaldehyde
Methyl salicylate 2-furaldehyde
1-chloropropane 1-chloro-2-methylpropane
Toluene Propanoic acid
RESULTS
Draw the structure of each compound. On your drawing, show all hydrogen atoms and label each
unique set A, B, C, etc. For the interpretation of your 1H NMR spectrum, assign each observed
signal using these labels. For the IR show the bond that gives rise to the important absorptions.
Discuss the number of signals, the chemical shift values, integration of the signals, and splitting
(multiplicity), including coupling constants (J values) if observed and interpretable.
Each person in the group should include the spectrums taken.
Chem 241 - Organic Chemistry 9
NAME DATE ________________
Introduction to NMR and IR Spectroscopy
Identifying Unknown Liquids WORKSHEET
Unknown # ______________
Please draw the molecule and identify and label the proton environments (A, B, C…)
NMR Results – Indicate the shift (ppm) for each proton environment labeled above
A B C D E
IR Results – Indicate the functional groups present and their position on the IR
Bond Type
Position
Unknown # ______________
Please draw the molecule and identify and label the proton environments (A, B, C…)
Chem 241 - Organic Chemistry 10
NMR Results – Indicate the shift (ppm) for each proton environment labeled above
A B C D E
IR Results – Indicate the functional groups present and their position on the IR
Bond Type
Position
Question
Are there any impurities in these unknowns? How can you tell. What evidence do you have?
Chem 241 - Organic Chemistry 11
EXPERIMENT TWO
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 of the solution rises almost 40°C. Both the acetanilide solution and the nitrating solution
(a mixture of HNO3, and H2SO4) must be chilled to about 10°C before the reaction is begun.
To prevent dinitration of the acetanilide, the nitrating mixture is added in small portions to the
acetanilide solution (and not vice versa) so that the concentration of HNO3, is kept at a minimum.
After all the HNO3, H2SO4 solution has been added, the reaction mixture is allowed to warm slowly
to room temperature. If the reaction mixture has been kept excessively cold during the addition, there
will be a relatively large amount of unreacted HNO3, present, which may cause the temperature to
rise above room temperature. If this should happen, the mixture must be rechilled.
The work-up procedure consists of removal of the acids and crystallization of the product. Every trace
of acid must be removed because hydrogen ions catalyze the hydrolysis of the amide to p-nitroaniline
or its protonated cation. Most of the acid is removed by pouring the reaction mixture onto ice and
water, then filtering the flocculent yellow precipitate of p-nitroacetanilide. The last traces of acetic
acid are removed by neutralization. Because bases also catalyze the hydrolysis of amides, the
neutralizing agent used is disodium hydrogen phosphate (Na2HPO4). This reagent reacts with acids to
yield NaH2PO4. The result is a buffered solution with a pH near neutral.
The crude product is air-dried before crystallization. If all of the acid was removed, the product will
be light yellow. A deep yellow to yellow-orange product is indicative of the presence of 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
H2SO4
HNO3
N
C
O
CH3H
NO2
Chem 241 - Organic Chemistry 12
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 m of glacial acetic acid
( T strong irritant), and warm the flask on a hot plate in a fume hood until the acetanilide
dissol es. ool the flask in an ice bath to about 20 then add 10 m of cold, conc. sulfuric acid. The
temperature of the mixture will rise to about 60 . hill the solution to about 10 in an ice bath. (The
solution will become very viscous.)
Mix 3.5 mL of conc. nitric acid and 5 mL of conc. sulfuric acid in a 50-mL flask, and chill the flask
in an ice bath. When both solutions are cold, slowly add the HNO3, H2SO4 solution, 1 mL at a time,
to the acetanilide solution. Keep the reaction flask in an ice bath so that the temperature of the
reaction mixture is maintained between 10-20°C. Stir the reaction mixture carefully after each
addition. The entire addition requires about 15 minutes.
After the addition is completed, allow the reaction flask to stand at room temperature for 30 minutes.
Monitor the temperature; if it rises above 25°C, chill the flask in an ice bath. Should the rechilling be
necessary, allow the flask to stand for 30 minutes or more at room temperature after the rechilling.
Pour the reaction mixture into a 250-mL beaker containing 100 mL of water and 25 g of cracked ice.
Using a large Buchner funnel, filter the heavy lemon-yellow precipitate with vacuum. Press out as
Chem 241 - Organic Chemistry 13
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.)
Chem 241 - Organic Chemistry 14
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).
Chem 241 - Organic Chemistry 15
4. Predict what would happen during the crystallization of p-nitroacetanilide from 95% ethanol if all
the acidic material had not been neutralized previously? Use an equation in your answer. You should
ask yourself, “What is the other 5% and what will it do to this reaction?”
Chem 241 - Organic Chemistry 16
EXPERIMENT THREE 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
Chem 241 - Organic Chemistry 17
An additional small amount of aspirin can be recovered from the mother liquor if it is allowed to
stand overnight. Despite this fact, it is not good practice to leave the bulk of the aspirin in acidic
solution for an extended period of time because it will undergo a slow hydrolysis to yield salicylic
acid and acetic acid, a typical acid-catalyzed ester hydrolysis.
EQUIPMENT
400-mL beaker (for hot water bath) dropper
two 125-mL Erlenmeyer flasks
10-mL and 100-mL graduated cylinders spatula
thermometer
vacuum filtration assembly
two watch glasses
CHEMICALS
acetic anhydride, 5.0 mL
salicylic acid, 2.8 g
conc. sulfuric acid, 3-4 drops
TIME REQUIRED: 1 hour plus overnight drying and time for a melting-point determination
STOPPING POINTS: after the initial vacuum filtration; while the product is crystallizing from
water; while the final product is being air-dried
SAFETY NOTE: Acetic anhydride is volatile and is a strong irritant.
PROCEDURE
Place 2.8 g of salicylic acid in a dry 125-mL Erlenmeyer flask, then add 5.0 mL acetic anhydride and
3-4 drops concentrated sulfuric acid. Mix the resultant white slurry thoroughly with a spatula, and
place the flask in a warm water bath (45-50°C) for 5-7 min. Swirl or stir the mixture occasionally to
dissolve all the solid material. Because the reaction is slightly exothermic, a small temperature rise
can be detected.
Allow the flask to cool. The aspirin begins to precipitate when the temperature of the solution is
about 35-40°C, and the mixture becomes semisolid. When this occurs, add 50 mL water and break up
any lumps with a spatula. Allow the mixture to stand for an additional 5 minutes, then chill the flask
in an ice bath and remove the crystals by vacuum filtration.
Crystallize the crude aspirin from 25 mL of warm water not exceeding 80°C (see Experimental Note).
Allowing the mother liquor to sit overnight may produce a second crop of crystals. Air-dry the
crystals and determine the percent yield and melting point.
Chem 241 - Organic Chemistry 18
EXPERIMENTAL NOTE
At temperatures exceeding 80°C, aspirin forms an oil that dissolves organic impurities from the
water; in this case, it may be difficult to redissolve the aspirin in water. If the solid does not dissolve
in 25 mL of water, add more water from a dropper. Let the mixture warm 2-4 minutes between
additions to allow the solid to dissolve.
Chem 241 - Organic Chemistry 19
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
Chem 241 - Organic Chemistry 20
3a) Commercial aspirin sometimes has a distinct acetic acid odor. Why?
3b) Would ingestion of such aspirin be harmful? Explain.
Chem 241 - Organic Chemistry 21
C
NaOHH2O
C
H O
C
HO O
H H
OH
2 x +
EXPERIMENT FOUR 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
Thermometer (0-250°C)
Bunsen burner
40 mL conc. HCl
Chipped ice
Blue litmus paper
Side arm flask
Buchner funnel
EXPERIMENT: In a small beaker dissolve 0.27 mole (18 g of 85% pure solid) of solid potassium
hydroxide in 18 mL of water and cool the solution to about 25 . lace 0.2 mole (21 g, 20 m ) of
benzaldehyde in a 125-mL Erlenmeyer flask (or narrow-mouth bottle) and to it add the potassium
hydroxide solution. Cork the flask firmly and shake the mixture thoroughly until an emulsion is
Chem 241 - Organic Chemistry 22
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.
Isolation of Benzyl Alcohol
To the mixture add just enough distilled water to dissolve the precipitate of potassium benzoate.
Shake the mixture thoroughly to facilitate solution of the precipitate. Extract the alkaline solution
with three or four 20-mL portions of methylene chloride to remove the benzyl alcohol and traces of
any unconverted benzaldehyde. Combine the methylene chloride extracts for isolation of benzyl
alcohol and reserve the aqueous solution to obtain the benzoic acid.
Concentrate the methylene chloride solution of benzyl alcohol by distillation on a steam bath using a
water-cooled condenser, until the volume of the residual liquid has been reduced to 15-20 mL. A
steam bath is just a beaker of boiling water into which the distillation flask is emersed. Cool the
remaining liquid, transfer it to a small separatory funnel (using 2-3 mL of methylene chloride to rinse
the distilling flask), and shake it thoroughly with two 5-mL portions of 20% aqueous sodium bisulfite
to remove any benzaldehyde. Wash the methylene chloride solution finally with two 10-mL portions
of water and dry it with 3-4 g of anhydrous magnesium sulfate. Filter the solution into a small dry
distilling flask and carefully distill off the methylene chloride. Attach a short air-cooled condenser
and distill the benzyl alcohol, by heating the flask directly with a luminous flame kept in motion.
Collect the material boiling at 200-206°C. The yield is 4-5 g.
Isolation of Benzoic Acid
To free the acid, pour the aqueous solution of potassium benzoate (from which the benzyl alcohol has
been extracted) into a vigorously stirred mixture of 40 mL of concentrated hydrochloric acid, 40 mL
of water, and 40-50 g of chipped ice. Test the mixture with indicator paper to make sure that it is
strongly acidic. Collect the benzoic acid with suction and wash it once with cold water. Crystallize
the product from hot water, collect the crystals, and allow them to dry thoroughly. The yield is about
8g.
Spectroscopy
Run an IR and NMR on your liquid sample and an IR on the solid. Use these spectra to identify your
two products.
Problem
Write equations for the preparation of benzaldehyde from
(a) benzene
(b) toluene
(c) benzoic acid
Chem 241 - Organic Chemistry 23
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 IR 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
Attach your NMR spectrum to this sheet and draw the compound based on the peaks present. Circle
the proton environments and indicate where they are on the NMR.
Chem 241 - Organic Chemistry 24
O
O
O
+
O
O
O
EXPERIMENT FIVE
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 a small beaker of paraffin wax, both covered by
a larger beaker. A typical yield is 2.5 g of colorless product mp 262-264°C. If the sample is tinged
with yellow and has a depressed melting point, recrystallize the product from xylene (20 mL per gram
of product).
Chem 241 - Organic Chemistry 25
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.
Chem 241 - Organic Chemistry 26
C
H3C C
CH3
C-C-C-C-BrAlCl3
EXPERIMENT SIX
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
thermometer (0-200°C)
EXPERIMENT
In a dry 250 mL round-bottomed flask fitted with an upright condenser, place 11g (7.8 mL) of n-butyl
bromide and 50 mL of benzene. To provide for the acid vapors evolved during the reaction do the
experiment in the hood.
Add 0.025 mole (3.25g) of pulverized anhydrous aluminum chloride and allow the reaction to
proceed in the cold, shaking the flask occasionally on a steam bath, and finally reflux the mixture on
a steam bath for about an hour. Cool the reaction mixture and pour it with stirring into a mixture of
40 g ice, 25 g water, and 6 mL of concentrated HCl. Stir thoroughly to dissolve the excess aluminum
compounds and transfer the mixture to a large separatory funnel. Separate the benzene layer and dry
it with 3-4 g anhydrous calcium chloride, and decant the dried liquid into a 250 mL round bottom
flask. Fit the flask with a fractionating column and distill the mixture. Distill very slowly but at a
Chem 241 - Organic Chemistry 27
regular rate. Save all the sample that distills above 130°C and put this into a 50 mL round bottom
flask and refractionate, keeping the ethylbenzene fraction which boils from 173-178°C.
Chem 241 - Organic Chemistry 28
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
Chem 241 - Organic Chemistry 29
C
HO CH3
C
O CH3
NaBH4
EXPERIMENT SEVEN
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 high boiling point, 1-phenylethanol cannot be distilled at atmospheric pressure.
Although it could be vacuum-distilled, distillation could not separate it from unreacted starting
material (if any) because the two compounds have boiling points only 1° apart. (An infrared spectrum
can be used to determine if any ketone is present in the product.)
Chem 241 - Organic Chemistry 30
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 reaction mixture between 30-50°C by
controlling the rate of addition and by cooling the beaker in the ice bath as necessary. As the
acetophenone is added, a white precipitate forms. The addition should take about 45 minutes. After
the addition is complete, allow the reaction mixture to stand at room temperature for 15 minutes with
occasional stirring (or continuous stirring if you are using a magnetic stirrer).
(Stopping Point)
In the fume hood, add about 10 mL of 3M HCl to the reaction mixture. After the reaction has
subsided, heat the mixture to boiling on a hot plate or steam bath in the fume hood until the mixture
separates into two layers.
Chem 241 - Organic Chemistry 31
(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 IR and NMR of your product. From these 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.)
Chem 241 - Organic Chemistry 32
Name DATE ________________
SODIUM BOROHYDRIDE REDUCTION WORKSHEET
Mass of Product Ref. Index CRC Boiling
Point
Theoretical
Yield (grams)
Actual Yield
(Percent)
Attach the IR and NMR 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
Chem 241 - Organic Chemistry 33
EXPERIMENT EIGHT
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.
Grignard apparatus
Chem 241 - Organic Chemistry 34
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
Chem 241 - Organic Chemistry 35
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°C) 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.
Chem 241 - Organic Chemistry 36
Place 2.4 g of oven-dried magnesium turnings in the round-bottom flask. To the dropping funnel, add
a well-mixed solution of 13.7 g of 1-bromobutane and 50 mL of anhydrous diethyl ether.
(CAUTION: flammable! See Safety Note 1; see also Experimental Note 2.)
To initiate the reaction, add 10-15 mL of the ether solution from the dropping funnel to the reaction
flask. Loosen the clamp holding the round-bottom flask and gently swirl the flask to mix the contents.
When the Grignard reagent begins to form, the ether solution will become cloudy and then begin to
boil. Turn on the condenser water at this time. If your Grignard reagent does not start to form within
5-10 minutes, follow the procedure outlined in Experimental Note 3. Because the reaction is
exothermic once initiated, do not add an excessive amount of 1-bromobutane to the magnesium at
any one time (see Safety Note 2).
After the reaction has been initiated, add the remaining ether solution dropwise at a rate that
maintains a gentle reflux. After all the solution has been added, close the stopcock of the dropping
funnel and heat the mixture at a gentle reflux for 15 minutes in a warm (50 ) water bath. s the
magnesium is consumed, the mixture will become darker colored. At the end of the reflux period,
proceed immediately to Step 2.
Step 2, Reaction of n-Butylmagnesium Bromide with Acetone. Chill the flask containing the
Grignard reagent with an ice bath. Pour 5.8 g of anhydrous acetone (not ordinary reagent grade) in the
dropping funnel, and add it a few drops at a time to the reaction mixture. After each addition, loosen
the clamps to the reaction assembly and gently swirl the reaction flask. (CAUTION: See Safety Note
3.)
When the addition of the acetone is completed, allow the reaction mixture to stand at room
temperature for 30 minutes or longer before going on to the hydrolysis step. If the mixture will be
standing for more than an hour, stopper the reaction flask with a glass stopper or a cork (not a rubber
stopper) to prevent the solvent from evaporating.
Step 3, Hydrolysis and Purification. Prepare 100 mL of 25% aqueous ammonium chloride. Mix 75
mL of this solution with 50 g of crushed ice in a 400-mL beaker. Transfer the remaining 25 mL of the
ammonium chloride solution to a 50-mL Erlenmeyer flask, and chill it in an ice bath. Slowly pour the
Grignard reaction mixture into the ice mixture in the beaker, stirring vigorously (see Experimental
Note 4). Rinse the reaction vessel into the ice mixture, first with the 25 mL of chilled NH4C1
solution, then with 25 mL of solvent ether. Transfer the contents of the beaker to a 400-mL
separatory funnel. (If a 250-mL separatory funnel must be used, divide the mixture into two batches
and process each separately.) Add solvent ether to bring the volume of the upper ether layer to about
50 mL, shake the funnel, and allow the layers to separate. Drain the lower aqueous layer into a 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.
Chem 241 - Organic Chemistry 37
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 distil the bulk of the
ether (bp 34.6°C), using a steam bath or heating mantle and an efficient condenser. Stop the
distillation when there is about 25 mL remaining in the distillation flask. Cool the flask and, using a
disposable pipet, transfer the residue to a 50-mL round-bottom flask for distillation of the product.
Wash the last traces of crude product from the 250-mL flask into the 50-mL flask with a few mL of
anhydrous diethyl ether.
Add fresh boiling chips and distil the product, collecting the fraction boiling at 135-143°C in a tared
receiver. A typical yield is 5.0 g (43%). (The yield may vary considerably, depending on the degree
of dryness of the anhydrous ether used in Step 1.) Determine the refractive index of the product. Place
the distilled product in a correctly labeled vial, and hand it in to your instructor.
EXPERIMENTAL NOTES
1) The purpose of the drying tube is to prevent atmospheric moisture from entering the reaction
vessel via the condenser and yet allow the reaction vessel to be open to the atmosphere so that gas
pressure does not build up. There are two types of drying tubes: curved (better) and straight (less
expensive). A straight drying tube must not be connected directly to the top of the condenser because
the dessicant can liquefy and drain into the condenser. Connect the straight tube to the condenser by a
short length of heavy-walled rubber tubing, as shown in Figure 10. In either type of drying tube, the
dessicant is held in place with loose plugs of glass wool. A one-hole rubber stopper may be used as a
secondary plug at the wide end of the drying tube.
2) Solvent ether contains an appreciable amount of water (up to 1-2%) and is totally unsuitable as a
Grignard solvent. Anesthesia ether contains ethanol, which makes it also unsuitable. Commercial
anhydrous ether is adequate only if a freshly opened can is used. Anhydrous ether must not be left
open to the air because it absorbs both oxygen and moisture. (Oxygen and ethers yield peroxides,
which can explode if the ether is distilled. Absorbed moisture will ruin a Grignard reagent.) Your
instructor will probably provide anhydrous ether for this experiment. In many laboratories, storeroom
personnel prepare anhydrous ether by passing solvent ether through a column containing molecular
sieves, which are adsorbents with pores that trap molecules of a certain size (in this case, H2O
molecules). Another procedure for the preparation of anhydrous ether from solvent ether and a
procedure for the testing of peroxides in anhydrous ether follow. If you find it necessary to prepare
your own anhydrous ether, allot an additional laboratory period.
Preparation of Anhydrous Diethyl Ether. With cooling, mix a 2:1 ratio of solvent ether and
conc. H2SO4 in a large round-bottom flask, and distill about two-thirds of the ether. (Do not
distill all the ether.) Any water and ethanol contaminating the ether will remain with the
sulfuric acid. To discard the residue, pour it onto cracked ice, allow the residual ether to
evaporate in the hood, then dilute the aqueous acid with water and pour it down the hood
drain with additional water. Add freshly prepared sodium wire or ribbon to the distilled ether,
then allow the ether to stand at least overnight in the fume hood with the fan on. Stopper the
container with a very loose-fitting cork or drying tube to allow the hydrogen gas to escape.
Chem 241 - Organic Chemistry 38
Sodium wire or ribbon is prepared by pressing sodium metal through a die, using a press. If a
sodium press is not available, the ether can be dried with finely diced sodium; however, diced
sodium is inferior to wire or ribbon. Another method is to add a few grams of CaCl2 to the
ether and allow the mixture to stand until hydrogen has ceased to be evolved. The dried ether
can then be decanted or (better) pipetted, using a rubber bulb, as needed. Commercial
anhydrous ether can be further dried with sodium wire without the sulfuric acid purification
step.
Peroxide Test. Shake 5 mL of ether with a solution of 1 mg of sodium dichromate and one
drop of dilute H2SO4 in 1 mL of water in a corked test tube. If the ether layer turns blue (from
perchromate ion), peroxides are present and must be removed.
Peroxide Removal. Shake the peroxide-contaminated ether with 5% aqueous ferrous sulfate
(FeSO4) solution acidified with H2SO4. The iron(II) ions are oxidized with concurrent
reduction of the peroxide. Aqueous sodium sulfite (Na2SO3) can be substituted for the ferrous
sulfate solution.
3) The most common cause of failure of initiation of the reaction leading to the Grignard reagent is
moisture (in the apparatus, in the ether, or on the magnesium turnings). In addition, in a humid
atmosphere, water will collect on the sides of a cold condenser. If the initial cloudiness becomes a
white precipitate, then the Mg is being converted to Mg(OH)2 by the water, and not to RMgX. If
excessive moisture is present, it is best to begin anew with dry equipment and reagents.
Sometimes, Grignard reagents are reluctant to form because of a magnesium oxide coating on the
metal turnings. The following procedure can often overcome this difficulty. First, warm the reaction
flask with a pan of warm water (about 50-60°C). This warming will cause the ether to boil (not a sign
of initiation, in this case). Remove the warm water bath and watch for the signs of initiation
(spontaneous boiling of the ether). This warming may be repeated if initiation does not occur.
If repeated warming does not initiate Grignard-reagent formation, add an additional 5 mL of the 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.
Chem 241 - Organic Chemistry 39
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.
Chem 241 - Organic Chemistry 40
Name DATE ________________
SYNTHESIS OF 2-METHYL-2-HEXANOL:
A GRIGNARD REACTION: WORKSHEET
Mass of Product Ref. Index CRC Boiling
Point
Theoretical
Yield (grams)
Actual Yield
(Percent)
Attach the IR and NMR 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.
Chem 241 - Organic Chemistry 41
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.
Chem 241 - Organic Chemistry 42
EXPERIMENT NINE
Using NMR and IR to Identify Reactants and Products
Of a Reaction and then use the Results to Predict a Mechanism
INTRODUCTION
This experiment relies on your ability to use NMR and IR to identify the reactants and products of an
unidentified reaction. The procedure is unusually general and gives no hint of the kind of reaction
you are doing and both reactants are only labeled as A and B. Your task will be to identify these
ingredients as well as the product that was made and then determine the mechanism of the reaction.
PROCEDURE
Using the NMR and IR determine the identity of your starting products.
EXPERIMENT
Dissolve 4.0 grams of solid NaOH to 40 mL of water in a beaker. Add 30 mL of 95% ethanol and
cool the solution to 20°C. Place 4.2 g of Component B and 1.2g of Component A in an Erlenmeyer
flask. Swirl the flask until a homogeneous solution is obtained.
Add approximately one-half of the Component A-B solution to the hydroxide solution with vigorous
stirring. Stir the mixture for 10 minutes and then add the reminder of the Component A-B solution.
Continue stirring for another 30 minutes.
Filter the yellow solid with vacuum, press it as dry as possible then transfer it to a clean beaker. Add
100 mL of water. Stir the mixture into a thick paste. If the pasty mixture is strongly alkaline, refilter
and rewash. If the paste is near-neutral, filter with vacuum to obtain the crude product. A typical
crude yield is 3.8 g. Crystalize the crude product from 95% ethanol or ethyl acetate. Determine the
melting point. Take the IR of the solid and determine the NMR by dissolving some of the product in
chloroform. The chloroform peak should be at 7.24.
Chem 241 - Organic Chemistry 43
Name DATE ________________
UNKNOWN REACTION
Mass of Product Melting Point CRC Boiling
Point
Theoretical
Yield (grams)
Actual Yield
(Percent)
Include the NMR and IR of the reactants and products for this reaction and label them.
1) Identity of Component A – draw and name it.
2) Identity of Component B – draw and name it.
3) Identity of the product – draw it.
4) What kind of reaction is occurring in this lab?
5) What is the mechanism for the formation of this product?
Chem 241 - Organic Chemistry 44
EXPERIMENT TEN 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 glycerin soap.
INTRODUCTION
The United States is the largest single consumer of fossil fuels in the world. Each year, the U.S.
consumes 125 billion gallons of gasoline and 60 billion gallons of diesel fuel. With current energy
consumption, the desire to find alternative fuels for our energy needs is increasing. One such
alternative fuel is vegetable oil. Vegetable oil offers the benefits of a greener synthetic route for
obtaining diesel fuel. This fuel source is commonly known as biodiesel, and can be synthesized on an
individual level or on an industrial scale.
The methods behind biodiesel synthesis have been known for quite a while. In recent years, however,
there has been significant interest in the production of biodiesel from the waste oils of the food
industry. Every year, fast food restaurants in the U.S. produce over 3 billion gallons of used cooking
oil. Since many gallons of this used oil inevitably end up in landfills and sewers, the production of
biodiesel from waste oil has the potential to significantly reduce environmental impact.
In this experiment you will synthesize diesel fuel from a triester of glycerol (a triacylglycerol or
triglyceride). This reaction is known as a transesterification reaction. Transesterification is the process
of transforming one type of ester into another type of ester. This reaction incorporates the use of the
strong base sodium methoxide in a base- catalysed nucleophilic addition/elimination reaction at the
carbonyl carbon of the triglyceride. This experiment is not entirely “Green.” The methanol used in
this experiment is derived from petroleum sources. Ethanol, derived from vegetable sources like
corn, could have been used but the product is less volatile and more difficult to make than the methyl
ester.
The overall mechanism is catalyzed by the presence of NaOH. In the first step of the reaction, NaOH
reacts with methanol in an acid-base reaction. The product of this reaction is the very strong base
sodium methoxide and water. In the second step, the sodium methoxide acts as a nucleophile and
attacks the three carbonyl carbons of the vegetable oil. This produces a tetrahedral intermediate that is
highly unstable. The overall result is the "cracking" of the triglyceride. The elimination of the
glycerol backbone leads to the formation of the three methyl esters (the biodiesel) and glycerol. The
NaOH is reproduced as a product in the reaction. If the biodiesel is removed from the mixture,
glycerol and unreacted NaOH and methanol remain. The glycerol can be converted to soap through a
saponification reaction if excess NaOH is used. Care must be exercised when using excess NaOH,
because using too much will produce a jelly like mix of glycerol and soap.
Chem 241 - Organic Chemistry 45
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).
Chem 241 - Organic Chemistry 46
In addition, you should answer the following questions and make them a part of your report.
1. What is the reaction that is occurring that produces biodiesel?
2. Most oils and fats contain palmitic and stearic acid as building blocks. Give the structure for both
these compounds.
3. Describe the role of sodium hydroxide in this reaction.
4. How “Green” is this experiment? Please answer the following,
a) Where did you get your oil/fat you used in this experiment and what would have happened to it
had you not converted it to biodiesel?
b) What was the source of your methanol? Is methanol made from natural sources or is it a product
of the oil industry? s methanol “Green”?
c) What was in the waste product and what did you with it?
Chem 241 - Organic Chemistry 48
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
Chem 241 - Organic Chemistry 49
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
+
Chem 241 - Organic Chemistry 50
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
-
Chem 241 - Organic Chemistry 51
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
Chem 241 - Organic Chemistry 52
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
Chem 241 - Organic Chemistry 53
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
Chem 241 - Organic Chemistry 54
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
+
+
Chem 241 - Organic Chemistry 55
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
Chem 241 - Organic Chemistry 56
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
Chem 241 - Organic Chemistry 57
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
the “inside of the diene.
+ + + +
+ + - -
+ - - +
+ - + -
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
+
+
-
-
+
+
-
-
Chem 241 - Organic Chemistry 58
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
Chem 241 - Organic Chemistry 59
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.
Chem 241 - Organic Chemistry 60
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
Chem 241 - Organic Chemistry 61
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
Chem 241 - Organic Chemistry 62
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
Chem 241 - Organic Chemistry 63
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
Chem 241 - Organic Chemistry 64
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
Chem 241 - Organic Chemistry 65
3) hoose any one of the following MR / R’s and draw the compound.
4a) Cyclopentadiene is not aromatic because it is not completely conjugated and it is not flat. There
are three forms of the molecule that are completely conjugated and one of them is aromatic. Please
draw all three forms and indicate which one is aromatic.
4b) Please draw the MO diagram for each of the molecules you drew above.
Chem 241 - Organic Chemistry 66
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
Chem 241 - Organic Chemistry 67
3) hoose any one of the following MR / R’s and draw the compound.
4a) Cyclopentadiene is not aromatic because it is not completely conjugated and it is not flat. There
are three forms of the molecule that are completely conjugated and one of them is aromatic. Please
draw all three forms and indicate which one is aromatic.
4b) Please draw the MO diagram for each of the molecules you drew above.
See above
Remove H+
Remove H Remove H-
Aromatic
Chem 241 - Organic Chemistry 68
Exam II
Aromatics
Electrophilic Substitution
MO Theory
Hückel Reaction
Chem 241 - Organic Chemistry 69
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+
Chem 241 - Organic Chemistry 70
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
Chem 241 - Organic Chemistry 71
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
Chem 241 - Organic Chemistry 72
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
Chem 241 - Organic Chemistry 73
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
Chem 241 - Organic Chemistry 74
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+
Chem 241 - Organic Chemistry 75
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
Chem 241 - Organic Chemistry 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 ________ ________ ________
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
Chem 241 - Organic Chemistry 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.
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
Chem 241 - Organic Chemistry 78
7) Please complete the following reactions. f there is no reaction, write “ o Reaction.”
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
Chem 241 - Organic Chemistry 79
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
Chem 241 - Organic Chemistry 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 _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
Chem 241 - Organic Chemistry 81
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
Chem 241 - Organic Chemistry 82
7) lease complete the following reactions. f there is no reaction, write “ o Reaction.”
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
Chem 241 - Organic Chemistry 83
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
Chem 241 - Organic Chemistry 84
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.
OCH3 CSH
Chem 241 - Organic Chemistry 85
5a) Please name three criteria that determines whether a molecule is aromatic.
1)
2)
3)
5b) Pyrrole is an aromatic compound. Please draw the compound and explain why it is aromatic.
5c) Please draw the aromatic form of 1,3,5 cycloheptatriene.
5d) The following compound is not currently aromatic. Can it be made aromatic? If so, draw the
aromatic form of the molecule. If not, explain why not.
N
Chem 241 - Organic Chemistry 86
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
Chem 241 - Organic Chemistry 87
7) lease complete the following reactions. f there is no reaction write “ o Reaction.”
C O
H
AlCl3
CH3Cl
HSO3
1. FeCl3, Cl2
2. NH3, NaNH2
1, CO, HCl, AlCl3
2. H2SO4, HNO3
3. LiAlH4
NO2
CH3
Fuming H2SO4
C-C-C-Cl
AlCl3
CC C
KMnO4, H+, H2O,
Cl2, 1000 psi, 300oC
NH2
FeCl3Cl2
Chem 241 - Organic Chemistry 88
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
Chem 241 - Organic Chemistry 89
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.
Cl Cl Cl Cl
NO2 NO2 NO2
+
+
+
Cl+
NO2
A
B
B
A
Most Stable
H O O HHSO3F
H+
H O O H
H
+HO
++ H2O
CH3
HO+
CH3
HHO
+
CH3
OH
+ H+
OCH3 CSH
Chem 241 - Organic Chemistry 90
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).
N
H
H
1,3,5-cycloheptatrieneshowing the electronsin one of the bonds tohydrogen
H
H
Remove the hydrogenwith the electrons so thatyou don't add any more electrons to the ring.
Emptyp orbital
Six total electronsin the ring.
Leaves asH
-
+
Aromatic cation
Chem 241 - Organic Chemistry 91
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
Chem 241 - Organic Chemistry 92
7) lease complete the following reactions. f there is no reaction write “ o Reaction.”
C O
H
AlCl3
CH3Cl
HSO3
1. FeCl3, Cl2
2. NH3, NaNH2
1, CO, HCl, AlCl3
2. H2SO4, HNO3
3. LiAlH4
NO2
CH3
Fuming H2SO4
C-C-C-Cl
AlCl3
CC C
KMnO4, H+, H2O,
Cl2, 1000 psi, 300oC
NH2
FeCl3Cl2
No Reaction - the ring is deactivated
NH2
NH2
CH3
NH2
NO2
CH3HO3S
CC C
COOH
H Cl H
Cl
Cl
H
HCl
Cl
H
H
Cl
NH2
Cl
Lindane - a pesticide
Chem 241 - Organic Chemistry 93
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.
Chem 241 - Organic Chemistry 94
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-
Chem 241 - Organic Chemistry 95
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
Chem 241 - Organic Chemistry 96
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
Chem 241 - Organic Chemistry 97
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
Chem 241 - Organic Chemistry 98
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-
Chem 241 - Organic Chemistry 99
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
Chem 241 - Organic Chemistry 100
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;
f the ester is hydrolyzed then you get a spontaneous decarboxylation of a β keto acid
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+
++
Chem 241 - Organic Chemistry 101
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
Chem 241 - Organic Chemistry 102
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.
Chem 241 - Organic Chemistry 103
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
Chem 241 - Organic Chemistry 104
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
Chem 241 - Organic Chemistry 105
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
Chem 241 - Organic Chemistry 106
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
Chem 241 - Organic Chemistry 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+
Chem 241 - Organic Chemistry 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.
5b) Please describe why aldehydes and ketones go through nucleophilic addition reactions and acids
tend to go through nucleophilic acyl substitions.
Chem 241 - Organic Chemistry 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.
CH O
C C C
O
OO
O
H
C C C C C
O OH
Chem 241 - Organic Chemistry 110
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
Chem 241 - Organic Chemistry 111
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
Chem 241 - Organic Chemistry 112
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+
Chem 241 - Organic Chemistry 113
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
Chem 241 - Organic Chemistry 114
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
Chem 241 - Organic Chemistry 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
Chem 241 - Organic Chemistry 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 rarely on acids or amides. This is not “a better lea ing group” question!
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
Chem 241 - Organic Chemistry 117
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
Chem 241 - Organic Chemistry 118
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
Chem 241 - Organic Chemistry 119
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
Chem 241 - Organic Chemistry 120
3a) Please draw the mechanism of the Hell-Volhardt-Zelinsky reaction using propanoic acid.
3b) Please draw the mechanism of the hydrolysis of a nitrile into an acid in base.
4a) Please explain why we almost always do nucleophilic substitutions on acid chlorides, anhydrides,
and esters, but rarely on acids or amides. This is not “a better lea ing group” question!
Acids and amides have OH and NH2 groups that will react with and neutralize any incoming
nucleophile. The other compounds mentioned do not ha e any H’s or H’s so they do not
suffer from this problem
4b) Please rank the following acids in order of increasing acidity (1 is lowest). Please explain your
reasoning.
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-
Chem 241 - Organic Chemistry 121
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
Chem 241 - Organic Chemistry 123
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?
Chem 241 - Organic Chemistry 124
Answer Key
Problem #1
Sanger – Gly must have been the AA on the far left side (amino side) of the protein
sequence. Lys has an NH2 on its side chain. That is why FDNB attacked it.
Chain = Gly ~
Carb A – Carb A attacks the AA on the other end of the protein (the carboxylic acid
side). Since Ser was released, it must have been the last AA in the chain.
Chain = Gly ~~~~~~~~~~~~~~~~~~~~~~~~~~Ser
Cyanobromide – This cleaves on the carboxyl side of Met. This means that anything
attached to the NH2 side of Met remains attached. There from each piece we deduce,
a) Gly is the first AA in the chain - Gly~(Ala~Lys)~ Met or Gly~( Lys~Ala)~ Met
b) Val~Met in this order because Val is attached to Met’s H2
c) Ser is the last AA so must be Arg~Ser
Chain = Gly ~(Ala~Lys)~Met~Val~Met~Arg~Ser or
Gly ~(Lys~Ala)~Met~Val~Met~Arg~Ser
Trypsin – All we need to do is to resolve the position of Ala with respect to Lys. The
first piece cleaved off does this for us. If the order had been Gly~Lys~Ala~ then trypsin
would have cleaved between Lys and Ala and you would have gotten a piece containing
just Gly+ ys, but you didn’t, you got Gly+ ys+ la which means that the order must
have been Gly~Ala~Lys. So the order of the protein must have been,
Final Chain = Gly~Ala~Lys~Met~Val~Met~Arg~Ser
Chem 241 - Organic Chemistry 125
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
Chem 241 - Organic Chemistry 126
Carbohydrate Problem Set
1) Galactose is the C4 epimer of glucose. Please draw lactose, which is a disaccharide, made by
bonding galactose to glucose using a 1,4’ link. Both sugars must be cyclic.
2) Please draw the ring structure of the C2 epimer of galactose.
3) Please draw the C3 epimer of glucose.
4) Please draw the ring structure of Talose.
5) Please draw the ring structure of Fructose.
6) What is a reducing sugar? Why is it reducing?
7) How do we determine whether a structure is D or L? Is R 3-hydroxybutanoic acid, D or L?
8) Draw lactose. It is galactose––1,4’ glucose.
9) Draw gentiobiose. It is glucose--1,6’ glucose
10) Show the complete mechanism for the base conversion of fructose into glucose.
11) Show the complete mechanism for the acid conversion of fructose into glucose.
Chem 241 - Organic Chemistry 127
Carbohydrate Problem Set
1) Galactose is the C4 epimer of glucose. Please draw lactose, which is a disaccharide, made by
bonding galactose to glucose using a 1,4’ link. Both sugars must be cyclic.
2) Please draw the ring structure of the C2 epimer of galactose.
3) Please draw the C3 epimer of glucose.
4) Please draw the ring structure of Talose.
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
Chem 241 - Organic Chemistry 128
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––1,4’ glucose.
9) Draw gentiobiose. It is glucose--1,6’ 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
Chem 241 - Organic Chemistry 129
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+ +
Chem 241 - Organic Chemistry 130
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
Chem 241 - Organic Chemistry 131
2) Approximately where would you expect to find a C=S bond in an I.R. spectrum? Show your work
and state your assumptions. C= 12, S=32, O=16. Your answer should be somewhere between 1000
and 3000. I want and exact anwser. Show your math.
3) Please explain why we almost always do nucleophilic substitutions on acid chlorides, anhydrides,
and esters, but rarely on acids nor amides. This is not “a better lea ing group” question!
4a) One of the products below was made using a Michael reaction and the other was made using a
Claisen reaction. Which is which?
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
Chem 241 - Organic Chemistry 132
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
Chem 241 - Organic Chemistry 133
7a) Please draw glycine (R = H) dissolved in a neutral solution.
7b) What are the four levels of protein structure? Describe each of them.
a)
b)
c)
d)
8) Galactose is the C4 epimer of glucose. Please draw lactose, which is a disaccharide, made by
bonding galactose to glucose using a 1,4’ link. Both sugars must be cyclic.
9) Please circle the terpene units found in the following compound.
CH3
CH3
CH3
CH3
Chem 241 - Organic Chemistry 134
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,
Chem 241 - Organic Chemistry 135
10 cont’d)
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
Chem 241 - Organic Chemistry 136
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?
12d) What is the “endo” rule?
OO
O
O
2x
Chem 241 - Organic Chemistry 137
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
Chem 241 - Organic Chemistry 138
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,
and esters, but rarely on acids nor amides. This is not “a better lea ing group” question!
Both acids and amides have H’s available because of the hydrogen bonding of the OH and NH2.
These acidic protons interfere with nucleophilic substitutions by neutralizing the nucleophile. That is
why acid derivatives other than acids and amides are used in most syntheses requiring acids.
4a) One of the products below was made using a Michael reaction and the other was made using a
Claisen reaction. Which is which?
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
Chem 241 - Organic Chemistry 139
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
-
Chem 241 - Organic Chemistry 140
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 1,4’ link. Both sugars must be cyclic.
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
Chem 241 - Organic Chemistry 141
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
Chem 241 - Organic Chemistry 142
10 cont’d)
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
Chem 241 - Organic Chemistry 143
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
12d) What is the “endo” rule?
A molecule is endo with the dienophile is oriented in such a way so that the electron withdrawing
groups is able to interact with the p orbitals of the diene.
OO
O
O
2x
O
O
O
O
+
Zero of Energy
HOMO
LUMO
+ +
+ -
+ +
+ -
+ +
+ -
+ +
+ -
+ +
+ -h
Chem 241 - Organic Chemistry 144
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
Chem 241 - Organic Chemistry 145
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.
NCCCC
O
C C N C C
N
O
C
C
C C NH2
O
HO
Cl
HO
OH
O
HCH
O
Chem 241 - Organic Chemistry 146
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).
Chem 241 - Organic Chemistry 147
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
Chem 241 - Organic Chemistry 148
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.
C C C
O
Cl
H
HH
H
H
a b c
Chem 241 - Organic Chemistry 149
7) Please give the product for each of the following reactions.
C C C Cl
C C C O C
O
N
O
O
C C C CH3
O
C C C C C
O O
2. LiAlH4
1. HCN
1. C-C-C-C-Br
2. N2H4, Heat
1. NaNH2
2. Benzaldehyde
3. H2O
1. NaNH2
2. H2O
C2H5NH2
COH
AlCl3, CH3Cl
O
N2H4, OH-,heat
OH
1. PCC
2. C2H5MgBr
3.Water, H+
C C C C NH2
O
HO
Heat
Cl
Chem 241 - Organic Chemistry 150
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?
Chem 241 - Organic Chemistry 151
9a) What are Hückel’s Rules?
9b) An OH peak in NMR is usually a singlet, why? And when would you expect it to be a triplet?
9c) What are the restrictions on Friedel Craft Alkylation?
10) Starting with alkanes, alcohols, benzene, or cyclopentane, synthesize two of the following
compounds.
C O
H
COOH
NH2
NO
Chem 241 - Organic Chemistry 152
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.
NCCCC
O
C C N C C
N
O
C
C
C C NH2
O
HO
Cl
HO
OH
O
HCH
O
2-aminoacetic acid methanal(formaldehyde)
5-aminopentanioic acid lactam
N,N,N-triethylamine
4-chloro-2-hydroxyphenol
diphenylmethanone(benzophenone)
N,N-diphenylbutanimide
Chem 241 - Organic Chemistry 153
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).
C C C C
O
OH
PBr3 C C C C
O
O P
Br
Br
BrH
+ -C C C C
O
O P Br
BrH
+
Br-
C C C C
O-
O P Br
BrH
+
Br
C C C C
O
Brketo-enol
C C C C
OH
Br
Br+
C C C C
OH
Br
Br+
C C C C
O
Br
Br
H+
C C C C
O
Br
Br
+ H+
H3C C CH3
O
NaNH2H3C C CH2
O
-
H3C C CH3
O
H3C C C
O
C
CH3
CH3
O-
H2O
H3C C C
O
C
CH3
CH3
OH
H
H
+ OH-
NaNH2
H3C C C
O
C
CH3
CH3
OH
H
-H3C C C
O
C
CH3
CH3H+ OH
-
C C O C C
O OH
+
C C O C C
O O H+
C C O C C
O O H
+
H2O
C C O C C
O O H
O H
H
+
C C O C C
O O H
O H
H+
C C O C C
O O H
O HH
+
C C OH
O
CCHO
OH +
+ CCHO
O
+ H+
CH3COCC
O
NaNH2 CH2COCC
O
- CH3COCC
O
+
H2
CCOCC
O
C
O
CH3
O C C
-
CCOCC
O
C
O
CH3
OCC+ -
Chem 241 - Organic Chemistry 154
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
NH2 NH2 NH2 NH2
Cl Cl Cl
++
+
NH2
Cl
+
A
B
A
BCl+
OH
O O HHHSO3F
O O HH
H
+OH
++ H2O
OH+
OH
OH
H+
OH
OH
+ H+
Chem 241 - Organic Chemistry 155
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.
C C C
O
Cl
H
HH
H
H
a b c
2.5
+
++++++
---+++
++--++
++-+--
+-++-+
+-+-+-
++
+-
HOMO
LUMO
Zeroof
Energy
h
Reaction occurs Photochemically
CH CH3A CH looking at a CH3 will getsplit into a quartet by thecombination of spins producedby the methyl group.
Chem 241 - Organic Chemistry 156
7) Please give the product for each of the following reactions.
C C C Cl
C C C O C
O
N
O
O
C C C CH3
O
C C C C C
O O
2. LiAlH4
1. HCN
1. C-C-C-C-Br
2. N2H4, Heat
1. NaNH2
2. Benzaldehyde
3. H2O
1. NaNH2
2. H2O
C2H5NH2
COH
AlCl3, CH3Cl
O
N2H4, OH-,heat
OH
1. PCC
2. C2H5MgBr
3.Water, H+
C C C C NH2
O
HO
Heat
Cl
C C C NH2
C C CHN C
O
C
C
HO
C C C C
O
C C C NH2
O
OH
N
O
H
No Reaction
Cl
HO
Chem 241 - Organic Chemistry 157
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
which lea es their hydrophilic “heads” poking out into
the water. This has the affect of making the surface of
the oil look hydrophilic which allows the oil to
emulsify in water, which is how soaps remove oils and
other dirt from clothing.
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.
C
C
C
O
O
O
C
C
C
O
O
O
C
C
C
O
O
O
C
C
P
O
O
O
O P O P O-
O O
O O
O
Fat (Triglyceride) Phospholipid
Fat, oilor dirt
Hydrophobichydrocarbon
Hydrophilicacid (head)
Chem 241 - Organic Chemistry 158
9a) What are Hückel’s Rules?
i Completely conjugate ring
ii Must be flat
iii No orbitals on the zero of energy
9b) An OH peak in NMR is usually a singlet, why? And when would you expect it to be a triplet?
The OH in an NMR is a singlet because hydrogen bonding allows the hydrogen to move on
and off the oxygen more rapidly that the NMR can “see” it. The hydrogen is not on the
oxygen long enough to cause splitting.
An OH would be a triplet if the alcohol were in the gas phase. As a gas, the hydrogen is not
allowed to leave the oxygen and would therefore be split by neighboring hydrogens.
9c) What are the restrictions on Friedel Craft Alkylation?
i The ring cannot be more deactivated that caused by a halogen
ii There cannot be any OH or NH2’s on the ring since they will react with the AlCl3
10) Starting with alkanes, alcohols, benzene, or cyclopentane, synthesize two of the following
compounds.
See next page
C O
H
COOH
NH2
NO
Chem 241 - Organic Chemistry 159
1. Br2, ht-ButO-, t-ButOH3. NBS4. t-ButO-, t-ButOH
C C C
Br1. t-ButO-, t-ButOH2. NBS3. KOH, Ether4. PCC
C C C O C O
H
1. HBr2. EtO-, EtOH
C O
H
1. FeCl3, Cl22. con H2SO4, con HNO3
3. Zn(Hg), HCl
Cl
NH2
1. CN-
2. H+, H2O, Heat
COOH
NH2
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