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LABORATORY!MANUAL!
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SCH!3434!!
ORGANIC!SYNTHESIS!

DEPARTMENT OF CHEMISTRY
KULLIYYAH OF SCIENCE
IIUM!
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CONTENTS

PAGE

General Guidelines for Laboratory Safety Rules

Components of Experimental Report

EXPERIMENT 1 : The Aldol Condensation Reaction: Preparation of


Benzalacetophenone (Chalcones)

EXPERIMENT 2 : Multistep Reaction Sequence: The Conversion of


Benzaldehyde of Benzilic Acid

EXPERIMENT 3 : Phase-Transfer Catalysis: Addition of Dichlorocarbene


to Cyclohexene

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EXPERIMENT 4 : Regioselective and Chemoselective Reduction of ,Unsaturated Carbonyl Compounds by NaBH4/Ba(OAc)2 as Reducing
System

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2!

General Guidelines for Laboratory Safety Rules


Please follow the following guidelines for your safety in the laboratory:
1. Every time you enter the lab, do not forget to wear goggles Students are
advised not to wear contact lens in the lab as the solvents (particularly organic
solvents) are mostly volatile and flammable.
2. Dress properly during a laboratory activity. Shoes must completely cover the
foot. No sandals allowed in the laboratory.

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3. Do not bring food and drink into the laboratory.
4. Be prepared for your work in the laboratory. Read all procedures thoroughly
before entering the laboratory.
Never fool around in the
laboratory. Horseplay, practical jokes, and pranks are dangerous and
prohibited.
5. Observe good housekeeping practices. Work areas should be kept clean and
tidy at all times
6. All chemicals in the laboratory are to be considered dangerous. Avoid
handling chemicals with fingers. Always use a tweezer.

3!

Components of Experimental Report

For each experiment done, a student is required to write a report and submit to the
respective lecturer. In your report, please include the following components:

a) Title and date


- What is the title of the experiment given and date of experiment was
conducted.
b) Introduction
% In the introduction, the student needs to write what is the aims/objectives
of the experiment, what are the instruments used and the balanced
chemical equations involved in the experiment.
c) Procedure of the experiment
% It is better to write in your own words (flow chart, mind map) as it will
reveal your understanding of the experiment carried out.
d) Data and Observations
% The observations are described as the progress in the experiment. It
includes (but not limited to) colour and temperature changes, appearance
of precipitate, the weight of reagent and products, etc.
e) Discussion of data and conclusion
% In this section, you are required to interpret the data obtained and
supported by appropriate references.
f) References
% The references should be taken from books, journals and website.

g) Questions
- Answer all the questions in the lab manual when applicable.

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Laboratory(Grading(Rubric(
Component

1 Introduction

Materials &
methods

Result

Discussion &
4 Conclusion

1-2

3-4

No real introduction. Weak


or
missing Either lacks clarity or Presents a clear summary of the
primary elements.
is missing one of the aims of the study and its
primary elements.
significance. Briefly describes
experimental design. Probably
includes one or more references
to supporting sources.
Methods
barely Some methods are Some methods are Gives a clear picture of the
mentioned.
omitted; others are presented so briefly methods and materials used.
presented
in
a and/or vaguely that it Does not use prescriptive
piecemeal,
vague is unclear how or language. Uses specific, not
form.
why they were done. general, terminology. Detailed,
May be some written step-by-step procedures are
as a protocol rather clearly referenced. Avoids long,
than a description.
redundant descriptions.
No
logical Data is presented Some data may be All figures and tables have titles
connection between haphazardly. It is missing, or legends and legends. All results are
methods and data. sometimes
not may be brief, vague clearly presented, with a logical
Irrelevant data may possible to tell what or uninformative.
sequence. Controls are clearly
be included, and material or procedure
indicated.
relevant data left was used to obtain the
out. No legends.
data.
Mostly a restatement Very little analysis of There may be some It is clear that the methods and
of
results.
No the results. Statements lack of clarity. Did results have been understood.
analysis given. No are vague and general. the writer understand The results (including controls)
recognition of error Inconsistencies
are why certain methods are related to the questions
sources.
No explained by 'human were used, and how posed and analyzed for their

Marks
(30)
/5

/5

/5

/5

understanding
controls.
No conclusion

Questions

Writing
6 Quality
(including
references)

of error' or
similar.

something the results could shed


light on the questions
asked?
Incomplete
Conclusion
shows analysis
of
little
effort
and inconsistencies and
reflection
unexpected results.

effectiveness.
Possible
explanations for inconsistencies
and/or unexpected results are
given.
Conclusion includes a summary
of the experiment, whether the
findings
supported
the
hypothesis, possible sources of
error, and what was learned
from the experiment

Conclusion includes a
general overview of
the experiment and
what was learned
from the experiment
Questions
not Questions answered Questions answered Questions
answered
and
answered
but with a lack but
with
little showed a good understanding
explanation
explanation
on the relevant topic with a
good support of full explanation
Frequent
Apparently
not An occasional error
No spelling or grammatical
grammatical errors: proofread for errors.
errors.
incomplete
sentences,
tense
changes,
misspellings.
Reference
not Reference
with Able to cite and write complete
following the format.
occasional error in reference using IIUM format
No reference at all.
format

/5

/5

30
(

6!

EXPERIMENT 1
The Aldol Condensation Reaction: Preparation of Benzalacetophenone
(Chalcones)
Apparatus:
50-mL Erlenmeyer flask
spatula
beaker (50 mL)
Bchner funnel (& flask)
Chemicals:
3-nitrobenzaldehyde
Acetophenone
95% ethanol
sodium hydroxide
Benzaldehyde reacts with a ketone in the presence of base to give ,-unsaturated
ketones. This reaction is an example of a crossed aldol condensation where the
intermediate dehydrates to produce the resonance-stabilised unsaturated ketone.
H
C6H5

O
+

C
O

H3C

HO-

H
C6H5

O
CH2 C R

OH

H2O

H
C6H5

O
C

Intermediate

Cross aldol condensations of this type proceed in high yield since benzaldehyde
cannot react with itself by an aldol condensation reaction because it has no hydrogen. Likewise, ketones do not react easily with benzaldehyde.
In this experiment, procedures are given for the preparation of benzalacetophenones
(chalcones). You should choose one of the substituted benzaldehydes and react it with
the ketone, acetophenone.
Procedure
Place 0.75 g (5 mmol) of 3-nitrobenzaldehyde (MW = 151.1) into a 50-mL
Erlenmeyer flask. Add 0.60 mL of acetophenone (MW = 120.2, d = 1.03 g/mL) and
4.0 mL of 95% ethanol to the flask containing the aldehyde. Swirl the flask to mix the
reagents and dissolve any solids present. It may be necessary to warm the mixture on
a steam bath or hot plate to dissolve the solid. If this is necessary, then the solution
should be cooled to room temperature before proceeding with the next step.
Add 0.5 mL of sodium hydroxide solution (note to instructor: reagent prepared by
dissolving 6.0 g NaOH into 10 mL of water). Swirl the mixture until it solidifies or
until the entire mixture becomes very cloudy.
Isolation of the crude product. Add 10 mL of ice water to the flask. If a solid is
present at this point, stir the mixture with a spatula to break up the solid mass. If an oil
is present, stir the mixture until the oil solidifies. Transfer the mixture to a beaker with

15 mL of ice water. Stir the precipitate to break it up and then collect the solid in a
Bchner funnel. Wash the product with cold water. Allow the solid to air dry for
about 30 minutes. Weigh the solid and determine the percentage yield.
Crystallisation of the Benzalacetophenone (Chalcone). Crystallise all of the sample
from hot 95% ethanol. Use about 4 mL of ethanol per gram of solid. Scratch the flask
to induce crystallisation while cooling.
Determine the melting point of your product.
Obtain the proton and carbon-13 NMR spectrum.
Questions:
1. Give the mechanism for the preparation of the benzalacetophenone using the
given aldehyde in the experiment.
2. Draw the structure of the cis and trans isomers of the compound that you
prepared. Why did you obtain the trans isomer?
3. Using proton NMR, how could you experimentally determine that you have
the trans isomer rather than the cis isomer?
4. Provide the starting materials needed to prepare the following compounds:
O
a) H3CH2CHC C C H

b)

C
H

C C C Ph
H3C

CH3

c) H3CO

Ph

O
CH C C
H

8!

CH

OCH3

EXPERIMENT 2
Multistep Reaction Sequence: The Conversion of Benzaldehyde of Benzilic Acid
Apparatus:
50-mL Erlenmeyer flask
Bchner funnel (vacuum filtration)
magnetic stirring bar
condenser (reflux) joint that can fit the flask
stirring hot plate
25-mL round-bottom flask
heating mantle
100-mL Erlenmeyer flask
filter paper
pH paper
50 or 100 mL- measuring cylinder
stopcock grease
Chemicals:
Thiamine hydrochloride
95% ethanol
NaOH
Benzaldehyde
Boiling stone
KOH
concentrated hydrochloric acid
concentrated nitric acid
The Experiment demonstrates multistep synthesis of benzilic acid starting from
benzaldehyde. First, benzaldehyde is converted to benzoin using a thiamine-catalysed
reaction. This part of the experiment demonstrates how a green reagent can be
utilised in organic chemistry. Then, nitric acid oxidises benzoin to benzil. Finally,
benzil is rearranged to benzilic acid.
A. Preparation of Benzoin by Thiamine Catalysis
In this experiment, two molecules of benzaldehyde will be converted to benzoin
condensation reaction:

O
2

Thiamine
hydrochloride

OH

Benzaldehyde

Benzoin

Thiamine hydrochloride is structurally similar to thiamine pyrophosphate (TPP),


which is a coenzyme universally present in all living systems. It catalyses several
biochemical reactions in natural systems.

9!

thiazole ring
NH2
N

N
N

H3C

NH2

CH3

O
S

OH OH
P O P OO
O

H3C

CH3

ClN

OH
S

Thiamine hydrochloride

TPP

Thiamine binds to an enzyme before the enzyme is activated. The enzyme also binds
to the substrate (protein). Without the coenzyme thiamine, no chemical reaction
would occur.The coenzyme is the chemical reagent.The protein molecule (enzyme)
helps and mediates the reaction by controlling stereochemica;, energetic and entropic
factors, but it is nonessential to the overall course of the reactions that it catalyses.
The most important part of the entire thiamine molecule is the central ring, the
thiazole ring, which contains nitrogen and sulphur. This ring constitutes the ragent
portion of the coenzyme. Experiments with the model compound 3,4dimethylthiazolium bromide found that it rapidly exchanged the C-2 proton for
deuterium in D2O solution. At a pD of 7 (no pH here), this proton was completely
exchanged in seconds! This indicates that the C-2 proton is more acidic than expected.
It is apparently easily removed because the conjugate base is a highly stabilised ylide.
An ylide is a compound or intermediate with positive and negative formal charges on
adjacent atoms.

H3C
C-2

H3C

H3C

H3C
S

N
H

D2O
28 oC

H3C N

Br-

H3C

N
D

Br-

The sulphur atom plays an important role in stabilising this ylide. This was shown by
comparing the rate of exchange of 1,3-dimethyl-imidazolium ion with the rate for the
thiazolium compound shown in the previous equation. The dinitrogen compound
exchanged its C-2 proton more slowly than the sulfur-containing ion. Sulfur, being in
the third row of the periodic chart has d orbitals available for bonding to adjacent
atoms. Thus is has fewer geometrical restrictions than carbon and nitrogen atoms do
and can form carbon-sulfur multiple bonds in situations in which carbon and nitrogen
normally would not.
In this experiment, we will utilise thiamine hydrochloride to catalyse the benzoin
condensation. The mechanism (only thiazole ring is shown) is shown below:

10!

CH3
R N

CH3
R

R N

S
B-

H
Ph

R N
B-

CH3

CH3

H B

R N

R
S

S
H
Ph OH

Ph
OH
H

Ph

Ph

O
+

OH
Ph

R N

R
S

CH3

CH3

CH3

R N

H B

S
Ph
H
O H
Ph OH
B-

R N

R
S

Ph
H
OH
Ph OH

Procedure
Add 1.5 g thiamine hydrochloride to a 50-mL Erlenmeyer flask. Dissolve the solid in
2 mL of water by swirling the flask. Add 15 mL of 95% ethanol and swirl the solution
until it is homogeneous. To this solution, add 4.5 mL of an aqueous sodium hydroxide
(instructor: dissolve 40 g of NaOH in 500 mL water) solution and swirl the flask
until the bright yellow colour fades to a pale yellow colour. Carefully measure 4.5
mL of pure benzaldehyde and add it to the flask. Swirl the contents of the flask until
they are homogeneous. Stopper the flask and allow it to stand in a dark place for at
least two days.
Isolation of Crude Benzoin. If crystals have not formed after two days, initiate
crystallisation by scratching the inside of the flask with a glass stirring rod. Allow
about 5 minutes for the crystals of benzoin to fully form. Place the flask, with crystals
into an ice bath for 5-10 minutes.
If for some reason the product separates as an oil, it may be helpful to scratch the
flask with a glass rod or seed the mixture by allowing a small amount of solution to
dry on the end of a glass rod and then placing this into the mixture. Cool the mixture
in an ice bath before filtering.
Break up the crystalline mass with a spatula, swirl the flask rapidly and quickly
transfer the benzoin to a Bchner funnel under vacuum. Wash the crystals with two 5mL portions of ice-cold water. Allow the benzoin to dry in the Bchner funnel by
drawing air through the crystals for about 5 minutes. Transfer the benzoin to a watch
glass and leave it in an oven set at about 100 oC for a few minutes to dry.
Weigh the benzoin and calculate the percentage yield based on the amount of
benzaldehyde used initially. Determine the melting point.
Purify the crude benzoin by crystallisation from hot 95% ethanol using Erlenmeyer
flask. After the crystals have cooled in an ice bath, collect the crystals on a Bchner
funnel. The product may be dried in a few minutes in an oven set at about 100 oC.
Determine the melting point of the purified benzoin.

11!

Questions:
1. The infrared spectra of benzoin and benzaldehyde are given. Interpret the
principal peaks in the spectra.

2. Draw a mechanism for the cyanide-catalysed conversion of benzaldehyde to


benzoin, The intermediate (shown in brackets), is thought to be involved in the
mechanism.
2

CHO

O OH
C CH

CNOH
C
CN

B. Preparation of Benzil
In this experiment, benzil is prepared by oxidation of an -hydroxyketone, benzoin
prepared earlier. This oxidation can be done with mild oxidising agents such as
Fehlings solution or copper sulphate in pyridine. In this experiment, it is performed
with nitric acid.

HNO3

OH

12!

Place 2.5 g of benzoin into a 25-mL round-bottom flask and add 12 mL of


concentrated nitric acid. Add a magnetic stirring bar and attach a water condenser.In a
hood, set up the apparatus for heating in a hot water bath. Heat the mixture in a hot
water bath at about 70 oC for 1 hour, with stirring. Avoid heating the mixture above
this temperature to reduce the possibility of forming a by-product. During the 1-hour
heating period, nitrogen oxide gases will be evolved. If it appears that gases are still
being evolved after 1 hour, continue heating for another 15 minutes but then
discontinue heating at that time.
Isolation of Crude Benzil. Pour the reaction mixture into 40 mL of cool water and
stir the mixture vigorously until the oil crystallises completely as a yellow solid.
Scratching or seeding will be necessary to induce crystallisation. Vacuum filter the
crude benzyl on a Bchner funnel and wash it well with cold water to remove the
nitric acid. Allow the solid to dry thoroughly by drawing air through the fiter. Weigh
the crude benzyl and calculate the percentage yield of the crude benzil.
Crystallisation of product. Purify the solid by dissolving it in hot 95% ethanol in an
Erlenmeyer flask using a hot plate as the heating source. Be careful not to melt the
solid on the hot plate. You can avoid melting the benzil by occasionally lifting the
flask from the hot plate and swirling the contents of the flask. You want the solid to
dissolve in the hot solvent rather than melt. You will obtain better crystals if you add
a little extra solvent after it dissolves completely. Remove the flask from the hot plate
and allow the solution to cool slowly. As the solution cools, seed it with a solid
product that forms on a spatula after the spatula is dipped into the solution. The
solution may become supersaturated unless this done and crystallisation will occur too
rapidlt. Yellow crystals are formed. Cool the mixture in an ice bath to complete the
crystallisation. Collect the product on a Bchner funnel. Continue drawing air through
the crystals on the Bchner funnel by suction for about 5 minutes. Then remove the
crystals and air-dry them.
Yield Calculation and Melting-Point Determination. Weigh the dry and calculate
the percentage yield. Determine the melting point. Obtain the infrared spectrum of
benzil. Compare the spectrum with benzoin and note the differences.

13!

C. Preparation of Benzilic Acid


In this experiment, benzilic acid will be prepared by causing the rearrangement of the
-diketone benzil.
O

Ph C

Ph

KOH

Ph C

O K+

K+ O

Ph C

OH

Ph

Ph

OH O
Ph C

OH

OH

H3O+

OH O
Ph C

O K+

Ph

Ph

Add 2.00 g benzil and 6 mL 95% ethanol to a 25-mL round-bottom flask. Place a
boiling stone in the flask and attach a reflux condenser. Be sure to use a thin film of
stopcock grease when attaching the reflux condenser to the flask. Heat the mixture
with a heating mantle or hot plate until the benzil has dissolved. Using a Pasteur
pipette, add dropwise 5 mL of an aqueous potassium hydroxide solution downward
through the reflux condenser into the flask. Gently boil the mixture with occasional
swirling of the contents of the flask. Heat the mixture at reflux for 15 minutes. The
mixture will be blue black in colour. As the reaction proceeds, the colour will turn to
brown, and the solid should dissolve completely. Solid potassium benzilate may form
during the reaction period. At the end of the heating period, remove the assembly
from the heating device and allow it to cool for a few minutes.
Crystallisation of Potassium Benzilate. Detach the reflux condenser when the
apparatus is cool enough to handle. Transfer the reaction mixture, which may contain
some solid, with a Pasteur pipette into a small beaker. Allow the mixture to cool to
room temperature and then cool in an ice-water bath for about 15 minutes until
crystallisation is complete. It may be necessary to scratch the inside of the beaker with
a glass stirring rod to induce crystallisation. Crystallisation is complete when virtually
the entire mixture has solidified. Collect the crystals on a Bchner funnel by vacuum
filtration and wash the crystals thoroughly with there 4-mL portions of ice-cold 95%
ethanol. The solvent should remove most of the colour from the crystals.
Transfer the solid, which is mainly potassium benzilate, to a 100-mL Erlenmeyer
flask containing 60 mL of hot (70 oC) water. Stir the mixture until all solid has
dissolved or until or appears that the remaining solid will not dissolve. Any remaining
solid will likely form a fine suspension. If solid does remain in the flask, gravity-filter
the hot solution through fast-fluted filter paper until the filtrate is clear. If no solid
remains in the flask, the gravity filtration step may be omitted. In either case, proceed
to the next step.
Formation of Benzilic Acid. With swirling of the flask, slowly add dropwise 1.3 mL
of concentrated hydrochloric acid to the warm solution of potassium benzilate. As the
solution becomes acidic, solid benzilic acid will begin to precipitate. Keep adding the
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14!

hydrochloric acid until the solid stays permanently and then start monitoring the pH.
The ideal pH should be about 2; if it is higher than this, add more acid and check the
pH again. Allow the mixture to cool to room temperature and then complete the
cooling in an ice bath. Collect the benzilic acid by vacuum filtration using a Bchner
funnel. Wash the crystals with two 30-mL portions of ice-cold water to remove
potassium chloride slat that sometimes coprecipitates with benzilic acid during the
neutralisation with hydrochloric acid. Remove the wash water by drawing air through
the filter. Dry the product thoroughly by allowing it to stand until the next laboratory
period.
Melting point and Crystallisation of Benzilic Acid. Weigh the dry benzilic acid and
determine the percentage yield. Determine the melting point of the dry product.
Recrystallise the product using hot water if necessary.
Questions:
1. Show how to prepare the following compounds starting from the appropriate
aldehyde.
OH

a)
H3CO

b)

C CO2H

OH
C CO2H

OCH3

2. Give the mechanisms for the following transformations:


a)

O
1) KOH

HO

CO2H

2) H+

b)
O
Ph C

O
C

Ph

-OCH

OH O
3

CH3OH

15!

Ph C
Ph

OCH3

Tranmittance

3. Interpret the infrared spectrum of benzilic acid.

16!

EXPERIMENT 3
Phase-Transfer Catalysis: Addition of Dichlorocarbene to Cyclohexene
Apparatus:
25-mL round-bottom flask
250-mL beaker
hot plate stirrer
magnetic stir bar
glass stopper
reflux apparatus (condenser that can fit the round-bottom flask joint)
125-mL separatory funnel
methylene chloride
Erlenmeyer flask (small & medium)
Pasteur pipette
Steam bath
Chemicals:
Cyclohexene
NaOH
Chloroform
benzyltriethylammonium chloride
anhydrous sodium sulphate
NaCl
A haloform, CHX3 will react with a strong base to give a highly reactive carbine
species CX2 by reactions (1) and (2). In the presence of an alkene, this carbine adds to
the double bond to produce a cyclopropane ring (3).

X
X C H
X
X
X

X
X C
X

O H

slow

(1)

(2)

X CH2+ XX

C
X CH2

H2O

C
(3)

Normally, the reaction has been carried out in one homogeneous phase in anhydrous
t-butyl alcohol solvent, using t-butoxide ion as the base [t-Bu = C(CH3)3].

17!

HCX3

Ot Bu +

C C

t-Bu-OH

+ HOt Bu + X-

C
X

Unfortunately, this technique requires time and effort to give good results. In addition,
water must be avoided to prevent conversionof the haloformand carbine to formate
ion and carbon monoxide by the undesirable base-catalysed reactions.
As an alternative to homogeneous reaction, a two-phase reaction can be considered
when the organic phase contains the alkene and a haloform CHX3 and the aqueous
phase contains the base OH. Unfortunately, under these conditions the reaction will
be very slow, because the two primary reactants CHX3 and OH are in different
phases. The reaction rate can be substantially increased, however, by adding a
quarternary ammonium salt such as benzyltriethylammonium chloride as a phasetransfer catalyst.
CH2CH3
CH2

CH2CH3

Cl-

CH2CH3
Other common catalysts are tetrabutylammonium bisulfate, trioctylmethylammonium
chloride and cetyltrimethylammonium chloride. All these catalysts have at least 13
carbon atoms. The numerous carbon atoms give the catalyst organic character
(hydrophobic) and allow it to be soluble in the organic phase. At the same time, the
catalyst also has ionic character (hydrophilic) and can therefore be soluble in the
aqueous phase.
Because of this dual nature, the large cation can cross the phase boundary efficiently
and transport a hydroxide ion from the aqueous phase to the organic phase. Once in
the organic phase, the hydroxide ion will react with the haloform to give
dihalocarbene by reactions 1 and 2. Water, a product of the reaction, will move from
the organic phase to the aqueous phase, thus keeping the water concentration in the
organic phase section on quaternary ammonium salt catalysis.

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Organic phase
CHX3 +

C C

C C
+

CHX3 + HO-

C
C
X

+
CX2 + H2O + R4- N
X
Phase boundary

R4N+ XAqueous phase


H2O + NaOH
Crown ethers are very expensive to ammonium salts and are not used as widely for
large-scale reactions. In some cases, however, these ethers may be necessary to obtain
an efficient and high-yield reaction.
In this experiment, you will prepare 7,7-dichlorobicyclo[4.1.0]heptane (also known as
7,7-dichloronorcarane) by the reaction

Cl
+ CHCl3 +

OH-

Cl

+ H2O + Cl-

Chloroform and base are used in excess in this reaction. Although most of the
chloroform reacts to give the 7,7-dichloronorcarane via carbine intermediate, a
significant portion is hydrolysed by the base to formate ion and carbon monoxide.
Bromoform, CHBr3, can be used to prepare the corresponding 7,7-dibromonorcarane
via the dibromocarbene.
Procedure
Pre-weigh a 25-mL round-bottom flask with glass stopper and transfer 2.0 mL of
cyclohexene to the flask in a hood. Stopper the flask and re-weigh it to determine the
weight of cyclohexene. Add 5.0 mL of 50% aqueous sodium hydroxide (instructor:
Dissolve 50 g of NaOH in 50 mL of water. Cool the solution to RT) to the flask,
being careful to avoid getting any solution on the glass joint. In a hood, add 5.0 mL of
chloroform to the round-bottom flask. Weigh 0.20 g of the phase-transfer catalyst,
benzyltriethylammonium chloride, on a smooth piece of paper and reclose the bottle
immediately (it is hygroscopic!). Add the catalyst to the flask and stopper it.
In a hood, prepare a hot water bath at 40 oC using a 250-mL beaker and hot plate.
Assemble a reflux apparatus and clamp the condenser so that the flask is immersed in
the water bath. Stir the mixture as rapidly as possible for 1 hour. An emulsion forms
during this time.

19!

Following this reaction time, remove the flask from the water bath and allow the
reaction mixture to cool to room temperature. Pour the reaction mixture into a small
beaker and remove the magnetic stir bar. Transfer the mixture to a 125-mL separatory
funnel. Add 8 mL of water and 5 mL of methylene chloride to the mixture. Shake the
mixture with venting for about 30 seconds and allow the layers to separate. Swirl the
funnel gently to help break up the emulsion. Drain the lower methylene chloride layer
into a small Erlenmeyer flask. The small amount of emulsion that forms at the
interface should be left behind with the aqueous layer. Add another 5-mL portion or
methylene chloride, shake the mixture for 30 seconds, and allow the layers to separate.
It may be necessary to swirl the funnel gently or tap the funnel gently with your finger
to help break up the emulsion. Combine the lower organic layer with the first extract.
Discard the remaining aqueous layer into the container for aqueous waste, avoiding
contact with the basic solution. Rinse the funnel with water and pour the combined
organic layers back into the separatory funnel. Extract the mixture with 10 mL of
saturated sodium chloride solution. Drain the lower methylene chloride layer,
avoiding any emulsion that might be present at the interface, into a dry Erlenmeyer
flask containing 0.5 g of anhydrous sodium sulphate. Stopper the flask and swirl it
occasionally for at least 10 minutes to dry the organic layer.
Using a dry Pasteur pipette, transfer about half of the dried organic layer to a dry,
preweighed centrifuged tube. Evaporate the methylene chloride, together with any
remaining cyclohexene and chloroform in a hood.
Following removal of methylene chloride, you are left with 7,7-dichloronorcarane of
sufficient purity for spectroscopy. Weigh the centrifuge tube, determine the weight of
product and calculate the percentage yield. Obtain the infrared spectrum.
Questions:
1. Why did you wash the organic phase with saturated sodium chloride solution?
2. What short chemical test could you make on the product to indicate whether
cyclohexene is present or absent?
3. Would you expect 7,7-dichloronorcarane to give a positive sodium-iodide-inacetone test?
4. Assign the C-H stretch for cyclopropane ring hydrogens in the infrared
spectrum.
5. Suggest why it may be necessary to use a large excess of chloroform in this
reaction.
6. A student obtained a proton NMR spectrum of the product isolate in this
experiment. The pectrum shows peaks at about 7.3 and 5.6 ppm.What do you
think these peaks indicate? Are they part of 7,7-dichloronorcarane spectrum?
7. Draw the structures of the products that you would expect from the reactions
of cis- and trans-2-butene with dichlorocarbene.
8. Draw the structures of the expected dichlorocarbene adduct of methyl
methacrylate (methyl 2-methylpropenoate). With compounds of this type,
another product could have been obtained. It is the chloroform adduct to the
double bond (Michael-type reaction). What would this structure look like?

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EXPERIMENT 4
Regioselective and Chemoselective Reduction of ,-Unsaturated Carbonyl
Compounds by NaBH4/Ba(OAc)2 as Reducing System
Apparatus:
10-mL round-bottom flask
Condenser (to fit the RB flask)
Magnetic stirrer
TLC paper plates
Chemicals:
Benzylideneacetone
Barium acetate
n-hexane
Ethyl acetate
dichloromethane
anhydrous sodium sulphate
Procedure
In a 10-mL round-bottom flask equipped with a magnetic stirrer and a condenser, a
solution of benzylideneacetone (0.146 g, 1 mmol) and Ba(OAc)2 (0.05 g, 0.2 mmol)
in CH3CN (3 mL) was prepared, and NaBH4 (0.076 g, 2 mmol) was added. The
resulting mixture was stirred under reflux conditions. TLC monitored the progress of
the reaction (eluent; n-hexane/EtOAc: 9/1). After completion of the reaction within 15
minutes, distilled water (5 mL) was added to the reaction mixture and it was stirred
for an additional 5 minutes. The mixture was extracted with CH2Cl2 (3 x 8 mL) and
dried over anhydrous sodium sulphate. Evaporation of the solvent afforded the pure 4phenyl-3-buten-2-ol.
Questions:
1. Define and explain the terms regioselective and chemoselective.
2. Reduction of ,-unsaturated carbonyl compounds can follow two pathways:
addition to carbonyl group and addition to conjugated double bonds.
a) Give the mechanism for each of the pathways
b) How the selectivity of the reactions are controlled?
References
1. Any organic chemistry reference books
2. Mohamadi, M., Setamdideh, D. and Khezri, B., (2013), Organic Chemistry
International, 13, 1-5.

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