11/30/2012
Derivatives of Carboxylic Acids
1968 Notable
Events
Reactions
of Acid Chlorides
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And
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StanfordFischer Esterification
Carboxylic Acid Derivatives
Carboxylic acid derivatives include a variety
of functional groups containing a
heteroatom group other than –OH attached
to a carbonyl group.
Examples include: –OR (esters), –OC(O)R
(acid anydrides), –NR1R2, (amides), –halide
(acid halides)
All of these derivatives can be hydrolyzed to
the carboxylic acid by a nucleophilic acyl
substitution reaction.
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Reactivity of Carboxylic Acid Derivatives
The reactivity of carboxylic acid derivatives
toward acyl substitution is shown below:
O
most
reactive
RC
O
X
O
RC
O
CR
O
RC
OR'
O
RC
OH
O
least
reactive
RC
N
Reactions of Acid Chlorides
Acid chlorides can be converted easily into esters,
the carboxylic acid, and amides. You will
examine two of these reactions today.
O
H2O
RC
OH
O
RC
X
O
R'OH
RC
NH3
OR'
O
RC
NH2
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Fischer Esterification
O
PhC
H+
OH
O
PhC
+ CH3OH
OCH3 + H2O
The direct reaction of a carboxylic acid with an
alcohol to form an ester will occur only in the
presence of acid catalyst.
This reaction, called Fischer esterification, is an
equilibrium reaction where the energies of the
products are very close to the energies of the
starting materials.
Fischer esterification
The equilibrium slightly favors product, but
significant starting material remains at
equilibrium.
O
PhC
H+
OH
+ CH3OH
Keq =
O
PhC
OCH3 + H2O
[PhCO2CH3] [H2O]
[PhCO2H] [CH3OH]

4.0
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Increase Ester Formation
O
O
H+
PhC
OH
PhC
+ CH3OH
OCH3 + H2O
[PhCO2CH3] [H2O]
[PhCO2H] [CH3OH]
Keq =

4.0
1. Remove one of the products as it is
formed.
2. Use large excess of other starting reagent.
Mechanism of Fischer Esterification
Acid acts as a catalyst at two points in this
mechanism.
H OH2
O
R
C
O
R
OH
C
H
OH2
O H
R'
C OH
R
OH
2
1
O
H
O
R'
H2O
H
3
R
C
OH2
H OH2
O
C O
R
OR'
5
O H
O H
O
H
R'
H
C
R
4
H OH2
OH
O
R'
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11/30/2012
Mechanism of Fischer Esterification
The second point of acid catalysis is in step
4.
H OH 2
O
R
C
O
OH
R
C
H
OH 2
O H
R'
C OH
R
OH
2
1
O
O
H
R'
H2O
H
3
H OH2
O
R
C
O H
C O
R
OR'
5
OH2
O
H
R'
O H
H
C
R
4
H OH2
OH
O
R'
Procedure
You WILL work in partners for this experiment.
Today’s lab has two parts. You will do the
intial steps in both parts today, and complete
them in lab next week.
Part I is the synthesis of methyl benzoate by
Fischer esterification. You will run the reaction
and isolate the crude product today. You will
store the crude product until next week when
you will distill the product and obtain an IR
spectrum.
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Procedure
In Part II today, you will run the reactions of
benzoyl chloride with water (hydrolysis)
and with ammonia (ammonolysis). Both
reactions form solid products which you will
isolate by filtration. Rinse the products well
with water on the filter pad, because you are
not going to do a recrystallization. You will
store the crystals in your section’s sample
drawer and obtain melting points next week.
Procedure – NEXT WEEK
Obtain m.p. values for your derivatives and
complete classification tests. Use this data to
determine the most likely structure of your
unknown.
You need to write this structure in your lab
note-book and get your TA to initial it before
you take your infrared spectrum.
Obtain an infrared spectrum of your
unknown.
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Structure Deduction
Reference spectra for the various unknowns
will be posted on the webpage for this
experiment on the Thursday after the
second week of this lab.
Use all of your data to deduce the structure
that best matches that data. Explain your
reasoning and any data that might appear
inconsistent in your laboratory report.
Safety
Sulfuric acid is toxic and corrosive. It will
burn skin and create holes in clothing.
Flush with water and then with aqueous
sodium bicarbonate.
Benzoyl chloride is a lachrymator (Quiz
question!)
Ammonium hydroxide is a solution of
ammonia gas in water and releases
ammonia vapor (corrosive toxin).
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Cleanup
Rinse all glassware used with benzoyl
chloride with acetone in the hood into a
waste bottle.
Aqueous phases may be disposed of in the
sink.
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