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CHAPTER 22: CARBOXYLIC ACID DERIVATIVES
GENERAL INFO
FAMILY
Acid Halide Anhydride Ester Amide Nitrile
EXAMPLES OF DERIVATIVES
Pear essence Apple essence Banana essence Pineapple essence
Caffeine stimulant
Melatonin Hormone, causes
drowsiness at night
Aspartame Artificial sweetener
Amygdalin Poison in apple seeds
X
O
O
O O
OR
O
NR2
OC NR
OH
O
Acid halideAnhydride
Ester
Amide
Nitrile
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NOMENCLATURE
ACID HALIDES The C=O is understood to be carbon #1. Ending is
–oyl halide.
ANHYDRIDES
We will only name symmetric anhydrides. Name one side with
ending –oic, then add anhydride. (C=O is always carbon #1.)
ESTERS
Name group on oxygen side as “alkyl,” then in a second word the
group on carbonyl side with ending –oate. (C=O is always carbon
#1.) Alkyl alkanoate.
Ph
O
OO
O
Ph
OH
O
HO
O P4O10+
O
O O
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AMIDES Name group on nitrogen side as “N-alkyl,” then consider
it a substituent and order alphabetically with other substituents.
C=O is always carbon #1. Ending is -amide.
SPECTROSCOPY
IR SPECTRA
1799 cm-1
1833, 1767 cm-1
1750 cm-1
1688 cm-1
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RESONANCE CONTRIBUTIONS
H3C–NH2
H3C–OH
H3C–Cl
Bond lengths1
IR C=O WAVENUMBER
Of all the carboxylic acid derivatives, why does an amide have
the lowest C=O absorption in its IR spectrum?
Why are the anhydride’s C=O absorptions in IR spectra at a
higher wavenumber than an ester’s?
1 Jones, M., Fleming, S.A., Organic Chemistry, 4th ed., Norton,
2010, pp. 1039.
Z
O
NH2
O
OCH3
O
Cl
O
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13C NMR SPECTRA
1H + 13C NMR SPECTRA OF AMIDES
Predict the total number of signals in the 13C NMR spectra of
each compound:
Carbon of carbonyl
Ald/Ket:185-220 ppm
Ester/Acid/Amide155-185 ppm
NH
H
O
N
H
H
Cl
2H
1H 3H
1H NMR of DMF 13C NMR of DMF
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NUCLEOPHILIC ACYL SUBSTITUTIONS
GENERAL PATTERN
GENERAL REACTIVITY
ACID HALIDE REACTIONS
TO CARBOXYLIC ACIDS
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TO ESTERS
TO AMIDES
EXAMPLES
N,N-diethyl-m-toluamide
(DEET)
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ANHYDRIDE REACTIONS
TO CARBOXYLIC ACIDS
TO ESTERS
TO AMIDES
EXAMPLES
OH
Protein
OO O+
succinyl anhydride “modified proteins”
Salicylic acid
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PHOSPHATE ESTERS IN BIOCHEMISTRY Step 1 of Glycolysis (Initial
metabolism of glucose):
Mechanism:
CARBOXYLIC ACID REACTIONS
FISCHER ESTERIFICATION
GENERAL REACTION
ATP
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MECHANISM
EXAMPLES
CH3OHH+OH
O+ H2O
OCH3
O
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REACTION TO AMIDES
INEFFICIENT REACTION (WE WON’T USE)
BETTER PROCESS (USE THIS ONE)
Thionyl Chloride Mechanism (FYI)
EXAMPLES
OH
OSOCl2
OH
O
ClSCl
O
OH
OS
O
ClCl
OH
OS
O
Cl OH
OS
O
Cl=
O
OS
O
ClH Cl
O
OS
O
Cl
Cl
O
OS
O
Cl
Cl Cl
OO S O Cl+ +
Phenacetin fever reducer in past (banned in 1983)
OEt is OH in Tylenol
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APPLICATION: NONESSENTIAL AMINO ACIDS
ESTER REACTIONS
HYDROLYSIS
GENERAL REACTIONS
MECHANISM AND ENERGY DIAGRAM
H3N O
O
O
O
H3N O
O
O
NH2aspartic acid asparagine
H3N O
O
H3N O
O
glutamic acid glutamineOO NH2O
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APPLICATION: BREAKDOWN OF NEUROTRANSMITTER
REACTION WITH GRIGNARD REAGENTS (IN SMITH CH. 20)
REACTION + MECHANISM
EXAMPLES
Devise a synthesis:
Nerve
Gap = synapse
Stream of molecules = neurotransmitters
Neurotransmitters (like acetylcholine) are released from one end
of the nerve across a synapse, which initiates a nerve impulse. To
be ready for another impulse, they have to be broken down
immediately. This is done by an enzyme (like
acetylcholinesterase).
O
O
NCH3
CH3CH3 acetylcholinesterase
acetylcholine
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AMIDE REACTIONS
HYDROLYSIS
REACTION + MECHANISM
con. OH-, H2O
NH2
O
con. H+, H2O
NH2
O
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NITRILE REACTIONS
HYDROLYSIS
REACTION + MECHANISM
EXAMPLES
NO
OH-, H2O
CNH+, H2O
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HYDRIDE REACTIONS WITH CO2H DERIVATIVES
REACTION WITH LiAlH4
OCH3
O a. LiAlH4 (excess)
b. H+ workup
OH
O a. LiAlH4 (excess)
b. H+ workup
a. LiAlH4 (excess)
b. H+ workupN
O
a. LiAlH4 (excess)
b. H+ workupC
N
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REACTION WITH DIBAL-H
LiAlH4
Lithium aluminum hydride DIBAL-H
Diisobutyl aluminum hydride
H Al
H
H
H
Li
HAl
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REACTION PRACTICE
PROVIDE THE REAGENTS
DESIGN A SYNTHESIS
O
OH
O
O
O
O
O
NH
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