Chapter 19
Carboxylic Acid Derivatives:
Nucleophilic Acyl Substitution
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Assignment
• Skip the following sections:
19.1, 19.11, 19.15, 19.16, 19.18,
19.21 and 19.32
These PowerPoint slides have been revised
for Fall 2007. Some additional sections
have been dropped or minimized!
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Problem Assignment
• In-Text:
1 a, c
4, 5a - d, 6 a - c
9 -11
15 - 19
21 - 23
31 - 40
• End-of-Chapter:
4
6-9
15
8 a, c
26, 27
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The addition/elimination
mechanism
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Nucleophilic
Acyl
Substitution
1)
Addition
..
:O :
:O :
slow
R
C
Y
R
_
+
C
Y
Nu
Nu:
2) Elimination
..
:O :
:O :
_
R
C
Nu
Y
R
C
+
Y:
Nu
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Sect. 19.2, 19.3 and 19.4
Nomenclature for acid chlorides,
acid anhydrides and esters
Only ester nomenclature on test!
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O
CH3 C
O
CH2 CH3
Acid part of ester Alcohol part of ester
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O
CH3 C
O
CH2 CH3
Ethyl ethanoate (IUPAC)
Ethyl acetate (common)
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O
CH3 CH
C
O
CH3
CH3
Methyl 2-methylpropanoate
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O
CH3 CH2 CH2 CH2 C
O
CH2 CH3
Ethyl pentanoate
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H
O
C
O
CH3
Methyl cyclohexanecarboxylate
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O
C
O
CH
CH3
CH3
Isopropyl benzoate or 2-methylethyl
benzoate
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Br
5
6
4
O
3
2
1O
Et
Ethyl 5-bromo-3,4-dimethylhexanoate
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Br
5
6
O
3
4
2
1 O
Et
Ethyl 5-bromo-3,4-dimethyl-2,4-hexadienoate
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Sect. 19.5 and 19.6:
Nomenclature for amides and
nitriles
Skip these sections! Not on test!
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Sect. 19.7: Mechanisms
Base hydrolysis of an ester
Ester
Na +
O
R
addition
O
O
CH 3
R
elimination
O
CH 3
HO
Na +
Na +
O
H
R
O
O-CH 3
O-H
sodium salt
of carboxylic
acid
O
R
H
O-CH 3
O
Na +
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Sect. 19.8/ 19.9: Preparation and
reactions of acid chlorides
O
R
C
O
OH
+
SOCl2
R
C
thionyl chloride
+
Cl
H
+
O
S
O
Cl
Important!!! Acid chlorides are key
intermediates for making esters, amides
and anhydrides!!!!
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Preparation of an Ester
O
C
R
Cl
acid chloride
R
H O
alcohol
O
C
R
O
R
H-Cl
ester
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Preparation of an Amide
O
C
Cl
R
R
H N
H
primary
amine
O
C
R
Cl
O
C
R
R
N
H
H-Cl
amide
O
C
R
H N
R
R
secondary
amine
amide
R
N
R
H-Cl
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Preparation of an Anhydride
O
O
C
R
Cl
acid chloride
H O
O
R
R
carboxylic
acid
O
O
R
H-Cl
anhydride
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Sect. 19.10: Reducing agents
• Review of reductions on acid chlorides.
• A look at the reduction of all the derivatives
of carboxylic acids.
• We talked about this in Chapter 16!
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Reactions of sodium borohydride
•
•
•
•
Aldehydes yield primary alcohols
Ketones yield secondary alcohols
Esters give no reaction!
Amides give no reaction!
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Reactions of lithium aluminum
hydride
• Aldehydes give primary alcohols
• Ketones give secondary alcohols
• Esters give primary alcohols from the
carboxylic acid part of the ester (Sect 19.20)
• Amides give primary amines!! (Sect 19.24)
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Sect. 19.11: skip
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Sect. 19.12: carboxylic acid
derivatives
Esters
Amides
Anhydrides
Nitriles
All of these functional groups will be
hydrolyzed in acidic or basic water to give the
parent carboxylic acid
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Sect. 19.13 and 9.14: Esters
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Esters as Flavoring Substances
O
CH3 C
O
O
CH2 CH2 CH
Isopentyl acetate
banana
CH3
CH2 CH3
O
O
CH2 CH
Isobutyl propionate
rum
CH3
O
CH3 C
O
Ethyl butyrate
pineapple
CH3
O
CH3 CH2 C
CH3 CH2 CH2 C
CH3
CH3 C
O
CH2 CH2 CH2 CH2 CH2 CH2 CH2 CH3
Octyl acetate
orange
O
O
CH2 CH2 CH3
Propyl acetate
pear
CH3 CH2 CH2 C
O
CH3
Methyl butyrate
apple
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Fischer Esterification
R
C
O
+
O
H
OH
+
R
OH
R
C
+
O
R
O
H
H
ESTERIFICATION REACTIONS ARE REVERSIBLE. You need
to push it to the right (ester) by removing water as it forms.
This reaction is acid catalyzed
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Fischer esterification is an acid catalyzed reaction
R
O
C
+
O
H
H
R
O
R C O-H
O
Et
H+
H
H
O
H
O
R C O-H
O
H
Et
addition
H
H
O
- H2O
R C O-H
elimination
O
Et
H
O
R C O-H
O
Et
- H+
H-O-Et
carbon hybridization
is sp2
H
O
C
carbon hybridization
is sp3
R
O-H
C
O-Et
R
H
O
C
O-Et
resonance!
- H+
R
O
C
O
Et
sp2carbon
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Sect. 19.15 and 19.16 -- skip
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Sect. 19.17: Hydrolysis of Esters
O
O
_
R
C
O
R +
OH
R
C
O
+
R
O
H
See slide for section 19.7 for mechanism of base hydrolysis
O
R
C
O
+
H
O
R +
H2O
R
C
OH
+
R
O
H
Mechanism of the acid catalyzed hydrolysis reaction is the
reverse of the Fischer esterification reaction!
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Sect. 19.18: skip
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Sect. 19.19: Reaction of Esters
with Organometallic Reagents
O
R
C
1) ether
O
R
+
MgBr
2 R
2) H2O, acid
OH
R
C
R
+
MgBr (OR)
+
MgBr (OH)
R
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Mechanism
Ester
ketone intermediate
MgBr
O
R
addition
O
O
CH 3
R
R
elimination
O
O
CH 3
R
BrMgO-CH 3
R
ketone, not
isolated!
MgBr-R
MgBr
O
R
R
MgBr-R
H3O+
O
addition
R
R
R
OH
R
HO-CH3 from
R
R
Tertiary alcohol
This reaction requires one mole of ester and two moles of a Grignard reagent
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Sect. 19.20: Reduction of Esters
Lithium aluminum hydride gives the primary alcohol
H
O
Aldehyde
intermediate
hydride from
LiAlH4
H
Et
O
Addition
O
H
Et
Elimination
O
O
O-Et
H
H
O
H
O
H
H3O+
H
H
OH
also HO-Et from ester
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Diisobutylaluminum hydride (DibalH) gives the aldehyde
hydride from
H
O
O
i-butyl
i-butyl
Al H
H
Et
Addition
O
O
H
Et
Elimination
i-butyl
i-butyl
O
Al
O-Et
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Sect. 19.21: skip
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Sect. 19.22 and 19.23:
Preparation and Reactions of
Amides
O
O
C
R
OH
+
R
R
C
Heat
R
NH2
NH
O
+
H
H
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Remember, also prepare amides
from acid chlorides
O
C
Cl
R
R
H N
H
O
C
R
R
N
H
H-Cl
primary
amine
O
C
R
Cl
R
H N
R
O
C
R
R
N
R
H-Cl
secondary
amine
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Amides, continued
• Keep this section simple, skip the DCC stuff
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Sect. 19.24: Reduction of amides
amides give primary amines with lithium aluminum hydride.
protonated
imine
intermediate
hydride from
H
LiAlH4
NH 2
H
H
NH 2
O
Addition
Elimination
H3Al-O
NH 2
amide
O-AlH3
protonated
imine
intermediate
H
H
H
NH 2
NH 2
primary amine
H
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Sect. 19.25 and 19.26: Reactions
of anhydrides
O
C
O
R
O
C
R
O
O
C
O
C
R
H O
R
O
C
R
O
R
alcohol
ester
R
H N
H
O
C
primary
amine
R
R
R
N
H
amide
HO
O
C
R
carboxylic acid
HO
O
C
R
carboxylic acid
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Preparation of aspirin and acetaminophen (Tylenol)
O
O
O
H
O
O
H
H3C
O
O
HO
H3C
O
CH 3
O
O
salicylic acid
H
N
H
O
H
O
CH 3
aspirin
H
N
H
H3C
O
O
CH 3
O
HO
CH 3
O
H3C
O
H
O
acetaminophen
(Tylenol)
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Sect. 19.27 and 19.28: preparation and reactions of nitriles
Nitrile
Na +
Br
C
N
SN2
C
4-bromobutane
Carbon is a
better nucleophile
than nitrogen
NaBr
H3O+
C
N
O-H
N
NH3
O
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Base-Promoted Hydrolysis of a
Nitrile (Part One)
1)
R
C
N:
_ ..
:O
..
_
: N:
2)
R
C
slow
R
C
:O
..
H
.. _
N:
H
: NH
..
OH + H2O
..
R
C
..
OH
..
_
+ OH
3)
: NH
R
C
..
OH
..
: NH2
R
C
..
O
..
Tautomerism
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Base-Promoted Hydrolysis of a
Nitrile (Part Two)
4)
.. _
: O:
:O :
R
C
_ ..
:O
..
5)
..
NH2
R
:O
..
H
.. _
: O:
R
C
:O
..
C
..
NH2
H
:O:
..
NH2
R
..
+ : NH2
C
:O
..
H
_
H
6)
: O:
R
C
..
+
OH
..
_
: O:
..
: NH
2
R
C
..
.. _
O
.. : + NH3
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Sect. 19.29: reduction of nitriles
with lithium aluminum hydride and
Hydrogen
NH 2
1) LiAlH4
Nitrile
2) H3O+
C
pentylamine
N
2 moles of H2
Palladium or Platinum
NH 2
pentylamine
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The remaining sections will not be
included on the third test.
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Sect. 19.30: Fats and oils
(Triglycerides)
O
O
R
C
O
CH2 O
C
H
O
CH2 O
C
C
R
R
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The Fatty Acids
O
CH3 (CH2)10 C
O
OH
O
CH3 (CH2)12 C
Lauric acid
OH
Myristic acid
CH3 (CH2)14 C
Palmitic acid
O
CH3 (CH2)16 C
OH
O
OH
CH3 (CH2)7 CH
Stearic acid
CH (CH2)7 C
OH
Oleic acid
O
CH3 (CH2)4 CH
CH CH2 CH
CH (CH2)7 C
OH
Linoleic acid
O
CH3 CH2 CH
CH CH
CH CH2 CH
CH (CH2)7 C
OH
Linolenic acid
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Sect. 19.31, 19.33, 19.34
• soaps
• proteins
• condensation polymers
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Wallace Carothers- commercialized
Nylon at DuPont
Source: Michigan State University, Department of Chemistry
http://www.chemistry.msu.edu/Portraits/PortraitsHH_collection.shtml
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Functional Group Interconversions
R
C
N
H2O
O
O
R
C
O
R’OH
H2O
R'
R
C
OH
O
H2O
SOCl2
R’OH
O
NH3
NR’2H
NH3
NR’2H
O
R
C
NH2
R
C
H2O
C
NR'2
R
OHCl
C
O
RCOOH
RCOOH
NH3
NR’2H
O
R
OH-
NH3
NR’2H
O
O
R
C
O
C
R
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