Transcript Anhydrides, Esters and Amides

19
General, Organic, and
Biochemistry, 8e
Bettelheim, Brown,
Campbell, & Farrell
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19-1
19 Introduction
• In this chapter, we study three classes of
compounds derived from carboxylic acids;
anhydrides, esters, and amides
• Each is related to a carboxyl group by loss of H2O.
O
RCOH
A carboxylic acid
O O
RCOCR'
An anhydride
-H2 O
O
O
RC- OH H- OCR'
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O
RCOR'
An ester
-H2 O
O
RCN H2
An amide
-H2 O
O
O
RC- OH H- OR' RC- OH H- NH 2
19-2
19 Anhydrides
• The functional group of an anhydride is two
carbonyl groups bonded to the same oxygen.
• The anhydride may be symmetrical (from two identical
acyl groups), or mixed (from two different acyl groups).
Your book does not discuss how to name the mixed
anhydrides so you will not be responsible for being
able to name a mixed anhydride.
• To name an anhydride, drop the word "acid" from the
name of the carboxylic acid from which the anhydride
is derived and add the word "anhydride”.
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O O
CH3 C-O-CCH3
Acetic anhydride
19-3
19 Esters
• The functional group of an ester is a carbonyl
group bonded to an -OR group.
• Both IUPAC and common names of esters are derived
from the names of the parent carboxylic acids.
• Name the alkyl or aryl group bonded to oxygen first,
followed by the name of the acid; replace the suffix -ic
acid by -oate.
• A cyclic ester is called a lactone.
O
CH3 COCH2 CH3
Ethyl ethanoate
(Ethyl acetate)
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O
O
O
O
Diethyl pentanedioate
(Diethyl glutarate)
O
O
A five-membered
lactone
19-4
19 Amides
• The functional group of an amide is a carbonyl
group bonded to a nitrogen atom.
• To name an amide, drop the suffix -oic acid from the
IUPAC name of the parent acid, or -ic acid from its
common name, and add -amide.
• If the amide nitrogen is also bonded to an alkyl or aryl
group, name the group and show its location on
nitrogen by N- ; two alkyl or aryl groups by N,N-di-.
O
O
CH3 CNH2
CH3 CNHCH3
Acetamide N -Methylacetamide
(a 1° amide)
(a 2° amide)
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O
HCN(CH3 ) 2
N ,N-D imethylformamide
(a 3° amide)
19-5
19 Amides
• A cyclic amide is called a lactam.

O
O
NH
b
NH
A four-memb ered lactam
(a b-lactam)
A seven-memb ered lactam
• The penicillins are referred to as b-lactam antibiotics.
HO
The p enicillins
differ in th e group
bond ed to th e
carbonyl carbon
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Theb-lactam rin g
O
N
NH2 H
O
S
N
CH3
CH 3
COOH
A moxicillin
19-6
19 Amides
• The cephalosporins are also b-lactam antibiotics.
O
The cephalosporins
differ in the group
bonded to the carbonyl
carbon...
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N
N H2 H
O
S
...and the group bonded
to this carbon of the
six-membered ring
N
CH3
COOH
Cephalexin (Keflex)
(a b-lactam antibiotic)
19-7
19 Fischer Esterification
• Fischer esterification is the most commonly used
preparation of esters (Chapter 18).
• In Fischer esterification, a carboxylic acid is reacted
with an alcohol in the presence of an acid catalyst,
such as concentrated sulfuric acid
O
H2 SO4
CH3 C-OH + H-OCH2 CH3
Eth anoic acid
Ethanol
(Acetic acid) (Ethyl alcohol)
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O
CH3 COCH2 CH3 + H2 O
Ethyl ethanoate
(Ethyl acetate)
19-8
19 Preparation of Amides
• In principle, we can form an amide by treating a
carboxylic acid with an amine and removing -OH
from the acid and an -H from the amine.
• In practice what occurs if the two are mixed is an acidbase reaction to form an ammonium salt.
• If this salt is heated to a high enough temperature,
water is eliminated and an amide forms.
O
CH3 C-OH + H2 NCH2 CH3
Acetic
Ethanamine
acid
(Ethylamine)
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O
+
CH3 C-O H3 NCH2 CH3
An ammonium
s alt
O
h eat
CH3 C-NHCH2 CH3 + H2 O
An amid e
19-9
19 Preparation of Amides
• It is much more common, however, to prepare amides
by treating an anhydride with an amine.
O O
CH3 C-O-CCH3 + H2 NCH2 CH3
Acetic anhdyride
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O
O
CH3 C-NHCH2 CH3 + CH3 COH
A n amid e
19-10
19 Hydrolysis of Anhydrides
• Hydrolysis is a chemical decomposition involving
breaking a bond and the addition of the elements of
water.
• Carboxylic anhydrides, particularly the low-molecularweight ones, react readily with water (hydrolyze) to
give two carboxylic acids.
O O
CH3 COCCH3 + H2 O
Acetic anhydride
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O
O
CH3 COH + HOCCH3
Acetic acid Acetic acid
19-11
19 Hydrolysis of Esters
• Esters hydrolyze only very slowly, even in boiling
water.
• Hydrolysis becomes considerably more rapid,
however, when the ester is heated in aqueous acid or
base.
• Hydrolysis of esters in aqueous acid is the reverse of
Fischer esterification.
• A large excess of water drives the equilibrium to the
right to form the carboxylic acid and alcohol (Le
Chatelier's principle).
O
CH3 COCH2 CH3
Ethyl acetate
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+
H2 O
H
+
O
CH3 COH + CH3 CH2 OH
Acetic acid
Ethanol
19-12
19 Hydrolysis of Esters
• We can also hydrolyze an ester using a hot aqueous
base, such as aqueous NaOH.
• This reaction is often called saponification, a reference
to its use in the manufacture of soaps.
• The carboxylic acid formed in the hydrolysis reacts
with hydroxide ion to form a carboxylic acid anion.
• Each mole of ester hydrolyzed requires one mole of
base.
O
CH3 COCH2 CH3+ N aOH
Ethyl acetate
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Sodium
hydroxide
H2 O
heat
O
CH3 CO - N a++ CH3 CH2 OH
Sodium
acetate
Ethanol
19-13
19 Hydrolysis of Amides
• Amides require more vigorous conditions for
hydrolysis in both acid and base than do esters.
• Hydrolysis in hot aqueous acid gives a carboxylic acid
and an ammonium ion.
• Hydrolysis is driven to completion by the acid-base
reaction between ammonia or the amine and the acid to
form an ammonium ion.
• Each mole of amide hydrolyzed requires one mole of
acid.
O
CH3 CH2 CH2 CNH2 + H2 O + HCl
Butanamide
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H2 O
heat
O
+ CH3 CH2 CH2 COH + NH4 Cl
Butanoic acid
19-14
19 Hydrolysis of Amides
• Hydrolysis of an amide in aqueous base gives a
carboxylic acid salt and ammonia or an amine.
• Hydrolysis is driven to completion by the acid-base
reaction between the carboxylic acid and base to form
a salt.
• Each mole of amide hydrolyzed requires one mole of
base.
O
CH3 CNH
A cetanilide
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+ NaOH
H2 O
heat
O
+
CH3 CO Na + H2 N
Sodiu m
acetate
Aniline
19-15
19 Reaction with Alcohols
• Anhydrides react with alcohols and phenols to
give an ester and a carboxylic acid.
O O
CH3 COCCH3 + HOCH2 CH3
Acetic anhydride
Ethanol
O
O
CH3 COCH 2 CH 3 + HOCCH3
Ethyl acetate
Acetic acid
• Aspirin is prepared by the reaction of salicylic
acid with acetic anhydride.
COOH
OH
Salicylic acid
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+
O
O
CH3 C- O-CCH3
Acetic anhydride
COOH
OCCH 3
O
Acetylsalicylic acid
(Aspirin)
+
O
CH3 C- OH
Acetic acid
19-16
19 Reaction with Amines
• Anhydrides react with ammonia and with 1° and
2° amines to form amides.
• Two moles of amine are required; one to form the
amide and one to neutralize the carboxylic acid
by-product.
O
O
CH3 C- O-CCH 3 + N H3
O
CH 3 C- OH + N H3
O
O
CH3 C- O-CCH3 + 2 N H3
Acetic
anhydride
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O
O
CH3 CN H 2 + CH3 C- OH
O
CH3 CO - N H4 +
O
O
CH3 CN H2 + CH3 CO - N H 4 +
Acetamide
Ammonium
acetate
19-17
19 Reaction with Amines
• Esters react with ammonia and with 1° and 2°
amines to form amides.
O
O
OCH2 CH3 + N H3
Ethyl 2-phenyl acetate
N H2 + CH3 CH2 OH
2-Phenylacetamide
• Thus, an amide can be prepared from a
carboxylic acid by first converting the carboxylic
acid to an ester by Fischer esterification and then
reaction of the ester with an amine.
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19-18
19 Reaction with Amines
• Amides do not react with ammonia or with
amines.
• You have a quiz next class on amines. It is a very
small amount of information with only two
reactions, so be prepared to complete the
reactions and be able to name the products.
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19-19
19 March Science Night
• For the remaining portion of class I want you to
discuss what you will be doing for the March
Science Night.
• Seniors: I need to know if you will be presenting
on your senior project, doing a new project or
being an assistant (helper) on the actual night.
• Juniors: I need to know what your project, talk or
activity will be. You may work in groups of up to
four students. If you are already doing a project
for Mr. Isel you don’t have to do one for me. Next
class I will be putting up a sign up sheet and a list
from 1B to see if you want to join two projects.
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19-20
19 Chapter 19
End
Chapter 19
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19-21