Chapter 10
Carboxylic Acids and Derivatives
Naming Carboxylic Acids and
Derivatives
Carboxylic Acids: RCOOH (RCO2H)
• The functional group of a carboxylic acid is a
carboxyl group (carbonyl & hydroxyl group)
• The general formula of an aliphatic carboxylic acid
is RCO2H
:
O:
:
C
:O
COOH
CO2H
H
• Simple open-chain carboxylic acids are names by
replacing the terminal –e of the alkane name with
–oic acid
• The –COOH carbon is always number C-1
• If the compound contains a carbon-carbon double
bond, change the infix -an- to -en-
CH2=CHCOOH
Propenoic acid
1
• Compounds that have a –COOH group bonded to a
ring are named by using the suffix –carboxylic
acid
• The carboxyl group takes precedence over most
other functional groups
OH
O
CH3 CHCH 2 CH2 CH2 CO 2 H
CH3 CCH2 CH 2 CH2 CO 2 H
5-Hydroxyhexanoic acid
5-Oxohexanoic acid
Acid Halides: RCOX
• The functional group of an acid halide is an acyl
group bonded to a halogen
– to name, change the suffix -ic acid to -yl halide
– the –carboxylic acid to -carbonyl
Ethanoyl chloroide
2
Acid Anhydrides: RCOOCOR’ (acid + acid)
• The functional group of an acid anhydride is
two acyl groups bonded to an oxygen atom
– the anhydride may be symmetrical (two
identical acyl groups) or mixed (two
different acyl groups)
– to name, replace acid of the parent acid O O
by anhydride
CH 3 COC
Amides: RCONH2 (acid + amine)
• The functional group of an amide is an acyl group
bonded to a nitrogen atom
– to name, drop -oic acid from the name of the
parent acid and add -amide
– if the amide nitrogen is bonded to an alkyl or
aryl group, name the group and show its location
on nitrogen by N– the –carboxylic acid to -carboxamide
Acetic benzoic anhydride
– if the amide nitrogen is bonded to an alkyl or
aryl group, name the group and show its location
on nitrogen by N-
Esters: RCOOR’ (acid + alcohol)
• The functional group of an ester is an acyl group
bonded to -OR or -OAr
– name the alkyl or aryl group bonded to oxygen;
follow by the name of the acid but with the suffix
-ic acid changed to -ate
– Cyclic esters are called lactones
• Cyclic amides are called lactams
• name the parent carboxylic acid, drop the suffix ic acid, and add -lactam
3
Nitriles: R-C≡N
• Compounds containing the -C≡N functional group
are called nitriles
• The nitrile carbon is numbered C-1
Occurrence and Properties of Carboxylic
Acids and Derivatives
• In the liquid and solid states, carboxylic acids are
associated by hydrogen bonding into dimeric
structures
• Carboxylic acids are polar compounds and form
very strong intermolecular hydrogen bonds through
both their C=O and OH groups
– This strong hydrogen bonding has a noticeable effect on
boiling points
– they are more soluble in water than alcohols, ethers,
aldehydes, and ketones of comparable molecular weight
– Water solubility decreases as the relative size of the
hydrophobic portion of the molecule increases
Hydrophobic region
Hydrophilic
region
(Water-hating)
(Water-loving)
Decanoic acid
(0.2 g/100 mL H2O)
4
Acidity of Carboxylic Acids
Acidity
• Carboxylic acids are weak acids
– values of pKa for most aliphatic and aromatic
carboxylic acids fall within the range 4 – 5
• The greater acidity of carboxylic acids relative to
alcohols is due to two factors:
1.the significant resonance stabilization of a
carboxylate anion compared with an alkoxide
anion
2.the electron-withdrawing inductive effect of the
adjacent carbonyl group on the O-H bond
5
• Electron-withdrawing substituents near the carboxyl
group increase acidity through their inductive effect
H
I
Br
Cl
F
CH2CO2H
CH2CO2H
3.18
CH2CO2H
2.90
CH2CO2H
2.86
CH2CO2H
2.59
4.76
Increasing acid strength
• Multiple substitution of electron-withdrawing groups
further increases acidity
• The inductive effect of an electron-withdrawing
substituent falls off rapidly with its distance from the
carboxyl group
Cl
Cl
Synthesis of Carboxylic Acids
• Oxidation of alkylbenzene (chapter 5)
Cl
CH3CH2CH2CO2H CH2CH2CH2CO2H CH2CH2CH2CO2H CH2CH2CH2CO2H
2.83
4.52
3.98
4.82
• Oxidation of primary alcohols and aldehydes
Increasing acid strength
6
• Prepared from nitriles, R-C≣N
RBr
RC≣N
RCOOH
• Carboxylic acid derivatives have an acyl carbon
bonded to a group that can leave as a stable anion
Nucleophilic Acyl Substitution
Reactions
• The more electron-poor the C=O carbon, the more
readily the compound reacts with nucleophiles
– halide ion is the weakest base and the best leaving
group; acid halides are the most reactive toward
nucleophilic acyl substitution
– amide ion is the strongest base and the poorest leaving
group
7
The Tetrahedral Intermediate
O
RC- OH H- Cl
O
O
RC- OH H- OCR'
O
RC- OH H- OR'
O
RC- OH H- NH 2
FIGURE 10.4 MECHANISM:
Mechanism of the Fischer
esterification reaction of a
carboxylic acid. The reaction is an
acid-catalyzed nucleophilic acyl
substitution.
Overview of Reactions
FIGURE 10.5
Road map for the
reactions of functional
groups in this chapter.
8
Reactions of Carboxylic Acids
1.
Conversion of Acids into Alcohols by
Reduction (RCOOH → RCH2OH)
• Lithium aluminum hydride (LiAlH4) reduces a carboxyl
group to a 1° alcohol
– reduction is most commonly carried out in diethyl ether
or THF
• it is not reduced by NaBH4, a reagent that readily reduces the
carbonyl groups of aldehydes and ketones
Selective Reduction
• The carboxyl group is not affected by catalytic
hydrogenation under conditions that easily reduce
aldehydes and ketones to alcohols.
O
X
O
Pt
CH 3 CCH 2 CH 2 CH 2 COH + H2
5-Oxohexanoic acid
25℃, 2 atm
OH
O
CH 3 CHCH 2 CH 2 CH 2 COH
5-Hydroxyhexanoic acid
• it is also possible to selectively reduce the carbonyl
group of an aldehyde or ketone using the less reactive
NaBH4
O
x
O
CCH 2 CH 2 CH 2 COH
2.
Conversion of Acids into Acid
Chlorides (RCOOH → RCOCl)
• Carboxylic acids are converted into acid chlorides by
treatment with thionyl chlorides
1. NaBH4
2. H2O
5-Oxo-5-phenylpentanoic acid
OH
O
CHCH 2 CH 2 CH 2 COH
5-Hydroxy-5-phenylpentanoic acid
9
3.
Conversion of Acids into Esters
(RCOOH → RCOOR’)
• Fischer esterification reaction
• Esters can be prepared by treatment of a carboxylic
acid with an alcohol in the presence of an acid
catalyst, most commonly H2SO4 or gaseous HCl
• Reversible reactions (depend on solvent)
4.
Conversion of Acids into Amides
(RCOOH → RCONH2)
• Amide are difficult to prepare directly from acids
• At high temperature
Chemistry of Acid Halides
• Acid chlorides are prepared from carboxylic acids by
reaction with thionyl chloride
10
• Acid chlorides are among the most reactive of the
various carboxylic acid derivatives and can be
converted into many other kinds of substances
1.
Conversion of Acids Chlorides into
Acids (RCOCl → RCOOH)
• Acid chlorides react with water to yield carboxylic
acids – the substitution of –Cl by –OH
Cl
2.
Conversion of Acids Chlorides into
Esters (RCOCl → RCOOR’)
• Acid chlorides react with alcohol to yield esters
• The reaction usually carried out in the presence of an
amine base such as pyridine, which reacts with HCl
and prevents it from causing side reaction
3.
Conversion of Acids Chlorides into
Amides (RCOCl → RCONH2)
• Acid chlorides react with ammonia and with amines
to give amide
• One extra equivalent of ammonia is added to react
with the HCl generated
11
Chemistry of Acid Anhydrides
• The reactions of acid anhydrides is similar to that of
acid chloride
• The best method for preparing acid anhydrides is
by a nucleophilic acyl substitution reaction of an
acid chloride with a carboxylic acid anion
(Tylenol)
Acid anhydrides are inefficient to use, and acid chlorides are
normally used instead
(Tylenol)
Acid anhydrides are inefficient to use, and acid chlorides are
normally used instead
12
• Ester are usually prepare from acids or acid chlorides
Chemistry of Esters
• Many simple esters are pleasant-smelling liquids that
are responsible for the fragrant odors of fruits and
flower
• Fat
1.
Conversion of Esters into Acids
(RCOOR’ → RCOOH)
• Ester are hydrolyzed either by aqueous base or by
aqueous acid to yield a carboxylic acid plus an
alcohol
• Hydrolysis in aqueous acid is the reverse of Fischer
esterification
(H2O, H2SO4)
13
• Hydrolysis in basic solution is called saponification
• Two differences between hydrolysis of ester in
aqueous acid and aqueous base:
1. In aqueous acid: acid is required in only catalytic
amounts.
• Reversible in aqueous acid.
2. In aqueous base: not just a catalyst, it is a reactant.
• Irreversible in aqueous base.
O
RCOCH3 + Na OH
2.
H2 O
O
-
RCO Na
+
+
CH3 OH
Conversion of Esters into Acohols by
Reduction (RCOOR’ → RCH2OH)
• Hydride ion (:H-) adds to the carbonyl group followed
by elimination of an alkoxide ion to yield an aldehyde
• Further reduction of the aldehyde gives the primary
alcohol
• Esters are reduced by treatment with LiAlH4 to yield
primary alcohols
14
3.
Conversion of Esters into Acohols by
Reaction with Grignard Reagents
(RCOOR’ → RCH2OH)
• Grignard reagent react with esters to
yield a tertiary alcohol in which two
of the substituents on the hydroxylbearing carbon are identical
Chemistry of Amides
• Amides are usually prepared by reaction of an acid
chlorides with an amine
15
1.
Conversion of Amides into Acids
(RCONH2 → RCOOH)
• Amides are much less reactive than acid chlorides,
acid anhydrides, and esters
• Amides undergo hydrolysis to yield carboxylic acids
plus amine on heating in either aqueous acid or base
Chemistry of Nitriles
• Nitriles are not acid derivatives, but the chemistries
of nitriles are so similar to carboxylic acids
• Both functional groups have a carbon atom with
three bonds to an electronegative atom, and both
contain a multiple bond
2.
Conversion of Amides into Amines
by Reduction (RCONH2 → RCH2NH2)
• Amides are reduced by LiAlH4
• The product of this reaction is an amine rather than
an alcohol
• This reaction does not occur with other carboxylic
acid derivatives
• The preparation of Nitriles is by the SN2 reaction
of cyanide ion with a primary alkyl halide
Reaction of Nitriles
16
• Like carbonyl groups, nitriles are strongly polarized
• The nitrile carbon atom is electrophilic and
undergoes attack by nucleophiles
1.
Conversion of Nitriles into Carboxylic
Acids (RCN → RCOOH)
• Nitriles are hydrolyzed in either acidic or basic
solution to yield carboxylic acids and ammonia (or
an amine)
2.
Conversion of Nitriles into Amines
by Reduction (RCN → RCH2NH2)
• Reduction of nitriles with LiAlH4 gives a primary
amines, just as reduction of an ester gives a
primary alcohol
3.
Conversion of Nitriles into Ketones
by Reaction with Grignard Reagents
• Grignard reagent add to nitriles to give
intermediate imine anions that can be hydrolyzed
to yield ketones
17
Polymers from Carbonyl Compounds:
Polyamides and Polyesters
• There are two main classes of synthetic polymers:
– Chain-growth polymers (chapter 4)
– Step-growth polymers
• Step-growth polymers are prepared by
polymerization reactions between two difunctional
molecules, with each new bond formed in a discrete
step, independent of all other bonds in the polymer
Nylons
Polyesters
• The best-known step-growth polymers are the
polyamides, or nylons
• Nylons are usually prepared by reaction between a
diacid and a diamine
• polyesters are usually prepared by reaction between a
diacid and a dialcohol
(at 280 oC)
18
Enzymes in Organic Synthesis
19