Nomenclature

1
Nomenclature
2
Nomenclature
IUPAC COOH group takes precedence
diacids longest C chain alkane ? alkanedioic
acid with position 1 being whichever end giving
the most economical numbering
cycloalkanes ? cycloalkanecarboxylic,
cycloalkanedicarboxylic, cycloalkanetricarboxylic
acids, etc., where point of COOH attachment is
position 1
benzene derivatives ? benzoic, benzenedicarboxylic
, benzenetricarboxylic acids, etc.
3
Structure Properties
Structure
H-Bonding
Acidity
NMR IR
MS
relative to aldehydes ketones, the OH lone pair
contributes new resonance structures in both
neutral and protonated forms (?-donation), which
add stability reduce the electrophilicity in
spite of the higher electronegativity of the OH
oxygen (?-withdrawal)
4
Structure Properties
carboxylic acids readily form H-bonded dimers
? high b.p.
(only ethanoic/acetic acid is ever used as a
solvent)
? appreciable m.p. for Cgt8 monoacids all diacids
these dimers are less polar than the monomer ?
soluble in less polar aprotic solvents
they similarly engage in H-bonding with H-bond
acceptors or donors (e.g. alcohols H2O) ?
soluble in polar protic solvents
the salts are ionic and only H-bond acceptors and
dissolve only in H-bond donors (e.g. alcohols
H2O) ? soluble in polar protic solvents
5
Structure Properties
carboxylate anions are stabilized by resonance
? carboxylic acids are ? somewhat acidic and
reversibly form ionic salts with bases
(useful in isolation by pH-controlled extraction)
6
Structure Properties
carboxylate anions are stabilized by resonance
? carboxylic acids are ? somewhat acidic and
reversibly form ionic salts with bases
(useful in isolation by pH-controlled extraction)
the acidity is affected by inductive and
resonance influences it is increased by nearby
e-withdrawing groups decreased by nearby
e-donating groups
or by conjugation
7
Structure Properties
8
Structure Properties
9
Structure Properties
10
Structure Properties
11
Structure Properties
12
Structure Properties
13
Structure Properties
14
Structure Properties
15
Structure Properties
16
Structure Properties
17
Structure Properties
18
Structure Properties
MS not as useful with carboxylic acids
M peak is often weak and common fragments
involve rearrangements
MW 116
19
Synthesis
from alcohols
from CO2
from nitriles amides
oxidation of primary alcohols with chromic acid
(M2Cr2O7/H2SO4 or CrO3/H2SO4) (Section 11-2)
also oxidation of aldehydes with these same
reagents or with Ag2O or Tollens reagent
(Section 18-20)
20
Synthesis
the carboxylation of Grignard reagents
mechanism
simple uncatalyzed nucleophilic Addition
constitutes a one-carbon chain extension
21
Synthesis
strong acid will hydrolyse nitriles to acids
since nitriles are available from SN2 reaction of
alkyl halides and tosylates with CN, ...
the substitution-hydrolysis sequence constitutes
a useful one-carbon extension
22
Synthesis
H2O
slower
- NH3
H2O
the hydrolysis is a two-stage process, involving
the corresponding 1º amide as intermediate
stage 1 nitrile to 1º amide by H-catalyzed
nucleophilic Addition
stage 2 1º amide to acid by H-catalyzed
nucleophilic Addition-Elimination
since this is slower than stage 1, the use of
mild conditions make it possible to stop after
stage 1 and obtain 1º amides from nitriles,
whereas stronger conditions are required for
stage 2
23
Synthesis
both stages are equilibria
stage 1 lies to the right by virtue of favourable
bond energies
stage 2 is driven to the right by virtue of an
acid-base equilibrium that removes the amine
product
which consumes acid
24
Synthesis
in general, amides of all kinds can be hydrolysed
to acids by the same stage 2 mechanism
25
Reactions
Preview
aldehydes ketones undergo nucleophilic
addition, addition-elimination
addition-elimination-addition reactions (Chap. 18)
carboxylic acids (and derivatives) also contain a
CO group, albeit less electrophilic, and can be
expected to undergo the same kinds of reactions,
albeit more reluctantly
carboxylic acids have an additional OH
substituent which is potentially a leaving group
(after protonation)
additions followed by loss of the OH group (after
protonation) results in a net substitution of OH
by an addition-elimination process
the hydrolysis of amides constitutes just such a
substitution the same substitution chemistry can
be anticipated for esters acid chlorides that
possess even better built-in leaving groups
(Chap. 21)
26
Reactions
? esters
? amides
? acid chlorides
reduction
alkylation
27
Reactions
? esters
? amides
? acid chlorides
reduction
alkylation
K 3.38
Fischer esterification
ester hydrolysis
reversible process ? equilibrium
favour esterification by
conducting the reaction in the alcohol or acid as
solvent
removing the H2O (drying agent, distilation) or
the ester (distilation)
favour ester hydrolysis by
conducting the reaction in H2O
removing the alcohol or acid (distilation)
28
Reactions
29
Reactions
this is the reverse of amide hydrolysis
problem 1 amines are basic and will consume any
acid provided as catalyst to form relatively
unreactive ammonium salts
R-NH2 H ? R-NH3
30
Reactions
this is the reverse of amide hydrolysis
problem 1 amines are basic and will consume any
acid provided as catalyst to form relatively
unreactive ammonium salts
problem 2 even without added acid, amines will
react with the carboxylic acid component to form
stable ammonium carboxylates
nevertheless, it is possible to heat ammonium
carboxylates to form amides (i.e. by thermal
condensation),
in which case the ammonium ion acts as a
(reluctant) acid catalyst with the equilibrium
driven forward by the expulsion of H2O as steam
31
Reactions
uses SOCl2 or (COCl)2
32
Reactions
uses SOCl2 or (COCl)2
irreversible and uphill driven forward by the
expulsion of gases
acid chlorides are used in esterification (Chap.
11), Friedel-Crafts acylation (Chap. 17) and
amide formation (Chap. 19)
acid chlorides are also used in the preparation
of aldehydes (Section 18-11 20-14), higher
alcohols (Section 10-9) and anhydrides (Chap. 21)
33
Reactions
34
Reactions
reduction to alcohols with LiAlH4 or BH3 (B2H6)
BH3 in restricted amounts is selective for COOH
reduction
35
Reactions
alkylation of acids (with 2 equiv. of an
organolithium) ? ketones
36
Reactions
Summary of Transformations
Notes
aldehydes can also be oxidized to carboxylic
acids with H2CrO4 reagents, or with Ag2O or
Tollens reagent
reactions with LiAlH4 or RLi actually proceed via
the carboxylate
37
Reactions
mechanism of alkylation
acid-base
uncatalyzed Addition
38
Reactions
mechanism of nitrile hydration
H-catalyzed addition
protonation
addition
H transfer
deprotonation
H-catalyzed elimination
mechanism of amide dehydration
protonation
H transfer
elimination
deprotonation
39
Reactions
mechanism of amide formation
addition
protonation
H transfer
elimination
deprotonation
H-catalyzed Addition-Elimination
40
Reactions
mechanism of amide hydrolysis
elimination
deprotonation
H transfer
protonation
addition
H-catalyzed Addition-Elimination
41
Reactions
mechanism of Fischer esterification
..
..
..
protonation
addition
proton transfer
elimination
deprotonation
H-catalyzed Addition-Elimination
42
Reactions
mechanism of ester hydrolysis
..
..
..
protonation
addition
proton transfer
elimination
deprotonation
H-catalyzed Addition-Elimination
43
Reactions
mechanism of reaction with SOCl2
44
Reactions
mechanism of reaction with SOCl2
uncatalyzed Addition
-Elimination
at S
uncatalyzed Addition
-Elimination
at C
the first part is the same as in the reaction of
SOCl2 with alcohols (Section 11-9)
45
Reactions
mechanism of reduction with LiAlH4
acid-base
uncatalyzed Addition
-Elimination
-Addition
46
Reactions
Summary of Mechanisms
mechanism
example transformation
H-Catalyzed
Hydration of Nitriles ? 1º Amides
Addition
Dehydration of 1º Amides ? Nitriles
Elimination
Hydrolysis of Amides
Addition-Elimination
Thermal Condensation of Ammonium Carboxylates
Fischer Esterification
Ester Hydrolysis
Uncatalyzed
Alkylation of Acids (Carboxylates) with
Organolithiums ? Ketones
Addition
Carboxylation of Grignards ? Carboxylates
Addition-Elimination
Conversion of Acids to Acid Chlorides with SOCl2
or (COCl)2
Addition-Elimination-Addition
Reduction of Acids with LiAlH4 ? 1º Alcohols
47
Reactions
reduction of acid chlorides to aldehydes with
LiAl(OtBu)3H
uncatalyzed Addition
-Elimination