Download Chapter 20: Carboxylic Acids and Nitriles

Chapter 20: Carboxylic Acids and Nitriles
Nomenclature:
O
O
Carboxylic acid
C
OH
H3C
OH
CH3COOH
IUPAC ending: -oic acid
(trivial name)
N
Nitrile
H3C
C
CH3CO2H
ethanoic acid
(acetic acid)
CH3C N
N
CH3CN
ethanenitrile
(acetonitrile)
IUPAC ending: nitrile
since the acid functional group must be at the end of a chain, it
must be numbered 1 – therefore, there is no need to include that number
when named as a substituent, it is also number 1 – the highest priority
Effect of substituents on acidity of carboxylic acids
O
R
Ka
OH
Ka = [H+] [RCOO ]
[RCOOH}
O
H+
+
R
O
O
R
O
and pKa = - log Ka
pKa
methanoic acid
HCO2H
3.75
ethanoic acid
CH3CO2H
4.75
propanoic acid
CH3CH2CO2H
4.87
butanoic acid
CH3(CH2)2CO2H
4.82
1
pKa ~16
pKa 4.75
Preparation of acids
Oxidation
of aromatic side chains
cleavage of alkenes, alkynes
of alcohols
2
Hydrolysis of nitriles
And, lastly, a Grignard-based preparation
O
C
OH
N
It is important to note that these carbons are at the same oxidation level
-- we can see this because each one has three bonds to a heteroatom
Remember, cyanide is a good nucleophile, so preparation of nitriles is easy
Other preparations of nitriles
20.9
O
R
More examples:
Mg
CO2
COOH
C
N
We have not yet discussed amides,
but look at these two structures.
What is the difference?
86%
COOH
Br
Li
O
R
We can, indeed, fairly easily dehydrate amides:
H3O+
dry Et2O
Cl
NH2
CO2
H3O+
dry Et2O
O
97%
Reductions – acids
Reactions of acids and nitriles
What do we expect?
O
OH
C
N
remember – acids are less reactive than aldehydes or ketones
-- NABH4 is less reactive than LAH
therefore, only LAH works on acids and derivatives
BH3 also works:
red sites are positive – therefore susceptible to nucleophilic attack
blue site is acidic, therefore pulled off by bases
3
Reductions – nitriles
H
H
R
C
Al
H
R
H
N
Li+
N
Li+
AlH3
R
N
AlH3
H
H
anion reacts with Lewis Acid AlH3, and
the resulting anion complexes with Li+
in a tight ion pair; this leaves the C=N
bond available for a second addition
H
H
Al
H
H
Li+
AlH3
R
R
N
H
H
I don’t like this description
-- it is better, I believe, shown
as on the next slide
Li+
AlH3
N
H
Li+
AlH3
and this species is hydrolyzed on
work-up to the 1° amine
this mechanism makes the following reaction more understandable:
Reaction of a nitrile with an organometallic reagent:
And finally, hydrolysis of nitriles:
HO
HO
R
HO
C
N
H
N
O
R
O
R1
R
C
MgBr
R1
N
N
+MgBr
R
this species has considerably
higher negative charge on the
N, resulting in a double bond
which is less susceptible to
further reaction
CN
H2SO4
H2O
∆
H2O
R1
H
N
R
H2O
R
H
HO
H
R
O
O
N
HO
H
N
H2O
NH2
HO
R
OH
+ NH
2
HO
R
now, hydrolysis gives
an imine which we know
further hydrolyzes to the
ketone
O
R
O
NH2
O
R
O
+ NH
2
this is the same as Fig 20.4 in the text
COOH
78%
you will note, however, that the amide is an intermediate in this
reaction – using milder conditions, it can be the product:
CN
HCl
H2O
40°, 1h
CONH2
80%
4