Acyl Substitution
19.1: Nomenclature of Carboxylic Acid Derivatives
(please read)
acid chloride
acid anhydride
ester
amide
acid anhydride
ester
amide
ester
amide
amide
O
C
SOCl2,
OH
O
C
+
Cl
SO2
HCl
Table 19.5
Esters react with Grignard reagents to give tertiary alcohols.
two equivalents of the Grignard reagent adds to the carbonyl
carbon. (Ch. 19.12)
10
12
NH2
pKa~ 10
OCH3
NH
HOCH3
pKa~ 16
13
14
19.14: Amides
amide bond has a large
dipole moment ~ 3.5 Debye
H2O = 1.85 D
NH3 = 1.5 D
H3CNO2 = 3.5
15
Increasing reactivity
16
R
OH
carboxylic acid
SOCl2
O
C
R'NH2
R
R
Cl
acid chloride
R'2NH
O
C
O
C
O
C
NH2
N
H
N
R'
unsubstitiuted
(1) amide
R'
mono-substitiuted
(2) amide
R'
di-substitiuted
(3) amide
O
C
H3O+
NH2
O
C
+
OH
NH3
O
C
NaOH, H2O
NH2
O
C
+
OH
NH3
18
Penicillin G
Amoxicillin
Cephalexin
O
R
NH2
Primary amide
nitrile
19
Acid-promoted hydrolysis:
20
nitriles
~ 3.9 D
MgBr
THF
N
C
H3O+
CH3
NH
C
R
CH3
O
C
CH3
21
22
H NMR:
Protons on the -carbon (next to the C=O) of esters and amides
have a typical chemical shift range of 2.0 - 2.5 ppm
1
=1.2
t,J=7.2Hz,3H
2.0
3H, s
=4.1
q,J=7.2Hz,2H
NH
1.1
3H, t, J= 7.0
3.4
2H, q, J= 7.0
23
14.2
60.3
170.9
21.0
CDCl3
21.0
14.8
34.4
170.4
CDCl3
24
= 119
25
C11H12O2
H NMR
7.5 7.3
2H, m 3H, m
6.4
1H, d,
J= 15.0
7.7
1H, d,
J= 15.0
4.2
2H, q,
J= 7.0
1.3
3H, t,
J= 7.0
IR
13
C NMR
130.2
128.8
127.9
144.5
134.9
166.9
60.5
118.2
CDCl3
14.3
TMS
26
C10H11N
3.72
(1H, t, J=7.1)
7.3
(5H, m)
1.92
(2H, dq, J=7.4, 7.1)
1.06
(3H, t, J=7.4)
129.0
128.0
127.3
38.9
29.2
11.4
135.8
120.7
CDCl3
TMS
27