1
10 J. CHEM. RESEARCH (S), 1997
J. Chem. Research (S),
Iodine as an Acetyl Transfer Catalyst†
1
997, 110–111†
Ruli Borah, Nabajyoti Deka and Jadab C. Sarma*
Organic Chemistry Division, Regional Research Laboratory, Jorhat - 785006, Assam, India
Iodine catalyses the acetylation of amines, phenols and alcohols, including tertiary ones, with acetic anhydride in excellent
yield.
3
The protection of hydroxy and amino groups by converting
them into acetates is one of the most fundamental and widely
used transformations in organic chemistry. Protection of such
functional groups is often necessary during the course of
various transformations in a synthetic sequence especially in
the construction of polyfunctional molecules such as nucleo-
sides, carbohydrates, steroids and natural products. Although
products as observed during base catalysed acetylation was
not evident here; in contrast the yield of acetate was found to
be almost quantitative (Table 1, entry 13). The acetylation of
4-hydroxy-4-methylpentan-2-one (entry 13) was even faster
than that of 2-methylpentane-3,4-diol (entry 6) or 4-acetoxy-
2-methylpentan-2-ol (entry 14). Polarization of the acetic
anhydride by forming a complex with iodine followed by
nucleophilic attack of the alcohol may give the acetate and
the unstable acylhypohalite which eliminates iodine to con-
tinue the reaction (Scheme 1).
1
several reagents are available for the acetylation of alcohols,
an acetic anhydride–pyridine mixture is most commonly used
2
for this purpose. 4-Dimethylaminopyridine (DMAP) is also
used and is more efficient and has wider scope. Recently
3
ROH
reagents like CoCl –acetic anhydride, MgI –diethyl ether–
2
2
4
5
acetic anhydride, functional polymers and polymer support
MeCO
6
O+ –I
MeCOOR + MeCOOI
reagents have been reported as alternative and versatile
MeCO
acylating agents. In most of these cases either a low yield is
observed or stringent reaction conditions are necessary.
We report here a mild, convenient and efficient catalyst for
the acetylation of alcohols. When an alcohol was treated with
acetic anhydride in the presence of a catalytic amount of
iodine at room temperature, the corresponding acetate was
obtained in excellent yield. The reaction proceeded rapidly at
ambient temperature with high yields of acetates also from
tertiary alcohols, (Table 1). The reaction was fast at high
MeCOO—I –I
MeCOO–
+
I2
Scheme 1
In a blank experiment, cholesterol was treated with acetic
anhydride for 10 h. No corresponding acetate was observed,
clearly indicating the importance of iodine as a catalyst in the
system.
Table 1
a
ꢀ1
Entry Compound
t/min T/°C Yield (%)
vmax/cm
H
d (60 MHz)
b
1
2
3
Cetyl alcohol
Octadecan-1-ol
Benzyl alcohol
30
5 h r.t.
30 r.t.
5 h r.t.
30 r.t.
5 h r.t.
r.t.
10
90
10
86
20
1725
1720
1725
2.05 (s, 3 H), 3.85 (t, 2 H, J 6 Hz)
2.0 (s, 3 H), 3.8 (t, 2 H, J 6 Hz)
1.95 (s, 3 H), 4.8 (s, 2 H)
b
b
b
b
1
1
1
100
100
100
100b
60
4
5
Cyclohexanol
Cholestanol
20
20
3
r.t.
r.t.
42
r.t.
r.t.
r.t.
42
1725
1725
2.0 (s, 3 H), 4.8 (brs, 1 H)
1.85 (s, 3 H), 4.4 (br, 1 H)
6
7
MeCH(OH)CH
2
CMe
2
OH
30
(2°)ǹ3 (diac) 1.8 (s, 3 H), 4.85 (sex, 1 H, J 6 Hz)
(1:1)
1725
9
0
95
Cholesterol
10
2
100
100
95
1.9 (s, 3 H), 4.4 (brs, 1 H)
8
9
Diosgenin
Carveol
a-Ionol
PhCH(OH)Me
60
30
30
20
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
r.t.
1730
1725
1725
1725
1725
1725
1730
1650
1660
1745
1745
1.85 (s, 3 H), 4.25 (brs, 1 H)
1.95 (s, 3 H), 4.9 (brs, 1 H)
1.95 (s, 3 H), 4.8–5.3 (brs, 4 H)
1.8 (s, 3 H), 5.5 (q, 1 H, J 6 Hz)
1.85 (s, 6 H), 4.35 (br, 2 H)
2.0 (s, 3 H)
90
1
0
1
2
3
4
5
6
7
8
100
100b
65
1
1
1
1
1
1
1
1
(20R)-20-hydroxypregna-5,16-dien-3b-yl acetate 120
MeCtO)CH
2
CMe
2
OH
OH
30
180
100
105
30
95
90
b
MeCH(OAc)CH
Butylamine
Aniline
2
CMe
2
1.8 (s, 3 H), 1.85 (s, 3 H), 4.85 (m, 1 H)
2.0 (s, 3 H), 7.8 (br5, 1 H)
2.0 (s, 3 H), 7.7 (br, 1 H)
1.95 (s, 3 H)
78
77
90
80
Phenol
Resorcinol
30
2.0 (s, 3 H)
a
All yields refer to isolated products which were characterised by direct comparison with authentic samples and also by spectral
b
analysis. Remainder is unreacted starting material.
temperatures (refluxing chloroform or dichloromethane,
entry 7) and also at high concentrations of acetic anhydride.
The problem of b-elimination in b-hydroxy carbonyl com-
pounds to yield a, b-unsaturated carbonyl compounds as side
Both aliphatic and aromatic amino groups as well as
phenols are also acetylated by this system in excellent
yield.
The reagent combination of acetic anhydride–pyridine or
acetic anhydride–DMAP is not suitable for acetylation of
3
base sensitive compounds. Pyridine and DMAP are both
*
†
To receive any correspondence.
toxic and in the case of polar compounds are sometimes
difficult to remove from the reaction mixture after
work-up. The present reagent combination circumvents these
This is a Short Paper as defined in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1997, Issue 1]; there is there-
fore no corresponding material in J. Chem. Research (M).