Molecular iodine catalyzed selective acetylation of alcohols with vinyl acetate

Article abstract of DOI:10.1016/j.tetlet.2006.03.182

Molecular iodine is found to catalyze the acetylation of alcohols efficiently with vinyl acetate. The reaction is mild and selective with good to high yields. Molecular iodine displays significant functional group tolerance, being compatible with methoxy, double bonds, spiroketals, ketals and phenolic hydroxyl functions.

Full text of DOI:10.1016/j.tetlet.2006.03.182

Tetrahedron Letters 47 (2006) 4065–4068
Molecular iodine catalyzed selective acetylation
of alcohols with vinyl acetate
J. W. John Bosco, Aditya Agrahari and Anil K. Saikia*
Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati 781 039, India
Received 17 February 2006; revised 24 March 2006; accepted 29 March 2006
Abstract—Molecular iodine is found to catalyze the acetylation of alcohols efficiently with vinyl acetate. The reaction is mild and
selective with good to high yields. Molecular iodine displays significant functional group tolerance, being compatible with methoxy,
double bonds, spiroketals, ketals and phenolic hydroxyl functions.
Ó 2006 Elsevier Ltd. All rights reserved.
Acetylation of hydroxy groups is an important and fre-
quently used transformation in organic synthesis.1 Acet-
yl chloride2 and acetic anhydride3 are usually employed
as acetylating agents in the presence of tributylphos-
phine4 or pyridine derivatives.5 Lewis acid catalysts such
as Sc(OTf)3,6 TMSOTf,7 Cu(OTf)2,8 TaCl4,9 In(OTf)3,10
In recent years, molecular iodine has drawn consider-
able attention as an inexpensive, non-toxic, non-metallic
and readily available catalyst for various organic trans-
formations under mild and convenient conditions in
excellent yields and with high selectivity.21
11
CoCl2 and yttria–zirconia based Lewis acids12 have
In continuation of our interest in iodine chemistry,22 we
chose this catalyst for the acetylation of alcohols with
vinyl acetate. Kaimal and his group have reported that
transesterification of alcohols can be performed with
esters in the presence of molecular iodine at reflux.23
We argued that if the carbonyl group and double bond
of vinyl acetate were activated by iodonium ions and
simultaneously reacted with a nucleophile, then acetyl-
ated products would be obtained in shorter times under
these mild conditions. This proved to be the case when
benzyl alcohol and vinyl acetate were stirred at room
temperature with a catalytic amount of molecular iodine
(10 mol %) yielding the corresponding acetate in good
yield24 (Scheme 1).
been reported to be efficient catalysts for this reaction.
Although these catalysts are effective, the acidic condi-
tions in acetic anhydride and the Lewis acid can lead
to cleavage of acid sensitive groups. Transesterification
with esters is an alternative method for the acetylation
of alcohols under mild conditions, but due to the revers-
ibility, high yields cannot be achieved. In this connec-
tion, vinyl acetate is a reagent of choice, since the
resultant enolate is converted to acetaldehyde, which is
unable to participate in the reverse reaction. Several
approaches towards the transformation of alcohols to
acetates using ꢀvinyl acetate are known. Among these,
the use of Cy2SmðthfÞ2,13 distanoxanes,14 iminophos-
phoranes,15 N-hetero-cyclic carbenes,16 TsOH or concd
H2SO4,17 PdCl2–CuCl2,18 Et2Zn19 and enzymes20 is
reported. However, the use of expensive and toxic metal
precursors is a serious concern in the aspect of green
chemistry. N-Heterocyclic carbenes are quite effective,
but they are difficult to prepare. Hence, there is a need
to develop more efficient methods and reagents as
catalysts.
In order to evaluate the efficiency of iodine as a catalyst,
the generality of the reaction was studied using various
aliphatic, benzylic and allylic alcohols (Table 1). Both
primary and secondary alcohols can be converted to
the corresponding acetates in good yields. Electron
donating groups accelerate the reaction of benzylic
OH
I2 / rt
OAc
R'
+ CH3CHO
OAc
+
R
R'
R
Keywords: Molecular iodine; Catalyst; Selective; Alcohol; Acetate;
Vinyl acetate.
Where R = R' = H, alkyl, aryl
Scheme 1.
*
Corresponding author. Tel.: +91 361 2582316; fax: +91 361
2690762; e-mail: asaikia@iitg.ernet.in
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.03.182

4066
J. W. J. Bosco et al. / Tetrahedron Letters 47 (2006) 4065–4068
Table 1. Acetylation of alcohols with vinyl acetate using molecular iodine
Entry
1
Substrate
Time (h)
4
Product
Yield (%)a
97
OH
OAc
OH
OAc
OAc
2
3
4
1.5
6
98
MeO
O2N
MeO
O2N
OH
93b
91
OH
OAc
4
OH
OAc
5
6
4.5
4
96
89
OH
OAc
OH
OAc
7
8
4
4
91
8
8
93b
OH
OAc
14
14
OH
OAc
9
4.5
89
OH
OAc
10
11
7
5
87
93
O
O
O
O
OH
OH
OAc
12
13
4.5
94b
OAc
O
O
O
O
H
H
4
78b
H
H
H
H
H
H
H
H
HO
AcO
OH
OAc
14
2
95b
HO
HO
HO
HO
OH
OAc
15
16
2
3
92b
OH
OAc
Trace
OH
OAc
17
12
0
1
a Yield refers to isolated yield. The compounds were characterized by H NMR, 13C and IR spectroscopy and by comparison with literature data.
b 4 equiv of vinyl acetate was used.

J. W. J. Bosco et al. / Tetrahedron Letters 47 (2006) 4065–4068
4067
Supplementary data
+
I
I
+
+
O
+H
H
Supplementary data associated with this article can
be found, in the online version, at doi:10.1016/j.tetlet.
2006.03.182.
O
OH
O
ROH
O
O
R
H
O
References and notes
Scheme 2.
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alcohols. Sterically hindered secondary alcohols (entries
11, 12 and 13) can also be acetylated in good yields.
Entries 10 and 13 testify the mildness of this method
towards acid sensitive groups. Phenols gave only trace
amounts of acetylated products and therefore alcohols
can be chemoselectively acetylated (entries 14 and 15).
Tertiary alcohols were found to react slowly under these
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18% yield after a prolonged reaction time (24 h), while
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acted. The reaction was completed quickly when carried
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ene and THF, but took longer. Thus, the reaction of
menthol was complete within 4.5 h with 94% yield when
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On the other hand, the same reaction took 13 h to com-
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in good yields. Under these reaction conditions, func-
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J. W. J. Bosco et al. / Tetrahedron Letters 47 (2006) 4065–4068
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24. Typical procedure for the molecular iodine catalyzed
acetylation of alcohols (entry 2): Molecular iodine
(0.1 mmol, 25.4 mg) was added to a mixture of p-
methoxybenzyl alcohol (1 mmol, 138.16 mg) and vinyl
acetate (3 mmol, 258 mg), which was stirred at room
temperature under a nitrogen atmosphere. When the
reaction was complete (TLC), it was extracted with ethyl
acetate (10 ml) and washed with saturated sodium
thiosulfate solution (4 ml). The organic layer was dried
over sodium sulfate and purified by column chromato-
graphy. The products were characterized by spectroscopic
methods. 1H NMR (400 MHz, CDCl3): d 2.07 (s, 3H, –O–
CO–CH3), 3.80 (s, 3H, O–CH3), 5.04 (s, 2H, –CH2–O–),
6.88 (d, J = 8.40 Hz, 2H, –ArH), 7.30 (d, J = 8.40 Hz, 2H,
–ArH); 13C NMR (100 MHz, CDCl3): d 20.96, 55.10,
65.94, 113.80, 127.80, 129.80, 159.28, 170.52; IR: 2950,
J. Org. Chem. 2001, 66, 7527; (d) Deka, N.; Sarma, J. C.
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1736, 1516, 1245, 1173, 1040 cmꢁ1
.