PAPER
1621
Silver Triflate Catalyzed Acetylation of Alcohols, Thiols, Phenols, and Amines
A
gO
T
f-Catalyzed
i
A
cety
m
lationof
A
lcohols,
a
T
hiols,
P
henols,
a
D
nd
A
mine
s
as, Debashis Chakraborty*
Department of Chemistry, Indian Institute of Technology Madras, Chennai-600 036, Tamil Nadu, India
Fax +91(44)22574202; E-mail: dchakraborty@iitm.ac.in
Received 4 February 2011
dustries, the development of environmentally benign or-
Abstract: A variety of alcohols, thiols, phenols, and amines were
subjected to acetylation reaction using acetic anhydride in the pres-
ence of catalytic quantity of silver triflate. The method described
has a wide range of applications, proceeds under mild conditions,
ganic reactions has become a crucial and demanding area
in modern organic chemical research. According to
Wender, the ‘ideal synthesis’ is one in which the target
does not involve cumbersome workup, and the resulting products components are readily obtained in one step and in quan-
are obtained in high yields within a reasonable time.
titative yields from readily available starting materials in
an environmentally acceptable process.27 Our continued
Key words: acetylation, silver triflate, alcohol, phenol, thiol, amine
interest in environmentally benign process prompted us to
explore the catalytic chemistry of Ag(I) salts.28 Herein, we
report that a number of alcohols, thiols, phenols, and
Functional group protection strategies are central to target
amines can be acetylated with acetic anhydride, in excel-
molecule synthesis. The acetylation of hydroxy and amino
lent yields, in the presence of catalytic amounts of AgOTf
under mild and solvent-free conditions.
groups is one of the most widely used transformations in
organic synthesis, and a variety of acylating agents have
been developed.1 The protection of hydroxyl, mercapto,
Initial attempts to optimize the reaction conditions for
and amino groups by esterification constitutes the major
backbone of many preparations of natural and synthetic
products such as perfumes, flavors, food additives, cos-
metics, pharmaceuticals, plasticizers, and polymers.2
Generally, esterification is carried out by acylation of al-
cohols, thiols, phenols, and amines with carboxylic acids
and more conveniently with anhydrides or acyl chlorides
in the presence of basic catalysts.2c The use of acetic acid
or a protic acid or acetic anhydride and pyridine is a com-
mon method for the synthesis of acetates.2b 4-(Dimethyl-
amino)pyridine (DMAP) and 4-pyrrolidinopyridine
(PPY) catalyze the acetylation of alcohols.3 Further, other
catalysts such as CoCl2,4 TaCl5/SiO2,5 ZnCl2,6 ZnO,7
InCl3,8 ZrCl4,9 LiClO4,10 Ru-catalysts,11 Mg(ClO4)2,12
SmI2,13 CeCl3,14 ZrOCl2·8H2O,15 montmorillonite,16
TMSCl,17 PTSA,18 NH2SO3H,19 distannoxane,20 ionic liq-
uids,21 solid supported reagents and lipase enzymes,22 and
various triflates23 have been used for acetylation. Recent
reports include the use of molecular iodine,24 3-nitroben-
zeneboronic acid,25 and La(NO3)3·6H2O,26 towards the
acetylation; however, perchlorates, particularly of lithi-
um, are known to be explosive and moisture sensitive. Al-
though a large number of methods for acetylation are
available, many suffer from limitations such as long reac-
tion times, harsh reaction conditions, use of expensive,
moisture sensitive and toxic catalysts, formation of side
products, and poor yields of the desired products. In view
of the demands of organic synthesis, there is still a need to
develop mild and efficient protocols for acetylation. With
increasing environmental concerns and the regulatory
constraints faced in the chemical and pharmaceutical in-
acetylation reaction were performed with benzyl alcohol
as a suitable substrate in the presence of acetic anhydride
and different Ag(I) salts. The conversion of benzyl alco-
hol to benzyl acetate was found to be extremely facile in
the presence of 1 mol% AgOTf at 60 °C. The reaction
took longer time periods when performed under ambient
conditions or in the presence of other Ag(I) salts (see Sup-
porting Information).
Having optimized the reaction conditions, we continued
our investigations with a variety of substrates namely al-
cohols, thiols (Table 1), phenols (Table 2), and amines
(Table 3). A very large variety of alcohols, thiols, phenols
and amines were subjected to acetylation reaction. The
product from every reaction was isolated in very high
yield after workup and column chromatography. The
structural identity of all the products were ascertained on
the basis of their spectral properties (1H, 13C NMR, and
mass spectra; see Supporting Information). In the absence
of a catalyst, using the same reaction conditions, the cor-
responding products were obtained in low yields (25–
30%) even after prolonged reaction time of 1.5 hours. The
general applicability and efficiency of this reaction is ev-
ident from the wide range of compounds studied.
The kinetic studies of the acetylation reaction with cate-
chol, cyclohexanol, 4-thiocresol, and 2,6-diisopropyl-
amine was explored next. High-pressure liquid
chromatography (HPLC) was used to determine the vari-
ous starting materials and products present as a function
of time. The concentrations of reactant and product for the
acetylation of catechol are shown in Figure 1. The con-
centration of catechol decreases steadily while that of the
product increases. The rates of such reactions were calcu-
lated. As an example, the acetylation of catechol can be
considered. Van’t Hoff differential method was used to
determine the order (n) and rate constant (k) (Figure 2).
SYNTHESIS 2011, No. 10, pp 1621–1625
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Advanced online publication: 12.04.2011
DOI: 10.1055/s-0030-1259999; Art ID: Z17211SS
© Georg Thieme Verlag Stuttgart · New York