cantly large amount of Al2O3 was used. Prompted by the
recent reports, we present our results herein.
Rea ction s on a Solid Su r fa ce. A Sim p le,
Econ om ica l, a n d Efficien t Acyla tion of
Alcoh ols a n d Am in es over Al2O3
The results of the reactions of a diverse range of
alcohols are collected in Table 1. Several features deserve
comment. An acid chloride was preferred over the cor-
responding acid anhydride. The reaction with acid an-
hydride was too slow to have practical application. Both
primary and secondary alcohols reacted very well; ter-
tiary alcohols did not react. The conversion of propargyl
alcohol into propargyl acetate on a 100 mmol scale (entry
6) proceeded just as well as the 1 mmol reaction. The
reaction was conducive to the acetylation of silicon-
containing alcohols; 3-trimethylsilyl-2-propyn-1-ol was
conveniently transformed into its acetate (entry 7). Diols
and triols having primary and secondary alcohol func-
tions were conveniently transformed into diacetates
and triacetates, respectively. Primary alcohols reacted at
least 5 times faster than secondary alcohols; tertiary
alcohols were completely resistant and did not undergo
acetylation. Acid chlorides other than AcCl reacted slower
as the reactions took comparatively longer time for
completion.
The reactions of â-naphthol and p-bromophenol with
AcCl (entries 16 and 17) were very slow in comparison
to those of the aliphatic alcohols. Even after vigorous
stirring for 16 h at 25 °C, the reactions were incomplete.
â-Naphthol and p-bromophenol did not react at all with
Ac2O (entries 16 and 17). This is in contrast to the use of
KF-Al2O3 that was very effective for the acetylation of
phenols.4 The poor reactivity of phenols with AcCl over
Al2O3 raised a genuine possibility of selective acylation
of primary and secondary alcohols in the presence of
phenols. Indeed, 3-(2-hydroxyphenyl)propanol furnished
only the expected monoacetate on reaction with 1.1 equiv
of AcCl. Thus, the present method is comparable to the
use of Pseudomonus cepacia PS lipase,6 twisted amides,7
and also the transesterification protocol that is catalyzed
by distannoxane.8
Veejendra K. Yadav* and K. Ganesh Babu
Department of Chemistry, Indian Institute of Technology,
Kanpur-208 016, India
vijendra@iitk.ac.in
Received September 26, 2003
Abstr a ct: Al2O3 brings about a rapid acylation of a range
of alcohols and amines with acid chlorides and acid anhy-
drides, respectively. Amines are easily Boc- and Cbz-pro-
tected on reaction with Boc-anhydride and Cbz-Cl, respec-
tively. The acylation of phenols is slow enough to allow che-
moselective acylation of alcohols and amines in the presence
of phenols.
The acylation, particularly the acetylation, of alcohols
and amines is an important transformation in organic
synthesis.1 Although numerous methods to achieve acy-
lation are known, newer methods continue to attract
attention for their experimental simplicity and effective-
ness. Reactions on solid surfaces are particularly impor-
tant because they allow easy recycling of the support. A
recent report claims acetylation of carbinols, thiols, and
amines using Ac2O-pyridine-Al2O3 in solvent-free con-
ditions under microwave irradiation.2 Whereas the acety-
lation of phenols, thiophenols, amines, and anilines was
reported, no example of the reaction of an alcohol has
appeared. More recently, HClO4 adsorbed on silica gel
was demonstrated to efficiently catalyze the acetylation
of phenols, thiols, alcohols, and aromatic amines with
Ac2O.3 The acetylation of aliphatic amines, however, was
not attempted. We have been interested in the develop-
ment of methods for acylation that (a) would avoid the
use of added acids and bases, (b) would avoid aqueous
workup and chromatographic purification, (c) are easy
to perform, and (d) are economical for application to
large-scale preparations. In this pursuit, we have re-
ported previously on the use of KF-Al2O3 as a solid
support reagent for the acetylation of alcohols, amines,
and phenols with AcCl/Ac2O.4 This method was found to
be more efficient than most other often-used methods.
We have now discovered that neutral Al2O3 alone pro-
motes a very efficient acylation of alcohols and amines
with noticeable differences from those of KF-Al2O3.
Though Al2O3 has been previously demonstrated to
promote the transesterification of alcohols with ethyl
acetate,5 the yields were generally poor and the reactions
also took considerably long time. Furthermore, a signifi-
The results of the acylation of amines are collected in
Table 2. It is significant to note that acid anhydrides were
preferred to the acid chlorides. All the amines reacted
very rapidly within 5-10 min. Aromatic amines that
were substituted by electron-attracting groups, e.g.,
p-nitroaniline (entry 2), reacted only a little slower
than those that possessed electron-donating groups, e.g.,
p-chloroaniline (entry 1). Amines could also be Boc- and
Cbz-protected conveniently by adopting the present
protocol in excellent yields. Boc-anhydride and Cbz-Cl,
respectively, were employed for the formation of Boc- and
Cbz-derivatives (entries 5, 7, 12 and 13).
The reactions of amines with Ac2O were so fast in
comparison to those of the aliphatic alcohols that the
* To whom correspondence should be addressed. Fax: +91-512-
597436.
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10.1021/jo035412f CCC: $27.50 © 2004 American Chemical Society
Published on Web 12/19/2003
J . Org. Chem. 2004, 69, 577-580
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