Tetrahedron Letters 47 (2006) 6825–6829
A mild and efficient acetylation of alcohols, phenols and amines
with acetic anhydride using La(NO3)3Æ6H2O as a catalyst
under solvent-free conditionsI;II
T. Srikanth Reddy, M. Narasimhulu, N. Suryakiran, K. Chinni Mahesh,
K. Ashalatha and Y. Venkateswarlu*
Natural Products Laboratory, Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 29 May 2006; revised 3 July 2006; accepted 14 July 2006
Available online 4 August 2006
Abstract—A wide variety of alcohols, phenols and amines are efficiently and selectively converted into the corresponding acetates by
treatment with acetic anhydride in the presence of catalytic amounts of La(NO3)3Æ6H2O under solvent-free conditions at room tem-
perature. The method is compatible with acid sensitive hydroxyl protecting groups such as TBDMS, THP, OBz, OBn, Boc and some
isopropylidenes and offers excellent yields of the mono acetates of 1,3-, 1,4- and 1,5-diols.
ꢀ 2006 Elsevier Ltd. All rights reserved.
Functional group protection strategies are central to
target molecule synthesis. The protection of alcohols,
phenols and amines are fundamental and useful trans-
formations in organic synthesis. Among the many
protecting groups for hydroxyls, phenols and amines,
acetate is used with high frequency. Although, numer-
ous methods are available for the preparation of
acetates using acetic acid and a protic acid, acetic anhy-
dride and pyridine are the most commonly used
reagents.1 4-(Dimethylamino)pyridine (DMAP) and
4-pyrrolidinopyridine (PPY) catalyze the acetylation of
alcohols.2 Further, other catalysts such as TaCl5,3
TMSOTf,4 Sc(OTf)3,5 Bu3P,6 CoCl2,7 montmorillonite
of alcohols, phenols and amines using acetic anhydride
in the presence of La(NO3)3Æ6H2O (Scheme 1).
In the course of our ongoing search for chemoselective
reagents, we identified La(NO3)3Æ6H2O as a mild and
efficient catalyst for the chemoselective tetrahydropyr-
anylation of primary alcohols,13 the chemoselective
deprotection of acetonides14 and for the synthesis of
quinazolinones.15 In continuation of these studies, we
found that La(NO3)3Æ6H2O is an efficient and mild
acidic catalyst for the acetylation of alcohols with
Ac2O under solvent-free conditions. In order to estab-
lish the catalytic activity of La(NO3)3Æ6H2O, we carried
out the acetylation of glucose diacetonide (1 mmol) with
acetic anhydride (1.2 mmol) using La(NO3)3Æ6H2O
(5 mol %) at room temperature which gave the corre-
sponding acetate in 96% yield (Table 1, entry 1).
Encouraged by the success of this reaction, various
primary, secondary, benzylic and allylic alcohols and
phenols (Table 1) and amines (Table 2) were subjected
K-10 and KSF,8 TMSCl,9 Sn(OTf)2, Cu(OTf)2 and In
10–12
(OTf)3
have been used for the acetylation of alco-
hols. However, most of these reported methods suffer
from one or more disadvantages like long reaction
times, harsh reaction conditions, the occurrence of side
reactions, toxic reagents, poor yields of the desired prod-
ucts and intolerance of other functional groups. Here,
we report a mild and efficient method for the acetylation
THPO
AcO
THPO
HO
Keywords: Lanthanum(III) nitrate hexahydrate; Alcohols; Phenols;
Amines; Acetylation; Solvent-free conditions.
O
La(NO3)3.6H2O
O
O
O
q IICT Communication No. 060702.
Ac2O, rt, 10-20 min
qq Reactions using lanthanum(III) nitrate hexahydrate paper 4.
O
BnO
O
BnO
Scheme 1.
*
Corresponding author. Tel.: +91 40 27193167; fax: +91 40
0040-4039/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.07.059