A mild and efficient acetylation of alcohols, phenols and amines with acetic anhydride using La(NO3)3·6H2O as a catalyst under solvent-free conditions

Article abstract of DOI:10.1016/j.tetlet.2006.07.059

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)₃·6H₂O under solvent-free conditions at room temperature. 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.

Full text of DOI:10.1016/j.tetlet.2006.07.059

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
27160512; e-mail: luchem@iict.res.in
0040-4039/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.07.059

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T. Srikanth Reddy et al. / Tetrahedron Letters 47 (2006) 6825–6829
Table 1. Acetylation of alcohols and phenols in the presence of lanthanum(III) nitrate hexahydrate
Entry
1
Substrate
Producta
Time (min)
15
Yieldb (%)
OAc
OH
O
O
OTHP
OH
OTHP
OAc
O
O
96
O
O
OBz
OH
OBz
OAc
O
O
O
O
O
O
2
15
95
O
O
OBz
OBz
OH
OBn
OAc
OBn
O
O
3
4
5
15
15
10
96
98
96
O
O
OTHP
OTHP
AcO
TsO
HO
O
O
TsO
OH
OAc
O
O
O
O
O
O
O
O
6
15
94
OH
OH
OAc
OAc
7
8
18
18
93
95
OH
OAc
MeO
MeO
OH
OAc
9
10
95
TBDMSO
TBDMSO
10
11
15
20
96
98
OH
NHBoc
OAc
NHBoc
HO
O
AcO
O
OH
Me
OAc
Me
O
12
13
20
15
95
96
EtO
EtO
OEt
OEt
O
OH
OAc
CHO
CHO
OH
OAc
14
15
15
15
95
96
Cl
Cl
OH
OAc
OMe
OMe

T. Srikanth Reddy et al. / Tetrahedron Letters 47 (2006) 6825–6829
6827
Table 1 (continued)
Entry
Substrate
Br
Producta
Br
Time (min)
Yieldb (%)
OH
OAc
Br
Br
O
O
16
20
98
Br
Br
Br
O
Br
O
O
O
HO
AcO
17
18
15
20
96
97
OH
OAc
COOH
OH
COOH
OAc
19
20
15
18
97
96
OH
OAc
O
O
OH
Br
OAc
Br
OH
OAc
Br
Br
21
22
18
20
95
96
Br
Br
OH
OAc
NO2
NO2
23
24
25
15
15
15
94
98
98
OH
OAc
OH
OAc
HO
OAc
90
+
OH
HO
HO
AcO
OAc
10
HO
OAc
OAc
80
+
26
20
98
OH
AcO
20
(continued on next page)

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T. Srikanth Reddy et al. / Tetrahedron Letters 47 (2006) 6825–6829
Table 1 (continued)
Entry
Substrate
Producta
Time (min)
Yieldb (%)
98
27
20
OAc
OAc
HO
OH
HO
80
+
AcO
20
OH
OAc
28
20
96
a All the compounds were characterized by 1H NMR and mass spectral data.
b Isolated yields after column chromatography.
Table 2. Acetylation of amines in the presence of lanthanum(III)
nitrate hexahydrate
is evident that acetic anhydride and lanthanum(III)
nitrate hexahydrate is an excellent combination for the
acetylation of alcohols, phenols and amines under sol-
vent-free conditions. Thiols and thiophenols could not
be acetylated using this method.
Entry Substrate
Producta
Time (min) Yield (%)b
NH2
NHAc
1
15
98
Typical experimental procedure: To a mixture of alcohol/
phenol/amine (1 mmol), and acetic anhydride (1.2
mmol), La(NO3)3Æ6H2O (10 mol %) was added. The
reaction mixture was stirred at room temperature for
the appropriate amount of time (Tables 1 and 2). After
completion of the reaction as monitored by TLC, water
was added to the reaction mixture and the product was
extracted into ethyl acetate (3 · 20 mL). The combined
organic layer was washed with brine and concentrated
in vacuum to give a crude mass, which was purified by
silica gel column chromatography to afford the corre-
sponding acetylated product.
NO2
NO2
NH2
NHAc
2
20
15
98
98
NO2
NO2
NH2
NHAc
3
Acknowledgements
CH3
NH2
CH3
The authors thank the Director, Indian Institute of
Chemical Technology, CSIR and DOD, New Delhi,
India, for financial support.
NHAc
CH3
CH3
4
5
15
20
98
98
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