N-bromosuccinimide (NBS), a novel and highly effective catalyst for acetylation of alcohols under mild reaction conditions

Article abstract of DOI:10.1055/s-2001-12321

A variety of alcohols were acetylated in good to excellent yields with acetic anhydride in the presence of a catalytic N-bromosuccinimide (NBS) in CH₂Cl₂ and at room temperature. The reactions are clean and almost in all cases no detectable byproduct were observed.

Full text of DOI:10.1055/s-2001-12321

LETTER
519
N-Bromosuccinimide (NBS), a Novel and Highly Effective Catalyst for
Acetylation of Alcohols under Mild Reaction Conditions
a
Babak Karimi,* Hassan Seradj
Department of Chemistry, Institute for Advanced Studies in Basic Sciences (IASBS), P. O. Box 45195-159, Gava Zang, Zanjan, Iran
Fax +98(0241) 449023, E-mail: karimi@iasbs.ac.ir
Received 16 December 2000
Abstract: A variety of alcohols were acetylated in good to excellent
yields with acetic anhydride in the presence of a catalytic N-bromo-
succinimide (NBS) in CH Cl and at room temperature. The reac-
tions are clean and almost in all cases no detectable byproduct were
observed.
2
2
Scheme 1 R = aryl, vinyl or alkyl
Key words: acetates, N-bromosuccinimide, acetic anhydride,
acetylation, acylation
ary, and sterically hindered tertiary alcohols. The results
are summarized in the Table. It is in general known that
diarylcarbinols can easily dimerize or dismutate in the
presence of a Lewis acid catalyst. However, benzhydrol
itself, as a model compound, was acetylated in 95% yield
The acetylation of alcohols is one of the most widely used
process for the protection of hydroxy groups, which is
routinely carried out by acid anhydrides or acid chlorides
11
1
2
using Ac O (2 equiv.) in the presence of NBS (5 mol%)
2
in the presence of tertiary amines, protic or Lewis acids,
3
without any dimerization (Table, entry 12). The second-
ary alcohols 1,4-cyclohexanediol, (+)-menthol, 1-phe-
nylethanol, 3 -cholesterol and dehydroepiandrosterone
were acetylated under the same conditions in good to ex-
cellent yields (Table, entries 7-11). It is noteworthy that in
the case of optically active alcohols the reactions proceed-
ed well with complete retention of configuration (Table,
entries 9-11). Interestingly, hindered tertiary alcohols
such as 1-methylcyclohexanol and adamantanol were also
converted to the corresponding acetates at room tempera-
ture in excellent yields as a model for acetylation of tertia-
ry alcohols (Table, entries 13,14).
or sometimes solid acid catalysts. Vedejs et al. reported in
1
993 on Bu P to have a similar catalytic effect as tertiary
3
amines (such as DMAP and pyridine) for the acetylation
4
of alcohols by acetic anhydride. Recently, elegant work
of Yamamoto and his co- workers disclosed the use of
Sc(OTf) , a commercially available and moisture stable
3
Lewis acid, to promote the efficient acylation of various
types of structurally diverse alcohols with acetic anhy-
5
dride. Very recently, it has been demonstrated that TM-
6
7
SOTf and Bi(OTf) is a more powerful catalyst than
3
Sc(OTf) for the rapid and efficient acylation of alcohols.
3
Although these methods produce good results in many in-
stances, there is still a demand to develop new mild meth- The actual role of NBS is not clear, as we have mentioned
ods for the acylation of alcohols in the presence of in our previous reports.8 However, a plausible explana-
b,c
+
inexpensive and bench top catalysts. In our development tion is that NBS might act as a source for Br , which in
of new methods for functional group transformations, we turn activates the carbonyl group of Ac O to produce the
2
are especially interested in exploring the potential use of highly reactive acylating agent 1 (Scheme 2). Acylating
8
various types of neutral or nearly neutral catalysts. Along agent 1 reacts with alcohol, which upon elimination of
this line, we found that NBS efficiently catalyzes the acet- NBS produces acetate 2 and acetic acid. However, at this
8
b,e
alization of carbonyl compounds, the conversion of al- time the precise role of NBS is not clear and the actual role
8
c
dehydes to 1,1-diacetates, and the deprotection of 1,3- of this reagent should be further studied in detail.
8
h
oxathiolanes under mild and nearly neutral reaction con-
ditions. We therefore investigated the possibility of devel-
oping new catalytic system for the acylation of alcohols
In summary we showed that NBS is a good catalyst for
acetylation of a variety of alcohols with acetic anhydride
under mild reaction conditions. The reactions are clean
and no detectable by-product was formed. The product
yields are good to high and the procedure is easy. Further
investigation on the new applications of NBS is ongoing
in our laboratories.
using Ac O in the presence of NBS. N-Bromosucinimide
2
is an inexpensive and commercially available reagent
which is traditionally used as an oxidizing agent or bromi-
9
nating agent. We now disclose a novel and efficient pro-
tocol for the acetylation of a variety of alcohols using
Ac O (1.5-5 mmol) and a catalytic amount of NBS (5-10
2
Acknowledgement
mol%) at room temperature under mild reaction condi-
1
0
tions (Scheme 1).
We appreciate the financial support of this work by Institute for Ad-
vanced Studies in Basic Sciences Research Council.
Compounds that were acetylated in this protocol are pri-
mary, allylic, benzylic, hindered and unhindered second-
Synlett 2001 No. 4, 519–520 ISSN 0936-5214 © Thieme Stuttgart · New York

5
20
B. Karimi, H. Seradj
LETTER
Table Acetylation of Alcohols Using Ac O in the Presence of NBS
2
Scheme 2
References and Notes
(
1) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
nd
Synthesis, Wiley: Ney York, 2 ed.; 1991. (b) Kocienski, P. J.
Protecting Groups, Thieme: Stuttgart, 1994.
(
2) Larock, R. C. Comprehensive Organic Transformations,
VCH Publishers /inc: New York, 1989, P 980. For more recent
leading references see: (a) Saravanan, P.; Singh, V. K.
Tetrahedron Lett. 1999, 40, 2611. (b) Chandrasekhar, S.;
Ramachander, T.; Takhi, M. Tetrahedron Lett. 1998, 39,
3263. (c) Damen, E. W. P.; Braamer, L.; Scheeren, H. W.
Tetrahedron Lett. 1998, 39, 6081. (d) Orita, A.; Mitsutome,
A.; Otera, J. J. Org. Chem. 1998, 63, 2420. (e) Breton, G. W.
J. Org. Chem. 1997, 62, 8952. (f) Orita, A.; Sakamoto, K.;
Hamada, Y.; Mitsutome, A.; Otera, J. Tetrahedron 1999, 55,
2
899.
3) (a) Li, T. S.; Li, A. X. J. Chem. Soc., Perkin Trans 1 1998,
913. (b) Ballini, R.; Bosica, G.; Carloni, L.; Maggi, R.;
Sartori, G. Tetrahedron Lett. 1998, 39, 6049. (c) Bhaskar, P.
M.; Loganathan, D. Tetrahedron Lett. 1998, 39, 2215.
4) (a) Vedejs, E.; Diver, S. T. J. Am. Chem. Soc. 1993, 115, 3358.
(
(
(
1
(b) Vedejs, E.; Bennett, N. S.; Conn, L. M.; Diver, S. T.;
Gingras, M.; Lin, S.; Oliver, P. A.; Peterson, M. J. J. Org.
Chem. 1993, 58, 7286.
5) (a) Ishihara, K.; Kubota, M.; Kurihara, H.; Yamamoto, H. J.
Am. Chem. Soc. 1995, 117, 6639. (b) Ishihara, K.; Kubota, M.;
Kurihara, H.; Yamamoto, H. J. Org. Chem. 1996, 61, 4560.
(c) Ishihara, K.; Kubota, M.; Yamamoto, H. Synlett 1996,
2
65.(d) Barrett, A. G. M.; Braddock, D. C. Chem. Commun.
(
a) Isolated Yield. (b) Yield refers to isolated pure diacetate.
1997, 351. (e) Zhao, H.; Pendri, A.; Greenwald, R. B. J. Org.
Chem. 1998, 63, 7559.
(
6) (a) Procopiou, P. A.; Baugh, S. P. D.; Flack, S. S.; Inglis, G.
G. A. J. Org. Chem. 1998, 63, 2342. (b) Procopiou, P. A.;
Baugh, S. P. D.; Flack, S. S.; Inglis, G. G. A. J. Chem. Soc.,
Chem. Commun. 1996, 2625.
anhydride (3-10 mmol) in CH Cl (10 mL), NBS (0.1-0.2
2
2
mmol) was added at room temperature and the mixture was
stirred until complete disappearance of starting material (as
monitored by TLC or GC). After completion, the reaction was
quenched with water (20 mL), and the mixture was extracted
(
7) Orita, A.; Tanahashi, C.; Kakuda, A.; Otera, J. Angew. Chem.
Int. Ed. 2000, 39, 2877.
8) Karimi, B.; Golshani, B. J. Org. Chem. 2000, 65, 7228. (b)
Karimi, B.; Ebrahimian, G. R.; Seradj, H. Org. Lett. 1999, 1,
(
with CH Cl (2 30 mL). The organic layer was separated,
2
2
and washed with saturated NaHCO (2 25 mL) and water (15
1737. (c) Karimi, B.; Seradj, H. Synlett 2000, 641. (d) Karimi,
3
mL) and dried over anhydrous Na SO . Evaporation of the
B.; Miri Ashtiani, A. Chem. Lett. 1999, 1199. (e) Karimi, B.;
Seradj, H.; Ebrahimian, G. R. Synlett 1999, 1456. (f)
Firouzabadi, H.; Karimi, B.; Eslami, S. Tetrahedron Lett.
2
4
solvent under reduced pressure gave the almost pure 1,1-
diacetate. Further purification of products was achieved by
column chromatography to afford pure acetate(s) (Table).
11) Gauttret, P.; El-Ghamarti, S.; Legrand, A.; Coutrier, D.; Rigo,
B. Synth. Commun. 1996, 26, 707.
1999,40, 4055. (g) Firouzabadi, H.; Iranpoor, N.; Karimi, B.
(
Synthesis 1999, 58. (h) Karimi, B.; Seradj, H.; Tabaei, M. R.
Synlett 2000, 1798.
(
9) Hudlicky, M. Oxidations in Organic Chemistry, ACS
Monograph 186, Washington DC, 1990.
Article Identifier:
437-2096,E;2001,0,04,0519,0520,ftx,en;G25800ST.pdf
(
10) General Procedure for Acetylation of Alcohols Using Ac O
2
1
and NBS. To a solution of alcohol (2 mmol) and acetic
Synlett 2001, No. 4, 519–520 ISSN 0936-5214 © Thieme Stuttgart · New York