An efficient and selective tosylation of alcohols with p-toluenesulfonic acid

Article abstract of DOI:10.1016/j.tetlet.2004.07.076

Silica chloride has been found to be an efficient catalyst for facile tosylation of alcohols directly with p-toluenesulfonic acid in methylene chloride under reflux. The process is associated with selective tosylation of secondary alcohols over primary al

Full text of DOI:10.1016/j.tetlet.2004.07.076

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 6717–6719
An efficient and selective tosylation of alcohols with
p-toluenesulfonic acidq
Biswanath Das,* V. Saidi Reddy and M. Ravinder Reddy
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 24 May 2004; revised 5 July 2004; accepted 16 July 2004
Abstract—Silica chloride has been found to be an efficient catalyst for facile tosylation of alcohols directly with p-toluenesulfonic
acid in methylene chloride under reflux. The process is associated with selective tosylation of secondary alcohols over primary
alcohols.
Ó 2004 Elsevier Ltd. All rights reserved.
Tosylation of alcohols is widely used in organic synthe-
sis.1 Tosylation is generally carried out2 with p-toluene-
sulfonyl chloride or anhydride in the presence of bases.
However, these tosylating agents are very reactive and
moisture sensitive. p-Toluenesulfonic acid (p-TsOH)
has also been used3 as a tosylating agent but in this case
expensive reagents such as trialkyl orthoformates, alkyl
ethers or esters are also used. Recently, the synthesis of
sulfonates has been carried out with organic base
adducts of arylsulfonyls such as 1-phenylsulfonylbenzo-
triazole and 1-(benzenesulfonyl)- and 1-(p-toluenesul-
fonyl)-3-methylimidazolium triflates but an appreciable
amount of side products were formed.4 Two other meth-
ods using Fe3+-montmorillonite clay5a and CoCl2Æ
6H2O5b have been used for direct tosylation with
p-TsOH. However, in the first case primary and second-
ary alcohols behaved very similarly (e.g., MeOH and
cyclohexanol both took 3h to generate the correspond-
ing tosylates in yields of 82% and 86%, respectively)
while in the second method, tosylation of long-chain
alcohols required longer times to give the products but
in poor yields (e.g., 1-decanol gave the corresponding
tosylate in 26% yield after 10h). Thus there are a limited
number of suitable direct tosylation methods for alco-
hols with p-TsOH and there is still a need to develop
efficient protocols for this purpose.
In continuation of our work6 on the development of
novel synthetic methodologies, we recently observed
that silica chloride is an efficient heterogeneous catalyst
for tosylation of alcohols with p-TsOH (Scheme 1).
Several alcohols were treated with p-TsOH in the pres-
ence of silica chloride in CH2Cl2 under reflux to give
the tosylation products (Table 1). Primary and second-
ary alcohols (except long-chain alcohols) afforded the
products in very high yields. However, with long-chain
alcohols the yields were only moderate (51–63%). Sec-
ondary alcohols required less time than primary alco-
hols. Thus a secondary alcohol can be tosylated
chemoselectively in the presence of primary alcohols.
As an example, when a mixture of 1-octadecanol and
cyclohexanol were refluxed with p-TsOH in CH2Cl2 in
the presence of silica chloride the two compounds were
converted into the corresponding tosylates in yields of
7% and 95%, respectively (Scheme 2). The selective tosyl-
ation was also observed by reacting a compound con-
taining both primary and secondary hydroxyl groups
with p-TsOH in the presence of silica chloride (Scheme
3). The yield of the mono-tosylate derived from the
secondary alcohol moiety was 86% while that of di-tosyl-
ated product was only 8%. Cholesterol (entry k), even
though a more complex secondary alcohol, produced
the tosylated product efficiently and in good yield (84%).
p-TsOH
silica chloride
Keywords: Alcohols; p-TsOH; Tosylation; Silica chloride; Selectivity.
q Part 48 in the series, ꢀStudies on novel synthetic methodologiesꢁ.
Corresponding author. Tel.: +9140 27713874; fax: +9140
27160512; e-mail: biswanathdas@yahoo.com
R
OH
R
OTs
CH2Cl2, reflux
*
Scheme 1.
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.07.076

6718
B. Das et al. / Tetrahedron Letters 45 (2004) 6717–6719
Table 1. Tosylation of alcohols using silica chloridea
Entry
a
Substrate
Product
Time (h)
2.0
Isolated yield (%)
86
OH
OTs
OTs
OH
b
c
1.5
2.0
91
89
OH
OTs
OH
OH
OTs
OH
d
2.5
80
OH
OTs
( )
( )
n
n
e
f
n = 7
n = 1 3
n = 1 5
n = 7
n = 13
n = 15
3.0
4.0
4.5
63
54
51
g
OH
OTs
h
i
1.0
2.5
95
87
OH
OTs
OTs
OH
j
2.0
1.5
94
84
k
TsO
HO
l
1
1
0
0
0
0
OTs
OH
OH
OTs
m
OTs
OH
n
o
1
1
0
0
0
0
OH
OTs
OTs
OH
OMe
OMe
p
1
0
0
CHO
CHO
a The structures of the products were established from their spectral (1H NMR and MS) data.
Phenols and tertiary alcohols did not undergo tosylation
under the present experimental conditions even after
10h.
The catalyst, silica chloride can easily be prepared7 from
the readily available materials, silica gel and thionyl
chloride. It does not dissolve and so can easily be re-

B. Das et al. / Tetrahedron Letters 45 (2004) 6717–6719
6719
Acknowledgement
OTs
( )
OH
( )
15
15
p-TsOH
(7%)
The authors thank CSIR, New Delhi for financial
assistance.
silica chloride
+
+
CH2Cl2, reflux, 1 h
OTs
OH
References and notes
(95%)
Scheme 2.
1. Greene, T. W.; Wuts, P. G. M. Protecting Groups in
Organic Synthesis, 3rd ed.; Wiley: New York, 1999.
2. (a) Kurita, K. Chem. Ind. (London) 1974, 345; (b) Kabalka,
G. W.; Varma, M.; Varma, R. S.; Srivastava, P. C.; Knapp,
F. F., Jr. J. Org. Chem. 1986, 51, 2386–2387; (c) Yoshida,
Y.; Sakakura, Y.; Aso, N.; Okada, S.; Tanabe, Y. Tetra-
hedron 1999, 55, 2183–2192; (d) Hartung, J.; Honig, S.;
Kneuer, R.; Schwarz, M.; Wenner, H. Synthesis 1997,
1433–1438.
OTs
p-TsOH
OH
silica chloride
CH2Cl2, reflux, 1 h
OH
OH
(86%)
+
3. Nitta, Y.; Arakawa, Y. Chem. Pharm. Bull. 1985, 33,
1380–1386.
OTs
4. (a) OꢁConnell, J. F.; Rapoport, H. J. Org. Chem. 1992, 57,
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Commun. 1994, 24, 205–216.
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Tetrahedron 2000, 56, 7291–7298; (b) Velusamy, S.; Kumar,
J. S. K.; Punniyamurthy, T. Tetrahedron Lett. 2004, 45,
203–205.
OTs
(8%)
Scheme 3.
moved from the reaction mixture. The only by-product
of the reaction is water and thus there is no problem
relating to removal of side products and the experimen-
tal procedure itself is very simple.8 The structures of the
products were established from their spectral (1H NMR
and MS) data.
6. (a) Ramesh, C.; Mahender, G.; Ravindranath, N.; Das, B.
Tetrahedron Lett. 2003, 44, 1465–1467; (b) Srinivas, K. V.
N. S.; Das, B. J. Org. Chem. 2003, 68, 1165–1167; (c)
Srinivas, K. V. N. S.; Mahender, I.; Das, B. Synlett 2003,
2419–2421; (d) Ramesh, C.; Ravindranath, N.; Das, B. J.
Org. Chem. 2003, 68, 7101–7103; (e) Das, B.; Banerjee, J.;
Ravindranath, N.; Venkataiah, B. Tetrahedron Lett. 2004,
45, 2425–2426.
In conclusion, we have developed a convenient, facile
and selective method for direct tosylation of alcohols
with p-TsOH using silica chloride as a heterogeneous
catalyst. p-TsOH is a cheaper tosylating agent than
p-TsCl or p-Ts2O. The present method is more environ-
mentally benign over the generally practiced tosylation
with p-TsCl/pyridine, which produces large amounts of
salt effluents. We feel our protocol is an attractive alter-
native to the existing procedures for tosylation of
alcohols.
7. Firouzabadi, H.; Iranpoor, N.; Hazarkhani, H. Tetrahe-
dron Lett. 2002, 43, 7139–7141.
8. General procedure for tosylation: The alcohol (1mmol) and
p-TsOH (1.2mmol) were dissolved in CH2Cl2 (10mL).
Silica chloride (100mg) was added and the mixture was
heated under reflux. The reaction was monitored by TLC.
After completion, the reaction mixture was filtered and the
concentrated filtrate was subjected to column chromato-
graphy over silica gel using EtOAc–hexane (1:4) as eluent to
obtain analytically pure tosylate.