ZrCl4 as an efficient catalyst for selective tosylation of alcohols with p-toluenesulfonic acid

Article abstract of DOI:10.1246/cl.2004.1428

Tosylation of alcohols has directly been carried out with p-toluenesulfonic acid in methylene chloride under reflux using ZrCl₄ as a catalyst. Primary alcohols were found to be tosylated chemoselectively over secondary alcohols.

Full text of DOI:10.1246/cl.2004.1428

1428
Chemistry Letters Vol.33, No.11 (2004)
ZrCl4 as an Efficient Catalyst for Selective Tosylation of Alcohols with p-Toluenesulfonic Acid1
Biswanath Dasꢀ and Vtukuri Saidi Reddy
Organic Chemistry Division-I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
(Received August 10, 2004; CL-040947)
Tosylation of alcohols has directly been carried out with p-
toluenesulfonic acid in methylene chloride under reflux using
ZrCl4 as a catalyst. Primary alcohols were found to be tosylated
chemoselectively over secondary alcohols.
somewhat low (86%) and the yield was not increased than 94%
with p-TsOH in excess (1.5 equiv.) The catalyst taken in excess
(0.2 and 0.5 equiv.) also retarded the yields of the tosylate (82
and 77%, respectively). The reaction conducted in CH3CN and
MeOH afforded the desired tosylate in poor yields (42 and
37%, respectively) while no product was obtained by performing
the reaction at 0 ꢁC and room temperature.
Following the above reaction condition different alcohols
were now heated under reflux with p-TsOH in CH2Cl2 in the
presence of ZrCl4 to form the tosylates (Table 1). Primary alco-
hols afforded the products in very high yields. Even long-chain
Tosylation of alcohols is an important transformation in or-
ganic synthesis.2 This transformation is usually achieved2,3 with
p-toluenesulfonyl chloride or anhydride which is very reactive
and moisture sensitive. The formation of the side products using
these reagents in the presence of a base is also a problem. For
direct use of p-toluenesulfonic acid (p-TsOH) as a tosylating
agent, trialkyl orthoformates, alkyl ethers or esters have been
employed.4 Recently two methods have also been developed
for tosylation of alcohols with p-TsOH utilizing Fe3þ-montmor-
a,b
Table 1. Tosylation of alcohols using ZrCl4
Entry
Substrate
Time
/ h
6
Isolated
Yield / %
Product
OTs
OH
illonite clay5a and CoCl2 6H2O.5b However, in the first case, the
.
a
95%
water formed in the reaction may block the acidic sites of the
catalyst inhibiting the rate of the reaction while in the second
case the catalyst is not suitable for tosylation of long chain
alcohols which would take longer time to form the tosylates in
poor yields. Herein, we wish to report a suitable method for
direct tosylation of alcohols with p-TsOH employing ZrCl4 as
a catalyst (Scheme 1).
OH
OTs
b
6.5
92
OH
OH
c
7
94
90
OTs
OTs
OH
d
6.5
OH
(
)
OTs
(
)
OH
n
n
e
f
g
n = 7
n = 13
n = 15
n = 7
n = 13
n = 15
7
10
10
85
82
79
p-TsOH
ZrCl4
R-OTs
R-OH
CH2Cl2, reflux
OTs
OH
54
h
10
Scheme 1.
OTs
OH
i
j
12
58
55
To examine the catalytic activity of different Lewis acids
such as AlCl3, SnCl4, TiCl4, ZrCl4, and HfCl4 phenyl propanol
(1 equiv.) was first treated with equimolar quanity of p-TsOH in
CH2Cl2 (10 mL) under reflux for 6 h in the presence of each cat-
alyst (0.1 equiv.) separately. ZrCl4 was found to the most effec-
tive catalyst in term of the yield of tosylate (87%) while AlCl3,
HfCl4, TiCl4, and SnCl4 formed the tosylates with the yields of
37, 28, 12, and 8%, respectively. Previously ZrCl4 was also veri-
fied6 to be highly effective for direct condensation of carboxylic
acids with alcohols.
12.5
OTs
OH
k
10
51
TsO
HO
l
14
14
0
0
OH
OTs
OH
OTs
m
The optimized condition of the present reaction was deter-
mined by tosylation of phenyl propanol (1 equiv.) with different
amount of p-TsOH (1.0, 1.2, and 1.5 equiv.) and also using ZrCl4
in variable quantities (0.1, 0.2, and 0.5 equiv.) Different solvents
such as CH2Cl2, CH3CN, and MeOH were employed and the
conversion was conducted at 0 ꢁC, room temperature and under
reflux. It was observed that phenyl propanol (1 equiv.) afforded
the corresponding tosylate in highest yield (94%) by heating
with p-TsOH (1.2 equiv.) in the presence of ZrCl4 (0.1 equiv.)
in CH2Cl2 (10 mL) under reflux for 7 h. However, when the re-
action was carried out with p-TsOH (1.0 equiv.) keeping all oth-
er parameters the same, the yield of the tosylate was found to be
OH
OTs
n
o
14
14
0
0
OH
OTs
OMe
OMe
CHO
CHO
aThe structure of the products were established from spectral
(1H NMR and MS) data.
bThe starting material was the remainder in the case of a secon-
dary alcohol and it could be recovered.
Copyright Ó 2004 The Chemical Society of Japan

Chemistry Letters Vol.33, No.11 (2004)
1429
alcohols were also converted smoothly to the tosylation prod-
ucts. However, secondary alcohols took longer times to produce
the tosylates in moderate yields. Thus the present catalyst cata-
lyzes chemoselectively the tosylation of primary alcohols over
secondary alcohols. To verify this, a mixture of 1-decanol and
2-butanol was treated with p-TsOH in the presence of ZrCl4 in
CH2Cl2 under reflux for 6 h (Scheme 2). The two compounds
were converted into the corresponding tosylates in yields of 81
and 4%, respectively.
is cheaper than p-TsCl and p-Ts2O, and it is also more simple
and eco-friendly than the methods using the latter two reagents
as there is no problem here related to side products. The present
procedure is thus expected to find useful applications for direct
tosylation of alcohols.
The authors thanks CSIR, New Delhi for financial assis-
tance.
References and Notes
1
2
3
Part 54 in the series, ‘‘Studies on Novel Synthetic Methodol-
ogies.’’
OTs
( )
OH
( )
7
p-TsOH
ZrCl4
7
81%
+
T. W. Greene and P. G. M. Wuts, ‘‘Protecting Groups in
Organic Synthesis,’’ 3rd ed., Wiley, New York (1999).
a) G. W. Kabalka, M. Varma, R. S. Varma, P. C. Srivastava,
and F. F. Knapp, Jr., J. Org. Chem., 51, 2386 (1986).
b) J. Hartung, S. Honig, R. Kneuer, and H. Wenner,
Synthesis, 1997, 1433. c) Y. Yoshida, Y. Sakakura, N.
Aso, S. Okada, and Y. Tanabe, Tetrahedron, 55, 2183
(1999). d) Y. Yoshida, K. Shimomishi, Y. Sakakura, S.
Okada, N. Aso, and Y. Tanabe, Synthesis, 1999, 1633.
Y. Nitta and Y. Arakawa, Chem. Pharm. Bull., 33, 1380
(1985).
a) B. M. Choudary, N. S. Chowdari, and M. L. Kantam, Tet-
rahedron, 56, 7291 (2000). b) S. Velusamy, J. S. K. Kumar,
and T. Punniyamurthy, Tetrahedron Lett., 45, 203 (2004).
K. Ishihara, S. Ohara, and H. Yamamoto, Science, 290, 1140
(2000).
General procedure for tosylation : To a solution of an alcohol
(1 mmol) and p-TsOH (1.2 mmol) in CH2Cl2 (10 mL) ZrCl4
(0.1equiv., 25 mg) was added. The mixture was heated under
reflux and the reaction was monitored by TLC. After com-
pletion, the mixture was filtered and the filtrate was concen-
trated. The residue was subjected to column chromatography
over silica gel using EtOAc–hexane (1:4) as eluent to pro-
duce pure tosylate.
+
OH
OTs
CH2Cl2, reflux
6 h
4%
Scheme 2.
The present method was found to be unsuitable for tosyla-
tion of tertiary alcohols and phenols. In the first case steric factor
of the intermediates may be the possible reason of not forming
the tosylates while in the second case ZrCl4 creates weak polar-
ization of the O=S< bond of p-TsOH and a phenol having poor
nucleophilicity is uncapable to attack the sulphur atom.
The catalyst, ZrCl4 is easily available and less costly. It is
now commercially utilized for its efficient catalytic activity as
well as mildness. The experimental procedure for tosylation is
simple7 and there is no problem for removal of side products.
The structures of the tosylates were settled from their spectral
(1H NMR and MS) data.
4
5
6
7
In conclusion, we have demonstrated that ZrCl4 is an effi-
cient catalyst for direct tosylation of alcohols with p-TsOH
and it catalyzes selectively the tosylation of primary alcohols
over secondary alcohols. The method is economic as p-TsOH
Published on the web (Advance View) October 2, 2004; DOI 10.1246/cl.2004.1428