Cobalt(II) catalyzed tosylation of alcohols with p-toluenesulfonic acid

Article abstract of DOI:10.1016/j.tetlet.2003.10.106

Cobalt(II) chloride hexahydrate (CoCl₂·6H₂O) has been found to catalyze the tosylation of both aliphatic and aromatic alcohols with p-toluenesulfonic acid (p-TsOH) in high yields in 1,2-dichloroethane under reflux (ca. 80°C). In the

Full text of DOI:10.1016/j.tetlet.2003.10.106

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 203–205
Cobalt(II) catalyzed tosylation of alcohols with p-toluenesulfonic
acid
Subbarayan Velusamy, J. S. Kiran Kumar and T. Punniyamurthy*
Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati 781039, India
Received 23 July 2003; revised 7 October 2003; accepted 17 October 2003
Abstract—Cobalt(II) chloride hexahydrate (CoCl2Æ6H2O) has been found to catalyze the tosylation of both aliphatic and aromatic
alcohols with p-toluenesulfonic acid (p-TsOH) in high yields in 1,2-dichloroethane under reflux (ca. 80 ꢀC). In the case of aliphatic
alcohols, secondary alcohols undergo tosylation chemoselectively in the presence of primary hydroxy groups.
ꢁ 2003 Elsevier Ltd. All rights reserved.
The tosylation of alcohols is a frequently used func-
OH
.
5 mol% CoCl2 6H2O
OTs
tional transformation in organic chemistry.1 Typically,
the moisture sensitive and very reactive sulfonyl chloride
or anhydride are usually employed as the tosylating
agents in the presence of bases.2 Sulfonic acids are also
used as tosylating agents but expensive alkylating agents
such as trialkyl orthoformate, alkyl ethers or esters are
needed instead of the alcohol.3 Recently, organic base
adducts of sulfonyls such as 1-phenylsulfonyl benzo-
triazole and aryl sulfonyl methylimidazolium salts have
been employed for sulfonate synthesis, however, signif-
icant amounts of by-products in the form of total
+ H2O
R
R'
R
R'
26-95%
R=alkyl, aryl; R'=alkyl, H
1 equiv p-TsOH
ClCH2CH2Cl
reflux
Scheme 1.
In the presence of a catalytic amount of CoCl2Æ6H2O,
the tosylation of 4-methoxylbenzyl alcohol was first
examined with p-TsOH (Table 1). Toluene, CH2Cl2,
dissolved salts are generated.4 More recently, Fe3þ
–
montmorillonite clay has been reported to catalyze the
tosylation of alcohols with p-TsOH.5 This method
works well with aliphatic alcohols but aromatic alcohols
give rearranged or polymeric products. Herein, we wish
to report a simple and efficient method for the direct
tosylation of both aliphatic and aromatic alcohols with
1 equiv of p-TsOH in the presence of CoCl2Æ6H2Oin
high yields (Scheme 1). This protocol also functions in
the absence of additives and the removal of water is not
warranted. In contrast to the Fe3þ–montmorillonite
catalyzed process,5 this methodology chemoselectively
catalyzes the tosylation of aliphatic secondary alcohols
in the presence of primary hydroxy groups in high
yields.
Table 1. Tosylation of 4-methoxybenzyl alcohol with p-TsOH and
CoCl2Æ6H2O
CH2OH
CH2OTs
.
5 mol% CoCl2 6H2O
p-TsOH
OMe
Solvent
CH2Cl2
Solvent
OMe
Time
(h)
Entry
Temperature
(ꢀC)
Yield
(%)a;b;c
1
2
3
4
Rt
14
1
67
95
41
78
ClCH2CH2Cl Reflux
CH3CN
Toluene
Reflux
Reflux
14
3
a A solution of the substrate (3 mmol), p-TsOH (3 mmol), CoCl2Æ6H2O
(5 mol %), and solvent (10 mL) was stirred for the appropriate time
and temperature.
Keywords: tosylation; alcohol; p-toluenesulfonic acid; catalyst;
cobalt(II) chloride hexahydrate.
b Isolated yield.
* Corresponding author. Tel.: +91-361-2690321; fax: +91-361-2690-
762; e-mail: tpunni@iitg.ernet.in
c The identity of the product was ascertained by NMR, IR, and mass
spectrometric analysis.
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doi:10.1016/j.tetlet.2003.10.106

204
S. Velusamy et al. / Tetrahedron Letters 45 (2004) 203–205
CH3CN, and ClCH2CH2Cl were employed as the sol-
vents. As expected, the reaction took place and afforded
4-methoxybenzyl tosylate in good yields when the
reaction mixtures were allowed to stir in the presence of
5 mol % CoCl2Æ6H2O. Among the solvents screened,
ClCH2CH2Cl was found to be suitable for this pro-
tocol and the highest yield of 95% was obtained
under reflux (ca. 80 ꢀC). The reactions in CH2Cl2,
CH3CN, and toluene were less effective and afforded the
tosylate in 41–78% yields. Control reactions without
CoCl2Æ6H2Ounder the same reaction conditions showed
no reaction.
alcohol, and geraniol, underwent tosylation to afford the
corresponding tosylates in 90–95% yields. In the case of
the aliphatic alcohols, secondary alcohols were tosylated
much faster compared to primary hydroxy groups. For
example, 2-butanol, cyclohexanol, menthol, and choles-
terol were transformed into the corresponding tosyl-
ates in 87–95% yields within 3.5 h, whereas decanol was
less reactive and afforded decyl tosylate in only 26% yield
after 10 h. When a mixture of cyclohexanol and n-hexa-
nol was allowed to react with 0.5 equiv p-TsOH for 1 h,
cyclohexanol underwent tosylation chemoselectively in
95% yield along with a trace of n-hexyl tosylate (Scheme
2). These studies clearly reveal that this methodology can
be applied for the chemoselective direct tosylation of
aliphatic secondary alcohols in the presence of primary
hydroxy groups. Furthermore, when the tosylation
of phenol and b-naphthol was examined, no reaction
was observed and the starting materials were recovered
intact.
The reactions of a series of other aromatic and alipha-
tic alcohols were next pursued with p-TsOH in
ClCH2CH2Cl as above (Table 2, entries 1–10).6 Benzylic
alcohols, benzyl-, 4-nitrobenzyl, and 1-phenylpropyl
alcohol, were converted to the corresponding tosylates
in 78–91% yields. Similarly, allylic alcohols, cinnamyl
Table 2. Cobalt(II) catalyzed tosylation of alcohols with p-TsOH6
Entry
Substrate
CH2OH
Time (h)
Product
CH2OTs
Yield (%)a;b;c
1
2.5
91
CH2OH
CH2OH
CH2OTs
CH2OTs
2
6
78
O2N
O2N
3
4
0.5
90
95
0.75
CH2OH
CH2OTs
CH2OTs
CH2OH
5
10
26
H15C7
H15C7
OH
OH
OTs
6
7
1.5
3.5
88
87
OH
OTs
OTs
1
1
95
93
8
9
OH
OTs
10
1
88
TsO
HO
a Substrate (3 mmol), p-TsOH (3 mmol), and CoCl2Æ6H2O(5 mol %) were dissolved in ClCH 2CH2Cl (10 mL) and the solution was stirred under reflux
(ca. 80 ꢀC) for the appropriate time.
b Isolated yield.
c Identification of the products was ascertained by NMR, IR, and mass spectrometric analysis.

S. Velusamy et al. / Tetrahedron Letters 45 (2004) 203–205
205
References and Notes
OTs
OH
.
trace
+
5 mol% CoCl2 6H2O
+
1. Greene, T. W.; Wuts, P. G. M. Protective Groups in
Organic Synthesis. 3rd ed. Wiley: New York, 1999.
2. (a) Kabalka, G. W.; Varma, M.; Varma, R. S.; Srivastava,
P. C.; Knapp, F. F., Jr. J. Org. Chem. 1986, 51, 2386; (b)
Yoshida, Y.; Sakakura, Y.; Aso, N.; Okada, S.; Tanabe,
Y. Tetrahedron 1999, 55, 2183; (c) Hartung, J.; Hunig, S.;
Kneuer, R.; Schwarz, M.; Wenner, H. Synthesis 1997,
1433.
OTs
OH
0.5 equiv p-TsOH
ClCH2CH2Cl
reflux, 1 h
95%
Scheme 2.
In conclusion, the present methodology describes a
simple procedure for the direct tosylation of alcohols
with p-TsOH in the presence of the inexpensive
CoCl2Æ6H2Oin high yields. It functions in the absence of
additives and generates water as the only by-product. In
the case of aliphatic alcohols, secondary alcohols are
transformed to the corresponding tosylates chemo-
selectively in the presence of the primary hydroxy groups.
3. Nitta, Y.; Arakawa, Y. Chem. Pharm. Bull. 1985, 33,
1380.
4. (a) OꢀConnell, J. F.; Rapoport, H. J. Org. Chem. 1992, 57,
4775; (b) Katritzky, A. R.; Zhang, G.; Wu, J. Synth.
Commun. 1994, 24, 205.
5. Choudary, B. M.; Chowdari, N. S.; Kantam, M. L.
Tetrahedron 2000, 56, 7291.
6. Alcohol (3 mmol), p-TsOH (3 mmol) and CoCl2Æ6H2O
(5 mol %) were dissolved in ClCH2CH2Cl (10 mL) and the
solution was stirred under reflux (ca. 80 ꢀC) for the
appropriate time (see Table 2). The reaction mixture was
then allowed to cool to ambient temperature and diethyl
ether (50 mL) was added. The catalyst was removed
by filtration and the filtrate was washed successively
with saturated NaHCO3 solution (3 · 10 mL), brine
(2 · 10 mL), and water (1 · 10 mL). Drying (Na2SO4) and
evaporation of the solvent on a rotary evaporator
afforded a residue, which was passed through a short
pad of silica gel using a mixture of ethyl acetate and
hexane as eluent to afford the analytically pure tosylate.
Acknowledgements
This work was supported by the Department of Science
and Technology (sanction no. SR/S1/OC-092002), New
Delhi and by the Council of Scientific and Industrial
Research (sanction no. 01(1804)/02/EMR-II), New
Delhi.