Selective sulfonylation of arenes and benzoylation of alcohols using lithium perchlorate as a catalyst under neutral conditions

Article abstract of DOI:10.1055/s-2002-25345

Sulfonylation of aromatics with p-toluenesulfonyl chloride and benzoylation of alcohols with benzoyl chloride using lithium perchlorate as a catalyst is described. The remarkable selectivity under neutral conditions is an attractive feature of this method.

Full text of DOI:10.1055/s-2002-25345

LETTER
735
Selective Sulfonylation of Arenes and Benzoylation of Alcohols Using Lithium
Perchlorate as a Catalyst Under Neutral Conditions
S
elective Sulfony
.
lationof
A
re
P
nes and Benz
.
oylationof
A
B
lcohols andgar,* V. T. Kamble, V. S. Sadavarte, L. S. Uppalla
Organic Chemistry Research Laboratory, School of Chemical Sciences, Swami Ramanand Teerth Marathwada University,
Handed-431 606, India
Fax +91(2462)29245; E-mail: vtkd@redifffmail.com
Received 16 October 2001
and practical method for the sulfonylation of aromatic
Abstract: Sulfonylation of aromatics with p-toluenesulfonyl chlo-
compounds (Scheme 1) and benzoylation of alcohols
(Scheme 2) using a catalytic amount of lithium perchlor-
ate.
ride and benzoylation of alcohols with benzoyl chloride using lithi-
um perchlorate as a catalyst is described. The remarkable selectivity
under neutral conditions is an attractive feature of this method
Key words: sulfonylation, benzoylation, lithium perchlorate, cata-
lyst, neutral conditions
Organosulfones are important intermediates in organic
synthesis1 as well as in industrial applications.2 Sulfones
are generally prepared by oxidation of the corresponding
sulfides and sulfoxides or by a displacement reaction of
sodium arenesulfinate with appropriate alkyl halide.3
Some metal halides,1a zeolites,4 Bronsted acids5 and
Scheme 1
6
Bi(OTf)3 have been reported to catalyze the sulfonylation
of arenes. Diaryl sulfones are synthesized using conven-
tional Lewis acid catalysts and are useful intermediates
for drug industry (e.g. diphenyl sulfone is used as an inter-
mediate for DAPSONE (4,4 -diamino-diphenyl sulfone,
effective for leprosy treatment).7 More recently indium
triflate,8 Fe(III) exchanged montmorillonite clay9 and
BiCl3-triflic acid10 has been successfully used for catalytic
sulfonylation of arenes. However, many of these proce-
dures generally require strong protic or Lewis acids, pro-
longed reaction times and high temperatures. Thus, the
use of an alternative method under neutral conditions
would extend the scope of useful sulfonylation reaction
for the synthesis of sulfones.
Scheme 2
The catalytic activity of the lithium perchlorate for sul-
fonylation of anisole (5 mL) with p-toluenesulfonyl chlor-
ide (5 mmol) under reflux conditions was studied
(Table 1) and it was found that application of less than 20
mol% of lithium perchlorate resulted in low yield of the
corresponding sulfone (Table 1, entries 2, 3) whereas use
of more than 20 mol% of lithium perchlorate did not im-
prove the yield (Table 1, entries 5–7). When attempts
were made to carry out sulfonylation of anisole with p-
toluenesulfonyl chloride in the absence of catalyst, lithi-
um perchlorate, it resulted in almost qantitative recovery
of the substrate (Table 1, entry 1).
In recent years lithium perchlorate has received consider-
able attention as a powerful reaction medium for effecting
various transformations11 such as cycloaddition reactions,
sigmatropic rearrangements, ring opening reactions of ep-
oxides, glycosidation reactions, selective carbonyl protec-
tion as dithioacetal, Michael reactions and aldol reactions.
Lithium perchlorate provides a convenient procedure to
carry out the reactions under essentially neutral conditons.
In addition, lithium perchlorate is found to retain its activ-
ity even in the presence of nitrogen containing com-
pounds. These special properties inherent to lithium
perchlorate prompted us to explore this catalyst for the
synthesis of sulfones from arenes and benzoates from
alcohols. In this communication, we describe a simple
Table 1 A Catalytic Study of LiClO4 for Sulfonylation of Anisole
(5 mL) with p-Toluenesulfonyl Chloride (1 mmol) at Reflux Temper-
ature
Entry
LiClO4 (mol %)
Time (h)
2.5
Yield (%)
1
2
3
4
5
6
7
–
–
0.01
0.05
0.10
0.20
0.50
1.00
2.5
30
40
85
90
89
88
2.5
2.5
2.5
2.5
Synlett 2002, No. 5, 03 05 2002. Article Identifier:
1437-2096,E;2002,0,05,0735,0738,ftx,en;D23801ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214
2.5

736
B. P. Bandgar et al.
LETTER
Various activated and unactivated aromatics reacted well
under the present reaction conditions to give the corre-
sponding sulfones in good to excellent yield.12 The results
for sulfonylation of aromatics are summarized in Table 2.
It is important to note that the selectivity of the reaction is
impressive in the reported examples wherein exclusively
para isomers of diaryl sulfones are obtained without de-
tection or isolation of ortho/meta isomers in trace amount.
On the other hand sulfonylation of toluene involving
Table 2 LiClO4-catalyzed Sulfonylation of Aromatics Under Re-
flux Temperature
En- Arene
try
Product
Time Yielda,b
(h)
(%)
1
4
84
2
4
85
84
83
13
AlCl3 or more recently reported protocol of sulfonyla-
6
tion using Bi(OTf)3 or In(OTf)310 yields a mixture of iso-
mers (e.g. ditolyl sulfones). In this regard the present
method is superior because it gives selectively para iso-
mer (e.g. p-tolyl sulfone) only in good yield (Table 2, en-
try 1). Further, the improvement in regioselectivity is also
observed using LiClO4 in sulfonylation of naphthalene
with p-toluenesulfonyl chloride giving only -isomer
without formation of -isomer in trace amount. On the
other hand sulfonylation of naphthalene using Fe(III) ex-
changed montmorillonite clay9 gave mixture of -and -
isomers. It is interesting to note that heterocyclic (Table 2,
entry 6) and unactivated aromatics (Table 2, entries 6–12)
also undergo sufonylation smoothly under these neutral
reaction conditions. However, these aromatic substrates
require longer reaction time as compared to activated aro-
matics (Table 2, entries 1–5). But the yields of sulfones
obtained from both activated as well as unactivated aro-
matics are good to excellent (Table 2).
3
4
3.5
3.5
5
6
2.5
8
90
82
7
8
6
6
8
5
5
5
76
77
80
85
85
84
In order to explore the scope and limitations LiClO4 as a
catalyst, it has been employed for benzoylation of alco-
hols under mild and neutral conditions. Benzoylation of
alcohols is a very important functional group transforma-
tion in synthetic organic chemistry. Benzoylation of alco-
hols in general is carried out by the treatment of alcohols
with acid anhydrides or acid halides under the influence of
a base.14,15 For example, the benzoylation of alcohols with
benzoyl chloride15 or with benzoyl triflate16 usually pro-
ceeds in the presence of pyridine. Several other proce-
dures for benzoylation of alcohols have been reported in
the literature.17 More recently, remarkably fast benzoyla-
tion of alcohols with benzoyl chloride in the presence of
base, N,N,N ,N -tetramethyl ethylene diamine (TMEDA)
at very low temperature (–78 °C) has been described.18
The development of a new practical methods which al-
lows transformation under essentially neutral conditions
should heighten the synthetic potentiality of the reaction.
The mild and selective protocol always attracts a great
deal of attention of organic chemists. We report here for
the first time catalytic benzoylation of alcohols with ben-
zoyl chloride using LiClO4 in THF under mild and neutral
conditions (Scheme 2).
9
10
11
12
a Yields are of pure isolated products.
b Products are characterized by their physical constants and spectral
analysis.
were inert and tertiary alcohols did not afford correspond-
ing benzoate esters. This may be due to steric hindrance
around hydroxyl group of secondary and tertiary alcohols.
It should be noted that primary alcoholic OH-group was
selectively benzoylated in the presence of secondary alco-
holic OH (Table 3, entries 11, 12) and tertiary alcoholic
OH (Table 3, entry 13). One of the most noteworthy fea-
tures of this method is that benzyl alcohols are selectively
benzoylated in the presence of phenolic OH-groups where
as reported methods involving base are not competitive
for benzyl alcohols and phenols. It may be also quite in-
teresting that the presence of an epoxide or a halogen
A variety of alcohols were converted to the corresponding
benzoates19 using benzoyl chloride in the presence of a
catalytic amount of LiClO4 in THF at 25 °C. The results
are presented in Table 3. The methodology appears to be
chemoselective as only primary alcohols (aliphatic, ben-
zylic, allylic and propargylic) were benzoylated under
these reaction conditions whereas the secondary alcohols
Synlett 2002, No. 5, 735–738 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Selective Sulfonylation of Arenes and Benzoylation of Alcohols
737
Equation 1
Equation 2
atom, which may show some reactivity under the basic
conditions of conventional methods, did not give any dis-
turbance to the present reaction (Table 3, entries 14, 15).
This may be attributed to the fact that the reaction pro-
ceeds under neutral conditions. The reaction was equally
effective when acetyl or pivaloyl chloride was used in-
stead of benzoyl chloride (Equation 1 and Equation 2).
However, acylation or benzoylation of alcohols with ace-
tic anhydride or benzoic anhydride did not proceed even
after stirring the reaction mixture for longer time (15 h)
and it resulted in almost quantitative recovery of the sub-
strate (Equation 3 and Equation 4).
Table 3 LiClO4-catalyzed Chemoselective Benzoylation of Alco-
hols at 25 °C
En- Alcohol
try
Product
Time Yielda
(h)
(%)
1
2
3
CH3(CH2)5OH
(CH3)2CH(CH2)2OH
CH3(CH2)5OBz
5
73
(CH3)2CH(CH2)2OBz
6
75
7
80
4
5
6
7
6
7
78
85
87
Equation 3
7
7
80
8
9
6
6
79
85
Equation 4
The present protocol is truly catalytic and more attractive
due to convenient and neutral reaction conditions as com-
pared to reported methods of benzoylations involving sto-
ichiometric amount of base. In conclusion, the present
results on sulfonylation of arenes and benzoylation of al-
cohols demonstrate the efficiency of LiClO4 as a catalyst
under almost neutral conditions and constitutes a useful
alternative to the commonly accepted procedures. The ef-
fectiveness of the protocol is manifested in its selectivity.
10
11
7
85
5.5 70
12
13
14
6
7
8
72
77
75
Acknowledgement
VSS thanks CSIR, New Delhi for fellowship.
References
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00
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17 (CH3)3COH
18 Ph3COH
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10
10
a Pure isolated products are characterized by comparison with authen-
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Synlett 2002, No. 5, 735–738 ISSN 0936-5214 © Thieme Stuttgart · New York

738
B. P. Bandgar et al.
LETTER
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added. The aq layer was washed with chloroform (3 5mL).
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alcohol (5 mmol), benzoyl chloride (5 mmol) and LiClO4 (1
mmol) was stirred for 7 h at 25 °C (Table 3, entry 3). After
completion of the reaction (TLC), the solvent was removed
under reduced pressure and the product was purified by
column chromatography on silica gel. Yield = 80%;
IR(neat): 712, 1065, 1107, 1272, 1450, 1716 cm–1; 1H NMR
(CDCl3): = 4.4 (s, 2 H), 7.3–7.4 (m, 5 H), 8.1–8.15 (m, 5
H); 13C NMR: = 70.2, 125.8, 127.77, 128.42, 128.61,
129.74, 130.55, 133.02, 141.78, 145.81, 175.9.
Yield = 90%; mp = 149 °C; IR (KBr): 683, 834, 1007, 1360,
1599, 2910, 3300 cm–1; 1H NMR (300 MHz, CDCl3):
=
2.36 (s, 3 H, CH3), 3.81 (s, 3 H, OCH3), 6.95 (d, 2 H, J = 8.3
Hz, Ar-H), 7.31 (d, 2 H, J = 7.4 Hz, Ar-H), 7.85 (d, 2 H,
J = 8.3 Hz, Ar-H), 7.90 (d, 2 H, J = 7.4 Hz, Ar-H).
Synlett 2002, No. 5, 735–738 ISSN 0936-5214 © Thieme Stuttgart · New York