Scope and limitations of HClO4-SiO2 as an extremely efficient, inexpensive, and reusable catalyst for chemoselective carbon-sulfur bond formation

Article abstract of DOI:10.1016/j.tet.2006.11.050

The scope and limitations of perchloric acid adsorbed on silica gel (HClO₄-SiO₂) as a highly efficient, inexpensive, and reusable catalyst for chemoselective carbon-sulfur bond formation by conjugate addition of thiols to α,β-unsatur

Full text of DOI:10.1016/j.tet.2006.11.050

Tetrahedron 63 (2007) 1200–1210
Scope and limitations of HClO4–SiO2 as an extremely
efficient, inexpensive, and reusable catalyst for
chemoselective carbon–sulfur bond formation
*
Gopal L. Khatik, Gaurav Sharma, Raj Kumar and Asit K. Chakraborti
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER),
Sector 67, S. A. S. Nagar, Punjab 160 062, India
Received 9 September 2006; revised 7 November 2006; accepted 16 November 2006
Available online 12 December 2006
Abstract—The scope and limitations of perchloric acid adsorbed on silica gel (HClO4–SiO2) as a highly efficient, inexpensive, and reusable
catalyst for chemoselective carbon–sulfur bond formation by conjugate addition of thiols to a,b-unsaturated ketones under solvent-free
conditions and at rt are reported. In the case of 1,3-diphenylpropenone, the reactions were best carried out either at 80 ꢀC under solvent-
free conditions or at rt in MeOH. The reaction of aryl, arylalkyl, alkyl thiols, and alkane dithiols with cyclic and acyclic a,b-unsaturated
ketones afforded excellent yields of the corresponding b-sulfidocarbonyls after 2 min to 2 h. In the case of dithiols, the bis-thia-Michael
adducts were formed. The rate of the reaction was found to be dependent on the electronic and steric factors of the a,b-unsaturated ketones
and the thiols. A substituent at the b-carbon of the a,b-unsaturated ketone offered steric hindrance for conjugate addition and such substrates
required longer times. In case of aromatic thiols, the presence of the nitro group reduced the nucleophilicity of the sulfhydryl sulfur atom
resulting in slower rate of reaction for 4-nitrothiophenol compared to that of thiophenol and 4-methylthiophenol. For alkane thiol, the reaction
rate was influenced by the steric crowding of the alkyl group attached to the sulfhydryl moiety. The rate of reaction for alkane thiols was
sluggish compared to that of aryl thiols. The influence of the b-substituent on the rate of thia-Michael addition was utilized for selective
reaction during inter-molecular competitions of cyclohexen-2-one versus 3-methyl-2-cyclohexenone, cyclohexen-2-one versus 4-methyl-
3-penten-2-one, and 4-phenyl-3-buten-2-one versus 4-methyl-3-penten-2-one with thiophenol with 100:0, 91:9, and 70:30 selectivities,
respectively. The difference in the rate of reaction of thiophenol and 4-nitrothiophenol was also reflected during the inter-molecular com-
petition for the reaction with cyclohexen-2-one with an excellent selectivity of 100:0. The influence of the steric factor of the alkyl group
in alkane thiol resulted in 62:38 selectivity during the inter-molecular competition of ethane thiol and tert-butanethiol with cyclohexen-2-
one. During inter- and intra-molecular competitions of thia- versus aza- and thia- versus oxa-Michael addition reactions, chemoselective
thia-Michael addition took place. The chemoselective thia-Michael addition over aza-Michael addition during intra-molecular competion
reactions with 2-aminothiophenol was utilized for an efficient one-pot synthesis of benzothiazepines.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
generated interest to develop new methodologies for
thia-Michael addition reaction.7
Carbon–sulfur bond formation by conjugate addition of
thiols to a,b-unsaturated carbonyl compounds, has versatile
applications in chemistry and biology as it plays critical
roles in the (i) biosynthesis,1 (ii) synthesis of bioactive
compounds,2 (iii) protection of the olefinic double bond of
conjugated enones3 (due to the ease of regeneration of the
double bond by copper(I)-induced4 and oxidative3 elimina-
tion of the sulfur moiety), and (iv) generation of b-acylvinyl
cation5 and homoenolate anion6 equivalents. These have
2. Results and discussion
We felt that the role of a metal catalyst is to induce electro-
philic activation of the a,b-unsaturated carbonyl compound
through coordination of the cationic center of the catalyst
with the carbonyl oxygen of the a,b-unsaturated carbonyl
compounds to increase the electrophilicity of the b-carbon
(Scheme 1).
In the search for a more effective catalyst, we thought that
a Lewis acid that can form a strong coordinate bond with
the carbonyl oxygen atom of the a,b-unsaturated carbonyl
compound should induce electrophilic activation more
effectively and enable the conjugate addition to take place
under mild conditions and in short times. Recently we
Keywords: C–S bond formation; Thia-Michael addition; Thiols; HClO4–
SiO2; Catalyst; Selectivity; Electronic effect; Steric effect; Inter-molecular
competition; Intra-molecular competition; Benzothiazepines; One-pot syn-
thesis.
* Corresponding author. Tel.: +91 172 2214683; fax: +91 172 2214692;
e-mail: akchakraborti@niper.ac.in
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.11.050

G. L. Khatik et al. / Tetrahedron 63 (2007) 1200–1210
1201
MX-
O
SH
O
MX
O
O
O
HClO4-SiO2
neat, rt
R1
R1
R1
+
MX
S
+
R2
R2
R2
1
R3SH
Scheme 2. The reaction of 1 with thiophenol in the presence of HClO4–
SiO2.
MX-
H
O
O
O
R1
R1
R1
Table 1. Reaction of 1 with thiophenol under the catalytic influence of
HClO4–SiO2 and various conditionsa
R3
R2
SR3
R2
SR3
R2
S+
Entry
1b
Mol %c
Thiophenol
(mmol)
Time
(min)
Yield
MX
H
(%)d,e
Scheme 1. The role of a metal catalyst in catalyzing the thia-Michael addi-
tion reaction.
1
2
3
2.5
5
10
1
0.1
0.01
2.75
5.5
11
2
5
20
99
90
85
have been engaged in the development of various elec-
trophilic activation catalysts derived from metal halides,
perchlorates, tetrafluoroborates, and protic acids adsorbed
on solid support for heteroatom acylation,8 epoxide ring
opening,9 and imine10/dithiolane11/carbamate12/acetal13/
acylal14 formation, and thia-Michael addition reactions.15
Although a comparison with the literature methods revealed
that the use of Cu(BF4)2$xH2O15a and Zn(ClO4)2$6H2O15b
to be improved procedures, it was observed that the reactions
with a,b-unsaturated ketones having an alkyl or an aryl sub-
stituent at the b-carbon took longer times (20 min–14 h).
Our recent observation revealed that water plays a novel dual
activation role in promoting the conjugate addition of thiols
to a,b-unsaturated ketones.16 However, this method also
does not work well with these substrates. This encouraged
us to develop a more effective catalyst. Recently we reported
for the first time17 that perchloric acid adsorbed on silica gel
(HClO4–SiO2) is an extremely effective electrophilic activa-
tion agent for acylation reactions8g and subsequently found
its application in dithiolane11a and carbamate12a formation.
We were happy to observe that this newly introduced catalyst
system has attracted the attention of other groups of re-
searchers for various synthetic transformations.18 Thus, we
planned to explore the catalytic efficiency of HClO4–SiO2
for the thia-Michael addition reaction19 as (i) the increasing
pressure from environmentalists has led to the search for
more friendly forms of catalysis and the leading contender
for an environmentally acceptable alternative process is the
use of supported reagents, (ii) the activity and selectivity of
a reagent dispersed on the surface of a support is often
improved (as the effective surface area of the reagent can be
increased up to one hundred times), (iii) the good thermal
and mechanical stabilities of supported reagents make them
easy to handle as they are generally low toxic, non-corrosive
free flowing powders, and their ease of separation from the
reaction mixture through filtration and the feasibility of
reuse make them suitable for meeting the requirement of
triple bottom line philosophy20 of green chemistry.
a
The a,b-unsaturated ketone was treated with the thiol in the presence of
the catalyst at rt (w25–30 ꢀC) under neat conditions.
Amount of 1 (in mmol) used for the reaction.
b
c
d
Mol % of HClO4–SiO2 used with respect to 1.
Isolated yield of the corresponding thia-Michael adduct after chromato-
graphic purification.
The product was characterized by IR, NMR, and MS.
e
We next planned to establish the superiority of HClO4–SiO2
over the reported catalysts, particularly Cu(BF4)2$xH2O15a
and Zn(ClO4)2$6H2O,15b so took 3-methyl-2-cyclohexen-
1-one (2) and 4-phenyl-3-buten-2-one (3) as representatives
of cyclic and acyclic a,b-unsaturated ketones, having an
alkyl and aryl group at the b-carbon, respectively. Thus, in
separate experiments, 2 and 3 were treated with various
thiols in the presence of HClO4–SiO2 (1 mol %) and the
results were compared with those obtained during the
Cu(BF4)2$xH2O and Zn(ClO4)2$6H2O-catalyzed reactions
(Table 2). The results clearly demonstrated that HClO4–SiO2
is a better suited catalyst in comparison to Cu(BF4)2$xH2O
and Zn(ClO4)2$6H2O. An interesting observation was made
during the reaction of 3, a solid a,b-unsaturated ketone, with
4-nitrothiophenol, a solid thiol (entry 22, Table 2). After
addition of HClO4–SiO2 to the heterogeneous mixture of 3
and 4-nitrothiophenol, a melt was obtained, which solidified
after stirring for 15 min. The TLC and IR of the crude reaction
mixture revealed that complete consumption of 3 took place.
This indicated that the use of HClO4–SiO2 as a catalyst should
enable the thia-Michael addition reaction to be carried out in-
volving a solid ketone and a solid thiol under solvent-free con-
ditions.
We next planned to establish the generality of the catalytic
efficiency of HClO4–SiO2 for reaction of thiols with other
a,b-unsaturated carbonyl compounds such as 1, 2-cyclo-
penten-1-one (4), 3-buten-2-one (5), 4-methyl-3-penten-2-
one (6), and 1,3-diphenylpropenone (7) (Table 3). Excellent
results were obtained in each case. The reactions were com-
pleted after 2 min to 2 h (TLC, IR, and GCMS). No aqueous
work-up was required for isolation of the product from the
reaction mixture. After completion of the reaction, the
mixture was diluted with Et2O and passed through a plug
of cotton to remove the catalyst, which separated out from
the cotton on drying. Although the reaction using solid
substrates such as 3 and 4-nitrothiophenol afforded excellent
results under solvent-free conditions and at rt (entry 22,
Table 2), in the case of 7 (a solid substrate), an initial attempt
in carrying out the reaction with thiophenol at rt under
To evaluate the catalytic effect of HClO4–SiO2, 2-cyclo-
hexen-1-one (1) was treated with thiophenol under various
conditions (Scheme 2, Table 1). Excellent results were
obtained using 0.01–1 mol % of HClO4–SiO2 affording the
thia-Michael adduct in 85–99% yields after 2–20 min under
solvent-free condition and at rt. However, for subsequent
studies we used 1 mol % of the catalyst for ease of han-
dling/weighing of the catalyst for small scale (2.5 mmol) re-
actions.

1202
G. L. Khatik et al. / Tetrahedron 63 (2007) 1200–1210
Table 2. Comparison of the catalytic efficiency of HClO4–SiO2 (A),
Cu(BF4)2$xH2O (B), and Zn(ClO4)2$6H2O (C) during conjugate addition
of 2 and 3 with various thiolsa
thia-Michael adduct was observed during the reaction of 7
with 4-nitrothiophenol after 2 h at rt under solvent-free con-
ditions. However, the desired thia-Michael adduct was ob-
tained in 75% yield after heating the reaction mixture at
80 ꢀC for 1 h. The poor yields obtained during the reaction
of 7 under solvent-free conditions were due to the fact that
the reaction did not proceed toward incompletion as evi-
denced by the presence of unconsumed starting materials
(IR and TLC). The initially formed thia-Michael adduct (a
solid compound) created a heterogeneous environment and
trapped the enone 7 and the thiol. This retarded the reaction
rate. However, excellent results were obtained when the re-
actions of 7 were carried out in MeOH. Initially a clear so-
lution was obtained after mixing 7 and the thiol in MeOH.
After the addition of the catalyst, the reaction mixture be-
came turbid and the product precipitated out after comple-
tion of the reaction and this served as visual means of
monitoring the reaction. The recovered catalyst was reacti-
vated on heating at 80 ꢀC under reduced pressure for 24 h
and reused (see Section 4).
Entry
Enone
Thiol
Cat
Time (min)
Yield (%)b,c
SH
O
2
R
1
2
3
4
5
6
R¼H
A
B
C
A
B
C
10
45
60
10
60
60
85
R¼H
83d
Nile
89
R¼H
R¼Me
R¼Me
R¼Me
83d
Nile
SH
7
8
9
A
B
C
10
45
60
81
81d
Nile
SH
O
10
11
12
A
B
C
30
60
60
80
82d
Nile
The rate of thia-Michael addition was influenced by the
steric factor of the substituent at the b-carbon atom of the
enone. In general, substrates having a b-methyl/phenyl
group required longer reaction time or higher reaction tem-
perature during the reaction with a common thiol compared
to that of the reaction of analogous enone devoid of a b-
methyl/phenyl group. The electronic factor associated with
the thiols also contributed to the overall rate of the reaction.
Comparison of the results of the reaction of thiophenol and
4-methylthiophenol with a common enone (compare entries
16 and 19, Table 2; entries 19 and 20, Table 3; entries 23 and
24, Table 3) revealed that the reaction rates were faster in
case of thiophenol although 4-methylthiophenol is expected
to be a better nucleophile compared to thiophenol. Thus,
apart from the nucleophilicity of the sulfur atom of the thiol,
the acidic property of the sulfhydryl hydrogen atom was im-
portant and thiols with better acidic character reacted at
a faster rate. This is in conformity with the proposed mech-
anism of electrophilic activation (Scheme 1). Thus, the lib-
eration/regeneration of the catalyst takes place more
efficiently for reactions with thiols in which the sulfhydryl
hydrogen atom possesses better acidic property. Therefore,
in general the reaction rates are faster with aromatic thiols
compared to those of aliphatic thiols. The longer time re-
quired in using 4-nitrothiophenol (compare entries 1 and 2
with entry 3 and entries 23 and 24 with entry 26, Table 3)
was due to the decrease in nucleophilicity of the sulfur
atom of 4-nitrothiophenol compared to that of thiophenol
and 4-methylthiophenol. The longer time required for conju-
gate addition of tert-butanethiol compared to that of ethane
thiol (compare entry 6 with 7, and entry 31 with 32, Table 3)
was due to the steric effect.
13
14
15
A
B
C
30
12 h
60
88
75d
Nile
SH
SH
O
Ph
3
R
16
17
18
19
20
21
22
23
24
R¼H
A
B
C
A
B
C
A
B
C
5
5
95
R¼H
86d
89f
90
R¼H
90
30
75
120
15
60
60
R¼Me
R¼Me
R¼Me
R¼NO2
R¼NO2
R¼NO2
84d
80f
80
60g
40g
SH
25
26
27
A
B
C
30
75
120
96
87d
82f
SH
O
28
29
30
A
B
C
20
20
120
90
88d
78f
31
32
33
A
B
C
60
14 h
6 h
98
80d
83f
SH
34
35
36
A
B
C
90
90
90
87
75
50
SH
a
The a,b-unsaturated ketone (2.5 mmol) was treated with the thiol
(2.75 mmol, 1.1 equiv) in the presence of the catalyst (1 mol %) at rt
(w25–30 ꢀC) under neat conditions.
Isolated yield of the corresponding thia-Michael adduct after chromato-
graphic purification.
The products were characterized by IR, NMR, and MS.
Ref. 15a.
The starting materials remained intact (TLC, IR, and GCMS).
Ref. 15b.
The thia-Michael adduct was formed in 30% yield after 15 min.
b
c
d
e
f
We planned to exploit the difference in the rate of reaction
because of the steric and electronic factors associated with
the Michael acceptors and the thiols for inter-molecular
competition studies (Scheme 3). Thus, equimolar mixtures
of (i) 1 and 2, (ii) 1 and 6, and (iii) 3 and 6 were treated
with thiophenol (1.1 equiv) to demonstrate the effect of the
substituent at the b-position of the enone and excellent selec-
tivities (GCMS) of 100:0, 91:9, and 70:30, respectively, in
favor of the thia-Michael addition of the substrate having
g
solvent-free conditions showed w20% conversion to the
thia-Michael adduct after 1 h. The conversion was increased
to 60% after 30 min at 80 ꢀC. No significant formation of the

G. L. Khatik et al. / Tetrahedron 63 (2007) 1200–1210
1203
Table 3. HClO4–SiO2-catalyzed conjugate addition of a,b-unsaturated car-
bonyl compounds with thiolsa
Table 3. (continued)
Entry
Enone
Thiol
SH
Time (min) Yield (%)b,c
Entry
Enone
Thiol
Time (min) Yield (%)b,c
SH
O
21
120
80
SH
R
O
1
R
Ph
1
2
3
R¼H
R¼Me
R¼NO2
2
2
10
99
99
80
Ph
7
60e
80f
80f
75e
60f
SH
22
23
24
25
26
R¼H
30
15
20
60
R¼H
4
5
2
5
99
80
R¼Me
R¼NO2
R¼NO2
120
SH
85d f
,
HS
27
28
45
60
SH
O
90d f
,
HS
SH
SH
SH
6
7
8
9
10
15
15
20
90
SH
SH
29
30
60
60
80f
90
75d
70d
HS
SH
SH
80f
HS
O
SH
R
O
SH
SH
31
32
60
79f
120
70f,g
4
N
S
33
SH
90
78f,h,i
10
11
R¼H
2
2
95
90
R¼Me
a
The a,b-unsaturated ketone (2.5 mmol) was treated with the thiol
(1.1 equiv) in the presence of HClO4–SiO2 (1 mol %) at rt (w25–30 ꢀC)
under neat conditions (except for entries 23, 24, and 26–33) at rt (except
for entries 8, 9, 22, and 25).
Isolated yield of the corresponding conjugate addition product obtained
after chromatographic purification.
SH
12
13
3
5
80
75
b
SH
SH
c
The products were characterized by IR, NMR, and MS.
The reaction was carried out by addition of the thiol (0.5 equiv) to the
magnetically stirred mixture of the enone and the catalyst at 0 ꢀC followed
by stirring at rt (w25–30 ꢀC).
d
O
e
f
The reaction was carried out at 80 ꢀC.
5
The reaction was carried out in MeOH.
The thia-Michael adduct was formed in 60% yield after 2 h when the re-
action was carried out in MeOH at rt.
The thia-Michael adduct was formed in 30% yield after 90 min when the
reaction was carried out in the presence of Cu(BF4)2$xH2O.
No significant amount of the thia-Michael adduct was formed after 90 min
when the reaction was carried out in the presence of Zn(ClO4)2$6H2O.
R
g
14
15
R¼H
2
2
85
80
R¼Me
h
i
SH
16
5
80
SH
O
less substitution at the b-position were observed. The
reaction of 1 (1 equiv) with an equimolar mixture of (i)
thiophenol and 4-nitrothiophenol and (ii) ethane thiol and
tert-butanethiol represented the selectivity of thia-Michael
addition during competition between thiols of varying elec-
tronic and steric factors, respectively. Excellent selectivity
(100:0) was observed in the former case. The moderate
selectivity (62:38) observed during the competition of
ethane thiol and tert-butanethiol may be due to the combined
effects of the steric electronic factors. Thus, while the steric
factor of tert-butanethiol should make its thia-Michael addi-
tion sluggish, the increased nucleophilicity due to the induc-
tive effect of the tert-butyl group enhances its rate of
reaction.
17
18
5
80
75
SH
SH
10
O
6
R
19
20
R¼H
90
120
85
80
R¼Me
(continued)

1204
G. L. Khatik et al. / Tetrahedron 63 (2007) 1200–1210
O
O
O
O
O
O
O
O
SH
SH
HClO4-SiO2
(1 mol%)
HClO4-SiO2
(1 mol%)
Ph
O
XH
R
+
+
+
+
rt, 2 min,
Neat
R
S
rt
S
S
S
S
S
S
Ph
XH
1
2
1 mmol
1 mmol
100 : 0
2.5 mmol 2.5 mmol 2.75 mmol
8: R = Ph; X = NH
9: R = Ph; X = O
10: R = Me; X = O
O
O
SH
HClO4-SiO2
(1 mol%)
rt, 2 min,
Neat
+
+
+
Scheme 5. Intra-molecular competition of thia- versus aza- and thia- versus
oxa-Michael addition reactions.
1
6
91 : 9
2.5 mmol 2.5 mmol 2.75 mmol
O
O
O
SH
and 81% yields after 15 and 30 min, respectively, at rt in
MeOH (Scheme 5). The reaction of 3 with an equimolar
amount of 2-hydroxythiophenol afforded the corresponding
thia-Michael adduct 10 as the sole product in 80% yield after
10 min at rt under solvent-free conditions (Scheme 5).
HClO4-SiO2
(1 mol%)
rt, 2 min,
Neat
+
+
Ph
+
Ph
6
3
70 : 30
O
2.5 mmol 2.5 mmol 2.75 mmol
SH
O
O
SH
HClO4-SiO2
(1 mol%)
To establish the generality of the chemoselective thia-
Michael addition over aza-Michael addition during intra-
molecular competition, various 1,3-diaryl propenones (11)
were treated with 2-aminothiophenol and 4-aminothio-
phenol (Table 4). In each case, exclusive chemoselectivity
for thia-Michael adduct formation was observed and the
corresponding b-sulfidocarbonyl derivatives were formed
in excellent yields.
NO2
+
+
+
rt, 2 min,
Neat
S
S
1
100 : 0
NO2
2.5 mmol 2.75 mmol 2.75 mmol
O
O
O
HClO4-SiO2
(1 mol%)
+
+
+
HS
HS
rt, 2 min,
Neat
S
S
1
2.5 mmol 2.75 mmol 2.75 mmol
62 : 38
The excellent yields of the thia-Michael adducts obtained
during the reaction of 1,3-diaryl propenones (11) with
2-aminothiophenol encouraged us to explore the feasibility
of this catalyst system for the development of a one-pot syn-
thesis of 1,6-diaryl-1,5-benzothiazepines as the intermedi-
ately formed thia-Michael adducts are expected to undergo
imine formation following a cyclodehydration process
(Scheme 6). The 1,5-benzothiazepine moiety is a privileged
class pharmacophore as compounds bearing this structural
unit possess a broad spectrum of biological activities21 and
has stimulated interest to develop new methodologies for
synthesis of 1,5-benzothiazepines. The common strategy
for the construction of the 1,5-benzothiazepine moiety is
Scheme 3. Inter-molecular competition during thia-Michael addition.
We next planned to evaluate the efficiency of HClO4–SiO2
during inter- and intra-molecular competition studies of
thia- versus aza- and thia- versus oxa-Michael addition reac-
tions involving a common Michael acceptor (Schemes 4 and
5). Thus, during the inter-molecular competition reactions,
the treatment of 7 separately with equimolar mixtures of
(i) thiophenol and aniline, and (ii) thiophenol and phenol
in MeOH at rt for 15 min afforded the thia-Michael adduct
in 80 and 90% yields, respectively, as the sole product and
no significant amount of the aza-Michael adduct was formed
(TLC comparison with authentic sample). Exclusive forma-
tion of the thia-Michael adduct (90% yield) was observed
when 3 was treated separately with equimolar mixtures of
(i) thiophenol and aniline, and (ii) thiophenol and phenol
at rt under solvent-free conditions for 5 min (Scheme 4).
Table 4. HClO4–SiO2-catalyzed chemoselective conjugate addition of 1,3-
diaryl propenones with aminothiolsa
Entry 1,3-Diaryl propenones
Aminothiols Time Yield
(min) (%)b,c
O
SH
O
SH
XH
HClO4-SiO2
(1 mol%)
Ph
O
R1
R2
R
+
+
Ph
R
11
R
S
rt
Ph
1
2
3
4
5
6
7
8
R1¼R2¼H
R¼2-NH2
R¼2-NH2
R¼2-NH2
R¼2-NH2
R¼2-NH2
R¼2-NH2
R¼4-NH2
R¼4-NH2
R¼4-NH2
R¼4-NH2
R¼4-NH2
15
20
15
15
25
20
45
25
30
50
45
85
82
85
92
91
90
85
90
88
85
86
R1¼H; R2¼Cl
R1¼Cl; R2¼H
R1¼H; R2¼NO2
R1¼H; R2¼OMe
R1¼OMe; R2¼H
R1¼R2¼H
1 mmol
1 mmol
1 mmol
R = Ph/Me; X = NH/O
Scheme 4. Inter-molecular competition of thia- versus aza- and thia- versus
oxa-Michael addition reactions.
R1¼H; R2¼NO2
R1¼Cl; R2¼H
R1¼H; R2¼OMe
R1¼OMe; R2¼H
9
10
11
The excellent chemoselectivity observed during the inter-
molecular competitive studies encouraged us to evaluate the
chemoselective thia-Michael addition reaction during intra-
molecular competition between a thiol and an amine moiety
and between a thiol and a phenol moiety. Thus, when 7 was
separately treated with equimolar amounts of 2-aminothio-
phenol and 2-hydroxythiophenol, the corresponding thia-
Michael adducts 87n and 9 were formed exclusively in 85
a
The 1,3-diaryl propenone (1 mmol) was treated with the aminothiophenol
(1 mmol) in the presence of HClO4–SiO2 (1 mol %) in methanol (1 mL) at
rt (w25–30 ꢀC).
Isolated yield of the corresponding thia-Michael adduct obtained after
chromatographic purification.
The products were characterized by IR, NMR, and MS.
b
c

G. L. Khatik et al. / Tetrahedron 63 (2007) 1200–1210
1205
the reaction of 1,3-diaryl-2-propenones with 2-aminothio-
phenols.22 The reported methodologies involve the use of
inorganic supports (2 g/mmol) under heating at 80 ꢀC for
3 h,23 HOAc (3 mL/mmol) in DMF under microwave irradi-
ation,24 HOAc or TFA (1 mL/mmol) in EtOH or PhMe under
reflux for 3–6 h,25 HOAc in DMF or EtOH at 60 ꢀC for 5 h
followed by rt for overnight,26 EtOH saturated with HCl
under reflux for 3 h,27 piperidine (1 mL/mmol) in toluene
under reflux for 8 h or pyridine (15 mL/mmol) under reflux
for 3 h.28 The disadvantages such as the use of high boiling
solvent (e.g., DMF) that is difficult to recover, excess
amounts of acid or base, need to use special apparatus, use
of corrosive (e.g., HCl gas, and TFA) and hazardous reagents
(e.g., pyridine), long reaction time, etc. necessitate to
develop a more effective synthetic procedure.
addition and the imine formation steps. In this regard, a
catalyst derived from a strong protic acid should be an ideal
and more effective contender.
Our initial attempt to carry out the cyclodehydration of 1,3-
diphenyl-1-(2-aminophenylsulfide)-2-propanone, obtained
by the reaction of 1,3-diphenyl-2-propenone and 2-amino-
thiophenol catalyzed by HClO4–SiO2, by heating under
reflux in MeOH without any catalytic assistance did not
produce any significant amount of the corresponding 1,5-
benzothiazepine derivative. We were delighted to observe
that the 2,3-dihydro-1,5-benzothiazepine was formed in
90% yield when 1,3-diphenyl-1-(2-aminophenylsulfide)-2-
propanone was heated under reflux for 40 min in MeOH in
the presence of HClO4–SiO2 (1 mol %). We next planned
for a one-pot synthesis of 2,3-dihydro-1,5-benzothiazepines
from 1,3-diaryl propenones by reaction with 2-aminothio-
phenol catalyzed by HClO4–SiO2 and the desired products
were formed in 80–90% yields by heating under reflux for
45–90 min in MeOH (Table 5).
O
H2N
+
R1
HS
R2
11
Path 'b'
Path 'a'
H2N
Table 5. One-pot synthesis of 2,3-dihydro-1,5-benzothiazepines (12) by
HClO4–SiO2-catalyzed tandem thia-Michael addition–cyclodehydration
reaction of 1,3-diaryl-2-propenones with 2-aminothiophenola
Entry 1,3-Diphenylpropenone
Time (min) Yield (%)b,c
O
S
N
SH
O
R1
R1
R2
III
R2
I
R2
R1
11
1
2
3
4
5
6
R1¼R2¼R3¼H
R1¼H; R2¼Cl
R1¼Cl; R2¼H
R1¼H; R2¼NO2
R1¼H; R2¼OMe
R1¼OMe; R2¼H
90
60
45
45
60
45
88
80
85
90
80
85
-
+
N
S H
HN
S
OH
R2
R1
R2
IV
II
R1
a
The reaction of 1,3-diaryl propenone (1 mmol), and 2-aminothiophenol
(1 mmol) was carried out in the presence of HClO4–SiO2 (1 mol %) in
methanol (1 mL) under reflux.
Isolated yield of the corresponding 2,3-dihydro-1,5-benzothiazepine (12)
obtained after chromatographic purification.
The products were characterized by IR, NMR, and MS.
b
c
N
S
HN
S
R2
R2
3. Conclusion
R1
13
R1
12
Scheme 6. Synthesis of benzothiazepines.
In conclusion, we have described herein the scope and
limitations of HClO4–SiO2 as a new and highly efficient
catalyst for chemoselective carbon–sulfur bond formation
by conjugate addition of thiols to a,b-unsaturated ketones.
The advantages include, (i) the use of a cheap, easy to
handle, and reusable catalyst, (ii) rt and non-anhydrous
reaction conditions, (iii) non-aqueous work-up and ease of
product isolation by filtration, (iv) short reaction times,
(vi) high yields, (v) excellent chemoselectivity during inter-
and intra-molecular competitions, and (vi) applicability for
an easy synthesis of 2,3-dihydro-1,5-benzothiazepines.
The construction of the 1,5-benzothiazepine moiety from 11
and 2-aminothiophenol may involve two pathways: (i)
conjugate addition of the sulfhydryl group of 2-aminothio-
phenol to the a,b-unsaturated carbonyl group of 11 leading
to the intermediate formation of the thia-Michael adduct I,
which on subsequent intra-molecular nucleophilic attack
by the NH2 group on the carbonyl carbon followed by
dehydration forms the 2,3-dihydro-1,5-benzothiazepine 12
(Path a)29 and (ii) condensation of the amino group of
2-aminothiophenol with the carbonyl group of 11 leading
to the intermediate formation of the aza-diene II, which on
subsequent intra-molecular conjugate addition by the sulf-
hydryl group forms the isomeric 2,5-dihydro-1,5-benzothi-
azepine 13 (Path b)24 (Scheme 6). Thus, the use of an
effective electrophilic activation agent should make synthe-
sis of benzothiazepines feasible under milder conditions and
in shorter times, as it would accelerate both the thia-Michael
4. Experimental
4.1. General
1
The H and 13C NMR spectra were recorded on a Bruker
Avance DPX 300 (300 MHz) spectrometer in CDCl3 using

1206
G. L. Khatik et al. / Tetrahedron 63 (2007) 1200–1210
TMS as an internal standard. The IR spectra were recorded
on a Nicolet Impact 400 spectrometer as KBr pellets for
solid and neat for liquid samples. Mass spectra were
recorded on QCP 5000 (Shimadzu) GCMS. The reactions
were monitored by TLC (Merck). Evaporation of solvents
(0.30 g, 2.75 mmol, 1.1 equiv) in the presence of the recov-
ered HClO4–SiO2 (0.05 g, 0.025 mmol, 1 mol %) afforded
3-phenylthiocyclohexanone (0.47 g, 93%) after work-up
and purification.
€
was performed under reduced pressure using a Buchi rotary
4.1.3. 1,3-Diphenyl-3-thiophenyl-propanone (entry 23,
Table 3). To a magnetically stirred mixture of 1,3-diphenyl-
propenone (7) (0.21 g, 1 mmol) and thiophenol (0.12 g,
1.1 mmol, 1.1 equiv) in MeOH (2 mL) was added HClO4–
SiO2 (0.02 g, 0.01 mmol, 1 mol %) and the reaction mixture
was stirred at rt (w25–30 ꢀC) till completion of the reaction
(15 min: TLC, IR) when the thia-Michael adduct precipi-
tated out. The reaction mixture was diluted with EtOAc
to dissolve the product (10 mL), filtered through a plug of
cotton (to separate the catalyst), and the cotton plug was
washed with EtOAc (2ꢂ1 mL). The combined filtrates were
concentrated, and the solid residue recrystallized (EtOH) to
afford 1,3-diphenyl-3-thiophenyl-propanone (0.26 g, 80%)
evaporator. Thiophenol, 4-methylthiophenol, 4-nitrothio-
phenol, a-toluenethiol, 2-furylmethanethiol, ethane thiol,
tert-butanethiol, 1,2-ethanedithiol, 1,3-propanedithiol,
2-mercaptothiazole, 2-aminothiophenol, 4-aminothiophe-
nol, 2-hydroxythiophenol, 2-cyclohexen-1-one, 3-methyl-
2-cyclohexen-1-one, 2-cyclopenten-1-one, 3-buten-2-one,
4-methyl-3-penten-2-one,
4-phenyl-3-buten-2-one,
Cu(BF4)2$xH2O, and Zn(ClO4)2$6H2O were purchased
from Aldrich, India. Silica gel (230–400 mesh) and aqueous
(48%) perchloric acid were procured from Spectrochem and
Loba Chemie, India, respectively. Aniline, phenol, other
reagents, and solvents were from SD Fine Chemicals, India.
1,3-Diphenyl-2-propenone,30 1-phenyl-3-(4-chlorophenyl)-
2-propenone,30 1-(4-chlorophenyl)-3-phenyl-2-propenone,30
1-phenyl-3-(4-nitro-phenyl)-2-propenone,30 1-phenyl-3-(4-
methoxyphenyl)-2-propenone,30 and 1-(4-methoxyphenyl)-
3-phenyl-2-propenone30 were prepared following reported
procedure.
1
as white solid identical (mp, IR, H and 13C NMR, and
MS) with an authentic sample.15a
4.1.4. Representative experimental procedure for inter-
molecular competition reaction (Scheme 3). To a magnet-
ically stirred mixture of 2-cyclohexen-1-one (1) (0.24 g,
2.5 mmol), 3-methyl-2-cyclohexen-1-one (0.27 g, 2.5 mmol)
(2), and thiophenol (0.30 g, 2.75 mmol, 1.1 equiv) was
added HClO4–SiO2 (0.05 g, 0.025 mmol, 1 mol %) and the
reaction mixture was stirred at rt (w25–30 ꢀC) for 2 min.
The reaction mixture was diluted with Et2O (2 mL), filtered
through a plug of cotton (to separate the catalyst), and the
cotton plug was washed with Et2O (2ꢂ1 mL). The combined
ethereal filtrates were concentrated and the isolated reaction
mixture, without further purification, was subjected to
GCMS column to afford 100% selectivity in favor of the
formation of 3-phenylthiocyclohexanone.
4.1.1. Preparation of perchloric acid adsorbed on silica
gel (HClO4–SiO2). The preparation of HClO4–SiO2 was
carried out following the reported procedure.8g,17 To the
suspension of silica gel (23.75 g, 230–400 mesh) in Et2O
(50 mL), HClO4 (1.25 g, 12.5 mmol, 1.78 mL of a 70%
aqueous solution of HClO4) was added and the mixture
was stirred magnetically for 30 min at rt. The Et2O was
removed under reduced pressure (rotary evaporator) and
the residue heated at 100 ꢀC for 72 h under vacuum to afford
HClO4–SiO2 (0.5 mmol gꢁ1) as a free flowing powder.
4.1.2. Representative experimental procedure for
conjugate addition of thiol to a,b-unsaturated ketone.
3-Phenylthiocyclohexanone (entry 1, Table 1). To a mag-
netically stirred mixture of 2-cyclohexen-1-one (1) (0.24 g,
2.5 mmol) and thiophenol (0.30 g, 2.75 mmol, 1.1 equiv)
was added HClO4–SiO2 (0.05 g, 0.025 mmol, 1 mol %)
and the reaction mixture was stirred at rt (w25–30 ꢀC) till
completion of the reaction (2 min: TLC and IR). The reac-
tion mixture was diluted with Et2O (2 mL), filtered through
a plug of cotton (to separate the catalyst), and the cotton plug
was washed with Et2O (2ꢂ1 mL). The combined ethereal
filtrates were concentrated, adsorbed on silica gel, charged
on a column of silica gel (60–120 mesh, 5 g), and eluted
with hexane (to eliminate any disulfide formed) followed
by 1:10 EtOAc–hexane to afford 3-phenylthiocyclohexa-
none (0.51 g, 99%, entry 1, Table 1) as colorless oil, identical
(IR, 1H and 13C NMR, and MS) with an authentic sample.15a
In a large-scale batch, 1 (0.96 g, 10 mmol) was treated with
thiophenol (1.1 g, 11 mmol, 1.1 equiv) in the presence of
HClO4–SiO2 (0.2 g, 0.1 mmol, 1 mol %) to afford 3-phenyl-
thiocyclohexanone (2.03 g, 99%) after work-up and purifi-
cation. The cotton plug retaining the recovered catalyst
was put on a rb flask (25 mL) and dried in a rotary evaporator
when the catalyst separated out from the cotton (0.16 g,
80%). The catalyst was activated on heating under reduced
pressure (10 mmHg) at 80 ꢀC for 24 h. The repetition of
the reaction of 1 (0.24 g, 2.5 mmol) with thiophenol
4.1.5. Representative experimental procedure for inter-
molecular competition of thia- versus aza-Michael addi-
tion reactions (Scheme 4). To a magnetically stirred
mixture of 1,3-diphenylpropenone (7) (0.21 g, 1 mmol),
aniline (0.093 g, 1 mmol) and thiophenol (0.11 g, 1 mmol)
in MeOH (2 mL) was added HClO4–SiO2 (0.02 g,
0.01 mmol, 1 mol %) at rt (w25–30 ꢀC) for 15 min. After
15 min the reaction mixture was diluted with EtOAc
(10 mL), filtered through a plug of cotton (to separate the
catalyst), and the cotton plug was washed with EtOAc
(2ꢂ1 mL). The combined filtrates were concentrated, and
the solid residue recrystallized (EtOH) to afford 1,3-
diphenyl-3-thiophenyl-propanone (0.26 g, 80%) as the sole
product indicating exclusive selectivity for thia-Michael
addition over aza-Michael addition.
4.1.6. Representative experimental procedure for intra-
molecular competition of thia- versus aza-Michael addi-
tion reactions (Scheme 5). To a magnetically stirred
mixture of 1,3-diphenylpropenone (7) (0.21 g, 1 mmol) and
2-aminothiophenol (0.13 g, 1 mmol, 1 equiv) in MeOH
(2 mL) was added HClO4–SiO2 (0.02 g, 0.01 mmol,
1 mol %) at rt (w25–30 ꢀC). After 15 min, the reaction mix-
ture was diluted with EtOAc (10 mL), filtered through a plug
of cotton (to separate the catalyst), and the cotton plug was
washed with EtOAc (2ꢂ1 mL). The combined filtrates were
concentrated, and the solid residue recrystallized (EtOH)

G. L. Khatik et al. / Tetrahedron 63 (2007) 1200–1210
1207
to afford 0.28 g (85%) of 3-(2-amino-phenylsulfanyl)-1,3-
diphenyl-propan-1-one as the sole product indicating exclu-
sive selectivity for thia-Michael addition over oxa-Michael
addition.
13, Table 2), 4-phenylthio-butan-2-one15a (entry 14, Table 3),
4-(4-methylphenylthio)-butan-2-one15a (entry 15, Table 3),
4-benzylthio-butan-2-one7h (entry 16, Table 3), 1-(furan-2-
ylmethylsulfanyl)-propan-2-one15a (entry 17, Table 3),
4-ethylthio-butan-2-one7h (entry 18, Table 3), 4-methyl-
4-phenylsulfanyl-pentan-2-one7l (entry 19, Table 3), 1,3-di-
phenyl-3-p-tolylsulfanyl-propan-1-one15a (entry 24, Table
3), 3-benzylsulfanyl-1,3-diphenyl-propan-1-one15b (entry
29, Table 3), 3-(furan-2-ylmethylsulfanyl)-1,3-diphenyl-
propan-1-one15b (entry 30, Table 3), 3-ethylsulfanyl-1,3-di-
phenyl-propan-1-one15b (entry 31, Table 3), 2,3-dihydro-2-
(4-chlorophenyl)-4-phenyl-1,5-benzothiazepine21 (entry 2,
Table 5), 2,3-dihydro-2-phenyl-4-(4-chlorophenyl)-1,5-
benzothiazepine23 (entry 3, Table 5), 2,3-dihydro-2-phen-
yl-4-(4-nitro-phenyl)-1,5-benzothiazepine23 (entry 4, Table
5), 2,3-dihydro-2-(4-methoxyphenyl)-4-phenyl-1,5-benzo-
thiazepine23 (entry 5, Table 5), 2,3-dihydro-2-phenyl-4-(4-
methoxyphenyl)-1,5-benzothiazepine23 (entry 6, Table 5), and
3-(2-amino-phenylsulfanyl)-1,3-diphenyl-propan-1-one (8)7n
were found to be identical with those reported in the literature.
The following compounds were unknown.
4.1.7. One-pot synthesis of 2,3-dihydro-2,4-diphenyl-1,5-
benzothiazepine (entry 1, Table 5). To a magnetically
stirred mixture of 1,3-diphenylpropenone (7) (0.21 g,
1 mmol) and 2-aminothiophenol (0.12 g, 1 mmol, 1 equiv)
in MeOH (2 mL) was added HClO4–SiO2 (0.02 g,
0.01 mmol, 1 mol %) and the reaction mixture was stirred
under reflux conditions till completion of the reaction
(90 min: TLC and IR). The reaction mixture was diluted
with EtOAc to dissolve the product (10 mL), filtered through
a plug of cotton (to separate the catalyst), and the cotton plug
was washed with EtOAc (2ꢂ1 mL). The combined filtrates
were concentrated and purification was done using column
chromatography to afford 2,3-dihydro-2,4-diphenyl-1,5-
benzothiazepine (0.27 g, 88%) as yellow solid identical
(mp, IR, 1H & 13C NMR, and MS) with an authentic
sample.23
4.1.8. Synthesis of 2,3-dihydro-2,4-diphenyl-1,5-benzo-
thiazepine from 1,3-diphenyl-1-(2-aminophenylsulfide)-
2-propanone. To a magnetically stirred mixture of
1,3-diphenyl-1-(2-aminophenylsulfide)-2-propanone (0.33 g,
1 mmol) in MeOH (2 mL) was added HClO4–SiO2
(0.02 g, 0.01 mmol, 1 mol %) and the reaction mixture was
stirred under reflux conditions till completion of the reaction
(40 min: TLC and IR). The reaction mixture was diluted
with EtOAc to dissolve the product (10 mL), filtered through
a plug of cotton (to separate the catalyst), and the cotton plug
was washed with EtOAc (2ꢂ1 mL). The combined filtrates
were concentrated and purification was done using column
chromatography to afford 2,3-dihydro-2,4-diphenyl-1,5-
benzothiazepine (0.28 g, 90%) as yellow solid identical
(mp, IR, 1H & 13C NMR, and MS) with an authentic
sample.23
4.1.8.1. 4-(4-Nitro-phenylsulfanyl)-4-phenylbutan-2-
one (entry 22, Table 2). Yellow solid, mp 68–70 ꢀC;
[Found: C, 63.80; H, 5.06; S, 10.65. C16H15NO3S requires
C, 63.77; H, 5.02; S, 10.64%]; nmax (KBr) 2925,
1712 cmꢁ1; dH (300 MHz, CDCl3) 2.11 (s, 3H), 3.08–3.11
(m, 2H), 4.95 (t, J¼6.9 Hz, 1H), 7.20–7.39 (m, 5H),
7.61 (d, J¼8.9 Hz, 1H), 8.02 (d, J¼8.6 Hz, 2H), 8.17
(d, J¼8.5 Hz, 1H); dC (75 MHz, CDCl3) 31.3, 46.8,
50.3, 124.4, 125.0, 126.9, 128.2, 128.5, 129.4, 140.7,
145.7, 205.2.
4.1.8.2.
4-tert-Butylsulfanyl-4-phenylbutan-2-one
(entry 34, Table 2). Colorless oil; [Found: C, 71.16; H,
8.54; S, 13.59. C14H20OS requires C, 71.14; H, 8.53; S,
13.57%]; nmax (Neat) 1717 cmꢁ1; dH (300 MHz, CDCl3)
1.18 (s, 9H), 2.01 (s, 3H), 2.85–2.90 (m, 2H), 4.41 (t,
J¼7.3 Hz, 1H), 7.13–7.18 (m, 1H), 7.22–7.31 (m, 2H),
7.38 (d, J¼7.3 Hz, 2H); dC (75 MHz, CDCl3) 30.8, 31.2,
42.5, 52.0, 44.1, 126.8, 127.6, 128.4, 144.5, 205.1.
The remaining reactions were carried out following these
general procedures. In each occasion, the spectral data (IR,
NMR and MS) of known compounds such as 3-phenyl-
thio-3-methylcyclohexan-1-one15a (entry 1, Table 2), 3-(4-
methylphenylthio)-3-methylcyclohexan-1-one15a (entry 4,
Table 2), 3-benzylthio-3-methylcyclohexan-1-one15a (entry 7,
Table 2), 3-(2-furfurylthio)-3-methylcyclohexan-1-one15a
(entry 10, Table 2), 3-ethylthio-3-methylcyclohexan-1-one15a
(entry 13, Table 2), 4-phenylthio-4-phenylbutan-2-one15b (entry
16, Table 2), 4-(4-methylphenylthio)-4-phenylbutan-2-one15b
(entry 19, Table 2), 4-benzylthio-4-phenylbutan-2-one15b (entry
25, Table 2), 4-(2-furfurylthio)-4-phenylbutan-2-one15b (entry
28, Table 2), 4-ethylthio-4-phenylbutan-2-one15b (entry 31,
Table 2), 3-(4-methylphenylthio)-cyclohexan-1-one16 (entry
2, Table 3), 3-(4-nitro-phenylsulfanyl)-cyclohexanone16
(entry 3, Table 3), 3-benzylthio-cyclohexan-1-one16 (entry
4, Table 3), 3-(furan-2-ylmethylsulfanyl)-cyclohexanone15b
(entry 5, Table 3), 3-ethylthio-cyclohexan-1-one15b (entry
6, Table 3), 3,30-[1,2-dithioethyl]biscyclohexane-1-one7q
(entry 8, Table 3), 3,30-[1,3-dithiopropyl]biscyclohexane-1-
one7q (entry 9, Table 3), 3-phenylsulfanyl-cyclopentanone7q
(entry 10, Table 3), 3-p-tolylsulfanyl-cyclopentanone7q
(entry 11, Table 3), 3-benzylsulfanyl-cyclopentanone7b,c
(entry 12, Table 3), 3-ethylsulfanyl-cyclopentanone16 (entry
4.1.8.3. 3-tert-Butylsulfanyl-cyclohexanone (entry 7,
Table 3). Colorless oil; [Found: C, 64.47; H, 9.76; S,
17.23. C10H18OS requires C, 64.46; H, 9.74; S, 17.21%];
nmax (Neat) 1712 cmꢁ1; dH (300 MHz, CDCl3) 1.25 (s,
9H), 1.65 (t, J¼8.2 Hz, 2H), 1.95–2.14 (m, 2H), 2.21–2.35
(m, 3H), 2.61–2.65 (m, 1H), 2.93 (d, J¼3.6 Hz, 1H); dC
(75 MHz, CDCl3) 23.6, 26.4, 30.5, 33.3, 39.7, 42.6, 49.8,
207.9.
4.1.8.4. 4-Methyl-4-p-tolylsulfanyl-pentan-2-one (entry
20, Table 3). Colorless oil; [Found: C, 70.24; H, 8.20; S,
14.40. C13H18OS requires C, 70.22; H, 8.16; S, 14.42%];
nmax (Neat) 1710 cmꢁ1; dH (300 MHz, CDCl3) 1.37 (s,
6H), 2.13 (s, 3H), 2.35 (s, 3H), 2.65 (s, 2H), 7.14 (d,
J¼7.6 Hz, 2H), 7.4 (d, J¼7.6 Hz, 2H); dC (75 MHz,
CDCl3) 21.7, 28.6, 32.7, 47.4, 54.9, 128.5, 130.0, 138.1,
139.7, 207.2.
4.1.8.5. 4-Benzylsulfanyl-4-methyl-pentan-2-one (entry
21, Table 3). Colorless oil; [Found: C, 70.20; H, 8.17; S,
14.43. C13H18OS requires C, 70.22; H, 8.16; S, 14.42%];

1208
G. L. Khatik et al. / Tetrahedron 63 (2007) 1200–1210
nmax (Neat) 1709 cmꢁ1; dH (300 MHz, CDCl3) 1.44 (s, 6H),
2.10 (s, 3H), 2.66 (s, 2H), 3.76 (s, 2H), 7.17–7.34 (m, 5H); dC
(75 MHz, CDCl3) 29.0, 32.7, 33.8, 44.8, 55.1, 127.5, 129.1,
129.5, 138.5, 207.2.
crystalline solid, mp 128–129 ꢀC; [Found: C, 68.57; H, 4.94;
N, 3.83; S, 8.75. C21H18ClNOS requires C, 68.56; H, 4.93; N,
3.81; S, 8.72%]; nmax (KBr) 1676, 3364 cmꢁ1; dH (300 MHz,
CDCl3) 3.48–3.69 (m, 2H), 4.47 (s, 2H), 4.72 (t, J¼7.1 Hz,
1H), 6.53 (t, J¼7.2 Hz, 1H), 6.68 (d, J¼7.7 Hz, 1H), 7.02–
7.21 (m, 6H), 7.41–7.57 (m, 3H), 7.89 (d, J¼7.3 Hz, 2H);
dC (75 MHz, CDCl3) 44.4, 46.7, 115.4, 115.7, 118.6, 128.6,
129.0, 129.2, 129.5, 131.4, 133.9, 137.1, 138.2, 140.8,
149.9, 197.4; m/z (APCI) 368 (MH+).
4.1.8.6.
3-(4-Nitro-phenylsulfanyl)-1,3-diphenyl-
propan-1-one (entry 25, Table 3). White solid, mp 87–
89 ꢀC; [Found: C, 69.60; H, 4.76; S, 8.79. C21H17NO3S
requires C, 69.40; H, 4.71; S, 8.82%]; nmax (KBr)
1679 cmꢁ1; dH (300 MHz, CDCl3) 3.61–3.66 (m, 2H),
5.20 (t, J¼6.8 Hz, 1H), 7.34–7.37 (m, 4H), 7.42–7.47 (m,
4H), 7.49–7.63 (m, 1H), 7.89–7.91 (m, 2H), 8.03–8.06 (m,
2H), 8.17–8.20 (m, 1H); dC (75 MHz, CDCl3) 45.6, 47.1,
124.4, 124.9, 126.9, 128.2, 128.4, 128.6, 129.2, 129.4,
129.5, 134.1, 140.8, 145.8, 196.7.
4.1.8.12.
3-(2-Amino-phenylsulfanyl)-1-(4-chloro-
phenyl)-3-phenyl-propan-1-one (entry 3, Table 4). White
crystalline solid, mp 100–102 ꢀC; [Found: C, 68.58; H, 4.93;
N, 3.85; S, 8.74. C21H18ClNOS requires C, 68.56; H, 4.93; N,
3.81; S, 8.72%]; nmax (KBr) 1685, 3364 cmꢁ1; dH (300 MHz,
CDCl3) 3.46–3.65 (m, 2H), 4.44 (s, 2H), 4.72 (t, J¼7.1 Hz,
1H), 6.52 (t, J¼7.2 Hz, 1H), 6.65 (d, J¼8.1 Hz, 1H), 7.05–
7.37 (m, 9H), 7.78 (d, J¼8.4 Hz, 2H); dC (75 MHz, CDCl3)
44.6, 47.6, 115.5, 116.2, 118.6, 127.9, 128.2, 129.0, 129.5,
130.0, 131.3, 135.6, 138.3, 140.2, 141.9, 150.1, 196.5; m/z
(APCI) 368 (MH+).
4.1.8.7. 3-[2-(3-Oxo-1,3-diphenyl-propylsulfanyl)-eth-
ylsulfanyl]-1,3-diphenyl-propan-1-one (entry 27, Table
3). White solid, mp 158–160 ꢀC; [Found: C, 75.24; H,
5.90; S, 12.59. C32H30O2S2 requires C, 75.26; H, 5.92; S,
12.56%]; nmax (KBr) 1675 cmꢁ1; dH (300 MHz, CDCl3)
2.43 (d, J¼3.1 Hz, 4H), 3.46–3.49 (m, 4H), 4.48 (s, 2H),
7.21–7.33 (m, 10H), 7.44 (d, J¼7.6 Hz, 4H), 7.53 (d,
J¼7.4 Hz, 2H), 7.88 (d, J¼7.1 Hz, 4H); dC (75 MHz,
CDCl3) 31.2, 44.4, 45.3, 127.3, 127.8, 128.0, 128.6, 133.2,
136.7, 141.8, 196.6; m/z (MALDI TOF/TOF) 533.69
(M+Na+), 549.688 (M+K+).
4.1.8.13. 3-(2-Amino-phenylsulfanyl)-3-(4-nitro-phen-
yl)-1-phenyl-propan-1-one (entry 4, Table 4). White
crystalline solid, mp 127–129 ꢀC; [Found: C, 66.67; H,
4.83; N, 7.45; S, 8.50. C21H18N2O3S requires C, 66.65; H,
4.79; N, 7.40; S, 8.47%]; nmax (KBr) 1675, 3467 cmꢁ1; dH
(300 MHz, CDCl3) 3.56–3.77 (m, 2H), 4.50 (s, 2H), 4.82
(t, J¼8.0 Hz, 1H), 6.50 (t, J¼7.1 Hz, 1H), 6.69 (d, J¼
7.7 Hz, 1H), 6.94–7.19 (m, 2H), 7.32–7.57 (m, 5H),
7.91 (d, J¼7.1 Hz, 2H), 8.05 (d, J¼8.0 Hz, 2H); dC
(75 MHz, CDCl3) 43.8, 46.4, 114.82, 115.5, 118.7, 124.1,
128.6, 129.0, 129.3, 131.7, 134.2, 136.8, 138.0, 147.4,
149.9, 196.9.
4.1.8.8.
3-[3-(3-Oxo-1,3-diphenyl-propylsulfanyl)-
propylsulfanyl]-1,3-diphenyl-propan-1-one (entry 28,
Table 3). White solid, mp 88–90 ꢀC; [Found: C, 75.51; H,
6.16; S, 12.24. C33H32O2S2 requires C, 75.53; H, 6.15; S,
12.22%]; nmax (KBr) 1682 cmꢁ1; dH (300 MHz, CDCl3)
1.64–1.71 (m, 2H), 2.17–2.45 (m, 4H), 3.49–3.57 (m, 4H),
4.47–4.54 (m, 2H), 7.16–7.88 (m, 16H), 7.89 (d, J¼7.3 Hz,
4H); dC (75 MHz, CDCl3) 29.0, 29.1, 30.7, 127.8, 128.4,
128.6, 129.0, 129.1, 133.7, 137.3, 142.6, 197.3; m/z (MALDI
TOF/TOF) 547 (M+Na+), 563.698 (M+K+).
4.1.8.14.
3-(2-Amino-phenylsulfanyl)-3-(4-meth-
oxyphenyl)-1-phenyl-propan-1-one (entry 5, Table 4). White
crystalline solid, mp 106–109 ꢀC; [Found: C, 72.72; H, 5.84;
N, 3.87; S, 8.85. C22H21NO2S requires C, 72.70; H, 5.82; N,
3.85; S, 8.82%]; nmax (KBr) 1679, 3362 cmꢁ1; dH (300 MHz,
CDCl3) 3.49–3.75 (m, 2H), 3.76 (s, 3H), 4.45 (s, 2H), 4.72 (t,
J¼7.1 Hz, 1H), 6.54 (t, J¼7.2 Hz, 1H), 6.68–6.79 (m, 3H),
7.08–7.25 (m, 4H), 7.41–7.57 (m, 3H), 7.88 (d, J¼7.7 Hz,
2H); dC (75 MHz, CDCl3) 44.8, 47.7, 114.3, 115.4, 116.5,
118.6, 128.6, 129.1, 129.2, 131.1, 133.8, 138.2, 149.9, 159.2,
197.8; m/z (APCI) 364 (MH+).
4.1.8.9. 3-tert-Butylsulfanyl-1,3-diphenyl-propan-1-
one (entry 32, Table 3). White solid, mp 73–75 ꢀC; [Found:
C, 76.44; H, 7.45; S, 10.72. C19H22OS requires C, 76.46; H,
7.43; S, 10.74%]; nmax (KBr) 1682 cmꢁ1; dH (300 MHz,
CDCl3) 1.22 (s, 9H), 3.46–3.50 (m, 2H), 4.65 (t, J¼
7.0 Hz, 1H), 7.15–7.20 (m, 2H), 7.40–7.53 (m, 6H), 7.89
(d, J¼7.9 Hz, 2H); dC (75 MHz, CDCl3) 31.6, 42.6, 44.4,
47.6, 126.8, 127.8, 128.1, 128.4, 128.5, 133.1, 136.9,
144.8, 197.0.
4.1.8.15.
3-(2-Amino-phenylsulfanyl)-1-(4-meth-
oxyphenyl)-3-phenyl-propan-1-one (entry 6, Table 4). White
crystalline solid, mp 104–105 ꢀC; [Found: C, 72.71; H, 5.83;
N, 3.86; S, 8.84. C22H21NO2S requires C, 72.70; H, 5.82; N,
3.85; S, 8.82%]; nmax (KBr) 1666, 3462 cmꢁ1; dH (300 MHz,
CDCl3) 3.45–3.65 (m, 2H), 3.83 (s, 3H), 4.46 (s, 2H), 4.73 (t,
J¼7.1 Hz, 1H), 6.52 (t, J¼7.3 Hz, 1H), 6.67 (d, J¼7.6 Hz,
1H), 6.89 (d, J¼7.2 Hz, 2H), 7.04–7.22 (m, 7H), 7.88 (d,
J¼8.1 Hz, 2H); dC (75 MHz, CDCl3) 43.6, 47.2, 55.5, 113.7,
114.8, 115.7, 117.9, 127.2, 127.6, 128.3, 129.8, 130.4, 130.5,
137.6, 141.8, 149.5, 163.6, 195.6; m/z (APCI) 364 (MH+).
4.1.8.10. 3-(4,5-Dihydro-thiazol-2-ylsulfanyl)-1,3-di-
phenyl-propan-1-one (entry 33, Table 3). White solid,
mp 130–132 ꢀC; [Found: C, 66.04; H, 5.26; N, 4.25; S,
19.53. C18H17NOS2 requires C, 66.02; H, 5.23; N, 4.28; S,
19.58%]; nmax (KBr) 1678 cmꢁ1; dH (300 MHz, CDCl3)
3.04–3.22 (m, 2H), 3.52–3.67 (m, 2H), 3.84–3.92 (m, 1H),
3.98–4.07 (m, 1H), 6.81 (t, J¼7.5 Hz, 1H), 7.31–7.35 (m,
5H), 7.43–7.48 (m, 2H), 7.54–7.59 (m, 1H), 7.98 (d,
J¼7.2 Hz, 2H); dC (75 MHz, CDCl3) 27.5, 38.7, 52.4,
56.6, 127.3, 128.2, 128.4, 128.7, 128.9, 133.5, 136.1,
136.7, 196.3, 196.6; m/z (EI): 327 (M+).
4.1.8.16. 3-(4-Amino-phenylsulfanyl)-1,3-diphenyl-
propan-1-one (entry 7, Table 4). White crystalline solid,
mp 98–99 ꢀC; [Found: C, 75.62; H, 5.70; N, 4.23; S, 9.60.
C21H19NOS requires C, 75.64; H, 5.74; N, 4.20; S,
4.1.8.11. 3-(2-Amino-phenylsulfanyl)-3-(4-chloro-
phenyl)-1-phenyl-propan-1-one (entry 2, Table 4). White

G. L. Khatik et al. / Tetrahedron 63 (2007) 1200–1210
1209
9.62%]; nmax (KBr) 1677, 3379, 3470 cmꢁ1; dH (300 MHz,
CDCl3) 1.58 (br s, 2H), 3.50–3.65 (dd, J¼6.5 Hz, 17.0 Hz,
2H), 4.70 (t, J¼7.1 Hz, 1H), 6.53 (d, J¼6.7 Hz, 2H), 7.10
(d, J¼6.8 Hz, 2H), 7.23–7.26 (m, 5H), 7.40–7.45 (m, 2H),
7.52–7.54 (m, 1H), 7.87 (d, J¼8.5 Hz, 2H); dC (75 MHz,
CDCl3) 44.2, 49.6, 115.3, 121.1, 127.1, 127.9, 128.1,
128.3, 128.6, 133.3, 136.6, 136.9, 141.5, 146.9, 197.3.
4.50–4.55 (m, 1H), 6.68 (t, J¼7.5 Hz, 1H), 6.97 (d,
J¼7.9 Hz, 1H), 7.04 (d, J¼7.9 Hz, 1H), 7.14–7.24 (m,
5H), 7.40–7.45 (m, 2H), 7.50–7.57 (m, 2H), 7.93 (d,
J¼7.2 Hz, 2H); dC (75 MHz, CDCl3) 44.1, 49.3, 115.9,
117.8, 120.8, 128.1, 128.2, 128.8, 129.2, 129.3, 132.4,
134.2, 136.9, 137.6, 141.9, 158.7, 197.8.
4.1.8.22. 4-(2-Hydroxy-phenylsulfanyl)-4-phenylbutan-
2-one (10) (Scheme 5). White solid, mp 74–76 ꢀC; [Found:
C, 70.60; H, 5.96; S, 11.79. C16H16O2S requires C, 70.56;
4.1.8.17. 3-(4-Amino-phenylsulfanyl)-3-(4-nitro-phenyl)-
1-phenyl-propan-1-one (entry 8, Table 4). Yellow solid,
mp 134–136 ꢀC; [Found: C, 66.63; H, 4.75; N, 7.42; S,
8.43. C21H18N2O3S requires C, 66.65; H, 4.79; N, 7.40; S,
8.47%]; nmax (KBr) 1678, 3380, 3493 cmꢁ1; dH (300 MHz,
CDCl3) 1.59 (br s, 2H), 3.55–3.71 (m, 2H), 4.74 (t,
J¼6.2 Hz, 1H), 6.51 (d, J¼8.5 Hz, 2H), 7.04(d, J¼8.5 Hz,
2H), 7.34 (d, J¼8.7 Hz, 2H), 7.42–7.47 (m, 2H), 7.55–
7.60 (m, 1H), 7.89 (d, J¼8.7 Hz, 2H), 8.07 (d, J¼
8.7 Hz, 2H); dC (75 MHz, CDCl3) 44.1, 49.5, 115.9, 119.9,
124.1, 128.9, 129.3, 134.1, 134.5, 137.0, 137.4, 147.3,
148.0, 150.1, 197.0; m/z (EI) 378 (M)+.
H, 5.92; S, 11.77%]; nmax (KBr) 1706, 3307 cmꢁ1
;
dH (300 MHz, CDCl3) 2.14 (s, 3H), 2.97–3.16 (m, 2H),
4.31–4.36 (m, 1H), 6.71 (t, J¼7.5 Hz, 1H), 6.95 (d,
J¼7.92 Hz, 1H), 7.03–7.09 (m, 3H), 7.17–7.26 (m, 4H);
dC (75 MHz, CDCl3) 31.0, 48.8, 48.8, 115.8, 117.5, 120.8,
127.9, 128.2, 129.1, 132.4, 137.6, 141.5, 158.5, 206.4; m/z
(EI) 272 (M+).
References and notes
4.1.8.18.
3-(4-Amino-phenylsulfanyl)-1-(4-chloro-
1. Fujita, E.; Nagao, Y. Bioorg. Chem. 1977, 6, 287.
phenyl)-3-phenyl-propan-1-one (entry 9, Table 4). White
solid, mp 124–126 ꢀC; [Found: C, 68.52; H, 4.97; N, 3.80; S,
8.69. C21H18ClNOS requires C, 68.56; H, 4.93; N, 3.81; S,
8.72%]; nmax (KBr) 1671, 3326, 3416 cmꢁ1; dH (300 MHz,
CDCl3) 1.56 (br s, 2H), 3.49–3.60 (m, 2H), 4.67 (t,
J¼7.2 Hz, 1H), 6.52 (d, J¼8.5 Hz, 2H), 7.09 (d, J¼8.5 Hz,
2H), 7.19–7.24 (m, 5H), 7.40 (d, J¼8.6 Hz, 2H), 7.80 (d,
J¼8.6 Hz, 2H); dC (75 MHz, CDCl3) 44.7, 50.1, 115.8,
121.4, 127.8, 128.4, 128.9, 129.4, 130.0, 135.7, 137.2,
140.2, 142.0, 147.5, 196.7; m/z (EI) 367 (M+).
2. (a) Fluharty, A. L. The Chemistry of the Thiol Group; Patai, S.,
Ed.; Wiley Interscience: New York, NY, 1974; p 589; Part 2; (b)
Kumar, A.; Salunkhe, R. V.; Rane, R. A.; Dike, S. Y. J. Chem.
Soc., Chem. Commun 1991, 485.
3. Trost, B. M.; Keeley, D. E. J. Org. Chem. 1975, 40, 2013.
4. Cohen, T.; Mura, A. J., Jr.; Shull, D. W.; Fogel, E. R.; Ruffner,
R. J.; Falck, J. R. J. Org. Chem. 1976, 41, 3218.
5. Bakuzia, P.; Bakuzis, M. L. F. J. Org. Chem. 1981, 46, 235.
6. Cherkauskas, J. P.; Cohen, T. J. Org. Chem. 1992, 57, 6.
7. (a) Zeolites: Sreekumar, R.; Rugmini, P.; Padmakumar, R.
Tetrahedron Lett. 1997, 38, 6557; (b) CdI2: Saito, M.;
Nakajima, M.; Hashimoto, S. Tetrahedron 2000, 56, 9589; (c)
InBr3: Bandini, M.; Cozzi, P. G.; Giacomini, M.; Melchiorre,
P.; Selva, S.; Umani-Ronchi, A. J. Org. Chem. 2002, 67,
3700; (d) Hf(OTf)3: Kobyashi, S.; Ogawa, C.; Kawamura,
M.; Sugiura, M. Synlett 2001, 983; (e) Na2CaP2O7: Zahouily,
M.; Abrouki, Y.; Rayadh, A. Tetrahedron Lett. 2002, 43,
7729; (f) KF/NP: Abrouki, Y.; Zahouily, M.; Rayadh, A.;
Bahlaouan, B.; Sebti, S. Tetrahedron Lett. 2002, 43, 8951; (g)
Bi(NO3)3: Srivastava, N.; Banik, B. K. J. Org. Chem. 2003,
68, 2109; (h) Bi(OTf)3: Alam, M. M.; Varala, R.; Adapa,
S. R. Tetrahedron Lett. 2003, 44, 5115; (i) Al2O3: Cheng, S.;
Comer, D. D. Tetrahedron Lett. 2002, 43, 1179; (j) NafionÒ
SAC-13: Wabnitz, T. C.; Yu, J.-Q.; Spencer, J. B. Synlett
2003, 1070; (k) Ionic liquids: Yadav, J. S.; Reddy, B. V. S.;
Baishya, G. J. Org. Chem. 2003, 68, 7098; (l) Ionic liquids:
Ranu, B. C.; Dey, S. S.; Hajra, A. Tetrahedron 2003, 59,
2417; (m) Ionic liquids: Ranu, B. C.; Dey, S. S. Tetrahedron
2004, 60, 4183; (n) InCl3: Ranu, B. C.; Dey, S. S.; Samanta,
S. ARKIVOC 2005, iii, 44; (o) I2: Chu, C.-M.; Gao, S.;
Sastry, M. N. V.; Yao, C.-F. Tetrahedron Lett. 2005, 46, 4971;
(p) KF/Al2O3: Yang, L.; Xu, L.-W.; Xia, C.-G. Tetrahedron
Lett. 2005, 46, 3279; (q) H3PW12O40: Firouzabadi, H.;
Iranpoor, N.; Jafari, A. A. Synlett 2005, 299; (r) SDS:
Firouzabadi, H.; Iranpoor, N.; Jafari, A. A. Adv. Synth. Catal.
2005, 347, 655; (s) b-Cyclodextrin: Krishnaveni, N. S.;
Surendra, K.; Rao, K. R. Chem. Commun. 2005, 669.
4.1.8.19.
3-(4-Amino-phenylsulfanyl)-3-(4-meth-
oxyphenyl)-1-phenyl-propan-1-one (entry 10, Table 4). White
solid; [Found: C, 72.68; H, 5.84; N, 3.84; S, 8.80.
C22H21NO2S requires C, 72.70; H, 5.82; N, 3.85; S, 8.82%];
nmax (KBr) 1681, 3375 cmꢁ1; dH (300 MHz, CDCl3) 1.56
(br s, 2H), 3.49–3.60 (m, 2H), 3.76 (s, 3H), 4.68 (t,
J¼7.2 Hz, 1H), 6.53 (d, J¼8.4 Hz, 2H), 6.76 (d, J¼8.6 Hz,
2H), 7.10–7.17 (m, 4H), 7.39–7.44 (m, 2H), 7.47–7.53 (m,
1H), 7.85 (d, J¼7.3 Hz, 2H); dC (75 MHz, CDCl3) 44.9,
50.0, 56.0, 114.2, 115.8, 128.6, 129.1, 129.4, 133.6, 134.0,
134.5, 137.1, 137.4, 147.4, 159.1, 198.0; m/z (EI) 363 (M+).
4.1.8.20.
3-(4-Amino-phenylsulfanyl)-1-(4-meth-
oxyphenyl)-3-phenyl-propan-1-one (entry 11, Table 4). White
solid, mp 138–140 ꢀC; [Found: C, 72.66; H, 5.83; N, 3.84; S,
8.81. C22H21NO2S requires C, 72.70; H, 5.82; N, 3.85; S,
8.82%]; nmax (KBr) 1670, 3368, 3465 cmꢁ1; dH (300 MHz,
CDCl3) 3.48–3.54 (m, 2H), 3.70 (br s, 2H), 3.85 (s, 3H), 4.70
(t, J¼7.2 Hz, 1H), 6.52 (d, J¼8.5 Hz, 2H), 6.89 (d,
J¼8.9 Hz, 2H), 7.10 (d, J¼8.5 Hz, 2H), 7.14–7.19 (m, 1H),
7.20–7.24 (m, 4H), 7.86 (d, J¼8.9 Hz, 2H); dC (75 MHz,
CDCl3) 44.3, 50.3, 56.0, 114.4, 115.8, 121.6, 122.5, 128.4,
128.8, 130.9, 131.4, 137.1, 142.2, 147.5, 164.1, 196.4; m/z (EI)
363 (M+).
4.1.8.21. 3-(2-Hydroxy-phenylsulfanyl)-1,3-diphenyl-
propan-1-one (9) (Scheme 5). White solid, mp 103–
106 ꢀC; [Found: C, 75.44; H, 5.45; S, 9.57. C21H18O2S re-
quires C, 75.42; H, 5.42; S, 9.59%]; nmax (KBr) 1682,
3347 cmꢁ1; dH (300 MHz, CDCl3) 3.48–3.71 (m, 2H),
8. (a) Chakraborti, A. K.; Shivani. J. Org. Chem. 2006, 71, 5785;
(b) Chakraborti, A. K.; Gulhane, R. Synlett 2004, 627; (c)
Chakraborti, A. K.; Gulhane, R.; Shivani. Synthesis 2004,
111; (d) Chakraborti, A. K.; Gulhane, R.; Shivani. Synlett

1210
G. L. Khatik et al. / Tetrahedron 63 (2007) 1200–1210
2003, 1805; (e) Chakraborti, A. K.; Sharma, L.; Gulhane, R.;
(d) Khan, A. T.; Parvin, T.; Choudhury, L. K. Synthesis 2006,
2497; (e) Das, B.; Venkateswarlu, K.; Majhi, A.; Reddy,
M. R.; Reddy, K. N.; Rao, Y. K.; Ravikumar, K.; Sridhar, B.
J. Mol. Catal. A: Chem. 2006, 246, 276.
Shivani. Tetrahedron 2003, 59, 7661; (f) Chakraborti, A. K.;
Gulhane, R. Tetrahedron Lett. 2003, 44, 6749; (g)
Chakraborti, A. K.; Gulhane, R. Chem. Commun. 2003, 1896;
(h) Chakraborti, A. K.; Gulhane, R. Tetrahedron Lett. 2003,
44, 3521.
19. After the completion of this work a related report appeared in
the literature [ Khan, A. T.; Ghosh, S.; Choudhury, L. H. Eur. J.
Org. Chem. 2006, 2226 ] and prompted us to report our results
on the scope and limitation of the use of this self-developed
catalyst for carbon–sulfur bond formation.
20. Tundo, P.; Anastas, P.; Black, D. S.; Breen, J.; Collins, T.;
Memoli, S.; Miyamoto, J.; Polyakoff, M.; Tumas, W. Pure
Appl. Chem. 2000, 72, 1207.
9. (a) Shivani; Chakraborti, A. K. J. Mol. Catal. A: Chem. 2006.
doi:10.1016/j.molcata.2006.08.047; (b) Chakraborti, A. K.;
Kondaskar, A.; Rudrawar, S. Tetrahedron 2004, 60, 9085; (c)
Chakraborti, A. K.; Rudrawar, S.; Kondaskar, A. Eur. J. Org.
Chem. 2004, 3597; (d) Chakraborti, A. K.; Rudrawar, S.;
Kondaskar, A. Org. Biomol. Chem. 2004, 2, 1277; (e) Chakra-
borti, A. K.; Kondasker, A. Tetrahedron Lett. 2003, 44, 8315.
10. Chakraborti, A. K.; Bhagat, S.; Rudrawar, S. Tetrahedron Lett.
2004, 45, 7641.
11. (a) Rudrawar, S.; Besra, R. C.; Chakraborti, A. K. Synthesis
2006, 2767; (b) Besra, R. C.; Rudrawar, S.; Chakraborti,
A. K. Tetrahedron Lett. 2005, 46, 6213.
12. (a) Chakraborti, A. K.; Chankeshwara, S. V. Org. Biomol.
Chem. 2006, 4, 2769; (b) Chankeshwara, S. V.; Chakraborti,
A. K. Synthesis 2006, 2784; (c) Chankeshwara, S. V.; Chakra-
borti, A. K. Tetrahedron Lett. 2006, 47, 1087; (d) Chankesh-
wara, S. V.; Chakraborti, A. K. J. Mol. Catal. A: Chem.
2006, 253, 198.
21. (a) Anticonvulsant: Sarro, G. D.; Chimirri, A.; Sarro, A. D.;
ꢀ
Gitto, R.; Grasso, S.; Zappala, M. Eur. J. Med. Chem. 1995,
30, 925; (b) Ca+2 Channel antagonist: Kurokawa, J.; Adachi-
Akahane, S.; Nagao, T. Eur. J. Pharmacol. 1997, 325, 229;
(c) Anti-HIV: Grandolini, G.; Perioli, L.; Ambrogi, V. Eur. J.
Med. Chem. 1999, 34, 701; (d) Squalene synthetase inhibitor:
Yang, X.; Buzon, L.; Hamanaka, E.; Liu, K. K.-C. Tetrahedron:
Asymmetry 2000, 11, 4447 and the references therein; (e) V2
Arginine vasopressin receptor antagonist: Urbanski, M. J.;
Chen, R. H.; Demarest, K. T.; Gunnet, J.; Look, R.; Ericson,
E.; Murray, W. V.; Rybczynski, P. J.; Zhang, X. Bioorg. Med.
Chem. Lett. 2003, 13, 4031; (f) HIV-1 Reverse transcriptase
inhibitor: Santo, R. D.; Costi, R. IL Farmaco 2005, 60, 385.
13. Kumar, R.; Chakraborti, A. K. TetrahedronLett. 2005, 46, 8319.
14. Kumar, R.; Thilagavathi, R.; Gulhane, R.; Chakraborti, A. K.
J. Mol. Catal. A: Chem. 2006, 250, 227.
ꢀ
22. Levai, A. J. Heterocycl. Chem. 2000, 37, 199 and the references
therein.
15. (a) Cu(BF4)2$xH2O: Garg, S. K.; Kumar, R.; Chakraborti,
A. K. Tetrahedron Lett. 2005, 46, 1721; (b) Zn(ClO4)2$
6H2O: Garg, S. K.; Kumar, R.; Chakraborti, A. K. Synlett
2005, 1370; (c) Montmorillonite K-10: Sharma, G.; Kumar,
R.; Chakraborti, A. K. J. Mol. Catal. A: Chem. 2006.
doi:10.1016/j.molcata.2006.08.021.
23. Kodomari, M.; Noguchi, T.; Aoyama, T. Synth. Commun. 2004,
34, 1783.
24. Patel, V. M.; Desai, K. R. Indian J. Chem. 2004, 43B, 199.
ꢀ
25. (a) Levai, A. J. Heterocycl. Chem. 2004, 41, 399; (b) Levai, A.
J. Heterocycl. Commun. 2002, 8, 227; (c) Levai, A.
ꢀ
ꢀ
J. Heterocycl. Commun. 2002, 8, 375.
16. Khatik, G. L.; Kumar, R.; Chakraborti, A. K. Org. Lett. 2006; 8,
2433.
17. HClO4–SiO2 is not commercially available and was prepared
for the first time by Chakraborti et al. (vide Ref. 8g) and was
patented [Chakraborti, A. K.; Gulhane, R. Indian Patent, 266/
DEL/2003 (10-3-2003)].
18. (a) Agarwal, A.; Rani, S.; Vankar, Y. D. J. Org. Chem. 2004, 69,
6137; (b) Misra, A. K.; Tiwari, P.; Madhusudan, S. K.
Carbohydr. Res. 2005, 340, 325; (c) Mukhopadhyay, B.;
Russell, D. A.; Field, R. A. Carbohydr. Res. 2005, 340, 1075;
26. Micheli, F.; Degiorgis, F.; Feriani, A.; Paio, A.; Pozzan, A.;
Zarantonello, P.; Seneci, P. J. Combi. Chem. 2001, 3, 224.
27. Pant, S.; Singhal, B.; Upreti, M.; Pant, U. Molecules 1998,
3, 159.
28. (a) Upreti, M.; Pant, S.; Dandia, A.; Pant, U. C. Indian J. Chem.
1997, 36B, 1181; (b) Pant, S.; Sharma, A.; Sharma, S. K.; Pant,
U. C.; Goel, A. K. Indian J. Chem. 1996, 35B, 794.
29. Dandia, A.; Sati, M.; Loupy, A. Green Chem. 2002, 4, 599.
30. Bhagat, S.; Sharma, R.; Sawant, D. M.; Sharma, L.;
Chakraborti, A. K. J. Mol. Catal. A: Chem. 2005, 244, 20.