Synthesis of functionalized 2-(arylthio)benzoates by formal [3+3] cyclizations of 3-arylthio-1-silyloxy-1,3-butadienes with 3-silyloxy-2-en-1-ones and 1,3-diacylcyclopropanes

Article abstract of DOI:10.1016/j.tet.2009.06.119

Functionalized 2-(arylthio)benzoates are prepared by formal [3+3] cyclizations of 3-arylthio-1-trimethylsilyloxy-1,3-butadienes with 3-silyloxy-2-en-1-ones and 1,1-diacylcyclopropanes.

Full text of DOI:10.1016/j.tet.2009.06.119

Tetrahedron 65 (2009) 7562–7572
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of functionalized 2-(arylthio)benzoates by formal [3þ3] cyclizations
of 3-arylthio-1-silyloxy-1,3-butadienes with 3-silyloxy-2-en-1-ones and 1,3-
diacylcyclopropanes
,
Inam Iqbal a, Muhammad Imran a, Nasir Rasool a b, Muhammad A. Rashid a, Munawar Hussain a,
,c,
Alexander Villinger a, Christine Fischer c, Peter Langer a
*
a
¨
Institut fu¨r Chemie, Universitat Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany
b G.C. University Faisalabad, Department of Chemistry, Faisalabad, Pakistan
c Leibniz-Institut fu¨r Katalyse e. V. an der Universita¨t Rostock, Albert-Einstein-Str. 29a, 18059 Rostock, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Functionalized 2-(arylthio)benzoates are prepared by formal [3þ3] cyclizations of 3-arylthio-1-trime-
thylsilyloxy-1,3-butadienes with 3-silyloxy-2-en-1-ones and 1,1-diacylcyclopropanes.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 22 April 2009
Received in revised form 28 June 2009
Accepted 29 June 2009
Available online 3 July 2009
Keywords:
Arenes
Cyclopropanes
Cyclizations
Sulfur compounds
1. Introduction
trimethylsilyloxy-3-penten-2-one with 1-methoxy-3-phenylthio-1-
trimethylsilyloxy-1,3-butadiene.15 Simple 2-(aryloxythio)benzoates
Functionalized diaryl sulfides are pharmacologically important
molecules which occur in various natural products. For example,
they are present in dibenzothiophenes,1 varacins (lissoclinotoxins),2
lissoclibadins,3 cyclic sulfides,4 and various other natural products
isolated from Streptomyces griseus.5 Diaryl sulfides are synthetically
available by reaction of arenes with sulfur6 and sulfur dichloride,7 by
condensation of organometallic reagents with chlorophenyl-sulfide8
and by base-mediated reaction of chloroarenes with thiophenols.9
These reactions often suffer from their low regioselectivity and from
the formation of polysulfides, due to the harsh reaction conditions.
An alternative approach to diaryl sulfides is based on the use of
sulfur-containing building blocks in cyclization reactions. Hilt and
co-workers reported a convenient approach to diaryl sulfides by
cobalt(I)-catalyzed [4þ2] cycloaddition of alkynyl sulfides with 1,3-
butadienes.10 Recently, we have studied11 the synthesis of 3- and
5-(arylthio)salicylates by TiCl4-mediated formal [3þ3] cyclizations12
of 1,3-bis(silyloxy)-1,3-butadienes13 with 3-silyloxy-2-en-1-ones.14
Chan et al. reported the synthesis of methyl 4,6-dimethyl-2-
(phenylthio)benzoate by TiCl4-mediated [3þ3] cyclization of 4-
have been prepared by catalytic cyclizations of 3-arylthio-1-trime-
thylsilyloxy-1,3-butadienes with 1,1,3,3-tetramethoxypropane.16 In
addition, the synthesis of 6-alkyl- and 6-aryl-2-(arylthio)benzoates
by cyclization of 3-arylthio-1-trimethylsilyloxy-1,3-butadienes with
3-alkoxy-2-en-1-ones has been reported.17 We have recently studied
the synthesis of 5-chloroethyl-2-(arylthio)benzoates by TiCl4-me-
diated domino ‘[3þ3] cyclization/homo-Michael’ reaction of
3-arylthio-1-trimethylsilyloxy-1,3-butadienes with 1,1-diacyl-
cyclopropanes.18 Herein, we provide a full account of this work. In
addition, we report a comprehensive study related to the formal
[3þ3] cyclization of 3-arylthio-1-trimethylsilyloxy-1,3-butadienes
with 3-silyloxy-2-en-1-ones. The reactions reported provide a con-
venient approach to substituted 2-(arylthio)benzoates and thio-
xanthones which are not readily available by other methods.
2. Results and discussion
3-Arylthio-1-trimethylsilyloxy-1,3-butadienes 3a–m were pre-
pared, as previously reported,15,18 by reaction of methyl acetoace-
tate (1a), methyl 3-oxopentanoate (1b), and methyl 3-oxohexanoate
(1c) with various thiophenols to give methyl 3-(arylthio)crotonates
2a–m (Scheme 1). The latter were subsequently transformed into
3a–m by deprotonation (LDA) and subsequent silylation.
* Corresponding author. Tel.: þ49 381 4986410; fax: þ49 381 4986412.
E-mail address: peter.langer@uni-rostock.de (P. Langer).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.06.119

I. Iqbal et al. / Tetrahedron 65 (2009) 7562–7572
7563
Table 1
Synthesis of 5a–v
O
O
SAr O
ArSH
R1
R1
OMe
OMe
3
4
5
Ar
R1
R2
R3
% (5)a
i
1a-c
2a-m (76-94%)
a
a
a
a
a
b
b
b
c
c
c
d
e
f
g
h
i
i
j
k
l
m
a
b
c
d
e
b
c
f
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
r
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
H
H
H
H
Me
Me
Me
Me
nPr
Me
Me
Ph
H
56
43
43
63
42
55
49
52
55
51
50
54
39
57
49
45
37
35
36
37
40
33
Me
Cl
PhS
H
Me
Cl
H
Me
Cl
H
H
H
H
H
H
H
Cl
H
H
SAr OSiMe3
OMe
ii
R1
H
Me
Me
Me
Et
Et
Et
H
Me
H
H
Me
H
H
Me
H
H
3a-m (78-96%)
Scheme 1. Synthesis of 3a–m. Conditions: (i) P4O10, CH2Cl2, 20 ꢁC, 18 h; (ii) (1) LDA,
THF, ꢀ78 ꢁC, 1 h; (2) Me3SiCl, ꢀ78/20 ꢁC, 14 h.
b
c
f
Ph
Ph
Ph
Me
Me
Ph
The TiCl4-mediated cyclization of 3a with 3-silyloxy-2-en-1-one
4a, prepared from acetylacetone, afforded the 2-(phenyl-
thio)benzoate 5a (Scheme 2). The best yields were obtained when
the reaction was carried out in a highly concentrated solution
(stoichiometric ratio: 3a/4a/TiCl4¼1.0/1.5/1.5). The solution was
slowly warmed from ꢀ78 to 20 ꢁC (20 h).
a
a
a
a
a
a
c
a
a
a
a
4-MeC6H4
4-MeC6H4
3-MeC6H4
4-EtC6H4
4-EtC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
3-ClC6H4
4-FC6H4
4-FC6H4
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
s
t
u
v
PhS
OSiMe3
OMe
TiCl4
CH2Cl2
O
SPh
H
H
Me
3a
OMe
Me
5a (56%)
a
_
Me3SiO
O
Isolated yields.
78 to 20 °C
14 h
Me
+
Me
Me
Products 5h and 5k were formed with very good regiose-
4a
lectivity. Only the isomers containing the phenyl group located
ortho to the ester group were isolated. The other isomers could not
be isolated. However, the yields of 5h and 5k the isolated products
were only moderate. This can be explained by practical reasons
(loss of material during the chromatographic purification) and by
hydrolysis of the diene (small amounts of methyl 3-(arylthio)-
crotonates 2 were isolated in some cases). Inspection of the crude
product mixture by 1H NMR and TLC suggests that the reaction
indeed proceeded with very good regioselectivity. The regiose-
lectivity is in agreement with the regiochemical result of the re-
action of 4f with 1,3-bis(silyloxy)-1,3-butadienes and might be
explained by steric reasons.12,15 The regioselective formation of 5e
is surprising, since the effective sizes of n-propyl and methyl group
are similar. The reaction of 1,3-bis(silyloxy)-1,3-butadienes with 4e
has not been previously studied. In general, the yields of products
5a–v are only moderate (33–63%). This can be again explained by
practical problems during the isolation and purification process.
Treatment of 2-(arylthio)benzoates 5b,c,e,f,g,i,j with concd sul-
furic acid resulted in an intramolecular Friedel–Crafts cyclization to
give the thioxanthones 6a–g in excellent yields (Scheme 4, Table 2).
TiCl4
H2O
_
O
SPh
TiCl4
O
Me3SiO
Me
OMe
OTiCl3
Me
+
Me
Me
A
D
1a
HCl
Me3SiCl
O
O
PhS
OMe
TiCl3
PhS
OMe
Me3SiCl
TiCl4
O
O
Me3SiO
Me
Me
Me
(Me3Si)2O
Me
B
C
Scheme 2. Possible mechanism of the formation of 5a.
The formation of 5a can be explained by reaction of 4a with TiCl4
to give intermediate A (Scheme 2). The attack of the terminal car-
bon atom of 3a onto A afforded intermediate B. The elimination of
TMS-siloxane (intermediate C) and subsequent cyclization gave
intermediate D. The elimination of titanium hydroxide (before or
during the aqueous work-up) and aromatization resulted in the
formation of product 5a. Due to the symmetrical structure of A, the
attack of 1a on either terminal allylic carbon atom would result in
the formation of the same product (5a).
S
R1
S
O
i
O
R2
R1
OMe
R2
Me
R3
Me
R3
5b,c,e,f,g,i,j
6a-g
Scheme 4. Synthesis of 6a–g. Conditions: (i) concd H2SO4, 20 ꢁC, 2 h.
The cyclization of dienes 3a–mwith 3-silyloxy-2-en-1-ones 4a–f
afforded the 2-(thioaryloxy)benzoates 5a–v (Scheme 3, Table 1).
Table 2
Synthesis of thioxanthones 6a–g
SAr OSiMe3
R1
3a-m
5
8
R1
R2
R3
% (6)a
SAr O
OMe
b
c
e
f
g
i
a
b
c
d
e
f
H
H
H
Me
Me
Et
Et
Me
Me
n-Pr
Me
Me
Me
Me
Me
Cl
H
Me
Cl
Me
Cl
98
97
95
97
97
95
96
R1
i
OMe
O
OSiMe3
R2
Me
R2
+
Me
R3
R3
4a-f
5a-v
j
g
a
Isolated yields.
Scheme 3. Synthesis of 5a–v.

7564
I. Iqbal et al. / Tetrahedron 65 (2009) 7562–7572
The structures of all products were elucidated by spectroscopic
(Scheme 6, Table 3). Products 8b–d,g,i,j,l,o, derived from the un-
symmetrical cyclopropanes 7b–d, were formed with very good
regioselectivity. This can be explained by regioselective attack of
the terminal carbon atom of diene 3 onto the acetyl rather than the
less reactive aroyl group of 7b–d.
methods. The structure of 6f was independently confirmed by X-ray
crystal structure analysis (Fig. 1).19
SAr
OSiMe3
SAr
O
OMe
3a,d,f,g,i,k,o
TiX4
OMe
(1.5 equiv.)
O
O
R2
X
R1
+
CH2Cl2
R1
R2
_
78
20 °C
8a-x
7a-e
Scheme 6. Synthesis of 8a–x. Reagents and conditions: (i) TiX4, CH2Cl2, ꢀ78/20 ꢁC,
14 h.
Table 3
Synthesis of 8a–x
a
3
7
8
Ar
R1
R2
X
%
Figure 1. Ortep plot of 8f.
a
a
a
a
a
a
a
d
d
d
i
a
b
c
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
r
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Me
Me
Ph
Ph
Et
Me
Ph
4-ClC6H4
4-FC6H4
Et
Me
Ph
Me
Ph
Cl
Cl
Cl
Cl
Br
Br
Br
Cl
Cl
Br
Cl
Cl
Br
Cl
Cl
Br
Br
Br
Cl
Br
Br
Br
Cl
Cl
48
47
43
40
28
58
40
40
41
45
43
47
41
35
33
41
40
40
43
40
38
42
44
40
The TiCl4-mediated cyclization of 3a with 1,1-diacetylcyclo-
propane (7a) afforded the 2-(phenylthio)benzoate 8a (Scheme 5).
During the optimization, the stoichiometry (1.5 equiv of TiCl4 and of
7a) played an important role. The yields dropped when only
1.0 equiv of TiCl4 and of 7a were employed. The yield also decreased
when an excess of 3a was used. The concentration (30 mL per mmol
of 3a) also proved to be an important parameter. A complex mixture
was obtained when the reaction was carried out in a highly con-
centrated solution (following the procedure given for the reaction of
3a with 4-(trimethylsilyloxy)pent-3-en-2-one, vide supra).
d
e
a
b
a
b
b
a
b
a
a
b
a
a
a
a
a
b
a
a
b
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
4-MeC6H4
4-MeC6H4
4-MeC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
3-(MeO)C6H4
3-(MeO)C6H4
3-(MeO)C6H4
3-ClC6H4
3-MeC6H4
3-MeC6H4
4-MeC6H4
4-EtC6H4
4-EtC6H4
4-EtC6H4
4-EtC6H4
Ph
Me
Ph
i
i
Me
Me
Ph
Me
Me
Me
Me
Me
Ph
o
o
o
k
f
OSiMe
SPh
3
SPh O
TiCl4
OMe
f
s
t
u
v
w
x
3a
OMe
(2 equiv.)
d
g
g
g
g
O
O
CH2Cl2
Me
Me
+
Me
Me
Cl
_
Me
Me
Ph
78
20 °C
8a (48%)
7a
a
Isolated yields.
TiCl4
_
_
(Cl3Ti)2O
Me3SiCl
+
The Me3SiOTf-catalyzed reaction of diene 3a with 3-for-
TiCl3
SPh O
mylchromone 9 afforded the highly functionalized diaryl sulfide 10
(Scheme 7). The formation of product 10 can be explained by
a domino ‘Michael/retro-Michael/Mukaiyama–Aldol’ reaction. This
type of reaction has been earlier reported for 1,3-bis(silyloxy)-1,3-
butadienes.22
O
SPh
OMe
OMe
Cl3TiO
Me
Cl3TiO
Me
O
_
TiCl4
Me
Cl_
H2O
Me
F
E
Scheme 5. Possible mechanism of the formation of 8a.
OSiMe3
OMe
SPh
3a
O
O
Cl
The formation of 8a can be explained by a domino ‘[3þ3] cycli-
zation/homo-Michael’ reaction. The TiCl4-mediated attack of the ter-
minal carbon atom of 3a onto 7a gave intermediate E, cyclization via
the central carbon atom gave intermediate F, and TiCl4-assisted
cleavage of the spirocyclopropane moiety and aromatization led to the
formation of the final product 8a. Reactions of acceptor-substituted
cyclopropanes have been classified by Danishefsky in terms of ‘strictly
nucleophilic ring openings’, ‘electrophilically assisted ring openings’
and ‘spiro-activations’.20 In the present case, a ‘spiro-activation’ is
combined with the activation by an electrophile.21
+
OMe
SPh
i , ii
O
O
Cl
OH
H
O
10 (22%)
9
Scheme 7. Synthesis of 10: Reagents and conditions: (i) Me3SiOTf (0.3 equiv) 20 ꢁC,
10 min; (ii) (1) 3a (1.3 equiv), CH2Cl2, 0/20 ꢁC, 12 h; (2) HCl (10%).
In conclusion, we have reported the synthesis of substituted 2-
(arylthio)benzoates and thioxanthones based on formal [3þ3]
cyclizations of 3-arylthio-1-trimethylsilyloxy-1,3-butadienes with
3-silyloxy-2-en-1-ones and 1,1-diacylcyclopropanes.
The cyclization of 1-trimethylsilyloxy-3-arylthio-1,3-butadienes
3a,d,f,g,i,k,o with 1,1-diacylcyclopropanes 7a–e, in the presence of
TiCl4 or TiBr4, afforded the 5-haloethyl-2-(arylthio)benzoates 8a–x

I. Iqbal et al. / Tetrahedron 65 (2009) 7562–7572
7565
3. Experimental section
3.1. General comments
1722 (m), 1663 (s), 1534 (m), 1434 (m), 1321 (s), 1223 (s), 1123 (m),
1024 (m), 768 (w), 713 (m) cmꢀ1. GC–MS (EI, 70 eV): m/z (%): 308
(Mþ, 37Cl, 37), 306 (Mþ, 35Cl, 41), 267 (100), 105 (89), 77 (34).
HRMS (EI): calcd for C15H17O2ClS [Mþ, 35Cl]: 306.06127, found
306.06139.
All solvents were dried by standard methods and all reactions
were carried out under an inert atmosphere. For 1H and 13C NMR
spectra the deuterated solvents indicated were used. Mass spec-
trometric data (MS) were obtained by electron ionization (EI,
70 eV), chemical ionization (CI, isobutane) or electrospray ioniza-
tion (ESI). For preparative scale chromatography silica gel 60
(0.063–0.200 mm, 70–230 mesh) was used.
3.2.4. Methyl 2,4-dimethyl-3,6-bis(phenylsulfanyl)benzoate (5d)
Starting with 4d (840 mg, 3.0 mmol), 3a (562 mg, 2.0 mmol),
TiCl4 (0.32 mL, 3.0 mmol), and CH2Cl2 (11 mL), 5d was isolated as
a highly viscous oil (485 mg, 63%). 1H NMR (250 MHz, CDCl3):
d
¼2.23 (s, 3H, CH3), 2.35 (s, 3H, CH3), 3.81 (s, 3H, OCH3), 6.87 (s, 1H,
ArH), 7.03 (m, 3H, ArH), 7.11 (m, 2H, ArH), 7.23 (m, 3H, ArH), 7.34
(m, 2H, ArH). 13C NMR (62 MHz, CDCl3):
3.2. General procedure for the synthesis of 2-
(thiophenoxy)benzoates 5a–v
d
¼19.1, 22.1 (CH3), 52.1
(OCH3), 125.1 (ArCH), 125.9 (2C, ArCH), 127.7 (ArCH), 129.0 (2C,
ArCH), 129.3 (2C, ArCH), 130.0 (C), 131.2 (ArCH), 132.0 (2C, ArCH),
134.5, 134.9, 135.1, 136.9, 141.1, 145.8, 168.8 (C). IR (neat):
~
To a dichloromethane solution (5 mL/mmol of 3) of 3 (1.0 mmol)
and of 4 (1.5 mmol) was added TiCl4 (1.5 mmol) at ꢀ78 ꢁC. The
solution was allowed to warm to 20 ꢁC within 20 h. To the solution
was added a saturated aqueous solution of NaHCO3 (15 mL). The
organic and the aqueous layer were separated and the latter was
extracted with diethyl ether (3ꢂ20 mL). The combined organic
layers were dried (Na2SO4), filtered, and the filtrate was concen-
trated in vacuo. The residue was purified by chromatography (silica
gel, EtOAc/n-heptane¼1:4).
n
¼ 3056ðwÞ, 2938 (w), 1721 (s), 1685 (m), 1512 (m), 1423 (m), 1236
(s), 1149 (s), 1056 (s), 728 (s), 681 (s), 538 (m) cmꢀ1. GC–MS (EI,
70 eV): m/z (%): 380 (100), 213 (26), 182 (25), 153 (16), 139 (20), 108
(8). HRMS (EI): calcd for C22H20O2S2 ([Mþ]): 380.06225, found
380.06228.
3.2.5. Methyl 4-methyl-6-(phenylsulfanyl)-6-propylbenzoate (5e)
Starting with 4e (600 mg, 3.0 mmol), 3a (562 g, 2.0 mmol), TiCl4
(0.32 mL, 3.0 mmol), and CH2Cl2 (11 mL), 5e was isolated as a highly
3.2.1. 2,4-Dimethyl-6-phenylsulfanyl-benzoic acid methyl
ester (5a)
Starting with 4a (387 mg, 2.3 mmol), 3a (420 mg, 1.5 mmol),
TiCl4 (0.25 mL, 2.3 mmol) and CH2Cl2 (9 mL), 5a was isolated as
a highly viscous oil (229 mg, 56%). 1H NMR (250 MHz, CDCl3):
viscous oil (255 mg, 42%). 1H NMR (250 MHz, CDCl3):
d
¼0.85 (t, 3H,
J¼7.1 Hz, CH3), 1.47 (m, 2H, CH2), 2.11 (q, 2H, J¼6.4 Hz, CH3), 2.24 (s,
3H, CH3), 3.80 (s, 3H, OCH3), 6.91 (s, 1H, ArH), 7.16 (m, 2H, ArH),
7.33 (m, 2H, ArH). 13C NMR (62 MHz, CDCl3):
24.3, 36.7 (CH2), 52.0 (OCH3), 126.8 (ArCH), 129.0 (2C, ArCH), 129.5
d
¼13.5, 19.7 (CH3),
d
¼2.05 (s, 3H, CH3), 2.13 (s, 3H, CH3), 3.67 (s, 3H, OCH3), 6.75–7.12
(C), 130.0 (ArCH), 131.3 (2C, ArCH), 135.5 (ArCH), 136.1, 139.9, 144.8,
(m, 7H, ArH). 13C NMR (63 MHz, CDCl3):
d
¼19.6, 21.1 (CH3), 52.0
160.2, 165.8 (C). IR (neat):
n
¼ 3045ðwÞ, 2978 (w), 1714 (s), 1675
~
(OCH3), 126.9 (ArCH), 129.0 (2C, ArCH), 130.4 (ArCH), 130.8 (2C,
ArCH), 131.0 (ArCH), 132.7, 134.0, 135.9, 136.1, 140.7 (ArC), 169.1 (C).
IR (neat):
(m), 1590 (s), 1460 (m), 1369 (s), 1269 (m), 1171 (m), 1024 (m), 751
(s), 690 (m) cmꢀ1. GC–MS (EI, 70 eV): m/z (%): 300 (40), 287 (46),
211 (23), 139 (23), 105 (23). HRMS (EI): calcd for C18H20O2S [Mþ]:
300.03177, found 300.03156.
~
n
¼ 3056ðwÞ, 2990 (w), 2947 (w), 2920 (w), 1726 (s),
1599 (m), 1581 (w), 1516 (w), 1476 (m), 1438 (s), 1378 (w), 1267 (s),
1257 (s), 1217 (m), 1188 (m), 1151 (s), 1078 (s), 1023 (m), 999 (w),
956 (w), 852 (m), 810 (m), 738 (s), 689 (s), 579 (m), 555 (w) cmꢀ1
.
3.2.6. Methyl 2,3,4,5-tetramethyl-6-(phenylsulfanyl)benzoate (5f)
Starting with 4b (450 mg, 2.4 mmol), 3b (859 mg, 2.9 mmol),
TiCl4 (0.37 mL, 3.6 mmol), and CH2Cl2 (14 mL), 5f was isolated as
a highly viscous oil (400 mg, 55%). 1H NMR (250 MHz, CDCl3):
GC–MS (EI, 70 eV): m/z (%): 272 (60), 241 (41), 240 (21), 239 (Mþ,
100), 198 (15), 197 (26), 165 (6), 91 (4). HRMS (EI): calcd for
C16H16O2S 272.08655, found 272.086221.
d
¼2.15 (s, 3H, CH3), 2.17 (s, 2ꢂ3H, CH3), 2.24 (s, 3H, CH3), 3.73 (s, 3H,
OCH3), 6.99 (m, 2H, ArH), 7.12 (m, 3H, ArH). 13C NMR (62 MHz,
CDCl3):
3.2.2. Methyl 2,3,4-trimethyl-6-(phenylsulfanyl)benzoate (5b)
Starting with 4b (558 mg, 3.0 mmol), 3a (562 g, 2.0 mmol), TiCl4
(0.32 mL, 3.0 mmol) and CH2Cl2 (10 mL), 5b was isolated as a yellow
d
¼16.5, 17.3, 17.8, 19.9 (CH3), 51.1 (OCH3), 124.0 (C), 125.1
(ArCH), 126.8 (2C, ArCH), 128.7 (2C, ArCH), 130.5, 137.5, 137.7, 138.0,
highly viscous oil (250 mg, 43%). 1H NMR (250 MHz, CDCl3):
d
¼2.00
139.1, 139.6, 170.1 (C). IR (neat):
n
¼ 3056ðwÞ, 2946 (w), 1729 (s),
~
(s, 3H, CH3), 2.04 (s, 3H, CH3), 2.05 (s, 3H, CH3), 3.65 (s, 3H, OCH3),
1598 (m), 1580 (m), 1422 (s), 1306 (m), 1232 (m), 1172 (s), 1068 (m),
737 (s), 688 (s) cmꢀ1. GC–MS (EI, 70 eV): m/z (%): 300 (Mþ, 86), 267
(100), 253 (12), 239 (10), 225 (7), 110 (89). HRMS (EI): calcd for
C18H20O2S [Mþ]: 300.11785, found 300.11812.
6.76 (s, 1H, ArH), 7.0 (m, 2H, ArH), 7.06 (m, 2H, ArH). 13C NMR
(62 MHz, CDCl3):
127.2 (C), 128.8 (2C, ArCH), 129.5 (2C, ArCH), 133.3 (ArCH), 133.7,
d
¼15.7,17.5, 20.6 (CH3), 52.6 (OCH3), 126.2 (ArCH),
~
136.0, 136.07, 137.2, 138.7, 169.7 (C). IR (neat):
n
¼ 3382ðwÞ, 2940
(s), 1712 (m), 1609 (m), 1530 (m), 1481 (m), 1311 (m), 1213 (m), 1162
(m), 1010 (m), 758 (w), 730 (m) cmꢀ1. GC–MS (EI, 70 eV): m/z (%):
286 (Mþ, 58), 253 (100), 240 (8), 211 (15), 178 (6). HRMS (EI): calcd
for C17H18O2S [Mþ] 286.10220, found 286.10225.
3.2.7. Methyl 3-chloro-2,4,5-trimethyl-6-(phenylsulfanyl)-
benzoate (5g)
Starting with 4c (550 mg, 2.6 mmol), 3b (943 mg, 3.1 mmol),
TiCl4 (0.42 mL, 3.9 mmol) and CH2Cl2 (11 mL), 5g was isolated as
a highly viscous oil (417 mg, 49%). 1H NMR (250 MHz, CDCl3):
3.2.3. Methyl 3-chloro-2,4-dimethyl-6-(phenylsulfanyl)-
benzoate (5c)
Starting with 4c (621 mg, 3.0 mmol), 3a (562 mg, 2.0 mmol),
TiCl4 (0.32 mL, 3.0 mmol) and CH2Cl2 (11 mL), 5c was isolated as
a highly viscous oil (350 mg, 57%). 1H NMR (250 MHz, CDCl3):
d
¼2.25 (s, 3H, CH3), 2.26 (s, 3H, CH3), 2.31 (s, 3H, CH3), 3.74 (s, 3H,
OCH3), 7.00 (m, 2H, ArH), 7.14 (m, 3H, ArH). 13C NMR (62 MHz,
CDCl3):
d
¼17.2, 17.3, 17.5 (CH3), 51.2 (OCH3), 123.6 (C), 125.5
(ArCH), 126 (C), 127.1 (2C, ArCH), 128.9 (2C, ArCH), 129.6, 136.0,
136.7, 139.4, 139.9, 166.2 (C). IR (neat):
~
n
¼ 3010ðwÞ, 2953 (w),
d
¼2.23 (s, 3H, CH3), 2.28 (s, 3H, CH3), 3.79 (s, 3H, OCH3), 7.01 (s,
1H, ArH), 7.16 (m, 2H, ArH), 7.33 (m, 2H, ArH). 13C NMR (75 MHz,
CDCl3):
1722 (s), 1601 (m), 1580 (m), 1434 (m), 1383 (s), 1234 (s), 1151 (s),
1009 (s), 732 (s), 685 (m) cmꢀ1. GC–MS (EI, 70 eV): m/z (%): 322
(Mþ, 37Cl, 28), 320 (Mþ, 35Cl, 74), 287 (100), 253 (17), 211 (10), 178
(20), 115. HRMS (EI): calcd for C17H17O2ClS [Mþ, 35Cl]: 320.06323,
found 320.06363.
d
¼18.1, 20.8 (CH3), 52.3 (OCH3), 127.0 (ArCH), 129.1 (2C,
ArCH), 130.0 (C), 130.5 (2C, ArCH), 133.0 (ArCH), 135.0, 135.7,
~
n
135.8, 136.6, 138.4, 168.3 (C). IR (neat):
¼ 3382ðwÞ, 2898 (s),

7566
I. Iqbal et al. / Tetrahedron 65 (2009) 7562–7572
3.2.8. Methyl 2-phenyl-4,5-dimethyl-6-(phenylsulfanyl)-
benzoate (5h)
3.2.12. 2,4-Dimethyl-6-(4-tolylsulfanyl)benzoic acid methyl
ester (5l)
Starting with 4f (500 mg, 2.0 mmol), 1b (743 mg, 2.0 mmol),
TiCl4 (0.34 mL, 3.1 mmol), and CH2Cl2 (12.5 mL), 5h was isolated
as a highly viscous oil (380 mg, 52%). 1H NMR (250 MHz, CDCl3):
Starting with 4a (387 mg, 2.3 mmol), 3d (441 g, 1.5 mmol), TiCl4
(0.25 mL, 2.3 mmol) and CH2Cl2 (9 mL), 5l was isolated as a highly
viscous oil (232 mg, 54%). 1H NMR (250 MHz, CDCl3):
d
¼2.12 (s, 3H,
CH3), 2.22 (s, 3H, CH3), 2.25 (s, 3H, CH3), 3.79 (s, 3H, OCH3), 6.80–
7.19 (m, 6H, ArH). 13C NMR (63 MHz, CDCl3):
d
¼2.23 (s, 3H, CH3), 2.25 (s, 3H, CH3), 3.48 (s, 3H, OCH3), 7.12 (m,
3H, ArH), 7.26 (m, 3H, ArH), 7.36 (s, 1H, ArH), 7.42 (m, 4H, ArH).
13C NMR (62 MHz, CDCl3):
d
¼19.6, 21.1, 21.3 (CH3),
d
¼13.6, 18.0 (CH3), 50.1 (OCH3), 124.0
52.0 (OCH3), 129.8 (ArCH), 129.9, 131.8 (2C, ArCH), 131.9 (ArCH),
(C), 125.9 (ArCH), 126.4 (2C, ArCH), 126.3 (C), 127.2 (2C, ArCH),
127.4 (2C, ArCH), 127.5 (2C, ArCH), 127.8 (ArCH), 131.5, 132.2 (C),
136.2 (ArCH), 137.5, 138.1, 138.7, 139.9, 166.2 (C). IR (neat):
~
133.1, 134.1, 135.9, 137.4, 137.9, 139.9 (ArC), 169.1 (C). IR (neat):
~
n
¼ 3018ðwÞ, 2947 (w), 2919 (w), 2863 (w), 2733 (w), 1726 (s),
1598 (m), 1560 (m), 1490 (m), 1435 (m), 1378 (w), 1267 (s), 1257 (s),
1217 (m), 1188 (m), 1151 (s), 1078 (s), 1023 (m), 999 (w), 956 (w),
852 (m), 810 (m), 738 (s), 689 (s), 579 (m), 553 (w) cmꢀ1. GC–MS
(EI, 70 eV): m/z (%): 286 (100), 255 (55), 255 (55), 254 (20), 253 (76),
240 (15), 239 (56), 212 (17), 211 (23), 197 (11), 165 (5), 91 (4). HRMS
(EI): calcd for C17H18O2S: 286.10220, found 286.101944.
n
¼ 3056ðwÞ, 2946 (w), 1730 (s), 1580 (m), 1476 (m), 1456 (s),
1384 (w), 1246 (s), 1146 (s), 1023 (m), 697 (s), 688 (s) cmꢀ1. GC–
MS (EI, 70 eV): m/z (%): 348 (Mþ, 100), 315 (89), 373 (26), 39 (9),
165 (18), 105 (7). HRMS (EI): calcd for C22H20O2S [Mþ]: 348.11785,
found 348.11834.
3.2.9. Methyl 5-ethyl-2,4-dimethyl-6-(phenylsulfanyl)benzoate (5i)
Starting with 4b (700 mg, 3.8 mmol), 3c (1.40 g, 4.5 mmol),
TiCl4 (0.61 mL, 5.6 mmol), and CH2Cl2 (19 mL), 5i was isolated as
a highly viscous oil (650 mg, 55%). 1H NMR (250 MHz, CDCl3):
3.2.13. 3,4,6-Trimethyl-2-(4-tolylsulfanyl)benzoic acid methyl
ester (5m)
Starting with 4a (387 mg, 2.3 mmol), 3e (462 mg, 1.5 mmol),
TiCl4 (0.25 mL, 2.3 mmol) and CH2Cl2 (9 mL), 5m was isolated as
a highly viscous oil (176 mg, 39%). 1H NMR (250 MHz, CDCl3):
d
¼0.80 (t, 3H, J¼7.4 Hz, CH3), 2.13 (s, 3H, CH3), 2.15 (s, 3H, CH3),
2.20 (s, 3H, CH3), 2.76 (q, 2H, J¼7.3 Hz, CH2), 3.67 (s, 3H, OCH3),
d
¼2.16 (s, 3H, CH3), 2.18 (s, 3H, CH3), 2.18 (s, 3H, CH3), 2.19 (s, 3H,
CH3), 3.79 (s, 3H, OCH3), 6.87–7.16 (m, 5H, ArH). 13C NMR (63 MHz,
CDCl3):
6.97 (m, 3H, ArH), 7.10 (m, 2H, ArH). 13C NMR (62 MHz, CDCl3):
d
¼13.5, 16.6, 16.9, 17.8 (CH3), 24.9 (CH2), 51.9 (OCH3), 123.2 (C),
d
¼16.9, 18.9, 20.9, 21.0 (CH3), 52.0 (OCH3), 127.5 (2C, ArCH),
125.0 (ArCH), 126.6 (2C, ArCH), 128.9 (2C, ArCH), 134.2, 137.0,
128.4 (ArCH), 129.6. (2C, ArCH), 131.8, 132.7, 133.9, 135.3, 138.8,
~
~
138.5, 140.3, 142.7, 145.1, 170.0 (C). IR (neat):
n
¼ 3056ðwÞ, 2946
139.0, 139.3 (ArC),169.6 (C). IR (neat):
n
¼ 2946ðwÞ, 2919 (w), 2863
(w), 1729 (s), 1580 (m), 1477 (m), 1434 (m), 1294 (m), 1224 (m),
1171 (s), 1024 (m), 736 (s), 688 (s) cmꢀ1. GC–MS (EI, 70 eV): m/z
(%): 314 (Mþ, 100), 281 (56), 267 (21), 239 (16), 211 (12), 177 (23),
105 (27). HRMS (EI): calcd for C19H22O2S [Mþ]: 314.13351, found
314.13418.
(w), 1728 (s), 1596 (m), 1490 (m), 1434 (m), 1383 (w), 1285 (s), 1223
(m), 1189 (m), 1140 (s), 1085 (m), 1015 (m), 965 (w), 948 (w), 853
(m), 803 (m), 751 (m), 626 (m), 557 (m) cmꢀ1. GC–MS (EI, 70 eV):
m/z (%): 300 (96), 269 (33), 268 (12), 267 (43), 253 (Mþ, 100), 226
(14), 225 (20), 211 (13), 192 (4), 91 (9), 65 (4). HRMS (EI): calcd for
C18H20O2S: 300.11767, found 300.117653.
3.2.10. Methyl 3-chloro-2,4-dimethyl-5-ethyl-6-(phenylsulfanyl)-
benzoate (5j)
Starting with 4c (650 mg, 3.1 mmol), 3c (1.10 g, 3.7 mmol),
TiCl4 (0.51 mL, 4.6 mmol), and CH2Cl2 (15.5 mL), 5j was isolated as
a highly viscous oil (524 mg, 50%). 1H NMR (250 MHz, CDCl3):
3.2.14. 2,4-Dimethyl-6-(m-tolylsulfanyl)benzoic acid methyl
ester (5n)
Starting with 4a (387 mg, 2.3 mmol), 3f (441 mg, 1.5 mmol),
TiCl4 (0.25 mL, 2.3 mmol) and CH2Cl2 (9 mL), 5n was isolated as
a highly viscous oil (232 mg, 54%). 1H NMR (250 MHz, CDCl3):
d
¼0.74 (t, 3H, J¼7.1 Hz, CH3), 2.11 (s, 3H, CH3), 2.22 (s, 3H, CH3),
2.65 (q, 2H, J¼7.4 Hz, CH2), 3.55 (s, 3H, OCH3), 6.92 (m, 3H, ArH),
7.10 (m, 2H, ArH). 13C NMR (62 MHz, CDCl3):
d
¼2.12 (s, 3H, CH3), 2.22 (s, 3H, CH3), 2.25 (s, 3H, CH3), 3.79 (s, 3H,
d
¼14.6, 18.9, 19.7
OCH3), 6.80–7.19 (m, 6H, ArH). 13C NMR (63 MHz, CDCl3):
d
¼19.6,
(CH3), 24.3 (CH2), 52.1 (OCH3), 126.1 (C), 126.6 (ArCH), 128.2 (2C,
21.1, 21.3 (CH3), 52.0 (OCH3), 129.8 (ArCH), 129.9, 131.8 (2C, ArCH),
ArCH), 131.0 (2C, ArCH), 133.6, 136.9, 139.0, 139.2, 142.3, 148.1,
131.9 (ArCH), 133.1, 134.1, 135.9, 137.4, 137.9, 139.9 (ArC),169.1 (C). IR
~
~
170.0 (C). IR (neat):
n
¼ 3053ðwÞ, 297 (w), 1727 (s), 1575 (m), 1431
(neat):
n
¼ 3018ðwÞ, 2947 (w), 2919 (w), 2863 (w), 2733 (w), 1726
(m), 1404 (m), 1280 (s), 1224 (s), 1152 (s), 1022 (s), 735 (s), 685
(s) cmꢀ1. GC–MS (EI, 70 eV): m/z (%): 336 (Mþ, 37Cl, 39), 334 (Mþ,
35Cl, 100), 301 (52), 287 (21), 224 (10), 197 (23), 105 (34). HRMS
(EI): calcd for C16H15O2ClS [Mþ, 35Cl]: 334.07888, found
334.07942.
(s), 1598 (m), 1560 (m), 1490 (m), 1435 (m), 1378 (w), 1267 (s), 1257
(s), 1217 (m), 1188 (m), 1151 (s), 1078 (s), 1023 (m), 999 (w), 956 (w),
852 (m), 810 (m), 738 (s), 689 (s), 579 (m), 553 (w) cmꢀ1. GC–MS
(EI, 70 eV): m/z (%): 286 (100), 255 (55), 255 (55), 254 (20), 253 (76),
240 (15), 239 (56), 212 (17), 211 (23), 197 (11), 165 (5), 91 (4). HRMS
(EI): calcd for C17H18O2S: 286.10220, found 286.101944.
3.2.11. Methyl 2-methyl-3-phenyl-5-ethyl-6-(phenylsulfanyl)-
benzoate (5k)
Starting with 4f (717 mg, 3.0 mmol), 3c (618 g, 2.0 mmol), TiCl4
(0.32 mL, 3.0 mmol), and CH2Cl2 (10 mL), 5k was isolated as
a highly viscous oil (362 mg, 50%). 1H NMR (250 MHz, CDCl3):
3.2.15. 2-(4-Ethylphenylsulfanyl)-4,6-dimethyl-benzoic acid methyl
ester (5o)
Starting with 4a (387 mg, 2.3 mmol), 3g (462 mg, 1.5 mmol),
TiCl4 (0.25 mL, 2.3 mmol) and CH2Cl2 (9 mL), 5o was isolated as
a highly viscous oil (221 mg, 49%). 1H NMR (250 MHz, CDCl3):
d
¼0.88 (t, 3H, J¼7.1 Hz, CH3), 2.25 (s, 3H, CH3), 2.73 (q, 2H, J¼6.4 Hz,
CH2), 3.80 (s, 3H, OCH3), 7.10 (m, 3H, ArH), 7.26 (m, 5H, ArH), 7.34 (s,
1H, ArH), 7.67 (m, 3H, ArH). 13C NMR (62 MHz, CDCl3):
d
¼1.14 (t, 3H, J¼7.2 Hz, CH3), 2.12 (s, 3H, CH3), 2.22 (s, 3H, CH3), 2.56
d¼13.7
(q, 2H, J¼7.2 Hz, CH2), 3.79 (s, 3H, OCH3), 6.82–7.21 (m, 6H, ArH). 13
C
(CH3), 20.1 (CH2), 24.4 (CH3), 51.8 (OCH3), 123.0 (2C, ArCH), 124.4
(ArCH), 125.3 (2C, ArCH), 127.7 (ArCH), 128.4 (2C, ArCH), 130.3 (2C,
ArCH), 130.2, 133.7, 134.9 (C), 136.3 (ArCH), 137.1, 139.1, 140.6, 144.2,
~
NMR (75 MHz, CDCl3):
(OCH3), 128.7 (2C, ArCH), 129.4, 129.9 (ArCH), 131.8 (2C, ArCH),
d
¼15.4, 19.6, 21.6 (CH3), 28.4 (CH2), 52.0
132.1, 133.2, 133.9, 135.9, 139.9, 143.6 (ArC), 169.2 (C). IR (neat):
~
148.2, 165.8 (C). IR (neat):
n
¼ 3058ðwÞ, 2947 (w), 1730 (m), 1597
n
¼ 3018ðwÞ, 2963 (w), 2928 (w), 2871 (w), 1727 (s), 1599 (m),
(m), 1579 (m), 1453 (m), 1271 (s), 1191 (s), 739 (s), 698 (s), 618 (m),
556 (m) cmꢀ1. GC–MS (EI, 70 eV): m/z (%): 362 (Mþ, 100), 331 (19),
315 (20), 271 (16), 225 (20),178 (13). HRMS (EI): calcd for C23H22O2S
[Mþ]: 362.13350, found 362.13303.
1491 (m), 1435 (m), 1404 (w), 1377 (w), 1266 (s), 1257 (s), 1217 (m),
1187 (m), 1152 (s), 1078 (s), 1016 (m), 965 (w), 947 (w), 849 (m), 810
(m), 778 (w), 738 (m), 579 (m), 555 (w) cmꢀ1. GC–MS (EI, 70 eV):
m/z (%): 300 (Mþ, 100), 284 (5), 283 (26), 282 (10), 281 (27), 267 (7),

I. Iqbal et al. / Tetrahedron 65 (2009) 7562–7572
7567
254 (20), 253 (97), 239 (7), 225 (15), 178 (5), 134 (4), 121 (19). HRMS
(EI): calcd for C18H20O2S: 300.11785, found 300.117168.
1085 (m), 1015 (m), 965 (w), 948 (w), 853 (m), 803 (m), 751 (m),
626 (m), 554 (m) cmꢀ1. GC–MS (EI, 70 eV): m/z (%): 322 (Mþ, 25),
320 (Mþ, 100), 266 (12), 262 (43), 253 (10), 226 (14), 225 (20), 211
(13), 192 (4), 91 (9), 63 (4). HRMS (EI): calcd for C17H17O2ClS:
320.58923, found 320.587603.
3.2.16. 2-(4-Ethylphenylsulfanyl)-3,4,6-trimethyl-benzoic acid
methyl ester (5p)
Starting with 4a (387 mg, 2.3 mmol), 3h (483 mg, 1.5 mmol),
TiCl4 (0.25 mL, 2.25 mmol) and CH2Cl2 (9 mL), 5p was isolated as
a highly viscous oil (212 mg, 45%). 1H NMR (250 MHz, CDCl3):
3.2.20. 2-(3-Chlorophenylsulfanyl)-4,6-dimethyl-benzoic acid
methyl ester (5t)
d
¼1.09 (t, 3H, J¼7.2 Hz, CH3), 2.16 (s, 3H, CH3), 2.18 (s, 3H, CH3), 2.19
(s, 3H, CH3), 2.47 (q, 2H, J¼7.2 Hz, CH2), 3.74 (s, 3H, OCH3), 6.93–7.17
(m, 5H, ArH). 13C NMR (75 MHz, CDCl3):
Starting with 4a (387 mg, 2.3 mmol), 3k (470 mg, 1.5 mmol),
TiCl4 (0.25 mL, 2.25 mmol) and CH2Cl2 (9 mL), 5t was isolated as
a highly viscous oil (171 mg, 37%). 1H NMR (250 MHz, CDCl3):
d
¼15.4, 16.9, 18.9 (CH3),
28.3 (CH2), 52.0 (OCH3), 127.6 (2C, ArCH), 128.4 (2C, ArCH), 128.5,
131.9 (ArC),132.8 (ArCH),134.1, 138.7, 139.0, 141.6 (ArC),169.7 (C). IR
(neat):
(s), 1596 (m), 1491 (m), 1433 (m), 1404 (w), 1383 (w), 1285 (s), 1242
(m), 1223 (m), 1187 (m), 1142 (s), 1119 (m), 1087 (m), 1052 (m), 1014
(m), 1004 (m), 821 (s), 789 (m), 751 (w), 721 (m) cmꢀ1. GC–MS (EI,
70 eV): m/z (%): 314 (Mþ, 100), 284 (5), 283 (26), 182 (10), 281 (27),
267 (7), 254 (20), 253 (97), 239 (7), 225 (15), 178 (5), 134 (4), 121
(19). HRMS (EI): calcd for C19H22O2S: 314.13350, found 314.133456.
d
¼2.18 (s, 3H, CH3), 2.38 (s, 3H, CH3), 3.77 (s, 3H, OCH3), 6.90–7.34
(m, 6H, ArH). 13C NMR (63 MHz, CDCl3):
d
¼18.1, 20.1 (CH3), 50.6
~
n
¼ 3016ðwÞ, 2963 (w), 2948 (w), 2928 (w), 2871 (w), 1729
(OCH3), 127.0, 128.1 (ArCH), 129.0 (2C, ArCH), 130.3 (ArC), 135.7 (2C,
ArCH), 137.1, 137.3, 139.2, 164.5 (ArC), 167.9 (C). IR (neat):
~
n
¼ 2945ðwÞ, 2918 (w), 2853 (w),1728 (s),1596 (m), 1491 (m),1435
(m), 1383 (w), 1285 (s), 1223 (m), 1189 (m), 1140 (s), 1085 (m), 1015
(m), 965 (w), 948 (w), 853 (m), 803 (m), 751 (m), 626 (m), 554
(m) cmꢀ1. GC–MS (EI, 70 eV): m/z (%): 308 (Mþ, 25), 306 (Mþ, 100),
266 (12), 262 (43), 253 (100), 226 (14), 225 (20), 211 (13),192 (4), 91
(9), 63 (4). HRMS (EI): calcd for C16H15O2ClS: 306.58923, found
306.587603.
3.2.17. 2-(4-Chlorophenylsulfanyl)-4,6-dimethyl-benzoic acid
methyl ester (5q)
Starting with 4a (387 mg, 2.3 mmol), 3i (470 mg, 1.5 mmol),
TiCl4 (0.25 mL, 2.3 mmol) and CH2Cl2 (9 mL), 5q was isolated as
a highly viscous oil (170 mg, 37%). 1H NMR (250 MHz, CDCl3):
3.2.21. 2(4-Fluorophenylsulfanyl)-4,6-dimethyl-benzoic acid
methyl ester (5u)
Starting with 4a (387 mg, 2.3 mmol), 3l (447 mg, 1.5 mmol),
TiCl4 (0.25 mL, 2.25 mmol) and CH2Cl2 (9 mL), 5u was isolated as
a highly viscous oil (174 mg, 40%). 1H NMR (250 MHz, CDCl3):
d
¼2.17 (s, 3H, CH3), 2.37 (s, 3H, CH3), 3.77 (s, 3H, OCH3), 6.90–7.34
(m, 6H, ArH). 13C NMR (63 MHz, CDCl3):
d
¼18.1, 20.1 (CH3), 49.9
(OCH3), 127.0, 128.1 (ArCH), 129.0 (2C, ArCH), 130.3 (ArC), 135.7 (2C,
d
¼2.14 (s, 3H, CH3), 2.23 (s, 3H, CH3), 3.80 (s, 3H, OCH3), 6.79–7.29
ArCH), 137.1, 137.3, 139.2, 164.5 (ArC), 167.9 (C). IR (neat):
(m, 6H, ArH). 13C NMR (63 MHz, CDCl3):
d
¼19.6, 21.1 (CH3), 52.0
~
n
¼ 2945ðwÞ, 2918 (w), 2853 (w), 1728 (s), 1596 (m), 1491 (m),1435
(OCH3), 130.2 (2C, ArCH), 130.8, 133.3 (ArCH), 133.7 (2C, ArCH),
~
(m), 1383 (w), 1285 (s), 1223 (m), 1189 (m), 1140 (s), 1085 (m), 1015
(m), 965 (w), 948 (w), 853 (m), 803 (m), 751 (m), 626 (m), 554
(m) cmꢀ1. GC–MS (EI, 70 eV): m/z (%): 308 (Mþ, 25), 306 (Mþ, 100),
266 (12), 262 (43), 253 (100), 226 (14), 225 (20), 211 (13),192 (4), 91
(9), 63 (4). HRMS (EI): calcd for C16H15O2ClS: 306.58923, found
306.587603.
136.1, 137.2, 137.9, 140.2 (ArCH), 169.1 (C). IR (neat):
n
¼ 2949ðwÞ,
2921 (w), 2737 (w), 1726 (s), 1599 (m), 1588 (m), 1561 (w), 1487 (s),
1436 (m), 1396 (w), 1378 (w), 1267 (s), 1219 (s), 1189 (m), 1152 (s),
1078 (s), 1012 (m), 965 (w), 947 (w), 827 (m), 810 (m), 738 (s), 689
(s), 579 (m), 554 (w) cmꢀ1. GC–MS (EI, 70 eV): m/z (%): 290 (66,
Mþ), 259 (46), 258 (22), 257 (100), 216 (17), 215 (28), 91 (4), 75 (2).
HRMS (EI): calcd for C16H15O2FS: 290.07713, found 290.077041.
3.2.18. 3-Chloro-6-(4-chlorophenylsulfanyl)-2,4-dimethyl-benzoic
acid methyl ester (5r)
Starting with 4c (460 mg, 2.3 mmol), 3i (470 mg, 1.5 mmol),
TiCl4 (0.25 mL, 2.25 mmol) and CH2Cl2 (9 mL), 5r was isolated as
a highly viscous oil (179 mg, 35%). 1H NMR (250 MHz, CDCl3):
3.2.22. 2-(4-Fluorophenylsulfanyl)-3,4,6-trimethylbenzoic acid
methyl ester (5v)
Starting with 4a (387 mg, 2.3 mmol), 3m (468 mg, 1.5 mmol),
TiCl4 (0.25 mL, 2.25 mmol) and CH2Cl2 (9 mL), 5v was isolated as
a highly viscous oil (161 mg, 33%). 1H NMR (250 MHz, CDCl3):
d
¼2.31 (s, 3H, CH3), 2.42 (s, 3H, CH3), 3.75 (s, 3H, OCH3), 6.90–7.19
(m, 5H, ArH). 13C NMR (63 MHz, CDCl3):
d
¼18.1, 20.9 (CH3), 52.4
d
¼2.19 (s, 3H, CH3), 2.22 (s, 3H, CH3), 2.41 (s, 3H, CH3), 3.88 (s, 3H,
(OCH3), 129.1 (2C, ArCH), 129.2 (ArCH), 131.5 (2C, ArCH), 133.0,
OCH3), 6.90–7.34 (m, 5H, ArH). 13C NMR (63 MHz, CDCl3):
d¼18.3,
133.8, 134.1, 135.5, 137.0, 138.7 (ArC), 168.2 (C). IR (neat):
18.6, 20.9 (CH3), 51.5 (OCH3), 127.0, 128.1 (ArCH), 129.0 (2C, ArCH),
~
n
¼ 2946ðwÞ, 2919 (w), 2863 (w),1728 (s),1596 (m),1490 (m),1434
130.3 (ArC), 135.7 (2C, ArCH), 137.1, 137.3, 139.2, 164.5 (ArC), 167.9
~
(m), 1383 (w), 1285 (s), 1223 (m), 1189 (m), 1140 (s), 1085 (m), 1015
(m), 965 (w), 948 (w), 853 (m), 803 (m), 751 (m), 626 (m), 557
(m) cmꢀ1. GC–MS (EI, 70 eV): m/z (%): 344 (25, Mþ), 342 (50, Mþ),
340 (100, Mþ), 268 (12), 267 (43), 253 (100), 226 (14), 225 (20), 211
(13), 192 (4), 91 (9), 65 (4). HRMS (EI): calcd for C16H14O2Cl2S:
341.01787, found 341.017653.
(C). IR (neat):
n
¼ 2945ðwÞ, 2918 (w), 2853 (w), 1728 (s), 1596 (m),
1491 (m), 1435 (m), 1383 (w), 1285 (s), 1223 (m), 1189 (m), 1140 (s),
1085 (m), 1015 (m), 965 (w), 948 (w), 853 (m), 803 (m), 751 (m),
626 (m), 554 (m) cmꢀ1. GC–MS (EI, 70 eV): m/z (%): 304 (Mþ, 100),
266 (12), 262 (43), 226 (14), 225 (20), 211 (13),192 (4), 91 (9), 63 (4).
HRMS (EI): calcd for C16H15O2ClS: 304.04523, found 304.045603.
3.2.19. 2-(4-Chlorophenylsulfanyl)-3,4,6-trimethyl-benzoic acid
methyl ester (5s)
3.3. General procedure for the synthesis of
thioxanthones 6a–g
Starting with 4a (387 mg, 2.3 mmol), 3j (490 mg, 1.5 mmol),
TiCl4 (0.25 mL, 2.25 mmol) and CH2Cl2 (9 mL), 5s was isolated as
a highly viscous oil (188 mg, 36%). 1H NMR (250 MHz, CDCl3):
To 5 (1.0 mmol) was added concd sulfuric acid (98%, 12 mL/
mmol of 5) at 20 ꢁC and the solution was stirred for 2 h. To the
solution was added ice water (50 mL). The organic and the aqueous
layer were separated and the latter was extracted with
dichloromethane (3ꢂ15 mL). The combined organic layers were
dried (Na2SO4), filtered, and the filtrate was concentrated in vacuo.
The residue was purified by chromatography (silica gel, heptanes/
EtOAc).
d
¼2.18 (s, 3H, CH3), 2.20 (s, 3H, CH3), 2.38 (s, 3H, CH3), 3.77 (s, 3H,
OCH3), 6.90–7.34 (m, 5H, ArH). 13C NMR (63 MHz, CDCl3):
d¼18.1,
18.3, 20.1 (CH3), 50.6 (OCH3), 127.0, 128.1 (ArCH), 129.0 (2C, ArCH),
130.3. (ArC), 135.7 (2C, ArCH), 137.1, 137.3, 139.2, 164.5 (ArC), 167.9
~
(C). IR (neat):
n
¼ 2945ðwÞ, 2918 (w), 2853 (w), 1728 (s), 1596 (m),
1491 (m), 1435 (m), 1383 (w), 1285 (s), 1223 (m), 1189 (m), 1140 (s),

7568
I. Iqbal et al. / Tetrahedron 65 (2009) 7562–7572
3.3.1. 1,2,3-Trimethylthioxanthone (6a)
3.3.6. 1,2,3-Trimethyl-4-ethylthioxanthone (6f)
Starting with 5b (114 mg, 1.0 mmol) and concd sulfuric acid, 6a
Starting with 5i (181 mg, 0.57 mmol) and concd sulfuric acid, 6f
was isolated as a highly viscous oil (270 mg, 98%). 1H NMR
was isolated as a colourless solid (102 mg, 97%), mp¼221 ꢁC. 1H
(250 MHz, CDCl3):
d
¼2.21 (s, 3H, CH3), 2.30 (s, 3H, CH3), 2.68 (s, 3H,
NMR (250 MHz, CDCl3):
d
¼1.15 (t, 3H, J¼7.5 Hz, CH3), 2.23 (s, 3H,
CH3), 7.31 (m, 1H, ArH), 7.40 (m, 3H, ArH), 8.30 (dd, 1H, 3J¼7.4 Hz,
CH3), 2.28 (s, 3H, CH3), 2.59 (s, 3H, CH3), 2.90 (q, 2H, J¼7.4 Hz, CH2),
4J¼2.1 Hz, ArH). 13C NMR (62 MHz, CDCl3):
d¼15.9, 19.1, 21.4 (CH3),
7.30 (m, 1H, ArH), 7.44 (m, 2H, ArH), 8.22 (m, 1H, ArH). 13C NMR
124.2, 125.0, 125.7 (ArCH), 127.0 (C), 129.4, 131.0 (ArCH), 132.4,
(62 MHz, CDCl3):
125.8 (ArCH), 127.8 (C), 128.8 (ArCH), 131.1 (ArCH), 132.2, 133.7,
d
¼12.9, 16.6, 16.8, 19.5 (CH3), 23.7 (CH2), 125.2,
~
134.9, 135.4, 135.7, 141.0, 141.1, 183.3 (C). IR (neat):
n
¼ 3023ðwÞ,
~
2918 (w), 1712 (m), 1671 (s), 1530 (m), 1493 (s), 1329 (m), 1216 (s),
1166 (m), 1019 (m), 7546 (w), 645 (m) cmꢀ1. GC–MS (EI, 70 eV): m/z
(%): 254 (100), 239 (46), 225 (34), 211 (12), 178 (13), 165 (15), 91 (8).
HRMS (EI): calcd for C16H14OS [Mþ]: 254.07799, found 254.07586.
134.5, 135.3, 135.6, 136.1, 139.0, 184.9 (C). IR (neat):
n
¼ 3064ðwÞ,
2927 (s), 1624 (s), 1585 (m), 1431 (m), 1382 (s), 1366 (s), 1203 (m),
1085 (s), 1028 (m), 748 (s), 643 (m) cmꢀ1. GC–MS (EI, 70 eV): m/z
(%): 282 (Mþ, 89), 267 (100), 253 (21), 224 (10), 126 (9), 113 (9), 69
(16). HRMS (EI): calcd for C18H18OS [Mþ]: 282.10729, found
282.10724.
3.3.2. 2-Chloro-1,3-dimethylthioxanthone (6b)
Starting with 5c (114 mg, 0.4 mmol) and cond sulfuric acid, 6b
was isolated as a highly viscous oil (114 mg, 97%). 1H NMR
3.3.7. 2-Chloro-1,3-dimethyl-4-ethylthioxanthone (6g)
(250 MHz, CDCl3):
d
¼2.38 (s, 3H, CH3), 2.83 (s, 3H, CH3), 7.16 (s, 1H,
Starting with 5j (302 mg, 0.92 mmol) and concd sulfuric acid, 6g
ArH), 7.45 (m, 3H, ArH), 8.31 (dd, 1H, 3J¼7.9 Hz, 4J¼2.0 Hz, ArH). 13
C
was isolated as a colourless solid (270 mg, 96%), mp¼81 ꢁC. 1H NMR
NMR (62 MHz, CDCl3):
(ArCH), 127.3 (C), 129.6, 131.7 (ArCH), 131.8, 135.0, 135.3, 136.7, 141.7,
141.9, 182.4 (C). IR (neat):
(m), 1590 (m), 1490 (m), 1319 (m), 1219 (m), 1176 (m), 1029 (m), 751
(w), 690 (m) cmꢀ1. GC–MS (EI, 70 eV): m/z (%): 276 (Mþ, 37Cl, 37),
274 (Mþ, 35Cl, 41), 267 (100), 105 (89), 77 (34). HRMS (EI): calcd for
C15H11OClS [Mþ, 35Cl]: 274.06127, found 274.06139.
d
¼19.8, 21.4 (CH3), 125.1 (2C, ArCH), 126.2
(250 MHz, CDCl3):
d
¼1.14 (t, 3H, J¼7.5 Hz, CH3), 2.03 (s, 3H, CH3),
2.40 (s, 3H, CH3), 2.85 (q, 2H, J¼7.2 Hz, CH2), 7.28–7.40 (m, 2H, ArH),
¼ 3375ðwÞ, 2978 (s), 1734 (m), 1675
7.47–7.89 (m, 2H, ArH). 13C NMR (62 MHz, CDCl3):
d
¼12.5, 18.0, 20.3
~
n
(CH3), 24.1 (CH2), 125.3 (ArCH), 126.3 (2C, ArCH), 129.0 (ArCH),
130.8, 131.7, 134.4, 136.3, 136.6, 137.6, 138.4, 139.4, 184.2 (C). IR
~
(neat):
n
¼ 3045ðwÞ, 2938 (w), 1711 (w), 1624 (s), 1587 (s), 1432 (s),
1373 (w), 1214 (s), 1174 (s), 1027 (s), 751 (m), 637 (s) cmꢀ1. GC–MS
(EI, 70 eV): m/z (%): 304 (Mþ, 37Cl, 30), 302 (Mþ, 35Cl, 100), 267 (23),
251 (12), 221 (10), 210 (8), 97 (15), 57 (27). HRMS (EI): calcd for
C17H15OClS [Mþ, 35Cl]: 302.05268, found 302.05282.
3.3.3. 1-Propyl-3-methylthioxanthone (6c)
Starting with 5e (50 mg, 0.16 mmol) and concd sulfuric acid, 6c
was isolated as a highly viscous oil (42 mg, 95%). 1H NMR (250 MHz,
CDCl3):
d
¼0.90 (t, 3H, J¼7.4 Hz, CH3), 1.60 (m, 2H, CH2), 2.55 (t, H,
3.4. General procedure for the synthesis of diaryl
sulfides 8a–x
J¼7.4 Hz, CH2), 2.81 (m, 3H, CH3), 7.10 (s,1H, ArH), 7.38 (m, 3H, ArH),
8.25 (dd, 1H, 3J¼7.2 Hz, 4J¼1.87 Hz, ArH). 13C NMR (62 MHz, CDCl3):
d
¼13.8, 23.4 (CH3), 24.8, 37.6 (CH2), 123.6, 125.1, 125.9 (ArCH), 127.2
To a dichloromethane solution (30 mL/mmol) of 3-arylthio-1-
trimethylsilyloxy-1,3-butadienes 3 (1.0 mmol) and 1,1-diacyclo-
propane 7 (1.5 mmol) was added TiX4 (1.5 mmol) at ꢀ78 ꢁC. The
solution was allowed to warm to ambient temperature within 14 h.
To the solution was added a diluted aqueous solution of HCL
(25 mL). The organic and the aqueous layer were separated and the
latter was extracted with dichloromethane (3ꢂ20 mL). The filtrate
was concentrated in vacuo and the residue was purified by chro-
matography (silica gel, EtOAc/n-heptane).
(C), 129.6, 131.0, 131.5 (ArCH), 132.1, 135.4, 139.2, 143.8, 146.5, 182.2
~
(C). IR (neat):
n
¼ 3056ðwÞ, 2973 (w), 1732 (m), 1625 (s), 1560 (m),
1460 (s), 1329 (s), 1249 (2), 1186 (s), 1029 (m), 723 (w), 690
(m) cmꢀ1. GC–MS (EI, 70 eV): m/z (%): 268 (100), 253 (7), 239 (34),
211 (36), 178 (10), 120 (7), 77 (8). HRMS (EI): calcd for C17H16OS
[Mþ]: 268.09164, found 268.09153.
3.3.4. 1,2,3,4-Tetramethylthioxanthone (6d)
Starting with 5f (118 mg, 0.39 mmol) and concd sulfuric acid, 6d
was isolated as a colourless solid (102 mg, 97%), mp¼221 ꢁC. 1H
3.4.1. Methyl 4,6-dimethyl-5-(2-chloroethyl)-2-
(phenylsulfanyl)benzoate (8a)
Starting with 7a (378 mg, 3.0 mmol), 3a (562 mg, 2.0 mmol),
TiCl4 (0.33 mL, 3.0 mmol) and CH2Cl2 (60 mL), 8a was isolated as
a highly viscous oil (322 mg, 48%). 1H NMR (250 MHz, CDCl3):
NMR (250 MHz, CDCl3):
d
¼2.32 (s, 3H, CH3), 2.35 (s, 3H, CH3), 2.45
(s, 3H, CH3), 2.68 (s, 3H, CH3), 7.40 (m, 1H, ArH), 7.52 (m, 2H, ArH),
8.30 (m, 1H, ArH). 13C NMR (62 MHz, CDCl3):
(CH3), 125.3, 125.8 (ArCH), 127.4, 128.4 (C), 128.9, 131.1 (ArCH),
d
¼16.5, 16.7, 17.6, 19.4
132.2, 134.4, 134.8, 135.8, 138.0, 139.4, 184.6 (C). IR (neat):
d
¼2.19 (s, 3H, CH3), 2.21 (s, 3H, CH3), 3.09 (t, 2H, J¼7.5 Hz, CH2), 3.43
(t, 2H, J¼7.1 Hz, CH2), 3.76 (s, 3H, OCH3), 6.96 (s, 1H, ArH), 7.11–7.21
(m, 5H, ArH). 13C NMR (62 MHz, CDCl3):
~
n
¼ 3064ðwÞ, 2916 (w), 1622 (s), 1587 (s), 1433 (s), 1490 (m), 1301
(s), 1204 (m), 1093 (s), 952 (m), 743 (s), 643 (m) cmꢀ1. GC–MS (EI,
70 eV): m/z (%): 268 (100), 253 (82), 239 (34), 184 (10), 119 (7), 69
(12). HRMS (EI): calcd for C17H16O2S [Mþ]: 268.09164, found
268.09113.
d
¼16.8, 20.1 (CH3), 33.0,
41.6 (CH2), 52.2 (CH3), 126.9.0 (CH), 129.04 (2C, CH), 130.3 (C), 130.5
(2C, CH),133.1 (CH), 134.1, 135.1, 136.0, 136.6, 138.9 (C), 169.3 (C]O).
IR (ATR):
(s), 1148 (s), 1039 (m), 1023 (m), 933 (w), 777 (w), 738 (s), 689 (s),
557 (w) cmꢀ1. GC–MS (EI, 70 eV): m/z (%): 336 (Mþ, 37Cl, 37), 334
(Mþ, 35Cl, 100), 301 (61), 285 (56), 267 (36), 253 (66), 210 (13), 115
(8), 77 (9). Anal. Calcd (%) for C18H19ClO2S (334.86): C, 64.56; H,
5.72. Found: C, 64.59; H, 5.84.
~
n
¼ 2948ðwÞ, 2871 (w), 1727 (s), 1579 (m), 1437 (m), 1268
3.3.5. 2-Chloro-1,3,4-trimethylthioxanthone (6e)
Starting with 5g (90 mg, 0.28 mmol) and concd sulfuric acid, 6e
was isolated as a colourless solid (78 mg, 97%), mp¼194 ꢁC. 1H NMR
(250 MHz, CDCl3):
d
¼2.50 (s, 3H, CH3), 2.53 (s, 3H, CH3), 2.86 (s, 3H,
CH3), 7.45 (m, 1H, ArH), 7.57 (m, 2H, ArH), 8.34 (m, 1H, ArH). 13C
NMR (62 MHz, CDCl3):
d
¼16.8, 18.7, 20.2 (CH3), 125.3, 126.3, 129.0
3.4.2. Methyl 4-methyl-5-(2-chloroethyl)-6-phenyl-2-
(phenylsulfanyl)benzoate (8b)
(ArCH), 130.0 (C), 131.6 (ArCH), 131.6, 132.3, 132.7, 134.0, 134.1, 137.8,
~
138.7, 183.9 (C). IR (neat):
n
¼ 3063ðwÞ, 2918 (s), 1732 (m), 1624 (s),
Starting with 7b (564 mg, 3.0 mmol), 3a (562 mg, 2.0 mmol),
TiCl4 (0.33 mL, 3.0 mmol) and CH2Cl2 (60 mL), 8b was isolated as
a highly viscous oil (278 mg, 47%). 1H NMR (250 MHz, CDCl3):
1588 (m), 1432 (m), 1378 (m), 1229 (m), 1155 (s), 1009 (s), 741 (s),
615 (m) cmꢀ1. GC–MS (EI, 70 eV): m/z (%): 290 (Mþ, 37Cl, 45), 288
(Mþ, 35Cl, 100), 253 (16), 225 (26), 208 (8), 119 (13), 69 (9). HRMS
(EI): calcd for C16H13OClS [Mþ, 35Cl]: 288.03701, found 288.03628.
d¼2.23 (s, 3H, CH3), 2.83 (t, 2H, J¼7.5 Hz, CH2), 3.22 (t, 2H, J¼7.4 Hz,
CH2), 3.31 (s, 3H, OCH3), 7.03 (s, 1H, ArH), 7.11–7.18 (m, 5H, ArH),

I. Iqbal et al. / Tetrahedron 65 (2009) 7562–7572
7569
7.23–7.30 (m, 4H, ArH). 13C NMR (125 MHz, CDCl3):
d
¼22.6 (CH3),
a highly viscous oil (228 mg, 30%). 1H NMR (250 MHz, CDCl3):
32.1, 42.2 (CH2), 51.7 (CH3), 128.5, 128.7 (CH), 128.9 (2C, CH), 129.0
(2C, CH), 129.2 (2C, CH), 130.8 (C), 131.2 (2C, CH), 133.5 (CH),
133.9,135.2, 136.3,137.1, 138.5, 140.0 (C), 168.1 (C]O). IR (ATR):
~
d
¼1.06 (t, 3H, J¼7.4 Hz, CH3), 1.13 (t, 3H, J¼7.5 Hz, CH3), 2.54 (m, 4H,
2ꢂCH2), 312 (m, 2H, CH2), 329 (m, 2H, CH2), 3.78 (s, 3H, OCH3), 6.98
(s, 1H, ArH), 7.12–7.21 (m, 5H, ArH). 13C NMR (62 MHz, CDCl3):
n
¼ 3022ðwÞ, 2947 (w), 1729 (s), 1573 (m), 1438 (s), 1270 (s), 1137
d
¼15.3, 15.9 (CH3), 24.4, 25.9, 30.1, 32.5 (CH2), 52.1 (CH3), 126.8
(s), 1023 (m), 739 (s), 699 (s), 595 (m), 557 (w) cmꢀ1. GC–MS (EI,
70 eV): m/z (%): 398 (Mþ, 37Cl, 28), 396 (Mþ, 35Cl, 75), 365 (7), 315
(100), 300 (10), 271 (23), 178 (8), 156 (6), 77 (2). HRMS (EI) calcd for
C23H21O2ClS [Mþ, 35Cl]: 396.09453, found 396.09453.
(CH), 129.0 (2C, CH), 130.4 (2C, CH), 130.9 (C), 131.6 (CH), 134.6,
~
136.0, 136.1, 140.2, 145.0 (C), 169.3 (C]O). IR (ATR):
n
¼ 2967ðwÞ,
2874 (w), 1728 (s), 1578 (m), 1438 (m), 1476 (m), 1271 (s), 1145 (s),
1023 (m), 983 (w), 739 (s), 688 (s), 579 (w) cmꢀ1. GC–MS (EI,
70 eV): m/z (%): 408 (Mþ, 81Br, 70), 406 (Mþ, 79Br, 69), 375 (100),
378 (88), 313 (19), 295 (37), 221 (8), 128 (13), 91 (5). Anal. Calcd (%)
for C20H23BrO2S (407.06): C, 58.97; H, 5.69. Found: C, 59.55; H, 6.04.
3.4.3. Methyl 4-methyl-5-(2-chloroethyl)-6-(4-chlorophenyl)-2-
(phenylsulfanyl)benzoate (8c)
Starting with 7c (333 mg, 1.5 mmol), 3a (281 mg, 1.0 mmol),
TiCl4 (0.16 mL, 1.5 mmol) and CH2Cl2 (100 mL), 8c was isolated as
a highly viscous oil (185 mg, 43%). 1H NMR (300 MHz, CDCl3):
3.4.7. Methyl 4-methyl-5-(2-bromoethyl)-6-phenyl-2-
(phenylsulfanyl)benzoate (8g)
d
¼2.14 (s, 3H, CH3), 2.71 (t, 2H, J¼7.5 Hz, CH2), 3.14 (t, 2H, J¼7.5 Hz,
CH2), 3.28 (s, 3H, OCH3), 6.94 (s, 1H, ArH), 6.99 (d, 2H, J¼8.4 Hz,
ArH), 7.08–7.22 (m, 7H, ArH). 13C NMR (62 MHz, CDCl3):
Starting with 7b (564 mg, 3.0 mmol), 3a (562 mg, 2.0 mmol),
TiBr4 (1.101 g, 3.0 mmol) and CH2Cl2 (60 mL), 8g was isolated as
a highly viscous oil (353 mg, 40%). 1H NMR (250 MHz, CDCl3):
d¼20.1
(CH3), 33.1, 42.3 (CH2), 51.9 (CH3), 127.4 (CH), 128.3 (2C, CH), 129.1
(2C, CH), 130.6 (2C, CH), 131.4 (C), 131.5 (2C, CH), 133.7 (CH), 133.9,
134.0, 134.9, 135.3, 136.4, 139.3, 139.5 (C), 168.0 (C]O). IR (ATR):
d
¼2.22 (s, 3H, CH3), 2.85 (m, 2H, CH2), 3.07 (m, 2H, CH2), 3.31 (s, 3H,
OCH3), 7.03 (s, 1H, ArH), 7.11–7.19 (m, 5H, ArH), 7.25–7.32 (m, 4H,
ArH). 13C NMR (62 MHz, CDCl3):
d
¼21.1 (CH3), 29.5, 33.7 (CH2), 51.7
~
n
¼ 2996ðwÞ, 2947 (w), 1729 (s), 1574 (m), 1438 (s), 1271 (s), 1191
(CH3), 127.3, 127.8 (C), 128.1 (CH), 129.1 (2C, CH), 129.2 (2C, CH),
(m), 1087 (s), 1001 (m), 836 (m), 739 (s), 598 (w) cmꢀ1. GC–MS (EI,
70 eV): m/z (%): 435 ([M]þ, [2ꢂ37Cl], 3), 433 ([M]þ, [37Cl], [35Cl], 15),
370 ([M]þ, [2ꢂ35Cl], 23), 349 (100), 314 (16), 285 (10), 271 (24), 156
(10), 77 (3). Anal. Calcd (%) for C23H20ClO2S (431.37): C, 64.04; H,
4.67. Found: C, 63.79; H, 4.86.
131.5 (2C, CH), 133.5 (C), 133.6 (2C, CH), 135.2, 135.3 (CH), 135.5,
~
137.9, 139.0, 140.7 (C), 168.2 (C]O). IR (ATR):
n
¼ 3021ðwÞ, 2846
(w), 1730 (s), 1573 (m), 1438 (m), 1268 (s), 1136 (s), 1089 (m), 1023
(m), 929 (w), 702 (s), 688 (s), 579 (m) cmꢀ1. GC–MS (EI, 70 eV): m/z
(%): 442 (Mþ, 81Br, 67), 440 (Mþ, 79Br, 64), 329 (15), 315 (100), 300
(10), 271 (24), 178 (11), 156 (10), 77 (3). Anal. Calcd (%) for
C18H19BrO2S (441.38): C, 62.59; H, 4.80. Found: C, 62.73; H, 4.98.
3.4.4. Methyl 4-methyl-5-(2-chloroethyl)-6-(4-fluorophenyl)-2-
(phenylsulfanyl)benzoate (8d)
Starting with 7d (618 mg, 3.0 mmol), 3a (562 mg, 2.0 mmol),
TiCl4 (0.33 mL, 1.5 mmol) and CH2Cl2 (60 mL), 8d was isolated as
a highly viscous oil (331 mg, 40%). 1H NMR (250 MHz, CDCl3):
3.4.8. Methyl 4,6-dimethyl-5-(2-chloroethyl)-2-(4-
methylphenylsulfanyl)benzoate (8h)
Starting with 7a (283 mg, 2.25 mmol), 3d (441 mg, 1.5 mmol),
TiCl4 (0.25 mL, 2.25 mmol) and CH2Cl2 (45 mL), 8h was isolated as
a highly viscous oil (208 mg, 40%). 1H NMR (250 MHz, CDCl3):
d
¼2.25 (s, 3H, CH3), 2.82 (t, 2H, J¼7.5 Hz, CH2), 3.23 (t, 2H, J¼7.4 Hz,
CH2), 3.37 (s, 3H, OCH3), 7.01 (s, 1H, ArH), 7.10 (d, 2H, J¼8.6 Hz, ArH),
7.14–7.33 (m, 7H, ArH). 13C NMR (62 MHz, CDCl3):
d¼20.1 (CH3),
d
¼2.18 (s, 3H, CH3), 2.21 (s, 3H, CH3), 2.22 (s, 3H, CH3), 3.03 (t,
J¼8.3 Hz, 2H, CH2), 3.44 (t, J¼8.3 Hz, 2H, CH2), 3.78 (s, 3H, OCH3),
6.93–7.07 (m, 5H, ArH). 13C NMR (62 MHz, CDCl3):
33.3, 42.0 (CH2), 51.8 (CH3), 115.0, 115.3, 127.4 (CH), 129.2 (2C, CH),
130.9, 131.0 (CH), 131.3 (C), 131.5 (2C, CH), 133.6 (CH), 133.6, 134.3,
135.0, 135.5, 139.3, 139.7 (C), 162.1 (d, J¼274.2 Hz, CF), 168.1 (C]O).
~
d
¼16.8 (CH3),
20.1 (CH3), 21.3 (CH3), 33.1 (CH2), 41.6 (CH2), 52.1 (OCH3), 111.3
(C), 127.9 (2CH), 128.9 (CH), 130.7 (C), 131.1, 132.8 (CH), 133.0,
IR (ATR):
n
¼ 2948ðwÞ, 2923 (w), 1730 (s), 1590 (s), 1508 (s), 1438
(s), 1156 (s), 1023 (m), 785 (m), 690 (s), 605 (m), 558 (w) cmꢀ1. GC–
MS (EI, 70 eV): m/z (%): 416 (Mþ, 37Cl, 24), 414 (Mþ, 35Cl, 74), 383 (5),
333 (100), 318 (9), 289 (15), 197 (6), 163 (13), 57 (21). HRMS (EI)
calcd for C23H20O2ClFS [Mþ, 35Cl]: 414.08518, found 141.08511.
134.0, 134.8, 135.5, 138.9, 169.3 (C). IR (ATR):
¼ 2948ðwÞ, 2921
~
n
(w), 2734 (w), 2249 (w), 1728 (s), 1588 (m), 1573 (m), 1473 (m),
1435 (m), 1392 (m), 1377 (m), 1325 (m), 1270 (sd), 1190 (s), 1140
(s), 1040 (s), 907 (s), 777 (s), 728 (s), 691 (s), 646 (m) cmꢀ1. GC–
MS (EI, 70 eV): m/z (%): 350 (Mþ, 37Cl, 38), 348 (Mþ, 35Cl, 100), 317
(29), 315 (37), 303 (10), 301 (10), 281 (24), 268 (13), 267 (63), 225
(12), 224 (10). HRMS (EI): calcd for C19H21O2ClS [Mþ] 348.09453,
found 348.094465.
3.4.5. Methyl 4,6-dimethyl-5-(2-bromoethyl)-2-(phenylsulfanyl)-
benzoate (8e)
Starting with 7a (378 mg, 3.0 mmol), 3a (562 mg, 2.0 mmol),
TiBr4 (1.101 g, 3.0 mmol) and CH2Cl2 (60 mL), 8e was isolated as
highly viscous oil (439 mg, 58%). 1H NMR (250 MHz, CDCl3):
d
¼2.17
3.4.9. Methyl 4-methyl-5-(2-chloroethyl)-2-(4-
methylphenylsulfanyl)-6-phenylbenzoate (8i)
Starting with 7b (283 mg, 2.25 mmol), 3d (441 mg, 1.5 mmol),
TiCl4 (0.25 mL, 2.25 mmol) and CH2Cl2 (45 mL), 8i was isolated as
a highly viscous oil (252 mg, 41%). 1H NMR (250 MHz, CDCl3):
(s, 3H, CH3), 2.20 (s, 3H, CH3), 3.10 (m, 2H, CH2), 3.26 (m, 2H, CH2),
3.76 (s, 3H, OCH3), 6.95 (s,1H, ArH), 7.07–7.19 (m, 5H, ArH). 13C NMR
(62 MHz, CDCl3):
126.9.0 (CH), 129.04 (2C, CH), 130.4 (C), 130.5 (2C, CH), 133.1 (CH),
d
¼16.8, 20.0 (CH3), 28.8, 33.5 (CH2), 52.2 (CH3),
133.9, 136.0, 136.1, 136.6, 138.7 (C), 169.3 (C]O). IR (ATR):
d
¼2.18 (s, 3H, CH3), 2.21 (s, 3H, CH3), 3.03 (t, J¼8.3 Hz, 2H, CH2), 3.44
(t, J¼8.3 Hz, 2H, CH2), 3.77 (s, 3H, OCH3), 6.96–7.28 (m, 10H, ArH).
13C NMR (62 MHz, CDCl3):
~
n
¼ 2947ðwÞ, 2923 (w), 1727 (s), 1579 (m), 1436 (m), 1267 (s), 1147
(s), 1129 (m), 1045 (m), 812 (m), 738 (s), 688 (s), 591 (m) cmꢀ1. GC–
MS (EI, 70 eV): m/z (%): 380 (Mþ, 81Br, 100), 378 (Mþ, 79Br, 98), 347
(68), 345 (53), 299 (20), 285 (50), 253 (68), 115 (12), 77 (9). Anal.
Calcd (%) for C18H19BrO2S (379.31): C, 57.00; H, 5.05. Found: C,
57.24; H, 5.13.
d
¼18.6 (CH3), 21.3 (CH3), 33.1 (CH2), 40.2
(CH2), 52.1 (OCH3), 127.8 (CH), 128.0, 128.8, 129.2 (2CH), 131.2, 132.3
(C), 132.4 (2CH), 132.5 (CH), 133.6, 134.7, 138.0, 139.1, 140.7, 144.1,
168.3 (C). IR (ATR):
1728 (s), 1588 (m), 1573 (m), 1473 (m), 1435 (m), 1392 (m), 1377 (m),
1325 (m), 1270 (sd), 1190 (s), 1140 (s), 1040 (s), 907 (s), 777 (s), 728
(s), 691 (s), 646 (m) cmꢀ1. GC–MS (EI, 70 eV): m/z (%): 350 (Mþ, 37Cl,
38), 348 (Mþ, 35Cl, 100), 317 (29), 315 (37), 303 (10), 301 (10), 281
(24), 268 (13), 267 (63), 225 (12), 224 (10). HRMS (EI): calcd for
C19H21O2ClS [Mþ] 348.09453, found 348.094465.
~
n
¼ 2948ðwÞ, 2921 (w), 2734 (w), 2249 (w),
3.4.6. Methyl 4,6-diethyl-5-(2-bromoethyl)-2-(phenylsulfanyl)-
benzoate (8f)
Starting with 7e (462 mg, 3.0 mmol), 3a (562 mg, 2.0 mmol),
TiBr4 (1.10 g, 3.0 mmol) and CH2Cl2 (60 mL), 8f was isolated as

7570
I. Iqbal et al. / Tetrahedron 65 (2009) 7562–7572
3.4.10. Methyl 4-methyl-5-(2-bromoethyl)-2-(4-
methylphenylsulfanyl)-6-phenylbenzoate (8j)
(10), 301 (10), 281 (24), 268 (13), 267 (63), 225 (12), 224 (10). HRMS
(EI): calcd for C18H18O2BrClS [Mþ] 411.98939, found 411.989037.
Starting with 7b (283 mg, 2.25 mmol), 3d (441 mg, 1.5 mmol),
TiBr4 (0.826 g, 2.25 mmol) and CH2Cl2 (45 mL), 8j was isolated as
a highly viscous oil (306 mg, 45%). 1H NMR (250 MHz, CDCl3):
3.4.14. Methyl 4,6-dimethyl-5-(2-chloroethyl)-2-(3-
methoxyphenyl-sulfanyl)benzoate (8n)
d
¼2.18 (s, 3H, CH3), 2.21 (s, 3H, CH3), 3.03 (t, J¼8.3 Hz, 2H, CH2), 3.39
(t, J¼8.3 Hz, 2H, CH2), 3.77 (s, 3H, OCH3), 6.96–7.66 (m, 10H, ArH).
13C NMR (62 MHz, CDCl3):
Starting with 7a (283 mg, 2.25 mmol), 3o (466 mg, 1.5 mmol),
TiCl4 (0.25 mL, 2.25 mmol) and CH2Cl2 (45 mL), 8n was isolated as
a highly viscous oil (191 mg, 35%). 1H NMR (250 MHz, CDCl3):
d
¼20.1 (CH3), 21.3 (CH3), 33.1 (CH2), 40.2
(CH2), 52.1 (OCH3), 127.8 (CH), 128.0, 128.8, 129.2 (2CH), 131.2, 132.3
(C), 132.4 (2CH), 132.5 (CH), 133.6, 134.7, 138.0, 139.1, 140.7, 144.1,
168.3 (C). IR (ATR):
1728 (s), 1588 (m),1573 (m), 1473 (m), 1435 (m), 1392 (m),1377 (m),
1325 (m), 1270 (sd), 1190 (s), 1140 (s), 1040 (s), 907 (s), 777 (s), 728
(s), 691 (s), 646 (m) cmꢀ1. GC–MS (EI, 70 eV): m/z (%): 350 (Mþ, 81Br,
100), 348 (Mþ, 79Br, 75), 317 (87), 315 (37), 303 (10), 301 (10), 281
(24), 268 (13), 267 (63), 225 (12), 224 (10). HRMS (EI): calcd for
C24H23O2BrS [Mþ] 454.05966, found 454.059387.
d
¼2.18 (s, 3H, CH3), 2.22 (s, 3H, CH3), 3.03 (t, J¼8.3 Hz, 2H, CH2),
3.44 (t, J¼8.3 Hz, 2H, CH2), 3.66 (s, 3H, OCH3), 3.78 (s, 3H, OCH3),
6.93–7.07 (m, 5H, ArH). 13C NMR (62 MHz, CDCl3):
~
n
¼ 2948ðwÞ, 2921 (w), 2734 (w), 2249 (w),
d
¼20.1 (CH3),
21.3 (CH3), 33.1 (CH2), 41.6 (CH2), 51.2 (OCH3), 52.1 (OCH3), 111.3 (C),
127.9 (2CH), 128.9 (CH), 130.7 (C), 131.1, 132.8 (CH), 133.0, 134.0,
~
134.8, 135.5, 138.9, 169.3 (C). IR (ATR):
n
¼ 2948ðwÞ, 2921 (w), 2734
(w), 2249 (w), 1728 (s), 1588 (m), 1573 (m), 1473 (m), 1435 (m), 1392
(m), 1377 (m), 1325 (m), 1270 (sd), 1190 (s), 1140 (s), 1040 (s), 907
(s), 777 (s), 728 (s), 691 (s), 646 (m) cmꢀ1. GC–MS (EI, 70 eV): m/z
(%): 366 (Mþ, 37Cl, 39), 364 (Mþ, 35Cl, 100), 317 (29), 315 (37), 303
(10), 301 (10), 281 (24), 268 (13), 267 (63), 225 (12), 224 (10). HRMS
(EI): calcd for C19H21O3ClS [Mþ] 364.09453, found 364.094465.
3.4.11. Methyl 4,6-dimethyl-5-(2-chloroethyl)-2-(4-chlorophenyl-
sulfanyl)benzoate (8k)
Starting with 7a (283 mg, 2.25 mmol), 3i (472 mg, 1.5 mmol),
TiCl4 (0.25 mL, 2.25 mmol) and CH2Cl2 (45 mL), 8k was isolated as
a highly viscous oil (237 mg, 43%). 1H NMR (250 MHz, CDCl3):
3.4.15. Methyl 4-methyl-5-(2-chloroethyl)-2-(3-methoxyphenyl-
sulfanyl)-6-phenylbenzoate (8o)
d
¼2.18 (s, 3H, CH3), 2.24 (s, 3H, CH3), 3.03 (t, J¼8.3 Hz, 2H, CH2),
3.46 (t, J¼8.3 Hz, 2H, CH2), 3.78 (s, 3H, OCH3), 6.93–7.29 (m, 5H,
ArH). 13C NMR (62 MHz, CDCl3):
Starting with 7b (283 mg, 2.25 mmol), 3o (466 mg, 1.5 mmol),
TiCl4 (0.25 mL, 2.25 mmol) and CH2Cl2 (45 mL), 8o was isolated as
a highly viscous oil (211 mg, 33%). 1H NMR (250 MHz, CDCl3):
d
¼21.1 (CH3), 21.3 (CH3), 33.1 (CH2),
41.6 (CH2), 52.1 (OCH3), 111.3 (C), 127.9 (2CH), 128.9 (CH), 130.7 (C),
131.1, 132.8 (CH), 133.0, 134.0, 134.8, 135.5, 138.9, 169.3 (C). IR (ATR):
~
n
d
¼2.18 (s, 3H, CH3), 3.03 (t, J¼8.3 Hz, 2H, CH2), 3.44 (t, J¼8.3 Hz, 2H,
CH2), 3.42 (s, 3H, OCH3), 3.77 (s, 3H, OCH3), 6.96–7.28 (m, 10H, ArH).
13C NMR (62 MHz, CDCl3):
¼ 2947ðwÞ, 2926 (w), 2736 (w), 2249 (w), 1728 (s), 1588 (m),
d
¼20.1 (CH3), 21.3 (CH3), 33.1 (CH2), 41.6
1573 (m), 1473 (m), 1435 (m), 1392 (m), 1377 (m), 1327 (m), 1270
(sd), 1190 (s), 1140 (s), 1040 (s), 907 (s), 777 (s), 728 (s), 691 (s), 645
(m) cmꢀ1. GC–MS (EI, 70 eV): m/z (%): 372 (Mþ, 37Cl, 37Cl, 14), 371
(Mþ, 35Cl, 37Cl, 70), 370 (Mþ, 35Cl, 35Cl, 100), 317 (29), 315 (37), 303
(10), 301 (10), 281 (24), 268 (13), 267 (63), 225 (12), 224 (10). HRMS
(EI): calcd for C18H18O2Cl2S [Mþ] 368.03991, found 368.040296.
(CH2), 52.1 (OCH3), 127.8 (CH), 128.0, 128.8, 129.2 (2CH), 131.2, 132.3
(C), 132.4 (2CH), 132.5 (CH), 133.6, 134.7, 138.0, 139.1, 140.7, 144.1,
~
168.3 (C). IR (ATR):
n
¼ 2948ðwÞ, 2921 (w), 2734 (w), 2249 (w),
1728 (s), 1588 (m), 1573 (m), 1473 (m),1435 (m), 1392 (m), 1377 (m),
1324 (m), 1270 (sd), 1190 (s), 1140 (s), 1040 (s), 907 (s), 777 (s), 728
(s), 691 (s), 646 (m) cmꢀ1. GC–MS (EI, 70 eV): m/z (%): 428 (Mþ, 37Cl,
38), 426 (Mþ, 35Cl, 100), 318 (29), 315 (37), 303 (10), 301 (10), 281
(24), 268 (13), 267 (63), 225 (12), 224 (10). HRMS (EI): calcd for
C24H23O3ClS [Mþ] 426.09453, found 426.094465.
3.4.12. Methyl 4-methyl-5-(2-chloroethyl)-2-(4-chlorophenyl-
sulfanyl)-6-phenylbenzoate (8l)
Starting with 7b (283 mg, 2.25 mmol), 3i (472 mg, 1.5 mmol),
TiCl4 (0.25 mL, 2.25 mmol) and CH2Cl2 (45 mL), 8l was isolated as
a highly viscous oil (303 mg, 47%). 1H NMR (250 MHz, CDCl3):
3.4.16. Methyl 4,6-dimethyl-5-(2-chloroethyl)-2-(3-
methoxyphenyl-sulfanyl)benzoate (8p)
d
¼2.18 (s, 3H, CH3), 3.03 (t, J¼8.3 Hz, 2H, CH2), 3.44 (t, J¼8.3 Hz, 2H,
CH2), 3.77 (s, 3H, OCH3), 6.93–7.26 (m, 5H, ArH). 13C NMR (62 MHz,
CDCl3):
Starting with 7a (283 mg, 2.25 mmol), 3o (466 mg, 1.5 mmol),
TiBr4 (0.826 g, 2.25 mmol) and CH2Cl2 (45 mL), 8p was isolated as
a highly viscous oil (251 mg, 41%). 1H NMR (250 MHz, CDCl3):
d
¼20.1 (CH3), 33.1 (CH2), 41.6 (CH2), 52.1 (OCH3), 127.8 (CH),
128.0, 128.8, 129.2 (2CH), 131.2, 132.3 (C), 132.4 (2CH), 132.5 (CH),
133.6, 134.7, 138.0, 139.1, 140.7, 144.1, 168.3 (C). IR (ATR):
~
n
d
¼2.18 (s, 3H, CH3), 2.22 (s, 3H, CH3), 3.03 (t, J¼8.3 Hz, 2H, CH2),
3.44 (t, J¼8.3 Hz, 2H, CH2), 3.66 (s, 3H, OCH3), 3.78 (s, 3H, OCH3),
6.93–7.07 (m, 5H, ArH). 13C NMR (62 MHz, CDCl3):
¼ 2947ðwÞ, 2921 (w), 2734 (w), 2249 (w),1728 (s),1588 (m),1577
d
¼20.1 (CH3),
(m), 1473 (m), 1435 (m), 1392 (m), 1377 (m), 1325 (m), 1270 (sd),
1190 (s), 1140 (s), 1040 (s), 907 (s), 777 (s), 728 (s), 691 (s), 646
(m) cmꢀ1. GC–MS (EI, 70 eV): m/z (%): 434 (Mþ, 37Cl, 37Cl, 12), 432
(Mþ, 35Cl, 37Cl, 61), 430 (Mþ, 35Cl, 35Cl, 85), 349 (100), 315 (37), 303
(10), 301 (10), 281 (24), 268 (13), 267 (63), 225 (12), 224 (10). HRMS
(EI): calcd for C23H20O2Cl2S [Mþ] 430.09453, found 430.094465.
21.3 (CH3), 33.1 (CH2), 41.6 (CH2), 51.2 (OCH3), 52.1 (OCH3), 111.3 (C),
127.9 (2CH), 128.9 (CH), 130.7 (C), 131.1, 132.8 (CH), 133.0, 134.0,
~
134.8, 135.5, 138.9, 169.3 (C). IR (ATR):
n
¼ 2948ðwÞ, 2921 (w), 2734
(w), 2249 (w), 1728 (s), 1588 (m), 1573 (m), 1473 (m), 1435 (m), 1392
(m), 1377 (m), 1325 (m), 1270 (sd), 1190 (s), 1140 (s), 1040 (s), 907
(s), 777 (s), 728 (s), 691 (s), 646 (m) cmꢀ1. GC–MS (EI, 70 eV): m/z
(%): 410 (Mþ, 81Br, 79), 408 (Mþ, 79Br, 100), 317 (29), 315 (37), 303
(10), 301 (10), 281 (24), 268 (13), 267 (63), 225 (12), 224 (10). HRMS
(EI): calcd for C19H21O3ClS [Mþ] 408.09853, found 408.094465.
3.4.13. Methyl 4,6-dimethyl-5-(2-bromooethyl)-2-(4-chlorophenyl-
sulfanyl)benzoate (8m)
Starting with 7a (283 mg, 2.25 mmol), 3i (472 mg, 1.5 mmol),
TiBr4 (0.826 g, 2.25 mmol) and CH2Cl2 (45 mL), 8m was isolated as
a highly viscous oil (252 mg, 41%). 1H NMR (250 MHz, CDCl3):
3.4.17. Methyl 4,6-dimethyl-5-(2-bromooethyl)-2-(3-chlorophenyl-
sulfanyl)benzoate (8q)
d
¼2.18 (s, 3H, CH3), 2.24 (s, 3H, CH3), 3.03 (t, J¼8.3 Hz, 2H, CH2),
3.46 (t, J¼8.3 Hz, 2H, CH2), 3.78 (s, 3H, OCH3), 6.93–7.29 (m, 5H,
ArH). 13C NMR (62 MHz, CDCl3):
Starting with 7a (283 mg, 2.25 mmol), 3k (472 mg, 1.5 mmol),
TiBr4 (0.826 g, 2.25 mmol) and CH2Cl2 (45 mL), 8q was isolated as
d
¼21.1 (CH3), 21.3 (CH3), 33.1 (CH2),
highly viscous oil (221 mg, 40%). 1H NMR (250 MHz, CDCl3):
d¼2.18
41.6 (CH2), 52.1 (OCH3), 111.3 (C), 127.9 (2CH), 128.9 (CH), 130.7 (C),
131.1, 132.8 (CH), 133.0, 134.0, 134.8, 135.5, 138.9, 169.3 (C). IR (ATR):
(s, 3H, CH3), 2.24 (s, 3H, CH3), 3.03 (t, J¼8.3 Hz, 2H, CH2), 3.46 (t,
J¼8.3 Hz, 2H, CH2), 3.78 (s, 3H, OCH3), 6.93–7.29 (m, 5H, ArH). 13
C
~
n
¼ 2947ðwÞ, 2926 (w), 2736 (w), 2249 (w). MS (EI, 70 eV): m/z (%):
NMR (62 MHz, CDCl3):
d
¼21.1 (CH3), 21.3 (CH3), 33.1 (CH2), 41.6
416 (29), 415 (20), 414 (100), 413 (16), 412 (Mþ, 74), 315 (37), 303
(CH2), 52.1 (OCH3), 111.3 (C), 127.9 (2CH), 128.9 (CH), 130.7 (C), 131.1,

I. Iqbal et al. / Tetrahedron 65 (2009) 7562–7572
7571
~
132.8 (CH), 133.0, 134.0, 134.8, 135.5, 138.9, 169.3 (C). IR (ATR):
168.3 (C). IR (ATR):
n
¼ 2948ðwÞ, 2921 (w), 2734 (w), 2249 (w),
~
n
¼ 2947ðwÞ, 2926 (w), 2736 (w), 2249 (w). MS (EI, 70 eV): m/z (%):
1728 (s), 1588 (m), 1573 (m), 1473 (m), 1435 (m), 1392 (m), 1377 (m),
1325 (m), 1270 (sd), 1190 (s), 1140 (s), 1040 (s), 907 (s), 777 (s), 728
(s), 691 (s), 646 (m) cmꢀ1. GC–MS (EI, 70 eV): m/z (%): 470 (Mþ, 81Br,
100), 468 (Mþ, 79Br, 75), 317 (87), 315 (37), 303 (10), 301 (10), 281
(24), 268 (13), 267 (63), 225 (12), 224 (10). HRMS (EI): calcd for
C25H25O2BrS [Mþ] 468.98939, found 468.989037.
416 (Mþ, 29), 415 (Mþ, 20), 414 (Mþ,100), 413 (Mþ,16), 412 (Mþ, 74),
315 (37), 303 (10), 301 (10), 281 (24), 268 (13), 267 (63), 225 (12),
224 (10). HRMS (EI): calcd for C18H18O2BrClS [Mþ] 411.98939, found
411.989037.
3.4.18. Methyl 4,6-dimethyl-5-(2-bromooethyl)-2-(3-
methylphenylsulfanyl)benzoate (8r)
3.4.22. Methyl 4,6-dimethyl-5-(2-bromoethyl)-2-(4-ethylphenyl-
sulfanyl)benzoate (8v)
Starting with 7a (283 mg, 2.25 mmol), 3g (441 mg, 1.5 mmol),
TiBr4 (0.826, 2.25 mmol) and CH2Cl2 (45 mL), 8v was isolated as
Starting with 7a (283 mg, 2.25 mmol), 3f (441 mg, 1.5 mmol),
TiBr4 (0.826 g, 2.25 mmol) and CH2Cl2 (45 mL), 8r was isolated as
a highly viscous oil (235 mg, 40%).1H NMR (250 MHz, CDCl3):
d
¼2.18
(s, 3H, CH3), 2.14 (s, 3H, CH3), 2.24 (s, 3H, CH3), 3.03 (t, J¼8.3 Hz, 2H,
CH2), 3.46 (t, J¼8.3 Hz, 2H, CH2), 3.78 (s, 3H, OCH3), 6.93–7.29 (m, 5H,
a highly viscous oil (170 mg, 42%). 1H NMR (250 MHz, CDCl3):
d¼1.15
(t, J¼7.5 Hz, 3H, CH2CH3), 2.13 (s, 3H, CH3), 2.21 (s, 3H, CH3), 2.23 (s,
3H, CH3), 2.54 (q, J¼7.5 Hz, 2H, CH2CH3), 3.03 (t, J¼8.3 Hz, 2H, CH2),
3.39 (t, J¼8.3 Hz, 2H, CH2), 3.77 (s, 3H, OCH3), 6.93–7.29 (m, 5H, ArH).
ArH). 13C NMR (62 MHz, CDCl3):
33.1 (CH2), 41.6 (CH2), 52.1 (OCH3), 111.3 (C), 127.9 (2CH), 128.9 (CH),
d
¼18.6 (CH3), 21.1 (CH3), 21.3 (CH3),
130.7 (C),131.1, 132.8 (CH),133.0,134.0, 134.8, 135.5, 138.9, 169.3 (C).
13C NMR (62 MHz, CDCl3):
(CH2CH3), 33.1 (CH2), 40.2 (CH2), 52.1 (OCH3), 111.3 (C), 127.9 (2CH),
d
¼18.7 (CH3), 20.1 (CH3), 21.3 (CH3), 28.5
~
IR (ATR):
n
¼ 2947ðwÞ, 2926 (w), 2736 (w), 2249 (w). MS (EI, 70 eV):
m/z (%): 394 (100), 392 (Mþ, 74), 315 (37), 303 (10), 301 (10), 281 (24),
268 (13), 267 (63), 225 (12), 224 (10). HRMS (EI): calcd for
C19H21O2BrS [Mþ] 391.98939, found 391.989037.
128.9 (CH),130.7 (C),131.1,132.8 (CH),133.0,134.0,134.8,135.5,138.9,
~
169.3 (C). IR (ATR):
n
¼ 2947ðwÞ, 2926 (w), 2736 (w), 2249 (w). MS
(EI, 70 eV): m/z (%): 408 (100), 406 (Mþ, 74), 315 (37), 303 (10), 301
(10), 281 (24), 268 (13), 267 (63), 225 (12), 224 (10). HRMS (EI): calcd
for C20H23O2BrS [Mþ] 405.98939, found 405.989037.
3.4.19. Methyl 4,6-dimethyl-5-(2-chloroethyl)-2-(3-
methylphenylsulfanyl)benzoate (8s)
Starting with 7a (283 mg, 2.25 mmol), 3f (441 mg, 1.5 mmol),
TiCl4 (0.25 mL, 2.25 mmol) and CH2Cl2 (45 mL), 8s was isolated as
a highly viscous oil (224 mg, 43%). 1H NMR (250 MHz, CDCl3):
3.4.23. Methyl 4,6-dimethyl-5-(2-chloroethyl)-2-(4-ethylphenyl-
sulfanyl)benzoate (8w)
Starting with 4a (283 mg, 2.25 mmol), 3g (441 mg, 1.5 mmol),
TiCl4 (0.25 mL, 2.25 mmol) and CH2Cl2 (45 mL), 8w was isolated as
d
¼2.18 (s, 3H, CH3), 2.21 (s, 3H, CH3), 2.22 (s, 3H, CH3), 3.03 (t,
J¼8.3 Hz, 2H, CH2), 3.44 (t, J¼8.3 Hz, 2H, CH2), 3.78 (s, 3H, OCH3),
6.93–7.07 (m, 5H, ArH). 13C NMR (62 MHz, CDCl3):
highly viscous oil (239 mg, 44%). 1H NMR (250 MHz, CDCl3):
d¼1.15
d
¼16.8 (CH3),
(t, J¼7.5 Hz, 3H, CH2CH3), 2.13 (s, 3H, CH3), 2.21 (s, 3H, CH3), 2.24 (s,
3H, CH3), 2.54 (q, J¼7.5 Hz, 2H, CH2CH3), 3.03 (t, J¼8.3 Hz, 2H, CH2),
3.39 (t, J¼8.3 Hz, 2H, CH2), 3.77 (s, 3H, OCH3), 6.93–7.29 (m, 5H,
20.1 (CH3), 21.3 (CH3), 33.1 (CH2), 41.6 (CH2), 52.1 (OCH3), 111.3 (C),
127.9 (2CH), 128.9 (CH), 130.7 (C), 131.1, 132.8 (CH), 133.0, 134.0,
134.8, 135.5, 138.9, 169.3 (C). IR (ATR):
n
¼ 2948ðwÞ, 2921 (w), 2734
ArH). 13C NMR (62 MHz, CDCl3):
(CH3), 28.5 (CH2CH3), 33.3 (CH2), 40.1 (CH2), 52.1 (OCH3), 111.3 (C),
d
¼18.7 (CH3), 20.1 (CH3), 21.3
~
(w), 2249 (w), 1728 (s), 1588 (m), 1573 (m), 1473 (m), 1435 (m), 1392
(m), 1377 (m), 1325 (m), 1270 (sd), 1190 (s), 1140 (s), 1040 (s), 907
(s), 777 (s), 728 (s), 691 (s), 646 (m) cmꢀ1. GC–MS (EI, 70 eV): m/z
(%): 350 (Mþ, 37Cl, 38), 348 (Mþ, 35Cl, 100), 317 (29), 315 (37), 303
(10), 301 (10), 281 (24), 268 (13), 267 (63), 225 (12), 224 (10). HRMS
(EI): calcd for C19H21O2ClS [Mþ] 348.09453, found 348.094465.
127.9 (2CH), 128.9 (CH), 130.7 (C), 131.1, 132.8 (CH), 133.0, 134.0,
~
134.8, 135.5,138.9, 169.3 (C). IR (ATR):
n
¼ 2947ðwÞ, 2926 (w), 2736
(w), 2249 (w) cmꢀ1. MS (EI, 70 eV): m/z (%): 364 (Mþ, 37Cl, 38), 362
(Mþ, 35Cl, 100), 317 (29), 315 (37), 303 (10), 301 (10), 281 (24), 268
(13), 267 (63), 225 (12), 224 (10). HRMS (EI): calcd for C20H23O2ClS
[Mþ] 362.09453, found 362.094465.
3.4.20. Methyl 4,6-dimethyl-5-(2-bromooethyl)-2-(4-
methylphenylsulfanyl)benzoate (8t)
3.4.24. Methyl 4-methyl-5-(2-chloroethyl)-2-(4-ethylphenyl-
sulfanyl)-6-phenylbenzoate (8x)
Starting with 7b (283 mg, 2.25 mmol), 3g (460 mg, 1.5 mmol),
TiCl4 (0.25 mL, 2.25 mmol) and CH2Cl2 (45 mL), 8x was isolated as
a highly viscous oil (248 mg, 40%). 1H NMR (250 MHz, CDCl3):
Starting with 7a (283 mg, 2.25 mmol), 3d (441 mg, 1.5 mmol),
TiBr4 (0.826 g, 2.25 mmol) and CH2Cl2 (45 mL), 8t was isolated as
a highly viscous oil (235 mg, 40%).1H NMR (250 MHz, CDCl3):
d¼2.18
(s, 3H, CH3), 2.14 (s, 3H, CH3), 2.24 (s, 3H, CH3), 3.03 (t, J¼8.3 Hz, 2H,
CH2), 3.46 (t, J¼8.3 Hz, 2H, CH2), 3.78 (s, 3H, OCH3), 6.93–7.29 (m, 5H,
d
¼1.15 (t, J¼7.5 Hz, 3H, CH2CH3), 2.13 (s, 3H, CH3), 2.23 (s, 3H, CH3),
ArH). 13C NMR (62 MHz, CDCl3):
33.1 (CH2), 41.6 (CH2), 52.1 (OCH3), 111.3 (C), 127.9 (2CH), 128.9 (CH),
d
¼18.6 (CH3), 21.1 (CH3), 21.3 (CH3),
2.54 (q, J¼7.5 Hz, 2H, CH2CH3), 3.03 (t, J¼8.3 Hz, 2H, CH2), 3.39 (t,
J¼8.3 Hz, 2H, CH2), 3.77 (s, 3H, OCH3), 6.96–7.66 (m, 10H, ArH). 13
C
130.7 (C), 131.1, 132.8 (CH), 133.0, 134.0, 134.8, 135.5, 138.9, 169.3 (C).
NMR (62 MHz, CDCl3):
d¼20.1 (CH3), 21.3 (CH3), 28.5 (CH2CH3), 33.1
~
IR (ATR):
n
¼ 2947ðwÞ, 2926 (w), 2736 (w), 2249 (w). MS (EI, 70 eV):
(CH2), 40.2 (CH2), 52.1 (OCH3), 127.8 (CH), 128.0, 128.8, 129.2 (2CH),
m/z (%): 394 (100), 392 (Mþ, 74), 315 (37), 303 (10), 301 (10), 281 (24),
268 (13), 267 (63), 225 (12), 224 (10). HRMS (EI): calcd for
C19H21O2BrS [Mþ] 391.98939, found 391.989037.
131.2, 132.3 (C), 132.4 (2CH), 132.5 (CH), 133.6, 134.7, 138.0, 139.1,
~
140.7, 144.1, 168.3 (C). IR (ATR):
n
¼ 2948ðwÞ, 2921 (w), 2734 (w),
2249 (w),1728 (s),1588 (m), 1573 (m),1473 (m),1435 (m), 1392 (m),
1377 (m),1325 (m),1270 (sd),1190 (s),1140 (s),1040 (s), 907 (s), 777
(s), 728 (s), 691 (s), 646 (m) cmꢀ1. MS (EI, 70 eV): m/z (%): 426 (Mþ,
37Cl, 38), 424 (Mþ, 35Cl, 100), 317 (29), 315 (37), 303 (10), 301 (10),
281 (24), 268 (13), 267 (63), 225 (12), 224 (10). HRMS (EI): calcd for
C20H23O2ClS [Mþ] 424.09453, found 424.094465.
3.4.21. Methyl 4-methyl-5-(2-bromoethyl)-2-(4-ethylphenyl-
sulfanyl)-6-phenylbenzoate (8u)
Starting with 7b (283 mg, 2.25 mmol), 3g (460 mg, 1.5 mmol),
TiBr4 (0.826 g, 2.25 mmol) and CH2Cl2 (45 mL), 8u was isolated as
a highly viscous oil (266 mg, 38%). 1H NMR (250 MHz, CDCl3):
d
¼1.15 (t, J¼7.5 Hz, 3H, CH2CH3), 2.13 (s, 3H, CH3), 2.54 (q, J¼7.5 Hz,
3.4.25. Methyl 5-(2hydroxy-5-chlorobenzoyl)-2-(thiophenoxy)-
benzoate (10)
Me3SiOTf (0.3 equiv) was added to 3-formylchromone 9 (1.0 equiv)
at 20 ꢁC. After stirring for 10 min, CH2Cl2 (8 mL) was added, the solu-
tion was cooled to 0 ꢁC and diene 3a (1.3 equiv) was addd. The mixture
was stirred at 20 ꢁC for 12 h and was subsequently poured into an
2H, CH2CH3), 3.03 (t, J¼8.3 Hz, 2H, CH2), 3.39 (t, J¼8.3 Hz, 2H, CH2),
3.77 (s, 3H, OCH3), 6.96–7.66 (m, 10H, ArH). 13C NMR (62 MHz,
CDCl3):
d¼20.1 (CH3), 21.3 (CH3), 28.5 (CH2CH3), 33.1 (CH2), 40.2
(CH2), 52.1 (OCH3), 127.8 (CH), 128.0, 128.8, 129.2 (2CH), 131.2, 132.3
(C), 132.4 (2CH), 132.5 (CH), 133.6, 134.7, 138.0, 139.1, 140.7, 144.1,

7572
I. Iqbal et al. / Tetrahedron 65 (2009) 7562–7572
3. (a) Davis, R. A.; Sandoval, I. T.; Concepcion, G. P.; Moreira da Rocha, R.; Ireland,
C. M. Tetrahedron 2003, 59, 2855; (b) Liu, H.; Fujiwara, T.; Nishikawa, T.; Mis-
hima, Y.; Nagai, H.; Shida, T.; Tachibana, K.; Kobayashi, H.; Mangindaan, R. E. P.;
Namikoshi, M. Tetrahedron 2005, 61, 8611.
4. Kaplan, M. L.; Reents, W. D. Tetrahedron Lett. 1982, 23, 373.
5. Hosoya, Y.; Adachi, H.; Nakamura, H.; Nishimura, Y.; Naganawa, H. Tetrahedron
Lett. 1996, 37, 9227.
6. See for example: (a) Dougherty, G.; Hammond, P. D. J. Am. Chem. Soc. 1935,
57, 117; (b) Glass, H. B.; Reid, E. E. J. Am. Chem. Soc. 1929, 51, 3428; For the
trifluoromethanesulfonic acid-catalyzed sulfurization of cycloalkanes, see:
(c) Olah, G. A.; Wang, Q.; Prakash, G. K. S. J. Am. Chem. Soc. 1990, 112, 3697.
7. See for example: Kemp, D. S.; Carey, R. I.; Dewan, J. C.; Galakatos, N. G.; Kerk-
man, D.; Leung, S.-L. J. Org. Chem. 1989, 54, 1589.
8. See for example: Chua, M.; Hoyer, H. Z. Naturforsch., B 1965, 20, 416.
9. (a) Campbell, J. R. J. Org. Chem. 1964, 29, 1830; (b) Baxter, I.; Ben-Haida, A.;
Colquhoun, H. M.; Hodge, P.; Kohnke, F. H.; Williams, D. J. Chem.dEur. J. 2000, 6,
4285.
aqueous solution of HCl (10%). The organic and the aqueous layer was
separated and the latter was extracted 3 times with 15 mL of CH2Cl2.
The combined filtrate was washed with 25 mL and dried over Na2SO4.
The solvent was removed under reduced pressure and crude product
was purified by chromatography (silica gel, EtOAc/n-heptane). Starting
with 3-formylchromone 9 (417 mg, 2.0 mmol), 1-trimethylsilyloxy-3-
thioaryloxy-1,3-butadiene 3a (562 mg, 2.0 mmol), and Me3SiOTf
(0.11 mL, 0.65 mmol), 10 was isolated as a highly viscous oil (174 mg,
22%). 1H NMR (250 MHz, CDCl3):
d
¼3.92 (s, 3H, OCH3), 6.82 (d,
J¼8.5 Hz, 1H, ArH), 6.95 (d, J¼8.2 Hz, 1H, ArH), 7.35–7.47 (m, 6H, ArH),
7.53–7.57 (m, 2H, ArH), 8.28 (d, J¼2.0 Hz,1H, ArH),11.64 (s,1H, OH). 13C
NMR (62 MHz, CDCl3):
d
¼52.5 (CH3), 119.5 (C), 120.2 (CH), 123.5, 125.9
(C), 126.6, 129.9 (CH), 130.1 (2C, CH), 130.8 (C), 131.7. 132.2, 132.3 (CH),
10. (a) Hilt, G.; Lu¨ ers, S. Synthesis 2003, 1784; (b) Hilt, G.; Lu¨ers, S.; Harms, K. J. Org.
Chem. 2004, 69, 624.
11. (a) Rashid, M. A.; Reinke, H.; Langer, P. Tetrahedron Lett. 2007, 48, 2321;
(b) Rashid, M. A.; Rasool, N.; Adeel, M.; Reinke, H.; Fischer, C.; Langer, P.
Tetrahedron 2008, 64, 3782.
12. For a review of [3þ3] cyclizations, see: Feist, H.; Langer, P. Synthesis 2007, 327.
13. For a review of 1,3-bis(silyloxy)-1,3-butadienes, see: Langer, P. Synthesis 2002,
441.
132.7 (C), 136.0 (2C, CH), 136.2 (CH), 150.1, 161.5, 165.8, 198.4 (C). IR
~
(ATR):
n
¼ 2952ðwÞ, 2922 (w),1720 (s),1629 (s),1582 (s),1463 (s),1310
(m), 1263 (s), 1046 (s), 952 (m), 722 (s), 643 (m), 536 (w) cmꢀ1. GC–MS
(EI, 70 eV): m/z (%): 400 (Mþ, 37Cl, 40), 398 (Mþ,35Cl,100), 365 (44), 337
(33), 244 (33), 184 (23), 155 (27), 99 (13); HRMS (EI) calcd for
C21H15ClO4S [Mþ, 35Cl]: 398.03687, found 398.03741.
14. (a) Chan, T. H.; Brownbridge, P. J. Am. Chem. Soc. 1980, 102, 3534; (b) Brown-
bridge, P.; Chan, T. H.; Brook, M. A.; Kang, G. J. Can. J. Chem. 1983, 61, 688.
15. (a) Chan, T. H.; Prasad, C. V. C. J. Org. Chem. 1986, 51, 3012; (b) Chan, T. H.;
Prasad, C. V. C. J. Org. Chem. 1987, 52, 110.
Acknowledgements
16. Imran, M.; Iqbal, I.; Rasool, N.; Rashid, M. A.; Langer, P. Synlett 2008, 2708.
17. Iqbal, I.; Imran, M.; Villinger, A.; Langer, P. Synthesis 2009, 297.
18. Rashid, M. A.; Rasool, N.; Iqbal, I.; Imran, M.; Langer, P. Tetrahedron Lett. 2008,
49, 2466.
Financial support by the State of Pakistan (HEC-scholarships for
M.A.R., N.R.and I.I.) and by the State of Mecklenburg-Vorpommern
(scholarship for M.I. and M.H.) is gratefully acknowledged.
19. CCDC-721314 contains all crystallographic details of this publication which are
available free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html or can be
ordered from the following address: Cambridge Crystallographic Data Centre,
12 Union Road, GB-Cambridge CB21EZ; fax: (þ44) 1223 336 033; or deposit@
ccdc.cam.ac.uk).
References and notes
1. Seeforexample:Mori, Y.;Taneda,S.;Hayashi, H.; Sakushima, A.;Kamata, K.;Suzuki,
A. K.; Yoshino, S.; Sakata, M.; Sagai, M.; Seki, K.-i. Biol. Pharm. Bull. 2002, 25, 145.
2. (a) Davidson, B. S.; Molinski, T. F.; Barrows, L. R.; Ireland, C. M. J. Am. Chem. Soc.
1991, 113, 4709; (b) Behar, V.; Danishefsky, S. J. J. Am. Chem. Soc. 1993, 115, 7017;
(c) Toste, F. D.; Still, I. W. J. J. Am. Chem. Soc. 1995, 117, 7261.
20. Danishefsky, S. J. Acc. Chem. Res. 1979, 66.
21. For
a spiro-activation, see for example: Zefirov, N. S.; Kozhushkov, S. I.;
Kuznetsova, T. S. Tetrahedron 1982, 38, 1693.
22. Appel, B.; Rotzoll, S.; Reinke, H.; Langer, P. Eur. J. Org. Chem. 2006, 3638.