Regioselective synthesis of 2-(Aryloxythio)benzoates by the first [3+3] cyclizations of 3-aryloxythio-1-silyloxybuta-1,3-dienes with 3-alkoxy-2-en-1-ones

Article abstract of DOI:10.1055/s-0028-1083287

Functionalized 2-(aryloxythio)benzoates were regio-selectively prepared by the first [3+3] cyclizations of 3-aryloxythio-1-trimethylsilyloxybuta-1,3-dienes with 3-alkoxy-2-en-1-ones. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0028-1083287

PAPER
297
Regioselective Synthesis of 2-(Aryloxythio)benzoates by the First
[3+3] Cyclizations of 3-Aryloxythio-1-silyloxybuta-1,3-dienes with
3-Alkoxy-2-en-1-ones
R
egiosel
n
ective Synthe
a
sis of 2-(A
m
ryloxythio)benzoates Iqbal,a Muhammad Imran,a Alexander Villinger,a Peter Langer*a,b
a
Institut für Chemie, Universität Rostock, Albert Einstein Str. 3a, 18059 Rostock, Germany
Leibniz-Institut für Katalyse an der Universität Rostock e.V., Albert Einstein Str. 29a, 18059 Rostock, Germany
Fax +49(381)4986412; E-mail: peter.langer@uni-rostock.de
b
Received 16 July 2008; revised 23 September 2008
tion.13 The synthesis of methyl 4,6-dimethyl-2-
(phenoxythio)benzoate by cyclization of 1-methoxy-1-tri-
methylsilyloxy-3-phenoxythiobuta-1,3-diene with 4-(tri-
methylsilyloxy)pent-3-en-2-one has also been reported.13
Recently, we have studied the synthesis of 2-aryloxythio-
5-(haloethyl)benzoates by cyclization of 3-aryloxythio-1-
silyloxybuta-1,3-dienes with 1,1-diacylcyclopropanes.14
Herein we report what are, to the best of our knowledge,
the first [3+3] cyclizations of 3-aryloxythio-1-silyloxybu-
ta-1,3-dienes with 3-alkoxy-2-en-1-ones. These reactions
provide a convenient and regioselective approach to ster-
ically encumbered and functionalized 2-(aryloxythio)ben-
zoates, which are not readily available by other methods.
In contrast to the coupling reactions outlined above, our
method relies on the assembly of one of the two arene
moieties.
Abstract: Functionalized 2-(aryloxythio)benzoates were regio-
selectively prepared by the first [3+3] cyclizations of 3-aryloxythio-
1-trimethylsilyloxybuta-1,3-dienes with 3-alkoxy-2-en-1-ones.
Key words: cyclizations, diaryl sulfides, regioselectivity, py-
ridines, silyl enol ethers
Diaryl sulfides are pharmacologically relevant com-
pounds that occur in a number of natural products. Prom-
inent examples include lissoclibadins, dibenzothiophenes,
cyclic sulfides, varacins (lissoclinotoxins), and related
natural products.1 Classic syntheses of diaryl sulfides
include, for example, reactions of arenes with sulfur2 or
sulfur dichloride,3 condensations of Grignard or organo-
lithium reagents with chlorophenyl sulfides4 or base-me-
diated reactions of thiophenols with chloroarenes.5 The
formation of polysulfides and low regioselectivities are
severe drawbacks of these methods. In contrast, transi-
tion-metal-catalyzed6 and metal-free7 C–S coupling reac-
tions allow the synthesis of diaryl sulfides under relatively
mild conditions. However, the scope of this approach is
limited by the fact that reactions of sterically encumbered
substrates are often difficult or not possible at all. In addi-
tion, the synthesis of the starting materials, substituted
aryl halides or triflates, can be difficult and tedious.
The reaction of b-keto esters 1a–c with various thiophe-
nols gave, following the procedure reported by Chan et
al.,13 the 3-(aryloxythio)alkanoates 2a–k (Scheme 1).
Deprotonation of 2a–k (LDA) and subsequent addition of
Me3SiCl afforded, again following the procedure reported
by Chan et al.,13 the 3-aryloxythio-1-silyloxybuta-1,3-
dienes 3a–k. The synthesis of 2a and 3a has been previ-
ously reported.13 Dienes 3a–k proved to be unstable and
had to be used directly after their preparation.
An interesting alternative for the synthesis of diaryl sul-
fides is based on the use of appropriate sulfur-containing
building blocks in cyclization reactions. Such reactions
have only scarcely been reported to date. Hilt and co-
workers reported the synthesis of diaryl sulfides by co-
balt(I)-catalyzed [4+2] cycloaddition of alkynyl sulfides
with buta-1,3-dienes.8 Some years ago, Chan and co-
workers developed9 a convenient approach to salicylates
based on formal [3+3] cyclizations10 of 1,3-bis(silyl-
oxy)buta-1,3-dienes11 with 3-siloxy-2-en-1-ones. We
have recently reported the application of this methodolo-
gy to the synthesis of 3- and 5-(aryloxythio)salicylates.12
Chan et al. developed an elegant synthesis of annulated
cyclohexanones by conjugate addition of 1-methoxy-1-
trimethylsilyloxy-3-phenoxythiobuta-1,3-diene to cyclo-
hex-2-en-1-ones and subsequent base-mediated cycliza-
O
O
SAr
O
ArSH
i
R1
R1
OMe
OMe
1a–c
2a–k (76–94%)
OSiMe3
OMe
SAr
R1
ii
3a–k (78–96%)
Scheme 1 Synthesis of 3a–k (for R1 and Ar, see Table 1). Reagents
and conditions: (i) P4O10, CH2Cl2, 20 °C, 18 h; (ii) 1) LDA, THF,
–78 °C, 1 h; 2) Me3SiCl, –78 → 20 °C, 14 h.
The TiCl4-mediated cyclization of 3-phenoxythio-1-silyl-
oxybuta-1,3-diene (3a) with 1-(methoxy)but-1-en-3-one
(4a) afforded methyl 6-methyl-2-(phenoxythio)benzoate
(5a) with very good regioselectivity (Scheme 2). Notably,
the formation of regioisomeric methyl 4-methyl-2-(phen-
oxythio)benzoate was not observed. The best yields were
obtained when the reaction was carried out in a highly
concentrated solution. The use of an excess (1.5 equiv) of
SYNTHESIS 2009, No. 2, pp 0297–0305
x
x
.
x
x
.2
0
0
8
Advanced online publication: 19.12.2008
DOI: 10.1055/s-0028-1083287; Art ID: T11608SS
© Georg Thieme Verlag Stuttgart · New York

298
I. Iqbal et al.
PAPER
SAr OSiMe3
OMe
PhS
OSiMe3
OMe
O
SPh
R1
OMe
O
SAr
O
OMe
3a
R1
3a–k
Me
i
OMe
i
Me
5a (53%)
+
OR
O
R2
4a
R2
TiCl4
5a–r
TiCl2(OH)OMe
Me3SiCl
4a–c
Scheme 3 Synthesis of 5a–r. Reagents and conditions: (i) 1) TiCl4,
CH2Cl2, –78 → 20 °C, 20 h; 2) NaHCO3, H2O.
O
SPh
O
PhS
OMe
TiCl3OMe
OMe
OTiCl2OMe
O
The cyclization of dienes 3a–k with 4a afforded the 2-aryl-
oxythio-6-methylbenzoates 5a–j (Scheme 3, Table 1).
The cyclization of dienes 3 with 3-ethoxy-1-(aryl)prop-2-
en-1-ones 4b,c, readily available by Heck reaction of eth-
ylvinyl ether with benzoyl chloride and 4-chlorobenzoyl
chloride,15 afforded the 6-aryl-2-(aryloxythio)benzoates
5k–r. The relatively low yields might be explained by de-
composition of the starting materials by HCl formed dur-
ing the reaction.
Me
Me
HCl
A
B
Scheme 2 Possible mechanism for the formation of 5a. Reagents
and conditions: (i) 1) TiCl4, CH2Cl2, –78 → 20 °C, 20 h; 2) NaHCO3,
H2O.
4a and of TiCl4 also proved to be important. The forma-
tion of 5a can be explained by TiCl4-mediated conjugate
addition of the terminal carbon atom of 3a onto 4a to give
intermediate A, cyclization via the central carbon atom
(intermediate B), and subsequent aromatization.
The structures of all products were established by spectro-
scopic methods. The structure of 5p was independently
confirmed by X-ray crystal structure analysis (Figure 1).16
Table 1 Synthesis of 5a–r
3
a
b
c
d
e
f
4
a
a
a
a
a
a
a
a
a
a
b
b
c
c
c
c
c
c
5
a
b
c
d
e
f
R1
H
Ar
R2
R
Yield(%)a 2 Yield (%)a 3 Yield (%)a 5
Ph
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
90
80
82
80
85
75
85
84
74
84
90
87
90
87
85
80
81
84
90
80
87
86
88
79
83
82
78
83
90
84
90
84
88
80
82
83
53
37
50
48
51
33
37
40
34
35
40
37
47
46
47
35
40
36
H
4-FC6H4
3-MeC6H4
3-ClC6H4
4-MeC6H4
2-naphthyl
4-MeC6H4
Ph
Me
H
Me
H
Me
H
Me
H
Me
g
h
i
g
h
i
Me
Me
Me
Et
H
Me
Me
4-FC6H4
Ph
Me
j
j
Me
a
k
a
k
e
b
h
j
k
l
Ph
Ph
H
4-ClC6H4
Ph
Ph
Et
m
n
o
p
q
r
H
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
4-ClC6H4
Et
H
4-ClC6H4
4-MeC6H4
4-FC6H4
Ph
Et
H
Et
H
Et
Me
Et
Et
Ph
Et
a Isolated yields.
Synthesis 2009, No. 2, 297–305 © Thieme Stuttgart · New York

PAPER
Regioselective Synthesis of 2-(Aryloxythio)benzoates
299
was isolated as a highly viscous oil (15.8 g, 80%, isomeric
ratio = 3:1).
IR (KBr): 3022 (w), 2986 (w), 2949 (w), 2868 (w), 2839 (w), 1709
(s), 1604 (s), 1491 (m), 1431 (m), 1378 (w), 1335 (m), 1269 (w),
1175 (s), 1104 (s), 1038 (m), 1019 (m), 809 cm–1 (s).
1H NMR (250 MHz, CDCl3): d = 2.39 (s, 3 H, CH3), 3.59 (s, 3 H,
OCH3), 5.11 (s, 1 H, CH), 6.85–7.44 (m, 4 H, Ar).
13C NMR (63 MHz, CDCl3): d = 19.8 (CH3), 51.2 (OCH3), 111.1
(CH), 128.3, 129.8, 129.9, 130.5, 135.6 (CH), 146.2, 160.7, 164.3
(C).
MS (EI, 70 eV): m/z (%) = 226 (M+, 59), 191 (38), 169 (19), 163
(100), 148 (31), 124 (39), 123 (17), 91 (27), 79 (12), 77 (19), 59
(18), 45 (15), 39 (19).
HRMS (EI): m/z calcd for C11H11FO2S (M+): 226.06952; found:
222.059604.
Figure 1 ORTEP plot of 5p (50% probability level)
In conclusion, we have reported a convenient and regio-
selective approach to functionalized 2-(aryloxythio)ben-
zoates by the first [3+3] cyclizations of 3-aryloxythio-1-
trimethylsilyloxybuta-1,3-dienes with 3-alkoxy-2-en-1-
ones.
3-(3-Methylphenylsulfanyl)but-2-enoic Acid Methyl Ester (2c)
Starting from 1a (9.30 g, 80.0 mmol), the respective arylthiol (9.90
g, 80.0 mmol), P4O10 (22.60 g, 80.0 mmol), and CH2Cl2 (80 mL), 2c
was isolated as a highly viscous oil (14.60 g, 82%, isomeric
ratio = 3:1).
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 spectrometric
data (MS) were obtained by electron ionization (EI, 70 eV), chemi-
cal ionization (CI, H2O), or electrospray ionization (ESI). For pre-
parative scale chromatography, silica gel (60–200 mesh) was used.
Melting points are uncorrected.
IR (KBr): 3021 (w), 2987 (w), 2946 (w), 2867 (w), 2838 (w), 1707
(s), 1608 (s), 1494 (m), 1433 (m), 1377 (w), 1335 (m), 1269 (w),
1104 (s), 1038 (m), 1019 (m), 807 cm–1 (s).
1H NMR (250 MHz, CDCl3): d = 2.38 (s, 3 H, CH3), 2.47 (s, 3 H,
CH3), 3.58 (s, 3 H, OCH3), 5.27 (s, 1 H, CH), 7.18–7.54 (m, 4 H,
Ar).
13C NMR (63 MHz, CDCl3): d = 19.9 (CH3), 21.7 (CH3), 50.9
(OCH3), 108.7 (CH), 129.8, 130.5, 130.6, 135.3, 135.7 (CH), 135.9,
160.7, 164.3 (C).
MS (EI, 70 eV): m/z (%) = 222 (M+, 59), 193 (38), 169 (19), 163
(100), 148 (31), 124 (39), 123 (17), 91 (27), 79 (12), 77 (19), 59
(18), 45 (15), 39 (19).
Compounds 2a–k; General Procedure
To a CH2Cl2 solution (1 mL/mmol of 1) of 1 (80.0 mmol) and the
respective arylthiol (80.0 mmol) was added P4O10 (80.0 mmol) at
20 °C and the mixture was stirred for 18 h. To the mixture was add-
ed 10% aq NaOH (80 mL). The aqueous and the organic layer were
separated and the latter was washed with brine (100 mL). The aque-
ous layer was extracted with CH2Cl2 (3 × 100 mL). The combined
organic layers were dried (Na2SO4), filtered, and the filtrate was
concentrated in vacuo. The residue was purified by chromatography
(silica gel, EtOAc–heptanes, 1:4) (Table 1). The products were iso-
lated as mixture of E/Z isomers. Only the signals of the major iso-
mer are listed.
HRMS (EI): m/z calcd for C12H14O2S (M+): 222.07090; found:
222.070604.
3-(3-Chlorophenylsulfanyl)but-2-enoic Acid Methyl Ester (2d)
Starting from 1a (9.30 g, 80.0 mmol), the respective arylthiol (11.50
g, 80.0 mmol), P4O10 (22.60 g, 90.0 mmol), and CH2Cl2 (80 mL), 2d
was isolated as a highly viscous oil (15.50 g, 80%, isomeric
ratio = 3:1).
3-(Phenylsulfanyl)but-2-enoic Acid Methyl Ester (2a)
Starting from 1a (9.3 g, 80 mmol), the respective arylthiol (8.80 g,
80.0 mmol), P4O10 (22.60 g, 90.0 mmol), and CH2Cl2 (80 mL), 2a
was isolated as a highly viscous oil (14.50 g, 80%, isomeric
ratio = 3:1).
IR (KBr): 3020 (w), 2982 (w), 2945 (w), 2920 (w), 2866 (w), 2838
(w), 1709 (s), 1605 (s), 1491 (m), 1431 (m), 1379 (w), 1335 (m),
1268 (w), 1175 (s), 1104 (s), 1036 (m), 1017 (m), 809 cm–1 (s).
1H NMR (250 MHz, CDCl3): d = 2.40 (s, 3 H, CH3), 3.69 (s, 3 H,
OCH3), 5.41 (s, 1 H, CH), 6.71–7.34 (m, 4 H, Ar).
13C NMR (63 MHz, CDCl3): d = 23.3 (CH3), 52.3 (OCH3), 111.3
(CH), 128.3, 129.8, 129.9, 130.5, 135.6 (CH), 139.9, 160.7, 166.4
(C).
MS (EI, 70 eV): m/z (%) = 244 (M+, 37Cl, 16), 242 (M+, 35Cl, 71),
191 (38), 164 (17), 163 (100), 148 (31), 124 (39), 123 (17), 91 (27),
79 (12), 77 (15), 59 (18), 45 (11), 39 (12).
IR (KBr): 3020 (w), 2980 (w), 2946 (w), 2920 (w), 2866 (w), 2838
(w), 1707 (s), 1604 (s), 1491 (m), 1431 (m), 1374 (w), 1335 (m),
1266 (w), 1175 (s), 1104 (s), 1038 (m), 1017 (m), 809 cm–1 (s).
1H NMR (250 MHz, CDCl3): d = 2.37 (s, 3 H, CH3), 3.59 (s, 3 H,
OCH3), 5.21 (s, 1 H, CH), 7.31–7.54 (m, 5 H, Ar).
13C NMR (63 MHz, CDCl3): d = 19.9 (CH3), 51.1 (OCH3), 110.1
(CH), 128.3, 129.8, 129.9, 130.5, 135.6 (CH), 135.9, 160.7, 164.3
(C).
MS (EI, 70 eV): m/z (%) = 222 (M+, 60), 191 (38), 164 (17), 163
(100), 148 (31), 124 (39), 123 (17), 91 (27), 79 (12), 77 (15), 59
(18), 45 (11), 39 (12).
HRMS (EI): m/z calcd for C11H12O2S (M+): 242.47097; found:
242.510684.
HRMS (EI): m/z calcd for C11H12O2S (M+): 208.07097; found:
208.090604.
3-(4-Methylphenylsulfanyl)but-2-enoic Acid Methyl Ester (2e)
Starting from 1a (9.30 g, 80.0 mmol), the respective arylthiol (9.90
g, 80.0 mmol), P4O10 (22.60 g, 80.0 mmol), and CH2Cl2 (80 mL), 2e
was isolated as a highly viscous oil (15.30 g, 85%, isomeric
ratio = 3:1).
3-(4-Fluorophenylsulfanyl)but-2-enoic Acid Methyl Ester (2b)
Starting from 1a (9.30 g, 80.0 mmol), the respective arylthiol (10.20
g, 80.0 mmol), P4O10 (22.60 g, 80.0 mmol), and CH2Cl2 (80 mL), 2b
Synthesis 2009, No. 2, 297–305 © Thieme Stuttgart · New York

300
I. Iqbal et al.
PAPER
IR (KBr): 3021 (w), 2987 (w), 2946 (w), 2867 (w), 2838 (w), 1707
(s), 1608 (s), 1494 (m), 1433 (m), 1377 (w), 1335 (m), 1269 (w),
1104 (s), 1038 (m), 1019 (m), 807 cm–1 (s).
1H NMR (250 MHz, CDCl3): d = 1.22 (t, J = 6.3 Hz, 3 H, CH3),
2.48 (q, J = 6.3 Hz, 2 H, CH2), 3.35 (s, 3 H, OCH3), 5.25 (s, 1 H,
CH), 6.93–7.21 (m, 5 H, Ar).
1H NMR (250 MHz, CDCl3): d = 2.38 (s, 3 H, CH3), 2.47 (s, 3 H,
CH3), 3.58 (s, 3 H, OCH3), 5.27 (s, 1 H, CH), 7.18–7.54 (m, 4 H,
Ar).
13C NMR (63 MHz, CDCl3): d = 19.9 (CH3), 21.9 (CH3CH2), 50.9
(OCH3), 108.7 (CH), 129.8, 130.5, 130.6, 135.7, 140.1 (CH), 159.1,
159.8, 164.3 (C).
13C NMR (63 MHz, CDCl3): d = 19.9 (CH3), 21.7 (CH3), 50.9
(OCH3), 108.7 (CH), 129.8, 130.5, 130.6, 135.3, 135.7 (CH), 135.9,
160.7, 164.3 (C).
MS (EI, 70 eV): m/z (%) = 222 (M+, 63), 195 (38), 169 (19), 163
(100), 148 (31), 124 (39), 123 (17), 91 (27), 79 (12), 77 (19), 59
(18), 45 (15), 39 (19).
MS (EI, 70 eV): m/z (%) = 222 (M+, 59), 193 (38), 169 (19), 163
(100), 148 (31), 124 (39), 123 (17), 91 (27), 79 (12), 77 (19), 59
(18), 45 (15), 39 (19).
HRMS (EI): m/z calcd for C12H14O2S (M+): 222.05090; found:
222.060602.
3-(4-Fluorophenylsulfanyl)pent-2-enoic Acid Methyl Ester (2i)
Starting from 1a (10.40 g, 80.0 mmol), the respective arylthiol
(10.20 g, 80.0 mmol), P4O10 (22.60 g, 90.0 mmol), and CH2Cl2 (80
mL), 2i was isolated as a highly viscous oil (14.10 g, 74%, isomeric
ratio = 3:1).
HRMS (EI): m/z calcd for C12H14O2S (M+): 222.07090; found:
222.070604.
3-(Naphth-2-ylsulfanyl)but-2-enoic Acid Methyl Ester (2f)
Starting from 1a (9.30 g, 80.0 mmol), the respective arylthiol (10.20
g, 80.0 mmol), P4O10 (22.6 g, 80.0 mmol), and CH2Cl2 (80 mL), 2f
was isolated as a highly viscous oil (15.5 g, 75%, isomeric
ratio = 3:1).
IR (KBr): 3024 (w), 2985 (w), 2946 (w), 2867 (w), 2837 (w), 1707
(s), 1608 (s), 1494 (m), 1433 (m), 1377 (w), 1335 (m), 1267 (w),
1102 (s), 1038 (m), 1019 (m), 807 cm–1 (s).
IR (KBr): 3021 (w), 2987 (w), 2946 (w), 2867 (w), 2838 (w), 1707
(s), 1608 (s), 1494 (m), 1433 (m), 1377 (w), 1335 (m), 1269 (w),
1104 (s), 1038 (m), 1019 (m), 807 cm–1 (s).
1H NMR (250 MHz, CDCl3): d = 1.30 (t, J = 6.3 Hz, 3 H, CH3), 2.32
(q, J = 6.3 Hz, 2 H, CH2), 3.40 (s, 3 H, OCH3), 5.20 (s, 1 H, CH),
7.01–7.82 (m, 4 H, Ar).
1H NMR (250 MHz, CDCl3): d = 2.37 (s, 3 H, CH3), 3.45 (s, 3 H,
13C NMR (63 MHz, CDCl3): d = 19.9 (CH3), 21.9 (CH3CH2), 50.9
(OCH3), 108.7 (CH), 129.8, 130.5, 135.7, 140.1 (CH), 159.1, 159.8,
160.5, 165.3 (C).
MS (EI, 70 eV): m/z (%) = 240 (M+, 63), 195 (38), 169 (19), 163
(100), 148 (31), 124 (39), 123 (17), 91 (27), 79 (12), 77 (19), 59
(18), 45 (15), 39 (19).
OCH3), 5.17 (s, 1 H, CH), 7.38–7.94 (m, 7 H, Ar).
13C NMR (63 MHz, CDCl3): d = 19.9 (CH3), 50.9 (OCH3), 108.7
(CH), 129.8, 130.5, 130.6, 135.3, 135.7, 135.9, 140.5 (CH), 159.1,
159.8, 160.1, 160.7, 164.3 (C).
MS (EI, 70 eV): m/z (%) = 258 (M+, 61), 193 (38), 169 (19), 163
(100), 148 (31), 124 (39), 123 (17), 91 (27), 79 (12), 77 (19), 59
(18), 45 (15), 39 (19).
HRMS (EI): m/z calcd for C12H13FO2S (M+): 240.07280; found:
240.067602.
HRMS (EI): m/z calcd for C15H14O2S (M+): 258.07090; found:
258.070604.
3-(Phenylsulfanyl)hex-2-enoic Acid Methyl Ester (2j)
Starting from 1a (11.50 g, 80.0 mmol), the respective arylthiol (8.80
g, 80.0 mmol), P4O10 (22.6 g, 90.0 mmol), and CH2Cl2 (80 mL), 2j
was isolated as a highly viscous oil (15.80 g, 84%, isomeric
ratio = 3:1).
3-(4-Tolylsulfanyl)pent-2-enoic Acid Methyl Ester (2g)
Starting from 1a (10.40 g, 80.0 mmol), the respective arylthiol (9.90
g, 80.0 mmol), P4O10 (22.6 g, 80.0 mmol), and CH2Cl2 (80 mL), 2g
was isolated as a highly viscous oil (16.10 g, 85%, isomeric
ratio = 3:1).
IR (KBr): 3024 (w), 2985 (w), 2946 (w), 2867 (w), 2837 (w), 1707
(s), 1608 (s), 1494 (m), 1433 (m), 1377 (w), 1335 (m), 1267 (w),
1102 (s), 1038 (m), 1019 (m), 807 cm–1 (s).
1H NMR (250 MHz, CDCl3): d = 1.10 (t, J = 6.3 Hz, 3 H, CH3), 1.70
(m, 2 H, CH2), 2.30 (q, J = 6.3 Hz, 2 H, CH2), 3.52 (s, 3 H, OCH3),
5.30 (s, 1 H, CH), 6.80–7.30 (m, 5 H, Ar).
13C NMR (63 MHz, CDCl3): d = 19.9 (CH3), 21.9 (CH3CH2), 22.9
(CH2CH2), 50.9 (OCH3), 108.7 (CH), 129.8, 130.5, 130.9, 135.7,
140.1 (CH), 159.1, 160.5, 165.3 (C).
MS (EI, 70 eV): m/z (%) = 236 (M+, 61), 193 (36), 167 (34), 161
(100), 148 (31), 124 (39), 123 (17), 91 (27), 79 (12), 77 (19), 59
(18), 45 (15), 39 (19).
IR (KBr): 3021 (w), 2987 (w), 2946 (w), 2867 (w), 2838 (w), 1707
(s), 1608 (s), 1494 (m), 1433 (m), 1377 (w), 1335 (m), 1269 (w),
1104 (s), 1038 (m), 1019 (m), 807 cm–1 (s).
1H NMR (250 MHz, CDCl3): d = 1.20 (t, J = 6.3 Hz, 3 H, CH3), 2.08
(s, 3 H, CH3), 2.41 (q, J = 6.3 Hz, 2 H, CH2), 3.34 (s, 3 H, OCH3),
5.21 (s, 1 H, CH), 6.81–7.12 (m, 4 H, Ar).
13C NMR (63 MHz, CDCl3): d = 19.9 (CH3), 21.1 (CH3), 29.3
(CH3CH2), 50.9 (OCH3), 108.7 (CH), 129.8, 130.5, 135.3, 135.9
(CH), 159.1, 159.8, 160.7, 164.3 (C).
MS (EI, 70 eV): m/z (%) = 236 (M+, 61), 193 (38), 169 (19), 161
(100), 148 (31), 124 (39), 123 (17), 91 (27), 79 (12), 77 (19), 59
(18), 45 (15), 39 (19).
HRMS (EI): m/z calcd for C13H16O2S (M+): 236.06020; found:
240.065202.
HRMS (EI): m/z calcd for C13H16O2S (M+): 236.07090; found:
236.070604.
3-(4-Chlorophenylsulfanyl)pent-2-enoic Acid Methyl Ester (2k)
Starting from 1a (10.40 g, 80.0 mmol), the respective arylthiol (80.0
mmol), P4O10 (22.60 g, 90.0 mmol), and CH2Cl2 (80 mL), 2k was
isolated as a highly viscous oil (3:1 isomeric ratio) (14.00 g, 70%,
isomeric ratio = 3:1). The product was used directly after its prepa-
ration for the synthesis of 3k.
3-(Phenylsulfanyl)pent-2-enoic Acid Methyl Ester (2h)
Starting from 1a (10.40 g, 80.0 mmol), the respective arylthiol (8.80
g, 80.0 mmol), P4O10 (22.60 g, 90.0 mmol), and CH2Cl2 (80 mL), 2h
was isolated as a highly viscous oil (14.90 g, 84%, isomeric
ratio = 3:1).
Compounds 3a–k; General Procedure
To a THF solution (1.2 mL/mmol of 2) of diisopropylamine (DIPA,
84.5 mmol) was added n-BuLi (84.5 mmol) at 0 °C. After stirring
IR (KBr): 3024 (w), 2985 (w), 2946 (w), 2867 (w), 2837 (w), 1707
(s), 1608 (s), 1494 (m), 1433 (m), 1377 (w), 1335 (m), 1267 (w),
1102 (s), 1038 (m), 1019 (m), 807 cm–1 (s).
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Regioselective Synthesis of 2-(Aryloxythio)benzoates
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for 45 min, 2 (65.0 mmol) was added at –78 °C. After stirring for 1
h, TMSCl (97.5 mmol) was added at –78 °C and the mixture was al-
lowed to warm to 20 °C during 18 h with stirring. The solvent was
removed in vacuo. To the residue was added heptane (100 mL) and
the mixture was filtered under an inert atmosphere. The filtrate was
concentrated in vacuo to give products 3, which were used without
further purification (Table 1). Due to their unstable nature, products
3 were used directly after their preparation and characterized only
by 1H NMR spectroscopy. The products were isolated as mixtures
of E/Z isomers. Only the signals of the major isomer are listed.
was isolated as a highly viscous oil (13.20 g, 79%, isomeric
ratio = 3:1).
1H NMR (250 MHz, CDCl3): d = 0.19 [s, 9 H, Si(CH3)3], 3.32 (s, 3
H, OCH3), 3.46 (s, 2 H, CH2), 5.29 (s, 1 H, CH), 7.01–7.51 (m, 7 H,
Ar).
[1-Methoxy-3-(4-methylphenylsulfanyl)penta-1,3-dienyl-
oxy]trimethylsilane (3g)
Starting from 2g (15.30 g, 65.0 mmol), DIPA (8.50 g, 84.5 mmol),
n-BuLi (5.40 g, 84.5 mmol) and TMSCl (10.50 g, 97.5 mmol), 3g
was isolated as a highly viscous oil (16.50 g, 83%, isomeric
ratio = 3:1).
1H NMR (250 MHz, CDCl3): d = 0.04 [s, 9 H, Si(CH3)3], 1.72 (s, 3
H, CH3), 2.08 (d, J = 5.5 Hz, 3 H, CH3), 3.15 (s, 3 H, OCH3), 6.03
(q, J = 5.5 Hz, 1 H, CH), 6.84 (s, 1 H, CH), 6.92–7.28 (m, 4 H, Ar).
[1-Methoxy-3-(phenylsulfanyl)buta-1,3-dienyloxy]trimethyl-
silane (3a)
Starting from 2a (13.50 g, 65.0 mmol), DIPA (8.50 g, 84.5 mmol),
n-BuLi (5.40 g, 84.5 mmol) and TMSCl (10.50 g, 97.5 mmol), 3a
was isolated as a highly viscous oil (16.30 g, 90%, isomeric
ratio = 3:1).
1H NMR (250 MHz, CDCl3): d = 0.17 [s, 9 H, Si(CH3)3], 3.34 (s, 3
H, OCH3), 3.47 (s, 2 H, CH2), 5.29 (s, 1 H, CH), 7.02–7.31 (m, 5 H,
Ar).
[1-Methoxy-3-(phenylsulfanyl)penta-1,3-dienyloxy)]trimethyl-
silane (3h)
Starting from 2h (14.40 g, 65.0 mmol), DIPA (8.50 g, 84.5 mmol),
n-BuLi (5.40 g, 84.5 mmol) and TMSCl (10.50 g, 97.5 mmol), 3h
was isolated as a highly viscous oil (15.6 g, 82%, isomeric
ratio = 3:1).
1H NMR (250 MHz, CDCl3): d = 0.04 [s, 9 H, Si(CH3)3], 2.12 (d,
J = 5.5 Hz, 3 H, CH3), 3.17 (s, 3 H, OCH3), 6.06 (q, J = 5.5 Hz, 1 H,
CH), 6.84 (s, 1 H, CH), 6.92–7.28 (m, 5 H, Ar).
[1-Methoxy-3-(4-fluorophenylsulfanyl)buta-1,3-dienyloxy]tri-
methylsilane (3b)
Starting from 2b (14.70 g, 65.0 mmol), DIPA (8.50 g, 84.5 mmol),
n-BuLi (5.40 g, 84.5 mmol) and TMSCl (10.50 g, 97.5 mmol), 3b
was isolated as a highly viscous oil (15.50 g, 80%, isomeric
ratio = 3:1).
1H NMR (250 MHz, CDCl3): d = 0.19 [s, 9 H, Si(CH3)3], 3.38 (s, 3
H, OCH3), 3.49 (s, 2 H, CH2), 5.34 (s, 1 H, CH), 7.08–7.51 (m, 4 H,
Ar).
[1-Methoxy-3-(4-fluorophenylsulfanyl)penta-1,3-dienyloxy]tri-
methylsilane (3i)
Starting from 2i (15.60 g, 65.0 mmol), DIPA (8.50 g, 84.5 mmol),
n-BuLi (5.40 g, 84.5 mmol) and TMSCl (10.50 g, 97.5 mmol), 3i
was isolated as a highly viscous oil (15.80 g, 78%, isomeric
ratio = 3:1).
1H NMR (250 MHz, CDCl3): d = 0.04 [s, 9 H, Si(CH3)3], 2.08 (d,
J = 5.5 Hz, 3 H, CH3), 3.15 (s, 3 H, OCH3), 6.05 (q, J = 5.5 Hz, 1 H,
CH), 6.84 (s, 1 H, CH), 6.92–7.28 (m, 4 H, Ar).
[1-Methoxy-3-(3-methylphenylsulfanyl)buta-1,3-dienyloxy)tri-
methylsilane (3c)
Starting from 2c (14.40 g, 65.0 mmol), DIPA (8.50 g, 84.5 mmol),
n-BuLi (5.40 g, 84.5 mmol) and TMSCl (10.50 g, 97.5 mmol), 3c
was isolated as a highly viscous oil (16.60 g, 87%, isomeric
ratio = 3:1).
1H NMR (250 MHz, CDCl3): d = 0.16 [s, 9 H, Si(CH3)3], 2.12 (s, 3
H, CH3), 3.35 (s, 3 H, OCH3), 3.48 (s, 2 H, CH2), 5.27 (s, 1 H, CH),
7.02–7.38 (m, 4 H, Ar).
[1-Methoxy-3-(phenylsulfanyl)hexa-1,3-dienyloxy]trimethyl-
silane (3j)
Starting from 2j (15.30 g, 65.0 mmol), DIPA (8.50 g, 84.5 mmol),
n-BuLi (5.40 g, 84.5 mmol) and TMSCl (10.50 g, 97.5 mmol), 3j
was isolated as a highly viscous oil (16.50 g, 83%, isomeric
ratio = 3:1).
1H NMR (250 MHz, CDCl3): d = 0.04 [s, 9 H, Si(CH3)3], 2.08 (m,
2 H, CH2), 2.6 (t, J = 5.5 Hz, 3 H, CH3), 3.15 (s, 3 H, OCH3), 6.05
(t, J = 5.5 Hz, 1 H, CH), 6.54 (s, 1 H, CH), 6.92–7.30 (m, 5 H, Ar).
[1-Methoxy-3-(3-chlorophenylsulfanyl)buta-1,3-dienyloxy]tri-
methylsilane (3d)
Starting from 2d (15.70 g, 65.0 mmol), DIPA (8.50 g, 84.5 mmol),
n-BuLi (5.40 g, 84.5 mmol) and TMSCl (10.50 g, 97.5 mmol), 3d
was isolated as a highly viscous oil (17.50 g, 86%, isomeric
ratio = 3:1).
[1-Methoxy-3-(4-chlorophenylsulfanyl)buta-1,3-dienyloxy]tri-
methylsilane (3k)
Starting from 2k (15.70 g, 65.0 mmol), DIPA (8.50 g, 84.5 mmol),
n-BuLi (5.40 g, 84.5 mmol) and TMSCl (10.50 g, 97.5 mmol), 3k
was isolated as a highly viscous oil (17.10 g, 84%, isomeric
ratio = 3:1).
1H NMR (250 MHz, CDCl3): d = 0.21 [s, 9 H, Si(CH3)3], 3.49 (s, 2
H, CH2), 5.32 (s, 1 H, CH), 7.04–7.37 (m, 4 H, Ar).
[1-Methoxy-3-(4-methylphenylsulfanyl)buta-1,3-dienyloxy]tri-
methylsilane (3e)
Starting from 2e (14.40 g, 65.0 mmol), DIPA (8.50 g, 84.5 mmol),
n-BuLi (5.40 g, 84.5 mmol) and TMSCl (10.50 g, 97.5 mmol), 3e
was isolated as a highly viscous oil (16.70 g, 88%, isomeric
ratio = 3:1).
1H NMR (250 MHz, CDCl3): d = 0.16 [s, 9 H, Si(CH3)3], 2.14 (s, 3
H, CH3), 3.37 (s, 3 H, OCH3), 3.48 (s, 2 H, CH2), 5.27 (s, 1 H, CH),
7.02–7.38 (m, 4 H, Ar).
1H NMR (250 MHz, CDCl3): d = 0.04 [s, 9 H, Si(CH3)3], 3.49 (s, 2
H, CH2), 5.32 (s, 1 H, CH), 7.04–7.39 (m, 4 H, Ar).
2-(Aryloxythio)benzoates 5a–r; General Procedure
To a CH2Cl2 solution (5 mL/mmol of 3) of 3 (1.0 mmol) and the ap-
propriate 4 (1.5 mmol) was added TiCl4 (1.5 mmol) at –78 °C. The
mixture was allowed to warm to 20 °C within 20 h. To the mixture
was added sat. aq NaHCO3 (15 mL). The organic and the aqueous
layers were separated and the latter was extracted with Et2O (3 × 20
mL). The combined organic layers were dried (Na2SO4), filtered,
and the filtrate was concentrated in vacuo. The residue was purified
by chromatography (silica gel, EtOAc–n-heptane, 1:4) (Table 1).
[1-Methoxy-3-(naphth-2-ylsulfanyl)buta-1,3-dienyloxy)tri-
methylsilane (3f)
Starting from 2f (10.40 g, 65.0 mmol), DIPA (8.50 g, 84.5 mmol),
n-BuLi (5.40 g, 84.5 mmol) and TMSCl (10.50 g, 97.5 mmol), 3f
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Methyl 4-Methyl-2-phenylsulfanylbenzoate (5a)
Starting from 3a (420 mg, 1.5 mmol), 4a (0.23 mL, 2.25 mmol),
TiCl4 (0.25 mL, 2.25 mmol), and CH2Cl2 (9 mL), 5a was isolated as
a highly viscous oil (205 mg, 53%).
1H NMR (250 MHz, CDCl3): d = 2.28 (s, 3 H, CH3), 3.79 (s, 3 H,
OCH3), 7.08–7.17 (m, 7 H, Ar).
13C NMR (63 MHz, CDCl3): d = 19.6 (CH3), 52.1 (OCH3), 126.9,
128.3, 129.6, 130.0, 130.1, 130.2, 131.2 (CHAr), 131.4, 134.7,
136.3, 137.7, 138.5 (C).
MS (EI, 70 eV): m/z (%) = 294 (M+, 37Cl, 16), 292 (M+, 35Cl, 71),
261 (71), 260 (18), 259 (100), 226 (15), 225 (37), 198 (16), 197
(29), 165 (8), 152 (6), 121 (9), 63 (5).
IR (KBr): 3056 (w), 2994 (w), 2948 (w), 2927 (w), 2857 (w), 1727
(s), 1606 (m), 1581 (m), 1476 (m), 1449 (s), 1437 (s), 1380 (w),
1266 (s), 1240 (s), 1188 (m), 1152 (m), 1105 (s), 1066 (s), 1023 (m),
954 (m), 738 (s), 688 cm–1 (s).
1H NMR (250 MHz, CDCl3): d = 2.27 (s, 3 H, CH3), 3.80 (s, 3 H,
OCH3), 7.05–7.24 (m, 8 H, Ar).
13C NMR (63 MHz, CDCl3): d = 18.6 (CH3), 51.1 (OCH3), 126.1,
128.1, 128.3, 128.9, 129.3, 130.1 (CHAr), 132.1, 134.7, 134.9,
135.6, 167.9 (C).
MS (EI, 70 eV): m/z (%) = 258 (M+, 69), 227 (46), 226 (22), 225
(100), 197 (15), 184 (33), 165 (8), 152 (6), 63 (3).
HRMS (EI): m/z calcd for C15H13ClO2S (M+, 35Cl): 292.03193;
found: 292.032372.
Methyl 4-Methyl-2-p-tolylsulfanylbenzoate (5e)
Starting from 3e (350 mg, 1.2 mmol), 4a (0.15 mL, 1.44 mmol),
TiCl4 (0.20 mL, 1.8 mmol), and CH2Cl2 (7 mL), 5e was isolated as
a highly viscous oil (166 mg, 51%).
IR (KBr): 3091 (w), 3063 (w), 2950 (w), 2924 (w), 2853 (w), 1728
(s), 1712 (s), 1661 (m), 1588 (s), 1485 (s), 1434 (m), 1272 (s), 1220
(s), 1154 (s), 1106 cm–1 (s).
HRMS (EI): m/z calcd for C15H14O2S (M+): 258.07090; found:
258.070766.
Methyl 2-(4-Fluorophenylsulfanyl)-4-methylbenzoate (5b)
Starting from 3b (440 mg, 1.5 mmol), 4a (0.23 mL, 2.25 mmol),
TiCl4 (0.25 mL, 2.25 mmol), and CH2Cl2 (9 mL), 5b was isolated as
a highly viscous oil (153 mg, 37%).
1H NMR (250 MHz, CDCl3): d = 2.25 (s, 3 H, CH3), 2.26 (s, 3 H,
CH3), 3.83 (s, 3 H, OCH3), 6.97–7.22 (m, 7 H, Ar).
13C NMR (75 MHz, CDCl3): d = 19.6 (CH3), 21.1 (CH3), 52.1
(OCH3), 128.7, 129.1 (CHAr), 129.8 (C), 129.9, 132.0 (CHAr),
132.3, 134.6, 135.5, 135.9, 137.7 (C).
MS (EI, 70 eV): m/z (%) = 3272 (M+, 100), 241 (50), 239 (64), 225
(56), 211 (11), 198 (20), 197 (30), 165 (10), 152 (4), 121 (10), 105
(85), 77 (6), 63 (4).
IR (KBr): 3091 (w), 3063 (w), 2950 (w), 2924 (w), 2853 (w), 1728
(s), 1712 (s), 1661 (m), 1588 (s), 1487 (s), 1434 (m), 1273 (s), 1220
(s), 1154 (s), 1107 (s), 1068 (s), 826 (s), 771 (s), 628 cm–1 (m).
1H NMR (250 MHz, CDCl3): d = 2.26 (s, 3 H, CH3), 3.83 (s, 3 H,
OCH3), 6.92–7.26 (m, 7 H, Ar).
13C NMR (75 MHz, CDCl3): d = 19.6 (CH3), 52.1 (OCH3), 116.1,
116.5, 129.1, 1295, 129.9 (CHAr), 130.4, 130.5 (C), 133.8, 133.9,
136.1 (CHAr), 160.4, 164.3, 168.8 (C).
MS (EI, 70 eV): m/z (%) = 276 (M+, 74), 245 (49), 244 (22), 243
(100), 215 (15), 202 (38), 170 (5), 121 (5), 63 (3).
HRMS (EI): m/z calcd for C16H16O2S (M+): 272.08655; found:
272.086425.
Methyl 4-Methyl-2-(naphth-2-ylsulfanyl)benzoate (5f)
Starting from 3f (660 mg, 2.0 mmol), 4a (0.3 mL, 3.0 mmol), TiCl4
(0.33 mL, 3.0 mmol), and CH2Cl2 (12 mL), 5f was isolated as a
highly viscous oil (203 mg, 33%).
HRMS (EI): m/z calcd for C15H13FO2S (M+): 276.06148; found:
276.061483.
IR (KBr): 3052 (w), 2991 (w), 2947 (w), 2952 (w), 2853 (w), 1727
(s), 1623 (w), 1584 (m), 1568 (m), 1499 (m), 1433 (m), 1379 (w),
1339 (w), 1264 (s), 1241 (s), 1189 (m), 1105 (s), 1066 (s), 1016 (m),
942 (m), 849 (m), 811 (s), 777 (s), 742 (s), 708 cm–1 (m).
1H NMR (250 MHz, CDCl3): d = 2.29 (s, 3 H, CH3), 3.80 (s, 3 H,
OCH3), 7.06–7.77 (m, 10 H, Ar).
Methyl 4-Methyl-2-m-tolylsulfanylbenzoate (5c)
Starting from 3c (441 mg, 1.5 mmol), 4a (0.23 mL, 2.25 mmol),
TiCl4 (0.25 mL, 2.25 mmol), and CH2Cl2 (9 mL), 5c was isolated as
a highly viscous oil (204 mg, 50%).
IR (KBr): 3091 (w), 3063 (w), 2950 (w), 2924 (w), 2853 (w), 1728
(s), 1712 (s), 1661 (m), 1588 (s), 1487 (s), 1434 (m), 1273 (s), 1220
(s), 1154 (s), 1107 cm–1 (s).
13C NMR (63 MHz, CDCl3): d = 18.7 (CH3), 51.1 (OCH3), 125.2,
125.5, 126.7, 126.8, 127.8, 128.2, 128.9, 129.1, 129.2 (CHAr),
131.3, 131.9, 132.4, 132.6, 135.1, 135.3, 167.9 (C).
1H NMR (250 MHz, CDCl3): d = 2.22 (s, 3 H, CH3), 2.27 (s, 3 H,
CH3), 3.82 (s, 3 H, OCH3), 7.03–7.18 (m, 7 H, Ar).
MS (EI, 70 eV): m/z (%) = 308 (M+, 100), 277 (32), 276 (16), 275
(81), 248 (10), 234 (22), 117 (6), 115 (5), 69 (3).
13C NMR (63 MHz, CDCl3): d = 19.6 (CH3), 21.27 (CH3), 52.1
(OCH3), 128.1, 128.5, 128.9, 129.0, 129.8, 129.9, 132.0 (CHAr),
135.1, 135.9, 136.2, 138.9, 168.9 (C).
HRMS (EI): m/z calcd for C17H18O3S (M+): 308.39414; found:
308.38943.
Methyl 3,4-Dimethyl-2-p-tolylsulfanyl)-3,4-dimethylbenzoate
(5g)
Starting from 3e (616 mg, 2.0 mmol), 4b (0.3 mL, 3.0 mmol), TiCl4
(0.33 mL, 3.0 mmol), and CH2Cl2 (12 mL), 5g was isolated as a
highly viscous oil (212 mg, 37%).
MS (EI, 70 eV): m/z (%) = 272 (M+, 100), 241 (54), 240 (16), 239
(72), 226 (16), 225 (73), 198 (22), 197 (35), 165 (11), 121 (9), 105
(5), 77 (6).
HRMS (EI): m/z calcd for C16H16O2S (M+): 272.08655; found:
272.086256.
IR (KBr): 3017 (w), 2948 (w), 2921 (w), 2734 (w), 1731 (s), 1656
(w), 1490 (m), 1431 (m), 1280 (s), 1203 (s), 1111 (s), 1085 (m), 802
(s), 754 (w), 718 cm–1 (m).
1H NMR (250 MHz, CDCl3): d = 2.14 (s, 3 H, CH3), 2.18 (s, 3 H,
CH3), 2.22 (s, 3 H, CH3), 3.76 (s, 3 H, OCH3), 7.17 (m, 6 H, Ar).
Methyl 2-(3-Chlorophenylsulfanyl)-4-methylbenzoate (5d)
Starting from 3d (470 mg, 1.5 mmol), 4a (0.23 mL, 2.25 mmol),
TiCl4 (0.25 mL, 2.25 mmol), and CH2Cl2 (9 mL), 5d was isolated as
a highly viscous oil (210 mg, 48%).
IR (KBr): 3058 (w), 2996 (w), 2949 (w), 2927 (w), 2856 (w), 1729
(s), 1662 (w), 1574 (m), 1563 (m), 1459 (m), 1451 (m), 1435 (m),
1337 (w), 1267 (s), 1242 (s), 1189 (m), 1106 (s), 1067 (s), 955 (w),
773 (s), 678 (m), 663 cm–1 (w).
13C NMR (75 MHz, CDCl3): d = 19.1 (CH3), 20.5 (CH3), 20.9
(CH3), 52.1 (OCH3), 127.7 CHAr), 128.5 (C), 129.6, 131.0, 131.4
(CHAr), 132.7, 133.4, 135.4, 140.7, 141.3 (C).
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MS (EI, 70 eV): m/z (%) = 286 (M+, 100), 255 (38), 254 (15), 253
(42), 240 (19), 239 (82), 225 (12), 212 (16), 211 (35), 193 (7), 178
(8), 91 (10).
Methyl 3-Phenylsulfanylbiphenyl-4-carboxylate (5k)
Starting from 3a (420 mg, 1.5 mmol), 4d (0.18 mL, 1.8 mmol),
TiCl4 (0.25 mL, 2.25 mmol), and CH2Cl2 (9 mL), 5k was isolated as
a highly viscous oil (192 mg, 40%).
HRMS (EI): m/z calcd for C17H18O2S (M+): 286.10220; found:
286.101482.
IR (KBr): 3056 (w), 3029 (w), 2992 (w), 2946 (w), 2838 (w), 1730
(s), 1711 (s), 1638 (w), 1597 (m), 1577 (m), 1556 (w), 1526 (m),
1475 (m), 1438 (s), 1415 (w), 1373 (w), 136 (w), 1258 (s), 1191 (s),
111 (s), 1060 (s), 1034 (m), 1017 (m), 999 (m), 955 (m), 888 (m),
846 (w), 750 (s), 732 (s), 688 (s), 650 (m), 632 cm–1 (m).
1H NMR (250 MHz, CDCl3): d = 3.53 (s, 3 H, OCH3), 7.16–7.32
(m, 13 H, Ar).
13C NMR (MHz, CDCl3): d = 52.1 (OCH3), 127.5, 127.7, 128.2,
128.4, 128.5, 129.2, 129.9, 130.7, 131.9 (CHAr), 132.6, 134.5,
135.0, 139.9, 140.9 (C).
Methyl 3,4-Dimethyl-2-phenylsulfanylbenzoate (5h)
Starting from 3a (440 mg, 1.5 mmol), 4b (0.23 mL, 2.25 mmol),
TiCl4 (0.25 mL, 2.25 mmol), and CH2Cl2 (9 mL), 5h was isolated as
a highly viscous oil (163 mg, 40%).
IR (KBr): 2949 (w), 2922 (w), 2855 (w), 1729 (s), 1588 (m), 1487
(s), 1432 (m), 1386 (m), 1281 (s), 1203 (s), 156 (s), 1111 cm–1 (s).
1H NMR (250 MHz, CDCl3): d = 2.19 (s, 3 H, CH3), 2.23 (s, 3 H,
CH3), 3.75 (s, 3 H, OCH3), 7.09–7.13 (m, 7 H, Ar).
13C NMR (63 MHz, CDCl3): d = 19.1 (CH3), 20.5 (CH3), 52.1
(OCH3), 125.5, 127.3 (CHAr), 127.8 (C), 128.8, 131.2, 131.4
(CHAr), 132.8, 137.0, 140.7, 141.4 (C).
MS (EI, 70 eV): m/z (%) = 320 (M+, 100), 290 (19), 289 (87), 271
(15), 261 (10), 260 (14), 240 (25), 163 (18), 152 (11), 131 (15), 110
(13), 105 (17), 77 (17), 69 (5).
MS (EI, 70 eV): m/z (%) = 272 (M+, 85), 241 (41), 240 (29), 239
HRMS (EI): m/z calcd for C20H16O2S (M+): 320.08655; found:
(100), 211 (26), 197 (35), 179 (10), 135 (5).
320.086676.
HRMS (EI): m/z calcd for C16H16O2S (M+): 272.08655; found:
272.086221.
Methyl 3-(4-Chlorophenylsulfanyl)biphenyl-4-carboxylate (5k)
Starting from 3g (370 mg, 1.2 mmol), 4d (0.22 mL, 1.3 mmol),
TiCl4 (0.2 mL, 1.7mmol), and CH2Cl2 (7 mL), 5k was isolated as a
highly viscous oil (157 mg, 37%).
Methyl 2-(4-Fluorophenylsulfanyl)-3,4-dimenthylbenzoate (5i)
Starting from 3b (620 mg, 2.0 mmol), 4b (0.3 mL, 3.0 mmol), TiCl4
(0.33 mL, 3.0 mmol), and CH2Cl2 (12 mL), 5i was isolated as a
highly viscous oil (197 mg, 34%).
IR (KBr): 3058 (w), 2996 (w), 2949 (w), 2927 (w), 2856 (w), 1729
(s), 1662 (w), 1574 (m), 1563 (m), 1459 (m), 1451 (m), 1435 (m),
1337 (w), 1267 (s), 1242 (s), 1189 (m), 1106 (s), 1067 (s), 955 (w),
773 (s), 678 (m), 663 cm–1 (w).
1H NMR (250 MHz, CDCl3): d = 3.53 (s, 3 H, OCH3), 7.18–7.32
(m, 12 H, Ar).
13C NMR (63 MHz, CDCl3): d = 52.1 (OCH3), 127.8, 128.2, 128.4,
129.0, 129.4, 130.1, 131.2, 132.8 (CHAr), 133.6, 133.6, 133.9,
135.7, 139.81, 141.1, 168.6 (C).
IR (KBr): 2949 (w), 2922 (w), 2855 (w), 1729 (s), 1588 (m), 1487
(s), 1432 (m), 1386 (m), 1281 (s), 1203 (s), 156 (s), 1111 (s), 1084
(m), 1010 (m), 813 (s), 790 (m), 626 cm–1 (s).
1H NMR (250 MHz, CDCl3): d = 2.18 (s, 3 H, CH3), 2.22 (s, 3 H,
CH3), 3.77 (s, 3 H, OCH3), 6.98–7.11 (m, 6 H, Ar).
13C NMR (75 MHz, CDCl3): d = 18.0 (CH3), 19.4 (CH3), 51.1
(OCH3), 114.7, 115.1 (CHAr), 127.2 (C), 128.5, 128.6, 130.3, 130.5
(CHAr), 131.8, 139.5, 140.3, 158.3, 162.2, 168.4 (C).
MS (EI, 70 eV): m/z (%) = 356 (M+, 37Cl, 39), 354 (M+, 35Cl, 100),
323 (36), 244 (15), 91 (7), 77 (5).
HRMS (EI): m/z calcd for C20H15ClO2S (M+): 354.06323; found:
MS (EI, 70 eV): m/z (%) = 290 (M+ 90), 259 (45), 258 (25), 257
(100), 229 (34), 216 (19), 215 (38), 197 (8), 77 (6), 51 (3).
354.063118.
HRMS (EI): m/z calcd for C16H15FO2S (M+): 290.07713; found:
290.077573.
Methyl 4¢-Chloro-3-phenylsulfanylbiphenyl-2-carboxylate
(5m)
Starting from 3a (400 mg, 1.5 mmol), 4e (0.37 mL, 1.8 mmol),
TiCl4 (0.25 mL, 2.25 mmol), and CH2Cl2 (9 mL), 5m was isolated
as a highly viscous oil (250 mg, 47%).
Methyl 3-Ethyl-4-methyl-2-phenylsulfanylbenzoate (5j)
Starting from 3b (460 mg, 1.5 mmol), 4c (0.23 mL, 2.25 mmol),
TiCl4 (0.25 mL, 2.25 mmol), and CH2Cl2 (9 mL), 5j was isolated as
a highly viscous oil (150 mg, 35%).
IR (KBr): 3057 (w), 2997 (w), 2947 (w), 2852 (w), 1728 (s), 1676
(w), 1596 (w), 1580 (m), 1573 (m), 1493 (m), 1438 (s), 1260 (s),
1192 (m), 1152 (w), 1115 (s), 1090 (s), 1061 (m), 1023 (m), 1012
(m), 900 (m), 836 (m), 741 (s), 688 cm–1 (s).
1H NMR (250 MHz, CDCl3): d = 3.56 (s, 3 H, OCH3), 7.21–7.32
(m, 12 H, Ar).
13C NMR (63 MHz, CDCl3): d = 52.2 (OCH3), 127.7, 128.3, 128.6,
129.3, 129.6, 130.0, 131.1, (CHAr), 133.9, 134.7, 134.9, 135.0,
138.4, 139.6, 168.4 (C).
MS (EI, 70 eV): m/z (%) = 356 (M+, 37Cl, 39), 354 (M+, 35Cl, 100),
323 (46), 287 (13), 260 (18), 259 (12), 258 (23).
IR (KBr): 3055 (w), 2965 (w), 2948 (w), 2928 (w), 2870 (w), 2738
(w), 1729 (s), 1580 (m), 1477 (m), 1432 (m), 1393 (w), 1323 (w),
1271 (s), 1200 (s), 1157 (m), 1111 (s), 1080 (m), 1058 (m), 1023
(m), 1013 (m), 959 (m), 893 (w), 826 (m), 790 (m), 736 (s), 688 (s),
636 cm–1 (m).
1H NMR (250 MHz, CDCl3): d = 1.00 (t, 2J = 7.5 Hz, 3 H,
CH2CH3), 2.23 (s, 3 H, CH3), 2.63 (q, 2J = 7.5 Hz, 2 H, CH2), 3.71
(s, 3 H, OCH3), 7.08–7.17 (m, 7 H, Ar).
13C NMR (75 MHz, CDCl3): d = 14.8, 19.1 (CH3), 26.7 (CH3CH2),
52.0 (OCH3), 125.3, 127.0, 128.7, 129.8, 131.6 (CHAr), 132.8,
137.9, 141.7, 146.5, 169.3 (C).
MS (EI, 70 eV): m/z (%) = 286 (M+, 100), 255 (22), 254 (23), 253
(59), 239 (47), 227 (12), 225 (16), 211 (26), 197 (19), 184 (14), 178
(14), 105 (30), 77 (10).
HRMS (EI): m/z calcd for C20H15ClO2S (M+): 354.06323; found:
354.063118.
Methyl 4¢-Chloro-3-(4-chlorophenylsulfanyl)biphenyl-2-car-
boxylate (5n)
Starting from 3g (470 mg, 1.5 mmol), 4e (0.37 mL, 1.8 mmol),
TiCl4 (0.25 mL, 2.25 mmol), and CH2Cl2 (9 mL), 5n was isolated as
a highly viscous oil (268 mg, 46%).
HRMS (EI): m/z calcd for C17H18O2S (M+): 286.10220; found:
286.102040.
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I. Iqbal et al.
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IR (KBr): 3445 (w), 3056 (w), 2947 (w), 2385 (w), 2075 (w), 1900
(w), 1728 (s), 1679 (m), 1572 (m), 1493 (m), 1474 (s), 1446 (m),
1388 (m), 1260 (s), 1190 (m), 1116 (m), 1090 (s), 1011 (s), 818 (s),
790 (s), 743 (m), 715 cm–1 (m).
1H NMR (250 MHz, CDCl3): d = 3.56 (s, 3 H, OCH3), 7.15–7.32
(m, 11 H, Ar).
MS (EI, 70 eV): m/z (%) = 392 (M+, 37Cl37Cl, 8), 390 (M+, 35Cl37Cl,
23), 388 (M+, 35Cl35Cl, 100), 359 (26), 357 (38), 321 (14), 294 (15),
258 (26), 151 (5), 159 (5), 129 (10), 75 (4).
1H NMR (250 MHz, CDCl3): d = 2.27 (s, 3 H, CH3), 3.54 (s, 3 H,
OCH3), 7.04–7.29 (m, 11 H, Ar).
13C NMR (75 MHz, CDCl3): d = 19.8 (CH3), 51.1 (OCH3), 124.7,
126.6, 127.5, 127.9, 128.8, 129.7, 130.7 (CHAr), 132.8, 135.6,
135.8, 137.0, 139.5, 142.0, 167.8 (C).
MS (EI, 70 eV): m/z (%) = 370 (M+, 37Cl, 39), 368 (M+, 35Cl, 100),
337 (52), 336 (23), 335 (60), 309 (13), 307 (27), 301 (23), 271 (13),
258 (18), 165 (13), 152 (10), 51 (4).
HRMS (EI): m/z calcd for C21H17ClO2S (M+): 368.06323; found:
368.062687.
HRMS (EI): m/z calcd for C20H14Cl2O2S (M+, 35Cl35Cl): 388.00861;
found: 388.008235.
Methyl 4¢-Chloro-4-ethyl-3-phenylsulfanylbiphenyl-2-carboxy-
late (5r)
Starting from 3a (440 mg, 1.5 mmol), 4g (0.37 mL, 1.8 mmol),
TiCl4 (0.25 mL, 2.25 mmol), and CH2Cl2 (9 mL), 5r was isolated as
a highly viscous oil (206 mg, 36%).
Methyl 4¢-Chloro-3-p-tolylsulfanylbiphenyl-2-carboxylate (5o)
Starting from 3e (400 mg, 1.5 mmol), 4e (0.37 mL, 1.8 mmol),
TiCl4 (0.25 mL, 2.25 mmol), and CH2Cl2 (9 mL), 5o was isolated as
a highly viscous oil (260 mg, 47%).
IR (KBr): 3021 (w), 2947 (w), 2920 (w), 2853 (w), 1903 (w), 1728
(s), 1650 (m), 1587 (m), 1546 (m), 1490 (s), 1445 (s), 1390 (m),
1256 (s), 1191 (m), 1115 (s), 1089 (s), 1061 (s), 1012 (s), 806 (s),
789 (s), 742 (m), 684 (m), 533 cm–1 (m).
1H NMR (250 MHz, CDCl3): d = 2.27 (s, 3 H, CH3), 3.58 (s, 3 H,
OCH3), 7.06–7.29 (m, 11 H, Ar).
13C NMR (63 MHz, CDCl3): d = 18.2 (CH3), 52.1 (OCH3), 128.5,
128.8, 129.4, 129.8, 130.5, 131.4, 133.0 (CHAr), 133.7, 134.0,
135.5, 136.2, 138.2, 139.7, 168.3 (C).
MS (EI, 70 eV): m/z (%) = 370 (M+, 37Cl, 39), 368 (M+, 35Cl, 100),
339 (14), 337 (36), 301 (8), 274 (10), 258 (12), 150 (6), 129 (4).
IR (KBr): 3055 (w), 2965 (w), 2947 (w), 2931 (w), 2870 (w), 1730
(s), 1673 (w), 1581 (m), 1496 (w), 1477 (m), 1459 (m), 1431 (m),
1403 (w), 1385 (w), 1271 (s), 1229 (m), 1214 (s), 1118 (s), 1092 (s),
1067 (m), 1023 (m), 1012 (s), 959 (m), 900 (m), 823 (s), 737 (s),
688 (s), 539 cm–1 (m).
1H NMR (250 MHz, CDCl3): d = 1.05 (t, 2J = 0.03 Hz, 3 H, CH3),
2.71 (q, 2J = 0.03 Hz, 2 H, CH2), 3.49 (s, 3 H, OCH3), 7.02–7.17 (m,
11 H, Ar).
13C NMR (75 MHz, CDCl3): d = 14.7 (CH3), 27.0 (CH3CH2), 52.1
(OCH3), 125.6, 127.39 (CHAr), 128.2 (C), 128.6, 128.8, 129.8,
130.1, 131.1 (CHAr), 133.1, 136.7, 137.4, 138.0, 140.9, 148.6, 168.8
(C).
MS (EI, 70 eV): m/z (%) = 384 (M+, 37Cl, 39), 382 (M+, 35Cl, 100),
350 (27), 349 (35), 335 (18), 315 (12), 307 (13), 297 (31), 271 (26),
258 (18), 245 (27), 237 (22), 178 (16), 165 (12), 105 (24).
HRMS (EI): m/z calcd for C21H17ClO2S (M+): 368.06323; found:
368.063118.
Methyl 4¢-Chloro-3-(4-fluorophenylsulfanyl)biphenyl-2-car-
boxylate (5p)
HRMS (EI): m/z calcd for C22H19ClO2S (M+): 382.07888; found:
Starting from 3b (440 mg, 1.5 mmol), 4e (0.37 mL, 1.8 mmol),
TiCl4 (0.25 mL, 2.25 mmol), and CH2Cl2 (9 mL), 5p was isolated as
a colorless solid (195 mg, 35%).
382.079023.
Acknowledgment
IR (KBr): 3091 (w), 3065 (w), 2992 (w), 2948 (w), 2851 (w), 1892
(w), 1711 (m), 1678 (m), 1587 (s), 1488 (s), 1445 (m), 1435 (m),
1397 (m), 1337 (m), 1272 (m), 1221 (s), 1193 (s), 1153 (s), 1105
(m), 1088 (s), 1012 (m), 898 (m), 829 (s), 813 (s), 790 (m), 733 (m),
637 cm–1 (m).
Financial support by the State of Pakistan (scholarship for I.I.) and
by the State of Mecklenburg-Vorpommern is gratefully acknowl-
edged.
1H NMR (250 MHz, CDCl3): d = 3.57 (s, 3 H, OCH3), 6.99–7.27
(m, 11 H, Ar).
References
13C NMR (75 MHz, CDCl3): d = 51.2 (OCH3), 115.4, 115.7, 127.2
(CHAr), 127.6, 128.5, 129.1, 129.2, 132.7, 133.7, 133.9 (CHAr),
134.4, 134.5, 136.6, 136.7, 137.3, 138.7, 167.4 (C).
MS (EI, 70 eV): m/z (%) = 374 (M+, 37Cl, 40), 372 (M+, 35Cl, 100),
343 (16), 341 (42), 305 (14), 278 (16), 276 (20), 168 (8), 152 (6),
138 (9).
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IR (KBr): 3055 (w), 2947 (w), 2920 (w), 2851 (w), 2735 (w), 2660
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1459 (m), 1431 (m), 1400 (m), 1277 (s), 1221 (s), 1189 (m), 1118
(s), 1092 (s), 1011 (s), 971 (m), 890 (m), 842 (m), 816 (s), 734 (s),
715 (m), 688 (s), 627 cm–1 (m).
Synthesis 2009, No. 2, 297–305 © Thieme Stuttgart · New York

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Synthesis 2009, No. 2, 297–305 © Thieme Stuttgart · New York