Application of directed metalation in synthesis. Part 4: Expedient synthesis of substituted benzo[b]thiophene and naphthothiophene

Article abstract of DOI:10.1016/S0040-4020(03)00710-5

A short, simple and inexpensive synthesis of several diversely substituted benzo[b]thiophenes and one naphthothiophene is described. The method involves introduction of methylsulfanyl group ortho- to the amide function of readily available N,N-diethylamides of aryl carboxylic acid by directed metalation. Thioindoxyls, obtained in high yields through side-chain deprotonation and cyclisation in one pot, are reduced to benzo[b]thiophene or napthothiophene.

Full text of DOI:10.1016/S0040-4020(03)00710-5

Tetrahedron 59 (2003) 4767–4774
Application of directed metalation in synthesis.
Part 4: Expedient synthesis of substituted benzo[b]thiophene
and naphthothiopheneq
*
Chandrani Mukherjee, Sukanta Kamila and Asish De
Department of Organic Chemistry, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700032, India
Received 3 February 2003; revised 8 April 2003; accepted 1 May 2003
Abstract—A short, simple and inexpensive synthesis of several diversely substituted benzo[b]thiophenes and one naphthothiophene is
described. The method involves introduction of methylsulfanyl group ortho- to the amide function of readily available N,N-diethylamides of
aryl carboxylic acid by directed metalation. Thioindoxyls, obtained in high yields through side-chain deprotonation and cyclisation in one
pot, are reduced to benzo[b]thiophene or napthothiophene. q 2003 Elsevier Science Ltd. All rights reserved.
1. Introduction
synthesis2,8 of polycondensed systems which include sulfur
analogues1,9 of bioactive natural products. Expedient access
to substituted benzo[b]thiophenes, preferably avoiding as
much possible use of expensive and environmentally
offensive thiols, is thus important. Some time ago we
developed a multistep synthesis10 of substituted benzo-
[b]thiophenes that did not use thiols as starting materials.
We have recently reported2 a short and expedient route to
various methoxybenzo[b]thiophenes. The method consist-
ing of sequential directed ortho-lithiation, side chain
deprotonation, cyclisation using tertiary amide function as
internal electrophile3 and borohydride reduction compares
favourably with earlier reported4,5 synthesis of these
compounds. Since the publication of our results,2 a paper6
appeared describing the synthesis of the key intermediate
used by us, by a procedure which is essentially a
modification of our method. The only difference is in the
use of ester instead of amide as the internal electrophile.
Importance of benzo[b]thiophene can be appreciated from
the numerous reports in the literature7 since the chemistry4,5
and the biological activities of these compounds were
reviewed. Thus benzo[b]thiophene derivatives have
exhibited7 biological activities e.g. anti-inflammatory,
analgesic, antiexudative, antipsychotic and enzyme
inhibiting properties. Benzo[b]thiophene and naphtho[2,1-
b]thiophene based diphosphanes have been developed7 as
C1-symmetric ligands for homogeneous stereoselective
catalysis. Diaryl substituted benzo[b]thiophenes have been
developed7 as novel photochromic materials. Substituted
benzo[b]thiophenes and partially hydrogenated benzo-
[b]thiophenes have been used as building blocks in the
We report here the further application of the method2
developed by us in the synthesis of other substituted
benzo[b]thiophenes and naphthothiophene establishing the
generality of this procedure.
q See Ref. 1.
Keywords: benzo[b]thiophene; directed metalation; thioindoxyl;
naphthothiophene; intramolecular cyclisation.
Scheme 1. Reagents and condition: (i) sec-BuLi/TMEDA/THF/2788
C/Me–S–S–Me, (ii)LDA/THF/2788C. (iii) NaBH4/MeOH/10% NaOH/
reflux for 10 h.
*
Corresponding author. Tel.: þ91-33-473-4971x246/253; fax: þ91-33-
473-2805; e-mail: ocad@mahendra.iacs.res.in
0040–4020/03/$ - see front matter q 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0040-4020(03)00710-5

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C. Mukherjee et al. / Tetrahedron 59 (2003) 4767–4774
2. Results and discussion
Table 1.
No.
Compound
Yield (%)
77
Nature
The starting materials used in the synthesis (Scheme 1) were
easily available N,N-diethylamides (1) of arylcarboxylic
acids. Methoxy benzamides were synthesized from com-
mercially available hydroxybenzoic acids. Under standard
directed metalation condition11 (sec-BuLi/TMEDA/
THF/2788C in argon atmosphere), deprotonation takes
place in the ortho-position of the tertiary amide function.
Deprotonation took place exclusively in the ortho-position
of the tertiary amide, when the molecule also contained
methoxy substituents reflecting the greater directing
power11 of tertiary amides. Even when a particular position
of the aromatic ring was under the simultaneous influence of
two methoxy groups as in the case of N,N-diethyl-2,4-
dimethoxybenzamide, exclusive deprotonation was
observed in the 6-position when 1.1 molar equiv. of
sec-BuLi was used. As expected, N,N-diethyl-3-methoxy-
benzamide was deprotonated in the 2-position under the
reinforcing effect of the directing influences of tertiary
amide and methoxy functions.
2a
2b
Gummy liquid
72
79
Solid
Solid
2c
2d
2e
2f
90
62
85
Oil
Oil
The lithio derivatives were quenched at 2788C with
dimethyl disulphide12 (2 molar equiv.) followed by stirring
at room temperature for 5 h. When N,N-diethyl benzamide
was treated with 2.5 molar equiv. of sec-BuLi and the
reaction mixture was stirred for 10 h at room temperature
methyl sulfanyl function was introduced in both the ortho-
position of the tertiary amide function along with the
formation of some mono substituted product (54:22). Close
Rf values of the starting tertiaryamides (1)
(R1¼R2¼R3¼R4¼H) and the methylsulfanyl substituted
products (5) necessitated repeated column chromatography
for the preparation of analytically pure sample of the
product. However even with partially pure 5, one could
smoothly proceed to the next step. For introduction of
methylsulfanyl group in the 3-position of N,N-diethylthio-
phene-2-carboxamide, silyl protection of the free a-position
was necessary. N,N-diethyl-3-methylsulfanyl-5-trimethyl-
silylthiophene-2-carboxamide (2k) was obtained from N,N-
diethyl-5-trimethylsilylthiophene-2-carboxamide13 in 78%
yield. Table 1 summarises the compounds obtained by
introducing methyl sulfanyl substituents ortho- to CONEt2.
Viscous liquid
2g
2h
2j
72
70
75
Gummy liquid
Solid
Solid
2k
2l
71
79
Viscous liquid
Gummy liquid
2m
69
Gummy liquid
Side chain deprotonation of 2 with 2.5 molar equiv. of
LDA11,14 was instantaneously followed by cyclisation to
afford the thioindoxyls 3. Our attempts to cyclise 2k for
access to a thienothiophene system, however, failed and we
got the starting material back. Cyclisation of N,N-diethyl-2-
methylsulfanyl-4-methoxy-5-trimethylsilylbenzamide (2c)
proceeded to give an extremely poor yield of the thioindoxyl
(3d) accompanied mostly by unreacted starting material and
some intractable decomposition product. Since the desilyl-
ated product, (2d) cyclised smoothly to afford 3e, it is
presumed that the presence of a bulky trimethylsilyl group
in the ortho-position might force the tertiary amide into a
position not easily accessible for the SCH22 anion for a
nucleophilic attack on the carbonyl carbon. Cyclisation of
N,N-diethyl-1-methylsulfanyl-3-methoxy-napthalene-3-
carboxamide (2l) afforded 2,3-dihydro-4-methoxy-
naptho[1,2-b]thiophen-3-one (3l) in 69% yield.

C. Mukherjee et al. / Tetrahedron 59 (2003) 4767–4774
4769
Though the thioindoxyls (Table 2) were susceptible to slow
decomposition upon prolonged exposure to air, they could
be kept under argon in the refrigerator with no visible sign
of deterioration and were fully characterized by analytical
and spectral data. As expected, the IR data of these
compounds do not show the presence of enol tautomers. It
was observed15 earlier that in solid state thioindoxyls exist
entirely in the keto form. Borohydride reduction16 of the
thioindoxyls in hot methanolic sodium hydroxide afforded
1
the substituted benzo[b]thiophenes in all but one case. H
Table 2.
NMR data and mpt/bpt of the benzo[b]thiophenes which
were earlier reported in the literature corresponded with
those of the compounds reported in this paper.Work up
consists of treatment with sulfuric acid (10%) after removal
of methanol. While reducing 3i (R1¼R2¼R4¼H, R3¼Me)
more concentrated sulfuric acid (20%) and prolonged
stirring were required during work up.
No.
Compound
Yield (%)
67
Nature
Solid
3a
3b
3c
3d
66
65
10
Solid
Solid
Solid
Table 3 summarises the benzo[b]thiophenes synthesized.
1
Melting/boiling points and H NMR data of the benzo-
[b]thiophenes earlier reported corresponded with the data on
the same compounds synthesized by us. However, all our
attempts to prepare 4-chlorobenzo[b]thiophene from 2,3-
dihydro-4-chlorobenzo[b]thiophene-3-one (3h) completely
failed.
3e
3f
69
78
Solid
Solid
Conversion of thioindoxyl to benzo[b]thiophene through
borohydride reduction should involve initial formation of
carbinol followed by dehydration. Borohydride reduction of
3h afforded 2,3-dihydro-3-hydroxy-4-chloro benzo[b]thio-
phene (6) in 75% yield which was fully characterized.
However attempts to dehydrate it with p-toluene sulphonic
acid resulted in the formation of an intractable mixture of
unidentifiable products and no trace of 4-chlorobenzo-
[b]thiophene was found. Methylation of 3h with aqueous
potassium hydroxide (20%) and dimethylsulphate afforded
3-methoxy-4-chlorobenzo[b]thiophene (7) in 72% yield.
Reduction of 3l afforded 4-methoxy-naptho[1,2-b]thio-
phene (4j), as expected, in 85% yield.
3g
3h
69
68
Solid
Solid
3i
3j
77
89
Solid
Solid
3. Conclusion
The procedure described above provides an expedient
access to diversely substituted benzo[b]thiophenes and its
simplicity constitutes a significant improvement over earlier
methods. Thioindoxyls which are key intermediates in the
present synthesis of benzo[b]thiophenes are obtained from
much simpler and readily available starting materials than
were needed earlier.4 The method also compares
favorably with a short and expedient synthesis17 of
benzo[b]thiophene which is elegant but uses thiols as
starting material. The present work is yet another demon-
stration of the power of directed metalation in the
regiocontrolled functionalisation of aromatic nuclei and
the subsequent utilisation of the introduced functionalities
for annelation purposes.
3k
3l
81
73
Solid
Solid

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C. Mukherjee et al. / Tetrahedron 59 (2003) 4767–4774
Table 3.
recorded in open capillaries on a hot stage apparatus. IR
spectra were recorded on a FTIR-8300, SHIMADZU
spectrometer, for solids in potassium bromide discs and
for liquids by placing a thin layer of the sample between two
potassium bromide discs. n-BuLi and sec-BuLi were
prepared in our laboratory by reacting molecularised lithium
with 1-chlorobutane in n-hexane (in the case of n-BuLi) or
2-chlorobutane in cyclohexane (in the case of sec-BuLi).
Molecularisation of lithium was done either by heating the
lithium in heavy paraffin liquid and then vigorous stirring
with a mechanical stirrer or under sonication. Strength of the
alkyl lithium was determined by titration against diphenyl
acetic acid.
No.
Compound
Yield (%)
67
Nature
Solid
4a
4b
45
82
77
Liquid
4c
Oil
4.1.1. Synthesis of 2-methylsulfanylbenzamides. To a
stirred solution of TMEDA (0.92 mL, 1.1 equiv.) and sec-
BuLi [6.21 mL, 1.1 equiv. of 1 M solution in cyclohexane]
in THF (15 mL) at 2788C, N,N-diethyl benzamide (1)
(R1¼R2¼R3¼R4¼H) (1 g, 5.6 mmol) was added through a
needle syringe system. Stirring was continued for 30 min
and dimethyl disulfide (1 mL, 2 equiv.) in THF (5 mL) was
added to the reaction mixture kept at 2788C. After stirring
the reaction mixture at the same teperature for 15 min it was
allowed to attain room temperature and kept for 6 h at that
temperature. After removal of the solvent under reduced
pressure, saturated solution of ammonium chloride was
added to the reaction mixture and it was extracted with
diethyl ether. The organic layer was washed with brine and
dried over anhydrous Na2SO4. Removal of solvent afforded
compound 2a (R1¼R2¼R3¼R4¼H) which was purified by
column chromatography using ethyl acetate–light
petroleum (3:17) as eluant. Gummy liquid (980 mg, 77%);
(Found C, 65.81; H, 6.00; N, 6.40. C12H13OSN requires C,
65.75; H, 5.93; N, 6.39%); nmax (NEAT): 1629 (CvO)
cm21; dH (300 MHz, CDCl3) 0.96 (3H, t, J¼7.1 Hz,
–CH2CH3), 1.19 (3H, t, J¼7.1 Hz, –CH2CH3), 2.34 (3H,
s, –SMe), 3.05 (2H, q, J¼7.1 Hz, –CH2CH3), 3.5 (2H, q,
J¼7.1 Hz, –CH2CH3), 7.09–7.11 (2H, m, Ar-3, 4H),
7.22–7.24 (2H, m, Ar-5, 6H); dC (75.5 MHz, CDCl3)
13.0, 14.3, 16.7, 39.2, 43.1, 125.8, 126.5, 127.5, 129.4,
135.2, 137.8, 169.6.
4d
Solid
4e
4f
73
71
Oil
Oil
4g
4h
92
73
Solid
Oil
4i
4j
85
79
Solid
Solid
4.1.2. N,N-Diethyl-2-methylsulfanyl-6-methoxybenz-
amide (2b, R15OMe, R25R35R45H). Compound 2b
(R1¼OMe, R2¼R3¼R4¼H) was synthesized following the
same procedure as stated above with (1 g, 4.8 mmol) of
2-methoxybenzamide, TMEDA (1.8 ml, 2.5 equiv.), sec-
BuLi [9.7 mL, 2.5 equiv. of 1.25 M solution in cyclohexane],
dimethyl disulfide (0.87 mL, 2 equiv.) and stirring at room
temperature for 10 h. Colourless needles, crystalised from
CCl4–petroleum ether (880 mg, 72%); mp 61–638C; (Found
C, 61.65; H, 7.39; N, 5.51. C13H19O2SN requires C, 61.66; H,
7.50; N, 5.53%); nmax (KBr): 1633 (CvO) cm21; dH
(300 MHz, CDCl3) 0.98 (3H, t, J¼7.1 Hz, –CH2CH3), 1.20
(3H, t, J¼7.1 Hz, –CH2CH3), 2.38 (3H, s, –SMe), 3.05 (2H,
q, J¼7.1 Hz, –CH2CH3), 3.34 (2H, q, J¼7.1 Hz, –CH2CH3),
3.72 (3H, s, –OMe), 6.65 (1H, dd, J¼8.30 Hz, 1.5, Ar-3H),
6.82 (1H, dd, J¼8.0, 1.5 Hz, Ar-5H), 7.20 (1H, dd, J¼8.3,
8.0 Hz, Ar-4H); dC (75.5 MHz, CDCl3) 12.9, 14.3, 16.7, 39.0,
42.9, 56.0, 108.5, 119.6, 129.9, 136.8, 155.9, 167.0.
4. Experimental
4.1. General
Commercially available solvents were distilled prior to use.
Light petroleum ether (bp 60–808C) was used for column
chromatography. Anhydrous sodium sulfate was used as
drying agent. THF, n-hexane, cyclohexane were dried by
the usual sodium-benzophenone-ketyl method. 1H NMR
spectra (300 MHz) and 13C, DEPT (75.5 MHz) were
recorded in CDCl3 solution on Bruker DPX-300 spec-
trometer. Chemical shift (d) are expressed in ppm using
tetramethylsilane as internal standard. Coupling constant (J)
values are given in Hz. Melting points (uncorrected) were
4.1.3. N,N-Diethyl-2-methylsulfanyl-5-methoxy-6-tri-
methylsilylbenzamide12 (2c, R15TMS, R25OMe,

C. Mukherjee et al. / Tetrahedron 59 (2003) 4767–4774
4771
R35R45H). Prepared in the same way as before.
Purification by column chromatography [eluant: ethyl
acetate–light petroleum (1:9)]; colourless solid (79%), mp
79–818C. (Found C, 59.18; H, 8.50; N, 4.21. C16H27O2NSSi
requires C, 59.07; H, 8.30; N, 4.30%); nmax (NEAT): 1631
(CvO) cm21; dH (300 MHz, CDCl3) 0.80 (9H, s, –SiMe3),
0.91 (3H, t, J¼7.2 Hz, –CH2CH3), 1.04 (3H, t, J¼7.2 Hz,
–CH2CH3), 2.12 (3H, s, –SMe), 2.81–2.93 (2H, m,
–CH2CH3), 3.53 (3H, s, –OMe), 3.64–3.71 (2H, m,
–CH2CH3), 6.57 (1H, d, J¼8.7 Hz, Ar-3H), 7.15 (1H, d,
J¼8.7 Hz, Ar-4H); dC (75.5 MHz, CDCl3) 0.5, 11.6, 12.7,
18.6, 38.1, 42.4, 54.7, 110.0, 124.5, 124.8, 133.6, 145.5,
163.4, 168.6.
1.0 Hz, Ar-4H), 6.81 (1H, dd, J¼8.3, 1.0 Hz, Ar-6H), 7.24
(1H, dd, J¼8.3, 7.9 Hz, Ar-5H); dC (75.5 MHz, CDCl3)
12.9, 14.2, 18.5, 39.0, 43.0, 56.3, 111.3, 118.6, 120.6, 130.3,
144.0, 160.5, 169.6.
4.1.7. N,N-Diethyl-2-methylsulfanyl-5,6-dimethoxybenz-
amide (2g, R15R25OMe, R35R45H). Prepared in the
same way as before. Purification by column chromato-
graphy [eluant: ethyl acetate–light petroleum (3:17)];
Gummy liquid (72%); (Found C, 59.55; H, 7.49; N, 4.96.
C14H21O3NS requires C, 59.36; H, 7.42; N, 4.94%); nmax
(NEAT): 1631 (CvO) cm21; dH (300 MHz, CDCl3) 1.07
(3H, t, J¼7.1 Hz, –CH2CH3), 1.27 (3H, t, J¼7.1 Hz,
–CH2CH3), 2.42 (3H, s, –SMe), 3.13 (2H, q, J¼7.1 Hz,
–CH2CH3), 3.50–3.60 (2H, m, –CH2CH3), 3.84 (3H, s,
–OMe), 3.86 (3H, s, –OMe), 6.87 (1H, d, J¼8.5 Hz, Ar-
3H), 7.09 (1H, d, J¼8.5 Hz, Ar-4H); dC (75.5 MHz, CDCl3)
12.8, 14.1, 18.7, 39.0, 43.2, 56.2, 61.9, 113.1, 126.0, 126.5,
134.6, 145.4, 151.9, 166.6.
4.1.4. N,N-Diethyl-2-methylsulfanyl-5-methoxybenz-
amide (2d, R15H, R25OMe, R35R45H). Desilylation
was done by refluxing the compound (370 mg, 1.33 mmol)
with CsF (350 mg, 2 equiv.) in DMF–water mixture (10:1).
After cooling, the mixture was evaporated to dryness in
vaccuo and the residue was extracted with ether, washed
with brine water. Drying and removal of solvent afforded
compound 2d (R1¼H, R2¼OMe, R3¼R4¼H) which was
purified by column chromatography [eluant: ethyl acetate–
light petroleum (3:17)]; colourless oil (260 mg,
90%);(Found C, 61.65; H, 7.80; N, 5.48. C13H19O2NS
requires C, 61.66; H, 7.50; N, 5.53%); nmax (NEAT): 1631
(CvO) cm21; dH (300 MHz, CDCl3) 1.03 (3H, t, J¼7.0 Hz,
–CH2CH3), 1.25 (3H, t, J¼7.0 Hz, –CH2CH3), 2.38 (3H, s,
–SMe), 3.11 (2H, q, J¼7.0 Hz, –CH2CH3), 3.50–3.60 (2H,
m, –CH2CH3), 3.76 (3H, s, –OMe), 6.72 (1H, d, J¼2.8 Hz,
Ar-6H), 6.84 (1H, dd, J¼8.6, 2.8 Hz, Ar-4H), 7.31 (1H, d,
J¼8.6 Hz, Ar-3H); dC (75.5 MHz, CDCl3) 12.9, 14.3, 19.1,
39.1, 43.1, 55.8, 112.0, 112.2, 115.6, 118.7, 125.0, 129.9,
133.0, 141.2, 159.0, 169.5.
4.1.8. N,N-Diethyl-2-methylsulfanyl-4,6-dimethoxybenz-
amide (2h, R15OMe, R25H, R35OMe, R45H). Pre-
pared in the same way as before; colourless solid (ether–
petroleum ether) (70%); mp 78–808C. (Found C, 59.65; H,
7.59; N, 4.86. C14H21O3NS requires C, 59.36; H, 7.42; N,
4.94%); nmax (KBr): 1637 (CvO) cm21; dH (300 MHz,
CDCl3) 1.01 (3H, t, J¼7.1 Hz, –CH2CH3), 1.23 (3H, t,
J¼7.1 Hz, –CH2CH3), 2.42 (3H, s, –SMe), 3.24 (4H, q,
J¼7.1 Hz, –CH2CH3), 3.76 (3H, s, –OMe), 3.78 (3H, s,
–OMe), 6.26 (1H, d, J¼2.0 Hz, Ar-3H), 6.40 (1H, d,
J¼2.0 Hz, Ar-5H); dC (75.5 MHz, CDCl3) 13.0, 14.2, 16.7,
39.1, 43.0, 55.8, 56.0, 96.0, 104.3, 119.7, 137.7, 157.1,
161.1, 167.1.
4.1.9. N,N-Diethyl-2-methylsulfanyl-6-chlorobenzamide
(2i, R15Cl, R35R45R55H). Prepared in the same way as
before; Crystaline colourless solid (ether–petroleum ether)
(75%); mp 56–578C. (Found C, 56.05; H, 6.49; N, 5.32.
C12H16ONSCl requires C, 56.03; H, 6.22; N, 5.44%); nmax
(KBr): 1624 (CvO) cm21; dH (300 MHz, CDCl3) 1.12 (3H,
t, J¼7.1 Hz, –CH2CH3); 1.28 (3H, t, J¼7.1 Hz, –CH2CH3),
2.46 (3H, s, –SMe), 3.15 (2H, q, J¼7.1 Hz, –CH2CH3),
3.61 (2H, q, J¼7.1 Hz, –CH2CH3), 7.17–7.26 (3H, m, Ar-
3, 4, 5H); dC (75.5 MHz, CDCl3) 13.0, 14.1, 16.8, 39.1,
43.0, 125.5, 126.7, 129.9, 131.2, 136.1, 137.9, 166.1.
4.1.5. N,N-Diethyl-2-methylsulfanyl-4-methoxybenz-
amide (2e, R15R25H, R35OMe, R45H). Compound 2e
(R1¼R2¼H, R3¼OMe, R4¼H) was synthesized following
the general procedure with 1.2 equiv. of sec-BuLi. Purifi-
cation by column chromatography [eluant: ethyl acetate–
light petroleum (3:17)]; Yellowish oil (62%); (Found C,
61.55; H, 7.81; N, 5.58. C13H19O2NS requires C, 61.66; H,
7.50; N, 5.53%); nmax (NEAT): 1627 (CvO) cm21; dH
(300 MHz, CDCl3) 1.08 (3H, t, J¼7.1 Hz, –CH2CH3), 1.27
(3H, t, J¼7.1 Hz, –CH2CH3), 2.44 (3H, s, –SMe), 3.14
(2H, q, J¼7.1 Hz, –CH2CH3), 3.58 (2H, q, J¼7.1 Hz,
–CH2CH3), 3.81 (3H, s, –OMe), 6.70 (1H, dd, J¼8.4,
2.3 Hz, Ar-5H), 6.80 (1H, d, J¼2.3 Hz, Ar-3H), 7.10 (1H, d,
J¼8.4 Hz, Ar-6H); dC (75.5 MHz, CDCl3) 13.0, 14.4, 16.5,
39.3, 43.2, 55.7, 110.5, 113.3, 127.8, 130.2, 137.1, 160.3,
169.7.
4.1.10. N,N-Diethyl-2-methylsulfanyl-4-methylbenz-
amide (2j, R15R25H, R35Me, R45H). Prepared in the
same way as before. Purification by column chromato-
graphy [eluant: ethyl acetate–light petroleum (1:9)];
Viscous liquid (71%); (Found C, 65.80; H, 7.99; N, 5.96.
C13H19ONS requires C, 65.82; H, 8.01; N, 5.90%); nmax
(NEAT): 1631 (CvO) cm21; dH (300 MHz, CDCl3) 0.98
(3H, t, J¼7.0 Hz, –CH2CH3), 1.06 (3H, t, J¼7.0 Hz,
–CH2CH3), 2.36 (3H, s, –Me), 2.37 (3H, s, –SMe), 3.29
(2H, q, J¼7.0 Hz, –CH2CH3), 3.36 (2H, q, J¼7.0 Hz,
–CH2CH3), 7.22 (1H, d, J¼3.0 Hz, Ar-3H), 7.27 (1H, dd,
J¼8.0, 3.0 Hz, Ar-5H), 7.67 (1H, d, J¼8.0 Hz, Ar-6H); dC
(75.5 MHz, CDCl3) 13.0, 16.8, 14.1, 21.7, 39.23, 93.0,
126.5, 126.6, 128.2, 134.9, 135.0, 139.3, 169.9.
4.1.6. N,N-Diethyl-2-methylsulfanyl-3-methoxybenz-
amide (2f, R15R25R35H, R45OMe). Prepared in the
same way as before. Purification by column chromato-
graphy [eluant: ethyl acetate–light petroleum (3:17)];
colourless viscous liquid (85%); (Found C, 61.95; H, 7.61;
N, 5.50. C13H19O2NS requires C, 61.66; H, 7.50; N, 5.53%);
nmax (NEAT): 1631 (CvO) cm21; dH (300 MHz, CDCl3)
0.96 (3H, t, J¼7.2 Hz, –CH2CH3), 1.20 (3H, t, J¼7.2 Hz,
–CH2CH3), 2.30 (3H, s, –SMe), 3.03 (2H, q, J¼7.2 Hz,
–CH2CH3), 3.28–3.39 (1H, m, –CH2CH3), 3.62–3.74 (1H,
m, –CH2CH3), 3.84 (3H, s, –OMe), 6.74 (1H, dd, J¼7.9,
4.1.11. N,N-Diethyl-3-methylsulfanyl-5-trimethyl-
silylthiophene-2-carboxamide (2k). Prepared in the same

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C. Mukherjee et al. / Tetrahedron 59 (2003) 4767–4774
way as before. Purification by column chromatography
[eluant: ethyl acetate–light petroleum (3:17)]; Gummy
liquid (79%); (Found C, 57.85; H, 8.59; N, 5.46. C13H23-
ONSSi requires C, 57.99; H, 8.55; N, 5.20%); nmax (NEAT):
1633 (CvO) cm21; dH (300 MHz, CDCl3) 0.08 (9H, s,
–SiMe3); 1.00 (6H, t, J¼7.1 Hz, –CH2CH3), 2.20 (3H, s,
–SMe), 3.20 (4H, q, J¼7.1 Hz, –CH2CH3), 6.70 (1H, s, Ar-
4H); dC (75.5 MHz, CDCl3) 0.2, 13.9, 18.5, 41.8, 134.0,
135.3, 138.0, 141.4, 164.5.
3.76 (2H, s, –SCH2–), 3.95 (3H, s, –OMe), 6.63 (1H, d,
J¼8.0 Hz, Ar-5H), 6.96 (1H, d, J¼7.9 Hz, Ar-7H), 7.45
(1H, dd, J¼8.0, 7.9 Hz, Ar-6H); dC (75.5 MHz, CDCl3)
40.6, 57.2, 107.9, 120.3, 120.7, 138.3, 158.2, 161.7, 199.2.
4.1.16. 2,3-Dihydro-4-trimethylsilyl-5-methoxybenzo-
[b]thiophene-3-one (3d, R15TMS, R25OMe, R35
R45H). Obtained as mixture with an extremely poor yield
of the thioindoxyl accompanied mostly by unreacted
starting material and some intractable decomposition
product, nmax (NEAT): 1693 (CvO) cm21; dH (300 MHz,
CDCl3) 0.12 {s, 9H, –Si(CH3)3}, 3.54 (s, 3H, –SH2), 3.55
(s, 3H, OMe), 7.13 (d, 1H, J¼8.5 Hz, Ar-6H), 7.20 (d, 1H,
J¼8.5 Hz, Ar-5H).
4.1.12. N,N-Diethyl-1-methylsulfanyl-3-methoxy-
naphthalene-2-carboxamide (2l). Prepared in the same
way. Purification by column chromatography [eluant: ethyl
acetate–light petroleum (3:17)]; Gummy liquid (69%);
(Found C, 65.85; H, 8.00; N, 5.96. C13H19ONS requires C,
65.82; H, 8.01; N, 5.90%); nmax (NEAT): 1735 (CvO)
cm21; dH (300 MHz, CDCl3) 1.03 (3H, t, J¼7.1 Hz,
–CH2CH3), 1.31 (3H, t, J¼7.1 Hz, –CH2CH3), 2.42 (3H,
s, –SMe), 3.07–3.15 (2H, m, –CH2CH3), 3.48–3.88 (2H,
m, –CH2CH3), 3.92 (3H, s, –OMe), 7.19 (1H, s, Ar-4H),
7.47–7.51 (2H, m, Ar-6, 7H), 7.75–7.78 (1H, m, Ar-5H),
8.52–8.53 (1H, m, Ar-8H); dC (75.5 MHz, CDCl3): 12.8,
13.9, 20.5, 39.0, 43.0, 56.0, 107.7, 125.4, 126.6, 127.4,
127.8, 130.1, 131.7, 135.1, 135.3, 153.7, 167.3.
4.1.17. 2,3-Dihydro-5-methoxysulfanylbenzo[b]thio-
phene-3-one (3e, R15H, R25OMe, R35R45H). Greenish
solid, crystalised from EtOH (69%); (Found C, 60.18; H,
4.49. C9H8O2S requires C, 60.00; H, 4.44%); mp 94–958C;
n
max (KBr): 1689 (CvO) cm21; dH (300 MHz, CDCl3) 3.82
(3H, s, –OMe), 3.83 (2H, s, –SCH2–), 7.16 (1H, d,
J¼2.7 Hz, Ar-4H), 7.21 (1H, dd, J¼8.5, 2.7 Hz, Ar-6H),
7.30 (1H, d, J¼8.5 Hz, Ar-7H); dC (75.5 MHz, CDCl3) 40.5,
55.8, 108.3, 125.5, 125.9, 129.9, 146.6, 158.1, 200.3.
4.1.13. Synthesis of thioindoxyl. To a stirred solution of
THF (10 ml) and n-BuLi (1.37 mL, 1.5 equiv.) at 2788C,
diisopropylamine (0.8 mL, 2.5 equiv.), was added through
needle syringe system. The mixture was allowed to reach
2308C and kept at that temperature for 1 h. Then it was
cooled again to 2788C and compound 2a
(R1¼R2¼R3¼R4¼H) (510 mg, 2.3 mmol) in THF (5 mL)
was added dropwise and stirring was continued for 30 min
at that temperature. The reaction mixture was then allowed
to attain ambient temperature and kept at that temperature
for 10 h. Usual ammonium chloride work up afforded 2,3-
dihydrobenzo[b]thiophene-3-one (3a, R1¼R2¼R3¼R4¼H)
which was purified by column chromatography [eluant:
ethyl acetate–light petroleum (1:9)]; colourless needles,
crystalised from EtOH (230 mg, 67%); mp 62–648C;
(Found C, 64.10; H, 4.30. C8H6OS requires C, 64.00; H,
4.00%); nmax (CHCl3): 1689 (CvO) cm21; dH (300 MHz,
CDCl3) 3.70 (2H, s, –SCH2–); 7.14 (1H, ddd, J¼7.5, 7.0,
1.2 Hz, Ar-6H), 7.35 (1H, dd, J¼7.5, 1.2 Hz, Ar-7H), 7.47
(1H, ddd, J¼7.7, 7.0, 1.2 Hz, Ar-5H), 7.70 (1H, dd, J¼7.7,
1.2 Hz, Ar-4H); dC (75.5 MHz, CDCl3) 39.6, 124.9, 125.1,
127.0, 131.3, 136.0, 154.6, 200.4.
4.1.18. 2,3-Dihydro-6-methoxybenzo[b]thiophene-3-one
(3f, R15R25H, R35OMe, R45H). Yellowish solid,
crystalised from EtOH (78%); mp 112–1138C; (Found C,
60.21; H, 4.57. C9H8O2S requires C, 60.00; H, 4.44%); nmax
(CHCl3): 1681 (CvO) cm21; dH (300 MHz, CDCl3) 3.81
(2H, s, –SCH2–), 3.88 (3H, s, –OMe), 6.75 (1H, dd, J¼8.5,
2.2 Hz, Ar-5H), 6.85 (1H, d, J¼2.2 Hz, Ar-7H), 7.70 (1H, d,
J¼8.5 Hz, Ar-4H); dC (75.5 MHz, CDCl3) 40.0, 56.2, 107.8,
113.7, 124.7, 128.4, 157.6, 166.3, 198.4.
4.1.19. 2,3-Dihydro-7-methoxybenzo[b]thiophene-3-one
(3g, R15R25R35H, R45OMe). Yellowish solid, crystal-
ised from EtOH (69%); (Found C, 60.14; H, 4.79. C9H8O2S
requires C, 60.00; H, 4.44%); mp 99–1018C; nmax (CHCl3):
1716 (CvO) cm21; dH (300 MHz, CDCl3) 3.78 (2H, s,
–SCH2–), 3.94 (3H, s, –OMe), 7.01 (1H, dd, J¼7.8,
1.0 Hz, Ar-6H), 7.19 (1H, dd, J¼7.8, 7.7 Hz, Ar-5H),
7.40 (1H, dd, J¼7.7, 1.0 Hz, Ar-4H); dC (75.5 MHz,
CDCl3) 39.8, 56.3, 115.5, 118.6, 126.7, 132.8, 143.8,
155.5, 200.7.
4.1.20. 2,3-Dihydro-4-chlorobenzo[b]thiophene-3-one
(3h, R15Cl, R25R35R45H). Colourless solid, crystalised
from EtOH (68%); mp 109–1108C; (Found C, 52.17; H,
2.99. C8H5OSCl requires C, 52.03; H, 2.71%); nmax (KBr):
1687 (CvO) cm21; dH (300 MHz, CDCl3) 3.83 (2H, s,
–SCH2–), 7.09 (1H, dd, J¼7.0, 1.0 Hz, Ar-5H), 7.24 (1H,
dd, J¼7.5, 1.0 Hz, Ar-7H), 7.35 (1H, dd, J¼7.5, 7.0 Hz, Ar-
6H); dC (75.5 MHz, CDCl3) 40.1, 123.5, 127.2, 135.8,
136.9, 157.4, 197.4.
4.1.14. 2,3-Dihydro-4-methylsulfanylbenzo[b]thiophene-
3-one (3b, R15SMe, R25R35R45H). Colourless solid,
crystalised from EtOH (66%); mp 121–1238C; (Found C,
55.32; H, 4.21. C9H8OS2 requires C, 55.10; H, 4.08%); nmax
(CHCl3): 1689 (CvO) cm21; dH (300 MHz, CDCl3) 2.39
(3H, s, –SMe), 3.72 (2H, s, –SCH2–), 6.84 (1H, dd, J¼7.8,
1.5 Hz, Ar-5H), 7.03 (1H, dd, J¼7.7, 1.5 Hz, Ar-7H), 7.34
(1H, dd, J¼7.8, 7.7 Hz, Ar-6H); dC (75.5 MHz, CDCl3)
14.1, 39.2, 119.3, 119.8, 126.7, 135.2, 145.1, 156.5, 199.8.
4.1.21. 2,3-Dihydro-6-methylbenzo[b]thiophene-3-one
(3i, R15R25H, R35Me, R45H). Pale yellow fluffy
solid, crystalised from EtOH (77%); (Found C, 65.93; H,
4.86. C9H8OS requires C, 65.85; H, 4.87%); mp 80–818C;
4.1.15. 2,3-Dihydro-4-methoxybenzo[b]thiophene-3-one
(3c, R15OMe, R25R35R45H). Light yellow solid
crystalised from EtOH (65%); (Found C, 60.22; H, 4.49.
C9H8O2S requires C, 60.00; H, 4.44%); mp 101–1048C;
nmax (CHCl3): 1683 (CvO) cm21; dH (300 MHz, CDCl3)
n
max (KBr): 1708 (CvO) cm21; dH (300 MHz, CDCl3) 2.33
(3H, s, –CH3), 3.69 (2H, s, –SCH2–), 6.93 (1H, dd, J¼7.9,
1.9 Hz, Ar-5H), 7.14 (1H, d, J¼1.9 Hz, Ar-7H), 7.58 (1H, d,

C. Mukherjee et al. / Tetrahedron 59 (2003) 4767–4774
4773
J¼7.9 Hz, Ar-4H); dC (75.5 MHz, CDCl3) 22.4, 39.7, 125.0,
[eluant: ethyl acetate–light petroleum (1:9)]; colourless
oil (82%), bp 808C/0.05 mm (lit18 bp 1418C/17 mm).
126.6, 126.7, 129.1, 147.6, 155.0, 199.9.
4.1.22. 2,3-Dihydro-4, 5-dimethoxybenzo[b]thiophene-3-
one (3j, R15R25OMe, R35R45H). White solid, crystal-
ised from EtOH (89%); (Found C, 57.26; H, 4.99.
C10H10O3S requires C, 57.14; H, 4.76%); mp 63–648C;
nmax (CHCl3): 1693 (CvO) cm21; dH (300 MHz, CDCl3)
3.73 (2H, s, –SCH2–), 3.79 (3H, s, –OMe), 3.89 (3H, s,
–OMe), 6.97 (1H, d, J¼8.5 Hz, Ar-6H), 7.10 (1H, d,
J¼8.5 Hz, Ar-7H); dC (75.5 MHz, CDCl3) 39.1, 56.2, 60.7,
117.9, 118.1, 120.9, 122.9, 144.8, 148.8, 196.9.
4.2.3. 5-Methoxybenzo[b]thiophene (4d, R15H,
R25OMe, R35R45H). Purified by column chromatog-
raphy [eluant: ethyl acetate–light petroleum (1:9)]; colour-
less solid (77%); mp 44–458C (lit17 mp 43–448C).
4.2.4. 6-Methoxybenzo[b]thiophene (4e, R15R25H,
R35OMe, R45H). Purified by column chromatography
[eluant: ethyl acetate–light petroleum (1:9)]; colourless oil
(73%); bp 82–838C/0.1 mm (lit4b,d bp 808C/0.1 mm).
4.1.23. 2,3-Dihydro-4, 6-dimethoxybenzo[b]thiophene-3-
one (3k, R15OMe, R25H, R35OMe, R45H). Colourless
needles, crystalised from EtOH (81%); (Found C, 57.16; H,
4.89. C10H10O3S requires C, 57.14; H, 4.76%); mp 97–
988C; nmax (NEAT): 1680 cm21; dH (300 MHz, CDCl3)
3.68 (2H, s, –SCH2–), 3.79 (3H, s, –OMe), 3.83 (3H, s,
OMe), 6.07 (1H, d, J¼1.8 Hz, Ar-6H), 6.37 (1H, d,
J¼1.8 Hz, Ar-5H); dC (75.5 MHz, CDCl3) 40.1, 56.2,
56.3, 96.0, 100.2, 113.9, 160.0, 161.8, 167.7, 196.4,
4.2.5. 7-Methoxybenzo[b]thiophene (4f, R15R25R35H,
R45OMe). Purified by column chromatography [eluant:
ethyl acetate–light petroleum (1:9)]; colourless oil (71%);
bp 878C/0.1 mm (lit19 bp 80–908C/0.1 mm).
4.2.6. 6-Methylbenzo[b]thiophene (4g, R15R25H,
R35Me, R45H). Purified by column chromatography
[eluant: ethyl acetate–light petroleum (1:4)]; Low melting
white solid (92%); (Found C, 72.98; H, 5.50. C9H8S
requires C, 72.97; H, 5.40%); dH (300 MHz, CDCl3) 7.66
(1H, dd, J¼8.2, 3.0 Hz, Ar-3H), 7.62 (1H, d, J¼3.0 Hz, Ar-
6H), 7.29 (1H, d, J¼5.4 Hz, Ar-5H), 7.23 (1H, d, J¼5.4 Hz,
Ar-2H), 7.14 (1H, d, J¼8.2 Hz, Ar-4H), 2.43 (3H, s, –CH3);
dC (75.5 MHz, CDCl3) 21.9, 122.6, 123.5, 123.9, 125.5,
126.6, 134.5, 137.7, 140.4.
4.1.24. 2,3-Dihydro-4-methoxynaphtho[1,2-b]thiophene-
3-one (3l). Yellowish solid, crystalised from EtOH (73%);
mp 103–1058C; (Found C, 67.86; H, 4.59. C13H10O2S
requires C, 67.82; H, 4.34%); nmax (CHCl3): 1681 (CvO)
cm21; dH (300 MHz, CDCl3) 3.87 (2H, s, –SCH2–), 3.99
(3H, s, –OMe), 6.81 (1H, s, Ar-5H), 7.39 (1H, ddd, J¼8.2, 7.0,
1.0 Hz, Ar-7H), 7.59 (1H, ddd, J¼8.2, 7.0, 1.2 Hz, Ar-8H), 7.70
(1H, dd, J¼8.2, 1.2 Hz, Ar-6H), 7.86 (1H, dd, J¼8.2, 1.0 Hz,
Ar-9H); dC (75.5 MHz, CDCl3) 40.2, 56.0, 103.1, 119.9, 124.7,
124.9, 127.7, 131.1, 138.0, 150.0, 156.4, 161.3, 198.3.
4.2.7. 4,5-Dimethoxybenzo[b]thiophene (4h,
R15R25OMe, R35R45H). Purified by column chroma-
tography [eluant: ethyl acetate–light petroleum (1:9)];
Yellowish oil (73%); (Found C, 61.76; H, 5.11. C10H10
O2S requires C, 61.85; H, 5.15%); bp 91–958C/0.1 mm; dH
(300 MHz, CDCl3) 3.93 (3H, s, –OMe), 3.99 (3H, s, –
OMe), 7.07 (1H, d, J¼8.7 Hz, Ar-6H), 7.37 (1H, d,
J¼5.5 Hz, Ar-2H), 7.42 (1H, d, J¼5.5 Hz, Ar-3H), 7.53
(1H, d, J¼8.7 Hz, Ar-7H); dC (75.5 MHz, CDCl3)
57.6, 61.6, 113.2, 118.1, 120.7, 127.3, 134.2, 135.6, 144.2,
148.9.
4.2. General procedure for the synthesis of
benzo[b]thiophene
To a solution of compound 3a (R1¼R2¼R3¼R4¼H) in
MeOH and 10% NaOH (6:1), NaBH4 (2 equiv.) in MeOH
and 10% NaOH solution (10:3) was added. This mixture
was heated to reflux for 1 h on steam bath and then allowed
to stand just under boiling condition for 12 h. After removal
of MeOH, the reaction mixture was acidified with 10%
sulfuric acid and extracted with ether. The organic layer was
washed with water and dried. Removal of solvent afforded
compound 4a (R1¼R2¼R3¼R4¼H) which was purified by
column chromatography [eluant: ethyl acetate–light
petroleum (1:9)]; colourless solid (67%), mp 32–338C
(lit4b,d mp 31–31.58C). All the compounds reported below
were synthesized in the same way.
4.2.8. 4,6-Dimethoxybenzo[b]thiophene (4i, R15OMe,
R25H, R35OMe, R45H). Purified by column chromatog-
raphy [eluant: ethyl acetate–light petroleum (1:9)]; colour-
less crystals (85%); (Found C, 61.98; H, 4.35. C10H10O2S
requires C, 61.85; H, 5.15%); mp 75–768C; dH (300 MHz,
CDCl3) 3.75 (3H, s, –OMe), 3.81 (3H, s, –OMe), 6.31 (1H,
d, J¼1.7 Hz, Ar-5H), 6.83 (1H, d, J¼1.7 Hz, Ar-7H), 7.05
(1H, d, J¼5.5 Hz, Ar-2H), 7.28 (1H, d, J¼5.5 Hz, Ar-3H);
dC (75.5 MHz, CDCl3) 55.8, 56.0, 96.2, 96.6, 120.6, 122.2,
125.4, 142.5, 155.7, 159.2.
4.2.1. 4-Methylsulfanylbenzo[b]thiophene (4b, R15SMe,
R25R35R45H). Purified by column chromatography
[eluant: ethyl acetate–light petroleum (1:9)]; Light yellow
gummy liquid (45%); (Found C, 59.98; H, 4.44. C10H10O3S
requires C, 60.00; H, 4.47%); dH (300 MHz, CDCl3) 2.57
(3H, s, –SMe), 7.23 (1H, dd, J¼8.0, 7.4 Hz, Ar-6H), 7.44–
7.53 (3H, m, Ar-2, 3, 5H), 7.80 (1H, d, J¼8.0 Hz, Ar-7H);
dC (75.5 MHz, CDCl3) 16.5, 122.9, 123.1, 125.0, 127.5,
127.6, 131.5, 140.2, 140.7.
4.2.9. 2,3-Dihydro-3-hydroxy-4-chlorobenzo[b]thio-
phene (6). Compound 6 was synthesized following the
general procedure of preparation of benzo[b]thiophene as
stated above. Purified by column chromatography [eluant:
ethyl acetate–light petroleum (1:4)]; Reddish white solid
(75%); mp 155–1568C; (Found C, 51.89; H, 3.80.
C8H7ClOS requires C, 51.47; H, 3.75%); nmax (KBr):
3226 (–OH) cm21; dH (300 MHz, CDCl3) 3.27 (1H, dd,
J¼12.5 Hz, 1.3, –SCH2–), 3.59 (1H, dd, J¼12.5, 6.03 Hz,
–SCH2–), 5.50 {1H, dd, J¼6.03, 1.3 Hz, –SCH2–
CH(OH)–}, 6.97–7.15 (3H, m, Ar-5, 6, 7H); dC
4.2.2. 4-Methoxybenzo[b]thiophene (4c, R15OMe,
R25R35R45H). Purified by column chromatography

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C. Mukherjee et al. / Tetrahedron 59 (2003) 4767–4774
York, 1954. (b) Iddon, B.; Scrowston, R. M. Advances in
Heterocyclic Chemistry; Katritzky, A. R., Boulton, A. J., Eds.;
Accademic: New York, 1970; Vol. 11. (c) Iddon, B. New
Trends in Heterocyclic Chemistry. Studies in Organic
Chemistry; 1979; Vol. 3. (d) Scrowston, R. M. Advances in
Heterocyclic Chemistry; Katritzky, A. R., Boulton, S. J., Eds.;
Academic: New York, 1970; Vol. 11, p 172. (e) Rajappa, S.
Comprehensive Heterocyclic Chemistrty; Katritzky, A. R.,
Rees, C. W., Eds.; Pergamon: New York, 1984; Vol. 4.
5. (a) Campaign, E.; Knapp, D. R.; Neiss, E. S.; Bosin, T. R. Adv.
Drug Res. 1970, 5, 1. (b) Bosin, T. R.; Campaign, E. Adv. Drug
Res. 1977, 12, 191.
(75.5 MHz, CDCl3) 40.8, 76.1, 121.5, 125.4, 131.5, 138.7,
144.0, 146.0.
4.2.10. 3-Methoxy-4-chlorobenzo[b]thiophene (7). To a
stirred solution of 2,3-dihydro-4-chlorobenzo[b]thiophene-
3-one 3h (R1¼Cl, R2¼R3¼R4¼H): equiv.) in 20% aqueous
potassium hydroxide solution, kept at room temperature,
dimethylsulphate (3 equiv.) was added through a pressure
equalizing dropping funnel. After stirring for 45 min the
reaction mixture was warmed to 60–708C for 1 h then
cooled and extracted with ether. The ether layer was washed
with water, dried and solvent removed to afford compound 7
which was purified by column chromatography [eluant:
ethyl acetate–light petroleum (1:4)]; colourless solid
(88%); mp 146–1478C; (Found C, 54.39; H, 3.79.
C9H7ClOS requires C, 54.40; H, 3.52%); dH (300 MHz,
CDCl3) 3.97 (3H, s, –OMe), 7.17 (1H, s, Ar-2H), 7.19 (1H,
dd, J¼8.0, 7.8 Hz, Ar-6H), 7.33 (1H, d, J¼7.8 Hz, Ar-5H),
7.56 (1H, d, J¼8.0 Hz, Ar-7H); dC (75.5 MHz, CDCl3) 65.3,
77.6, 123.5, 126.9, 128.0, 131.4, 131.4, 140.3, 149.6.
6. Cabiddu, M. G.; Cabiddu, S.; Cadoni, E.; Montis, S.; Fattuoni,
C.; Melis, S.; Usai, M. Synthesis 2002, 875. Use of
commercially available methyl 2-methylthiobenzoate by the
authors restricted them to only the parent thioindoxyl carrying
no substituent in the benzene ring.
7. (a) Connor, D. T.; Catenko, W. A.; Mullicans, M. D.;
Sorenson, R. J.; Unanjst, P. C.; Weibest, R. J.; Adolphson,
R. L.; Kennedy, J. A.; Tueson, D. O.; Wright, C. W.; Connoy,
M. C. J. Med. Chem. 1992, 35, 958. (b) Hrib, N. J.; Jurcak,
J. G.; Bregna, D. E.; Dunn, R. W.; Geyer, H. M. J. Med. Chem.
1992, 35, 2712. (c) Boschelli, D. H.; Kramer, J. B.; Khatana,
S.; Sorenson, R. J.; Ferrin, M.; Wright, C. D.; Lisch, M. E.;
Imsa, K. J. Med. Chem. 1995, 38. (d) Benincori, T.; Gladioli,
S.; Rizzo, S.; Sannicolo, F. J. Org. Chem. 2001, 66, 5940.
(e) Sannicolo, F.; Benincori, T.; Rizzo, S.; Gladioli, S.;
Pulacchine, S.; Zotti, G. Synthesis 2001, 2327. (f) Hendrickx,
A.; Samat, A.; Guglielmetti, R. Synthesis 2002, 213.
8. (a) Bhattacharya, S.; De, A.; Ewing, D. F. J. Chem. Soc.,
Perkin Trans. 1 1994, 689. (b) Ghosh, S. C.; De, A. J. Chem.
Soc., Perkin Trans. 1 1998, 2559.
4.2.11. 4-Methoxynaphtho[b]thiophene (4j). Purified by
column chromatography [eluant: ethyl acetate–light
petroleum (1:9)]; colourless crystals (79%); mp 66–678C;
(Found C, 72.91; H, 4.65. C13H10OS requires C, 72.89; H,
4.67%); dH (300 MHz, CDCl3) 3.97 (3H, s, –OMe), 6.87
(1H, s, Ar-5H), 7.33 (2H, m, Ar-7, 8H), 7.37 (1H, d,
J¼5.3 Hz, Ar-2H), 7.54 (1H, d, J¼5.3 Hz, Ar-3H), 7.73
(1H, dd, J¼8.1, 1.5 Hz, Ar-6H), 7.96 (1H, dd, J¼8.1,
1.5 Hz, Ar-9H); dC (75.5 MHz, CDCl3) 55.7, 101.5, 122.2,
123.8, 124.5, 124.8, 125.3, 126.3, 127.9, 131.6, 132.9,
139.9, 153.9.
9. Kamila, S.; Mukherjee, C.; De, A. Tetrahedron Lett. 2001, 42,
5955.
Acknowledgements
10. Datta, S.; De, A. J. Chem. Soc., Perkin Trans. 1 1989, 603.
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Thanks are due to the Council of Scientific and Industrial
Research (New Delhi) for financial assistance (Project No.
01(1573)/99/EMR-II) and for providing S. K. with a Senior
Fellowship.
12. Mills, R. J.; Taylor, N. J.; Snieckus, V. J. Org. Chem. 1989, 54,
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