C. Gain et al.
Bioorganic & Medicinal Chemistry 37 (2021) 116112
125.3, 128.3, 129.2, 129.5, 130.2, 150.6, 128.6, 128.8, 129.9, 135.2,
137.7, 166.9, 181.3 ppm; HRMS: calcd for C16H8O3: 248.0473 [M+],
found 248.0472.
the previous synthesis, asoff white solid; Yield: 270 mg (1 mmol, 84%);
mp:106–108 ◦C; IR(KBr) νmax: 2358 cmꢀ 1; 1H NMR (500 MHz, CDCl3): δ
= 2.53 (s, 3H), 3.72 (s, 2H), 6.76 (s, 1H), 7.07 (d, J = 3.0 Hz,1H), 7.19 (t,
J = 4.5 Hz, 1H), 7.41 (d, J = 8.5 Hz, 1H), 7.49 (d, J = 5.0 Hz, 1H), 7.79
(d, J = 8.5 Hz, 1H) ppm; 13C NMR (125 MHz, CDCl3): δ = 16.3, 22.1,
118.4, 121.5, 122.9, 123.8, 125.8, 126.8, 127.6, 128.2, 128.3, 138.2,
139.5, 142.0, 142.8 ppm; HRMS (ESI+): m/z [M+Na]+ calcd for
4-Bromo-6,7-dihydro-2-methylbenzo[b]thiophene-5-carbalde-
hyde (29): 2.3 ml PBr3 (24.4 mmol) was added drop wise to an ice cold
mixture of 2.5 ml DMF (27.2 mmol) in 10 ml chloroform at 0–5 ◦C and
the stirring was continued for 30 min protecting from moisture. A so-
lution of 2-methyl-6,7-dihydrobenzo[b]thiophen-4(5H)-one (28) (1.28
gm, 7.7 mmol) in 5 ml chloroform was added drop wise to it. The re-
action mixture was gradually allowed to attain r.t. and stirring was
continued for another 16 hrs when the reaction was found to be
completed. It was poured into ice cold saturated sodium acetate solu-
tion, stirred well for about 5 min and extracted with chloroform (3 × 20
ml). Combined chloroform layer was washed successively with cold
brine solution, NaHCO3 solution and finally with brine solution and
dried (anhyd. Na2SO4). After removal of the solvent, resulting crude
product was purified by column chromatography [silica gel. (100–200
mesh) / P.E (60–80 ◦C)-EtOAC: 1:50] to obtain the title compound 29 as
C15H11NaNS2: 292.0231; found: 292.0236.
2-[2-Methyl-4-(2-thienyl)benzo[b]thiophen-5-yl]acetic
acid
(34): 260 mg (0.97 mmol) of the nitrile derivative 33 on hydrolysis with
4 ml 30% KOH in EtOH (reflux for 20 hrs) afforded the compound 34 as
a white solid after usual work up and purification. Yield: 140 mg (0.49
mmol, 50%); mp: 170–172 ◦C; IR (KBr) νmax: 1699 cmꢀ 1; HRMS (ESI+):
m/z [M+Na]+ calcd for C15H12O2NaS2: 311.0176; found: 311.1094.
9-Methylnaptho[1,2-b:7,8-b′]bisthiophen-4-ol (35): Cyclization
of the carboxylic acid 34 (120 mg, 0.42 mmol) with a mixture of 4.2 ml
trifluoroacetic anhydride and 1.5 ml trifluoroacetic acid, afforded the
compound 35 as a dark coloured semi solid mass, after usual work up
and purification. Yield: 90 mg (0.33 mmol, 80%); 1H NMR (500 MHz,
CDCl3): δ = 2.78 (s, 3H), 5.47 (br s, 1H), 7.15 (s, 1H), 7.62 (d, J = 5.0 Hz,
1H), 7.65 (d, J = 8.5 Hz, 1H), 7.73 (d, J = 5.5 Hz, 1H), 7.82 (d, J = 8.5
Hz, 1H) 8.03 (s, 1H) ppm; 13C NMR (125 MHz, CDCl3): δ = 16.6, 107.0,
120.3, 120.5, 120.8, 122.2, 123.0, 125.2, 130.3, 130.7, 136.3, 137.0,
141.2, 148.5, 211.40 ppm; HRMS (ESI+): m/z [M+H]+ calcd for
C15H11OS2: 271.0173; found: 271.3785.
light yellow solid. Yield 1.45 gm (73%), mp: 70–72 ◦C; IR (KBr) νmax
:
1634 cmꢀ 1; 1H NMR (400 MHz, CDCl3): δ = 2.38 (s, 3H), 2.69–2.64 (m,
2H), 2.79–2.75 (m, 2H) 6.90 (s, 1H), 9.97 (s, 1H) ppm; 13C NMR (100
MHz, CDCl3): δ = 15.2, 22.5, 23.9, 124.7, 129.1, 135.3, 135.6, 137.1,
142.0, 192.4 ppm; HRMS (ESI+): m/z [M+H]+ calcd. for C10H10O81Br:
258.9615; found: 258.9158.
6,7-Dihydro-2-methyl-4-(2-thienyl)benzo[b]thiophene-5-car-
baldehyde (30): 700 mg (2.69 mmol) the bromoaldehyde 29 was
subjected to Suzuki coupling reaction (reaction time 10 hrs) with 2-thi-
opheneboronic acid (410 mg, 3.2 mmol) under the identical reaction
condition, as used previously, afforded the compound 30 as orange
yellow solid after usual work up and purification. Yield: 430 mg (1.65
9-Methylnaphtho[1,2-b:7,8-b′]bisthiophen-4,5-dione (36): The
phenolic compound 35 (80 mg, 0.3 mmol) on oxidation with 450 mg of
Fremy’s salt in 1/6 (M) Na2HPO4 solution (30 ml) and MeOH (12 ml) for
overnight at 0–4 ◦C, afforded the o-quinone derivatives 36 as a deep
violet solid, after usual work up and purification. Yield: 65 mg (0.23
mmol, 61%), mp: 54–56 ◦C; IR (KBr) νmax: 1645 cmꢀ 1
;
1H NMR (400
mmol, 77%); mp: 227–228 ◦C; IR (KBr) νmax: 1686 & 1657 cmꢀ 1
;
1H
MHz), (CDCl3): δ = 2.37 (s, 3H), 2.78–2.83 (m, 2H), 2.83–2.91 (m, 2H),
6.52 (s, 1H), 7.0 (d, 1H, J = 3.2 Hz), 7.09 (d, ill split, J ~5 Hz, 1H), 7.46
(dd, J = 4.8 Hz & 1.6 Hz, 1H), 9.75 (s,1H) ppm; 13C NMR (75 MHz,
CDCl3): δ = 15.1, 21.8, 22.6, 124.1, 126.9, 127.5, 130.2, 131.8, 135.8,
135.9, 136.7, 141.3, 143.5, 192.2 ppm; HRMS (ESI+): m/z
[M+H]+calcd for C14H13OS2: 261.0330; found: 261.1271 & [M+Na]+
calcd for C14H12NaOS2: 283.0227; found: 283.1413.
NMR (400 MHz, CDCl3 + DMSO‑d6): δ = 2.67 (s, 3H), 7.53 (d, J = 5.6
Hz, 1H), 7.69 (d, J = 5.6 Hz, 1H), 7.87 (d, J = 8.4 Hz, 1H), 7.91 (d, J =
8.4 Hz, 1H), 8.14 (s, 1H) ppm; 13C NMR (125 MHz, CDCl3): δ = 21.6,
125.8, 128.2, 129.1, 131.2, 131.9, 133.0, 139.7, 142.1, 151.1, 152.6,
178.9, 185.0 (2C short, sample was poorly soluble even in DMSO‑d6;
possibly 2 quaternary carbons didn’t appeared with this number of
scanning) HRMS (ESI+): m/z [M+H]+ calcd for C15H9O2S2: 284.9966;
found: 284.8027 & [M+Na]+ calcd for C15H8O2NaS2: 306.9863; found:
306.7510.
2-Methyl-4-(2-thienyl)benzo[b]thiophene-5-caraldehyde (31):
420 mg (1.61 mmol) of compound 30 and 440 mg (1.94 mmol) of DDQ
in 20 ml dry benzene was refluxed (24 hrs) protecting from moisture and
after usual work up,furnished the compound 31 as pale yellow solid.
Yield: 360 mg (1.40 mmol, 86%), mp: 104–106 ◦C; IR (KBr) νmax: 1676
6,7-Dihydro-2-Methyl-4-(3-thienyl)-benzo[b]thiophene-5-car-
baldehyde (37): 705 mg (2.71 mmol) the bromoaldehyde 29 was
subjected to Suzuki coupling reaction with 3-thiopheneboronic acid
(410 mg, 3.2 mmol) under the identical reaction condition, afforded the
compound 37 after usual work up and purification as pale yellow solid;
yield: 475 mg (1.82 mmol, 67%); mp: 55–56 ◦C; IR (KBr)νmax: 1649
cmꢀ 1; 1H NMR (400 MHz, CDCl3): δ = 2.31 (s, 3H), 2.71–2.75 (m, 2H),
2.81–2.85 (m, 2H), 6.31 (s, 1H), 7.02 (dd, J = 1.2 & 4.8 Hz,1H), 7.24
(dd, ill split, J = 1.2 & 2.8 Hz, 1H), 7.35 (dd, J = 3.2 & 4.8 Hz, 1H), 9.59
(s, 1H) ppm; 13C NMR (100 MHz, CDCl3): δ = 15.2, 21.5, 22.8, 124.0,
125.9, 126.4, 129.2, 130.6, 135.7, 136.0, 136.9, 141.5, 146.1, 192.6
ppm; HRMS (ESI+): m/z [M+H]+ calcd for C14H13OS2: 261.0330;
found: 261.0750 & [M+Na]+ calcd for C14H12OS2Na: 283.0227; found:
283.689.
cmꢀ 1
;
1H NMR (400 MHz, CDCl3): δ = 2.47 & 2.50 (both s, total 3H),
6.95 (br s, 1H), 7.09 and 7.1 (both d, ill split, J = 4.8 Hz, total 1H), 7.13
& 7.14 (both d, J = 3.2 Hz, total 1H), 7.46 & 7.48 (both br s, ill split,
total 1H), 7.78 (d, J = 8.8 Hz, 1H), 7.83 (d, J = 8.4 Hz, 1H), 9.97 (s, 1H)
ppm; 13C NMR (75 MHz, CDCl3): δ = 16.2, 121.4, 121.5, 122.3, 127.2,
127.3, 130.0, 131.4, 133.1, 135.8, 140.9, 142.7, 144.8, 191.9 ppm;
HRMS (ESI+): m/z [M+H]+ calcd for C14H11OS2: 259.0173; found:
259.0110 & [M+Na]+ calcd for C14H10NaOS2: 281.0071; found:
280.9917.
[2-Methyl-4-(2-thienyl)benzo[b]thiophene-5-yl]methanol
(32): 350 mg (1.35 mmol) of the aldehyde 31 on reduction with NaBH4
(1.35 mmol) in ethanol for 2 hrs at r.t. and after usual work up, afforded
the compound 32 as a yellowish oil. Yield: 320 mg (1.23 mmol, 91%); 1H
NMR (300 MHz, CDCl3): δ = 2.13 (br s, 1H), 2.49 & 2.54 (both s, total
3H), 4.59 & 4.68 (both s, total 2H), & 6.78 & 6.88 (both s, total 1H), 7.03
(d, J = 2.4 Hz, 1H), 7.11 & 7.12 (both d, J = 3.6 Hz, total 1H), 7.37 (d, J
= 8.4 Hz, 1H), 7.39–7.41 (m, 1H), 7.71 (d, J = 8.1 Hz, 1H) ppm; NMR
(400 MHz, CDCl3): δ = 16.2, 63.0, 121.5, 122.2, 123.8, 126.0, 127.1,
127.2, 127.8, 135.9, 138.7, 138.8, 141.3, 141.5 ppm; HRMS (ESI+): m/z
[M]+ calcd for C14H12OS2: 260.0330; found: 260.1869.
2-Methyl-4-(3-thienyl)benzo[b]thiophene-5-carbaldehyde
(38): 420 mg (1.61 mmol) of compound 37 and 440 mg (1.94 mmol) of
DDQ in 20 ml dry benzene was refluxed for 24 hrs protecting from
moisture. After usual work up, the compound 38 was obtained as pale
yellow solid.yield: 370 mg (1.43 mmol, 89%); mp: 102–103 ◦C; IR (KBr)
νmax: 1673 cmꢀ 1; 1H NMR (400 MHz, CDCl3): δ = 2.56 (s, 3H), 6.91 (s,
1H), 7.23 (dd, J = 0.8 & 4.8 Hz, 1H), 7.36 (dd, J = 2.8 & 4.8 Hz, 1H),
7.51 (dd, J = 2.8 & 4.8 Hz, 1H), 7.81 (d, J = 8.4 Hz, 1H), 7.90 (d, J = 8.4
Hz, 1H), 9.99 (s, 1H) ppm; 13C NMR (100 MHz, CDCl3): δ = 16.3, 121.6,
121.7, 121.8, 125.9, 126.1, 130.0, 130.9, 136.1, 136.2, 140.5, 142.5,
145.2, 192.4 ppm; HRMS (ESI+): m/z [M+H]+ calcd for C14H11OS2:
259.0173; found: 259.0254.
2-[2-Methyl-4-(2-thienyl)benzo[b]thiophene-5-yl]acetonitrile
(33): The compound 32 (310 mg, 1.19 mmol) was converted to the
nitrile derivative 33 under the identical reaction condition, as used for
13