Syntheses of [1,2,3]selenadiazolo[4,5-e]benzofuran or benzothiophene, [1,2,3]thiadiazolo[4,5-e]benzofuran or benzothiophene, and 2-benzofuranyl-1,3,4-oxodiazole derivatives

Article abstract of DOI:10.1002/jhet.5570400305

Dehydrogenation of ethyl 3-methyl-4-oxo-4,5,6,7-tetrahydrobenzofuran-2-carboxylate 1 with 2,2′-azobisisobutyronitrile and N-bromosuccinimide gave ethyl 4-hydroxy-3-methylbenzofuran-2-carboxylate 3. Reaction of compounds 3-4 with hydrazine hydrate afforded

Full text of DOI:10.1002/jhet.5570400305

May-Jun 2003
427
Syntheses of [1,2,3]Selenadiazolo[4,5-e]benzofuran or
Benzothiophene, [1,2,3]Thiadiazolo[4,5-e]benzofuran or
Benzothiophene, and 2-Benzofuranyl-1,3,4-oxodiazole Derivatives
M. Shekarchi, F. Ellahiyan, T. Akbarzadeh and A. Shafiee*
Department of Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
Received October 21, 2002
Dehydrogenation of ethyl 3-methyl-4-oxo-4,5,6,7-tetrahydrobenzofuran-2-carboxylate 1 with 2,2′-azobi-
sisobutyronitrile and N-bromosuccinimide gave ethyl 4-hydroxy-3-methylbenzofuran-2-carboxylate 3.
Reaction of compounds 3-4 with hydrazine hydrate afforded the corresponding hydrazides 5a-b. The reac-
tion of 5a-b with aldehydes yielded substituted hydrazones 6a-l. Compounds 7a-d were prepared from
compounds 6a-d and bromine in acetic acid. Lead tetraacetate oxidation of compounds 6e-l afforded substi-
tuted oxadiazoles 8e-l. Selenium dioxide oxidation of 4-oxo-4,5,6,7-tetrahydrobenzofuran semicarbazones
9, 14a and 4-oxo-4,5,6,7-tetrahydrobenzothiophene 14b gave the tricyclic 1,2,3-selenadiazoles 10, 15a and
15b respectively. Reaction of semicarbazones 9, 14a and 14b with thionyl chloride afforded the corre-
sponding 1,2,3-thiadiazoles 12, 16a and 16b respectively.
J. Heterocyclic Chem., 40, 427 (2003).
The risk of opportunistic fungal infection has been greatly
tance to conventionally utilized antimicrobial drugs has
diverted scientist attention toward new compounds [2-3].
In view of the potential biochemical and physiological
activity of benzo[b]furan, benzo[b]thiophene, oxadiazole,
selendiazole and thiadiazole derivatives [4-10], it was
increased due to the increasing number of immuno-
compromised patient, such as those infected with HIV-1,
organ-transplants and those under cancer chemotherapy [1].
On the other hand the rising incidence of microbial resis-

428
M. Shekarchi, F. Ellahiyan, T. Akbarzadeh and A. Shafiee
Vol. 40
thought worthwhile to prepare some fused derivatives of
these structures as possible effective drugs against tropical
diseases [11].
The desired compounds were synthesized according to
Schemes 1 and 2.
the latter reaction by using 2,2′-azobisisobutyronitrile
(AIBN) instead of U.V. light increased the reaction yield
to 98% (method B) [15]. Methylation of compound 3 with
equivalent iodomethane gave compound 4. Addition of
hydrazine hydrate to esters 3 and 4 gave the correspond-
ing hydrazides 5a and 5b in high yield. Condensation of
compounds 5a and 5b with different aldehydes in the
presence of concentrated sulfuric acid afforded the corre-
sponding hydrazones 6a-l. The attempted cyclization of
6a-d with bromine in glacial acetic acid containing anhy-
drous sodium acetate according to the literature [16], did
not give the expected 1,3,4-oxadiazoles 8a-d but rather
gave predominately the arylaldehyde 5,7-dibromo-4-
hydroxy-3-methylbenzofuran-2-carboxy hydrazones 7a-
d. In addition, refluxing 4-hydroxybenzofurans 6a-d with
lead tetraacetate in glacial acetic acid [17] resulted in
decomposition of the starting material. However the reac-
tion of 4-methoxybenzofurans 6e-l under the latter condi-
tion gave the desired 1,3,4-oxadiazoles 8e-l in good yield.
In addition compound 8e could be demethylated to the
desired compound 8a with boron tribromide in
dichloromethane [18].
The reaction of compound 1 with semicarbazide
hydrochloride afforded the corresponding semicarbazone
9 which was oxidized with selenium dioxide to give 4,5-
dihydro-1,2,3-selenadiazolo[4,5-e]benzofuran (10). The
reaction of compound 9 with thionyl chloride did not give
4,5-dihydro-[1,2,3]thiadiazolo[4,5-e]benzofuran 11, but
this compound was oxidized under the experimental con-
dition and ethyl 8-methyl-[1,2,3]thiadiazolo[4,5-e]benzo-
furan-7-carboxylate (12) was obtained [19,20].
Semicarbazones of 6,6-dimethyl-4-oxo-2-phenyl-
4,5,6,7-tetrahydrobenzofuran and benzothiophene (14a
and 14b) were obtained from the reaction of related 4-oxo-
benzofuran and benzothiophene 13a and 13b [21-23], with
semicarbazide hydrochloride. These compounds 14a and
14b were reacted with either selenium dioxide or thionyl
chloride to afford the corresponding 4,5-dihydro-4,4-
dimethyl-7-phenyl-[1,2,3]selenadiazolo[4,5-e]benzofuran
(15a), 4,5-dihydro-4,4-dimthyl-7-phenyl-[1,2,3]selenadia-
zolo[4,5-e]benzothiophene (15b), 4,5-dihydro-4,4-
dimethyl-7-pheyl-[1,2,3]thiadiazolo[4,5-e]benzofuran
(16a), 4,5-dihydro-4,4-dimethyl-7-phenyl-[1,2,3]thiadia-
zolo[4,5-e]benzothiophene (16b) respectively.
According to previous reports dehydrogenation of
4-oxo-4,5,6,7-tetrahydrobenzofurans has been achieved
by heating with sulfur or 2,3-dichloro-5,6-dicyano-1,4-
benzoquinone (DDQ)[12]. Alternatively bromination fol-
lowed by dehydrobromination can give 4-hydroxybenzo-
furan [13]. In the present work the transformation of
4-oxo-4,5,6,7-tetrahydrobenzofuran into 4-hydroxybenzo-
furan was achieved by α-bromination of compound 1 with
phenyltrimethylammonium perbromide in dry tetrahydro-
furan and subsequent dehydrobromination with a weak
base like triethylamine in 35% yield (method A) [14].
Also, heating compound 1 with N-bromosuccinimide in
carbon tetrachloride in the presence of U.V. light gave
compound 3 in one step and in 80% yield. Modification of
EXPERIMENTAL
Melting points were taken on a Kofler hot stage apparatus and
1
are uncorrected. H nmr spectra were recorded on a Brucker FT-
80 spectrometer. Tetramethylsilane was used as an internal stan-
dard. The infrared spectra were acquired on a Nicolet 550-FT
spectrometer. The mass spectra were run on a Finnigan TSQ 70
spectrometer at 70 eV. Elemental analyses were carried out with
a Perkin-Elmer Model 240-C apparatus. The results of elemental
analyses (C, H, N) were within ±0.4% of the calculated values.

Syntheses of [1,2,3]Selenadiazolo[4,5-e]benzofuran
429
May-Jun 2003
Table 1
Comp.
R
R
R
3
Ar
Mp °C
Yield
(%)
Formula
Calcd. Found
C
Calcd. Found Calcd.
H
Found
N
1
2
6a
6b
OH
OH
H
H
313-315
348-350
85
67
C
C
H
ClN O
2 3
62.11
52.48
62.30
52.61
3.98
3.82
3.71
3.73
8.52
8.68
17 13
H
H
H
N O
20.40
20.28
15 13
5
5
6c
OH
OH
H
H
H
H
315-316
358-359
72
55
C
C
H
N O
54.72
60.18
54.92
60.48
3.37
3.86
3.54
3.63
12.76
12.38
12.53
12.18
15 11
3
6
6d
H N O
17 13 3 5
6e
6f
OMe
OMe
H
H
H
H
190-192
243-246
83
78
C
C
H
ClN O
2 3
63.07
56.05
63.38
56.32
4.41
3.81
4.11
3.68
8.17
8.31
18 15
H
N O
12.22
12.45
16 13
3
6
6g
6h
OMe
OMe
H
H
H
H
278-280
256-258
68
65
C
C
H
N O
61.19
61.19
61.37
61.49
4.28
4.28
4.46
4.58
11.89
11.89
11.63
11.94
18 15
3
5
H
N O
3
18 15
5
6i
6j
OMe
OMe
H
H
H
H
282-284
244-246
58
75
C
C
H
N O
61.19
55.75
61.39
55.93
4.28
3.64
4.58
3.82
11.89
10.84
11.93
10.59
18 15
3
5
H
ClN O
3
18 14
5
6k
6l
OMe
OMe
H
H
H
H
296-298
264-266
81
78
C
C
H
N O
5 5
53.78
57.31
53.46
57.51
4.23
3.74
4.56
3.63
19.61
7.43
19.42
7.65
16 15
H
Cl N O
2 2 3
18 17
7a
7b
OH
OH
Br
Br
Br
Br
324-326
358-360
76
73
C
C
H
Br ClN O 41.97
41.73
35.75
2.28
2.21
2.41
2.45
5.76
5.53
17 11
2
2 3
H
Br N O
2 5 5
35.95
13.98
13.71
15 11
7c
OH
OH
Br
Br
Br
Br
230-232
337-339
79
58
C
C
H Br N O
2 3 6
36.99
41.07
36.78
41.31
1.86
2.23
1.63
2.57
8.63
8.45
8.41
8.68
15
9
7d
H Br N O
17 11 2 3 5

430
M. Shekarchi, F. Ellahiyan, T. Akbarzadeh and A. Shafiee
Vol. 40
Table 2
Comp.
Ar
mp°C
Yield
%
Formula
Calcd.
C
Found Calcd. Found Calcd. Found
H
N
8e
8f
210-212
244-246
216-220
83
87
82
C
H
ClN O
2 3
63.45
56.31
61.54
63.27
56.68
61.73
3.84
3.98
3.59
3.43
8.22
8.45
12.59
12.32
18 13
C
H
N O
3.25
3.73
12.31
12.00
16 11
3
6
8g
C
C
C
H N O
18 13 3
5
8h
8i
219-221
249-252
78
69
H
N O
61.54
61.54
61.69
61.38
3.73
3.73
3.65
3.48
12.00
12.00
12.21
12.31
18 13
3
5
H
N O
3
18 13
5
8j
294-296
284-286
65
70
C
H
ClN O
3 5
56.04
54.09
56.29
54.32
3.14
3.70
3.31
3.43
10.90
19.71
10.68
19.89
18 12
8k
C H N O
16 13 5 5
8l
251-253
88
C
H
Cl N O
2 2 3
57.62
57.31
3.22
3.45
7.50
7.79
18 12
Ethyl 3-Methyl-4-oxo-4,5,6,7-tetrahydrobenzofuran-2-car-
boxylate (1).
5-bromo-3-methyl-4-oxo-4,5,6,7-tetrahydrobenzofuran-2-car-
boxylate (2), methanol (20 ml) and triethylamine (0.4 g, 20
mmoles) was refluxed for two hours. The methanol was
removed, water was added and the precipitate was crystallized
from carbon tetrachloride to give 0.77g (35%) of compound 3,
mp 138-140 °C; ir (potassium bromide): ν 3340, 2919, 1710,
Compound 1 was prepared according to the reported methods
[12] in 90% yield, mp 88-90 °C; ir (potassium bromide): ν 2985,
-1
1
1735, 1655, 1460, 1352 cm ; H-nmr (deuteriochloroform):
δ 4.38 (q, 2H, CH ), 2.92 (t, 2H, CH ), 2.55 (s, 3H, CH ), 2.51
2
2
3
-1
1
1516, 1444, 1275 cm ; H-nmr (deuteriochloroform): δ 7.13 (m,
(t, 2H, CH ), 2.18 (m, 2H, CH ), 1.39 ppm (t, 3H, CH ); ms: m/z
2
2
3
2H, aromatic), 6.57 (m, 1H, aromatic), 4.45 (q, 2H, CH ), 2.77 (s,
2
+
(%) 222 (M , 100), 194 (69), 177 (41), 166 (44), 150 (25).
+
3H, CH ), 1.43 ppm (t, 3H, CH ); ms: m/z (%) 220 (M , 100),
3
3
Anal. Calcd. for C
H O : C, 64.85; H, 6.35. Found: C,
12 14 4
191 (60), 175 (43), 147 (37), 118 (20), 91 (19), 65 (10).
64.73; H, 6.59.
Anal. Calcd. for C
H O : C, 65.53; H, 5.49. Found: C,
12 12 4
Ethyl 4-Hydroxy-3-methylbenzofuran-2-carboxylate (3).
65.32; H, 5.51.
Method A.
Method B.
To a stirring solution of compound 1 (2.22 g, 10 mmoles) in
THF (20 ml) a solution of phenyltrimethylammonium perbro-
mide (3.75 g, 10 mmoles) in THF (20 ml) was added. The mix-
ture was stirred at room temperature for 48 hours and filtered.
The filtrate was evaporated under reduced pressure. The residue
was dissolved in dichloromethane and washed with sodium
bicarbonate solution, dried (sodium sulfate) and evaporated
under reduced pressure. A solution of crude yellow oil, ethyl
A solution of compound 1 (2.22 g, 10 mmoles) in wet carbon
tetrachloride (40 ml) was heated to reflux and NBS (1.87 g, 10
mmoles) and AIBN (40 mg) were added in one portion to the
refluxing solution under N atmosphere. When all the NBS was
2
converted to succinimide the reaction mixture was cooled to
room temperature. The succinimide was removed by filtration
and washed with CCl (2×4 ml). The solvent was evaporated
4
under reduced pressure to give the crude product which was

Syntheses of [1,2,3]Selenadiazolo[4,5-e]benzofuran
431
May-Jun 2003
crystallized from carbon tetrachloride to give 2.15 g (98%) of
compound 3, mp and mixed melting point with an authentic sam-
ple (see method A) was 138-140 °C. It is worthy to mention that
when dry carbon tetrachloride was used the reaction did not go to
completion.
Anal. Calcd. for C H ClN O ; C, 62.11; H, 3.98; N, 8.52.
17 13 2 3
Found: C, 62.30; H, 3.71; N, 8.68.
Compounds 6b-l were prepared similarly (see Table 1).
p-Chlorobenzaldehyde 5,7-Dibromo-4-hydroxy-3-methyl-ben-
zofuran-2-carboxy hydrazone (7a).
Ethyl 4-Methoxy-3-methylbenzofuran-2-carboxylate (4).
To a solution of compound 6a (1.64 g, 5 mmoles) and anhy-
drous sodium acetate (1.64 g, 20 mmoles) in galcial acetic acid
(10 ml), bromine (0.44 g, 5.5 mmoles) was added under an
atmosphere of argon and stirred at room temperature for 1 hour.
The mixture was poured into water (40 ml). The crude product
was collected by filtration and crystallized from methanol:
diethyl ether (7:3) to give 1.84 g (76%) of compound 7a, mp
323-325 °C; ir (potassium bromide): ν 3581, 3247, 1680, 1603,
To a solution of compound 3 (2.2 g, 10 mmoles), iodomethane
(1.42 g, 10 mmoles) in dry acetone (30 ml) and potassium car-
bonate (1.38 g, 10 mmoles) were added and the mixture was
refluxed for 10 hours. The solvent was removed under reduced
pressure and the residue was treated with 50 ml of water. The
mixture was extracted with diethyl ether (3× 20 ml). The com-
bined organic layers were dried (sodium sulfate) and evaporated
under reduced pressure to give the crude product which was
crystallized from methanol to give 1.64g (70%) of compound 4
as a white solid, mp 85-87 °C; ir (potassium bromide): ν 3075,
-1
1
1480, 1337, 1050, 748 cm ; H-nmr (dimethyl-sulfoxide-d ): δ
6
11.9 (brs, 1H, NHCO), 8.52 (s, 1H, -N=CH-), 7.69 (m, 5H, aro-
+
matic), 2.68 (s, 3H, Me); ms: m/z (%) 486 (M , 37), 432 (18),
-1
1
2955,1710, 1680, 1444, 1326, 1214 cm ; H-nmr (deuterio-
chlorform): δ 7.14 (m, 2H, aromatic), 6.61 (m, 1H, aromatic),
4.43 (q, 2H, CH ), 3.91 (s, 3H, OCH ), 2.72 (s, 3H, CH ), 1.42
348 (100), 219 (52).
Anal. Calcd. for C
H Br ClN O : C, 41.97; H, 2.28; N,
17 11 2 2 3
5.76. Found: C, 41.73; H, 2.41; N, 5.53.
2
3
3
ppm (t, 3H, CH ).
Compounds 7b-7d were prepared similarly (see Table 1).
3
Anal. Calcd. for C
66.88; H, 6.12.
H O : C, 66.66; H, 6.02. Found: C,
13 14 4
2-[3-Methyl-4-methoxybenzofuran-2-yl]-5-[4-chlorophenyl]-
1,3,4-oxodiazole (8e).
4-Hydroxy-3-methylbenzofuran-2-carboxylic Acid Hydrazide
(5a).
A suspension of compound 6e (1.71 g, 5 mmoles) and lead
tetraacetate (4.43 g, 10 mmoles) in glacial acetic acid (50 ml) was
refluxed for 4 hours. After cooling the precipitate was collected
by filtration and washed with 4 N HCl (50 ml) to remove any lead
compounds and crystallized from ethyl acetate:diethyl ether (7:3)
to give 1.4 g (83%) of compound 8e, mp 210-212 °C; ir (potas-
To a solution of compound 4 (2.2 g, 10 mmoles) in methanol
(15 ml) hydrazine hydrate (2.5 g, 20 mmoles) was added and
stirred at room temperature for 48 hours. The mixture was filtered
and crystallized from water:methanol (1:1) to give 1.65 g (80%)
of compound 5a, mp 149-150 °C; ir (potassium bromide):ν 3344,
-1
1
sium bromide): ν 2914, 1603, 1485, 1280 cm ; H-nmr (deuteri-
ochloroform): δ 7.66 (m, 6H, aromatic), 6.72 (m, 1H, aromatic)
-1 1
3108, 1634, 1291, 1050, 947, 717 cm ; H-nmr (dimethyl sulfox-
+
ide-d ): δ 7.69 (brs, 1H, NHCO), 7.15 (m, 2H, aromatic), 6.63 (d,
3.96 (s, 3H, OCH ), 2.84 (s, 3H, CH3); ms: m/z (%) 340 (M ,
6
3
+
1H, aromatic), 2.71 ppm (s, 3H, Me); ms:m/z (%) 206 (M , 17),
100), 324 (22), 267 (10), 234 (20), 138 (62).
175 (56), 119 (19), 91 (42), 65 (79), 39 (100).
Anal. Calcd. for C
H ClN O : C, 63.45, H, 3.84; N, 8.22.
18 13 2 3
Anal. Calcd. for C
H
N O : C, 58.00; H, 4.90; N, 13.59.
Found: C, 63.27; H, 3.98; N, 8.45.
10 10 2 3
Found: C, 58.25; H, 4.83; N, 13.37.
Compounds 8f-l were prepared similarly (see Table 2).
4-Methoxy-3-methylbenzofuran-2-carboxylic Acid Hydrazid
2-[4-Hydroxy-3-methyl-benzofuran-2-yl]-5-[4-chlorophenyl]-
(5b).
1,3,4-oxadiazole (8a).
This compound was obtained from 4, similarly to 5a, mp 160-
162 °C; ir (potassium bromide):ν 3324, 3216, 1654, 1603, 1495,
To a suspension of compound 8e (3.41 g, 10 mmoles) in dry
dichloromethane (30 ml), a solution of boron tribromide (2.5 g,
10 mmoles) in dichloromethane (10 ml) was added at 0-5 °C and
stirred for 48 hours. The solvent was removed under reduced
pressure. The residue was stirred with water (20 ml) to hydrolyze
excess reagent and boron complexes. The product was collected
by filtration to give the crude product which was crystallized
from methanol:diethyl ether (7:3) to give 2.21 g (65%) of com-
pound 8a , mp 289-290 °C; ir (potassium bromide): ν 3347,
-1
1
1280 cm ; H-nmr (deuteriochloroform): δ 7.69 (brs, 1H,
NHCO), 7.26 (q, 1H, aromatic), 7.00 (d, 1H, aromatic), 6.63 (d,
1H, aromatic), 4.01 (brs, 2H, NH ), 3.92 (s, 3H, OCH ), 2.77
2
3
ppm (s, 3H, CH ).
3
Anal. Calcd. for C H N O : C, 59.99; H, 5.49; N, 12.72.
11 12
2 3
Found: C, 59.75; H, 5.65; N, 12.95.
p-Chlorobenzaldehyde 4-Hydroxy-3-methylbenzofuran-2-car-
boxyhydrazone (6a).
-1
1
2919, 1603, 1480, 1337 cm ; H-nmr (dimethyl sulfoxide-d6): δ
10.37 (s, 1H, OH), 8.38 (m, 4H, aromatic), 7.23 (m, 2H, aro-
To a solution of compound 5a (2.06 g, 10 mmoles) in methanol
(50 ml) p-chlorobenzaldehyde (2.81 g, 20 mmoles) and sulfuric
acid (1 ml) were added. The mixture was stirred at room temper-
ature for 2 hours. The precipitate was collected by filtration and
crystallized from ethanol to give 2.71 g (85%) of compound 6a,
mp 313-315 °C; ir (potassium bromide): ν 3247, 1680, 1603,
matic), 6.73 (m, 1H, aromatic), 2.79 ppm (s, 3H, CH ); ms: m/z
(%) 328 (7), 326 (M , 46), 291 (60), 188 (100).
3
+
Anal. Calcd. for C H ClN O : C, 62.49; H, 3.39; N, 8.57.
17 11
2 3
Found: C, 62.41; H, 3.32; N, 8. 53.
Ethyl 3-Methyl-4-oxo-4,5,6,7-tetrahydrobenzofuran-2-carboxy-
late Semicarbazone (9).
-1
1
1480, 1337, 1147 cm ; H-nmr (dimethyl sulfoxide-d ): δ 11.92
6
(brs, 1H, NHCO), 10.25 (brs, 1H, OH), 8.15 (s, 1H, N=CH ), 7.19
This compound was prepared accoriding to the reported meth-
+
(m, 7H, aromatic), 2.71 (s, 3H, CH ); ms: m/z (%) 328 (M , 5),
ods [19] in 85% yield; mp 232-235 °C; ir (potassium bromide): ν
3
-1
1
181 (15), 121 (10), 91 (100).
3520, 3404, 3222, 1704, 1680, 1564, 1434 cm ; H-nmr

432
M. Shekarchi, F. Ellahiyan, T. Akbarzadeh and A. Shafiee
Vol. 40
(dimethyl sulfoxide-d ): δ 9.66 (s, 1H, NH), 6.47 (brs, 2H, NH ),
This compound was prepared according to the reported meth-
6
2
4.41 (q, 2H, CH ), 2.97 (t, 2H, CH ), 2.57 (s, 3H, CH ), 2.55 (t,
ods [21,23] in 66% yield, mp 73-75 °C; ir (potassium bromide): ν
3054, 2930, 1670, 1564, 1375 cm ; H-nmr (deuteriochloro-
form): δ 7.63 (m, 5H, aromatic), 6.81 (s, 1H, aromatic), 2,81 (s,
2
2
3
1
1
2H, CH ), 2.22 (m, 2H, CH ), 1.48 ppm (t, 3H, CH ); ms: m/z
2
2
3
+
(%) 279 (M , 70), 262 (45), 236 (30), 206 (15), 163 (25), 105
(60), 91 (100).
2H, CH ), 2.39 (s, 2H, CH ), 1.18 ppm (s, 6H, 2×CH ); ms: m/z
2
2
3
+
Anal. Calcd. for: C
H
N O : C, 55.91; H, 6.14; N, 15.05.
(%) 256 (M , 70), 239 (23), 183 (30), 127 (30), 82 (100), 62 (40).
13 17
3 4
Found: C, 56.01; H, 6.21; N, 15.21.
Anal. Calcd. for C H OS: C, 74.96; H, 6.29. Found: C,
16 16
74.92; H, 6.32.
Ethyl 4,5-Dihydro-7-methyl[1,2,3]selenadiazolo[4,5-e]benzofu-
ran-7-carboxylate (10).
6,6-Dimethyl-4-oxo-2-phenyl-4,5,6,7-tetrahydrobenzofuran
Semicarbazone (14a).
To a stirring mixture of compound 9 (1.00 g, 3.6 mmoles) in
glacial acetic acid, selenium dioxide (400 mg, 3.6 mmoles) was
added slowly. The mixture was refluxed in a hot water bath for
3 hours. The mixture was cooled, filtered and water (15 ml) was
added to the filtrate. The filtrate was extracted with chloroform
(3×15 ml), dried (sodium sulfate) and the solvent was evapo-
rated. The residue was purified by preparative tlc on silica gel
using chloroform:methanol (40:1) as eluent. The desired com-
pound was crystallized from petroleum ether to give 111 mg
(10%) of 10, mp 139-140 °C; ir (potassium bromide): ν 2919,
This compound was prepared according to the reported
method [21] in 83% yield, mp 189-191 °C; ir (potassium bro-
mide): ν 3449, 1645, 1564, 1415 cm ; H-nmr (deuteriochloro-
form): δ 8.15 (s, 2H, NH ), 7.51 (m, 5H, aromatic), 6.85 (s, 1H,
-1
1
2
aromatic), 2.67 (s, 2H, CH ), 2.29 (s, 2H, CH ), 1.14 ppm (s, 6H,
2
2
+
2×CH ); ms: m/z (%) 297 (M , 38), 254 (100), 222 (40), 182
3
(25), 105 (20), 97 (40), 69 (42), 55 (60), 43 (100).
Anal. Calcd. for C
Found: C, 68.51; H, 6.21; N, 14.23.
H N O : C, 68.67; H, 6.44; N, 14.13.
17 19 3 2
-1
1
1710, 1516, 1444, 1275 cm ; H- nmr (deuteriochloroform): δ
4.41 (q, 2H, CO CH ), 3.34 (m, 4H, CH -CH ), 2.75 (s, 3H,
6,6-Dimethyl-4-oxo-2-phenyl-4,5,6,7-tetrahydrobenzothiophene
Semicarbazone (14b).
2
2
2
2
+
CH ), 1.41 ppm (t, 3H, CH ); ms: m/z (%) 313 (62), 312 (M ,
3
3
60), 284 (100), 282 (55), 280 (22), 211 (10), 102 (25), 91 (35),
65 (24).
This compound was prepared according to the reported meth-
ods [21] in 76% yield, mp180-183 °C; ir (potassium bromide): ν
-1
1
Anal. Calcd. for C
H N O Se: C, 46.32; H, 3.89; N, 9.00.
3409, 3311, 1681, 1606, 1485 cm ; H-nmr (deuteriochloro-
12 12 2 3
Found: C, 46.50; H, 3.78; N, 8.84.
form): δ 7.84 (s, 1H, NH), 7.55 (m, 5H, aromatic), 6.99 (s, 1H,
aromatic), 2.77 (s, 2H, CH ), 2.30 (s, 2H, CH ), 1.14 ppm (s, 6H,
2
2
Ethyl 8-Methyl[1,2,3]thiadiazolo[4,5-e]benzofuran-7-carboxy-
late (12).
+
2×CH ); ms: m/z (%) 313 (M , 28), 268 (100), 224 (19), 195
3
(69), 180 (28), 111 (29), 97 (45), 55 (65).
A mixture of compound 9 (1.00 g, 3.6 mmoles) and thionyl
chloride (20 ml) was heated on a steam bath for 2 hours. After
cooling, water was added and the mixture was neutralized with
10% sodium carbonate solution, extracted with chloroform (2 ×
20 ml) and dried (sodium sulfate). The solvent was removed
under reduced pressure. The residue was purified by preparative
tlc on silica gel using chloroform:methanol (30:1) as eluent. The
desired compound was crystallized from petroleum ether to give
130 mg (14%) of compound 12, mp 86-88 °C; ir (potassium bro-
Anal. Calcd. for C
Found: C, 65.28; H, 6.08; N, 13.39.
H N OS: C, 65.15; H, 6.11; N, 13.41.
17 19 3
4,5-Dihydro-4,4-dimethyl-7-phenyl-[1,2,3]selenadiazolo[4,5-e]-
benzofuran (15a).
This compound was obtained from 14a, similar to 10 mp 115-
117 °C (from chloroform); H-nmr (deuteriochloroform);:δ 7.59
1
(m, 6H, aromatic), 3.02 (s, 2H, CH ), 1.52 ppm (s, 6H, 2×CH );
2
3
+
ms: m/z (%) 329 (M , 2), 273 (10), 139 (100).
Anal. Calcd. for C N OSe: C, 58.36; H, 4.28; N, 8.51.
-1
1
mide): ν 3078, 2919, 1716, 1557, 1449, 1270 cm ; H-nmr (deu-
teriochloroform): δ 7.98 (ABq, J=8.9 Hz, 2H, aromatic), 4.52 (q,
H
16 14
2
Found: C, 58.12; H, 4.21; N, 8.66.
2H, CO CH ), 3.12 (s, 3H, CH ), 1.49 ppm (t, 3H, CH ); ms: m/z
2
2
3
3
+
4,5-Dihydro-4,4-dimethyl-7-phenyl-[1,2,3]selenadiazolo[4,5-e]-
benzothiophene (15b).
(%) 263 (100), 262 (M , 98), 234 (90), 206 (85), 189 (70), 162
(100), 133 (78), 107 (60), 89 (80), 69 (60), 63 (45).
Anal. Calcd. for C
Found: C, 54.79; H, 4.01; N, 10.39.
H N O S: C, 54.95; H, 3.84; N. 10.68.
12 10 2 3
This compond was obtained from 14b, similar to 10; mp 122-
125 °C (chloroform); H-nmr (deuteriochloroform): δ 7.61 (m,
1
6H, aromatic), 2.99 (s, 2H, CH ), 1.50 ppm (s, 6H, 2×CH ); ms:
6,6-Dimethyl-4-oxo-2-phenyl-4,5,6,7-tetrahydrobenzofuran
(13a).
2
3
+
m/z (%) 345 (M , 65), 317 (40), 238 (57), 104 (100), 77 (65).
Anal. Calcd. for C N SSe: C, 55.65; H, 4.09; N, 8.11.
H
16 14
2
This compound was prepared according to the reported meth-
Found: C, 55.87; H, 3.92; N, 8.32
ods [23] in 41% yield, mp 83-85 °C; ir (potassium bromide): ν
-1
1
3028, 2949,1665, 1580, 1370, 1360 cm ; H-nmr (deuteriochlo-
4,5-Dihyro-4,4-dimethyl-7-phenyl-[1,2,3]thiadiazolo[4,5-e]-
benzofuran (16a).
roform): δ 7.51 (m, 5H, aromatic), 6.67 (s, 1H, aromatic), 2.81 (s,
2H, CH ), 2.40 (s, 2H, CH ), 1.17 ppm (s, 6H, 2×CH ); ms: m/z
(%) 240 (M , 40), 184 (87), 156 (40), 128 (10), 112 (25), 105
(100), 83 (95).
2
2
3
This compound was obtained from 14a, similar to 12; mp 108-
110 °C (methanol); H-nmr (deuteriochloroform): δ 7.47 (m, 6H,
+
1
aromatic), 3.00 (s, 2H, CH ), 1.51 ppm (s, 6H, 2×CH ); ms: m/z
2
3
Anal. Calcd. for C
H O : C, 79.97; H, 6.71. Found: C,
16 16 2
+
(%) 282 (M , 8), 254 (7), 178 (15), 149 (25), 105 (100), 77 (42),
51 (25).
79.94; H, 6.61.
Anal. Calcd. for C
H N OS: C, 68.06; H, 4.00; N, 9.92.
6,6-Dimethyl-4-oxo-2-phenyl-4,5,6,7-tetrahydrobenzothiophene
16 14 2
(13b).
Found: C, 68.28; H, 4.24; N, 9.80.

Syntheses of [1,2,3]Selenadiazolo[4,5-e]benzofuran
433
May-Jun 2003
[7] T. Nakib, M. J. Meegan, A. M. Looney and M. L. Burke, Eur.
J. Med. Chem., 27, 971 (1992).
[8] K. Matsuda, H. Toyoda, T. Yoshida, S. Harada, H. Sakamoto
and Y. Ishiguro, Japan Kokai Patent 279, 210 (1993); Chem. Abstr., 122,
74580y (1995).
4,5-Dihydro-4,4-dimethyl-7-phenyl-[1,2,3]thiadiazolo[4,5-e]-
benzothiophene (16b).
This compound was obtained from 14b, similar to 12; mp 104-
1
106 °C (methanol): H-nmr (deuteriochloroform): δ 7.56 (m, 6H,
aromatic), 3.01 (s, 2H, CH ), 1.48 ppm (s, 6H, 2×CH ); ms: m/z
(%) 298 (M , 37), 267 (100), 237 (100), 208 (35), 148 (80), 104
(100), 77 (60).
[9] B. Shivararna Holla, R. Gonsalves and Sh. Shenoy, Eur. J.
Med. Chem., 35, 267 (2000).
[10] I. Lalezari, A. Shafiee and S. Yazdani, J. Pharm. Sci., 63, 628
(1974).
2
3
+
Anal. Calcd. for C
H N S ; C, 64.40; H, 4.73; N, 9.39.
16 14 2 2
[11] G. T. Seaborg, Science, 9, 223 (1984).
Found: C, 64.29; H, 4.64; N, 9.27.
[12] S. Yamaguchi, K. yamamoto, T. Ueda, T. Morikawa and Y.
Kawase, Bull. Chem. Soc., Jpn., 62, 4066 (1989).
[13] A. N. Grinev, V. M. Lyubchanskaya, C. ya. Uretskaya, T. F.
Volasova, Khim Geterotsikl. Soedin., 7, 87, (1976); Chem. Abstr., 85,
142937q (1976).
Acknowledgement.
This work was partially supported by a grant from the
International Organization for Chemical Sciences in
Development (IOCD) and research council of Tehran Univesity
of Medical Sciences.
[14] R. Singh, H. Bhagavateeswaran and N. Anand, Indian
J. Chem., 21B, 853 (1982).
[15] P. Zhang, R. Liu and J. M. Cook, Tet. Lett., 36, 3103 (1995).
[16] M. Mano, T. Seo, T. Matsuno and K. Imai, Chem. Pharm.
Bull., 24, 2871 (1976).
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