Synthesis of derivatives of thiophene using methyl 2-isothiocyanatobenzoate

Article abstract of DOI:10.1002/jhet.5570380204

A variety of 2-substituted thiophenes is readily obtained from 2-(2-thienyl)-4H-3,1-benzothiazin-4-one (2), which is formed when thiophene reacts with methyl 2-isothiocyanatobenzoate (1) in the presence of anhydrous stannic chloride.

Full text of DOI:10.1002/jhet.5570380204

Mar-Apr 2001
Synthesis of Derivatives of Thiophene Using Methyl
2-Isothiocyanatobenzoate
343
L. M. Deck*, S. D. Turner, J. A. Deck and E. P. Papadopoulos
Department of Chemistry, University of New Mexico, Albuquerque, New Mexico 87131
Received April 26, 2000
A variety of 2-substituted thiophenes is readily obtained from 2-(2-thienyl)-4H-3,1-benzothiazin-4-one
(2), which is formed when thiophene reacts with methyl 2-isothiocyanatobenzoate (1) in the presence of
anhydrous stannic chloride.
J. Heterocyclic Chem., 38, 343 (2001).
Methyl 2-isothiocyanatobenzoate (1) has been used
methoxide in methanol converts 2 to thioamide 3, which is
oxidized by hydrogen peroxide to the corresponding amide,
N-(2-methoxycarbonylphenyl)thiophene-2-carboxamide
(4). Brief heating of 2 with ethanolic ammonia yields N-(2-
aminocarbonylphenyl)thiophene-2-thiocarboxamide (5),
whereas a more prolonged treatment results in cyclization
and formation of 2-(2-thienyl)-4(3H)-quinazolinone (6).
Analogous reactions of 2 with hydrazine and methyl-
hydrazine lead to 3-amino-2-(2-thienyl)-4(3H)-quinazoli-
none (7a) and 3-methylamino-2-(2-thienyl)-4(3H)-quina-
zolinone (7b), respectively. Deamination of 7a with nitrous
acid [17] yields the anticipated quinazolinone 6. Also, the
thiazinone ring of 2 undergoes ring opening in aqueous
extensively for the synthesis of a wide variety of hetero-
cyclic compounds [1-16]. In this paper we report the
results of a brief investigation of the use of this reagent for
the synthesis of a number of derivatives of thiophene,
which parallel the results of an earlier reported synthesis of
derivatives of pyrrole [11].
In the presence of anhydrous stannic chloride, thiophene
reacts with 1 to form 2-(2-thienyl)-4H-3,1-benzothiazin-4-
one (2), presumably by cyclization of the initially formed
N-(2-methoxycarbonylphenyl)thiophene-2-thiocarboxam-
ide (3). The thiazinone ring of 2 opens up readily upon
treatment with nucleophilic reagents. Thus, sodium

344
L. M. Deck, S. D. Turner, J. A. Deck and E. P. Papadopoulos
Vol. 38
Table 1
13
C-nmr Shifts in Dimethyl-d Sulfoxide
6
Compound
X
Y
Compound
X
Y
2
6
7a
7b
9
S
–
H
NH
NHCH
–
3
4
5
S
O
S
OCH
OCH
3
3
N
N
N
O
NH
OH
OH
NH
2
2
8
S
3
10
11
12
O
O
O
2
NHCH Ph
2
1
2
3
4
5
6
7
8
9
10
11
12
Y
2
3
4
5
6
7a
133.1 128.8 130.1 140.9 154.7
134.9 128.5 125.2 148.0 187.2
132.5 128.4 128.9 139.4 159.4
135.0 128.8 125.4 149.2 185.3
132.1 128.5 129.4 137.3 148.6
133.6 127.1 133.9 135.2 149.4
147.8 130.8
139.5 127.0
139.9 120.7
139.4 122.7
147.8 125.9
146.9 127.0
146.9 127.1
140.3 125.4
146.0 126.3
140.8 119.8
140.0 119.9
139.8 120.3
136.5
133.0
134.3
131.5
134.7
134.4
134.6
133.1
136.8
134.3
132.2
132.3
129.0 124.4 119.2 182.2
127.4 130.6 125.3 166.2
123.3 130.7 116.9 168.0
124.3 128.5 123.9 170.4
126.3 126.9 120.8 161.8
126.2 126.0 119.3 161.1
126.8 126.0 119.9 160.5
126.6 131.3 123.9 168.4
128.6 128.1 116.6 158.3
122.9 131.3 116.4 170.0
122.6 128.4 118.8 171.2
122.9 128.3 119.9 168.6
52.6(CH )
3
52.6(CH )
3
7b 134.5 126.8 133.6 134.6 149.2
8
9
10
11
12
36.6(CH )
3
135.2 128.7 125.0 148.7 186.6
133.4 128.7 131.6 133.6 153.0
132.5 128.4 128.7 139.6 159.4
132.6 128.4 128.8 139.9 159.3
132.4 128.4 128.5 139.2 159.3
138.9(i)
127.2(o) 42.6(CH )
2
128.2(m) 126.9(p)
were recorded on a Beckman IR-33 spectrophotometer using
mineral oil mulls. Proton and carbon-13 nmr spectra were
sodium hydroxide to give, after acidification, carboxylic
acid 8. Upon refluxing in t-butylbenzene, 8 undergoes
cyclization with loss of hydrogen sulfide to form 2-(2-
thienyl)-4H-3,1-benzoxazin-4-one (9). The structure of
this compound is established by its rapid hydrolysis to car-
boxylic acid 10, which is also obtained by oxidation of
compound 8 with hydrogen peroxide. Similarly, the oxazi-
none ring of 9 undergoes ring opening upon treatment with
sodium methoxide, ammonia, and benzylamine to afford
ester 4, amide 11, and N-benzylamide 12, respectively.
The structures assigned to compounds 2-12 are consis-
tent with their infrared, proton nmr, and C-13 nmr spectra.
Table 1 contains the C-13 nmr spectroscopic data for all of
the compounds mentioned above. Use of HMQC and
HMBC along with literature data of model compounds
[18-22] allowed the assignments of signals to specific car-
bon atoms of these compounds.
obtained in DMSO-d on a Bruker AC250 spectrometer.
6
Chemical shifts are in ppm (δ) relative to TMS as internal stan-
dard. The symbols used to describe proton nmr spectra in the fol-
lowing experimental procedures are shown on the structures
below.
2, 6, 7a, 7b, 9
3–5, 8, 10–12
X and Y as in Table 1.
2-(2-Thienyl)-4H-3,1-benzothiazin-4-one(2).
EXPERIMENTAL
A mixture of thiophene (2.0 g, 23.8 mmol), methyl 2-isothio-
cyanatobenzoate (3.41 g, 17.6 mmol) and stannic chloride
(5 ml, 42.7 mmol) was stirred at room temperature for 16 hours.
To the resulting dark green semi solid was added ice, water and
Reagent grade solvents were used without further purification.
Melting points were determined in capillaries with a Thomas-
Hoover Uni-Melt apparatus and are uncorrected. Infrared spectra

Mar-Apr 2001
Synthesis of Derivatives of Thiophene Using Methyl 2-Isothiocyanatobenzoate
345
concentrated hydrochloric acid. The aqueous solution was
decanted and the sticky solid was triturated first with hexane
and then with ethanol to give 2.45 g (57%) of 2, mp 125-127°.
Recrystallization from ethanol gave the pure compound as buff
as buff crystals, mp 204-205°; ir: 3430, 3150 (N-H), 1640 (C=O)
-1
1
cm ; H nmr: δ 7.23 (dd, 1H, thiophene H , J = 5.1, 3.9 Hz),
b
7.33 (dt, 1H, ArH , J = 7.6, 1.1 Hz), 7.58 (dt, 1H, ArH , J = 7.8,
c
b
1.5 Hz), 7.73 (dd, 1H, thiophene H , J = 3.8, 1.1 Hz), 7.86 (dd,
a
-1
1
crystals, mp 127-128°; ir: 1650 (C=O) cm ; H nmr: δ 7.25
1H, thiophene H , J = 5.1, 1.0), 7.88 (dd, 1H, ArH , J = 7.9, 1.4
c
d
(dd, 1H, thiophene H , J = 4.8, 3.9 Hz), 7.62 (dt, 1H, ArH , J =
Hz), 8.39 (s, 2H, NH ), 8.87 (dd, 1H, ArH , J = 8.9, 0.9 Hz), 13.2
b
c
2
a
7.5, 1.1 Hz), 7.81 (dd, 1H, ArH , J = 7.8, 0.7 Hz), 7.83 (dd, 1H,
(s, 1H, NH).
Anal. Calcd. for C H N OS : C, 54.94; H, 3.84; N, 10.68.
a
thiophene H , J = 3.8, 1.0 Hz), 7.94 (dt, 1H, ArH , J = 7.8, 1.5
a
b
12 10
2
2
Hz), 7.98 (dd, 1H, thiophene H , J = 5.0, 0.9 Hz), 8.11 (dd, 1H,
Found: C, 55.02; H, 3.72; N, 10.68.
2-(2-Thienyl)-4(3H)-quinazolinone (6).
Method A.
c
ArH , J = 7.9, 1.3 Hz).
d
Anal. Calcd. for C H NOS : C, 58.75; H, 2.88; N, 5.71.
12
7
2
Found: C, 58.58; H, 2.74; N, 5.63.
A mixture of compound 2 (0.60 g, 2.45 mmol) and ethanolic
ammonia (ethanol saturated with ammonia at 0°, 12 ml) was
heated in a closed flask on a water bath for 16 hours. The result-
ing solution was cooled and filtered to give 0.45 g (80%) of 6, mp
282.5-284°. Recrystallization from ethanol gave the pure com-
pound as buff crystals, mp 284-286° (lit [23] mp 288-289°; lit
N-(2-Methoxycarbonylphenyl)thiophene-2-thiocarboxamide (3).
A mixture of compound 2 (0.50 g, 2.04 mmol), sodium
methoxide (0.30 g, 5.55 mmol) and methanol (10 ml) was heated
in a water bath for 5 minutes. The resulting mixture was diluted
with water (20 ml), acidified with concentrated hydrochloric acid
and filtered to give 0.55 g (97%) of compound 3, mp 128-129°.
Recrystallization from methanol gave the pure compound as buff
-1
1
[24] mp 285-286°); ir: 3195(N-H), 1675 (C=O) cm ; H nmr: δ
7.22 (dd, 1H, thiophene H , J = 4.9, 3.8 Hz), 7.49 (dt, 1H, ArH ,
b
c
-1 1
crystals, mp 129.5-131°; ir: 1690 (C=O) cm ; H nmr: δ 3.76 (s,
J = 7.8, 1.0 Hz), 7.64 (d, 1H, ArH , J = 8.2 Hz), 7.79 (dt, 1H,
a
3H, CH ), 7.23 (dd, 1H, thiophene H , J = 4.8, 3.9 Hz), 7.43 (dt,
3
b
ArH , J = 7.7, 1.5 Hz), 7.85 (dd, 1H, thiophene H , J = 5.0, 1.0
b
c
1H, ArH , J = 7.7, 1.1 Hz), 7.68 (dt, 1H, ArH , J = 7.8, 1.5 Hz),
c
b
Hz), 8.11 (d, 1H, ArH , J = 7.9 Hz), 8.21 (dd, 1H, thiophene H ,
d
a
7.83 (dd, 1H, thiophene H , J = 3.8, 1.1 Hz), 7.86 (dd, 1H, thio-
a
J = 3.8, 1.1 Hz), 12.6 (s, 1H, NH).
phene H , J = 5.0, 1.0 Hz), 7.93 (dd, 1H, ArH , J = 7.9, 1.1 Hz),
c
d
Anal. Calcd. for C H N OS: C, 63.14; H, 3.53; N, 12.27.
12
8 2
7.95 (dd, 1H, ArH , J = 7.8, 1.5 Hz), 11.8 (s, 1H, NH).
a
Found: C, 63.01; H, 3.67; N, 12.26.
Anal. Calcd. for C H NO S : C, 56.29; H, 4.00; N, 5.05.
13 11
2 2
Method B.
Found: C, 56.00; H, 3.84; N, 5.01.
N-(2-Methoxycarbonylphenyl)thiophene-2-carboxamide (4).
Method A.
To an ice cold mixture of compound 7a (0.30 g, 1.23 mmol)
and concentrated hydrochloric acid (2 ml) was added sodium
nitrite (0.20 g) dissolved in cold water (6 ml). After the evolution
of nitrogen had ceased, the mixture was diluted with water (10
ml) and was allowed to stand for 2 hours. Following filtration,
the product was washed thoroughly with 10% aqueous sodium
hydrogen carbonate to give 0.25 g (89%) of 6, mp 281-284°.
A mixture of compound 3 (0.23 g, 0.83 mmol), acetic acid (2
ml) and 30% hydrogen peroxide (2 ml) was allowed to stand for
2 hours. The resulting mixture was diluted with water and fil-
tered to give 0.14 g (65%) of compound 4 as a buff solid, mp
170-171°. Recrystallization from petroleum ether (bp 35-
60°)/ethyl acetate gave the pure compound, mp 170-171°; ir:
3-Amino-2-(2-thienyl)-4(3H)-quinazolinone (7a).
-1
1
Hydrazine (95%, 2 ml) was added to compound 2 (0.50 g, 2.04
mmol) and the mixture was heated in a water bath for 30 minutes.
After cooling, water was added and the mixture was filtered to
give 0.50 g (100%) of 7a, mp 198-199.5°. Recrystallization from
ethanol gave the pure compound as buff crystals, mp 198-200°;
3255 (N-H), 1690, 1630 (C=O) cm ; H nmr: δ 3.85 (s, 3H,
CH ), 7.19 (dt, 1H, ArH , J = 7.5, 1.1 Hz), 7.24 (dd, 1H, thio-
3
c
phene H , J = 5.0, 3.8 Hz), 7.63 (dt, 1H, ArH , J = 7.8, 1.6 Hz),
b
b
7.77 (dd, 1H, thiophene H , J = 3.8, 1.1 Hz), 7.87 (dd, 1H, thio-
a
phene H , J = 5.0, 1.0 Hz), 7.96 (dd, 1H, ArH , J = 7.9, 1.5 Hz),
c
d
-1
1
ir: 3350 (N-H), 1675 (C=O), 1615 (C=N) cm ; H nmr: δ 5.95
8.34 (dd, 1H, ArH , J = 8.4, 0.9 Hz), 11.5 (s, 1H, NH).
a
(s, 2H, NH ), 7.21 (dd, 1H, thiophene H , J = 5.1, 3.9 Hz), 7.49
Anal. Calcd. for C H NO S: C, 59.76; H, 4.24; N, 5.36.
2
b
13 11
3
(dt, 1H, ArH , J = 7.6, 1.2 Hz), 7.66 (dd, 1H, ArH , J = 8.2, 1.0
Found: C, 59.51; H, 4.10; N, 5.43.
c
a
Hz), 7.81 (dt, 1H, ArH , J = 7.7, 1.5 Hz), 7.85 (dd, 1H, thiophene
b
Method B.
H , J = 5.1, 1.2 Hz), 8.12 (dd, 1H, ArH , J = 8.0, 1.1 Hz), 8.41
c
d
(dd, 1H, thiophene H , J = 3.9, 1.2 Hz).
A mixture of compound 9 (0.30 g, 1.31 mmol), sodium
methoxide (0.15 g, 2.80 mmol) and methanol (10 ml) was heated
briefly and then was allowed to stand at room temperature for 1
hour. Dilution with water (30 ml) and filtration gave 0.30 g
(88%) of 4, mp 169-171°.
a
Anal. Calcd. for C H N OS: C, 59.24; H, 3.73; N, 17.27.
12
9 3
Found: C, 59.28; H, 3.66; N, 17.23.
3-Methylamino-2-(2-thienyl)-4(3H)-quinazolinone (7b).
A mixture of compound 2 (0.50 g, 2.04 mmol) and methylhy-
drazine (2 ml) was heated in a water bath for 30 minutes. The
product was mixed with water (20 ml) and the resulting semisolid
was triturated with ethanol to give 0.20 g (39%) of compound 7b,
mp 122-124°. Recrystallization from ethanol gave the pure com-
pound, mp 127-128°; ir: 3320 (N-H), 1665 (C=O), 1605 (C=N)
N-(2-Aminocarbonylphenyl)thiophene-2-thiocarboxamide (5).
A mixture of compound 2 (0.50 g, 2.04 mmol) and ethanolic
ammonia (ethanol saturated with ammonia at 0°, 10 ml) was
heated briefly in a stoppered flask on a water bath and the result-
ing solution was allowed to stand at room temperature for 1 hour.
Dilution with water (30 ml) and acidification with concentrated
hydrochloric acid gave 0.50 g (93%) of compound 5, mp 200-
202°. Recrystallization from ethanol afforded the pure compound
-1 1
cm ; H nmr: δ 2.68 (d, 3H, CH , J = 5.6 Hz), 6.72 (q, 1H, NH,
3
J = 5.6 Hz), 7.22 (dd, 1H, thiophene H , J = 4.8, 3.9 Hz), 7.49 (dt,
b
1H, ArH , J = 7.9, 0.9 Hz), 7.66 (d, 1H, ArH , J = 8.0 Hz), 7.81
c
a

346
L. M. Deck, S. D. Turner, J. A. Deck and E. P. Papadopoulos
Vol. 38
(dt, 1H, ArH , J = 7.6, 1.3 Hz), 7.86 (dd, 1H, thiophene H , J =
added. The mixture was allowed to stand for 30 minutes and then
it was diluted with water (20 ml) and acidified with concentrated
hydrochloric acid to give 0.16 g (85%) of 10, mp 210-211°.
b
c
5.0, 1.1 Hz), 8.12 (dd, 1H, ArH , J = 8.0, 1.5 Hz), 8.36 (dd, 1H,
d
thiophene H , J = 3.9, 1.1Hz).
a
Anal. Calcd. for C H N OS: C, 60.68; H, 4.31; N, 16.33.
Found: C, 60.80; H, 4.25; N, 16.38.
13 11
3
N-(2-Aminocarbonylphenyl)thiophene-2-carboxamide (11).
A mixture of compound 9 (0.60 g, 2.63 mmol) and ethanolic
ammonia (10 ml) was kept in a stoppered flask at room tempera-
ture for 2 hours and was then filtered to give 0.56 g (86%) of 11,
mp 182-183°. Recrystallization from petroleum ether (bp 35-
60°)/ethyl acetate gave the pure compound mp 182-183° (lit [26]
mp 280-283°); ir: 3450, 3360, 3200 (N-H), 1655, 1620 (C=O)
N-(2-Carboxyphenyl)thiophene-2-thiocarboxamide (8).
Benzothiazinone 2 (0.50 g, 2.04 mmol) was heated with 10%
aqueous sodium hydroxide (10 ml) in a water bath for 30 minutes
to obtain a clear solution. Ice water was added to the cooled solu-
tion which was acidified with concentrated hydrochloric acid to
give 0.50 g (93%) of compound 8, mp 164-165°. This product
was recrystallized from methanol to give pure 8, mp 165-166°; ir:
-1
1
cm ; H nmr: δ 7.16 (dt, 1H, ArH , J = 7.6, 1.2 Hz), 7.25 (dd,
c
1H, thiophene H , J = 5.0, 3.8 Hz), 7.55 (dt, 1H, ArH , J = 7.9,
b
b
-1 1
1655 (C=O) cm ; H nmr: δ 7.22 (dd, 1H, thiophene H , J = 5.0,
1.5 Hz), 7.69 (dd, 1H, thiophene H J = 3.8, 1.1 Hz), 7.88 (dd,
b
a,
3.8 Hz), 7.39 (dt, 1H, ArH , J = 7.6, 1.1 Hz), 7.65 (dt, 1H, ArH ,
1H, ArH , J = 8.0, 1.3 Hz), 7.89 (dd, 1H, thiophene H , J = 5.0,
c
b
d
c
J = 7.8, 1.6 Hz), 7.78 (dd, 1H, thiophene H , J = 3.8, 1.1 Hz), 7.84
1.0 Hz), 8.41 (s, 2H, NH ), 8.55 (dd, 1H, ArH , J = 8.0, 1.0 Hz),
a
2
a
(dd, 1H, thiophene H , J = 5.0, 1.0 Hz), 8.00 (dd, 1H, ArH , J =
13.0 (s, 1H, NH).
c
d
7.9, 1.5 Hz), 8.34 (dd, 1H, ArH , J = 8.6, 0.8 Hz), 12.1 (s, 1H,
Anal. Calcd. for C H N O S: C, 58.52; H, 4.09; N, 11.37.
a
12 10
2 2
NH).
Found: C, 58.79; H, 4.23; N, 11.19.
Anal. Calcd. for C H NO S : C, 54.73; H, 3.45; N, 5.32.
12
9
2 2
N-[2-(Benzylaminocarbonyl)phenyl]thiophene-2-carboxamide
(12).
Found: C, 54.88; H, 3.61; N, 5.32.
2-(2-Thienyl)-4H-3,1-benzoxazin-4-one (9).
A mixture of compound 9 (0.68 g, 2.98 mmol), benzene (10
ml) and benzylamine (0.40 g, 3.74 mmol) was refluxed for 30
minutes. Filtration of the cooled reaction mixture gave 0.93 g
(93%) of 12, mp 153-155°. The pure compound was obtained by
recrystallization from petroleum ether (bp 35- 60°)/ethyl acetate
as buff crystals, mp 155-156° (lit [26] mp 156-158°) ; ir: 3290
A mixture of compound 8 (1.63 g, 6.19 mmol) and t-butylben-
zene (20 ml) was refluxed for 18 hours, and allowed to cool. The
resulting mixture was diluted with petroleum ether (bp 63-75°;
50 ml) and filtered to give 1.08 g (76%) of 9, mp 132-134°.
Recrystallization from petroleum ether (bp 35-60°)/ethyl acetate
gave the pure compound as buff crystals, mp 134-135° (lit[25]
mp 133-134°; lit [26] mp 125-127°); ir: 1770 (C=O), 1615 (C=N)
-1
1
(N-H), 1652, 1615 (C=O) cm ; H nmr: δ 4.53 (d, 2H, CH J =
2,
5.9 Hz), 7.20 (dt, 1H, ArH , J = 7.7, 1.2 Hz), 7.24 (dd, 1H, thio-
c
-1 1
cm ; H nmr: δ 7.28 (dd, 1H, thiophene H , J = 5.0, 3.8 Hz), 7.58
b
phene H , J = 5.0, 3.7 Hz), 7.27-7.38 (m, 5H, PhH), 7.56 (dt, 1H,
b
(dt, 1H, ArH , J = 7.6, 1.1 Hz), 7.63 (dd, 1H, ArH , J = 7.9, 0.7
c
a
ArH , J = 7.8, 1.4 Hz), 7.69 (dd, 1H, thiophene H , J = 3.9, 1.1
b
a
Hz), 7.92 (dt, 1H, ArH , J = 7.8, 1.6 Hz), 7.93 (dd, 1H, thiophene
b
Hz), 7.88 (dd, 1H, thiophene H , J = 5.0, 1.1 Hz), 7.90 (dd, 1H,
c
H , J = 5.0, 1.2 Hz), 7.98 (dd, 1H, thiophene H , J = 3.8, 1.2 Hz),
c
a
ArH , J = 7.8, 1.3 Hz), 8.52 (dd, 1H, ArH , J = 8.4, 1.0 Hz), 9.46
d
a
8.11 (dd, 1H, ArH , J = 7.8, 1.1 Hz).
d
(t, 1H, CH NH, J = 5.8 Hz), 12.5 (s, 1H, NH).
2
Anal. Calcd. for C H NO S: C, 62.88; H, 3.08; N, 6.11.
12
7
2
Anal. Calcd. for C H N O S: C, 67.84; H, 4.79; N, 8.33.
19 16
2 2
Found: C, 62.86; H, 3.02; N, 5.90.
N-(2-Carboxyphenyl)thiophene-2-carboxamide (10).
Method A.
Found: C, 68.11; H, 4.91; N, 8.24.
REFERENCES AND NOTES
A mixture of compound 9 (0.20 g, 0.87 mmol) and 10% aque-
ous sodium hydroxide (5 ml) was heated in a water bath for 5
minutes to form a solution which was diluted with water (30 ml),
cooled and acidified with concentrated hydrochloric acid to give
0.18 g (84%) of 10, mp 208-210°. Recrystallization from petro-
leum ether (bp 35-60°)/ethyl acetate gave the pure compound mp
210-211° (lit[26] mp 210-212°); ir: 3310 (N-H), 1670, 1690
[1] J. C. Howard and G. Klein, J. Org. Chem., 27, 3701
(1962).
[2] E. Cherbuliez, B. Willhalm, O. Espejo, S. Jaccard and J.
Rabinowitz, Helv. Chim. Acta, 50, 1440 (1967).
[3] E. Cherbuliez, B. Willhalm, S. Jaccard and J. Rabinowitz,
Helv. Chim. Acta, 50, 2563 (1967).
[4] E. Cherbuliez, O. Espejo, B. Willhalm and J. Rabinowitz,
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[5] P. Thieme and H. Koenig, Synthesis, 426 (1973).
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30, 863 (1976).
[7] V. P. Arya, R. S. Grewal, C. L. Kaul, J. David and V.
Honkan, Indian J. Chem. Sect. B, 15, 133 (1977).
[8] H. J. Kabbe, Liebigs Ann. Chem., 398 (1978).
[9] C. Nguyen, Y. Saegusa and Y. Iwakura, J. Heterocyclic
Chem., 19, 541 (1982).
-1 1
(C=O) cm ; H nmr: δ 7.18 (dt, 1H, ArH , J = 7.5, 0.9 Hz), 7.25
c
(dd, 1H, thiophene H , J = 4.8, 3.9 Hz), 7.63 (dt, 1H, ArH , J =
b
b
7.8, 1.5 Hz), 7.73 (dd, 1H, thiophene H , J = 3.8, 1.0 Hz), 7.90
a
(dd, 1H, thiophene H , J = 5.0, 1.0 Hz), 8.03 (dd, 1H, ArH , J =
c
d
7.9, 1.5 Hz), 8.55 (d, 1H, ArH , J = 8.3 Hz), 12.1 (s, 1H, NH).
a
Anal. Calcd. for C H NO S: C, 58.29; H, 3.67; N, 5.66.
12
9
3
Found: C, 58.56; H, 3.76; N, 5.42.
Method B.
To a chilled solution of compound 8 (0.20 g, 0.76 mmol) in
10% aqueous sodium hydroxide (2 ml) was added 30% hydrogen
peroxide (2 ml) and the resulting mixture was kept in an ice bath
for 2 minutes. After a 15 minute period of standing at room tem-
perature, a second portion (2 ml) of 30% hydrogen peroxide was
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