Synthesis and reactions of some 2-methyl-4-oxo-4H-1-benzopyrans and 2-methyl-4-oxo-4H-1-benzo[b]-thiopheno[3,2-b]pyrans

Article abstract of DOI:10.1080/10426500210228

2-Methyl-4-oxo-4H-1-benzothiophenopyran (3) was prepared together with its thio analoge 4. A facial conversion of 3 and some 2-methyl-4-oxo-4 H-1-benzopyrans (5) to 2-oxo-2 H-1-pyrans and 2(1H)-pyridones was achieved under the influence of some carbon nucleophiles (NCCH₂R). The behavior of the active methyl group of 3 or 5 toward benzaldehyde, ethyl oxalate, and phthalic anhydride was discussed, where the styryl derivatives 12, 16, the pyruvates 20, 24, and phthalide 33 were obtained, respectively. Bromination of 12, 16, followed by reaction with phenylenediamine and 2-aminothiophenol, led to the formation of quinoxalinyl and benzothiazinyl derivatives. Treatment of the pyruvic acids derived from 20, 24 with phenylenediamine gave quinoxalinyl derivatives, but with benzaldehyde and aniline, atophan analogues were formed. In addition, compound 33 was isomerized to the corresponding phthalone derivative. Compound 3 was allowed to react with amines, hydrazine, hydroxylamine, thiourea, and guanidine, where opening of the pyrone ring was observed and alkylaminobutene, pyrazole, isoxazole, aminopyrimidine, thioxopyrimidine derivatives were obtained, respectively.

Full text of DOI:10.1080/10426500210228

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Synthesis and Reactions of Some 2-Methyl-4-oxo-4 H
-1-benzopyrans and 2-Methyl-4-oxo-4 H -1-benzo[ b ]-
thiopheno[3,2- b ]pyrans
S. S. Ibrahim a , H. M. El-Shaaer a & A. Hassan a
a Department of Chemistry, Faculty of Education, Ain-Shams University, Roxy, Cairo, Egypt
Version of record first published: 27 Oct 2010.
To cite this article: S. S. Ibrahim, H. M. El-Shaaer & A. Hassan (2002): Synthesis and Reactions of Some 2-Methyl-4-oxo-4 H -1-
benzopyrans and 2-Methyl-4-oxo-4 H -1-benzo[ b ]-thiopheno[3,2- b ]pyrans, Phosphorus, Sulfur, and Silicon and the Related
Elements, 177:1, 151-172
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SYNTHESIS AND REACTIONS OF SOME
2-METHYL-4-OXO-4H-1-BENZOPYRANS
AND 2-METHYL-4-OXO-4H-1-BENZO[b]-
THIOPHENO[3,2-b]PYRANS
S. S. Ibrahim, H. M. El-Shaaer, and A. Hassan
Department of Chemistry, Faculty of Education, Ain-Shams
University, Roxy, Cairo, Egypt
(Received May 6 2001.)
2-Methyl-4-oxo-4H-1-benzothiophenopyran (3) was prepared together
with its thio analoge 4.
A facial conversion of 3 and some
2-methyl-4-oxo-4H-1-benzopyrans (5) to 2-oxo-2H-1-pyrans and 2(1H)-
pyridones was achieved under the influence of some carbon nu-
cleophiles (NCCH2R). The behavior of the active methyl group of
3 or 5 toward benzaldehyde, ethyl oxalate, and phthalic anhy-
dride was discussed, where the styryl derivatives 12, 16, the pyru-
vates 20, 24, and phthalide 33 were obtained, respectively. Bromi-
nation of 12, 16, followed by reaction with phenylenediamine and
2-aminothiophenol, led to the formation of quinoxalinyl and ben-
zothiazinyl derivatives. Treatment of the pyruvic acids derived from
20, 24 with phenylenediamine gave quinoxalinyl derivatives, but with
benzaldehyde and aniline, atophan analogues were formed. In addi-
tion, compound 33 was isomerized to the corresponding phthalone
derivative. Compound 3 was allowed to react with amines, hy-
drazine, hydroxylamine, thiourea, and guanidine, where opening of
the pyrone ring was observed and alkylaminobutene, pyrazole, isox-
azole, aminopyrimidine, thioxopyrimidine derivatives were obtained,
respectively.
Keywords: Benzopyrans; benzothiophene; IR; NMR spectrum
INTRODUCTION
4-Oxo-4H-1-benzopyrans (trivial name chromones) and their deriva-
tives have been receiving great attention as some of them proved
3
to be of special importance in medicine and other applications.1
Some other 4-oxo-4H-1-pyrans fused to heterocyclic rings have been
Address correspondence to S. S. Ibrahim, Department of Chemistry, Faculty of Edu-
cation, Ain-Shams University, Roxy, Cairo, Egypt.
151

152
S. S. Ibrahim et al.
synthesized, for example 4-oxo-4H-1-pyridobenzopyrans.4 Herein we
tried to prepare other derivatives containing a pyran ring fused to the
benzo[b]thiophene moiety and describe their reactions together with
some other benzopyrans.
RESULTS AND DISCUSSION
2-Methyl-4-oxo-4H-1-benzo[b]thiopheno[3,2-b]pyran (3) was prepared
via the reaction of 2-acetyl-3-hydroxybenzo[b]thiophene (1) with ethyl
acetate in the presence of sodium metal under Claisen condensation
conditions to give the diketone 2. Cyclization of 2 with concentrated
sulphuric acid gave the target compound 3 (Scheme 3), which was in-
soluble in 5% aqueous sodium hydroxide solution and gave no colour
with ferric chloride, indicating the absence of free OH group. The struc-
ture of compounds 2 and 3 was inferred from their elemental analysis
and IR spectra. The 1H NMR spectrum of 3 showed no signal for O H
but showed the characteristic bands of the fused pyrone ring.
2-Methyl-4-thio-4H-1-benzo[b]thiopheno[3,2-b]pyran (4) was ob-
tained by heating 3 with phosphorus pentasulphide in boiling benzene
(Scheme 3).
It is known that the pyrone ring of 2-methyl-4-oxo-4H-1-benzopyrans
are susceptible to ring opening under the influence of nitrogen nu-
cleophiles such as, amines,5 thiourea,6 guanidine,6 hydrazine,7 and
hydroxylamine,8 but the effect of carbon nucleophiles has not been dis-
cussed. In the present work, 2-methyl-4-oxo-4H-1-benzopyrans (5a,b)
were allowed to react with some carbon nucleophiles, namely, ethyl
cyanoacetate, cyanoacetamide, and malononitrile in ethanolic EtONa,
where cleavage of the pyrone ring was observed, followed by cyclization
to give different heterocyclic products (Scheme 1). With ethyl cyanoac-
etate, compounds 5a,b gave 2-oxo-2H-1-pyran derivatives 6a,b, the 1H
NMR spectrum of compound 6a being an example, displayed neither
signals for the ethyl ester nor a signal for the H-3 of the -pyrone ring
in the starting compound. Reaction of 5a,b with either cyanoacetamide
or malononitrile gave the same 2(1H)-pyridone derivatives 9a,b. For-
mation of 9a,b from cyanoacetamide may be explained via opening of
the pyrone ring of 5a,b at C-2 to give intermediate 8, which then cy-
clized. With malononitrile, the intermediate 7 so formed was subjected
to hydrolysis of one of its cyano groups to give intermidiate 8, which
then cyclized.
Investigation of the reactivity of the newly synthesized benzothio-
phenopyran derivative 3 towards the same carbon nucleophiles indi-
cated that the susceptibility of the pyrone ring to cleavage was not

Benzopyrans
153
SCHEME 1
altered, and it behaved similarly to the other benzopyrans 5a,b. Thus,
reaction of compound 3 with ethyl cyanoacetate gave the 2-pyranone
derivative 10, while with either cyanoacetamide or malononitrile the
pyridone derivative, 11 was obtained (Scheme 3).

154
S. S. Ibrahim et al.
In earlier work we found that 2-methyl-4-oxo-4H-1-benzopyrans con-
densed with aromatic aldehydes to give the corresponding 2-styryl
derivatives.7 In the present work when 2-methylbenzopyran deriva-
tive 5c was allowed to react with benzaldehyde, the 2-styryl derivative
12b was obtained (Scheme 2). Its structure was assigned the expected
transconfiguration on the basis of its 1H NMR spectrum which showed
a signal for a doublet (1 H, J = 17 Hz) at 6.81.
SCHEME 2
2-Styryl-4-oxo-4H-1-benzopyrans 12a9 and 12b were used success-
fully for the synthesis of 2-heterocyclic derivatives (flavone analogues).
Thus bromination of compounds 12a,b with bromine led to the forma-
tion of 1,2-dibromophenylethane derivatives 13a,b (Scheme 2), the 1H
NMR spectrum of 13a being an example, showed signals at 4.22–4.27
[m, 2 H, (CH Br)2], 6.43 (s, 1 H, H-3), and 7.31–8.25 ppm (m, 9 H, Ar-H).
On reacting compounds 13a,b with 2-phenylenediamine or 2-
aminothiophenol, two novel and interesting systems were formed and
characterized as tetrahydroquinoxaline derivatives 14a,b and benzoth-
1
iazine derivatives 15a,b respectively (Scheme 2). The H NMR spec-
trum of compound 14a showed signals at 3.82–3.87 (m, 2 H, quinox-
aline H-2 + H-3), 5.61–5.72 (b, 2 H, two NH), 6.46 (s, 1 H, H-3), and
1
7.32–8.31 ppm (m, 13 H, Ar-H), while the H NMR spectrum of 15a
showed signals at 3.72–3.77 (m, 2 H, SCH CHN), 5.92 (b, 1 H, NH),
6.51 (s, 1 H, H-3), and 7.13–8.24 ppm (m, 13 H, Ar-H).
Testing the reactivity of the 2-methyl group of 2-methyl-4-oxo-4H-1-
benzo[b]thiopheno[3,2-b]pyran (3) toward aromatic aldehydes showed

Benzopyrans
155
that it condensed easily with benzaldehyde in the presence of sodium
1
ethoxide to give the trans 2-styryl derivative 16 (Scheme 3). Its H
NMR spectrum showed signals at 6.52 (s, 1 H, H-3), 6.91 (d, 1 H, CH,
J = 16 Hz), and 7.32–8.21 ppm (m, 10 H, Ar-H and vinyl-H).
Bromination of compound 16 with bromine in acetic acid took place
easily to afford the dibromophenylethyl derivative 17. Reacting the lat-
ter compound with 2-phenylenediamine and 2-aminothiophenol led to
the formation of the 2-quinoxalinyl and 2-benzothiazinyl derivatives 18
and 19 respectively (Scheme 3).
In our laboratory we previously discovered the condensation of di-
ethyl oxalate with 2-methyl-4-oxo-4H-1-benzopyrans,10 in the presence
of sodium metal to give the corresponding pyruvate ester. In continua-
tion with this work and in order to prepare 2-heterocyclic benzopyrans
(flavone analogues), 2-methylbenzopyrone derivatives 5c and 3 were
allowed to react with diethyl oxalate following the same procedure (in
case of 5c sodium ethoxide was used instead of sodium metal) to give
the pyruvate esters 20b (Scheme 4) and 24 (Scheme 5), respectively.
Compound 20b and 24 gave a color with aqueous ferric chloride,
1
their IR spectra showed bands at 3250–2500cm
(intramolecular
hydrogen bonded OH), and the 1H NMR spectrum of 24 showed signals
at 1.31 (t, 3 H, CH3), 4.32 (q, 2 H, CH2), 6.21 (s, 1 H, H-3), 6.77 (s, 1 H,
CH C), 7.43–7.96 (m, 4 H, Ar-H), and 11.11 ppm (s, 1 H, enol OH). This
indicates that the enol form is more predominant than the keto form.
Treatment of compounds 20a,10 20b, and 24 with 10% aqueous sul-
phuric acid gave the corresponding pyruvic acids 21a,b and 25, which
were exclusively found in the enol forms. They gave a violet color
with aqueous FeCl3, and their IR spectra showed broad band centered
1
at 3140–2800 cm for intramolecular hydrogen bonded OH and car-
boxylic OH.
Preparing a novel 2-heterocyclic pyrons was successfully accom-
plished using the previous pyruvic acids. Thus dihydroquinoxaline
derivatives 22a,b and 26 (Schemes 4 and 5) were prepared by react-
ing the former pyruvic acids 21a,b and 25 with 2-phenylenediamine.
In addition, when the pyruvic acids 21a,b and 25 were allowed to react
with benzaldehyde and aniline, the atophan11 analogues 23a,b and 27
1
were formed, respectively (Schemes 4 and 5). The H NMR spectrum
of compound 27 showed signals at 6.47 (s, 1 H, H-3), 7.28–8.06 (m, 13
H, Ar-H), and 9.35 ppm (s, 1 H, COOH).
It has been reported that the pyrone ring of 2-methyl-4-oxo-4H-1-
benzopyrans was susceptible to opening under the influence of nitro-
8
gen nucleophiles.5 In the present work, the pyrone ring of compound
3 was tested toward some nitrogen nucleophiles including aliphatic
amines, hydroxylamine, hydrazine hydrate, thiourea, and guanidine

156
S. S. Ibrahim et al.
SCHEME 3
hydrochloride (Scheme 6). In each case, cleavage of the pyrone ring was
observed.
Reaction of 3 with butylamine and cyclohexylamine led to the forma-
tion of the 2-alkylaminobutenyl derivatives 28a,b. Compounds 28a,b
regenerate the starting compound 3 upon treatment with concentrated

Benzopyrans
157
SCHEME 4
sulphuric acid or boiling with dilute hydrochloric acid. Refluxing
the thio analogue 4 with butylamine and cyclohexylamine affected
desulphurization of the thione group and formation of the former enam-
ines 28a,b.
The action of hydrazine hydrate on 3 or 4 resulted in the same pyra-
zole derivative 29 (Scheme 6) as a result of opening of the pyrone ring
and subsequent recyclization to give the product. When compound 3

158
S. S. Ibrahim et al.
SCHEME 5
was allowed to react with hydroxylamine hydrochloride in boiling pyri-
dine, the isoxazole derivative 30 was formed. Moreover, compound 30
was formed via the action of hydroxylamine hydrochloride on compound
4, where desulphurization of the thione group was observed (Scheme 6).
Recently in our laboratory a novel conversion of -benzopyrans to
pyrimidine derivatives was investigated.6 We made use of this con-
version for the synthesis of derivatives of benzo[b]thiophene carrying
the pyrimidine moiety. Thus, when compound 3 was allowed to react
with guanidine hydrochloride and thiourea in the presence of potas-
sium hydroxide, the pyrimidine derivatives 31 and 32 were obtained,
respectively (Scheme 6).

Benzopyrans
159
SCHEME 6
2-Methylnaphthopyrone has been shown to condense with ph-
thalic anhydride in the presence of zinc chloride to give phthalidene
derivative.12 In the present work, we tested the reactivity of the
2-methyl group in the benzothiophenopyran 3 toward phthalic
anhydride. Performing the reaction using zinc chloride gave a tarry
product from which no pure material could be isolated. However, us-
ing sodium acetate at elevated temperature gave the phthalide 33

160
S. S. Ibrahim et al.
(60%) (Scheme 6). Compound 33 isomerized easily to the 1,3-indandione
derivative 34 in the presence of sodium methoxide, similar to other
phthalides.13 The IR spectrum of compound 33 showed a sharp band at
1
1810 cm corresponding to C O of lactone, while that of 34 displayed
no bands for lactones but showed a band at 1700 cm 1 arising from C O
of indandione. Both 33 and 34 showed bands characteristic of C O of a
-pyrone.
EXPERIMENTAL
Melting points were incorrected and were recorded in open capillary
tubes on a Gallenkamp 595-MFB melting point apparatus. IR spec-
tra were measured on a Perkin-Elmer 598-IR spectrophotometer using
samples in KBr disks ( , cm 1). 1H NMR spectra were determined
on a Jeol FX-90 NMR spectrometer (90 MHz) using DMSO-d6 as
solvent and TMS as an internal standard. Mass spectra were taken
on a Hewlett Packard MS-5988, direct inlet (electron beam energy
70 eV).
2-Acetoacetyl-3-hydroxybenzo[b]thiophene (2)
To a mixture of 2-acetyl-3-hydroxybenzo[b]thiophene (1) (10 g, 0.05
mol) and ethyl acetate (55 ml), was added small pieces of sodium
metal (4 g). The reaction mixture was heated under reflux for 4 h
and left overnight at room temperature. The product was treated with
crushed ice (300 g), acidified with dilute acetic acid, and aerated un-
til a yellow solid deposited, which was collected by filtration, dried,
and crystallized from petroleum ether 60–80 to give compound 2 as
a white crystals. Compound 2 was soluble in 5% aqueous sodium hy-
droxide solution and gave a violet color with aqueous ferric chloride
solution.
2-Methyl-4-oxo-4H-1-benzo[b]thiopheno[3,2-b]pyran (3)
2-Acetoacetyl-3-hydroxybenzo[b]thiophene (2) was dissolved in con-
centrated sulphuric acid, and the mixture was left for 5 min. The
resulting dark brown solution was poured on ice-cold water, and the
solid so obtained was filtered off and crystallized from ethanol to give
the titled compound 3 in almost theoretical yield. Compound 3 was
insoluble in 5% aqueous sodium hydroxide solution and gave no color
with ferric chloride solution.

Benzopyrans
161
2-Methyl-4-thio-4H-1-benzo[b]thiopheno[3,2-b]pyran (4)
A mixture of compound 3 (1 g, 0.004 mol) and phosphorus pentasul-
phide (1 g, 0.004 mol), in dry benzene (50 ml), was refluxed for 2 h.
The reaction mixture was filtered while hot. The solvent was evap-
orated and the product 4 crystallized from ethanol as deep orange
needles.
6-(2-Hydroxy-substituted phenyl)-3-cyano-4-methyl-
2-oxo-2H-1-pyrans 6a,b and 6-(3-Hydroxybenzo[b]-
thiopheno)-3-cyano-4-methyl-2-oxo-2H-1-pyran (10)
To a mixture of 3, 5a, or 5b (0.003 mol) and sodium ethoxide solution
(0.003 mol sodium in 5 ml absolute ethanol) in absolute ethanol (5 ml)
was added ethyl cyanoacetate (0.003 mol). The mixture was refluxed for
4 h on a boiling water bath, cooled, and acidified with 50% hydrochloric
acid. The solid obtained was filtered off and crystallized from the proper
solvent to give 10 and 6a,b respectively.
6-(2-Hydroxy substituted phenyl)-3-cyano-4-methyl-2-
(1H)pyridones 9a,b and 6-(3-Hydroxybenzo[b]thiopheno)-
3-cyano-4-methyl-2(1H)pyridone (11)
To a solution of 3, 5a, or 5b (0.003 mol) and sodium ethoxide solu-
tion (0.003 mol sodium in 5 ml absolute ethanol), in absolute ethanol
(5 ml) was added malononitrile or cyanoacetamide (0.003 mol). The
mixture was refluxed for 15 min on a boiling water bath. The orange
reaction mixture was poured onto dilute hydrochloric acid, and the yel-
low solid so formed was filtered off to give compounds 11 and 9a,b
respectively.
2-Styryl-6-nitro-4-oxo-4H-1-benzopyran (12 b)
and 2-Styryl-4-oxo-4H-1-benzo[b]thiopheno[3,2-b]
pyran (16)
Compound 3 or 5c (0.5 g, 0.002 mol) was dissolved in the least
amount of absolute ethanol and treated with sodium ethoxide solution
(0.002 mol sodium dissolved in 5 ml absolute ethanol). Benzaldehyde
(0.24 ml, 0.002 mol) was added, and the mixture was left overnight at
room temperature. The orange product formed was filtered off to give
the styryl derivatives 16 and 12b respectively. Compounds 16 and 12b
were insoluble in 5% aqueous sodium hydroxide and did not give color
with ferric chloride.

162
S. S. Ibrahim et al.
2-(1,2-Dibromo-2-phenylethyl)-4-oxo-4 H-1-benzopyrans
13a,b and 2-(1,2-Dibromo-2-phenylethyl)-4-oxo-4H-1-
benzo[b]thiopheno[3,2-b]pyran (17)
To a stirred solution of 12a, 12b, or 16 (0.002 mol) in acetic acid
(3 ml) was added dropwise over a period of 20 min a solution of bromine
(0.003 mol) in 5 ml of acetic acid. The mixture was then stirred for
3 h, and the white precipitate formed was filtered off, washed with
acetic acid (5 ml), and recrystallized from the proper solvent to give
compounds 13a,b and 17 respectively.
2-(3-Phenyl-1,2,3,4-tetrahydro-2-quinoxalinyl)-4-oxo-4H-
1-benzopyrans 14a,b and 2-(3-Phenyl-1,2,3,4-tetrahydro-
2-quinoxalinyl)-4-oxo-4H-1-benzo[b]thiopheno-[3,2-b]pyran
(18)
To a solution of compounds 13a, 13b or 17 (0.0007 mol) in a mixture
of ethanol (7 ml) and pyridine (3 ml) was added 1,2-phenylenediamine
(0.0007 mol). The mixture was refluxed for 4 h and then left to stand
overnight followed by treatment with cold dilute acetic acid. The solid
deposited was collected by filtration and crystallized from the proper
solvent to give compounds 14a,b and 18 respectively.
2-[2(or 3)-Phenyl-2,3,4-trihydrobenzothiazin-3-(or 2)-yl]-
4-oxo-4H-1-benzopyrans 15a,b and 2-[2(or 3)-Phenyl-
2,3,4-trihydrobenzothiazin-3(or 2)-yl]-4-oxo-4H-
1-benzo[b]thiopheno[3,2-b]pyran19
To a solution of compound 13a, 13b, or 17 (0.0007 mol) in a mixture
of ethanol (5 ml) and pyridine (3 ml) was added o-aminothiophenol
(0.0008 mol). The mixture was refluxed for 2 h and then left
overnight. Afterward, the mixture was poured onto cold, dilute acetic
acid. The solid deposited was collected by filtration and crystal-
lized from the proper solvent to give compounds 15a,b and 19
respectively.
Ethyl Pyruvates 20a,b and 24
a. To a mixture of 5c (0.003 mol) and diethyl oxalate (2 ml) was added
sodium ethoxide solution (0.2 g sodium dissolved in 10 ml abso-
lute ethanol). The reaction mixture was left overnight and then
poured onto acidified, cold water. The yellow solid deposited was col-
lected by filtration to give compound 20b which gave a green color

Benzopyrans
163
with aqueous ferric chloride and was soluble in 5% aqueous sodium
hydroxide.
b. To a mixture of compound 3 or 5a (0.005 mol), diethyl oxalate
(2 ml), and dry diethyl ether (50 ml) was added sodium metal (0.4 g
small pieces). After shaking and stirring, a vigorous reaction took
place. The reaction was left for 0.5 h for completion and then was
stoppered and left overnight at room temperature. Acidification with
dilute acetic acid gave the yellow pyruvic ester derivatives 24 and
20a respectively. Each gave a violet color with aqueous ferric chloride
and were soluble in 5% aqueous sodium hydroxide. Compound 20a
was identical to an authentic sample prepared according to Jones.9
Pyruvic Acids 21a,b and 25
A suspension of compound 20a, 20b, or 24 (0.5 g) in dilute sulphuric
acid (30 ml, 10%) was stirred on a boiling water bath for 3 h, then left
to cool, and then was filtered off. The solid obtained was washed thor-
oughly with water to give compounds 21a,b and 25 respectively, both
of which gave characteristic colors with the ferric chloride test. Com-
pound 21a was found to be identical to an authentic sample9 prepared
by hydrolysis of ester 20a using aqueous potassium hydroxide solution
(MP and mixed MP).
2-[(2-Oxo-1,2-dihydroquinoxalin-3-yl)methyl]-4-oxo-4 H-
1-benzopyrans 22a,b and 2-[(2-Oxo-1,2-
dihydroquinoxalin-3-yl)methyl]-4-oxo-4H-1-
benzo[b]thiopheno[3,2-b]pyran (26)
A mixture of compound 21a, 21b, or 25 (0.002 mol), 1,2-phenyl-
endiamine (0.002 mol) and ethanol (10 ml) was refluxed on a boiling
water-bath for 30 min. The solid so obtained on cooling was filtered off
and crystallized from the appropriate solvent to give compounds 22a,b
and 26, respectively.
2-(4-Carboxy-2-phenylquinolin-3-yl)-4-oxo-4 H-1-
benzopyrans 23a,b and 2-(4-Carboxy-2-phenylquinolin-
3-yl)-4-oxo-4H-1-benzo[b]thiopheno[3,2-b]Pyran (27)
A mixture of compound 21a, 21b, or 25 (0.002 mol) and benzalde-
hyde (0.2 ml, 0.003 mol), in ethanol (5 ml) was boiled and then aniline
(0.18 ml, 0.002 mol) in ethanol (5 ml) was added slowly with frequent
shaking over 15 min. The mixture was refluxed on a boiling water bath
for 3 h and allowed to stand overnight. The solid formed was filtered

164
S. S. Ibrahim et al.
off and crystallized from the suitable solvent to give compounds 23a,b
or 27 respectively.
2-(3-Alkylamino-2-butenyl-1-oxo)-3-hydroxybenzo[ b]-
thiophenes 28a,b
a. To a solution of compound 3 (0.002 mol) in ethanol (5 ml) was added
butylamine (0.004 mol) or cyclohexylamine (0.004 mol). The mixture
was then refluxed for 15 min and kept overnight at room tempera-
ture. The solid obtained was filtered off to give compounds 28a and
28b respectively, both of which were soluble in 5% aqueous sodium
hydroxide solution and gave a violet color with aqueous ferric chlo-
ride solution.
b. Compounds 28a and 28b were also prepared starting from the pyran-
thione 4 and the appropriate alkylamines in a reaction time of 30 min
using the same above method (MP and mixed MP).
3-Hydroxy-2-(3-methylpyrazol-5-yl)benzo[ b]-
thiophene (29)
a. To a solution of 3 (0.002 mol), in the least amount of ethanol was
added a solution of hydrazine hydrate (2 ml) in ethanol (5 ml). The re-
action mixture was refluxed for 1 h, left to cool, and then diluted with
water. The solid formed was collected and crystallized from ethanol
to give compound 29, which was soluble in 5% aqueous sodium hy-
droxide solution and gave a green color with aqueous ferric chloride
solution.
b. Compound 29 was also prepared by refluxing compound 4 and excess
hydrazine hydrate following the above procedure.
3-Hydroxy-2-(3-methylisoxazol-5-yl) benzo[ b]-
thiophene (30)
a. A mixture of compound 3 (0.002 mol), pyridine (10 ml), and excess
hydroxylamine hydrochloride (0.8 g), dissolved in water (5 ml), was
refluxed for 1 h. The cooled mixture was acidified with dilute acetic
acid, and the solid that precipitated was filtered off and crystallized
from ethanol to give compound 30 which was soluble in 5% aqueous
sodium hydroxide solution and gave a green color with aqueous ferric
chloride solution.
b. Compound 30 was also prepared by refluxing a mixture of compound
4 and hydroxylamine hydrochloride for 2 h following the above
procedure.

Benzopyrans
165
2-(2-Amino-4-methylpyrimidin-6-yl)-3-hydroxybenzo[ b]-
thiophene (31)
A mixture of 3 (0.5 g, 0.002 mol), guanidine hydrochloride (0.5 g,
0.005 mol), potassium hydroxide (0.25 g, 0.004 mol), dissolved in
3 ml of water, and methanol (20 ml) was refluxed for 3 h. The so-
lution was cooled, diluted with water, and acidified with acetic acid.
The solid obtained was filtered off and crystallized from ethanol
to give yellow needles of compound 31, which was soluble in 5%
sodium hydroxide solution and gave a green color with ferric chloride
solution.
3-Hydroxy-2-(6-methyl-2-thioxo-3-hydropyrimidin-4-yl)-
benzo[b]thiophene (32)
A mixture of 3 (0.5 g, 0.002 mol), thiourea (0.5 g, 0.006 mol), potassium
hydroxide (0.25 g, 0.004 mol), dissolved in 1 ml of water, and ethanol
(20 ml) was refluxed for 3 h. The solution was then cooled and acidified
with dilute HCl where upon a yellow solid was obtained, which was
filtered off and crystallized from anisole to give compound 32. The latter
was soluble in 5% aqueous sodium hydroxide solution and gave a violet
color with ferric chloride solution.
2-(3-Phthalidenemethylene)benzo[ b]thiopheno[3,2-b]-
Pyran-4-one (33)
A mixture of 3 (1 g, 0.004 mol), phthalic anhydride (3 g, 0.02 mol),
and fine powdered anhydrous sodium acetate (1.5 g) was heated at
245–255 C for 30 min. After cooling the reaction mixture was tritu-
rated with dilute sodium carbonate solution, and the solid obtained
was washed with hot ethanol (20 ml), filtered off, and crystallized from
benzyl alcohol to give the brownish yellow product 31.
2-(1,3-Dioxoindan-2-yl)benzo[b]thiopheno[2,3-b]
Pyran-4-one (34)
To a suspension of compound 33 in absolute methanol (10 ml) was
added sodium methoxide solution (prepared from 0.5 g of sodium metal
and 10 ml of methanol). The mixture was heated under reflux for 1 h.
The resulting deep orange solution was cooled, diluted with water,
and then acidified with cold dilute sulphuric acid. The solid product
obtained was recrystallized from benzyl alcohol to afford the golden
yellow compound 34.

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S. S. Ibrahim et al.
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