Chemoselective pathway to 3-heteroaryliminomethyl- 4-oxo-4H-chromenes: Reaction of 4-oxo-4H-chromene- 3-carboxaldehyde thiosemicarbazones with electrophiles in basic media

Article abstract of DOI:10.1080/10426500701851309

The imidazole 4-6 and pyrimidine derivatives 8-11 containing chromone moiety have been obtained through reactions of thiosemicarbazones 1a-c with some electrophiles in basic media. Compound 12 was also used as a precursor for preparation of some novel 1-[(4-oxo-4H-chromen-3-ylmethylene)amino] [1,3,5]triazine derivatives 13-16. The formulations of all new products were verified based on their elemental and spectral analysis. Copyright Taylor & Francis Group, LLC.

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Chemoselective Pathway to
3-Heteroaryliminomethyl-
4-Oxo-4H-Chromenes:
Reaction of 4-Oxo-4H-
chromene- 3-carboxaldehyde
Thiosemicarbazones with
Electrophiles in Basic Media
Tarik El-Sayed Ali a & Wafaa Ramzy Abdel-Monem a
a Department of Chemistry, Faculty of Education,
Ain Shams University, Roxy, Cairo, Egypt
Version of record first published: 12 Aug 2008.
To cite this article: Tarik El-Sayed Ali & Wafaa Ramzy Abdel-Monem (2008):
Chemoselective Pathway to 3-Heteroaryliminomethyl- 4-Oxo-4H-Chromenes: Reaction
of 4-Oxo-4H-chromene- 3-carboxaldehyde Thiosemicarbazones with Electrophiles
in Basic Media, Phosphorus, Sulfur, and Silicon and the Related Elements, 183:9,
2161-2172
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Phosphorus, Sulfur, and Silicon, 183:2161–2172, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500701851309
Chemoselective Pathway to 3-Heteroaryliminomethyl-
4-Oxo-4H-Chromenes: Reaction of 4-Oxo-4H-chromene-
3-carboxaldehyde Thiosemicarbazones with
Electrophiles in Basic Media
Tarik El-Sayed Ali and Wafaa Ramzy Abdel-Monem
Department of Chemistry, Faculty of Education, Ain Shams University,
Roxy, Cairo, Egypt
The imidazole 4–6 and pyrimidine derivatives 8–11 containing chromone moiety
have been obtained through reactions of thiosemicarbazones 1a-c with some elec-
trophiles in basic media. Compound 12 was also used as a precursor for preparation
of some novel 1-[(4-oxo-4H-chromen-3-ylmethylene)amino] [1,3,5]triazine deriva-
tives 13–16. The formulations of all new products were verified based on their ele-
mental and spectral analysis.
Keywords Basic media; chromone; electrophiles; thiosemicarbazones
INTRODUCTION
It is known that chromones (4H-chromen-4-ones) are widespread in
the plant kingdom in a variety of forms and the parent compounds
of important flower and fruit pigments.1 Many natural and synthetic
chromone derivatives have unique biological and pharmacological
activities, including antiviral,2,3 antiallergic,4,5 antimicrobial,6–9 and
neuroleptic activity.10 Reactivity of chromones towards nucleophiles
provides a useful route in the preparation of variety of new hetero-
cyclic systems. Thus, we report here, synthesis of some new nitrogen
heterocyclic systems containing chromone moiety through reaction of
thiosemicarbazones 1a-c with some electrophiles under basic media.
Thiosemicarbazones 1a-c have two nucleophilic centers, the first is
(NH2) amino group and the second one is ( NH C S) thioimide group.
The amino group reacted with the electrophilic reagent first, followed
by nitrogen atom not sulfur in thioimide, although the sulfur atom more
Received 29 September 2007; accepted 14 November 2007.
Address correspondence to Tarik El-Sayed Ali, Department of Chemistry, Fac-
ulty of Education, Ain Shams University Roxy, 11711, Cairo, Egypt. E-mail: tarik
elsayed1975@yahoo.com
2161

2162
T. El-Sayed Ali and W. R. Abdel-Monem
SCHEME 1
nucleophilicity than nitrogen atom. This can be explained on the basis
of attack by the anion of N C S on electrophile, which is strong nu-
cleophile rather than by the sulfur atom in basic medium (pyridine or
DMF).11,12
RESULTS AND DISCUSSION
Coutinho and Fernandes13 obtained the thiazole derivative 2 by reac-
tion of thiosemicarbazone 1a with phenacyl bromide in DMSO, which
underwent ring transformation by boiling in DMF or ethylene glycol to
yield 4-(2-hydroxybenzoyl)-1H-pyrazole (3) (Scheme 1). However, upon
carry out reaction 1a with phenacyl bromide in boiling DMF and drops
of piperidine afforded the imidazole derivative 4 and not 2. Also, boil-
ing 4 in DMF or ethylene glycol, no product could be isolated except 4,
which support its structure (Scheme 1). Compound 4 was confirmed by
careful analysis of its spectral data. IR spectrum showed bands of NH,
C O, C N and C S at 3118, 1621, 1587, and 1221 cm−1, respectively.
1H NMR spectrum showed further light on 4 as it showed broad signal
at δ 11.54 ppm consistent with for NH of imidazole ring and multiplet
signals attributable to aromatic protons at 7.03–7.88 ppm. Moreover, its

Chromene-3-Carboxaldehyde Thiosemicarbazones
2163
mass spectrum showed the molecular ion peak at m/z 347 (M+, 15.27%)
(Table I).
When compound 1a was allowed to react with dichloroacetic acid
in boiling DMF containing few drops of piperidine, 3-[(4-oxo-4H-
chromen-3-ylmethylene)amino]-2-thioxo-2,3-dihydroimidazol-4-one (5)
(Scheme 1) was formed and identified by IR spectrum which showed
absorption bands at 1624, 1676, and 1283 cm−1 corresponding to
1
C Opyrone, C Oimidazole and C S, respectively. Also, its H NMR
spectrum showed multiplet signals for C5 H of imidazole and H 2 of
chromone moieties at δ 8.09–8.11 ppm, while its mass spectrum showed
the molecular ion peak at m/z 285 (M+, 25.03%) (Table I).
Unexpectedly, upon reaction thiosemicarbazone 1a with chloroac-
etamide in boiling pyridine, 2-[(4-oxo-4H-chromen-3-ylmethylene)
hydrzino]imidazolidin-4-one (6) was smoothly obtained, rather than
the expected product of type 7 (Scheme 1). The formula of imidazo-
lidinone 6 was deduced from elemental analysis and spectral data.
Thus, its IR spectrum showed disappearance of C S group and ap-
pearance of stretching vibration bands for NH and C O imidazolinone
1
around 3208 and 1722 cm−1, respectively. Also, its H NMR spectrum
revealed the characteristic signals at δ 3.8 and 9.21, 10.37 ppm or CH2
and NH, NH protons, respectively of imidazolidinone ring. (Table I).
The suggested mechanism for formation of compound 6 is removing
HCl molecule by reaction 1a and cholroacetamide to give the inter-
mediate A then nucleophilic attack of amino group at thione group
C S to give intermediate B followed by elimination of H2S molecule
(Scheme 2).
The present work was extended to investigate the interaction of
thiosemicarbazone 1b with ethyl cyanoacetate in boiling DMF in
the presence of piperidine to afford the pyrimidinone derivative 8
(Scheme 3). IR spectrum of 8 revealed NH, C O pyrimidinone and C S
groups in the region 3433–3268, 1697, and 1234 cm−1, respectively. Its
1H NMR spectrum revealed the expected characteristic signals CH2 and
NH, NH protons at δ 3.88 and 9.55, 10.08 ppm, respectively. Moreover,
mass spectrum of 8 showed a molecular ion peak at m/z 393 (M+, 1.93%)
(Table I).
Also, reaction of 1a with malononitrile in boiling DMF con-
taining piperidine as catalyst afforded 1-[(4-oxo-4H-chromen-3-
ylmethylene)amino]-4,6-diamino-2-thioxo-2H-pyrimidine (9) in good
yield (Scheme 3). Formula of 9 was elucidated from elemental analysis
and spectral data. Thus, IR spectrum of 9 showed two strong bands
at 3413, 3137 (NH2, NH) and one strong at 1246 cm−1 (C S), while
1
its H NMR spectrum showed two characteristic signals at δ 3.85 and
4.09–4.12 ppm that have been assigned to NH2, NH2 protons (Table I).

2164

2165

2166
T. El-Sayed Ali and W. R. Abdel-Monem
SCHEME 2
Furthermore,
the
6-amino-2-thioxo-1,2-dihydropyrimidine-5-
carbonitrile derivative 11 was prepared by reaction of 1c with
arylidenemalononitrile 10 in boiling DMF containing few drops of
piperidine (Scheme 3). The IR spectrum of 11 showed vibrations bands
at 3422, 3217 cm−1 (NH2) and 2216 cm−1 (CN). The 1H NMR spectrum
showed signal at δ 3.85 (NH2) and multiplet signals at δ 7.08–8.01
ppm for aromatic ring, H-9 and H-2 of chromone moiety. Also, its
mass spectrum revealed at m/z 451 (M + 3, 10.46%) corresponding the
suggested structure (Table I).
Reaction of 1a with potassium thiocyanate in refluxing dimethyl-
sulfoxide with a few drops of concentrated hydrochloric acid, gave 1-
{[(4-oxo-4H-chromen-3-ylmethylene) hydrazino]carbonthioyl}thiourea

Chromene-3-Carboxaldehyde Thiosemicarbazones
2167
SCHEME 3
(12) (Scheme 4). The structure of 12 was rigidly established by studying
its spectroscopic properties. Thus, IR spectrum showed strong bands in
the regions of 3250 -3121 (NH2, NH) and 1220–1153 cm−1 (C S). Also,
1
its H NMR spectrum revealed characteristic signals at δ 11.39 and
11.72, 12.20 ppm for NH2 and NH, NH, respectively (Table I).
Compound 12 was used as a precursor for preparation of 1-[(4-
oxo-4H-chromen-3-ylmethylene)amino][1,3,5]triazine derivatives 13–
16. Thus, cyclocondensation of 12 with methyl chloroformate and /or
carbon disulfide in boiling pyridine gave the 1,3,5-triazine derivatives
13 and 14, respectively (Scheme 4). Structures of 13 and 14 were es-
tablished based on their elemental analysis and spectral data. The IR
spectra showed the presence of broad band at 3183 cm−1 for OH in com-
pound 13, while showed characteristic band at 1243 cm−1 for C S in
compound 14. 1H NMR spectrum of 13 exhibited characteristic signals
at δ 10.37 and 11.12 ppm for NH and OH protons, respectively, while
compound 14 exhibited a broad signal at δ 10.01 ppm for NH protons
besides the expected signals of chromone ring (Table I).
Finally, 6-phenyl-2,4-dithioxo-3,4-dihydro[1,3,5]triazine 15 and 4,6-
dithioxo-1,4,5,6-tetrahydro[1,3,5]triazine-2-carboxylic acid 16 deriva-
tives have been obtained from reaction of 12 with benzoyl chloride
and/or trichloroacetic acid in boiling pyridine, respectively (Scheme 4).
The IR spectra of compounds 15 and 16 showed bands at regions 3197–
3365 cm−1 for NH, OH groups and 1617–1611 cm−1 for C O of chromone
moieties. A good evidence for the assigned structures was given from
their 1H NMR spectra as they showed signals at δ 11.54 ppm (NH tri-
azine) in compound 15 and two characteristic signals at δ 9.56 and 12.20
ppm corresponding to (NH triazine) and OH, respectively in compound

2168
T. El-Sayed Ali and W. R. Abdel-Monem
SCHEME 4
16. Moreover, their mass spectra revealed at m/z 342 (M+, 2.31%) and
365 (M + 3, 6.35%) corresponding the expected formulas of 15 and 16,
respectively (Table I).
EXPERIMENTAL
Melting points were determined on a digital Stuart SMP-3 apparatus.
Infrared spectra were measured on Perkin-Elmer 293 spectrophotome-
ter (cm−1), using KBr disks. 1H NMR spectra were measured on Gemini-
200 spectrometer (200 MHz), using DMSO-d6 as a solvent and TMS (δ)
as the internal standard. The mass spectra were measured on a HP MS
5988 mass spectrometer via a direct inlet operating at 70 eV. Elemental
microanalyses were performed at the microanalysis center at Bulgarian
Academy of Science, Sofia, Bulgaria. The physical and spectral data
of the new compounds are listed in Tables I and II. 6-Substituted-4-
oxo-4H-chromene-3-carboxaldehyde thiosemicarbazones (1a-c)14 were
prepared by published methods in literature.

Chromene-3-Carboxaldehyde Thiosemicarbazones
2169
TABLE II The Physical and Analytical Data of The New Compounds
4–16
Calculated/found (%)
Compd.
No.
M.p. ◦
(yield%)
C
Solvent of
crystallization
Formula (m.wt.)
C
H
N
4
5
178–180
77%
115–117
80%
128–130
49%
155–157
67%
265–267
78%
148–150
43%
116–118
90%
206–208
77%
DMF/EtOH
EtOH
C19H13N3O2S
(347.40)
65.69
65.35
54.73
54.52
57.78
57.43
42.76
42.51
53.67
53.43
59.00
58.62
47.05
46.71
46.98
46.72
44.81
44.53
58.15
57.83
46.66
46.34
3.77
3.69
2.47
2.30
3.73
3.61
2.31
2.24
3.54
3.38
3.15
2.88
3.29
3.15
2.43
2.33
2.31
2.17
3.08
2.92
2.24
2.09
12.10
11.93
14.73
14.51
20.73
20.48
14.25
13.98
22.35
21.97
15.64
15.38
18.29
17.90
16.86
16.59
16.08
15.81
14.28
13.99
15.55
15.29
C13H7N3O3S
(285.28)
6
EtOH
C
13H10N4O3
(270.25)
8
MeOH
C14H9BrN4O3S
(393.22)
9
Isopropanol
EtOH
C
14H11N5O2S
(313.34)
11
12
13
14
15
16
C22H14ClN5O2S
(447.91)
diluted EtOH
EtOH
C
12H10N4O2S2
(306.37)
C
13H8N4O3S2
(332.36)
188–190
59%
260–262
85%
204–206
71%
DMF/EtOH
EtOH
C
13H8N4O2S3
(348.43)
C19H12N4O2S2
(392.46)
DMF/EtOH
C
14H8N4O4S2
(360.37)
1-[(4-Oxo-4H-chromen-3-ylmethylene)amino]-5-phenyl-2-
thioxo-2,3-dihydro-imidazole (4)
A mixture of compound 1a (2.47 g, 10 mmol) and phenacyl bromide
(1.99 g, 10 mmol) in dimethylformamide (50 ml) containing two drops
of piperidine, was refluxed for 8 h. The solution was cooled and poured
onto ice water. The solid obtained was filtered off and crystallized from
the proper solvent to give 4 (Table II).
3-[(4-Oxo-4H-chromen-3-ylmethylene)amino]-2-thioxo-2,3-
dihydroimidazol-4-one (5)
A mixture of compound 1a (2.47 g, 10 mmol) and dichloroacetic acid
(1.40 g, 10 mmol) in dimethylformamide (50 ml) containing two drops
of piperidine, was refluxed for 8 h. The solution was cooled and poured
onto ice water. The solid obtained was filtered off and crystallized from
the proper solvent to give 5 (Table II).

2170
T. El-Sayed Ali and W. R. Abdel-Monem
2-[(4-Oxo-4H-chromen-3-ylmethylene)hydrazino]imidazolidin-
4-one (6)
A mixture of compound 1a (2.47 g, 0.01 mol) and chloroacetamide
(0.91 g, 0.01 mol) in dry pyridine (50 ml) was refluxed for 10 h. The
solution was cooled and poured onto ice HCl. The solid obtained was
filtered off and crystallized from the proper solvent to give 6 (Table II).
6-Imino-3-[(6-bromo-4-oxo-4H-chromen-3-
ylmethylene)amino]-2-thioxo-tetrahydropyrimidin-4-one (8)
A mixture of compound 1b (3.26 g, 10 mmol) and ethyl cyanoacetate
(1.11 g, 10 mmol) in dimethylformamide (50 ml) containing two drops
of piperidine was refluxed for 12 h. The solution was cooled and poured
onto ice water. The solid obtained was filtered off and crystallized from
the proper solvent to give 8 (Table II).
1-[(4-Oxo-4H-chromen-3-ylmethylene)amino]-4,6-diamino-2-
thioxo-2H-pyrimidine (9)
A mixture of compound 1a (2.47 g, 10 mmol) and malononitrile (0.66 g,
10 mmol) in dimethylformamide (50 ml) containing two drops of piperi-
dine was refluxed for 8 h. The solution was cooled and poured onto
ice water. The solid obtained was filtered off and crystallized from the
proper solvent to give 9 (Table II).
6-Amino-4-(4-methylphenyl)-1-[(6-chloro-4-oxo-4H-chromen-
3-ylmethylene) amino]-2-thioxo-1,2-dihydropyrimidine-
5-carbonitrile (11)
A mixture of compound 1c (2.81 g, 10 mmol) and arylidenemalononitrile
10 (1.68 g, 10 mmol) in dimethylformamide (50 ml) containing two drops
of piperidine was refluxed for 10 h. The solution was cooled and poured
onto ice water. The solid obtained was filtered off and crystallized from
the proper solvent to give 11 (Table II).
1-{[(4-Oxo-4H-chromen-3-ylmethylene)hydrazino]
carbonthioyl}thiourea (12)
A mixture of compound 1a (2.47 g, 10 mmol) and potassium thio-
cyanate (0.97 g, 10 mmol) in dimethylsulfoxide (50 ml) in the presence
of concentrated hydrochloric acid (0.5 ml) was refluxed for 4 h. The

Chromene-3-Carboxaldehyde Thiosemicarbazones
2171
solution was cooled and poured onto ice water. The solid obtained was
filtered off and crystallized from the proper solvent to give 12 (Table II).
1-[(4-Oxo-4H-chromen-3-ylmethylene)amino]-4,6-dithioxo-
3,4-dihydro-6-hydroxy-1,3,5-triazine (13)
A mixture of compound 12 (3.06 g, 10 mmol) and methyl chlorofor-
mate (0.92 g, 10 mmol) in dry pyridine (50 ml) was refluxed for 6 h.
The solution was cooled and poured onto ice HCl. The solid obtained
was filtered off and crystallized from the proper solvent to give 13
(Table II).
1-[(4-Oxo-4H-chromen-3-ylmethylene)amino]-2,4,6-trithioxo-
1,2-tetrahydro-1,3,5-triazine (14)
A mixture of compound 12 (3.06 g, 10 mmol) and carbon disulfide (1.14 g,
20 mmol) in dry pyridine (50 ml) was refluxed for 10 h. The solution was
cooled and poured onto ice HCl. The solid obtained was filtered off and
crystallized from the proper solvent to give 14 (Table II).
1-[(4-Oxo-4H-chromen-3-ylmethylene)amino]-6-phenyl-
2,4,dithioxo-3,4-tetrahydro-1,3,5-triazine (15)
A mixture of compound 12 (3.06 g, 10 mmol) and benzoyl chloride (1.40 g,
10 mmol) in dry pyridine (50 ml) was refluxed for 6 h. The solution was
cooled and poured onto ice HCl. The solid obtained was filtered off and
crystallized from the proper solvent to give 15 (Table II).
1-[(4-Oxo-4H-chromen-3-ylmethylene)amino]-4,6-dithioxo-
1,4,5,6-tetrahydro-1,3,5-triazine-2-carboxylic acid (16)
A mixture of compound 12 (3.06 g, 10 mmol) and trichloroacetic acid
(1.74 g, 10 mmol) in dry pyridine (50 ml) was refluxed for 8 h. The
solution was cooled and poured onto ice HCl. The solid obtained
was filtered off and crystallized from the proper solvent to give 16
(Table II).
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