Synthesis of some new chromene derivatives, part 6

Article abstract of DOI:10.1080/00397911003632915

Reactions of 2-amino-5-oxo-2-phenyl-5,6,7,8-tetrahydro-4H-chromen-3- carbonitrile (1a) with a variety of reagents leading to the synthesis of chromens have been investigated to explore the use of this exceptionally reactive nitrile in heterocyclic synthes

Full text of DOI:10.1080/00397911003632915

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Synthesis of Some New Chromene
Derivatives, Part 6
A. A. Fadda a & E. H. E. Youssif b
a Department of Chemistry, Faculty of Science, Mansoura University,
Mansoura, Egypt
b Department of Chemistry, Faculty of Education, Suez Canal
University, Suez, Egypt
Published online: 31 Jan 2011.
To cite this article: A. A. Fadda & E. H. E. Youssif (2011): Synthesis of Some New Chromene
Derivatives, Part 6, Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 41:5, 677-694
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Synthetic Communications1, 41: 677–694, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911003632915
SYNTHESIS OF SOME NEW CHROMENE DERIVATIVES,
PART 6
A. A. Fadda1 and E. H. E. Youssif2
1Department of Chemistry, Faculty of Science, Mansoura University,
Mansoura, Egypt
2Department of Chemistry, Faculty of Education, Suez Canal University,
Suez, Egypt
Abstract
Reactions
of
2-amino-5-oxo-2-phenyl-5,6,7,8-tetrahydro-4H-chromen-3-
carbonitrile (1a) with a variety of reagents leading to the synthesis of chromens have been
investigated to explore the use of this exceptionally reactive nitrile in heterocyclic synthesis.
Keywords Bifunctional reagents; chromen; hydrazine hydrate; triethyl orthoformate
INTRODUCTION
Previous papers have shown that pyran derivatives possess pronounced
chemical and biological properties.[1–3] Substituted pyridines show acaricidal, insecti-
cidal, and herbicidal activities.[4] Moreover, pyrimidines are important analgesic and
anti-inflamatory agents.[5,6] Compounds having a combination of cyclohexylpyran
with pyridine and=or pyrimidine moieties can be expected to possess medicinal
properties. In addition, some compounds of this class, notably 3-phenylcoumarin
containing an azole ring, have found applications as fluorescent brightening agents.[7]
In contrast to most other types of tumor inhibitory compounds, many of which
exhibit toxicity, mutagenicity, and other undesirable properties, pyranopyridine
and pyranopyrimidine compounds tend to show minimal side effects.
Received November 21, 2009.
Address correspondence to A. A. Fadda, Department of Chemistry, Faculty of Science, Mansoura
University, Mansoura 35516, Egypt. E-mail: afadda2@yahoo.com
677

678
A. A. FADDA AND E. H. E. YOUSSIF
Formation of a new fused heterocyclic ring is an important task for hetero-
cyclic chemists. o-Aminonitriles, in their versatile role as synthetic intermediates,
are ideally suited because they consist of multifunctional building units for promising
new compounds in one or two easy reaction steps. In the past few years, one of the
authors has been involved in an exploration of the potential of activated nitriles in
heterocyclic synthesis.[8–12] From these facts and as part of this program, the reac-
tivity of 2-amino-5-oxo-2-phenyl-5,6,7,8-tetrahydro-4H-chromen-3-carbonitrile (1a)
toward a variety of reagents has been investigated to explore the use of this excep-
tionally reactive nitrile in heterocyclic synthesis.
RESULTS AND DISCUSSION
Refluxing 1a with neat triethyl orthoformate for 5 h afforded the correspond-
ing N-(3-cyano-5-oxo-4-aryl-5,6,7,8-tetrahydro-4H-chromen-2-yl)-formimidic acid
ethyl esters 2a, b. The infrared (IR) spectrum of 2a displayed absorption bands at
1680 and 2210 cmꢀ1 a,b-unsaturated ketone (CN) and revealed no absorption fre-
quency in the NH region. 1H NMR spectrum showed a triplet at d 1.60 and a quartet
at d 4.35 assigned to the CH3 and CH2 protons, respectively, and two singlet signals
=
at d 3.9 and 4.2 ppm attributable to CHO and C4-H protons, respectively. The
cyclohexanone protons appeared at d 1.9–2.7 and the aromatic protons at d
7.2–7.4 as multiplets.
When compound 2a was stirred, cold, with hydrazine hydrate and=or phe-
nyl hydrazine in dioxane for 3 h, the products 2-(hydrazinomethylene-amino)
chromen-3-carbonitrile 3a, b, respectively, were isolated. Thus, CN, NH, and
NH2 bands can be detected in the IR spectrum of the compound 3a. Boiling
compounds 3a, b in ethanol led to the cyclized products 4-imino-3-amino-
3,4,6,7,8,10-hexahydro-9-oxa-1,3-diaza-anthracen-5-one (4a) and its 3-amino
phenyl derivatives 4b, respectively. Assignment of 4 to the reaction product
was based on (a) correct values in elemental analysis, (b) the IR spectrum of
4a displayed absorption bands at 3410 and 3372 cmꢀ1 (NH2) and no absorption
1
band for the cyano group was observed, and (c) the H NMR spectrum of 4a
showed peaks at d 4.93 (singlet for NH2 exchangeable protons) and d 8.45
(broad singlet NH exchangeable protons), in addition to the expected NMR
pattern for C10-H, aromatic, and cyclohexanonyl protons. Compounds 4a, b
could be obtained directly from 2a by refluxing with ethanolic hydrazine
hydrate or phenyl hydrazine, respectively (Scheme 1).
However, refluxing the ethanolic solution of 1a with hydrazine hydrate in the
presence of a catalytic amount of piperidine yielded the corresponding 3-amino-4-
phenyl-4,6,7,8-tetrahydro-1H-chromeno[2,3-c]pyrazol-5-one (5). Its IR spectrum
displayed absorption bands at NH2 and NH regions (3430–3350, 3304 cmꢀ1) and
showed no absorption at the CN region. Also, the structure of 5 was judged by
1H NMR spectrum, where broad bands at d 6.93 and 8.00 ppm were assigned to
the NH2 and NH protons, respectively.
The reaction is proposed to proceed as shown in the mechanism in Scheme 1 by
addition of the hydrazine molecule to the cyano group, followed by loss of the
ammonia molecule during refluxing for a prolonged time, with the formation of
the isolable product 5.

SYNTHESIS OF SOME NEW CHROMENE DERIVATIVES, PART 6
679
Scheme 1. Synthetic mechanism for the formation of 4-imino-3-amino-3,4,6,7,8,10-hexahydro-9-oxa-1,3-
diaza-anthracen-5-one (4a) and its 3-aminophenyl derivative 4b.
Similarly, heating an equimolar mixture of 1a and o-phenylenediamine,
o-aminophenol, and=or o-aminothiophenol in absolute ethanol in the presence of
a catalytic amount of piperidine for a long time afforded the corresponding
2-amino-3-(benzoimidazol-2-yl)-4-phenyl-4,6,7,8-tetrahydrochromen-5-one (6) and
its 3-(benzoxazol-2-yl) and 3-(benzothiazol-2-yl) derivatives 7 and 8, respectively.
Structures 6, 7, and 8 were established by the correct analyses and compatible
spectroscopic data. In general, the IR spectra showed an absorption band at
3430–3350 cmꢀ1 resulting from the stretching frequency of the NH2 group and the
1
disappearance of the CN group, while in the H NMR spectra the NH2 protons
appeared at d 6.8 ppm as singlet signal.
Many condensed heterocyclic systems, especially when linked to a pyrimidine
ring, play an important role as analgesic, antihypertensive, antipyretic, and
anti-inflammatory drugs and pesticides, herbicides, and plant-growth regula-
tors.[13,14] Furthermore, the chromeno[2,3-d]pyrimidine and pyranopyrimidine[15,3]
ring systems have gained biological interest because of the formal isoelectronic
relation between this ring and purine.[16] These observations encouraged us to
synthesize some of these new products with expected biological activity.
The reactions of o-aminonitriles with urea and thiourea were reported to afford
condensed 4-amino-pyrimidin-2-one and 4-amino-pyrimidin-2-thione derivatives,
respectively.[17,18] Therefore, refluxing compound 1a with thiourea in absolute
ethanol in the presence of sodium ethoxide for 6 h afforded 4-amino-10-phenyl-
2-thioxo-1,2,6,7,8,10-hexahydro-9-oxa-1,3-diaza-anthracen-5-one (9). Its IR spec-
trum revealed absorption peaks at 3450–3350, 3310, and 1310 cmꢀ1 corresponding
=
to the NH2, NH, and C S functions, respectively. The structure of product 9 was
further assigned by both elemental analysis and spectroscopic measurements. The
1H NMR revealed peaks at d 1.9–2.7 cyclic CH2 protons, singlet signal at d 4.1
due to C10-H, two singlets at d 6.8 and 8.2 ppm corresponding to the NH2 and
NH (exchangeable), and a multiplet at d 7.1–7.7 ppm for aromatic protons.

680
A. A. FADDA AND E. H. E. YOUSSIF
Scheme 2. Reaction of enaminonitrile 1a with carbon disulfide: formation of pyrimidinedithione derivative 11.
A fused thiazinedithione derivative 11 was synthesized by reaction of o-amino-
nitrile 1a with carbon disulfide. Subsequent rearrangement by the action of alkali led
to the formation of fused pyrimidine dithione 11. Thus, 1a and carbon disulfide
(refluxed in pyridine) initially gave chromeno[2,3-b]thiazin-9-thione (10), most likely
via the intermediate A (Scheme 2).
Compound 11 gave correct values in elemental analyses and displayed no
absorption at the CN region in its IR spectrum. Also, the 1H NMR spectrum showed
C10-H at d 4.2 ppm, singlet broad NH exchangeable at 6.58, and singlet broad for
NH (exchangeable) protons at d 9.08 (Scheme 2).
In addition, when the o-aminonitrile 1a was stirred in refluxing ethanol with
cyanamide in the presence of a catalytic amount of piperidine, the product
2,4-diamino-10-phenyl-6,7,8,10-tetrahydro-9-oxa-1,3-diaza-anthracen-5-one
(12)
was isolated. Thus, NH and NH2 signals can be detected in the IR spectrum, in
the regions 3430–3350 cmꢀ1 and 3310 cmꢀ1, respectively and no absorption for the
1
cyano group was observed. The H NMR spectrum of 12 showed broad peaks at
d 4.93 and 6.95 for two amino group protons.
o-Aminonitrile 1a was expected to react with aromatic aldehyde to afford the
chalcone 13; however, all the data suggested the N-condensation product 5-oxo-
4-phenyl-2-[(1-phenyl-meth-(E)-ylidene)-amino]-5,6,7,8-tetrahydro-4H-chromen-3-
carbonitrile (14), which undergoes cyclization with thioglycolic acid to afford the
N-substituted 5-oxo-2-(4-oxo-2-phenyl-thiazolidin-3-yl)-4-phenyl-5,6,7,8-tetrahydro-
4H-chromen-3-carbonitrile (15) (Scheme 3). All structures were confirmed by ana-
lytical and spectral data.
The IR spectrum of 14 displayed absorption bands at 2220 and 1620 cmꢀ1 cor-
=
responding to the CN and C N functions and showed no absorption at the NH2
region. A combination of the 1H NMR and correct values of elemental analysis con-
firmed the cyclized structure of 15. The 1H NMR spectrum revealed three singlet sig-
nals at d 2.8, 3.9, and 4.2 attributable to S-CH2, S-CH, and C4-H protons,
respectively, while its IR spectrum showed bands at 1680 cmꢀ1 due to the amidic
carbonyl group (Scheme 3).
Condensed 2,4-diamino-3-cyano-10-phenyl-6,7,8,10-tetrahydro-9-oxa-1-aza-
anthracen-5-one (16) is readily prepared by the reaction of o-aminonitrile 1a with

SYNTHESIS OF SOME NEW CHROMENE DERIVATIVES, PART 6
681
Scheme 3. Formation of Schiff base 14 followed by reaction with thioglycolic acid.
malononitrile in dimethylformemide (DMF) with a catalytic amount of triethyl-
amine (TEA). The IR spectrum of compound 16 showed absorption bands at
1
3450–3350 and 2220 cmꢀ1 due to NH2 and nitrile function, while its H NMR spec-
trum revealed peaks at d 4.9 and 8.1 as singlet signals corresponding to two amino
groups’ protons.
On the other hand, 4-amino-3-cyanopyridine-2-one derivative 17 is obtained
by the reaction of 1a with ethyl cyanoacetate in DMF solution containing a catalytic
amount of TEA.
The IR spectrum showed absorption bands at 3450–3350, 3310, 2219, 1676,
and 1170 cmꢀ1 corresponding the stretching frequencies of NH2, NH, CN, amidic
CO, and C-O-C functions, respectively, and showed no absorption around the
1730 cmꢀ1 region due to the carbonyl ester function. Also, the structure of 17 was
1
judged by H NMR spectrum, where broad bands at d 6.80 and 8.00 ppm were
assigned to the NH2 and NH protons, respectively.
Compound 1a reacted also with phenacyl cyanide to afford 4-amino-3-cyano-
2,10-diphenyl-6,7,8,10-tetrahydro-9-oxa-1-aza-anthracen-5-one (18) on refluxing in
DMF containing a catalytic amount of piperidine for 6 h. Compound 18 could be
obtained also by reaction of 1a with benzylidene malononitrile in a mixture of
DMF=ethanol (1:1) in the presence of a catalytic amount of piperidine on refluxing
for 6 h. The reaction is thought to proceed via the sequence shown in the following
synthetic route (Scheme 4).
The IR spectrum of 18 displayed absorption band at 3430–3380 cmꢀ1 (NH2)
1
and 2220 cmꢀ1 (CN). A combination of H NMR and correct values of elemental
1
analyses confirmed the cyclized structure 18. H NMR spectrum showed broad
bands at d 6.7 ppm, characteristic of NH2 protons (Scheme 4).
In addition, refluxing ethanolic solution of o-aminonitrile 1a with the phenacyl
bromide in the presence of anhydrous potassium carbonate afforded the N-phenacyl
derivative 19, which could not be cyclized further.
The IR spectrum of compound 19 showed absorption bands at 3190, 2220, and
1
1695 cmꢀ1 characteristic of NH, CN, and CO functions. Moreover, the H NMR
revealed two singlet signals at d 4.1 and 4.3 ppm due to C4-H and CH2 protons, respect-
ively, while an NH exchangeable proton appeared as a broad band at d 6.9 ppm.
Several reactions for both aromatic and heterocyclic o-aminonitriles with for-
mic acid and with the usual acylating agents have been reported.[19] The o-formyl
or the o-acylaminonitriles so formed are of considerable interest because of their

682
A. A. FADDA AND E. H. E. YOUSSIF
Scheme 4. Synthesis of 4-amino-3-cyano-2,10-diphenyl-6,7,8,10-tetrahydro-9-oxa-1-aza-anthracen-5-one
(18) by reaction of 1a with activated nitriles.
conversion by an acid or base to the corresponding pyrimidines. Thus, it has been
found that compound 1a reacts with formic acid in absolute ethanol to afford
N-(3-cyano-5-oxo-4-phenyl-5,6,7,8-tetrahydro-4H-chromen-2-yl)-formamide (20),
which cyclized to the corresponding pyrimidine-4-one 21 on treatment with alkaline
hydrogen peroxide. The reaction proceeds by initial hydration of the nitrile group to
the carboxamide, which then undergoes cyclization in an alkaline medium (Scheme 5).
The structure of both compounds 20 and 21 were confirmed by both elemental
and spectral analyses. Thus, the IR spectrum of 20 showed bands at 3310, 2220, and
1
1680 cmꢀ1 corresponding to the NH, CN, and aldehydic carbonyl functions. H
NMR spectrum revealed new bands at d 8.1 and 10.2 ppm due to the NH and alde-
hydic protons. In addition, the 1H NMR spectrum of compound 21 showed the dis-
appearance of a proton at d 10.2 and showed new signal at d 4.8 ppm due to C2-H.
=
Moreover, its IR spectrum showed a new peak at 1620 attributable to the C N func-
tion and the disappearance of a band at 2200 cmꢀ1 for the CN group (Scheme 5).
Similarly, acylation of the readily available o-aminonitrile 1a with the acid
anhydride or acid chloride gave the acylaminochromene 22.
Scheme 5. Formation of pyrimidine-4-one derivative 21 via the reaction of 1a with formic acid followed by
oxidation.

SYNTHESIS OF SOME NEW CHROMENE DERIVATIVES, PART 6
683
Scheme 6. Reaction of enaminonitrile 1a with phenylisothiocyanate.
The IR spectrum of compound 22 revealed absorption bands at 3310, 2220,
1676, and 1170 cmꢀ1 corresponding to the NH, CN, CO, and C-O-C functions.
1H NMR spectrum showed a new broad band at d 6.8 due to the NH and a singlet
signal for CH3 protons at d 2.8.
Refluxing compound 1a with chloroacetyl chloride in pyridine for 3 h afforded
N-(3-cyano-5-oxo-4-phenyl-5,6,7,8-tetrahydro-4H-chromen-2-yl)-chloroacetamide
(23). The structure of 23 was confirmed by both elemental and spectral analyses.
1
Both the IR and H NMR spectra gave data similar to compound 23.
Isocyanates and isothiocyanates were reported to react with o-aminonitrile to
give initially the corresponding substituted ureido or thioureido derivatives, which
readily cyclized to the corresponding fused heterocyclic system when heated alone
or in boiling ethanolic sodium ethoxide. Therefore, refluxing 1a with phenylisothio-
cyanate in DMF containing a catalytic amount of TEA afforded thiourea derivative
24, which cyclized on prolonged heating to the corresponding 4-amino-
thiopyrimidine derivative 25 (Scheme 6). The IR spectrum of 24 showed absorption
bands at 3350, 3310, 2220, and 1310 cmꢀ1 corresponding to two NH groups, CN,
=
and C S functions. Compound 25 gave an IR spectrum similar to that of 24, except
1
for the appearance of NH2 peaks at 3450–3350 cmꢀ1. The H NMR spectra of both
24 and 25 together with their mass spectra gives more conformational data for the
proposed structures (Scheme 6). Results are shown in Table 1.
EXPERIMENTAL
All melting points are recorded on a Gallenkamp electric melting-point appar-
atus. The IR spectra (t cmꢀ1, KBr) were measured on a Perkin-Elmer infrared spec-
trophotometer, model 157, grating. The H NMR spectra were run on a Varian
1
spectrophotometer at 200 MHz using tetramethylsilane (TMS) as an internal refer-
ence and dimethylsulfoxide (DMSO-d6) as solvent. The mass spectra (EI) were
run at 70 eV with Kratos MS equipment and=or a Varian MAT 311 A spectrometer.
Elemental analyses (C, H, and N) were carried out at the Microanalytical Center of

684
A. A. FADDA AND E. H. E. YOUSSIF
Table 1. Results of the synthesized compounds
Yield
(%)
Entry
Substrate
Reagent
Product
CH(OC2H5)3
(CH3CO)2O
2a, 80
2b, 90
1
NH2NHX=Dioxane,
0 ꢁC or EtOH, Reflux
4a, 40
4b, 50
2
NH2NH2.H2O
EtOH, pip.
3
63
6, 44
7, 46
8, 80
4
1a
5
1a
CS2 =pyridine
11, 58
(Continued )

SYNTHESIS OF SOME NEW CHROMENE DERIVATIVES, PART 6
685
Table 1. Continued
Yield
(%)
Entry
Substrate
Reagent
Product
6
1a
40
7
8
1a
1a
NH2CN
48
76
Ac2O, PhCHO
14
15
9
14
1a
43
48
10
CH2(CN)2= DMF= TEA
11
12
13
1a
1a
1a
CNCH2COOEt
55
67
42
=
PhCH C(CN)2
PhCOCH2Br
14
15
1a
20
HCOOH, EtOH
H2O2, K2CO3
20
21
56
40
(Continued )

686
A. A. FADDA AND E. H. E. YOUSSIF
Table 1. Continued
Yield
(%)
Entry
Substrate
Reagent
Product
16
1a
Ac2O or CH3COCl
70
17
1a
ClCH2COCl
74
18
19
1a
1a
PhNCS, DMF
PhNCS, DMF=TEA
24
25
58
46
Cairo University, Giza, Egypt. The results were found to be in good agreement
(ꢂ0.3%) with the calculated values. Compounds 1a, b were prepared according to
the previously reported work.[20]
N-(3-Cyano-5-oxo-4-aryl-5,6,7,8-tetrahydro-4H-
chromen-2-yl)-formimidic Acid Ethyl Ester 2a, b
A mixture of triethylorthoformate and acetic anhydride (30 cm3, 2:1) was
added to 1a (0.005 mol). The reaction mixture was heated for 5 h under reflux
condition, then left to cool and kept at ꢀ5 ꢁC overnight for complete precipitation.
The separated solid product was filtered off and recrystallized from ethanol to give
colorless needles 2a, b.
Compound 2a. Mp 170 ꢁC; 80%; IR (KBr) nmax cmꢀ1: 2210 (CN), 1680 (a,b-
1
=
=
unsaturated ketone), 1640 (C N), 1600 (C C), 1170 (C-O-C); H NMR (CDCl3-d6)
d ppm 1.6 (t, 3H, CH3), 1.9–2.7 (m, 6H, 3-CH2), 3.9 (s, 1H, CHO), 4.2 (s, 1H, C4-H),
4.35 (q, 2H, CH2), 7.2–7.4 (m, 5H, Ar-H); MS: m=z (%) 322 (Mþ, 100%). Calcd. for
C19H18N2O3 (322): C, 70.80; H, 5.60. Found: C, 70.72; H, 5.41.
Compound 2b. Yield 90%; mp 148 ꢁC; IR (KBr) nmax cmꢀ1: 2200 (CN), 1680
(a,b-unsaturated ketone), 1640 (C N), 1600 (C C), 1175 (C-O-C); 1H NMR
(CDCl3-d6) d ppm 1.6 (t, 3H, CH3), 1.9–2.7 (m, 6H, 3-CH2), 3.9 (s, 1H, CHO), 4.2
(s, 1H, C4-H), 4.35 (q, 2H, CH2), 7.2–7.4 (m, 4H, Ar-H); MS: m=z (%) 340 (Mþ,
100%). Calcd. for C19H17N2O3F (340): C, 67.06; H, 5.00. Found: C, 67.15; H, 5.10.
=
=
2-(Hydrazinomethyleneamino)-5-oxo-4-phenyl-5,6,7,8-
tetrahydro-4H-chromen-3-carbonitrile (3a, b)
A solution of (2a, 0.005 mol) in dioxane (20 cm3) was treated with hydrazine
hydrate and=or phenylhydrazine (0.005 mol). The reaction mixture was stirred at

SYNTHESIS OF SOME NEW CHROMENE DERIVATIVES, PART 6
687
0 ꢁC for 3 h; the separated material was collected by filtration, dried well, and recrys-
tallized from ethanol to give the corresponding compounds 3a, b.
Compound 3a. Yield 65%; mp 235 ꢁC; IR (KBr) nmax cmꢀ1: 3410–3372
=
(NH2), 3300 (NH), 2220 (CN), 1685 (a,b-unsaturated ketone), 1640 (C N), 1610
1
=
(C C), 1175 (C-O-C); H NMR (CDCl3-d6) d ppm 1.9–2.7 (m, 6H, 3-CH2), 4.2
(s, 1H, C4-H), 4.93 (s, 2H, exchangeable NH2), 7.1–7.5 (m, 5H, Ar-H), 8.45 (bs,
1H, exchangeable NH); MS: m=z (%) 308 (Mþ, 40%). Calcd. for C17H16N4O2
(308): C, 66.23; H, 5.19. Found: C, 66.12; H, 5.05.
Compound 3b. Yield 55%; mp 216 ꢁC; IR (KBr) nmax cmꢀ1: 3410–3370
=
(NH2), 3300 (NH), 2200 (CN), 1685 (a,b-unsaturated ketone), 1630 (C N), 1600
1
=
(C C), 1175 (C-O-C); H NMR (CDCl3-d6) d ppm 1.9–2.7 (m, 6H, 3-CH2), 4.2
(s, 1H, C4-H), 6.8 (bs, 1H, exchangeable NH), 7.1–7.6 (m, 10H, Ar-H), 8.4 (bs,
1H, exchangeable NH). Calcd. for C23H20N4O2 (384): C, 71.88; H, 5.21. Found:
C, 71.68; H, 5.16.
4-Imino-3-amino-3,4,6,7,8,10-hexahydro-9-oxa-
1,3-diaza-anthracen-5-one (4b)
Pathway A. A mixture of 2a (0.005 mol) and hydrazine hydrate and=or phe-
nylhydrazine (0.005 mol) in absolute ethanol (30 cm3) was refluxed for 6 h and left to
cool at room temperature overnight. The precipitated solid was filtered off and
recrystallized from dry benzene to yield compounds 4a, b, respectively.
Pathway B. A solution of 3a, b (0.005 mol) in absolute ethanol (30 cm3) was
refluxed for 3 h. The reaction mixture was concentrated to half its volume and then
left to cool at room temperature overnight. The separated material was filtered off
and recrystallized from dry benzene to yield compounds 4a, b, respectively.
Compound 4a. Yield 40%; mp 105 ꢁC; IR (KBr) nmax cmꢀ1: 3410–3372
=
=
(NH2), 3310 (NH), 1680 (a,b-unsaturated ketone), 1640 (C N), 1600 (C C),
1
1170 (C-O-C); H NMR (CDCl3-d6) d ppm 1.9–2.7 (m, 6H, 3-CH2), 4.2 (s, 1H,
C10-H), 4.93 (s, 2H, exchangeable NH2), 7.1–7.5 (m, 5H, Ar-H), 8.45 (bs, 1H,
exchangeable NH). Calcd. for C17H16N4O2 (308): C, 66.23; H, 5.19. Found: C,
66.16; H, 5.07.
Compound 4b. Yield 50%; mp 138 ꢁC; IR (KBr) nmax cmꢀ1: 3400–3350
=
=
(NH2), 3300 (NH), 1680 (a,b-unsaturated ketone), 1635 (C N), 1600 (C C), 1175
1
(C-O-C); H NMR (CDCl3-d6) d ppm 1.9–2.7 (m, 6H, 3-CH2), 4.2 (s, 1H, C10-H),
6.8 (s, 1H, exchangeable NH2), 7.1–7.6 (m, 10H, Ar-H), 8.08 (bs, 1H, exchangeable
NH); MS: m=z (%) 384 (Mþ, 10%). Calcd. for C23H20N4O2 (384): C, 71.88; H, 5.21.
Found: C, 71.68; H, 5.12.
3-Amino-4-phenyl-4,6,7,8-tetrahydro-1H-chromeno
[2,3-c]pyrazol-5-one (5)
Equimolar amounts of 1a (0.005 mol) and hydrazine hydrate (0.005 mol) in
absolute ethanol (30 cm3) in the presence of a catalytic amount of piperidine (four

688
A. A. FADDA AND E. H. E. YOUSSIF
drops) were refluxed for 12 h. The reaction mixture was left to cool at room tempera-
ture and then poured into cold water for complete precipitation. The solid products
were filtered off and recrystallized from aqueous ethanol to give the corresponding
compound 5. Yield 63%; mp 186 ꢁC; IR (KBr) nmax cmꢀ1: 3430–3350 (NH2), 3304
=
=
(NH), 1685 (a,b-unsaturated ketone), 1635 (C N), 1600 (C C), and 175 (C-O-C);
1H NMR (DMSO-d6) d ppm 1.9–2.7 (m, 6H, 3-CH2), 4.2 (s, 1H, C4-H), 6.93 (bs,
2H, exchangeable NH2), 7.1–7.6 (m, 5H, Ar-H), 8.0 (bs, 1H, exchangeable NH).
Calcd. for C16H15N3O2 (281): C, 68.33; H, 5.34. Found: C, 68.20; H, 5.16.
2-Amino-3-(benzoimidazol-2-yl)-4-phenyl-4,6,7,8-
tetrahydrochromen-5-one (6) and Its 3-(Benzoxazol-2-yl) and
3-(Benzothiazol-2-yl) Derivatives (7 and 8)
Equimolar amounts of 1a (0.005 mol), o-phenylenediamine, o-aminophenol,
and=or o-aminothiophenol in absolute ethanol (30 cm3) in the presence of a catalytic
amount of piperidine (four drops) were refluxed for 30 h. The reaction mixture was
concentrated to half its volume and then left to cool at room temperature overnight.
The solid products were filtered off and recrystallized from a mixture of acetic acid–
ethanol (1:2) to give the corresponding compounds 6, 7, and 8, respectively.
Compound 6. Yield 44%; mp 232 ꢁC; IR (KBr) nmax cmꢀ1: 3430–3350 (NH2),
=
=
3310 (NH), 1685 (a,b-unsaturated ketone), 1645 (C N), 1610 (C C), 1180 (C-O-C);
1H NMR (CDCl3-d6) d ppm 1.7–2.6 (m, 6H, 3-CH2), 4.5 (s, 1H, C4-H), 6.8 (s, 2H,
exchangeable NH2), 7.1–7.6 (m, 9H, Ar-H), 7.9 (bs, 1H, exchangeable NH); MS: m=z
(%) 357 (Mþ, 10%). Calcd. for C22H19N3O2 (357): C, 73.95; H, 5.32. Found: C,
73.77; H, 5.14.
Compound 7. Yield 46%; mp 110 ꢁC; IR (KBr) nmax cmꢀ1: 3430–3350 (NH2),
1
=
=
1680 (a,b-unsaturated ketone), 1640 (C N), 1600 (C C), 1175 (C-O-C); H NMR
(CDCl3-d6) d ppm 1.7–2.6 (m, 6H, 3-CH2), 4.5 (s, 1H, C4-H), 6.8 (s, 2H, exchange-
able NH2), 7.1–7.6 (m, 5H, Ar-H); MS: m=z (%) 258 (Mþ, 10%). Calcd. for
C22H18N2O3 (358): C, 73.74; H, 5.03. Found: C, 73.53; H, 5.22.
Compound 8. Yield 80%; mp 225 ꢁC; IR (KBr) nmax cmꢀ1: 3340–3300 (NH2),
1
=
1685 (a,b-unsaturated ketone), 1630 (C N), 1180 (C-O-C); H NMR (CDCl3-d6) d
ppm 1.7–2.7 (m, 6H, 3-CH2), 4.5 (s, 1H, C4-H), 7.0–7.7 (m, 9H, Ar-H), 7.9 (s, 2H,
NH2); MS: m=z (%) 374 (Mþ, 22%). Calcd. for C22H18N2O2S (374): C, 70.59; H,
5.81. Found: C, 70.51; H, 4.72.
4-Amino-10-phenyl-2-thioxo-1,2,6,7,8,10-hexahydro-9-
oxa-1,3-diaza-anthracen-5-one (9)
A mixture of 1a (0.005 mol) and thiourea (0.005 mol) in absolute ethanol (20 ml)
and sodium ethoxide [0.023 g sodium metal in (20 cm3) absolute ethanol, 0.005 mol]
was refluxed for 6 h. The reaction mixture was left to cool at room temperature, then
poured into ice-cold water (50 cm3) and neutralized with diluted hydrochloric acid.
The separated material was filtered off and recrystallized from ethanol to yield com-
pound 9. Yield 40%; mp 125 ꢁC; IR (KBr) nmax cmꢀ1: 3450–3350 (NH2), 3310 (NH),

SYNTHESIS OF SOME NEW CHROMENE DERIVATIVES, PART 6
689
=
=
=
1685 (a,b-unsaturated ketone), 1640 (C N), 1610 (C C), 1310 (C S), 1180 (C-O-C);
1H NMR (CDCl3-d6) d ppm 1.9–2.7 (m, 6H, 3-CH2), 4.1 (s, 1H, C10-H), 6.8 (bs, 2H,
exchangeable NH2), 7.1–7.7 (m, 5H, Ar-H), 8.2 (bs, 1H, exchangeable NH); MS: m=z
(%) 325 (Mþ, 10%). Calcd. for C17H15N3O2S (325): C, 62.77; H, 4.62. Found: C,
62.52; H, 4.35.
10-Phenyl-2,4-dithioxo-1,2,6,7,8,10-hexahydro-9-oxa-
1,3-diaza-anthracen-5-one (11)
Carbon disulfide (0.005 mol) was added to a solution of 1a (0.005 mol) in dry
pyridine (30 cm3). The reaction mixture was refluxed on a water bath for 6 h, then
left to cool at room temperature, poured into cold water, and neutralized with
diluted hydrochloric acid for complete precipitation. The obtainable solid was
filtered off, washed with water, dried well, and recrystallized from methanol to
yield compound 11. Yield 58%; mp 165 ꢁC; IR (KBr) nmax cmꢀ1: 3300 (NH), 1680
(a,b-unsaturated ketone), 1610 (C C), 1320 (C S), 1175 (C-O-C); 1H NMR
(CDCl3-d6) d ppm; 1.9–2.7 (m, 6H, 3-CH2), 4.2 (s, 1H, C10-H), 6.58 (bs, 1H,
exchangeable NH2), 7.1–7.7 (m, 5H, Ar-H), 9.08 (bs, 1H, exchangeable NH); MS:
m=z (%) 342 (Mþ, 10%). Calcd. for C19H17N2O3F (340): C, 59.65; H, 4.09. Found:
C, 59.37; H, 4.00.
=
=
2,4-Diamino-10-phenyl-6,7,8,10-tetrahydro-9-oxa-
1,3-diaza-anthracen-5-one (12)
Equimolar amounts of 1a (0.005 mol) and cyanamide (0.005 mol) in absolute
ethanol (30 cm3) in the presence of a catalytic amount of piperidine (four drops) were
refluxed with stirring for 12 h and left to cool at room temperature. The reaction
mixture was poured into cold water (50 cm3) for complete precipitation. The obtain-
able solid was filtered off, washed with water, dried well, and recrystallized from
aqueous ethanol to yield compound 12. Yield 48%; mp 135 ꢁC; IR (KBr) nmax
cmꢀ1: 3440–3350 (NH2), 1685 (a,b-unsaturated ketone), 1640 (C N), 1600 (C C),
=
=
1
=
1310 (C S), 1175 (C-O-C); H NMR (CDCl3-d6) d ppm 1.9–2.7 (m, 6H, 3-CH2),
4.2 (s, 1H, C10-H), 4.93, 6.95 (bs, 2H, NH2), 7.2–7.7 (m, 5H, Ar-H); MS: m=z (%)
307 (Mþ, 10%). Calcd. for C17H16N4O2 (308): C, 66.23; H, 5.19. Found: C, 66.12;
H, 5.28.
5-Oxo-4-phenyl-2-[(1-phenyl-meth-(E)-ylidene)-
amino]-5,6,7,8-tetrahydro-4H-chromen-3-carbonitrile (14)
A mixture of 1a (0.005 mol) and benzaldehyde (0.005 mol) in glacial acetic acid
(30 cm3) was heated under reflux for 1 h, cooled, and poured into crushed ice. The
produced solid was filtered off, washed with water, dried well, and recrystallized
from methanol to yield the corresponding compound 14. Yield 76%; mp 135 ꢁC;
IR (KBr) nmax cmꢀ1: 2220 (CN), 1685 (a,b-unsaturated ketone), 1620 (C N),
=
1
=
1600 (C C), 1175 (C-O-C); H NMR (CDCl3-d6) d ppm 1.7–2.9 (m, 5H, 3-CH2),
4.2 (s, 1H, C4-H), 4.8 (s, 1H, CH), 7.2–7.8 (m, 10H, Ar-H). Calcd. for
C23H18N2O2 (354): C, 77.97; H, 5.08. Found: C, 77.64; H, 5.00.

690
A. A. FADDA AND E. H. E. YOUSSIF
5-Oxo-2-(4-oxo-2-phenyl-thiazolidin-3-yl)-4-phenyl-
5,6,7,8-tetrahydro-4H-chromen-3-carbonitrile (15)
A mixture of 14 (0.005 mol) and thioglycolic acid (0.005 mol) in dry dioxane
(30 cm3) was heated under reflux for 12 h, cooled, and neutralized with aqueous
sodium carbonate. The separated solid was filtered off, dried well, and recrystallized
from ethanol to give compound 15. Yield 43%; mp 268 ꢁC; IR (KBr) nmax cmꢀ1: 2220
=
(CN), 1690 (a,b-unsaturated ketone), 1680 (amidic carbonyl), 1600 (C C), 1175
(C-O-C); 1H NMR (CDCl3-d6) d ppm; 1.7–2.6 (m, 6H, 3-CH2), 2.8 (s, 2H,
S-CH2), 3.9 (s, 1H, S-CH), 4.2 (s, 1H, C4-H), 7.2–7.8 (m, 10H, Ar-H). Calcd. for
C25H20N2O3S (428): C, 70.10; H, 4.67. Found: C, 69.92; H, 4.53.
2,4-Diamino-3-cyano-10-phenyl-6,7,8,10-tetrahydro-9-oxa-
1-aza-anthracen-5-one (16) and 4-Amino-3-cyano-1H-
10-phenyl-6,7,8,10-tetrahydro-9-oxa-1-aza-anthracen-2,5-dione (17)
General procedure. Malononitrile (0.005 mol) and=or ethyl cyanoacetate
(0.005 mol) were added to a solution of 1a (0.005 mol) in DMF (30 cm3) followed
by a few drops of TEA (four drops). The reaction mixture was refluxed for 6 h, left
to cool at room temperature overnight, and then poured into cold water (50 cm3).
The obtainable solid was filtered off, washed with water, dried well, and recrystal-
lized from ethanol to give compounds 16 and 17, respectively.
Compound 16. Yield 48%; mp 150 ꢁC; IR (KBr) nmax cmꢀ1: 3450–3350
=
=
(NH2), 2220 (CN), 1685 (a,b-unsaturated ketone), 1640 (C N), 1610 (C C), 1175
1
(C-O-C); H NMR (CDCl3-d6) d ppm; 1.7–2.9 (m, 6H, 3-CH2), 4.5 (s, 1H, C10-
H), 4.9 (bs, 2H, exchangeable NH2), 7.1–7.7 (m, 5H, Ar-H), 8.1 (bs, 2H, exchange-
able NH2); MS: m=z (%) 332 (Mþ, 10%). Calcd. for C19H16N4O2 (332): C, 68.67; H,
4.82. Found: C, 68.55; H, 4.64.
Compound 17. Yield 55%; mp 195 ꢁC; IR (KBr) nmax cmꢀ1: 3450–3350
(NH2), 3310 (NH), 2219 (CN), 1690 (a,b-unsaturated ketone), 1676 (amidic car-
1
=
bonyl), 1610 (C C), 1175 (C-O-C); H NMR (CDCl3-d6) d ppm 1.7–2.8 (m, 6H,
3-CH2), 4.5 (s, 1H, C10-H), 6.8 (bs, 2H, exchangeable NH2), 7.1–7.7 (m, 5H,
Ar-H), 8.0 (bs, 1H, exchangeable NH). Calcd. for C19H15N3O3 (333): C, 68.47; H,
4.50. Found: C, 68.33; H, 4.28.
4-Amino-3-cyano-2,10-diphenyl-6,7,8,10-tetrahydro-9-oxa-
1-aza-anthracen-5-one (18)
Method A. Phenacylcyanide (0.005 mol) was added to a solution of 1a
(0.005 mol) in DMF (30 cm3) followed by a few drops of piperidine. The reaction
mixture was refluxed for 6 h, cooled, and poured into ice-cold water for complete
precipitation. The precipitated solid was collected by filtration and recrystallized
from aqueous methanol to yield compound 18. Yield 67%; mp 135 ꢁC; IR (KBr)
nmax cmꢀ1: 3430–3380 (NH2), 2220 (CN), 1685 (a,b-unsaturated ketone), 1640
1
=
=
(C N), 1620 (C C), 1175 (C-O-C); H NMR (CDCl3-d6) d ppm 1.7–2.7 (m, 6H,
3-CH2), 4.2 (s, 1H, C10-H), 6.7 (bs, 2H, exchangeable NH2), 7.1–7.8 (m, 10H,

SYNTHESIS OF SOME NEW CHROMENE DERIVATIVES, PART 6
691
Ar-H); MS: m=z (%) 393 (Mþ, 15%); calcd. for C25H19N3O2 (393): C, 76.34; H, 4.83.
Found: C, 76.11; H, 4.72.
Method B. Equimolar amounts of 1a (0.005 mol) and benzylidine malononi-
trile (20a, 0.005 mol) were refluxed for 6 h in a mixture of DMF and ethanol (1:1) in
the presence of a few drops of piperidine (four drops). The reaction mixture was left
to cool, poured into ice-cold water for complete precipitation, then filtered off and
recrystallized from aqueous methanol to yield compound 18.
2-(Phenacylamino)-5-oxo-4-phenyl-5,6,7,8-tetrahydro-4H-
chromen-3-carbonitrile (19)
A mixture of 1a (0.005 mol) and phenacyl bromide (0.005 mol) in absolute
ethanol (30 cm3) in the presence of anhydrous potassium carbonate (0.005 mol) as
a catalyst was refluxed for 3 h. The reaction mixture was left to cool at room tem-
perature overnight. The separated material was filtered off and recrystallized from
ethanol to yield compound 19. Yield 42%; mp 180 ꢁC; IR (KBr) nmax cmꢀ1: 3190
1
(NH), 2220 (CN), 1695 (carbonyl), 1620 (C C), 1180 (C-O-C); H NMR (CDCl3-
=
d6) d ppm 1.7–2.8 (m, 6H, 3-CH2), 4.1 (s, 1H, C4-H), 4.3 (s, 2H, CH2), 6.9 (bs,
1H, exchangeable NH), 7.1–7.8 (m, 10H, Ar-H); MS: m=z (%) 384 (Mþ, 10%). Calcd.
for C24H20N2O3 (384): C, 75.00; H, 5.21. Found: C, 75.00; H, 5.12.
N-(3-Cyano-5-oxo-4-phenyl-5,6,7,8-tetrahydro-4H-
chromen-2-yl)-formamide (20)
Equimolar amounts of 1a (0.005 mol) and formic acid (0.005 mol) in absolute
ethanol (30 cm3) were refluxed for 2 h. The reaction mixture was concentrated and
left to cool at room temperature overnight for complete precipitation. The separated
solid was collected by filtration and recrystallized from aqueous ethanol to yield
compound 20. Yield 56%; mp 230 ꢁC; IR (KBr) nmax cmꢀ1: 3310 (NH), 2220
=
(CN), 1695 (a,b-unsaturated ketone), 1680 (aldehydic carbonyl), 1610 (C C), 1175
1
(C-O-C); H NMR (CDCl3-d6) d ppm 1.7–2.9 (m, 6H, 3-CH2), 4.2 (s, 1H, C4-H),
7.1–7.6 (m, 5H, Ar-H), 8.1 (bs, 1H, exchangeable NH), 10.2 (s, 1H, CHO); MS:
m=z (%) 294 (Mþ, 25%). Calcd. for C17H14N2O3 (294): C, 69.39; H, 4.76. Found:
C, 69.13; H, 4.52.
10-Phenyl-6,7,8,10-tetrahydro-4,5-dioxo-9-oxa-1,3-diaza-
anthracene (21)
A solution of 20 (0.002 mol) in potassium carbonate (10%, 10 cm3) and hydro-
gen peroxide (5 cm3) was refluxed for 1 h. The reaction mixture was left to cool at
room temperature for complete precipitation. The separated solid was collected by
filtration and recrystallized from ethanol to yield compound 21. Yield 40%; mp
205 ꢁC; IR (KBr) nmax cmꢀ1: 3310 (NH), 1685 (a,b-unsaturated ketone), 1620
(C N), 1600 (C C), 1170 (C-O-C); 1H NMR (CDCl3-d6) d ppm 1.7–2.9 (m,
=
=
6H, 3-CH2), 4.3 (s, 1H, C10-H), 4.8 (s, 1H, C2-H), 7.1–7.6 (m, 5H, Ar-H), 8.1

692
A. A. FADDA AND E. H. E. YOUSSIF
(bs, 1H, exchangeable NH). Calcd. for C17H14N2O3 (294): C, 69.39; H, 4.76. Found:
C, 69.13; H, 4.52.
2-(Acetylamino)-5-oxo-4-phenyl-5,6,7,8-tetrahydro-4H-
chromen-3-carbonitrile (22)
Method A. A solution of 1a (0.005 mol) in acetic anhydride (20 cm3) was
refluxed for 2 h, left to cool at room temperature, and poured into ice-cold water
for complete precipitation. The precipitated solid was filtered off, washed with water,
dried well, and recrystallized from acetic acid to yield compound 22. Yield 70%; mp
130 ꢁC; IR (KBr) nmax cmꢀ1: 3410–3372 (NH2), 2220 (CN), 1690 (a,b-unsaturated
1
ketone), 1676 (amidic carbonyl), 1610 (C C), 1180 (C-O-C); H NMR (CDCl3-d6)
=
d ppm 1.7–2.6 (m, 6H, 3-CH2), 2.8 (s, 3H, CH3), 4.2 (s, 1H, C4-H), 6.8 (bs, 1H,
exchangeable NH), 7.1–7.5 (m, 5H, Ar-H); MS: m=z (%) 308 (Mþ, 50%). Calcd.
for C18H16N2O3 (308): C, 70.13; H, 5.19. Found: C, 70.23; H, 5.32.
Method B. Acetyl chloride (0.005 mol) was added to a solution of 1a
(0.005 mol) in dry pyridine (30 cm3) and refluxed on water bath for 3 h. The reaction
mixture was left to cool at room temperature, poured into ice-cold water, and neu-
tralized with diluted hydrochloric acid for complete precipitation. The separated
material was collected by filtration, washed with water, dried well, and recrystallized
from acetic acid to yield compound 22.
N-(3-Cyano-5-oxo-4-phenyl-5,6,7,8-tetrahydro-4H-
chromen-2-yl)chloroacetamide (23)
A mixture of 1a (0.005 mol) and chloroacetyl chloride (0.005 mol) in dry pyri-
dine (30 cm3) was refluxed on a water bath for 3 h and left to cool at room tempera-
ture. The reaction mixture was poured into cold water (50 cm3) and neutralized with
diluted hydrochloric acid for complete precipitation. The obtainable solid was fil-
tered off, washed with water, dried well, and recrystallized from methanol to yield
compound 23. Yield 74%; mp 159 ꢁC; IR (KBr) nmax cmꢀ1: 3310 (NH), 2220
=
(CN), 1690 (a,b-unsaturated ketone), 1670 (amidic carbonyl), 1600 (C C), 1175
1
(C-O-C); H NMR (CDCl3-d6) d ppm 1.7–2.6 (m, 6H, 3-CH2), 2.9 (s, 3H, CH3),
4.4 (s, 1H, C4-H), 6.8 (bs, 1H, exchangeable NH), 7.1–7.5 (m, 5H, Ar-H). Calcd.
for C18H15N2O3Cl (342.5): C, 63.07; H, 4.38. Found: C, 62.95; H, 4.15.
2-(Phenylthiouryl)-5-oxo-4-phenyl-5,6,7,8-tetrahydro-4H-
chromen-3-carbonitrile (24)
A mixture of 1a (0.005 mol) and phenylisothiocyanate (0.005 mol) in DMF
containing a catalytic amount of TEA (four drops) was refluxed for 6 h and left to
cool at room temperature. The reaction mixture was poured into cold water for com-
plete precipitation, then filtered off, washed with water, dried well, and recrystallized
from aqueous methanol to yield compound 24. Yield 58%; mp 112 ꢁC; IR (KBr)
nmax cmꢀ1: 3350, 3310 (two NH), 2220 (CN), 1685 (a,b-unsaturated ketone), 1600
1
=
=
(C C), 1310 (C S), 1175 (C-O-C); H NMR (CDCl3-d6) d ppm 1.7–2.6 (m, 6H,

SYNTHESIS OF SOME NEW CHROMENE DERIVATIVES, PART 6
693
3-CH2), 4.4 (s, 1H, C4-H), 4.93 (s, 2H, exchangeable NH2), 6.8 (bs, 1H, exchangeable
NH), 7.1–7.8 (m, 10H, Ar-H), 8.2 (bs, 1H, exchangeable NH); MS: m=z (%)
401 (Mþ, 10%). Calcd. for C23H19N3O2S (401): C, 68.83; H, 4.74. Found: C,
68.62; H, 4.66.
4-Amino-10-phenyl-2-thioxo-6,7,8,10-tetrahydro-9-oxa-
1,3-diaza-anthracen-5-one (25)
Method A. An equimolar mixture of 1a (0.005 mol) and phenylisothiocyanate
(0.005 mol) in DMF (30 cm3) in the presence of TEA (four drops) was refluxed for
10 h. The reaction mixture was left to cool and poured into cold water for complete
precipitation. The separated solid was filtered off, washed with water, dried well, and
recrystallized from ethanol to yield compound 25. Yield 46%; mp 180 ꢁC; IR (KBr)
nmax cmꢀ1: 3450–3350 (NH2), 1685 (a,b-unsaturated ketone), 1600 (C C), 1175
=
1
(C-O-C); H NMR (CDCl3-d6) d ppm 1.7–2.6 (m, 6H, 3-CH2), 4.5 (s, 1H, C10-H),
6.9 (bs, 1H, exchangeable NH), 7.1–7.8 (m, 10H, Ar-H). Calcd. for C23H19N3O2S
(401): C, 68.83; H, 4.74. Found: C, 68.62; H, 4.66.
Method B. A few drops of TEA was added to a solution of 24 (0.002 mol) in
DMF. The reaction mixture was refluxed for 6 h, then left to cool, filtered off,
washed with water, dried well, and recrystallized from ethanol to yield compound 25.
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