A simple and convenient synthesis of isolated fused heterocycles based on: 6-Phenyl-2-thioxo-2,3-dihydropyrimidin-4(5H)-one and 5-acetyl-6-phenyl-2-thioxo-2,3-dihydropyrimidin-4(5H)-one

Article abstract of DOI:10.3987/COM-16-13467

The reaction of 6-phenyl-2-thioxo-2,3-dihydropyrimidin-4(5H)-one 1 with acetyl chloride in acetic anhydride in the presence of sodium acetate afforded 5-acetyl-6-phenyl-2-thioxo-2,3-dihydropyrimidin-4(5H)-one 2 which reacted with bromine, hydrazine hydrate, phenylhydrazine, cyanothioacetamide, aldehydes and (malononitrile/sulfur) to give 2-thioxo-2,3-dihydropyrimidine derivatives 4, 7a,b, 8, 10 and 11 respectively. In the present investigation 6-phenyl-2-thioxo-2,3-dihydropyrimidin-4(5H)-one 1 was reacted with chloroacetyl chloride to yield the corresponding compound 13. Compound 1 was reacted with some electrophilic reagents such as (benzylidene-cyanothioacetamide derivatives, 2-cyano-2-cyclopentylethanethioamide, 2-cyano-2-cyclohexylethanethioamide and aromatic diazonium salts) to give compounds 23, 27a,b and 35 respectively. The newly synthesized heterocycles were characterized on the basis of their chemical properties and spectral data.

Full text of DOI:10.3987/COM-16-13467

HETEROCYCLES, Vol. 92, No. 8, 2016
1397
HETEROCYCLES, Vol. 92, No. 8, 2016, pp. 1397 - 1414. © 2016 The Japan Institute of Heterocyclic Chemistry
Received, 14th March, 2016, Accepted, 31st May, 2016, Published online, 9th June, 2016
DOI: 10.3987/COM-16-13467
A SIMPLE AND CONVENIENT SYNTHESIS OF ISOLATED FUSED
HETEROCYCLES
BASED
ON:
AND
6-PHENYL-2-THIOXO-2,3-ꢀ
5-ACETYL-6-PHENYL-2-ꢀ
DIHYDROPYRIMIDIN-4(5H)-ONE
THIOXO-2,3-DIHYDROPYRIMIDIN-4(5H)-ONE
1
1
Mohamed Ahmed Mahmoud Abdel Reheim, * Ibrahim Saad Abdel Hafiz,
and Mohamed Ahmed Elian1
1
Department of Chemistry, Faculty of Science, Arish University, Arish 45511,
Egypt. E-mail: dr.mohamedabdelreheim@gmail.com
Abstract – The reaction of 6-phenyl-2-thioxo-2,3-dihydropyrimidin-4(5H)-one 1
with acetyl chloride in acetic anhydride in the presence of sodium acetate afforded
5
-acetyl-6-phenyl-2-thioxo-2,3-dihydropyrimidin-4(5H)-one 2 which reacted with
bromine, hydrazine hydrate, phenylhydrazine, cyanothioacetamide, aldehydes and
malononitrile/sulfur) to give 2-thioxo-2,3-dihydropyrimidine derivatives 4, 7a,b,
(
8
,
10
and
11
respectively.
In
the
present
investigation
6-phenyl-2-thioxo-2,3-dihydropyrimidin-4(5H)-one
1 was reacted with
chloroacetyl chloride to yield the corresponding compound 13. Compound 1 was
reacted with some electrophilic reagents such as (benzylidene-cyanothioacetamide
derivatives,
ethanethioamide and aromatic diazonium salts) to give compounds 23, 27a,b and
5 respectively. The newly synthesized heterocycles were characterized on the
basis of their chemical properties and spectral data.
2-cyano-2-cyclopentylethanethioamide,
2-cyano-2-cyclohexyl-
3
INTRODUCTION
Heterocyclic compounds have drawn special attention in organic chemistry because of their abundance in
1
natural products and their diverse biological properties. Pyrimidine and its derivatives have been
recognized as important heterocyclic compounds due to their variety of chemical and biological
significance to medicinal chemistry.2-4 As antiviral, antibacterial, antimalarial, antihypertensive and
5
6
7
8
9
anti-inflammatory agents. In addition, pyrimidine derivatives form the basis of a large number of
pharmacological products with anticancer and tein kinase inhibitory activity.10 Many substituted
pyrimidine rings play an important role as analgesic, antipyretic also as pesticides, herbicides, plant growth

1398
HETEROCYCLES, Vol. 92, No. 8, 2016
regulators and organic calcium channel modulators.11-17 In continuation of our search of new compounds
with anticipated biological activity, we aimed to obtain new compounds of the fused thiophene system,
with similar therapeutic properties and other noteworthy chemical and biological activities.
RESULTS AND DISCUSSION
The key intermediate 5-acetyl-6-phenyl-2-thioxo-2,3-dihydropyrimidin-4(5H)-one 2 was prepared in good
yield from the reaction of 6-phenyl-2-thioxo-2,3-dihydropyrimidin-4-(5H)-one 1 with acetyl chloride in
acetic anhydride and sodium acetate at reflux temperature. The infrared spectrum of compound 2 revealed
-1
absorption bands at 3318, 3046, 1698 and 1374 cm for amino, aromatic, carbonyl and thiocarbonyl
1
function groups, respectively. H-NMR spectrum of compound 2 showed the following signals at G 3.36 (s,
1
3
3
H, CH
compound 2 showed the following signals at G 27.0, 56.3, 127.1, 127.1, 127.1, 127.1, 130.1, 133.1, 160,
70.1, 179.1, 200. Also, its mass spectrum showed a molecular ion peak at m/z 246 (M+).18
3
), 3.84 (s, 1H, CH), 7.31-7.72 (m, 5H, aromatic H), 10.62 (s, 1H, NH); C-NMR spectrum of
1
Bromination of 5-acetyl-6-phenyl-2-thioxo-2,3-dihydropyrimidin-4(5H)-one 2 with bromine in acetic acid
gave 5-(2-bromoacetyl)-6-phenyl-2-thioxo-2,3-dihydropyrimidin-4(5H)-one 4. The structure of compound
1
4
was established through microanalysis, IR, H-NMR, mass spectral data and chemical reactivity. So,
acetonitrile derivative 5 was prepared in excellent yield by reaction of compound 4 with potassium cyanide
in aqueous ethanol. The structure of compound 5 was characterized by analytical and spectral data. The IR
-1 1
spectrum of compound 5 showed bands 3388 (NH), 2225 (CN), 1694, 1637 (2CO) cm , H-NMR spectrum
of compound 5 in DMSO-d
6
revealed signals at G 3.84 (s, 1H, CH), 4.10 (s, 2H, CH
2
), 7.23-7.75 (m, 5H,
+
aromatic H), 10.62 (s ,1H, NH). Its mass spectrum showed a molecular ion peak m/z at 271 (M ) with a base
peak at 116 and other significant peaks appeared at 197 (86%), 218 (79%) and 262 (89%).19,20 Treatment of
compound
2
with
hydrazine
hydrate
afforded
3-methyl-4-phenyl-1H-pyrazolo[3,4-d]pyrimidine-6-(7H)-thione 7a which was established by the
1
disappearance of two carbonyl group in the infrared spectrum. Its H-NMR spectrum showed a singlet
signal at G 2.27 ppm assigned for the methyl group and at G 10.65, 10.80 ppm assigned for 2NH groups. The
+
mass spectrum revealed a molecular ion peak at m/z 244 (M +2) corresponding to the molecular formula

HETEROCYCLES, Vol. 92, No. 8, 2016
1399
C
12
H
10
4
N S. Similarly, when compound 2 was treated with phenylhydrazine in ethanolic solution afforded
compounds 7b. The structure of compound 7b was proved by analytical and spectral data.
Cyclocondensation of compound 2 with cyanothioacetamide in pyridine solution yielded the
5-methyl-4-phenyl-2,7-dithioxo-1,2,7,8-tetrahydropyrido[2,3-d]pyrimidine-6-carbonitrile 8 in good yield.
The structure of compound 8 was confirmed on the basis of its analytical and spectral data. So, the IR
spectrum showed the disappearance of carbonyl group and showed absorption bands at 3327, 3177 cm-1
-1
due to 2NH groups in addition to the absorption band at 2206 cm which can be assigned to CN group. Its
1H-NMR spectrum in DMSO-d
displayed signals characteristic for amino, methyl and aromatic protons,
6
the mass spectrum of compound 8 is in agreement with the proposed structure. An equimolar quantity of
aromatic aldehydes 9a-c and methyl ketone 2 react in the presence of sodium hydroxide to give chalcones
derivatives by cross aldol condensation reaction. The structures of the synthesized compounds were
1
confirmed by IR, H-NMR and mass spectra. The IR spectrum of compound 10a as example was
-1
characterized by disappearance of methyl group and showed an absorption bands at 1629 cm due to the
1
carbonyl group. Its H-NMR spectrum in DMSO-d
6
revealed signals at G 3.43 (s, 1H, CH), 5.44 (br s, 1H,
CH-olefinic), 6.86 (br s, 1H, CH-olefinic),7.19-7.87 (m, 11H, aromatic H and NH). The mass spectrums of
compound 10a-c are in agreement with the proposed structure.21-23 In addition to this the behaviour of
thioxo-2,3-dihydropyrimidin-4(5H)-one derivative 2 toward active methylene reagent and elemental sulfur
was also investigated. Thus, compound 2 reacted with a mixture of malononitrile and elemental sulfur to
afford the thiophene derivative 11 (Scheme 2). Assignment of structure 11 for the reaction product was
based on its compatible spectroscopic data. Thus, its IR spectrum showed absorption band at 3428, 3320
cm-1
-(2-Chloroacetyl)-6-phenyl-2-thioxo-2,3-dihydropyrimidin-4(5H)-one 13 was obtained by treatment of
compound 1 with chloroacetyl chloride in dry toluene. The structure of the newly synthesized compound
for
NH
,
3212
cm-1
for
NH
and
2204
cm-1
for
CN
group.24
2
5
1
13
was confirmed by IR, H-NMR, C-NMR and mass spectra. Compound 13 underwent an intramolecular
heterocyclization, upon boiling in toluene to afford
-phenyl-2-thioxo-1,2-dihydrofuro[2,3-d]pyrimidin-5(6H)-one 14. The mass spectrum of compound 14 is
4
in agreement with the proposed structure. On the other hand, when respective aryl amines were treated with
ammonium thiocyanate under acidic conditions. It led to the formation of substitution arylthioureas
1
5a-c.25

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HETEROCYCLES, Vol. 92, No. 8, 2016
Compound 13 and 15a-c were refluxed in dry acetone for 12
h
to afford
2-thioxo-2,3-dihydropyrimidin-4(5H)-one derivatives 16a-c. All the synthesized compounds were
1
characterized by IR, H-NMR and mass spectra. The IR spectrum of compound 16a as example showed
-1
-1
1
bands at 3417, 3343 cm for 2NH and band at 1675 cm for carbonyl group. H-NMR spectra showed the
following signals at G 3.98 (s, 1H, CH), 5.44 (s, 1H, CH-thiazole), 7.17-7.60 (m, 10H, aromatic H),
9.00-9.80 (hump, 2H, 2NH) (Scheme 3).

HETEROCYCLES, Vol. 92, No. 8, 2016
1401
The active methylene group in pyrimidinethione derivative 1 was exploited to synthesize novel
tetrahydropyrido[2,3-d]pyrimidine-6-carbonitrile 23a-d and pyrido[2,3-d]pyrimidine-6'-carbonitrile 27a,b
derivatives
through
its
reaction
with
some
electrophiles.
Thus,
the
tetrahydropyrido[2,3-d]pyrimidine-6-carbonitrile 23a-d derivatives were obtained in quantitative yield
from the reaction of 1 with arylidene-cyanothioacetamide 18a-d in ethanolic piperidine. Compounds
were confirmed on the basis of the spectroscopic analysis. Thus, IR spectrum of compound 23a as
revealed the presence of characteristic bands for amino and cyano functional groups. In addition, the
1H-NMR spectrum of compound 23a in DMSO-d
revealed the absence of methylene moiety. The
6
of compound 23a was supported by its mass spectrum which revealed molecular ion peak at m/z 374 (M+).
The expected pyrimidine 22 formations was ruled out on the basis of analytical and spectral data.26
Similarly, cyclocondensation of 6-phenyl-2-thioxo-2,3-dihydropyrimidin-4-(5H)-one
1
with
cyclopentanone or cyclohexanone and cyanothioacetamide (1:1:1 molar ratio) afforded
pyrido[2,3-d]pyrimidine-6'-carbonitrile of type 27a,b. Compounds 27a,b were confirmed based on the
-1
spectroscopic data. Thus, the infrared spectrum of 27a showed 2NH at 3354, 3215 cm and CN at 2198
-1
+
27
cm . Mass spectrum of 27a showed amolecular ion peak at m/z 354 (M +2) with a base peak at m/z 84.
Condensation of compound 1 with aromatic aldehydes 9a-d in ethanol at reflux temperature in the
of potassium hydroxide produced the 2-thioxo-2,3-dihydropyrimidin-4-(5H)-one derivatives 28a-d. The
structure of the isolated product 28a-d was verified by elemental analysis and spectroscopic methods IR,
1H-NMR and mass spectra.28

1402
HETEROCYCLES, Vol. 92, No. 8, 2016
Compounds 28b,d were reacted with thiourea in ethanol in the presence of potassium hydroxide to yield
dihydropyrimido[4,5-d]pyrimidine-2(1H)-thione derivatives 30b,d. The structures of all products 30b,d

HETEROCYCLES, Vol. 92, No. 8, 2016
1403
were established on the basis of IR, H-NMR, mass and elemental analysis.29,30 Our intention was
1
extended to prepare pyrimidine derivatives with incorporating an active amino heterocyclic moiety. Thus,
6-phenyl-2-thioxo-2,3-dihydropyrimidin-4(5H)-one 1 reacted with equimolar amounts of malononitrile
and elemental sulfur in dioxane/TEA solution to afford in 69% yield the corresponding
6-amino-4-phenyl-2-thioxo-1,2-dihydrthieno[3,2-d]pyrimidine-7-carbonitrile 31. The structure of 31 was
1
established through microanalysis, IR, H-NMR and mass spectral data. The IR spectrum of compound
-1
1
3
1 revealed the existence of absorption band at 2211 cm corresponding to the CN group. The H-NMR
spectrum of compound 31 revealed the presence of singlet signals for the NH group at G 12.10 ppm. The
2
+
mass spectra showed molecular ion peak at m/z 284 (M ) besides a base peak at m/z 128. Refluxing of
compound 31 with triethyl orthoformate in the presence of acetic anhydride yielded the ethoxymethylene
amino derivatives 32. The IR spectrum of 32 showed bands at 3316 (NH), 2930 (CH-aliph), 2218 (CN)
-1
1
and 1620 cm (C=N), the H-NMR spectrum of 32 in CDCl
3
revealed signals at G 1.36 (t, 3H, CH
), 6.98-8.02 (m, 6H, aromatic H and CH-olefinic), 12.75 (s, 1H, NH). Attempts cyclization of
2 using hydrazine aiming at preparation of a series of fused pyrimidines failed and afforded the
3
), 4.39
(
q, 2H, CH
2
3
thienopyrimidine 31 in a quantitive yield.27, 31, 32
(
1)
CH (CN) /S
ArCHO
9a-d)
2
2
(
Ph
Ph
N
S
N
Ar
9
,28 a, Ar = C H
S
N
H
O
S
N
H
NH2
6
5
b, Ar = C H -Cl-p
6
4
CN
(28a-d)
c, Ar = C H -OMe-p
(
31)
6
4
d, Ar = C H -OH-p
H N
6
4
2
S
H N
2
Ar
Ph
N
NH
CH(OEt)3
NH NH
2
2
S
N
H
N
H
S
(
29)
Ph
Ar
Ph
N
S
N
N
2
9,30 b, Ar = C H -Cl-p
6 4
d, Ar = C H -OH-p
6
4
S
N
H
32)
N
CHOEt
S
N
H
N
H
SH
CN
(
(
30b,d)
Scheme 5

1404
HETEROCYCLES, Vol. 92, No. 8, 2016
Compound 1 could be readily coupled with aryldiazonium salts to yield the corresponding arylazo
derivatives 34a-c or isomeric structure 35. The structure of 35a-c were established through microanalysis,
1
IR, H-NMR, mass spectra and its chemical reactivity of this molecule to active methylene reagent. So,
treatment of compounds 35a-c with malononitrile without solvent in the presence of ammonium acetate
afforded pyrimido[5,4-c]pyridazine-4-carbonitrile derivatives 38a-c in quantitative yield. The structures
of 38a-c were established through elemental analysis and spectral data. The IR spectrum of 38a as
-1
1
example showed bands at 3328, 3181 (2NH), 2195 cm (CN). Its H-NMR spectrum in CDCl exhibited
3
signals at G 6.95-7.93 (m, 12H, aromatic H and 2NH), mass spectrum of 38a showed a molecular ion peak
+
S.33, 34
m/z at 358 (M +2) corresponding to the molecular formula C19
H
12
N
6
Ph
Ph
Ph
N
O
N-Ar
+
-
N
O
NHAr
N
N
N
Ar N NCl
(
33a-c)
S
N
H
S
N
H
O
S
N
H
(
1)
(34)
(35)
3
3-38 a, Ar = C H
6 5
b, Ar = C H -Cl-p
6
4
CH (CN)
2
c, Ar = C H -Me-p
2
6
4
Ar
NH
Ph
Ph
N
Ar
Ph
N
N
H
N ..
N
N
N
N
Ar
N
-
H O
N
2
S
N
H
NH
S
N
H
NH
S
CN
38a-c)
CN
H OH CN
(36)
OH
(37)
(
Scheme 6
EXPERIMENTAL
All melting points were measured using Akofler Block instrument and are uncorrected. IR spectra (KBr)
-1
1
were recorded on a FTIR 5300 spectrometer (υ, cm ). The H-NMR spectra were recorded in DMSO-d
6
,
CDCl at 300 MHz on a Varian Gemini NMR. 1000 EX mass spectrometer at 70 eV. The purity of
3
synthesized compounds was checked by Thin layer chromatography TLC (aluminum sheets) using
n-hexane, EtOAc (9:1, V/V, 7:3 V/V) eluent. Elemental analyses were carried out by the Microanalytical
Research Center, Faculty of Science, Cairo University.
Preparation of compound (2). A mixture of pyrimidinethione derivatives 1 (0.01 mol) and acetyl
chloride (0.01 mol) in acetic anhydride and sodium acetate was heated under reflux for 9 h. The reaction

HETEROCYCLES, Vol. 92, No. 8, 2016
1405
mixture was allowed to cool and poured into crushed ice then acidified with HCl. The separated solid was
filtered, washed with water and crystallized from the proper solvent to give 2.
5
-Acetyl-6-phenyl-2-thioxo-2,3-dihydropyrimidin-4(5H)-one (2). It was obtained as yellow crystals
o
-1
from EtOH; yield (85%); Mp 140-142 C; IR (KBr) Q cm 3318 (NH), 3046 (CH-arom), 1698 (CO),
1
1
1
2
5
374 (C=S); H-NMR (DMSO-d
6
) G 3.36 (s, 3H, CH ), 3.84 (s, 1H, CH), 7.31-7.72 (m, 5H, aromatic H),
3
1
3
0.62 (s, 1H, NH); C NMR G 27.0, 56.3, 127.1, 127.1, 127.1, 127.1, 130.1, 133.1, 160, 170.1, 179.1,
+
00; MS: m/z (%) 246 (M ). Anal. Calcd for C12
H
10
N
2
2
O S (246): C, 58.52; H, 4.09; N, 11.37. Found: C,
8.53; H, 4.10; N, 11.38%.
o
Preparation of compound (4). To a hot solution (60 C) of 2 (0.01 mol) in acetic acid (40 mL), bromine
0.01 mol) in acetic acid (10 mL) was added dropwise with stirring for 10 min. The reaction mixture was
(
allowed to attain room temperature and was poured into ice/water, the formed solid product was collected
by filtration and crystallized from the proper solvent to give 4.
5-(2-Bromoacetyl)-6-phenyl-2-thioxo-2,3-dihydropyrimidin-4(5H)-one (4). It was obtained as yellow
o
-1
crystals from EtOH; yield (59%); Mp 200-202 C; IR (KBr) Q cm 3259 (NH), 3077 (CH-arom), 2985
1
(
CH-aliph), 1658, 1641 (2CO); H-NMR (DMSO-d
6
) G 3.60 (s, 1H, CH), 4.18 (s, 2H, CH
2
), 6.12-7.00 (m,
S (324): C,
+
5
H, aromatic H), 8.97 (s, 1H, NH); MS: m/z (%) 325 (M +1). Anal. Calcd for C12
H
9
BrN
2
O
2
4
4.32; H, 2.79; N, 8.61. Found: C, 44.33; H, 2.81; N, 8.62%.
o
Preparation of compound (5). To a hot solution (50 C) of 4 (0.01 mol) in EtOH (40 mL), a solution (in
5
mL water) of potassium cyanide (0.01 mol) was added dropwise. The reaction mixture was left at room
temperature for 4 h with stirring. The solid product, formed upon pouring into ice/water containing HCl
to pH 6) was collected by filtration and crystallized from the proper solvent to give 5.
-Oxo-3-(6-oxo-4-phenyl-2-thioxo-1,2,5,6-tetrahydropyrimidin-5-yl)propanenitrile (5). It was
(
3
o
-1
obtained as white crystals from EtOH; yield (80%); Mp 150-152 C; IR (KBr) Q cm 3388 (NH), 2225
1
(
CN), 1694, 1637(2CO); H-NMR (DMSO-d
6
) G 3.84 (s, 1H, CH), 4.10 (s, 2H, CH
2
), 7.23-7.75 (m, 5H,
+
aromatic-H), 10.62 (s, 1H, NH); MS: m/z (%) 271 (M ). Anal. Calcd for C13
H
9
N
3
O
2
S (271): C, 57.55; H,
3
.34; N, 15.49. Found: C, 57.56; H, 3.35; N, 15.51%.
Preparation of compound (7a). A mixture of dihydropyrimidinone derivative 2 (0.01 mol) and
hydrazine hydrate (3 mL) in EtOH was heated under reflux for 12 h. The reaction mixture was allowed to
cool. The separated solid was filtered, washed with EtOH and crystallized from the proper solvent to give
7
3
a.
-Methyl-4-phenyl-1H-pyrazolo[3,4-d]pyrimidine-6(7H)-thione (7a). It was obtained as white crystals
o
-1
1
from EtOH; yield (72%); Mp 225-227 C; IR (KBr) Q cm 3430, 3264 (2NH); H-NMR (DMSO-d
6
) G
2
.27 (s, 3H, CH ), 7.01-8.49 (m, 5H, aromatic H), 10.65 (s, 1H, NH), 10.80(s, 1H, NH); MS: m/z (%) 244
3

1406
HETEROCYCLES, Vol. 92, No. 8, 2016
+
(
M +2). Anal. Calcd for C12
H
10
4
N S (242): C, 59.48; H, 4.16; N, 23.12. Found: C, 59.49; H, 4.18; N,
23.13%.
Preparation of compound (7b). A mixture of dihydropyrimidinone derivative 2 (0.01 mol) and phenyl-
hydrazine (0.01 mol) in EtOH containing catalytic amount of piperidine was heated under reflux for 12 h.
The reaction mixture was allowed to cool and poured into crushed ice then acidified with HCl. The
separated solid was filtered off, washed with water and crystallized from the proper solvent to give 7b.
3
,4-Diphenyl-1H-pyrazolo[3,4-d]pyrimidine-6(7H)-thione (7b). It was obtained as brown crystals from
o
-1
EtOH; yield (84%); Mp 100-102 C; IR (KBr) Q cm 3454 (NH), 3055 (CH-arom), 2923 (CH-aliph);
1H-NMR (CDCl
) G 2.46 (s, 3H, CH
), 7.21-7.50 (m, 10H, aromatic H), 8.10 (s, 1H, NH); MS: m/z (%)
S (318): C, 67.08; H, 3.97; N, 18.41. Found: C, 67.09; H, 3.99; N,
3
3
+
3
1
20 (M +2). Anal. Calcd for C18
H
14
N
4
8.42%.
Preparation of compound (8). A mixture of dihydropyrimidinone derivative 2 (0.01 mol) and
cyanothioacetamide (0.01 mol) in pyridine (30 mL) was heated under reflux for 12 h. The reaction
mixture was allowed to cool and poured into crushed ice then acidified with HCl. The separated solid was
filtered, washed with water and crystallized from the proper solvent to give 8.
5-Methyl-4-phenyl-2,7-dithioxo-1,2,7,8-tetrahydropyrido[2,3-d]pyrimidine-6-carbonitrile (8). It was
o
-1
obtained as brown crystals from EtOH; yield (81%); Mp 180-182 C; IR (KBr) Q cm 3327, 3177 (2NH),
1
2
925 (CH-aliph), 2206 (CN); H-NMR (DMSO-d
6
) G 1.91 (s, 3H, CH ); 7.41-7.97 (m, 7H, aromatic H
3
1
3
and 2NH); C NMR G 12.5, 79.4, 103.2, 120.6, 126.9, 126.9, 128.1, 128.1, 129, 134.1, 151.9, 160, 163,
+
1
63.8, 179; MS: m/z (%) 311 (M +1). Anal. Calcd for C15
H
10
N
4
2
S (310): C, 58.04; H, 3.25; N, 18.05.
Found: C, 58.05; H, 3.27; N, 18.06%.
General procedure for the preparation of compound (10a-c). A mixture of dihydropyrimidinone
derivative 2 (0.01 mol), appropriate aromatic aldehydes 9a-c (0.01 mol) and 10% aqueous sodium
hydroxide (10 mL) in EtOH (50 mL) was stirred at room temperature for about 3 h. The resulting solid
was filtered off, washed with water, dried and crystallized from the proper solvent to give 10a-c.
6
-Phenyl-5-(3-phenylacryloyl)-2-thioxo-2,3-dihydropyrimidin-4(5H)-one (10a). It was obtained as
o
-1
white crystals from EtOH; yield (79%); Mp 300-302 C; IR (KBr) Q cm 3455 (NH), 1629 (CO);
1H-NMR (DMSO-d
) G 3.43 (s, 1H, CH), 5.44 (br s, 1H, CH-olefinic), 6.86 (br s, 1H, CH-olefinic);
6
+
7
.19-7.87 (m, 11H, aromatic H and NH); MS: m/z (%) 335 (M +1). Anal. Calcd for C19
H
14
N
2
2
O S (334):
C, 68.24; H, 4.22; N, 8.38. Found: C, 68.25; H, 4.24; N, 8.39%.
-(3-(4-Chlorophenyl)acryloyl)-6-phenyl-2-thioxo-2,3-dihydropyrimidin-4(5H)-one (10b). It was
5
o
-1
obtained as yellow crystals from EtOH; yield (68%); Mp 210-212 C; IR (KBr) Q cm 3468 (NH), 1659,
1
1
630 (2CO); H-NMR (CDCl
3
) G 3.38 (s, 1H, CH); 5.90 (br s, 1H, CH-olefinic), 6.85 (br s, 1H,

HETEROCYCLES, Vol. 92, No. 8, 2016
1407
+
CH-olefinic), 6.87-7.55 (m, 10H, aromatic H and NH); MS: m/z (%) 369 (M +1). Anal. Calcd for
S (368): C, 61.87; H, 3.55; N, 7.60. Found: C, 61.88; H, 3.57; N, 7.61%.
-(3-(4-Methoxyphenyl)acryloyl)-6-phenyl-2-thioxo-2,3-dihydropyrimidin-4(5H)-one (10c). It was
C
19
H13ClN
2
O
2
5
o
-1
obtained as yellow crystals from EtOH; yield (64%); Mp 190-192 C; IR (KBr) Q cm 3438 (NH), 2922
CH-aliph), 1797, 1627 (2CO); MS: m/z (%) 364 (M+). Anal. Calcd for C20 S (364): C, 65.92; H,
.43; N, 7.69. Found: C, 65.93; H, 4.45; N, 7.70%.
(
H
16
N
2
O
3
4
Preparation of compound (11). A mixture of dihydropyrimidinone derivative 2 (0.01 mol),
malononitrile and sulfur (0.01 mol) in DMF (50 mL) containing catalytic amount of piperidine was
heated under reflux for 12 h. The reaction mixture was allowed to cool and poured into crushed ice then
acidified with HCl. The separated solid was filtered, washed with water and crystallized from the proper
solvent to give 11.
2-Amino-4-(6-oxo-4-phenyl-2-thioxo-1,2,5,6-tetrahydropyrimidin-5-yl)thiophene-3-carbonitrile (11).
o
-1
It was obtained as brown crystals from EtOH; yield (81%); Mp 182-184 C; IR (KBr) Q cm 3428, 3320
1
(NH
2
), 3212 (NH), 2923 (CH-aliph), 2204 (CN), 1629 (CO); H-NMR (DMSO-d
6
) G 3.03 (s, 1H, CH),
6
.40 (s, 2H, NH
2
), 7.49-7.84 (m, 6H, aromatic H and CH-thiophene), 11.76 (s, 1H, NH); MS: m/z (%) 327
M +1). Anal. Calcd for C15 OS (326): C, 55.20; H, 3.09; N, 17.17. Found: C, 55.21; H, 3.11; N,
7.18%.
+
(
H
10
N
4
2
1
Preparation of compound (13). A mixture of pyrimidinethione derivative 1 (0.01 mol) and chloroacetyl
o
chloride 12 (0.01 mol) in dry toluene (30 mL) at 0-5 C. The reaction mixture was stirred for 4 h at room
o
temperature and reflux for 6 h. The solid obtained was washed with petroleum ether (40-60 C) and kept
in refrigerator. The solid obtained was recrystallized from the proper solvent to give 13.
5-(2-Chloroacetyl)-6-phenyl-2-thioxo-2,3-dihydropyrimidin-4(5H)-one (13). It was obtained as white
o
-1
crystals from EtOH; yield (77%); Mp 140-142 C; IR (KBr) Q cm 3476 (NH), 2980 (CH-aliph), 1776,
-1
1
1
711 (2CO) cm ; H-NMR (DMSO-d
6
) G 2.40 (s, 1H, CH), 4.07 (s, 2H, CH ), 5.25-7.12 (m, 5H,
2
aromatic H), 8.39 (s, 1H, NH); 13C NMR G 46.0, 53.1, 127.1, 127.1 128.1, 128.1, 129.0, 130.7, 160.9,
+
1
70.2, 179.1, 200; MS: m/z (%) 282 (M +2). Anal. Calcd for C12
H
9
ClN O
2 2
S (280): C, 51.34; H, 3.23; N,
9
.98. Found: C, 51.35; H, 3.25; N, 9.99%.
o
Preparation of compound (14). Compound 13 (2.80 g) in toluene (30 mL) was fused for 8 h at 170 C.
The reaction mixture was left to stand; the solid product so formed was collected by filtration and
recrystallized from the proper solvent to give 14.
4-Phenyl-2-thioxo-1,2-dihydrofuro[2,3-d]pyrimidin-5(6H)-one (14). It was obtained as pale brown
o
-1
crystals from EtOH; yield (81%); Mp 160-162 C; IR (KBr) Q cm 3224 (NH), 2954 (CH-aliph), 1655
1
(
CO); H-NMR (DMSO-d
6
) G 4.33 (s, 2H, CH ), 6.94-7.28 (m, 6H, aromatic H and NH); MS: m/z (%)
2

1408
HETEROCYCLES, Vol. 92, No. 8, 2016
+
2
44 (M ). Anal. Calcd for C12
1.49%.
H
8
N
2
2
O S (244): C, 59.00; H, 3.30; N, 11.47. Found: C, 59.01; H, 3.31; N,
1
General procedure for the preparation of compound (16a-c). A mixture of compound 13 (0.01 mol)
and thiourea derivatives 15a-c (0.01 mol) in dry acetone (30 mL) was heated under reflux for 12 h. The
reaction mixture was evaporated in vacuo. The separated solid was filtered, washed with ether and
crystallized from the proper solvent to give 16a-c.
6-Phenyl-5-(2-(phenylamino)thiazol-4-yl)-2-thioxo-2,3-dihydropyrimidin-4(5H)-one (16a). It was
o
-1
obtained as pale yellow crystals from Et O; yield (79%); Mp 174-176 C; IR (KBr) Q cm 3417, 3343
2
1
(
2NH), 2977 (CH-aliph), 1675 (CO); H-NMR (DMSO-d
6
) G 3.98 (s, 1H, CH), 5.44 (s, 1H, CH-thiazole),
+
7
.17-7.60 (m, 10H, aromatic H), 9.00-9.80 (hump, 2H, 2NH); MS: m/z (%) 378 (M ). Anal. Calcd for
C
19
H
14
N
4
OS
2
(378): C, 60.30; H, 3.73; N, 14.80. Found: C, 60.31; H, 3.75; N, 14.81%.
5-(2-(4-Chlorophenylamino)thiazol-4-yl)-6-phenyl-2-thioxo-2,3-dihydropyrimidin-4(5H)-one (16b).
o
-1
It was obtained as pale yellow crystals from EtOH; yield (74%); Mp 182-184 C; IR (KBr) Q cm 3473,
1
3
415 (2NH), 2977 (CH-aliph), 1675 (CO); H-NMR (DMSO-d
6
) G 4.29 (s, 1H, CH), 5.44 (s, 1H, CH-
+
thiazole), 7.16-7.50 (m, 9 H, aromatic H), 8.60-10.40 (hump, 2H, 2NH); MS: m/z (%) 415 (M +3). Anal.
Calcd for C19
H13ClN
4
OS
2
(412): C, 55.27; H, 3.17; N, 13.57. Found: C, 55.28; H, 3.18; N, 13.59%.
Methyl-4-(4-(6-oxo-4-phenyl-2-thioxo-1,2,5,6-tetrahydropyrimidin-5-yl)thiazol-2-ylamino)benzoate
o
-1
(
16c). It was obtained as pale yellow crystals from EtOH; yield (76%); Mp 198-200 C; IR (KBr) Q cm
1
3
419, 3343 (2NH), 2976 (CH-aliph), 1745, 1676 (2CO); H-NMR (DMSO-d
6
) G 2.51 (s, 3H, OCH ), 4.14
3
(s, 1H, CH), 5.46 (s, 1H, CH- thiazole), 7.19-7.53 (m, 9H, aromatic H), 10.00-10.80 (s, 2H, 2NH); MS:
+
m/z (%) 435 (M -1). Anal. Calcd for C21
H
16
N
4
O
3
S (436): C, 57.78; H, 3.69; N, 12.84. Found: C, 57.79;
2
H, 3.71; N, 12.85%.
General procedure for the preparation of compound (23a-d). A mixture of compound 1 (0.01 mol) and
benzylidene-cyanothioacetamide derivatives 18a-d (0.01 mol) in EtOH with catalytic amount of
piperidine was heated under reflux for 10 h. The reaction mixture was allowed to cool and poured into
crushed ice then acidified with HCl. The separated solid was filtered, washed with water and crystallized
from the proper solvent to give 23a-d.
7-Mercapto-4,5-diphenyl-2-thioxo-1,2,5,8-tetrahydropyrido[2,3-d]pyrimidine-6-carbonitrile (23a). It
o
-1
was obtained as pale yellow crystals from EtOH; yield (73%); Mp 118-120 C; IR (KBr) Q cm 3339,
1
3
4
3
1
208 (2NH), 2931 (CH-aliph), 2198 (CN); H-NMR (DMSO-d
6
) G 1.65 (hump, 1H, SH), 4.18 (s, 1H,
H-pyridine), 6.94-7.93 (m, 10H, aromatic H), 8.40 (hump, 1H, NH), 10.00 (s, 1H, NH); MS: m/z (%)
+
74 (M ). Anal. Calcd for C20
4.92%.
H
14
N
4
S (374): C, 64.15; H, 3.77; N, 14.96. Found: C, 64.12; H, 3.73; N,
2

HETEROCYCLES, Vol. 92, No. 8, 2016
1409
5-(4-Chlorophenyl)-7-mercapto-4-phenyl-2-thioxo-1,2,5,8-tetrahydropyrido[2,3-d]pyrimidine-6-
o
carbonitrile (23b). It was obtained as pale yellow crystals from EtOH; yield (76%); Mp 110-112 C; IR
-1
1
(
KBr) Q cm 3325, 3189 (2NH), 2940 (CH-aliph), 2214 (CN); H-NMR (CDCl
3
) G 1.65 (hump, 1H, SH),
+
4
.34 (s, 1H, 4H-pyridine), 6.73-8.01 (m, 11H, aromatic H and 2NH); MS: m/z (%) 409 (M +1). Anal.
Calcd for C20
H13ClN
4
S
2
(408): C, 58.74; H, 3.20; N, 13.70. Found: C, 58.75; H, 3.22; N, 13.71%.
7-Mercapto-5-(4-methoxyphenyl)-4-phenyl-2-thioxo-1,2,5,8-tetrahydropyrido[2,3-d]pyrimidine-6-
o
carbonitrile (23c). It was obtained as pale yellow crystals from EtOH; yield (69%); Mp 98-100 C; IR
-
1
1
(
KBr) Q cm 3331, 3179 (2NH), 2935 (CH-aliph), 2213 (CN); H-NMR (CDCl
.82 (s, 3H, OCH
3
) G 1.62 (hump, 1H, SH),
1
3
3
5
1
3
5
3
), 5.91 (s, 1H, 4H-pyridine), 6.82-7.54 (m, 11H, aromatic H + 2NH); C NMR G 37.2,
4.2, 76.8, 80.0, 117.1, 117.1, 120.0, 127.1, 127.1, 128.1, 128.1, 129.0, 130.0, 130.3, 130.6, 136, 138.6,
+
54.3, 155.3, 160.2, 179.0; MS: m/z (%) 404 (M ). Anal. Calcd for C21
H
16
N
4
OS (404): C, 62.35; H,
2
.99; N, 13.85. Found: C, 62.36; H, 4.01; N, 13.86%.
-(2,4-Dichlorophenyl)-7-mercapto-4-phenyl-2-thioxo-1,2,5,8-tetrahydropyrido[2,3-d]pyrimidine-6-
o
carbonitrile (23d). It was obtained as pale yellow crystals from EtOH; yield (80%); Mp 116-118 C; IR
-
1
1
(
(
(
KBr) Q cm 3346, 3207 (2NH), 3086 (CH-arom), 2938 (CH-aliph), 2192 (CN); H-NMR (CDCl ) G 1.68
3
hump, 1H, SH), 5.61 (s, 1H, 4H-pyridine), 7.27-8.22 (m, 8H, aromatic H ), 10.18 (s,1H, NH), 10.42
+
s,1H, NH); MS: m/z (%) 445 (M +3). Anal. Calcd for C20
H12Cl
2
N
4
S (442): C, 54.18; H, 2.73; N, 12.64.
2
Found: C, 54.15; H, 2.70; N, 12.62%.
General procedure for the preparation of compound (27a,b). A mixture of compound 1 (0.01 mol),
cyclohexanone (or cyclopentanone) (0.0l mol) and cyanothioacetamide (0.01 mol) in EtOH containing
catalytic amount of piperidine was heated under reflux for 10 h. The reaction mixture was allowed to cool
and poured into crushed ice then acidified with HCl. The separated solid was filtered, washed with water
and crystallized from the proper solvent to give 27a,b.
7
'-Mercapto-4'-phenyl-2'-thioxo-2',8'-dihydro-1'
H
-spiro[cyclopentane-1,5'-pyrido[2,3-
d
]pyrimidine-
o
6
'-carbonitrile (27a). It was obtained as pale brown crystals from EtOH; yield (82%); Mp 270-272 C;
-
1
1
IR (KBr) Q cm 3354, 3215 (2NH), 2930 (CH-aliph), 2198 (CN); H-NMR (DMSO-d
SH), 1.17-1.23 (m, 4H, 2CH ), 1.51-1.98 (m, 4H, 2CH ), 6.73-8.11 (m, 5H, aromatic H), 8.54 (hump, 2H,
NH); 13C NMR G 25.6, 27.0, 27.0, 38.1, 38.1, 79.0, 100.1, 120.2, 126.9, 126.9, 128.1, 128.1, 129.1,
6
) G 0.85 (br, 1H,
2
2
2
1
+
30.1, 137.1, 147.9, 160.1, 179.1; MS: m/z (%) 354 (M +2). Anal. Calcd for C18
H
16
N
4
S (352): C, 61.34;
2
H, 4.58; N, 15.90. Found: C, 61.35; H, 4.60; N, 15.91%.
7
6
'-Mercapto-4'-phenyl-2'-thioxo-2',8'-dihydro-1'H-spiro[cyclohexane-1,5'-pyrido[2,3-d]pyrimidine-
o
'-carbonitrile (27b). It was obtained as brown crystals from EtOH; yield (75%); Mp 140-142 C; IR
-1
1
(
KBr) Q cm 3336, 3185 (2NH), 2935 (CH-aliph), 2194 (CN); H-NMR (DMSO-d ) G 1.32 (hump, 1H,
6

1410
HETEROCYCLES, Vol. 92, No. 8, 2016
SH), 1.34-1.38 (m, 2H, CH
aromatic H), 7.95 (s, 2H, 2NH); MS: m/z (%) 367 (M +1). Anal. Calcd for C19
.95; N, 15.29. Found: C, 62.28; H, 4.97; N, 15.30%.
2
), 1.51-1.79 (m, 4H, 2CH
2
), 2.56-2.89 (m, 4H, 2CH
2
), 6.94-7.28 (m, 5H,
(366): C, 62.27; H,
+
H
18
N
4 2
S
4
General procedure for the preparation of compound (28a-d). A mixture of compound 1 (0.01 mol) and
appropriate aromatic aldehydes 9a-d (0.01 mol) in ethanolic potassium hydroxide (50 mL, 10%) was
heated under reflux for 8 h. The reaction mixture was allowed to cool and poured into crushed ice then
acidified with HCl. The resulting solid was filtered off, washed with water, dried and crystallized from
the proper solvent to give 28a-d.
5
-Benzylidene-6-phenyl-2-thioxo-2,3-dihydropyrimidin-4-(5H)-one (28a). It was obtained as white
o
-1
crystals from EtOH; yield (70%); Mp 180-182 C; IR (KBr) Q cm 3178 (NH), 2924 (CH-aliph), 1653
1
(
CO); H-NMR (DMSO-d
6
) G 5.15 (s, 1H, CH-oliffinic), 7.13-8.01 (m, 11H, aromatic H + NH); MS: m/z
OS (292): C, 69.84; H, 4.14; N, 9.58. Found: C, 69.85; H,
+
(
%) 294 (M +2). Anal. Calcd for C17
H
12
N
2
4.16; N, 9.59%.
5
-(4-Chlorobenzylidene)-6-phenyl-2-thioxo-2,3-dihydropyrimidin-4-(5H)-one (28b). It was obtained
o
-1
as yellow crystals from EtOH; yield (81%); Mp 218-220 C; IR (KBr) Q cm 3404 (NH), 2925 (CH-aliph),
1
1
684 (CO); H-NMR (CDCl
3
) G 7.27-8.05 (m, 10H, aromatic H and CH-oliffinic), 10.00 (s, 1H, NH);
OS (326): C, 62.48; H, 3.39; N, 8.57. Found: C,
+
MS: m/z (%) 328 (M +2). Anal. Calcd for C17
H11ClN
2
6
2.45; H, 3.37; N, 8.54%.
5-(4-Methoxybenzylidene)-6-phenyl-2-thioxo-2,3-dihydropyrimidin-4-(5H)-one (28c). It was obtained
o
-1
as yellow crystals from EtOH; yield (68%); Mp 100-102 C; IR (KBr) Q cm 3197 (NH), 2926
1
(
CH-aliph), 1671 (CO); H-NMR (DMSO-d
6
) G 3.90 (s, 3H, OMe), 8.73-8.95 (m, 9H, aromatic H,
+
CH-oliffinic and NH); MS: m/z (%) 322 (M ). Anal. Calcd for C17
H
12
2
N OS (322): C, 67.06; H, 4.38; N,
8
.69. Found: C, 67.07; H, 4.39; N, 8.71%.
5-(4-Hydroxybenzylidene)-6-phenyl-2-thioxo-2,3-dihydropyrimidin-4-(5H)-one (28d). It was
o
-1
obtained as pale yellow crystals from EtOH; yield (68%); Mp 200-202 C; IR (KBr) Q cm 3420 (NH),
1
2
924 (CH-aliph), 1665 (CO); H-NMR (DMSO-d
6
) G 7.03-8.88 (m, 12H, aromatic H, CH-oliffinic, NH
S (308): C, 66.22; H, 3.92; N, 9.08. Found:
+
and OH); MS: m/z (%) 308 (M ). Anal. Calcd for C17
H
12
N
2
O
2
C, 66.23; H, 3.94; N, 9.10%.
General procedure for the preparation of compound (30b,d). To boiling solution of compound 28b,d
0.01 mol) in ethanolic potassium hydroxide (30 mL, 10%), thiourea (0.01 mol) was added. The reaction
(
mixture was refluxed for 20 h, then allowed to cool and poured into crushed ice then acidified with HCl.
The separated solid was filtered, washed with water and crystallized from the proper solvent to give
3
0b,d.

HETEROCYCLES, Vol. 92, No. 8, 2016
1411
5-(4-Chlorophenyl)-7-mercapto-4-phenyl-5,8-dihydropyrimido[4,5-d]pyrimidine-2(1H)-thione (30b).
o
-1
It was obtained as pale yellow crystals from EtOH; yield (64%); Mp 205-207 C; IR (KBr) Q cm 3369,
1
3
4
1
1
175 (2NH), 3064 (CH-arom), 2966 (CH-aliph); H-NMR (DMSO-d
6
) G 1.17 (s, 1H, SH), 5.43 (s, 1H,
13
H-pyrimidine), 6.67-7.73 (m, 10H, aromatic H and NH), 9.78 (hump, 1H, NH); C NMR G 49.6, 79.0,
26.9, 126.9, 127.1, 127.1, 128.1, 128.1, 129.1, 130.0, 130.0, 130.1, 133.0, 138.9, 155.0, 160.0, 160.9,
+
79.2; MS: m/z (%) 386 (M +2). Anal. Calcd for C18
H13ClN
4
2
S (384): C, 56.17; H, 3.40; N, 14.56.
Found: C, 56.18; H, 3.42; N, 14.58%.
-(4-Hydroxyphenyl)-7-mercapto-4-phenyl-5,8-dihydropyrimido[4,5-d]pyrimidine-2(1H)-thione
5
o
-1
(
30d). It was obtained as white crystals from EtOH; yield (61%); Mp 310-312 C; IR (KBr) Q cm 3425,
1
3
212 (2NH), 2927 (CH-aliph); H-NMR (DMSO-d
6
) G 1.67 (hump, 1H, SH), 6.24 (s, 1H, 4H-pyrimidine),
6
.85-8.12 (m, 10H, aromatic H and NH), 9.78 (s, 1H, OH), 10.80 (s, 1H, NH); MS: m/z (%) 366 (M+).
Anal. Calcd for C18
H
14
N
4
OS (366): C, 58.99; H, 3.85; N, 15.29. Found: C, 59.00; H, 3.87; N, 15.30%.
2
Preparation of compound (31). Method (A): A solution of compound 1 (0.01 mol), malononitrile and
sulfur (0.01 mol) in dioxane (30 mL) containing catalytic amount of TEA was heated under reflux for 12
h. The reaction mixture was allowed to cool and poured into crushed ice then acidified with HCl. The
separated solid was filtered, washed with water and crystallized from the proper solvent to give 31.
Method (B): to a solution of compound 32 (0.01 mol) in dry benzene (30 mL), hydrazine hydrate (10 mL)
was added with stirring at room temperature for 1 h, the obtained product was filtered off, dried and
recrystallized from dioxane to give compound 31.
6
-Amino-4-phenyl-2-thioxo-1,2-dihydrthieno[3,2-d]pyrimidine-7-carbonitrile (31). It was obtained as
o
-1
brown crystals from EtOH; yield (69%); Mp 114-116 C; IR (KBr) Q cm 3336, 3200 (NH ), 2939
2
1
(
CH-aliph), 2211 (CN); H-NMR (DMSO-d
6
) G 7.36-8.90 (m, 5H, aromatic H), 10.63 (hump, 1H, NH),
+
1
2.10 (hump, 2H, NH
2
) ; MS: m/z (%) 284 (M ). Anal. Calcd for C13
H
8
N
4
S (284): C, 54.91; H, 2.84; N,
2
1
9.70. Found: C, 54.92; H, 2.85; N, 19.71%.
Preparation of compound (32). A mixture of compound 31 (2.82 g) and triethylorthoformate (3 mL) in
acetic anhydride (10 mL) was heated under reflux for 6 h. The reaction mixture was evaporated in vacuo.
The separated solid was filtered, washed with ether and crystallized from the proper solvent to give 32.
Ethyl-N-[7-cyano-4-phenyl-2-thioxo-1,2-dihydrthieno[3,2-d]pyrimidin-6-yl]formimidate (32). It was
o
-1
obtained as brown crystals from EtOH; yield (65%); Mp 100-102 C; IR (KBr) Q cm 3316 (NH), 2930
1
(
CH-aliph), 2218 (CN), 1620 (C=N); H-NMR (CDCl
3
) G 1.36 (t, 3H, CH
3
), 4.39 (q, 2H, CH ), 6.98-8.02
2
(
m, 6H, aromatic H and CH-oleffinic), 12.75 (s, 1H, NH); 13C NMR G 15.2, 19.2, 60.8, 119.5, 121.1,
+
1
27.1, 127.1, 129, 129.2, 130.1, 132.3, 133, 158.9, 159.0, 160.0, 179.1; MS: m/z (%) 340 (M ). Anal.
Calcd for C16
H
12
N
4
S (340): C, 56.45; H, 3.55; N, 16.46. Found: C, 56.46; H, 3.57; N, 16.47%.
2

1412
HETEROCYCLES, Vol. 92, No. 8, 2016
General procedure for the preparation of compound (35a-c). A cold suspension of aryldiazonium salts
33a-c (0.002 mol) (prepared from 0.002 mol of aromatic amine with the appropriate quantities of sodium
o
nitrite and hydrochloric acid) was gradually added to a cold solution (0-5 C) of compound 1 (0.002 mol)
in EtOH (50 mL) containing anhydrous sodium acetate (5 g) with continuous stirring for 1 h. The
resulting reaction product was filtered off, washed with water and crystallized from the proper solvent to
give compounds 35a-c.
6
-Phenyl-5-(phenylhydrazono)-2-thioxo-2,3-dihydropyrimidin-4(5H)-one (35a). Formed as brown
o
-1
crystals from EtOH; yield (86%); Mp 100-102 C; IR (KBr) Q cm 3218, 3184 (2NH), 3053 (CH-arom),
1
1
676 (CO); H-NMR (CDCl
3
) G 6.92-7.79 (m, 11H, aromatic H and NH), 12.71 (s, 1H, NH); MS: m/z
OS (308): C, 62.32; H, 3.92; N, 18.17. Found: C, 62.33; H, 3.94;
+
(
%) 308 (M ). Anal. Calcd for C16
H
12
N
4
N, 18.18%.
-(2-(4-Chlorophenyl)hydrazono)-6-phenyl-2-thioxo-2,3-dihydropyrimidin-4(5H)-one (35b). Formed
5
o
-1
as yellow crystals from EtOH; yield (89%); Mp 110-112 C; IR (KBr) Q cm 3429, 3186 (2NH), 3082
1
(
CH-arom), 1652 (CO); H-NMR (CDCl
3
) G 6.91-7.78 (m, 10H, aromatic H and NH), 12.72 (s, 1H, NH);
OS (342): C, 56.06; H, 3.23; N, 16.34. Found: C,
+
MS: m/z (%) 342 (M ). Anal. Calcd for C16
H11ClN
4
56.07; H, 3.25; N, 16.35%.
6-Phenyl-2-thioxo-5-(p-tolyldiazenyl)-2,3-dihydropyrimidin-4(5H)-one (35c). Formed as brown
o
-1
crystals from EtOH; yield (82%); Mp 98-100 C; IR (KBr) Q cm 3181 (NH), 3059 (CH-arom), 2962
1
(
CH-aliph), 1678 (CO); H-NMR (DMSO-d
6
) G 3.34 (s, 3H, CH
+
3
),7.00-7.80 (m, 10H, aromatic H and
OS (322): C, 63.33; H, 4.38; N,
NH), 10.61 (s, 1H, NH); MS: m/z (%) 322 (M ). Anal. Calcd for C17
7.38. Found: C, 63.34; H, 4.40; N, 17.39%.
H
14
N
4
1
General procedure for the preparation of compound (38a-c). A mixture of compounds 35a-c (0.01
mol), malononitrile (0.01 mol) and ammonium acetate (2 g) was exposed to microwave irradiation (power
input 20%) for 3 min, the reaction mixture was allowed to reach room temperature, then diluted with
EtOH with stirring and solid product that formed, was filtrated and crystallized from the proper solvent to
give 38a-c.
3
-Imino-2,8-diphenyl-6-thioxo-2,3,5,6-tetrahydropyrimido[5,4-c]pyridazine-4-carbonitrile
(38a).
o
-1
Formed as red crystals from EtOH; yield (79%); Mp 122-124 C; IR (KBr) Q cm 3328, 3181 (2NH),
1
+
2
195 (CN); H-NMR (CDCl
Anal. Calcd for C19 S (356): C, 64.03; H, 3.39; N, 23.58. Found: C, 64.04; H, 3.40; N, 23.60%.
-(4-Chlorophenyl)-3-imino-8-phenyl-6-thioxo-2,3,5,6-tetrahydropyrimido[5,4-c]pyridazine-4-
3
) G 6.95-7.93 (m, 12H, aromatic H and 2NH); MS: m/z (%) 358 (M +2).
H
12
N
6
2
o
-1
carbonitrile (38b). Formed as brown crystals from EtOH; yield (74%); Mp 134-136 C; IR (KBr) Q cm
1
3
335, 3209 (2NH), 2195 (CN); H-NMR (CDCl
3
) G 6.95-8.47 (m, 11H, aromatic H and 2NH); MS: m/z

HETEROCYCLES, Vol. 92, No. 8, 2016
1413
+
(
%) 392 (M +2). Anal. Calcd for C19
H
11ClN S (390): C, 58.39; H, 2.84; N, 21.50. Found: C, 58.40; H,
6
2.85; N, 21.52%.
3
-Imino-8-phenyl-6-thioxo-2-p-tolyl-2,3,5,6-tetrahydropyrimido[5,4-c]pyridazine-4-carbonitrile
o
-1
(
(
(
38c). Formed as brown crystals from EtOH; yield (76%); Mp 116-118 C; IR (KBr) Q cm 3340, 3212
1
2NH), 3030 (CH-arom), 2916 (CH-aliph), 2193 (CN); H-NMR (CDCl
3
) G 1.23 (s, 3H, CH ), 7.23-7.52
3
13
m, 11H, aromatic H and 2NH); C NMR G 18.9, 80.1, 113.1, 119.2, 120.3, 127.1, 127.1, 128.6, 129.2,
+
1
29.2, 129.8, 130.1, 130.8, 133.1, 133.3, 151.2, 153.4, 160.0, 162.1, 179.1; MS: m/z (%) 370 (M ). Anal.
Calcd for C20
H
14
6
N S (370): C, 64.85; H, 3.81; N, 22.69. Found: C, 64.86; H, 3.82; N, 22.71%.
ACKNOWLEDGEMENTS
The authors are very grateful to Prof. Dr. A. E. Khodair, Department of Chemistry, Faculty of Science,
Suez Canal University, Ismailia, Egypt, for valuable support and reviewing this manuscript.
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