Synthesis of some new pyrimidine derivatives of expected antimicrobial activity

Article abstract of DOI:10.1080/10426500701557286

2-(2-Arylvinyl)-6-methyl-4-mercapto-5-acetylpyrimidine derivatives 3a - d, were synthesized form the reaction of the appropriate isothiocyanate derivatives 1 with , -unsaturated aminoketone 2. Compound 3 was alkylated with methyl iodide, ethyl chloroaceta

Full text of DOI:10.1080/10426500701557286

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Phosphorus, Sulfur, and Silicon
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Synthesis of Some New
Pyrimidine Derivatives of
Expected Antimicrobial Activity
A. H. Moustafa a , H. A. Saad a , W. S. Shehab a & M.
M. El-Mobayed a
a Chemistry Department, Faculty of Science ,
Zagazig University , Zagazig, Egypt
Published online: 20 Feb 2008.
To cite this article: A. H. Moustafa , H. A. Saad , W. S. Shehab & M. M. El-Mobayed
(2007) Synthesis of Some New Pyrimidine Derivatives of Expected Antimicrobial
Activity, Phosphorus, Sulfur, and Silicon and the Related Elements, 183:1, 115-135,
DOI: 10.1080/10426500701557286
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Phosphorus, Sulfur, and Silicon, 183:115–135, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500701557286
Synthesis of Some New Pyrimidine Derivatives
of Expected Antimicrobial Activity
A. H. Moustafa, H. A. Saad, W. S. Shehab,
and M. M. El-Mobayed
Chemistry Department, Faculty of Science, Zagazig University,
Zagazig, Egypt
2-(2-Arylvinyl)-6-methyl-4-mercapto-5-acetylpyrimidine derivatives
3a−d, were
synthesized form the reaction of the appropriate isothiocyanate derivatives 1 with
α,β-unsaturated aminoketone 2. Compound 3 was alkylated with methyl iodide,
ethyl chloroacetate and/or bromosugar to afford 6, 9, and 22a−c respectively.
Cyanoethylation of 3b afforded 6b which upon cyclization with hydrazine hy-
drate gave pyrazolopyrimidine 7. Bromination of 6b gave dibromo compound 8.
Thieno[2,3-d]pyrimidines 10 and 12 were obtained by ring closure of the alkylated
product 9 with TEA/EtOH and/or through cyclization of the hydrazide 11 with
NaOEt/EtOH. While, Thieno[2,3-d]pyrimidine 14 was obtained directly by alkyla-
tion of 3b with chloroacetone in both TEA/EtOH and Na2CO3 solution. The cycload-
dition products 15 and 16 were obtained by reaction of 3b with diethylmaleate and
/or maleic anhydride. Formation of 1,3,4-oxadiazole 17, pyrazoles18 and 19 where
obtained by treating the hydrazide 11 with carbon disulphide, triethyl orthoformate
and acetylacetone respectively. While, reaction of 11 with p-chlorobenzaldehyde re-
sulted in the Schiff’s base 20 which, cyclizes with thioglycolic acid to afford thia-
zolidone 21. Hydrolysis of 22a−c in TEA/MeOH afforded the free sugar 23a−c
.
13
1
The structures of all the new compounds were confirmed using IR, H, and
C
NMR spectra and microanalysis. Selected members of the synthesized compound
were screened for antimicrobial activity.
Keywords Pyrazolopyrimidine; thieno[2,3-d]pyrimidines; thiazolidone and bromosugar
INTRODUCTION
The 5-substituted pyrimidines and their nucleoside derivatives have
been the subject of many studies mainly due to their elevated antiviral
Received 5 May 2007; accepted 5 June 2007.
We gratefully to Dr. Hasan Abd El-Salam Assistant Prof. Of microbiology, Faculty of
Pharmacy, Zagazig University, Zagazig, Egypt for performance of the biological assay.
Also, we are indebted to the Faculty of Chemistry, University of Konstanz, Germany, for
carrying out all the analysis and spectra involved in this manuscript.
Address correspondence to H. A. Saad, Chemistry Department, Faculty of Science
Zagazig University, Zagazig, Egypt. E-mail: h saadzag@yahoo.com
115

116
A. H. Moustafa et al.
and anticancer activities.1,2 On the other hand, the functionality of
the 6-position of pyrimidines showed important anti-HIV-1 activity3,4
and antirubella virus activity.5,6 A verity of anticancer drugs made
from pyrimidine derivatives are currently in clinical use, as for ex-
ample some of these compounds applied successfully for the treat-
ment of several neoplastic diseases such as leukemia and testicular
cancer, while the effect of anticancer drugs on solid tumors is weak.
The hydrazinopyrimidine-S-carbonitrile derivatives have anti-tumoral
activities.7 Also, pyrimidine derivatives are very well known in medici-
nal chemistry for their therapeutic applications,8,9 such as, analgesic,10
antihypertensive,11 antipyretic,12 and anti-inflammatory13 drugs. Also
applications of pyrimidine compounds are extended to agriculture as a
pesticides,14 and plant growth regulators.15
In view of the pharmacological importance of thienopyrimidine16 and
in continuation of our previous work on the synthesis of biologically ac-
tive pyrimidines and thienopyrimidines, we aimed to obtain new com-
pounds with some fused pyrimidine systems, which are expected to
possess notable chemical and biological activities.
DISCUSSION
The synthesis of 5-acetyl-6-methyl-2-[(E)-2-(2-aryl)vinyl]pyrimidine-4-
thiol 3a–d has been achieved by the dehydrative cyclization of ary-
lacryloyl isothiocyanate 1 with 4-aminopent-3-en-2-one (enaminone) 2
as reported17,18 (Scheme 1).
In general, the 1H NMR spectra of 3 exhibited two doublets at δ 6.89
and 7.79 ppm for the two trans ethylenic protons (α-H) and (β-H) with
J = 15.9–16.0 Hz in addition to the signal of the thiol group at δ 14.02
ppm, respectively. The compounds 3c,d known as in literature.17,18
The irradiation of the doublet of doublet signal of thiophene protons for
3b at δ 7.18 changes the signals at δ 7.54, 7.75 ppm to singlet signals
with disappearance of the signal at 7.18 ppm and the irradiation of
the signal at δ 7.54 ppm led to the disappearance of this signal with
appearance of the two doublets at δ 7.28 and 7.75 ppm irradiation of
the signal at δ 7.75 ppm changes the signals at δ 7.18, 7.54 ppm to two
doublets with the disappearance of the signal at 7.75, and this in-turn
confirmed the structure.
The alkylation of 5-acetyl-6-methyl-2-[(E)-2-(2-thienyl)vinyl]
pyrimidine-4-thiol 3b with methyl iodide in ethanolic ethoxide gave
5-acetyl-6-methyl-4-(methylthio)-2-[(E)-2-(2-thienyl)vinyl]pyrimidine
6a, while, alkylation (cyanoethylation) with acrylonitrile in pyridine

New Pyrimidine Derivative
117
SCHEME 1
afforded Michael type adduct 5-acetyl-4-(2-propinonitrylthio)-6-
methyl-2-[(E)-2-(2-thienyl)vinyl]pyrimidine 6b and not the isomeric
products 4 and 5. An evidence in confirmation the structures of
compounds 6a,b is their conversion into pyrazolo[3,4-d]pyrimidine
derivative 7 by reaction with hydrazine hydrate in n-butanol.16,19 The
IR spectra of 7 showed the disappearance of the carbonyl group of
acetyl pyrimidine at 1688 cm−1 and also the disappearance of the
(CN) group at 2370 cm−1, and 1H, 13C NMR spectra indicated the
disappearance of the two triplets of CH2CH2 of the compound 6b at
δ 3.01, 3.55 ppm and δ 17.6, 24.8 ppm, and also the disappearance of
the signal of S-CH3 methyl group of 6a at δ 3.01 ppm, respectively
(Scheme 1).
1H NMR of 7 showed a signal at δ 2.46, 2.59 ppm for 2CH3 groups
and presence of broad signal at δ 6.38 ppm characterized for NH group
of pyrazzole ring.
Bromination of 5-acetyl-4-(2-propinonitrylthio)-6-methyl-2-[(E)-2-
(2-thienyl)vinyl]pyrimidine 6b in carbon tetrachloride gave 5-acetyl-
2-[1,2-dibromo-2-(2-thienyl)ethyl]-4-(2-propinonitrylthio)-6-methylpy-
1
rimidine 8 (Scheme 1). The structure of 8 was confirmed from its H

118
A. H. Moustafa et al.
NMR spectra, which showed the presence of two doublet protons at δ
4.92 and 5.45 ppm and the disappearance of the olefinic protons at δ
6.89 and 7.89 ppm.
SCHEME 2
Alkylation of 3b with ethyl chloroacetate under basic condition gave
the carboethoxymethylated derivatives 9 (Scheme 2). The absorption
bands in their IR spectra showed bands between 1737–1744 and 1685–
1690 cm−1 indicating the presence of the ester carbonyl and C O for
acetyl at position-5, respectively. The 1H NMR spectrum of 9 showed the
presence of the ethyl group at δ 1.19 (t) and 4.12 (q) ppm. The 13C NMR
spectrum of 9 showed signals at δ 14.1, 22.6, 31.2, 32.3, and 60.9 ppm
for the CH3 (ester), CH3 (acetyl) CH3 in 6-position, CH2S and CH2O
groups. The irradiation of the signal at δ 1.19 ppm changed the quartet
at 4.12 ppm to singlet and the irradiation at δ 7.16 ppm changed the
signals at 7.46 and 7.68 ppm to a singlet confirming the structure of 9.
Heating compound 9 in ethanol and triethylamine gave the cyclized
ethyl 4,5-dimethyl-2-[(E)-2-(2-thienyl)vinyl]thieno[2,3-d]pyrimidine-6-
carboxylate 10.
The IR of compound 10 shows the disappearance of the band at 1690
cm−1 characteristic to the C O of the acetyl group in compound 9, while
the 1H NMR spectrum of 10 showed the disappearance of the signal at δ
4.08 ppm which is characteristic to the CH2S group. Reaction of 9 with
hydrazine hydrate in boiling ethanol afforded the hydrazide 11, which
on heating under basic condition gave 4,5-dimethyl-2-[(E)-2-(2-thienyl)-
vinyl]thieno[2,3-d]pyrimidine-6-carbohydrazide 12. The structures of
1
compounds 11 and 12 were confirmed by their IR and H, 13C NMR
spectra.
Alkylation of 3b with chloroacetone in sodium carbonate solution
gave the thieno[2,3-d]pyrimidine 14 not the expected S-alkyl product

New Pyrimidine Derivative
119
13, compound 14 was proved by refluxing 3b with chloroacetone in
presence of absolute ethanol and few drops of triethylamine, where,
the same product was obtained (Scheme 3).
SCHEME 3
1
The H NMR spectrum of 14 showed the presence of three methyl
groups at δ 2.61, 2.86, and 2.91 ppm, and absence of SCH2 group, re-
spectively. The 13C NMR spectrum of 14 showed signals at δ 16.3, 24.6,
and 30.8 ppm for the 3CH3 groups.
Treatment of 3b with diethyl maleate in pyridine and few drops
of piperidine gave a product assigned the structure of diethyl 4,5-
dimethyl-2-[(E)-2-(2-thienyl)vinyl]-7H-thiopyrano[2,3-d]pyrimidine-
6,7-dicarboxylate 15. This cyclization has been proved by 1H NMR
spectrum, which exhibited two triplets at δ 1.20, 1.29 ppm and two
quartets at 4.19, 4.23 ppm for two unsymmetrical ethyl groups and
methinyl proton at δ 3.80 ppm. The IR spectrum gave a two carbonyl
bands at 1735 and 1686 cm−1. 4,5-Dimethyl-2-[(E)-2-(2-thienyl)vinyl]-
6H-furo[3ꢀ,4ꢀ,5,6]thiopyrano[2,3-d]pyrimidine-6-(8aH)dione 16 was
obtained by cycloaddition of compound 3b with maleic anhydride in

120
A. H. Moustafa et al.
refluxing xylene and few drops of piperidine. The 1H NMR of 16 showed
the presence of a singlet at δ 3.80 ppm for methinyl proton and two
singlet signal at δ 2.56, 2.68 ppm for 2CH3 groups. The IR spectrum
gave a broad band between 1810–1702 cm−1 characteristics for two
anhydride carbonyl groups.
2-({5-Acetyl-6-methyl-2-[(E)-2-(2-thienyl)vinyl]pyrimidin-4-yl}thio)-
acetylhydrazide 11 was reacted with carbon disulfide in pyridine to
afford the corresponding 5-acetyl-4-{[(5-mercapto-1,3,4-oxadiazol-2-
yl)methyl]thio}-6-methyl-2-[(E)-2-(2-thienyl)vinyl]pyrimidine
17.19
The IR spectrum of 17 showed bands at 2370, 1685 cm−1 for SH and
CO stretching frequencies, and the 1H NMR spectrum showed a signal
at δ 2.45, 2.88, and 12.52 ppm for the CH3, CH3CO, and SH groups
(Scheme 4).
SCHEME 4
Treatment of carbohydrazide 11 with triethyl orthoformate in
acetic acid gave 5-acetyl-6-methyl-4[(3-oxo-pyrazol-4-yl)thio]-2-[(E)-2-
1
(2-thienyl)vinyl]-pyrimidine 18. The H NMR spectrum of 18 showed
signals at δ 2.48, 2.93, and 6.48 ppm for CH3, CH3CO, and pyrazole
protons. 13C NMR spectrum showed two carbon sp3 and 14 lines sp2

New Pyrimidine Derivative
121
characterized all carbon atoms in the compound and two carbonyl
groups. The IR spectrum showed the bands at 1711 and 1653 cm−1
indicated the presence of two carbonyl groups, respectively. Reaction
of 11 with acetylacetone in ethanol and sodium ethoxide gave the
corresponding 5-acetyl-(4-{[2-(3,5-dimethyl-1H-pyrazol-1-yl)-2-oxoeth-
yl]thio}-6-methyl-2-[(E)-2-(2-thienyl)vinyl]pyrimidine 1919 (Scheme 4).
The absorption bands in its IR spectrum showed a broad band at 1684
cm−1 for 2C O groups, with the disappearance of NH and NH2 bands,
while the 1H NMR spectrum gave signals at δ 2.30, 2.61, 281, 3.12, and
3.91 ppm, which characterized for 4CH3 and CH2S groups, respectively.
Its 13C NMR spectrum showed signals at δ 21.5, 32.1, 24.3, 30.2, and
51.5 ppm for four CH3 and CH2S groups.
When carbohydrazide 11 was reacted with p-chlorobenzaldehyde in
ethanol in presence of few drops of acetic acid gave 2({5-acetyl-6-
methyl-2-[( E)-2-(2-thienyl)-vinyl]pyrimidin-4-yl}thio-Nꢀ-[(1Z)-(4-chlo-
rophenyl)-methylene]acetohydrazide 2019,20 (Scheme 4).
The absorption bands in its IR spectrum showed bands at 1719 and
1653 cm−1 indicating the presence of ketone C O and amide C O. The
1H NMR spectrum of 22 showed the presence of signals at 2.71, 2.89,
and 4.25 for 2 CH3 and CH2S beside two doublet signals at δ 7.32, 7.79
ppm with (J = 9.8 Hz) characteristic to p-chlorophenyl and at δ 8.79
and 12.01 ppm for CH N and NH groups, respectively.
Heating compound 20 with thioglycolic acid in boiling pyridine
gave 2({5-acetyl-6-methyl-2-[(E)-2-(2-thieyl)vinyl]pyrimidin-4-yl}thio)-
1
N-[2-(4-chlorophenyl)-4-oxo-1,3-thiazolidin-3-yl]acetamide 21. The H
NMR spectrum of 21 showed the signals at δ 2.68, 2.86, 4.21, 4.32, 5.98
ppm characterized for 2CH3, CH2S, SCHAr, COCH2S of (thiazolidine
ring) and presence of two doublet for p-chlorophenyl at δ 7.35, 7.80 ppm
with J = 9.70 Hz, with presence of singlet signal at δ 10.21 ppm for NH
group, respectively (Scheme 4).
Reaction of 3b–d with 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl-
bromide in the presence of aqueous potassium hydroxide gave 5-
acetyl-6-methyl-2[(E)-2-(2-aryl)vinyl]-4-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-tetra-O-acetyl-β-D-
glucopyranosylthio)pyrimidine 22a–c.21,22 The structure of compounds
22a–c was confirmed on the basis of their elemental analysis and
spectral data, their IR spectra showed a broad band at 1765–1745
cm−1 for the acetoxy carbonyl groups in addition to absorption band
at 1696 cm−1 due to the carbonyl of pyrimidine. Also, the 1H NMR
spectrum of 22a showed the presence of singlet signals at δ 1.76, 1.96,
2.00, 2.02 ppm characteristic to the presence of four OAc, in addition to
two methyl groups at δ 2.49, 2.58 ppm. In 24b the IR spectrum showed
a broad band at 1748 and 1698 cm−1 characteristic to the acetoxy
carbonyl and the carbonyl in pyrimidine ring. Its 1H NMR showed

122
A. H. Moustafa et al.
SCHEME 5
four OAc in addition to two methyl groups in pyrimidine ring and two
doublet for p-chlorophenyl at δ 7.51, 7.82 ppm with coupling constant
(J = 9.8 Hz). The IR spectrum of 22c showed bands at 1755–1728 cm−1
for acetoxy carbonyl in addition to a band at 1660 cm−1 for a carbonyl
1
in pyrimidine ring. It’s H NMR showed a singlet signals at δ 1.84,
2.03, 2.04, 2.07, 2.47, and 2.57 ppm characteristic to four (OAc) and
two (CH3) groups, respectively.
In compound 22c, the irradiation of signal at δ 3.99 ppm change the
signals at δ 4.15 ppm to doublet of doublet and at δ 5.13 ppm to doublet,
and irradiation the signal at δ 5.13 ppm change the signals at δ 3.99 and
5.41 ppm to doublet. Irradiation of the signal at δ 5.77 ppm changed
the signal at δ 6.04 ppm into a singlet signal, also the irradiation of
the signal at δ 5.41 ppm changed the signals at δ 5.13, 5.27 ppm into
a doublet. The irradiation of signal at δ 6.04 ppm change the signal
at δ 5.27 ppm into a doublet and disappears the signal at d 6.04 ppm,
this assigned the position of sugar protons. The irradiation of signal
at δ 8.01 ppm change the signal at δ 7.17 ppm to a singlet signal with
disappearance of the signal at δ 7.17 ppm, which assigned the structure
of trans ethylenic protons.13C NMR of 22c shows signals at δ 20.5, 20.6,
20.7, 22.7, 29.7, 31.6, 62.2, 68.4, 69.1, 74.1, 76.5, and 80.3 ppm charac-
teristics to the sugar moiety and two methyl groups in pyrimidine ring.
All sugar protons are irradiated by 1H NMR spectrometer LA 400 MHz
and illustrated in the experimental section. Hydrolysis of compounds
22a–c in methanol in presence of triethylamine afforded the product
5-acetyl-6-methyl-2-[(E)-2-(aryl)vinyl]-4-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-tetrahydroxy-β-D-
glucopyranosylthiopyrimidine 23a–c. The 1H NMR of 23a–c in
(DMSO/D2O) were carried out to prove the hydrolysis and are shown
in the experimental section.

New Pyrimidine Derivative
123
TABLE I Antimicrobial Activity of Compounds 3b, 10, 15, 17, and 23a
Comp.
No.
S.
aureus
S.
lutea
B.
subtilis
P.
K.
E.
coli
C.
aeruginosa
peneumonie
albicans
3b
10
15
17
23a
Penicillin
Nystatin
—
10
12
10
—
15
—
25
25
20
25
—
17
—
20
18
15
20
—
20
—
20
20
15
20
—
13
—
15
15
10
15
—
14
—
16
17
18
15
—
15
—
—
—
—
20
—
—
15
Inhibition zones = mm; minimum inhibitory concentration = µg/ml.
The IR spectrum of 23a–c showed the presence of a very broad band
at 3400 cm−1 characterized for the hydroxyl groups of sugar moiety
in addition to the carbonyl group of pyrimidine ring at 1689 cm−1
respectively.
,
The results of the antimicrobial activity of compounds 3b, 10, and
15 showed interesting degrees of antibacterial activity. Penicillin was
used as a reference to evaluate the potency of the tested compounds.
Compounds 3b, 10, and 15 showed higher antibacterial activity than
the standard drug (penicillin). Compound 23a did not show any activity
against the tested microorganisms, while, compound 17 showed higher
activity against C. albicans than the standard drug (Nystatin), and
was higher activity against Gram +ve, and Gram −ve bacteria. The
results of biological activities encourage further work on such a ring
system (Table 1).
EXPERIMENTAL
Melting points were determined with a melt temperature apparatus
and are uncorrected. IR spectra were recorded with a Perkin-Elmer
1
model 1600 FTIR spectrometer as KBr discs. The H and 13C NMR
spectra were determined with a JEOL-JNM-LA 400 and 100 MHz spec-
trometer. The chemical shifts are expressed on the δ (ppm) scale using
TMS as an internal standard. Elemental analyses were determined on
a Perkin-Elmer 240 (microanalysis).
5-Acetyl-6-methyl-2-[(E)-2-(2-aryl)vinyl]pyrimidine-4-thiol
(3a–d)—General Procedure
A mixture of arylacryloyl isothiocyanate 123 (10 mmol) and 4-
aminopent-3-en-2-one (enaminone) 2 (1.98 ml, 20 mmol) in 20 ml dry

124
A. H. Moustafa et al.
acetone was stirred for 3 h, then, an equivalent amount of sodium
hydroxide solution (0.4 g/10.0 ml) was added. After the reaction was
completed, neutralized with hydrochloric acid (6 ml, 30% soln.) to com-
plete precipitation, the solid thus separated was collected by filtration,
washed several times with water, dried, and recrystallized from ethanol.
5-Acetyl-6-methyl-2-[(E)-2-(2-naphthyl)vinyl]pyrimidine-4-thiol
(3a)
Yellow powder (yield: 45%), m.p. 230–232◦C. IR (KBr): 2371 (SH),
1
1690 (C O), 1634 (C N) cm−1. H NMR (DMSO-d6): δ = 2.22 (s, 3H,
CH3), 2.55 (s, 3H, CH3CO), 7.30 (d, 1H, J = 16.0 Hz, HβC CH), 7.58–
8.19 (m, 7H, Ar-H), 8.12 (d, 1H, J = 16.0 Hz, C CHα) and 13.2 (s, 1H,
SH).13C NMR (DMSO-d6): δ = 21.6, 30.2 (2 CH3), 118.8, 123.1, 126.8,
127.4, 127.6, 128.4, 128.7, 130.0, 131.9, 132.8, 133.6, 135.7, 141.2, 154.9,
(C C and Ar-C), 156.8, 178.2, 202.1 (2 CN and C S). Anal. Calcd. for
C19H16N2OS (320.4): C, 71.22; H, 5.03; N, 8.74. Found: C, 71.03; H, 5.24;
N, 8.81.
5-Acetyl-6-methyl-2-[(E)-2-(2-thienyl)vinyl]pyrimidine-4-thiol
(3b)
Yellow powder (yield: 44%), m.p. 200–202◦C. IR (KBr): 2369 (SH),
1686 (C O) and 1624 (CN) cm−1. 1H NMR (DMSO-d6): δ = 2.17 (s, 3H,
CH3), 2.53 (s, 3H, CH3CO), 6.91 (s, 1H, J =15.9 Hz, HC CHα), 7.18
(dd, 1H, J = 3.50 Hz), 7.54 (d, 1H, J = 3.5 Hz), 7.75 (d, 1H, J = 5.07
Hz), 8.15 (d, 1H, J = 16.0 Hz, HβC CH) and 11.36 (s, 1H, SH). The
irradiation of the doublet of doublet signal of thiophene protons for 3b
at δ 7.18 changes the signals at δ 7.54, 7.75 ppm to a singlet signals with
disappearance of the signal at 7.18 ppm and the irradiation of the signal
at δ 7.54 ppm led to the disappearance of this signal with appearance
of the two doublets at δ 7.28 and 7.75 ppm irradiation of the signal at δ
7.75 ppm changes the signals at δ 7.18, 7.54 ppm to two doublets with
the disappearance of the signal at 7.75 as illustrated in the spectrum,
and this intern confirmed the structure.13C NMR (DMSO-d6): δ = 21.5
(CH3), 30.3 (CH3CO), 117.0, 128.6, 129.8, 132.3, 134.2, 135.4, 139.6,
154.7 (Ar-C), 165.4 (CN), 181.7 (C O) and 202.1 (C S). Anal. Calcd. for
C13H12N2OS2 (276.3): C, 56.49; H, 4.38; N, 10.14. Found: C, 56.61; H,
4.37; N, 10.25.
5-Acetyl-6-methyl-4-(methylthio)-2-[(E)-2-(2-thienyl)vinyl]
pyrimidine (6a)
A solution of compound 3b (2.76 g, 10 mmol) and methyl iodide (1.4
g, 10 mmol) in ethanolic sodium ethoxide (0.23 g/20 ml ethanol), the
reaction mixture was refluxed for 1 h, then allowed to cool and poured

New Pyrimidine Derivative
125
into ice water. The solid product obtained after acidification with hy-
drochloric acid (6 ml, 30% soln.) was filtered off, washed with water,
dried, recrystallization from ethanol to afford a colorless powder (yield:
80%) m.p. 90–92◦C. 1H NMR (DMSO-d6): δ = 2.41 (s, 3H, CH3), 2.58 (s,
3H, CH3CO), 3.01 (s, 3H, SCH3), 6.91 (d, 1H, J = 16.0 Hz, HC CHα),
7.17 (dd, 1H, J = 3.52 Hz, thiophene-H), 7.50 (d, 1H, J = 3.50 Hz,
thiophene-H), 7.68 (d, 1H, J = 5.10 Hz, thiophene-H), 8.14 (d, 1H, J =
16.0 Hz, HβC CH).13C NMR (DMSO-d6): δ = 22.2, 25.3, 31.2 (3 CH3),
124.2, 128.1, 129.0, 130.2, 132.1, 134.2, 140.8, 161.2, 162.0, 162.8, 179.8
(Ar-C, 2 C N and C O). Anal. Calcd. for C14H14N2OS2 (290.4): C, 57.90;
H, 4.86; N, 9.65. Found: C, 58.01; H, 4.87; N, 9.75.
5-Acetyl-4-(2-propinonitrylthio)-6-methyl-2-[(E)-2-(2-
thienyl)vinyl]pyrimidine (6b)
To a solution of compound 3c (2.76 g, 10 mmol) in (20 ml) pyridine,
acrylonitrile (0.53, 10 mmol) was added and the reaction mixture was
stirred at room temperature for 2 h, then poured into ice water. The solid
product obtained after acidification with hydrochloric acid (6 ml, 30%
soln.), filtered off, washed with water, dried, and recrystallized from
benzene to afford an orange powder (yield: 33%), m.p. 108–110◦C. IR
1
(KBr): 2370 (C≡N), 1687 (C O) cm−1. H NMR (DMSO-d6): δ = 2.41
(s, 3H, CH3), 2.59 (s, 3H, CH3CO), 3.01 (t, 2H, J = 6.60 Hz, CH2),
3.55 (t, 2H, J = 6.60 Hz, CH2), 6.90 (d, 1H, J = 16.0 Hz, HC CHα),
7.17 (dd, 1H, J = 3.51 Hz, thiophene-H), 7.51 (d, 1H, J = 3.60 Hz,
thiophene-H), 7.68 (d, 1H, J = 5.08 Hz, thiophene-H), 8.14 (d, 1H, J =
16.0 Hz, HβC CH). 13C NMR (DMSO-d6): δ = 17.6, 22.3, 24.8, 31.2
(2 CH3, 2 CH2), 119.2 (C≡N), 125.0, 128.4, 128.5, 129.2, 130.4, 131.8,
140.2, 161.3, 161.8, 163.2, 202.0 (Ar-C, 2 C N and C O). Anal. Calcd.
for C16H15N3OS2 (329.4): C, 58.33; H, 4.59; N, 12.76. Found: C, 58.50;
H, 4.29; N, 12.82.
3,4-Dimethyl-6-[(E)-2-(2-thienyl)vinyl]-1H-pyrazolo[3,4-
d]pyrimidine (7)
A mixture of appropriate S-alkylated derivatives 6a,b (10 mmol) and
hydrazine hydrate 98% (0.2 ml, 40 mmol) in n-butanol (10 ml) was
heated under reflux for 3 h. The precipitate obtained upon cooling was
collected, dried and recrystallized from ethanol to afford a pale yellow
powder (yield: 56%) m.p. 228–229◦C. 1H NMR (DMSO-d6): δ = 2.46 (s,
3H, CH3), 2.59 (s, 3H, CH3), 6.38 (br, 1H, NH), 6.91 (d, 1H, J = 16.0 Hz,
HC CHα), 7.17 (dd, 1H, J = 3.52 Hz, thiophene-H), 7.50 (d, 1H, J =
3.50 Hz, thiophene-H), 7.68 (d, 1H, J = 5.10 Hz, thiophene-H), 8.14
(d, 1H, J = 16.0 Hz, HβC=CH). 13C NMR (DMSO-d6): δ = 20.8, 31.0 (2
CH3), 125.0, 128.4, 128.5, 129.2, 130.4, 131.8, 140.1, 161.3, 161.8, 163.1,

126
A. H. Moustafa et al.
166.8 (Ar-C and 3 C N). Anal. Calcd. for C13H12N4S (256.3): C, 60.91;
H, 4.72; N, 21.86. Found: C, 61.03; H, 4.80; N, 21.7.
5-Acetyl-2-[1,2-dibromo-2-(2-thienyl)ethyl]-4-(2-
propinonitrylthio)-6-methylpyrimidine (8)
To a stirred suspension of compound 6b (3.29 g, 10 mmol) in (20
ml) carbon tetrachloride, bromine (1.6 g, 10 mmol) in (10 ml) carbon
tetrachloride was added dropwise at room temperature during 30 min.
After complete addition, the stirring was continued for 3 h, the solid
thus separated was collected, dried, and recrystallized from ethanol to
give a pale yellow powder (yield: 60%), m.p. 120–123◦C (dec.). 1H NMR
(DMSO-d6): δ = 2.41 (s, 3H, CH3), 2.58 (s, 3H, CH3CO), 3.01 (t, 2H, J =
6.60 Hz, CH2), 3.55 (t, 2H, J = 6.60 Hz, CH2), 4.91 (d, 1H, J = 12.6
Hz, CHBr), 5.45 (d, 1H, J = 12.7 Hz, CHBr), 7.17 (dd, 1H, J = 3.51 Hz,
thiophene-H), 7.51 (d, 1H, J = 3.50 Hz, thiophene-H), 7.68 (d, 1H, J =
5.10 Hz, thiophene-H).13C NMR (DMSO-d6): δ = 17.6, 22.3, 24.8, 31.2,
36.2, 38.8 (2 CH3, 2 CH2, 2 CHBr), 119.2 (C≡N), 125.0, 128.5, 129.2,
131.8, 140.2, 161.3, 161.8, 162.1, 202.0 (Ar-C, 2 C N and C S). Anal.
Calcd. for C16H15Br2N3OS2 (489.2): C, 39.28; H, 3.09; N, 8.59. Found:
C, 39.40; H, 3.12; N, 8.54.
Ethyl (5-acetyl-6-methyl-2-[(E)-2-(aryl)vinyl]pyrimidin-4-
ylthio)acetate (9)
A mixture of thiol derivative 3b (10 mmol), sodium acetate (1.00
g, 12 mmol) and ethyl chloroacetate (1.22 g, 10 mmol) in ethanol (20
ml) was heated under reflux for 2 h, then allowed to cool, poured into
water. The precipitate formed was collected, washed with water, dried,
and recrystallized from petroleum ether 60–80. A pale yellow powder
(yield: 36%) m.p. 90–92◦C. IR (KBr): 1744, 1690 (2 C O) and 1623 (C N)
cm−1. 1H NMR (DMSO-d6): δ = 1.19 (t, 3H, J = 7.03 Hz, CH3), 2.45 (s,
3H, CH3), 2.60 (s, 3H, CH3CO), 4.08 (s, 2H, CH2S), 4.12 (q, 2H, J =
7.03 Hz, CH2), 6.84 (d, 1H, J = 16.0 Hz, HβC CH), 7.16 (dd, 1H, J =
3.50 Hz, thiophene-H), 7.46 (d, 1H, J = 3.50 Hz, thiophene-H), 7.68 (d,
1H, J = 5.07 Hz, thiophene-H), 8.08 (d, 1H, J = 16.0 Hz, HC CHα).
13C NMR (DMSO-d6): δ = 14.1, 22.6, 31.2, 32.3, 60.9 (3 CH3, CH2S
and OCH2), 125.0, 128.3, 128.5, 128.6, 131.9, 140.2, 161.6, 161.8, 164.3,
168.6, 201.6 (Ar-C, 2 C N and 2C O). Anal. Calcd. for C17H18N2O3S2
(362.5): C, 56.33; H, 5.01; N, 7.73. Found: C, 56.52; H, 4.95; N, 7.82.
Ethyl 4,5-dimethyl-2-[(E)-2-(2-thienyl)vinyl]thieno[2,3-
d]pyrimidine-6-carboxylate (10)
To a solution of compound 9 (3.62 g, 10 mmol) in ethanol, a few drops
of triethylamine was added and then heated under reflux for 1 h, cooled,

New Pyrimidine Derivative
127
and poured into ice water. The solid product formed was filtered off,
dried, and recrystallized from ethanol to afford a yellow crystals (yield:
50%) m.p. 296–297◦C. IR (KBr): 1703 (C O), 1621 (C N) and 1180
(C O) cm−1.1H NMR (DMSO-d6): δ = 1.18 (t, 3H, J = 7.03 Hz, CH3),
2.91 (s, 3H, CH3), 2.94 (s, 3H, CH3), 4.19 (q, 2H, J = 7.03 Hz, CH2), 6.84
(d, 1H, J = 16.0 Hz, HβC CH), 7.17 (dd, 1H, J = 3.50 Hz, thiophene-
H), 7.46 (d, 1H, J = 3.5 Hz, thiophene-H), 7.68 (d, 1H, J = 3.51 Hz,
thiophene-H), 8.09 (d, 1H, J = 16.0 Hz, HC CHα).13C NMR (DMSO-
d6): δ = 14.8, 22.7, 23.8, 52.9 (3 CH3 and OCH2), 125.4, 125.9, 127.9,
128.1, 128.3, 130.1, 131.0, 139.4, 140.5, 159.9, 163.7, 164.7, 167.1 (Ar-C,
2 C N and C O). Anal. Calcd. for C17H16N2O2S2 (344.4): C, 59.28; H,
4.68; N, 8.13. Found: C, 59.26; H, 4.86; N, 8.50.
2-({5-Acetyl-6-methyl-2-[(E)-2-(2-thienyl)vinyl]pyrimidin-4-
yl}thio)acetohydrazide (11)
To a solution of compound 9 (3.62 g, 10 mmol) hydrazine hydrate 98%
(1.3 ml/40 mmol) was added and the reaction mixture was refluxed for
1 h, then allowed to cool. The solid product was filtered off and recrys-
tallized from ethanol to give a colorless crystals (yield: 42%) m.p. 210–
212◦C. IR (KBr): 3400 (NH), 1710, 1695 (2 C O), 1621 (C N) cm−1.1H
NMR (DMSO-d6): δ = 2.41 (s, 3H, CH3), 2.91 (s, 3H, CH3CO), 3.42 (br,
2H, NH2), 3.98 (s, 2H, CH2S), 6.83 (d, 1H, J = 16.0 Hz, HβC CH), 7.17
(dd, 1H, J = 3.50 Hz, thiophene-H), 7.46 (d, 1H, J = 3.51 Hz, thiophene-
H), 7.68 (d, 1H, J = 5.08 Hz, thiophene-H), 8.08 (d, 1H, J = 16.0 Hz,
HC CHα), 9.08 (br, 1H, NH).13C NMR (DMSO-d6): δ = 15.1, 23.8, 52.7
(2CH3 and CH2S), 125.4, 125.9, 127.9, 128.1, 128.4, 130.1, 131.0, 139.4,
140.5, 163.7, 164.7, 167.2 (Ar-C, 2 C N and 2 C O). Anal. Calcd. for
C15H16N4O2S2 (348.4): C, 51.70; H, 4.63; N, 16.08. Found: C, 52.61; H,
4.58; N, 16.12.
4,5-Dimethyl-2-[(E)-2-(2-thienyl)vinyl]thieno[2,3-d]pyrimidine-
6-carbohydrazide (12)
To a solution of compound 11 (3.48 g, 10 mmol) in ethanol (20 ml),
sodium ethoxide (0.23 g/10 ml ethanol) was added and the solution
was heated under reflux for 1 h, cooled, poured into water, neutral-
ized with hydrochloric acid (6 ml, 30% soln.). The solid product formed
was collected by filtration, washed with water and recrystallized from
ethanol affording a colorless powder (yield: 63%) m.p. 240–241◦C. IR
(KBr): 3420 (NH), 1676 (C O) cm−1.1H NMR (DMSO-d6): δ = 2.90 (s,
3H, CH3), 2.93 (s, 3H, CH3), 3.76 (br, 2H, NH2), 6.83 (d, 1H, J = 16.0
Hz, HβC CH), 7.17 (dd, 1H, J = 3.50 Hz, thiophene-H), 7.46 (d, 1H,
J = 3.50 Hz, thiophene-H), 7.68 (d, 1H, J = 5.09 Hz, thiophene-H),
8.09 (d, 1H, J = 16.0 Hz, HC CHα), 12.1 (br, 1H, NH). Anal. Calcd. for

128
A. H. Moustafa et al.
C15H14N4OS2 (330.4): C, 54.52; H, 4.27; N, 16.96. Found: C, 54.59; H,
4.32; N, 16.86.
6-Acetyl-4,5-dimethyl-2-[(E)-2-(2-thienyl)vinyl]thieno[2,3-
d]pyramidine (14)
Method A. A mixture of compound 3c (2.76 g, 10 mmol) in aque-
ous sodium carbonate (10 ml, 10% soln.) and chloroacetone (1.10 g,
12 mmol) was stirred for 3 h at room temperature and neutralized with
hydrochloric acid (6 ml, 30% soln.). The solid product formed was col-
lected by filtration, washed with water and recrystallized from ethanol
affording a pale yellow crystals (yield: 45%) m.p. 253–255◦C.
Method B. A mixture of compound 3c (2.76 g, 10 mmol) and
chloroacetone (1.10 g, 12 mmol) in ethanol (20 ml) and few drops of
triethylamine was allowed to reflux for 1 h after that, the reaction mix-
ture was cooled. The solid precipitated filtered off, washed with water
and recrystallized from ethanol to afford pale yellow crystals (yield:
35%) m.p. 254–256◦C.
IR (KBr): 1671 (C O), 1622 (C N) cm−1.1H NMR (DMSO-d6): δ =
2.61 (s, 3H, CH3), 2.86 (s, 3H, CH3), 2.91 (s, 3H, CH3), 6.92 (d, 1H, J =
16.0 Hz, HβC CH), 7.12 (dd, 1H, J = 3.50 Hz, thiophene-H), 7.46 (d,
1H, J = 3.50 Hz, thiophene-H), 7.61 (d, 1H, J = 5.08 Hz, thiophene-
H), 8.10 (d, 1H, J = 16.0 Hz, HC CHα).13C NMR (DMSO-d6): δ = 16.3,
24.6, 30.8 (3CH3), 125.7, 128.0, 128.3, 128.4, 129.7, 131.2, 134.5, 137.5,
140.6, 160.2, 165.3, 167.3, 192.6 (Ar-C, 2 C N and C O). Anal. Calcd.
for C16H14N2OS2 (314.4): C, 61.12; H, 4.49; N, 8.91. Found: C, 61.18; H,
4.38; N, 9.01.
Diethyl 4,5-dimethyl-2-[(E)-2-(2-thienyl)vinyl]-7H-
thiopyrano[2,3-d]pyramid-ine-6,7-dicarboxylate (15)
A mixture of compound 3b (2.76, 10 mmol), diethyl maleate (1.70 g,
10 mmol) in pyridine (20 ml) and few drops of piperidine was reflux for 6
h, poured into ice water, then the pH was adjusted to 7 with hydrochlo-
ric acid. The solid separated was filtered off, washed with water, and
recrystallized from benzene affording pale yellow crystals (yield: 45%)
m.p. 240–241◦C. IR (KBr): 1735 (C O) ester, 1686 (C O) conjugated
ester, 1623 (C N), 1155 (C O) cm−1.1H NMR (DMSO-d6): δ = 1.20 (t,
3H, J = 7.03 Hz, CH3), 1.29 (t, 3H, J = 7.03 Hz, CH3), 2.46 (s, 3H,
CH3), 2.61 (s, 3H, CH3), 3.80 (s, 1H, methinyl-H), 4.19 (q, 2H, J = 7.03
Hz, CH2), 4.23 (q, 2H, J = 7.03 Hz, OCH2), 6.92 (d, 1H, J = 16.0 Hz,
HβC CH), 7.12 (dd, 1H, J = 3.50 Hz, thiophene-H), 7.46 (d, 1H, J =
3.50 Hz, thiophene-H), 7.61 (d, 1H, J = 5.08 Hz, thiophene-H), 8.10 (d,
1H, J = 16.0 Hz, HC CHα). Anal. Calcd. for C21H22N2O4S2 (430.5): C,
58.58; H, 5.15; N, 6.51. Found: C, 58.50; H, 5.18; N, 6.61.

New Pyrimidine Derivative
129
4,5-Dimethyl-2-[(E)-2-(2-thienyl)vinyl]-6H-furo
[3ꢀ,4ꢀ,5,6]thiopyrano-[2,3-d]pyrimidine-6,8-(8aH)-dione (16)
A mixture of compound 3c (2.76 g, 10 mmol), maleic anhydride (0.9
g, 10 mmol) and few drops of piperidine in (20 ml) xylene was reflux
for 16 h, the solid product that obtained after cooling was collected by
filtration, dried and recrystallized from benzene to afford a pale yellow
crystals (yield: 42%) m.p. 260–262◦C. IR (KBr): 1810–1702 (br), (2C O)
anhydride, 1602 (C N) cm−1.1H NMR (DMSO-d6): δ = 2.56 (s, 3H, CH3),
2.68 (s, 3H, CH3), 3.81(s, 1H, methinyl-H), 6.92 (d, 1H, J = 16.0 Hz,
HβC CH), 7.12 (dd, 1H, J = 3.50 Hz, thiophene-H), 7.46 (d, 1H, J =
3.50 Hz, thiophene-H), 7.61 (d, 1H, J =5.08 Hz, thiophene-H), 8.14 (d,
1H, J = 16.0 Hz, HC CHα). Anal. Calcd. for C17H12N2O3S2 (356.4): C,
57.29; H, 3.39; N, 7.86. Found: C, 57.38; H, 3.48; N, 7.92.
5-Acetyl-4-[(5-mercapto-1,3,4-oxadiazol-2-yl)methyl]thio-6-
methyl-2-[(E)-2-(2-thienyl)vinyl]pyrimidine (17)
To a solution of compound 11 (3.48 g, 10 mmol) in pyridine (20 ml),
carbon disulfide (1 ml) was added and the reaction mixture heated
under reflux for 12 h, cooled, poured into ice-water, then the pH was ad-
justed to 7 with hydrochloric acid, the solid separated was filtered off,
washed with water, dried and recrystallized with methanol to give a
pale brown powder (yield: 46%), m.p. 118–120◦C. IR (KBr): 2370 (SH),
1685 (C O), 1623 (C N) cm−1.1H NMR (DMSO-d6): δ = 2.45 (s, 3H,
CH3), 2.88 (s, 3H, COCH3), 4.36 (s, 2H, SCH2), 6.94 (d, 1H, J = 16.0
Hz, HβC CH), 7.13 (dd, 1H, J = 3.50 Hz, thiophene-H), 7.52 (d, 1H,
J = 3.50 Hz, thiophene-H), 7.65 (d, 1H, J = 5.08 Hz, thiophene-H),
8.19 (d, 1H, J = 16.0 Hz, HC CHα), 12.52 (s, 1H, SH). Anal. Calcd. for
C16H14N4O2S3 (390.5): C, 49.21; H, 3.61; N, 14.35. Found: C, 49.28; H,
3.68; N, 14.50.
5-Acetyl-6-methyl-4-[(3-oxo-pyrazol-4-yl)thio]-2-[(E)-2-(2-
thienyl)vinyl]pyrimidine (18)
A mixture of compound 11 (3.48 g, 10 mmol) and triethyl orthofor-
mate (1.40 g, 10 mmol) in acetic acid (20 ml) was refluxed for 3 h, then
allowed to cool, and poured into water. The solid product formed was
collected by filtration, washed, dried, and recrystallized from ethanol
affording pale yellow crystals (yield 56%) m.p. 120–122◦C. IR (KBr):
1711 (C O), 1653 (C O) cm−1 (for pyrazolone ring).1H NMR (DMSO-
d6): δ = 2.48 (s, 3H, CH3), 2.93 (s, 3H, CH3CO), 6.48 (s, 1H, pyrazol-
H), 6.94 (d, 1H, J = 16.0 Hz, HβC CH), 7.13 (dd, 1H, J = 3.50 Hz,
thiophene-H), 7.52 (d, 1H, J = 3.50 Hz, thiophene-H), 7.65 (d, 1H, J =
5.08 Hz, thiophene-H), 8.19 (d, 1H, J = 16.0 Hz, HC CHα).13C NMR

130
A. H. Moustafa et al.
(DMSO-d6): δ = 21.5, 30.2 (2 CH3), 117.0, 118.3, 128.5, 128.6, 129.8,
132.3, 134.2, 135.4, 139.1, 139.6, 154.7, 165.4, 178.4, 181.7 (Ar-C, 2
C N and 2C O). Anal. Calcd. for C16H12N4O2S2 (356.4): C, 53.92; H,
3.39; N, 15.72. Found: C, 54.01; H, 3.48; N, 15.89.
5-Acetyl-(4-{[2-(3,5-dimethyl-1H-pyrazol-1-yl)-2-oxo-ethyl]
thio}-6-methyl-2-[(E)-2-(2-thienyl)vinyl]pyrimidine (19)
To a mixture of compound 11 (3.48, 10 mmol) and acetylacetone (1
ml, 10 mmol) in ethanol (20 ml), sodium ethoxide solution was added
(0.23 g, 10 ml ethanol) and the reaction mixture was heated under reflux
for 3 h., cooled, diluted with water and acidified with hydrochloric acid
(6 ml, 30% solution). The solid that separated was filtered off, dried
and recrystallized from ethanol affording orange crystals (yield: 30%)
m.p. 268–269◦C. IR (KBr): 1684 (br) (2C O), 1611 (C N) cm−1.1H NMR
(DMSO-d6): δ = 2.30 (s, 3H, CH3), 2.61 (s, 3H, CH3CO), 2.81 (s, 3H,
CH3), 3.12 (s, 3H, CH3), 3.91 (s, 2H, SCH2), 6.94 (d, 1H, J = 16.0 Hz,
HβC CH), 7.13 (dd, 1H, J = 3.50 Hz, thiophene-H), 7.52 (d, 1H, J =
3.50 Hz, thiophene-H), 7.65 (d, 1H, J = 5.08 Hz, thiophene-H), 8.19 (d,
1H, J = 16.0 Hz, HC CHα).13C NMR (DMSO-d6): δ = 21.5, 32.1, 24.3,
30.2 (4 CH3), 51.5 (SCH2), 117.1, 118.3, 128.6, 128.7, 129.9, 132.2, 132.6,
134.2, 135.4, 139.1, 139.6, 154.7, 165.5, 178.4, 181.8 (Ar-C, 3 C N and
2 C O). Anal. Calcd. for C20H20N4O2S2 (412.5): C, 58.23; H, 4.89; N,
13.58. Found: C, 58.52; H, 4.80; N, 13.59.
2-(5-Acetyl-6-methyl-2-[(E)-2-(2-thienyl)vinyl]pyrimidin-4-
ylthio)-Nꢀ-[(1Z)-(4-chlorophenyl)methylene]acetohydrazide
(20)
A mixture of compound 11 (3.48 g, 10 mmol), p-chlorobenzaldehyde
(1.40 g, 10 mmol) in ethanol (20 ml) and acetic acid (1 ml) was refluxed
for 3 h. The solid product formed after cooling was collected by filtration
washed with water, dried, and recrystallized from ethanol affording a
colorless powder (yield: 72%) m.p. 279–280◦C. IR (KBr): 3158 (NH),
1719 (C O), 1653 (C O) amide, 1625 (C N) cm−1.1H NMR (DMSO-
d6): δ = 2.71 (s, 3H, CH3), 2.89 (s, 3H, CH3CO), 4.25 (s, 2H, SCH2), 6.94
(d, 1H, J = 16.0 Hz, HβC CH), 7.13 (dd, 1H, J = 3.50 Hz, thiophene-H),
7.32 (d, 2H, J = 9.80 Hz, Ar-H), 7.52 (d, 1H, J = 3.50 Hz, thiophene-H),
7.65 (d, 1H, J = 5.08 Hz, thiophene-H), 7.79 (d, 2H, J = 9.80 Hz, Ar-
H), 8.19 (d, 1H, J = 16.0 Hz, HC CHα), 8.79 (s, 1H, N CH), 12.01 (s,
1H, NH). Anal. Calcd. for C22H19ClN4O2S2 (470.9): C, 56.10; H, 4.07;
N, 11.90. Found: C, 56.28; H, 4.18; N, 12.01.

New Pyrimidine Derivative
131
2-[(5)-Acetyl-6-methyl-2-[(E)-2-(2-thienyl)vinyl]pyrimidin-4-
yl)thio]-N-[2-(4-chlorophenyl)-4-oxo-1,3-thiazolidin-3-
yl]acetamide (21)
A mixture of compound 20 (4.70 g, 10 mmol) and thioglycolic acid
(0.70 ml, 10 mmol) in pyridine (20 ml) was heated under reflux for 12
h, cooled, poured into ice-water, then the pH was adjusted to 7 with
hydrochloric acid, the solid separated was filtered off, washed with wa-
ter, dried and recrystallized with ethanol affording gray crystals (yield:
41%) m.p. 280–281◦C. IR (KBr): 3210 (NH), 1698, 1685, and 1653 (3
C O) cm−1.1H NMR (DMSO-d6): δ = 2.68 (s, 3H, CH3), 2.86 (s, 3H,
CH3CO), 4.21 (s, 2H, SCH2), 4.32 (s, 1H, SCHAr), 5.98 (COCH2S, thi-
azolidine ring), 6.94 (d, 1H, J = 16.0 Hz, HβC CH), 7.13 (dd, 1H, J =
3.50 Hz, thiophene-H), 7.35 (d, 2H, J = 7.90 Hz, Ar-H), 7.52 (d, 1H, J =
3.50 Hz, thiophene-H), 7.55 (d, 1H, J = 5.08 Hz, thiophene-H), 7.80 (d,
2H, J = 7.90 Hz, Ar-H), 8.19 (d, 1H, J = 16.0 Hz, HC CHα), 10.21 (s,
1H, NH). Anal. Calcd. for C24H21ClN4O3S3 (545.1): C, 52.88; H, 3.88;
N, 10.28. Found: C, 52.78; H, 3.89; N, 10.59.
5-Acetyl-6-methyl-2-[(E)-2-(2-aryl)vinyl]-4-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-tetra-O-
acetyl-β-D-glucopyranosylthio)pyrimidine (22a–c)—General
Procedure
To a solution of compound 3b and 3c,d17 (10 mmol) in aqueous potas-
sium hydroxide (0.56 g, 10 mmol) in distilled water (10 ml) was added a
solution of 2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl bromide (4.11 g,
10 mmol) in acetone (30 ml). The reaction mixture was stirred for 4 h at
room temperature until the starting material was consumed (TLC). The
mixture was evaporated under reduced pressure and the residue was
washed with distilled water to remove the potassium bromide formed.
The solid product was dried and recrystallized from ethanol.
5-Acetyl-6-methyl-2-[(E)-2-(2-thienyl)vinyl]-4-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-tetra-
O-acetyl-β-D-glucopyranosylthio)pyrimidine (22a)
Pale gray crystals (yield: 20%) m.p. 115–117◦C. IR (KBr): 1745, 1696,
1663 (C O) cm−1 for acetyl and ketone groups, 1626 (C N) cm−1.1H
NMR (DMSO-d6): δ = 1.76, 1.96, 2.00, 2.02 (4s, 12H, 4 OCOCH3), 2.49
ꢀ
(s, 3H, CH3), 2.58 (s, 3H, COCH3, pyrimidine), 3.88 (m, 1H, H−5 ), 4.17
ꢀ
ꢀꢀ
ꢀ
(m, 2H, H−6 ,6 ), 4.95 (t, 1H, J = 9.00 Hz, H−4 ), 5.11 (t, 1H, J = 9.0 Hz,
ꢀ
ꢀ
ꢀ
H
−2 ), 5.60 (t, 1H, J = 9.0 Hz, H−3 ), 6.23 (d, 1H, J = 12.0 Hz, H−1 ), 6.94
(d, 1H, J = 16.0 Hz, HβC CH), 7.13 (dd, 1H, J = 3.50 Hz, thiophene-
H), 7.52 (d, 1H, J = 3.50 Hz, thiophene-H), 7.65 (d, 1H, J = 5.08 Hz,
thiophene-H), 8.19 (d, 1H, J = 16.0 Hz, HC CHα). Anal. Calcd. for

132
A. H. Moustafa et al.
C27H30N4O10S2 (606.6): C, 53.45; H, 4.98; N, 4.62. Found: C, 53.56; H,
4.96; N, 4.68.
5-Acetyl-6-methyl-2-[(E)-2-(2-chlorophenyl)vinyl]-4-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-
tetra-O-acetyl-β-D-glucopyranosylthio)pyrimidine (22b)
A pale brown powder (yield: 25%) m.p. 102–104◦C. IR (KBr): 1748
(br), 1698 (C O) cm−1 for acetyl and ketone groups, 1635 (C N)
cm−1.1H NMR (DMSO-d6): δ = 1.76, 1.96, 2.01, 2.03 (4s, 12H, 4
ꢀ
ꢀꢀ
OCOCH3), 2.48 (s, 3H, CH3), 2.59 (s, 3H, COCH3), 4.02 (m, 2H, H−6 ,6 ),
ꢀ
ꢀ
4.17 (m, 1H, H−5 ), 4.97 (t, 1H, J = 9.0 Hz, H−4 ), 5.13 (t, 1H, J = 9.0
ꢀ
ꢀ
ꢀ
Hz, H−2 ), 5.64 (t, 1H, J = 9.0 Hz, H−3 ), 6.28 (d, 1H, J = 12.0 Hz, H−1 ),
7.31 (d, 1H, J = 16.0 Hz, HC CHα), 7.51 (d, 2H, J = 9.8 Hz, Ar-H), 7.82
(d, 2H, J = 9.8 Hz, Ar-H), 8.15 (d, 1H, J = 16.0 Hz, HβC CH). Anal.
Calcd. for C29H31ClN2O10S (635.1): C, 54.84; H, 4.92; N, 4.41. Found: C,
55.00; H, 4.89; N, 4.52.
5-Acetyl-6-methyl-2-[(E)-2-(phenyl)vinyl]-4-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-tetra-O-
acetyl-β-D-glucopyranosylthio)pyrimidine (22c)
Colorless crystals (yield: 25%) m.p. 132–133◦C. IR (KBr): 1755–1728
(br), 1660 (C O) cm−1 for acetyl groups, 1636 (C N) cm−1.1H NMR
(CDCl3): δ = 1.89, 2.03, 2.04, 2.07 (4s, 12H, 4 OCOCH3), 2.47 (s, 3H,
ꢀ
ꢀ
ꢀꢀ
CH3), 2.57 (s, 3H, COCH3), 3.99 (m, 1H, H−5 ), 4.15-4.20 (m, 2H, H
),
−6 ,6
ꢀ
ꢀ
5.13 (t, 1H, J = 9.0 Hz, H−4 ), 5.27 (t, 1H, J = 9.0 Hz, H−2 ), 5.41 (t, 1H,
ꢀ
ꢀ
J = 9.0 Hz, H−3 ), 6.04 (d, 1H, J = 10.5 Hz, H−1 ), 7.17 (d, 1H, J =
16.0 Hz, HC CHα), 7.38–7.65 (m, 5H, Ar-H), 8.01 (d, 1H, J = 16.0 Hz,
HβC CH). Irradiation of signal at δ 3.99 ppm change the signals at
δ 4.15 ppm to doublet of doublet and at δ 5.13 ppm to doublet, and
irradiation of the signal at δ 5.13 ppm change the signals at δ 3.99 and
5.41 ppm to doublet. Irradiation of the signal at δ 5.77 ppm changed
the signal at δ 6.04 ppm into a singlet signal, also the irradiation of
the signal at δ 5.41 ppm changed the signals at δ 5.13, 5.27 ppm into
a doublet. The irradiation of signal at δ 6.04 ppm change the signal
at δ 5.27 ppm into a doublet and disappear the signal at d 6.04 ppm,
this assigned the position of sugar protons. The irradiation of signal
at δ 8.01 ppm change the signal at δ 7.17 ppm to a singlet signal with
disappear the signal at δ 7.17 ppm, which assigned the structure of
trans ethylenic protons.13C NMR (CDCl3): δ = 20.5, 20.6, 20.7, 22.7,
29.7, 31.6, 62.2, 68.4, 69.1, 74.1, 76.5 (6 CH3 and sugar carbon), 80.3,
126.6, 127.8, 128.2, 128.9, 129.6, 130.2, 135.5, 139.7, 162.1, 162.2, 162.9,
169.3, 169.4, 170.1, 170.5, 201.5 (Ar-C, 2 C N and 5 C O). Anal. Calcd.
for C29H32N2O10S (600.6): C, 57.99; H, 5.37; N, 4.66. Found: C, 58.02;
H, 5.48; N, 4.68.

New Pyrimidine Derivative
133
5-Acetyl-6-methyl-2-[(E)-2-(aryl)vinyl]-4-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-
tetrahydroxy-β-D-glucopyranosylthio)pyrimidine
(23a–c)—General Procedure
A mixture of compound 22a–c (10 mmol) in methanol (30 ml), 1 ml of
triethylamine and few drops of water were stirred overnight at room
temperature under nitrogen gas, the solvent was then removed under
vacuo, and the residue was washed with chloroform to extract unreacted
materials. The remaining residue was recrystallized from ethanol.
5-Acetyl-6-methyl-2-[(E)-2-(2-thienyl)vinyl]-4-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-
tetrahydr-oxy-β-D-glucopyranosylthio)pyrimidine (23a)
Gray crystals (yield: 36%) m.p. 140–142◦C. IR (KBr): 3400 (very broad
band) (OH), 1689 (C O), 1623 (C N) cm−1.1H NMR (DMSO-d6/D2O):
ꢀ
δ = 2.49 (s, 3H, CH3), 2.57 (s, 3H, COCH3), 4.00 (m, 1H, H−5 ), 5.02
ꢀ
ꢀꢀ
ꢀ
(m, 2H, H
), 5.32 (d, 1H, J = 5.40 Hz, H−4 ), 5.43 (d, 1H, J = 4.80
−6 ,6
ꢀ
ꢀ
Hz, H−2 ), 5.58 (d, 1H, J = 6.30 Hz, H−3 ), 5.62 (d, 1H, J = 9.90 Hz,
ꢀ
H
−1 ), 6.63 (d, 1H, J = 16.0 Hz, HβC CH), 7.13 (dd, 1H, J = 3.50 Hz,
thiophene-H), 7.47 (d, 1H, J = 3.50 Hz, thiophene-H), 7.63 (d, 1H, J =
5.08 Hz, thiophene-H), 8.06 (d, 1H, J = 16.0 Hz, HC CHα). Anal. Calcd.
for C19H22N2O6S2 (438.5): C, 52.04; H, 5.06; N, 6.39. Found: C, 51.99;
H, 5.14; N, 6.41.
5-Acetyl-6-methyl-2-[(E)-2-(4-chlorophenyl)vinyl]-4-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-
tetrahydr-oxy-β-D-glucopyranosylthio)pyrimidine (23b)
A pale brown powder (yield: 25%), m.p. 103–104◦C. IR (KBr): 3400
(very broad band) for (OH), 1685 (C O) and 1620 (C N) cm−1.1H NMR
(DMSO-d6/D2O): δ = 2.49 (s, 3H, CH3), 2.58 (s, 3H, COCH3), 3.68 (m,
ꢀ
ꢀ
ꢀꢀ
ꢀ
1H, H−5 ), 4.48 (m, 2H, H
), 5.02 (d, 1H, J = 5.40 Hz, H−4 ), 5.16 (d,
−6 ,6
ꢀ
ꢀ
1H, J = 4.80 Hz, H−2 ), 5.44 (d, 1H, J = 6.30 Hz, H−3 ), 5.61 (d, 1H, J =
ꢀ
9.80 Hz, H−1 ), 7.20 (d, 1H, J = 16.0 Hz, HC=CHα), 7.47 (d, 2H, J =
8.40 Hz, Ar-H), 7.79 (d, 2H, J = 8.40 Hz, Ar-H), 7.98 (d, 1H, J = 16.0
Hz, HβC CH). Anal. Calcd. for C21H23ClN2O6S (466.94): C, 54.02; H,
4.96; N, 6.00. Found: C, 54.31; H, 5.01; N, 6.11.
5-Acetyl-6-methyl-2-[(E)-2-(phenyl)vinyl]-4-(2‘,3‘,4‘,6‘-
tetrahydroxy-β-D-glucopyranosylthio)pyrimidine (23c)
White crystals (yield: 20%) m.p. 120–122◦C. IR (KBr): 3379 (very
broad band) (OH), 1685 (C O) and 1636 (C N) cm−1.1H NMR (DMSO-
ꢀ
d6/D2O): δ = 2.46 (s, 3H, CH3), 2.58 (s, 3H, CH3CO), 3.67 (m, 1H, H−5 ),
ꢀ
ꢀꢀ
ꢀ
4.45 (m, 2H, H
), 5.02 (d, 1H, J = 5.40 Hz, H−4 ), 5.17 (d, 1H, J =
−6 ,6
ꢀ
ꢀ
4.80 Hz, H−2 ), 5.45 (d, 1H, J = 6.40 Hz, H−3 ), 5.62 (d, 1H, J = 9.90 Hz,
ꢀ
H
−1 ), 7.23 (d, 1H, J = 16.0 Hz, HC CHα), 7.41–7.74 (m, 5H, Ar-H), 8.00

134
A. H. Moustafa et al.
(d, 1H, J = 16.0 Hz, HβC CH). Anal. Calcd. for C21H24N2O6S (432.5):
C, 58.32; H, 5.59; N, 6.48. Found: C, 58.01; H, 5.6; N, 6.56.
ANTIMICROBIAL ACTIVITY
The antimicrobial activities of some newly synthesized compounds
were screened for their antibacterial and antifungal activity against
six species of bacteria and one fungi, namely Staphylococcus aureus,
Sarcina lutea, Bacillus subtilis as Gramm +ve, Pseudomonas aerug-
inosa, Klebseilla pneumonie, Escherichia coli as Gram –ve, and Can-
dida albicans as Fungi, using a cup plate agar diffusion method.24 The
tested compounds were dissolved in DMF to get a solution of 1 mg/mL
concentration. The inhibition zones were measured in (mm) at the end
of an incubation period of 48 h at 37◦C. Dimethylformamide showed no
inhibition zones. The fungi cultures were maintained on dextrose agar
medium. Penicillin and Nystatin were used as reference.
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