Synthesis and reactions of some novel mercaptopyrimidine derivatives for biological evaluation

Article abstract of DOI:10.1080/10426500801963590

4-Mercapto-5-acetylpyrimidine derivative was used as a precursor for preparation of some novel thieno[2,3-d]pyrimidine, pyrazolo[2,3-d]pyrimidine, isothiazolo [5,4-d] pyrimidine, pyrrolo[4,5-d]pyrimidine, and pyrimidio[4,5-d]pyrimidine derivatives. Furthermore, some of the prepared products were revealed promising antimicrobial activities. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426500801963590

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Phosphorus, Sulfur, and Silicon
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Synthesis and Reactions
of Some Novel
Mercaptopyrimidine
Derivatives for Biological
Evaluation
H. H. Sayed a , A. H. Moustafa b , N. M. Yousif a , M.
G. Assy b & M. A. Abd El-Halim b
a Photochemistry Department , National Research
Centre , Dokki, Cairo, Egypt
b Chemistry Department, Faculty of Science ,
Zagazig University , Zagazig, Egypt
Published online: 12 Aug 2008.
To cite this article: H. H. Sayed , A. H. Moustafa , N. M. Yousif , M. G. Assy & M.
A. Abd El-Halim (2008) Synthesis and Reactions of Some Novel Mercaptopyrimidine
Derivatives for Biological Evaluation, Phosphorus, Sulfur, and Silicon and the Related
Elements, 183:9, 2318-2329, DOI: 10.1080/10426500801963590
To link to this article: http://dx.doi.org/10.1080/10426500801963590
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Phosphorus, Sulfur, and Silicon, 183:2318–2329, 2008
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500801963590
Synthesis and Reactions of Some Novel
Mercaptopyrimidine Derivatives for Biological Evaluation
H. H. Sayed,1 A. H. Moustafa,2 N. M. Yousif,1 M. G. Assy,2
and M. A. Abd El-Halim2
1Photochemistry Department, National Research Centre, Dokki, Cairo,
Egypt
2Chemistry Department, Faculty of Science, Zagazig University,
Zagazig, Egypt
4-Mercapto-5-acetylpyrimidine derivative was used as a precursor for prepara-
tion of some novel thieno[2,3-d]pyrimidine, pyrazolo[2,3-d]pyrimidine, isothiazolo
[5,4-d] pyrimidine, pyrrolo[4,5-d]pyrimidine, and pyrimidio[4,5-d]pyrimidine
derivatives. Furthermore, some of the prepared products were revealed promising
antimicrobial activities.
Keywords Isothiazolo[5,4-d]pyrimidine; pyrimidine; pyrimidio[4,5-d]pyrimidine;
pyrrolo[4,5-d]pyrimidine; thieno[2,3-d]pyrimidine
INTRODUCTION
The synthesis of pyrimidine and condensed pyrimidines has attracted
the attention of medicinal chemists because of their potential phar-
macodynamic properties. Numerous publications describe the synthe-
sis of condensed pyrimidines possessing a variety of pharmacological
activities such as anticonvulsant,1 anti-inflammatory,2 bactericidal,3
fungicidal,4 and antifertility activities.5 In conjunction with our previ-
ous work on the synthesis of pyrimidine thione derivatives for biological
evaluations,6–11 a series involving a simple pyrimidine thione moiety
is described.
RESULTS AND DISCUSSION
The present study was directed to synthesis of several novel fused
pyrimidines and pyrimidine derivatives by heteroannulation and
Received October 24, 2007; accepted December 16, 2007.
Address correspondence to H. H. Sayed, Photochemistry Department, National
Research Centre, Dokki, Cairo, Egypt. E-mail: hayamsayed@yahoo.com.
2318

Some Novel Mercaptopyrimidine Derivatives
2319
SCHEME 1
functionlization of 5-acetyl-4-mercaptopyrimidines.12,13 Aroyl isothio-
cyanates are versatile building units that have been extensively uti-
lized in organic synthesis.14,15 Thus, the addition of nucleophilic enam-
inic carbon of β-enaminone 2 to the electrophilic carbon of isothiocy-
nate 1, afforded the open form 4. Base induced cyclization of 4 using
sodium hydroxide yielded 4-mercapto-5-acetylpyrimidine derivatives 5
(Scheme 1).
Compound 5 seemed to have suitably located functionality for further
reactivity and heterocyclization. Thus, compound 5 was reacted with an
activated halomethylene derivative in basic medium to give thienopy-
rimidine 7a-d presumably via the alkylthio derivative 6a-d. Compound
6a reacted with hydrazine hydrate to produce the pyrazolopyrimidine
8. Oxidation of compound 6d with KMnO4 in the presence of H2SO4
afforded thienopyrimidine dioxide 9.
Qinoxazinyl thienopyrimidine 10 was the end product of the reac-
tion of compound 7c with Ac2O followed by refluxing with formamide
(Scheme 2, See Experimental).
When compound 5 was reacted with NaOCl in the presence
of NH4OH, the resulting sulfonation and intramolecular cycliza-
tion yielded isothiazolopyrimidine 11. Cyanoethylation of com-
pound 5 was also investigated. Thus, the addition of mercaptopy-
rimidine 5 to acrylonitril in the presence of triethyl amine gave
6-carboxamidomethylthienopyrimidine 12 through an intermediate
Michael adduct. Oxidation of compound 5 using iodine gives disul-
phide 13. The present study is also directed toward the functionlization

2320
H. H. Sayed et al.
SCHEME 2
of compound 5 through the chemical transformation of the mercapto
function. Thus, Treatment of mercaptopyrimidine 5 with H2O2 in acetic
acid resulted in desulfurization and the formation of m-chlorophenyl-
6-methyl-5-acetyl-pyrimidine 14. Compound 5 underwent hydrolysis
when reacted with hydrogen peroxide in basic medium producing
4-hydroxy pyrimidine 15 (Scheme 3).
The action of chlorine in acetic acid successfully converted mercap-
topyrimidine 5 into chloropyrimidine 16 instead of the expected 4-
pyrimidines sulphonyl chloride derivatives 17. The conversion of such
mercapto function to chloro functionality on a pyrimidine ring by chlo-
rination in acetic medium is usually considered to proceed by rear-
rangment of the unstable sulphonyl chloride intermediate by an SN1
mechanism (similar rearrangment for pyridine-2-sulphonyl chloride
was proved) 16 (Scheme 4).
4-Chloro-5-acetylpyrimidine derivative 16 was fused with glycine,
guanidium cyanide, and arylamines to afford pyrrolo[4,5-d]pyrimidine
18 pyrimido[4,5-d]pyrimidine 19 and arylaminopyrimidine 20a,b
derivatives, respectively.

Some Novel Mercaptopyrimidine Derivatives
2321
SCHEME 3
Biological Evaluation
Antimicrobial Activity of Some Newly
Synthesized Compounds
The in vitro antimicrobial activity of the synthesized compounds
was tested against several pathogenic representatives: Escherichia coli,
Bacillus subtilis, Candida albicans, and Aspergillus niger. All microor-
ganisms used were obtained from Chemistry of Natural and Microbial

2322
H. H. Sayed et al.
SCHEME 4
Products Department, National Research Centre, Cairo, Egypt. Disc
diffusion sensitivity test was done in the manner identical to that of
Bauer et al.17 Media for disc sensitivity tests were nutrient agar and
Muller-Hinton agar (MHA), purchased from Difco, (USA). The nonster-
ile powder of the tested compounds was dissolved in sterile DMSO to
yield 2 µg mL−1 passed through 0.2 µm membrane filter (Millipore
Corp., USA). The filtrates were dispensed as 2 mL samples into sterile,
small screw-capped vials and kept stored at −15◦C. DMSO as a solvent
showed no inhibition zones. The results were compared to Streptomycin
as a reference drug.
The antimicrobial activity of some newly synthesized compounds 7b,
8, 9, 13, 18, and 20b were tested and the results are shown in Table I.
Evaluation of the new compounds established that compounds 7, 9, 18,
and 20b were slightly active against Gram positive and Gram negative
bacteria. On the other hand, it was found that compounds 9 and 18
revealed activity against yeast more effectively than the other tested
compounds while compounds 7, 8, 9, 18, and 20b revealed slight to
strong antifungal activities. In particular, compound 9 revealed anti-
fungal activity more effective than the other tested compounds and the
reference drug.

Some Novel Mercaptopyrimidine Derivatives
2323
TABLE I Antimicrobial Activity of Some Synthesized Compoundsa
Disc diffusion test (mm)
Microorganisms
Bacteria
Tested
compd. no.
& stander
Gram negative Gram positive
Escherichia coli Bacillus subtillis Candida albicans Aspergillus niger
Yeast
Fungi
Streptomycinb
7b
8
+ + +
+ + +
+ + +
−
+
++
+
+
+
+
+
+
+
+
−
+
−
+
+
−
9
++
−
+ + +
−
13
18
20b
++
−
++
+
aγ = 2 µg/mL−1 in DMSO. bγ = 25 µg/mL−1 in DMSO, Lot. 30730, Bioanalyse
(Turkey). + + + highly sensitive (14–16 mm); ++ fairly sensitive (12–14 mm); +
slightly sensitive (10–12 mm); and − not sensitive.
EXPERIMENTAL
All melting points are uncorrected and were measured using an Elec-
trothermal IA 9100 apparatus. Analytical data were performed by Vario
El Mentar apparatus, organic microanalysis section, National Research
Centre. Their results were found to be in agreement with the calculated
values ( 0.5%). The IR spectra (KBr) were recorded on a Pye Unicam
Sp-3–300 and Shimadzu FTIR 8101 PC infrared spectrophotometer.
The NMR spectra were recorded on a Varian Mercury VX-300 NMR
1
spectrometer. H spectra were run at 300 MHz in dimethylsulphoxide
(DMSO-d6). Chemical shifts are quoted in δ and were related to that of
the solvents. The Mass spectra were recorded on a Shimadzu GCMS-
QP-1000EX mass spectrometer at 70 ev. Microanalysis were carried out
at the microanalytical unit, Cairo University (Cairo, Egypt).
Reagent—N-substituted Chloroacetamide
The synthesis of N-substituted chloroacetamide was accomplished ac-
cording to the procedure of Widman by adding the appropriate aromatic
amine to chloro acetylchloride.18
N-β-Amino-α-acetyl-1-thiocrotonyl-m-chlorobenzamid (4)
A mixture of m-chlorobenzoylchloride (0.01 mol), ammonium thio-
cyanate (0.015 mol) and β-enaminone (0.01 mol) in acetone (20 ml)

2324
H. H. Sayed et al.
was stirred for 1/2 h. The reaction mixture was poured onto ice water,
filtered off, dried, and recrystallized from benzene to give red crystals of
compound 4 in 78.3% yield; m.p. 150◦C;. Anal. calcd. for C13H13ClN2O2S
(296.77): C, 52.61; H, 4.42; N, 9.44. Found C, 52.70; H, 4.43; N, 9.46.
2-m-Chlorophenyl-6-methyl-4-mercapto-5-
acetylpyrimidine (5)
A solution of 4 (0.01 mol) in sodium hydroxide solution (0.01 mol) was
stirred at room temperature for 1/2 h., the yellow crystals obtained
upon acidification using HCl (0.01 mol) was collected by filtration and
crystallized from ethanol into yellow crystals of 5 in 56.1% yield; m.p.
1
280◦C; IR spectrum (KBr, ν, cm−1): 1670 (CO), 1010 (SH); H NMR
spectrum (DMSO-d6, δ ppm): 2.7 (s, 3H, CH3), 2.9 (s, 3H, CH3), 7.4–8.0
(m, 4H, Ar’Hs), 10.74 (s, 1H, SH); MS m/z (%): 278 (M+, 10.93). Anal.
calcd. for C13H11ClN2OS (278.76).: C, 56.10; H, 3.98; N, 10.05. Found C,
56.11; H, 3.99; N, 10.07.
2-m-Chlorophenyl-4-carboxymethylthio-6-methyl-5-acetyl
pyrimidine (6a) and 4-Carboethoxymethylthio-6-methyl-
5-acetylpyrimidine (6d)
A mixture of 5 (0.01 mol), chloroacetic acid and/or ethyl bromo acetate
and sodium carbonate (0.02 mol) was stirred at room temperature for
1 h, the colorless precipitate obtained upon acidification with HCl (0.01
mol) was collected by filtration and crystallized from ethanol into col-
orless crystals of 6a and 6d.
6a: in 71.4% yield; m.p. 160◦C; IR spectrum (KBr, ν, cm−1): 1711(CO
ester), 1650 (CO acetyl); Anal. calcd. for C17H17ClN2O3S (364.85): C,
55.97; H, 4.70; N, 7.68. Found C, 56.03; H, 4.71; N, 7.69.
6d: in 58.7% yield; m.p. 120◦C; IR spectrum (KBr, ν, cm−1):
3449 (OH), 1711(CO acidic), 1650 (CO acetyl), Anal. calcd. for
C15H13ClN2O3S (336.79): C, 53.49; H, 3.89; N, 8.32. Found C, 53.57;
H, 3.90; N, 8.33.
Ethyl-2-m-chlorophenyl-4,5-dimethylthieno[2,3-d]pyrimidine-
6-carboxylate (7a)
A mixture of compound 6a (0.01 mol) and few drops of triethyl amine
in ethanol (15 ml) was heated under reflux for 1 h. After cooling, the
precipitate was collected and crystallized from acetone into colorless
crystals of 7a in 49.8% yield; m.p. 170–175◦C; IR spectrum (KBr, ν,
1
cm−1): 1677 (CO); H NMR spectrum (DMSO-d6, δ ppm): 1.45 (t, 3H,

Some Novel Mercaptopyrimidine Derivatives
2325
CH3), 2.9 (s, 3H, CH3), 2.99 (s, 3H, CH3), 4.43 (q, 2H, CH2), 7.2–8.4 (m,
4H, Ar’Hs); Anal. calcd. for C17H15ClN2O2S (346.83): C, 58.87; H, 4.36;
N, 8.08. Found C, 58.95; H, 4.37; N, 8.09.
2-m-chlorophenyl-4,5-dimethylthieno[2,3-d]pyrimidine-6-
carboxanilide (7b)
A mixture of compound 5 (0.01 mol) N-phenylchloroacetamide (0.01
mol) and sodium ethoxide (0.01 mol) was refluxed for 2 h., the precipi-
tate obtained upon cooling was collected and crystallized from acetone
into colorless crystals of 7b in 59.7% yield; m.p. 280◦C; IR spectrum
1
(KBr, ν, cm−1): 3461 (NH), 1641(CO); H NMR spectrum (DMSO-d6,
δ ppm): 2.8 (s, 3H, CH3), 2.9 (s, 3H, CH3), 6.8–7.6 (m, 9H, ArH’s), 10.62
(s, 1H, NH); MS m/z (%): 393 (M+, 25.33). Anal. calcd. for C21H16ClN3OS
(393.89): C, 64.04; H, 4.09; N,10.67. Found C, 64.11; H, 4.10; N, 10.69.
4-{[2-m-chlorophenyl-4,5-dimethylthieno[2,3-d]pyrimidine-6-
carbonyl]-amine}-benzoic acid (7c)
A mixture of compound 5 (0.01 mol), N-O-carboxyphenyl chloroac-
etamide (0.01 mol), and sodium ethoxide (0.01 mol) was refluxed for
2 h., the precipitate obtained upon cooling was collected and crystal-
lized from acetone into colorless crystals of 7c in 55.3% yield; m.p.
290◦C; MS m/z (%): 438 (M+, 21.76). Anal. calcd. for C22H16ClN3O3S
(437.9): C, 60.34; H, 3.68; N, 9.60. Found C, 64.11; H, 4.10; N, 10.69.
Pyrazolo[2,3-d]pyrimidine (8)
A mixture of 6a (0.01 mol) and hydrazine hydrate (0.01 mol) in ethanol
into (20 ml) was heated under reflux for 3 h., after cooling the colorless
precipitate was collected and crystallized from ethanol.
Colorless crystals of 8 in 45.4% yield; m.p. 180◦C; IR spectrum (KBr,
ν, cm−1): 3444 (NH); MS m/z (%): 258 (M+, 35.45). Anal. calcd. for
C13H11ClN4 (258.71): C, 60.35; H, 4.29; N, 21.66. Found C, 60.45; H,
4.30; N, 21.70.
Ethyl-2-m-chlorophenyl-4,5-dimethylthieno[2,3-d]
pyrimidine7,7-dioxide-6-carboxylate (9)
A solution of 6d (0.01 mol) in chloroform (10 ml) and sulphuric acid
(2 ml, 98%) was cooled to 0◦ and then potassium permanganate (0.1 mol)
was added slowly in Portions. The solution was set aside at room tem-
perature, made alkaline, decolorized with acetone, and extracted with

2326
H. H. Sayed et al.
chloroform. After evaporation to dryness the residue was crystallized
from ethanol as colorless crystals 9 in 40% yield; m.p. 180–181◦C; IR
spectrum (KBr, ν, cm−1): 3449 (OH), 1654 (CO), 1160 (SO2); MS m/z
(%): 351 (M+, 11.06). Anal. calcd. for C15H11ClN2O4S (350.78): C, 51.36;
H, 3.16; N, 7.99. Found C, 51.43; H, 3.17; N, 8.00.
2-m-chlorophenyl-6-qunoxazinyl-4,5-dimethylthieno [2,3-d]
pyrimidine (10)
A mixture of compound 7c (0.01 mol), and acetic anhydride (5 ml)
sodium acetate (0.01 mol) in acetic acid (20 ml) was heated under re-
flux for 3 h. The solid obtained upon concentration was collected and
refluxed with formamide for 5 hours the solid obtained crystallized from
benzene into colorless crystals of 10 in 42.2% yield; m.p. 300◦C; IR spec-
trum (KBr, ν, cm−1): 1653 (CO), 3421 (NH); 1H NMR spectrum (DMSO-
d6, δ ppm): 2.8 (s, 3H, CH3), 2.9 (s, 3H, CH3), 7.6–8.3 (m, 8H, ArH’s), 8.46
(s, 1H, NH). MS m/z (%): 421 (M+, 9.91). Anal. calcd. for C22H17ClN4OS
(420.92): C, 62.78; H, 4.07; N, 13.31. Found C, 62.84; H, 4.08; N, 13.33.
2-m-chlorophenyl-4,5-dimethylisothiazolo[5,4-d]
pyrimidine (11)
A solution of sodium hypochloride (125 ml, 5%) was added dropwise over
a period of 20 min to a stirred solution of pyrimidine 5 (0.01 mol) in aque-
ous sodium hydroxide solution (90 ml, 3.3%), and ammonium hydroxide
(90 ml, 3.3%) at room temperature. The solid obtained was collected,
washed with water and then crystallized from ethanol to give colorless
crystals of 11 in 40.8% yield; m.p. 120◦C; IR spectrum (KBr, ν, cm−1):
1654 (C N); MS m/z (%): 275 (M+, 38.77). Anal. calcd. for C13H10ClN3S
(275.02): C, 56.72; H, 3.66; N, 15.27. Found C, 56.61; H, 3.61; N, 15.21.
6-carboxamidomethylthienopyrimidine 12
A mixture of 1 (0.01 mol), acrylonitrile (0.01 mol) and triethyl amine
(3 drops) in ethanol (10 ml) was heated under reflux for 1 h. After cool-
ing the precipitate was collected and crystallized from ethanol to give
colorless crystals of 12 in 65% yield; m.p. 89–90◦C; IR spectrum (KBr,
ν, cm−1): 3369 (NH), 1649 (CO); 1H NMR spectrum (DMSO-d6, δ ppm):
2.24 (s, 3H, CH3), 2.55 (s,3H,CH3), 3.8(s, 2H,CH2), 6.5 (s, 2H,NH2),
7.5–8.1 (m, 4H,ArH’s). MS m/z (%): 331 (M+, 9.67). Anal. calcd. for
C16H14ClN3OS (331.82): C, 57.92; H, 4.25; N, 12.66. Found C, 58.00; H,
4.26; N, 12.69.

Some Novel Mercaptopyrimidine Derivatives
2327
Bis[2-m-chlorophenyl-6-methyl-5-acetylpyrimidyl] disulfide 13
Iodine (0.01 mol) was added to a solution of 5 (0.01 mol) in acetic acid
(20 ml) and left at room temperature for 1/2 h. The resulting yellowish
precipitate was collected by filtration, washed with water, and crystal-
lized from ethanol into yellowish crystals of 13 in 12.23% yield; m.p.
150◦C; IR spectrum (KBr, ν, cm−1): 1655.3 (CO); MS m/z (%): 554 (M+,
46.07). Anal. calcd. for C26H20Cl2N4O2S2 (554.04): C, 56.31; H, 3.64; N,
10.11. Found C, 56.22; H, 3.63; N, 10.09.
2-m-Chlorophenyl-6-methyl-5-acetylpyrimidine 14
A mixture of compound 5 (0.01 mol), hydrogen peroxide (60 ml, 30%)
and acetic acid (20 ml) was shaken for 5 min, an exothermic reaction
occurred (the temperature rise to 60◦C). The solution was heated gently
tell boiling for 3 min, after cooling in ice water and scratching the solid
produced was recrystallized from ethanol to give colorless crystals of
14 in 44.4% yield; m.p. 180◦C; IR spectrum (KBr, ν, cm−1): 1699 (CO);
Anal. calcd. for C15H12N6 (276.30): C, 63.40; H, 4.51; N, 11.38. Found
C, 63.29; H, 4.49; N, 11.36.
2-m-chlorophenyl-6-methyl-5-acetylpyrimidine-4-one 15
A mixture of compound 5 (0.01 mol) hydrogen peroxide (60 ml, 30%)
and sodium hydroxide (0.01 mol) was shaken for 5 min, the flask con-
tent was allowed to stand at room temperature for 1/2 h., the colorless
precipitate obtained upon acidification with HCl (0.1 mol) was collected
and crystallized from ethanol into colorless crystals of 15 in 42.1% yield;
m.p. 170.◦C; IR spectrum (KBr, ν, cm−1): 1699 (CO), 3445 (OH); 1H NMR
spectrum (DMSO-d6, δ ppm): 2.2 (s, 3H, CH3), 2.3 (s,3H,CH3), 7.4–8 (m,
4H, ArH’s), 13.19 (s, 1H,OH). Anal. calcd. for C13H11ClN2O2 (262.05):
C, 59.53; H, 4.23; N, 10.69. Found C, 59.44; H, 4.22; N, 10.66.
2-m-chlorophenyl-4-chloro-6-methyl-5-acetylpyrimidine 16
Chlorine gas was bubbled through a suspension of 5 (5g) in acetic acid
(50 ml, 25%) for about 2 h at 10◦C, the resulting precipitate was collected
by filtration washed with water, dried and crystallized from acetone into
colorless crystals of 16 in 74.6% yield; m.p. 100◦C; IR spectrum (KBr,
ν, cm−1): 3382, 3280 (NH2), and 2220 (CN) 1672 (CO); Anal. calcd. for
C13H10Cl2N2O (281.14): C, 55.54; H, 3.59; N, 9.96. Found C, 55.71; H,
3.60; N, 10.00.

2328
H. H. Sayed et al.
Pyrrolopyrimidine 18
A solution of compound 17 (0.01 mol) and glycine (0.01 mol) in DMF
(20 ml) was heated under reflux for 2 h; the resulting colorless crystals
was collected by filtration and crystallized from ethanol to give colorless
crystals of pyrrolopyrimidine 18 in 35.7% yield; m.p. 185◦C; IR spectrum
(KBr, ν, cm−1): 3594 (OH), 3444 (NH), 1648 (CO); MS m/z (%): 302 (M+,
8.28). Anal. calcd. for C15H12ClN3O2 (301.73): C, 59.71; H, 4.01; N, 13.93.
Found C, 59.71; H, 4.02; N, 13.91.
7-Amino-2-m-chlorophenyl-4,5-dimethylpyrimidio[4,5-d]
pyrimidine 19
A mixture of 17 (0.01 ml) and guanidinum cyanate (0.01 mol) was fused
on oil bath at 170◦C, for 2 h., the solid mass obtained upon air cooling
was refluxed with ethanol, the precipitate obtained upon cooling was
collected and crystallized from ethanol into colorless crystals of 19 in
40.8% yield; m.p. 130◦C; IR spectrum (KBr, ν, cm−1): 3366, 3179 (NH2);
MS m/z (%): 286 (M+, 29.10). Anal. calcd. for C14H12ClN5 (285.74): C,
58.85; H, 4.23; N, 24.51. Found C, 58.93; H, 4.24; N, 24.56.
4-Arylamino-2-m-chlorophenyl-6-methyl-5-
acetylpyrimidine 20a
A solution of 17 (0.01 mol) and appropriate aromatic amine (0.01 mol)
(aniline, p-toludine and/or anthranilic acid) in DMF (20 ml) was re-
fluxed for 2 h. The resulting colorless precipitate was collected by filtra-
tion and crystallized from ethanol to colorless crystals of 20a in 63.3%
yield; m.p. 150◦C; IR spectrum (KBr, ν, cm−1): 3455 (NH),1661 (CO); 1H
NMR spectrum (DMSO-d6, δ ppm): 2.7 (s, 3H, CH3), 3.00 (s, 3H, CH3),
7.1–8 (m, 8H, ArH’s), 10.3 (s, 1H, NH). MS m/z (%): 337 (M+, 9.28). Anal.
calcd. for C19H16ClN3O (337.81): C, 67.56; H, 4.77; N, 12.44. Found C,
67.61; H, 4.71; N, 12.41.
2-m-chlorophenyl-6-methyl-4(2-phenylhydrazino)-
5-acetylpyrimidine 20b
A mixture of compound 17 (0.01 mol) and phenylhydrazine (0.01 mol)
in ethanol (20 ml) was heated under reflux for 2 h. The resulting pre-
cipitate was collected by filtration was recrystallized from ethanol into
colorless crystals of 20b in 48.5% yield; m.p. 180◦C; IR spectrum (KBr,
ν, cm−1): 3455 (NH), 1661(CO); Anal. calcd. for C19H17ClN4O (352.82):
C, 64.68; H, 4.86; N, 15.88. Found C, 64.71; H, 4.81; N, 15.91.

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