Site selectivity in reaction of hydrazonoyl halides with 2-(aroylmethyl)-6-methylpyrimidin-4(3H)-ones

Article abstract of DOI:10.3184/030823408X382081

Reaction of hydrazonoyl halides 1 with 2-(aroylmethyl)-6-methylpyrimidin- 4(3H)-ones 3 proved to be site selective and gave 2-(3-acetyl-1,5-diarylpyrazol- 4-yl)-6-methylpyrimidin-4(3H)-ones 5 via dehydrative cyclisation of the hydrazone intermediates 4. T

Full text of DOI:10.3184/030823408X382081

688 RESEARCH PAPER
DECEMBER, 688-692
JOURNAL OF CHEMICAL RESEARCH 2008
Site selectivity in reaction of hydrazonoyl halides with
2-(aroyl methyl )-6-methylpyrim idin-4(3H )-ones
Ahmad S. Shawali* and Thoraya A. Farghaly
Department of Chemistry, Faculty of Science, University of Cairo, Giza, Egypt
Reaction of hydrazonoyl halides 1 with 2-(aroylmethyl)-6-methylpyrimidin-4(3H)-ones
3 proved to be site selective
and gave 2-(3-acetyl-1,5-diarylpyrazol-4-yl)-6-methylpyrimidin-4(3H)-ones
5 via dehydrative cyclisation of the
hydrazone intermediates 4. The structures of both 4 and 5 were elucidated by spectral data and alternative synthesis.
The mechanism of the reaction was discussed.
Keywords: site selectivity, hydrazonoyl halides, 2-(aroylmethyl)-6-methylpyrimidin-4(3H)-ones
Hydrazonoyl halides 1 are well known synthons and their
reactions have been extensively investigated.I-9 Although
there have been diverse studies on reactions of such halides 1
with various enamines 2,7 their reactions with 2-aroylmethyl-
R-C(X)=NNHAr
C;~H
6-methyl-pyrimidin-4(3H)-ones
3, which were reported
H
COR
in 1988 and were shown to exist in the ketene aminal form
3B (Fig. 1)10 have not been explored hitherto. In view of
this finding and in continuation of our research work on the
chemistry ofhydrazonoyl halides,I-9 it was thought interesting
to study reactions of hydrazonoyl halides with the latter 1,2-
cyclic ketene aminals 3B (Scheme 1). Our objective of this
study is to explore the site selectivity in such reactions as they
can theoretically lead to one or more of the products 4 -11
(Schemes 1 and 2).
2
Fig. 1
Results and discussion
analysis of the crude products isolated. This finding indicates
that the studied reactions are site selective. Mass spectra
and elemental analysis data of the isolated products were
consistent with each of the isomeric structures 5 (Scheme 1)
and 8-11 (Scheme 2). However, JR, IH and 13CNMR spectra
were found consistent with structure 5. For example, the mass
The starting compounds 3 were prepared from 6-methyl-
2-thiouracil as previously described.1OReaction of 3 with
each of the a-ketohydrazonoyl halides lA-C in ethanol in
the presence of sodium ethoxide at room temperature gave,
in each case, one isolable product as evidenced by TLC
~NH
) l .A.
+ R-C(X)=NNHC6H4Z
H3C
N
CH2COC6H4Y
1
3
-HOH
3
Y
H
a
X, CI or Br
b
c
4-CH3
4-CI
R : A, CH3CO; B, PhCO; C, 2-thienoyl; D, Ph; E, EtOCO; F, PhNHCO
Y / Z : a, H/H; b, H/4-CH3; c, H/4-CI; d,H/4-N02; e,4-CHiH;
f, 4-CHi4-CH3; g, 4-CHi4-CI; h, 4-CH i4-N02;
i, 4-CI/H; j, 4-CI/4-CH 3; k, 4-CI/4-CI; I, 4-CI/4-NO
2
Scheme
1
* Correspondent. E-mail: as_shawali@mail.com

JOURNAL OF CHEMICAL RESEARCH 2008 689
spectra of compounds 5 were consistent with their structures.
They revealed in each case the respective molecular ion peaks
together (M+ + 1) peak. Such peaks were not the base peaks,
however. In addition, the spectra revealed characteristic peaks
at m/z values corresponding to C6H5, XC6H4, XC6H4N2,
XC6H4CN and C5H5N20 ionic fragments. The latter fragment
corresponds to 6-methyl-4(3H)-pyrimidinone ring residue. The
IR spectra of the products prepared revealed in each case two
carbonyl bands and one NH band in the regions 1682-1655,
1654-1624 and 3286-3080 em-I, respectively. In addition, the
IH NMR spectra ofthe isolated products showed, in each case,
one NH signal at 8 11.80-10.16. This chemical shift value
while it is similar to that of pyrimidin-4(3H)-one derivative
(8l1.2-10.2),1l it is different from that of hydrazone NH (16.2-
16.0).12On the basis of these spectral findings, structures 8-11
(Scheme 2) were discarded and the isolated products from the
studied reaction were thus assigned structure 5 (Scheme 1).
This conclusion was further evidenced by the 13C NMR
spectrum of the product 5Ab taken as a typical example of the
series prepared. This spectrum revealed the carbonyl carbon
signal at 8 162.10 indicating that the adjacent nitrogen is of
pyrrole type i.e. sp3-hybrised.12-14
lH), 7.43-7.99 (m, l5H), 11.63 (s, lH) and 14.44 (s, lH)
which are consistent with the assigned structure 4Da.
When the latter hydrazone 4Da was heated with phosphorus
oxychloride, it underwent cyclisation and afforded a product
that was identified as 2-(1,3,5-triphenylpyrazol-4-yl)-6-
methylpyrimidin-4(3H)-one 5Da. The IR spectrum of the
latter showed only one carbonyl band and one NH band at
1667 and 3186 em-I, respectively. Its IH NMR spectrum in
DMSO-d6 showed four characteristic signals at 8 2.06 (s, 3H),
6.25 (s, lH), 7.62-7.98 (m, 15 H) and 12.83 (s, lH) which
are consistent with its assigned structure 5Da. The assigned
structure 5Da was substantiated by its alternative synthesis.
Thus, reaction of3a with benzoyl chloride in ethanolic sodium
ethoxide yielded 2-(dibenzoylmethyl)-5-methylpyrimidin-
4(3H)-one 12. Treatment of the latter with phenylhydrazine
in acetic acid at 60°C gave a product that proved identical
in all respects (m.p., mixed m.p., IR and mass spectra) with
5Da prepared above by reaction of 4Da with phosphorus
oxychloride (Scheme 3).
Similar reactions of
ethoxycarbonyl-methanehydrazonoyl cWorides IE and N-aryl
C-phenylaminocarbonyl-methanehydrazonoyl cWorides IF
3
with each of N-aryl C-
The formation of the products 5 can be rationalised as
follows. As compounds 3 have been shown to exist in the
ketene aminal tautomeric form 3B (Scheme 1),10,12,15they
will act, like other ketene aminals, as carbon rather than
nitogen nucleophiles. Thus, reactions of 3 with 1 will start
with the formation of the hydrazone derivatives 4 (Scheme 1),
which in turn undergo in situ dehydrative cyclisation under
the employed reaction conditions, to give 5 as end products.
The assigned structure 5 and the suggested pathway were
evidenced by isolation of the intermediate hydrazone 4 and
alternative synthesis of 5. For this purpose, we investigated
the reaction of N-phenyl benzenecarbohydrazonoyl cWoride
IDa with 3a in ethanol in the presence of sodium ethoxide at
room temperature. In our hands, such a reaction yielded one
product that was identified as 4Da. Its IR spectrum showed
two carbonyl band at 1670 and 1632 cm-I and two NH bands
at 3421 and 3180 em-I. Its IH NMR spectrum revealed
characteristic signals at 8 2.18 (s, 3H), 6.47 (s, lH), 6.63 (s,
afforded in all cases only the respective hydrazones 4E and
4F as end products. Attempts to cyclise the latter hydrazones
by heating them in acetic acid, xylene or in ethanol in the
presence of sodium ethoxide failed, however. The structures
of such products were confirmed by their spectra (MS, IR and
IH NMR) and elemental analyses (see Experimental).
In conclusion, the studied reactions of 1 with 3 are site
selective and depending on the structure of the hydrazonoyl
halide used, they can yield either the hydrazone derivatives
4 or 2-(1,3,5-trisubstitutedpyrazol-4-yl)-6-methylpyrimidin-
4(3H)-ones 5 as end products. The latter type of products
having both pyrazole and pyrimidinone residues are expected
to be of biological interest. This is because several pyrazole
and pyrimidinone derivatives have been reported to display a
wide range of potent biological activities.16-3oThe compounds
5 prepared herein will be screened for their biological activity
and the results will published in due course.
11
10
Scheme
2

690 JOURNAL OF CHEMICAL RESEARCH 2008
+
PhC(CI)=NNHPh
1Da
l
N
-HCI
o
£:):NH
COPh
H
H3C
)lNH
~tCOPh
Ph
) l .
.
4Da
NNHPh
H3C
N
m.A
Ph
0
12
I
PhNHNH2•
Scheme
3
2-[3-Acetyl-I-( 4-chlorophenyl)-5-phenyl-pyrazol-4-
yl] -6-methyl
Experimental
pyrimidin -4(3H)-one (5Ac): Red crystals (1.40 g, 70%), m.p. 216-
217°C; IR (KEr) 3136, 1658, 1624 cm-I; IH NMR (DMSO-d6) 2.23
(s, 3H, CH3), 2.30 (s, 3H, CH3), 5.80 (s, lH,ArH), 7.54-7.87 (m, 9H,
ArH), 11.79 (s, lH, NH); MS m/z (%) 405 (M+ + 1,2),404 (M+, 2),
229 (25), 228 (29),227 (12), 201 (12), 199 (10), 151 (28), 106 (10),
105 (100), 84 (28), 77 (88); AnaL Calcd for C22H17ClN402(404.86):
C,65.27; H,4.23; N, 13.84. Found: C, 65.10; H, 4.50; N, 13.48%.
2-[3 -Acetyl-I-( 4-nitrophenyl)-5 -phenyl-pyrazol-4-yl] -6-methyl
pyrimidin-4(3H)-one (5Ad): Red powder (1.20 g, 60%), m.p. 230-
232°C; IR (KEr) 3080, 1662, 1624 cm-I; IH NMR (DMSO-d6) 2.23
(s, 3H, CH3), 2.31 (s, 3H, CH3), 5.80 (s, lH, ArH), 7.54-7.87 (m,
9H,ArH), 11.80 (s, lH, NH); MS m/z (%) 417 (M+ + 2,22),416 (M+
+ 1,46),415 (M+, 40), 410 (32), 278 (43),250 (18), 153 (27), 138
(22), 122 (20), 108 (22), 105 (100), 91 (24),77 (99); AnaL Calcd for
C22H17Ns04(415.41): C,63.61; H,4.12; N, 16.86. Found: C, 63.35;
H, 4.00; N, 16.51%.
All melting points were determined on an electrothermal Gallenkamp
apparatus and are uncorrected. Solvents were generally distilled and
dried by standard literature procedures prior to use. The IR spectra
were measured on a Pye-Unicam SP300 instrument in potassium
bromide discs. The IH and BC NMR spectra were recorded on a
Varian Mercury VXR-300 spectrometer (300 MHz for IH NMR
and 75 MHz for BC NMR) and the chemical shifts were related to
that of the solvent DMSO-d6• The mass spectra were recorded on a
GCMS-Q1000-EX Shimadzu and GeMS 5988-A HP spectrometers,
the ionising voltage was 70 eY. Elemental analyses were carried out
by the Microanalytical Centre of Cairo University, Giza, Egypt. 2-
Aroylmethyl-6-methylpyrimidine-4(3H)-ones 3a-c were prepared as
previously described. I0
Reaction of of hydrazonoyl halides (IA-C) with 2-aroylmethyl-6-
methylpyrimidine-4(3H)-ones (3)
2-[3-Acetyl-5-( 4-methylphenyl)-I-phenyl-pyrazol-4-yl]
-6-methyl-
To a solution of a given compound 3 (5 mmole) in ethanolic sodium
ethoxide solution, prepared by dissolving sodium metal (0.12 g,
5 mmole) in absoute ethanol (20 ml), was added the appropraite
hydrazonoyl halide IA-C (5 mmoles). The reaction mixture was left
while being stirred overnight at room temperature. The precipitate
was filtered, washed with water and finally crystallised from ethanol
to give the respective products 5A-C, respectively. When the above
procedure was repeated using ID-F in place of IA-C, the products
obtained were the intermediate hydrazone derivatives 4D-F. The
physical constants and the spectral data of the products 5A-C and
4D-F isolated are listed below.
2-[3-Acetyl-I, 5-Diphenyl-pyrazol-4-yl] -6-methylpyrimidin-4(3H)-
one (5Aa): Orange powder (1.10 g, 62%), m.p. 220-222°C; IR (KBr)
3097, 1659, 1624 cm-I; IH NMR (DMSO-d6) 2.15 (s, 3H, CH3), 2.23
(s, 3H, CH3), 5.73 (s, lH,ArH), 7.48-7.77 (m, lOH,ArH), 11.68 (s,
lH, NH); MS m/z (%) 371 (M+ + 1, 1), 370 (M+, 2), 228 (23), 227
(10),200 (16),151 (24), 105 (100), 84 (31), 77 (83); AnaL Calcd for
C22HISN402(370.41): C,71.34; H,4.90; N, 15.13. Found: C, 71.22;
H, 4.65; N, 15.00%.
pyrimidin-4(3H)-one (5Ae):Red needles (1.20 g, 60%), m.p. 200-
201°C; IR (KBr) 3286,1674, 1631 cm-I; IH NMR (CDC13)2.20 (s,
3H, CH3), 2.40 (s, 3H, CH3), 2.80 (s, 3H, CH3), 6.05 (s, lH, ArH),
7.22-7.80 (m, 9H, ArH), 10.95 (s, lH, NH); MS m/z (%) 386 (M+ +
2, 12), 385 (M+ + 1, 56), 384 (M+, 60), 367 (32), 293 (39),292 (37),
266 (11), 120 (10), 119 (100), 106 (19), 91 (77), 84 (22), 77 (51);
Anal. Calcd for C23H20N402(384.44): C,71.86; H,5.24; N, 14.57.
Found: C,72.00; H, 5.53; N, 14.24%.
2-[3 -Acety 1-1,5 -di- (4-m ethy Ipheny I)-pyrazol-4 -y l]-6-methy I
pyrimidin-4(3H)-one (5At): Orange needle crystals (1.20 g, 62%),
m.p. 230-232 °C; IR (KBr)3128, 1662, 1624 cm-I; IHNMR (CDC13)
2.20 (s, 3H, CH3), 2.35 (s, 3H, CH3), 2.40 (s, 3H, CH3), 2.64 (s, 3H,
CH3), 6.06 (s, lH,ArH), 6.99-7.83 (m, 8H,ArH), 10.16 (s, lH, NH);
MS m/z (%) 399 (M+ + 1,3), 398 (M+, 2), 243 (28),242 (19), 241
(12),214 (14), 151 (21), 119 (100), 91 (52), 84 (21), 77 (5); AnaL
Calcd for C24H22N402(398.47): C,72.34; H,5.57; N, 14.06. Found:
C, 72.09; H, 5.42; N, 14.20%.
2-[3-Acetyl-5-( 4-methylphenyl)-I-( 4-chlorophenyl)-pyrazol-4-yl]-
6-methylpyrimidin-4(3H)-one (5Ag): Red powder (1.40 g, 62%), m.p.
210-212°C; IR (KBr) 3150, 1666, 1630 em-I; IH NMR (CDC13)
2.23 (s, 3H, CH3), 2.44 (s, 3H, CH3), 2.86 (s, 3H, CH3), 6.08 (s, lH,
ArH), 6.91-7.83 (m, 8H, ArH), 10.94 (s, lH, NH); MS m/z (%) 420
(M+ + 2,2),419 (M+ + 1, 5), 418 (M+, 8),292 (35), 243 (21),242
(20),241 (24),214 (15), 151 (21), 119 (100), 91 (66),84 (23), 77 (5);
Anal. Calcd for C23HI9ClN402 (418.89): C,65.95; H,4.57; N, 13.38.
Found: C, 65.70; H, 4.36; N, 13.09%.
2-[3-Acetyl-5-( 4-methylphenyl)-I-( 4-nitrophenyl)-pyrazol-4-yl] -6-
methyl-pyrimidin-4(3H)-one (5Ah): Red needles (1.30 g, 60%), m.p.
222-223°C; IR (KBr)3160, 1666, 1624 cm-I; IHNMR (CDC13)2.25
(s, 3H, CH3), 2.40 (s, 3H, CH3), 2.44 (s, 3H, CH3), 5.75 (s, lH,ArH),
2-[3 -Acetyl-I-( 4-methylphenyl)-5
-phenyl-pyrazol-4-yl]
-6-
methyl-pyrimidin-4(3H)-one (5Ab): Orange powder (1.20 g, 64%),
m.p. 199-200°C; IR (KBr) 3097,1662,1627 cm-I; IHNMR (DMSO-
d6) 2.22 (s, 3H, CH3), 2.30 (s, 3H, CH3), 2.50 (s, 3H, CH3), 5.78
(s, lH, ArH), 7.42-7.85 (m, 9H, ArH), 11.80 (s, lH, NH); BC NMR
(DMSO-d6)20.27, 22.00, 24.83, 114.87, 120.59, 121.25, 126.26,
128.11, 128.34, 128.62, 129.38, 129.70, 129.93, 130.88, 133.11,
139.20, 152.97, 162.10, 194.68; MS m/z (%) 385 (M+ + 1, 7), 384
(M+, 8), 228 (29),200 (18), 151 (29), 105 (100), 84 (25), 77 (80);
Anal. Calcd for C23H20N402(384.44): C,71.86; H,5.24; N, 14.57.
Found: C, 71.59; H, 5.05; N, 14.80%.

JOURNAL OF CHEMICAL RESEARCH 2008 691
7.22-8.26 (m, 8H,ArH), 10.77 (s, lH, NH); MS m/z (%) 431 (M++ 2,
5),430 (M+ + 1,20),429 (M+, 9), 411 (14),292 (10), 120 (100), 119
(62),91 (50),76 (9); Anal. Calcd for C23HI9Ns04 (429.44): C,64.33;
H,4.46; N, 16.31. Found: C, 64.52; H, 4.21; N, 16.30%.
Ethyl 2, 4-dioxo-3-(6-methyl-4-oxo-3H-pyrimidin-2-yl)-4-(methyl-
phenyl)-butanoate-2-phenylhydrazone
(4Ee): Pale yellow needles
(1.3 g, 60%), m.p. 205-206°C; IR (KEr) 3402, 3190, 1735, 1670,
1624 cm-I; IH NMR (CDCI3) 1.26 (t, J= 7 Hz, 3H, CH3), 1.96 (s,
3H, CH3), 2.28 (s, 3H, CH3), 4.29 (q,J= 7 Hz, 2H, CH2), 5.28 (s, lH,
CH), 5.93 (s, lH, ArH), 7.05-7.55 (m, 9H, ArH), 11.33 (s, lH, NH),
14.06 (s, lH, NH). MS m/z (%) 433 (M+ + 1,4),432 (M+, 3), 388
(12),299 (22), 186 (5), 134 (11), 119 (100), 91 (75),77 (32); Anal.
Ca1cd for C24H2~404 (432.48): C, 66.65; H, 5.59; N, 12.95. Found:
C, 66.60; H, 5.32; N, 13.00%.
3-(6-Methyl-4-oxo-3H-pyrimidin-2-yl)-4-oxo-4-phenyl-2-(phenyl-
hydrazono)butanilide (4Fa): Pale yellow powder (1.60 g, 70%),
m.p. 218-220°C; IR (KEr) 3395, 3236, 1690, 1681, 1620 cm-I;
IH NMR (DMSO-d6) 2.45 (s, 3H, CH3), 5.53 (s, lH, CH), 5.95
(s, lH, ArH), 7.05-7.86 (m, 15H, ArH), 10.21 (s, lH, NH), 10.86
(s, lH, NH), 14.82 (s, lH, NH); MS m/z (%) 467 (M+ + 1, 1),466
(M+, 2), 346 (14), 345 (15), 229 (9), 118 (5), 105 (100), 91 (33),
77 (96); Anal. Calcd for C27H23Ns03(465.52): C,69.66; H,4.98; N,
15.04. Found: C, 69.60; H, 5.30; N, 15.10%.
2-[3-Acetyl-5 -(4-chlorophenyl)-I-phenyl-pyrazol-4-yl]
-6-methyl
pyrimidi-4(3H)-one (5Al): Orange powder (1.30 g, 66%), m.p. 286-
288°C; IR (KEr) 3132, 1655, 1624 cm-I; IH NMR (DMSO-d6) 2.19
(s, 3H, CH3), 2.45 (s, 3H, CH3), 5.72 (s, lH,ArH), 7.07-7.80 (m, 9H,
ArH), 11.19 (s, lH, NH); MS m/z (%) 406 (M+ + 2,1),405 (M+ + 1,
1),404 (M+, 1), 264 (20), 234 (24), 151 (49), 139 (100), 113 (18),
111 (54), 84 (21), 75 (28); Anal. Calcd for C22H17C1N402(404.86):
C,65.27; H,4.23; N, 13.84. Found: C, 65.22; H, 4.51; N, 13.70%.
2-[3-Acetyl-5-( 4-chlorophenyl)-I-( 4-methylphenyl)-pyrazol-4-yl]-
6-methyl pyrimidin-4(3H)-one (5Aj): Orange platelets (1.50 g, 70%),
m.p. 276-278°C; IR(KBr)3131, 1658, 1631 cm-I; IHNMR(DMSO-
d6) 2.18 (s, 3H, CH3), 2.28 (s, 3H, CH3), 2.49 (s, 3H, CH3), 5.72 (s,
lH, ArH), 7.20-7.79 (m, 8H, ArH), 11.23 (s, lH, NH); MS m/z (%)
420 (M+ + 2, 1),419 (M+ + 1, 1),418 (M+, 10),262 (60), 234 (22),
233 (18), 151 (46), 141 (34), 139 (100), 113 (17), 111 (50), 106 (25),
91 (14), 84 (21), 77 (18); Anal. Ca1cd for C23HI9CIN402 (418.89):
C,65.95; H,4.57; N, 13.38. Found: C, 65.62; H, 4.31; N, 13.20%.
2-[3 -Acetyl-I, 5-di- (4-chI orop heny I)-pyrazol-4 -y l]-6-methyl
3-(6-Methyl-4-oxo-3H-pyrimidin-2-yl)-4-oxo-4-(
4-methylphenyl)-
2-(phenylhydrazono)butanilide (4Fe): Pale yellow needles (1.60 g,
65%), m.p. 209-210°C; IR (KBr) 3394, 3232, 3028, 1712, 1678,
1620 cm-I; IH NMR (DMSO-d6) 2.27 (s, 3H, CH3), 2.34 (s, 3H,
CH3), 5.40 (s, lH, CH), 5.81 (s, lH,ArH), 6.95-8.13 (m, 14H,ArH),
10.07 (s, lH, NH), 10.71 (s, lH, NH), 14.75 (s, lH, NH); MS m/z (%)
479 (M+, 2),397 (11), 345 (9), 301 (6),226 (7), 134 (6), 119 (100),
91 (61), 77 (36); Anal. Ca1cd for C28H2SNs03 (479.54): C,70.13;
H,5.25; N, 14.60. Found: C, 70.00; H, 5.30; N, 14.30%.
pyrimidin-4(3H)-one
(5Ak): Orange powder (1.40 g, 66%),
m.p. 270-272°C; IR(KBr)3130, 1660, 1629cm-I; IHNMR(DMSO-
d6) 2.12 (s, 3H, CH3), 2.21 (s, 3H, CH3), 5.74 (s, lH,ArH), 7.42-7.78
(m, 8H, ArH), 11.74 (s, lH, NH); MS m/z (%) 441 (M+ + 2, 2), 440
(M+ + 1, 5), 439 (W , 10), 438 (3), 264 (20), 263 (20), 261 (30),
234 (25), 151 (51),139 (100), 113 (19), 111 (51), 84 (45), 75 (47);
Anal. Calcd for C22HI6C12N402(439.30): C,60.15; H,3.67; N, 12.75.
Found: C,60.00; H, 3.95; N, 12.51%.
2-[3-Acetyl-5-( 4-chlorophenyl)-I-( 4-nitrophenyl)-pyrazol-4-yl]-
6-methyl pyrimidin-4(3H)-one (5Al): Red needles (1.40 g, 62%),
Cyclisation of 4Da into 5Da
A mixture of 4Da (0.0025 mole) and phosphourus oxychloride
(10 ml) was refluxed for 10 h, then the reaction mixture was cooled
and neutralised with sodium carbonate. The solid, that precipitated,
was filtered off and crystallised from ethanol to give 5Da.
Dark yellow needles (0.50 g, 50%), m.p.180-181°C; IR (KBr)
3186, 1667 cm-I; IH NMR (DMSO-~) 2.06 (s, 3H, CH3), 6.25 (s,
lH, ArH), 7.62-7.96 (m, 15H, ArH), 12.83 (s, lH, NH); MS m/z
(%) 404 (M+, 1), 402 (32),401 (78), 400 (56), 399 (71), 198 (22),
150 (16), 141 (32), 139 (70), 136 (100), 113 (33), 111 (95),91 (12),
75 (64); Anal. Ca1cd for C26H2oN40 (404.48): C,77.21; H,4.98; N,
13.85. Found: C, 77.57; H, 4.80; N, 13.62%.
m.p.158-159°C;IR(KBr)3085,
1682, 1630cm-I; IHNMR(DMSO-
d6)2.19 (s, 3H, CH3), 2.49 (s, 3H, CH3), 5.73 (s, lH,ArH), 7.13-8.50
(m, 8H, ArH), 11.32 (s, lH, NH); MS m/z (%) 451 (M+ + 2, 1),450
(M+ + 1, 1),449 (M+, 2), 410 (100), 368 (14), 341 (56),313 (50),285
(56), 274 (34), 262 (49), 163 (33), 139 (88), 111 (27), 90 (40), 76
(32); Anal. Ca1cd for C22HI6CINS04 (449.86): C,58.74; H,3.59; N,
15.57. Found: C, 58.59; H, 3.24; N, 15.25%.
2-[3 -Benzoy I-I ,5 -diphenyl-pyrazol-4- yl] -6-m ethy lpyrimidin-
4(3H)-one (5Ba): Orange powder (1.73 g, 80%), m.p. 226-227°C;
IR (KBr) 3413, 1678, 1654 em-I; IH NMR (DMSO-d6) 2.49 (s, 3H,
CH3), 6.05 (s, lH, ArH), 7.48-7.81 (m, 15H, ArH), 10.76 (s, lH,
NH); MS m/z (%) 432 (M+, 10), 429 (67), 363 (80), 291 (99), 203
(100),181 (80), 154 (80), 136 (80), 112 (73),104 (73), 75 (73); Anal.
Calcd for C27H2oN402(432.49): C,74.99; H,4.66; N, 12.95. Found:
C, 74.70; H, 4.38; N, 12.67%.
2-[3-thenoyl-I-( 4-chlorophenyl)-5-phenyl-pyrazol-4-yl] -6-methyl-
pyrimidin-4(3H)-one (5Cc): Orange powder (1.54 g, 65%), m.p.
197-198°C; IR (KBr) 3078,1681,1654 cm-I; IH NMR (DMSO-d6)
2.39 (s, 3H, CH3), 6.01 (s, lH,ArH), 7.51-8.59 (m, 12H,ArH), 10.63
(s, lH, NH); MS m/z (%) 474 (M+ + 2,1),473 (M+ + 1,1),472 (M+,
1),372 (2), 283 (1), 177 (3), 134 (2), 113 (6), 111 (100), 109 (1), 83
(6),76 (3); Anal. Calcd for C2sH17C1N402S(472.5): C,63.49; H,3.60;
N, 11.85. Found: C,63.21; H, 3.34; N, 11.60%.
1,3-Diphenyl-2-(6-methyl-4-oxo-3H-pyrimidin-2-yl)-propane-1,3-
dione-I-phenylhydrazone (4Da): Pale yellow needles (1.40 g, 65%),
m.p. 238-239°C; IR (KBr) 3421, 3180, 1670, 1632 cm-I; IH NMR
(DMSO-d6) 2.18 (s, 3H, CH3), 6.05 (s, lH, CH), 6.47 (s, lH, ArH),
7.43-7.99 (m, 15H, ArH), 11.63 (s, lH, NH), 14.44 (s, lH, NH); MS
m/z (%) 423 (M++ 1,5),422 (M+, 11), 195 (18),194 (100),105 (76),
91 (91), 77 (84); Anal. Ca1cd for C2~22N402 (422.49): C,73.92;
H,5.25; N, 13.26. Found: C,73.70; H, 5.10; N, 13.00%.
Alternate synthesis of5Da
To a solution of compound 3a (1.14 g, 5 mmole) in ethanolic sodium
ethoxide solution prepared by dissolving sodium metal (0.12 g,
5 mmoles) in absolute ethanol (20 ml), was added benzoyl chloride
(0.70 g, 5 mmoles). The reaction mixture was left whilst being stirred
for 3 days at room temperature. The precipitate was filtered, washed
with water and finally crystallised from ethanol to give compound
12 as pale yellow powder, (0.58 g, 35%), m.p. 204-206°C; IR (KBr)
3421, 1678, 1658 cm-I; IH NMR (DMSO-d6) 2.15 (s, 3H, CH3), 5.59
(s, lH, CH), 5.75 (s, lH, ArH), 7.51-7.80 (m, lOH, ArH), 11.76 (s,
lH, NH); MS m/z (%) 333 (M+ + 1, 10),332 (M+, 21), 227 (18),223
(31),122 (25),118 (14),109 (72),105 (90), 77 (100); Anal. Ca1cd for
C2oHI~203 (332.36): C,72.28; H,4.85; N, 8.43. Found: C, 72.05; H,
4.60; N, 8.05%.
To a solution of compound 12 (1.66 g, 5 mmole) in acetic acid
(20 ml), was added phenyl hydrazine (0.54 g, 5 mmole). The reaction
mixture was left while being stirred for 2 days at 60°C in water bath.
The precipitate was filtered, washed with water and finally crystallised
from ethanol to give compound 5Da which found identical in all
respects with that produced from method A
3-(4-M ethylpheny 1)-2-(6-methyl-4-oxo-3H-pyrimidin-
2-yl)-I-
phenyl propane-I,3-dione-I-phenylhydrazone (4De): Pale yellow
powder (1.69 g, 72%), m.p. 194-195°C; IR (KBr) 3409, 3100,1685,
1631 em-I; IH NMR (CDCI3) 2.04 (s, 3H, CH3),2.15 (s, 3H, CH3),
5.47 (s, lH, CH), 5.74 (s, lH, ArH), 6.89-7.65 (m, 14H, ArH), 9.90
(s, lH,NH), 14.17 (s, lH, NH);Anai. Ca1cdforC27H2~402(436.52):
C,74.29; H,5.54; N, 12.83. Found: C,74.00; H, 5.72; N, 12.51%.
Received 27 August 2008; accepted 15 October 2008
Paper 08/0130 doi:l0.3184/030823408X382081
Published online: 10 December 2008
Ethyl
2,4-dioxo-3-(6-methyl-4-oxo-3H-pyrimidin-2-yl)-4-phenyl-
butanoate-2-phenylhydrazone (4Ea): Pale yellow powder (1.25 g,
60%), m.p. 220-222°C; IR (KBr) 3464, 3171, 1701, 1659, 1639 cm-I;
IH NMR (CDCI3) 1.38 (t, J = 7 Hz, 3H, CH3), 2.07 (s, 3H, CH3),4.36
(q,J= 7 Hz, 2H, CH2), 5.46 (s, lH, CH), 5.66 (s, lH,ArH), 7.02-7.60
(m, lOH,ArH), 11.05 (s, lH, NH), 14.21 (s, lH, NH). MS m/z (%) 420
(M+ + 2, 1),419 (M++ 1,4),418 (M+, 6), 374 (14), 298 (10), 118 (3),
105 (100), 91 (41),77 (79); Anal. Calcd for C23H22N404(418.46): C,
66.02; H, 5.30; N, 13.39. Found: C, 66.20; H, 5.40; N, 13.61%.
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