A convenient route for the synthesis of 4-aryl- and 4-aminopyrimidines

Article abstract of DOI:10.1007/s00706-004-0192-8

A series of ureidopropenenitriles were synthesised by Knoevenagel condensation of ArCOCH₂CN and HC(OEt)₃ in presence of ureas in a one potreaction. These ureidopropenenitriles were cyclised to 4-aryl-5-cyano-3-substituted pyrimidines (in acid) or to 4-amino-5- benzoylpyrimidines (in base) in 60-70% yields. The amine pyrimidine derivatives were further converted to substituted uracils by hydrolysis with isopentyl nitrite in DMF. Alkylation of uracils furnished 1,3-dimethyluracil derivatives with DMS in alkali. All new compounds were characterised by spectral and analytical methods. Springer-Verlag 2004.

Full text of DOI:10.1007/s00706-004-0192-8

Monatshefte f€ur Chemie 135, 1529–1538 (2004)
DOI 10.1007/s00706-004-0192-8
A Convenient Route for the Synthesis
of 4-Aryl- and 4-Aminopyrimidines
ꢀ
and Naresh S. Badgujar
Madhukar N. Jachak , Chanda D. Tantak, Raghunath B. Toche,
Post Graduate Department of Chemistry, K.R.T. Arts, B.H. Commerce &
A.M. Science College, Nashik, 422002, India
Received January 7, 2004; accepted (revised) February 2, 2004
Published online September 24, 2004 # Springer-Verlag 2004
Summary. A series of ureidopropenenitriles were synthesised by Knoevenagel condensation of
ArCOCH2CN and HC(OEt)3 in presence of ureas in a one pot reaction. These ureidopropenenitriles were
cyclised to 4-aryl-5-cyano-3-substituted pyrimidines (in acid) or to 4-amino-5-benzoylpyrimidines (in
base)in60–70% yields. The amine pyrimidine derivativeswerefurther converted tosubstituteduracils by
hydrolysis with isopentyl nitrite in DMF. Alkylation of uracils furnished 1,3-dimethyluracil derivatives
with DMS in alkali. All new compounds were characterised by spectral and analytical methods.
Keywords. Parasubstituted benzoylacetonitrile; 4-Arylpyrimidone; 5-Aroyluracils; 4-Aminopyrimi-
done; 1,3-Dimethyluracils.
Introduction
Several 4-arylpyrimidine derivatives have recently emerged as the integral back-
bone of calcium channel blockers, antihypertensive agents, and antagonists [1–5].
Furthermore several marine alkaloids containing a pyrimidine nucleus display
interesting antifungal activity [6, 7]. H. Junek and MNJ have reported the synthesis
of cytosine derivatives using cyanoacetaldehyde, DMF-acetal, and ureas [8]. In an
earlier communication the synthesis of 5-benzoylcytosine derivatives starting with
ureidopropenenitriles has been reported [9]. As a part of ongoing interest in this
area we now report the synthesis of ureidopropenenitriles 4, 4-arylpyrimidines 5,
and 4-aminopyrimidines 6.
Results and Discussion
In a previous communication [9] we have reported the one-pot synthesis of urei-
dopropenenitriles 4 using benzoylacetonitrile, triethyl orthoformate, and urea or
ꢀ
Corresponding author. E-mail: mn_jachak@hotmail.com

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M. N. Jachak et al.
substituted ureas. Herein we report the synthesis of 4 using substituted benzoyl-
acetonitriles 1a–1c and their transformation to pyrimidine derivatives 5, 6, 7, and 8.
Thus, the mixture of substituted benzoylacetonitriles 1 triethyl orthoformate and
urea or substituted ureas 3 on heating at 70ꢁC furnishes 4 in high yields. All
ureidopropenenitriles were characterized by spectral and analytical methods. These
ureidopropenenitriles 4 could be cyclised to pyrimidine derivatives 5 or 6 in acid or
on basic medium. Thus, 4a, 4h, 4i, and 4n when refluxed in acetic acid yielded 4-
arylpyrimidine derivatives 5 in good yields. On refluxing 4 in ethanol=sodium
ethoxide furnished the 4-aminopyrimidine derivatives 6, with the exception of
1
4h and 4s. In the H NMR spectrum of compounds 6 it was observed that the
N–H proton of the NH2 group at position 4 gave two different signals at ꢀ ¼ 8.80
and 9.90 ppm. This may be due to H-bonding with the carbonyl oxygen of aroyl
at position 5 (Scheme 1). Compounds 6 on heating in DMF in the presence
of isopentyl nitrite at 65ꢁC furnished uracil derivatives 7 in 80–90% yields
(Scheme 2).
Scheme 1

Synthesis of 4-Aryl- and 4-Aminopyrimidines
1531
Scheme 2
Scheme 3
It was noted from literature that compounds containing an alkyl or sugar moiety
on the pyridine nitrogen display anticancer activity [10], hence we attempted alkyl-
ation of 7. Thus, methylation of 7 with DMS in alkali furnished the 1,3-dimethyl
uracil derivatives 8 (Scheme 3). However, attempts to derivatise with sugar resi-
dues were unsuccessful. All new compounds 5, 6, 7, and 8 were characterized by
1
IR, H NMR and elemental analysis.
Experimental
Melting points (uncorrected): Gallenkamp Melting Point Apparatus; IR Spectra (KBr-compression
1
mould): Schimadzu IR-408; H NMR spectra: Varian XL-300 (300MHz), DMSO-d6, CDCl3, TMS;
elemental analysis: HOSLI CH-Analyser; the results were in agreement with calculated values.
General Procedure for the Synthesis of 2-Aroyl-3-ureido-
or -thioureidopropenenitriles 4a–4s
A mixture of 0.01 mol of 1, 2.22 g of 2 (0.015 mol) and 0.012mol of urea, substituted urea, or thiourea
3a–3x was heated at 60–70ꢁC in an oil bath for 30min (TLC check). The resulting solid was stirred in
30cm3 of petroleum ether, filtered, dried, and recrystallised.
2-(4-Chlorobenzoyl)-3-ureidopropenenitrile (4a, C11H8ClN3O2)
Yield 2.11 g (84%), mp 202–203ꢁC (DMF ethanol); IR: ꢁꢀ¼ 3400, 2240, 1750, 1700 cmꢂ1; 1H NMR:
ꢀ ¼ 6.75 (bs, NH2), 7.49–7.62 (m, Ar–H), 7.84 (d, J ¼ 12.5Hz, ¼CH), 8.28 (d, J ¼ 12.5Hz, NH) ppm.

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M. N. Jachak et al.
2-(4-Chlorobenzoyl)-3-methylureidopropenenitrile (4b, C12H10ClN3O2)
Yield 1.41 g (53%), mp 184–185ꢁC (ethanol); IR: ꢁꢀ¼ 3450, 3250, 2250, 1750, 1710cmꢂ1; 1H NMR:
ꢀ ¼ 2.68 (d, J ¼ 5 Hz, CH3), 7.18 (bs, NH), 7.60–7.81 (m, Ar–H), 7.80 (d, J ¼ 12.5Hz, ¼CH), 11.31
(d, J ¼ 12.5 Hz, NH) ppm.
2-(Chlorobenzoyl)-3-ethylureidopropenenitrile (4c, C13H12ClN3O2)
1
Yield 2.41 g (86%), mp 213–214ꢁC (methanol); IR: ꢁꢀ¼ 3330, 2240, 1740, 1640cmꢂ1; H NMR:
ꢀ ¼ 1.05 (t, J ¼ 7.5 Hz, CH3), 3.25 (q, J ¼ 7.5 Hz, CH2), 7.34 (d, J ¼ 7.5 Hz, NH), 7.61–7.72 (m, Ar–
H), 8.35 (d, J ¼ 12.5 Hz, ¼CH), 11.65 (d, J ¼ 12.5Hz, NH) ppm.
2-(4-Chlorobenzoyl)-3-phenylureidopropenenitrile (4d, C17H12ClN3O2)
1
Yield 2.60g (80%), mp 225–226ꢁC (DMF); IR: ꢁꢀ¼ 3500, 3100, 2250, 1740, 1695cmꢂ1; H NMR:
ꢀ ¼ 7.15 (s, NH), 7.31–7.55 (m, Ar–H), 7.65–7.80 (m, Ar–H), 7.95 (d, J ¼ 12.5Hz, ¼CH), 11.92 (d,
J ¼ 12.5Hz, NH) ppm.
3-Allylureido-2-(4-chlorobenzoyl)propenenitrile (4e, C14H12ClN3O2)
Yield 2.61g (89%), mp 195–196ꢁC (ethanol); IR: ꢁꢀ¼ 3400, 2250, 1750, 1660cmꢂ1
;
1H NMR:
ꢀ ¼ 3.82 (d, J ¼ 6 Hz, CH2), 5.18 (dd, J ¼ 10.6, 6.0Hz, ¼CH2), 5.85 (m, ¼CH), 7.45 (t, J ¼ 12 Hz,
NH), 7.68–7.82 (m, Ar–H), 8.38 (d, J ¼ 12.5Hz, ¼CH), 11.62 (d, J ¼ 12.5Hz, NH) ppm.
3-Benzylureido-2-(4-chlorobenzoyl)propenenitrile (4f, C18H14ClN3O2)
Yield 2.65 g (78%), mp 204–205ꢁC (DMF:ethanol); IR: ꢁꢀ¼ 3320, 2230, 1740, 1655cmꢂ1; 1H NMR:
ꢀ ¼ 4.42 (d, J ¼ 8 Hz, CH2), 7.21–7.45 (m, Ar–H), 7.65–7.82 (m, Ar–H), 8.35 (d, J ¼ 12.5 Hz, ¼CH),
8.90 (t, J ¼ 8 Hz, NH) 11.75 (d, J ¼ 12.5Hz, NH) ppm.
2-(4-Chlorobenzoyl)-3-methylthioureidopropenenitrile (4g, C12H10ClN3OS)
Yield 1.80 g (64%), mp 205–206ꢁC (ethanol); IR: ꢁꢀ¼ 3370, 3250, 3220, 2240, 1640cmꢂ1; 1H NMR:
ꢀ ¼ 3.04 (s, CH3), 7.60–7.73 (m, Ar–H), 7.96 (d, J ¼ 12.5Hz, ¼CH), 8.92 (bs, NH), 11.43 (d,
J ¼ 12.5Hz, NH) ppm.
2-(4-Bromobenzoyl)-3-ureidopropenenitrile (4h, C11H8BrN3O2)
Yield 2.05 g (70%), mp 198–199ꢁC (ethanol); IR: ꢁꢀ¼ 3450, 3300, 2250, 1710, 1670 cmꢂ1; 1H NMR:
ꢀ ¼ 6.73 (bs, NH2), 7.41–8.01 (m, Ar–H), 8.32 (d, J ¼ 12.5Hz, ¼CH), 11.55 (d, J ¼ 12.5 Hz, NH) ppm.
2-(4-Bromobenzoyl)-3-methylureidopropenenitrile (4i, C12H10BrN3O2)
Yield 2.15 g (70%), mp 198–199ꢁC (ethanol); IR: ꢁꢀ¼ 3450, 3330, 2250, 1750, 1710cmꢂ1; 1H NMR:
ꢀ ¼ 2.73 (s, CH3), 7.15 (bs, NH, exchangeable with D2O), 7.67–7.71 (m, Ar–H), 8.29 (d, J ¼ 12.5Hz,
¼CH), 11.70 (d, J ¼ 12.5 Hz, NH, exchangeable with D2O) ppm.
2-(4-Bromobenzoyl)-3-ethylureidopropenenitrile (4j, C13H12BrN3O2)
Yield 2.15 g (67%), mp 180–181ꢁC (ethanol); IR: ꢁꢀ¼ 3350, 3250, 2210, 1750, 1650cmꢂ1; 1H NMR:
ꢀ ¼ 1.04 (t, J ¼ 7.5 Hz, CH3), 3.22 (q, J ¼ 7.5 Hz, CH2), 7.14 (s, NH), 7.59–7.74 (m, Ar–H), 8.26 (d,
J ¼ 12.5Hz, ¼CH), 11.84 (d, J ¼ 12.5Hz, NH, exchangeable with D2O) ppm.

Synthesis of 4-Aryl- and 4-Aminopyrimidines
1533
3-Benzylureido-2-(4-bromobenzoyl)propenenitrile (4k, C18H14BrN3O2)
Yield 2.46 g (76%), mp 195–196ꢁC (DMF); IR: ꢁꢀ¼ 3320, 2230, 1740, 1655 cmꢂ1; 1H NMR: ꢀ ¼ 4.31
(d, J ¼ 8 Hz, CH2), 7.50–7.55 (m, Ar–H), 7.56–7.65 (m, Ar–H), 7.85 (s, NH, exchangeable with D2O),
8.44 (d, J ¼ 12.5 Hz, ¼CH), 11.59 (d, J ¼ 12.5Hz, NH, exchangeable with D2O) ppm.
2-(4-Bromobenzoyl)-3-methylthioureidopropenenitrile (4l, C12H10BrN3OS)
Yield 2.43 g (75%), mp 180–181ꢁC (ethanol); IR: ꢁꢀ¼ 3450, 3330, 2250, 1750, 1710cmꢂ1; 1H NMR:
ꢀ ¼ 3.04 (d, J ¼ 5 Hz, CH3), 7.45 (d, J ¼ 5 Hz, NH), 7.60–7.76 (m, Ar–H), 8.80 (d, J ¼ 12.5Hz, ¼CH),
11.25 (d, J ¼ 12.5Hz, NH) ppm.
3-Allylureido-2-(4-bromobenzoyl)propenenitrile (4m, C14H12BrN3O2)
Yield 2.24 g (65%), mp 190–191ꢁC (ethanol); IR: ꢁꢀ¼ 3300, 3200, 2200, 1740, 1650cmꢂ1; 1H NMR:
ꢀ ¼ 3.81 (d, J ¼ 6 Hz, CH2), 5.52 (dd, J ¼ 10.6, 6.0 Hz, ¼CH2), 5.81 (m, ¼CH), 7.43 (bs,
NH, exchangeable with D2O), 7.45–7.89 (m, Ar–H), 8.23 (d, J ¼ 12.5Hz, ¼CH), 11.70 (d,
J ¼ 12.5Hz, NH, exchangeable with D2O) ppm.
2-(4-Methylbenzoyl)-3-ureidopropenenitrile (4n, C11H11N3O2)
Yield 1.81 g (78%), mp 204–205ꢁC (DMF ethanol); IR: ꢁꢀ¼ 3397, 3294, 2212, 1738, 1705,
1
1630 cmꢂ1; H NMR: ꢀ ¼ 2.36 (s, CH3), 6.77 (bs, NH2), 7.35–7.52 (m, Ar–H), 8.30 (d, J ¼ 12.6Hz,
¼CH), 11.60 (d, J ¼ 12.6 Hz, NH) ppm.
2-(4-Methylbenzoyl)-3-methylureidopropenenitrile (4o, C13H13N3O2)
Yield 2.00 g (82%), mp 204–205ꢁC (ethanol); IR: ꢁꢀ¼ 3374, 3138, 2217, 1693, 1620cmꢂ1; 1H NMR:
ꢀ ¼ 2.41, 2.52 (2s, 2CH3), 7.41–7.75 (m, Ar–H), 7.93 (bs, NH), 8.20 (d, J ¼ 12.5 Hz, ¼CH), 12.92 (bs,
NH) ppm.
3-Ethylureido-2-(4-methylbenzoyl)propenenitrile (4p, C14H15N3O2)
1
Yield 2.11 g (81%), mp 144–145ꢁC (methanol); IR: ꢁꢀ¼ 3400, 3300, 2245, 1740, 1650cmꢂ1; H
NMR: ꢀ ¼ 1.10 (t, J ¼ 7.5 Hz, CH3), 2.42 (s, CH3), 3.62 (d, J ¼ 7.5 Hz, CH2), 7.08 (bs, NH), 7.29–
7.82 (m, Ar–H), 8.23 (d, J ¼ 12.5Hz, ¼CH), 11.89 (d, J ¼ 12.5Hz, NH) ppm.
2-(4-Methylbenzoyl)-3-phenylureidopropenenitrile (4q, C18H15N3O2)
1
Yield 2.80g (92%), mp 232–233ꢁC (DMF); IR: ꢁꢀ¼ 3400, 3300, 2445, 1740, 1650cmꢂ1; H NMR:
ꢀ ¼ 2.44 (s, CH3), 7.08 (bs, NH), 7.07–7.52 (m, Ar–H), 7.62–7.83 (m, Ar–H), 9.95 (d, J ¼ 12.5Hz,
¼CH), 12.02 (d, J ¼ 12.5 Hz, NH) ppm.
3-Allylureido-2-(4-methylbenzoyl)propenenitrile (4r, C15H15N3O2)
Yield 2.00 g (74%), mp 140–141ꢁC (aqueous ethanol); IR: ꢁꢀ¼ 3300, 3200, 2200, 1740, 1650cmꢂ1
;
1H NMR: ꢀ ¼ 2.42 (s, CH3), 3.83 (d, J ¼ 6 Hz, CH2), 5.28 (dd, J ¼ 10.6, 6.0Hz, ¼CH2), 5.78 (m,
¼CH), 7.43 (bs, NH), 7.65–7.89 (m, Ar–H), 8.47 (d, J ¼ 12.5Hz, ¼CH), 11.89 (d, J ¼ 12.5 Hz, NH)
ppm.

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M. N. Jachak et al.
2-(4-Methylbenzoyl)-3-methylthioureidopropenenitrile (4s, C13H13N3OS)
Yield 2.00 g (77%), mp 204–205ꢁC (ethanol); IR: ꢁꢀ¼ 3450, 3330, 2250, 1750, 1710cmꢂ1; 1H NMR:
ꢀ ¼ 2.44 (s, CH3), 3.10 (d, J ¼ 6 Hz, CH3), 7.41 (bs, NH), 7.59–7.62 (m, Ar–H), 7.86 (d, J ¼ 12.5Hz,
¼CH), 12.44 (d, J ¼ 12.5 Hz, NH) ppm.
General Procedure for the Synthesis of 5-Cyanopyrimidine Derivatives 5a, 5h, 5i, 5n
A solution of 0.01mol of 4 in 30cm3 of glacial acetic acid was refluxed for 24h (TLC check). After
removal of acetic acid under reduced pressure, the solid residue was washed with acetonitrile, and
recrystallized.
4-(4-Chlorophenyl)-2[1H]-pyrimidine-5-carbonitrile (5a, C11H6ClN3O)
1
Yield 0.60 g (48%), mp 276–277ꢁC (ethanol); IR: ꢁꢀ¼ 3100, 2240, 1700, 1660, 1620, 1600 cmꢂ1; H
NMR: ꢀ ¼ 7.65–7.88 (m, Ar–H), 8.90 (s, ¼CH), 13.07 (bs, NH), ppm.
4-(4-Bromophenyl)-2[1H]-pyrimidine-5-carbonitrile (5h, C11H6BrN3O)
1
Yield 1.33g (48%), mp 270–271ꢁC (acetonitrile); IR: ꢁꢀ¼ 2250, 1700, 1670, 1640, 1610 cmꢂ1; H
NMR: ꢀ ¼ 7.45–7.79 (m, Ar–H), 8.91 (s, ¼CH), 9.34 (bs, NH), ppm.
4-(4-Bromophenyl)-3-methyl-2[1H]-pyrimidine-5-carbonitrile (5i, C12H8BrN3O)
Yield 1.55g (60%), mp 194–195ꢁC (acetonitrile); IR: ꢁꢀ¼ 2210, 1690, 1660 cmꢂ1; 1H NMR: ꢀ ¼ 3.20
(s, CH3) 7.58–7.86 (m, Ar–H), 8.91 (s, ¼CH), ppm.
4-(4-Methylphenyl)-2[1H]-pyrimidine-5-carbonitrile (5n, C12H9N3O)
1
Yield 0.5 g (47%), mp 249–251ꢁC (acetonitrile); IR: ꢁꢀ¼ 3200, 2225, 1787, 1665, 1662cmꢂ1; H
NMR: ꢀ ¼ 2.41 (s, CH3) 7.39–7.40 (m, Ar–H), 8.40 (s, ¼CH), 10.02 (s, NH), ppm.
General Procedure for the Synthesis of 4-Amino-5-benzoyl-2(1H)-pyrimidine
Derivatives 6a–6g, 6i–6r
To a solution of 0.01 mol of 4, 0.23g of sodium ethoxide (freshly cut Na in 10 cm3 of dry ethanol) in
40cm3 of dry ethanol was refluxed for 1 h. The solvent was removed under reduced pressure and the
residue was dissolved in 100 cm3 of cold H2O and acidified with 2 N HCl. The obtained solid was
recrystallized.
4-Amino-5-(4-chlorobenzoyl)-2[1H]-pyrimidone (6a, C11H8ClN3O2)
1
Yield 1.00 g (40%), mp 359–361ꢁC (methanol); IR: ꢁꢀ¼ 3450, 1720, 1670 cmꢂ1; H NMR: ꢀ ¼ 7.93
(bs, NH), 7.56–7.63 (m, Ar–H), 7.88 (s, ¼CH), 8.23 (s, NH) ppm.
4-Amino-5-(4-chlorobenzoyl)-3-methyl-2[1H]-pyrimidone (6b, C12H10ClN3O2)
1
Yield 1.50 g (56%), mp 232–233ꢁC (DMF ethanol); IR: ꢁꢀ¼ 3400, 1670 cmꢂ1; H NMR: ꢀ ¼ 3.37 (s,
CH3), 7.50–7.56 (m, Ar–H), 8.21 (s, ¼CH), 8.65 (s, NH), 9.81 (s, NH) ppm.

Synthesis of 4-Aryl- and 4-Aminopyrimidines
1535
4-Amino-3-ethyl-5-(4-chlorobenzoyl)-2[1H]-pyrimidone (6c, C13H12ClN3O2)
1
Yield 0.50g (18%), mp 260–261ꢁC (ethanol); IR: ꢁꢀ¼ 3400, 1670, 1600cmꢂ1; H NMR: ꢀ ¼ 1.17 (t,
J ¼ 7.5 Hz, CH3), 3.91 (q, J ¼ 7.5 Hz, CH2), 7.48–7.64 (m, Ar–H), 8.19 (s, ¼CH), 8.77 (s, NH,
exchangeable with D2O), 9.91 (s, NH) ppm.
4-Amino-5-(4-chlorobenzoyl)-3-phenyl-2[1H]-pyrimidone (6d, C17H12ClN3O2)
Yield 0.60 g (18%), mp 259–261ꢁC (ethanol); IR: ꢁꢀ¼ 3200, 1660cmꢂ1; 1H NMR: ꢀ ¼ 7.36–7.61 (m,
Ar–H), 7.58–7.69 (m, Ar–H) 8.06 (s, ¼CH), 11.00 (bs, NH2) ppm.
3-Allyl-4-amino-5-(4-chlorobenzoyl)-2[1H]-pyrimidone (6e, C14H12ClN3O2)
Yield 1.50g (52%), mp 245–247ꢁC (DMF ethanol); IR: ꢁꢀ¼ 3400, 1670cmꢂ1; 1H NMR: ꢀ ¼ 4.62 (d,
J ¼ 6.0 Hz, CH2), 5.17 (dd, J ¼ 6.2, 10.0Hz, CH2), 5.86 (m, ¼CH), 7.58–7.63 (m, Ar–H) 8.22 (s,
¼CH), 8.62 (s, NH), 9.92 (s, NH) ppm.
4-Amino-3-benzyl-5-(4-chlorobenzoyl)-2[1H]-pyrimidone (6f, C18H14ClN3O2)
1
Yield 1.80 g (53%), mp 276–278ꢁC (DMF); IR: ꢁꢀ¼ 3200, 1670, 1610 cmꢂ1; H NMR: ꢀ ¼ 5.24 (s,
CH2), 7.21–7.30 (m, Ar–H), 8.27 (s, ¼CH), 8.70 (s, NH), 9.90 (s, NH) ppm.
4-Amino-5-(4-chlorobenzoyl)-3-methyl-2[1H]-thiopyrimidone (6g, C12H10ClN3OS)
1
Yield 1.60 g (60%), mp 300–301ꢁC (DMF); IR: ꢁꢀ¼ 3283, 3153, 1618 cmꢂ1; H NMR: ꢀ ¼ 2.62 (s,
CH3), 7.59–7.60 (m, Ar–H), 8.02 (s, ¼CH), 8.82 (s, NH), 9.80 (s, NH) ppm.
4-Amino-5-(4-bromobenzoyl)-3-methyl-2[1H]-pyrimidone (6i, C12H10BrN3O2)
Yield 1.69 g (55%), mp 279–281ꢁC (ethanol); IR: ꢁꢀ¼ 3400, 3150, 3000, 1670, 1610cmꢂ1; 1H NMR:
ꢀ ¼ 3.31 (s, CH3), 7.46–7.74 (m, Ar–H), 8.20 (s, ¼CH), 9.82 (s, NH), 11.25 (s, NH) ppm.
4-Amino-5-(4-bromobenzoyl)-3-ethyl-2[1H]-pyrimidone (6j, C13H12BrN3O2)
Yield 2.06 g (64%), mp 263–264ꢁC (DMF); IR: ꢁꢀ¼ 3400, 3150, 1670, 1630 cmꢂ1; 1H NMR: ꢀ ¼ 2.45
(t, J ¼ 7.5 Hz, CH3), 5.29 (q, J ¼ 7.5 Hz, CH2), 8.80–9.06 (m, Ar–H), 9.02 (s, ¼CH), 10.15 (s, NH,
exchangeable with D2O), 11.26 (s, NH, Exchangeable with D2O) ppm.
4-Amino-3-benzyl-5-(4-bromobenzoyl)-2[1H]-pyrimidone (6k, C18H14BrN3O2)
1
Yield 1.95g (51%), mp 253–254ꢁC (DMF); IR: ꢁꢀ¼ 3310, 3250, 1680, 1655, 1610cmꢂ1; H NMR:
ꢀ ¼ 5.29 (s, CH2), 7.29–7.64 (m, Ar–H), 8.83 (s, NH, exchangeable with D2O), 9.02 (s, 1H, ¼CH),
10.01 (s, NH, exchangeable with D2O) ppm.
4-Amino-5-(4-bromobenzoyl)-3-methyl-2[1H]-thiopyrimidone (6l, C12H10BrN3OS)
1
Yield 1.87 g (58%), mp 257–258ꢁC (DMF); IR: ꢁꢀ¼ 3300–3100, 3000, 1660, 1630 cmꢂ1; H NMR:
ꢀ ¼ 3.31(s, CH3), 7.54–7.75 (m, Ar–H), 8.03 (s, ¼CH), 8.85 (s, NH), 9.95 (s, NH) ppm.
3-Allyl-4-amino-5-(4-bromobenzoyl)-2[1H]-pyrimidone (6m, C14H12BrN3O2)
Yield 1.70 g (51%), mp 250–252ꢁC (DMF ethanol); IR: ꢁꢀ¼ 3400, 3200, 1670, 1610cmꢂ1
;
1H
NMR: ꢀ ¼ 3.77 (d, J ¼ 6.0 Hz, CH2), 5.09 (dd, J ¼ 6.5, 10.0Hz, CH2), 5.76 (m, ¼CH), 7.58–7.72

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M. N. Jachak et al.
(m, Ar–H), 8.22 (s, ¼CH), 8.62 (s, NH, exchangeable with D2O), 9.92 (s, NH, exchangeable with
D2O) ppm.
4-Amino-5-(4-methylbenzoyl)-2[1H]-pyrimidone (6n, C12H11N3O2)
Yield 1.05 g (46%), mp 328–330ꢁC (DMF); IR: ꢁꢀ¼ 3350, 1720, 1670, 1610 cmꢂ1; 1H NMR: ꢀ ¼ 3.30
(t, CH3), 7.33–7.81 (m, Ar–H), 8.22 (s, ¼CH), 8.63 (bs, NH), 9.86 (bs, NH) ppm.
4-Amino-3-methyl-5-(4-methylbenzoyl)-2[1H]-pyrimidone (6o, C13H13N3O2)
Yield 1.21 g (49%), mp 259–260ꢁC (DMF ethanol); IR: ꢁꢀ¼ 3410, 3110, 1670, 1610 cmꢂ1; 1H NMR:
ꢀ ¼ 2.37 (s, CH3), 3.27 (s, CH3), 7.29–7.32 (m, Ar–H), 8.22 (s, ¼CH), 8.63 (bs, NH), 9.86 (bs, NH)
ppm.
4-Amino-3-ethyl-5-(4-methylbenzoyl)-2[1H]-pyrimidone (6p, C14H15N3O2)
Yield 0.31g (12%), mp 183–184ꢁC (ethanol); IR: ꢁꢀ¼ 3400, 3150, 1740, 1640cmꢂ1
;
1H NMR:
ꢀ ¼ 2.38 (s, CH3), 2.45 (t, J ¼ 7.5 Hz, CH3), 5.29 (q, J ¼ 7.5 Hz, CH2), 8.80–9.06 (m, Ar–H), 9.02
(s, ¼CH), 10.15 (s, NH, exchangeable with D2O), 11.26 (s, NH, exchangeable with D2O) ppm.
4-Amino-5-(4-methylbenzoyl)-3-phenyl-2[1H]-pyrimidone (6q, C18H15N3O2)
1
Yield 0.50 g (16%), mp 234–236ꢁC (methanol); IR: ꢁꢀ¼ 3300, 3110, 1650, 1630cmꢂ1; H NMR:
ꢀ ¼ 2.38 (s, CH3), 7.12–7.38 (m, Ar–H), 7.40–7.84 (m, Ar–H), 7.99 (s, ¼CH), 11.20 (bs, NH), 11.81
(bs, NH) ppm.
3-Allyl-4-amino-5-(4-methylbenzoyl)-2[1H]-pyrimidone (6r, C15H15N3O2)
Yield 1.50 g (56%), mp 164–165ꢁC (ethanol); IR: ꢁꢀ¼ 3150, 1680 cmꢂ1; 1H NMR: ꢀ ¼ 2.45 (s, CH3),
4.84 (d, J ¼ 6.0 Hz, CH2), 5.37 (dd, J ¼ 6.5, 10.0Hz, CH2), 5.88 (m, ¼CH), 7.23–7.62 (m, Ar–H), 8.57
(s, ¼CH), 10.44 (bs, NH, exchangeable with D2O), 11.20 (bs, NH, exchangeable with D2O) ppm.
General Procedure for the Synthesis of Uracil Derivatives 7a–7f
To a solution of 0.01 mol of 6 in 20 cm3 of DMF 1.5 cm3 of isopentyl nitrite in 7 cm3 of DMF was
added over a period of 10 min and the reaction mixture was stirred for 30min at 60–65ꢁC. After
removal of solvent under reduced pressure the oily residue was triturated with acetonitrile to furnish a
solid. It was collected, washed with cold acetonitrile, and recrystallized.
5-(4-Chlorobenzoyl)-3-methyluracil (7a, C12H9ClN2O3)
1
Yield 1.20 g (45%), mp 295–296ꢁC (methanol); IR: ꢁꢀ¼ 3350, 3200, 1720, 1660, 1645cmꢂ1; H
NMR: ꢀ ¼ 3.35 (s, CH3), 7.45–7.88 (m, Ar–H), 7.91 (d, J ¼ 12.5Hz, ¼CH), 8.96 (bs, NH) ppm.
5-(4-Chlorobenzoyl)-3-ethyluracil (7b, C13H11ClN2O3)
1
Yield 1.46 g (52%), mp 270–271ꢁC (methanol); IR: ꢁꢀ¼ 3320, 1725, 1660, 1640cmꢂ1; H NMR:
ꢀ ¼ 1.06 (s, CH3), 3.76 (q, J ¼ 7.5 Hz, CH2), 7.52–7.55 (m, Ar–H), 7.94 (d, J ¼ 12.5 Hz, ¼CH), 11.90
(bs, NH) ppm.

Synthesis of 4-Aryl- and 4-Aminopyrimidines
1537
3-Allyl-5-(4-chlorobenzoyl)uracil (7c, C14H11ClN2O3)
1
Yield 1.46 g (50%), mp 220–222ꢁC (aqueous ethanol); IR: ꢁꢀ¼ 3250, 3200, 1725, 1680cmꢂ1; H
NMR: ꢀ ¼ 4.54 (d, J ¼ 5.2 Hz, CH2), 5.21 (dd, J ¼ 5.2, 10.0Hz, CH2), 5.85 (m, ¼CH), 7.40–7.69
(m, Ar–H), 8.09 (d, J ¼ 12.5Hz, ¼CH), 10.98 (bs, NH), ppm.
5-(4-Bromobenzoyl)-3-methyluracil (7d, C12H9BrN2O3)
1
Yield 1.85 g (60%), mp 285–286ꢁC (methanol); IR: ꢁꢀ¼ 3090, 2900, 1730, 1668, 1630cmꢂ1; H
NMR: ꢀ ¼ 3.65 (s, CH3), 7.61–7.80 (m, Ar–H), 7.92 (d, J ¼ 12.5Hz, ¼CH), 10.95 (bs, NH) ppm.
3-Methyl-5-(4-methylbenzoyl)uracil (7e, C13H12N2O3)
Yield 0.85g (33%), mp 277–278ꢁC (ethanol); IR: ꢁꢀ¼ 3200, 1725, 1670, 1640cmꢂ1
;
1H NMR:
ꢀ ¼ 2.50, 3.31 (2s, 2CH3), 7.52–7.72 (m, Ar–H), 7.80 (d, J ¼ 12.6Hz, ¼CH), 11.89 (bs, NH) ppm.
3-Ethyl-5-(4-methylbenzoyl)uracil (7f, C14H14N2O3)
Yield 1.70 g (66%), mp 274–275ꢁC (DMF ethanol); IR: ꢁꢀ¼ 3150, 1725, 1660, 1650 cmꢂ1; 1H NMR:
ꢀ ¼ 1.07 (s, CH3), 2.50 (s, CH3), 3.76 (q, J ¼ 7.5 Hz, CH2), 7.52–7.72 (m, Ar–H), 7.94 (d, J ¼ 12 Hz,
¼CH), 11.89 (bs, NH) ppm.
General Procedure for the Synthesis of Uracil Derivatives 8a and 8b
To a stirred solution of 0.001 mol of 7 in 5 cm3 of aqu. NaOH 0.001 mol DMS was added dropwise at
45ꢁC and the mixture was stirred for 30min. Then the reaction mixture was poured into 30cm3 of ice
cold H2O. The separated solid was filtered, washed with cold H2O, and recrystallized.
5-(4-Chlorobenzoyl)-1,3-dimethyluracil (8a, C13H11ClN2O3)
1
Yield 0.15 g (54%), mp 170–171ꢁC (methanol); IR: ꢁꢀ¼ 1730, 1660, 1640, 1600cmꢂ1; H NMR:
ꢀ ¼ 3.36, 3.53 (2s, 2CH3), 7.51–7.70 (m, Ar–H), 7.80 (s, ¼CH) ppm.
1,3-Dimethyl-5-(4-methylbenzoyl)uracil (8b, C14H14N2O3)
Yield 0.16g (62%), mp 224–226ꢁC (methanol); IR: ꢁꢀ¼ 1720, 1670, 1600cmꢂ1; 1H NMR: ꢀ ¼ 2.50 (s,
CH3), 3.36, 3.53 (2s, 2CH3), 7.40–7.69 (m, Ar–H), 7.96 (s, ¼CH) ppm.
Acknowledgements
The authors thanks to Nashik District Maratha Vidya Prasark Samaj’s, Nashik, and Principal, K.R.T.
Arts B.H. Commerce & A.M. Science college, Nashik for academic leave and facilities. RBT and CDT
thank UGC for financial support and Dr. V. Balasubramaniyam for useful discussion.
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