Synthesis and spectral studies of some 2-oxopyrimidine-1(2H)-yl]- pyrrolidine-2,5-dione derivatives

Article abstract of DOI:10.14233/ajchem.2013.13726

1-Amino-5-(4-methylbenzoyl)-4-(4-methylphenyl)pyrimidine-2(1H)-one/-thione (1a,b) reacted with various carboxylic anhydrides (2a-d) under different conditions and given the new amide and imide derivatives (3a-h). The newly synthesized compounds were chara

Full text of DOI:10.14233/ajchem.2013.13726

Asian Journal of Chemistry; Vol. 25, No. 5 (2013), 2716-2718
http://dx.doi.org/10.14233/ajchem.2013.13726
Synthesis and Spectral Studies of Some
2-Oxopyrimidine-1(2H)-yl]-pyrrolidine-2,5-dione Derivatives
ZÜLBIYE ÖNAL
Department of Chemistry, Erciyes University, Kayseri, Turkey
Corresponding author: Fax: +90 352 4374931; Tel: +90 352 2076666, E-mail: zulbiye@erciyes.edu.tr
(Received: 13 March 2012; Accepted: 19 November 2012)
AJC-12437
1-Amino-5-(4-methylbenzoyl)-4-(4-methylphenyl)pyrimidine-2(1H)-one/-thione (1a,b) reacted with various carboxylic anhydrides (2a-d)
under different conditions and given the new amide and imide derivatives (3a-h). The newly synthesized compounds were characterized
by elemental analysis, IR, 1H and 13C NMR spectral data. All the compounds were compared with their previous analogues.
Key Words: N-Aminopyrimidine derivatives, Anhydride, Condensation, Amide, Imide.
on a Leco-932 CHNS-O elemental analyser, model 1108. A
Shimadzu FT-IR-8400 model spectrophotometer was used for
IR spectra (4000-400 cm-1 region), usingATR techniques. The
1H- and 13C-NMR spectra were measured with a BrukerAvance
III 400 MHz spectrometer and the chemical shifts were
recorded in ppm units. After completion of the reactions,
solvents were evaporated with a rotary evaporator (Buchi RE
model 111). The reactions were followed by TLC using DC
Alufolien Kieselgel 60 F254 Merck and a Camag TLC lamp
(254/366 nm). Solvents and all other chemical reagents were
purchased from commercial suppliers and were of reagent
grade quality. Solvents were dried by refluxing with the
appropriate drying agents and distilled before use.
N-[5-(4-methylbenzoyl)-4-(4-methylphenyl)-2-
oxopyrimidine-1(2H)-yl]pyrrolidine-2,5-dione (3a): 0.2 g
of 1-Amino-5-(4-methylbenzoyl)-4-(4-methylphenyl)-
pyrimidine-2(1H)-one (1a) and 0.62 g succinic anhydride (2a)
(1:10 molar ratio) were heated at 180 ºC for at 1 h without
any solvent. Then, the residue was treated with dry ether and
filtered and the so formed crude product was recrystallized
from n-butanol; yield 0.15 g (60 %), white crystals; m.p. 330
ºC; IR: ν = 3030 (aromatic C-H), 2930 (aliphatic C-H), 1740-
1680-1650 (C=O), 1580-1500 (C=C and C=N), 1220-1050
(anhydride's C-O stretch), 800-700 cm-1 (pyrimidine ring); 1H
NMR (DMSO-d6): δ = 8.90 (s, 1H, pyrimidine ring.), 7.77-
6.84 (m, 8H, ArH), 2.60-2.45 ppm (-CH2-CH2-), 2.25, 2.05
ppm (s, 6H, 2x - CH3); 13C NMR (DMSO-d6): δ = 191.50 (s,
benzoyl's C=O), 162.30 (s, anhydride's 2(C=O), 152.30 (s,
pyrimidine ring, C=O), 143.01-122.20 (m, aromatic C), 31.15
(s, -CH2-CH2-), 23.15, 21.14 ppm (s, 2 × CH3C6H4-). Elemental
INTRODUCTION
Pyrimidines are interested in biological and medicinal
properties (herbicidal, antibacterial, antifungal, antiviral1-4.
Some of them are frequently encountered in many drugs used
for the treatment of hypothyroidy, hypertension, cancer chemo-
therapy or HIV infection5-8. 1-Amino-5-(4-methylbenzoyl)-
4-(4-methylphenyl)pyrimidine-2(1H)-one/-thione are synthe-
sized in two steps from 4-(4-methylbenzoyl)-5-(4-methyl-
phenyl)furan-2,3-dione9,10. It should start with a nucleophilic
attack of the -NH2 group of semi-/thiosemicarbazones at the
C-5 position of the furandione ring similar to a Micheal-type
addition10. Their hydrolysis afforded the 1-aminopyrimidine
derivatives exhibiting a free -NH2 moiety, which were applied
to several subsequent reactions. The reactions of 1-amino-
pyrimidine derivatives with 1,3-dicarbonyl compounds, iso-
cyanates and isothiocyanates have been reported in different
conditions11-17
.
For these reasons, the aim of this study was to synthesized
various pyrimidine derivatives to make notable contributions
to this class of heterocyclic compounds that are generally well
known for their potential biologicial activities1-8. In the present
study, we carried out the reactions between 1-amino-5-(4-
methylbenzoyl)-4-(4-methylphenyl)pyrimidine-2(1H)-one/-
thione (1a,b) with succinic anhydride phthalic anhydride,
benzoic anhydride and maleic anhydride (2a-d), respectively
as shown in Scheme-I.
EXPERIMENTAL
Melting points were determined on an electrothermal 9200
apparatus and are uncorrected. Microanalyses were performed

Vol. 25, No. 5 (2013)
Studies of Some 2-Oxopyrimidine-1(2H)-yl]-pyrrolidine-2,5-dione Derivatives 2717
analysis (%): Found (calcd.): C = 68.55 (68.82), H = 4.80
(4.77), N = 10.51 (10.47).
1H, pyrimidine ring), 7.90-6.79 (m, 15H, aromatic), 2.35-2.10
ppm (s, 6H, 2x-CH3); C NMR (DMSO-d6): δ = 187.51 (s,
13
N-[5-(4-methylbenzoyl)-4-(4-methylphenyl)-2-
oxopyrimidine-1(2H)-yl]pyrrolidine-2,5-dione (3b): 0.2 g
of 1-Amino-5-(4-methylbenzoyl)-4-(4-methylphenyl)-
pyrimidine-2(1H)-thione (1b) and 0.59 g succinic anhydride
(2a) (1: 10 molar ratio) were heated at 170 ºC for at 2 h without
any solvent. Then, the residue was treated with dry ether and
filtered and the so formed crude product was recrystallized
from n-butanol; yield 0.16 g (66.6 %), yellow crystals; m.p.
330 ºC; IR: ν = 3040 (aromatic C-H), 2945 (aliphatic C-H),
1745-1680-1650 (C=O), 1590-1510 (C=C and C=N), 1240
(C=S), 1220-1050 (anhydride's C-O stretch), 800-700 cm-1
benzoyl's C=O), 170.50 (s, pyrimidine ring, C=S), 170.10 (s,
anhydride's 2(C=O), 144.01-118.68 (m, aromatic C), 23.15,
21.45 ppm (s, 2 × CH3C6H4-). Elemental analysis (%): Found
(calcd.): C = 72.32 (72.15), H = 4.01 (4.26), N = 9.18 (9.35).
N-[5-(4-Methylbenzoyl)-4-(4-methylphenyl)-2-
oxopyrimidin-1(2H)-yl]benzamide (3e): 0.2 g of 1-Amino-
5-(4-methylbenzoyl)-4-(4-methylphenyl)pyrimidine-2(1H)-
one (1a) and 1.4 g benzoic anhydride (2c) (1: 10 molar ratio)
were homogeneously mixed. The mixture was heated at 80 ºC
for at 2 h without any solvent. After cooling to room tempe-
rature the residue was treated with dry ether and the formed
crude product recrystallized from n-butanol; yield: 0.18 g
(68 %), white crystals; m.p. 270 ºC; IR: ν = 3500-3400
(carbonyl overtone, 3203 (-N-H), C=O), 3040 (aromatic
C-H), 2945 (aliphatic C-H), 1750-1660-1645 (C=O), 1580-
1520 (aromatic ring, skeleton vib.), 1235 (C=S), 1220-1050
(anhydride C-O stretch), 800-700 (pyrimidine ring); 1H NMR
(DMSO-d6): 12.11 (s, 1H, N-H), δ = 8.96 ppm (s, 1H, pyrimidine
ring), 7.95-6.70 (m, 13H, aromatic), 2.35-2.20 ppm (s, 6H,
2x-CH3); 13C NMR (DMSO-d6): δ = 190.51 (s, benzoyl's C=O),
167.10 (s, amide, C=O), 151.30 (s, pyrimidine ring, C=O),
138.39-114.90 (m, aromatic C), 23.15, 21.14 ppm (s,
2xCH3C6H4-). Elemental analysis (%): Found (calcd.): C =
73.55 (73.74), H = 4.83 (5.00), N = 9.79 (9.92).
N-[5-(4-Methylbenzoyl)-4-(4-methylphenyl)-2-thioxo-
pyrimidin-1(2H)-yl]benzamide (3f): 0.2 g of 1-Amino-5-(4-
methylbenzoyl)-4-(4-methylphenyl)pyrimidine-2(1H)-thione
(1b) and 1.34 g benzoic anhydride (2c) (1: 10 molar ratio)
were homogeneously mixed. The mixture was heated at 80 ºC
for at 3 h without any solvent. After cooling to 0.16 g (64 %),
yellow crystals; m.p. 270 ºC; IR: ν = 3500-3400 (carbonyl
overtone, 3220 (-N-H), C=O), 3050 (aromatic C-H), 2940
(aliphatic C-H), 1750-1660 (C=O), 1600-1540 (aromatic ring,
skeleton vib.), 1220-1050 (anhydride C-O stretch), 800-700
(pyrimidine ring); 1H NMR (DMSO-d6): 12.11 (s, 1H, N-H),
δ = 8.96 ppm (s, 1H, pyrimidine ring), 7.95-6.70 (m, 13H,
aromatic), 2.35-2.20 ppm (s, 6H, 2x-CH3); 13C NMR (DMSO-
d6): δ = 190.51 (s, benzoyl's C=O), 172.30 (s, pyrimidine ring,
C=S), 167.10 (s, amide, C=O), 140.39-110.10 (m, aromatic
C), 22.40, 20.10 ppm (s, 2xCH3C6H4-). Elemental analysis (%):
Found (Calcd.): C = 71.25 (71.05), H = 4.70 (4.82), N = 9.32
(9.56), S = 7.18 (7.30).
1
(pyrimidine ring); H NMR (DMSO-d6): δ = 8.80 (s, 1H,
pyrimidine ring), 7.80-6.70 (m, 8H, ArH), 2.50-2.45 ppm
(-CH2-CH2-), 2.25, 2.15 ppm (s, 6H, 2x-CH3); 13C NMR
(DMSO-d6): δ = 190.10 (s, benzoyl's C=O), 171.30 (s,
pyrimidine ring, C=S), 162.30 (s, anhydride's 2(C=O), 145.01-
115.20 (m, aromatic C), 31.15 (-CH2-CH2-), 23.15, 21.14 ppm
(s, 2xCH3C6H4-). Elemental analysis (%): Found (calcd.):
C= 66.45 (66.17), H = 4.31 (4.59), N = 10.23 (10.07), S =
8.05 (7.48).
2-[5-(4-Methylbenzoyl)-4-(4-methylphenyl)-2-oxopyri-
midine-1(2H)-yl]-1H-isoindole-1,3(2H)-dione (3c): 0.2 g of
1-Amino-5-(4-methylbenzoyl)-4-(4-methylphenyl)pyrimidine-
2(1H)-one (1a), a large excess of phthalic anhydride (2b), 0.88
g (molar ratio 1: 10) were homogeneously mixed. The mixture
in a 50 mL round bottomed flask by fitting calcium chloride
guard tube was heated at 190 ºC for 1 h without any solvent.
After cooling to room temperature the residue was treated with
dry ether and the so formed crude product recrystallized from
acetic acid; yield: 0.15 g (57 %), white crystals; m.p. 305 ºC;
IR: ν = 3500-3400 (carbonyl overtone, C=O), 3040 (aromatic
C-H), 2950 (aliphatic C-H), 1745-1670-1640 (C=O), 1540-
1480 (aromatic ring, skeleton vib.), 1220-1050 (anhydride
1
C-O stretch), 800-700 (pyrimidine ring); H NMR (DMSO-
d6): δ = 8.90 ppm (s, 1H, pyrimidine ring), 7.90-6.79 (m,
15H, aromatic), 2.30-2.15 ppm (s, 6H, 2x-CH3); 13C NMR
(DMSO-d6): δ = 198.51 (s, benzoyl's C=O), 160.10 (s,
anhydride's 2(C=O), 151.30 (s, pyrimidine ring, C=O), 145.01-
115.20 (m, aromatic C), 23.15, 21.14 ppm (s, 2xCH3C6H4-).
Elemental analysis (%): Found (calcd.): C = 72.32 (72.15), H
= 4.01 (4.26), N = 9.18 (9.35).
2-[5-(4-Methylbenzoyl)-4-(4-methylphenyl)-2-thioxo-
pyrimidine-1(2H)-yl]-1H-isoindole-1,3(2H)-dione(3d): 0.2
g of 1-Amino-5-(4-methylbenzoyl)-4-(4-methylphenyl)-
pyrimidine-2(1H)-thione (1b), a large excess of phthalic
anhydride (2b), 0.88 g (molar ratio 1: 10) were homogeneously
mixed. The mixture in a 50 mL round bottomed flask by fitting
calcium chloride guard tube was heated at 190 ºC for 2 h
without any solvent. After cooling to room temperature the
residue was treated with dry ether and the so formed crude
product recrystallized from acetic acid; yield: 0.17 g (61 %),
yellow crystals; m.p. 305 ºC; IR: ν = 3500-3400 (carbonyl
overtone, C=O), 3040 (aromatic C-H), 2935 (aliphatic C-H),
1745-1660-1650 (C=O), 1600-1450 (aromatic ring, skeleton
vib.), 1245 (C=S), 1220-1050 (anhydride C-O stretch), 800-
700 (pyrimidine ring); 1H NMR (DMSO-d6): δ = 9.01 ppm (s,
1-[5-(4-Methylbenzoyl)-4-(4-methylphenyl)-2-
oxopyrimidin-1(2H)-yl]-1H-pyrrole-2,5-dione (3g): 0.2 g of
1-Amino-5-(4-methylbenzoyl)-4-(4-methylphenyl)pyrimidine-
2(1H)-one (1a) and 0.61 g maleic anhydride (2d) (1: 10
molar ratio) were heated at 50 ºC for at 2 h without any solvent.
Then, the residue was treated with dry ether and filtered and
the so formed crude product was recrystallized from n-
butanol; yield 0.15 g (65 %), yellow crystals; m.p. 330 ºC IR:
ν = 3045 (aromatic C-H), 2950 (aliphatic C-H), 1730-1655-
1640 (C=O), 1600-1520 (C=C and C=N), 1220-1050
(anhydride's C-O stretch), 800-700 cm-1 (pyrimidine ring); 1H
NMR (DMSO-d6): δ = 9.01 (s, 1H, pyrimidine ring.), 7.80-
6.53 (m, 10H,ArH), 2.35, 2.10 ppm (s, 6H, 2x-CH3); 13C NMR
(DMSO-d6): δ = 190.50 (s, benzoyl group, C=O), 160.30 (s,

2718 Önal
Asian J. Chem.
O
anhydride's 2(C=O), 151.30 (s, pyrimidine ring, C=O), 141.01-
118.20 (m, aromatic C), 130.15 (d, -CH=CH-), 21.80, 21.20
ppm (s, 2xCH3C6H4-). Elemental analysis (%): Found (calcd.):
C = 67.81 (67.92), H = 3.42 (3.53), N = 11.10 (11.32).
1-[5-(4-Methylbenzoyl)-4-(4-methylphenyl)-2-oxopyri-
midin-1(2H)-yl]-1H-pyrrole-2,5-dione (3h): 0.2 g of 0.2 g
1-Amino-5-(4-methylbenzoyl)-4-(4-methylphenyl)-
pyrimidine-2(1H)-thione (1b) and 0.58 g maleic anhydride
(2d) (1: 10 molar ratio) were heated at 50 ºC for at 3 h without
any solvent. Then, the residue was treated with dry ether and
filtered and the so formed crude product was recrystallized
from n-butanol; yield 0.14 g (61 %), yellow crystals; m.p.
330 ºC; IR: ν = 3035 (aromatic C-H), 2940 (aliphatic C-H),
1745-1660 (C=O), 1595-1490 (C=C and C=N), 1235 (C=S),
1220-1050 (anhydride's C-O stretch), 800-700 cm-1 (pyrimidine
ring.); 1H NMR (DMSO-d6): δ = 8.91 (s, 1H, pyrimidine ring),
7.90-6.83 (m, 10H, ArH), 2.35, 2.10 ppm (s, 6H, 2x-CH3); 13C
NMR (DMSO-d6): δ = 190.20 (s, benzoyl C=O), 169.30 (s,
pyrimidine ring, C=S), 160.30 (s, anhydride's 2(C=O), 142.01-
110.20 (aromatic C), 131.20 (-CH=CH-), 23.20, 21.40 ppm
(s, 2xCH3C6H4-). Elemental analysis (%): Found (calcd.): C =
62.05 (62,21), H = 3.78 (3.72), N = 10.36 (10.16), S = 7.90
(7.60).
O
O
O
N
X
N
N
Ar
N
Ar
O
O
O
O
Ar
N
Ar
N
X
O
3a; X= O
O
3c; X= O
3
b; X= S
2a
2b
O
O
3
d; X= S
O
NH2
Ar
N
O
O
O
Ar
N
X
Ph
O
(1a,b)
O
Ph
2c
2d
O
O
O
O
NH
Ar
N
N
X
Ar
N
O
Ar
N
X
O
Ar
N
3e; X= O
f; X= S
3g; X= O
3
3h; X= S
Scheme-I
ACKNOWLEDGEMENTS
The author is grateful for the financial support given by
the Research Foundation of Erciyes University.
RESULTS AND DISCUSSION
REFERENCES
The reactions of 1-amino-5-(4-methylbenzoyl)-4-(4-
methylphenyl)pyrimidine-2(1H)-one/-thione (1a,b) with acid
anhydride derivatives (2a-e) yielded N-acyl derivatives11
(3a-h). Several amides and imide derivatives (3a-h) were
easily obtained in moderate yields (57-68 %) from nucleophilic
addition of 1a,b to the corresponding compounds of 2a-d
(Scheme-I). The reactions were performed by heating them
without any solvent up to 50-190 ºC (see experimental section).
The structure of N-[5-(4-methylbenzoyl)-4-(4-methylphenyl)-
2-oxopyrimidine-1(2H)-yl]pyrrolidine-2,5-dione (3a) was
confirmed by its elemental analysis, IR, 1H NMR and 13C NMR
specroscopic data (Scheme-I). The absorption bands of (C=O)
groups were found to be at 1720, 1700, 1670, 1650 cm-1. The
absorption band of aliphatic C-H groups were found to be at
2930 cm-1. The 1H NMR signals were found to be at δ = 8.90
(s, 1H, pyrimidine ring) and 7.77-6.84 ppm (m, 8H, ArH).
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1
The H NMR spectrum showed peaks of -CH2-CH2- at δ =
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2.60-2.45 and 2.25, 2.05 ppm (s, 6H, 2x-CH3). The 13C NMR
signals were observed at δ = 191.50 (benzoyl group, C=O),
162.30 ppm (anhydride's 2(C=O). Finally, the elemental
analysis data along with spectroscopic data (details see
experimental part) confirm the structure of 3a. The results of
measurements of 3b-h were given in experimental section.