80
S. Saeed, N. Rashid, P. G. Jones, and A. Tahir
Vol 48
thiocyanate (0.01 mol) in acetone (50 mL) and the reaction
mixture was refluxed for 30 min. After cooling at room tem-
perature, a solution of 2-amino-4,6-dimethylpyrimidine (0.01
mol) in acetone (25 mL) was added and the resulting mixture
refluxed for 1.5 h. The reaction mixture was poured into five
times its volume of cold water when the thiourea precipitated
as a solid. The product was recrystallized from dichlorome-
thane: ethanol (1:2) mixture.
N-(4,6-dimethylpyrimidin-2-yl)-N0-(thiophene-5-carbonyl) thi-
ourea (3a). Elemental analysis for C12H12N4OS2 (MW ¼
292.38) in wt % calc. C ¼ 62.1, H ¼ 3.28, N ¼ 8.36, S ¼
9.55 and found to be C ¼ 62.12, H ¼ 3.34, N ¼ 8.18, S ¼
9.43. m.p. 115ꢂC, yield 93 %. IR (KBr pellet) in cmꢀ1: 3362
(free NH), 3215 (assoc. NH),1670 (C¼¼O), 1529 (benzene
ring), 1140 (C¼¼S); 1H NMR (400 MHz, DMSO-d6) in d
(ppm) and J (Hz): 12.80 (1H, br s, NH), 11.63 (1H,br s, NH),
7.62 (1H, d, J ¼ 7.2 Hz, Thiophene CH), 7.15 (1H, dd, J1 ¼
7.5 Hz, J2 ¼ 8.2 Hz, Thiophene CH),7.03 (1H, d, J ¼ 6.7 Hz,
Thiophene CH), 6.50 (1H, s, pyrimidine-5-H), 1.23 (6H,s, py-
rimidine-CH3); 13C NMR (300 MHz, DMSO-d6) in d (ppm):
179.2 (C¼¼S), 168.9 (C¼¼O), 159.5, 153.0, 138.6, 137.3, 135.1,
128.4, 28.0 (2C); FAB MS, m/z (%): 292.
N-(4, 6-dimethylpyrimidin-2-yl)-N0-(4-nitrobenzoyl) thiou-
rea (3b). Elemental analysis for C14H13N5O3S (MW ¼ 331.35) in
wt % calc. C ¼ 50.75, H ¼ 3.92, N ¼ 21.14, S ¼ 9.66 and found
to be C ¼ 50.62, H ¼ 3.95, N ¼ 21.12, S ¼ 9.65, m.p 168–169ꢂC,
yield 91%. IR (KBr pellet) in cmꢀ1: 3332 (free NH), 3205(assoc.
NH), 1685 (C¼¼O), 1529 (benzene ring), 1140 (C¼¼S), 1404
(CAN stretching); IH NMR (400 MHz, DMSO-d6) in d (ppm) and
J (Hz): 12.80 (1H, br s, NH), 11.63 (1H,br s, NH), 7.75 (2H, d, J
¼ 8.2 Hz), 7.65 (2H, d, J ¼ 6.9 Hz), 6.40 (1H, s, pyrimidine-5-H),
1.23 (6H, s, pyrimidine-CH3); 13C NMR (300 MHz, DMSO-d6) in
d (ppm): 180.3 (C¼¼S), 167.0 (C¼¼O), 159.4,154.3,151.0, 128.0,
121.4, 28.9(2C) ; FAB MS, m/z (%): 331.
General procedure for synthesis of fused heterocyclic
compounds. To a solution of compounds (3a–d) in 20 mL of
acetone, an equimolar quantity of bromine was added dropwise
with cooling in a water bath. After addition, the flask with the
reaction mixture was stirred at room temperature for about 4
h. At the end of the reaction, the resulting precipitate was col-
lected by filtration; the crude product was purified by column
chromatography using petroleum ether/ethyl acetate to yield
corresponding compound 4a–d.
N-[(2E)-5,7-dimethyl-2H-[1,2,4] thiadiazolo [2,3-a] pyrimi-
din-2-ylidene] thiophene-2-carboxamide (4a). Elemental anal-
ysis for C12H10N4OS2 (MW ¼ 290.36) in wt % calc. C ¼
49.65, H ¼ 3.49, N ¼ 19.30, S ¼ 22.06 and found to be C ¼
49.67, H ¼ 3.46, N ¼ 19.28, S ¼ 22.09. m.p 185ꢂC, yield 86
%. IR (KBr pellet) in cmꢀ1: 1683 (C¼¼O), 1587 (aromatic
I
C¼¼C),1403 (CAN stretching); H NMR (400 MHz, DMSO-d6)
in d (ppm) and J (Hz): 7.62 (1H, d, J ¼ 7.2 Hz, Thiophene
CH), 7.15 (1H, dd, J1 ¼ 7.5 Hz, J2 ¼ 8.2 Hz, Thiophene CH),
7.03 (1H, d, J ¼ 6.7 Hz, Thiophene CH),6.21(1H, s, pyrimi-
dine-5-H), 1.28 (6H,s, pyrimidine-CH3); 13C NMR (300 MHz,
DMSO-d6) in d (ppm): 168.2 (C¼¼O), 165.0 (C¼¼N), 161.6,
154.2,151.3,145.3,136.0,128.6, 26.8 (2C) ; FAB MS, m/z (%):
290.
N-[(2E)-5,7-dimethyl-2H-[1,2,4]thiadiazolo[2,3-a]pyrimidin-
2-ylidene]-4-nitrobenzamide (4b). Elemental analysis for
C14H11N5O3S (MW ¼ 329.33) in wt % calc. C ¼ 51.04, H ¼
3.34, N ¼ 21.27, S ¼ 9.72 and found to be C ¼ 51.24, H ¼
3.34, N ¼ 22.01, S ¼ 9.75. m.p 210–212ꢂC, yield 79%. IR
(KBr pellet) in cmꢀ1: 1686 (C¼¼O), 1615 (C¼¼N stretching),
1592 (aromatic C¼¼C), 1510 (NO2); IH NMR (400 MHz,
DMSO-d6) in d (ppm) and J (Hz): 7.74 (2H, d, J ¼ 8.1 Hz),
7.66 (2H, d, J ¼ 6.7 Hz), 6.20 (1H, s, pyrimidine-5-H) , 1.28
(6H,s, pyrimidine-CH3); 13C NMR (300 MHz, DMSO-d6) in d
(ppm):169.1(C¼¼O),166.4(C¼¼N),162.4
,153.5,141.2,130.0,
N-(4,6-dimethylpyrimidin-2-yl)-N0-(4-methylbenzoyl) thiou-
rea (3c). Elemental analysis for C15H16N4OS (MW ¼ 300.37)
in wt % calc. C ¼ 59.98, H ¼ 5.37, N ¼ 18.65, S ¼ 10.67
and found to be C ¼ 59.97, H ¼ 5.39, N ¼ 18.66, S ¼ 10.67,
m.p 136ꢂC, yield 91%. IR (KBr pellet) in cmꢀ1: 3338 (free
NH), 3218 (assoc. NH), 1677 (C¼¼O), 1527 (benzene ring),
1143 (C¼¼S), 1404 (CAN stretching); IH NMR (400 MHz,
DMSO-d6) in d (ppm) and J (Hz): 12.80 (1H, br s, NH), 11.63
(1H, br s, NH), 7.75 (2H, d, J ¼ 8.2 Hz), 7.65 (2H, d, J ¼ 6.9
Hz), 6.40 (1H, s, pyrimidine-5-H), 1.24 (6H, s, pyrimidine-
CH3), 0.93(3H,s, CH3Ph); 13C NMR (300 MHz, DMSO-d6) in
d (ppm): 180.3 (C¼¼S), 167.0 (C¼¼O), 159.4, 154.3, 151.0,
128.0, 121.4, 28.2 (2C), 23.5 ; FAB MS, m/z (%): 300.
121.4 , 26.1 (2C) ; FAB MS, m/z (%): 329.
N-[(2E)-5,7-dimethyl-2H-[1,2,4]thiadiazolo[2,3-a]pyrimidin-
2-ylidene]-4-methylbenzamide (4c). Elemental analysis for
C15H14N4OS (MW ¼ 298.36) in wt % calc. C ¼ 60.38, H ¼
4.73, N ¼ 18.78, S ¼ 10.75 and found to be C ¼ 60.36, H ¼
4.76, N ¼ 18.79, S ¼ 10.74. m.p 192–193ꢂC, yield 89%. IR
(KBr pellet) in cmꢀ1: 1684 (C¼¼O), 1625 (C¼¼N stretching),
I
1575 (aromatic C¼¼C); H NMR (400 MHz, DMSO-d6) in d
(ppm) and J (Hz): 7.69 (2H, d, J ¼ 7.5 Hz), 7.52 (2H, d, J ¼
7.1 Hz), 6.25 (1H, s, pyrimidine-5-H), 1.27 (6H, s, pyrimidine-
CH3), 0.94 (3H,s, CH3Ph); 13C NMR (300 MHz, DMSO-d6) in
d
(ppm): 168.2 (C¼¼O),165.0 (C¼¼N),162.4,153.5,141.2,
130.0,121.4,26.6(2C),21.9 ; FAB MS, m/z (%): 298.
N-[(2Z)-5,7-dimethyl-2H-[1,2,4]thiadiazolo[2,3-a]pyrimidin-
N-butyryl-N0-(4,
6-dimethylpyrimidin-2-yl)
thiourea
(3d). Elemental analysis for C11H16N4OS (MW ¼ 252.33) in
wt % calc. C ¼ 52.36, H ¼ 6.39, N ¼ 22.20, S ¼ 12.71 and
found to be C ¼ 52.36, H ¼ 6.41, N ¼ 22.18, S ¼ 12.73, m.p
125–126ꢂC, yield 91%. IR (KBr pellet) in cmꢀ1: 3331 (free
NH), 3216(assoc. NH), 1681 (C¼¼O), 1529 (benzene ring),
1140 (C¼¼S), 1404 (CAN stretching); IH NMR (400 MHz,
DMSO-d6) in d (ppm) and J (Hz): 12.80 (1H, br s, NH), 11.63
(1H, br s, NH), 6.45 (1H, s, pyrimidine-5-H), 1.25 (6H, s, py-
rimidine-CH3), 2.48 (2H, t, ACH2, J ¼ 7.3 Hz), 1.95 (2H, m,
ACH2), 0.93 (3H, t, ACH3 , J ¼ 7.1 Hz); 13C NMR (300
MHz, DMSO-d6) in d (ppm): 180.3 (C¼¼S), 167.0 (C¼¼O),
159.4, 154.3, 151.0, 128.0, 121.4, 60.3, 45.5,28.1 (2C),23.2 ;
FAB MS, m/z (%): 252.
2-ylidene]butanamide
(4d). Elemental
analysis
for
C11H14N4OS (MW ¼ 250.32) in wt % calc. C ¼ 52.78, H ¼
5.64, N ¼ 22.38, S ¼ 12.81 and found to be C ¼ 52.75, H ¼
5.66, N ¼ 22.38, S ¼ 12.84. m.p 178ꢂC, yield 85%. IR (KBr
pellet) in cmꢀ1: 1678 (C¼¼O), 1605 (C¼¼N stretching), 1587
I
(aromatic C¼¼C); H NMR (400 MHz, DMSO-d6) in d (ppm)
and J (Hz): 7.74 (2H, d, J ¼ 8.1 Hz), 7.66 (2H, d, J ¼ 6.7
Hz), 6.26 (1H, s, pyrimidine-5-H) , 1.29 (6H, s, pyrimidine-
CH3), 2.48 (2H, t, ACH2, J ¼ 7.3 Hz), 1.95 (2H, m, ACH2),
0.93 (3H, t, ACH3 , J ¼ 7.1 Hz); 13C NMR (300 MHz,
DMSO-d6) in d (ppm):167.8(C¼¼O),165.5(C¼¼N),162.4 ,153.5,
141.2, 130.0, 121.4, 61.5, 45.1, 27.9, 22.1, 20.0 ; FAB MS, m/
z (%): 250.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet