714
V. Alagarsamy, V. R. Solomon, P. Parthiban, K. Dhanabal, S. Murugesan,
G. Saravanan, G. V.Anjana
Vol 45
sulphate (0.02 mol) (CAUTION: Highly toxic compound and
must be handled in high performance fume hood) was added
gradually keeping the reaction mixture stirring in freezing
mixture for 2 h. The reaction mixture was then poured into ice
water. The solid obtained was collected by filtration, washed
with water, dried and recrystallized from ethanol. Methyl
anthranilate (0.01 mol) and the above prepared N-(4-ethyl
phenyl)-methyl dithiocarbamic acid (0.01 mol), were dissolved
in ethanol (20 mL). To this anhydrous potassium carbonate (100
mg) was added and refluxed for 22 h. The reaction mixture was
cooled in ice and the solid that separated was collected by
filtration and purified by dissolving in 10% alcoholic sodium
hydroxide solution and re-precipitated by treating with dilute
hydrochloric acid. The solid obtained was collected by filtration,
washed with water, dried and re-crystallized from ethanol. Yield
= 81%, mp 265-266 °C; IR (KBr) cm-1: 3210 (NH), 1690 (C=O),
NMR (CDCl3): δ 1.1-1.2 (t, 3H, CH2CH3), 1.5-1.6 (t, 3H,
CH2CH3), 2.6-2.7 (q, 3H, CH2CH3), 2.8-2.9 (q, 2H, CH2CH3),
7.2-7.8 (m, 8H, ArH); MS (m/z): 318 [M+].
4-(4-Ethylphenyl)-1-propyl-4H-[1,2,4]triazolo[4,3-a]quin-
azolin-5-one (IV). IR (KBr) cm-1: 1682 (C=O), 1606 (C=N); 1H
NMR (CDCl3): δ 0.8-0.9 (t, 2H, CH2CH2CH3), 1.1-1.3 (sext, 2H,
CH2CH2CH3), 1.6-1.7 (t, 3H, CH2CH3), 2.1-2.2 (q, 3H,
CH2CH3), 2.6-2.7 (t, 3H, CH2CH2CH3), 7.3-8.0 (m, 8H, ArH);
MS (m/z): 332 [M+].
1-Chloromethyl-4-(4-ethylphenyl)-4H-[1,2,4]triazolo[4,3-a]-
quinazolin-5-one (V). IR (KBr) cm-1: 1686 (C=O), 1603 (C=N);
1H NMR (CDCl3): δ 1.3-1.4 (t, 3H, CH2CH3), 2.5.2.6 (q, 3H,
CH2CH3), 3.5 (s, 2H, CH2), 7.2-7.9 (m, 8H, ArH); MS (m/z):
338 [M+], 340 [M+ +2].
4-(4-Ethyl phenyl)-1-(pyrrolidinyl)-4H-[1,2,4]triazolo[4,3-
a]quinazolin-5-one (VI). A mixture of 1-chloromethyl-4-(4-
ethylphenyl)-4H-[1,2,4]triazolo[4,3-a]quinazolin-5-one (V)
(0.01 mol), pyrrolidine (0.05 mole) and anhydrous potassium
carbonate (100 mg) in dioxan (25 mL) were taken in a round
bottomed flask and refluxed for 37 h, cooled and poured into ice
water. The solid obtained was collected by filtration, washed
with water, dried and recrystallized from ethanol-benzene
(50:50). Adopting this procedure compounds VII-X were
1
1218 (C=S); H NMR (CDCl3) δ: 1.3-1.4 (t, 3H, CH2CH3), 2.1-
2.2 (q, 3H, CH2CH3), 7.3-8.0 (m, 8H, ArH), 10.1 (br s, 1H, NH,
D2O exchangeable); MS (m/z) 282 (M+). Anal. Calcd for
C16H14N2OS: C, 68.06; H, 5.00; N, 9.92. Found: C, 68.09; H,
5.02; N, 9.86.
3-(4-Ethyl phenyl)-2-methylsulfanyl-3H-quinazolin-4-one
(5). The compound 4 (0.01 mol) was dissolved in 40 mL of 2%
alcoholic sodium hydroxide solution. To this dimethyl sulphate
(0.01 mol) was added drop wise with stirring. The stirring was
continued for 1 h, the reaction mixture was then poured into ice
water. The solid obtained was collected by filtration, washed
with water, dried and recrystallized from ethanol-chloroform
(75:25) mixture. Yield = 85%, mp 151-153 °C; IR (KBr) cm-1:
1
prepared. IR (KBr) cm-1: 1681 (C=O), 1606 (C=N); H NMR
(CDCl3): δ 1.2-1.4 (m, 4H, CH2-Pyrrolidinyl), 1.7-1.9 (m, 4H,
CH2-Pyrrolidinyl), 2.0-2.1 (t, 3H, CH2CH3), 2.3-2.4 (q, 3H,
CH2CH3), 7.1-7.7 (m, 8H, ArH); MS (m/z): 373 [M+].
4-(4-Ethylphenyl)-1-(piperidinyl)-4H-[1,2,4]triazolo[4,3-a]-
quinazolin-5-one (VII). IR (KBr) cm-1: 1687 (C=O), 1610
1
1
1681 (C=O); H NMR (CDCl3) δ: 1.5-1.6 (t, 3H, CH2CH3), 2.3-
(C=N); H NMR (CDCl3): δ 1.1-1.4 (m, 6H, CH2-Piperidyl),
2.4 (q, 3H, CH2CH3), 2.7 (s, 3H, SCH3), 7.2-7.8 (m, 8H ArH);
MS (m/z) 296 (M+). Anal. Calcd for C17H16N2OS: C, 68.89; H,
5.44; N, 9.45. Found: C, 68.86; H, 5.47; N, 9.41.
1.7-1.9 (m, 4H, CH2-Piperidyl), 2.0-2.1 (t, 3H, CH2CH3), 2.3-2.4
(q, 3H, CH2CH3), 7.4-8.0 (m, 8H, ArH); MS (m/z): 387 [M+].
4-(4-Ethylphenyl)-1-(morpholinyl)-4H-[1,2,4]triazolo[4,3-
a]quinazolin-5-one (VIII). IR (KBr) cm-1: 1678 (C=O), 1608
3-(4-Ethyl phenyl)-2-hydrazino-3H-quinazolin-4-one (6).
Compound 5 (0.01 mol) was dissolved in ethanol (25 mL). To
this hydrazine hydrate (99%) (0.1 mol) and anhydrous potassium
carbonate (100 mg) was added and refluxed for 39 h. The
reaction mixture was cooled and poured into ice water. The
solid so obtained was collected by filtration, washed with water,
dried and recrystallized from chloroform-benzene (25:75)
mixture. Yield = 85%, mp 187-189 °C; IR (KBr) cm-1: 3362,
1
(C=N); H NMR (CDCl3): δ 1.3-1.5 (m, 4H, CH2-Morpholinyl),
1.9-2.1 (m, 4H, CH2-Morpholinyl), 2.3-2.4 (t, 3H, CH2CH3), 2.6-
2.7 (q, 3H, CH2CH3), 7.2-7.8 (m, 8H, ArH); MS (m/z): 389 [M+].
4-(4-Ethylphenyl)-1-(piperazinyl)-4H-[1,2,4]triazolo[4,3-a]-
quinazolin-5-one (IX). IR (KBr) cm-1: 1688 (C=O), 1612
1
(C=N); H NMR (CDCl3): δ 1.0-1.2 (m, 4H, CH2-Piperazinyl),
1.5-1.7 (m, 4H, CH2-Piperazinyl), 1.8-1.9 (t, 3H, CH2CH3), 2.4-
2.5 (q, 3H, CH2CH3), 7.0-7.7 (m, 8H, ArH); 9.9 (s, 1H, NH, D2O
Exchangeable ); MS (m/z): 388 [M+].
4-(4-Ethylphenyl)-1-(4-methylpiperazinyl)-4H-[1,2,4]tria-
zolo[4,3-a]quinazolin-5-one (X). IR (KBr) cm-1: 1678 (C=O),
1609 (C=N); 1H NMR (CDCl3): δ 1.3-1.5 (m, 4H, CH2-
Piperazinyl), 1.6-1.8 (m, 4H, CH2-Piperazinyl), 2.0-2.1 (t, 3H,
CH2CH3), 2.5-2.6 (q, 3H, CH2CH3), 2.8 (s, 2H, CH3), 7.2-7.9 (m,
8H, ArH); MS (m/z): 402 [M+].
Pharmacology. The synthesized compounds were evaluated
for antihistaminic and sedative-hypnotic activities. The animals
were maintained in colony cages at 25±2°C, relative humidity of
45-55%, under a 12 h light and dark cycle; they were fed standard
animal feed. All the animals were acclimatized for a week before
use. The Institutional Animal Ethics committee approved the
protocol adopted for the experimentation of animals.
Antihistaminic activity. A modification of the technique of
Van Arman [14] was adopted to determine the antihistaminic
potential of the synthesized compounds. Male Dunkin Hartley
Guinea pigs (250-300 g) were fasted for 12 h. Six animals were
taken in each group. The test compounds, was administered
orally at a dose of 10 mg/kg in 1% CMC and challenged with
1
3281 (NHNH2), 1686 (C=O); H NMR (CDCl3): δ 1.6-1.7 (t,
3H, CH2CH3), 2.2-2.3 (q, 3H, CH2CH3) 5.3 (br s, 2H, NH2 D2O
exchangeable), 7.4-8.1 (m, 8H, ArH), 9.8 (br s, 1H, NH D2O
exchangeable); MS (m/z) 280 (M+). Anal. Calcd for C16H16N4O:
C, 68.55; H, 5.75; N, 19.99. Found: C, 68.59; H, 5.74; N, 19.95.
(4-Ethyl phenyl)-4H-[1,2,4] triazolo [4,3-a] quinazolin-5-
one (I). Compound 6 (0.01 mol) and formic acid (25 mL) was
taken in a round bottomed flask and refluxed for 38 h, cooled
and poured into ice water. The solid obtained was collected by
filtration, washed with water, dried and recrystallized from
1
ethanol. IR (KBr) cm-1: 1683 (C=O), 1605 (C=N); H NMR
(CDCl3): δ 1.2-1.3 (t, 3H, CH2CH3), 2.3-2.4 (q, 3H, CH2CH3),
7.2-7.5 (m, 4H, ArH), 7.6 (s, 1H, ArH), 7.8-8.1 (m, 4H, ArH);
MS (m/z): 290 [M+].
4-(4-Ethylphenyl)-1-methyl-4H-[1,2,4]triazolo[4,3-a]quin-
1
azolin-5-one (II). IR (KBr) cm-1: 1670 (C=O), 1608 (C=N); H
NMR (CDCl3): δ 1.5 (s, 3H, CH3), 1.9-2.0 (t, 3H, CH2CH3), 2.6-
2.7 (q, 3H, CH2CH3), 7.2-7.8 (m, 8H, ArH); MS (m/z): 304
[M+].
1-Ethyl-4-(4-ethylphenyl)-4H-[1,2,4]triazolo[4,3-a]quinaz-
1
olin-5-one (III). IR (KBr) cm-1: 1689 (C=O), 1612 (C=N); H