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A.M. El-Sayed et al. / Il Farmaco 54 (1999) 56–63
ture was refluxed for 4 h. After cooling, the precipitate
was filtered off and crystallized from a suitable solvent
to afford compounds 8a,b.
concentrated and cooled to r.t. The obtained product
was filtered off and crystallized from the appropriate
solvent to give compounds 21–24 (cf. Table 1).
MS: Compound 21: m/e (relative intensity)%: 245
(58.6), 218 (16.4), 171 (30.73), 55 (100).
2.4. Reaction of coumarin hydrazones (2a,b) with oxalyl
chloride: general procedure
MS: Compound 23: m/e (relative intensity)%: 290
(5.16), 254 (15.12), 238 (17.4), 139 (35.05), 20 (100).
Oxalyl chloride (0.01 mol) was added to a solution of
compounds 2a,b (0.02 mol) in dry benzene (30 ml). The
reaction mixture was refluxed for 6 h under dry condi-
tions. After cooling, the formed precipitate compounds
9a,b was filtered and crystallized from the appropriate
solvent (cf. Table 1).
2.9. Synthesis of 2,3-dihydrobenzo- or (6-nitrobenzo)-
pyrazo[2,3-c]-3-pyrazole-3-thione (25a,b): general pro-
cedure
Alcoholic potassium hydroxide solution (0.01 mol in
7 ml ethanol/3 ml water) was added to a solution of
coumarin hydrazone or 6-nitrocoumarin hydrazone
(0.01 mol) in ethanol (50 ml), carbon disulfide (0.01
mol) was added to the mixture while stirring. After 1 h,
the reaction mixture was refluxed until the hydrogen
sulfide ceased (ꢀ20 h). The reaction mixture was con-
centrated, cooled to r.t. and poured on ice-water (100
ml) and filtered. The filtrate was acidified with concen-
trated hydrochloric acid. The precipitate obtained was
filtered off and crystallized from the appropriate sol-
vent to give compounds 25a,b (cf. Table 1).
2.5. Synthesis of N,N%-di[2-imino-benzopyrane(6-nitro-
benzopyrane)]piperazine-2,3,5,6-tetraone (10a,b)
To a solution of compounds 9a,b (0.005 mol) in dry
benzene (30 ml), oxalyl chloride (0.005 mol) was added.
The reaction mixture was refluxed and the crude
product was crystallized from the appropriate solvent
to give compounds 10a,b (cf. Table 1).
MS: Compound 25a: m/e (relative intensity)%: 202
(76.6), 187 (12.9), 177 (3.88), 160 (100).
2.6. Synthesis of ꢀ-aroylcoumarin hydrazones
The appropriate acid hydrazide (benzoic, isonico-
tinic, nicotinic, p-aminobenzoic hydrazide or p-ni-
trobenzoic) (0.01 mol) was added to thiocoumarins
(1a,b) (0.01 mol) in ethanol (30 ml) in presence of two
drops of triethylamine. The reaction mixture was
refluxed until the hydrogen sulfide ceased (ꢀ10 h). The
reaction mixture was concentrated. After cooling, the
precipitate compounds 11a,b–15a,b were filtered off
and crystallized from the appropriate solvent (cf. Table
1).
2.10. Reaction of 3-benzylthio-2,3-dihydro[1]benzo-
pyrano[2,3-c]pyrazole (25a) with benzyl chloride
Compound 25a (0.003 mol) was dissolved in sodium
hydroxide solution (30 ml, 10%) and ethanolic solution
of benzylchloride (0.003 mol) in 30 ml ethanol was
added. The reaction mixture was refluxed for 1 h. After
cooling, the precipitate was filtered off, washed with
water and crystallized from ethanol to afford com-
pound 26a (cf. Table 1).
2.11. Reaction of compound 25a with acyl chlorides:
general procedure
2.7. Reaction of ꢀ-aroylcoumarin hydrazones (11–15)
with phosphorus pentasulfide: general procedure
A solution of acid chloride (acetyl chloride, benzoyl
chloride or 4-nitrobenzoyl chloride), (0.01 mol) in 10 ml
dry toluene was added to a solution of compound 25a
(0.01 mol) in toluene (30 ml) in presence of two drops
of triethylamine and the reaction mixture was stirred
overnight. The mixture was filtered and the solution
was evaporated under reduced pressure. The residual
solid was crystallized from the appropriate solvent to
yield compounds 27a–29a (cf. Table 1).
To a solution of the appropriate v-aroylcoumarin
hydrazone (0.005 mol) in dry pyridine (25 ml), phos-
phorus pentasulfide (0.005 mol) was added. The reac-
tion mixture was refluxed for 7–10 h and filtered. The
filtrate was cooled to r.t. The solid product was filtered
and crystallized from the appropriate solvent to give
the corresponding thio product compounds 16–20 (cf.
Table 1).
2.8. Synthesis of 3-aryl-[1]benzopyrano[2,3-c]pyrazole
compounds 21–24: general procedure
2.12. Mannich reaction on 2,3-dihydrobenzopyrano-
[2,3-c]pyrazole-3-thione (25a): general procedure
The appropriate v-aroylcounarin or thiocoumarin
hydrazone (0.005 mol) was refluxed in N,N-dimethy-
laniline (20 ml) for 7–9 h. The reaction mixture was
Formaldehyde (1.5 ml; 40% solution) was added to a
solution of compound 31a (0.002 mol) in ethanol (20
ml). The reaction mixture was refluxed for 2 h. After
El-Sayed, Ahmed M.
