A new synthesis of oxadiazole, thiazolidinone, N-phthalimidoamino carbonyl and arylidene derivatives with potential antimicrobial activity.

Condensation of carbohydrazide derivatives Ia, b with dimethyl acetylenedicarboxylate and acetylenedicarboxylic acid yielded benzofuran derivatives II a-d. Reaction of Ib with aromatic aldehydes formed products III a-d. Treatment of compounds III a-d with mercaptoacetic acid yielded the cyclocondensation products (IVa-d). Phthalic anhydride reacted with compounds (Ia, b)to form products (Va, b). It has been found that both khellin and visnagin (VIa, b)react with aromatic aldehydes to give arylidene derivatives (VIIa-e). Condensation of diphenyl nitrilamine with 2-arylidene furochromones VII derivatives afforded cyclo-adducts (VIII a-i). The antibacterial activities of the selected compounds were tested against Staphylococcus aureus, B. subtilis, E. coli, Pseudomonas, Salmonella and Erwinia with good results.

Synthesis and antimicrobial activity of some benzofuran derivatives.

The Friedel-Craft's acylation of 2,3-diphenyl-5-methylbenzofuran 1a with succinic anhydride gives beta-(2,3-diphenyl-5-methylbenzofuranoyl)propionic acid 1b. Acid 1b reacts with hydrazines yielding the corresponding tetrahydropyridazinones 2. 4,5-Dihydro-1,2-oxazin-6H-6-one 6 is formed by reaction of 1b with hydroxylamine hydrochloride. The reaction of the pyridazinone 2a with dialkyl sulfates, ethyl chloroacetate, Grignard reagents, amines in presence of formaldehyde (Mannich reaction), o-amino-phenol and thiourea has been investigated. The antimicrobial activities of compounds 1a-c, 2a-c, e, f, 4a, b and 5a, b as well as 7b are studied.

Synthesis of some benzofuran and furocoumarin derivatives for possible biological activity.

Condensation of 5-formyl-6-methoxy-2,3-diphenylbenzofuran (I) and 6-formyl-5-methoxy-2,3-diphenylbenzofuran (II) with aliphatic or aromatic primary amines led to the formation of the corresponding anils (IIIa-k and IVa-c). The anils (IIIa,f,k or IVa-c) reacted with ethyl cyanoacetate, ethyl acetoacetate, or diethyl malonate to form the respective esters (Va-c or VIa-c). When Va-c or VIa-c were treated with pyridine hydrochloride, demethylation occurred followed by cyclization to form the corresponding furocoumarins (VIIa-c or VIIIa-c). Reduction of the anils using sodium borohydride furnished the corresponding Mannich bases (Xa-d and XI). The antimicrobial activity of compounds IIIi, IVc, Va, VIa, and VIIIa was investigated.

Chemistry of 8-chloroberberine.

8-Chloroberberine (V), obtained by treatment of oxyberberine (I) with phosphorus oxychloride, is a reactive intermediate. Treatment with ammonia, methylamine, n-propylamine, aniline, and p-toluidine furnished the 8-berberinylidene derivatives IV and VII-X. Reaction of V with malononitrile, ethyl acetoacetate, and ethyl malonate anions yielded the 8-berberinylidene derivatives XII-XIV. Acid hydrolysis of XIV gave 8-berberinylacetic acid (XV) whose reduction provided 8-canadinylacetic acid (XVI). Grignard reagents react readily with V. Methylmagnesium iodide, ethylmagnesium iodide, and benzylmagnesium iodide led to 8,8-dimethyldihydroberberine (XVII), 8,8-diethyldihydroberberine (XIX), and the benzyl derivative XX, respectively. Sodium borohydride reduction of XX gave rise to 8-benzylcanadine (XXI).

Reactions of hydroxybenzofurans. VI. Syntheses of benzofuran chalcones, hydrazones and pyrazolines of potential biological activity.

Condensation of 5-acetyl-6-methoxy- (I) and 6-acetyl-5-methoxy-2,3-diphenylbenzofuran (II) with aromatic aldehydes gave the chalcones IIIa--f and IVa--f, respectively. Reaction of the chalcones IIIa--f and IVa--f with hydrazine hydrate-acetic acid mixture yielded the corresponding N-acetyl pyrazolines Va--f and VIa--f. The chalcones IIIa--f and IVa--f reacted with phenylhydrazine in ethanol to yield the corresponding phenylhydrazones VIIa--f and VIIIa--f. The latter hydrazones cyclize easily with boiling glacial acetic acid to the corresponding pyrazoline derivatives (IXa--f and Xa--f). The antibacterial activity of the chalcones and pyrazolines was investigated.