Abstract
A series of N-substituted-3-methyl-4-(5-alkyl- or 5-aryl-2-furfurylidene)-2-pyrazolin-5-ones(7-9)a-c have been synthesised by the reaction of N-substituted-3-methyl-2-pyrazolin-5-ones 6a-c with 5-alkyl- or 5-aryl-2-furfuraldehyde. The compounds were evaluated for their antibacterial activity against both Gram-positive and Gram-negative bacteria.
Nitrofuran derivatives are endowed with broad spectrum of antibacterial activities and find applications as commercial drugs'. Attempts have been made to modify the structures of the nitrofuran drugs by introducing carrier molecules during drug design(2), with a view to reducing the toxicity. Substituted 5-pyrazolones possess various biological activities 3. Prompted by these observation and in continuation of our program directed towards developing new approaches for synthesis polyfunctionally substituted diazines of potential activity(4-7), it was thought worthwhile to synthesis and study the biological activities of the title compounds having 5-alkyl- or 5-arylfuran moiety in place of 5-nitrofuran with a view to minimise the toxicity.
For the synthesis of the target compound 5a-c sequence of reactions is Summarized in the following :
beta-(dibenzothien-4-oyl)acrylic acid was allowed to react with hydrazine hydrate in boiling ethanol to furnish 6-(dibenzothien-4-yl)pyridazin-3(2H)-one1 (Scheme I) which upon subsequent reaction with POCl3/PCl5 on steam bath yielded the corresponding 3-chloropyridazine derivative(4) 2 in fairly good yield. Reaction of 2 with thiourea in boiling ethanol furnished 6-(dibenzothein-4-yl)pyridazin-3(2H)-thione(8) 3 which underwent facile nucleophilic substitution with hydrazine hydrate to yield the key intermediate(9) 5a. On the other hand, the reaction of I and 3 with ethyl chloroacetate in the presence of dry acetone and anhydrous K2CO3 yielded 4a,b which subsequently converted to their corresponding, hydrazides 5b,c by treatment with hydrazine hydrate in refluxing ethanol (10,11).
The required 3-methyl-5-pyrazolones 6a-c suitably substituted at position I by 6-(dibenzothien-4-yl)pyridazin-3-yl, 6-(dibenzothien-4-yl)pyridazin-3-yloxyacetyl and 6-(dibenzothien-4-yl)pyridazin-3-ylthioacetyl were conveniently prepared by refluxing the respective hydrazides with ethyl acetoacetate in boiling ethano 14. In order to study the structure-activity relationship, 5-methyl-, 5-(4-nitrophenyl)- and 5-(4-chlorophenyl)furfurals were employed for the condensation. The pyrazolones 6a-c were then refluxed with the alkyl- and/ or arylfurfurals in acetic acid medium employing sodium acetate as the catalyst to furnish the corresponding N-substituted-3-methyl-4-(5-alkyl- or 5-aryl-2-furfurylidene)-2 -pyrazolin-5-ones (7-9)a-c (Scheme II). The structures of the above compounds were confirmed from their physical and spectral data.