Application of Pfitzinger Reaction in Synthesis of Hetero Ring Annelated Quinoline Carboxylic Acid Derivatives

Taruna Yadav1,*, Neelam K. Yadav1, Manju Yadav2, Bhawani Singh3 and D. Kishore1

1Department of Chemistry, Banasthali University, Banasthali-304 022, India

2Department of Chemistry, RPS Degree College, Balana, Mahendergarh-123 029, India

3Department of Pure & Applied Chemistry, University of Kota, Kota-324 005, India

*Corresponding author: E-mail: taruna1311@gmail.com

Abstract

The diazotized 8-aminoquinoline (4) was reacted with 2-(hydroxymethylidine)cyclohexanone and N-benzyl 3-(hydroxymethylidine)-piperidine-4-one (5, 6) (generated from the reaction of cyclohexanone and N-benzyl-4-piperidone with ethyl formate in the presence of NaOEt) under the conditions of Japp-Klingemann reaction, followed by Fisher-indolization of the resulting hydrazones in acid, formed the quinolinooxocarbazole (7) and N-benzyl quinolinooxoazacarbazole (8), respectively. Pfitzinger reaction of compounds 7 and 8 with isatin in alkali afforded the corresponding quinoline carboxylic acid derivatives 10 and 11, respectively. In accord to generally accepted mechanism of Pfitzinger reaction, we suggest that the reaction of compounds 7 and 8 with isatin in alkali proceeds with the formation of isatoic acid which undergoes instantaneous cyclocondensation with carbonyl species 7 and 8 to generate compounds 10 and 11, respectively.

Keywords

Quinoline, Carbazole, Azacarbazole, Japp-Klingemann reaction, Pfitzinger reaction, Quinoline 4-carboxylic acid.

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