Studies on the synthesis of furobenzisoxazole derivatives

Abstract

Zonisamide, a 1,2-benzisoxazole derivative, is an important antiepileptic agent available on the market [1,2]. It has a close resemblance to indole and the 1,2-benzisoxazole nucleus can be substituted for the indole nucleus as far as auxin (plant cell growth substance) like activity is concerned [3]. Several 3-substituted 1,2-benzisoxazole derivatives have been reported to show anticonvulsive activity [4]. 1,2-Benzisoxazole phosphoradiamidates as a novel antitumor prodrug via bioreductive activation have been also studied [5]. Flucloxacillin, Oxacillin, Cloxacillin, and Dicloxacillin belong to the class of new isoxazole penicillins in current clinical use [6].Some furobenzisoxazole derivatives are reported to possess hypotensive, uricosuric, and diuretic activities and, hence, are useful as therapeutics for the treatment of hyperuricemia, edema, and hypertension [7,8], which prompted us to synthesize new furobenzisoxazole derivatives. Several reports are available in the literature for the synthesis of 1,2-benzisoxazole [9-11], but not much work has been done for the synthesis of furobenzisoxazole. We report herein the synthesis of some new furobenzisoxazole derivatives from hydroxyfurocoumarin.We have synthesized new hydroxyfurocoumarin, which on Posner reaction [12] with hydroxylamine gave furobenzisoxazole. New derivatives of furobenzisoxazole have been synthesized, and interesting observations have been recorded during the course of studies.As shown in Scheme 1, 1-(6-hydroxy-3-methylbenzofuran-5-yl)ethanone 1 [13] and 1-(4-hydroxy-3-methyl-benzofuran-5-yl)ethanone 2 [13] on reaction with pulverized sodium and diethyl carbonate [14] gave new linear 5-hydroxy-3-methylfuro[3,2-g]chromen-7-one 3 and angular 7-hydroxy-3-methylfuro[3,2-g]chromen-7-one 4 isomers, respectively. The structures of both compounds were confirmed by their 1 H NMR spectra.

7‐(2‐Oxoalkoxy)coumarins: Synthesis and Anti‐Inflammatory Activity of a Series of Substituted Coumarins

“…After several careful recrystallizations from ethanol the product formed crystals. Yields of recrystallized products vary largely depending on the substitution but were generally good when compared with the yields reported in the literature .…”

Synthesis of Tetracyclic 8-Aza-Naphthalen-9-Ones and Oxa-Naphthalen-9-One

“…[1][2][3] Naphthyl and coumarinyl biaryl piperazine derivatives are reported as highly potent human-β-secretase inhibitors, 4 I k β α kinase inhibitors 5 and antipsychotic agents. 6 In view of their biological activities and in continuation of our work on benzopyrone derivatives, 7,8 we describe here a synthesis of tetra cyclic 8-aza-naphthalen-9-ones and 7,8-dioxa-naphthalen-9-one.…”

“…Pechmann condensation 9 of β-naphthol with ethyl acetoacetate gave 1-methylbenzo[f]chromen-3-one 1. Bromination of 1 with N-bromosuccinimide in the presence of benzoyl peroxide and light(100W bulb) in refluxing chloroform was expected to give 1-bromomethylbenzo[f]chromen-3-one, 8 but instead gave 2-bromo-1-methylbenzo[f]chromen-3-one 2. The structure of 2 was confirmed by its 1 H NMR.…”

“…When we have condensed 2 with different aromatic primary amines in dimethyl formamide (DMF), expecting to get the 1-amino methyl derivative of benzo[f]chromen-3-ones, as we have prepared furopsoralenamines, 8 the product obtained was tetracyclic 3a-d. Carnduff 12,13 observed that alkaline hydrolysis of 2-bromo-1-methylbenzo[f]chromen-3-one gave two unusual products involving skeletal rearrangement but they have not reported the 1 H NMR in support of their structure. 2 on condensation with p-toluidine which gave 8-ptolyl-7a,8,10,10a-tetrahydro-7-oxa-8-aza-pentaleno[1,2-a] naphthalene-9-one 3a.…”