New ω-bromoacylisatins and isoindigos derived therefrom

Abstract

Isatin is a widely known natural compound occurring in various plant species, e.g., Isatis tinctoria L. and Couropita guianancis aubl. [1, 2]. Isatin was also isolated as a human adrenaline metabolite [3]. Extensive studies on the synthesis and reactivity of isatins have led to the discovery of new diverse aspects of organic reactions. Numerous methods for the preparation of various heterocyclic systems have been developed starting from isatin; in particular, spiro pyrrolidines, quinolines, indoles, β-lactams, oxindoles, and other heterocycles possessing a considerable potential of biological activity have been obtained [4, 5]. Isatin derivatives containing a reactive bromoalkyl fragment have recently attracted strong interest. These compounds were used to synthesize various conjugates with known biologically active compounds (including medicinal agents) which also showed high antibacterial [6–8], antiviral [9], and antitumor activity [10, 11]. The existing methods for the preparation of N-bromoalkylisatins are few in number and are not free from disadvantages related to side formation of alkylenediisatins. In the present communication we describe a new synthetic approach to 1-(ω-bromoacyl)isatins, which is based on acylation of isatin sodium salt (I) with ω-bromoalkanoyl chlorides II and III. The reactions were carried out in anhydrous benzene at 15°C, and the corresponding 1-(ω-bromoacyl)isatins IV and V were obtained in high yields (88–89%). Compound IV was converted into isoindigo derivative VI according to the procedure described by us previously [12]. Almost quantitative formation of hexaethylphosphoric triamide (according to the P NMR data) and high yield of VI indicated that the reaction is not accompanied by side quaternization of initial phosphorous triamide.