Condensed isoquinolines 22. Synthesis and properties of 6,11-dihydro-13H-isoquino-[3,2-b]quinazolin-13-ones

Abstract

Keywords: anthranilic acid, o-bromomethylphenylacetonitrile, 6,11-dihydro-13H-isoquino[3,2-b]-quinazol-13-one, rearrangement.Derivatives of the isoquino[3,2-b]quinazoline series are relatively inaccessible and consequently have been little studied. Currently the syntheses of just two derivatives of this heterosystem have been described -6,11-dihydro-13H-isoquino[3,2-b]quinazolin-6-one [2] and 6,11-dihydro-13H-isoquino[3,2-b]quinazolin-13-one (1) [3,4]. Antifungal activity of the latter has been observed [3]. A relatively simple method for the synthesis of derivatives of isoquino[3,2-b]quinazolin-13-one 1 consists of the thermal rearrangement of the isomeric derivatives of 7,12-dihydro-5H-isoquino-[2,3-a]quinazolin-5-one (2) [4,5]. We have previously studied [1] the reaction of o-bromomethylphenylacetonitrile (o-BMPA) with anthranilic acids and their esters, by which a series of Ar-substituted isoquino[2,3-a]quinazolines were obtained. These, in their turn, opened a route to Ar-substituted isoquino [3,2-b]quinazolines, which are difficult to obtain by other methods. In this paper we have studied the characteristics of this reaction, determined by the structure of the substituted anthranilic acids 3a-f.As has been shown earlier [6,7], the reaction of o-BMPA with anthranilic acids and their functional derivatives is a multistep process including the formation of 2-aryl-1,4-dihydro-3(2H)-isoquinolinium bromides 4. In the case of esters of anthranilic acids, isolation of the intermediates was difficult because of their high reactivity which led directly to the cyclic product 2a. In the case of the acids 3a-c, formation of the isoquinolinimines 4a-c was not successfully recorded [1].