Condensed isoquinolines 25. Alkylation of 6,11-dihydro-13H-isoquino[3,2-b]quinazolin-13-one

Abstract

We have previously studied alkylation, one of the characteristic reactions of enamines, using benzimidazo[1,2-b]isoquinolin-11(5H)-one [2, 3] and 7,12-dihydro-5H-isoquino[2,3-a]quinazolin-5-one [4,5] as examples. It seemed of interest to investigate the characteristics of this reaction for the linear isomer -6,11-dihydro-13H-isoquino[3,2-b]quinaxolin-13-one (1) which had been shown previously [1] to be ambident as nucleophilic agent with the example of reactions with carbonyls. We had previously [4] obtained the hydrobromides of 6-benzyl-substituted derivatives of compound 1 by rearrangement of the corresponding compounds with an angular structure. However, under the reaction conditions (170-180°C) the process was accompanied by oxidation of both the starting materials and the final reaction products [6]. Thus this method of rearrangement was not suitable for the preparation of the 5-substituted or disubstituted derivatives of isoquino[3,2-b]quinazoline.In the present work we have carried out the direct alkylation of the isoquinoquinazoline 1 by heating it with 1 equiv. of benzyl halides in 2-propanol solution in the presence of i-PrONa. The yields of compounds 2 reached 70-80%. Use of a two-fold excess of a benzyl halide gave the formation of the disubstituted compound 3 under these conditions (Tables 1-3).

Condensed isoquinolines 31. Reaction of 5-aryl-3-halo-12H-isoquino[2,3-a]quinazolines with electrophilic reagents

“…The formation of alkylation products of the isoquinoquinazolines 1a,b with phenacyl bromides upon heating a mixture of the reagents in acetonitrile was unexpectedly successful. It should be noted that an oxidation and not alkylation frequently occurs in this reaction in the case of condensed isoquinolines [6,9]. Oxidation also occurs in the reaction with 5-arylisoquino[2,3-a]quinazolines but gives the 5-aryl-7-(2-aryl-2-oxoethyl)-3-haloisoquino[2,3-a]quinazolin-13-ium bromides 5a-c.…”