Synthesis, characterization and crystal structure of some novel partially hydrogenated isoquinolines and their fused heterocyclic systems

Abstract

AbstractKetonic hydrolysis of 7‐acetyl‐4‐cyano‐1,6‐dimethyl‐6‐hydroxy‐8‐phenyl‐5,6,7,8‐tetrahydro‐isoquinoline‐3(2H)‐thione (1) via heating with aqueous solution of potassium hydroxide resulted in both deacetylation and dehydration affording new 7,8‐dihydroisoquinoline scaffold (7,8‐DHISQ) 2. Two simple mechanistic approaches are postulated for this synthesis. One of them was supported by converting 7‐acetyl‐4‐cyano‐1,6‐dimethyl‐8‐phenyl‐7,8‐dihydroisoquinoline‐3(2H)‐thione (3) into 7,8‐DHISQ 2 via heating with aqueous solution of potassium hydroxide. Compound 2 was used as a key intetermediate for synthesizing other 7,8‐DHISQ's 4 and 6, as well as 7,8‐dihydrothienoisoquinoline 7. Reaction of compound 3 with 2‐chloroacetamide (8) by refluxing in ethanol containing sodium acetate gave 7‐acetyl‐1‐amino‐5,8‐dimethyl‐6‐phenyl‐6,7‐dihydrothieno[2,3‐c] isoquinoline‐2‐carboxamide (10) which was converted into full aromatized pyrimidothienoisoquinoline 12 on treatment with triethyl orthoformate. Reaction of 3 with both hydrazine hydrate and hydroxylamine hydrochloride afforded tetrahydropyrazolo‐isoquinoline 13 and tetrahydroisoxazoloisoquinoline 14, respectively. Reaction of 14 with N‐(4‐chlorophenyl)‐2‐chloroacetamide (15) produced (N‐phenylcarbamoylmethylthio)tetra‐hydroisoxazoloisoquinoline 16 which was coverted into tetrahydroisoxazolothieno‐isoquinoline 17 upon heating with sodium ethoxide. Also, crystal structures of compounds 4 and 13 were determined via X‐rays diffraction analysis.