Abstract
Ketonic 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.