Methyl iodide → 2-Methyl-2,3,5,6,7,8-hexahydro-3,8-isoquinolinedione

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Reaction Steps

The compounds of the present invention are prepared from a novel process which utilizes dihydroresorcinol as the starting material. Dihydroresorcinol is allowed to react with a chlorinating reagent such as phosphorous trichloride to afford 3-chloro-2-cyclohexen-1-one. Reaction with cyanoacetamide and sodium hydride results in α-cyano-3-oxo-1-cyclohexen-1-acetamide, which is then contacted with a dialkylformamide acetal, for example, dimethylformamide diethylacetal or dimethylformamide dineopentyl acetal, or trialkylorthoformate, for example triethylorthoformate, to produce 2,3,5,6,7,8-hexahydro-3,8-dioxo-4-isoquinolinecarbonitrile. Elimination of the cyano group is effected by heating with hydrobromic acid, thus affording 2,3,5,6,7,8-hexahydro-3,8-isoquinolinedione. Heating with an alkyl halide produces the corresponding 6-alkoxy-7-aza-1-tetralone together with the N-alkylated derivative. Typically, 2,3,5,6,7,8-hexahydro-3,8-isoquinolinedione is heated in benzene at the reflux temperature with methyl iodide and silver carbonate to yield 7-aza-6-methoxy-1-tetralone together with 2-methyl-2,3,5,6,7,8-hexahydro-3,8-isoquinolinedione.

Provenance & Evidence