Sodium hydride → 3,8-Dioxo-2,3,5,6,7,8-hexahydroisoquinoline-4-carbonitrile

HRID 596815Notes

Reaction equation

HRID 596815 reaction equation
[H-].[Na+].C(O[CH:6]([O:10]CC)[N:7]([CH3:9])C)C.C(OC(OCC(C)(C)C)N(C)C)C(C)(C)C.[C:29]([CH:31]([C:35]1[CH2:40][CH2:39][CH2:38][C:37](=[O:41])[CH:36]=1)C(N)=O)#[N:30]>>[O:10]=[C:6]1[C:31]([C:29]#[N:30])=[C:35]2[C:36]([C:37](=[O:41])[CH2:38][CH2:39][CH2:40]2)=[CH:9][NH:7]1

Participants

5

Reactant 4

HCID 24758Sodium hydrideHCID 70913Dimethylformamide diethylacetalHCID 786231,1-Bis(2,2-dimethylpropoxy)-N,N-dimethylmethanamineHCID 21404771alpha-Cyano-3-oxo-1-cyclohexen-1-acetamide

Product 1

HCID 222665143,8-Dioxo-2,3,5,6,7,8-hexahydroisoquinoline-4-carbonitrile

Procedure

The novel compounds of the present invention originate from a novel process which utilizes dihydroresorcinol as the starting material. That substance thus is allowed to react with a chlorinating reagent such as phosphorus trichloride to afford 3-chloro-2-cyclohexen-1-one. Reaction with cycnoacetamide and sodium hydride results in α-cyano-3-oxo-1-cyclohexen-1-acetamide, which is contacted with a dialkylformamide acetal, for example dimethylformamide diethyl acetal or dimethylformamide dineopentyl acetal, 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 or cycloalkyl halide produces the corresponding 6-alkoxy and 6-cycloalkoxy 7-aza-1-tetralones together with the N-alkylated or N-cycloalkylated derivatives. 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.

Sources & evidence

ORD record
ord-395fdc1b6d8544a3b32a986eadf071bb
Source dataset
uspto-grants-1977_03
Patent number
US04012391

Reaction notes

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