1,3 -Isoquinolinediones

A mixture consisting of 4 grams of 1,2,3,4-tetrahydro-4,4-dimethyl-7-methoxy-isochromane-dione-(1,3) (MP 95° to 97°C), 2.53 grams of 4-aminosulfonyl-phenyl-(2)-ethylamine and 150 ml of xylene was heated for 2 hours at its boiling point in an apparatus provided with a water separator. Thereafter, the reaction mixture was allowed to cool and was then vacuum-filtered, and the filter cake was recrystallized from n-propanoi in the presence of activated charcoal. 2.9 grams (58% of theory) of 1,2,3,4-tetrahydro-4,4-dimethyl-2-(p-amino-sulfonylphenyl-(2)-ethyl]-7-methoxy-isoquinolinedione-(1,3), MP 203° to 205°C, of the formula below were obtained. 

Thioxo-2,3-dihydro[l, 2,4]triazino[6,5-c]isoquinolin-6-one 189 was obtained (75ZOR2407) by the cyclization of the 3-thiosemicarbazone 188 with alkali. Compound 188 was prepared by the reaction of 3-anilino-1,4-dihydro- 1,4-isoquinolinedione 187 or the ether 186 with thiosemicarbazide. Compound 187 was obtained by reaction of the ether 186 in benzene with aniline. The ether 186 was obtained from the alkylation of 179 (R = H) via its silver salt 185. 

Heteroatoms can also participate in the ring expansion reaction mentioned above. For example, a hydroxyl methoxyallenylphthalan gave rise to a 4-isochromanone derivative. A hydroxymethoxyallenylisoindolinone afforded an isoquinolinedione derivative efficiently (Scheme 16.23) [27, 28]. 

Benzyl-l-cyano-l,2-dihydroisoquinoline behaves quite differently to the isomeric quinoline (Section V,G,6) and through cycloaddition and dehydrogenation yields 399.861 Isoquinolinediones (400 R = H and Me)... 

Subsequently, the reaction mixture was stirred for 5 hours on an ice bath and was then allowed to stand overnight at -2°C. Thereafter, the reaction solution was admixed with water, the precipitate formed thereby was separated by vacuum-filtration, the filtrate was admixed with more water, and the aqueous solution was acidified with 2N hydrochloric acid. A greasy substance precipitated out which crystallized after a brief period of contact with boiling methanol. 2.6 grams (85% of theory) of l,2,3,4-tetrahydro-2-[p-(N -cyclohexyl-ureido-N-sulfonyl)-phenethyl]-4,4-dimethyl-7-methoxy-isoquinolinedione-(l,3), MP 180° to 182°C, were obtained. 

By electrolysis of 2-bromoamides in DMF the aminal esters (492 Scheme 89) are accessible. In the reaction of benzoylphenyl ketene with the isoquinolinedione (493) the heterocyclic aminal ester (494) is formed. Another heterocyclic aminal ester (496) was obtained from a hydrazinoyl chloride and a benzoxazine derivative (495). ... 

Regiospecific cycloaddition of the hydrazone (35.6) to the 5,8-quinolinedione occurs at ambient temperature. The isomeric 5,8-isoquinolinedione, however, reacts differently (see Chapter 84, Section II. 1). An inter-ring C—C bond is formed when a 2-oxocyclohexyloxybenzene is treated with sulphuric acid. 

Pyranopyridines have been obtained by a one-pot reaction of 10 and unsaturated ketones. Benzopyranopyridines 109 have been prepared from isoquinolinediones 108. Another synthesis was performed by condensation of an u-hydroxyaraldehyde with a cyclic methyl ketone followed by treatment with 10. Pyranobenzodiazepines 111 have been obtained by condensation of 10 with benzodiazepinones 110 4-Dicyanomethylene-l,3-benzoxazines 113 were formed by treating dithiazolidine derivatives 112 with 10. ... 

Similar carbopalladation-ring expansion was observed in the Pd-catalyzed reaction of the (hydroxy)- methoxyallenylisoindoline bearing an iodophenyl moiety 59. In this case, carbopalladation of the allene to form the r-allylpalladium is followed by rearrangement-ring expansion, as shown by 60, to give the isoquinolinedione... 

The allenyl alcohol without the iodophenyl moiety 62 alone undergoes the Pd-catalyzed rearrangement-ring expansion to give the isoquinolinedione 63 [11]. 

The 4,5-isoquinolinedione 24 which was obtained in situ by a process similar to that used for the synthesis of Z. reacted with benzyne to afford norcepharadione B (25a) (Scheme 8) (Ref. 11). 

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