3- isochromane-1,4-diones

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. 

A -0-2-Isocephem-4-carboxylic acid, 1-P-phenoxyacetamido-3-methyl-1 -oxo-synthesis, 1, 430 Isochroman, 1,3-diphenyl-synthesis, 3, 787, 788 Isochroman, 3,4-diphenyI-conformation, 3, 631 Isochroman, 2-methyl-synthesis, 3, 788 Isochroman, 3-phenyl-synthesis, 3, 788 Isochroman, (-)-)-(i )-3-phenyI-stereoselective synthesis, 3, 789 Isochroman-4-carboxylic acid, l-oxo-3-phenyl-synthesis, 3, 860 Isochroman-I,3-diones, 4-acyI-synthesis, 3, 831 Isochromanols dehydration, 3, 767 isochroman synthesis from, 3, 789 Isochroman-1-one, 3-aryl-synthesis, 3, 858, 860... 

The synthesis of homophthalic acids has been achieved by carboxylation of the dianion derived from o-methylbenzoic acids (82JCS(Pl)llll). Acetylation is hindered by substitution at the 5-position of the isochroman-l,3-dione and yields of the isocoumarins are reduced in these cases. Deuteration at C-4 can be achieved by deuterating the 4-carboxylic acid, followed by decarboxylation. 

Carboxybenzyl aryl ketones are formed together with the isocoumarin when homophthalic anhydride (isochroman-l,3-dione) is used to acylate aromatic molecules under Friedel-Crafts conditions (51JOC1064) and the 7-methoxy derivative behaves in a similar fashion (66JIC615). Some care in the choice of Lewis acid is necessary in view of the formation of the tropone derivative (504) in the acylation of hydroquinone (Scheme 181) (55JCS2244). 

Isochroman-5,8-diones (300) were prepared by oxidation of 5,8-dimethoxy-isochromans with AgO and nitric acid (82SC279). This system is present as a structural moiety in some natural quinones, such as eleutherin (51HCA561), kalafungin (68MI1), nanaomycins (75MI2, 75MI3 76CC320), and other compounds. 

Arylthio)isochromane-l,4-diones 155 (X = S R = Ph, 4-ClC6H4, 4-02NC6H4, etc.) are completely enolized to 155b, while their 5,A-dioxides 155 (X = S02) show the solvent-dependent keto-enol equilibria in which the oxo species are dominating (78CB2859). 

Dihydroisocoumarins.—Diazoethyl ketones (227), on warming with acid, gave isochroman-2,4-diones (228) in good yield, and their reduction with NaBH4 yielded the dihydroisocoumarins (229).3,3-Disubstituted dihydroisocoumarins (232), related to some natural compounds, have been svnthe-... 

Reaction with homophthalic acid. If the reaction of homophthalic acid with POCI3 and DMF is carried out at 0°, the major product is the isochromane-1,3-dione (2). If the reaction is conducted at 100°, the major product is the iso-quinolone (3). Treatment of (2) with hydrochloric acid in methanol results in formation of the methyl ester of isocoumarin-4-carboxylic acid (4). 

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