Isocoumarins homophthalic acid

Homofolic acid, 5,11-methenyl-tetrahydro-biological activity, 3, 327 Homofolic acid, tetrahydro-biological activity, 3, 327 Homoisoflavanones occurrence, 3, 722 thermoisomerization, 3, 722 thermolysis, 3, 728 Homolytic reactions heterocyclic compounds reviews, 1, 74 Homophthalic acid isocoumarins synthesis from, 3, 830 synthesis, 3, 830 Homophthalic anhydride isochroman-l-one synthesis from, 3, 860 20a-Homoporphyrin nomenclature, 1, 30 Homopterocarpin isolation, 4, 998 ( )- D- Homotestosterone synthesis, 1, 453 Homer-Emmons reaction chromene synthesis by, 3, 749 Hortiacine isolation, 3, 149 Hortiamine isolation, 3, 149... 

A number of approaches to the isocoumarin ring system are based on the facile ring closure of homophthalic acid and its derivatives and hence a major synthetic task lies in the preparation of these compounds. 

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. 

Substituted isocoumarins can easily be accessed via the condensation of acyl chlorides with homophthalic acid, which proceeds in short reaction times under microwave irradiation in high yield (Equation 326) <2005MI532>. 

Isocoumarins. - Indanones such as (203), as their enol esters, have been ozon-olysed to give the dihydroisocoumarin-3-ol, which yielded the isocoumarin (204) when heated with toluene-p-sulphonic acid. 3-Arylisocoumarins have been synthesized, in good yield, by heating homophthalic acids with aroyl chlorides. Phthalaldehydic esters (205) react with A/ -acylglycines to give isocoumarin-3-carboxylic acids, e.g (206). ... 

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). 

The formation of the isocoumarin skeleton in the total synthesis of achlisocoumarins I and II involved the cyclocondensation in neat conditions of a homophthalic acid with methyl 3-arylpropanoate or methyl ( )-... 

Without additional reagents Isocoumarins from homophthalic acids... 

ZnO-CuO hybrid nanoparticles were used as a catalyst for cycloaddition reactions between azides (19) and aUcyne (20) under ultrasound-assisted conditions to afford substituted triazole derivatives (21) (Park et al. 2012) (Scheme 9.5). A green and efficient ZnO nanoparticle-catalyzed synthesis of (/w-isoquinolinones (26) from 3-substimted isocoumarins (24) and heptadiamines (25) is also reported in the literature (Scheme 9.6) (Krishnakumar et al. 2012). The 3-substituted isocoumarins (24) required were synthesized from homophthalic acid (22) and various acid chlorides (23). Khazaei et... 

A convenient and efficient route to isocoumarins has been described starting from readily available substituted indan-l-ones, which are first converted to the enol form with trifluoroacetic anhydride, then cleaved with ozone. Isocoumarin-4-carboxylic acid is easily prepared from homophthalic acid by addition of Vilsmeier reagent followed by hydrolysis. 

A vigorous Claisen condensation ensues when a homophthalic ester and methyl formate are treated with sodium ethoxide and the active methylene group is formylated. Cyclization takes place with ease in acidic media to produce a methyl isocoumarin-4-carboxylate (50JCS3375). Hydrolysis under acid conditions is sometimes accompanied by polymerization, but the use of boron trifluoride in acetic acid overcomes this problem. Decarboxylation may be effected in the conventional manner with copper bronze, though it sometimes accompanies the hydrolysis. 

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). 

Artemidinal 46, the naturally occurring 3-formyl isocoumarin has been synthesised in good yield, which was then converted to the biologically active isocoumarin-3-carboxylic acid 55 The natural isocoutnarin 56 was also synthesised from the parent homophthalic anhydride as shown below... 

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