4-Methoxyphthalic acid

Proof of the structure [xi] was sought and found by the oxidation of phenyldihydrothebaine with alkaline potassium permanganate, which resulted in the production of benzaldehyde, benzoic acid, and 4-methoxyphthalic acid. By exhaustive methylation of the methyl ether the optically active (+)-3 4-dimethoxy-2-(5-methoxy-2-vinylphenyl) stilbene [xn] (prepared by Freund [1], but stated to be optically inactive) was obtained, and permanganate oxidation of this afforded 5 6 5 -trimethoxydiphenaldehyde [xm] (also obtained by the ozonoly-sis of [xn]) and 5 6 5 -trimethoxydiphenic acid [xrv] (also obtained by oxidation of [xm]). This acid was identified with an authentic specimen prepared in stages from 4-acetoxy-3 6-dimethoxyphenanthrene quinone (acetylthebaolquinone [xv]) [6-7, 9-10],... 

Further oxidation of thebaol-9 10-quinone affords an acid claimed by Freund to be 3-methoxyphthalic acid [73], but that is clearly 4-methoxyphthalic acid. 

Laureline has one methoxyl, an AT-methyl, and a methylenedioxy group. Oxidation with permanganate yields 4-methoxyphthalic acid, so that if laureline is an aporphine, which seemed most probable, it should have structure XXXIV. When degraded by Hofmann s method it yielded... 

The correctness of the assumption that the parent vinyl carboxylic acid of LXIII must have the structure LXIV was shown by the oxidation of LXIV to 4,5,5 -tricarboxy-2,2 -dimethoxydiphenyl ether (LXV) and comparison with the compound synthesized by the Ullmann condensation of 4-iodo-5-methoxyphthalic acid with isovanillic acid (69) or by the condensation of 3-methyl-4-acetyl-6-methoxyphenol with 3-bromoanisic acid followed by oxidation (69). The natural LXV and the synthetic compound were identical in all respects. When the three degradation products, LXIV, LIX and trimethylamine, were pieced together the structure LXVI for bebeerine was arrived at, the positions of the phenolic groups being assigned arbitrarily. 

CyelizatioH with rearrangement. In connection with studies directed toward a synthesis of anthracycline antibiotics, Sih and co-workers treated the tetra-hydronaphthyl ester of 3-methoxyphthalic acid (1), prepared as shown, with BF3 etherate at 90°. The product (2) is formed by a Fries rearrangement followed by cyclodehydration. 

The methyl ether of W-acetyliodocolchinol (HI C. OH - C. OMe) is oxidised by hot permanganate solution to 4-iodo-5-methoxyphthalic acid (IV). The latter is unchanged when the substituents are interchanged in position (as required by the more recent results of Barton, Cook and Loudon described below), so these observations imply the presence of a benzene ring in -acetyliodocolchinol, with iodine as a... 

Other reagents used for the preparation of lactones from acid anhydrides are lithium borohydride [1019], lithium triethylborohydride (Superhydride ) [1019] and lithium tris sec-butyl)borohydride (L-Selectride ) [1019]. Of the three complex borohydrides the last one is most stereoselective in the reduction of 3-methylphthalic anhydride, 3-methoxyphthalic anhydride, and 1-methoxynaphthalene-2,3-dicarboxylic anhydride. It reduces the less sterically hindered carbonyl group with 85-90% stereoselectivity and is 83-91% yield [1019]. 

McAlees et al. studied the hydrogenation of various phthalic anhydrides over 10% Pd-C in ethyl acetate.62 Hydrogenation of phthalic anhydride gave o-toluic acid in high yield. Either 3- or 4-substituted phthalic anhydrides may give phthalides and/or 2-(hydroxymethyl)benzoic acids in addition to o-toluic acids. In the case of 4-methoxyphthalic anhydride, the product mixture contained 35% of 2-(hydroxymethyl)-... 

Another synthesis of isoochracinic acid (27), utilises an interesting application of Wittig reaction. 3-Methoxyphthalic anhydride on reaction with carbobenzyl-oxymethylenetriphenyl phosphorane, followed by hydrogenation and demethylation furnishes 21. It may be noted that 3-methoxyphthallc anhydride can be readily obtained by aromatic lithiation of N,N-diethyl w-methoxy benzamide followed by treatment with COj (vide supra). 

Alkaloid occurring in New Zealand Laurdia. Tablets from EtOH. M.p. 97°. [a]i — 98-5° in EtOH. Sol. oonc. HgSO to bluish-red sol. Readily oxidises in an-. Acid ox. —y meDo-phanio acid. Aik. ox. —y 4-methoxyphthalic anhydride. Exhaustive methylation, followed by oxidation and dist. —> methoxy-methylene-dioxy-phenanthrene, m.p. 132°. Exerts convulsive action on nerve c of spinal cord. 

Amino-4-hydroxy-1,3-benzenedicarboxylic acid Me ether, di-Me ester, in A-70155 Dimethyl 4-amino-5-methoxyphthalate, in A-70152... 

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