Phthalaldehydic acids

Checked by Lee Irvin Smith, R. T. Arnold, and Walter Frajola. 

In the reaction flask A is placed 134 g. (1 mole) of phthalide (Note 1). In flask B is placed 160 g. (53.5 cc., 1 mole) of bromine. The oil bath is maintained at 140-155°, and the stream of carbon dioxide is started when the temperature of the phthalide has reached 140°. The temperature inside flask A is maintained at 135-150 (oil bath 140-155°) during the course of the reaction 

While still warm, the reaction mixture is transferred to a 250-cc. modified Claisen flask (Org. Syn. Coll. Vol. 1, 1941, 130) fitted fox distillation under reduced pressure. Any hydrogen bromide remaining in the reaction mixture is removed by heating at 120° under the vacuum of a water pump. The product is then distilled under reduced pressure. The fore-run of less than 15 g. 

The distilled product is pure enough for use in the subsequent hydrolysis, but it may be purified by recrystallization from 100 cc. of carbon tetrachloride. Upon cooling, 100 g. of pure 2-bromo-phthalide melting at 75° is obtained. An additional 30 to 40 g. of slightly yellow material is obtained by concentrating the mother liquor-. 

The crude product is recrystallized from 400 cc. of hot water and dried in the air. The recrystallized product is white, melts at 95-96°, and weighs 97-102 g. (78-83 per cent of the theoretical amount based on the bromo compound or 65-68 per cent based on the phthalide). 

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Dich1oromethy1)-2-(trichioromethy1)henzene [2741-57-3] the end product of exhaustive side-chain chlorination of o-xylene (80) is an iatermediate ia the manufacture of phthalaldehydic acid [119-67-5]. 

In a similar manner, phthalazine or its alkyl- or aryl-substituted derivatives are obtainable from 1,2-diacylarenes (Scheme 76). Phthalaldehydic acid and its analogs are transformed by hydrazines into the corresponding phthalazin-l(2//)-ones. Phthalazin-l(2iT)-one itself is prepared from naphthalene by oxidation, subsequent treatment with hydrazine and decarboxylation as shown in Scheme 77 (55YZ1423,64FRP1335759). 4-Substituted phthalazin-l(2iT)-ones are prepared in a similar way from 2-acylbenzoic acids. 3-Hydroxyphthalides,... 

Phthalaldehydic acid (o-formylbenzoic acid) gives the NMR spectra set 32. In what form does the compound actually exist ... 

Phthalaldehyde Acid (16, 68) By chlorination of phthalide, followe by hydrolysis with boiling water and crystallization from benzene. Austin and Bousquet, U. S. pat. 2,047,946 [C. A. 30,6on (rg36)]. 

B) Phthalaldehydic Acid.—The entire distillate is placed in a 500-cc. flask and covered with 230 cc. of water. The flask is equipped with a mechanical stirrer and is heated on a steam cone. The hydrolysis is complete when the layer of 2-bromophthalide has disappeared (about thirty minutes). The reaction mixture is then placed in a refrigerator overnight, during which time the entire mass solidifies. The product is filtered, washed with two 50-cc. portions of ice water, and dried in the air. The yield of crude product melting at 60-65° (Note 5) is 140-160 g. 

Phenyl thiocarbamide, pi58 a-Phenyl-o-tohiic acid, b84 Phenyl m-tolyl ether, p76 Phloroglucinol, t318 Phorone, d613 Phthalaldehydic acid, 37... 

A variety of cyclic products have been prepared from educts containing carbonyl as well as carboxylic groups. Thus, Hanusch-Kompa and Ugi prepared a large number of five-membered cyclic gamma-lactam compounds like 44 from levulinic acid. Other carbonylic acids can lead to compounds like 45, which is made from phthalaldehyde acid, valine methylester, and tert-butylisocyanide. The products like 46 and 47 can result from the U-4CR and further cyclization. 

Diphenylbenzo[( ]furan has been observed in a number of other reactions. When benzocyclobutadienequinone (172), monothiophthalic anhydride (173), chlorophthalide (the chloride of o-phthalaldehydic acid, 174),and 2-cyanobenzaldehyde (175) are treated with phenylmagne-sium bromide, 138 could be obtained. This last reaction, which yields an imine in the primary stage, has also been conducted with p-methoxy-phenylmagnesium bromide. ... 

Dihydroisoindolo[2,l-a]quinazoline (e.g. 82) was claimed (54JCS2354 80AP729) to be the product of the reaction between 2-aminobenzylamine and phthalaldehyde (80AP729) or phthalaldehydic acid (54JCS2354). The... 

The 13C NMR spectrum of phthalic dichloride shows additional signals for a five-membered cyclic pseudo halide, characterized by an sp3 carbon shift of 104 ppm. This shift value is also observed for laevulic acid chloride, which exists in the cyclic form only. Similarly, phthalaldehyde acid (o-formylbenzoic acid) turns out to be hydroxyphthalide, as indicated by a hemiacetal carbon shift of 98.4 ppm. 

Phthalaldehydic acid - [CHLOROCARBONS ANDCHLOROHYDROCARBONS - BENZYL CHLORIDE, BENZAL CHLORIDE AND BENZOTRICHLORIDE] (Vol 6)... 

Phloroglucinol, t305 Phorone, d529 Phthalaldehydic acid, f33 m-Phthalic acid, bl6 p-Phthalic acid, bl7 Phthalonitrile, d236... 

Crounse and Desai29 showed further that 2-(/>-tolyl)benzo[6]furan with Schiff s base derived from terephthalaldehydic acid and aniline gives, on treatment with excess potassium r-butoxide, the corresponding stilbene carboxylic acid. Schiff s base derived from phthalaldehydic acid and aniline exists30 as the 3-anilinophthalide (40). Nevertheless, this also reacts similarly with, for example, the naphthofuran (39) to form 2-(2 -carboxystilben-4-yl)naphtho [ 1,2-6]furan (41).29 Analogous car-... 

During the synthesis of the isocoumarin moiety of heliquinomycin, diethyl bromomalonate and phthalaldehydic acid 1137 condense to form the dihydroisocoumarin 1138 in excellent yield (Equation 442) <2000TL29>. 

Photoflood lamps, 20, 84, 104 Phthalaldehydic acid, 23, 74 Phthalic acid, 24, 45 Phthalic anhydride, 20, 70 27, 78 Phthalic anhydride, tetraiodo-, 27, 78... 

On treatment with acids or bases, both the monomethoxy and the dimethoxy six-membered ring peroxide are converted into the methyl ester of o-phthalaldehydic acid or into o-phthalaldehydic acid, depending on the reaction conditions. Oxidation with hydrogen peroxide yields o-phthalic acid.87 The hydrogenation of 135 in the presence of a Lindlar catalyst leads to o-phthaldialdehyde (yield =... 

This strategy has been used to convert o-bn mobcnzaldehydes into phthalaldehydic acids (equation I). 

Finally, four different examples of solvent-dependent ringichain tautomerism should be mentioned [77, 210]. The equilibrium between phthalaldehydic acid / 18a) and phthalide (18b), which in decalin lies in favor of (18b) (90 cmol/mol phthalide at 20 °C), is strongly shifted towards the open-chain form (18a) in the hydrogen-bond accepting solvent dimethyl sulfoxide (only 5 cmol/mol phthalide) [78]. 

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