Phthalylacetic acid

Phthalic anhydride may be used as the carbonyl compound in the Perkin reaction see the preparation of phthalylacetic acid under Ninhytlrin (Section VIII,14),... 

Phthalylacetic acid. Heat a mixture of 30 g. of phthalic anhydride, 40 ml. of acetic anhydride and 5 g. of potassium acetate under reflux in an oil bath at 155-165° for 15 minutes. Pour the reaction mixture into ice-cold water, collect the yellow precipitate by suction filtration, wash it three times with 25 ml. of water and once with 10 ml. of 50 per cent, ethanol. Dry the. product at 100° the yield of crude plithalylaeetie acid is 20 g. Recrystallise from hot methanol yellow needles, m.p. 245-246°, are obtained. 

Indane-1 3-dione (1 3-diketohydrindene). Method A. To a solution of sodium methoxide, prepared from 6 1 g. of sodium and 200 ml. of anhydrous methanol, add 15 g. of phthalylacetic acid and allow to stand for 1 hour at room temperature collect the yellow precipitate by suction filtration. Mix the yellow solid with 150 ml. of 10 per cent, sulphuric acid, heat on a steam bath until no more carbon dioxide is evolved (15-20 minutes), filter the hot solution and allow to cool. Collect the yellow crystals by filtration at the pump, wash with a httle water and dry at 100°. The yield of crude 1 3-indanedione, m.p. 125-126°, is 7 g. RecrystaUise from hght petroleum, b.p. 80-100°, and thus obtain the pure product, m.p. 129-130°. 

Ninhydrin (also named 1 2 3-triketoindane or 1 2 3-triketohydrindene hydrate) is prepared most simply from the inexpensive phthalic anhydride (I). The latter is condensed with acetic anhydride in the presence of potassium acetate to give phthalylacetic acid (II) reaction of the latter with sodium methoxide in methanol yields 1 3-indanedionecarboxylic acid, which is decomposed upon warming with dilute hydrochloric or sulphuric acid to indane-1 3-dione (or 1 3-diketohydrindene) (III). Selenium dioxide oxidation of (III) affords indane-1 2 3-trione hydrate (ninhydrin) (IV). 

Phthalic anhydride, 681, 753, 984, 985 purification of, 507 Phthalide, 753, 772 Phthalimide, 753, 754, 771 Phthalimides, N-substituted, 423 Phthalonitrile, 983 Phthalylacetic acid, 995 Physical constants, determination of, 1028-1037... 

Fig. 3. Gabriel and Michael s 1877 conversion of phthalylacetic acid (3) to tribenzoylenebenzene and Wislicenus s 1887 synthesis of truxone from indane-l,3-dione (5) both products turned out to have the same structure (4).

Phthalic anhydride, when used as the carbonyl component in the Peikin reaction, affords, on treatment with acetic anhydride and potassium acetate, phthalylacetic acid (15 equation 12) a-Arylacetic acids also react with aromatic aldehydes to afford a-arylcinnamic acids (Ogliaro modirication of the Pericin condensation, equation 7) this type of reaction presumably involves the formation of the mixed anhydride of phenylacetic acid and acetic acid and/or phenylacetic anhydride. This modirication is also illustrative of the equilibrium that is established between acid, acid salt and acid anhydrides under the conditions of the reaction. 

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