Phthalic Anhydride saponification

Reaction of phthalic anhydride (70-1) with the ylide from ethyl triphenylphos-phoniumacetate leads to the condensation product (70-2), which in effect consists of a cyclic enol anhydride. Treatment of this product with hydrazine leads to the hydrazone-hydrazide (70-3). Alkylation of the anion from removal of the hydrazide proton with the substituted benzyl bromide (70-4) affords the alkylation product (70-5). Saponification then leads to the aldose reductase inhibitor ponalrestat (70-6) [79]. 

Formation of quinuclidine-3-carboxylic acid derivatives (68) from these reactions was conclusive proof of saponification of the ethoxy-carbonyl group at position 2 of the diester (61). A similar reaction takes place with diethyl quinuclidine-2,3-dicarboxylate.100 This is in agreement with the known principle of easier saponification of a- than j8-amino acid esters. Some 3-(j8-acyloxyethyl)-2-diethylaminomethyl-quinuclidines (69, 70)123 on distillation at atmospheric pressure cyclize with loss of ester and formation of a new tricyclic system, quinuclidino[2,3-c]piperidine (72). The same reaction takes place by heating the corresponding amino alcohol (71) with phthalic anhydride in the presence of benzenesulfonic acid.123... 

Resolution of alcohols can be achieved following derivatization with phthalic anhydride. Racemic l-undecyn-3-ol was converted into a phthalic monoester derivative and resolved with (R)-(+)-NEA (eq 2). Liberation of the resolved phthalic ester and saponification yielded (R)-(+)-alcohol in 92% optical purity (eq 2). Similarly, the (S)-(-) alcohol is obtained upon resolution with (S)-(-)-NEA (eq 2). 

To a 5-mL flask with a capillary inlet attached to a source of dry nitrogen, was added 4.72 g of the Diels-Alder cycloadduct from cyclooctatriene and dimethyl acetylenedicarboxylate. The flask was connected to a 25-cm tube, which served as an air-cooled condenser, and which led to a trap cooled with liquid nitrogen. The system was evacuated at 100 mmHg, and the flask was heated in a bath at 200° C for 20 min. The flask was cooled, and nitrogen was admitted. The trap contained 0.97 g cyclobutene (95%), which was solid at the temperature of liquid nitrogen and liquefied when placed in a dry ice bath at —78°C. The residue from the pyrolysis of cycloadduct was shown to be dimethyl phthalate by comparing its infrared spectrum with the spectrum of an authentic sample and by saponification to phthalic acid, isolated by sublimation as phthalic anhydride. 

Phthalic anhydride in alkyl resins was first saponified, precipitated as potassium phthalate, the alcoholate was dissolved in sulphuric acid and the curve was recorded in the presence of tetramethylammonium bromide. < > However, the application of the two-phase saponification, mentioned in the previous paragraph, seems to be more convenient. 

It is esterifiable with benzoyl chloride (using pyridine) and was recovered from the steam-distillation residue by saponification. For purposes of purification it was again treated with phthalic anhydride at an increased temperature. Unfortunately, in this manipulation part of it was decomposed. The pure alcohol C (,H oO has a pleasant, roselike odour. Its constants were as follows boiling-point 76 to 77 (4 to 5 mm.), 210 to 212 (ordinary pressure), 0 9422, od -h 43 38 wdjoo 1 46678. 

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