Abstract: 4-Anilinomethylene-2-phenyl-2-oxazolin-5-one (4) is an important compound in the class of 2-Substituted 4-heteromethylene-2-oxazolin-5-one (I). The classical Erlenmeyer Azlactone Synthesis is one of the most common process to synthesize Azlactones or 5(4H)-Oxazolones. The method employs the condensation of aromatic aldehydes with hippuric acid in acetic anhydride in the presence of fused sodium acetate, but it fails to produce 4-Anilinomethylene-2-phenyl-2-oxazolin-5-one (4) directly. In view to explore, attempts were made to synthesize 4-Anilinomethylene-2-phenyl-2-oxazolin-5-one (4) using five disciplined route and its solvolysis and aminolysis based products. 2-Phenyl-2-oxazolin-5-one (3) was generated by cyclizing hippuric acid (1) with either ethyl chloroformate (2a) or benzene sulphonyl chloride (2b) or p-toluene sulphonyl chloride (2c) in the presence of triethylamine base in dry benzene at room temperature, which declines the risk of high pressure development associated with solution phase reaction. The triethylamine salts produced were filtered under  suction and the resultant intermediate (3) was allowed to condensed with N,N’-Diphenyl formamidine. On refluxing for 15 minutes, the resulting product 4-Anilinomethylene-2-phenyl-2-oxazolin-5-one (4) was obtained in good yield. Further, 4-Anilinomethylene-2-phenyl-2-oxazolin-5-one (4) was also prepared on treatment with aniline in one flask directly from 4-Ethoxymethylene-2-phenyl-2-oxazolin-5-one (5) which in turn was synthesized by heating hippuric acid (1) with ethyl orthoformate in presence of acetic anhydride.

When a mixture of hippuric acid (1), ethyl orthoformate  and phenyl isothiocyanate with the molar ratio of 1:1.1:1.2 was heated at 130o-140oC for 30 minutes in presence of pyridine as base, 4 was obtained directly along with hippuranilide (6) with 20% and 16% yields respectively.(SCHEME- 1) On solvolysis and aminolysis of 4-Anilinomethylene-2-phenyl-2-oxazolin-5-one (4) afford a variety of products either by the attack of nucleophiles through the cleavage of 1, 5-bond of the oxazolone ring or first by exchanging the anilino moiety followed by 1, 5- bond cleavage and subsequent recyclization. Accordingly, 3-Anilino-2-benzoylamino acrylic acid (7) by hydrolysis, Ethyl 3-anilino-2-benzoylamino acrylate (8) by ethanolysis, methyl 3-anilino-2-benzoylamino acrylate (9) by methanolysis, 4-benzoylamino-3-pyrazolin-5-one (11), and 4-benzamido-1-phenyl-3-pyrazolin-5-one (12) by hydrazinolysis with hydrazine and phenyl hydrazine respectively were synthesized using 4-Anilinomethylene-2-phenyl-2-oxazolin-5-one (4) as a synthon. (SCHEME-2)

 Key words: 4-Anilinomethylene-2-phenyl-2-oxazolin-5-one, Synthon, Solvolysis, Hydrazinolysis, 5(4H)-Oxazolone, 3-Pyrazolin-5-one. 

PDF | DOI: 10.17148/IARJSET.2023.10562

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