Benzoylaminocinnamic azlactone

Geometric isomerism is possible in the unsaturated azlactones, and there has been speculation in the literature concerning the existence of the two forms. > > The cis and trans isomers of benzoylaminocro-tonic azlactone and of benzoylaminocinnamic azlactone have b n isolated. ... 

The cis and tram isomers of an unsaturated azlactone were obtained for the first time by this method. a-Benzoylamino-/3-methoxybuwith acetic anhydride yields a mixture of the isomeric benzoylaminocrotonic azlactones. The labile isomer is less soluble and hence readily isolated in the pure state. It is rapidly converted into the stable isomer by heat or by the action of cold pyridine. The two isomeric benzoylaminocinnamic azlactones have been prepared in a similar manner. ... 

An 80-90% yield of o-benzoylaminocinnamic azlactone I is obtained in the above preparation if 1 cc. of pyridine is added to the reaction mixture. 

Procedures. The preparation of df- phenylalanine by the reduction and cleavage of a-benzoylaminocinnamic azlactone with phosphorus, hydriodic acid, and acetic anhydride, and the preparation of the same amino add from a-acetaminocinnamic acid by catalytic reduction and hydrolysis, are described in Organic Syntheses. ... 

Azlactone of a-benzoylaminocinnamic acid. Place a mi.xture of 27 g. (26 ml.) of redistilled benzaldehyde, 45 g. of Mppuric acid (Section IV,54), 77 g. (71-5) ml. of acetic anhydride and 20-5 g. of anhydrous sodium acetate in a 500 ml. conical flask and heat on an electric hot plate with constant shaking. As soon as the mixture has liquefied completely, transfer the flask to a water bath and heat for 2 hours. Then add 100 ml. of alcohol slowly to the contents of the flask, allow the mixture to stand overnight, filter the crystalline product with suction, wash with two 25 ml. portions of ice-cold alcohol and then wash with two 25 ml. portions of boiling water dry at 100°. The yield of almost pure azlactone, m.p. 165-166°, is 40 g. Recrystallisation from benzene raises the m.p. to 167-168°. 

The reduction may be carried out by the same procedure starting from a-benzoylaminocinnamic acid, and in this way slightly higher yields are obtained. The azlactone may be converted into the free acid in the following way. 

In a 12-1. flask fitted with a mechanical stirrer, 62.3 g. (0.25 mole) of the azlactone is suspended in 6 1. of water, and II g. (0.275 mole) of sodium hydroxide is added as a lo per cent solution. The mixture is heated on the steam bath with stirring until solution is complete. This requires three to four hours. The hot solution is filtered and acidified with hydrochloric acid. The Of-benzoylaminocinnamic acid separates as white prisms in the hot solution, and when cold it is filtered. The yield is 55.5-64.5 g. (83-96.5 per cent) of almost pure product melting... 

The azlactones of a-benzoylaminocinnamic acids have traditionally been prepared by the action of hippuric acid (1, Ri = Ph) and acetic anhydride upon aromatic aldehydes, usually in the presence of sodium acetate. The formation of the oxazolone (2) in Erlenmeyer-Plochl synthesis is supported by good evidence. The method is a way to important intermediate products used in the synthesis of a-amino acids, peptides and related compounds. The aldol condensation reaction of azlactones (2) with carbonyl compounds is often followed by hydrolysis to provide unsaturated a-acylamino acid (4). Reduction yields the corresponding amino acid (6), while drastic hydrolysis gives the a-0X0 acid (5). ... 

The azlactone of a-benzoylaminocinnamic acid is reduced to DL-phenylalanine ° by stirring a mixture of the azlactone, a large excess of red phosphorus, and acetic anhydride (125 ml.), adding 50% hydrogen iodide in the course of 1 hr., and refluxing the mixture for 3-4 hrs. Reduction of 3-chloroindazole to indazole is accomplished... 

Reduction, Reduction of the azlactone of a-benzoylaminocinnamic acid to phenylalanine is carried out by refluxing with hydriodic acid, red phosphorus, and acetic anhydride. The function of the phosphorus is to destroy iodine as formed. A... 

The azlactones of a-benzoylaminocinnamic acids have always been prepared by the action of hippuric acid and acetic anhydride upon aromatic aldehydes, usually in the presence of sodium acetate. The procedure given here is essentially that of Kropp and Decker. ... 

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