Hippuric acid Erlenmeyer azlactone synthesis

In 1959, Crawford and Little reported superior yields of 3 in reactions of aromatic aldehydes by using isolated, crystalline 2-phenyloxazol-5-one (2, Ri = Ph) compared to direct reaction with hippuric acid (1, Ri = Ph). An early report by Boekelheide and Schramm on the use of ketones in the Erlenmeyer azlactone synthesis includes treatment... 

The Erlenmeyer azlactone synthesis (Scheme 1.8.5.7) combining a hippuric acid derivative, acetic anhydride and an aldehyde to form a didehydroazlactone. This azlactone approach has been extensively used for the synthesis of amino acids. 59... 

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 preparation of the first unsaturated azlactone was reported in 1883 by Plochl/40 who condensed benzaldehyde with hippuric acid in presence of acetic anhydride. This approach was later used by Erlenmeyer/41 who extended the procedure to include other aldehydes and also established the usefulness of azlactones as intermediates in the synthesis of DHAs. The method involves the condensation of an A-acylglydne 4 with aldehydes and ketones in the presence of acetic anhydride and anhydrous sodium acetate (Scheme 2)J41 t5l Other catalysts such as copper(II) acetate/46 lead acetate/47,48 potassium carbonate/49 or potassium hydrogen carbonate 50 have also been used. The reaction proceeds via formation of an azlactone 5, which then condenses with the appropriate aldehyde or ketone to give unsaturated azlactone 6. Reaction of 6 with a nucleophile such as OH, OR, or NHR leads to the corresponding A-acyl-DHA derivatives 7. Reaction with the sodium salt of an amino acid gives a DHA containing dipeptide acid. 51 ... 

Arylidene-2-phenyl-5(47/)-oxazolones (azlactones) 121 were prepared via Erlenmeyer synthesis from aromatic aldehydes 119 and hippuric acid 120 employing calcium acetate under solvent-free conditions with microwaves irradiation <04TL425>. 

The Erlenmeyer amino acid synthesis962 depends on condensation of an aldehyde with hippuric acid this gives an alkylidene azlactone, which is an intermediate in the synthesis, being converted into an <%-amino acid by reduction and hydrolysis. 

Azlactones 22 are intermediates in the Erlenmeyer synthesis (1893) of cr-amino acids. They are made by the action of acetic anhydride/sodium acetate upon a mixture of A-benzoylglycine (hippuric acid) 21 and benzaldehyde via 2-phenyloxazol-5(4//)-one 20 ... 

For instance, N-benzoyl glycine (26, hippuric acid) can be transformed to a 4-alkylidene azlactone (27) by treatment of 26 and an aldehyde (a) with Ac20/Na0Ac via intermediate formation of the azlactone 25 and (b) with polyp hosphoric acid via intermediate formation of alkylidene hippuric acid (28). Under the conditions of (b), ketones can be used in the Erlenmeyer synthesis. 

While the classical Erlenmeyer synthesis of azlactones (condensation of aldehydes with hippuric or aceturic acid in the presence of acetic... 

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