Azlactones Subject

This reaction has been modified to heat amino acid with trifiuoroacetic anhydride to form 4-substituted-2-(trifluoromethyl)-6-oxazolone, which can react with the succeeding amino acid to form peptide. The azlactone with a saturated side chain can be prepared from Qf-keto acid and subjected to the peptide synthesis. 

So, when p-methoxybenzaldehyde is allowed to react with hippuric acid (N-benzoylglycine), not only does aldol condensation occur but the product of that condensation is also subject to cyclization to an azlactone. Reduction and hydrolysis of the azlactone (oxazolone) produces an amino acid and benzoic acid, and, since a methoxy group is present in this particular synthesis, its cleavage is required and thus reduction here was effected with red phosphorus and HI. These reactions are shown in Scheme 12.43. 

In the proposed mechanism, it is assumed that the azlactone I reacts with the acid II to form a mixed anhydride if the acid II can also form an azlactone, the mixed anhydride can rearrange itself either to give azlactone I and acid II, or azlactone II and acid I. The hypothesis of the mixed anhydride as the important intermediate in racemization could, of course, be used for the interpretation of all the results discussed in this section, including those for which the temporary formation of an azlactone was assumed. But the fact that acetylproline was not racemized under the conditions used by du Vigneaud indicates that the azlactone cannot be discarded as an intermediate. To what extent each of these two mechanisms operates in a given case, is a subject for further research. 

Attempts to establish the relative configurations of such pairs of isomers have been the subject of several investigations. 69.72,75,76 Buckles et cd. suggested tentative structural assignments for 53a and 53b and their respective benzamido acids on the basis of ultraviolet spectral data and by comparison of physical properties with those of model compounds. They pointed out that it is not possible to establish structural relationships from configurations of the diastereomeric 2-benzamido-3-methoxy-3-phenylpropionic acids (54), each of which, on treatment with acetic anhydride, give mixtures of the azlactones. Similar observations have been made by others. ... 

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