Unsaturated 5 -oxazolones amides

In general, the reaction of unsaturated 5(4//)-oxazolones 497 with nitrogen nucleophiles effects ring opening to give the corresponding unsaturated acylamino amides 498 (Scheme 7.158). Depending on the nucleophile, for example, amines, hydrazines, oximes, and so on, the products obtained can be cyclized and this process allows the synthesis of a wide variety of new heterocyclic compounds. 

There are a number of comprehensive studies reported of the reactions of a particular unsaturated oxazolone with nitrogen nucleophiles. On the other hand, unsaturated 5(4/f)-oxazolones react with a variety of amines to yield acylamino amides with interesting agrochemical properties. ... 

The mechanism of the aminolysis and the electronic effects of substituents at C-2 or C-4 on the kinetics of amide bond formation have been studied. In some cases, ring opening with amines occurs with partial isomerization of the exocyclic double bond. However, with more hindered compounds, such as unsaturated oxazolones derived from ketones, ring opening is stereospecific.Ring opening using diamines has also been described. Selected examples of dehydroamino acid amides prepared by aminolysis of unsaturated 5(4//)-oxazolones are shown in Table 7.40 (Fig. 7.51). 

Amino acids " " and aminobenzoic acids " " react as nitrogen nucleophiles to effect ring opening of unsaturated 5(4//)-oxazolones. Cyclization of the intermediate acylamino amide has opened the way for the synthesis of new series of imidazolones that now incorporate a carboxylic acid moiety into the N-1 substituent. These compounds are readily further elaborated into derivatives with diverse biological activity. 

TABLE 7.41. iV-ACYLAMINO ACID AMIDES FROM REDUCTIVE AMINOLYSIS OF UNSATURATED 5(4i7)-OXAZOLONES... 

On the other hand, if a 2-phenyl-5(4//)-oxazolone 547 is the starting material, A -(benzoyl)dehydroamino acid amides 548 or unsaturated imidazolones 549 are... 

TABLE 7.40 N-ACYL DEHYDROAMINO ACID AMIDES FROM AMINOLYSIS OF UNSATURATED 5(4//)-OXAZOLONES, 237... 

Oxazolones are attacked by a variety of electrophiles at C(4) these reactions, which require the presence of bases, proceed through the enolate anions (197). This type of anion adds to carbonyl compounds, a key step in the Erlenmeyer synthesis of unsaturated azlactones (equation 35) (see Section 4.18.4.3.4). The anions are intermediates in the formation of the amides (198) when oxazolones are treated with enamines (Scheme 15) (71JCS(C)598>. 

However, most nucleophiles attack 5-oxazolones at the carbonyl group and the products are derivatives of a-amino acids formed by acyl-oxygen fission. Thus the action of alcohols, thiols, ammonia and amines leads, respectively, to esters, thioesters and amides orthophosphate anion gives acyl phosphates (Scheme 18). The use of a-amino acids in this reaction results in the establishment of a peptide link. Cysteine is acylated at the nitrogen atom in preference to the sulfur atom. Enzymes, e.g. a-chymotrypsin and papain, also readily combine with both saturated and unsaturated azlactones. A useful reagent for the introduction of an a-methylalanine residue is compound (202). Both the trifluoroacetamido and ester groups in the product are hydrolyzed by alkali to give a dipeptide. The alkaline hydrolyzate may be converted into the benzyloxycarbonyl derivative, which forms a new oxazolone on dehydration. Reaction with an ester of an amino acid then yields a protected tripeptide (equation 45). 

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