2-phenyl-4-substituted-5 -oxazolones

Natural products, synthesis via aziridine intermediates, 39, 181 New developments in the chemistry of oxazolones, 21, 175 Nitration of phenyl-substituted heterocycles, 58, 215 Nitrenes, carbenes and, intramolecular reactions of, 28, 231... 

Phenyl azide appears as a rather unreactive 1,3-dipole. Of the azomethine imines that follow, sydnone is more stable than the open cyano-derivative. Diazomethane is a very reactive compound, but double phenyl substitution reduces its reactivity. The highest rate coefficients are those of reactions of the mesoionic oxazolone. Reactivity varies by five or six orders of magnitude from azide to mesoionic oxazolone. 

The reaction of 5(4H)-oxazolones (32) and miinchnones with triphenylvinylphos-phonium bromide (33) provides a mild synthesis of substituted pyrroles (34) (Scheme 11). The cycloaddition-elimination reactions of 5-imino-l,2,4-thiadiazolidin-3-ones with enamines and ester enolates produce 2-iminothiazolidines. " Chiral isomtinchnone dipoles show jr-facial diastereoselectivity with IV-phenyl- or A -methyl-maleimide in refluxing benzene. ... 

Additional examples of the utility of ring cleavage and recyclization of 4(5Ff)-oxazolones to prepare interesting heterocycles have been described (Scheme 6.16). Ttreatment of 4-aminothymol 53 with 54 in refluxing pyridine yields the 4-imidazolidinones 55 evaluated as antimicrobial and antimbercular agents. The authors listed an extensive series of analogues (25 compounds) but reported a yield for only one example, 55 (63% for Ri = Ph, R2 = 4-MeO—CeKt). Condensation of 2-phenyl-4(5F/)-oxazolone 56 with substituted hydrazines affords excellent yields of the 1,2,4-triazoles 57, important precursors to the previously unknown l(r/)-l,2,4-triazole-5-carboxaldehydes 58. Representative examples are shown in Table 6.3 (Fig. 6.8). 

On heating, 4-(isopropoxy)-2-phenyl-2-(trifluoromethyl)-5(2/i/)-oxazolone 65 underwent decarboxylation to the alkoxy-substituted nitrile ylide 66 that was trapped in a 1,3-dipolar cycloaddition by trifluoroacetophenone to generate 68." Other dipolarophiles reacted similarly. In the absence of a dipolarophile, cyclization of 66 yielded the isoindole 67 (Scheme 7.16 Table 7.11, Fig. 7.12). 

Some unusual reactions have been described for 2-(4-chlorophenyl)-2-(3,3-dimethylallyl)-4-phenyl-5(277)-oxazolone 84. This compound undergoes a Lewis acid-catalyzed rearrangement to give a tetrahydrofuropyrrole 85. On the other hand, depending on the reaction conditions, thermolysis of 84 produces the azabicyclohexene 86 or a substituted 2,3-dihydropyridine 87 together with the caged compound 88 formed by dimerization of the 2,3-dihydropyridine and the azabicyclohexene (Scheme 7.21). " ... 

Recently, a new and generally applicable procedure for efficient a-alkylation of 2-phenyl-4-substituted-5(47/)-oxazolones 149 and 151 has been described. A valuable feature of this approach is that, depending on the availability and ease of preparation of the starting oxazolone and the reactivity of the electrophile, two complementary approaches are available (Scheme 7.44). This synthetic methodology opens interesting possibihties for the synthesis of novel a-amino acids that combine two side chains of proteinogenic and non-proteinogenic amino acids— so-called chimeras . 

An asymmetric alkylation of 2-phenyl-4-substituted-5(47/)-oxazolones 152 has been described recently. This approach is based on palladium-catalyzed... 

When carbonyl compounds are used as electrophiles reaction with 4-monosub-stituted-5(4//)-oxazolones affords substituted serines after subsequent hydrolytic ring opening of the initial aldol product. As an example, 4-methyl-2-phenyl-5(4//)-oxazolone 193, prepared from alanine, reacts with benzaldehyde in a base-catalyzed addition to give, after hydrolysis, a 3 1 mixture of threo- and... 

Similarly, reaction of 2-dimethylaminomethylene-3-oxoalkanoates or 2-di-methylaminomethylene-1,3-cyclohexanediones with 2-phenyl-5(4/7)-oxazolone 146, generated in situ from hippuric acid, affords 6-substituted 3-(benzoyl-amino)-2-oxo-2//-pyran-5-carboxylates 204 and 3-(benzoylamino)-7,8-dihydro-2//-l-benzopyran-2,5(6//)-diones 206, respectively. These compounds showed strong local anesthetic activity (Scheme 7.62). ... 

Azine A1-Oxides. Quinoline and isoquinoline 7/-oxides react readily with 2-phenyl-5(47/)-oxazolone 209 (Rj = Ph) and 2-methyl-5(47/)-oxazolone 209 (Ri = Me) in the presence of acetic anhydride to afford 2-substituted 4-(quinol-2-yl)- 210 and 4-(isoquinol-l-yl)-5(4//)-oxazolones 211, respectively, in good yields... 

Upon the coordination mode of the 5(4/i/)-oxazolone to the metal atom. Reaction of [n-Bu3PMCl2]2 with 2-phenyl-4-substituted-5(4//)-oxazolones 331 generates the corresponding palladium(II) and platinum(II) complexes 332 (Scheme 7.108)."" ... 

Reaction of hippuric acid and A, A -dimethylacetamide in the presence of phosphorous oxychloride affords 4-[l-(dimethylamino)ethylidene]-2-phenyl-5(4//)-oxazolone 424 " ° that is converted to 4-benzoylaminopyrazolones 425 via ring opening and cyclization with hydrazines (Scheme 7.139). " ° 4-(A, Af-Dimethyl-aminomethylene)-2-substituted-5(477)-oxazolones react similarly. 

Chloromethylene)-2-phenyl-5(4H)-oxazolone 394 and 2-(acyloxymethyl-ene)-5(4H)-oxazolone" mainly give a mixture of 2-hetero substituted spirocyclo-propanes. For example, the 2-chloro derivatives 654 and 655 have been isolated and further elaborated to both stereoisomers of l-amino-2-chlorocyclopropanecar-boxylic acid 656 and 657 (Scheme 7.208). 

Similarly, 4-(furan-2-ylmethylene)-2-phenyl-1 -substituted-5(477)-imidazolones 820, evaluated as antibacterial and antifungal agents, have been synthesized from the 4-(furan-2-yhnethylene)-2-phenyl-5(4//)-oxazolone 819 (Scheme 7.253). ° Using 4-arylmethylene-2-phenyl-5(4//)-oxazolones as substrates and 2-amino-5-methyl-l,3,4-thiadiazoles as nucleophiles the synthesis of the corresponding... 

Tsuge and Noguchi469 prepared the 3-benzamido-4-oxo-4//-pyrido-[l,2-a]pyrimidine and its methyl substituted derivatives from 2-amino-pyridines and 2-phenyl-4-ethoxymethylene-5-oxazolone in boiling ethanol, without the isolation of the condensation products of type 94. The pyrido-pyrimidine was formed from 2-amino-6-methylpyridine, but in a longer reaction period and in low percentage yield. Condensation product 94 was cyclized in ethanol or polyphosphoric acid or acetic acid. 3-Benzamido-2-methyl-4-oxo-4A/-pyrido[l,2- ]pyrimidine was synthetized from 2-amino-pyridine and the appropriate oxazolone derivative. 

Hydrazino-5,6-diphenyl-l,2,4-triazine (289) reacts with 4-benzylidene-2-phenyl-5(4//)-oxazo-lones (290) and 4-benzylidene-3-methyl-5(4//)-isoxazolones (291) in toluene to products (292), (293) substituted in the hydrazino group, the first by acylation by the oxazolone, the second by arylraethylidene group transfer (Scheme 53) <88JHC1813>. 

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