2-aryl-4-phenyl-5 -oxazolones

The A7-(a-hydroxyphenacyl)urethanes 8 react smoothly with aromatics in concentrated sulfuric acid to give Friedel-Crafts type products 9, which are readily converted into 4-aryl-5-phenyl-2(3/l)-oxazolones 10 on heating or by treatment with phosphorus pentachloride (Fig. 5.4)." ... 

The reaction of 2-aryl-4-phenyl-5(4/b-oxazolones 22 with 4-methylenetriazoles 23 was also studied. The direction of the alkylation was strongly dependent on the nature of the substituent on the aromatic ring at C-2 in 22. Thus, oxazolones with electron-rich aryl substituents gave predominantly alkylation at C-4 to yield 24. In contrast, the isomeric products 25 are preferentially obtained when using substrates with electron-withdrawing substituents (Scheme 7.7). 

The alkylation of 2-aryl-4-phenyl-5(4//)-oxazolones like 22 is strongly dependent upon the nature of the substituent on the aromatic ring at C-2. For electron-rich... 

Racemization is not encountered when 4-unsubstituted-5(477)-oxazolones or 4,4-disubstituted-5(477)-oxazolones are used as reagents. Indeed, 4-unsubstituted-5(47/)-oxazolones function as glycine synthons in the synthesis of A-acylglycyl-a-amino acids. For example, aminolysis of 2-(trifluoromethyl)-5(47/)-oxazolone with a-methylphenylalanine affords A-(trifluoroacetyl)glycyl-a-methylphenylalanine. 4,4-Disubstituted-5(4//)-oxazolones, readily available by alkylation of the monosubstituted derivatives, are very useful intermediates in the synthesis of peptides that incorporate ot,ot-disubstituted amino acids. As an example, 4-(aryl-methyl)-2-phenyl-4-(trifluoromethyl)-5(4//)-oxazolones 260 are key intermediates... 

In a similar manner, aldazines afford pyridazinones 317 (Scheme 7.104). 1,3-Diazadienes such as l-aryl-4-(dimethylamino)-2-phenyl-l,3-diaza-l,3-butadienes or l-aryl-4-(dimethylamino)-2-methylthio-l,3-diaza-l,3-butadienes react with oxazolones and give rise to pyrimidin-6-ones 319 and 320 as single diastereo-... 

Finally, reaction of 2,4-diphenyl-5(4//)-oxazolone 322 with 4-phenyl-A -tosyl-1-azabuta-1,3-diene was found to be highly dependent on the experimental conditions. At room temperature the sole product was 323 that arises from alkylation of 322 by addition at the imine carbon. However, heating 322 and 4-phenyl-A-tosyl-1-azabuta-1,3-diene gave rise to several products including a 2-pyridone 324, 2,3,6-triphenylpyridine 325, and the pentasubstituted pyrroles 326 and 327. The authors postulated two different reaction mechanisms. Here, both a 1,3-dipolar cycloaddition of the oxazolone and a nucleophilic addition of the oxazolone are possible and that may account for the formation of 324—327. The marked differences in reactivity of 4-phenyl-A-tosyl-l-azabuta-l,3-diene relative to A-alkyl- or A-aryl-1-aza-1,3-dienes was attributed to the powerful electron-withdrawing nature of the tosyl group (Scheme 7.107). ... 

For carbon nucleophiles sequential addition of 2-potassio-2-nitropropane and oxygen to 4-arylidene-2-phenyl-5(47/)-oxazolones 623 has been reported (Scheme 7.200). The process involves a Michael reaction of the 2-nitropropane anion followed by reaction with molecular oxygen and elimination of nitrous acid to yield 2-aryl butenoic acid imides 626. 

The Diels-Alder reaction of (Z)-4-arylidene-2-phenyl-5(4//)-oxazolone 707 and Danishefsky s diene is best conducted in toluene at reflux to produce both the endo and the exo stereoisomers of 708. Base treatment of the cycloadduct mixture promotes aromatization through spontaneous oxidative decarboxylation to give 3-aryl-4-benzamidophenols that are converted to 3-aryl-4-aminophenols 709 by acid... 

The 7i-donor behavior of 4-arylmethylene-2-phenyl-5(47/)-oxazolones 762 with the 7i-acceptor tetracyanoethylene has also been studied. The initially formed charge-transfer complex is converted via intermediate 763 to a new compound for which a 2-aryl-l-benzamido-3,3,4,4-tetracyanocyclobutanecarboxylic acid 764 has been proposed on the basis of the NMR spectral data (Scheme 7.233). Charge-transfer complexes of 2-aryl-4-arylidene-5(47/)-oxazolones with di- and trinitrobenzene as n acceptors have also been prepared. ... 

The circular dichroism of cis- and trans- 2-oxazolidinones (59 R = H or Me) has been measured (79T2009). Geometrical isomerism round the exocyclic double bond in 4-(aryl-methylene)-5-(4//)-oxazolones (60), the unsaturated azlactones, is a well-studied phenomenon (75S749). It has been shown by X-ray crystallography (74T351) that the stable form of 4-benzylidene-2-phenyl-5(4//)-oxazolone has the (Z) configuration (61). It isomer-izes to the labile (E) form (62) in polyphosphoric acid and the change is reversed in pyridine. 

H)-Oxazolones are formed by the spontaneous cyclization of /3-oxo isocyanates (equation 134). Similarly, o-hydroxyphenyl isocyanate, produced by the Curtius rearrangement of the azide of salicylic acid or by the action of sodium hypochlorite on salicylamide, forms benzoxazolone (equation 135). An analogous reaction is the formation of IV-phenyl-benzoxazolone by the action of thionyl chloride on the hydroxamic acid shown in equation (136) (78TL2325). Pyrolysis of aryl azidoformates affords benzoxazolones by nitrene insertion (equation 137) (81CC241). 

Azlactones can be hydrolyzed to the corresponding acids with either alkaline or acidic reagents, the alkalies being conaderably more effeo- tive. The ease of the reaction depends to a marked extent upon the nature of the substituents on the oxazolone ring. Unsaturation in the 4-position or an aryl group in the 2-position stabilizes the mdecule. Thus 2-methyl-4-benzyl-5-oxazolone is hydrolyzed by water at room temperature, 2-methyl-4-benzal-5-oxazolone by boiling aqueous acetone, and 2-phenyl-4-benzal-5-oxazolone by boiling 1% aqueous sodium hydroxide. ... 

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