4-methyl-2-phenyl-5 -oxazolone

Methyl-2-phenyl-5-oxazolone (22) reacts with excess phenyl-magnesiuin bromide to give 2-benzainido-1,1-diphenyl-1-propanoP (23). With excess ethylmagnesium bromide, 22 forms a dimer, N,N -... 

In contrast, when the same reaction was carried out on 4-(bromomethyIene)-2-phenyI-5(4H)-oxazolone 658 (X = Br) or 4-(iodomethylene)-2-phenyl-5(4//)-oxazolone 658 (X = serendipitous formation of the 2-(halomethyl)spirocy-clopropanes 659 and 660 was observed. Both diastereoisomers of 2,3-methano-methionine 663 and 664 have been prepared from the isolated 2-(bromomethyl)-spirocyclopropane oxazolones, 659 and 660, respectively. The isolated 2-(iodo-methyl)spirocyclopropane oxazolones have been hydrolyzed to furnish the... 

Diazoalkanes add to the carbon-carbon double bonds of 2,3-diphenylthiirene 1-oxide and 1,1-dioxide. The adducts lose SO or SO2 to give pyrazoles and related compounds (Scheme 103) (80CB1632). Mesoionic oxazolones (75CLH53), 4-methyl-5-phenyl-l,2-dithiolene-3-thione (80JOU395) and pyrylium betaines (72JOC3838) react similarly via intermediate adducts (Scheme 104). Enamines (Scheme 96) and ynamines add to the double bond of 2,3-diarylthiirene 1,1-dioxides to give acyclic and cyclic sulfones by a thermal. 

Oxazol-5(2H)-one, 2-benzylidene-4-methyl-tautomerism, 6, 186 Oxazol-5(2ff)-one, 2-methylene-isomerization, 6, 226 Oxazol-5(2H)-one, 2-trifluoromethyl-acylation, 6, 201 Oxazol-5(4ff)-one, 4-allyl-thermal rearrangements, 6, 199 Oxazol-5(4H)-one, 4(arylmethylene)-Friedel-Crafts reactions, 6, 205 geometrical isomerism, 6, 185 Oxazol-5(4ff)-one, 4-benzylidene-2-phenyl-configuration, 6, 185 photorearrangement, 6, 201 Oxazol-5(4ff)-one, 4-benzyl-2-methyl-Friedel-Crafts reactions, 6, 205 Oxazol-5(4ff)-one, 4-methylene-in amino acid synthesis, 6, 203 Oxazol-5(4ff) -one. 2-trifluoromethyl-hydrolysis, 6, 206 Oxazolones... 

Modification of the Erlenmeyer reaction has been developed using imines of the carbonyl compounds, obtained with aniline," benzylamine or n-butylamine. Ivanova has also shown that an A-methylketimine is an effective reagent in the Erlenmeyer azlactone synthesis. Quantitative yield of 19 is generated by treatment of 3 equivalents of 2-phenyl-5(4ff)-oxazolone (2) (freshly prepared in benzene) with 1 equivalent of iV-methyl-diphenylmethanimine (18) in benzene. Products resulting from aminolysis (20), alkali-catalyzed hydrolysis (21), and alcoholysis (22) were also described. 

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. ... 

Three synthetic approaches for benzopyrones have been developed that use Gly as starting material. Hippuric acid was transformed with acetic anhydride into 2-phenyl-5(4//)oxazolone or further into its 4-ethoxy-methylene derivative, then reacted with cyclic 1,3-dicarbonyI compounds (such as like dimedone) to form 100 [90LA501 92H(33)843]. On the other hand, when hippuric acid was transformed into methyl 2-benzoyl-amino-3-dimethylaminopropenoate, it reacted with resorcinol to give a 7-hydroxybenzopyrone derivative (89JHC1273). 

Alkylation of 2,4-disubstituted-5(477)-oxazolones can be conveniently performed via phase-transfer catalysis. For example, the substrate and an alkyl halide are dissolved in an organic solvent and stirred with an aqueous sodium carbonate solution containing tetrabutylammonium bromide as a phase-transfer catalyst. 4,4-(Diarylmethyl)-2-phenyl-5(4/f)-oxazolones can be prepared in one-step by dialkylation of 146 using magnesium methyl carbonate and the corresponding... 

Michael Reaction. 5(47/)-Oxazolones undergo base-catalyzed conjugate addition to activated unsaturated compounds to afford the corresponding C-4 Michael adducts. For example, base-catalyzed addition of a 4-monosubstituted-5(4//)-oxazolone 157 to methyl propiolate yields a mixture of diastereomeric methyl 3-(5-oxo-2-phenyl-2-oxazolin-4-yl)acrylates 158. Hydrolytic ring opening of 158 and subsequent oxidation with lead tetraacetate affords 3-acylacrylates 160... 

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... 

Monosubstituted-5(4//)-oxazolones behave differently upon reaction with imines. Here, 4-methyl-2-phenyl-5(4/7)-oxazolone 196 (Ri = Ph, R2 = Me) reacts with imines derived from 2-furancarboxaldehyde or 2-thiophenecarboxaldehyde to give 3-amino-p-lactams 197. On the other hand, 196 reacts with chlorosul-fonyl isocyanate in a [2 + 2] cycloaddition to give dioxazabicycloheptanones 198 as shown in Scheme 7.60. ... 

Reaction of carbon disulfide with 2-phenyl-5(4//)-oxazolone 146 followed by S-alkylation with a methyl hahde gives 4-[bis(methylthio)methylene]-2-phenyl-5(4//)-oxazolone. The solvolysis and aminolysis of this compound have also been studied. ... 

Enamines and Formamidines. Enamines, prepared from methylpyridines, methyl-pyridazines, methylpyrimidines or methyltriazine, and A, A -dimethylformamide dimethylacetal or ferf-butoxybis(dimethylamino)methane, react with 2-phenyl-5(4//)-oxazolone 146 to afford the unsaturated 5(477)-oxazolones 199 and 201 that are intermediates in the synthesis of fused pyridones 200 and pyridotriazi-nones 202, respectively (Scheme 7.61). ... 

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... 

A number of points should be considered to determine the most appropriate experimental conditions for the desired reaction and, to that end, the kinetics of hydrolysis and ionization of 4-methyl-2-phenyl-, 4-benzyl-2-phenyl-, and 4-benzyl-2-methyl-5(4//)-oxazolones have been investigated. Deprotonation of 5(477)-oxazolones in aqueous media, which leads to racemization of optically active 5(477)-oxazolones, is a fast process that competes with the ring opening. The difference between the rate constant for racemization and the ring opening is greater in solvents with dielectric constants less than water and thus, oxazolones racemize faster than they hydrolyze. 

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... 

The authors applied the same synthetic strategy to racemic 4-alkyl -(iodo-methyl)-2-phenyl-5(4/ )-oxazolones 266 and obtained a diastereomeric mixture of oxazolines 267 and 268 (Scheme 7.86). The diastereoisomers were separated chromatographicaUy and then converted into dipeptides incorporating an a-alkyl-serine residue. ... 

Reaction of unsaturated 5(4//)-oxazolones with appropriate nucleophiles affords new unsaturated 5(4//)-oxazolone analogues used as intermediates to prepare a variety of interesting compounds. 4-(Chloromethylene)-5(4/i/)-oxazolones react with a variety of nucleophiles. For example, 4-(chloromethylene)-2-phenyl-5(4F/)-oxazolone 395 reacts with imidazole to afford 4-[(imidazol-l-yl)methyl-ene]-2-phenyl-5(4F/)-oxazolone 396. The authors found no evidence for the product derived from carbon-carbon bond formation, that is, 4-[(imidazol-4-yl)methylene]-2-phenyl-5(4//)-oxazolone (Scheme 7.126). 

The hydrolysis and alcoholysis reactions have been extended to the heterocyclic series. A systematic study has been published of the hydrolysis of unsaturated oxazolones derived from a selection of heterocyclic aldehydes. A detailed study of the synthesis and stereospecific hydrolysis and methanolysis of the (Z) and ( ) isomers of 2-methyl (or phenyl)-4-(thienylmethylene)-5(4F/)-oxazo-lones 435 and 437 has also been described (Scheme 7.144). The synthesis of 2-acylamino-3-(indol-3-yl or carbazol-3-yl)acryhc acid derivatives as potential antifertility agents via oxazolone hydrolysis has also been published. ... 

For amides obtained by stereospecific ring opening of (Z)- and ( )-2-phenyl-4-(a-phenylethylidene)-5(477)-oxazolone 505 and 508, cyclization gives the imida-zolone 510 or 4-methyl-l-phenyl-3-isoquinolinecarboxylic acid anilide 507. The products are determined by the double-bond geometry in the starting material and by the experimental conditions (Scheme 7.161). ... 

Deacetylation of 4-[(o-acetoxy)benzylidene]-2-phenyl-5(47/)-oxazolone also immediately affords 602. The starting oxazolone was obtained by cyclodehydration of the corresponding cinnamic acid precursor or by condensation of hippuric acid with 2-acetoxybenzaldehyde in the absence of base. In examples using 2-hydroxy-acetophenone, 4-methyl-3-(acylamino)coumarins are obtained. ... 

The stereochemistry of the double bond in 4-(a-arylethylidene)-2-phenyl-5(4//)-oxazolones can be determined by measurements of long-range heteronuclear selective carbon-13 proton nuclear Overhauser enhancements. In the (Z)-isomers 774, large nuclear Overhauser enhancements are observed for the carbonyl carbon atom upon presaturation of the methyl group (Fig. 7.65). These effects are much smaller for the ( ) isomers. ... 

The phenyl group of trisubstituted 4-benzylidene-5(4//)-oxazolones is nearly planar whereas the styryl moieties in (Z)-2-phenyl-4-(a-phenylethylidene)-5(4//)-oxazolone and fZ)-2-methyl-4-(a-phenylethylidene)-5(4//)-oxazolone show significant deviations from planarity. ... 

Dipolar cycloaddition of 4-arylmethyleneisoxazol-5-ones 794 and 2-methyl-4-phenyl-5(4//)-oxazolone 795 leads to pyrrole-3-carboxyhc acids that have been isolated as hydroxamates 796. The authors carried out this cycloaddition-nitrile oxide addition as a one-pot reaction (Scheme 7.243). ... 

Finally, new palladium(II) and platinum(II) complexes from 4-benzyl-4-methyl-2-phenyl-5(477)-oxazolone or C2 symmetric bis(oxazolone) ligands have been... 

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... 

A new method for the synthesis of 4(3//)-qumazolinones 822 and 1,4-benzo-diazepine-2,5-diones 823 from reaction of 4-aryhnethylene-2-methyl- 821 (Rj = Me) or 4-arylmethylene-2-phenyl-5(4/i/)-oxazolones 821 (Rj = Ph) with o-aminobenzamide has also been reported (Scheme 7.254). ... 

Recently, the cyclopropanation of (Z)-4-benzyIidene-2-phenyl-5(4//)-oxazolone 621 with phenyldiazomethane was reported to give the spirocyclopropane, rac- 21 in very high yield. Subsequent ring opening and hydrolysis of rac- 21 generated frani-l-amino-2,3-diphenyl-l-cyclopropanecarboxylic acid, rac-828 (cadiPhe) (Scheme 7.256). This new, constrained phenylalanine analogue induces a y-tum in the sohd state when incorporated into model dipeptides. The enantiomers of the Al-Boc (Boc = tert-butyloxycarbonyl) methyl ester of 828 have been resolved by HPLC. 

---