2-Phenyl-S-oxazolone

Some new bactericidal and fungicidal derivatives of purine and pyrazolo[l,2,4]triazine have been synthesized by the reaction of 4-arylidene-2-phenyl-S-oxazolones with different nucleophilic reagents <99IJC(B)445>. A variety of pyrazolo[3,2-c][l,2,4]-triazin-3-yl 55, 59 and l,2,4-triazolo[33-c][l,2,4]-triazin-3-yl-phosphonic acid dialkyl esters 56, 60 have been synthesized from diazobetaines of pyrazoles 57 and ttiazoles 58 and monocarbanions of certain phosphonates, respectively <99H513>. 

Compounds of special interest whose preparation is described include 1,2,3-benzothiadiazole 1,1-dioxide (a benzyne precursor under exceptionally mild conditions), bis(l,3-diphenylimida-zolidinylidene-2) (whose chemistry is quite remarkable), 6-(di-methylamino)fulvene (a useful intermediate for fused-ring non-benzenoid aromatic compounds), diphenylcyclopropenone (the synthesis of which is a milestone in theoretical organic chemistry), ketene di(2-melhoxyethyl) acetal (the easiest ketene acetal to prepare), 2-methylcyclopentane-l,3-dione (a useful intermediate in steroid synthesis), and 2-phenyl-S-oxazolone (an important intermediate in amino acid chemistry). 

Barbituric acid, 32, 7 Barium D-gulonate, 36, 39 Behenic acid, 37, 69 Beilstein test, 34, 38 Benzaldehyde, 30, 100 33, 70 34, 65 Benzaldehyde, p-AMINO, 31, 6 />-DIMETHYLAMINO-, 33, 27 Benzaldehyde, purification of, 33, 71 Benzalmalonic acid, ethyl ester, 37, S 4-Benzal-2-phenyl-5-oxazolone, 37, S Benzamidine, N,N -diphenyl-, 31, 48 N-phenyl-, 36, 64 Benzanilide, 31, 48... 

Benzal-2-phenyl-5-oxazolone, 37, S Benzamidine, N,N -diphenyl-, 31, 48 N-phenyl-, 36, 64 Benzanilide, 31,48... 

Aminothiophenol added dropwise to a vigorously stirred soln. of startg, 2-phenyl-5-oxazolone in acetic acid at 25°, and worked up after 15 min - product. Y 85%. F.e.s. A.R. Katritzky et al., Synth. Commun. 18, 651-8 (1988). 

Benzoyl-DL-phenylalanine allowed to react 24 hrs. at room temp, with the equimolar amount of dicyclohexylcarbodiimide in dioxane 4-benzyl-2-phenyl-5-oxazolone. Y ca. 100%. F. e. s. I. Z. Siemion and K. Nowak, Roczniki Chem. 34, 1479 (1960). 

Dichlorobenzaldehyde, hippuric acid, and sulfur trioxide-dimethylformamide heated 15-20 min. on a steam bath 4-(2,4-dichlorobenzylidene)-2-phenyl-5-oxazolone. Y 90%.— This method is remarkable for its good yields and speed of reaction. F. e. s. E. Baltazzi and E. A. Davis, Chem. Ind. 1962, 929 -alkyll-dene-y-enollactones s. Ghem. Ind. 1962, 1653. 

A paste prepared from 4-ethoxymethylene-2-phenyl-5-oxazolone and tetrahydro-furan mixed with indoline 4-(5-indolinylmethylene)-2-phenyl-5-oxazolone. Y 80%. F. e. and steps s. H. Behringer and P. Duesberg, B. 96, 377 (1963). 

Benzylidene-2-phenyl-5-oxazolone mixed with a methanolic soln. of hydroxyl-amine acetate prepared from hydroxylamine hydrochloride and K-acetate, stirred 1 hr. at 18-20° and pH 5-6.5 a-benzamidocinnamohydroxamic acid. Y 87-94%. F. e. s. N. K. Kochetkov et al., 2EC. 29, 68 (1959) C. A. 53, 21783e. 

A mixture of 4-o-methoxybenzylidene-2-phenyl-5-oxazolone, ethanol, and water treated during 1 min. with 85%-hydrazine hydrate, and the product isolated after 2-5 min. -> a-benzoylamino-o-methoxycinnamic hydrazide (Y 98.1%) refluxed 5 min. with excess 1 N NaOH 6-hydroxy-5-o-methoxybenzyl-3-phenyl-1,2,4-triazine (Y 99.5%). F. e. s. K. Nalepa and J. Slouka, M. 98, 412 (1967). 

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. ... 

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... 

To extend this methodology, Diels-Alder reactions of several (Z)-4-arylidene (heteroarylidene)-2-phenyl-5(47/)-oxazolones with butadiene, 2,3-dimethylbuta-diene, cyclopentadiene and Danishefsky s diene have been studied. This work demonstrated that the products depended on the nature of the aromatic ring and the diene used. " An interesting application of this methodology is the synthesis of racemic epibatidine 729, a new alkaloid with a 7-azabicyclo[2.2.1]heptane skeleton that has proven to be a very potent analgesic. Preparation of 729 began with the Diels-Alder adduct 726 obtained from (Z)-4-[5 -(2 -chloropyridyhnethylene)]-2-... 

Sustmann, R. Korth, H. G. Carbonsaure-, Thiocarbonsaurehalogenide bzw. Carbon-saure-halogenid-imide. Houben-Weyl, Metho-den der Organischen Chemie 1985, E5, 589. Smith, C. W. Rasmussen, R. S. Spectroscopic evidence concerning the structure of 2-phenyl-4,4-dimethyl-5(4)-oxazolone hydrobromide. 

Tsuge and Noguchi S prepared the 3-benzamido-4-oxo-4//-pyrido-[1,2-u]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-4//-pyrido[l,2- ]pyrimidine was synthetized from 2-amino-pyridine and the appropriate oxazolone derivative. 

Phenyl-4-benzylidene-5-oxazolone refluxed 1 hr. in ether-chloroform, with O-benzylhydroxylamine —. a-benzamido-O-benzylcin-namohydroxamic acid. Y 78%. (F. e. s. E. Shaw and J. McDowell, Am. Soc. 71, 1691 (1949).)... 

The 2-oxazolin-S-ones are excellent acylating agents for a variety of enzymes. Thus, 2-phenyloxazolin-5-one and 4,4-dimethyl-2-phenyl-2-oxazolin-S-one react with a-chymotrypsin, trypsin, and papain to form stable acyl enzymes.15-18 The azlactone from p-nitrobenzoylvaline reacted with a-chymotrypsin and trypsin, and it was observed that the enzymic activity of chymotrypsin decreased with increasing number of p-nitrobenzoylvaline residues.19 The reaction of a-chymotrypsin with 2 has been studied extensively.20-25 In this reaction, the oxazolone dis-... 

Turner s group have used Lipozyme and Novozyme as effective catalysts for the DKR of various 2-phenyl-4-substituted-5(4//)-oxazolones in the presence of an alcohol, yielding the corresponding chiral iV-benzoylamino acid esters, as shown in Scheme 3.21. 

Azlactones are named as derivatives of amino acids, of oxazolone (Chemical Abstrads and Beilstein s Handbudi), and of dihydrooxazole (British usage). Thus the condensation product of benzaldehyde with hippuric acid maybe called benzoyl-a-aminocinnamic azlactone, 2-phenyl-... 

Hydroxyindazoles. A soln. of 2-(4-methoxyphenyl)-4-phenyl-4-(2,4,6-trinitro-phenyl)-5(4//)-oxazolone in methanol refluxed for 3 h in the presence of a little /7-TsOH - 4,6-dinitro-3-phenyl-l//-indazol-l-ol. Y 78%. F.e. and 6-nitro-lff-pyrazolo 4,3- pyridin-l-ols from the corresponding dinitropyridyl analogs s. M. D Anello et al., Chem. Ber. 121, 67-73 (1988). 

Anhydro [a Dhenyl-hippars uie-pbei l ester], Ueieht 5 Phencay 2.4 diphenyl-oxazol 14, 470 s. a. 27,120. x-Diphenyl >X [4-o -phenyl] oxaxol, Oxybenzilam 27 II100. 3.4.5-Triphenyl-oxazolon (2) 271295,... 

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