4-benzyl-5 -oxazolones

Phenyl-4-benzyl-6-oxazolone. Ten grams of benzoyl-dl-/3-phenyl-alanine is heated on the steam bath for thirty minutes with 100 cc. of acetic anhydride. The solution is concentrated in vacuum, and the syrupy residue is dissolved in 100 cc. of petroleum ether, b.p. 60-110 . The solution is decanted from a small amount of insoluble material and is cooled. Practically pure 2-phenyl-4-benzyl-5-oxazolone crystallizes in long needles, m.p. 69-71° yield 7.5 g. (80%). 

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. ... 

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... 

The one-pot reaction of the a-(difluoromethyl)-p-sulfinylenamine 70 with trifluoroacetic anhydride in CHCI3, followed by treatment with silica gel affords 4-(difluoromethyl)-5-p-tolylthio-2(3//)-oxazolone 74 (Fig. 5.18). This reaction proceeds via a Pummerer-type rearrangement, followed by [l,3]-proton shift and the simultaneous elimination of trifluoroacetic acid and benzyl alcohol. ... 

The reaction of aliphatic and aromatic ketone oximes 97 with a dialkyl carbonate 98 in the presence of K2CO3 at 180-190 °C yields 3-alkyl-4,5-disubstituted-2(3//)-oxazolones 104 in 22-48% yields. Mechanistically, it is proposed that N-alkylation of the initially formed oxime O-carbonate 99 yields 100, which affords the enamine 101 in the presence of base. A [3,3] sigmatropic rearrangement ensues to produce 102, which then cyclizes to 104. In cases where 97 contains two methylene groups in proximity to the C=N bond, one of which is benzylic, the above reaction sequence is regioselective for the benzylic methylene group (Fig. 5.25 Table 5.6, Fig. 5.26). ... 

Condensation of benzyl glycinate -toluenesulfonate salt with 4,5-diphenyl-1,3-dioxol-2-one affords 154, which can be converted to the 4,5-diphenyl-3-substituted-2(3//)-oxazolones 155 by sequential treatment with an aldehyde/LiHMDS followed by diaminosulfur trifluoride (DAST). Hydrogenolysis then affords the p-fluoro-a-amino acids 156 in excellent yields without any concomitant cleavage of the... 

Acetyl-2(3//)-oxazolone 84 serves as a good 1,3-dipolarophile in the [3+2] cycloaddition to A-alkyl-a-phenylnitrones 239, giving a mixture of the four possible isomers 240-243, but with the predominant formation of the exo-syn adduct 240 (Fig. 5.59). Diastereoselective cycloadditions proceed when mixtures of optically active 3-(2-exo-alkoxy-l-apocamphanecarbonyl)-2(3/7)-oxazolones and A-benzyl- and A-ferf-butyl-a-phenylnitrones are heated at 110 °C ... 

Acetone-sensitized [2+2]-photocycloaddition of 2(3//)-oxazolones 247a to maleic anhydride and dimethylmaleic anhydride gives the corresponding anti-cyclobutane cycloadducts 253 as the major products. Similar photoreaction of 2(37/)-oxazolones with 1,6-anhydro-4-(9-benzyl-2,3-dideoxy- 3-D-e 7t/ira-2-hex-enopyranose 254 results in the exclusive formation of the anh-cyclobutane-type adduct 255 (Fig. 5.61). ... 

Alternatively, alkylation of 4-benzyl-2-(trifluoromethyl)-5(2//)-oxazolone 16 in the presence of mild base using active alkyl halides as electrophiles occurs at C-4 " Subsequent aminolysis of a 4,4-dialkyl-5(4f/)-oxazolone like 17 gave an Al-(trifluoroacetyl)-a,a-dialkylglycine amide 18 that was used to prepare important peptides incorporating an a,a-dibenzylglycine unit (Scheme 7.5). 

Alkylation of saturated 5(4//)-oxazolones at C-4 is a well-known reaction that can be achieved under a wide variety of conditions. Numerous articles have described this reaction as a means to prepare 4,4-dialkyl-5(477)-oxazolones 147 that are valuable intermediates to prepare ot,ot-disubstituted a-amino acids. For instance,2-phenyl-5(4//)-oxazolone 146 readily obtained from hippuric acid and A,A -dicyclohexylcarbodiimide (DCC), is alkylated at C-4 with allyl, benzyl, or phenacyl halides if the reaction is conducted in dipolar aprotic solvents in the presence of weak bases. Hydrolysis of the resulting 5(477)-oxazolones leads to a,a-dialkylglycines 148 (Scheme 7.43). 

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. 

The use of chiral organometaUic compounds as catalysts in the enantioselective hydrolysis of saturated oxazolones was reported several years ago and the mechanism of the hydrolysis of 4-benzyl-2-methyl-5(4//)-oxazolone catalyzed by the copper(II) complex of (5)-[(A-benzylprolyl)amino]benzaldoxime has been described. ... 

Dimerization of 5(4//)-oxazolones affords two different products depending on the reaction conditions. In one case, 4-benzyl-2-phenyl-5(4F/)-oxazolone 291 was converted to the pyrrolidinedione 292 with potassium carbonate followed by acidic hydrolysis (Scheme 7.96). ... 

It is well known that hydrogenation of dehydroamino acid derivatives derived from ring opening of unsaturated 5(4H)-oxazolones affords new racemic amino acids and, in some cases, enantiomerically pure compounds. On the other hand, a number of attempts have been made to hydrogenate the double bond of the unsaturated oxazolone itself. For example, 4-benzyl-2-methyl-5(4//)-oxazolone was prepared from 4-benzylidene-2-methyl-5(4H)-oxazolone using Raney Ni as a catalyst. This process is reported to be a general procedure to prepare saturated oxazolones directly (Scheme 7.194). 

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... 

Padwa and Hamilton examined other aziridines where the nitrogen was unsubstituted.43 44 cis-1,2-Diphenylaziridine (21) on refluxing with DMAD in benzene gave 85% of the adduct 22 DEAD was also used. tranj-2-Benzoyl-3-phenylaziridine (23) gave the pyrrole 24 with DMAD the latter was also synthesized from 4-benzyl-2-phenyl-5-oxazolone (26), via 25, which was oxidized with selenium dioxide to 24. 

Treatment of saturated azlactones with aromatic compounds under Friedel-Crafts conditions gives acylamino ketones in high yield (equation 46). 4-Benzyl-2-methyl-5(4H)-oxazolone undergoes an intramolecular reaction to yield an acetamidoindanone (equation 47). Friedel-Crafts reactions of 4-(arylmethylene)-5(4H)-oxazolones are complicated by the presence of an additional electrophilic centre (cf. 201) and may follow three courses. The unsaturated azlactone (189) adds benzene under the influence of aluminum chloride to form the saturated azlactone (207) in inert solvents (189) undergoes an intramolecular acylation to yield a mixture of the indenone (208) and the isoquinoline (209 Scheme 20). 

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