4-benzylidene-5 -oxazolones

The reaction of 2-phenyl-4-benzylidene-5-oxazolone with hydrazine forms 4-benzamido-5-phenyl-3-pyrazolidinone.319,1342 Both 2-pyrazolin-5-ones and 3-pyrazolin-5-ones have been reduced catalytically to 3-pyrazolidinones.1491,1592 Heymons and Rohland647 have treated 3-methyl-l,2-diphenyl-3-pyrazolin-5-one with sodium and carbon dioxide and claimed to have obtained a carboxylic acid, presumably by intermediate addition of sodium to the double bond (eq. 246). A number of... 

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).)... 

Benzyl.4.benzyliden.oxazolon-(S) 27, 226. 2-PhenyI.4-[4-methyl-benzyUden]-oxazo lon.(5) 27 I 299. 

Phenyl-4- [2-nitro 3-methoxy 4 aceto -benzyliden]-oxazolon-(5) 27 I 369. 

Efficient photo-isomerization of water-soluble 1,4-diaryl-l,3-butadiene dendrimers (19) occurred in high quantum yield (Scheme 11). " E-Z photoisomerization of benzylidene-oxazolones (Z-20) and ( -20) was also reported as molecular photo-swiches. The ring size effects of aromatics of styrylbenzothiazol (21) were examined (Scheme 12). ... 

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 member of this class which has been studied most thoroughly is 2-benzylidene-4-methyl-5(2 )-oxazolone (57). This compound may be prepared by ring closure of either 3-bromo-2-phenylacetamido-propionic acid or A-(a-halophenylacetyl)alanine (56) [Eq. (30)]. These reactions presumably proceed via unstable halogeno-5(4IT)-oxazolones, which rapidly lose hydrogen halide. 

TABLE 6.5. 5-(BENZYLIDENE)-2-SUBSTITUTED-4(5//)-OXAZOLONES EROM 5-(BENZYLIDENE)-2-(METHYLTHIO)-4(5/7)-OXAZOLONE... 

The first attempt to prepare 2-phenyl-4-(phosphoranylidene)-5(4//)-oxazolone 219 started with l-benzoylamino-(2,2-dichloroethenyl)triphenylphosphonium chloride 216 and involved the complex reaction sequence shown in Scheme 7.67. The structure and properties of 219 were studied and it was shown that 219 underwent Wittig olefination with benzaldehyde to give the well-known (Z)-4-benzylidene-2-phenyl-5(477)-oxazolone. ... 

There are cases in which appropriate modification of one unsaturated oxazolone yields a new unsaturated oxazolone analogue. Most of the examples described in the literature involve modification of the substituent on the exocyclic double bond. For example, a series of 4-[2-hydroxy-3-(aminomethyl)benzylidene]-5(4//)-oxazo-lones 382 that were evaluated for bactericidal and fungicidal activities were obtained from Mannich reaction of 4-(2-hydroxybenzylidene)-5(4//)-oxazolones 381 (Scheme 7.123). ... 

A study on the combined use of a chiral substrate obtained by alcoholysis of a 4-benzylidene-5(4//)-oxazolone with a chiral alcohol coupled with hydrogenation using a chiral catalyst has also been described. This work shows that the matching effect of double asymmetric induction in hydrogenation can be modulated by a solvent effect. 

Unsaturated 5(4H)-oxazolones undergo a Friedel-Crafts reaction with aromatic hydrocarbons in the presence of a Lewis acid. In particular, a 2-aryl-4-benzylidene-5(4H)-oxazolone 598 reacts with o- or p-xylene in the presence of aluminum chloride via ring opening and subsequent dearylation to yield 599 as indicated in Scheme 7.191. ... 

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. ... 

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). 

Although it is well known that sulfur nucleophiles are excellent candidates for Michael reactions, they have scarcely been examined with unsaturated oxazolones. Nevertheless, 4-methyltoluene-a-thiol reacts with 4-benzylidene-2-methyl-5 (4//)-oxazolone 614 to give 615 as a mixture of erythro and threo isomers (Scheme 7.197). ° ... 

Since (Z)- and ( )-stereoisomers of unsaturated oxazolones can be obtained using appropriate isomerization procedures, cis and trans isomers of cyclopropane derivatives can be obtained in a stereoselective manner, although special care must be taken with experimental conditions to obtain the best stereoselectivity. Both racemic cis- and fraui-l-amino-2-phenylcyclopropanecarboxylic acid 641 and 644 have been obtained from the corresponding (Z)- or ( )-4-benzylidene-2-phenyl-5(4//)-oxazolone 621 and 642 using diazomethane. Care was taken to affect the... 

Z)-4-Benzylidene-2-phenyl-5(4//)-oxazolone 621 also reacts with cyclopenta-diene in the presence of a Lewis acid. In this case, the reaction leads to a mixture of cycloadducts 699 and 700 derived from endo and exo attack of the diene. The mixture of 699 and 700 can be separated chromatographically or simply by... 

Electrochemical reduction of 4-benzylidene-2-methyl-5(47/)-oxazolone to produce racemic Al-acetylphenylalanine has been accomplished using lead and cadmium cathodes. ... 

Electron impact mass spectrometry is not effective to distinguish between the (Z) and (E) isomers of 4-benzylidene-2-phenyl-5(4//)-oxazolone and 4-(a-phenylethyl-idene)-2-phenyl-5(4//)-oxazolones because the spectra show only minor differences... 

Other structural features of unsaturated-5(4//)-oxazolones can be deduced from crystallographic data including the effect on planarity of substituents on the exocyclic double bond. For example, 4-benzylidene-5(4//)-oxazolones show a completely planar conformation that favors strong electronic conjugation in both (2)990 isomers. The same effect has been reported for other 4-arylidene-... 

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. ... 

In the context of the nucleophihc ring-opening reactions, the mechanism of the reaction of 4-benzylidene-2-methyl-5(4/l/)-oxazolone with n-butylamine has been studied. 

Benzylidene-2-methyloxazol-5-one. Warm a mixture of 29 g (0.25 mol) of acetylglycine, 39.5 g (37.5 ml, 0.37 mol) of redistilled benzaldehyde [Expt 6.133, Note (1)], 15 g (0.183 mol) of anhydrous sodium acetate and 63.5 g (59 ml, 0.62 mol) of acetic anhydride in a 500-ml flask (equipped with a reflux condenser) on a water bath with occasional stirring until solution is complete (10-20 minutes). Boil the resulting solution for 1 hour, cool and leave in a refrigerator overnight. Stir the solid mass of yellow crystals with 60 ml of cold water, transfer to a Buchner funnel and wash well with cold water. (If the odour of benzaldehyde is still apparent, wash with a little ether.) Recrystallise from carbon tetrachloride or from ethyl acetate-light petroleum. The yield of the oxazolone, m.p. 150°C, is 35 g (76%). 

Benzylidene-2-phenyloxazol-5-one. Place a mixture of 27 g (26 ml, 0.25 mol) of redistilled benzaldehyde, 45 g (0.25 mol) of benzoylglycine, 77 g (71.5 ml, 0.75 mol) of acetic anhydride and 20.5 g (0.25 mol) of anhydrous sodium acetate in a 500-ml conical flask and heat on an electric hotplate with constant shaking. As soon as the mixture has liquefied completely, transfer the flask to a water bath and heat for 2 hours. Then add 100 ml of ethanol slowly to the contents of the flask and allow the mixture to stand overnight. Filter the crystalline product with suction, wash with two 25 ml portions of ice-cold alcohol and then wash with two 25 ml portions of boiling water dry at 100 °C. The yield of almost pure oxazolone, m.p. 165-166 °C, is 40g (64%). Recrystallisation from benzene raises the m.p. to 167-168 °C. 

Heterogeneous catalysts modified by the addition of chiral substances have been used to hydrogenate olefins asymmetrically, but only a few effective chiral heterogeneous catalyst systems have been found. Palladium deposited on silk fibroin was used to hydrogenate 4-benzylidene-2-methyl-5-oxazolone asymmetrically to give, after hydrolysis, optically active phenylalanine (Fig. lc). The optical purity1 of the product was found to be dependent on the origin of the fibroin and its chemical pretreatment (4-6). 

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)-OxazoIones (78) are unstable with respect to the 4//-isomers (79) however, the 2-trifluoromethyl derivatives are unique in that the 2//-forms (78 R1 = CF3) are favoured (62LA(658)128). This was evident from the NMR spectra of numerous derivatives containing phenyl or alkyl groups at C(4) (64CB2023). While 2,2-disubstituted 5(2//)-oxazolones (80) have a fixed structure, the 2-methylene derivatives, such as 2-benzylidene-4-methyl-5(2H)-oxazolone (81), are in potential tautomeric equilibrium with 5(4//)-oxazolones, e.g. (82). However, compound (81) exists entirely in this form, no doubt because it is stabilized by conjugation of the phenyl group with the exocyclic double bond. 

The (Z) isomer (189) of 4-benzylidene-2-phenyl-5(4//)-oxazolone rearranges to the (E) form on irradiation. The photodimerization of compound (190) in solution results in the centrosymmetric cyclobutane derivative (191). A different kind of photodimerization occurs when the oxazolone (192) is irradiated in the solid state, compound (193) being formed (79TL2461, 79TL3139). 

The 5(2H)-oxazolones (213) present two sites, C(4) and C(5), to nucleophilic attack they usually react at the latter. The benzylidene derivative (214), the most thoroughly studied member of this class, possesses an additional electrophilic centre at the exocyclic carbon atom. However, alkaline hydrolysis of this compound affords phenylacetamide and benzoylformic acid by acyl-oxygen fission (equation 50). a-Keto acids are also obtained when 2-trifluoromethyl-5(4//)-oxazolones are hydrolyzed, the reaction involving preliminary isomerization to a 5(2//)-oxazolone. The example shown in equation (51) represents the first non-enzymatic synthesis of an optically active a-keto acid. An instance of nucleophilic attack at C(4) of a 5(2//)-oxazolone is the formation of the oxazolidinone (215) in a Grignard reaction (equation 52). However, the typical behaviour of unsaturated pseudooxazolones like (214) is conjugate addition of a nucleophile, followed by further transformations of the resulting 5(4F/)-oxazoIones. This is illustrated by the reaction of compound (214) with benzene in the presence of aluminum chloride to yield, after aqueous work-up, the acylamino acid (216 equation 53). 

When 4-benzylidene-2-methyl-5-oxazolone (45) is prepared by the Erlenmeyer procedure, a light yellow product is generally isolated. Rufenacht showed that pure 45 is white and that the colored... 

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