4-arylidene-2-phenyl-5 -oxazolones

Base-catalyzed cyclization of A -benzoyl-a-chloroacetamide is a classical method used to prepare 2-phenyl-4(5//)-oxazolone. Extension of this methodology to the A -aroylcinnamides 35 afforded a series of 5-arylidene analogues 37 albeit in unstated yield (Scheme 6.12). " Thus, acylation of the sodium salt of a benzamide with a cinnamoyl chloride gave the imides 35 that were converted to 36 via a bromination-dehydrobromination sequence. Cyclization to 37 was affected with sodium hydride in 1,2-dimethoxyethane (DME). The authors noted that catalytic reduction of 37 afforded the 5-(arylidene)oxazolidine from which 37 could be regenerated in the presence of air. 

Displacement of the chlorine atom in 395 by sodium thiomethoxide or other mercaptans was reported recently. The same authors also described an efficient synthesis of 4-arylidene-2-phenyl-5(477)-oxazolones 399 from 395 and organo-stannanes via palladium catalyzed Stille reaction (Scheme 7.128). Selected examples are shown in Table 7.36 (Fig. 7.47). 

TABLE 7.36. SYNTHESIS OE 4-ARYLIDENE-2-PHENYL-5(477)-OXAZOLONES EROM STILLE REACTION OF 4-(CHEOROMETHYEENE)-2-PHENYL-5(4/7)-OXAZOLONE ... 

Reaction of 4-arylidene-2-phenyl-5(4//)-oxazolones 593 with A-phenacylpyri-dinium bromide proceeds by the same sequence to give oxazolo[5,4-/>]pyridines 594 (Scheme 7.188) while the reaction of 4-(aminomethylene)-2-phenyl-5(4//)-oxazolone 418 and phenyl isothiocyanate gives pyrimidin-2-thiones 595 (Scheme 7.189). In this latter case initial attack of the exocylic amino group produces an intermediate thiourea (not shown) that subsequently cyclizes to 595. 

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... 

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-... 

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. ... 

Studies of the UV-visible absorption spectra of 4-arylidene-2-phenyl-5(4//)-oxazolones show that the sign of the solvatochromism is substituent dependent in hydrogen-bonding solvents. On the other hand, in non-hydrogen-bonding solvents all substiments show a positive solvatochromism. ... 

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>. 

The exo double bond of 4-alkylidene and 4-arylidene-5(4//)-oxazolones undergoes cycloaddition reactions with 1,3-dipolar reagents. For example, nitrile oxides add to 2-phenyl-4-ethoxymethylene-5(4//)-oxazolone (88) to give spirocyclic products that may be hydrolyzed to 4-aminoisooxazoles... 

Arylidene-2-phenyl-5(47/)-oxazolones (azlactones) 121 were prepared via Erlenmeyer synthesis from aromatic aldehydes 119 and hippuric acid 120 employing calcium acetate under solvent-free conditions with microwaves irradiation <04TL425>. 

With the same kind of molecule and the same method of synthesis, 4-arylidene-2-phenyl-5(41-f)-oxazolones were synthesized by the Erlenmeyer reaction from aromatic aldehydes and hippuric acid using calcium acetate under solvent-free conditions (Eq. 27) [113] ... 

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