4-arylidene-5 -oxazolones

In contrast to the saturated azlactones, the Friedel-Crafts reaction of 2-substituted-4-arylidene-5-oxazolones is quite complex and may follow several different courses, often concurrently, depending on both reaction conditions and structural variations in the arylidene ring. This behavior is readily interpreted in terms of the a,)S-unsaturated carbonyl moiety and the cross-conjugated system containing nitrogen, both of which provide potential reaction sites in addition to the lactone carbonyl group. The reaction has been investigated " ... 

The behavior of unsaturated azlactones with organometallic reagents has been studied in detail. Arylmagnesium halides and phenyllithium attack 4-arylidene-5-oxazolones at the carbonyl carbon to give ring-opened amido tertiary alcohols (26) and oxazolines (27) (by ring closure), usually as mixtures [Eq. (17)]. The nature of the... 

Arylidene-5-oxazolones undergo a ring-opening reaction with aromatic thiols and a second mole of thiol is then incorporated to give products such as 48. ... 

The difference is interestingly exemplified in the differing modes of reaction of hydrazoic acid with some alkylidene (and arylidene) oxazolone derivativesThe alkylidene compound 174 behaves as an a, -unsaturated carbonyl compound with the hydrazoic acid adding to the exocyclic double bond. A subsequent ring opening with further addition leads to the formation of the diazide 175 (equation 75). In contrast the exocyclic double bond of the arylidene compound 176 is unreactive, and nucleophilic attack occurs at the... 

In contrast to these ring-opening reactions, it was observed by Horner and Schwahn that 4-arylidene-(isopropylidene and cyclo-hexylidene)-oxazolones react with alkyl Grignard reagents by conjugate addition to give saturated azlactones 29a as the only products [Eq. (18)]. 

Avenoza A., Busto J. H., Cativiela C., Peregrina G. M. and Zurbano M. M. The use of 4-Hetaryliden- and 4-Aryliden-5(4H)-Oxazolones as Dienophiles in the Diels-Alder Reactions in Targets in Heterocyclic Systems-Chemistry and Properties vol 3. 1999, Eds. Attanasi O. A. and Spinelli D., Pb. Soc. Chim. Ital. Keywords hetero-Diels-Alder reactions... 

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. 

Many other applications have been described for these compounds and the hst is so extensive that it is impossible to cover each example here. Nevertheless, it is noteworthy that appropriately substituted 4-arylidene-5(4r/)-oxazolones, for example, 359 and 360 have been reported as organic Iruninophores" " and electrophotographic light-sensitive materials," respectively. The use of apoca-rotenoid derivatives such as 362 as monomolecular films has also been described." For new materials, a number of water-insoluble oxazolones have been used for dyeing or printing synthetic fibers" and, in this context, 4-(pyren-1-ylmethylene)-2-substituted-5(4/i/)-oxazolones 357, prepared from pyrene-1-carboxaldehyde, have... 

Iminophosphoranes derived from readily available ot-azidocinnamates react with aroyl chlorides to give the corresponding 2-aryl-4-arylidene-5(4//)-oxazolones 37 2 500,501 AjteiTjatively, these iminophosphoranes are converted to the corresponding 2-arylamino-4-arylidene-5(4//)-oxazolones 373 via heterocyclization of an intermediate carbodiimide as shown in Scheme 7.119 (Table 7.32, Fig. 7.43). ° ... 

The exocyclic double bond of 4-arylidene-5(47/)oxazolones 383 reacts with diazomethane in a 1,3-dipolar cycloaddition reaction to give the corresponding... 

TABLE 7.35. SYNTHESIS OE 4-(a-ARYEETHYLIDENE)-5(4ff)-OXAZOLONES FROM REACTION OF 4-ARYLIDENE-5(4ff)-OXAZOLONES WITH DIAZOMETHANE ... 

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 ... 

Both stereoisomers of a 4-(a-arylethylidene)-5(477)-oxazolone 441 and 443, undergo stereospecihc hydrolysis-methanolysis to furnish the corresponding (Z) and (E) isomers of 2-acetylamino(or benzoylamino)-3-aryl-2-butenoic acid or methyl ester, 442 and 444, respectively (Scheme 7.146). ° The requisite starting oxazolones were prepared by condensation of an acetophenone with an acylglycine or by methylene insertion into the vinyl C—H bond of a 4-arylidene-5(4//)-oxazolone. 

Bis-4-arylidene-5(4//)-oxazolones are easily obtained from aromatic dialdehydes by the Erlenmeyer synthesis. Such bis(oxazolones) react with a,co-diamines to provide a convenient approach to macrolactams.Tandem Erlenmeyer condensation-macrolactamization (TECM) has been used to prepare analogues of naturally occurring, biologically active cyclic peptides such as bastadin-5. 

Starting unsaturated 5(477)-oxazolones 4-aIkylidene(arylidene)-5(4/y)-oxazolones 573 lead to dihydropyridone derivatives 574, whereas 4-(ethoxymethylene)-5(4//)-oxazolones 575 give pyridones 576 (Scheme 7.182). 

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. 

Hydride reduction of a 4-arylidene-5(4H)-oxazolone can also be considered as a nucleophilic ring opening. Here, this process, shown in Scheme 7.190, generates a-(benzoylamino)cinnamyl alcohols 597. °... 

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. ... 

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-... 

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