Aryl-substituted 5- oxazoles

Extreme differences between 5% palladium-on-carbon and platinum oxide were found on reduction of the 5-aryl substituted oxazole 14. Over palladium, 15 was formed in quantitative yield by hydrogenolysis of the benzyl hydroxyl, whereas over Pt, scission of the oxazole occurred to give 13 quantitatively (48). Hydrogenation of 15 over platinum oxide gave the phenethylamide 16. 

The synthesis of 2-acyloxazoles has always been a challenging task. Their synthesis through the use of metallated oxazole is troubled by its ring opened form (as an enolate isonitrile) which is predominant. A very useful new procedure for this synthetic approach is offered by the use of i-PrMgCl as a metallating reagent and a Weinreb amide 102 as the electrophile. This procedure was applied both to 5-(hetero)-aryl substituted oxazoles and unsubstituted oxazoles <07JOC5828>. 

Aryl-substituted oxazoles are reducible [275] at rather negative potentials [—1.0 to —2.1 V (SCE)], and the electrode reaction consumes in most cases six electrons 2-(l-naphthyl)-5-phenyloxazole, however, consumes two electrons. 

Aryl-substituted oxazoles are strongly fluorescent. In solution they are suitable as luminous substances for liquid scintillation counters and optical brighteners. 4,4 -Bisoxazol-2-ylstilbene is added to washing agents. During the washing process, it is absorbed by the fibers so that the clothes appear to be whiter than white as a result of its blue fluorescence. 

The reaction of aryl aldehydes with benzotriazol-l-ylmethyl isocyanide (154), obtained in two steps from benzotriazole, formaldehyde and formamide, gives 5-aryl-substituted oxazoles in 35-69% yields (Scheme 71) <89TL6657>. 

The dipole moments of the oxazole molecule determined by dielectric218 and Stark-effect measurements in the microwave spectrum233 are 1.4 and 1.5 0.1 D, respectively. On the basis of small inertial defects in oxazole, Mackrodt et al.m have concluded that the molecule is planar. There is a complete lack of data on the dipole moment of simple alkyl-substituted oxazoles. On the other hand, the values of the dipole moments of a number of aryl-substituted oxazoles have been reported (see Table V). As might be expected, a nitro substituent into the para position of a phenyl ring attached to oxazole increases the value of dipole moment by 2.0-3.5 D. 

Efforts to isolate the initial alkyne oxazole [4 + 2] cycloadducts have been unsuccessful, and only the furan cycloaddition products have been detected in the reaction mixtures. The Diels-Alder reaction of alkyl- or aryl-substituted oxazoles with neutral, conjugated, or electron-deficient al-kynes displays little regioselectivity whereas polarized, electron-rich oxazoles (e.g., 1, = OEt) do participate in regioselective, intermolecu-... 

In 1909, Robinson demonstrated the utility of acylamidoketones as intermediates to aryl-and benzyl-substituted 1,3-oxazoles through cyclization with sulfuric acid. Extension of sulfuric acid cyclization conditions to alkyl-substituted oxazoles can give low yields, for example 10-15% for 2,5-dimethyl-l,3-oxazole. Wiegand and Rathbum found that polyphosphoric acid can provide alkyl-substituted oxazoles 4 in yields equal to or greater than those obtained with sulfuric acid. Significantly better yields are seen in the preparation of aryl- and heteroaryl-substituted oxazoles. For example, reaction of ketoamides 5 with 98% phosphoric acid in acetic anhydride gives oxazoles 6 in 90-95% yield. ... 

Workers at SmithKline Beecham extended the synthetic access to interesting mono- and di-substituted oxazoles through an improved procedure for aryl-substituted... 

Monosubstituted and 4,5-disubstituted oxazoles were easily obtained from aryl-substituted tosylmethyl isocyanides and aldehydes . Tosyloxazoles 107, prepared from TosMIC 106 and carboxylic acid chlorides, led to 5-substituted derivatives 108 through ultrasound-promoted desulfonylation <00JCS(P1)527>. 

Bis(trifluoromethyl)oxazol-5(2//)-ones are carbonyl-group protected, carboxyl-group activated, a-oxoacid derivatives that undergo reaction with benzene-1,2-diamine to yield quinoxa-lin-2(1 7)-one or its 3-alkyl- or 3-aryl-substituted derivatives. ... 

Reaction of A, A -dialkyl dichloromethaniminium chlorides 1501 with 2-aminoacetophenones 1502 provides a general route to the formation of 5-aryl substituted 2-(dialkylamino)-l,3-oxazolium salts 1503 these can also be prepared from the corresponding 5-aryl substituted 2-(dialkylamino)-l,3-oxazoles by alkylation with (Me0)2S02. Treatment of 1503 with NH4OAC gives Tsubstituted 4-aryl-2-(dialkylamino)-177-imidazoles 1504 (Scheme 388) <1999HCA1981>. 

Doucet has reported that activated aryl chlorides can be employed in the arylation of thiazoles if PdCl(dppb)C3H5 catalyst is used (Scheme 6) [42], Acetyl, formyl, nitro, cyano, ester, and trifluoromethyl substituted aryl chlorides are reactive. However, 4-chlorofluorobenzene was not reactive. Use of the same catalyst system was shown to be effective for the arylation of oxazole and benzoxazole with activated aryl chlorides [43],... 

Infrared absorption spectral data for several oxazole derivatives,86 90 including alkyl-98 186 and aryl-263 264 substituted oxazoles, 2-amino- and substituted-amino derivatives109 112 136, 5-amino179 198-201 and 5-alkoxy-oxazoles,66 carboxylic acids,112 147 esters,126 179 184 carboxamides,199 200 4-acetyloxazoles,147 halogenoalkyl oxazoles,91 oxazolines,262 and benzoxazoles262 have been reported. 

TABLE 1.14. MICROWAVE ASSISTED SYNTHESIS OF 2-PHENYL-4-SUBSTITUTED OXAZOLES AND 4,5-DISUBSTITUTED 2-PHENYLOXAZOLES FROM ARYL KETONES, BENZONITRILE, AND MERCURY(II)TOSYLATE ... 

TABLE 1.73. 2-ALKENYL(ARYL)OXAZOLES OR 2-ALKENYL(ARYL)-5-SUBSTITUTED OXAZOLES FROM PALLADIUM-CATALYZED CROSS-COUPLING OF OXAZOL-2YLZINC CHLORIDES"... 

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