5-nitro-2-phenyloxazole

Nitro-2-phenyloxazole, obtained by thermal isomerization of the corresponding nitroi-soxazole, is found to undergo Diels-Alder reactions with 2,3-dimethylbuta-l,3-diene (see Eq. 

Nitro-2-phenyloxazole 271a undergoes Diels-Alder [4 + 2] cycloaddition with both electron-rich and electron-poor dienophiles to give an oxazoline 273 that may not be isolable due to the facile aromatization to a fused oxazole 274. Examples are shown in Table 8.22 (Scheme 8.77). 

Isoxazoles with electron-withdrawing substituents readily undergo cycloaddition reaction as dienophiles. For example, the nitroisoxazoles (382) react with 2,3-dimethylbutadiene to form the adduct (383) (90JOC1227). Similar reaction with 4-nitro-2-phenyloxazole (384) leads to (386) possibly via initial adducts (385) (93CC978). 

For isoxazoles the first step is the fission of the weak NO bond to give the diradical 69 which is in equilibrium with the vinylnitrene 70. Recyclization now gives the substituted 27/-azirine 71 which, via the carbonyl-stabilized nitrile ylide 72, can give the oxazole 73. In some cases the 27/-azirine, which is formed both photochemically and thermally, has been isolated, in other cases it is transformed rapidly into the oxazole. Thermal isomerization of 4-nitro-3-phenylisoxazole derivatives to 4-nitro-2-phenyloxazoles works well by heating in xylene at 155 C in the presence of FeCl3Si02 <1998JOC6050>. 

The structure of 5-substituted 4-nitro-2-phenyloxazoles obtained by recyclization of the corresponding isoxazoles was determined by H and 13C NMR [501, 502] (Table 3.18). 

Nitro-2-phenyloxazole was isolated (29%) as a result of temperature transformation (155°C) of corresponding nitroisoxazole in xylene with a trace amount of same acid and confirmed by IR spectroscopy (Scheme 3.46) [501, 502] ... 

Diels-Alder reactions in which the oxazole is the dienophile have been discovered. Thus, 4-nitro-2-phenyloxazole (58) reacts with 2,3-dimethylbuta-1,3-diene or cyclohexa-1,3-diene across the C(4)—C(5) bond (Scheme 15) <93CC978>. 

Isolated examples of 1,3-azoles serving as It components in cycloadditions include the reaction of 4-nitro-2-phenyloxazole with dienes across the 4,5-bond and the intramolecular imidazole example shown below where the diene is electron-deficient and the process is completed by loss of hydrogen cyanide. ... 

Nitro-2-phenyloxazole 86 functions as a dienophile with a variety of unactivated dienes. Thus 86 reacted with a fivefold excess of 2,3-dimethyl-1,3-butadiene, 87, in a sealed tube at 110°C to give a 71% yield of the bicyclic oxazole 89 and 13% of 5,6-dimethyl-2-phenylbenzoxazole 90 (Fig. 3.24). Although the intermediate cycloadduct 88 could not be isolated in this case, cyclohexadiene and 86 gave a separable mixture of the endo- and ejco-2-oxazolines in 33 and 30% yield, respectively. In addition to all-carbon dienes, 86 reacted with l-(dimethylamino)-3-methyl-l-azabuta-1,3-diene 91 at 55°C in chloroform to provide, via loss of nitrous acid and dimethylamine from intermediate adduct 92, a 30% yield of the oxazolo[4,5-h]pyridine 93. ... 

In 1972, van Leusen, Hoogenboom and Siderius introduced the utility of TosMIC for the synthesis of azoles (pyrroles, oxazoles, imidazoles, thiazoles, etc.) by delivering a C-N-C fragment to polarized double bonds. In addition to the synthesis of 5-phenyloxazole, they also described reaction of TosMIC with /7-nitro- and /7-chloro-benzaldehyde (3) to provide analogous oxazoles 4 in 91% and 57% yield, respectively. Reaction of TosMIC with acid chlorides, anhydrides, or esters leads to oxazoles in which the tosyl group is retained. For example, reaction of acetic anhydride and TosMIC furnish oxazole 5 in 73% yield. ... 

Attempts to carry out substitution reactions on oxazoles in acid media, such as nitration with nitric and sulfuric acids or chlorosulfonation, fail because the highly electron-deficient oxazolium cation is involved. Phenyloxazoles are nitrated at the para positions of the phenyl groups 2,5-diphenyloxazole affords 5-(4-nitrophenyl)-2-phenyloxazole, as expected. Nitrooxazoles are now available by the action of dinitrogen tetroxide on the corresponding iodo compounds (81JHC885). Benzoxazoles are nitrated at the benzene ring thus 2-methyl-benzoxazole gives a mixture of 5- and 6-nitro derivatives. 

The presence of amino substituents in the 2- or 5-position activates the oxazole ring (4-aminooxazoles are unknown). Thus 2-amino-3-aryloxazoles yield the derivatives (127 X = Cl or Br) on halogenation, and nitration of 2-dimethylamino-4-phenyloxazole afforded 2-dimethylamino-5-nitro-4-(4-nitrophenyl)oxazole, the sole example of direct nitration of the oxazole ring. 5-Dialkylamino-2-phenyloxazoles react with trifluoroacetic anhydride to form the ketones (128) and they couple with arene diazonium fluoroborates the products (129) readily rearrange to 1,2,4-triazoles (130) in DMSO solution. 

The direct entry of a nitro group into the oxazole ring (1,3-oxazole) (exclusively at position 5) has only been reported twice [163, 164], Thus, 2-dimethylamino-4-(4-nitrophenyl)-5-nitrooxazole was isolated when 2-dimethylamino-4-phenyloxazole was heated [163] (Scheme 17). 

Aminothiazole is converted by the action of ethyl nitrate into the 5-nitro derivative [352], As already mentioned 2-phenyloxazole and 2-phenylthiazole are nitrated into benzene ring by the sulfuric-nitric acid mixture. At the same time their nitration under conditions excluding protonation of the azole ring (with the use of acetylnitrate or /V-nitropicolinium tetrafluoroborate as nitrating agent) leads to the 5-nitro derivatives [353] (Scheme 40). 

Methoxycarbonyl)-4,6-dinitrophenyl]-2-(4-methoxyphenyl)-4-phenyloxazol-5(4//)-one affords methyl 2-(4-methoxyphenyl)-7-nitro-4-phenylquinazoline-5-carboxylate (33%) on reflux in methanol in the presence of a catalytic amount of p-toluenesulfonic acid. ... 

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