Oxazole nitration

Nitration of monocyclic compounds is summarized in Table 4. Substitution occurs in the expected positions. The reaction conditions required are more vigorous than those needed for benzene, but less than those for pyridine. Ring nitration of oxazoles is rare, but (114) has been obtained in this way (74AHC(17)99). 

Oxazole, 2-dimethylamino-4-phenyl-nitration, 6, 190 Oxazole, 2,5-diphenyl-irradiation, 6, 189 nitration, 6, 190 oxidation, 6, 187 reduction, 6, 194 synthesis, 6, 222 Oxazole, 4,5-diphenyl-mercuration, 6, 190 2-substituted... 

The ceric ammonium nitrate (CAN) promoted oxidation of oxazoles with various substitution patterns was investigated and yielded the corresponding imides 108 in good yields, tolerating a wide variety of functional groups and substituents on the oxazole moiety <06OL5669>. 

Corey s retrosynthetic concept (Scheme 9) is based on two key transformations a cationic cyclization and an intramolecular Diels-Alder (IMDA) reaction. Thus, cationic cychzation of diene 50 would give a precursor 49 for epf-pseudo-pteroxazole (48), which could be converted into 49 via nitration and oxazole formation. Compound 50 would be obtained by deamination of compound 51 and subsequent Wittig chain elongation. A stereocontroUed IMDA reaction of quinone imide 52 would dehver the decaline core of 51. IMDA precursor 52 should be accessible by amide couphng of diene acid 54 and aminophenol 53 followed by oxidative generation of the quinone imide 52 [28]. 

Methyl-3-phenylisoxazole is nitrated as a conjugate acid at the meta position but as the free base at the para position of the phenyl group (79AHC(25)147). Phenyl groups attached to oxazole rings are nitrated or sulfonated in the para position, with relative reactivities of the phenyl groups in the order... 

For the recifeiolide synthesis, the oxazole carbanion was alkylated with iodo THP ether (340) (an 85 15 mixture of (E)- and (Z)-isomers). Acid hydrolysis of the THP group, photooxygenation and cyclization gave a mixture of (E)- and (Z)- ( )-recifeiolide (341) from which the pure (E)-form could be isolated by chromatography on silver nitrate-impregnated silica gel (Scheme 74). 

Sec. II.B] NITRATION OF PHENYL-SUBSTITUTED HETEROCYCLES 239 5. Oxazoles and Isoxazoles... 

However, the only product obtained on nitration of 5-methyl-3-phenylis-oxazole-4-carboxylic acid is the 3-nitrophenyl product (91U PI). 

Phenylthiazole, like 2-phenyloxazole, is also nitrated (and brominated) at the 5-position of the heterocyclic ring. The thiazole is less reactive than the oxazole ring. In nitration of the protonated thiazole, the predominant product is 2-(4-nitrophenyl)-thiazole (85CS295), in contrast to the nitration of 2-phenyloxazole, which gives predominantly 2-(3-nitrophenyl)oxazole (84CHE713). 

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. 

Nitration of 2-methylbenzoxazole yields a 4 1 mixture of 6- and 5-nitro derivatives (cf. 2). Phenyl groups attached to oxazole at C(2), C(4), or C(5) are nitrated in the para-positions and the resulting (nitrophenyl)oxazoles can be reduced chemically to the corresponding amino compounds. 

Abstract Synthesis methods of various C- and /V-nitroderivativcs of five-membered azoles - pyrazoles, imidazoles, 1,2,3-triazoles, 1,2,4-triazoles, oxazoles, oxadiazoles, isoxazoles, thiazoles, thiadiazoles, isothiazoles, selenazoles and tetrazoles - are summarized and critically discussed. The special attention focuses on the nitration reaction of azoles with nitric acid or sulfuric-nitric acid mixture, one of the main synthetic routes to nitroazoles. The nitration reactions with such nitrating agents as acetylnitrate, nitric acid/trifluoroacetic anhydride, nitrogen dioxide, nitrogen tetrox-ide, nitronium tetrafluoroborate, V-nitropicolinium tetrafluoroborate are reported. General information on the theory of electrophilic nitration of aromatic compounds is included in the chapter covering synthetic methods. The kinetics and mechanisms of nitration of five-membered azoles are considered. The nitroazole preparation from different cyclic systems or from aminoazoles or based on heterocyclization is the subject of wide speculation. The particular section is devoted to the chemistry of extraordinary class of nitroazoles - polynitroazoles. Vicarious nucleophilic substitution (VNS) reaction in nitroazoles is reviewed in detail. 

The isoxazoles (1,2-oxazoles) are nitrated exclusively at position 4. Isoxazole itself is nitrated with difficulty, and the yield of the nitro derivative does not exceed 3.5% [165, 166], With nitronium tetrafluoroborate as nitrating agent it is possible to increase the yield of 4-nitroisoxazole to 35% [167],... 

In benzoxazoles and their 2-substituted derivatives the nitro group is presumably introduced into the position 6 [131-135], In the nitration of 2-methylbenzoxazole a mixture of 80% of 6-nitro- and 20% of 5-nitro isomer was isolated. 2-Phenylbenz-oxazole is first nitrated to the position 6 [136,137], The nitration of benzoxazolones-2 and benzoxazolthiones-2 proceeds in an analogous way [138-141],... 

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