Benzoxazoles, rearrangement

Benzoxazoles are produced in high yield from a-acylphenol oximes by a Beckmann rearrangement using zeolite catalysts <95SC3315>. The reaction of the o-benzoquinone 40 with aromatic aldehyde oximes produces the benzoxazoles 41 <95ZOR1060>. The fused oxazolium salts 43 (R = Me, Et, Pr , or Ph R2 = Me or Pr ) are formed from tropone and nitrilium hexachloroantimonates 42 <96JPR598>. 

Cu-catalyzed domino reactions have been used for the synthesis of carbocycles, as well as for heterocycles such as indoles, benzoxazoles, and quinoxalines. A very useful process is also the combination of the formation of allyl vinyl ethers, followed by a Claisen rearrangement. 

A simple montmorillonite K 10 clay surface is one among numerous acidic supports that have been explored for the Beckmann rearrangement of oximes (Scheme 6.27) [54]. However, the conditions are not adaptable for the aldoximes that are readily dehydrated to the corresponding nitriles under solventless conditions. Zinc chloride has been used in the above rearrangement for benzaldehyde and 2-hydroxyacetophe-none, the later being adapted for the synthesis of benzoxazoles. 

Rare-earth exchanged [Ce ", La ", Sm"" and RE (RE = La/Ce/Pr/Nd)] Na-Y zeolites, K-10 montmorillonite clay and amorphous silica-alumina have also been employed as solid acid catalysts for the vapour-phase Beckmann rearrangement of salicylaldoxime 245 to benzoxazole 248 (equation 74) and of cinnamaldoxime to isoquinoline . Under appropriate reaction conditions on zeolites, salicyl aldoxime 245 undergoes E-Z isomerization followed by Beckmann rearrangement and leads to the formation of benzoxazole 248 as the major product. Fragmentation product 247 and primary amide 246 are formed as minor compounds. When catalysts with both Br0nsted and Lewis acidity were used, a correlation between the amount of Br0nsted acid sites and benzoxazole 248 yields was observed. 

Photocycloaddition of an alkene to the thione group of 13 gave the thietane 14 which was stable at room temperature, but on refluxing 14 in toluene an iminothietane 15 and/or a 2-substituted benzoxazole were obtained by rearrangement processes <99JCS(P1)1151>. 

Benzoxazoles.1 Benzoxazoles (2) are obtained in generally good yield by Beckmann rearrangement of the oxime of 2 -hydroxyacetophenones (1) using POCl3-DMA in CH3CN at 30° (equation I). The method is applicable to synthesis of hydroxy-substituted benzoxazoles, which are usually difficult to prepare. 

Benzoxazole is attacked by dimethyl acetylenedicarboxylate at the nitrogen atom the resulting betaine, a 1,4-dipole, adds a second molecule of the ester to form the rearranged... 

Thermal dehydration of o- (acylamino)phenols is the method of choice for the preparation of benzoxazoles (equation 96) and other annulated oxazoles. 0,iV-Diacyl derivatives of o-aminophenols cyclize at lower temperatures than do the monoacyl compounds. The synthesis is often carried out by heating the aminophenol with the carboxylic acid or a derivative, such as the acid chloride, anhydride, an ester, amide or nitrile. The Beckmann rearrangement of oximes of o-hydroxybenzophenones leads directly to benzoxazoles (equation 97). 

The formation of oxazoles by the Cornforth rearrangement, which is a useful synthetic procedure, is described in Section 4.18.3.1.2(i). Oxazoles are also satisfactorily prepared by reduction of their IV-oxides (see next section) with zinc and acetic acid. Treatment of oxazoles and benzoxazoles with alkylating agents gives quaternary salts. 

Benzoxazoles, 2-substituted, ipso attack in rearrangements of, 56, 133 Benzoxazoles, 2-benzamido-, formation in photorearrangement, 56, 82 Benzoxazoles, 2-chloro-, 59, 274... 

The configuration of the oxime is important to the course of the reaction. Thus, while the j8-oxime (11) gives the indoxazene or its degradation products, the a-oxime (12) undergoes a Beckmann rearrangement, finally yielding benzoxazole (13). This difference in reaction pathway between stereoisomeric oximes was used in the determination of their configurations.7,8 22,23... 

Again, the configuration of the oxime is of significance. The acetate (20, R = Ph) provides the indoxazene smoothly on pyrolysis, while its isomer (21) gives only a small yield of the same product.42 A Beckmann rearrangement diverts the pyrolysis of some of the oxime benzoate (22) to the formation of the benzoxazole (23).43... 

Substituted salicylaldehydes react with hydrazoic acid in sulfuric acid to give indoxazenes 50,51 up to 15% of the corresponding 2-aminobenzoxazole (32) may be obtained as a by-product. The reaction is a variant of the Schmidt reaction, in which the intermediate nitre-nium ion may cyclize at once to the indoxazene, or rearrange and react with more hydrazoic acid, ultimately providing the benzoxazole. 

An interesting result has been obtained in a study of the dechlorination of polychlorobenzenes by direct irradiation in acetonitrile in addition to dechlorination, products resulting from rearrangement of the chlorine atoms to positions mefa to their original point of attachment are observed. Thus orfho-dichlorobenzene was found to yield mainly chlorobenzene along with small amounts of para-dichlorobenzene the authors speculate that the rearrangement products are formed by recombination of an aryl-chlorine radical pair. In another novel result photolysis of pentachlorophenol in acetonitrile is found to give small amounts of the benzoxazole (160). ... 

Oxazines—see Benzoxazine Oxazoles—see Benzoxazoles Oxazohdines, formation of 1420 Oxepines, rearrangement of 824, 826-830 Oxetenes, formation of 1059 Oxidants, biologically active 913 Oxidation,... 

The kinetics of a further series of isoxazole-2//-azirine rearrangements at 165-185°C has been investigated.62 The activation parameters for 3-phenyl-5-methoxyisoxazole (AH = 38 + 1 kcal/mol AS = 3.6 2 eu) are in good accord with the postulated initial N—O bond breakage [DH°(PhO— NR2) = 38-39 kcal/mol63]. The photochemical64 and thermal65 conversion of benzisoxazoles to benzoxazoles appears to involve an intermediate spiroazirine. 

However with 2,4,6-trisubstituted phenols electron-transfer occurs followed by nucleophilic attack by nitrile solvent. Alkyl group rearrangement or loss ultimately leads to benzoxazole products. 

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