Isoxazole, 5- -3-phenyl

Despite the weak basicity of isoxazoles, complexes of the parent methyl and phenyl derivatives with numerous metal ions such as copper, zinc, cobalt, etc. have been described (79AHC(25) 147). Many transition metal cations form complexes with Imidazoles the coordination number is four to six (70AHC(12)103). The chemistry of pyrazole complexes has been especially well studied and coordination compounds are known with thlazoles and 1,2,4-triazoles. Tetrazole anions also form good ligands for heavy metals (77AHC(21)323). 

Isoxazoles unsubstituted in the 3-position react with hydroxide or ethoxide ions to give )3-keto nitriles (243) -> (244). This reaction involves nucleophilic attack at the 3-CH group. 1,2-Benzisoxazoles unsubstituted in the 3-position similarly readily give salicylyl nitriles (67AHC(8)277), and 5-phenyl-l,3,4-oxadiazole (245) is rapidly converted in alkaline solution into benzoylcyanamide (246) (61CI(L)292). A similar cleavage is known for 3-unsubstituted pyrazoles and indazoles the latter yield o-cyanoanilines. 

Methyl groups on C-linked phenyl attached to oxazoles, isoxazoles and oxadiazoles react with benzylidineaniline to give stilbene derivatives (Scheme 51) <78AHC(23)l7l). 

The first 1,2-benzisoxazole, 3-phenyl-l,2-benzisoxazole, was obtained from the treatment of o-bromobenzophenone oxime with alkali in 1892 (1892CB1498,1892CB3291). 2,1-Benzisoxazole has been known since 1882, being obtained as a reduction product of o-nitrobenzaldehyde with tin and hydrochloric acid (1882CB2105). In general, benzisoxazoles behave much like substituted isoxazoles. Numerous structural ambiguities occur in the early literature of these two systems, and these have been discussed in the above reviews. 

Although isoxazoles are comparatively weak electron donors, complexes with numerous metal ions, notable metal(II) ions, have been reported. The ligands include isoxazole and its methyl, phenyl, amino and hydroxy derivatives. They are listed with references in Table 5. 

The iso)tazole ring is rather resistant to sulfonation. However, on prolonged heating with chlorosulfonic acid, 5-methyl-, 3-methyl- and 3,5-diraethyl-isoxazoles are converted into a mixture of the sulfonic acid and the corresponding sulfonyl chloride. The sulfonic acid group enters the 4-position even when other positions are available for substitution. The sulfonation of the parent isoxazole occurs only under more drastic conditions (20% oleum) than that of alkyl isoxazoles isoxazole-4-sulfonic acid is obtained in 17% yield. In the case of 5-phenylisoxazole (64), only the phenyl nucleus is sulfonated to yield a mixture of m-and p-arenesulfonic acid chlorides (65) and (66) in a 2 1 ratio (63AHC(2)365). 

The condensation of 5-phenyl-3-(p-tolyl)isoxazole (210) with benzylidineaniline gave the stilbene derivative (211) (78AHC(23)l7l). 

The treatment of 3-acylisoxazoles (438) with hydroxylamine hydrochloride gives furazan ketones (439). On the other hand, furazan ketones (439) rearrange to 3-acylisoxazoles (438) with a loss of hydroxylamine under the influence of a mineral acid. Thus, by refluxing phenacylphenylfurazan with concentrated alcoholic hydrogen chloride, 3-benzoyl-5-phenyl-isoxazole is formed similarly, phenyl(phenacylphenyl)furazan gives 3-benzoyl-3,5-diphenyl-isoxazole (62HC(17)1, p. 35). 

Chloro- and 5-bromo-isoxazoles have been prepared by reaction of 5-isoxazolones with the appropriate phosphoryl halide (77JMC934). 3-Phenyl-5-trifluoromethylisoxazole has been synthesized by reaction of benzonitrile iV-oxide with 3,3,3-trifluoropropyne (77JMC934). 

When compound (443), which contains alkene and alkyne moieties, was reacted with benzonitrile oxide, both an isoxazoline (444) and isoxazole (445) were produced, with the former predominating. Oxidation of (444) with permanganate produced 3-phenyl-2-isoxazoline-5-carboxylic acid (446) (67ZOR82i). The reaction of 1-trimethylsilylbut-l-yne-3-ene produced only a compound which reacted at the alkenic unit. Oxidation of the adduct also produced (446) (68ZOB1820). These reactions are shown in Scheme 102. 

The reaction of a dibromochalcone with hydroxylamine hydrochloride in pyridine gave three products with the expected 2-isoxazoline product as the predominate compound. A ring bromination product and an isoxazole were also isolated (70UC796). The reaction of hydroxylamine with /S-thiosulfates of propiophenone at reflux produced 3-phenyl-2-isoxazo-line (455). At room temperature a bis-Michael product (456) was produced. The reaction with N -phenylhydroxylamine yielded a mono-Michael type product (457) (74CPB1990). 

Nitrones or aci-nitro esters react with alkenes to give in some cases A/-substituted isoxazolidines and in others 2-isoxazolines. When the intermediate isoxazolidines were observed, a number of procedures transformed them into the 2-isoxazolines. Acrylonitrile and phenyl rzcf-nitrone esters produced an A/-methoxyisoxazolidine. Treatment with acid generated a 2-isoxazole while treatment with base generated an oxazine (Scheme 118) (68ZOR236). When an ethoxycarbonyl nitrone ester was reacted with alkenes, no intermediate isoxazolidine was observed, only A -isoxazolines. Other aci-mtro methyl esters used are shown in Scheme 118 and these generate IV-methoxyisoxazolidines or A -isoxazolines which can be further transformed (72MI41605). 

Phenyldiazonium salts react with malonaldioxime to produce a 2-isoxazoline (7 IGEPl 920245), and the diazo ketone (484) when photolyzed gave a mixture of 2-isoxazoline and an isoxazole by a 1,5 carbon-hydrogen insertion. A phenyl migration was apparently not involved (Scheme 124) (66CC689). 

Isoxazole, 3-amino-4-nitrosophenyl-synthesis, 6, 409 Isoxazole, 3-amino-5-phenyl-chlorination, 6, 24 Isoxazole, 5-amino-3-phenyI-reactions, 6, 54... 

Isoxazole, 3-anilino-4-nitroso-5-phenyI-thermolysis, 6, 417 Isoxazole, 3-anilino-5-phenyl-bromination, 6, 24 Isoxazole, 3-(p-anisyl)-5-phenyl-synthesis, 6, 63... 

Isoxazole, 3-benzohydroximoyl-4-benzoyI-5-phenyl-furazans from, 6, 417 Isoxazole, 4-benzoyI-synthesis, 6, 69 Isoxazole, 5-benzoyl-synthesis, 6, 69... 

Isoxazole, 5-( p-bromophenyl)-3-phenyl-synthesis, 6, 63 Isoxazole, 3-chloro-reduction, 6, 58 4-substituted reactions, 6, 58... 

Isoxazole, 3-chloro-5-hydroxymethyl-oxidation, 6, 27 Isoxazole, 4-chloromethyI-reactions, 6, 53 Isoxazole, 5-chloro-3-phenyl-reactions, 6, 58 Isoxazole, 3-cyano-reactions, 6, 30 Isoxazole, diacyl-synthesis, 6, 79 Isoxazole, 3,4-dialkyl-synthesis, 6, 83 Isoxazole, 3,5-dialkyl-synthesis, 6, 83 Isoxazole, 4,5-dialkyl-synthesis, 6, 83 Isoxazole, 3,5-diamino-2-amino-l-azirines from, 7, 89 Isoxazole, 3,5-diaryl-synthesis, 6, 63 Isoxazole, 2,5-dihydro-synthesis, 6, 79 Isoxazole, 4,5-dihydro-dehydrogenation, 6, 4... 

Isoxazole, 3-hydroxy-5-phenyl-photolysis, 6, 13 Isoxazole, 5-(o-hydroxyphenyl)-synthesis, 6, 79 Isoxazole, hydroxystyryl-applications, 6, 128 Isoxazole, 4-iodo-... 

Isoxazole, 4-iodo-3,5-dimethyl-reactions, 6, 59 Isoxazole, 3-iodo-5-phenyl-synthesis, 6, 86 Isoxazole, 3-isopropenyl-oxidation, 6, 27, 54 polymerization, 6, 54 Isoxazole, 3-isopropenyl-5-methyI-polymers, 1, 282... 

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