3-Isoxazole carbaldehydes

Hydrogenolysis in the presence of Raney-Ni of derivatives 29 and 30, coming from Baylis-Hillman adducts of 3-isoxazole carbaldehydes, generated enaminones 31a,b that underwent ring-closure reactions to afford substituted 2-pyrrolidinones 32, 1,5-dihydro-2-pyrrolones 33, and iV-substituted pyrrolidines 34 in good yields <05JOC353>. 

Isoxazole-3-carbaldehyde has been obtained as a minor product from the reaction of acetylene with a mixture of nitric oxide and nitrogen dioxide (61JOC2976). Although 3-aryl-4-formylisoxazoles have been synthesized in good yields from the reaction of benzonitrile Af-oxides with 3-(dimethylamino)-2-propen-l-one (71S433), the parent member of the series, isoxazole-4-carbaldehyde, has never been reported. It may possibly be obtained by the addition of fulminic acid to 3-(dimethylamino)-2-propen-l-one. 

Isoxazole-5-carbaldehyde was prepared by the manganese dioxide oxidation of 5-hydroxymethylisoxazole (67T4697), the latter being formed from sodium fulminate and propargyl alcohol in greater than 90% yield. 

Isoxazole-4-carbaldehyde, 6, 84 Isoxazole-4-carbaldehyde, 5-methyl-3-phenyl-oxidation, 6, 27, 53 Isoxazole-5-carbaldehyde synthesis, 6, 84 Isoxazole-3-carboxylic acid esters... 

The reverse process has also been examined. 2-Phenyloxazole is converted in a similar fashion to 3-phenyl-2//-azirine-2-carbaldehyde on irradiation in benzene or cyclohexane.128 Further rearrangement to the corresponding isoxazole can be effected thermally but not photochemically. A competing pathway leading to the formation of 4-phenyloxazole has also been observed and is thought to involve a bicyclic intermediate arising by 2,5-bonding. 

Isoxazole (as well as isoxazoline, and isoxazolidine) analogues of C-nucleosides related to pseudouridines 25 and 27 have been regioselectively synthesized by 1,3-dipolar cycloaddition (1,3-DC) of nitrile oxides (and nitrones) derived from uracyl-5-carbaldehyde 24 and 2,4-dimethoxypyrimidine-5-carbaldehyde 26 respectively <06T1494>. 

In many synthetic pathways, isoxazoles have been used as latent /3-ketonitrile functionalities. Reactions of 5-ribofuranosylisoxazole-4-carbaldehyde 52 with 1,2-diaminobenzenes led to Schiffs bases 53, converted to 3-cyano-l,5-benzodiazepine C-nucleosides 54 through isoxazole ring opening (Scheme 13) <2000CAR681>. 

Bicyclic A(0-Mti-homonucleoside analogues such as 591 were synthesized through 1,3-dipolar cycloaddition of an enantiopure 3-hydroxy-l-pyrroline A -oxide and protected allyl alcohol and subsequent introduction of thymine by a Mitsunobu reaction <2003T5231>. Furthermore, isoxazole, isoxazoline, and isoxazolidine analogues of (7-nucleo-sides such as 592-594 were synthesized by 1,3-dipolar cycloaddition of nitrile oxides and nitrones derived from uracil-5-carbaldehydes with suitable dipolarophiles <2003T4733, 2006T1494>. 

The oxadiazole 140, related to ribavirin, has been prepared by cyclization of a known sugar-protected amidoxime. The 4 -thio-analogues 141 (X = O, S) of furanfurin and thiophenfurin (Vol. 29, p. 283), themselves analogues of ribavirin, have been prepared by condensation between the heterocycles, as their ethyl esters, with 0-protected derivatives of 4 -thioribofuranosyl acetate. The thiophene compound ( thiophenthiofurin ) had cytotoxicity towards cancer cell lines, but less so than thiophenfurin. A previously-known 2,5-anhydroglucose derivative 142 has been converted to the pyrazole 143, and some related compounds. Some pyrazole iso-C-nucleosides are mentioned in Chapter 2. Various 3-cyano-2-(P-D-ribofuranosyl)-1,5-benzodiazepines have been prepared by a novel ring transformation of 5-(tri-0-benzoyl-p-D-ribofuranosyl)isoxazole-4-carbaldehyde. ... 

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