Oxadiazoline

A -1,2,4-Oxadiazoline, 5-methyl-3-phenyl-dipole moment, 6, 379 synthesis, 6, 381... 

Aldimines, Ketimines, and Related Compounds as Dipolarophiles Reactions of aldimines with nitrile oxides proceed readily to give 1,2,4-oxadiazolines independently of the nature of substituents both in dipole and dipolarophile molecules. 1,2,4-Oxadiazolines were prepared by the regiospe-cihc 1,3-dipolar cycloaddition of nitrile oxides with fluoro-substituted aldimines (295). Phosphorylnitrile oxides gave with azomethines, PhCH NR, phosphory-lated 1,2,4-oxadiazolines 129 (296). Expected 1,2,4-oxadiazolines were also obtained from azomethines, derived from 4-formylcoumarine (179) and 1,3-diphenylpyrazole-4-carbaldehyde (297). 

Poly(ethylene glycol) supported liquid-phase syntheses by both the reaction of (polyethylene glycol (PEG))-supported imines with nitrile oxides, generated in situ from aldoximes, (300) and 1,3-dipolar cycloadditions of nitrile oxide, generated in situ on soluble polymers with a variety of imines (301, 302) have been described. The solid-phase synthesis of 1,2,4-oxadiazolines via cycloaddition of nitrile oxide generated in situ on solid support with imines has also been elaborated (303). These syntheses of 1,2,4-oxadiazolines provide a library of 1,2,4-oxadiazolines in good yields and purity. 

The reaction of 3-amino-5,5-dimethyl-2-phenyl-l,2,4-oxadiazoline and EMME at 100°Cfor 1 hr or the heating of A-( 1,2,4-oxadiazolin-3-yl)amino-methylenemalonate (1129) at 120°C for 2 hr afforded [l,2,4]oxadiazolo[4, 3- ]pyrimidine-6-carboxylate (1128) (63JCS6028). 

Substituted 1,2,4-oxadiazoles were prepared by addition of nitrile oxides to imines or hydrazones. It has been reported that interaction of hydroximoyl chlorides 262 with chiral hydrazones 263 in the presence of EtsN leads to intermediates 264 with diastereoselectivity up to 97%. A subsequent N-N bond cleavage to remove chiral auxiliary by formic acid leads to 1,2,4-oxadiazolines 265 with ee up to 91% (equation 113). ... 

The conversion of 5-amino-3,5-diphenyl-1,2,4-oxadiazoline (48) into 5-mercapto-3-phenyl-l,2,4-thiadiazole (47)78 under the influence... 

As another important mechanistic type, fragmentation into at least three products that are formed more or less simultaneously has to be mentioned. Such [5 - 2 + 2 + 1] reactions were encountered in 2-pyrrolidinones (65, 67), certain pyrazolidine derivatives (68, 72, 73), l,2,4-triazolidine-3-ones (69) and l,2,4-triazolidine-3,5-diones (70), 2//-pyrrol-2-ones (71), 1,3-dithiolane 1-oxides (78), 1,2,3,4-thiatriazoles (74), 1,2,4-oxadiazolines (75), and in several rings containing sulfur in an oxidized state (76-79,82). Most of these molecules have an exocyclic double bond. 

Diphenyl-1,2,4-oxadiazolin-5-one undergoes a similar cleavage with evolution of carbon dioxide on photolysis in dioxane [Eq. (18)].66 The reactive intermediate formed on photolysis of 2,4-diphenyl-l,3,4-oxadiazolin-5-one forms dihydropyrazole, pyrazole, and 1,2,4-triazole derivatives by cycloaddition to conjugated alkenes, acetylenes, and nitriles [Eq. (19)], respectively.66... 

The 1,3-dipolar cycloaddition reaction of benzonitrile oxide to the imine function of a benzothiazepine yielded the fused 1,2,4-oxadiazoline 77 <1995EJMC925>. 

As in the case of other CSPs, the chiral resolution is effected by the structure of the solute. The chiral resolution of amino acids may be considered as the best example for this study. The work of Fukushima et al. [20] (i.e., the chiral resolution of amino acids) indicated the different behavior of the chiral resolution on (i8 )-/V-3,5-dinitrobcnzoyl-l -naphthylglycine CSP. Altomare etal. [142] studied the chiral resolution of a series of 3-phenyl-4-(l-adamantyl)-5-A-phcnyl-A2-1,2,4-oxadiazolines on A,Af,-(3,5-dinitrobenzoyl)-l(7 ),2( )-diaminocyclohcxanc CSP. The effect of the influence of aromatic ring substituents on enantioselectivity was studied by traditional linear free-energy-related equations and comparative molecular field analysis methods. The authors reported that an increase in retention was favored by the re-basicity and the hydrophilicity of the solutes. In... 

Arenecarbonitrile oxides add to the dicyano-ketene ethylene acetal 82 to yield 1,2,4-oxadiazoles 83 (95SC2379). The formation of the oxadiazole 86 by the action of nitronium tetrafluoroborate in acetonitrile on the ester 84 is thought to proceed by way of the a-carbonyl cation 85, which undergoes a 1,2-shift of a methyl group (95TL3039). The high-pressure reaction of nitrones with cyanides to yield 1,2,4-oxadiazolines, e.g. 87 and 88, has been reported (95SYM498). 

It has been demonstrated that N-hydroxytryptophan can be converted to /3-carbolines in two ways (Fig. 41). Pictet-Spengler reaction of 1 with acetals provided the N -hydroxytetrahydro-/8-carbolines (2) (287). A modified Bischler-Napieralski reaction of 1 with trimethylorthoformate gave N -0X0-3,4-dihydro-/3-carbolines (3), the nitrone function of which can undergo 1,3-dipolar cycloaddition with alkenes (288) and nitriles (289), providing isoxazolidine (4) and dehydro-1,2,4-oxadiazoline (5), annulated TBCs, respectively. Nitrone 3 also was obtained by oxidation of the N-hydroxy-j8-carboline 2 with 2,3-dichloro-5,6-dicyano-l, 4-benzoquinone (DDQ). N-Oxygenated TBCs showed no affinity for the benzodiazepine and tryptamine receptors (290). Unfortunately, no toxicity data were recorded for these substituted hydroxylamines. 

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