1,3-dipolar cycloaddition 2,3-dihydro-1.2.4-oxadiazoles

Microwave irradiation induces 1,3-dipolar cycloadditions of nitrones, such as 152, with aliphatic and aromatic nitriles in the absence of solvent. The products of these reactions are the corresponding 2,3-dihydro-l,2,4-oxadiazoles 156 (Scheme 9.48). The use of microwaves led to yields that were always higher than those obtained with classical heating, with the differences being more significant with the less reactive nitriles [99]. 

The treatment of imidazo-l,2,4-oxadiazol-5-thiones 142 (Equation 20) with ethanolic HC1 results in a retro-1,3-dipolar cycloaddition of the imidazo ring to give an azomethine ylide together with the 4,5-dihydro-l,2,4-oxadiazol-5-thiones 143 <2003PS881>. 

The use of a PEG-supported imine 326 allows the imine to be the supported component (Scheme 55). 1,3-Dipolar cycloaddition then proceeds smoothly to give the supported 4,5-dihydro-l,2,4-oxadiazoles 327, which were cleaved easily from the polymer with methoxide to give the 4,5-dihydro-l,2,4-oxadiazoles 328 <2003SL1064>. 

Dipolar cycloaddition of nitrile oxide at the C=N bond of indole imino esters 130, followed by elimination of the alcohol moity gives oxadiazole derivatives 131 (Scheme 1.26) (298). Reaction of N-arylbenzamidines with arenenitrile N-oxides (generated in situ from oximoyl chlorides) produce unstable 5-amino-4,5-dihydro-1,2,4-oxadiazoles which, on aqueous acidic treatment hydrolyze to open-chain N-benzoyloxy-N -arylareneamidines (299). 

I.3.4.2.4. Heterocumulenes The 1,3-dipolar cycloaddition of substituted ben-zonitrile oxides to the C=N group of chlorocarbonyl isocyanate C1C(0)N=C=0 gives 3-aryl-4-chlorocarbonyl-5-oxo-4,5-dihydro-l,2,4-oxadiazoles 172 in 75%-80% yield (340). A similar reaction with chlorosulfonyl isocyanate, C1S02N=C=0, affords 4-unsubstituted oxadiazolinones 173 (341). 

The 2-methyl-4,5-dihydrooxazoles (358 Z = O) or 2-methyl-4,5-dihydrothiazole (358 Z = S) undergo 1,3-dipolar cycloaddition reactions with benzonitrile A -oxide to give the corresponding 7a-methyl-3-phenyl-5,6-dihydro-7a//-oxazolo[3,2- ][l,2,4]oxadiazoles (16) or -thiazolo[3,2-c ]-[l,2,4]oxadiazoles (17) (Equation (121)) <92T7703>. 

Dipolar cycloaddition of nitrones to free and coordinated nitriles as routes to govern the process of the synthesis of 2,3-dihydro-l,2,4-oxadiazoles 06IZV1803. 

Scheme 13.5 Platinum(II)-mediated dipolar cycloaddition of oxazoline -oxides to nitriles and liberation of free 2,3a-disubstituted 5,6-dihydro-3aH-[l,3]oxazolo[3,2-ii][l,2,4]oxadiazoles [24],...

Among other important heterocycles obtained by high-pressure 1,3-dipolar cycloadditions are 2,3-dihydro-l,2,4-oxadiazole derivatives. These could be obtained by the addition of nitrones to nitrile triple bond, as shown by Eguchi (Scheme 56) [85]. Product 233 was obtained in high yield, whereas under usual thermal conditions (120 °C, 12h) yield was 54%. 

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