Oxadiazol-5-imines

This new class of meso-ionic compounds have been recently synthesized.107 iV-Methyl-iV-benzoylhydrazine (147, R1 = Me, R2 = Ph) and aryl isocyanide dichlorides (ArN CCl yield 1,3,4-oxadiazolium chlorides (154, R1 = Me, R2 = Ph, R3 = Ar), which with diazomethane give the meso-ionic l,3,4-oxadiazol-2-imines (153) as yellow crystalline compounds. Subsequently this synthetic method107 has been extended by the use of acylisocyanide dichlorides. These reagents yield the 1,3,4-oxadiazol-2-imines 153, R3 = SO2R,107b and 153, R3 = COR.107c 

The derivative 153, R1 = Me, R2 = R3 = Ph, has a dipole moment (ju = 7.56 D) in accord with its meso-ionic structure.108 The meso-ionic l,3,4-oxadiazol-2-imine (153, R1 = Me, R2 = R3 = Ph) reacts with aniline giving the guanidine derivative 155.107  

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The endoxytriazolines originally described by Busch were later formulated either as meso-ionic l,2,4-triazol-3-ones (200) or as meso-ionic l,3,4-oxadiazol-2-imines (153). This ambiguity has now been... 

The aromatic Claisen rearrangement was employed in the synthesis of building blocks for various macrocyclic compounds, such as pendant-capped porphyrins , multidentate macrocycles containing 1,3,4-oxadiazole, imine and phenol subunits, as well as to prepare longithorone B, a sixteen-membered farnesylated para-benzoquinone . 

The addition of diazo compounds generally leads to three membered tings, although in special cases, linear adducts with an intact diazo group [110] or l,3,4-oxadiazol-3-ines [111] can be isolated Most diazo compounds are unstable and yield oxirans and aziridines [112,113,114] Aziridines are obtained exclusively on reaction of certain polyfluorinated acyl imines with diazomethane [115]... 

Likewise, trifluoromethyl-substituted nitrile imines [172] and nitnle oxides [173,174, 7 75] have been used to synthesize tnfluoromethyl substituted five-membered ring systems of the pyrazole, isomzole, isoxazohne, and 1,2,4-oxadiazole... 

The cycloaddition of nitrile oxide 235 to the 4-iminobenzopyran-2-one 236 gave the fully conjugated 1,2,4-oxadiazole 238 directly, a reaction that most likely proceeds via loss of methanol from the intermediate 237 (Scheme 36) <1996JHC967>. Similarly, nitrile oxide 239 reacted with imine 240 to give the 1,2,4-oxadiazole 242 via the nonisolable intermediate 241 <2002PJC1137>. 

The range of imines that are suitable for reaction has been extended to include the fluoro-substituted aldimines 317 <2002JCM131> and N-unsubstituted imines 319 <1999AXC2158, 2002PJC1137, 2003TL2015>, thus allowing access to 5-fluoroalkyl-4,5-dihydro-l,2,4-oxadiazoles 318 and 4-unsubstituted 4,5-dihydro-l,2,4-oxadiazoles 320 as shown in Equations (60) and (61), respectively. 

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>. 

One example of a spiro-4,5-dihydro-l,2,4-oxadiazole has appeared, whereby the spiro[indoloquinazoline]-4,5-dihydro-l,2,4-oxadiazoles 337 were prepared in good yields from the imines 336 (Equation 69) <2005SC765>. 

Closure of the oxadiazole ring is still achieved through cycloaddition between pyridine iV-oxides and isocyanates, affording adducts such as 142 (Scheme 38) <1995T6451>. Nonaromatic imine fV-oxides exhibited similar reactivities, since azasugar-derived fV-oxides as a mixture of 143 and 144 underwent cycloaddition reactions in the presence of phenyl isocyanate or trichloroacetonitrile. Compounds 145 and 146 (Scheme 39) were obtained from the aldoxime W-oxide 143 two other regioisomeric heterocycles arose from the ketoxime derivative 144 <1996T4467>. 

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). ... 

Kohlensaure-anilid-(2-benzoyl-hydrazid) reagiert mil Dichlor-triphenyl-phosphoran/Triethyl-amin iiber Benzonitril-(anilinocarbonyl-imin) in einer 1,5-Elektrocyclisierung zu 2-Anilino-5-phenyl-1,3,4-oxadiazol (87% Schmp. 21 4 2 1 5 )420 ... 

Carbonsaure-nitril-imine (vgl. Bd. E14b, S. 33) sind auch Zwischenstufen bei anderen 1,3,4-Oxadiazol-Syn-thesen, z. B. bei der Ringumwandlung von Tctrazolen (vgl. S. 590)421 oder der Oxidation von 2-Acyl-hydrazonen und Kohlensaure-(2-alkyliden-hydrazid)-aminen mit Blei(lV)-acetat (S. 581). 

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