A3-l ,3,4-Oxadiazolines

There are three nonconjugated reduced systems derived from 1,3,4-oxadiazole 1, namely 2,3-dihydro-l,3,4-oxadia-zole (A2-l,3,4-oxadiazoline) 5, 2,5-dihydro-l,3,4-oxadiazole (A3-l,3,4-oxadiazoline) 6, and 2,3,4,5-tetrahydro-l,3,4-oxadiazole (1,3,4-oxadiazolidine) 7. 

A2-1,3,4-Oxadiazolin-5-ones acylation, 6, 439 alkylation, 6, 439 biological activity, 6, 445 melting point, 6, 430 synthesis, 6, 441, 442 tautomerism, 6, 430 A3- l,3,4-Oxadiazolin-2-ones 5,5-disubstituted IR spectra, 6, 429 PE spectra, 6, 430 A3-1,3,4-Oxadiazolin-5-ones ionization potential, 6, 428... 

In recent years there has been a growing interest in the use of carbonyl ylides as 1,3-dipoles for total synthesis.127-130 Their dipolar cycloaddition to alkenic, alkynic and hetero multiple bonded dipolaro-philes has been well documented.6 Methods for the generation of carbonyl ylides include the thermal and photochemical opening of oxiranes,131 the thermal fragmentation of certain heterocyclic structures such as A3-l,3,4-oxadiazolines (141) or l,3-dioxolan-4-ones132-134 (142) and the reaction of carbenes or car-benoids with carbonyl derivatives.133-138 Formation of a carbonyl ylide by attack of a rhodium carbenoid... 

Warkentin and Zoghbi [87] have demonstrated the synthesis of novel spiro-(S-lactam oxadiazolines 57 (Scheme 15) by the reaction of differently substituted acid chloride 55 and 2-amino-A3-l,3,4 oxadiazolines 56 using triethylamine in dichloromethane. 

Thermolysis of 2-acetoxy-2-methoxy-5,5-dimethyl-A3-l,3,4-oxadiazoline affords acetoxy(methoxy) carbene.60 The thermal rearrangement of acetoxy(methoxy) car-bene to methyl pyruvate was studied by DFT at the B3PW91/6-31G(d,p) level. The conformation of the carbene was considered, as were competing fragmentations to radical pairs. The authors concluded that the reaction is a concerted 1,2-migration rather than a fragmentation-recombination process. 

Three 3 + 2-cycloreversions of 2-acetoxy-2-methoxy-5,5-dimethyl-A3-l,3,4-oxadiazolines have been examined by DFT methods.8 The lowest activation energies have been found for cycloreversion to 2-diazopropane and acetic methylcarbonic anhydride and for cycloreversion to nitrogen and a carbonyl ylide. Those are the reactions that have also been observed experimentally. 

Fragmentation of 2-phenylimino-A3-l,3,4-oxadiazoline 49 includes break of five a-bonds in the substrate and formation of five new n-bonds.93... 

Bicydopropylidene (1) reacts with dimethoxycarbene generated thermally from the diazirine at 25 °C to give a complex mixture of products [116b]. The cycloaddition of several dialkoxycarbenes generated in situ from the corresponding 2,2-dialkoxy-A3-l,3,4-oxadiazolines of type 134 with bicydopropylidene (1) affords the dialkyl acetals of dispiro[2.0.2.l]heptanone 135 (Scheme 29 ) [125]. 

There is no published example of a cyclopropanation of the double bond in chlorocyclopropylideneacetate 1-Me with retention of the chlorine atom. Thus, attempted cyclopropanations under Simmons-Smith [37] or Corey [38] conditions failed [25]. The treatment of the highly reactive methylenecyclopropane derivative 1-Me with dimethoxycarbene generated by thermal decomposition of 2,2-dimethoxy-A3-l,3,4-oxadiazoline 26 (1.5 equiv. of 26,PhH, 100 °C,24 h),gave a complex mixture of products (Scheme 7) [39], yet the normal cycloadduct 28 was not detected. The formation of compounds 29 - 33 was rationalized via the initially formed zwitterion 27, resulting from the Michael addition of the highly nucleophilic dimethoxycarbene to the C,C-double bond of 1-Me. The ring closure of 27 to the normal product 28 is probably reversible, and 27 can rearrange or add a second dimethoxycarbene moiety and a molecule of acetone to form 33. 

The most studied reactions of A3-l,3,4-oxadiazolines are thermal and photochemical ring cleavage, generally with loss of a molecule of nitrogen. 

Hydrogenation of oxadiazoline (59) over Raney nickel and of oxadiazolinimine (60c) over palladium charcoal yields hydrazones, probably by reduction to oxadiazolidines followed by ring opening. A3-l,3,4-Oxadiazolin-2-imines may be hydrolyzed to the corresponding oxadiazolinones in cold acid. 

Lactones of azocarboxylic acids are remarkably reactive. In the presence of phenyl isocyanate, the imino isocyanate formed from reactive 2-hydrazono-A3-l,3,4-oxadiazolines via a 1,3-dipolar cycloreversion is intercepted to give [l,2,4]triazolo[l,2-a]-[l,2,4]triazole-l,3,5-triones by means of two subsequent [2 + 3] cycloadditions via azomethine imine intermediates (Scheme 10) (76T2685). 

A3-l,3,4-Oxadiazolines as versatile sources of reactive intermediates 00JCS(P1)2161. 

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