1.2.4- Oxadiazolines, synthesis

Isoxazoli dino[2,3-6][A -l,2,5]oxadiazoline synthesis, 6, 997 Isoxazolidone, 5-hydroxy-synthesis, 6, 112 Isoxazoline, 5-hydroxy-synthesis, 6, 61 Isoxazoline, 3-nitro-/V-oxides... 

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

A -1,3,4-Oxadiazoline, fluoromethyl-rearrangement, 6, 437 Oxadiazolines alkylation, 6, 431 irradiation, 6, 437 mass spectra, 6, 380 oxirane synthesis from, 7, 117-118 ring cleavage... 

A -l,3,4-Oxadiazoline-5-thione, 2-phenyl-alkylation, 6, 440 Oxadiazolinethiones acylation, 6, 432 Mannich reaction, 6, 431 pK 6, 435 ring cleavage, 6, 433 Oxadiazoline-5-thiones acidity, 6, 435 stability, 6, 431 A -Oxadiazoline-5-thiones biological activity, 6, 445 synthesis, 6, 441 A -1,3,4-Oxadiazoline-5-thiones... 

Pyrrolidino[l,2-6][l,3,4]oxadiazoline, 5-phenyl-biological activity, 6, 1024 Pyrrolidino[2,1 -6][1,3]oxazolidines synthesis, 5, 137 Pyrrolidino[l,2-6]pyrazolines synthesis, 5, 148... 

The 1,3,4-oxadiazole 113 is formed from the azo compound 112 by the action of triphenylphosphine <96SL652>. A general synthesis of 1,3.4-oxadiazolines consists in boiling an acylhydrazone with an acid anhydride (e.g., Scheme 18) <95JHC1647>. 2-Alkoxy-2-amino-l,3,4-oxadiazolines are sources of alkoxy(amino)carbenes the spiro compound 114, for instance, decomposes in boiling benzene to nitrogen, acetone and the carbene 115, which was trapped as the phenyl ether 116 in the presence of phenol <96JA4214>. 

N-donor ligand. The reaction appears to proceed via an acyclic iminoplatinum(II) intermediate that undergoes a subsequent intramolecular cyclization. Some mechanistic aspects of this versatile reaction have been elucidated.225,226 A4-l,2,4-oxadiazolines have been prepared by the [2+3] cycloaddition of various nitrones to coordinated benzonitrile in m-[PtCl2( D M SO)(PhCN)] precursors.227,228 Racemic and chiral [PtCl2(PhMeSO)(PhCN)] complexes have also been used in order to introduce a degree of stereoselectivity into the reaction, resulting in the first enantioselective synthesis of A4-l,2,4-oxadiazolines, which can be liberated from the complexes by the addition of excess ethane-1,2-diamine. 

The reaction of ADC compounds with carbenes and their precursors has already been discussed in Section IV,A- In general, the heterocyclic products are not the result of 1,2-addition but of 1,4-addition of the carbene to the —N=N—C=0 system.1 Thus the ADC compound reacts as a 4n unit in a cheletropic reaction leading to the formation of 1,3,4-oxadiazolines. Recent applications include the preparation of spiro-1,3,4-oxadiazolines from cyclic diazoketones and DEAZD as shown in Eq. (14),133 and the synthesis of the acyl derivatives 85 from the pyridinium salts 86.134 The acyl derivatives 85 are readily converted into a-hydroxyketones by a sequence of hydrolysis and reduction reactions. 

The synthesis of cephem derivative 99 involved S-alkylation of 5-methyl oxadiazoline-2-thione with the appropriate tosylate <2000BMC2317>. 

The synthesis and properties of heat-resistant polyazomethines containing 2,5-disubstituted oxadiazole fragments, being insulators convertible into semiconductors by doping with iodine, have been described. The radical copolymerization of alkenes with the fluorescent co-monomer 2-/-butyl-5-(4 -vinyl-4-biphenylyl)-l,3,4-oxadiazole has resulted in useful macromolecular scintillators. Anionic polymerization of 2-phenyl-l,3,4-oxadiazolin-5-one has produced a nylon-type product <1996CHEC-II(4)268>. 

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. 

At the opposite end of the philicity spectrum, nucleophilic carbenes have proven useful in synthesis. Warkentin" pioneered the thermolysis of oxadiazolines as precursors for (CH30)2C and related dioxacarbenes (Scheme 7.3). Dimethoxycarbene generated from an oxadiazoline undergoes a variety of intermolecular reactions." One example is the ring enlargement of strained cyclic ketones, for example, cyclo-butanone. In this reaction, the nucleophilic carbene initiates the ring expansion by... 

Barrans and co-workers14,85 86 used the ubiquitous benzamidoxime (Section II, A) as a starting point for the synthesis of A2- and A3-oxa-diazolines [Eq. (29)]. By displacement of the hydrogen on N-4 in the A2-oxadiazoline (19), the anion 20 was obtained. Alkylation of this anion... 

One other synthesis of a A3-oxadiazoline was obtained unintentionally. Hull and Farrand114 refluxed cyanamide and phenylhydroxyl-amine in acetone expecting to obtain the disubstituted hydroxylamine (23). Instead, the solvent acetone had condensed with the hypothetical... 

---