Oxadiazoles and Oxadiazolines

The structure of 1,2,4-oxadiazoles has not been in dispute since covalent structures can be drawn from the methods of synthesis. The geometry of the ring was estimated for theoretical calculations years before X-ray measurements were available. Microwave spectra and recently fluorescence spectra have been used to determine the dipole moments of oxadiazoles and oxadiazolines, the latter being high by comparison (Table 7). Electron densities were calculated for 5-methyl-3-phenyl-l,2,4-oxadiazole (88) and its 2,3-dihydro derivative (89) (77JOC1555). 

Reductions of oxadiazoles to oxadiazolines and oxadiazolidines were conspicuous by their absence in the description of their syntheses (Section III). Reagents vigorous enough to reduce the double bonds in an oxadiazole ring also break the ring. It was early reported8 that zinc and hydrochloric acid acted on 3,5-diphenyloxadiazole to give benzonitrile. 

Enough 1,2,4-oxadiazoles and their reduced derivatives have been made that there is general agreement on where to expect the C=N absorption in the IR spectrum, i.e. 1560-1590 cm-1. In the partially reduced (oxadiazoline) ring the A2 double bond appears at 1550-1565 cm-1 and the NH bands at 3320 and 3220-3250 cm-1. In an amino derivative, 5-amino-3-phenyl-l,2,4-oxadiazole, the C=N bond absorbs at higher frequency (1660 cm"1) (63PMH(2)229>. 

The chemical shifts of the ring protons are lowered by quaternization as shown by the values of S (TFA) 10.7 and 9.3 p.p.m. for the 2- and 5-protons in 3-phenyl-l,3,4-oxadiazolium perchlorate. A S (CDC13) value of 2.58 p.p.m. for the methyl protons in 2-methyl-l,3,4-oxadiazole reflects the low electron density at the ring carbon atom. The value of the chemical shift of the proton or protons in the O-alkyl or A-alkyl group assists in differentiating between isomeric 2-alkoxy-l,3,4-oxadiazoles and 4-A-alkyl-A2-1,3,4-oxadiazolin-5-ones. 

UV spectra of substituted 1,3,4-oxadiazoles are similar to those of similarly substituted benzenes, particularly in the case of 2-phenyl- and 2,5-diphenyl-l,3,4-oxadiazole (Amax (EtOH) 247.5 nm, log e 4.26, and 280 nm, log e 4.44 respectively). However, no absorption above 200 nm is shown by 1,3,4-oxadiazole itself and calculated values (Section 4.23.2.1) for its long wavelength absorption are in the region of 200 nm compared with Amax ca. 260 nm for benzene. 2-Methyl- and 2-ethoxycarbonyl-l,3,4-oxadiazole, and A2-l,3,4-oxadiazoline-5-thione have the following Amax (log e) values respectively 206 nm (2.62) (methanol), 243 nm (3.2) and 260 nm (4.12) (ethanol). 

In the IR field, the oxadiazole ring has been characterized primarily by the bands at about 970 cm-1,37,151 1020-1030 cm-1,60 151 due to the C—O bond and at 1560-1640 cm-1,35 36 44a-55 85 181-152 due to the C=N valence vibration. 2,5-Dialkyl derivatives in this case fall in the longer-wavelength region35,36,44a>151 and oxadiazoline thiones in the shorter-wavelength region.65 The C=0 absorption in 1,3,4-oxadiazolin-5-ones lies at 1740-1785 cm-1 even in condensed systems.76,78,116... 

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>. 

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. 

Microwaves were used to support S-arylation of 5-substituted oxadiazoline-2-thiones <2000BMC69> and <2000M1207>. 5-(4-Pyridyl)oxadiazoline-2-thiones treated with 2-haloesters also afforded A-alkyl derivatives <2000CHE851>. A similar reaction occurred in the case of 5-pyrazolyloxadiazoline-2-thiones <2000JFA5312>. Organophosphorus derivatives of 1,3,4-oxadiazole were obtained by the reaction of bis(oxadiazolinethiones) with 0,0-diethylchlorophosphate (Scheme 21) <1998JFA1609>. 

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>. 

The crystal structures of 5-methyl-5-(2-methylprop-l-enyl)-2-phenyl-4-(4-phenylthiazol-2-yl)-A -1,3,4-oxadiazoline <90ZC26> and the rubidium and silver salts of 2-phenyl-A -l,3,4-oxadiazolin-5-one <85JOC4461> have been analyzed. A crystal study of bis-[2-(5-phenyl-l,3,4-oxadiazol-2-yl)-methyl] ether produced bond lengths and angles and showed the rings to be nearly coplanar <87AX(C)2166>. 

Most 1,3,4-oxadiazoles are thermally stable (unlike many A -l,3,4-oxadiazolines, see Section 4.06.6.2) and high temperatures are needed to induce ring cleavage. At 700°C oxadiazolinones (12) lose carbon dioxide to form a nitrilimine which undergoes further reaction, with loss of nitrogen. For example, 4-phenylbut-l-en-3-yne was formed on heating oxadiazolinone (12 R = ethynyl)... 

In contrast, the oxidation of oxadiazolines (method S) can be used to synthesize oxadiazoles from aromatic amidoximes and aliphatic aldehydes. 

Muchall et al. (98CC238) have recently investigated the gas-phase thermolysis of 2,5-dihydro-2,2-dimethoxy-2,5,5-trimethyl-l//-l,2,4-oxadiazole (75) by PE spectroscopy. Decomposition of 75 was induced by means of a continuous wave (CW) C02 laser as directed heat source at 26 W, which corresponds to a temperature of 500 50°C. When the PE spectra of acetone, tetramethoxyethene, and dimethyl oxalate were subtracted from the pyrolysis spectrum, a sim-ple spectrum remained that could be identified as that of dimethoxycarbene. Thermolysis in solution (94JA1161) had shown formation of tetramethoxyethene, and FVP experiments (92JA8751) gave dimethyl oxalate, both of which arise from the common precursor, dimethoxycarbene. Thermolysis of oxadiazolines similar to 75 in solution affords dialkoxycarbenes via an intermediate carbonyl ylide (94JOC5071). 

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