Oxadiazole aromaticity

Polyfluoroalkyl- andperfluoroalkyl-substituted CO and CN multiple bonds as dipolarophiles. Dmzo alkanes are well known to react with carbonyl compounds, usually under very mild conditions, to give oxiranes and ketones The reaction has been interpreted as a nucleophilic attack of the diazo alkane on the carbonyl group to yield diazonium betaines or 1,2,3 oxadiazol 2 ines as reaction intermediates, which generally are too unstable to be isolated Aromatic diazo compounds react readily with partially fluorinated and perfluorinated ketones to give l,3,4-oxadiazol-3-ines m high yield At 25 °C and above, the aryloxa-diazolines lose nitrogen to give epoxides [111]... 

The benzofuroxtin [benzofurazan oxide, 3,4-benzo-l,2,6-oxa-diazole-2-oxide, or 2,1,3-benzoxadiazole-l-oxide (1)] ring system has been reviewed briefly on several occasions, notably by Kaufman and Picard,Boyer, and Behr. The mqst recent of these covers the literature until 1959, and since that date there have been many advances in the subject. This, we feel, justifies the field being covered once more, and its separation from the monocyclic 1,2,5-oxadiazole oxides—the furoxans. We consider also other furoxano-fused compounds in this chapter, subject to the limitation that the ring adjacent to the furoxan is aromatic and six-membered. 

Phenoxaphosphine ring-containing poly (1,3,4-oxa-diazoles) were synthesized by cyclodehydration of poly-hydrazides obtained from (BCPO) and aliphatic and aromatic dihydrazines [152]. All these polymers are soluble in formic acid, w-cresol and concentrated H2SO4. The polyhydrazides yield transparent and flexible films when cast from DMSO solution under reduced pressure at 80-100°C. The polyhydrazides exhibit reduced viscosities of 0.24-0.40 dl/g in DMAC. Phenoxaphosphine ring-containing oxadiazole polymers showed little degradation below 400°C. 

An alternative approach utilizes polymeric analogs of PBD. The oxadiazole unit may be in the polymer main chain or attached as a side chain. A reasonable device performance has been demonstrated in poly(aromatic oxadia/ole)s [71—74. ... 

Finally, a series of 2-chloromethyl-5-aryl-1,3,4-oxadiazoles 82 were prepared by reaction of aromatic hydrazides 81 and a chloromethylorthofor-mate used as the solvent under microwave activation [62]. Potentially, the chloromethyl group could imdergo nucleophiUc substitution expanding the scope of this reaction (Scheme 28). 

Recently, Kraft and Osterod [157] reported the synthesis of poly(aramide) dendrimers possessing either electron-deficient 1,3,4-oxadiazole (70) or aromatic systems (71) linked by amide units to a central triphenylmethane unit (Fig. 31). 

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]. 

Multinuclear NMR data have been recorded for molsidomine 12 and its metabolite SIN-1 13, confirming that both are closed ring structures and that the positive charge is accommodated at the N3 position <1996CHE1358>. The c C4-C5 coupling constants for selected 1,2,3-oxadiazoles lie between 69.4 and 89 Hz, but correlation of these values with measures of bond order and aromaticity is difficult due to substituent effects <2000MRC617, 2002JST269>. 

The reaction of the stable and readily available N-protected (a-aminoacyl)benzotriazoles 215 (Equation 36) with amidoximes 206 in ethanol gave the N-protected 5-amino-substituted 1,2,4-oxadiazoles 216 in high yield, under mild conditions and with good (>97%) retention of chirality <2005ARK36>. The method is also applicable to aromatic (V-acylbenzotriazoles, giving access to 5-aryl-l,2,4-oxadiazoles in 73-82% yield. 

The oxidation of aromatic aldoximes with ceric ammonium nitrate produces nitrile oxides which undergo subsequent cycloaddition to nitriles to produce 1,2,4-oxadiazoles (Equation 47) <1997PJC1093>. The anodic oxidation of aromatic aldoximes in the presence of acetonitrile has been reported to give low yields of either 3-aryl-5-methyl-1,2,4-oxadiazoles (2-25%) or 3,5-bis-aryl-l,2,4-oxadiazoles (6-28%), although the synthetic utility of this route is limited by competitive deoximation to the carbonyl being the major reaction pathway <1997MI3509>. 

Ab initio electron correlated calculations of the equilibrium geometries, dipole moments, and static dipole polarizabilities were reported for oxadiazoles <1996JPC8752>. The various measures of delocalization in the five-membered heteroaromatic compounds were obtained from MO calculations at the HF/6-31G level and the application of natural bond orbital analysis and natural resonance theory. The hydrogen transfer and aromatic energies of these compounds were also calculated. These were compared to the relative ranking of aromaticity reported by J. P. Bean from a principal component analysis of other measures of aromaticity <1998JOC2497>. 

C-H and N-H bond dissociation energies (BDEs) of various five- and six-membered ring aromatic compounds (including 1,2,5-oxadiazole) were calculated using composite ab initio CBS-Q, G3, and G3B3 methods. It was found that all these composite ab initio methods provided very similar BDEs, despite the fact that different geometries and different procedures in the extrapolation to complete incorporation of electron correlation and complete basis set limit were used. A good quantitive structure-activity relationship (QSAR) model for the C-H BDEs of aromatic compounds... 

Electrophilic substitution of the ring hydrogen atom in 1,3,4-oxadiazoles is uncommon. In contrast, several reactions of electrophiles with C-linked substituents of 1,3,4-oxadiazole have been reported. 2,5-Diaryl-l,3,4-oxadiazoles are bromi-nated and nitrated on aryl substituents. Oxidation of 2,5-ditolyl-l,3,4-oxadiazole afforded the corresponding dialdehydes or dicarboxylic acids. 2-Methyl-5-phenyl-l,3,4-oxadiazole treated with butyllithium and then with isoamyl nitrite yielded the oxime of 5-phenyl-l,3,4-oxadiazol-2-carbaldehyde. 2-Chloromethyl-5-phenyl-l,3,4-oxadiazole under the action of sulfur and methyl iodide followed by amines affords the respective thioamides. 2-Chloromethyl-5-methyl-l,3,4-oxadia-zole and triethyl phosphite gave a product, which underwent a Wittig reation with aromatic aldehydes to form alkenes. Alkyl l,3,4-oxadiazole-2-carboxylates undergo typical reactions with ammonia, amines, and hydrazines to afford amides or hydrazides. It has been shown that 5-amino-l,3,4-oxadiazole-2-carboxylic acids and their esters decarboxylate. 

Dendrimers, which contain an electron-deficient 1,3,4-oxadiazole ring and aromatic systems linked by amide units to triphenylmethane core, were synthesized (Scheme 16) <1997CC1435>. 

Dipicryl-l,3,4-oxadiazole has been described as an initiating explosive, 2,5-dimethyl-l,3,4-oxadiazole has been used to extract aromatic hydrocarbons from mixtures with alkanes. The use of 4,4 -carbonyl-bis(2-phenyl-5-oxo-l,3,4-oxadiazole) as a blowing agent for foaming thermoplastic compositions (e.g., polycarbonates) has been described < 1996CHEC-II(4)268>. 

---