Oxadiazole compounds

As 1,2,5-thiadiazole analogues, potent HlV-1 reverse transcriptase inhibitors, some simple 1,2,5-oxadiazoles, compounds 4-6 (Fig. 9), have been synthesized using the traditional Wieland procedure as key for the heterocycle formation [121]. Such as thiadiazole parent compounds, derivative with chlorine atoms on the phenyl ring, i.e., 5, showed the best anti-viral activity. Selectivity index (ratio of cytotoxic concentration to effective concentration) ranked in the order of 5 > 6 > 4. The activity of Fz derivative 6 proved the N-oxide lack of relevance in the studied bioactivity. These products have been claimed in an invention patent [122]. On the other hand, compound 7 (Fig. 9) was evaluated for its nitric oxide (NO)-releasing property (see below) as modulator of the catalytic activity of HlV-1 reverse transcriptase. It was found that NO inhibited dose-dependently the enzyme activity, which is hkely due to oxidation of Cys residues [123]. 

A related series of 5-substituted-2-amino-oxadiazole compounds have also been prepared in a one-pot procedure using a microwave-assisted cyclisation procedure (Scheme 6.26)164. Rapid preparation of the pre-requisite ureas from the mono acyl hydrazines and various isocyanates (or the isothiocyanate) was easily achieved by simple mixing. The resulting products were then cyclo dehydrated by one of the two procedures either by the addition of polymer-supported DMAP and tosyl chloride or alternatively with an immobilised carbodiimide and catalytic sulphonic acid. Purity in most cases was excellent after only filtration through a small plug of silica but an SCX-2 cartridge (sulphonic acid functionalised - catch and release) could be used in the cases where reactions required additional purification. 

There have been several attempts to relate mobilities to ionization or oxidation potentials (Enokida et al., 1990 Scott et al., 1990 Kanemitsu et al., 1991, 1992 Kitamura and Yokoyama, 1991). Scott et al. studied a series of hydrazone compounds in a polyarylate. The oxidation potentials of the donor compounds varied from 0.53 to 1.04 V. The results showed that the zero-field mobilities increase with increasing oxidation potential. In contrast, Enokida et al. investigated a series of butadiene, hydrazone, and oxadiazole compounds doped into a PC and concluded that the mobilities increased with decreasing ionization potential. Kitamura and Yokoyama studied a series of hydrazone compounds in a PC and concluded that the mobilities were independent of the ionization potential. While the reason for these discrepancies is not clear, it should be noted that the study of Scott and coworkers involved zero-field... 

An interesting rearrangement was observed35,36 during the preparation of4-hydroxy-JV-(5-methyl-3-isoxazolyl)-2-methyl-2/M,2-benzothiazine-3-carboxamide 1,1-dioxide (43) (Eq. 9). Sodium methoxide cleaved the benziso-thiazoline derivative 40 to the expected benzoate ester 41, but this was cyclized by base to a 4-hydroxy-2//-1,2-benzothiazine (42) with simultaneous conversion of the isoxazole moiety to an oxadiazole. Compound 42 was N-methylated by methyl iodide and the product converted to the desired amide 43 by treatment with triethylamine in xylene, a process which simultaneously reconverts the oxadiazole side chain to an isoxazole. 

Electron-impact-induced fragmentation patterns of 2,5-bis(p-dichloromaleimidophenyl) 1,3,4-oxadiazole (compound c) 3,3-bis(p-dichloromaleimidophenyl)phthalide (compound d) and 10,10-bis(p-dichloromaleimidophenyl)anthrone (compound f) are given in Figure 1. The common features present in the mass spectra of these compounds are summarized in Table II. A low-intensity molecular ion peak was observed in most of these monomers, with the exception of compounds (a) and (b). Loss of carbon dioxide from the molecular ion (M-44) was indicated only in compound (d), which contains a phthalide group. Carbon dioxide may be eliminated from this site. Similar fragmentation patterns have earlier been obtained with corresponding bismaleimides and biscitraconimides (15). 

Aromatic oxadiazole compounds such as 2-(4-biphenyl)-5-(4-teft-butyl-phenyl)-1,3,4-oxadiazole (PBD) have been used as electron transporting materials in organic light emitting diodes (15-17). Multi-layered polymeric LEDs with improved... 

Interestingly, polymer 18 was found to emit blue-purple light. Aromatic oxadiazole compounds are known to show blue electroluminescence (40-42), Main chain oxadiazole polymers can also be made fluorescent by proper modification of the chemical structure. Pei and Yang (43,44) have reported a new oxadiazole polymer 25 with both a flexible linkage and solubilizing alkoxy side-chains (Scheme 7). An LED of structure ITO/polyaniline/polymer 25/Al has an external quantum efficiency close to 0.1 % and a tum-on voltage around 4.5 V. 

Starburst oxadiazole compounds have been mentioned for the first time in a thermodynamic study of the structure-property-relationship in low molecular weight organic glasses [19, 20]. Upon rapid cooling these compounds form glasses with TgS between 77 and 169 °C. 

We have used three different approaches for the preparation of starburst oxadiazole compounds, which are schematically shown in Fig. 2.2. 

Figure 2.3 DSC scan of the staiburst oxadiazole compound 34, 3rd heating and cooling, with 20 K/min.

The thermal stability has been monitored by thermogravimetric measurements. In most cases the onset of decomposition is in the range from 330-370 °C. The oxadiazole compound 32 with a triphenyl benzene core shows a somewhat higher thermal stability up to 410 °C. 

Yang X, Wang Z, Fang X, Yang X, Wu F, Shen Y (2007) Synthesis of difluoiomethylene-containing 1,2,4-oxadiazole compounds via the reaction of 5-(difluoroiodomethyl)-3-phenyl-... 

---