Oxadiazoles, reduction

Oxygen-containing azoles are readily reduced, usually with ring scission. Only acyclic products have been reported from the reductions with complex metal hydrides of oxazoles (e.g. 209 210), isoxazoles (e.g. 211 212), benzoxazoles (e.g. 213 214) and benzoxazolinones (e.g. 215, 216->214). Reductions of 1,2,4-oxadiazoles always involve ring scission. Lithium aluminum hydride breaks the C—O bond in the ring Scheme 19) 76AHC(20)65>. 

Catalytic reduction of 1,2,4-oxadiazoles also breaks the N—O bond e.g. (264) gives (265). Benzofuroxan can be reduced under various conditions to benzofurazan (266), the dioxime (267) or o-phenylenediamine (268) (69AHC(10)l). Reduction by copper and hydrochloric acid produced o-nitroanilines (Scheme 30) (69AHC(lO)l). 

Oxadiazoles — see also Furazans electrochemical reduction, 5, 73 mass spectra, 6, 522... 

Treatment of intermediate 31 with 2.2 equiv of 4-FB A in EtOH at 72 °C afforded 35 as a white crystalline solid in 90% isolated yield (Scheme 6.9). Hydrogenation in the presence of 5% of Pd/C and 1 equiv of MsOH, efficiently removed the Cbz-protected group. MsOH was used to prevent fluoride reduction resulting in low levels of the des-fluoro by-product. Catalyst filtration, followed by neutralization of the crude reaction mixture with NaOH, afforded free amine 36 as a white crystalline product in 99% isolated yield. Free-amine 36 was isolated as a dihydrate which necessitated drying prior to coupling with oxadiazole chloride 2. 

Electrochemical reduction of 3-phenylsydnone 89 and its 3-(4-methoxy)phenyl and 3(4-methyl)phenyl analogues represents a new method for the preparation of 2,4-dihydro-3-aryl-l,2,3-oxadiazole-5-ones <2006CCA273, 2006MI776>. The products were isolated in 82 to 88% yield, and their proposed structures are supported by melting point, elemental analysis, IR, proton NMR, and mass spectral data. 

The reduction of the Wang resin-bound 1,2,4-oxadiazole 107 (Equation 15) with LiAlH4 resulted in reductive cleavage from the resin and a reductive ring opening of the 1,2,4-oxadiazole to furnish the amidoxime 108 <1999BML2101>. 

Electrochemical reduction of the 5-(bromodifluoromethyl)-l,2,4-oxadiazole 168 in the presence of tetrakis (dimethylamino)ethylene (TDAE) generates the 5-(difluoromethyl) anion which reacts with aldehydes to give the 5-g. 

The dimeric 2,3-dihydro-l,2,4-oxadiazole palladium(n) complex 182 (Equation 27) reacts with aqueous methylamine to liberate the ligand 183 <2003JCD2544>. A similar process has also been applied to platinum(lv)-bound complexes 184, using pyridine to liberate the 2,3-dihydro-l,2,4-oxadiazole <2000JA3106>. Reduction of the platinum(iv) complexes 184 (Equation 28) gives the corresponding platinum(n) complexes 185 <2001IC264>. 

The 4,5-dihydro-l,2,4-oxadiazol-5-one 119 (see also Scheme 12) undergoes Wadsworth-Emmons reaction to give the alkene 190 (Scheme 25). Reduction of the ester with Red-Al and subsequent bromination of the alcohol gave the bromofluoroalkenyl-substituted 4,5-dihydro-l,2,4-oxadiazol-5-one 191, demonstrating the robustness of this ring system <2004T10907>. 

The electron spin resonance (ESR) spectra of free radicals obtained by electrolytic or microsomal reduction of several potential antiprotozoal 1,2,5-oxadiazoles were characterized and analyzed. Ab initio MO calculations were performed to obtain the optimized geometries, and the theoretical hyperfine constant was carried out using Zerner s intermediate neglect of differential overlap (ZINDO) semi-empirical methodology. DFT was used to rationalize the reduction potentials of these compounds <2003SAA69>. 

The relationship between the herbicidal activity of 1,2,5-oxadiazole iV-oxides and some physicochemical properties potentially related to this bioactivity, such as polarity, molecular volume, proton acceptor ability, lipophilicity, and reduction potential, were studied. The semi-empirical MO method AMI was used to calculate theoretical descriptors such as dipolar moment, molecular volume, Mulliken s charge, and the octanol/water partition coefficients (log Po/w) <2005MOL1197>. 

The reduction of furoxans to give furazans is also a well-known process. For example, the triethylphosphite reduction of compounds 38 and 39 affords the l,2,4-oxadiazolyl-l,2,5-oxadiazole 40. Deoxygenation of the iV-oxide moieties in furoxans 38, 39, and 41 also takes place under conditions of mass spectrometry <2000J(P2)473>. 

Mesoionic derivatives are generally synthesized from the parent 1,2,3-thiadiazoles. A new method based on the rearrangement of oxadiazoles under reductive conditions has been reported. For example, the oxadiazole 70 when... 

Bipolar Molecular Glasses. Recently, bipolar molecular glasses have been described that allow both injection of holes and electrons (Fig. 3.30). 2- 4-[bis(4-methylphenyl)amino]phenyl -5-(dimesitylboryl)thiophene (PhAMB-lT, 68) and 2- 4-[bis(9,9-dimethylfluorenyl)amino]phenyl -5-(dimesitylboryl)thiophene (F1AMB-1T, 69) show oxidation potentials of 0.62 and 0.58 V, and reduction potentials of —2.13 and —2.01 V vs. Ag/0.01 Ag+, respectively [145]. Oxidation as well as reduction leads to stable radical ions. With the conversion rules given above, the HOMO and LUMO levels can be estimated to be approximately at —5.3 and —2.8 eV. In comparison, for the bipolar compound 70, consisting of triarylamine and oxadiazole moieties, the values are —5.5 and — 2.7eV [129]. However, in this case no data on the stability of the radical ions are available. 

A photo-induced electron transfer (from either the sensitizer in its excited state to the oxadiazole in its ground state or from the electron-donor reagent such as triethylamine to the excited oxadiazole) has been suggested as an explanation for the breaking of the O—N bond of 5-aryl-3-methoxy-(or 5-aryl-3-phenyl-)-l,2,4-oxadiazoles (71) upon irradiation. The resulting oxadiazole radical anion underwent either a heterocycliza-tion to give quinazolin-4-ones or reduction to give open-chain products. 

As described, other nucleophilic reactions in the anthraquinone series also involve the production of anion-radicals. These reactions are as follows Hydroxylation of 9,10-anthraquinone-2-sulfonic acid (Fomin and Gurdzhiyan 1978) hydroxylation, alkoxylation, and cyanation in the homoaromatic ring of 9,10-anthraquinone condensed with 2,1,5-oxadiazole ring at positions 1 and 2 (Gorelik and Puchkova 1969). These studies suggest that one-electron reduction of quinone proceeds in parallel to the main nucleophilic reaction. The concentration of anthraquinone-2-sulfonate anion-radicals, for example, becomes independent of the duration time of the reaction with an alkali hydroxide, and the total yield of the anion-radicals does not exceed 10%. Inhibitors (oxygen, potassium ferricyanide) prevent formation of anion-radicals, and the yield of 2-hydroxyanthraquinone even increases somewhat. In this case, the anion-radical pathway is not the main one. The same conclusion is made in the case of oxadiazoloanthraquinone. 

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