Furazan derivatives

The side products of the reaction between benzoylnitromethane 279 and dipolarophiles (norbornene, styrene, and phenylacetylene) in the presence of l,4-diazabicyclo[2.2.2]octane (DABCO) were identified as furazan derivatives (Scheme 72). The evidence reported indicates that benzoylnitromethane gives the dibenzoylfuroxan as a key intermediate, which is the dimerization product of the nitrile oxide. The furoxan then undergoes addition to the dipolarophile, hydrolysis, and ring rearrangement to the final products (furazans and benzoic acid) <2006EJ03016>. 

Alkylation of silyloxy-furazan derivative (20) with triethyl orthoformate yields a mixture of 2-ethyl-l,2,5-oxadiazol-3(2//)-one (21) and O-ethyl compound (22) (Equation (1)) <93T5905> compound (21), which was characterized by its distinctive spectroscopic properties, is a rare example of a tricoordinate A-substituted 1,2,5-oxadiazole. 

Einige Furazan-Derivate werden in der Pharmazie verwendet280 z. B. ... 

Rearrangement of furazan derivatives were studied by Boschi and coauthors [67]. 4-Phenyl-1,2,5-oxadiazole sulfone 130 (Scheme 45) heated in acetone containing sodium hydroxide rearranged to sulfinic acid derivative 132. After expulsion of SO2,3-acetamido-4-phenylfurazan 133 was formed in 86% yield. Amido-sulfide 131 under similar conditions underwent hydrolysis only to afford the respective acid. 

Oximes 21 and 22, and the furazan derived from 22, were not rearranged.4 It should be noted that an X-ray structure determination of 22 showed it to have the. E-configuration, as shown,32 In the benzo-fused series a similar rearrangement, 23 -> 24, has been reported.33 34... 

Combretafurazans (1,2,5-oxadiazole) are more potent in vitro cytotoxic compounds compared to combretastatins in SH-SY5Y neuroblastoma cells (yet maintaining similar structure-activity relationship and pharmacodynamic profiles). In particular the furazan derived from Combretastatin A-4 and 3 -deoxy-3 amino Combretastatin A-4 exhibited IC50 values about 4 times lower with respect to Combretastatin A-4. 

A] are comparable with the dimensions of sulphathiazole (97), rather than with the dimensions of either (94), (95), or (96), thus suggesting limited delocalization within the five-membered ring. However, the influence of the thiazole moiety on the benzene ring is evidenced in particular by the length of the C(8)-C(9) bond [1.353(6) A], which parallels the effects observed in the furazan derivatives (89), (90), (91), and (92). Rather similar distortions... 

Furazan derivatives of TATB have not been chemically produced in large amount, so the 50 % drop height has not been measured. However from Kamlets s oxygen balance relationship [23], furazan should not be more sensitive than TATB. It may therefore, not have any role in contributing to sensitivity. However furazan is produced by the separation of a water molecule from TATB. Thus the formation of each furazan group will be accompanied by the release of 59 kcal/mole of heat. This can be identified with the exothermic step needed to sustain the reaction. Thus the... 

Interestingly, the ferrocene derivative 12 reacted with NH2OH HCl in pyridine to give furazan 13 in 46% yield (86ZOB1110) (Scheme 4). 

Sheremetev and co-workers employed diazo compounds of type 60, prepared from the corresponding amines in moderate yields as alternative excellent precursors for the preparation of side-chain-functionalized derivatives (Scheme 29). Several furazans bearing reactive groups or cyclopropyl or five-membered heterocyclic substituents have been prepared by standard procedures (99MI6). 

An elegant synthesis of a wide range of carbonyl derivatives of furazan from di-3,3 -isoxazolyl ketone with MHR as key step was developed in 1946 by Quil-ico and Freri (46G3). The intermediate acetaldoxime derivative was produced in 85% yield. It was converted regioselectively into the functionalized acetylfurazans (Scheme 57). 

All these furoxan derivatives may be reduced to the corresponding furazans with SnCb/HCl/AcOH (64ERP1329349, 77RZC1531, 94IZV679, 94RCB630). 

Aldehydes and ketones of furazans and furoxans have many properties resembling those of the aryl derivatives. Reduction of the carbonyl compounds with... 

Ylidene-substituted furazans, which may be used in some cases without purification, are excellent building blocks for the construction of heteroaryl substituted derivatives. Simple variations in the substituents on the furazan ring, the active methylene compounds, and reagents can lead to a variety of products (99MI7) (Scheme 68). 

Haloacetyl groups have also a synthetic potential. Thus, pesticidal (alkylthio)-vinyl esters of phosphorus acid derivatives have been prepared by the introduction and subsequent displacement of two chlorine atoms in the acetyl moiety attached to the furazan ring (Scheme 69) [73GEP(0)2144393]. 

The dinitromethane derivatives 135 and 136 were obtained by nitration of oximes of monoacyl furazans and furoxans with dinitrogen tetroxide [36G819, 37G518, 63T(S)143] or nitric acid (37G388, 97MI11, 97ROC1760) (Scheme 79). 

Another example of this rearrangement has been used to prepare 1,2,3-triazole 146 from furazanic phenylhydrazone 147 (Scheme 84) [93JCS(P1)2491]. Interestingly, furoxanic Z-phenylhydrazones 150 underwent thermal recyclization to 1,2,3-triazole A-oxides 152, evidently through intermediate 151. Treatment of the hydrazone 150 with rerr-BuOK leads to the nitromethyl derivative 149 [OOOMIl] (Scheme 84). Lead tetraacetate oxidation of 147 with subsequent Lewis acid treatment of the initially formed intermediate afforded indazole 148 (Scheme 84) (85JHC29). 

Alkylamino-substituted furazans can be obtained by reduction of acylamino derivatives. The chlorine atom at the side chain may be replaced with a nucleophile (Scheme 114) (85MI1, 88AP77, 89AP579, 89MI1, 92AP151). 

Dilution of a solution of diazonium salts in sulfuric acid with water affords triazene derivatives (95IZV1315,95RCB1269). Treatment of a bridged bis(amino) furazans 200 with nitrous acid in acetic or hydrochloric acid gives macrocyclic triazene 201 (Scheme 132) (95MI4). 

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