Benzo oxadiazole

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. 

Although benzofuroxan (Bfx) and furoxan (Fx) were first synthesized over 100 years ago, it was not until the middle of the 20th century that its relevant bioactivities were identified. Bfx s and Fx s relevant biological behaviors convert these systems in one of the most current study heterocycles in medicinal chemistry. Formally, these compounds are 1,2,5-oxadiazole hf-oxide derivatives, specifically Bfx should be named as benzo[l,2-c][l,2,5]oxadiazole 1-oxide and Fx as 1,2,5-oxadiazole 2-oxide, however, the common trivial... 

Furoxans and Benzofuroxans (1,2,5-Oxadiazole Oxides and Benzo-1,2,5-Oxadiazole... 

Ab initio calculations, correlations of molecules geometries, spectroscopic data with chemical properties, and quanta-tive structure-activity relationship have been conducted for both furazans and furoxans. Thus, the structures of 1,2,5-oxadiazole (furazan) and benzo[c][l,2,5]oxadiazole (benzofurazan) have been calculated by ab initio and Becke3-LYP... 

The applications of 1,2,5-oxadiazole iV-oxide and benzo[c][l,2,5]oxadiazole iV-oxide derivatives as compounds which have herbicidal activity are known. For example, the most active compound, butylcarbamoylbenzoL] 1,2,5-oxadiazole iV-oxide, displayed herbicidal activity at concentrations as low as 24 gha-1 <2000JFA2995>. The preparation of 5,7-disubstituted 4,6-dinitrobenzofuroxane derivatives (2-chlorophenylamino, 2,5-dichlorophenyl-amino, 2-hydroxyphenylamino, or 4-bromophenylamino), which are useful as agricultural arachnicides and bactericides, was described <2005RUP2255935>. 

Amino-3-methylisoxazole, 1502 2-Amino-4-methyloxazole, 1500 5-Amino-3-methylthio-l,2,4-oxadiazole, 1192 Ammonium A-nitrosophenylaminooxide, 2399 2-Aza-l,3-dioxolanium perchlorate, 0898 Azoformaldoxime, 0815 Bis(l-benzo[d]triazolyl) carbonate, 3598 Bis(l-benzo[d]triazolyl) oxalate, 3629 Bis(trifluoromethyl) nitroxide, 0638 2-/er/-Buty 1-3 -phenyloxaziridine, 3406 Calcium bis(O-hydroxylamide). 3930 Calcium hydroxide O-hydroxylamide, 3929... 

Dioximes of a-diketones such as benzil on oxidation with IBTA are converted into 1,2,5-oxadiazole-A-oxides (furoxans) in high yields (75S445) (Eq. 35). Benzo- (Scheme 46) and pyrido-oxadiazoles (Eq. 36) are formed when o-nitroaniline and 3-amino-2-nitropyridine are subjected to similar oxidation. 

Benzofurazans are thermally more stable but can be cleaved photolytically. For example, benzo-furazan itself in benzene affords cyanoisocyanate (17) and azepine (18), the latter being formed by reaction of the solvent with the putative intermediate acylnitrene (19) (Scheme 5) further supporting evidence for the proposed pathway is provided by trapping the nitrile oxide precursor with dimethyl acetylenedicarboxylate and isolation of the methylurethane derivative of the isocyanate <75JOC2880>. Photolysis of diphenylfurazan yields benzonitrile, diphenylfuroxan and 3,5-diphenyl-1,2,4-oxadiazole. 

Oxadiazoles and their benzo derivatives find use in applications as diverse as pharmaceuticals, analytical reagents, propellants and explosives, starting materials in organic synthesis, and for polymer preparation and modification. 

Furazane mit einem anellierten Benzol-Ring werden als Benzofurazane I bczcichnet auch Na-men wie 3,4-Benzo-l, 2,5-oxadiazol und 2,1,3-Benzoxadiazol sind (insbesondere in der alteren Literatur) verwendet worden. 

Wird ein Benzol-Ring an ein Furoxan anelliert, erhalt man Benzofurazan-l-oxid (Benzofuro-xan, I). Nach Chemical Abstracts wird dieser Heterocyclus als Benzofurazan-1-oxid bezeichnet zudem findet man die Benennungen 3,4-Benzo-l,2,5-oxadiazol-2-oxid, 2,1,3-Benzoxadiazol-1-oxid und 2,1,3-Benzoxadiazol-N-oxid2. 

R.M. Paton, 1,2,5-Oxadiazoles and their Benzo Derivatives, in A. R. Katritzky u. C. W. Rees, Comprehensive Heterocyclic Chemistry, K. T. Potts, Vol. 6, S. 393, Pergamon Press, Oxford 1984. 

An alternahve method had been reported in the literature [12] to prepare [1,2,4] triazolo[4,3-a]piperazines (Route B, Scheme 5.9) via the condensahon of a chloromethyl oxadiazole with 1,2-phenylenediamine to afford the benzo fused compounds. The reachon condihons reported for this approach were harsh and the yields were low, presumably due to the poor nucleophilicity of 1,2-phenylenedi-amine. However, we felt that the synthesis of 3 could potentially be accomplished under milder reachon condihons because of the enhanced nucleophilicity of... 

A unique example is found in 2,1-benzisoxazole (40), which undergoes N-methylation 1.9 times faster than isoxazole (37).122 This is the only known example of rate acceleration resulting from benzo-fusion. Other interesting comparisons involve 2,1,3-benzoxadiazole (benzofurazan, 41), and 1,2,5-oxadiazole (furazan, 42),123 and also isothiazole (37), and 2,1-benzisothiazole (40).122 For these two pairs essentially no change in reactivity results when the azole is converted into its benzolog. 

The photolysis of acyl azides has also been studied, and in some respects these appear to behave analogously. Pivaloyl azide, for example, adds to cyclohexene to give a 26% yield of an aziridine [Eq. (85)],321 and the assumption is that this addition again occurs via a nitrene. The photodecomposition of acetyl azide (295) in benzo-nitrile and phenylacetylene, on the other hand, affords322 2-methyl-5-phenyl-l,3,4-oxadiazole (296) and 2-methyl-5-phenyloxazole (297),... 

---