Benzofuroxans tautomerization

Two new studies of the benzofuroxan tautomerism 60 (Scheme 5.45) have been reported [103] in addition to H and NMR spectroscopy (not very differentiating), the nucleus was of great help. 

In spite of the usefulness of the Beirut reaction, mechanistically it is not well understood. It has been suggested that the first step involves the nucleophilic attack by the enolate or the enamine at N-3 of the benzofuroxan to yield an intermediate iV-oxide (Scheme 50) which subsequently undergoes tautomerism to an hydroxylamino derivative. This intermediate then cyclizes to the dihydroquinoxaline 1,4-dioxide. This suggestion has not been proven, and indeed there is evidence that benzofuroxan is in equilibrium with 1,2-dinitrosobenzene... 

The tautomeric structure leads to ambiguities in the nomenclature of compounds in this series. Thus, 5-methyl- and 6-methylbenzo-furoxan denote two different molecules which, because of their interconversion, cannot be isolated separately at normal temperatures. Throughout this review, when we intend to refer to the ambiguous mixture, we shall use the system employing the lowest numbers. The above methyl derivative, for example, will be described as 6-methyl-benzofuroxan regardless of the form adopted in the crystal. When a... 

The 1-oxide 3-oxide tautomerism [Eq. (3), p. 4] has been discussed earlier (Sections II and III,C) in connection with the problem of the structure of benzofuroxan. A second type of rearrangement involves the furoxan ring and an adjacent substituent group, and arose out of a suggestion of Bailey and Case that 4-nitro-benzofuroxan might be a resonance hybrid of type (57)-(-> (58), rather than 57. NMR ruled out this possibility the three protons present in... 

Intermediates involved in the tautomerization of furoxans gave rise to speculations about their structure. Systematic calculations on possible intermediates being involved in the reaction of furoxan [92JCC177] and benzofuroxan 79 showed that dinitrosoethylene and dinitrosobenzene 81 are the most likely ones (Scheme 50) [94JOC6431, 94JPC12933]. 

Keywords Benzofuroxan Furoxan Ring-chain tautomerism... 

The kinetic parameters of tautomeric equilibrium of 5(6)-fluoro-6(5)-R-benzofuroxans were derived from the measurement of the temperature dependence of the 111 and 19F NMR spectra (Scheme 3) <2004RJ01167>. 

The principal methods for forming the heterocyclic ring of benzofuroxans involve oxidation of o-quinone dioximes, thermolysis of o-nitroaryl azides, and oxidation of o-nitroanilines (Scheme 25). Ring chain tautomerism (Section 4.05.5.2.1) for the A -oxides of asymmetrically substituted benzofuroxans is more facile than for monocyclic analogues and mixtures of isomers may result. Benzofuroxans are also formed by Boulton-Katritzky rearrangement of 7-nitro-2,l-benzisoxazoles and 4(7)-nitrobenzofuroxans (Section 4.05.5.2.5). 

Another example of ring-chain tautomerism with participation of a substituent is the interconversion of furoxan-2- and furoxan-5-oxides (104a 104b). The equilibration is presumed to proceed via an intermediate cis- 1,2-dinitrosoalkene (105). In the benzofuroxan series the involvement of the corresponding 1,2-dinitrosoarenes as intermediates has been firmly established by matrix isolation experiments (91CC1178, 91JOC5216,92CL57). 

As well as the previous chapter on the Hammett equation,1 the importance of the approach has found expression in specific areas in other contributions to these volumes side chain reactivities of thiophenes 17 tautomerism 18 reactions of azines with nucleophiles 19,20 formation of benzofuroxans by decomposition of o-nitrophenyl azides 21 acid dis-... 

Benzotrifuroxan (15 n = 1 and the thiadiazolo compound (16) have also been studied they both have longer than average N(l)—0(2) bonds, 1.48 and 1.47 A, respectively. In contrast the two endocyclic N—O distances in 4,6-dinitrobenzofuroxan are almost the same. Benzofuroxans usually crystallize in the tautomeric form which predominantes in solution. 

Proton resonance techniques provided the hrst clear-cut evidence for the unsymmetrical structure of benzofuroxans and for their tautomerism. The unsymmetrical (ABCD) spectrum observed at low temperature (-40 °C) becomes well-resolved and symmetrical (A2B2) above... 

Tautomerism between the 2-oxides and 5-oxides is a consistent feature of furoxan chemistry, cis- Dinitrosoalkenes and o-dinitroso.arenes are likely intermediates, although definitive evidence has not yet been presented. A number of reactions have, however, been rationalized in terms of such dinitroso species e.g. the formation of the bisazoxy compound (39) from benzofuroxan and p-anisyl azide (75TL3577). 

The pioneering work of Katritzky is presented as a complete interpretation for the proton spectra of benzofuroxan and four nitro-derivatives [757], The temperature dependence of the spectra enables to calculate AG for the tautomeric change of the benzofuroxan heterocyclic ring [757],... 

Although the possibility of anthranil-A-oxide formation may be recognized, there are certain difficulties in the way of accepting at least one of the foregoing examples. The two generalized systems (181 and 182) differ, in certain conformations, only in their electron distribution, and interconversion would be expected to occur so readily as to preclude isolation of other than the energetically more stable form. Several examples may be cited to bear this out. Thus, 2-phenyl-benzotriazole-1-oxide (181, X = N, Y = NPh) is well-known,320 but no evidence for the independent existence of o-nitrosoazobenzene (182, X = N, Y=NPh) is available. The rapid tautomerism of benzofuroxan (181, X = N, Y = 0) from the 1- to the 3-oxide structure, through... 

Ouino.xaline di-.Af-oxides are not formed in the reaction of benzofuroxan v/ith malonic acid or malonales however, benzofuroxan reacts smoothly with ethyl cyanoacetate in the presence of a strong base such as l,5-diazabicyclo[4.3.0]non-5-ene (DBN) or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) with the elimination of alcohol to give 3-hydroxyquinoxaline-2-carbonitrile 1,4-dioxide. According to spectroscopic studies, the tautomeric equilibrium is shifted towards l-hydroxy-2-oxo-l,2-dihydroquinoxalin-3-carbonitrile 4-oxide. 

It should be noted that pyrolysis of either of the substituted nitro-phenylazidcs 213 and 214 yields the same single compound Thus a tautomerism must occur between the products 216 and 217, probably via the dinitroso derivative 215, to give the more stable isomer . In the case where X = Cl or Br this has been shown, by an X-ray crystallographic study, to be the 5-substituted benzofuroxan 217... 

---