N-oxides and related compounds. Part XXXVII. The effect of methyl and aza-substituents on the tautomeric equilibrium in benzofuroxan

Abstract

NorwichProton magnetic resonance is used to study the tautomeric equilibria of a number of methyl-substituted benzofuroxans and pyrido r2,3-c]furoxans. Large influences (ca. 0.5-1 kcal./mole) are exerted by methyl and azasubstituents adjacent to the heterocyclic ring.EXTENSIVE studies from this laboratory and elsewhere have shown that benzofuroxan exhibits a rapid tautomeric rearrangement [(I) =+= (II)].2 The effects of 4-and 5-substituents t on this equilibrium are known for a series of 5-monosubstituted derivatives; for other related work see ref. 2. The present work is concerned with the effect of the methyl and aza-substituents. Previously, long-range couplings have hindered detailed interpret ation of low-t emperature methylbenzof uroxan ~p e c t r a ,~ and azabenzofuroxans (pyridofuroxans) have been difficult to prepare. We have sought new synthetic routes and have applied decoupling techniques to simplify the spectral analyses.Benzofuroxans in this paper are =umbered throughout as in (I) and (11). Where a tautomeric pair of compounds is being considered it is usually referred to by assigning to the substituent(s) the lowest numerical value(s) . Pyridofuroxans are named as azabenzofuroxans for clarity.Part XXXVI, A.The effect of a 5(6)-methyl group is small. Preparation of Com~ozcnds.-2-Azido-3-nitrotoluenedid not yield 4-methylbenzofuroxan on pyrolysis ; in this it resembled other sterically hindered azides.5 Attempted 0-iodosobenzene diacetate oxidation of 2-amino-3-nitrotoluene also failed (contrast its successful use 6 with the 3,2-isomer) but pyrolysis of 3-azido-2-nitrotoluene succeeded.The preparation of 4-azabenzofuroxan by pyrolysis of 4 G. Englert,

Enthalpies of combustion of 5-methoxybenzofurazan, 5-methoxybenzofurazan-1-oxide, 5-methylbenzofurazan-1-oxide, 5-chlorobenzofurazan-1-oxide and 4-nitro-benzofurazan-1-oxide: the dissociation enthalpies of the N–O bonds

“…From six calibrations, o(calor)=(25185.722.0) J·K −1 for an average mass of water added to the calorimeter of 5222.5 g. The energy corrections for the electrical ignition, combustion of the cotton thread fuse, combustion of hexadecane, carbon formation, and nitric acid formation were the same as for the static-bomb measurements: the nitric acid was determined using the Devarda's alloy method. The sample, in pellet form, was ignited in oxygen at a pressure p=3.04 MPa with a volume of 20.00 cm 3 As 2 O 3 (aq) of concentration 0.08904 mol·dm −3 added to the bomb. No evidence was found for oxidation of the As 2 O 3 (aq) after the bomb had been charged with oxygen and left for 5 h at room temperature.…”

“…The tautomerism of substituted benzofurazan-1-oxides has been studied by 1 H n.m.r., (2,3) and can occur thermally or photochemically. (4) This tautomerism is believed to proceed via a diorthonitrosobenzene derivative, thus:…”

Phenazine as an Anticancer Agent

“…In all cases the products 46-48 were characterized and evaluated as a nonseparable mixture of 7-and 8-isomers which is the result of the well known tautomerism of benzofuroxan reactant at room temperature (Boulton et al 1967;1970;Cerecetto et al 2005b), used in this work for the preparation of phenazine dioxide derivatives (Cerecetto et al 2005a).…”

Preparation of phenazine N5,N10-dioxides: Effects of benzofuroxan substituents in the outcome of their expansion reaction with phenolates

“…[9][10][11][12][13][14][15][16][17] Thermodynamic equilibrium concentrations are dependent on a number of factors, such as solvent, temperature, nature and position of the substituents on the ring. 6,7,[18][19][20][21][22] Under the same conditions (solvent and temperature) in 5(6)-substituted benzofuroxans the presence of an electron withdrawing group generally favors the 6-tautomer over the 5-tautomer while the opposite occurs with an electron releasing group. [23][24][25] In our knowledge, studies related to benzofuroxan tautomerism and reactivity have not been described.…”

“…When substituted benzofuroxans and phenolates are used, the reactions yield a mixture of 6-and 9-or 7-and 8-isomers. [3][4][5] The formation of the isomers is the result of the well known tautomerism of the benzofuroxans 6,7 (i.e. Figure 2), thus the tautomeric forms can react with the carbanion in a non-selective fashion and with similar probability.…”