4‐phenyl‐4H‐pyrazolo[3,4‐c] furazans. The reactions of 3,4‐dacylfuroxans with phenylhydrazine and with aniline

Abstract

Materials Restwch, Central Research I)ivision, The National Cash Register Company ' l~t i r w dif'f'erent 3,iE-diacylfuroxans (1) are shown to give :i-substituted-J -phenyl-4,5-dioximino-2-pyrazolines (2) upon reaction with phenylhydrazine. The compounds 2 were dehydrated t o O-sut~stitutt:d-4-phenyl-~~~f-pyrazolo~:~,4~] furazaris. (3) and thermally converted t o :{-substituted .. 5-iminoanilino-iE-acylfurazans (10).l'c.rkin ( 1) trt:att:d methyl dimethy1acc:toacetate with nitric: acid to obtain a "glyoximc: peroxide" that with phenylhydrazine gave "methyl phenylaminoisotriazoxole-tJimethylmalonylate"; this in turn upon treatment with aqueous hase gave an acid of semi-empirical constitution ( l 6 t I 5 [ ( : 3 N 4 0 ] ( :~l e 2 ( ; 0 2 t 1 to which it was "difficult to assign a satisfactory formula". Perkin suggested a structure containing a I ,5 -dehydro (valence -bridged)-I Jdihydro-I ,?J,iE-tetrazine nucleus, whose improbability has previously been noted (2). Our curiosity as to the structure of the acid led us to rcirivtstigate these arid related reactions. h ' e assumed that tht: "glyoxime peroxide" was in fact Ic, a ;i,il.-diacylf'uroxan ( 3 ) , and thus for comparison purposes we began liy rt:-examining the reported reactions of' the diacetyl and dilttxizoyl furoxans. 1)iacetylfuroxan (Ib) has been reported (4) to give with 1iniitt:d or excess phenylhydrazine merely the monophenylhydrazone (m.p. I f) I -162") o r the diphenylhydrazone (1n.p. 176"), rt:spectively. liowevt:r, neither elemental analyses nor any chemical evidence for these assignments were given. 1)itwizoylfuroxan ( l a ) reportedly reacts with phenylhydrazine to give benzoylphenylhydrazine and a yellow material (2a) of empirical formula 5 I1 N 4 0 2 , which upon heating in acetic acid or acetic anhydride affords a diff'erent substance (3a) heretofore formulated as an isomer of 2a (5) o n the basis of a single nitrogen analysis.Formulas A , H, and (; have been proposed as structures for 2a and 3a, and thert: has been extensive discussion as t o which formula should be assigned to which compound (5-8).1 he initial unstahle reaction product of l a and phenyl-r .The compounds 1 react with aniline to give :Ihydrazine was presumed to have structure 4 (5Jj). This formula, which implies addition of one molecule of phenylhydrazine t o a carbonyl group and one to the ring (;=N+O function, could readily give A and H, and lead t o C after a single Heckmann rearrangement.

1,2,5‐Oxadiazole (Furazan) Derivatives from Benzoylnitromethane and Dipolarophiles in the Presence of DABCO: Structure and Intermediates

“…[14] 84-85°C; ref. [15] 83-85°C). in chloroform (0.7 mL) was stirred for 20 h in a sealed vessel (Schlenk) at 60°C.…”

Formation of [15N]3 N-(4-Phenyl-furazan-3-yl)-benzamide by a Furoxan to Furazan Rearrangement during the Attempted Synthesis of [15N]3 2-Oxy-4-phenylfurazan-3-carbonitrile

“…The work of Bertelson et al . on the reaction of aniline with dibenzoyl furoxan is of particular relevance and Scheme 1 illustrates the analogous mechanism with 15 NH 3 and 5 as the substrate.

…”

“…Re-attack of HCO 15 NH 2 on the nitrile oxide to form N -(1,2-bis-hydroxyimino-2-phenyl-ethyl)-formamide 10 is evidently more favorable than addition of a further molecule of 15 NH 3 . In the case of dibenzoylfuroxan, one of the oxime nitrogen atoms can attack the benzoyl carbonyl group to give an unstable nitrosoisoxazole which rearranges, spontaneously or on heating, to the colorless furazan. , It does appear more likely that their proposed open-chain amidoxime structure was actually a 5-hydroxy-3-amino-isoxazol-4-one oxime. However, since a second carbonyl group is unavailable on 10 , the only option is for one of the oxime oxygen atoms to attack the other oxime nitrogen atom followed by condensation to generate furazan 11 directly without going via an intermediate isoxazole.…”

“…However, a meaningful comparison can be drawn with the classical studies on furoxan to furazan rearrangements described in a comprehensive and authoritative review by Gasco and Boulton. 13 The work of Bertelson et al 14 on the reaction of aniline with dibenzoyl furoxan is of particular relevance and Scheme 1 illustrates the analogous mechanism with 15 NH 3 and 5 as the substrate.…”

A New Synthetic Approach to Pyrazolo[3,4-c]-1,2,5-oxadiazoles

“…Namely, the Mohr's methodology 8 which involves the preparation of 6-methyl-4-phenyl-4H-pyrazolo[3,4-c]-1,2,5-oxadiazole by oxidation of 5-methyl-4nitroso-2-phenyl-2H-pyrazol-3-ylamine with an alkaline aqueous solution of potassium hypochlorite. Whereas, Bertelson 9 et al reported the synthesis of 4,6-diphenyl-4H-pyrazolo [3,4-c]-1,2,5-oxadiazole from 1,3-diphenyl-4,5-dioximino-2-pyrazoline by heating in acetic anhy-dride. We envisaged that the pyrazolo[3,4-c]-1,2,5 oxadiazole nucleus could be generated through a single step and with a minimal work-up by oxidation, mediated by lead(IV) acetate, of 5-methyl-4-nitroso-2-phenyl-substituted-2H-pyrazol-3-ylamine, 8-14.…”