Formazan methylation

With the synthesis of the benzylidene hydrazones of selenazoles, it was possible to prepare formazans containing a selenazole ring. Of the compounds already described (Section I,C,1), 2-benzylidene-hydrazino-4,5-diphenyl- and 2-benzylidenehydrazino-4-methyl-5-carb-ethoxy-selenazole were used to couple with diazonium salts in order... 

As the reaction sequence of Scheme 12-38 can be stopped at the stage of the oo-methylglyoxal phenylhydrazone (12.78), it is possible to synthesize asymmetrically substituted formazanes (12.80, Ar = Ar ) by reacting acetone with one equivalent of a diazonium ion ArNJ under acidic conditions and then coupling the co-methyl-glyoxal phenylhydrazone with Ar NJ in alkaline solution. 

Other methylketones and differently activated methyl compounds can also be used to synthesize formazanes in the same manner, as was shown, for example, in early work by Wahl and Lebris (1954) on the coupling with 2-methylbenzothiazole (Scheme 12-39). 

Ethyl formate34,52 or orthoformate5 3,54 reacts with two equivalents of phenylhydrazine to yield 1,5-diphenylformazan (11) the reaction takes place under acidic conditions and involves an oxidation. Under basic conditions, ethyl nitrate reacts at the methylene position to yield 3-methyl-1,5-diphenylformazan (37) which can also be obtained from the reaction of phenyl-azoethane (38) with isoamyl nitrite (Scheme 4).8,68 Aryl hydrazines react with a variety of s-triazines (39) to yield 1,5-diaryl formazans with hydrogen, methyl, or phenyl groups in the 3-position as in 40 (Eq. 6).56 Hydrazines have also been reported to react with benzotrichloride55,658 and sym-diamino tetrazine659 to yield formazans. 

Absorption spectra of formazans have been studied in detail. Almost all formazans exhibit UV/visible spectra between 300 and 600 nm.1,2,12,13,40,62,325 326 The absorption maxima are very sensitive to substituent effects. For example, the 1,5-diphenyl formazan 185 when X is hydrogen, methyl, phenyl, cyano, and mercapto shows a band at 420, 410, 470, 504, and 590nm in ethanol, respectively. The 3-chloro derivative 186 when X is hydrogen, iodine, bromine, chlorine, and fluorine has a band at 433,433,430,421, and 417 nm, respectively. Table 13 shows the influence of substituents on the absorption maxima in the trisubstituted formazans 3. Table 14 shows the influence of substituents on the absorption maxima of... 

In warm mineral acid, formazans (195) rearrange to a benzotriazine (196) eliminating an amine (Scheme 29).8,26 27 334 338 339 H owever, when R is methyl, phenylazo, or oxalyl, the main product is the phenazine 197 along with a trace amount of the benzotriazine.340 The mechanism of this reaction is not well understood.341 345... 

The alkylation of formazan anions (166) with methyl iodide yields the A-methylformazan (202) which cannot be prepared by direct methods (Scheme 31).4 However, formazans that contain hydroxyaryl (203) or heterocyclic groups (205) alkylate preferentially on these groups to yield the alkylation products 204349 and 206,346-348 respectively (Eqs. 24,25). Although formazans are resistant to acylation,334,350 351 it can be accom-... 

Verdrazyls, e.g., 210, are a class of cyclic free radicals, with characteristic ESR spectra and intense colors. They represent a special case of oxidation of formazans and can be obtained from the methylation of and simultaneous or subsequent dehydrogenation of formazans.359-361 Ver-... 

Double Coupling of Diazonium Compounds. Some compounds with an activated methyl group can form symmetric formazans with strong diazo compounds by double coupling ... 

Anodic oxidation of formazanes in MeCN-TEAP at a platinum anode produces tetrazolium salts in good yield [120, 121]. The ring closure probably takes place through the dication. A similar anodic coupling is the oxidation of 2-acetylpyridine phenyl-hydrazone to 3-methyl-l-phenyl-8-azaindazolium perchlorate [41], of benzilmonoxime phenylhydrazone to 2,4,5-triphenyl-1,2,3-triazole-1-oxide, and of 3-hydroxyiminomethyl-eneamino-6-chloropyridazine to 6-chloro-5-triazole[l,5-Z>]pyridazine-3-oxide [74, 122]. 

These sugar compounds show all the characteristic properties of the formazans a brilliant red color, complexing with salts of heavy metals, and ready oxidation to colorless compounds. Nevertheless, further evidence was sought, in order to prove that they really belong to the formazan group. According to all current views on the mechanism of formazan formation, secondary phenylhydrazones, such as a 2-methyl-2-phenyl-... 

The formazan reaction offers a means for clarifying the structure of the mixed A and mixed B osazones. The former was described by Voto6ek and Vondra6ek as acyclic n-glucose l-(iV -phenyl)-2-(Ar -methyl-A -phenyl)osazone, and the latter as acyclic n-glucose l-(A -methyl-i r -phenyl)-2-(V -phenyl)osazone. The Percivals assigned the same n-fruc-topyranose l-(Ar -phenyl)-2-(V -methyl-Ar -phenyl)osazone structure to the compounds, but differentiated them as probable syn and avli forms. 

Of these proposed structures, only that of the n-glucose l-(A -methyl-V -phenyl)-2-(A -phenyl)osazone, suggested by Voto6ek and Vondrafek for mixed osazone B, is theoretically unsuited for formazan formation since... 

However, since mixed osazone A undergoes no formazan reaction, even in alkaline solution, it would appear that the n-glucose l-(iV -methyl-iV -phenyl)-2-(iV -phenyl)osazone structure, - hitherto thought to be incapable of coupling, should be assigned to this substance (instead of to the mixed osazone B). This view is fully confirmed by recent work of Henseke and Hautschel. ... 

The fact that, from periodate-oxidized methyl a-n-glucopyranoside, a mono-(formazan) could be prepared,constitutes evidence in favor of the latter s hemiacetal structure (or the hydrate form) as expressed in the preceding formula. 

Performing immunoblot analysis and quantification of formazan produced by its specific NADPH diaphorase activity, Planitzer et al. (2001) found nNOS to be enriched in rat skeletal muscles with a high proportion of fast-switch myofibres. The NO donors l-hydroxy-2-oxo-3-(N-methyl-6-aminohex-yl)-3-methyl-l-triazene (NOC-9) and S-nitroso-N-acetyl-D,L-penidllamine both reduced cytochrome oxidase activity in all myofibres. 

N=N— 1 azobenzene, methyl orange, benzocinnoline, formazane —N N j benzenediazonium chloride, diazotised sulfanilic acid... 

The structure present in (XX) is necessary for the reaction it therefore takes place neither with hydrazones derived from JV-substituted phenylhydrazines, for example, methyl phenylhydrazine, nor with any hydrazones derived from ketoses, nor with cyclic aldose phenylhydrazones. The reaction has proved of value in distinguishing these different forms of hydrazone . The reversible oxidation of the coloured formazans into colourless tetrazolium derivatives (XXIII) has proved of value as an indicator in biological S5rstems. 

Benzyl-1 //-benzimidazol-2-yl)-3-methyl-1 -(4-nitrophenyl) formazan, B-00172 1 -(5-Chloro-2-pyridylazo)-2-naphthol, C-00259... 

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