Phenylhydrazine, reaction with methyl

On reaction with /V-methyl- /V-phenylhydrazine, however, the hydrazone (47) can be isolated, which on further treatment with anhydrous trifluoroacetic acid gives an A/-aLkenylpyrazole (48) (eq. 9). 

It was reported only recently that A-methyl transfer from an oxaziridine to an amine occurs with formation of an N—N bond (79JA6671). N—N bond forming reactions with A-unsubstituted oxaziridines had been found immediately after discovery of this class of compound (64CB2521) and have led to simple hydrazine syntheses (79AHC(24)63). Secondary amines like diethylamine or morpholine are A-aminated by (52) in the course of some minutes at room temperature with yields exceeding 90% (77JPR195). Further examples are the amination of aniline to phenylhydrazine, and of the Schiff base (96) to the diaziridine (97). 

Katritzky and co-workers studied the mechanism of this reaction in detail. His work involved a NMR study of 16 reactions of methyl-, phenyl-, 1,2-dimethyl-, and l-methyl-2-phenylhydrazine with /3-keto esters. In many cases starting materials, intermediates, and products were detected simultaneously. Most reactions proceed by nucleophilic addition of the less hindered hydrazine nitrogen atom to the keto carbon of the keto ester. For example, the pathway given in Scheme 3 for the reaction of methyl 3-oxobutanoate 9 with methyl- or phenyUiydrazine 2 (R = Me or Ph) was found to be dominant. The initially formed addition product 10 dehydrates to hydrazone 11, which then isomerizes to hydrazone 12. Intermediate 12 then cyclizes to pyrazol-3-one 13, which tautomerizes to the kinetically more stable pyrazol-3-otie 14 [87JCS(P2)969]. 

Woodward s strychnine synthesis commences with a Fischer indole synthesis using phenylhydrazine (24) and acetoveratrone (25) as starting materials (see Scheme 2). In the presence of polyphosphor-ic acid, intermediates 24 and 25 combine to afford 2-veratrylindole (23) through the reaction processes illustrated in Scheme 2. With its a position suitably masked, 2-veratrylindole (23) reacts smoothly at the ft position with the Schiff base derived from the action of dimethylamine on formaldehyde to give intermediate 22 in 92% yield. TV-Methylation of the dimethylamino substituent in 22 with methyl iodide, followed by exposure of the resultant quaternary ammonium iodide to sodium cyanide in DMF, provides nitrile 26 in an overall yield of 97%. Condensation of 2-veratryl-tryptamine (20), the product of a lithium aluminum hydride reduction of nitrile 26, with ethyl glyoxylate (21) furnishes Schiff base 19 in a yield of 92%. 

Data of Alves el al. (1978), in 20% ethanol. The intermolecular reference reaction is the general acid catalysed addition of phenylhydrazine to the methyl ether, calculated from feH,o using a = 0.35 and determined for the reaction with o-methoxybenzaldehyde (Bastos and do Amaral, 1979). The EM, which is in some doubt because of possible mechanistic complications, is determined by comparison of the rate constant given (dm3 mol-1 s 1) with the third order rate constant for the reference reaction... 

Metamizole sodium Methamizole sodium, l-phenyl-2,3-dimethyl-4-methylaminopyra-zolone-5-A -sodium methansulfonate (3.2.16), is synthesized in a multi-stage synthesis from acetoacetic ester and phenylhydrazine. Their reaction leads to the formation of 1-phenyl-3-methylpyrazolone-5 (3.2.9). Methylation of this product with methyl iodide gives 1-phenyl-... 

Very little conclusive evidence for the position of the methyl group in 2-methyl-D-mannose is available. Pacsu and Trister4 showed that the sugar reacted with phenylhydrazine in the cold to give a phenylhydrazone but not a phenylosazone. More drastic conditions were required to form the phenylosazone, during which reaction the methyl group was lost with the formation of D-glucosazone. 

The structure of this sugar was established as follows (a) reaction with phenylhydrazine yielded 4-methyl-D-glucosazone 11 (b) oxidation (HOBr) yielded a methylmannonolactone, which exhibited the properties that are characteristic of 8-lactones.7... 

The reaction of 2-thiovioluric acid (69) with hydrazine hydrate in boiling ethanol afforded triazolopyrimidine derivative 70, but in boiling acetic acid yielded N-acetyltriazolo[4,5-d]pyrimidine derivative 71. In the same manner, the N-phenyl and A-methyl-l, 2,3-triazolo derivatives 72 and 73 were obtained through the condensation of 69 with phenylhydrazine and with methylhydrazine, respectively (91MI1) (Scheme 13). 

Diphenylhydrazine is oxidized to diphenylnitrosamine (50%) by potassium superoxide. The same reagent also oxidizes 1-methyl-1-phenylhydrazine, but here the nitrosamine is a minor product the major reaction is deamination. A better meAod of oxidative deamination of some 1,1-disubstituted hydrazines and hydrazinium salts is reaction with nitrous acid. Thus, several hydrazinium salts MezRN NHi X were deaminated to the tertiary amine by treatment with nitrous acid. The method has also been used to deaminate IV-aminoheterocyclic compounds for example, some 1,2,3-triazoles are conveniently prepared by deamination of the corresponding 1-aminotriazoles with nitrous acid. °... 

In a similar reaction, phenylhydrazine converted methyl 2-methyl-2-(trimethylsiloxy)cyclo-propanecarboxylate (11) into the phenylhydrazone of methyl 4-oxopentanoate. The formation of hydrazine adducts can be rationalized by ring opening to the y-oxocarboxylates and reaction with the oxocarbonyl group. 

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