Phenylhydrazine, reaction with products

In an altogether different type of approach, the hydrazone is formed in situ as a lithium salt. Wilson et al. (80JHC389) described this approach in the one-pot synthesis of 5-aryl-2-phenylpyrazol-3-ones 72a-f from the corresponding hydrazones 65a-f (Scheme 20). The latter were obtained by condensing ketones 64a-f with phenylhydrazine. Treatment of hydrazones 65a-f with n-butyllithium in dry THF, followed by the addition of half a molar equivalent of diethyl carbonate 67 and then quenching the reaction mixture with hydrochloric acid, produced pyrazol-3-ones 72a-f, along with products 71. The yields of the products 72 are in the range 22-97%. Four intermediates—66a-f, 68a-f, 69a-f, and 70a-f— were proposed for this reaction. 

The cyclization of l-alkoxybut-l-en-3-ynes with hydrazine was first achieved by Franke and Kraft (55AG395). By heating 1-methoxybut- l-en-3-yne with hydrazine sulfate in an aqueous alcohol medium they obtained 3(5)-methylpyrazole (13) in high yield. Winter (63HCA1754) used the cyclization of 1-methoxybut-l-en-3-yne with hydrazine hydrate and phenylhydrazine to establish the structure of the initial enyne ether [in this case a mixture of l-phenyl-3(5)-propylpyrazoles was obtained]. The reaction with hydrazine sulfate gives only one product, 3(5)-propyl-pyr azole. 

Reducing sugars can be detected by reaction with phenylhydrazine to yield a hydrazone product, except the result of the reaction is not what one might imagine giving the structure of aldoses and ketoses. Glucose, for example, can react with phenylhydrazine to yield the anticipated... 

Disubstituted 1,2,3-triazoles are usually minor components in the product mixtures obtained from reactions of triazole with electrophiles (see Section 5.01.5). The few regioselective syntheses of such compounds include a reaction of aminoacetophenones 1235 with hydrazines. The reaction with methylhydrazine proceeds well without any catalysis, but that with phenylhydrazine requires cupric chloride as a catalyst. It is assumed that hydrazone 1236 that forms in the first step is in a tautomeric equilibrium with its azo form 1237. However, it is not clear how bond formation between the nitrogen atoms and oxidation to the triazole system occurs. 4-Aryltriazoles 1238 are obtained in 50-66% yield (Scheme 205) <2003SC3513>. 

Under the action of phenylhydrazine or 5-amino-3-phenylpyrazole on pyran 59b only benzaldehyde phenylhydrazone 271 is formed, probably, as the result of pyran retro-cleavage (82M53). A similar reaction with malononitrile, leading to pyran 59a, a product of formal displacement of a cyanoacetic moiety, possibly results from a similar cleavage (82M53) (Scheme 108). 

Carboxy-2-pyridylthio)propionic acids, prepared by the reaction of 2-mercatopyridin-3-carboxylic acid with 3-bromopropionic acid in aqueous KOH, undergo cyclization upon treatment with anhydrous sodium acetate and acetic anhydride to afford 2,3-dihydrothiopyrano[2,3-3]pyridin-4(4//)-ones. These products undergo further reaction with phenylhydrazine to give the phenylhydrazone (isolated) and then Fischer indole cyclization to give novel 5/7,1177-pyrido[2, 3 2,3]thiopyrano[4,3-3]indoles <2000JHC379>. 

Poly(chalcones) (183), which themselves are the products of Knoevenagel condensation of aromatic dialdehydes and diacetyl compounds, have been transformed into polylpyrazo-lines) (185) by reaction with phenylhydrazine (184) (72MI11107). The reaction (Scheme 88) was conveniently conducted in excess phenylhydrazine and yielded polymers which were described as being brilliantly fluorescent in solution. The poly(pyrazolines) (185) exhibited glass transition temperatures between 150 and 210 °C and were stable, in some cases, up to 630 °C. 

The oxidation of phenylhydrazine and 1,2-disubstituted hydrazines to hydrazones and diazenes by CI2C proceeds via formation of unstable azomethine imines.95 The conversion of alcohols into alkyl halides is achieved by reaction with CCI4 (or CBr4) in DMF under electrochemical reduction.96 The reaction of dihalocarbene X2C with DMF to form a Vilsmaier reagent (93) is proposed as the key process. The reaction of simple isocyanates (RNCO) with dimethoxycarbene normally gives hydantoin-type products. In the reaction with vinyhsocyanates such as (94), however, hydroindoles (95) are formed in good yields.97... 

Reaction of C-acetyl-7V-(2-benzimidazolyl)methanehydrazonoyl chloride 21b with phenylhydrazine yielded a product that was assigned structure 271. No spectral data were given to substantiate such an assignment, however (83MI1). Also, hydrazinolysis of 10b with hydrazine hydrate gave the hydrazidine 272 (80JHC209). 

Some reactions of 2,3,4-trisubstituted isoxazolium salts (exemplified by 70) leading to ring transformations, are summarized in Scheme 14.180 Other active methylene compounds such as ethyl acetoacetate and cyano-acetamide give analogous results to those with diethyl malonate products of base-induced ring opening by ethoxide are also obtained. When the reaction with phenylhydrazine is carried out in the presence of sodium hydroxide in ethanol the product is 71, presumably formed via the im-inoketene 72. 

Rather surprisingly, the product of the reaction between the 3,4-diphenyl-l,2-dithiolium salt and ammonia in ethanol was found to contain 4,5-diphenyltrithione, but no isothiazole, although the reaction with phenylhydrazine gave a 95% yield of the corresponding pyrazole.46... 

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. °... 

Scheme 11. The Fischer Indole reaction of phenylhydrazine (I) with 3-heptanone (II) giving two indole products.

Bisbromomethyl derivatives are cyclized by reaction with liquid methylamine at - 80 C [2061]. Hydrazine and its simple derivatives sometimes behave as mono-functional compounds, for example, in a reaction with the dibromoarylacetic ester (81.1) [2658, 2687]. Under these conditions, phenylhydrazine ves a mixture of the isoindole and isoindoline. An unconventional synthesis of a fused pyrrole is that in which a dihalide is heated with ethyl chloroacetate and pyridine in DMF. The pyridine reacts and becomes an integral part of the product [2985]. 

Methyl 2-trimethylsilyloxycyclopropanecarboxylates behave as 4-oxoalkanoate equivalents and react with hydrazine to give 4,5-dihydro-3(2/f)-pyridazinones in excellent yield, though pyridazines are not formed with phenylhydrazine <84S786>. A mixture of regioisomers is obtained when cis-aconitic anhydride is allowed to react with methylhydrazine free base in dimethoxyethane, but reaction with the sulfate in water gives the 4-carboxymethyl compound as the sole product <83H(20)2347>. 

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