Phenyl phenylhydrazine

Di(phenyl)-phenylhydrazine. See Triphenyl-hydrazine in future volume... 

Fructose (V) under similar conditions gives first the phenylhydrazonc (Va) by the direct condensation of the >C 0 group of carbon atom 2 with one molecule of phenylhydrazine. The second molecule of phenylhydrazine then oxidises the primary alcohol group of carbon atom 1 to the -CHO group by removal of two atoms of hydrogen, which as before serve to reduce the phenyl-hydrazine to aniline and ammonia. The compound (Vb) which is thus produced then undergoes direct condensation with the third molecule of phenylhydrazine, giving the osazone of fructose, or fructosazone (Vc). 

Phenylhydrazine on exposure to light slowly darkens and eventually becomes deep red in colour salts of the base share this property but to a lesser degree, the sulphate and acetate (of the common salts) being most stable to light. Phenylhydrazine is largely used in organic chemistry to characterise aldehydes and ketones as their phenyl-hydrazones (pp. 342, 345), and carbohydrates as their osazones (pp. 136-140). It is readily reduced thus in the process of osazone formation some of the phenylhydrazine is reduced to aniline and ammonia. On the... 

Mix 6 2 ml. (6 4 g.) of pure ethyl acetoacetate and 5 ml. of pure phenylhydrazine in an evaporating-basin of about 75 ml. capacity, add 0 5 ml. of acetic acid and then heat the mixture on a briskly boiling water-bath (preferably in a fume-cupboard) for I hour, occasionally stirring the mixture with a short glass rod. Then allow the heavy yellow syrup to cool somewhat, add 30-40 ml. of ether, and stir the mixture vigorously the syrup may now dissolve and the solution shortly afterwards deposit the crystalline pyrazolone, or at lower temperatures the syrup may solidify directly. Note. If the laboratory has been inoculated by previous preparations, the syrup may solidify whilst still on the water-bath in this case the solid product when cold must be chipped out of the basin, and ground in a mortar with the ether.) Now filter the product at the pump, and wash the solid material thoroughly with ether. Recrystallise the product from a small quantity of a mixture of equal volumes of water and ethanol. The methyl-phenyl-pyrazolone is obtained... 

Prepare a solution of phenylhydrazine by dissolving 1 0 g. of phenyl-hydrazine hydrochloride and 1 5 g. of crystallised sodium acetate in 10 ml. of water if the resulting solution is turbid, filter. Add a solution of 0 5 ml. of cycZohexanone in 8 ml. of water to the reagent... 

Liberate the free base by adding to the phenylhydrazine hydrochloride 125 ml. of 25 per cent, sodium hydroxide solution. Extract the phenyl-hydrazine with two 40 ml. portions of benzene, dry the extracts with 25 g. of sodium hydroxide pellets or with anhydrous potassium carbonate thorough drying is essential if foaming in the subsequent distillation is to be avoided. Most of the benzene may now be distilled under atmospheric pressure, and the residual phenylhydrazine under reduced pressure. For this purpose, fit a small dropping funnel to the main neck of a 100 ml. Claisen flask (which contains a few fragments of porous porcelain) and assemble the rest of the apparatus as in Fig. II, 20, 1, but do not connect the Perkin triangle to the pump. Run in about 40 ml. of the benzene, solution into the flask, heat the latter in an air bath (Fig. II, 5, 3) so that... 

Phenyl-3-oxopropanoic acid (25 mmol) and EtjN (87.5 mmol) were dissolved in THF (150 ml) and cooled to —40°C. Ethyl chloroformate (27.5 mmol) was added dropwise to this solution and then the reaction mixture was stirred for 30 min at —20°C. Di-n-hexylamine (27.5 mmol) was added to the suspension and it was stirred at room temperature for an additional hour. The reaction mixture was diluted with water (100 ml) and extracted with ether (400 ml). The extract was washed with aq. 5% HCl (100 ml) and brine (2 X 100 ml) and dried over NajSO. The crude amide was obtained by removal of the solvent in vacuo and phenylhydrazine (25 mmol) was added. The mixture was heated to 100°C for 30 min. The residue was held in vacuo to remove the water formed and then powdered ZnCl2 (125 mmol) was added. The mixture was heated at 170"C with manual stirring for 5 min. The cooled residue was dissolved in acetone (100 ml) and diluted with ether (500 ml). Water (100 ml) was added. The organic layer was separated and washed successively with 5% aq. HCl (100 ml) and brine (2 x 100 ml) and dried over NajSO. The solvent was removed in vacuo, and the residue was recrystallized from EtOAc-hexane. The yield was 79%. 

Phenyl-l,2-dithiolylium salt (483) with hydrazine, methylhydrazine or phenylhydrazine yielded the corresponding pyrazole (485) via the intermediates (484a-c). The ring-fused system (486) is a convenient source of the ring-fused pyrazole (487) when treated with hydrazine (see Chapter 4.31). 

If there is no phenyl substituent in the 3-position the amination ability decreases. The acyloxaziridine (104) yields only 11% of a semicarbazide derivative with piperidine. In the presence of strong bases an intramolecular amination competes. Compound (104) reacts with methoxide within a couple of seconds to give phenylhydrazine carboxylic ester (106), and with cyclohexylamine to give the substituted semicarbazide (107). A diaziridinone (105) is assumed to be the common intermediate, formed by an intramolecular reaction from deprotonated (104) (67CB2600). 

Phenyl ether-diphenyl mixture (vapour) Phenylethylene, see Styrene, monomer Phenyl glycidyl ether Phenylhydrazine Phosdrin (Mevinphos )... 

Normally, phenylhydrazine reacts with the enol form of 1,1,1-trifluorometh-ylpentane-2,4-dione to give 5-methyl-l-phenyl-3-tnfluoromethylpyrazole as the major product. However, the use of pyrrolidine as a transient carbonyl-blocking group can completely reverse the regiochemistry of the addition and leads to 3-methyl-l-phenyl-5-trifluoromethylpyrazole [102] (equation 88)... 

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]. 

More recently, Tietze and Steinmetz (96SL667) used the patented polystyrene-resin methodology for for the solid-phase synthesis of a large number of diverse )3-keto esters 40a-h. These were reacted with phenylhydrazine in THF at room temperature to give hydrazones 41a-h that were then cychzed into 2-phenyl 5-substituted pyrazol-3-ones 42a-h by heating in toluene at 1(X)°C (Scheme 12). 

To obtain information about the cyclization pathway, an analogous reaction was carried out with phenylhydrazine (in this case, positions 3 and 5 of the forming pyrazole are nonequivalent) (69ZOR1179). The only reaction product (yield 65%) appeared to be l-phenyl-5-methylpyrrazole (108). 

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. 

Likewise, the ynaminoketones with phenylhydrazine give a similar mixture of isomerie l-phenyl-3-dialkylammo-5-methylpyrazoles (369) and l-phenyl-5-dialkylamino-3-methylpyrazoles (370) in the same 3 4 ratio (87ZOR1635). 

Pyridine has been phenylated with the following free-radical sources benzenediazonium chloride with aluminum trichloride the Gomberg reaction " phenylhydrazine and metal oxides A -nitroso-acetanilide dibenzoyl peroxide phenylazotriphenylmethane di-phenyliodonium hydroxide and electrolysis of benzoic acid. ° Although 2-phenylpyridine usually accounts for over 50% of the total phenylated product, each of the three phenyl derivatives can be obtained from the reaction by fractional recrystallization of the... 

Under more vigorous conditions such as prolonged heating, the degradation of these isoxazoles is also effected by weaker nucleophilic reagents. Thus, 5-methylisoxazole (113) on treatment with ammonia is partly converted into cyanoacetoneimine (112) and when refluxed with phenylhydrazine yields l-phenyl-3-methyl-5-aminopyrazole (115), in the latter case undoubtedly via the intermediate formation of cyanoacetone (114). ... 

Treatment of 5-(dichlorophenylmethyl)-3-phenyl[ 1,2,4]triazin-6( 1H)-one 357 or the respective ketone with hydrazine or phenylhydrazine gave 358, which were cyclized with acetic acid to pyrazolo[4,3-c][ 1,2,4]triazines 359 (84PHA504 85MI2) (Scheme 77). 

Phenyl glycidyl ether Phenylhydrazine Phenyloxirane Phosdrin... 

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. 

Condensation with phenylhydrazine results in phenyl-pyrazole 262. The regiospecificity results from intermediate phenylhydrazone formation of the more... 

Hydrazones are also useful substrates in the preparation of pyrazoles. Reaction of N-monosubstituted hydrazones with nitroolefins led to a regioselective synthesis of substituted pyrazoles <060L3505>. lf/-3-Ferrocenyl-l-phenylpyrazole-4-carboxaldehyde was achieved by condensation of acetylferrocene with phenylhydrazine followed by intramolecular cyclization of the hydrazone obtained under Vilsmeier-Haack conditions <06SL2581>. A one-pot synthesis of oxime derivatives of l-phenyl-3-arylpyrazole-4-carboxaldehydes has been accomplished by the Vilsmeier-Haack reaction of acetophenone phenylhydrazones <06SC3479>. 

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