Hydrazine, phenyl-, reaction product with

Iwakawa et al. studied the reaction of 3-acetonyl-5-cyano-l,2,4-thiadiazole 72 with a series of 4-substituted phenylhydrazine hydrochlorides. When electron-donating substituents were used (e.g., methyl and methoxy) in the phenyl ring of the hydrazine, the reaction proceeded via a Fischer-indole mechanism to give indoles 73 as the sole product. In contrast, reaction of 72 with phenylhydrazine and 4-chlorophenylhydrazine gave only small amounts of indole 72, but much higher yields of the pyrazole 74. The authors described in detail the respective reaction mechanisms... 

It was reported that 7-chloro-3-phenyl-4H-pyridazino[6,1 -c ]-1,2,4-triazine underwent reaction with hydrazine to give the unexpected product (146) (69AC(R)552). However, it was later established that the assigned structure for this reaction product was incorrect, and the correct hydrazino structure (147) for this product was confirmed by an independent synthesis (70S180). 

The stereoselective synthesis of both trans-88 and cis isomers 89 of pyrazo-lines was reported in [62] (Scheme 2.22). The configuration of the reaction products depends on the conditions of the cyclocondensation involving unsaturated ketones 87 and methyl(phenyl)hydrazines or (thio)semicarbazide. In boiling pyridine the treatment yields only raws-pyrazolines, while reaction in ethanol with catalytic amounts of hydrochloric acid leads mainly to the cis... 

The products are known as oximes from hydroxyl amine and hydra-zones from the hydrazine. Phenyl hydrazine yields phenyl hydrazones of the particular aldehyde or ketone with which it reacts. The reaction is of value in connection with the carbohydrates because these react as aldehyde or ketone compounds and because the hydrazones formed undergo further reaction with phenyl hydrazine. 

The relative ratio of these products depends on the excess of derivatization reagent and the pH of the reaction mixtures. The chemical origin of products of the reaction of phenyl hydrazine with unsaturated carbonyl compounds depends on the same factors and, moreover, on the order of the components mixing (it exerts the influence on the current pH of reaction media). The 2-pyrazolines have resulted, in some cases, as the sole reaction products instead of hydrazones ... 

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]. 

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. 

Condensation of ethyl acetoacetate with phenyl hydrazine gives the pyrazolone, 58. Methylation by means of methyl iodide affords the prototype of this series, antipyrine (59). Reaction of that compound with nitrous acid gives the product of substitution at the only available position, the nitroso derivative (60) reduction affords another antiinflammatory agent, aminopyrine (61). Reductive alkylation of 61 with acetone in the presence of hydrogen and platinum gives isopyrine (62). Acylation of 61 with the acid chloride from nicotinic acid affords nifenazone (63). Acylation of 61 with 2-chloropropionyl chloride gives the amide, 64 displacement of the halogen with dimethylamine leads to aminopropylon (65). ... 

Dimethyl-I,l -biphenyl has been prepared by a wide variety of procedures, but few of these are of any practical synthetic utility Classical radical biarjl syntheses such as the Gomberg reaction or the thermal decomposition of diaroyl peroxides give complex mixtures of products m which 4,4 dimethyl-l.l -biphenyl is a minor constituent A radical process maj also be involved in the formation of 4,4 dimethyl-1, l -biphenyl (13%) by treatment of 4-bromotoluene with hydrazine hydrate 5 4,4 -Dimethyl-l,l -biphenyl has been obtained in moderate to good yield (68-89%) by treatment of either dichlorobis(4-methyl phenyl)tellurium or l,l -tellurobis(4-methylbenzene) with degassed Raney nickel in 2 methoxyethyl ether 6... 

Electrophilic substitution of the ring hydrogen atom in 1,3,4-oxadiazoles is uncommon. In contrast, several reactions of electrophiles with C-linked substituents of 1,3,4-oxadiazole have been reported. 2,5-Diaryl-l,3,4-oxadiazoles are bromi-nated and nitrated on aryl substituents. Oxidation of 2,5-ditolyl-l,3,4-oxadiazole afforded the corresponding dialdehydes or dicarboxylic acids. 2-Methyl-5-phenyl-l,3,4-oxadiazole treated with butyllithium and then with isoamyl nitrite yielded the oxime of 5-phenyl-l,3,4-oxadiazol-2-carbaldehyde. 2-Chloromethyl-5-phenyl-l,3,4-oxadiazole under the action of sulfur and methyl iodide followed by amines affords the respective thioamides. 2-Chloromethyl-5-methyl-l,3,4-oxadia-zole and triethyl phosphite gave a product, which underwent a Wittig reation with aromatic aldehydes to form alkenes. Alkyl l,3,4-oxadiazole-2-carboxylates undergo typical reactions with ammonia, amines, and hydrazines to afford amides or hydrazides. It has been shown that 5-amino-l,3,4-oxadiazole-2-carboxylic acids and their esters decarboxylate. 

B. 4-Phenyl-l-carbethoxysemicarbazide. In a 1-1. three-necked round-bottomed flask equipped with a liquid-sealed mechanical stirrer (Note 3), a constant-pressure dropping funnel, and a reflux condenser fitted with a drying tube containing silica gel is placed a solution of 52 g. (0.5 mole) of ethyl hydrazine-carboxylate in 550 ml. of dry benzene (Note 4). The solution is cooled in an ice bath, and the stirrer is started. To the solution is added 59.7 g. (55 ml., 0.5 mole) of phenyl isocyanate (Note 5) dropwise over a period of 45 minutes. After about one-half of the isocyanate has been added, a white precipitate of the product appears, and the reaction mixture becomes progressively thicker. After addition is complete the ice bath is removed, and the mixture is stirred at room temperature for 2 hours and then is heated under reflux for 2 hours. The suspension is allowed to cool to room temperature, and 4-phenyl-1-carbethoxysemi-carbazide is isolated by suction filtration, washed with 500 ml. of benzene, and dried in a vacuum desiccator. The yield is 108 g. (97%), m.p. 151-152°. The product is not further purified before being used in the next step. It may be recrystallized from ethyl acetate to yield white crystals, m.p. 154-155°, vmax 1645, 1687, 1797, and 3300 cm.-1 (Note 6). 

Reaction of the 2-acetoxy-3(2//)-furanones (526) with monosubstituted hydrazines gives good yields of the pyridazinium-5-olates (527) together with varying amounts of isomeric products. Alkyl derivatives (527 R = alkyl) have also been prepared by base-catalyzed alkylation (Mel, Me2SO4, PhCH2Cl) of 3-methyl-6-phenyl-5-ethoxycarbonyl-4( 1 //)-pyridazinone. Reduction of the diphenyl compound 527 (R = Ar = Ph) by zinc and hydrochloric acid gives 3-ethoxycarbonyl-5-hydroxy-5-methyl-l,2-diphenyl-2-pyrrolin-4-one (528 R = Ar = Ph) (Scheme 21... 

A similar type of internal coordination has been observed starting from hydrazine derivatives. Thus, reaction of dimethylchloromethylsilyl chloride with trimethylsilyl-derivative of l-phenyl-2-acetylhydrazine leads to transsilylation product that rearranges into the O — Si compound. However, this isomerization did not occur when starting from l-phenyl-2-trifluoroacetylhydrazine.51... 

A number of ferrocene-containing 1,3,4-oxadiazoIes have been prepared. The reaction of ferrocenecarboxhydrazide with triethyl orthoformate gave three products, the principal one being 2-ferro-cenyl-l,3,4-oxadiazole (126 R = H). 76 2-Phenyl-5-ferrocenyl-l,3,4-oxadiazole (126 R = CgH5) and 2,5-diferrocenyl-l,3,4-oxadiazole (126 R = ferrocenyl) were prepared from the appropriate 1,2-diacyl-hydrazines.117 A number of other ferrocenyloxadiazoles, including the bis compound 127, were prepared in a similar manner.117 The oxadi-... 

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