Acetophenone phenylhydrazone

The present procedure was developed from those of Wallach and Freylon, based upon the general method discovered by Leuckart. a-Phenylethylamine also can be prepared satisfactorily by the reduction of acetophenone oxime with sodium and absolute alcohol or sodium amalgam, but the reagents are more expensive and the processes less convenient. The amine has been obtained by reducing acetophenone oxime electro-lytically, by reducing acetophenone phenylhydrazone with sodium amalgam and acetic acid, from a-phenylethyl bromide and hexamethylenetetramine, and by the action of methyl-magnesium iodide upon hydrobenzamide, as well as by other methods of no preparative value. 

An important general method of preparing indoles, known as the Fischer Indole synthesis, consists in heating the phenylhydrazone of an aldehyde, ketone or keto-acfd in the presence of a catalyst such as zinc chloride, hydrochloric acid or glacial acetic acid. Thus acetophenone phenylhydrazone (I) gives 2-phenylindole (IV). The synthesis involves an intramolecular condensation with the elimination of ammonia. The following is a plausible mechanism of the reaction ... 

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>. 

Prepare acetophenone phenylhydrazone by warming a mixture of 20 g (0.167 mol) of acetophenone and 18 g (0.167 mol) of phenylhydrazine (CAUTION, in handling) with 60 ml of ethanol and a few drops of glacial acetic acid. Filter the cold reaction mixture, wash the solid with dilute hydrochloric acid followed by about 12 ml of cold rectified spirit. Recrystallise a small portion from ethanol and thus obtain a sample of pure acetophenone phenylhydrazone as a white solid, m.p. 106 °C. 

Treatment of a mixture of acetophenone phenylhydrazone and dimethyl acetylenedi-carboxylate with aluminium chloride gives the ene hydrazone 98, which undergoes a spontaneous Fischer indole reaction to yield the pyrrole 99 with elimination of aniline (equation 41)62. 

Acetophenone phenylhydrazone, heated with zinc chloride at 170°, affords 2-phenylindole in yield of 72-80%. "... 

The Fischer indole synthesis can be carried out very simply and without use of an acid catalyst by heating a phenylhydrazone in ethylene glycol for a sufficient period. Acetophenone phenylhydrazone afforded 2-phenylindole in 54% yield after... 

Mit aromatischen Carbonsaure-chloriden sind 4-Aroyl-l H-pyrazole zuganglich, z. B. aus zwei mol Benzoylchlorid pro mol Acetophenon-phenylhydrazon 4-Benzoyl-1,3,5-triphenyl-lH-pyrazol( 100% Schmp. 174-176°) und aus 4-Methyi-acetophenon-phenylhydrazon4-Ben-zoyl-1,5-diphenyI-3-(4-methyl-phenyl)-lH-pyrazol (72% Schmp. 170- 172 )748 ... 

Acetophenon-phenylhydrazon und Butindisaure-dimethylester cyclisieren bei 190° in Gegen-wart von Aluminiumoxid (30 min Bombenrohr/Benzol) zu 4,5-Dimethoxycarbonyl-l, 3-diphe-ny l-1 H-pyrazol (59% Schmp. 154°)950. (Methyl-nitrosamino)-essigsaure und Butindisaure-dimethylester bilden beim Erhitzen in Acetanhydrid 3,4-DimethoxycarbonyI-1-methyl-1 H-pyrazol (60% Schmp. 68 69°)951 ... 

Acetophenone phenylhydrazone 908 Equimolar amounts of acetophenone (40 g) and phenylhydrazine (36 g) are heated for 1 h on the water-bath, and the product is dissolved in hot ethanol (80 ml). On rubbing and cooling in ice, the phenylhydrazone crystallizes, amounting to 54-57 g after washing with 25 ml of ethanol a further 4-10 g are provided by concentration of the mother liquor and washings. When dried over calcium chloride in a vacuum-desiccator, the phenylhydrazone (total yield 61-64 g, 87-91 %) has m.p. 105-106°. 

Detailed directions for the preparation of 2-phenylindole from acetophenone phenylhydrazone are given in Organic Syntheses 94... 

A mixture of freshly prepared acetophenone phenylhydrazone (53 g) and powdered anhydrous zinc chloride (250 g) is stirred manually while heated in an oil-bath at 170°. After 3-4 min the mass liquefies and white fumes are evolved. The oil-bath is then removed and stirring continued for a further 5 min, after which working up affords a 72-80% yield of 2-phenylindole, m.p. 188-189°. 

Acetophenone phenylhydrazone (XXVI) yields the hydrazidoyl bromide XXVII upon bromination in glacial acetic acid ( ). 

AlClg added under argon to a mixture of acetophenone phenylhydrazone and dimethyl acetylenedicarboxylate in benzene, and stirred 1 hr. at room temp. 2,3-bis(methoxycarbonyl)-5-phenylpyrrole. Y 74%. F. e. s. J. Barluenga, F. Palacios, and V. Gotor, Synthesis 1975, 642. 

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