Phenylhydrazine, reaction with ketones

The classic and most convenient synthesis of the indole moiety is that of Emil Fischer. Recent examples of its use for drug synthesis includes one preparation of the nonsteroidal antiinflammatory agent, indoxole (2). Reaction of ketone 1 with phenylhydrazine in acetic acid leads directly to indoxole (2). Alternately, anisoin (3) can be reacted... 

Constitution of the Esters of the (3-Ketocarboxylic Acids and of the P-Diketones.—Ethyl acetoacetate is taken as example. It reacts like a ketone with phenylhydrazine, bisulphite, and other ketone reagents on the other hand it shows an acid reaction, it dissolves in alkalis, and gives the colour reaction with ferric chloride characteristic of ends and also of phenols. From this double behaviour it was formerly concluded that it was either purely ketonic or purely enolic and that the reactions in the other form were to be attributed to a rearrangement caused by the reagents used. The true state of affairs was first disclosed by... 

Reactions characterizing aziridinyl ketones as polyfunctional compounds are also described in the literature. An example is a widely studied [11, 15, 72, 73, 74] reaction of ketones 18 with phenylhydrazine in which the main products are pyrazole derivatives 55. 

Given the structure or name of an aldehyde or ketone, write an equation for its reaction with the following nucleophiles alcohol, cyanide ion, Grignard reagent or acetylide, hydroxylamine, hydrazine, phenylhydrazine, 2,4-dinitrophenylhydrazine, primary amine, lithium aluminum hydride, and sodium borohydride. 

The oxidants dimethyl sulfoxide and nitroso compounds react easily with oL-bromo ketones and convert them into a-dicarbonyl compounds. The reaction with nitroso compounds is usually carried out in the presence of pyridine and proceeds through a nitrone stage. Phenacyl bromide (a-bromoacetophenone) is thus transformed first into phenacylpyridinium bromide and further, with nitrosobenzene, into a-ketoaldonitrone, which is subsequently treated with hydroxylamine to give phenylglyoxal monoxime or with phenylhydrazine to give phenylglyoxal osazone [985] (equation 411). 

Most classes of VOCs found in indoor environments are sampled onto sorbents by adsorption but highly reactive VOCs like carbonyl compounds are sampled by chemical reactions with the sorbent. Thus aldehydes and ketones are sampled by their reactions with sorbent gels coated with 2,4-dinitro-phenylhydrazine to form stable hydrazones [38-40]. Similarly, formaldehyde has been sampled by its reaction with N-benzylethanolamine to give 3-benzyl-oxazolidine [41,42]. 

Phenylhydrazones are best prepared in dilute acetic acid solution use of more concentrated acetic acid can lead to formation of 1-acetyl-1-phenyl-hydrazine, m.p. 130-131° (corr.) if there is a neighboring hydroxyl group, which can lead to osazone formation, and if this is to be avoided, then any acidity is unfavorable and the reaction should be carried out as near the neutral point as possible. Condensation usually occurs in the cold, and almost always on short warming on the water-bath. A solvent is often unnecessary. <%,/ -Unsaturated aldehydes and ketones may cyclize to pyrazole derivatives on reaction with phenylhydrazine. 

Due to the presence of carbonyl, aldehyde or ketone radicals, sugars are capable of addition reactions with nucleophilic reagents such as phenylhydrazine (C6H5-NH-NH2). The addition of three phenylhydrazine molecules to an aldose (Figure 3.12) leads to the formation of osazone, a crystallized product with specific physicochemical characteristics, especially its melting point. This makes it possible to identify the corresponding sugar. 

DFT calculations have probed electronic effects in the reaction of 2-arylhydrazono acetic acid with pyruvic acid to give (2Z)- and (2 )-3-aryl acrylic acids. Rearrangement of 11 (Z)-arylhydrazones of 5-amino-3-benzoyl-l,2,4-oxadiazole to give 2-aryl-5-phenyl-(2//-triazol-4-yl)ureas has been studied in toluene, with catalysis by TEA or piperidine, and compared to earlier results in more polar media. The kinetics of the acetophenone-phenylhydrazine reaction has been studied for a variety of solvents and ketone ring substituents. ... 

FIGURE 22.33 Reaction between phenylhydrazine and the ketone form of the substituted enol leads to a phenylhydrazone different from the one formed in the reaction of Figure 22.32. Aniline is now eliminated to give a diimine. Reaction with a third equivalent of phenylhydrazine leads to the osazone. 

Ludwig Elnorr (Munich, 2 December 1859-Jena, 5 June 1921), a pupil of Baeyer, Bunsen, and Emil Fischer, was associate professor in Wurzburg (1888) and professor in Jena (1889). He did much work on pyrazolones (1883-1911) by condensing acetoacedc ester and phenylhydrazine he obtained 3-methyl-i-phenylpyrazolone, which on methylation forms antipyrine. He synthesised quinoline, pyrazole derivatives from jS-diketones or ketonic esters and phenylhydrazine, and pyrrole derivatives, and discovered morpholine. He worked on diacetylsuccinic ester, acetylacetone," and acetoacetic ester, from the point of view of tautomerism, calling them allelotropic mixtures (see p. 816), and ised the colour reaction with ferric chloride in detecting the enol-forms. He woiiced on aminoethyl ether and diaminoethyl ether. ... 

Another reaction that is characteristic of a-hydroxy aldehydes or ketones, which has been found of value for the characterisation of sugars, is the formation of osazones with phenylhydrazine. This reagent reacts with either an aldose... 

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. 

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