Phenylhydrazones

Usually prepared by the action of NaCN on benzaldehyde in dilute alcohol. It is oxidized by nitric acid to benzil, and reduced by sodium amalgam to hydrobenzoin PhCHOHCHOHPh by tin amalgam and hydrochloric acid to des-oxybenzoin, PhCH2COPh and by zinc amalgam to stilbene PhCH = CHPh. It gives an oxime, phenylhydrazone and ethanoyl derivative. The a-oxime is used under the name cupron for the estimation of copper and molybdenum. 

Benzaldehyde Phenylhydrazone. CeHsCHtN NHCeH. (Semi-micro Scale.)... 

Dissolve 0 3 ml. of glacial acetic acid in 2 ml. of water in a 25 ml. conical flask, and add 0 4 ml. (0 44 g.) of phenylhydrazine. Mix thoroughly to obtain a clear solution of phenylhydrazine acetate and then add 0 2 ml. (0 21 g.) of benzaldehyde. Cork the flask securely and shake the contents vigorously. A yellow crystalline mass of the hydrazone soon begins to separate. Allow to stand for 15 minutes, with occasional shaking, and then filter the solid product at the pump, wash first with very dilute acetic acid and then with water, and finally drain thoroughly. Recrystallise the material from rectified or methylated spirit, the benzaldehyde phenylhydrazone being thus obtained in fine colourless needles, m.p. 157 yield, 0 4 g. 

Acetophenone similarly gives an oxime, CHjCCgHjlCtNOH, of m.p. 59° owing to its lower m.p. and its greater solubility in most liquids, it is not as suitable as the phenylhydrazone for characterising the ketone. Its chief use is for the preparation of 1-phenyl-ethylamine, CHjCCgHslCHNHj, which can be readily obtained by the reduction of the oxime or by the Leuckart reaction (p. 223), and which can then be resolved by d-tartaric acid and /-malic acid into optically active forms. The optically active amine is frequently used in turn for the resolution of racemic acids. 

Aldehydes and ketones may frequently be identified by their semicarbazones, obtained by direct condensation with semicarbazide (or amino-urea), NH,NHCONH a compound which is a monacidic base and usually available as its monohydrochloride, NHjCONHNH, HCl. Semicarbazones are particularly useful for identification of con jounds (such as acetophenone) of which the oxime is too soluble to be readily isolated and the phenylhydrazone is unstable moreover, the high nitrogen content of semicarbazones enables very small quantities to be accurately analysed and so identified. The general conditions for the formation of semicarbazones are very similar to those for oximes and phenylhydrazones (pp. 93, 229) the free base must of course be liberated from its salts by the addition of sodium acetate. 

If ethyl acetoacetate is warmed with an equivalent quantity of phenyl hydrazine, the corresponding phenylhydrazone (A) is readily formed. On... 

The Fischer Indolisation Reaction occurs when the phenylhydrazone of a suitable aldehyde or ketone undergoes cyclisation with loss of ammonia, under the influence of various reagents, such as zinc chloride, ethnnolic hydrogen chloride, or acetic acid. For example, the phenylhydrazone of acetophenone (p. 257) when heated with zinc chloride gives 2 phenylindole. ... 

For the mechanism of this reaction, see Robinson and Robinson,1918, H3i 639 1924, 145, 827.) The reaction is of wide application for example, the use of methyl-phenyl-hydrazine, CsH5(CHj)> -iN H, in the above reaction gives i-methyl-2-phenylindole, whereas pyruvic acid, CH CO COOH, when converted to its phenylhydrazone and then indolised, gives indole-2-carboxylic... 

Form phenylhydrazones, 2,4-dinitrophenylhydrazones and semicarbazones. (Many oximes are too soluble for ready isolation.)... 

The phenylhydrazones of formaldehyde and acetaldehyde are difficult to isolate and are seldom prepared. 

A) Phenylhydrazones and 2,4-Dinitrophenylhydrazones (see 2 abo e). The latter are often to be preferred to phenylhydrazones because (a) the phenylhydrazones may separate as syrups, and also may decompose in hot solvents cf. p. 257), ( ) the 2,4 dinitrophenylhydrazones are often formed in the cold or with only brief warming, are much less soluble, and have higher m.ps. (p. 263). 

Then add 3 drops of acetophenone (or about 0 3 g. of powdered benzo-phenone dissolved in 1 ml. of acetic acid) and shake the mixture. A precipitate of the phenylhydrazone is produced on scratching. 

Values given in parentheses in Phenylhydrazone column are B.ps. Di-deriv. f Mono dcriv. Two forms. 

Experimental details for the preparation of oximes, phenylhydrazones and p-nitrophenylhydrazones will be found under Aromatic Aldehydes, Section IV,135,4-6. 

Phenylhydrazones (compare Section III,74,C). Dissolve 0-5 g, of colourless phenylhydrazine hydrochloride and 0 8 g. of sodium acetate in 5 ml. of water, and add a solution of 0-2-0-4 g. of the aldehyde (or ketone) in a little alcohol (free from aldehydes and ketones). Shake the mixture until a clear solution is obtained and add a little more alcohol, if necessary. Warm on a water bath for 10-15 minutes and cool. Filter ofiF the crystalline derivative, and recrystalhse it from dilute alcohol or water sometimes benzene or light petroleum (b.p. 60-80°) may be used. 

The use of liquid phenylhydrazine in the preparation of phenylhydrazones is not recommended for beginners because of the liiglily poisonous character of the liquid (see Section IV,89). A phenylhydrazine reagent may, however, be used. 

Section IV, 135,5), but are unaflFected by the dimedone reagent (Section 111,70, 2). The general reactions are similar to those already given under Aliphatic Ketones (Section 111,74). Owing to their higher molecular weight, such derivatives as oximes and phenylhydrazones are frequently quite satisfactory. 

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

Prepare acetophenonephenylhydrazone by warming a mixture of 20 g. of acetophenone (Section IV, 136) and 18 g. of phenylhydrazine on a water bath for 1 hour. Dissolve the hot mixture in 40 ml. of rectihed spirit, and shake or stir to induce crystallisation. Cool the mixture in ice, filter and wash with 12 ml. of rectified spirit. Dry in a vacuum desiccator over anhydrous calcium chloride for at least half an hour. The yield of phenylhydrazone, m.p. 105-106 , is 28 g. 

The acetone test reagent consists of a 0 1 per cent, solution of 2 4-dinitro-phenylhydrazine and is prepared as follows Dissolve 0-25 g. of 2 4-dinitrophenyl-hydrazine in 60 ml. of water and 42 ml. of concentrated hydrochloric acid by warming on a water bath cool the clear yellow solution and dilute to 250 ml. with water. The acetone test is considered negative when 5 ml. of the reagent and 4-5 drops of the distillate give no cloudiness or precipitate of acetone 2 4-dinitro-phenylhydrazone within 30 seconds. After a negative test is obtained, it is stron y recommended that the mixture in the flask be refluxed for 5-10 minutes with complete condensation and then to collect a few drops of distillate for another test. If no acetone is now detected, the reduction is complete. 

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