Phenylhydrazine reagent, preparation

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. 

Phenylhydrazine is prepared on a large scale by this method. The base is an indispensable reagent for characterising aldehydes and ketones (phenylhydrazones) and for many syntheses, particularly for the technical production of antipyrine and pyramidone. Study the course of these syntheses. The salts of phenylhydrazine contain only one molecule of acid. 

H) Preparation of Phenylhydrazones. Place 0.5 ml of benzaldehyde in a tube, and add 5 ml of phenylhydrazine reagent. Stopper the tube securely, shake the contents vigorously for 1-2 minutes, and allow to stand for 10 minutes, with occasional shaking. Filter the crystals with suction, and wash first with one per cent acetic acid and then with water. The yield is about 1 g. If it is desired to determine the melting point, the product is recrystallized from methanol or ethanol. 

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... 

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. 

Imine formation from such reagents as hydroxylamine and 2,4-dinitro-phenylhydrazine is sometimes useful because the products of these reactions— oximes and 2,4-dinitrophenylhydrazones (2,4-DNPs), respectively—are often crystalline and easy to handle. Such crystalline derivatives are occasionally prepared as a means of purifying and characterizing liquid ketones or aldehydes. 

One of the most characteristic reactions of the aminochromes is the ready formation of mono-derivatives with typical ketone reagents, e.g. semicarbazide, phenylhydrazine, etc. A relatively large number of derivatives of this nature have been prepared because of then-reported hemostatic activity (cf. refs. 2 and 3). Compounds of this type that had been described in the literature prior to December 1959 are listed in a previous review (Heacock3). Some further examples of this class of compounds have been described recently. They are N-ethylnoradrenochrome semicarbazone (84) (orange-red needles, m.p.180 215°)65 7-iodoadrenochrome methyl ether semicarbazone... 

The reagent may alao be prepared by dissolving 1 ml. of phenylhydrazine in a solution of 1 ml. of glacial acetic acid and 10 ml. of water. This procedure is not so convenient as that from the solid hydrochloride because of the poisonous character of phenylhydrazine (both liquid and vapour). If the liquid is accidentally spilled on the skin, wash it at once with dilute acetic acid, followed by soap and water. 

Sulfurous acid and its salts are inexpensive reducing agents which are, however, usable only in special cases. These reagents frequently give sulfonation simultaneously with reduction (cf. the preparation of l-naphthylamine-2,4-disulfonic acid from 1-nitronaphthalene, and of l-amino-2-naphthol-4-sulfonic acid from nitroso- -naphthol, pages 178 and 201). Also, in the reduction of diazobenzene to phenylhydrazine, a N-sulfonic acid is formed first and this must be split by vigorous treatment with hydrochloric acid (see pages 96 and 128). 

Diphenylhydrazine is oxidized to diphenylnitrosamine (50%) by potassium superoxide. The same reagent also oxidizes 1-methyl-1-phenylhydrazine, but here the nitrosamine is a minor product the major reaction is deamination. A better meAod of oxidative deamination of some 1,1-disubstituted hydrazines and hydrazinium salts is reaction with nitrous acid. Thus, several hydrazinium salts MezRN NHi X were deaminated to the tertiary amine by treatment with nitrous acid. The method has also been used to deaminate IV-aminoheterocyclic compounds for example, some 1,2,3-triazoles are conveniently prepared by deamination of the corresponding 1-aminotriazoles with nitrous acid. °... 

In order to reduce an orange dye which is formed when the diazonium salt is added to the bisulfite solution, a small amount of zinc and acetic acid is added. To prepare the base, the hydrochloride is treated with excess 30 per cent sodium hydroxide solution, and the oily base is extracted with ether. The ethereal extract is dried and, after removal of ether, is distilled under reduced pressure. Substituted phenylhydrazines, such as p-nitrophcnylhydrazine and p-bromophenylhydrazine, are prepared in the same manner. Arylhydrazines are strong bases forming characteristic salts, which are important reagents in the identification of aldehydes, ketones, and sugars (see preparation of phenylhydrazones and osazones). 

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