Phenylhydrazine hydrochloride

Liberate the free base by adding to the phenylhydrazine hydrochloride 125 ml. of 25 per cent, sodium hydroxide solution. Extract the phenyl-hydrazine with two 40 ml. portions of benzene, dry the extracts with 25 g. of sodium hydroxide pellets or with anhydrous potassium carbonate thorough drying is essential if foaming in the subsequent distillation is to be avoided. Most of the benzene may now be distilled under atmospheric pressure, and the residual phenylhydrazine under reduced pressure. For this purpose, fit a small dropping funnel to the main neck of a 100 ml. Claisen flask (which contains a few fragments of porous porcelain) and assemble the rest of the apparatus as in Fig. II, 20, 1, but do not connect the Perkin triangle to the pump. Run in about 40 ml. of the benzene, solution into the flask, heat the latter in an air bath (Fig. II, 5, 3) so that... 

If desired, the phenylhydrazine hydrochloride may be purified by recrystai-lisation. The crude hydrochloride is boiled with 6 times its weight of water and a few grams of decolourising carbon. After filtering, a volume of concentrated hydrochloric acid equal in volume to one-third of the solution is added, and the mixture cooled to 0°. Pure white crystals are obtained in 85-90 per cent, yield. 

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. 

Method D. Dissolve 25 g. of colourless phenylhydrazine hydrochloride (recrystal-lise, if necessary) in 250 ml. of water warming may be required. Add 45 g. of crystallised sodium acetate to the cold solution and shake until dissolved. Add 0-6 g. of decolourising carbon, shake, and filter into a dark bottle. The reagent should not be kept for longer than 1 month. 

A solution of 4% aq. H2SO4, (301) was heated to 50"C over 30-60 min. Nitrogen was bubbled through the solution during this time. 4-(Cyano-methyl)phenylhydrazine hydrochloride (1080g, 4.77 mol) was added as a solid to the heated mixture. After it had dissolved, A,A-dimethyl-4,4-dimethoxy-butanamine (965 g, 5.98 mol) was added over a period of 30 min. The mixture was then heated at reflux for 2 h. The reaction mixture was cooled and diluted with portions of 30%o aq. NH4OH (21 total) over 0.5 h at a rate to maintain the temperature at 25-30°C. The product was then extracted into isopropyl acetate (3 x 101). The solution was concentrated to 31 which led to a precipitate which was isolated by filtration and washed with cold isopropyl acetate to give 827.4 g (76%) of product. 

Copper(Il) complexes 18a-f of methyl or ethyl 3-oxobutanoate la, 2-bromo-3 oxobutanoate lb, 2-(anilinocarbonyl)-3-oxobutanoate Ic, 3-oxo-3- rfienylpro-panoate Id, 2-bromo-3-oxo-3-phenylpropanoate le, or 3-aniHno-2-benzoyl-3-oxopropanoate If were reacted with phenylhydrazine hydrochloride and sodium ( )... 

They are best prepared by heating the aldehyde in alcoholic solution, on the water-bath, under a reflux condenser, with slightly more than the equimolecular quantity of phenylhydrazine hydrochloride, with acetate of sodium added. Thirty to sixty minutes is usually sufi cient for the reaction. 

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... 

Filter the crystals of phenylhydrazine hydrochloride at the pump, press the salt as dry as possible on the funnel, wash with hydrochloric acid (1 3), and then decompose in a separating funnel containing 150 c.c. of 4iV-sodium hydroxide solution and ether. Extract twice with ether, dry the ethereal solution of the base with anhydrous potassium carbonate, and finally distil the phenylhydrazine in vacuo, using an Anschiitz-Thiele adapter (Fig. 17, p. 22). Boiling point 120°/12 mm. Yield about 30 g. 

To the hot solutions are now added about one-third of their volume of concentrated hydrochloric acid (2 1. to each portion) and the mixtures cooled, first in running water, then in a freezing mixture, to o°. The phenylhydrazine hydrochloride precipitates in the form of slightly yellowish or pinkish crystals which may be filtered off and dried. 

The free base is liberated by adding to the phenylhydrazine hydrochloride 1 1. of a 25 per cent solution of sodium hydroxide. The phenylhydrazine separates and is taken up with benzene (two 300-cc. portions). The combined extractions are well dried with 200 g. of solid sodium hydroxide, poured off, and distilled. Most of the benzene may be distilled under ordinary pressure, and the remainder, and any low-boiling impurities, under diminished pressure. The pure phenylhydrazine boils at 137-138°/18 mm., and is obtained as a pale-yellow liquid. It can be crystallized on cooling in an ice bath the crystals melt at 23°. The crude phenylhydrazine from two lots of aniline... 

The phenylhydrazine hydrochloride may be purified by crystallizing from water. A 6oo-cc. portion of water is used for ioo g. of crude hydrochloride, and the solution boiled a short time with a few grams of animal charcoal. After filtering, 200 cc. of concentrated hydrochloric acid are added, and the mixture cooled to o°. Pure white crystals in a yield of 85-90 g. are obtained. 

If the sodium sulfite-diazonium salt mixture is acidified before warming or before becoming dark, the red color of the solution does not disappear on heating, and the precipitated phenylhydrazine hydrochloride obtained is colored red. 

In order to obtain the maximum yield, it is necessary to cool the hydrochloric acid solution of the phenylhydrazine hydrochloride from 200 to o°, before filtration. From 5 to 10 per cent of product separates between these two temperatures. When this is done, no more phenylhydrazine hydrochloride is obtained by concentration of the mother liquor. An increase in the amount of hydrochloric acid above 2 1. for the precipitation of the hydrochloride produces no increase in yield of product. 

Potassium iodate is a fairly strong oxidizing agent that may be used in the assay of a number of pharmaceutical substances, for instance benzalkonium chloride, cetrimide, hydralazine hydrochloride, potassium iodide, phenylhydrazine hydrochloride, semicarbazide hydrochloride and the like. Under appropriate experimental parameters the iodate reacts quantitatively with both iodides and iodine. It is, however, interesting to observe here that the iodate titrations may be carried out effectively in the presence of saturated organic acids, alcohol and a host of other organic substances. 

A host of other pharmaceutical substances, namely cetrimide, hydralazine hydrochloride, phenylhydrazine hydrochloride may be assayed by titration with potassium iodate as mentioned in Table 13.3. 

Phenylhydrazine. 10 g of freshly distilled aniline are added to a solution of 30 g coned hydrochloric acid in 75 cc of water and diazotized with 30 cc of water containing 8 g sodium nitrite, with external cooling below 5°. 30 g sodium chloride are added with very fast stirring and cooling of -5°. A solution of 60 g of stannous chloride in 25 g coned hydrochloric acid are then added and allowed to stand. Phenylhydrazine hydrochloride separates after 4-12 hours and is filtered off, washed with a saturated NaCl solution, treated with an excess caustic soda solution, and extracted with ether. The ethereal solution is dried with caustic potash, the ether is removed by evaporation, and the phenylhydrazine is purified by freezing or distilling in vacuo. Tield 10 g 90% theoretical. 

The intermediacy of phenylhydrazones 369 (R = H = Me) is suggested in the transformation of some 2-alkylindoles into the corresponding pyrazoles 370 by the reaction with phenylhydrazine hydrochloride in refluxing acetic-hydrochloric acid (Scheme 58) (76CJC1020). Here, after preliminary acetylation at C(3) of the indole by the acetic-hydrochloric... 

Phosgene reacts with phenylhydrazine hydrochloride, and the product is directly treated with aniline to afford 1,4-diphenylsemicarbazide [59] (Eq. 23). 

Phenylhydrazine Hydrochloride Phenylhydrazinium Chloride Phenyl Hydroxide Phenylmethanol Phenylmethyl Alcohol Phenylmethyl Amine Phenylphosphine Dichloride Phenylphosphine Thiodichloride Phenylphosphonothioic Dichloride Phenyl Phosphonous Dichloride Phenylpropylene 1 -Phenyltetradecane 1-Phenylundecane Phosgene Phosphoric Acid Phosphoric Sulfide... 

Phenylhydrazine Hydrochloride — Fire Hazards Flash Point (deg. F) Not pertinent... 

---