4- phenylhydrazine

Phenylhydrazine is used in the manufacture of dyes and pharmaceuticals as a stabilizer for explosive as a reagent for aldehydes, ketones, and sugars in chemical analysis and in organic synthesis. 

Pale yellow crystals or an oily liqnid darkens when exposed to light or air mp 19.5°C bp 243.5°C (decomposes) slightly soluble in water, readily dissolves in alcohol, ether, acetone, benzene, chloroform, and dilute acids. 

TLV-TWA 0.1 mg/m (ACGIH 1989) TWA skin 0.1 mg/m (MSHA and OSHA) IDLH 25 mg/m (NIOSH) carcinogenicity Animal Inadequate Evidence (lARC). 

Noncombustible solid. Reactions with strong oxidizers may become vigorous to violent. 

Phenylhydrazine caused adverse reproductive effect when dosed intraperitoneally in pregnant mice. It caused jaundice, anemia, and behavioral deficit in offspring. 

CeHsNHa-HCl+NaNOa+HCl - C6H5N2Cl+NaCl+2 H20 C6H5N2Cl+4H(Na2S03) - C6HSNHNH2 HC1 

In a 12-I. round-bottom flask, fitted with a mechanical stirrer, are placed 1045 cc. of concentrated commercial hydrochloric acid (sp. gr. 1.138). The flask is surrounded with a freezing mixture of ice and salt, and when the contents are at o°, stirring is started and 500 g. of cracked ice are added then 372 g. of aniline, also cooled to o°, are run in during five minutes. The mixture is treated with 500 g. more of cracked ice, and a cold solution (o°) of 290 g. of technical sodium nitrite dissolved in 600 cc. of water are allowed to run in slowly (twenty to thirty minutes) from a dropping funnel, the end of which is drawn to a small tip, and reaches nearly to the bottom of the flask. During this addition, the stirrer is operated rather vigorously, and the temperature is kept as near o° as possible by the frequent addition of cracked ice (about 1 kg). 

In the meantime, a sodium sulfite solution is prepared by dissolving 8go g. of sodium hydroxide, of about 90 per cent purity, in about 1 1. of water and then diluting to 6 1. A few drops of phenolphthalein solution are added and sulfur dioxide passed in, first until an acid reaction is indicated and then for two or three minutes longer. During the addition of the sulfur dioxide, the solution is cooled with running water. On account of the strong alkaline solution, the original color produced by 

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-ec. 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 i37-i38°/i8 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 

Place 130 ml. of concentrated hj drochloric acid in a 1 - 5 litre round-bottomed flask, equipped ith a mechanical stirrer and immersed in a freezing mixture of ice and salt. Start the stirrer and, when the temperature has fallen to about 0°, add 60 g. of finely-crushed ice (1), run in 47 5 g. (46 5 ml.) of pure aniline during about 5 minutes, and then add another 60 g. of crushed ice. Dissolve 35 g. of sodium nitrite in 75 ml. of water, cool to 0-3°, and run in the cold solution from a separatory funnel, the stem of which reaches nearly to the bottom of the flask. During the addition of the nitrite solution (ca. 20 minutes), stir vigorously and keep the temperature as near 0° as possible by the frequent addition of crushed ice. There should be a slight excess of nitrous acid (potassium iodide-starch paper test) at the end of 10 minutes after the last portion of nitrite is added. 

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 

CAUTION. Phenylhydrazine is highly poisonous and produces unpleasant bums in contact with the skin. Wash off immediately any liquid which has come into contact with the skin first with 2 per cent, acetic acid, then with soap and water. 

The base, which has a brown colour, is filtered and dissolved m hot spirit, with the addition of a few diops of concentrated ammonia. Yield, about 8 grams. 

Reaction.—Make a solution of 4 grams stannous chloride in TO c.c. cone, hydrochloric acid, add 2 grams aminoazobenzene, and boil for a few minutes. On cooling ciystals of the hydrochlorides of aniline and yi-phenylenediamine separate out. The liquid is filtered and washed with a little cone, hydrochloric acid to remove the tin salts. If the precipitate is dissolved in water and made alkaline with caustic soda, a mixture of liquid aniline and solid/-phenylenediamine is precipitated, from which the former may be removed by filtering, washing, and draining on a porous plate. 

The aniline is dissolved in the concentrated hydrochloiic acid and cooled to 0° in a freezing mixture. The solution of 

Reactions.— i. Add a few drops of phenylhydrazine to 2 c.c. of water, then a drop or two of copper sulphate solution and excess of caustic soda. Cuprous oxide is precipitated with eftervescence and benzene separates, CbHjNH.NHj-tcCliO- -C HB-t-Nj-t-Cu O-t-HoO. The same reaction takes pkicc if the phenylhydrazine is dissolved in dilute acetic acid and copper sulphaie solution added and warmed. 

Add to a few drops of phenylhydrazine an equal quantity of glacial acetic acid, dilute with a little water, and Reid a 

Mssolve 10 g. of p-nitroaniline (Section IV,51) in a mixture of 21 ml. of concentrated hydrochloric acid and an equal volume of water, and cool rapidly to 0° in order to obtain the hydrochloride of the base in a fine state of division. Diazotise in the usual way (see Section IV,68) by the gradual addition of a solution of 6 0 g. of sodium nitrite in 12 ml. of water. Continue the stirring for a few minutes, filter the solution rapidly, and add it from a separatory funnel to an ice-cold solution of 41 g. of sodium sulphite (90 per cent. Na2S03,7H20) in 100 ml. of water containing 4 g. of sodium hydroxide (1) stir the mixture during the addition which requires about 5 minutes. (If the diazonium solution is added too rapidly, an orange-red precipitate of sodium p-nitrodiazobenzene sulphonate is produced, and is apt to form a resin.) AUow the solution to stand for 

6 minutes, acidify with 70 ml. of concentrated hydrochloric acid, and heat on a water bath at 25° for 3 minutes, when yellow needles commence to separate. Allow to stand overnight, filter off the crystals, heat them with 20 ml. of concentrated hydrochloric acid on a water bath for 

Dissolve 47 g. (0-5 mole) of aniline in a mixture of concentrated hydrochloric acid and water (100 c.c. of each) and diazotise the well-cooled solution, in the manner repeatedly described, with a solution of 38 g. of sodium nitrite in 100 c.c. of water. Before diazotising the aniline, prepare as concentrated a solution as possible in water of 158 g. (1-25 mole) of neutral anhydrous sodium sulphite or of 315 g. of the hydrated (7 H20) salt. The sulphite content of this solution is equivalent to the amount of hydrochloric acid taken, and represents a 25 per cent excess in respect of the aniline. 

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. 

After being cooled for some time in water the preparation should solidify completely and it sbould dissolve in dilute acetic acid with- 

The method of Y. Meyer, reduction of the diazonium chlorides to arylhydrazines with strongly acid stannous chloride solution, is less elegant. The difference in the actions of stannous salt in acid and in alkaline solution should be noted. 

Emil Fischer s classical method here described proceeds via the phenyl ewifi-diazosulphonate1 which had already been prepared by Strecker and Romer, and frequently separates in beautiful orange-yellow crystals at the beginning of the reaction. 

National Institute for Occupational Safety and Health Criteria for a Recommended Standard. .. Occupational Exposure to Glycidyl Ethers. DHEW (NIOSH) Pub No 78-166, pp 1-196. Washington, DC, US Government Printing Office, 1978 

Terrill JB, Lee KP The inhalation toxicity of phenylglycidyl ether. I. 90-day inhalation study. Toxicol Appl Pharmacol 42 263-269, 1977 

Lee KP, Schneider PW, Trochimowicz HJ Morphological expression of glandular differentiation in the epidermoid nasal carcinomas induced by phenylglycidyl ether inhalation. Am J Pathol m-.m-m, 1983 

lARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Humans, Vol 71, Re-evaluation of some organic chemicals, hydrazine and hydrogen peroxide, pp 1525-1527. Lyon, International Agency for Research on Cancer, 1999 

Kodama JK, Guzman RJ, Dunlap NK, et ah Some effects of epoxy compounds on the blood. Arch Environ Health 2 50-61, 1961 

of sodium hydroxide (1) stir the mixture during the addition which requires about 5 minutes. (If the diazonium solution is added too rapidly, an orange-red precipitate of sodium p-nitrodiazobenzene sulphonate is produced, and is apt to form a resin.) Allow the solution to stand for 

In the meantime, prepare a sodium sulphite solution as follows. In a 

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Brady s reagent A solution of 2,4-dinitro-phenylhydrazine sulphate in methanol. Gives characteristic crystalline yellow to deep red 2,4-dinitrophenylhydrazone products with aldehydes and ketones. 

Phenylhydrazine condenses with acetoacetic ester to give a pyrazolone derivative which on methylation gives phenazone. The sulphonic acid similarly gives rise to the tartrazine dyestuffs. It is used to make indole derivatives by the Fischer process. 

CgH,oN20. Colourless crystalline solid, m.p. 121 °C. Made by reacting phenylhydrazine with ethyl acrylate to obtain the hydrazide which cyclizes to the product. Its major commercial importance is as a photographic developing agent, being used particularly in conjunction with hydroquinone. 

Hydrazine and its alkylated derivatives are used as rocket fuels in organic chemistry, substituted phenylhydrazines are important in the characterisation of sugars and other compounds, for example aldehydes and ketones containing the carbonyl group C=0. 

Fructose (V) under similar conditions gives first the phenylhydrazonc (Va) by the direct condensation of the >C 0 group of carbon atom 2 with one molecule of phenylhydrazine. The second molecule of phenylhydrazine then oxidises the primary alcohol group of carbon atom 1 to the -CHO group by removal of two atoms of hydrogen, which as before serve to reduce the phenyl-hydrazine to aniline and ammonia. The compound (Vb) which is thus produced then undergoes direct condensation with the third molecule of phenylhydrazine, giving the osazone of fructose, or fructosazone (Vc). 

Phenylhydrazine is, however, frequently supplied in the form of its hydro chloride or sulphate, since these salts on exposure to light darken less rapidly than the free base. If these salts are used, however, osazone formation is unsatisfactory, partly because the mineral acid formed by hydrolysis of... 

Dissolve I g. of glucose (or fructose) in 5 ml. of water in a boiling-tube. In another tube dissolve 2 ml. of glacial acetic acid in 5 ml. of water, add 2 ml. of phenylhydrazine, and shake until... 

Dissolve I g. of pinacol (preparation, p. 148) in 20 ml. of water, and add 20 ml. of the 5% aqueous sodium periodate solution. After 15 minutes, distil the clear solution, collecting the first 5 ml. of distillate. Treat this distillate with 2,4-dinitro-phenylhydrazine solution A (p. 263). Acetone 2,4-dinitrophenyl-hydrazone rapidly separates from the solution when filtered off, washed with a small quantity of ethanol, and dried, it has m.p. 126-127°, and after recrystallisation from ethanol it has m.p. 128°. 

Benzenediazonium chloride reacts in solution with sodium sulphite to give benzenediazonium sodium sulphonate, which when treated with sulphurous acid undergoes reduction to phenylhydrazine sodium sulphonate. The latter readily hydrolyses in the presence of concentrated hydrochloric acid to give... 

Benzenediazonium chloride also undergoes direct reduction to phenylhydrazine... 

Suspend the crude hydrochloride in some water in a separating-funnel and add 20% sodium hydroxide solution until the mixture is definitely alkaline and the crude phenylhydrazine base floats as a deep red oil on the surface. Now extract the phenylhydrazine twice with benzene (using about 30 ml. of benzene on each occasion) and dry the united benzene extracts with powdered... 

Phenylhydrazine on exposure to light slowly darkens and eventually becomes deep red in colour salts of the base share this property but to a lesser degree, the sulphate and acetate (of the common salts) being most stable to light. Phenylhydrazine is largely used in organic chemistry to characterise aldehydes and ketones as their phenyl-hydrazones (pp. 342, 345), and carbohydrates as their osazones (pp. 136-140). It is readily reduced thus in the process of osazone formation some of the phenylhydrazine is reduced to aniline and ammonia. On the... 

Add 2 -3 drops of phenylhydrazine to about 2 ml. of Fehling s solution in a test-tube and shake the mixture vigorously nitrogen is evolved and reddish-brown cuprous oxide is precipitated. The reaction proceeds rapidly on gentle warming, more slowly in the cold. 

Phenylhydrazine is usually dissolved in acetic acid for hydrazone formation if a salt of phenylhydrazine with an inorganic acid is used, it must be mixed with an excess of sodium acetate (see preparation of osazones, p. 137). 

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. 

Mix 6 2 ml. (6 4 g.) of pure ethyl acetoacetate and 5 ml. of pure phenylhydrazine in an evaporating-basin of about 75 ml. capacity, add 0 5 ml. of acetic acid and then heat the mixture on a briskly boiling water-bath (preferably in a fume-cupboard) for I hour, occasionally stirring the mixture with a short glass rod. Then allow the heavy yellow syrup to cool somewhat, add 30-40 ml. of ether, and stir the mixture vigorously the syrup may now dissolve and the solution shortly afterwards deposit the crystalline pyrazolone, or at lower temperatures the syrup may solidify directly. Note. If the laboratory has been inoculated by previous preparations, the syrup may solidify whilst still on the water-bath in this case the solid product when cold must be chipped out of the basin, and ground in a mortar with the ether.) Now filter the product at the pump, and wash the solid material thoroughly with ether. Recrystallise the product from a small quantity of a mixture of equal volumes of water and ethanol. The methyl-phenyl-pyrazolone is obtained... 

Dissolve 8 8 g. (9 0 ml.) of cyclohexanone in 50 ml. of glacial acetic acid, add 8 ml. of phenylhydrazine, and boil the solution under reflux for 5 minutes. Cool the solution, when the tetrahydrocarbazole will crystallise out. Filter at the pump, drain well, and recrystallise either from aqueous ethanol or (better) from aqueous acetic acid. The recrystallisation should be performed rapidly, for the tetrahydrocarbazole undergoes atmO" spheric oxidation in hot solutions after recrystallisation, the compound should be dried in a vacuum desiccator and not in an oven. Repeated recrystallisation should be avoided. The tetrahydrocarbazole, after thorough drying, is obtained as colourless crystals, m.p. 118° yield of recrystallised material, 11 g. 

To a few drops of formalin solution add a few drops of dinitro-phenylhydrazine reagent A (p. 263) a yellow precipitate is produced in the cold. Acetaldehyde and acetone give orange-coloured precipitates. Dissolve water-insoluble compounds e.g-y benzaldehyde, salicylalde-hyde, acetophenone and benzophenone) in a small volume of methanol before adding reagent B. With benzophenone the precipitate forms slowly. 

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