Syntheses of Phenylhydrazine
[Org Syn Coll Vol 1, pp 442-445]
In a 12-liter round-bottomed flask, fitted with a mechanical stirrer, is placed 1045 ml of concentrated commercial hydrochloric acid (d 1.138). The flask is surrounded with a freezing mixture of ice and salt, and, when the contents are at 0°C, stirring is started and 500g of cracked ice is added, or more ice can be added and the external cooling dispensed with; then 372g (364 ml, 4 moles) of aniline, also cooled to 0°C, is run in during five minutes. The mixture is treated with 500g more of cracked ice, and a cold solution (0°C) of 290g (4 moles) of technical sodium nitrite dissolved in 600 cc. of water is allowed to run in slowly (twenty to thirty minutes) from a separatory 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 0°C as possible by the frequent addition of cracked ice (about 1 kg).
In the meantime, a sodium sulfite solution is prepared by dissolving 890g (20 moles) of sodium hydroxide, of about 90 per cent purity, in about 1 l. of water and then diluting to 6 l. 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 the phenolphthalein is very faint, but this slowly increases until it becomes deep just before the acid point is reached. It is best to remove a small sample of the liquid from time to time, dilute with three or four volumes of water, and add a drop more of phenolphthalein (It is very important that there is no excess alkali left, or the yields of phenylhydrazine will be greatly diminished).
The sodium sulfite solution is placed in a 12-l. flask and cooled to about 5°C. Approximately 500g of cracked ice is added, and then, with mechanical stirring, the diazonium salt solution is run in as rapidly as possible. The mixture becomes a bright orange-red. The flask is now warmed to about 20°C on a steam bath, until the solid sodium sulfite, which has separated while cooling, redissolves. The total amount of liquid is now about 10 l. One-half of this is poured into another 12-l. flask, and both halves are warmed on the steam bath to 60-70°C, until the color becomes quite dark (thirty to sixty minutes). Sufficient hydrochloric acid (300-400ml) is now added (*) to each flask to make the solutions acid to litmus. The heating is continued and the color gradually becomes lighter until, after four to six hours, the solutions have become nearly colorless; they may be heated overnight, if desired.
To the hot solutions is now added about one-third of their volume of concentrated hydrochloric acid (2000ml to each portion), and the mixtures are cooled, first in running water, then in a freezing mixture, to 0°C. The phenylhydrazine hydrochloride precipitates in the form of slightly yellowish or pinkish crystals which may be filtered off and dried. The phenylhydrazine hydrochloride may be purified by crystallizing from water. A 600 ml. portion of water is used for 100g of crude hydrochloride, and the solution boiled a short time with a few grams of activated charcoal. After filtering, 200 ml of concentrated hydrochloric acid is added, and the mixture cooled to 0°C. Pure white crystals in a yield of 85-90g are obtained.
The free base is liberated by adding to the phenylhydrazine hydrochloride 1000ml of a 25% solution of sodium hydroxide. The phenylhydrazine separates and is taken up with benzene (2x300 ml portions). The combined extractions are well dried with 200g of solid sodium hydroxide (it is important that there are no trace of water or phenylhydrazine hydrochloride left), 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°C at18 mmHg, and is obtained as a pale yellow liquid. It can be crystallized on cooling in an ice bath; the crystals melt at 23°C. The crude phenylhydrazine from two lots of aniline (744g) is best distilled at one time and gives 695-725 g. of pure product (80-84 per cent of the theoretical amount).
[Mann & Saunders, Practical Organic Chemistry, 3rd Ed]
Phenyl diazonium chloride reacts in solution with sodium sulfite (Na2SO3) to give phenyl diazonium sodium sulfonate, 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 phenylhydrazine hydrochloride, from which the free base can be isolated by the action of caustic alkalis.
Phenyl diazonium chloride also undergoes direct reduction to phenylhydrazine when treated with an acid solution of stannous chloride (e.g., a solution in hydrochloric acid) but the yields are not so high as those obtained by the above sulphonate method.
Required: Aniline 20ml, hydrochloric acid 50ml, sodium nitrite 17g, sodium carbonate (anhydrous) 17g, sodium sulphite (7H20) 115g.
First prepare a solution of phenyl diazonium chloride from 20ml (20.5g) aniline by adding a solution of 17g of sodium nitrite in 40ml of water in small portions to a well-stirred solution of the aniline in 50ml of concentrated hydrochloric acid and 50ml of water, the temperature of the mixture being kept between 5-10°C. While this solution is standing, dissolve 17g of anhydrous sodium carbonate in 70ml of warm water in a 800ml beaker, and then add 115g of finely powdered crystalline sodium sulphite (Na2SO3 * 7H2O) and continue warming the solution at 40-50°C for a few minutes, so that the greater part of the sulfite dissolves. Then cool the solution in ice-water until the temperature is between 5-10°C, some of the sulfite meanwhile crystallizing out again. Now add the diazonium solution slowly to the well-stirred sulfite solution: the mixture becomes red in colour, and a deep red oil separates and later solidifies as orange-coloured crystals (sometimes the orange crystals separate without the intermediate formation of the oil). When the addition of the diazo solution is complete, continue stirring the mixture for 5-10 minutes, and then warm it to 30°C on a water-bath (in a fume-cupboard) and pass in a stream of sulfur dioxide (made by dropping H2SO4 on NaHSO3 or Na2SO3 crystals in a kipp's apparatus) until the solution is saturated and no more gas is absorbed: the excess of sodium sulfite and the orange crystals dissolve up at this stage. Now heat the solution to 70°C and add 150ml of concentrated hydrochloric acid with stirring. Within a few minutes, crystals of phenylhydrazine hydrochloride separate out: cool the mixture in ice-water for 30 minutes with occasional stirring and then filter at the pump and drain thoroughly.
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 30ml of benzene on each occasion) and dry the united benzene extracts with powdered anhydrous potassium carbonate. After the mixture has been allowed to stand for 20-30 minutes, filter at the pump, and wash the residual carbonate with a small quantity of dry benzene. The benzene has now to be distilled off at atmospheric pressure and the residual phenylhydrazine at reduced pressure. For this purpose, fit a small dropping-funnel to the main neck of a 60ml Claisen flask, cork the other neck, and fit a water-condenser to the side-arm. Run about 30ml of the benzene solution into the flask, and heat the latter in an oil-bath, controlling the temperature of the bath so that the benzene distills gently over. Allow the remainder of the solution to run in from the dropping-funnel as fast as the benzene itself distills over. When the benzene has been almost entirely removed, set up for a vacuum distillation. Distil the phenylhydrazine carefully from an oil-bath and collect a fraction boiling over a range of about 3°C, e.g., at 127-130°C at 22 mmHg. The phenylhydrazine is thus obtained as a very pale yellow (almost colourless) oil of d 1.10: it has a characteristic odour and is only slightly soluble in water. Yield, 16-17g. Pure phenylhydrazine has mp 23°C; it boils at 242-243°C at atmospheric pressure with partial decomposition. 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.
JCS 125(1), 313 (1924)
The most satisfactory method of preparing this substance appears to be the following: p-Anisidine (38 grams) is mixed with concentrated hydrochloric acid (300 ml), when a thick, crystalline paste of the hydrochloride separates. This is well stirred and diazotised at 0°C with a solution of sodium nitrite (20.7 grams in 90 ml of water). A well-cooled solution of stannous chloride (210 grams in concentrated hydrochloric acid, 180 ml) is added to the purple diazonium solution, and this causes the separation of a yellow, crystalline solid which, after standing for two or three hours, becomes colourless. After being collected and thoroughly pressed, the mass is decomposed by shaking with caustic potash solution (400 ml of 25 per cent.), care being taken to keep the mixture well cooled. The free base separates as a light brown, crystalline solid, which is collected, washed with a very little water, and dried over sulfuric acid in a vacuum desiccator. The hydrazine is purified by dissolving in the minimum of hot benzene, filtering, and adding about three volumes of light petroleum, which precipitates the base in shining plates, mp. 65°C. Yield 44%.