Oxime hydrochloride

Keywords aldehyde, ketone, calcium oxide, hydroxylamine hydrochloride, oxime... 

Since hydroxylamine is usually available only in the form of its salts, e.g., the hydrochloride or sulphate, the aqueous solution of these salts is treated with sodium acetate or hydroxide to liberate the base before treatment with the aldehyde or ketone. Most oximes are weakly amphoteric in character, and may dissolve in aqueous sodium hydroxide as the sodium salt, from which they can be liberated by the addition of a weak acid, e.g., acetic acid. 

Place 80 g, of hydroxylamine sulphate (or 68-5 g. of the hydrochloride), 25 g. of hydrated sodium acetate, and 100 ml. of water in a 500 ml. flask fitted with a stirrer and a reflux water-condenser, and heat the stirred solution to 55-60°. Run in 35 g (42 nil,) of -hexyl methyl ketone, and continue the heating and vigorous stirring for ij hours. (The mixture can conveniently be set aside overnight after this stage.) Extract the oily oxime from the cold mixture twice with ether. Wash the united ethereal extract once with a small quantity of water, and dry it with sodium sulphate. Then distil off the ether from the filtered extract, preferably using a distillation flask of type shown in Fig. 41 (p. 65) and of ca, 50 ml, capacity, the extract being run in as fast as the ether distils, and then fractionally distil the oxime at water-pump pressure. Collect the liquid ketoxime, b.p. 110-111713 mm. Yield, 30-32 g. 

Chill the concentrated solution of the amine hydrochloride in ice-water, and then cautiously with stirring add an excess of 20% aqueous sodium hydroxide solution to liberate the amine. Pour the mixture into a separating-funnel, and rinse out the flask or basin with ether into the funnel. Extract the mixture twice with ether (2 X25 ml.). Dry the united ether extracts over flake or powdered sodium hydroxide, preferably overnight. Distil the dry filtered extract from an apparatus similar to that used for the oxime when the ether has been removed, distil the amine slowly under water-pump pressure, using a capillary tube having a soda-lime guard - tube to ensure that only dry air free from carbon dioxide passes through the liquid. Collect the amine, b.p. 59-61°/12 mm. at atmospheric pressure it has b.p. 163-164°. Yield, 18 g. 

Cyclohexanone oxime. Add 20 g. (21 ml.) of cyclohexanone to a solution of 17 g. of hydroxylamine hydrochloride in 40 ml. of water, and cool the mixture in ice-water. Add a solution of 13 g. of anhydrous sodium carbonate in 40 ml. of water slowly to the mixture, stirring the latter with a 100° thermometer, and maintaining the temperature of the mixture at 20-25° meanwhile. The oxime rapidly separates. Stir the complete mixture at intervals, and after 10 minutes filter the oxime at the pump, drain thoroughly and dry it in a (vacuum) desiccator. Yield of crude oxime, 20 g. Recrystallise from petroleum (b.p. 100-120 ) and dry over paraffin wax (p. 19). Yield of pure oxime, 16 g., m.p. 88°. 

B) Oximes. Dissolve i g. of the quinone in 5 ml. of glacial acetic acid. Dissolve i g. of hydroxylamine hydrochloride in 10 ml. of 10% aqueous sodium acetate solution and shake the mixture for 5 minutes. Cool, filter off the dioxime and recrystallise from ethanol. (M.ps., p. 549.)... 

Dissolve 5 g. of hydroxylamine hydrochloride in 10 ml. of water in a small conical flask and add a solution of 3 g. of sodium hydroxide in 10 ml. of water. Cool the solution in cold or ice water, and add 6 g. (7-6 ml.) of acetone slowly. Cool the flask, shake well, and leave overnight, during which time the oxime may crystallise out. If no crystals appear, cork the flask and shake vigorously when the acetoxime usually separates as colourless crystals. Filter the crystals at the pump, dry rapidly between filter paper (yield 2- 6 g.) and determine the m.p. (59°). Extract the filtrate with two 20 ml. portions of ether, and remove the solvent a further 0 - 5 g. of acetoxime (m.p. 60°) is obtained. Recrystallise from light petroleum, b.p. 40-60° CAUTION inflammable) to obtain the pure acetoxime, m.p. 60°. Acetoxime sublimes when left exposed to the air. 

Dissolve 2 5 g. of hydroxylamine hydrochloride and 4 g. of crystallised sodium acetate in 10 ml. of water in a small flask or in a test-tube. Warm the solution to about 40° and add 2 5 g. of cyclohexanone. Stopper the vessel securely with a cork and shake vigorously for a few minutes the oxime soon separates as a crystalline solid. Cool in ice, filter the crystals at the pump, and wash with a little cold water. RecrystaUise from light petroleum, b.p. 60-80°, and dry the crystals upon filter paper in the air. The yield of pure cycZohexanone oxime, m.p. 90°, is 2 -5 g. 

Oximes. The method given for semicarbazones (see 2) may be employed use 1 g. of hydroxylamine hydrochloride, 2 g. of crystallised sodium acetate and 0 5 g. of the aldehyde or ketone. It is usually advisable to warm on a water bath for 10 minutes. 

For water insoluble aldehydes or ketones, the following alternative procedure may be used. Reflux a mixture of 0-6 g. of the aldehyde or ketone, 0 5 g. of hydroxylamine hydrochloride, 5 ml. of ethanol and 0 5 ml. of pyridine on a water bath for 15-60 minutes. Remove the alcohol either by distillation (water bath) or by evaporation of the hot solution in a stream of air (water pump). Add 5 ml. of water to the cooled residue, cool in an ice bath and stir until the oxime crystallises Filter off the solid, wash it with a little water and dry. Recrystallise from alcohol (95 per cent, or more dilute), benzene, or benzene - light petroleum (b.p. 60-80°). 

In a 250 ml. conical flask mix a solution of 14 g. of sodium hydroxide in 40 ml. of water and 21 g. (20 ml.) of pure benzaldehyde (Section IV,115). Add 15 g. of hydroxylamine hydrochloride in small portions, and shake the mixture continually (mechanical stirring may be employed with advantage). Some heat is developed and the benzaldehyde eventually disappears. Upon coohiig, a crystalline mass of the sodium derivative separates out. Add sufficient water to form a clear solution, and pass carbon dioxide into the solution until saturated. A colourless emulsion of the a or syn-aldoxime separates. Extract the oxime with ether, dry the extract over anhydrous magnesium or sodium sulphate, and remove the ether on a water bath. Distil the residue under diminished pressure (Fig. 11,20, 1). Collect the pure syn-benzaldoxime (a-benzald-oxime) at 122-124°/12 mm. this gradually solidifies on cooling in ice and melts at 35°. The yield is 12 g. 

Oximes (compare Section III,74,B). The following procedure has wide application. Dissolve 0-5 g. of hydroxylamine hydrochloride in 2 ml. of water, add 2 ml. of 10 per cent, sodium hydroxide solution and 0-2 g. of the aldehyde (or ketone). If the latter is insoluble, add just sufficient alcohol to the mixture to give a clear solution. Heat the mixture under reflux for 10-15 minutes, and then cool in ice. If crystals separate, filter these off, and recrystallise from alcohol, dilute alcohol, benzene or light petroleum (b.p. 60-80°). If no solid separates on cooling, dilute with 2-3 volumes of water, filter the precipitated sohd, and recrystallise. 

Bfflizophenone condenses with hydroxylamine hydrochloride in the presence of excess of sodium hydroxide solution to 3deld benzophenone oxime, m.p. 142° ... 

Reactions with Amines and Amides. Hydroxybenzaldehydes undergo the normal reactions with aUphatic and aromatic primary amines to form imines and Schiff bases reaction with hydroxylamine gives an oxime, reaction with hydrazines gives hydrazones, and reactions with semicarbazide give semicarbazones. The reaction of 4-hydroxybenzaldehyde with hydroxylamine hydrochloride is a convenient method for the preparation of 4-cyanophenol (52,53). 

An assay method for benzaldehyde involves condensing benzaldehyde with hydroxyl amine hydrochloride to form an oxime. The released hydrochloric acid is then titrated. 

The assay method involves the reaction of benzaldehyde with hydroxylamine hydrochloride in an alcohoHc solution. Benzaldehyde oxime, water, and hydrochloric acid are the products of the reaction. The hydrochloric acid formed is then titrated with standard caustic solution to determine the benzaldehyde assay. 

Toray. The photonitrosation of cyclohexane or PNC process results in the direct conversion of cyclohexane to cyclohexanone oxime hydrochloride by reaction with nitrosyl chloride in the presence of uv light (15) (see Photochemical technology). Beckmann rearrangement of the cyclohexanone oxime hydrochloride in oleum results in the evolution of HCl, which is recycled to form NOCl by reaction with nitrosylsulfuric acid. The latter is produced by conventional absorption of NO from ammonia oxidation in oleum. Neutralization of the rearrangement mass with ammonia yields 1.7 kg ammonium sulfate per kilogram of caprolactam. Purification is by vacuum distillation. The novel chemistry is as follows ... 

Cyclohexanone purity is most readily deteanined by gas-Hquid chromatography over DC-710 or carbowax 20M-on-chromosorb. Impurities such as cyclohexane, ben2ene, cyclohexanol, and phenol do not interfere. In the absence of other carbonyl compounds cyclohexanone may be deterrnined by treatment with hydroxylamine hydrochloride, which forms the oxime, as follows ... 

Dihydromorphinone, Cj,Hjg03N, and derivatives. Dihydromorphinone (LIII MeO HO) is formed when morphine in solution is treated with relatively large quantities of platinum or palladium catalyst under various conditions.It melts at 262-3° and yields an oxime, m.p. > 234°. The hydrochloride is the drug known as dilaudid. On 0-methyla-tion dihydromorphinone yields dihydrocodeinone (see above), and when dissolved in ether and treated with methyllithium the corresponding tertiary alcohol, 6-methyldihydromorphine, CigHggOgN, m.p. 209-211°, Wd ° 14i7° (EtOH), is formed. This on methylation with diazomethane gives 6-methyldihydrocodeine as described above (Small and Rapoport... 

Dimethyl ketals and enol ethers are stable to the conditions of oxime formation (hydroxylamine acetate or hydroxylamine hydrochloride-pyridine). Thioketals and hemithioketals are cleaved to the parent ketones by cadmium carbonate and mercuric chloride. Desulfurization of thioketals with Raney nickel leads to the corresponding methylene compounds, while thioenol ethers give the corresponding olefin. In contrast, desulfurization of hemithioketals regenerates the parent ketone. ... 

A mixture of 3 -hydroxypregna-5,l6-dien-20-one acetate (10 g), 70 ml of ethanol and 2 ml of methoxylamine is refluxed for 12 hr (Note methoxyl-amine hydrochloride leads to oxime formation). After cooling, another 1.75 ml of methoxylamine is added and the reaction is refluxed for another 12 hr. The solvent is removed in vacuo and the residue is dissolved in ether. Hydrogen chloride gas is passed into the ether solution and the white crystalline salt (113) is filtered off and washed with ether (85% yield crude mp 228-229°). 

Hydroxypregna-5,16-dien-20-one Acetate Oxime 3j5-Hydroxy-pregna-5,16-dien-20-one acetate (30 g) is dissolved in 300 ml of anhydrous pyridine and 6.75 g of hydroxylamine hydrochloride is added. The mixture is stirred until solution is achieved, left in a tightly closed container at room temperature for 4 days and then poured into 1.5 liters of water. The flask is rinsed with water and the combined separated crystals are collected on a Buchner funnel, washed with water and dried to constant weight in an oven at 100°. Yield 30 g (96.5% of theory) mp 220-223°. 

The fi-compound is dissolved in 50 c c. pure dry ether, and dry hydiogen chloride is passed in with constant shaking to prevent the delivery tube from becoming blocked. Colourless crystals of the hydrochloride of the /3-o ime separate and aie filtered and washed with dry ether and then placed in a separating funnel and covered with a layer of ether. A. concentrated solution of sodium carbonate is gradually added with constant shaking until no further effervescence is observed. Sodium chloride is precipitated and the /3-oxime dissolves in the ether. The ether extract is sepaiated, dehydrated over sodium sulphate, and the ether remoi ed as rapidly as possible at the ordinary temperature by evaporation in vacuo. The residue crystallises, and when pressed on a porous plate leaves a mass of small silky needles, m. p. 126—130A It may be re-... 

Nitrosyl chloride reacts with aliphatic hydrocarbons at room temperature under the influence of light to give a complex mixture of substitution products. When the reaction is run on cyclohexane at —25°, however, the pure oxime hydrochloride crystallizes from the reaction mixture with virtually no side products. 

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