Preparation of Oximes

30 Grams of 4-benzyloxy-3,5-dimethoxy-nitrostyrene are dissolved in 90 cc. of glacial acetic acid and 180 cc. of alcohol and then mixed, while cooling, with 30 grams of zinc dust. After filtering the excess ol zinc dust, the residue is mixed with water and extracted several times with ether. After the ether has been distilled, the residue, consisting of the oxime of the 4-benzyloxy-3,5-dimethoxy-l-phenyl-acetaldehyde. 

Instead of zinc dust also other heavy metals, such as iron powder or alumina in the form of amalgam can be used. Source Friedrich 1911 

Hydroxylamine and its hydrochloride may have mutagenic effects. Should either of these substances contact your skin, immediately flood the affected area with water. 

Preparation Sign in at www.cengage.com/login to read the MSDSs for the chemicals used or produced in this procedure. 

Dissolve 0.5 g of hydroxylamine hydrochloride in 5 mL of water and 3 mL of 3 A4 sodium hydroxide solution, and add 0.5 g of the aldehyde or ketone. If the carbonyl compound is insoluble in water, add just enough ethanol to give a clear solution. Warm the mixture on a steam bath or boiling-water bath for 10 min then cool it in an ice-water bath. If crystals do not form immediately, scratch the side of the tube with a glass rod at the air-liquid interface to induce crystallization. Recrystallize the oxime from water or aqueous ethanol. 

In some cases, the use of 3 mL of pyridine and 3 mL of absolute ethanol in place of the 3 mL of 3 A4 sodium hydroxide solution and 5 mL of water is more effective. A longer heating period is often necessary. After finishing heating, pour the mixture into an evaporating dish and remove the solvent with a current of air in a hood. Grind the solid residue with 3-4 mL of cold water and filter the mixture. Recrystallize the oxime from water or aqueous ethanol. 

Flush excess reagent and filtrates down the drain. 

In the aliphatic series, nitrosation is mainly used for preparation of oximes,244 which are always obtained instead of the true nitroso compounds unless rearrangement can be avoided by choice of special conditions. In general, the reaction is more successful the more strongly the hydrogen to be replaced is activated by electron-attracting groups. 

Bis(hydroxyimino)acetone 253 A solution of crude acetonedicarboxylic acid (150 g) in water (275 ml) is thoroughly cooled in an ice-salt bath and treated dropwise, with stirring, with a solution of sodium nitrite (100 g) in water (200 ml) whilst the temperature is not allowed to rise above 0°. The mixture is then cooled to —5° and the precipitate formed is collected at once and washed with small amounts of ice-water. An additional quantity is obtained by adding cold 6N-nitric acid (200 ml) to the filtrate. The white product is washed four times with small amounts of ice-water and dried over sulfuric acid in a vacuum-desiccator it decomposes at 133°. The yield is 59 g (51 %). 

Sodium nitrite (18.5 g), dissolved in a little water, is added slowly to a solution of benzoyl-acetic ester (50 g) in glacial acetic acid (125 g) at 5-8°. Part of the resultant oxime crystallizes the remainder is precipitated when the solution is kept for 2-3 h below room temperature and then treated with ice-water. It crystallizes from hot ethanol in large tablets, m.p. 120 to 121° (52 g). 

Diethyl acetonedicarboxylate can be only mononitrosated when attempting dinitrosation with pentyl nitrite, von Pechmann258 obtained diethyl 4-hy-droxyisooxazole-3,5-dicarboxylate  

Nitrosation of -substituted / -keto esters is accompanied by loss of the acyl group. -Alkyl- x-(hydroxyimino)acetic esters, which are important for preparation of x-amino259 and x-keto acids,260 are obtained in this way from C-alkylacetoacetic esters  

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For the preparation of oximes, pheuylhydrazones and p nitrophenyl-hydrazones (where applicable), see under Aromatic Aldehydes, Section IV,135,4-d. 

H2NOH-HC1, Pyr, 60°. This is the standard method for the preparation of oximes. Ethanol or methanol can be used as cosolvents. 

The experimental conditions used to prepare oximes depend mostly on the nature of the parent materials and the basicity of the reaction medium usually, reactions proceed smoothly at pH close to neutral. In organic chemistry, it is generally beheved that reactions of RR C=0 and hydroxylamine at a pH close to neutral proceed through nucleophilic attack of the nitrogen electron pair on the electrophilically activated C=0 carbon. Usually, the preparation of oximes via condensation of the carbonyl compounds and hydroxylamine hydrochloride needs long reaction times . 

In 1999, Hajipour reported that silica gel, without any base, could be a useful catalyst for the preparation of oximes in dry media coupled with microwave irradiation. Hydroxylamine hydrochlorides were reacted with several aliphatic and aromatic aldehydes and ketones affording the desired oximes. 

The chemical applications of ultrasound (Sonochemistry) have become an exciting new field of research during the past decade. Recently, Li and coworkers have found an efficient and convenient procedure for the preparation of oximes via the condensation of aldehydes and ketones in ethanol with hydroxylamine hydrochloride under ultrasound irradiation (Scheme 8). Compared with conventional methods, the main advantages of the sonochemical procedure are milder conditions, higher yields and shorter reaction periods. The reason may be the phenomenon of cavitations produced by ultrasound. 

The preparation of oximes from olefins is a valuable approach for the synthesis of nitrogen-containing compounds such as amino acids and heterocycles. Okamoto and colleagues have reported that a catalytic reduction-nitrosation of styrenes 31 with ethyl nitrite and tetrahydroborate anion by the use of bis(dimethylglyoximato)cobalt(II) complex afford the corresponding acetophenone oximes 32 (Scheme 23). 

Addition of ammonia and its derivatives to carbonyl compounds preparation of oximes and imine derivatives (Schiff s bases)... 

Identification and preparation of oxime ester photopolymerization initiators that do not cause film discoloration or deteriorated by heat while remaining highly light sensitive. 

I) Preparation of Oximes. (1) Acetoxime. Dissolve 1 g of hy-droxylamine hydrochloride in 2 ml of water. Add 3 ml of 20 per cent sodium hydroxide solution (or 0.6 g of solid sodium hydroxide dissolved in 2 ml of water). Add 2 ml of acetone, cork securely, and shake vigorously for one minute. Allow to stand overnight. If crystals do not appear, seed with a minute amount of the oxime, and allow to stand for some time. Filter the crystals with suction and allow to dry. Place in a tube or bottle immediately. 

For the preparation of oximes by nitrosation of compounds containing active methylene groups see page 428. 

The cheaper sodium hydroxylamine-A,A-disulfonate may be used for preparation of oximes in place of the relatively expensive hydroxylamine. This salt is readily obtained from sodium nitrite, sodium hydrogen sulfite,... 

Experimental details for the preparation of oximes, phenylhydrazones and p-nitrophenylhydrazones will be found under Aromatic Aldehydes, Section lV,135, -fi. 

Oximes, which are valuable intermediates for the conversion of oxoalkyl phosphonic diesters into those of aminoalkylphosphonic acids (Chapter 4, Section IV.C. 1. d), are also readily available, although it is necessary to prepare them with some care. Nevertheless, the feature of interest here is their ready degradability, particularly under aqueous conditions, and which has been intensively investigated by Breuer and coworkers. The necessity for care in the preparation of oximes of acylphosphonic diesters, is illustrated by the synthesis of dimethyl [a-(hydroxyimino)benzyl]phosphonate this compound exists in the thermodynamically more stable ( ) form which, under the influence of acid is converted into the less stable (Z) form, and both forms have been separately characterized by X-ray crystallography. The geometric isomers of the oxime differ in their behaviour under basic conditions with NaOH-MeOH, the ( ) form undergoes monodealkylation, whereas the (Z) isomer decomposes to dimethyl phosphate and benzonitrile. In aqueous solution, ( )-[a-(hydroxyimino)benzyl]phosphonic acid also decomposes into benzonitrile together with phosphoric acid, in a manner which is pH dependent, and consistent with a dissociative mechanism that involves the early formation of monomeric metaphosphate. ... 

Hydroxylammoniuna phosphate serves as a convenient reagent for the preparation of oximes the saturated aqueous solution has a pH of about 5, the pH of maximum rate of oxime formation. 

In the preparation of oximes the hydroxylaminc is employed An the form of the /rcc fiasco the hydrochlo-ride as potassium hydroxylamiucsulphonate dihydroxylaminc hydrochloride, A Idoximcs... 

Preparation of phenylhydrazones, 68. Preparation of parabromophenylhydrazine, 72. Substituted hy-flrazones, 73. Indirect method, 74. Preparation of oximes, 80. Preparation of scmicarbazones, 84, 87. Preparation of scmicarbazinc salts, 84. Preparation of thiosemicarbazine derivatives, 88. Preparation of semioxamazine, 90. Preparation of amidoguanidine derivatives, 90. Paramidodimcthylaniline derivatives. 

FIGURE 14.7 Derivatization for ESI-MS/MS. (A) Preparation of the dimethylaminoethylester of dihydroxycholestanoic acid bis acetate. (B) Preparation of aminoethanesulfonate derivative of chenodeoxycholic acid. (C) Formation of sulfate ester of cholesterol. (D) Preparation of oxime of testosterone. 

For the preparation of oximes using hydroxylamine hydrochloride as the reagent see... 

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