Sodium derivatives

Two independent n.m.r. studies of the effect of alkali-metal cations (Na ) on the conformational equilibrium of the acetylacetonate ion have been effected. Experiments have demonstrated that the two configurations 

The crystal structure of the high-temperature modification of Na TCNQ has been determined at 353 The Na ion is surrounded almost octahedrally by the six negatively charged N atoms of different TCNQ ions, with Na N distances 0.2421—0.2560 nm the co-ordination geometry is very similar to that of the low-temperature phase. 

---

Note. The sodium hydroxide must be accurately weighed out, for an excess will dissolve the oxime as the sodium derivative.)... 

Although the acetylation of alcohols and amines by acetic anhydride is almost invariably carried out under anhydrous conditions owing to the ready hydrolysis of the anhydride, it has been shown by Chattaway (1931) that phenols, when dissolved in aqueous sodium hydroxide solution and shaken with acetic anhydride, undergo rapid and almost quantitative acetylation if ice is present to keep the temperature low throughout the reaction. The success of this method is due primarily to the acidic nature of the phenols, which enables them to form soluble sodium derivatives, capable of reacting with the acetic... 

Dissolve a small portion of the sodium derivative in a few mi. of water in a test-tube, and add one drop of ferric chloride solution. A deep red coloration is produced, but rapidly disappears as the iron is precipitated as ferric hydroxide. The sodium (derivative (A) of the nitromethane wh dissolved in water undergoes partial hydrolysis,... 

The addition of the sulphuric acid first neutralises the sodium hydroxide, and then gives a weakly acidic and therefore colourless solution. The sodium derivative (A) then undergoes further partial hydrolysis in order to re-establish the original equilibrium, and the sodium hydroxide thus formed again produces the pink coloration, which increases in depth as the hydrolysis proceeds. 

When the above tests have been completed, wash thoroughly with water all apparatus contaminated with the sodium derivative, since the latter, if allowed to dry, becomes very explosive. 

Williamson s lethod, more particularly lor hydroxy- and thloT (mercapto) compounds. The substance is treated either directly with sodium or (more usually) with a solution of sodium methoxide in methanol, to give the sodium derivative. The latter is then boiled with methvl iodide. 

Toluene-/ sulplionamide is almost insolubb in cold water, but dissolves readily in sodium hydroxide solution (as the sodium derivative) aid is immediately reprecipitated on the addition of strong acids. To show the formation of the sodium derivative, dissolve about o-2 g. of metallic sodium in about 10 ml, of ethanol, cool the solution, and then add it to a solution of 1 g. of the sulphonamide in 20 ml. of cold edianol. On shaking the mixture, fine white crystals of the sodium derivative, CH,C,HjSO,NHNa, rapidly separate, and may be obtained pure by filtering at the pump, and washing firet with a few ml. of ethanol, and then with ether. 

It is readily prepared by the action of metallic sodium on dry ethyl acetate. The reaction, which occurs only in the presence of a trace of ethanol, is complex, but may be considered (in effect) as a condensation of two molecules of ethyl acetate under the influence of sodium ethoxide, the sodium derivative of the enol form being thus obtained. Clearly, only a trace of ethanol is thus initially... 

Refractionation of the low-boiling impurities gives a further quantity of the acetoacetate, but if the initial distillation has been carefully conducted, the amount recovered is less than i g., and the refractionation is not worth while. If possible, complete the preparation in one day. If this is not possible, it is best to allow the cold crude sodium derivative (before acidification) to stand overnight, the flask being closed by a cork carrying a calcium chloride tube the yield will now fall to about 38 g. Alternatively, the crude ester may be allowed to remain overnight in contact with the sodium sulphate, but in this case the yield will fall to about 30 g. 

Mono and Di-iubstitution Derivatives. The enolic sodium derivative of ethyl acetoacetate (E) is prepared by mixing ethanolic solutions of the ester and of sodium ethoxide. It should not be prepared by the direct action of metallic sodium on the ester, as the reaction is slow and the nascent hydrogen evolved reduces some of the ester to ethyl p4iydroxy- butyrate, CH3CH(OH)CHjCOOEt. 

When the sodium derivative, which is used in ethanol it solution without intermediate isolation, is boiled with an alkyl halide, e.g., methyl iodide,... 

Acyl halides, both aliphatic and aromatic, react with the sodium derivative, but the product depends largely on the solvent used. Thus acetyl chloride reacts with the sodium derivative (E) suspended in ether to give mainly the C-derivative (t) and in pyridine solution to give chiefly the O-derivative (2). These isomeric compounds can be readily distinguished, because the C-derivative (1) can still by enolisation act as a weak acid and is therefore... 

Substitution Derivatives of Ethyl Malonate, Ethyl malonate resembles ethyl acetoacetate in that it gives rise to mono- and di-substituted derivatives in precisely similar circumstances. Thus when ethanolic solutions of ethyl malonate and of sodium ethoxide are mixed, the sodium derivative (A) of the enol form is produced in solution. On boiling this solution with an alkyl halide, e.g, methyl iodide, the methyl derivative (B) of the keto form is obtained. When this is treated again in ethanolic solution with sodium ethoxide, the... 

When an ethanolic solution of the sodium derivative of ethyl malonate is. shaken with a solution of iodine, the latter withdraws the sodium, and the ethyl malonate residues link together in pairs to give the tetra-ethyl ester of... 

Ethane tetracarboxylic ethyl ester can be regarded as composed of two malonic ester residues, each acting as a mono-alkyl substituent to the other. The two remaining hydrogen atoms therefore still retain acidic properties, and consequently the ester gives with sodium ethoxide a di-sodium derivative. 

Solubility in sodium carbonate solution. Note that phenols, when soluble in water, will also dissolve in NagCOg solution, but usually loithout evolution of CO, i.e., without the formation of a sodium derivative. This reaction can therefore be used to distinguish between carboxylic adds and most phenols. See Section 5, p. 330. 

The equilibrium of the last step (3), which is not actually part of the condensation mechanism, is far to the right because of the greater basic strength of the ethoxide ion as compared to (IV), and this largely assists the forward reactions in (1) and (2). The reaction mixture contains the sodium derivative of the keto-ester, and the free ester is obtained upon acidification. 

Malonic ester, like acetoacetic ester (Section 111,151), when treated with an equivalent of sodium ethoxide, forms a mono-sodium derivative, which is of great value in synthetical work. The simplest formulation of the reaction is to r rd it as an attack of the basic ethoxide ion on a hydrogen atom in the CH, group the hydrogen atoms in the CHj group are activated by the presence of the two adjacent carbethoxyl groups ... 

RCH=N—ONa and R R C=N—ONa) which may be filtered off and washed with methanol to remove traces of sodium methoxide. It should be kept moist with methanol the sodium derivative, if allowed to dry, may become very explosive. Also, upon contact with a trace of water, it is liable to decompose with explosive violence. The sodium derivative may be dissolved by successively adding small quantities to cold water with continual stirring. 

Crystalline derivatives, suitable for identification and characterisation are dealt with in Section IV, 114, but the preparation of the following, largely liquid, derivatives will be described in the following Sections. When phenols are dissolved in aqueous sodium hydroxide solution and shaken with acetic anhydride, they undergo rapid and almost quantitative acetylation if the temperature is kept low throughout the reaction. This is because phenols form readily soluble sodium derivatives, which react with acetic anhydride before the latter undergoes appreciable hydrolysis, for example ... 

Higher alkyl ethers are prepared by treating the sodium derivative of the phaiol (made by adding the phenol to a solution of sodium ethoxide in ethyl alcohol) with the alkyl iodide or bromide (Williamson synthesis), for example ... 

The preparation of the sodium derivative of the phenol may be avoided by heating the enol and alkyl halide in the presence of potassium carbonate and acetone, for example ... 

Dissolve 1 0 g. of the compound in 5 ml. of dry chloroform in a dry test-tuhe, cool to 0°, and add dropwise 5g. (2-8 ml.) of redistilled chloro-sulphonic acid. When the evolution of hydrogen chloride subsides, allow the reaction mixture to stand at room temperature for 20 minutes. Pour the contents of the test-tube cautiously on to 25 g. of crushed ice contained in a small beaker. Separate the chloroform layer and wash it with a httle cold water. Add the chloroform layer, with stirring, to 10 ml. of concentrated ammonia solution. After 10 minutes, evaporate the chloroform on a water bath, cool the residue and treat it with 5 ml. of 10 per cent, sodium hydroxide solution the sulphonamide dissolves as the sodium derivative, RO.CgH4.SO,NHNa. Filter the solution to remove any insoluble matter (sulphone, etc.), acidify the filtrate with dilute hydrochloric acid, and cool in ice water. Collect the sulphonamide and recrystallise it from dilute alcohol. 

It is not advisable to treat the crude jo-nitroplieriol with sodium hydroxide solution in order to convert it into the sodium derivative alkali causes extensive resiniflcation. 

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. 

Decant the liquid layer into a 2 5 litre flask, and dissolve the sodium derivative of acetylacetone in 1600 ml. of ice water transfer the solution to the flask. Separate the impiue ethyl acetate layer as rapidly as possible extract the aqueous layer with two 200 ml. portions of ether and discard the ethereal extracts. Treat the aqueous layer with ice-cold dilute sulphimic acid (100 g. of concentrated sulphiu-ic acid and 270 g. of crushed ice) until it is just acid to htmus. Extract the diketone from the solution with four 200 ml. portions of ether. Leave the combined ether extracts standing over 40 g. of anhydrous sodium sulphate (or the equivalent quantity of anhydrous magnesium sulphate) for 24 hours in the ice chest. Decant the ether solution into a 1500 ml. round-bottomed flask, shake the desiccant with 100 ml. of sodium-dried ether and add the extract to the ether solution. Distil off the ether on a water bath. Transfer the residue from a Claisen flask with fractionating side arm (Figs. II, 24, 4r-5) collect the fraction boiling between 130° and 139°. Dry this over 5 g. of anhydrous potassium carbonate, remove the desiccant, and redistil from the same flask. Collect the pure acetji-acetone at 134r-136°. The yield is 85 g. 

Mesityl oxide (Section 111,79) (I) condenses with ethyl malonate in the presence of sodium ethoxide to give the sodium derivative of (II) this upon hydrolysis with aqueous potassium hydroxide, followed by acidification, gives the cyclic diketone 5 5-dimethyl-l 3-cycfohexanedione (III), of which the enoUc form is 5 5-dimethyldihydroresorcinol (IV) ... 

Diethylbarbituric acid. In a dry 250 ml. distilling flask, fitted with a thermometer reaching to within 3-4 cm. of the bottom and a condenser, place 51 g. of clean sodium and add 110 g. (140 ml.) of super-dr ethyl alcohol (Section 11,47,5). When all the sodium has reacted, introduce 20 g. of ethyl diethylmalonate and 7 0 g. of dry imea (dried at 60 for 4 hours). Heat the flask in an oil bath and slowly distil off the ethyl alcohol. As soon as the temperature of the liquid reaches 110-115°, adjust the flame beneath the bath so that the contents of the flask are maintained at this temperature for at least 4 hours. Allow the flask to cool somewhat, add 100 ml. of water and warm until the solid (veronal-sodium) dissolves. Pour the solution into a beaker, and add a further 100 ml. of water but containing 7 0 ml. of concentrated siilplmric acid this will hberate the veronal from the sodium derivative. The veronal usually crystallises out if it does not, add a few more drops of dilute sulphuric acid until the solution is acid to Congo red. Heat the contents of the beaker, with stirring and the addition of more water if necessary, until all the veronal dissolves at the boiling point. Allow the hot solution to cool, filter off the crystals of veronal and diy in the air. The yield is 12 g., m.p. 190°. 

An alternative method of purification, well adapted for large scale practice, is as follows. Dissolve the crude sulphapyridine in 1-05 mols of 30 per cent. u>/v sodium hydroxide, salt out the sodium derivative with excess of sodium chloride,... 

Organosodium compounds are prepared from sodium and other organometaUic compounds or active methylene compounds by reaction with organic haUdes, cleavage of ethers, or addition to unsaturated compounds. Some aromatic vinyl compounds and aHyUc compounds also give sodium derivatives. 

Both 4,5-dimethylisoxazole and 3,4-dimethylisoxazole are formed on treatment of the sodium derivative of a-methylacetaldehyde with hydroxylamine hydrochloride. The two isomers can be separated by fractional distillation <62HC(17)1, p. 54). 4,5-Dialkylisoxazole or 3,4-dialkylisoxazole can be obtained as the sole reaction product from an appropriate nitrile iV-oxide and an appropriate vinyl acetate. 

If the reaction mixture is allowed to become too thick for efficient stirring, or if the temperature of the oil bath is raised above 115-120°, the solid sodium derivative will cake on the sides of the flask. This makes the complete removal of the reaction mixture from the flask and the decomposition of the sodium derivative more difficult. 

---