Sulphuric acid, hydrolysis

HC CH(0H) CH20H. optically active. D-glyceraldehyde is a colourless syrup. May be prepared by mild oxidation of glycerol or by hydrolysis of glyceraldehyde acetal (prepared by oxidation of acrolein acetol). DL-glyceraldehyde forms colourless dimers, m.p. IBS-S C. Converted to methylglyoxal by warm dilute sulphuric acid. The enantiomers... 

Hydrolysis of Aspirin. Gently boil a mixture of i g. of aspirin and 15 ml. of 10% sodium hydroxide solution in a 50 ml. conical flask under reflux for 20 minutes. Then cool the solution thoroughly and add dilute sulphuric acid until the precipitation of the... 

Boil a mixture of 5 ml. (4 g.) of acetonitrile and 75 ml. of 10% aqueous sodium hydroxide solution in a 200 ml. flask under a refluxwater-condenser for 30 minutes, when hydrolysis will be complete. Detach the condenser and boil the solution in the open flask for a few minutes to drive off ull free ammonia. Then cool the solution, and add dilute sulphuric acid (i volume of concentrated acid 2 volumes of water)... 

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. 

Hydrolysis to p-Nitroaniline. For this purpose use 70 sulphuric acid, the usual reagent employed for the hydrolysis of anilides (p. 108). Add 5 g. of the recrystallised />-nitro-acetanilide to 30 ml. of 70%sulphuric acid, and boil the mixture gently under a reflux water-condenser for 20 minutes. Then pour the clear hot solution into about 150 ml. of cold water, and finally add an excess of sodium hydroxide solution until precipitation of the yellow p-nitroaniline is complete. Coo the mixture in ice-water if necessary, and then filter at the pump, wash well... 

Benzamide from Benzonitrile. (A) Although benzonitrile when boiled with 70% sulphuric acid undergoes ready hydrolysis to benzoic acid (see above), treatment with hot 90% sulphuric acid gives the intermediate benzamide. This difference arises partly from the difference in temperature employed, but also... 

Hydrolysis of />-Tolunitrile. As in the case of benzonitrile, alkaline h> drolysis is preferable to hydrolysis by 70% sulphuric acid. Boil a mixture of 5 g. of p-tolunitrile, 75 ml. of 10% aqueous sodium hydroxide solution and 15 ml. of ethanol under a reflux water-condenser. The ethanol is added partly to increase the speed of the hydrolysis, but in particular to prevent the nitrile (which volatilises in the steam) from actually crystallising in the condenser. The solution becomes clear after about i hour s heating, but the boiling should be continued for a total period of 1-5 hours to ensure complete hydrolysis. Then precipitate and isolate the p-toluic acid, CH3CgH4COOH, in precisely the same way as the benzoic acid in the above hydrolysis of benzonitrile. Yield 5 5 g. (almost theoretical). The p-toluic acid has m.p. 178°, and may be recrystallised from a mixture of equal volumes of water and rectified spirit. 

Hydrolysis of Benzanilide. For this hydrolysis, it is necessary to use 70% sulphuric acid (see Hydrolysis of Acetanilide, p. 108). Add I g. of benzanilide to 10 ml. of 70% sulphuric acid, and boil the mixture gently in a small flask under a reflux water-condenser for 30 minutes. Hydrolysis will now be complete, but much of the benzoic acid will have vaporised in the steam and then solidified in the conden-... 

The aniline and the monomethylaniline can be obtained from their respective sulphonyl derivatives by hydrolysis with 70% sulphuric acid (preparation, p. 109), the mixture of the sulphonyl compound and the acid being gently boiled under reflux to illustrate the separation of the three amines, however, this is not necessary. 

The method of hydrolysis depends on the nature of the product. It is usually sufficient to add dilute sulphuric acid to the ethereal solution and to shake thoroughly, when the magnesium enters the aqueous solution, whilst the organic compound remains in the ether. Alternatively, however, the ethereal solution may be poured on to ice and water, and then treated with dilute sulphuric acid. Should the product be affected by this acid, the hydrolysis can be carried out with an aqueous solution of ammonium chloride. In the following examples the hydrolysis is usually shown as a simple double decomposition... 

The residue in the flask will contain the sodium (or potassium) salt of the acid together with excess of alkali. Just acidify with dilute sulphuric acid and observe whether a crystalline acid separates if it does, filter, recrystallise and identify (Section 111,85). If no crystaUine solid is obtained, the solution may be just neutralised to phenolphthalein and the solution of the alkali salt used for the preparation of a crystaUine derivative. This wiU confirm, if necessary, the results of hydrolysis by method 1. If the time factor is important, either method 1 or the product of the caustic alkali hydrolysis may be used for the identification of the acid. 

Aliphatic amides may be hydrolysed by boiling with 10 per cent, sodium hydroxide solution to the corresponding acid (as the sodium salt) the alkahne solution should be acidified with dilute sulphuric acid any water-soluble acid may then be distilled from the solution. Alternatively, hydrolysis may be eflfected with 10-20 per cent, sulphuric acid. The resulting ahphatic acid (usually a liquid) may be characterised as detailed in Section 111,85. 

For those nitriles which yield water-insoluble amides e.g., the higher alkyl cyanides), hydrolysis to the amide often leads to a satisfactory derivative. The hydration is eflfected by warming a solution of the nitrile in concentrated sulphuric acid for a few minutes, cooling and pouring... 

By the hydrolysis of dialkyl cyanamides with dilute sulphuric acid this method gives pure secondary amines. The appropriate dialkyl cyanamide is prepared by treating sodium cyanamide (itself obtained in solution from... 

Ketonic hydrolysis to di-iso-propyl ketone. Mix 15 g. of the ester with 30 ml. of glacial acetic acid, 10 ml. of water and 10 ml. of concentrated sulphuric acid, and reflux in a flask coimected by a ground glass joint... 

If only the monocarboxybc acid is required, the ester after hydrolysis with potash may be strongly acidified with sulphuric acid and the mixture heated under reflux the mineral acid promotes decarboxylation at a temperature just above 100°. The net result is the replacement of the halogen atom of the alkyl halide by —CH COOH thus in the above example ... 

Sulphonamides are most readily identified by hydrolysis with concentrated hydrochloric acid or with 80 per cent, sulphuric acid (for experimental details, see Section K.,7,12) ... 

In general, however, the diacetyl derivatives are unstable in the presence of water, undergoing hydrolysis to the mono-acetyl compound, so that when they (or a mixture of mono- and di-acetyl derivatives) are crystallised from an aqueous solvent, e.g., dilute alcohol, only the mono-acetyl derivative is obtained. A further disadvantage of the use of acetic anhydride in the absence of a solvent is that all the impm-ities in the amine are generally present in the reaction product. Heavily substituted amines, t.g., 2 4 6-tribromoaniline, react extremely slowly with acetic anhydride, but in the presence of a few drops of concentrated sulphuric acid as catalyst acetylation occurs rapidly, for example ... 

Benzoyl compounds are readily hydrolysed by heating with about 70 per cent, sulphuric acid (alkaline hydrolysis is very slow for anilides) ... 

Hydrolysis of benzanilide. Place 5 g. of benzanilide and 50 ml. of 70 per cent, sulphuric acid in a small flask fitted with a reflux condenser, and boU gently for 30 minutes. Some of the benzoio acid will vapourise in the steam and solidify in the condenser. Pour 60 ml. of hot water down the condenser this will dislodge and partially dissolve the benzoic acid. Cool the flask in ice water filter off the benzoic acid (anifine sulphate does not separate at this dilution), wash well with water, drain, dry upon filter paper, and identify by m.p. (121°) and other tests. Render the filtrate alkaline by cautiously adding 10 per cent, sodium hydroxide solution, cool and isolate the aniline by ether extraction. Recover the ether and test the residue for anifine (Section IV,100). 

From the nitrile. By refluxing a mixture of the aromatie nitrile (with —CN group in aide chain) with alcohol and concentrated sulphuric acid simultaneous hydrolysis and esterification occurs, for example ... 

The acid is hberated upon acidification. Hydrolysis may also be efifected (but less readily and usuaUy not quite so satisfactorily) by boiling with dilute h3 drochloric acid (1 1) or 20 per cent, sulphuric acid ... 

Benzanilide and similar compounds are very slowly hydrolysed by concentrated hydrochloric acid hydrolysis is quite rapid with 60-70 per cent, sulphuric acid (for experimental details, see Section IV,52). In the preliminary experiment boil 0 5-1 Og. of the compound with 10-20 ml. of dilute sulphuric acid (1 1 by volume) imder reflux for 20-30 minutes. Dilute with 10ml.of water and filteroflfanyacid which may be precipitated if the carboxyhc acid is hquid and volatile, distil it directly from the reaction mixture. Render the residue alkaline and isolate the base as above. 

Hydrolysis may be effected with 10-20 per cent, sodium hydroxide solution (see p-Tolunitrile and Benzonitrile in Section IV,66) or with 10 per cent, methyl alcoholic sodium hydroxide. For diflScult cases, e.g., a.-Naphthoniirile (Section IV,163), a mixture of 50 per cent, sulphuric acid and glacial acetic acid may be used. In alkahne hydrolysis the boiling is continued until no more ammonia is evolved. In acid hydro-lysis 2-3 hours boiling is usually sufficient the reaction product is poured into water, and the organic acid is separated from any unchanged nitrile or from amide by means of sodium carbonate solution. The resulting acid is identified as detailed in Section IV,175. 

When acetone is condensed with ethyl cyanoacetate in the presence of a solution of anhydrous ammonia in absolute alcohol at —5°, the ammonium salt of the dicyano-imlde (I) is precipitated. Upon dissolving this salt in water and adding excess of concentrated hydrochloric acid, the crystalline dicyano-imide (II) is obtained. Hydrolysis of the last-named with strong sulphuric acid affords p p dimethylglutaric acid (III). 

The epoxides may be converted into 1 2-glycols by hydrolysis. In some cases the 1 2-glycol may be produced directly by carrying out the epoxidation in the presence of water. If the 1 2-glycol is desired, it is usually better to employ performic acid or peracetic acid, the latter best in the presence of a trace of sulphuric acid. An epoxide is first formed, followed by the hydroxy-formate or hydroxy-acetate, and ultimately the 1 2-glycol ... 

A further improvement is embodied in the Klndler variation of the Willgerodt reaction this consists in heating the ketone with approximately equal amounts of sulphur and a dry amine instead of aqueous ammonium polysulphide. The principal product is a thioamide, and hydrolysis with acid or alkali affords the carboxylic acid, usually in good yield. 

Bromination of quinaldine (I) (Section V,2) with bromine in glacial acetic acid in the presence of anhydrous sodium acetate aflFords dilute sulphuric acid gives quinaltiinic acid (III). 

It may be converted into dibromofluorescein diacetate as follows. Reflux a mixture of 10 g. of dibromofluorescein, 40 ml. of redistilled acetic anhydride and 1 drop of concentrated sulphuric acid for 1 hour, pour into water, filter, wash, and dry the resulting diacetate (95 per cent, yield) has m.p. 210°. Upon recrystallisation from acetic anhydride or nitrobenzene, the pure diacetate (colourless or pale yellow plates), m.p. 211°, is obtained. Hydrolysis with alcoholic sulphuric acid gives a quantitative yield of pure dibromofluorescein, m.p. 285°. 

Complete hydrolysis may be efiected by boiling either with 10 per cent, sodium hydroxide solution or with 10 per cent, sulphuric acid for 1-3 hours. It is preferable to employ the non-volatile sulphuric acid for acid hydrolysis this... 

Nitriles. These are best hydrolysed by boiling either with 30-40 per cent, sodium hydroxide solution or with 50-70 per cent, sulphuric acid during several hours, but the reaction takes place less readily than for primary amides. Indeed the latter are intermediate products in the hydrolysis ... 

Sulphonatnides. Sulphonamides are very resistant to the normal reagents for hydrolysis. Heating with 80 per cent, sulphuric acid at 160-170° results in rapid hydrolysis ... 

Hydrolysis of a substituted amide. A. With 10 per cent, sulphuric acid. Reflux 1 g. of the compound (e.g., acetanilide) with 20 ml. of 10 per cent, sulphuric acid for 1-2 hours. Distil the reaction mixture and collect 10 ml. of distillate this will contain any volatile organic acids which may be present. Cool the residue, render it alkaline with 20 per cent, sodium hydroxide solution, cool, and extract with ether. Distil off the ether and examine the ether-soluble residue for an amine. 

Hydrolysis of a nitrile to an acid. Reflux 1 g. of the nitrile with 6 ml. of 30-40 per cent, sodium hydroxide solution until ammonia ceases to be evolved (2-3 hours). Dilute with 5 ml. of water and add, with coohng, 7 ml. of 50 per cent, sulphuric acid. Isolate the acid by ether extraction, and examine its solubility and other properties. 

---