Dimethyl sulphate

Copper I) sulphate, C112SO4. Grey solid, CU2O plus dimethyl sulphate. 

Copper(l) sulphate, CU2SO4, is obtained as a white powder by heating together dimethyl sulphate and copper(I) oxide ... 

Dimethyl Sulphate Method for hydroxy compounds and for primary and secondary amines, acid amides, etc. The substance is dissolved or suspended in water, a small excess (above the theoretical) of sodium hydroxide added and then the theoretical quantity of dimethyl sulphate, the mixture being finally shaken without external warming. Methylation is usually rapid, the dimethyl sulphate being converted to methyl hydrogen sulphate... 

Dimethyl sulphate is poisonous, both when the hot vapour is inhaled and even when the cold liquid is spilt on the hands, and considerable care should be eyercised in its use cf. pp. 215, 218, 526). 

The Formaldehyde-Formic Acid Method, This method applies to primary and secondary amines, which when boiled with a formalin-formic acid mixture undergo complete methylation to the corresponding tertiary amine. This method has the advantage over the dimethyl sulphate method in that quaternary salts clearly cannot be formed. 

Experiments involving the use of dimethyl sulphate should be carried out by students only under immediate supervision. Not only is the vapour of dimethyl sulphate highly poisonousy but the cold liquid itself is absorbed easily through the skin, with toxic results individual susceptibility to ditnethyl sulphate poisoning varies and may be very high. If the sulphate is splashed on to the hands, wash immediately with plenty of concentrated ammonia solution in order to hydrolyse the methyl sulphate before it can be absorbed through the skin (see p. 528). 

Toluene-p-sulphonamide can be similarly converted into the dimethyl-amide, but the methylation now occurs in two definite stages. First the sulphonamide dissolves in the sodium hydroxide to form the mono-sodium salt (see p. 252), which then reacts with the dimethyl sulphate to give the mono-... 

Dissolve log. of powdered toluene-p-sulphonamide in 6o ml. of 10% aqueous sodium hydroxide (2 5 mols.) diluted with 50 ml. of water to moderate the reaction. Then, using the same precautions as in the previous preparation, add 127 ml. (17 g., 2 3 mols.) of dimethyl sulphate and shake the mixture vigorously. The crystalline dimethylamide rapidly separates from the warm... 

This preparation illustrates the use of dimethyl sulphate to convert a primary amino group into the secondary monomethylamino group, without the methy-lation proceeding to the tertiary dimethylamino stage. The methylation of anthranilic acid is arrested at the monomethylamino stage by using i-i molecular equiN alents of sodium hydroxide and of dimethyl sulphate. The reactions can be considered as ... 

A fresh sample of dimethyl sulphate should be employed an old sample, or one that has been frequently exposed to the air, should be shaken with water, separated, dried over sodium sulphate, and distilled (b.p. 188"). 

Dissolve 2 g. of anthranilic acid in 12 8 ml. of 5% aqueous sodium hydroxide, or in 16 ml. of A -NaOH solution in a 50 ml. conical flask. (It is essential that the concentration of the hydroxide solution is accurately known.) Add i-6 ml. of dimethyl sulphate, and shake the securely-stoppered flask vigorously. 

The preparation of these compounds in the laboratory is not recommended and is rarely worth while because of the cheapness of the commercial products. Dimethyl sulphate is a heavy liquid, boiling at 188-6°, and is practically without odour. The vapour is highly poisonous and the substance should only be used in a fume cupboard with a good draught. The liquid itself is readily absorbed through the skin, with toxic results. 

Dimethyl sulphate is of particular value for the methylation of phenols and sugars. The phenol is dissolved in a slight excess of sodium hydroxide solution, the theoretical quantity of dimethyl sulphate is added, and the mixture is heated on a water bath and shaken or stirred mechanically (compare Section IV, 104). Under these conditions only one of the methyl groups is utilised the methyl hydrogen sulphate formed in the reaction reacts with the alkali present. -... 

Diethyl sulphate, b.p. 210° (decomp.), does not ordinarily react so vigor ously as dimethyl sulphate, but is nevertheless of great value for ethylations. It is somewhat leas poisonous than the methyl analogue, but the same pre cautions should be taken. Both sulphates should be stored in glass stoppered bottles sealed with paraffin wax, for they attack cork. 

Methyl and ethyl ethers of phenols are most conveniently prepared by alkylation with dimethyl sulphate and diethyl sulphate respectively in weakly alkaline solution, for example ... 

Equip a 500 ml, three-necked flask with a separatory funnel, a mercury-sealed mechanical stirrer and a reflux condenser. Place a solution of 21 g. of sodium hydroxide in 200 ml. of water and also 47 g. of pure phenol in the flask, and stir the mixture cool the warm mixture to about 10° by immersing the flask in an ice bath. Place 63 g. (47 ml.) of dimethyl sulphate in the separatory funnel. 

CAUTION, Doth the vapour and the liquid dimethyl sulphate are highly poisonous. Inhalation of the vapour may lead to giddiness and even to more serious results. The cold liquid is easily absorbed through the skin, with toxic results. If the dimethyl sulphate is accidentally splashed upon the hands, wash immediately... 

Add the dimethyl sulphate dropwise during 1 hour whilst stirring the mixture vigorously. Then reflux for 2 hours, with stirring, in order to complete the methylation. Allow to cool, add water, transfer to a separatory funnel, remove the lower layer, and wash once with water, twice with dilute sulphuric acid, and then with water until the washings are neutral to litmus. Add some sodium chloride to each washing as this will facilitate the separation of the two layers for anisole is 0- 996). Dry over anhydrous calcium chloride or magnesium sulphate, and distil from an air bath. Collect the anisole at 151-154°. The yield is 40 g. 

Naphthyl methyl ether (nerolin). Use 36 0 g. of p-naphthol, 10-5 g. of sodium hydroxide in 150 ml. of water, and add 31 -5 g. (23 -5 ml.) of dimethyl sulphate whilst the mixture is cooled in ice. Warm for 1 hour at 70-80°, and allow to cool. Filter oflF the naphthyl methyl ether at the pump, wash with 10 per cent, sodium hydroxide solution, then liberally with water, and drain thoroughly. Recrystallise from benzene or methylated spirit. The yield is 33 g., m.p. 72°. 

CAUTION. Diethyl sulphate is poisonous, but to a less degree than dimethyl sulphate. Similar precautions should, however, be taken (see above). 

Dimethyl sulphate may be purified (a) by allowing it to stand over anhydrous potassium carbonate until it is neutral to Congo red paper, or (6) by washing, just before use, with an equal volume of ice water, followed by one-third of its volume of cold, saturated sodium bicarbonate solution. 

This substance may be conveniently methylated with dimethyl sulphate to 3deld 1-phenyl-2 3-dimethyl-5-pyrazolone or antipyrin (III) ... 

Alkylation Hazards arise from the alkylating agents, e.g. dimethyl sulphate (suspected human carcinogen), hydrogen fluoride (highly toxic irritant gas) Thermal alkylation processes require higher temperatures and pressures, with associated problems... 

---