Organic Syntheses Part 8

1. Procedure

TECHNICAL anthranilic acid (generally about 95 per cent pure) (685 g.) is dissolved in 1.5 l. of water and 500 cc.

of concentrated hydrochloric acid (sp. gr. 1.17), by heating.

The insoluble dark impurity present in small amounts is filtered off, and the filtrate is transferred to a 10-l. crock and chilled with stirring. It is then mixed with a mush of 2.5 kg.

of ice and 750 cc. of concentrated hydrochloric acid. The crock is cooled externally with ice, and the contents stirred continuously.

When the temperature reaches about 3'0, a filtered solution of 360 g.

of sodium nitrite in 700 cc. of water is dropped in slowly, through a long capillary tube reaching below the surface of the liquid, until a faint but permanent reaction to starch pota.s.sium iodide paper is obtained; the temperature is kept between 3'0 and 5'0. This operation requires all but about 30 cc.

of the nitrite solution and occupies one and a half to two hours.

To the solution of the diazonium salt are now added 848 g.

of dimethylaniline; this may be done rapidly, as the temperature does not rise appreciably. Stirring is continued for one hour, the temperature being kept at 5'0 Five hundred cc. of a filtered solution of 680 g. of crystallized sodium acetate diluted to 1200 cc.

are then added, and the stirring continued for four hours.

If a foamy solid rises to the surface during this time and refuses to become incorporated by the stirrer, a few drops of ethyl acetate may be added to reduce the foam. The mixture is allowed to stand overnight in an ice bath which is well insulated by several thicknesses of burlap; the temperature must be kept below 7'0 to get a good yield of product.

The remainder of the sodium acetate solution is then added with stirring, and after the mixture has been stirred for an additional period of one to three hours, the temperature is allowed to rise slowly to 20-25'0 in the course of twenty-four hours.

Just enough sodium hydroxide solution is then added, with stirring, to cause the mixture to have a distinct odor of dimethylaniline (about 240 cc. of a 40 per cent solution are generally required), and the mixture is allowed to stand for forty-eight hours or longer at room temperature (20-25'0).

The solid is then filtered off, washed first with water, then with 400 cc.

of 10 per cent acetic acid (to remove the dimethylaniline) and finally with distilled water. The last filtrate is generally pale pink.

The solid is sucked as dry as possible, spread out on a tray in order to allow most of the water to evaporate (fifteen to twenty hours) and then suspended in 4 l. of methyl alcohol in a 12-l. flask.

This mixture is stirred on the steam bath under a reflux condenser for one to two hours, allowed to cool slowly, and then chilled in an ice bath and filtered. The solid product is washed with a second 4 l.

of cold methyl alcohol. After being dried in air, the product varies in weight from 820 to 870 g.

The product is extracted with boiling toluene in the following manner: 150 g. are placed in a fluted filter paper of 29 cm.

diameter in a 25-cm. gla.s.s funnel which pa.s.ses through the cork of a 2-l. flat-bottom conical flask containing 1250 cc.

of toluene (Fig. 2). The flask is heated on an electric stove, and a 12-l. round-bottom flask is placed on the funnel to act as a condenser, cold water being run through the flask.

The toluene is boiled until the condensed liquid runs through almost colorless (this requires from four to ten hours). The heating is then discontinued, and, as soon as the liquid ceases to boil, the flask is removed to a bath containing water at 90-100'0; the level of the water should be slightly above the level of the liquid in the flask. This arrangement permits the temperature to fall slowly so that large crystals are obtained.

In the meantime a second conical flask containing 1250 cc.

of toluene is attached to the funnel, and a new charge of 150 g.

of crude methyl red is placed in the paper. When extraction is complete it is found that a certain amount of black amorphous insoluble matter remains on the filter; this is discarded.

The crystals of methyl red are filtered off and washed with a little toluene. The weight of pure material is 755-805 g.

The mother liquors are concentrated to one-fourth of their volume, and the crystals which separate on cooling are recrystallized from fresh toluene. The recovered toluene can, of course, be employed again. The total yield of pure methyl red is 790--840 g.

It melts at 181-182'0.

The watery mother liquors from the crude methyl red are rendered alkaline with sodium hydroxide and distilled until no more dimethylaniline pa.s.ses over. In this way 250 to 400 g.

of moist dimethylaniline are recovered.

2. Notes

The amount of hydrochloric acid indicated must not be reduced; otherwise, diazoamino compounds are formed.

It is essential to keep the temperature low while unreacted diazobenzoic acid remains in solution, in order to avoid decomposition.

If this precaution is not taken, the yields are considerably diminished, through the formation of tarry by-products.

The use of a capillary tube for the addition of sodium nitrite prevents loss of nitrous acid by local reaction at the surface of the acid solution. The tube should not be tightly connected to the dropping funnel, but should be so arranged that air is sucked through with every drop. In this way, the entrance of the acid liquor into the capillary is prevented.

The formation of the azo compound takes place slowly on the addition of the dimethylaniline, but the speed of the reaction is greatly increased when the hydrogen ion concentration is lowered by the addition of the sodium acetate. It is nevertheless necessary to allow the reaction mixture to stand a long time; if the product be filtered off after only twenty-four hours, a further quant.i.ty of dye will separate from the filtrate on standing.

The hydrochloride of methyl red is only sparingly soluble in cold water, and is apt to separate in blue needles if the acidity is not sufficiently reduced.

The alcoholic filtrate, obtained on digesting and was.h.i.+ng the crude methyl red, contains a more soluble red by-product which gives a brownish-yellow solution in alkali. The methyl alcohol may be recovered with very little loss by distillation; it is, however, impracticable to attempt to recover any methyl red from the residue, owing to the tarry nature of the by-product. The proportion of this by-product is greatly increased if the temperature of the mixture is allowed to rise too soon after the addition of the sodium acetate.

Methyl red is described as crystallizing in needles from glacial acetic acid; on recrystallization from toluene it separates in plates.

When the methyl red is crystallized from toluene, it sometimes separates in the form of bright-red lumps, probably on account of too rapid crystallization. Under these conditions it is advisable to crystallize again, using a somewhat larger amount of toluene.

It is advisable to t.i.trate the crude anthranilic acid with standard alkali and phenolphthalein before starting the experiment.

In checking these directions, an 80 per cent anthranilic acid was used; it gave a correspondingly lower yield of methyl red (650-700 g.). The yield of methyl red is about 65 to 70 per cent based on the dimethylaniline actually used up, but only 58-63 per cent based on the anthranilic acid actually present in the technical anthranilic acid employed.

3. Other Methods of Preparation

Methyl red was first prepared[1] by diazotization of anthranilic acid in alcoholic solution, the product being allowed to react with dimethylaniline in the same solvent. It has been stated[2] that this process does not work satisfactorily and yields a different product, of brownish-red color.

The preparation of methyl red in aqueous solution has been described by two workers, one of whom[3] gives but few details and claims a nearly quant.i.tative yield; the other[4] gives fuller details and states the yield to be 43.1 per cent of the theory.

The recrystallization of methyl red from toluene is stated[5]

to yield a product melting at 183'0.

[1] Ber. 41, 3905 (1908).

[2] Chem. Zentr. 1910, (1), 960; 1910, (11), 1561.

[3] J. Chem. Soc. 97, 2485 (1910).

[4] C. A. 14, 3406 (1920)

[5] J. Chem. Soc. 99, 1334 (1911).

XIII

_p_-NITROBENZOIC ACID

(_p_)NO2C6H4CH>3s> + 3O(Na2Cr2O7 + H2SO4)--> (_p_)NO2C6H4CO2H + 3H2O

Prepared by O. KAMM and A. O. MATTHEWS. Checked by H. T. CLARKE and W. W. HARTMAN.

1. Procedure

IN a 5-l. round-bottom flask, fitted with a mechanical stirrer, are placed 680 g. of sodium dichromate, 1500 cc. of water, and 230 g. of _p_-nitrotoluene. Stirring is started, and 1700 g.

of concentrated sulfuric acid are allowed to flow in during about thirty minutes. The heat of dilution of the sulfuric acid will cause the nitrotoluene to melt, and rapid oxidation will soon take place.

The last half of the sulfuric acid must be added gradually, in order to prevent too violent a reaction. Since a small amount of nitrotoluene is volatilized, it is advisable to carry on this work under a hood.

After the sulfuric acid has been added and the spontaneous heating of the reaction mixture has subsided, the mixture is heated to gentle boiling for about half an hour. After the reaction mixture has cooled, 2 l. of water are added, the cooled solution is filtered through a cloth filter, and the product washed with about 1 l. of water.

In order to remove the chromium salts as completely as possible, the crude nitrobenzoic acid is warmed on the water bath and agitated with 1 l. of dilute (5 per cent) sulfuric acid solution.

After cooling, the product is again filtered. It is then dissolved in 5 per cent sodium hydroxide solution, filtered from any chromium hydroxide remaining, and also from unchanged nitrotoluene.

The filtrate, which should be light yellow or greenish in color, is acidified with dilute sulfuric acid, with stirring.

It is usually preferable to run the alkaline solution into the dilute sulfuric acid, rather than to use the reverse procedure, for the precipitation of the nitro acid. The precipitated product is filtered with suction, washed thoroughly, and dried. The product should possess only a light-lemon color. The yield should be 230-240 g.

(80-85 per cent of the theoretical amount).