Organic Syntheses Part 13

1. Procedure

IN a 5-l. round-bottom flask (Pyrex) is placed a mixture of 500 g.

of phthalic anhydride and 400 g. of 28 per cent ammonium hydroxide.

The flask is fitted with an air condenser not less than 10 mm.

in diameter and is then slowly heated with a free flame until the mixture is in a state of quiet fusion at a temperature of about 300'0. It requires about one hour before all the water has gone and about one and a half to two hours before the temperature of the reaction mixture reaches 300'0 and the mixture is a h.o.m.ogeneous melt.

It is advisable, during the heating, to shake the flask occasionally; some material sublimes into the condenser and must be pushed down with a gla.s.s rod. The hot reaction mixture is now poured out into a crock, covered with a paper to prevent loss by sublimation, and allowed to cool. The product is practically pure without further treatment, and melts at 232-235'0. The yield is 470-480 g.

(94-95 per cent of the theoretical amount).

Phthalimide may also be made by using 500 g. of phthalic anhydride and 500 g. of ammonium carbonate which has been previously ground in a mortar. The subsequent procedure is the same as when aqueous ammonia is used. Frequent shaking is necessary, and the sublimed material must be occasionally pushed back into the reaction flask.

About two hours are required for completion.

2. Notes

Several smaller runs of 25 g. of phthalic anhydride gave the same percentage yield.

Phthalimide may be recrystallized from water, but only about 4 g.

of phthalimide will dissolve in a liter of boiling water.

It may also be crystallized from alcohol, in which solvent it dissolves to the extent of five parts in a hundred at boiling temperature.

On a large scale, it would be advisable to collect the small amount of ammonia given off during the reaction.

If desired, the product obtained by pouring the reaction ma.s.s into the crock may be treated with hot water to soften the cake, broken up with a gla.s.s rod, transferred to a flask and boiled with water for a few minutes. This treatment, however, is quite unnecessary; for all practical purposes, the crude cake, as it is obtained, may be ground up and used directly.

3. Other Methods of Preparation

Phthalimide has been formed by heating ammonium phthalate;[1]

by heating acid ammonium phthalate;[2] by pa.s.sing dry ammonia over heated phthalic anhydride;[3] by treating phthalyl chloride with dry ammonia;[4] by heating phthalamide;[5] by heating phthalic anhydride with ammonium thiocyanate;[6] by heating phthalic anhydride with urea;[7] by heating phthalic anhydride with ammonium carbonate;[1b]

by heating phthalic acid with nitriles;[2b] by fusing _o_-cyan.o.benzoic acid;[3b] and by the action of potash on _o_-cyan.o.benzaldehyde.[4b]

[1] Jahresb. 1868, 549; Ann. 19, 47 (1836); 41, 110 (1842); 42, 220 (1842); 205, 300 (1880); 215, 181 (1882).

[2] Jahresb. 1847-1848, 590.

[3] Am. Chem. J. 3, 29 (1881).

[4] Am. Chem. J. 3, 28 (1881).

[5] Ber. 39, 2278 (1906).

[6] Ber. 19, 1398 (1886),

[7] Ber. 10, 1166 (1877); Am. Chem. J. 18, 333 (1896); J. Am. Chem. Soc. 32, 116 (1910); Z. angew. Chem. 32, I, 301 (1919).

[1b] J. Am. Chem. Soc. 42, 1282 (1920).

[2b] J Am. Chem. Soc. 18, 680 (1896); 20, 654 (1898).

[3b] Rec. trav. chim. (I) 11, 93 (1892).

[4b] Ber. 30, 1698 (1897).

Of these, the first three are the only ones which need be considered as methods for the preparation of phthalimide.

It was found that the third was by no means easy to bring about: dry phthalic anhydride is apparently only superficially affected by the dry ammonia, and it was difficult to introduce sufficient heat into the loose ma.s.s of crystals to cause the reaction to start.

XXI

QUINOLINE

/ / C3H5(OH)3 + C6H5NH2 + 4O(C6H5NO2)--> + 4H2O / n/

Prepared by H. T. CLARKE and ANNE W. DAVIS. Checked by ROGER ADAMS and A. W. SLOAN.

1. Procedure

IN a 5-l. round-bottom flask, fitted with an efficient reflux condenser of wide bore, are placed, in the following order, 80 g.

of powdered crystalline ferrous sulfate, 865 g. of glycerol (c. p.), 218 g. of aniline, 170 g. of nitrobenzene, and 400 cc.

of concentrated sulfuric acid (sp. gr. 1.84). The contents of the flask are well mixed and the mixture heated gently over a free flame.

As soon as the liquid begins to boil, the flame is removed, since the heat evolved by the reaction is sufficient to keep the mixture boiling for one-half to one hour. If the reaction proceeds too violently at the beginning, the reflux condenser may be a.s.sisted by placing a wet towel over the upper part of the flask. When the boiling has ceased the heat is again applied and the mixture boiled for five hours.

It is then allowed to cool to about 100'0 and transferred to a 12-l. flask; the 5-l. flask is rinsed out with a small quant.i.ty-of water.

The 12-l. flask is then connected with the steam-distillation apparatus shown in Fig. 3, a 12-l. flask being used as a receiver; steam is pa.s.sed in (without external heat) until 1500 cc.

have distilled (ten to thirty minutes). This removes all the unchanged nitrobenzene (10-20 cc.). The current of steam is then interrupted, the receiver is changed, and 1500 g.

of 40 per cent sodium hydroxide solution are added cautiously through the steam inlet. The heat of neutralization is sufficient to cause the liquids to boil and thus become thoroughly mixed.

Steam is then pa.s.sed in as rapidly as possible until all the quinoline has distilled. In this process, 6-8 l. of distillate are collected (two and a half to three and a half hours are required, unless a very efficient condensing apparatus is used, under which conditions the distillation may be complete in one-half to one and a half hours).

The distillate is allowed to cool, and the crude quinoline separated.

The aqueous layer of the distillate is again distilled with steam until all the quinoline has been volatilized and collected in about 3 l. of distillate.

These 3 l. of distillate are then mixed with the first yield of quinoline and 280 g. (150 cc.) of concentrated sulfuric acid are added.

The solution is cooled to 0-5'0, and a saturated solution of sodium nitrite added until a distinct excess of nitrous acid is present (as shown either by starch-pota.s.sium iodide paper or by the odor).

This generally requires 50 to 70 g. of sodium nitrite.

The mixture is then warmed on a steam bath for an hour, or until active evolution of gas ceases, and is then distilled with steam until all the volatile material has been expelled (41. of distillate will result) The receiver is then changed and the mixture in the distillation flask is neutralized, as before, with 700 g.

of 40 per cent sodium hydroxide solution. The quinoline is distilled exactly as described above, the aqueous portions of the distillate being distilled with steam until all the quinoline has been isolated.

The crude product is then distilled under reduced pressure, and the fraction which boils at 110-114'0/14 mm. is collected.

The foreruns are separated from any water which may be present, dried with a little solid alkali, and redistilled. The total yield is 255-275 g.

(84-91 per cent of the theoretical amount based on the aniline taken).

2. Notes

Although these directions have been used many times with results exactly as described, in a few cases the yields have dropped to 60-65 per cent without any apparent reason. At present no explanation can be given for this.

In the Skraup synthesis of quinoline the princ.i.p.al difficulty has always been the violence with which the reaction generally takes place; it occasionally proceeds relatively smoothly, but in the majority of cases gets beyond control, with consequent loss of material through the condenser. By the addition of ferrous sulfate, which undoubtedly functions as an oxygen carrier, the reaction is extended over a longer period of time. It is thus possible to work with much larger quant.i.ties of material when ferrous sulfate is employed.