In a
5-l. three-necked round-bottomed flask, a homogeneous slurry of the following compounds is made by mixing in the order given (Note
1):
588 g. (2.45 moles) of powdered arsenic oxide (Note
2),
588 g. (3.5 moles) of 3-nitro-4-aminoanisole (Note
3), and
1.2 kg. (950 ml., 13 moles) of u.s.p. glycerol. The flask is fitted with an
efficient mechanical stirrer and a
500-ml. dropping funnel in which is placed
315 ml. (579 g., 5.9 moles) of concentrated sulfuric acid (sp. gr. 1.84). With good mechanical stirring the
sulfuric acid is dropped into the orange reaction mixture over a period of 30–45 minutes. During this addition, the temperature spontaneously rises to 65–70°.
The stirrer and dropping funnel are removed, and a
thermometer is inserted in one neck of the flask by means of a stopper so that the bulb is well below the surface of the reaction mixture. A 10-mm. bent glass tube is attached to the second neck by a
rubber stopper and attached through a
trap to a
water aspirator (Note
4). The third neck is closed with a stopper, and the flask and its contents are weighed. The flask, clamped in place in an
oil bath which rests on a hot plate (Note
5), is evacuated, and heat is carefully applied at such a rate that the internal temperature slowly rises to 105° (Note
6). The mixture is kept between 105° and 110° until the loss in weight amounts to 235–285 g. (Note
7), which requires approximately 2–3 hours, depending on the efficiency of the aspirator. If the temperature shows any tendency to rise above 110°, the oil bath should be lowered and the mixture cooled.
When the removal of the water is complete, the suction tube is removed and the stirrer and dropping funnel are replaced. The internal temperature is raised with extreme care to 118° and is held rigidly between 117° and 119° during the subsequent addition of
438 g. (236 ml.) of concentrated sulfuric acid (sp. gr. 1.84) from the dropping funnel. The
sulfuric acid must be added dropwise over a period of 2.5–3.5 hours, and the temperature
must not vary from 117–119° (Note
8). After the addition is complete the temperature is maintained at 120° for 4 hours (Note
9) and finally at 123° for 3 hours. The reaction mixture is cooled below 100°, diluted with 1.5 l. of water, and allowed to cool overnight, preferably with stirring (Note
10). The diluted reaction mixture is poured with stirring into a mixture of
1.8 l. (1580 g.) of concentrated ammonium hydroxide (sp. gr. 0.9) and 3.5 kg. of ice in a
12-l. enameled pail. The resultant thick slurry is filtered through a
large Büchner funnel (24–30 cm.), and the filtrate is discarded. The earth-colored precipitate is washed with four 700-ml. portions of water and then transferred to a
3-l. beaker and stirred with
1 l. of methanol for 15 minutes. The slurry is filtered and this process repeated (Note
11). The crude product at this point is a light chocolate brown and weighs about
800 g. when dried. It is purified by boiling for 30 minutes with
4.5 l. of chloroform (Note
12) to which has been added
30 g. of decolorizing carbon. The
carbon and other humus-like material are removed by filtration from the hot
chloroform solution by means of a 24-cm. warm Büchner funnel. The insoluble material is boiled with
500 ml. of chloroform, the resultant mixture filtered, and the combined filtrates concentrated by distillation from a
steam bath to a volume of 1.5–2.5 l., at which point crystals of the
6-methoxy-8-nitroquinoline separate. The solution is then cooled to 5°, and the first crop of crystals is obtained by collection on a 24-cm. Büchner funnel. The crystals are transferred to a
1-l. beaker, stirred with
400 ml. of methanol for 15 minutes, and again collected on a Büchner funnel and washed with
200 ml. of methanol. The product consists of light-tan crystals which weigh
435–500 g. and melt at
158–160° (Note
13). By concentrating the filtrate to 400–500 ml., a second crop of crystals weighing
25–65 g. is obtained which, after washing with
methanol in the same way as above, melts at
158–159°. The total yield is
460–540 g. (
65–76%) (Note
14), (Note
15).