Checked by Cliff S. Hamilton and Marjorie Debrunner.
1. Procedure
In a
2-l. beaker equipped with a mechanical stirrer and immersed in an ice-salt bath is placed a solution of
75 g. (1.87 moles) of sodium hydroxide in 800 ml. of water. To the solution is added, with stirring,
95.8 g. (30.7 ml., 0.6 mole) of bromine. When the temperature of the solution reaches 0°,
60 g. (0.49 mole) of nicotinamide (Note
1) is added all at once with vigorous stirring. After being stirred for 15 minutes, the solution is clear. The ice-salt bath is replaced by a bath containing water at 75°, and the solution is stirred and heated at 70–75° for 45 minutes.
The solution is cooled to room temperature, saturated with
sodium chloride (about 170 g. is required), and extracted with
ether in a
continuous extractor (Note
2). The extraction time is 15–20 hours. The
ether extract is adjusted to a volume of 1 l., dried over
4–5 g. of sodium hydroxide pellets, and filtered, and the
ether is removed by distillation from a steam bath. The residue crystallizes on cooling. The yield of dark red crystals melting at
61–63° is
39–41 g. (
85–89%).
The crude product is dissolved in a mixture of
320 ml. of benzene and
80 ml. of ligroin (b.p.
60–90°) and heated on a
steam bath with
5 g. of Norit and
2 g. of sodium hydrosulfite for 20 minutes. The hot solution is filtered by gravity, allowed to cool slowly to room temperature, and then chilled overnight in a refrigerator. The product is isolated by gravity filtration (Note
3), washed on the filter with
25 ml. of ligroin, and dried in a
vacuum desiccator. The yield of white crystals melting at
63–64° amounts to
28–30 g. (
61–65%). By concentrating the combined filtrate and washings to a volume of 150 ml., an additional 2–3g. of pale yellow crystals melting at
62–64° can be obtained. The total yield of
3-aminopyridine is
30–33 g. (
65–71%).
2. Notes
1. The
nicotinamide should be finely powdered to facilitate rapid solution.
2. The continuous extractor described by Pearl
2 was used. If the material is extracted in a
separatory funnel, four
800-ml. portions and ten 500-ml. portions of ether are required to give the above yield.
3. Since
3-aminopyridine is somewhat hygroscopic, it tends to liquefy if collected on a suction filter.
3. Discussion
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