Org. Synth. 1958, 38, 3
DOI: 10.15227/orgsyn.038.0003
2-BENZYLAMINOPYRIDINE
[Pyridine, 2-benzylamino-]
Submitted by Yaïr Sprinzak
1
Checked by Max Tishler and Matthew A. Kozlowski.
1. Procedure
A 500-ml. Claisen flask with a 35-mm. indented side arm (Note 1) is attached downward to a Liebig condenser for distillation. A thermometer, held by a cork stopper, is inserted through the neck of the flask and adjusted so that its bulb is close to the bottom. The flask is heated by means of an electric mantle or air bath. To the flask are charged 94 g. (1.0 mole) of 2-aminopyridine (Note 2), 150 g. (1.4 moles) of benzyl alcohol, and 9 g. of 85% potassium hydroxide. The mixture is heated to boiling and boiled vigorously enough to cause slow distillation of water accompanied by as little benzyl alcohol as possible (Note 3). The temperature of the boiling mixture rises gradually from 182° to 250° during a period of 30 minutes. The mixture is maintained at 250° for 3 minutes, then allowed to cool. The distillate amounts to 19–20 ml. of a water-rich layer and 2–4 ml. of a benzyl alcohol-rich layer.
The residual product is cooled to about 100°
(Note 4) and poured into 250 ml. of water. The crystallized solid is crushed and collected on a
12-cm. Büchner funnel. Slight suction is applied at first, but, after most of the mother liquor has been removed, the crystals are pressed down with strong suction. The product is then washed thoroughly with water. After drying, the yield of colorless
2-benzylaminopyridine (Note 5) and
(Note 6), m.p.
95–96°, amounts to
180–183 g. (
98–99% of the theoretical amount). The product may be recrystallized from
isopropyl alcohol with
90% recovery. For each gram of amine 3 ml. of solvent is employed. The melting point of recrystallized material is
96.0–96.7° (cor.), lit.
2 m.p.
97–98°.
2. Notes
1.
A
short Vigreux column or any other short column for distillation may be used.
2.
2-Aminopyridine was obtained from Matheson, Coleman and Bell, Inc., East Rutherford, New Jersey.
3.
If the reaction mixture is heated too strongly or the vapors are inadequately fractionated, correspondingly greater amounts of
benzyl alcohol will distill, with concomitant loss of yield. The distillate should be clear, not milky.
4.
If the product has partially solidified, it should be melted for easy handling.
5.
By essentially the same procedure
N,N'-dibenzyl-p-phenylenediamine has been obtained in
92% yield. The heating period requires 1 hour, and the final temperature is 260°.
6.
N-Benzylaniline has been obtained in
90–94% yield by an appropriate modification
3 of this method.
3. Discussion
For
2-benzylaminopyridine the methods of preparation of significance are condensation of
2-pyridinesulfonic acid and
benzylamine,
4 condensation of the alkali metal salts of
2-aminopyridine with
benzyl chloride5 or
benzyl alcohol,
6 reductive alkylation of
2-aminopyridine in the presence of
benzaldehyde and formic acid,
2 oxidation of
N-benzyl-N-pyridylaminoacetonitrile or
N-benzyl-N-pyridylaminoacetaldoxime,
7 and the method described here modified by use of an inert solvent.
8
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
formic acid (64-18-6)
benzaldehyde (100-52-7)
potassium hydroxide (1310-58-3)
isopropyl alcohol (67-63-0)
N-Benzylaniline (103-32-2)
benzyl chloride (100-44-7)
Benzyl alcohol (100-51-6)
2-aminopyridine (504-29-0)
benzylamine (100-46-9)
2-Benzylaminopyridine,
Pyridine, 2-benzylamino- (6935-27-9)
2-pyridinesulfonic acid
N-benzyl-N-pyridylaminoacetonitrile
N-benzyl-N-pyridylaminoacetaldoxime
N,N'-dibenzyl-p-phenylenediamine
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