Org. Synth. 1943, 23, 71
DOI: 10.15227/orgsyn.023.0071
β-PHENYLETHYLAMINE
[Phenylethylamine]
Submitted by John C. Robinson, Jr. and H. R. Snyder.
Checked by Nathan L. Drake and Daniel Draper.
1. Procedure
In a
2-l. bomb are placed
1 kg. (8.55 moles) of pure (Note 1) benzyl cyanide and 1 tablespoon of
Raney nickel catalyst (p. 181). After the cap is securely fastened down,
150 ml. of liquid ammonia is introduced
(Note 2).
Hydrogen is introduced until the pressure is about 2000 lb. The bomb is then heated to 120–130° and shaking is begun. The reduction is complete well within an hour
(Note 1). The bomb is cooled and opened, and the contents are removed. The bomb is rinsed with a little
ether, and the combined liquids are filtered from the catalyst. The
ether is removed, and the residue is fractionated under reduced pressure. The yield is
860–890 g. (
83–87%) of
β-phenylethylamine, b.p.
90–93°/15 mm. (Note 3),
(Note 4),
(Note 5).
2. Notes
1.
Benzyl cyanide, prepared according to
Org. Syntheses Coll. Vol. 1, 107 (1941), should be distilled from Raney
nickel. Minute traces of halide have a strong poisoning effect on the catalyst. If the reduction does not occur within an hour, the contents of the bomb should be removed and filtered. New catalyst is then added and the process is repeated.
2.
The presence of
ammonia in the reduction mixture reduces the amount of secondary amine formed. For directions for introducing the liquid
ammonia, see
Note 1 to the preparation of
α-phenylethylamine (p. 718).
3.
If several runs are made, a small amount of the secondary amine may be recovered from the combined residues.
Di-(β-phenylethyl)-amine boils at
155–157°/4 mm.4.
Similarly
n-amyl cyanide has been converted to
n-hexylamine, b.p.
128–130°, in
67–70% yields.
5.
It has been reported (R. N. Icke and C. E. Redemann, private communication) that
β-phenylethylamine, as well as several substituted β-phenylethylamines, may be prepared in excellent yields by catalytic reduction of the corresponding cyanides in 10
N methanolic
ammonia. An example of this procedure follows. Commercial
anhydrous methanol is saturated with
ammonia gas at 0°; this solution is approximately 10
N. A solution of
58.5 g. (0.5 mole) of benzyl cyanide in
300 ml. of 10 N methanolic ammonia (the ratio of
ammonia to
benzyl cyanide should be at least 5:1 in order to minimize the formation of the secondary amine) is placed in a
high-pressure hydrogenation bomb,
5–10 ml. of settled Raney nickel catalyst (p. 181) is added, the bomb is closed, and
hydrogen is introduced until the pressure is 500–1000 lb. The bomb is shaken and heated to 100–125° until absorption of
hydrogen ceases (about 2 hours). The bomb is cooled and opened, and the contents are removed. The bomb is rinsed with two or three
100-ml. portions of methanol, and the combined liquids are poured through a
fluted filter to remove the catalyst. (
Caution! If the catalyst becomes dry, it is likely to ignite.) The solvent and the
ammonia are removed by distillation, and the residue is fractionated through a
short column. The yield of
β-phenylethylamine boiling at
92–93°/19 mm. (
62–63°/4 mm.) is
51–54.5 g. (
84–90%). The hydrochloride, after crystallization from dry
ethanol, melts at 218–219°. This procedure has also been used for preparation of the following β-phenylethylamines from the cyanides; the yields of amines were uniformly high:
3,4-dimethoxyphenylethylamine, b.p.
119–119.5°/1 mm.;
o-methylphenylethylamine, b.p.
67°/0.5 mm.;
m-methylphenylethylamine, b.p.
68°/2 mm.;
p-methylphenylethylamine, b.p.
71°/2 mm.; and
3,4-methylenedioxyphenylethylamine, b.p.
109°/2 mm.
3. Discussion
β-Phenylethylamine has been made by a number of reactions, many of which are unsuitable for preparative purposes. Only the most important methods, from a preparative point of view, are given here. The present method is adapted from that of Adkins,
1 which in turn was based upon those of Mignonac,
2 von Braun and coworkers,
3 and Mailhe.
4 Benzyl cyanide has been converted to the amine by catalytic reduction with
palladium on charcoal,
5 with
palladium on barium sulfate,
6 and with Adams' catalyst;
7 by chemical reduction with
sodium and
ethanol,
8 and with
zinc dust and mineral acids.
9 Hydrocinnamic acid has been converted to the azide and thence by the Curtius rearrangement to
β-phenylethylamine;
10 also the Hofmann degradation of
hydrocinnamide has been used successfully.
11 β-Nitrostyrene,
12 phenylthioacetamide,
13 and the
benzoyl derivative of mandelonitrile14 all yield
β-phenylethylamine upon reduction. The amine has also been prepared by cleavage of
N-(β-phenylethyl) phthalimide15 with
hydrazine; by the Delépine synthesis from
β-phenylethyl iodide and
hexamethylenetetramine;
16 by the hydrolysis of the corresponding urethan and
urea;
17 by reduction of
phenylacetaldoxamine;
18 and by catalytic reduction of
O-carbethoxymandelonitrile in the presence of acids.
19
More recent methods for preparation of the amine include the
lithium aluminum hydride reduction of
β-nitrostyrene20 and of
phenylacetamide.
21The
Raney nickel reduction of the nitrile in the presence of
formamide is reported to give an 87% yield of the formylated primary amine.
22
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
benzoyl derivative of mandelonitrile
phenylacetaldoxamine
ethanol (64-17-5)
ammonia (7664-41-7)
methanol (67-56-1)
ether (60-29-7)
formamide (75-12-7)
hydrogen (1333-74-0)
nickel,
Raney nickel (7440-02-0)
barium sulfate (7727-43-7)
zinc (7440-66-6)
sodium (13966-32-0)
palladium (7440-05-3)
Benzyl cyanide (140-29-4)
urea (57-13-6)
hydrazine (302-01-2)
Hydrocinnamic acid (501-52-0)
hexamethylenetetramine (100-97-0)
β-Nitrostyrene (102-96-5)
α-Phenylethylamine (3886-69-9)
Phenylethylamine,
β-Phenylethylamine (64-04-0)
lithium aluminum hydride (16853-85-3)
n-amyl cyanide (628-73-9)
Di-(β-phenylethyl)-amine
3,4-dimethoxyphenylethylamine (120-20-7)
3,4-methylenedioxyphenylethylamine (1484-85-1)
hydrocinnamide (102-93-2)
phenylthioacetamide (645-54-5)
N-(β-phenylethyl) phthalimide
β-phenylethyl iodide (17376-04-4)
O-carbethoxymandelonitrile
Phenylacetamide (103-81-1)
n-hexylamine (111-26-2)
o-methylphenylethylamine
m-methylphenylethylamine
p-methylphenylethylamine (3261-62-9)
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