Org. Synth. 1943, 23, 68
DOI: 10.15227/orgsyn.023.0068
α-PHENYLETHYLAMINE
[Benzylamine, α-methyl-]
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
720 g. (6 moles) of pure acetophenone and 1 tablespoon of
Raney nickel catalyst
(p. 181). After the cap and gauge block are securely fastened,
700 ml. (30 moles) of liquid ammonia is introduced
(Note 1). The mixture is hydrogenated at 150° under 5000–3500 lb.
(Note 2). The reaction is allowed to continue as long as
hydrogen is absorbed, generally 4–6 hours. The bomb is cooled, the excess
ammonia is allowed to escape, and the contents are filtered from the catalyst. The mixture is cooled in an
ice bath, acidified to Congo red with
concentrated hydrochloric acid (200–300 ml.), and steam-distilled for 10–12 hours to remove excess
acetophenone (Note 3). The residue is then cooled and added slowly to
200 g. of solid sodium hydroxide in a flask surrounded by an ice bath. The amine is separated, and the aqueous layer is extracted with three
150-ml. portions of benzene. The extracts and amine are combined and dried over
solid sodium hydroxide. After removal of the
benzene, the residue is fractionated under diminished pressure. The yield of
α-phenylethylamine (Note 4), b.p.
80–81°/18 mm., is
320–380 g. (Note 5) (
44ndash;52%).
2. Notes
1.
Liquid
ammonia is introduced into the large bomb as follows: The cap and gauge block of the large bomb are tightened in place. The inner gas inlet tube is removed from the cap assembly of a smaller bomb (capacity about 250 ml.). This bomb is equipped with a test-tube-type liner which is kept chilled in a
bath of Dry Ice while it is filled with liquid
ammonia. This test tube is then placed in the small bomb, and the cap and gauge block are quickly (15–30 seconds) tightened. The bomb is then filled with
hydrogen under high pressure and connected with the larger bomb by means of a short length of the conventional steel pressure tubing. The smaller bomb is inverted, and the valves are opened. This operation will introduce about
150 ml. of liquid ammonia at one time and may be repeated as often as necessary.
2.
A booster pump is required, for it is quite important to keep the pressure above the minimum value of about 3500 lb. The temperature of the reduction is above the critical temperature of
ammonia, and the pressure will not fall much below 3500 lb. At this point
hydrogen must be pumped into the bomb until the pressure is about 5000 lb.; this process is repeated until the reaction is complete. If a safety disk is to be incorporated into the line, it
must not be made of
copper, as
ammonia, even under 2–3 atm., rapidly attacks
copper. A
special disk of steel,
nickel, or other suitable material is required.
3.
It is necessary to heat the flask externally with a flame or the volume of the solution will greatly increase during the lengthy steam distillation.
4.
According to the submitters,
methyl amyl ketone (800 g.) and
ammonia (600 ml.) have been converted to
2-aminoheptane, b.p.
139–141°, in exactly the same manner, in
50–55% yields. A slightly modified procedure was used in the preparation of
n-heptylamine and
furfurylamine.
Heptaldehyde (320 g.) was dissolved in
500 ml. of methanol, and
150 ml. of liquid ammonia was added; the reduction was conducted as above.
n-Heptylamine, b.p.
57–58°/23 mm., was obtained in yields of
53–63%. Freshly distilled
furfural (290 g.) was dissolved in
500 ml. of methanol,
150 ml. of liquid ammonia was introduced, and the reduction carried out as usual. The product was removed, filtered, and fractionated directly.
Furfurylamine, b.p.
144–146°, was obtained in
50% yield.
5.
The yields are based upon the amount of
acetophenone initially used and do not make allowances for the material recovered from the steam distillation. A small amount of
di-(α-phenylethyl) amine, b.p.
61–62°/2 mm., may be recovered from the residues.
3. Discussion
α-Phenylethylamine has been prepared by reducing
acetophenone with
hydrogen at high pressures over
nickel catalysts in the presence of
ammonia;
1,2 with
hydrogen at low pressures over a
nickel catalyst in the presence of
ammonia-saturated
ethanol;
3 and with
hydrogen at low pressures over a
platinum catalyst in the presence of
ammonia-saturated
methanol containing
ammonium chloride (
69% yield).
4
l-α-Phenylethylamine has been prepared through the
oxime of d-α-phenylethyl methyl ketone by the Beckmann rearrangement;
5 from
d-phenylmethylacethydroxamic acid by the Lossen rearrangement;
5 from
d-hydratropic azide;
6,7 from
d-hydratropic acid by the Schmidt reaction;
5 from
d-hydratropamide by treatment with
alkaline hypobromite;
8 and by the reduction of
acetophenone oxime with
lithium aluminum hydride.
9
Other methods of preparing
α-phenylethylamine are reviewed in
Org. Syntheses Coll. Vol. 2, 503 (1943), where detailed directions are given for the preparation of this amine from
acetophenone and
ammonium formate. The procedure given above was based upon that of Schwoegler and Adkins.
2Methods of preparing
d- and l-α-phenylethylamine, based on the resolution of
dl-α-phenylethylamine, are reviewed in
Org. Syntheses Coll. Vol. 2, 506 (1943), where detailed directions are given for the resolution of this amine by
l-malic and d-tartaric acids.
This preparation is referenced from:
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
D- and L-α-Phenylethylamine
oxime of d-α-phenylethyl methyl ketone
l-malic and d-tartaric acids
ethanol (64-17-5)
hydrochloric acid (7647-01-0)
ammonia (7664-41-7)
Benzene (71-43-2)
methanol (67-56-1)
ammonium chloride (12125-02-9)
hydrogen (1333-74-0)
sodium hydroxide (1310-73-2)
platinum (7440-06-4)
copper (7440-50-8)
nickel (7440-02-0)
Acetophenone (98-86-2)
hypobromite
Furfural (98-01-1)
Methyl amyl ketone (110-43-0)
α-Phenylethylamine,
Benzylamine, α-methyl-,
dl-α-phenylethylamine,
l-α-Phenylethylamine (3886-69-9)
ammonium formate (540-69-2)
di-(α-phenylethyl) amine
acetophenone oxime
lithium aluminum hydride (16853-85-3)
2-aminoheptane (123-82-0)
furfurylamine (617-89-0)
d-hydratropic acid (492-37-5)
heptaldehyde (111-71-7)
n-heptylamine (111-68-2)
d-phenylmethylacethydroxamic acid
d-hydratropic azide
d-hydratropamide
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