Org. Synth. 1945, 25, 89
Submitted by Roland N. Icke, Burnett B. Wisegarver, and Gordon A. Alles.
Checked by H. R. Snyder and James H. Saunders.
To 51.2 g. (1 mole) of 90% formic acid in a 500-ml. round-bottomed flask (Note 1), cooled in running tap water, is added slowly 24.2 g. (0.2 mole) of β-phenylethylamine. To the resulting clear solution are added 45 ml. (0.6 mole) of formaldehyde solution (concentration, 37%) (Note 2) and a small boiling stone. The flask is connected to a reflux condenser and is placed in an oil bath which has been heated to 90–100°. A vigorous evolution of carbon dioxide begins after 2–3 minutes, at which time the flask is removed from the bath until the gas evolution notably subsides (15–20 minutes); then it is returned to the bath and heated at 95–100° for 8 hours.
After the solution has been cooled, 100 ml. of 4 N hydrochloric acid is added and the solution is evaporated to dryness under reduced pressure (water pump) from a water bath; the receiver is cooled in an ice bath. The pale yellow syrupy residue (or crystalline solid) is dissolved in 60–75 ml. of water, and the organic base is liberated by the addition of 50 ml. of 18 N sodium hydroxide solution. The upper (organic) phase is separated, and the lower (aqueous) phase is extracted with two 30-ml. portions of benzene. The combined organic base and benzene extracts are dried over 10 g. of anhydrous granular potassium carbonate (Note 3). After the benzene has been distilled slowly under slightly reduced pressure from a 125-ml. Claisen flask, the pressure is lowered further, and the product is distilled. The yield of colorless β-phenylethyldimethylamine boiling at 97–98°/22 mm. (Note 4) is 22–24.7 g. (74–83%) (Note 5).
A flask of this size is used because of the tendency of the solution to froth during the gas evolution. Frothing usually is not bad with this amine but is quite bothersome when the higher aliphatic amines (decylamine
) are methylated.
was used. The commercial aqueous-methanolic solution contains 37% formaldehyde
by weight. It is sometimes called "40% formalin" because 100 ml. of the solution contains 40 g. of formaldehyde
If complete separation of the benzene
extracts from the aqueous solution is difficult, it is advantageous to dry the benzene
solution roughly over 10 g. of the anhydrous potassium carbonate
and to decant the resulting clear solution into another flask where it may be dried over 5 g. of fresh drying agent. The spent drying agent is rinsed with 15–20 ml. of benzene
, and the rinsings are added to the main solution.
Another boiling point is 66–68°/6 mm.
If the product is distilled through a short column (12–15 cm.) packed with glass helices
, it boils constantly at 98°/22 mm.
The recovery is somewhat lower when a column is used.
The product gives a negative carbylamine test and hence contains no significant amount of unchanged primary amine.
This methylation procedure is quite generally satisfactory for simple primary and secondary amines. For methylation of a secondary amine only half as much formaldehyde
is required, although a larger amount does no harm. The submitters also have prepared, in uniformly good yields, benzyldodecylmethylamine
(b.p. 180–182°/4 mm.
) from benzyldodecylamine
, and α-amylhexyldimethylamine
(b.p. 115°/16 mm.
) from α-amylhexylamine
. It is reported1
that the reaction can be successfully applied to the methylation of butylamine
, and α-phenyl-α-aminobutyric acid
The procedure given above is an adaptation of the methylation method first used by Sommelet and Ferrand2
and developed more fully by Clarke, Gillespie, and Weisshaus.1 β-Phenylethyldimethylamine
has been prepared from β-phenylethylamine
by alkylation with dimethyl sulfate
by the reaction of β-phenylethylamine
and of N-methyl-β-phenylethylamine
by catalytic reduction of phenylacetonitrile
in the presence of dimethylamine
by the reaction of dimethylamine
with β-phenylethyl chloride6,7,8
and with β-phenylethyl bromide
and by the reaction of phenylacetaldehyde
This preparation is referenced from:
Chemical Abstracts Nomenclature (Collective Index Number);
potassium carbonate (584-08-7)
hydrochloric acid (7647-01-0)
sodium hydroxide (1310-73-2)
formic acid (64-18-6)
carbon dioxide (124-38-9)
dimethyl sulfate (77-78-1)
β-phenylethyl chloride (622-24-2)
β-phenylethyl bromide (103-63-9)
Phenethylamine, N,N-dimethyl- (1126-71-2)
α-phenyl-α-aminobutyric acid (33875-38-6)
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