Org. Synth. 1945, 25, 89
DOI: 10.15227/orgsyn.025.0089
[Phenethylamine, N,N-dimethyl-]
Submitted by Roland N. Icke, Burnett B. Wisegarver, and Gordon A. Alles.
Checked by H. R. Snyder and James H. Saunders.
1. Procedure
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).
2. Notes
1. 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 to octadecylamine) are methylated.
2. U.S.P. formaldehyde 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.
3. 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.
4. 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.
5. 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, benzylamine, tetramethylenediamine, piperidine, and α-phenyl-α-aminobutyric acid.
3. Discussion
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;3 by the reaction of β-phenylethylamine and of N-methyl-β-phenylethylamine with formaldehyde;4 by catalytic reduction of phenylacetonitrile in the presence of dimethylamine;5 by the reaction of dimethylamine with β-phenylethyl chloride6,7,8 and with β-phenylethyl bromide;8 and by the reaction of phenylacetaldehyde with dimethylamine.9
This preparation is referenced from:

References and Notes
  1. Clarke, Gillespie, and Weisshaus, J. Am. Chem. Soc., 55, 4571 (1933).
  2. Sommelet and Ferrand, Bull. soc. chim. France, (4) 35, 446 (1924).
  3. Johnson and Guest, J. Am. Chem. Soc., 32, 761 (1910).
  4. Decker and Becker, Ber., 45, 2404 (1912); Ann., 395, 344 (1913).
  5. Buck, Baltzly, and Ide, J. Am. Chem. Soc., 60, 1789 (1938).
  6. Barger, J. Chem. Soc., 95, 2193 (1909).
  7. Tiffeneau and Fuhrer, Bull. soc. chim. France, (4) 15, 173 (1914).
  8. v. Braun, Ber., 43, 3209 (1910).
  9. Ger. pat. 291,222 [Frdl., 12, 802 (1914–1916)].

Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)

potassium carbonate (584-08-7)

hydrochloric acid (7647-01-0)

Benzene (71-43-2)

sodium hydroxide (1310-73-2)

formaldehyde (50-00-0)

formic acid (64-18-6)

carbon dioxide (124-38-9)

dimethyl sulfate (77-78-1)

piperidine (110-89-4)

phenylacetonitrile (140-29-4)

dimethylamine (124-40-3)

Butylamine (109-73-9)

β-phenylethyl chloride (622-24-2)

β-phenylethyl bromide (103-63-9)

benzylamine (100-46-9)

phenylacetaldehyde (122-78-1)

β-Phenylethylamine (64-04-0)

Phenethylamine, N,N-dimethyl- (1126-71-2)

decylamine (2016-57-1)

octadecylamine (124-30-1)




α-amylhexylamine (33788-00-0)

α-phenyl-α-aminobutyric acid (33875-38-6)

N-methyl-β-phenylethylamine (589-08-2)

tetramethylenediamine (110-60-1)