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Gordon A. Alles
J. Am. Chem. Soc. 54, 271-274 (1932)

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In a previous paper1 it was demonstrated with dl-β-phenylisopropylamine that the introduction of a methyl group into the side chain of β-phenylethylamine furnishes a compound differing from the latter with regard to certain of its effects when administered as a drug compound. The dl-β-phenylisopropylamine exerts a pressor effect for a longer period of time and is quite effective after oral administration.

The syntheses of the parent dl-β-phenylisopropylamine and the desired methoxy derivative are reported in this paper; the physiological studies of the compounds prepared will be reported in another place.

The synthesis of β-phenylethylamines is often accomplished, especially for proof of structure, by condensing an aromatic aldehyde with nitromethane under suitable conditions and complete reduction of the beta-nitrostyrene so formed, to the hydrogenated amine derivative. It was found that a similar preparative process can be carried out with nitroethane in place of nitromethane, the resultant product being a dl-β-phenylisopropylamine.

The initial condensation step in the process was found to be most simply carried out by the method of Knoevenagel and Walther3. The second step, the complete reduction, involves considerable difficulty but the described electrolytic reduction method gives fair yields of the desired amines while several attempts at catalytic hydrogenation or reduction with various metals or their amalgams were not at all successful.


The details of preparation of the dl-β-phenylisopropylamine and its 4-methoxy derivative differ only in the aldehyde used and the intermediate and final products isolated.

Condensation of Aldehyde and Nitroethane

0.2 Mole of aldehyde, 0.2 mole of nitroethane and 0.02 mole of n-amylamine were mixed and set aside at room temperature in the dark. After a day water began to separate from the mixture; after several days the mixture became quite solid. After two weeks, the mixture was dissolved to a homogeneous solution by warming with 50 ml of ethanol and then on cooling a fine crystal product was obtained. From benzaldehyde, 0.15 mole of phenylnitropropylene melting at 65-66C was obtained. The melting point of this compound has been reported as 64C2. From anisaldehyde, 0.15 mole of 4-methoxyphenylnitropropylene melting at 43-44C was obtained. The melting point of this compound has been reported as 48C3.

Reduction of Phenylnitropropylenes

0.1 Mole of phenylnitropropylene dissolved in a catholyte of 100 ml of ethanol, 50 ml of acetic acid and 50 ml of 12 N sulfuric acid was placed above a 40 cm2 mercury cathode in a porous cell surrounded by a 3 N sulfuric acid anolyte with a water-cooled lead anode. Four amperes was passed for twenty hours and the temperature in the catholyte was kept between 30-40C.

The resultant catholyte was partially evaporated, then made strongly alkaline and the separated basic layer taken up with benzene. The desired amine was then extracted from the benzene by just neutralizing with dilute hydrochloric acid and separating the aqueous layer. This was then evaporated and the product crystallized. From phenylnitropropylene, 0.02 mole of dl-β-phenylisopropylamine hydrochloride melting at 144-145C was obtained. The melting point of this compound has been reported as 145-147C4. From 4-methoxy-phenylnitropropylene, 0.02 mole of dl-β-4-methoxyphenylisopropylamine hydrochloride melting at 205-209C was obtained. The melting point of this compound has bees reported as 210C2.


  1. Piness, Miller and Alles, J. Am. Med. Assn. 94, 790 (1930)
  2. Mannich and Jacobsohn, Ber. 43, 189 (1910)
  3. Knoevenagel and Walther, Ber. 37, 4502 (1904)
  4. Hey, J. Chem. Soc. 18 (1930)