β-Arylethylamines can be generated in good yield by a variety of synthetic procedures¹. The most applicable method involves a Knoevenagel condensation of appropriately substituted benzaldehydes with nitroalkane²; LiAlH₄² or Raney nickel reduction³ (elevated temperature, pressure) of the intermediate β-nitrostyryl derivative then affords the phenethylamine. Since we observed incomplete reduction of phenolic β-nitrostyrenes using LiAlH₄ in ethereal solvents, we investigated the reactivities of the recently developed hydride reductants.

We describe a general preparative method for the generation of a pharmacologically interesting series using sodium bis-(2-methoxyethoxy)- aluminum dihydride (Red-Al) As the reductant. Aliphatic nitro-compounds are reduced to amines using this reducing agent^4,5; by contrast, aryl nitro-compounds afford azo-, azoxy-, or hydrazo-compounds^4,5 depending on conditions and manner of addition of the reductant. In our laboratory, β-nitrostyryl derivatives are smoothly reduced to β-phenethylamines in yields comparable to or greater than that afforded by other methods (Table 1).

Preparation of two of the β-nitrostyrenes by generalized methods¹ gave large amounts of dimeric byproducts, And instead we used a procedure, initially recorded by Ho et al.⁶ which should find general application particularly where substitution on the benzaldehyde renders it electronically less reactive or sterically hindered to attack by nitroalkane anion, And the nitrostyryl derivative that does form begins to dimerize. Preliminary results in Table 2; reflux times are critical.