SYNTHESIS: A solution of 20 g 3,4,5-trimethoxybenzaldehyde, 40

mL nitromethane, and 20 mL cyclohexylamine in 200 mL of acetic

acid was heated on the steam bath for 1 h. The reaction mixture was
then diluted slowly and with good stirring, with 400 mL H2O, which
allowed the formation of a heavy yellow crystalline mass. This was
removed by filtration, washed with H2O, and sucked as dry as
possible. Recrystallization from boiling MeOH (15 mL/g) yielded, after
filtration and air drying, beta-nitro-3,4,5-trimethoxystyrene as bright
yellow crystals weighing 18.5 g. An alternate synthesis was effective,
using an excess of nitromethane as solvent as well as reagent, if the
amount of ammonium acetate catalysis was kept small. A solution of
20 g 3,4,5-trimethoxybenzaldehyde in 40 mL nitromethane
containing 1 g anhydrous ammonium acetate was heated on the
steam bath for 4 h. The solvent was stripped under vacuum and the
residual yellow oil was dissolved in two volumes of hot MeOH,
decanted from some insolubles, and allowed to cool. The crystals
formed are removed by filtration, washed with MeOH and air dried
yielding 14.2 g. of bright yellow crystals of beta-nitro-3,4,5-
trimethoxystyrene. The use of these proportions but with 3.5 g
ammonium acetate gave extensive side-reaction products even when
worked up after only 1.5 h heating. The yield of nitrostyrene was, in
this latter case, unsatisfactory.

To a gently refluxing suspension of 2 g LAH in 200 mL Et2O, there

was added 2.4 g beta-nitro-3,4,5-trimethoxystyrene as a saturated
Et2O solution by use of a Soxhlet extraction condenser modified to
allow the continuous return of condensed solvent through the
thimble. After the addition was complete, the refluxing conditions
were maintained for another 48 h. After cooling the reaction mixture,
a total of 150 mL of 1.5 N H2SO4 was cautiously added, destroying
the excess hydride and ultimately providing two clear phases. These
were separated, and the aqueous phase was washed once with 50 mL
Et2O. There was then added 50 g potassium sodium tartrate,
followed by sufficient NaOH to bring the pH >9. This was then
extracted with 3x75 mL CH2Cl2, and the solvent from the pooled
extracts was removed under vacuum. The residue was distilled at
120-130 °C at 0.3 mm/Hg giving a white oil that was dissolved in 10
mL IPA and neutralized with concentrated HCl. The white crystals that
formed were diluted with 25 mL Et2O, removed by filtration, and air
dried to provide 2.1 g 3,4,5-trimethoxyphenethylamine hydrochloride
(M) as glistening white crystals. The sulfate salt formed spectacular
crystals from water, but had a broad and uncharacteristic mp. An
alternate synthesis can employ 3,4,5-trimethoxyphenylacetonitrile, as
described under beta-D.