hi tricky,
otto likes your thoughts on phenethylamine-synthesis. further otto is pretty sure that most of the steps will work. drawback might be that the synth is somewhat lengthy.
to the 1. step:
it is possible. check out Tetrahedron Letters 1976, p 3495.
in a 200 ml RBF equipped w/ stirrer, reflux condenser and dropping funnel a mixture of 6.6g (0.1 mol) solid powdered 85% KOH, 80 ml freshly destilled acetonitrile and 2 ml aliquat 336 (PTC!) was added. after having reached reflux a solution of 0.1 mol of the aldehyde in 15 ml acetonitrile (fr. dest'd.) is added. reflux was maintained for additional 10 min. then, the solution was poored onto 200 g of crushed ice.
the product was extracted using 2 portions of DCM, the extracts dried over Na2SO4 and the solvent removed in vacuo.
yields of the corresponding cinnamonitriles (ArCH=CH-CN)
for:
p-(CH3)2-C6H4-CHO 55%
piperonal 45%
p-CH3O-C6H4-CHO 30%
to the 2. step:
this can be done by catalytic hydrogenation using Pd/C at r.t. the nitrile won't be affected.
to the 3. step:
this is known to work too. it is normally done by reacting the nitrile w/ conc. H2SO4 at r.t. (then aqueous workup). otto has no idea though, how aromatic ether groups would behave under such conditions.
however, uemuras epoxidation procedure (acetonitrile/MeOH/H2O2/alkene) gives acetamide as a byproduct. thus the use of H2SO4 could be circumvent.
otto means: make a solution of your product from step 2 in MeOH, add an alkene and H2O2, each of the latter 1 mol per mol of nitrile to be hydrolyzed.
t the 4. and 5. step:
this is a one-pot reaction. it gives variing yields and is tricky.
procedure:
1.2 mol Br2 is added to a solution of 6 mol NaOH in 2 l of water. this solution is then cooled to -5°C and 1 mol of the amide is added under stirring. the temp. should not exceed 40°C, otherwise cooling is applied.
the mixture is stirred overnight and the reaction then quenched w/ 20 g Na2SO3. then, the mixture is acidified to pH 2 under cooling, stirred for 15 min, and made basic again w/ 50% NaOH or KOH. the solution is extracted w/ ether, the etheral phase dried over Na2SO4 and then evaporated. the residue is destilled in vacuo.
yields of the amines from corresponding carboxylic acid amides:
acetamide to methylamine 70%
phenylacetamide to benzylamine 80%
this reaction can be found on rhodiums page too. just look for methylamine.
otto has some suggestions on the synthesis route, too. instead of acetonitrile one could use simple acetone giving the benzalacetone:
Ar-CHO + CH3COCH3 --> Ar-CH=CHCOCH3 + H2O
then catalytic reduction:
Ar-CH=CHCOCH3 + H2 --> Ar-CH2CH2COCH3
then schmidt-rearrangement:
Ar-CH2CH2COCH3 + NaN3 + H2SO4 -->
Ar-CH2CH2NHCOCH3 + N2 + NaHSO4.
the resulting acetyl derivative of the corresponding phenethylamine must then only be hydrolyzed. otherwise one could do some chemistry to the aromatic ring while the amine is protected.
otto
