mellow (Newbee)
07-16-02 12:31
No 333330
      MDP-alanine from DOPA - How?  Bookmark   

If a friend of mine wanted to go about making MDP-alanine from DOPA how would she go about doing it?

The Williamson synth:

DOPA + base + CH2X2 __> MDP-alanine    [X = halide]

is not immediately on, is it? - because the halide will react with the carboxylic (preferentially) giving a cross-linked (phenol - CH2 - carboxylic) polymer.

Can she protect ONLY the carboxylic acid by esterifying it with methanol in a Fischer esterification first?


1) DOPA + MeOH (+ HCl catalyst) __> DOPA methyl ester.

followed by:

2) DOPA methyl ester + CH2X2 (+ alkali) __> MDP-alanine methyl ester.

PS: given that she wants to finally end up with an ester - is this the preferred way to do it?

I guess she then intends to proceed by:

3) MDP-alanine methyl ester + benzaldehyde __> MDP-alanine methyl ester imine

4) MDP-alanine methyl ester imine + CH3I (+ base) __> alpha-methyl-MDP-alanine methyl ester imine

5) followed by hydroylisis of the imine and the ester to:

6) Finally decarboxylation to MDA

(Well I assume that would be possible but I'm sure she would get the necessary license first anyway)

Sorry for the intrusion but my last chemistry class was 15 years ago and I've done hardly any since - certainly nothing novel like this - so I find it hard to give her any good advice.
(Hive Bee)
07-24-02 04:38
No 336525
      Decarboxylation will give a phenethylamine, not ...  Bookmark   

Decarboxylation will give a phenethylamine, not an amphetamine. However I would be interested in if there is any bioactivity for such a phenethylamine, Shulgin didnt find any sign of activity but maybe with an MAOI or something....
07-24-02 17:22
No 336729
      DOPA is alpha-alkylated with a methyl group  Bookmark   

I disagree, the end product will be MDA.

Maybe my explanation was inadequate. After step 3, the Hydrogen on the alpha-carbon (next to the carboxyl group) is very acid (due to the two electron withdrawing groups near to it). So in strong base it is easily substituted with a methyl group so that the alpha-carbon is alkylated.

Instead of methyl iodide you could use fluoro,iodo-methane (CH2FI) so this would be a possible way to make MDP-(1-fluoro,2-amino-propane).

Again I ask anyone here - is there anything wrong with this? - that could stop it working.
(Hive Prodigy)
07-24-02 20:31
No 336802
      methylenation  Bookmark   

I was once told publically by Rhodium that one of my schemes would not work due to my methylenation step on a catechol-isopropylamine, that would have made a MD-amphetamine after the reaction.

I was told that the amine function could not withstand the conditions of the reaction, those being base and DCM. More info I wish I had, but I dont. But I do remember him saying it wouldn't work.
(Chief Bee)
04-24-03 11:50
No 429173
      Methylenation is not possible with a free amine  Bookmark   

The conditions able to alkylate the phenols (base, alkyl halide, heat) will also be able to alkylate the nitrogen, causing polymerization or other side-reactions. For the methylenation to work, you need to protect the nitrogen with a suitable amine protection group (for example by making the BOC-amide, which is easily cleaved by acid afterwards).
04-24-03 13:03
(Rated as: insignificant)
04-24-03 14:46
No 429205
      Phenolates (from phenoles and a strong base)...  Bookmark   

Phenolates (from phenoles and a strong base) are way more basic than amines... It might work without amine protection.