mescaline by 1atm Hydrogenation

transistor child · gnome

Sodium borohydride doesn't reduce carboxylic acids at all.
LAH would form the alcohol. As far as I know there is no practical way to stop the reduction at the aldehyde (it's possible, but uses hard to get and expensive reagents).

joe_aldehyde · huxleys associate

anime · Sun Jun 19, 2005 2:58 pm

mk-1 · Sun Jun 19, 2005 6:34 pm

but if u want to use the acid without going thru the benzaldehyde, look here -
Rhodium Mescsline Synth

spicybrown · Tue Jun 28, 2005 7:17 am

Since this method wasn't based solely on a Bee's report (and is instead from a published article), I'd assume it works. I mean, it makes sense that it should be possible.

I've been thinking about this however, and the fact that they report lower yields if the hydrogenation isn't done at 0ºC. Pd/C can reduce double bonds at 1atm H2. It can also reduce aromatic nitro groups at 1atm. Reducing alkyl nitro groups on the other hand requires different conditions. In a nitrostyrene, the nitro is conjugated with the aromatic ring; I assume this is why they have success reducing it with Pd/C and only 1atm H2. In this reduction, the double bond reduction and nitro group reduction will happen at different rates. I'd imagine that if the double bond gets reduced first, the nitro group becomes unreactive to the standard 1atm H2 conditions present. Lowering the temperature may lead to a lower rate of reduction of the double bond relative to that of the nitro group. I'd wager a bet that the side product in the reaction they report is the nitroalkane.

This leads me to a thought- I bet better yields can be obtained by doing the following two setp one-pot reaction: carry out the reduction as stated, at 0ºC for 3 hours. Then, warm to room temp, remove the H2 atmosphere and toss in something like potassium formate. If I'm right about the side product being the nitroalkane, this ought to reduce the remaining nitroalkane CTH-style. I suppose it may be necessary to neutralize the reaction mixture first. Don't know. Well I'm going to experiment with this hydrogenation this weekend anyway. I'll let ya'll know.

Oh and somebody stated the dangers of working with Pd/C.. This is no joke. Ideally you should evacuate the reaction vessel of atmosphere and backfill with something heavier than air, like argon, before adding the Pd/C to your presumably flammable solvent.

-SpicyBrown

loki · guinea pig

regarding scaling, if the temperature requires 0 degrees temperature to be maintained the larger the flask the harder it is to maintain temperatures (less surface per volume). If a reaction is exothermic, endothermic or only occurs within a small temperature range it is hard to keep the temperature controlled the bigger the reaction gets. This applies more so to roundbottom flasks than flatbottoms of course, being spherical the decreased surface is more of a problem.

the alchemist · Thu Jun 30, 2005 12:34 am

I don't think that would work so well.

Converting the acid to a methyl ester and reducing it to an aldehyde with DIBAL would be better. You could even reduce the ester to an alcohol with LAH and oxidize the alcohol up to the aldehyde with IBX or Swern.

spicybrown · Sat Jul 16, 2005 7:41 am

So somebody who sometimes talks about random shit to me says they tried this reduction on 3,4,5-trimethoxy-beta-nitrostyrene and it didn't work very well. Then they told me that a little while later somebody clued them into the fact that the bottle of Pd/C (from a commercial source) used was considerably less active than is desirable, and this reaction will be tried again at a later date with "the good shit."

By "it didn't work," this isn't to say it completely failed. Analysis of the reaction mixture by LCMS showed definite product present, but the conversion didn't go far enough to even be worth working up.

-SpicyBrown

anime · Sun Jul 17, 2005 11:06 pm

The Reduction at 1atm.
(Bull. Chem. Soc. Jpn., 63(4), 1252-1254 (1990))
According to the authors of the original article, the reaction works at higher temperature but gives lower yields :

"The hydrogenations of 3,4-methylenedioxy-β-nitrostyrene (1), 4-hydroxy-3-methoxy-β-nitrostyrene (5), and 3-hydroxy-4-methoxy-β-nitrostyrene (7) at 0°C gave higher yields of the corresponding phenethylamines in comparison with those at room temperature. The low yields of phenethylamines at higher temperature might be due to the palladium induced formation of imine metal hydride intermediates4."

One might also consider the amount of catalyst used in this reaction. With most catalytic hydrogenations a smaller amount of catalyst is used per gram of reactant.

This article is in the Rhodium archive, unfortunately synthetikals version is not complete.