amine catalyist in Norephedrine synth

[welt]

for the synth outlined at

[url=https://www.thevespiary.org/talk/index.php?topic=9020.msg45840100#msg45840100" class="bbc_link" target="_blank" rel="noopener noreferrer">Post 458401

(HumbleBee: "Norephedrine from benzaldehyde", Methods Discourse)=1&vc=1]

can a different tertiary amine be used in place of triethylamine ? 
or would the old art with alkalimetal catalyst be easier ?

[Bandil]

Yes - alkalihydroxides will do the job. They will however give a lower overall yield and a lower yield of the desired norephedrine stereoisomer. So depending on the intended use of your product, you should consider the following. If you simply want to reduce it to plain amphetamine, the alkalihydroxide "condensation" is fine. Also, if you have the balls(stupid enough?) to use cyanogen bromide, it's also a fine intermediate for 4-mar.

However, if you want to run the non-toxic cyanate route for trans-4-mar, you really should go for the trialkylamine route. Most lower trialkylamines will work as a catalyst, with the correst stereoisomer as the major product. From emperical knowledge I know that tributylamine will work quite well. The exact yield of the outcome using this as a catalyst, has not been measured.

Read

this

(https://www.thevespiary.org/rhodium/Rhodium/chemistry/para-fluoro-4-mar.html) for an example of the trialkylamine reaction.

Regards
Bandil

[welt]

so regular benzaldehyde should react the same as the halogenated version as oulined in that synth ?

also dosnt condensation with nitroethane with a trietheylamine normaly form norpesudoephedrine unless its chilled to -10degC ?

[Bandil]

Yes - it will work with benzaldehyde aswell! Theoretically it should dehydrate a little easier than the halogenated version, so treat it with a little care untill it has been reduced to PPA.

The reason for the low temperature is to push the equilibrium between norpseudoephedrine and norephedrine pushed well to the right. If done at RT you will end up with a close to 1:1 ratio of the two. Still useable - but it's a stupid place to cut corners. You will get atleast +50% yield of the desired stereoisomer, by running the reaction cold.

So, stay cool  

Regards
Bandil

[Xicori]

Yes, the condensation works quite well, but do not use the Reduction with Zn/Formic or with Ammonium Formate.

Swim tried it 3 times - and got no yield every time!

[Bandil]

Xicori>
Yes, I've had my doubts about the Zn/formate reduction of nitroalcohols. Tried it with the fluoro version, but the product was never GC'ed, so I can't be sure of the result.

I would think that the acidic environment in which the formate reductions runs splits the nitroalcohol back to the benzaldehyde and actually reduces the nitroethane to ethylamine to a large extent.

Is it possible to use Pd/C reduction for the nitro group, without hurting the alcohol group? I've read about reduction methods of aminoalcohols (ephedrine) with catalytic hydrogenation. But that was under pressure... Any idea how potassium formate as the hydrogen donor will affect this under CTH conditions? This way, the pH is surely kept basic at all times...

Guess theres only one way to find out  

Regards
Bandil

[Xicori]

High Bandil!

I think this may be worth a try:

https://www.thevespiary.org/rhodium/Rhodium/chemistry/nitro2amine.cth.pd-af.html

swil would give it a go this hour, if there would be any nitroethane left But this is going to change with time!

Would be gerat if you could try it on a small scale!

best wishes,
xicori

[welt]

couldn’t one use Aluminum mercury reduction with this to reduce it or is it too likely to take out the OH group as well
Although that would not be all bad
I think I remember some one saying that zinc powder and H2SO4 would do it or is that just my mind playing tricks on me

[welt]

Would hexamine (such as taken from fire starters) work as a tertiary amine in this synth, because that would be amazing
Any thoughts people?