phenethylamine isomers

[Limpet_Chicken]

Without going any further into sourcing territory than simply 'as typically sold as a 'supplement', is this typically a racemate, or would taking it to the lab to perform a chiral resolution be necessary? as I've just been reading some interesting material on transamination of certain aryl alkyl ketones using Arthrobacter strains using 1-phenethylamine as an amino-donor, such as phenylacetones to amphetamines in an enantioselective manner, and substituted acetophenones to the corresponding phenethylamines. This is enantioselective for the R-isomer, whilst Brevibacterium linens (from limburger cheese) is capable of a similar feat, but selective for the S-isomer of the amino-donor, which at least in the former case, the transaminase enzyme can be induced by exposure to low levels of sec-butylamine.

Just thought it would be a really interesting experiment, to attempt an enzymatic enantioselective biosynthesis of D-amphetamine from unsubstituted P2P, since P2P routes to this desirable compound typically result in a racemic product (question-since the corresponding ketoxime is achiral, what is the result, stereochemistry-wise of boveault-blanc reduction of P2P ketoximes?)

 

[Dresden]

PEA is achiral. It has no racemic form.

 

[sekio]

1-phenylethylamine is chiral. 2-phenylethylamine is not. The commonly sold supplement is 2-PEA. 1-PEA is used in chemistry as a chiral auxillary.

1-PEA: (note the chiral center which has resp. H, CH3, NH2, C6H5 on its 4 substituents)

2-PEA:

The imine of phenyl-2-propanone with 1-phenylethylamine would be chiral, but not on the amphetamine backbone. It would be N-((R/S)-1-phenylethyl) phenyl 2-propanimine.

 

[Limpet_Chicken]

Pardon my ignorance, I've never looked before, since simple phenethylamine itself isn't something I've had any use for, but which is the one commonly sold as a 'supplement', 1-phenethylamine or 2-phenethylamine? since the enzymes in either bacterium are R- and S- selective, with only the one isomer being used as an donor for the amine group to transaminate the ketone(s)

Could be most interesting were something like 2,5-dimethoxy-4-X-P2Ps, the P2P precursors for various TMA analogs or MDP2P to be used as substrate, so the R- and S-enantiomers could be selectively formed and tested both separately and in varying proportions.

 

[Hodor]

Pardon my ignorance, I've never looked before, since simple phenethylamine itself isn't something I've had any use for, but which is the one commonly sold as a 'supplement', 1-phenethylamine or 2-phenethylamine?

2-PEA aka beta-PEA.

 

[clubcard]

1-phenylethylamine is chiral. 2-phenylethylamine is not. The commonly sold supplement is 2-PEA. 1-PEA is used in chemistry as a chiral auxillary.

1-PEA: (note the chiral center which has resp. H, CH3, NH2, C6H5 on its 4 substituents)

2-PEA:

The imine of phenyl-2-propanone with 1-phenylethylamine would be chiral, but not on the amphetamine backbone. It would be N-((R/S)-1-phenylethyl) phenyl 2-propanimine.

Yep - 1-PEA is my pick for making chiral IPAs. Optical resolution is a pain (I am bad chemist). The body-load from chiral (R) 2,5-OMe 4-X compounds is much lower.... some of the (S) isomers are entactogens. I'm surprised that people aren't placing an -F onto the β methylene. Seems a convenient way around the laws in many countries (safety first - just because it's legal doesn't mean it's safe. Some idiot released p,4-dimethylaminorex that killed a few people. p-Me aminorex isn't an MAOI, the 4 derivative IS. I asked Dr. Dave... but obviously some people believe that because it didn't kill them, it's inherently safe. I even have the paper on the deaths from 'Seratonia'.

 

[Dresden]

I would call

1-amino-1-phenyl-ethane, but I dunno, maybe that's just me.

 

[Limpet_Chicken]

This isn't for chiral resolution, actually. But follow-up data-gathering on a microbial transamination, whereby ketones are aminated enzymatically, and it seems that 1-phenethylamine is the best amino-group donor, using Brevibacterium linens, although at least for making straight up amphetamine itself, it looks like it won't be useful for aminating plain P2P, this substrate seems to give no yield of product whatsoever, much better results were had with 3,4-dimethoxy-P2P, and with 4-methoxy-phenylacetone, during their tests, but of course, nobody, myself included, wants para-methoxyamphetamine. Although it could still be interesting to try it on the 2,5-dimethoxy, 2,5-dimethoxy-4-X- or 3,4,5-methoxy-substituted phenylacetones. In this general scheme, the bacterial enzymes transfer the amino group from 1-phenethylamine to the ketone forming the corresponding chiral amphetamine. There are a couple of bacterial species capable of this transformation, and usefully, both one selective for the R-isomer and one for the S-isomer, providing, potentially, an interesting way, if these substitution patterns give any yield worthwhile, of preparing enantioselective routes to psychedelic amphetamines.

 

[clubcard]

This isn't for chiral resolution, actually. But follow-up data-gathering on a microbial transamination, whereby ketones are aminated enzymatically, and it seems that 1-phenethylamine is the best amino-group donor, using Brevibacterium linens, although at least for making straight up amphetamine itself, it looks like it won't be useful for aminating plain P2P, this substrate seems to give no yield of product whatsoever, much better results were had with 3,4-dimethoxy-P2P, and with 4-methoxy-phenylacetone, during their tests, but of course, nobody, myself included, wants para-methoxyamphetamine. Although it could still be interesting to try it on the 2,5-dimethoxy, 2,5-dimethoxy-4-X- or 3,4,5-methoxy-substituted phenylacetones. In this general scheme, the bacterial enzymes transfer the amino group from 1-phenethylamine to the ketone forming the corresponding chiral amphetamine. There are a couple of bacterial species capable of this transformation, and usefully, both one selective for the R-isomer and one for the S-isomer, providing, potentially, an interesting way, if these substitution patterns give any yield worthwhile, of preparing enantioselective routes to psychedelic amphetamines.

It is - as sekio said, chiral auxillary. You end up with a chiral product and hydrogenation removes the N-benzyl moiety (N-benzyl is a common protecting group). In the 1960s it was how dexamphetamine was made. Maybe it still is. It's very convenient because as long as you abstract the H2O, the imine is easily reduced and benzyl removed in a single reaction. When you are working in the tens or hundreds of Kgs, making the racemate is both costly and difficult to resolve. It's molar-efficiency makes it attractive to chemical engineers. You don't want to have to resolve the enantiomers, oxidize the (R) isomer and place it back into the feedstock. Solvent management, a field I admire from a distance.

 

[sekio]

Just a quicky mention of microbial "reactions" - usually they have such poor volume efficiency (often in mmols per L... yikes) and also can make product isolation tricky (hydrolysed cell components can be wonderful surfactants/foamers/emulsifiers). So wherever posssible I would try to use an isolated/bound/purified enzyme rather than whole live cells.