Sciencemadness Discussion Board - Possible N-ethyl-2-phenylethylamine Synthesis Variations

Possible N-ethyl-2-phenylethylamine Synthesis Variations

Aurelian - 2-7-2013 at 08:09

Hi,

Curious compound popped into my head earlier this morning. I'm interested in the compound N-ethyl-2-phenylethylamine.

Let's propose an easy reaction.

Pretty sure it's not possible to carry out the reaction between anhydrous ethanol + phenylethylamine to yield N-ethyl-2-phenylethylamine and h2o.

The other idea I had was a chloroethane reaction with phenylethylamine yielding N-ethyl-2-phenylethylamine and hydrochloric acid.

Any thoughts?

[Edited on 2-7-2013 by Aurelian]

Nicodem - 2-7-2013 at 08:26

Quote: Originally posted by Aurelian

Pretty sure it's not possible to carry out the reaction between anhydrous ethanol + phenylethylamine to yield N-ethyl-2-phenylethylamine and h2o.

Why not? It might not be the highest yielding or the most practical method, but just why not?

Quote:

The other idea I had was a chloroethane reaction with phenylethylamine yielding N-ethyl-2-phenylethylamine and hydrochloric acid.

I liked your other idea more. Chloroethane does not sound like the reagent of choice for such a reaction when one is after a preparative method. Do you happen to have any references saying otherwise?

Quote:

Any thoughts?

Yes, my thought is that threads without any references belong to the Beginnings section, which leads me to suggest you to read the forum guidelines.

Aurelian - 2-7-2013 at 08:51

Sorry no sources! All from my head. Just wanted thoughts from others on this. Thanks.

Quote:

Why not? It might not be the highest yielding or the most practical method, but just why not?

The reaction was carried out earlier, but I was slightly worried about any H2O interfering with the yields. I've got to do a work-up, and see about yields.

Please feel free to move it to the beginners section. It was related to organic chemistry, and so I put it in this section. Your choice captain.

Was also considering N,N-diethyl-2-phenylethylamine from the same anhydrous ethanol + 2-phenylethylamine route just with 2mol of anhydrous ethanol instead of 1mol. Will try this with part of the prepared N-ethyl-2-phenylethylamine.

Anybody want pictures?

[Edited on 2-7-2013 by Aurelian]

zed - 4-7-2013 at 14:38

Seems possible. Take Phenethylamine, convert it to an amide. Take the amide, dissolved in a large volume of anhydrous Ethanol, and force it through a long coil of tubing heated at 350C.. A catalyst might be required.

With a little luck, the product will be the amide of N-Ethyl-2-Phenethylamine. Hydrolyse the Amide to recover your final product... N-Ethyl-2-Phenethylamine!

US Patent 3,674,851 July 4th, 1972

[Edited on 4-7-2013 by zed]

solo - 4-7-2013 at 18:13

......there is a method of reducing phenylalanine to phenethylamine in two step sequence ..."one pot sequence for the decarboxylation of alpha amino acids"(laval-golding).......solo

One pot sequence for the decarboxylation of alpha amino acids
Laval, Bernard T. Golding
Synlett
2003, No. 4, Print: 12 03 2003.

[Edited on 5-7-2013 by solo]

Attachment: one pot sequence for the decarboxylation of alpha amino acids.pdf (66kB)
This file has been downloaded 546 times

sonogashira - 4-7-2013 at 22:49

Quote: Originally posted by Aurelian

Was also considering N,N-diethyl-2-phenylethylamine from the same anhydrous ethanol + 2-phenylethylamine route just with 2mol of anhydrous ethanol instead of 1mol. Will try this with part of the prepared N-ethyl-2-phenylethylamine.

Anybody want pictures?

[Edited on 2-7-2013 by Aurelian]

You can perform mono- or di-alkylation very selectively with the system you described - and in near quantitative yields - using several ruthenium- or iridium- based hydrogen-transfer catalysts. RuCl2(PPh3)2 is the easiest (and cheapest) to make - you will need only 1 mol % relative to the amine.

maxpayne - 5-7-2013 at 09:07

Alcohols readily swaps for amine, but I also think that a reference or someone's personal experimental details would be nice. I do not have such experience but this seems to be so basic chemistry, and I'm looking forward to see a procedure without catalyst, without the concerns on yields.

So please, if anyone can share experience about particular reaction, post it here.

Aurelian - 5-7-2013 at 13:17

Hi all, thanks for the replies.

Some results from mono-alkylation of PEA. Stoichiometric amounts of PEA + anhydrous ethanol (in slight excess) was reacted in a 500ml FB boiling flask with stir-bar, and reflux condenser. Reflux was carried out for a couple of hours. After reflux the flask was put in the freezer to freeze precipitate, and after cooling almost all the mass had precipitated. Very little liquid was left over (maybe 10ml from a total 250ml I started with), and everything had crystallized.

This shows that mono-alkylation proceeded successfully without need of catalysts.

The remaining liquid was drained, and more anhydrous ethanol was added (250ml again). Same process was carried out, freeze precipitated, but this time about 100ml was left-over/unreacted.

This shows that part of the material was di-alkylated successfully, but a percentage was still left in the mono-alkyl state.

Thoughts? I'm not too much of an organic chemistry wizard. My main area of expertise is actually inorganic & nanoparticle chemistry.

[Edited on 5-7-2013 by Aurelian]

sonogashira - 5-7-2013 at 13:24

...and to think that people have wasted so much time and money with precious metal catalysts...!

[Edited on 5-7-2013 by sonogashira]

Aurelian - 5-7-2013 at 13:41

First image is of the completed mono-alkylation of PEA after freeze precipitation.

The second is just after adding more anhydrous ethanol just before carrying out the second alkylation to the di-alkyl.

Uses of the finished product? Well, research purposes only.

[Edited on 5-7-2013 by Aurelian]

sonogashira - 5-7-2013 at 13:47

Was your PEA a liquid or a solid?

Aurelian - 5-7-2013 at 13:51

PEA only exists as a liquid when in the freebase form.

Why do you ask?

So what do I have in mind next to try? Let's try this process with anhydrous isopropyl alcohol. Should produce an interesting novel PEA compound too!

N,N-diisopropyl-2-phenylethylamine

[<a href="u2u.php?action=send&username=bfesser">bfesser</a>: merged sequential posts]

[Edited on 7/8/13 by bfesser]

Nicodem - 6-7-2013 at 13:38

Quote: Originally posted by Aurelian

This shows that mono-alkylation proceeded successfully without need of catalysts.

You better stop mocking on the scientific method on a science forum! I should send this thread to Detritus, but I'll give it a second chance for those who, unlike you, at least have some respect for science.

maxpayne - 7-7-2013 at 03:58

Quote: Originally posted by Aurelian

Hi all, thanks for the replies.

Some results from mono-alkylation of PEA. Stoichiometric amounts of PEA + anhydrous ethanol (in slight excess) was reacted in a 500ml FB boiling flask with stir-bar, and reflux condenser. Reflux was carried out for a couple of hours. After reflux the flask was put in the freezer to freeze precipitate, and after cooling almost all the mass had precipitated. Very little liquid was left over (maybe 10ml from a total 250ml I started with), and everything had crystallized.

This shows that mono-alkylation proceeded successfully without need of catalysts.

The remaining liquid was drained, and more anhydrous ethanol was added (250ml again). Same process was carried out, freeze precipitated, but this time about 100ml was left-over/unreacted.

This shows that part of the material was di-alkylated successfully, but a percentage was still left in the mono-alkyl state.

Thoughts? I'm not too much of an organic chemistry wizard. My main area of expertise is actually inorganic & nanoparticle chemistry.

[Edited on 5-7-2013 by Aurelian]

What makes you think that you achieved mono alkylation of amine and complete reaction after first reflux?

Aurelian - 8-7-2013 at 12:12

It's obvious isn't it?

Quote: Originally posted by Nicodem

Quote: Originally posted by Aurelian

This shows that mono-alkylation proceeded successfully without need of catalysts.

Wow?

Calm down please! What the hell did I ever do to you?

I am a scientist, and I love science. You took that statement completely out of context, and twisted it to form your own opinion of myself. You know NOTHING about me.

[Edited on 8-7-2013 by Aurelian]

[<a href="u2u.php?action=send&username=bfesser">bfesser</a>: merged sequential posts]

[Edited on 7/8/13 by bfesser]

solo - 8-7-2013 at 12:20

.....how did you verify your success, did you test your end product ....MP, solubility, NMR...hence it's not so obvious just because you got an end product.....solo

Aurelian - 8-7-2013 at 12:25

Bioassay actually.

I am certain of my skills.

PEA is not so active. It gets attacked by MAOI.

Mono-ethyl-PEA is slightly active. It's somewhat stimulating.

Di-ethyl-PEA is even more active. It's stimulating for a few minutes, and then it begins to act on the mu-opioid receptors.

Source: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=3750...

sonogashira - 8-7-2013 at 12:45

The boil in ethanol technique?! It works with any chemical to give the product you want it to be! I don't even think this is a joke! Some nanomaterials chemist....!

[Edited on 8-7-2013 by sonogashira]

Aurelian - 8-7-2013 at 12:46

Well, who's joking who? :cool:

Some "solvents" do react with what is being dissolved. This happened to have worked the way I figured it would.

No clue.

Experiment, work, labor, and try. If it doesn't work, oh well, find another way, and begin again. No big issue.

[<a href="u2u.php?action=send&username=bfesser">bfesser</a>: merged sequential posts to remove unnecessary quoting]

[Edited on 7/8/13 by bfesser]

sonogashira - 8-7-2013 at 12:50

You're kidding yourself then, obviously!

[<a href="u2u.php?action=send&username=bfesser">bfesser</a>: removed unnecessary quoting]

[Edited on 7/8/13 by bfesser]

Aurelian - 8-7-2013 at 12:51

Try the reaction yourself, and then get back with me.

On the subject of nano-particles. Would you like to see some 15nm gold nano-particles after being centrifuged? Sure you do. I'll show you.

goldnanoparticles.jpg - 4kB

[<a href="u2u.php?action=send&username=bfesser">bfesser</a>: merged sequential posts & removed unnecessary quoting]

[Edited on 7/8/13 by bfesser]

bfesser - 8-7-2013 at 13:11

Can we please try to keep the nested-quotes under control, fellas?

<strong>Aurelian</strong>, if you continue to make annoying sequential posts and using nested quotes instead of editing, I'll lock the thread. I'm getting tired of cleaning up your mess.

[Edited on 7/8/13 by bfesser]