Sciencemadness Discussion Board

Which route would you take too Phenylpropanolamine?

MrNyeTheSciGuy - 2-12-2013 at 00:48

Hello everyone,

I am curious as to which route you would take? My goals are to find the simplest route, without needing to buy precursors or lab equipment from Sigma-aldrich. I'm just a Student/Hobbyist at the moment, so any help would be wonderfully appreciated.


1. Propiophenone -> alpha-bromo Propiophenone -> Cathinone -> PPA

2. Propenyl benzene -> Propenyl benzene chlorohydrin -> PPA

3. Propenyl benzene -- Peracetic Acid or Oxone--> 1-Phenyl-1,2-epoxypropan --NaN3--> 1-Phenyl-2-azido-1-propanol --Zn/NH4Cl--> PPA

4. Via Akabori Reaction


My thoughts

1. Seems simple
2. Seems simple
3. Looks Difficult
4. Low yield, plus a waste of Benzaldehyde. Seems like the hardest part is getting the final PPA out of everything else.

If any of these routes are mistaken or if I seem to bee missing a more practical route, I'd appreciate it if you would let me know. I have not experimented yet and I would like to explore the theoretical before I waste time in the lab.

Plus I have UTFSE and gone through my basic Organic Chem Books, but I am asking for the more experienced Chemists opinions. Thank You.



turd - 2-12-2013 at 01:32

If I had unlimited access to the reactants, I would choose the classic route #1 (via bromopropiophenone). But then I have access to autoclaves, which may be necessary for the amination.

BTW: A general problem with phenylpropanolamine is the stereochemistry. There are diastereomers. :(

:) thanks for the reply Turd

MrNyeTheSciGuy - 2-12-2013 at 01:45

Thanks for the reply T :)

I sadly am not as blessed to have access to autoclaves :( But you did bring a good point on the stereochemistry, I forgot to mention that for my purposes I'm pretty sure it doesn't matter, correct me if I'm wrong but Trans 4-methylaminorex does not need a specific Chiral center in its synthesis , since it is racemic. I could be wrong though Since I am still a novice in organic chem and I'm still trying to get my head around Stereochem. I'm just very interested in nootropics and the like, and I'm bored of making more recreation chemicals. I know I left all that out above but I was worried the discussion of nootropics would be frowned upon.

turd - 2-12-2013 at 03:06

Quote: Originally posted by MrNyeTheSciGuy  
I'm pretty sure it doesn't matter, correct me if I'm wrong but Trans 4-methylaminorex does not need a specific Chiral center in its synthesis , since it is racemic. .

Well, if you want rac. trans 4-methylaminorex, you don't need a specific chiral center, but you do need a specific relationship of the two chiral centers. Unless your reactions are regioselective (or would that be stereoselective?) you're going to handle two compounds with slightly different physical properties - not nice if you want to crystallize / distill them. Of course the stereochemistry of the phenylpropanolamine might indeed not matter if the follow-up reaction racemizes one of the stereogenic centers.

https://www.erowid.org/archive/rhodium/chemistry/4-mar.stere...

Mr_Magnesium - 2-12-2013 at 03:37

Isonitrosopropiophenone looks promising

http://www.google.com.au/patents/US3090812
^

keep searching

[Edited on 2-12-2013 by Mr_Magnesium]

Once again Thank You!!!

MrNyeTheSciGuy - 2-12-2013 at 06:10

I really do appreciate your help guys, and Ts got me dusting off my notes alright here we go. The synthesis I am referring to Uses Norephedrine with potassium Cyanate. This should only be able to produce the Trans Isomer from the authors notes but as I understand it after looking over your resources(T) there is a possible 3 types of trans? 4r/5r 4s/5s and dl Trans depending on type of PPA used?(Am I getting any of this right?) Now in the notes it says you gave the Cis Isomer will be produced with norephdrine with Cyanogen bromide, but since I'm using Cyanate salts the Author Said the trans should only be produced. This is where im having difficulty( And I apologize not being more educated with stereochemisty) That since the potassium cyanate is being used it doesn't matter the centers point as long as they are 1s/2r 1r/2s. To be honest I'm pretty lost now. Here is my resource for the procedure and as you can see its very simple except the PPA which will probably be simple as well as soon as I understand this. I apologize for being a lazy reduction chemist for most of my experiments and I'm just venturing out into other reactions(I'm very interested in electrolysis as well. Sorry about the rant here (Trans 4 - methylaminorex synth resource located at bottom) , and any other suggestions or reading materials to better grasp stereo chemistry would greatly be appreciated, and with that said I'm off to use the the search engine.

about.mdma.ch/000458588.html

- Synth route for Trans 4 - methyaminorex as you can see everything is soo simple besides the PPA and I don't want that to be the roadblock to my experiments. Thank you.


[Edited on 2-12-2013 by MrNyeTheSciGuy]

turd - 2-12-2013 at 07:59

Quote: Originally posted by MrNyeTheSciGuy  
The synthesis I am referring to Uses Norephedrine with potassium Cyanate. This should only be able to produce the Trans Isomer from the authors notes

This is a different situation than yours. Norephedrine is a natural product with a well defined stereochemistry. You propose to start from non-chiral, non-diastereomeric reactants.
Quote:
there is a possible 3 types of trans? 4r/5r 4s/5s and dl Trans depending on type of PPA used?

Since trans-4-methylaminorex (trans-4MA) is chiral there are indeed two versions of that molecule which are related by mirroring. Since they are isometric (same interatomic distances and angles), they have the same physical properties and the same energy. Thus using only non-chiral reactants, as you propose, you will always get an equal amount of both isomers (i.e. the racemate).

The same is true the cis-4MA. But since cis-4MA and trans-4MA are energetically not equivalent, you will generally get non-equal proportions of racemic cis- and racemic trans-4MA. The exact ratio will depend on the selectivity of your synthesis route. To know what final composition you can expect you will have to study the literature or wait for one of the o-chem experts who can predict this from the reaction mechanism.