Sciencemadness Discussion Board

Possible Precurser from Basil (phenylpropene)

Pasrules - 4-3-2015 at 19:18

I was sitting at university today and thought up a mechanism which is still short of completion.

Firstly I am employed in the food and pharmaceutical industry and currently studying medicinal chemistry at university. The reason for this topic is just a bit of fun to point out that they can't regulate everything unless suddenly basil becomes the new herb to ban, I don't know what my Italian grandfather would say about that.

Disclaimer: The chemical products formed by this posed mechanism are precursors to pharmaceutical and/or illicit drugs.

Now to the theory side of things i'll start by talking about Anisole (methoxybenzene).



Firstly Cleavage of the methoxy (ether) is mentioned in catalytic cleavage of ethers by Lewis Acid

The section that interested me was the clevage of ethers by addition of conc. Sulphuric acid which less regulated than iodine. However clevage by iodic acid is more accepted as the main mechanism due to Sn2 reactions Acidic clevage of ethers.

This leaves us with phenol which is known to be converted to benzene by heating with zinc metal Preperation of benzene.

However I am searching alternate methods of removing the hydroxyl group from phenol as the R group attached to benzene may be attacked.

Estragole an analogous chemical with respect to anisole can be separated from steam distilled basil oil which would yield a common precursor phenylpropene if the above mechanism worked as planed.

Things to take into consideration are the effect of heating with zinc to remove the hydroxyl group in relation to the reactivity of the double bond. I don't believe this poses an issue.
If this did pose an issue which i will probably have to test myself unless i can dig up a paper, could be averted by the addition of hydroxylamine to the double bond.

P.S if this gets moved to whimsy because of its nature than i want access to whimsy!... please :)


[Edited on 5-3-2015 by Pasrules]

Etaoin Shrdlu - 4-3-2015 at 19:36

Trying to take hydroxyl groups off aromatic rings is often an exercise in futility.

Pasrules - 4-3-2015 at 19:47

It does seem that way which is probably why Pholedrine is in the category of 'designer drugs' although used medically as an eye drop test.
Designer drug p-methoxymethamphetamine

It would also seem so due to the production of PMMA which completely ignores my proposed mechanism and just takes advantage of the double bond to create an analogue of methamphetamine.

[Edited on 5-3-2015 by Pasrules]

Zombie - 4-3-2015 at 21:05

I'll throw in some Olive oil, and perhaps some home grown garlic, if you can make this work.

I think it is WAY easier to grow Ephedra, (or so I read).

Why do sooooooooooooo many people take the long way around?

If you want to make dope, grow the plant. If you want to make "Super pot" change one lousy molecule.

I love this forum, and I admire the VERY schooled people that reside here! No Doubt!

Beating around the bushes sucks.
Why try to turn aspirin into LSD when Rye seed is in bread. (I read that too).

Just sayin'

Pasrules - 4-3-2015 at 21:47

Similar to the nitric acid challenge where you can't use any nitrates. When people take the long way round they discover new things on the way.
Now we just need someone to bring the pasta.

Oh and the money involved in drugs is a great motivator for the discovery of chemistry. Commercially of course :)

[Edited on 5-3-2015 by Pasrules]

Zombie - 4-3-2015 at 22:21

LOL....

I do get it.

It's just so easy to walk across the street. Maybe I'm too old to walk around the house first.

Pasta sounds good tho. :D

Maybe I'll try to flour a pine tree!

Chemosynthesis - 5-3-2015 at 02:17

Regulatory agencies with their chemists know that preventing synthesis and diversion of narcotics for illicit use is futile, but there is a belief that regulation decreases production and diversion. Clearly debatable and not necessarily a view held by the public or politicians, but not a view assailed by the production of more narcotics.
Quote: Originally posted by Pasrules  
I was sitting at university today and thought up a mechanism which is still short of completion.
Seems very short of completion in that there are no arrows, intermediates, transition states.... You mean a scheme?

The production of different analogs that aren't bioisosteres is actually secondary to the chemical feasibility of transforming a phenol to a benzene, though practical feasibility is dubious. Relative cost per product on the chemistry side and binding affinity profiles (thus efficacy and/or metabolism) on the pharmacology side are two particular reasons for potentially synthesizing different chemicals of the same general pharmacophore model, as well as differences in regulation in some locales.

And zinc is pretty unlikely to affect your alkene, assuming you still have it and not a phenyl hydrogen bisulfate or a beta hydroxy ethyl phenol that needs eliminating.
Quote: Originally posted by Pasrules  
If this did pose an issue which i will probably have to test myself unless i can dig up a paper, could be averted by the addition of hydroxylamine to the double bond.

P.S if this gets moved to whimsy because of its nature than i want access to whimsy!... please :)


[Edited on 5-3-2015 by Pasrules]
Uh, what? Hydroxylamine as an alkene protecting group?

Without references, this seems more suited to Beginnings to me. No peer reviewed literature, reaction conditions, etc.

[Edited on 5-3-2015 by Chemosynthesis]

Pasrules - 5-3-2015 at 04:31

There is no need for another synth of amphetamine in any detail, to be reasonable I'm looking at ways to convert a phenol to benzene. I chose a precursor to methamphetamine as most of the people on the forum know about it for the reason of shooing cooks and personal chemical interest of course. I thought an R group containing hydrocarbons and amines or just a double bond seemed like a good ball park for things to be mindful of when changing the phenol.
And no hydroxyl amine is in no way a protecting group. It's purpose was to pose wether to remove the hydroxyl from the precursor or final product.

And I like the idea of calling it a scheme as it is only to poke a bit of fun.

Chemosynthesis - 5-3-2015 at 07:52

I meant like reaction scheme or 'scheme' without the structures. Less detailed than a mechanism as mechanisms have electron arrow pushing that isn't here. I don't see many structures or IUPAC nomenclatures either, but it's a start.
Quote: Originally posted by Pasrules  
There is no need for another synth of amphetamine in any detail
That's a bit of a different topic from not posting any peer reviewed references or data in the organic chemistry section rather the Beginnings section isn't it? Why bring amphetamines up at all if you are going to then completely avoid any detail whatsoever in the chemistry itself? Plenty of other molecules to use. They might lack the personal interest of yours, but it would get into the actual chemistry. Things like the yields, solvents, intermediate steps including potential addition of water or hydrogen bisulfate (not hydroxylamine) to the alkene and subsequent reformation via elimination, attempting to desulfonate your ring where applicable (J. Chem. Soc., Perkin Trans. 2, 1972, 962-965), or if your reaction will be expected to take until the heat death of the universe to work out. Hydrobromic acid can be sourced in many places from over-the-counter supplies, though I can't speak for everywhere, and is an infinitely superior choice for ether cleavage, generally speaking. Not really sure why you used a sciencemadness post as a source without an experimental. Did you read the attached document in the thread? There is a reason your other source uses HI for cleaving a methoxy-methyl ether.
Quote:
to be reasonable I'm looking at ways to convert a phenol to benzene. I chose a precursor to methamphetamine as most of the people on the forum know about it for the reason of shooing cooks and personal chemical interest of course. I thought an R group containing hydrocarbons and amines or just a double bond seemed like a good ball park for things to be mindful of when changing the phenol.

Seems like just asking in Beginnings instead of using examples that get "shooing" would have been reasonable and succinctly comprehensible, as I am lost on what you are getting at with hydroxyl amine if you just wanted to ask this. Breaking aromaticity is not easy, so you will get ridiculous if any suggestion from a hobbyist perspective. On paper, you would probably get a cyclohexanone or cyclohexanol/cyclohexane like derivative before you easily get benzene. Kind of like a Zincke-Suhl to benzene dienol, then a reverse Friedel Crafts. Alternate Example perhaps in Compt. Rend. 1903, 137, 1025.
Just maybe you could then dehydrogenate this to a benzene derivative ala
DOI: 10.1016/j.ijhydene.2009.06.018
For the sake of simplicity, I am assuming you avoid hydrodealkylation. I haven't checked if this is the case. You might need to just go back and use a Friedel Crafts on plain old benzene to get what would have been step 1. In this scenario, you might as well just use benzoic acid to benzene and then continue from there.
Quote:

And no hydroxyl amine is in no way a protecting group. It's purpose was to pose wether to remove the hydroxyl from the precursor or final product.
Not a protecting group. Okay, good. At least we can agree on that so far. Now, what do you mean? You said addition of hydroxylamine to the double bond. I am assuming you mean the alkene of one of your chemicals. Is this a named reaction or can you use IUPAC nomenclature of your product and reactants? I fail to see how adding hydroxylamine to a double bond has anything to do with the phenol. You are looking for ways to convert phenol to benzene or you're speculating on a route to a substituted amphetamine from some kind of non-cyclic reverse Cope elimination I am unfamiliar with? Confused here.

[Edited on 5-3-2015 by Chemosynthesis]

Pasrules - 5-3-2015 at 16:07

Thankyou Chemosynthesis for a needed schooling i'm going to go and manipulate with the methods you mentioned.