Tyrosine -> Mescaline

[Rhodium]

Chem Pharm Bull 23, 2179 (1975)

Tyrosine -Cl₂-> 3,5-Dichloro-4-hydroxyphenylacetonitrile

Then followed by standard procedures:

-NaOMe/CuBr-> Syringonitrile -MeI-> 3,4,5-Trimethoxyphenylacetonitrile -> Mescaline

[PrimoPyro]

I thought you said dichlorobenzenes were not reactive to NaOMe?? Does the CuBr make that big a difference?

Can you react p-dichlorobenzene (99% in mothballs) with NaOMe and CuBr to get p-dimethoxybenzene?

PrimoPyro

[EDIT]Also, since p-dihalobenznes are so deactivated, would chloromethylation proceed at a controllable rate, unlike chloromethylation of 1,4-dimethoxybenzene, forming the bischloromethyl derivative?[/EDIT]

[Antoncho]

I wonder if aromatic chlorides will bee reasonably reactive in this rxn... Rhodium, did you mean anything specific here and what do you think?

Apart from that, this rxn scheme is truly awesome - that slick trick with simultanious chlorination and convertion to nitrile.... I wonder if this could bee pulled with bromine instead of chlorine? Seems possible, no?


Rhodium, you're the best!



Antoncho

[Antoncho]

This could bee even more interesting:

dichlorobenzene ---> p-diCl-benzyl chloride ---> p-diCl-benzaldehyde

(say, similar to

Post 321291

(Antoncho: "An interesting chloromethylation procedure", Chemistry Discourse) - however, here it should bee needed to emloy harder conditions, maybee temp could bee increased, or yet more specifically , this

Post 250939

(Antoncho: "Re: A safe an easy way to chloromethylate.", Novel Discourse))


diCl-BA ---> diMeO-BA


Again, the question of Ar-Cl species' reactivity is haunting me here...






Antoncho

[Rhodium]

Chlorobenzenes aren't as reactive as the bromo/iodo counterparts, and longer reaction times than usual are probably required, and you can expect a lower yield than with the other halides. However, as both tyrosine and chlorine (KMnO4/HCl) are dirt cheap, yield is not much of an issue.

What if bromine would work just as good as chlorine in the reaction? Dunno...

[Aurelius]

wouldn't there be competition for condensation of the aldehydes with NaOMe in solution?  what about protection of the aldehyde first?

[PrimoPyro]

Aurelius, I had to think for a moment as to what you meant. I assume you mean Aldol Condensation between two molecules of aldehyde? I think water is needed to catalyze that reaction, or at least a protic solvent, right?

NaOMe will react with any benzyl chlorides formed as well, forming methyl benzyl ethers.

But that benzyl chloride could easily form some other useful group before conversion of the aryl chlorides to alkoxides.

PrimoPyro

[Rhodium]

Aldol condensation? With the aid of what alpha hydrogens?

Edit: ...or what ALDEHYDES are you talking about in the first place?

[SPISSHAK]

You can inject tricoserus pachanoi with tyrosine, or any mescaline producing catus with tyrosine and boost it's mescaline production.
It's a slow enzymatic process, though.

[PrimoPyro]

Wrong name perhaps? I believe he meant condensation of any benzaldehydes,catalyzed by base, if one tried to perform a conversion of 2,5-dichlorobenzaldehyde to 2,5-dimethoxybenzaldehyde with NaOMe. I guess I got the name wrong?

PrimoPyro

[Aurelius]

aurelius believes it's called "claisen" condensation, correct?  auto-oxidation-reduction reactions
simultaneous formation of alcohol and acid (or salt thereof)

[Rhodium]

No, that's a "canizzaro reaction".

[Aurelius]

ok, so aurelius can't always recall the names, but knows the chemistry.

[GC_MS]

This article (tyrosine -> PMA) might be helpful as well:
H Kohno, T Iwakuma, K Yamada. A simple and efficient procedure for the synthesis of optically active 4-methoxy-alfa-methylphenylethylamine from tyrosine, Synthetic Commun 28(11) (1998) 1935-1946.
Helpful as in 'applicable to other synthetic routes'. I don't have it though...
Ave Hive, synthetisandi te salutant!

[Psi_Locybe]

Well, re:'what happens with bromine,' the thought-train I'd been musing on used either iodine or bromine, and IMO was simpler...

I2 + tyrosine -> 3,5iodotyrosine + NaOH -> 3,4,5OHphenylalanine (which I kinda wanna munch in its own right - sounds like an interesting non-essential amino acid)

...and then, of course, decarboxylation in, say, thujone, a little MeI, and I think we all know what I delusionally believe would result...

...only *I* got the idea from :

http://www.ajinomoto.co.jp/ajinomoto/A-Life/e_aminoscience/bc/amino_18.html

...according to which, this whole damned chain should fall under the "idiot high school kid cooking in a jelly jar" level of difficulty... the first step is apparently damn-near-automatic, with all the reaction sensitivity of CO2 synthesis via NaCO3H + GAA...

...the article also asserts that Br2 would react identically to I2...

...however, I found this thread via a desperate search for better recrystallization info for tyrosine than this article gives - the H2O solubilities given, while they seem useable for small-scale recrystallization at first, have a simple problem - the solubilities of phenylalanine, which is also common in the same organic sources (lima beans, soy, sesame, almonds, etc...)

...U.S. patent 6,294,579 (no, I *don't* have the link, sorry) suggests that tyrosine is more soluble in alkaline than neutral solution, which may help - hot basic water -> cold salt water - but again, I don't know about phenylalanine's behavior...

...also, I don't know exactly how tyrosine/phenylalanine respond under blacklight - do they flouresce?

...I'm dirt-ass poor (actually, since you refer to both Cl and tyrosine as 'dirt cheap,' *beyond* dirt-ass poor), so these little tidbits are vital to a ghetto lab - I don't have the luxury of paying health food stores out the ass for precursor, and it would probably become a point of pride if I *was* wealthy enough - although I'd probably have better resources to do the deed with in such a case...

::sigh::  Naked in the woods,

[Rhodium]

If you write [ patent ] US6294579 [ /patent ] without the spaces, the result is a nice patent link:

Patent US6294579

[Psi_Locybe]

...result is a nice patent link...

  Nice!  Thanks for the info/coding! 

BTW, am I to presume that the brevity implies that there is no recourse but to recrystallize a phenylalanine/tyrosine mixture from h2o and pray it glows with the alpha-carboxyl? (EG 'no good recrystallization solvents')

...or just the "I don't feel like dealing with it?"

[zorohydride]

Hello Rho

Starting from amino acids is brilliant because they are plentiful, legal, and rarely watched; however, the synthesis appears to be an elegant multistep and laborious [or labratorious]project. I would suggest starting with Syringaldehyde, which is not watched and probably less GrIeF! Plus you can do that really cool version of 4-Allyl-Mescaline that appears to work at 50MG and is much smoother. I have had some experience with converting PHE to PHE-ol and the n-methyl analogs and it's work.