Author Topic: Production of 2-Methyl-3-phenylserine.  (Read 5827 times)

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Rhodium

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Akabori Literature
« Reply #20 on: August 18, 2003, 05:09:00 PM »
As requested in

Post 448664

(roger2003: "Akabori literature", Methods Discourse)
. I believe that the last one is wrong, and deals with the Akabori Reduction (amino acids to amino aldehydes), rather than the Akabori Reaction (benzaldehyde/amino acid condensation) we are interested in.
So - roger2003 and others, better check your references in the fduture so that you know that the articles are dealing with the correct transformation.



The Akabori Amino Acid Reduction



Synthese von Imidazol-Derivaten aus -Amino-säuren
1. Mitteilung: Eine neue Synthese von Desaminohistidin und ein Beitrag zur Kenntnis der Konstitution des Ergothioneins.

Shiro Akabori

Chem. Ber. 66, 151-158 (1933)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/akabori-1933.pdf)




Eine Neue Darstellungsweise Von Aminen Aus -Aminocarbonsäuren
Klaus Dose

Chem. Ber. 90, 1251-1258 (1957)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/akabori-1957.pdf)

Abstract

Eine Methode zur Darstellung von Aminen aus -Aminocarbonsäuren durch Decarboxylierung bei Gegenwart aromatischer Aldehyde wird beschrieben und der Mechanismus dieser Reaktion elektronentheoretisch gedeutet. Die Reaktionsgemische werden durch Hochspannungspherographie im mikropräparativen und analytischen Maßstab aufgetrennt und u.a. mit Hilfe kolorimetrischer Methoden bestimmt.




2-Mercaptoglyoxalines. Part IX. The Preparation of 1,5-Disubstituted 2-Mercaptoglyoxalines from -Amino-acids
A. Lawson & H.V. Morley

J. Chem. Soc. 1695-1698 (1955)

(https://www.thevespiary.org/rhodium/Rhodium/pdf/akabori-1955.pdf)

Abstract

The reduction of -amino-acid esters by the Akabori procedure and condensation of the resulting carbonyl compounds with thiocyanate at pH 4 gives 1,5-disubstituted 2-mercaptoglyoxalines (III). The constitution of these compounds is proved by synthesis of the derivative (IV, R = H, R' = Me, R" = Propyl) obtained by Wolff-Kishner reduction of (III, R = Me). These ketones (III) have been converted into thiazolo(3',2'-1,2)glyoxalines (IX) by ring closure.

Aurelius

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AGHHHHHH!!!!!!!!!!!!!
« Reply #21 on: August 18, 2003, 05:17:00 PM »
Blasted German!!!!!!!! 

Would somebody please translate and type the first two articles in Rhodium's post?

(And BTW, in the General Discourse Forum, I've got a request for another german article to be translated and typed. It's about Psilocybin and Psilocin in Mushrooms.  I can only get a VERY vague picture of what's in that article- It's in this thread:

Post 450823 (missing)

(Aurelius: "Cland Drug Labs J. For Sci 15,1, 51-64 (1970)", General Discourse)


Please, somebee, do this favor for (ahem-me-ahem) the Hive... For the love of bees, please?)


DRIVEN

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Decarboxylation attempt #1 results.
« Reply #22 on: August 19, 2003, 07:49:00 AM »
Experiments were conducted to answer the question about the identity of the ppt that formed after the decarboxylation.

It was reasoned that if the ppt was PPA-HCl, it would turn into an oil when the mixuture is basified strongly.  The entire post reaction was basified.  There was difficulty in determining the pH of the DMF mixuture using pH paper as the solution acted very much like xylene, specifically in the way that it's pH can't be reliably tested with pH paper. Dispite this an excess of 40% NaOH was added that exceeded at least the known molarity of the phenylserine. The ppt did not dissolve. The DMF was thought to be interfering with the process so the ppt was filtered out. The filtrate (DMF) was saved. About 100 ml of water ws added to the isolated ppt, it did not dissolve, the pH was very basic. At this point it was suspected that the ppt was phenylserine sodium salt because, at this pH the phenylserine has negative charges on the carboxyic acid group and the alcohol group giving it a total negative charge where if it was the PPA free base, it would be an oil.

Decarboxylation attempt #2 will involve dissolving the salt in DMSO and heating to 190 deg C.

This is based on some important points that have recently come to light.

a) The phenylserine will be charged at any pH, therefore it will always bee ionized and have limited solubility in non polar solvents. Therefore the choice of solvent for decarboxylation will be limited to the polar spectrum.

b) It is likely that the decarboxylation of this phenylserine will require more heat than what can be offered by the boling temperature of DMF (~150).

DMSO is both polar and of high BP so its next in line.  Aurelius, now I know what you were getting at with recommending DMSO ::) ....)

DRIVEN  :)


SPISSHAK

  • Guest
Also consider mechanism
« Reply #23 on: October 10, 2003, 12:00:00 AM »
you notice in the akabori reaction a 2 fold excess of aldehyde is used?
Well it has a carbonyl group that forms a shiff's base with the amino acid, this shiff's base may abstract a proton from the carboxylic acid causing it to form  a leaving group.
This mechanism applies to alpha amino acids (those seperated by one carbon)
In this case it's a beta amino acid so I don't know if the same holds true.
Looking at DMSO you see the carbonyl group in the middle?
with it's high B.P., polarity and carbonyl group capable of forming the shiff's base I would react the "serine" in the free acid form with the proton dangling from that carboxyl group, as opposed to it's sodium or potassium salt as this effect can not take place in this instance.
who knows it might just work! :)
for instance you could just use the classical akabori reaction by heating benzaldehyde and alanine in DMSO.
this would serve both as a solvent and a decarboxylation promoter, we'll see.'

allow me to correct myself, It would seem wiser to first form the alanine bezaldehyde serine derivative and then decarboxylate using a high boiling polar solvent with a sulfonyl (not carbonyl) function (like dmso)
I fear using dmso as a sovent in a straight akabori condensation/decarboxylation reaction might interfere.
The advantage here is that you can form this shiff's base intermediate which will facilitate the decarboxylation of the COOH+ group by proton abstraction to the shiff's base.
but the interatomic distance in a alpha VS beta amino acid (like the one you are referring too) may cause this not to work.

DRIVEN

  • Guest
Could a willing bee take this over?
« Reply #24 on: October 10, 2003, 07:33:00 PM »
Hey fellow beez,

Driven is unable to continue the experimental on this project. Yes, D is feeling the pain... All these hypothesis and no way to test. Argh.

Are there any takers? Common, it's a lot of fun  ;D .

DRIVEN


ahgreich

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so where didbee leave off?
« Reply #25 on: October 11, 2003, 12:10:00 AM »
letbee get this right: the desire is to first create the serine derivitive of bzH and Alanine, then react the derivitive with another mole of BzH in DMSO?

DRIVEN

  • Guest
Almost
« Reply #26 on: October 11, 2003, 08:49:00 AM »
ahgreich, your half way there,

1) React dl-alanine with BzH to form the 2-methyl-3-phenylserine. D (among others) showed this to work.

2) Decarboxylate the phenylserine to form phenylpropanolamine.  Has yet to be done.

Driven


algebra

  • Guest
decarboxylation
« Reply #27 on: October 11, 2003, 08:57:00 PM »
Is it really possible to abstract and generalize from amino acid decarboxylation literature to derive a procedure for decarboxying 2-methyl3phenylserine? - here you have another methyl group hanging off the carbon where the carboxylic and amino groups are - that has to change change many factors.?

maybe use hypochlorite  to get to PAC (phenylacetylcarbinol or hydroxy-p2p) - aka streker degradation with aqueous hypochlorite.

SPISSHAK

  • Guest
alternately
« Reply #28 on: October 11, 2003, 09:55:00 PM »
i just purveyed a cold medicine expired  07/2001 it contains, acetylsalicylic acid, chlorphenerimine maleate, and phenylpropranolamine bitartrate.
perhaps a trip to Mexico is in order?
I am inaware of any laws prohibiting the importation of otc cold medicine from Mexico, especially otc cold remedies.

BTW: the decarboxylation worked on a beta amino acid with the classic akabori reaction, why not in this case???

algebra

  • Guest
decarb///
« Reply #29 on: October 12, 2003, 06:44:00 AM »
no man, not questioning that it *can* be decarboxylated only that maybe much of detail in the literature *may* not be relevant.., like ph or buffers or solvent. another alternative might be heating with a cyclic ketone,

https://www.thevespiary.org/rhodium/Rhodium/chemistry/decarboxpha.html



there is some suggestion that the Akabori works much better when the amine is secondary rather than primary - dont know if this is referable to the aldol condensation or decarboxylation. anybee know if its possible to methylate alanine with formaldehyde forming the imine then Al/Hg to reduce? - would be cleaner than using methyl iodide.