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Author: Subject: Acyl chloride/ MeOH = esterification?
GreenD
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[*] posted on 13-4-2011 at 18:05
Acyl chloride/ MeOH = esterification?


What the hell is going on in this step. It is the first step in one of my lab procedures:

L-Phenylalanine ->
(1): Acetyl Chloride (1.2 eq) / MeOH (6 vol)
(2): NaHCO3/H2O, ClCO2Et

The product of the first reaction is the methyl-esterification.
The product of (2) is the N-ethyl formate addition to the nitrogen.

>WHY< is acetyl chloride here. >WHY< is there not some kind of initiator (MeSO3H, H2SO4?)
How can phenylalanine, a beta-amino-acid undergo esterification with methanol (in methanol) and acetyl chloride?!
!!
Halpz.

Edit: Dear god I am sorry. I will keep this up as a frame of shame

[Edited on 14-4-2011 by GreenD]
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[*] posted on 15-4-2011 at 05:21


Acyl chlorides are very reactive and react immediately with the alcool to form ester and HCl.
I think phenylalanine has the function to absorbe the HCl!
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[*] posted on 15-4-2011 at 05:54


The acetyl chloride is the initiator. On mixing it with the methanol it reacts to form hydrogen chloride and methyl acetate.
The hydrogen chloride then catalyses the esterification.
See here;

http://www.springerlink.com/content/y5832279488gn657/

and an even nicer reference;

http://www.jbc.org/content/161/1/259.full.pdf



[Edited on 15-4-2011 by ScienceSquirrel]
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smuv
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[*] posted on 15-4-2011 at 07:07


Thanks for that paper (second one), it really helped with something I was working on.




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GreenD
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[*] posted on 15-4-2011 at 15:22


Thanks alot!

Although I just googled "acid catalyzed esterification"
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chemoleo
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[*] posted on 15-4-2011 at 16:44


Isn't that a very very inefficient way of esterifcation of free hydroxyls?
Actually I'm still not sure I understand what the second paper is about, i.e. quoted from the beginning:

Quote:

Freudenberg and Jacob (9) recently reported that acid chlorides were
more effective t,han hydrochloric acid as catalysts for the csterification of
organic acids. Various acids wcrc quantitatively transformed t)o the
methyl or ethyl est,ers by treatment with t,he rcspect,ivc alcohol and small
amounts of acetyl or other acid chlorides for 1 day at room temperat.urc.
This reaction has now been applied to proteins. Several proteins were
found to dissolve in cold absolute alcohols within a few minutes to an hour
after the addition of catalytic am0unt.s of acetyl chloride. Through
protein group analyses, alkoxyl determinations, and experiments with model
compounds, it was demonstrated that esterification of the carboxyl groups
had occurred. The amino, phenolic, and thiol groups did not react (really?); tryptophane
was unaffected.


How exactly is this meant to work?




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[*] posted on 15-4-2011 at 19:25


Methanol / acetyl chloride is quoted as a esterification reagent on an analytical and preparative scale in dozens of references, just try a quick Google, so it must have something going for it :D
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smuv
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[*] posted on 15-4-2011 at 19:41


Chemoleo, its just a Fischer esterification. It is useful, mostly due to its mildness and economy (assuming solvents are recycled), good to excellent yields are achievable even on preparative scales (not just for a few mgs of protein in mLs of solvent). I wouldn't be surprised if most of the commercial amino acid esters that you biochemists love to use were industrially made this way. Also, if you drive it with a desiccant, yields are quantitative.

Can take a while to reach equilibrium though...




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[*] posted on 15-4-2011 at 20:18


It makes anhydrous methanolic HCl (and equimolar methyl acetate). I do this frequently to prepare fatty acid methyl esters (FAMEs) for analysis via GC. Excess (we use acetyl chloride) acyl chloride scrounges up whatever free or evolved water there might be (on analytical scale, anyway). The reactions are quantitative (>90%) when heated (sealed, Hach tubes are great) at 120°C for an hour. I usually use a mixed solvent, e.g. MeOH:Benzene 4:1. Once the rxn is complete, I wash it with NaHCO3(sat) and the benzene:methyl acetate layer rises to the top where it can be collected (I add an internal std. at this point, methyl nervonate for FAMEs).

Cheers,

O3




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[*] posted on 14-10-2015 at 12:14


I am doing this exact reaction (phenylalanine/acetyl chloride in methanol, then ethyl chloroformate), towards a synthesis of (S)-4-benzyl-2-oxazolidinone. My question is:

Can the acetyl chloride be replaced with HCl gas? Is its only purpose to generate HCl in situ? Is methyl acetate just a side product, or does it take part in the reaction in any way?

From the papers posted above, it seems like the replacement should work. The authors say acetyl chloride is more convenient, which is most certainly not true if one can't easily get it (ethyl chloroformate is hard enough). HCl gas just requires sulfuric acid and salt.

I think the answer is probably yes, but I want to be completely sure before I use any ethyl chloroformate.

[Edited on 14-10-2015 by Cheddite Cheese]




As below, so above.
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