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Monosodium Glutamate

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More thoughts on this:

Use of Stephen's aldehyde synthesis with 4-carboxy-butylnitrile (which is synthesized by the oxidative decarboxylation of glutamic acid by TCCA as I discussed above), to get to 4-carboxy-butanal in practically one step.
It requires Tin(II) chloride, which isn't toooo pricey. This is a simpler alternative, if you wish to not do that messy decarbonylation with sulfuric acid.

And, aldehydes such as 4-carboxy-butanal can be reduced by bisulfites like sodium bisulfite (which is commonly sold as sodium metabisulfite, for use in beer brewing) in ~90% yield, cleanly. As you can see, this is far easier to get than NaBH4 and just as effective really.

And yeah, that Shroomery picture IS really confusing, you're not the only ones who were confused by it =/ !
 
hussness said:
I've just looked at the reaction. The shroomery jpg contains a different mechanism for the reaction than the one listed on Organic Syntheses. I'm skeptical but not completely dismissive about the proposed mechanism in the Organic Syntheses article, but the transition state mechanism on the shroomery jpeg doesn't make any sense. Under conditions of strong base both acids would be deprotonated. I tried to explain all of the flaws in this mechanism, but unless there are about five steps I'm not seeing, it doesn't make any sense. The biggest problem seems to be the violation of the carbonyl carbon octet.
Click to expand...

Dude. You're seriously going to burn my mechanism because of one simple mistake like that? Just add two equivalents of sodium hydroxide and eliminate a 'H' on the mechanism and its fixed. Its not a flaw in the mechanism, its a simple error that most chemists would overlook when evaluating the entire thing.

That mechanism was what I proposed before I saw the one posted on organic synthesis. Apparently the main reason why this reaction works is because of the alpha carboxylic acid stabiolizing the carbocation before the final cyclization. Having the carboxylic acid alpha to it prevents the carbocation from rearranging into secondary/tertiary structures and leaving you with a big mess as retired chemist was hinting at.

And what flaw do you see in the carbonyl carbon octet? Are you sure you know what you're talking about..?
 
Please tell me what you are confused about so I can explain it clearly! It makes sense to the professors I showed it to.. surely It should make sense to you guys.

In the second step once the far end carboxylic acid kicks off the N2 molecule it forms a positively charged oxygen, this loses a proton to get to the next step. This is normally assumed when a mechanism like that is drawn. I just implied it with the two arrows.


And yes, Im skipping steps in the formation of the diazzonium ion. I didnt think it was necessary to include that as its a mechanism that has been studied and shown over and over on the internet. Whats needed is displayed.



edit- are you talking about MY (Acyl) post or Wiccan_Seekers post?
 
Hussness... the decarbonylation step is carried out in a separate step. One wouldnt complete the ester hydrolysis and carry out the decarbonylation immediately after.

I suppose I forgot to mention that acid catalyst is used. My bad.. I think?

The fact that they were protonated should have hinted at that, I think.
 
hussness said:
Under conditions of strong base both acids would be deprotonated. I tried to explain all of the flaws in this mechanism, but unless there are about five steps I'm not seeing, it doesn't make any sense. The biggest problem seems to be the violation of the carbonyl carbon octet.
Click to expand...

Out of this whole reaction your debating that you can hydrolyze an ester? You seem to not understand how these things work, let me introduce you to my friend the tetrahedral intermediate:

http://www.chem.ucalgary.ca/courses/351/Carey5th/Ch20/ch20-3-3-1.html


and your pissed that the acid wasn't deprotonated in his drawing? Perhaps he should have drawn the carboxylic acid resonance structures to? Perhaps explain what makes these structures acidic? Who cares man, this isn't a journal writeup.


And please explain why two base equivalents are needed? You really don't even need one in theory, just heat w/ water. Base is a catalyst
 
I think he is missing the fact that mechanisms such as the one above are "outlines" not actual syntheses.

Also, I think he may have forgotten that in a decarbonylation carbon monoxide is lost, carbon monoxide has a lone pair along with a double bond to oxygen.
 
Acyl said:
I think he is missing the fact that mechanisms such as the one above are "outlines" not actual syntheses.

Also, I think he may have forgotten that in a decarbonylation carbon monoxide is lost, carbon monoxide has a lone pair along with a double bond to oxygen.
Click to expand...

so is that what he meant about the octet rule then, the carbon monoxide? So either carbon monoxide doesn't exist (which is nice cuz I know someone who's parents died from it) or esters don't hydrolyze... either way, this is clearly an advancement of the science
 
These posts are becoming unnecessarily vitriolic, and this is basically a synth discussion, so it needs to be closed.
 
Well whats wrong with the transition state? I know four arrows is probably more than one sees in organic I, but its still logical and pretty easy to follow wouldnt you say?

Oxidation and reduction of the carbonyl, oxidation of the alcohol and the loss of water all at once. Im just curious, if someone says theres something wrong with what Ive done I usually ask about it.
 
hussness said:
These posts are becoming unnecessarily vitriolic, and this is basically a synth discussion, so it needs to be closed.
Click to expand...


Sorry if your offended. I didn't mean it to sound like I was jumping on you out of nowhere.

I just didn't think your post made much sense, so I replied. Anyways, I don't think there's anything wrong with the ester hydrolysis. Who knows about the following reaction, I haven't looked at the refrence, though I've seen alpha hydroxy carboxylic acids behaving in weird ways.

But if you still want to explain, go for it. And check out the ester mechanism link I posted that might explain some things. Pretty much all carbonyls are postulated to react in that way, it's a very common mechanism w/ esters, ketones, carboxylic acids and aldehydes.
 
I don't think anyone has a problem with the ester hydrolysis. That part is pretty straight forward. What is a little difficult to swallow is the mechanism for the decarbonylation. Sure all the arrow pushing is legal and all, but just the things you have happening seem a little, well, unlikely. Are you saying all of that is happening in a concerted mechanism? Or have you compressed a couple steps into one? I'm not saying that the mechanism is wrong, just why do you think it would follow through a decarbonylation, i.e. do you have any references to back it up?

Not an attack or anything, just that decarbonylations tend to be a little exotic and not really seen under normal conditions.
 
Yeah, I posted a reference to the decarbonylation of citric acid (another alpha-hydroxy acid). Its in the first page, its an org-syn article.

I agree, decarbonylations are quite exotic and all kinds of shit is happening at the temperatures and conditions needed for one to occur. But if you look at the mechanism.. how else could it be done? There is no way you can hope to separate the mechanism Ive drawn into more than one step, if it occurs with that product it must be concerted.

The mechanism isnt set in stone, Ive never seen a mechanism for a decarbonylation. I am not claiming to have elucidated it, I proposed a theory, I havent done any experiments on it.

You can say its unlikely but that doesnt do much for anyone.. I cant see any other ways for that product to expel carbon monoxide. If you separate the arrows ive drawn into multiple steps you would get incredibly unreasonable intermediates, think about it...
 
im with hussness, it is a poorly drawn mechanism at best and probably not the true intermediate.
i thought there was going to be a tighter noose on synth talk?
 
Usually when someone claims a mechanism is poorly drawn they give a reason.

Its a reasonable mechanism that was looked over by a couple professors, I dont understand what you think is wrong with it. Do you just not understand it?
 
kidamnesiac said:
im with hussness, it is a poorly drawn mechanism at best and probably not the true intermediate.
i thought there was going to be a tighter noose on synth talk?
Click to expand...

What's wrong with the mechanism?

And the decarbonylation appears to be sound. The refrence previously given completes this reaction:

CV1P0010.gif


upwards of 85% theoretical.

And I found plenty of refrences finding this very reaction happens in lactic acid-->acetaldehyde in reliable enough yields to be used as an analytical technique. Sure you should be skeptical anytime someone proposes a carbon bond breakage, but carbon monoxide is a stable leaving group, and refrences have been provided.
 
the most obvious reason is that you are showing protonated carboxylic acids in a basic solution. trying to push out water in a basic solution is also incorrect. i could go on, it's not worth it.

^The rxn above is via a different method, acid catalyzed vs. base catalyzed. carbon DIoxide is a much better leaving group...
 
It's getting to the point where we should just have a synthesis/general illegality forum, with the disclaimer, "Everything stated in this forum is probably illegal, and does not represent the views of Bluelight. Everyone here is free game for narcs, the FBI, and related gov't organizations." 8)
 
kidamnesiac-

Thats not an error in the logic, I dont see why you are trying to throw the entire mechanism in the garbage because of that. You say you can go on, but you dont.

Also, the pic that johnm214 posted is infact a decarbonylation, not a decarboxylation. If you're trying to tell me that a carbon dioxide is a much better leaving group than carbon monoxide I dont even know what to say. Organic I and II only teach so much I suppose?
 
Dont get me wrong, im not saying this mechanism is absolutely correct. I cant say its not correct.. i have no means to study it.

What I am saying is that it is reasonable. I drew this mechanism out before I realized it was under acidic conditions, I was under the impression that it was purely thermal before I ran into that one reference I pointed to you. The fact that its under acidic conditions shouldnt change much about the mechanism.

Im not getting defensive over the fact that you guys are burning on it, im getting defensive because you dont really seem to know what you're talking about when you say its not right. Im trying to spark some discussion here, you're calling it wrong but you're not saying why other than "the carboxylic acid isnt protonated". Which is kind of childish if you ask me.. What other reasons are you neglecting to mention? You and two other people have said the exact same thing, that youve got several reasons its not right.. yet all you seem to mention is the carboxylic acid proton!

Yes, the carboxylic acid isnt protonated, whats your point? Cant you figure out that it would be a separate step and the mechanism I posted isnt the ACTUAL synthesis? Its a rough outline.

If you would like to criticize work, Im not going to be upset, I welcome criticism. Im just asking you to tell me what is actually wrong with it, please come up with a mechanism that you think is correct so we can have an intelligent discussion.
 
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