[collin_det]

Hi.

I have a question regarding the hydrolysis of an ester. I have this para-amino-benzoic acid methyl ester and wants to hydrolyse it into PABA. I have hydrolysed it for over 24 h in conc. HCl, but still there were something remaining. It took two days to get it all hydrolysed.

But when I hydrolysed the same ester molecule, but without the aromacity, then the ester was gone in short time. I would rather have used alkaline conditions, but it was easier with the acid, as it gave me the needed HCl salt directly, just evaporate. I did not remove the formed methanol, but just keept refluxing on it, this could be one of the reasons? But I did it in under g scale, so I dont think it could be it. I used alot of excess water and conc. acid.

Is the reason that the ester is partly steric hindered, because of the aromacity and that the amine is para directing, giving rise to a less electrophillic carbonyl on the ester, so the water have difficulties attacking? Or is it something else?

I think methyl esters normally are easily hydrolysed, but if they are aromatic, then maybe they are hindered?

Please HELP.

Thanks

[discodermolide]

Hi.

I have a question regarding the hydrolysis of an ester. I have this para-amino-benzoic acid methyl ester and wants to hydrolyse it into PABA. I have hydrolysed it for over 24 h in conc. HCl, but still there were something remaining. It took two days to get it all hydrolysed.

But when I hydrolysed the same ester molecule, but without the aromacity, then the ester was gone in short time. I would rather have used alkaline conditions, but it was easier with the acid, as it gave me the needed HCl salt directly, just evaporate. I did not remove the formed methanol, but just keept refluxing on it, this could be one of the reasons? But I did it in under g scale, so I dont think it could be it. I used alot of excess water and conc. acid.

Is the reason that the ester is partly steric hindered, because of the aromacity and that the amine is para directing, giving rise to a less electrophillic carbonyl on the ester, so the water have difficulties attacking? Or is it something else?

I think methyl esters normally are easily hydrolysed, but if they are aromatic, then maybe they are hindered?

Please HELP.

Thanks

Use basic conditions, then extract the basic aqueous solution of the salt with a solvent.
Take the aqueous layer and acidify it firstly to get the acid, then further acidification to the isoelectric point will give the internal salt.

[collin_det]

Thanks for the answer.

I would also guess that using basic conditions would make it better out, but I am afraid, when I extract it (because it is an aminoacid) that something would get lost, as it would be hard to predict at which pH I would be able to get it all organic. The amine needs very alkaline conditions to be apolar, whereas the carboxylic acid would be charged even at around pH 2-2 and up.

Does anyone have any idea on the mechanism, why this ester is so stable? Normally I think that these conditions would yield the carboxylic acid pretty fast.

Thank you.

[AC Prabakar]

By assuming that the amine group in the moiety is not protonated the following reason (mechanism attached in attachment) seems to be good.

This is only possible mechanism and i don't have any data or supporting literature.

The electrophilic nature of "C=O" of ester can be reduced by the amino group present at para position as shown in mechanism in attachment.Which may leads to the slow protonation of "O" of "C=O" ester.
 
I hope this will hold good..

[collin_det]

Thank you for your answer.

I think it is the right answer.