Sciencemadness Discussion Board

Methyl anthranilate to anthranilic acid

DocX - 31-5-2022 at 12:53

Ok, I'm giving this a go. I'm posting it in Beginnings since it's a simple hydrolysis reaction really, and the questions I have are truly noobish.

Starting from methyl anthranilate, I should be able to produce anthranilic acid and methanol by a simple hydrolysis of the ester.

Now, researching hydrolysis reactions I understand that they can be performed in basic as well as acidic conditions, but I can't for the life of me figure out which would be best for this reaction, and what pH I should aim for.

Methyl anthranilate is readily available OTC, and if this reaction pans out it would be a great source for anthranilic acid.

I'm thinking using a stoichiometric amount of sodium hydroxide to the methyl anthranilate, just let stand with stirring in slightly above room temp, and then distill off the methanol and water. Though I'm not sure what would happen to the sodium, anthranilic acid should be precipitating out, right? Or what other steps should be necessary?

Texium - 31-5-2022 at 16:04

Under basic conditions, you’d end up with sodium anthranilate in solution, and you’d need to neutralize it with acid to precipitate out the free anthranilic acid. Acetic acid is recommended for this because it’s harder to overshoot the ideal pH with it than it is with a strong acid like HCl. If you overshoot and the pH becomes too low, you’ll protonate the amine and it will once again become soluble in water.

Fery - 31-5-2022 at 19:28

https://www.sciencemadness.org/whisper/viewthread.php?tid=15...

DocX - 31-5-2022 at 21:30

THANK YOU! I am so sorry, I really searched and searched like crazy, partially because I knew I had read about it somewhere on the forum. So I used “methyl anthranilate”, “anthranilic acid”, “methyl anthranilate to anthranilic acid”, both through Google and on this sites search engine, and read through a lot of threads about methaqualone and scents and indigo but I just COULD NOT GODDAMN FIND THIS ONE.
As much as I love this site, I do hate it’s search function. But there it is. Feel free to scrap the thread, dear mod.

Otherwise, I’ll make the conversion as soon as I get my MA. And do another write- up here.

DocX - 31-5-2022 at 21:33

Quote: Originally posted by Texium  
Under basic conditions, you’d end up with sodium anthranilate in solution, and you’d need to neutralize it with acid to precipitate out the free anthranilic acid. Acetic acid is recommended for this because it’s harder to overshoot the ideal pH with it than it is with a strong acid like HCl. If you overshoot and the pH becomes too low, you’ll protonate the amine and it will once again become soluble in water.


Yes, I managed to find mentions about the zwitterionic nature of anthranilic acid, but no details. What IS the ideal pH? And how do you find out?

Jenks - 1-6-2022 at 04:07

Quote: Originally posted by Fery  
https://www.sciencemadness.org/whisper/viewthread.php?tid=15...

"Subject: Large scale anthranilic acid prep"
Why does this not show up in the search results when I search for the word "anthranilic"?

DocX - 1-6-2022 at 07:07

And what if I hydrolyse it in ACIDIC conditions?
Wouldn't adding acid give me the desired product directly? But at what pH?

Tsjerk - 2-6-2022 at 04:29

Quote: Originally posted by DocX  

Yes, I managed to find mentions about the zwitterionic nature of anthranilic acid, but no details. What IS the ideal pH? And how do you find out?


What you are looking for is the isoelectric point, pI. You have a pKa and a pKb, with those you can calculate pI.

DocX - 7-6-2022 at 10:04

Quote: Originally posted by Tsjerk  
Quote: Originally posted by DocX  

Yes, I managed to find mentions about the zwitterionic nature of anthranilic acid, but no details. What IS the ideal pH? And how do you find out?


What you are looking for is the isoelectric point, pI. You have a pKa and a pKb, with those you can calculate pI.


Ok! But I thought you needed two pKa values to calculate the pI? My understanding of this is really rusty, it was 15 years since I did this.

But in this case it would be the pI of anthranilic acid. The pKa:s for anthranilic acid is 2.17 for the carboxyl group and 4.85 for the amino group, giving us (2.17+4.85)/2= 3.51 for pI.

Right?

[Edited on 20222222/6/8 by DocX]

SuperOxide - 1-7-2022 at 15:50

DocX - Have you given this a shot yet? I just got 300g of Methyl Anthranilate in (which I ordered months ago, totally forgot about it even), so I was tempted to give this a try. However, the MA is supposed to be colorless, and the MA I got is definitely not colorless (here's after I poured it into a more suitable container):

So I will have to do a vacuum distillation there first.

Fery - 2-7-2022 at 02:30

Hi SuperOxide, I got the same methylanthranilate from ebay (plastic bottle) as you and later also from es-drei.de (glass bottle).
I immediately transferred the ebay sample from plastic bottle into a glass bottle but it was only very weak yellowish (approximately 10 times paler than your).
You can certainly purify it by vacuum distillation like aniline, look at the post of vacuum distillation of aniline by Texium here: https://www.sciencemadness.org/whisper/viewthread.php?tid=15... Don't distill at ordinary pressure as oxygen from air easily oxidizes the product at elevated temperatures. Perhaps steam distillation could be used when no vacuum available but I doubt (oxygen displaced by steam and T slightly less than 100 C) and would certainly go via vacuum. But I think it is pure enough as oxidation products of anilines are very strong coloring agents so even traces of oxidation turned your product darker.
So I expect only little of impurities in your sample and maybe purifying it is only a waste of time as some oxidation happens during hydrolysis and workup into anthranilic acid too.
If you get not pure enough anthranilic acid you can try the soxhlet extractor + hexane purification method which is already posted somewhere in the forum.
I have also few old commercial samples of anthranilic acid, one in dark glass flushed with N2 never opened so its quality is unknow and one in white glass where the color of crystals seems very good but the color of dust adhering at the walls of empty part of the bottle is somewhat darker (only brownish, not too much dark), but there is only a trace amount of the acid dust adhering on the walls of empty part of the bottle).

SuperOxide - 2-7-2022 at 21:02

Quote: Originally posted by Fery  
Hi SuperOxide, I got the same methylanthranilate from ebay (plastic bottle) as you and later also from es-drei.de (glass bottle).
I immediately transferred the ebay sample from plastic bottle into a glass bottle but it was only very weak yellowish (approximately 10 times paler than your).
You can certainly purify it by vacuum distillation like aniline, look at the post of vacuum distillation of aniline by Texium here: https://www.sciencemadness.org/whisper/viewthread.php?tid=15... Don't distill at ordinary pressure as oxygen from air easily oxidizes the product at elevated temperatures. Perhaps steam distillation could be used when no vacuum available but I doubt (oxygen displaced by steam and T slightly less than 100 C) and would certainly go via vacuum. But I think it is pure enough as oxidation products of anilines are very strong coloring agents so even traces of oxidation turned your product darker.
So I expect only little of impurities in your sample and maybe purifying it is only a waste of time as some oxidation happens during hydrolysis and workup into anthranilic acid too.

Thanks for the input. I have a pretty good vacuum pump so I'll definitely take the vacuum pump route. Just the time saved having to do the steam distillation workup (separation, drying, etc) makes the vacuum worth it.
In regards to its stability - I can do my best to keep it away from oxygen and water, but is there anything I can add to stabilize it for storage? I didn't see anything about it being light sensitive. Regardless, I don't think ill use all of it for the AA synthesis, just some to experiment with. Honestly, I've done enough AA synth/experiments that I would be fine never doing one again. I just am curious to see if the methyl anthranilate leads to better purity (or as far as I could tell). It would be really cool if I could actually obtain a very pure and colorless sample this way (this is the best I've been able to do thus far)
Quote: Originally posted by Fery  

If you get not pure enough anthranilic acid you can try the soxhlet extractor + hexane purification method which is already posted somewhere in the forum.
Yep, I was active on that thread. I actually tried it twice, and what I noticed was two things.


  1. It takes soooo incredibly long to get even a small sample that it's just too impractical for any amount other than an analytical sample.
  2. It seems water is a huge factor in discoloration. I actually had it almost totally white, but then the water recryst immediately fucked it over. I repeated the whole thing with MeOH only recryst and that was much better - But such a small yield! Was taking too long (think over 12 hours)


Fery - 2-7-2022 at 22:55

Hi SuperOxide, use that good vacuum pump. I used 2-stage oil rotary vacuum pump from ebay for distilling o-nitrotoluene and it reduced b.p. from 220 C to 70 C.
Perhaps the anthranilic acid could be purified by vacuum sublimation too using such strong vacuum as used for vacuum distillation of methyl anthranilate. That would also completely dry the acid.
Very likely even small amount of water dissolves the acid and makes it prone to oxidation.

[Edited on 3-7-2022 by Fery]

DocX - 3-7-2022 at 05:32

Quote: Originally posted by SuperOxide  
DocX - Have you given this a shot yet? I just got 300g of Methyl Anthranilate in (which I ordered months ago, totally forgot about it even), so I was tempted to give this a try. However, the MA is supposed to be colorless, and the MA I got is definitely not colorless (here's after I poured it into a more suitable container):

So I will have to do a vacuum distillation there first.


No, I’m sorry to say I haven’t. I ordered my Methyl Anthranilate from a source I ordered many other things from with rapid and secure delivery. Based in … Ukraine. Needless to say, it didn’t arrive.
Also, I just had a larger order of solvents mysteriously disappear on the way, so I’m getting a little paranoid and don’t want to order anything new for a while.

SuperOxide - 3-7-2022 at 10:09

Quote: Originally posted by Fery  
Hi SuperOxide, use that good vacuum pump. I used 2-stage oil rotary vacuum pump from ebay for distilling o-nitrotoluene and it reduced b.p. from 220 C to 70 C.

Nice. I got two [almost new] UN726FTP pumps off of GovDeals.com. And they are beautiful!. They get down to like -23 inHg, which definitely isn't as good as your two stage pump, but it's pretty good (at least compared to my other pumps).
Quote: Originally posted by Fery  
Perhaps the anthranilic acid could be purified by vacuum sublimation too using such strong vacuum as used for vacuum distillation of methyl anthranilate. That would also completely dry the acid.
Are you sure you can sublimate anthranilic acid? That would be fun to try...

DraconicAcid - 3-7-2022 at 11:20

There was a thread here somewhere in which someone described the purification of anthranilic acid to snow-white crystals by soxhlat extraction with a low-polarity solvent. It extracted the acid and left the more polar impurities behind.

Fery - 3-7-2022 at 12:27

https://en.wikipedia.org/wiki/Anthranilic_acid
boiling point 200 C (sublimes)
small scale vacuum sublimation of something else in the gift book from teodor:

IMG_20220703_111151_9_sm.jpg - 211kB

SuperOxide - 3-7-2022 at 14:52

Quote: Originally posted by DraconicAcid  
There was a thread here somewhere in which someone described the purification of anthranilic acid to snow-white crystals by soxhlat extraction with a low-polarity solvent. It extracted the acid and left the more polar impurities behind.

Yep, I replied both in that thread and mentioned it above in one of the replies in this thread ;)

Quote: Originally posted by Fery  
https://en.wikipedia.org/wiki/Anthranilic_acid
boiling point 200 C (sublimes)
small scale vacuum sublimation of something else in the gift book from teodor:


Well, that's quite interesting. I got a vacuum sublimation apparatus delivered just on Friday. This could be a fun test run for it :D Thank you very much for the reference/source.