Sciencemadness Discussion Board

Large scale anthranilic acid prep

mr_bovinejony - 20-2-2021 at 20:09

All credit goes to a user formerly known as loft on another forum.

45 grams of methyl anthranilate is added to 200 ml of a 2M solution of NaOH. This is refluxed for 4 hours with stirring. After the 4 hours this is cooled down and the top water layer is decanted from the small bit of oil at the bottom. 20% hardware store hcl is added until the stir bar doesn't work, and this is filtered. Presumably the anthranilic acid but still waiting for it to dry so I can get a melting point.

Probably the most easiest synthesis for this stuff that I've found. The product filtered off is pure white. I have reason to believe this is the product because the mother liquor which was filtered off was acidifed again to crash out more, but more acid than necessary was added and it all dissolved again. Zwitterionic I think is the word used for anthranilic acid, which dissolves when ph is too high or too low. But I made no effort to recover it.

I think I probably have around 30 to 35 grams of the powder but I'll update after it's dried. Reflux should be held longer until no oil remains after cooling for a higher yield. Loft gets a 99% yield in his prep which I think is definitely achievable. Don't know why people struggle with this one, it seems very simple

Bubbles - 22-2-2021 at 12:46

Methyl anthranilate 50ml or 58g was added to 150ml 3M NaOH solution and heated to 80C in a 600ml beaker. Quickly, all dissolved (about 30 min), indicating conversion to anthranilic acid. After 45 min there was added 40ml GAA in 160ml water. Beaker, now full of precipitate, was cooled with a cold water bath and then placed in freezer for a bit until ~8C. The off-white precipitate was filtered and washed with water. Yield=49g or 94%

[Edited on 22-2-2021 by Bubbles]

karlos³ - 22-2-2021 at 12:59

Oh bubbles you're here too! :)
Of course you are :D

I miss the very nice grape flavour of that stuff, guess next time I'm going to get me some too, making IBX and DMP.
Quote: Originally posted by mr_bovinejony  
All credit goes to a user formerly known as loft on another forum.

He's called attic on here :P

[Edited on 22-2-2021 by karlos³]

Benignium - 22-2-2021 at 21:16

Quote: Originally posted by karlos³  

I miss the very nice grape flavour of that stuff, guess next time I'm going to get me some too, making IBX and DMP.


Have you made IBX and/or DMP before? I wasn't aware of these compounds, they seem very useful and I'd appreciate any writeups you may have.

Texium - 22-2-2021 at 21:47

It’s something that I was really wanting to do, back before I became a grad student and thus forfeited all my time to do my own chemistry. I got as far as making some 2-iodobenzoic acid.

mr_bovinejony - 23-2-2021 at 06:30

I got as far as ibx but the dmp failed for some reason

https://www.thevespiary.org/talk/index.php?topic=18228.0

SuperOxide - 26-3-2021 at 08:43

Very interesting... I have 500g of phthalimide that I will probably never use, which I could make the anthranilic acid from. But I was wondering if this was a viable reaction route (which I was sure it was).

Good job guys, glad I found this.

mr_bovinejony - 26-3-2021 at 08:59

I recently did a run of 150 grams of the grape stuff, ill have more product than I'll ever need now. Recrystalization is fun too, although the size of the run made it difficult. I have one half of pure white and the other half is the tan color

SuperOxide - 26-3-2021 at 10:04

Quote: Originally posted by mr_bovinejony  
I recently did a run of 150 grams of the grape stuff, ill have more product than I'll ever need now. Recrystalization is fun too, although the size of the run made it difficult. I have one half of pure white and the other half is the tan color
Pictures, or it didn't happen ;)

Fery - 26-3-2021 at 10:50

Btw the methyl anthranilate is available at https://shop.es-drei.de/ester/11927/anthranilsaeuremethylest...
I've bought it from there
1 L for 73 EUR
100 ml 14 EUR
check also the price of delivery and countries where they send by currier (DHL, DPD).

mr_bovinejony - 17-4-2021 at 10:58

https://imgur.com/ujQ4mhy

https://imgur.com/tnqXB1u

https://imgur.com/p92ZDLC

Here are some pictures from a 200 ml prep. The one I am holding came from the glass pie dish, it shows nicely the crystalline structure and difference of color when left in open air. These were both from the same batch, and recrystallized from boiling dilute hcl. Evaporated over 3 weeks

karlos³ - 17-4-2021 at 11:14

Quote: Originally posted by Fery  
Btw the methyl anthranilate is available at https://shop.es-drei.de/ester/11927/anthranilsaeuremethylest...
I've bought it from there
1 L for 73 EUR
100 ml 14 EUR
check also the price of delivery and countries where they send by currier (DHL, DPD).

Yeah I order that from the thais, perfumersworld.
Its not exceptionally cheaper, not at all, but it slips right through the EU customs, so its much better to order from there than from the inside.

By the way(hint, hint!), check their products, they have LOTS of other cool things for the home chemist :)
I just made an order of almost 200$, and it landed here(DE) in just four days!
Only once in seven orders I had to pick it up from customs(despite having phenylacetic esters, helional and whatnot included), but only had to pay importation tax.

SuperOxide - 17-4-2021 at 13:44

Quote: Originally posted by mr_bovinejony  
https://imgur.com/ujQ4mhy

https://imgur.com/tnqXB1u

https://imgur.com/p92ZDLC

Here are some pictures from a 200 ml prep. The one I am holding came from the glass pie dish, it shows nicely the crystalline structure and difference of color when left in open air. These were both from the same batch, and recrystallized from boiling dilute hcl. Evaporated over 3 weeks


Heyy, very nice. I was expecting some nice white crystals though from your original post ;-)

RustyShackleford - 17-4-2021 at 14:29

Wow. Your anthranilic acid looks awful considering you started from the ester. Recrystallize it from water bare minimum, or better soxhlet it with heptane to get pure white crystals.

mr_bovinejony - 17-4-2021 at 14:44

Eh that's what happens when its left out in the open for 3 weeks!

SuperOxide - 17-4-2021 at 16:19

Quote: Originally posted by RustyShackleford  
Wow. Your anthranilic acid looks awful considering you started from the ester. Recrystallize it from water bare minimum, or better soxhlet it with heptane to get pure white crystals.

Are you spying on me?! jk. That's what I'm doing - literally right now :D

I have 20g of anthranilic acid (which was already through a water recryst), with some distilled/dried heptanes. Been in the soxhlet for a few hours now. I may just let it run overnight (though I'm slightly uncomfortable knowing there's boiling heptane in the kitchen), and see how well it works. I did a small scale earlier and it went for like 5 hours and it was less than a ~28% yield (only got 2.8g out of 10g), so it needs to run for a lonnnng fricken time.

I'm sure you got this from the anthranilic acid purification thread by B.D.E, which is where I will post the results (yield and photos) after I'm done. Likely tomorrow.

[Edited on 18-4-2021 by SuperOxide]

SuperOxide - 17-4-2021 at 20:42

Quote: Originally posted by mr_bovinejony  
Eh that's what happens when its left out in the open for 3 weeks!

This got me thinking - Have you ever had a white (or even slightly off white) purified product? Or does it always end up taking on that brownish color? I ask because when I synth anthranilic acid from phthalimide (ACS grade, even), the crude product looks almost white, as seen here:
crude-anthranilic-acid.jpeg - 27kB

But when I recrystallize the crude product in boiling water, the product comes out looking light brownish in color:
anthranilic-acid-recryst.jpeg - 107kB

I've tried tweaking various things such as the temperature during the reaction or how quickly/slowly I add the reagents, how concentrated they are, or what solvent I use in the recryst, it always comes out the same:
anthranilic-acid-recryst-multi.jpeg - 195kB
(The middle one is a different color because I took it out of the ice bath a little too early when adding the phthalimide. All other runs were the same color as on the two sides).

So when you say:
Quote:
The product filtered off is pure white.

are you talking about the crude product?... because if that's the case, then I'm a little less impressed, lol. (don't take that as an insult, this is still a much better synthesis route than using phthalimide).

[Edited on 18-4-2021 by SuperOxide]

mr_bovinejony - 18-4-2021 at 04:35

From what I've seen, the hoffman route usually gives a brown product. When I was filtering this product from the boiling dilute hcl, it turned to pure white crystals when it hit the cold crystallizing dish which is where that statement came from. It was very nice to look at, I should have covered it before it was left alone

SuperOxide - 18-4-2021 at 07:07

Quote: Originally posted by mr_bovinejony  
From what I've seen, the hoffman route usually gives a brown product. When I was filtering this product from the boiling dilute hcl, it turned to pure white crystals when it hit the cold crystallizing dish which is where that statement came from. It was very nice to look at, I should have covered it before it was left alone
For sure. I would love to see if it can yield a more pure product than the Hoffman route.

mr_bovinejony - 18-4-2021 at 07:23

I definitely think so, even with the brown discoloration it had a very sharp melting point.

SuperOxide - 18-4-2021 at 08:16

Quote: Originally posted by mr_bovinejony  
I definitely think so, even with the brown discoloration it had a very sharp melting point.

As did the recryst product from the Hoffman route.

Regardless, this route is still wayyyy better, and much higher yielding. You just teased me with the "yields a white product" part - especially considering I just spent over 12 hours running a soxhlet extractor with heptane to purify some anthranilic acid, and while it's almost white (just barely off white), it's so low yielding that I'll never try it again, lol.

mr_bovinejony - 18-4-2021 at 08:31

The hoffman reaction is bullshit for any chemical lol. I weighed all this yesterday and it was 210 grams. Way more than I'll ever need.

Just remembered I added my old batch to the new stuff. So 180 grams from 200 mls of the grape stuff

[Edited on 18-4-2021 by mr_bovinejony]

SuperOxide - 18-4-2021 at 15:23

Quote: Originally posted by mr_bovinejony  
The hoffman reaction is bullshit for any chemical lol. I weighed all this yesterday and it was 210 grams. Way more than I'll ever need.
Pardon my noobness - but why do you say that? Chemistry is a relatively new hobby to me, and the anthranilic acid synthesis from phthalimide was my first hofmann rearrangement reaction (I think... in the beginning I was just copying procedures online without looking into the chemistry behind it, so perhaps I did it and didn't even realize it). But I'm curious why you say it's bullshit for any reaction and what you mean by that.
Quote: Originally posted by mr_bovinejony  
Just remembered I added my old batch to the new stuff. So 180 grams from 200 mls of the grape stuff
I too have more than I will likely ever use (I think 100g of the anthranilic acid), so I doubt I'll ever need to make more, but if I do then I definitely will use this route!

karlos³ - 18-4-2021 at 15:56

Quote: Originally posted by mr_bovinejony  
The hoffman reaction is bullshit for any chemical lol

Said the guy who uses the hofmann for his favorite substance :P

mr_bovinejony - 18-4-2021 at 17:45

@oxide I just don't like the reaction, titration of store bought bleach is a pain and temperature control during the reaction is hard. It may be different now that I upgraded my hotplate, but I'm in no rush to do it again

@carl I've done the hoffman twice and it's provided me with enough compound to last at least two more years :P sometimes you gotta go through pain to get to the good stuff

SuperOxide - 19-4-2021 at 13:00

Quote: Originally posted by mr_bovinejony  
@oxide I just don't like the reaction, titration of store bought bleach is a pain and temperature control during the reaction is hard. It may be different now that I upgraded my hotplate, but I'm in no rush to do it again
The bleach titration is a little tedious, but nothin too bad. As for the temperature, just lots of salt and ice does the trick for me.

I've decided I'm going to do it one more time (even though I have a lot of anthranilic acid), I want to test a recryst of the crude product (which is almost white) with solvents other than water (MeOH, ether, chloroform/heptane, etc). I have a feeling that may yield some nicer crystals.

karlos³ - 19-4-2021 at 13:16

Quote: Originally posted by mr_bovinejony  

@carl I've done the hoffman twice and it's provided me with enough compound to last at least two more years :P sometimes you gotta go through pain to get to the good stuff

Oh look who's talking, its mister large scale bragging again :P
Hehehe :D

SuperOxide - 19-4-2021 at 13:27



MJ-popcorn.gif - 308kB

njl - 19-4-2021 at 14:06

Quote: Originally posted by karlos³  
Quote: Originally posted by mr_bovinejony  
The hoffman reaction is bullshit for any chemical lol

Said the guy who uses the hofmann for his favorite substance :P


Details?

karlos³ - 19-4-2021 at 14:43

Quote: Originally posted by SuperOxide  



No need for this, we are actually quite good friends and I'm just teasing my pal :D

mr_bovinejony - 19-4-2021 at 15:32

My inability to do reactions under a 3 gram scale has been my downfall. But when it works its the greatest feeling ever :D

SuperOxide - 19-4-2021 at 16:45

Quote: Originally posted by karlos³  
Quote: Originally posted by SuperOxide  



No need for this, we are actually quite good friends and I'm just teasing my pal :D

Oh I know. I got the feeling you two were just messing about. :)
Quote: Originally posted by mr_bovinejony  
My inability to do reactions under a 3 gram scale has been my downfall. But when it works its the greatest feeling ever :D

I know how you feel! When I do a reaction on a small scale, even when it works it's not too exciting. I try to keep smaller scale reactions to test runs or POC's.

[Edited on 20-4-2021 by SuperOxide]