Sciencemadness Discussion Board

Halobenzenes by decarboxylation of halobenzoic acids

notoxicshit - 11-6-2016 at 07:39

I have pulled an all-nighter on cheap and efficent halobenzene production from not exceedingly harmful substance that can be had OTC.
It was one of my most disappointing all-nighters because they usually end with the euphoric realization that shit can be turned into gold.

A theoretically very promising substrate is benzoic acid for several known reasons. I have a huge pot of benzoate: cheap, OTC, harmless.
I have experience in benzene production via CaO/benzoate decarboxylation. It works fine.

So my main idea was to halogenate benzoic acid or its salt by hypohalite and then find a way to selectively decarboxylate it to yield the halobenzenes without removing the halogen substituents by accidentally turning them into hydroxy groups.
It would be awesome if this could be done by the CaO dry distillation method.

I couldn't find anyone trying to do that. Why?

Someone with a formal education please judge if there is a chance to get the carboxy off before the halogene.
[ I suppose that halogens differ in their resilience to hydrolysis (is that what flicks the substituent off?). I'd estimate that electronegativity is what mediates this resilience. So the likelihood of being accidently removed goes Iodine > bromine > chlorine > fluorine, right?]

If that theoretically possible, the rest is only apparatus construction and finding the right conditions.
A problem to be circumvented will most likely be the relatively high bp of halobenzenes.
Introduction of an inert gas may solve this by physically removing the volatile components formed. Less preferably vacuum application.
[I propose a setup like the one used in the old fashioned destructive distillation process of phenylacetic acid/acetate by slowly bleeding in CO2]

Please discuss everything I wrote.

Feel free to contribute other cheap, OTC and relatively non-toxic ideas for the production of halobenzenes.

Harm reduction ideas for established, toxic procedures are also very welcome, like I am dreaming of a total synthesis in one long freaky two-sided apparatus starting with benzoate on one side and an alkali halide salt on the other one, meeting in middle in the form of benzene and halogene without ever leaving the flask, ready to be distilled.

But now enough of the talking, please provide your wisdom and I will get the project started with great enthusiasm.

clearly_not_atara - 11-6-2016 at 07:57

Silver salts of some acids can be made by using the aqueous acid + silver + H2O2. Since benzoic acid is compatible with hydrogen peroxide under ordinary conditions it could be worth a try.

Reaction of the silver salt with a halogen in dry DCM or acetonitrile gives the desired product.

NitreRat - 11-6-2016 at 13:14

@notoxicshit
Do you have a reference for the halogenation of benzoic acids with hypochlorites?
Most halo-benzoic acids can be easily decarboxylated to the corresponding aryl halide.

@clearly_not_atara
I believe the reaction you're referring to of silver salts with a halogen is the Hunsdiecker reaction. I seem to remember reading that it gave very poor yields (<5%) with benzoic acids. If you're going to working with elemental chlorine or bromine you may as well also work with benzene and AlCl3.



[Edited on 6/12/2016 by NitreRat]

CuReUS - 11-6-2016 at 21:26

Quote: Originally posted by NitreRat  
@notoxicshit
Do you have a reference for the halogenation of benzoic acids with hypochlorites?

http://www.ijsrp.org/research-paper-0714/ijsrp-p3182.pdf
http://pubs.rsc.org/en/content/articlelanding/1934/jr/jr9340...
benzoic acid to o-chlorobenzoic acid,benzoic acid to o-bromobenzoic acid (non-hypochlorite route)http://pubs.rsc.org/en/content/articlelanding/1995/p1/p19950...
Quote: Originally posted by NitreRat  

@clearly_not_atara
I believe the reaction you're referring to of silver salts with a halogen is the Hunsdiecker reaction. I seem to remember reading that it gave very poor yields (<5%) with benzoic acids.

That's true.Even the kochi modification will not help in this case
https://en.wikipedia.org/wiki/Kochi_reaction

brominating benzoic acid(to form o-bromobenzoic acid) followed by decarboxylation is better-http://onlinelibrary.wiley.com/doi/10.1002/chem.201303200/fu...
benzoic acid can be directly converted to bromobenzene but the yield is terrible(20%) - http://pubs.acs.org/doi/abs/10.1021/jo00167a027

[Edited on 12-6-2016 by CuReUS]

notoxicshit - 13-6-2016 at 08:46

Interesting direction, the first post directed me. But it all has flaws. The old, initial Kochi reaction with Pb acetate doesn't work on benzoic acid and Kochi is a dickhead for publishing the recent online version of his review about modifications and tuning of his procedure in a form unavailable to public.
Can't access it, neither one of the two universities I visit can.
Pb is undesirable first.

Researching halodecarboxylation or decarboxylation halogenation first made me euphoric because of the seemingly awesome copperhalide and palladiumhalide catalysis of halogenation or even cyanation (non-toxic reagents!) until I became aware of the fact that they use DMSO at 160°C AND 1 atm oxygen pressure.
Heat, no deal, pressure, no deal, but both at once... I'm open for easy apparatus ideas.
As well, DMSO seems to be not recyclable, what sucks big time to me.

So, pretty disappointed about what initially looked great.

I am basically back to the idea of brute force decarboxylation of the aforementioned monohalobenzoic acids.
I'd love to hear opinions about what happens when I throw those substrates into the olde benzene dry distillation apparatus, maybe applying CO2 just like folks did back then with the infamous PAA to P2P destructive distillation.

So happy contribution, please.

Praxichys - 13-6-2016 at 10:20

What about :

- Reflux benzoic acid with urea to get benzamide.

- Halogenate the arene with hypohalite. Use excess hypohalite to run hofmann degradation on the amide, eliminating CO2 and leaving you with a haloaniline.

- Diazotize and either pyrolyze or halogenate (sandmeyer) to leave you with the monohalobenzene or a dihalobenzene. In fact, you could effectively convert the amine group to hydroxyl, halogen, or nitro. (Although there might be trouble with the N2 elimination with the halogens hanging around - you'd have to try it.)

On an interesting side note, this would be a good synthetic method to OTC catechol, starting from salicylic acid.

notoxicshit - 13-6-2016 at 10:51

Besides the fact I do know from recent reading on this board that Benzamide synthesis is far harder than refluxing with urea, this route is pretty wasteful and time consuming. I do have very restricted access to chemicals because I live in the land of rules and laws. So even nitrite I have to prepare.
So I have to decline that proposal, unfortunately, but thank you very much.

I'm afraid that would be a rather complicated attempt at making catechol, I have just recently read an awesome paper about hydroxy benzoic acids into all kinds of dihydroxy benzoic aids (catechol as well) by attack if hydroxy radicals generated with the help of some simple iron salt, sulfate if I recall correctly.
I don't remember how they made catechol exactly but the very easy aforementioned brute force decarboxylation will surely work on hydroxy benzoic acids. There are other decarboxylation techniques where di or trihalo benzoic acids are turned into di/trihydroxy compounds by some usual reagent generating hydroxy radicals as well.
Those are favourable ways to catechol in my opinion.


Crowfjord - 13-6-2016 at 12:34

Quote: Originally posted by notoxicshit  
they use DMSO at 160°C AND 1 atm oxygen pressure.


This doesn't sound bad to me. It's below DMSO's boiling point, and 1 atm is ambient pressure. Unless that was a typo. Oxygen is easy enough to generate, and an air condenser would keep any DMSO vapor under control.

notoxicshit - 13-6-2016 at 16:15

Actually I did not take the time to look into the paper but there was exactly "O² 1 atm
DMSO 160°C"
in the abstract of the paper.

I assumed this to be a pressurized reaction.
Why should they write 1 atm when its just oxygen to be blown in at normal pressure?

I guess I will take a closer look and tell you what's up.

Any tips & tricks for DMSO recycling or is it inpracticable in this case?
I'll see how much solvent is needed.

Thanks anyway!

Crowfjord - 13-6-2016 at 17:02

What is the reference you are talking about? I would like to see it.

DMSO can be distilled, as far as I know. I don't see why one couldn't reuse it by purifying in this way, unless there is something that could react with it.

notoxicshit - 13-6-2016 at 17:17



Take this example of halodecarboxylation as a teaser:

http://250kb.de/scKBDg7

The recycling of the solvent is in my opinion a problem, as its higher boiling (189°C) than for example Bromobenzene (156°C).
I'd have to distill the bromobenzene out of the DMSO.
Maybe you have experienced, too, that it's hard to remove even relatively volatile compounds when they are solved in high boiling oils or products.
Take ether boiling ether out of sulfuric acid. You wont get it all out easily.

Think of Iodobenzene - with 188° bp it has the same boiling point.
A different workup has to be developed for that.

Let's also discuss the apparatus and the schlenk line they're using and how it could be circumvented/"chemhacked"



Here is the paper I talk about.

Attachment: decarboxylative halogen&cyanation paper.pdf (1.2MB)
This file has been downloaded 382 times

[Edited on 14-6-2016 by notoxicshit]

Crowfjord - 13-6-2016 at 17:33

In that case, you should probably dilute the DMSO with water until the halobenzene is not longer soluble, separate, then purify from there (I have done this after alkylating phenols in DMSO or DMF). Thanks for the paper, I'll check it out in a little while.

If I was to try this, I think I would generate O2 with hydrogen peroxide and a catalyst like iodide salt, and bubble that through the reaction mixture until the system was purged. Then either plug the system, or maybe cap with a balloon and keep adding oxygen and maintain a little pressure in the system as the reaction runs. The authors were able to get some product with just air, so any enrichment of oxygen content should be an improvement.

[Edited on 14-6-2016 by Crowfjord]

CuReUS - 13-6-2016 at 22:46

Quote: Originally posted by notoxicshit  
Interesting direction, the first post directed me. But it all has flaws. The old, initial Kochi reaction with Pb acetate doesn't work on benzoic acid and Kochi is a dickhead for publishing the recent online version of his review about modifications and tuning of his procedure in a form unavailable to public.
Can't access it, neither one of the two universities I visit can.
Pb is undesirable first.

I don't understand.Are you saying that I am wrong ? what do you mean by "it all has flaws"

notoxicshit - 14-6-2016 at 02:54

No, i mean that every procedure I discovered afterwards has certain disadvantages like expensive metals, toxic reagents or fancy apparatus.

However I believe that 1 additional atm is not that much and an ordinary RBF might withstand it, even upon being heated to 160°C.
Another thing that SUCKS are the 20 h reaction time. That's expensive.

And btw I have an oxygen tank

[Edited on 14-6-2016 by notoxicshit]