I have been investigating oxidation of n acetyl ortho toluidine to n acetyl anthranilic acid for a novel quinazoline compound I want to synthesise.
I have been trying to find a reference for the oxidation using permanganate and magnesium sulfate as a H+ source, but it seems to be a very elementary
oxidation, probably referenced elsewhere in the oxidation of phenyl alkyl compounds to carboxylic acids.
I understand that the oxidation is carried out by the trace amounts of manganese heptoxide formed in acidic conditions with permanganate ions.
in 1300ml dH2O, 20g n acetyl o toluidine and 50g anhydrous magnesium sulfate are dissolved. To this is added 50g potassium permanganate is added, and
the mixture stirred at 85C for 3hours.
Excess permanganate is neutralized with denatured alcohol, then the reaction mix is filtered hot through celite with vacuum filtration by buchner. N
acetyl anthranilic acid is precipitated from the filtrate via addition of 10% sulfuric acid.
Would it be possible to reduce solvent volumes by incorporating acetone or other oxidation resistant co-solvent to help solvate the n acetyl o
toluidine? 1.3L of reaction mix is rather annoying. This acetone could be evaporated off.
Also, why wouldnt sodium dichromate work in place of permanganate? Is it not strong enough to produce complete conversion of the toluidine to the
anthranilic acid?
Oh and there is one other thing. There is a writeup on erowid that details the synthesis of n acetyl ortho toluidine by refluxing o toluidine and GAA
in excess for 3hrs.
I cant find any references for this; but I assume it is similar to the reaction of ammonium acetate undergoing thermal decomposition to acetamide?
Refs, but only for acetylation of phenols by GAA
Why could this not be applied to the acetate salt of anthranilic acid? Anthranilic acetate + excess GAA -- heat --> n acetyl anthranilic acid
cheers
[Edited on 7-9-2014 by Templar]
[Edited on 7-9-2014 by Templar]Scr0t - 8-9-2014 at 04:46
The acetone may undergo some degree of oxidation to AcOH & CO2 also since it's quite volatile it will reduce the reaction temperature.
Oxidation of the methyl group can be done under neutral-alkaline conditions with KMnO4, e.g. toluene -> benzoic acid.
PhMe + 2KMnO4 -> PhCOOK + 2MnO2 + KOH + H2O
The MgSO4 is used to mop up the formed KOH which could hydrolyze the N-acetyl group present.
Quote:
There is a writeup on erowid that details the synthesis of n acetyl ortho toluidine by refluxing o toluidine and GAA in excess for 3hrs.I cant find
any references for this...
Ah I see... I'm surprised, I didnt think permanganate would work without acidic/basic conditions. Thanks for the link.
Another interesting possibility could be combining anthranilic acid with an excess of GAA to acetylate it. I think I posted in another thread about
this... its possible to do in good yield with toluidine, and I couldnt see it forming an anhydride with the GAA combining with the carboxylic acid
group.
It should drive off the water and force the equilibrium from the acetate to the amide. Similar te ammonium acetate -> acetamide.
