Hexavalent
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Toluene to Anthranilic acid
Could someone please check this synthesis for me, please?
We begin with toluene, which is sulfonated with sulfuric acid under reflux to yield p-toluenesulfonic acid. This is then nitrated at the o-position,
before the sulfonyl group is removed by refluxing with 60% sulfuric acid. The methyl group on the toluene is then oxidized by potassium permanganate
to yield a carboxyl group, and the nitro group is then reduced using zinc/ammonium chloride in acetone (or an acetone/water mix) to an amine group,
yielding anthranilic acid.
I am fairly confident this will work as I have performed a majority of the steps before using identical or similar compounds and have discussed it
with the more experienced DJF90.
UC235 has a video on making p-toluenesulfonic acid (based upon an OrgSyn prep), and I have attempted the synthesis myself previously.
I have myself also performed the oxidation of toluene and got the final product (in that case, benzoic acid) in good yield. Many videos are
available online describing the process.
DJF90 has showed me some of his research group's notes, including those on reducing nitro functional groups with Zn/NH4Cl in an
acetone/water mixture.
[Edited on 20-11-2012 by Hexavalent]
"Success is going from failure to failure without loss of enthusiasm." Winston Churchill
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mr.crow
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This may be of interest, lots of experimental reports Here. Just don't make drugs at the end.
Sulfonic acid is a meta director and a moderate deactivator. Instead of youtube perhaps you can search for papers and request them in the References
forum. It would be a very interesting method to get the pure o-nitro product.
Double, double toil and trouble; Fire burn, and caldron bubble
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Methyl.Magic
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You can directly buy o-nitrobenzoic acid or o-nitrotoluene, it's easier.
Otherwise you can acetylate aniline and transform the actophenone to the acid with hypochlorite.
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Hexavalent
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Quote: Originally posted by Methyl.Magic  | You can directly buy o-nitrobenzoic acid or o-nitrotoluene, it's easier.
Otherwise you can acetylate aniline and transform the actophenone to the acid with hypochlorite. |
Yeah, I'm aware of that. This synthesis was mainly just as a 'proof of concept' and to practice these techniques for when you get to compounds that
you can't simply buy off the shelf.
"Success is going from failure to failure without loss of enthusiasm." Winston Churchill
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Cloner
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This is a better way than what I tried (just using nitrotoluenes) and I like it, provided you do get a good yield of ortho isomer.
In any case, the oxidation step works but it is tricky. You want to use a small amount of hydroxide in your reaction, as some is used up if I remember
correctly. It also takes a while and of course, workup stinks to high heavens, as does any mistake that allows nitrotoluene to escape.
This reaction has a side reaction that kills yield. If the oxidation is not done right, you will get a lot of gas evolution upon acidification. Also,
you don't want to add solid permanganate too fast (more side reaction) but also not too slowly (severely diminished yield) or all KMnO4 dissolved in
water (too much reaction volume). Perhaps one of the modern oxidants can do this thing better than permanganate. In any case, if done correctly the
yield can be 70-80% but I did not attain that.
[Edited on 20-11-2012 by Cloner]
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UnintentionalChaos
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| Quote: Originally posted by Hexavalent |
UC235 has a video on making p-toluenesulfonic acid (based upon an OrgSyn prep), and I have attempted the synthesis myself previously.
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It's Vogel 5th Edition.
My reduction of 3-nitrophthalhydrazide to luminol using thiourea dioxide and ammonia is also a solid approach to reducing deactivated aryl nitro
groups.
Department of Redundancy Department - Now with paperwork!
'In organic synthesis, we call decomposition products "crap", however this is not a IUPAC approved nomenclature.' -Nicodem
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Nicodem
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What is the reference for this?
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DJF90
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I mentioned it to him in a private communication based on posts Sauron made and from similar Orgsyn procedures mentioned in the related threads.
However on having a friend perform a reaxys search for me (I no longer have access since finishing uni and I'm too lazy to visit the library this
week) it appears there is very little on the nitration of TsOH (p-toluenesulphonic acid+BF3+HNO3 => 3-nitro-4-methylbenzenesulfonic acid).
Alternatively the nitration of TsCl with conc. HNO3 gives 90% yield of the nitrated sulfonyl chloride, which is desulfonated to 2-nitrotoluene using
KOH in methanol in 80% yield. Its a shame the latter conditions cannot be applied to the sulfonic acid itself (a 1904 paper using conc. H2SO4 and
conc. HNO3 on p-TsOH was mentioned but no yields were reported).
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