ortho nitration of p-toluenesulfonic acid(QUESTIONS)

Hey there

I just made some p-TsOH*H₂O, and I'm hoping on nitrating its ortho position to make an easy precursor of o-toluidine and anthranilic acid.

Although the reaction seems like a "classic" textbook example for using SO₃H as a protection group, I couldn't find anything about it online(which made me a bit nervous).

My only experience with aromatic nitration was in the preparation of picric acid from salicylic acid(an easy "all the way" nitration of a phenol).

So before trying anything, I hoped to hear some of the public wisdom in regard to the reaction conditions. My current plan is to dissolve the TsOH in an excess of H₂SO₄(96%) and then gradually add ~1.1eq of NaNO₃(s) while keeping the temperature on around 55C. afterward if that won't work, I would try again at 70C and so on.

Does that sound right to you? also, is there a way to monitor the progress of the nitration?
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The reaction scheme:

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P.S I'm aware that some people are annoyed by others asking questions instead of simply trying and failing. But my time and reagents are limited, and I just want to make sure I'm on the right track.

Also, I almost always report back on my attempts(usually with pictures), so I do "give back" in a way.

Thanks ahead, B.D.E

Quote: Originally posted by Tsjerk

Have you seen the HNO3 in DCM nitration of toluene? Chemplayer has a video on it on Bitchute. I'm planning on doing this reaction soon, I should get some technical toluene, KNO3 and DCM soon. Chemplayer says he couldn't get the product to freeze at -12 (mp o-nitrotoluene ~ -10). [Edited on 14-6-2020 by Tsjerk]

Quote: Originally posted by njl

I just tried the dcm nitration and I honestly have never seen something so beautiful. No thermal runaway, no ice, reactants are easy to dry, barely any fuming, easy workup. Just all around good experience.

And that settles it - I'm definitely gonna try it

May I ask for how long you kept the reaction going, at what temperatures(~) and what was your recovered yield?
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Just as a side note, I'm actually quite glad I didn't had to use all of my beautiful white pTsOH:


I get that it might look ordinary to some of you, but for me this is the first time it didn't ended up as a brownish sludge. So I quit happy I get to keep it for a while

[Edited on 14-6-2020 by B.D.E]

Quote: Originally posted by njl

I don't remember the yield but I left the solution of dcm/HNO3/toluene stirring overnight (probably 12 hours total).

Quote: Originally posted by chemplayer...

Wish we had had the set-up to characterise the product of this reaction a bit better. Definitely an ortho-rich product though at the very least. Would like to see just how selective the reaction is. Please be a little bit careful as too high a concentration of nitric acid in DCM has been reported to be unstable!

Quote: Originally posted by Boffis

@B.D.E; I am currently trying to prepare 2-amino-4-chlorophenol-6-sulphonic acid which is an azo dye intermediate. The theory is easy, the practical details are a little more difficult. I have found that at room temperature nitration of 4-chlorophenol-2-sulphonic acid is rapid even in 85% sulphuric acid with sodium nitrate solution but there is significant displacement of the sulphonic acid group by a nitro group to give a mixture of the desired product plus 2,6-dinitro-4-chlorophenol and 2-nitro-4-chlorophenol. The mixture is easily separated but represents significant loss. However, if nitration is carried out at about 0 C the desired 2-nitro-4-chlorophenol-6-sulphonic acid is obtained in good yield with minimal nitrophenols. I suspect that you will find that low temperature nitration will favour o-nitration over displacement of the sulphonic acid group in the p-position. Incidently I came a cross an article (that I am currently trying to locate) that suggests that nitrous acid tend to favour displacement of sulphonic acid groups in aromatic compounds so purity of your nitric acid may be an issue. I have also found that the use of sodium nitrate is best avoided because the separation of sodium salts at low temperatures makes the mixture very difficult to stir and therefore make temperature control difficult. I don't know how easily toluene sulphonic acid will nitrate, I suspect less easily than my chlorophenol sulphonic acid so you may need conc sulphuric and conc nitric acid but try and keep the temperature low. Let us know how you get on.

Well, the DCM nitration didn't went very well to say the least.
I started by mixing 0.2n of KNO₃(oven dried and crushed in a mortar) with 0.188n of H₂SO₄(96.1%). After some stirring a thick "gel" had formed.

I added ~75gr of DCM and the gel transformed into a "breakable" solid. I broke the solid into small pieces and allowed the mixture to stir in an ice bath.

After about an hour, I weighted 0.22n of toluene and diluted it with additional ~25gr of DCM. I added the toluene/DCM mixture into the HNO₃/DCM solution slowly(3ml at a time), and the mixture had turned orange-red. After the addition was over, I left the mixture to stir for about 7-8 hours in the ice bath(ice bath: T₀~0C, T_f~18C).

After 7-8 hours I poured the content of the flask into a a sinter funnel and filtered the solids off. I transferred the filtrate into a separatory funnel, washed with ~20mL of dH₂O, and removed the top aqueous layer. I then added about 20mL of saturated K₂CO₃ slowly(to avoid boiling off the DCM), afterwards the DCM layer was on top. I decanted both layers and this is what I was left with:


I connected a distillation apparatus to the "DCM layer" and distilled everything that came under 105C. Afterwards I was left with a very small amount of crude product.

I transfered the product via pipette into a test tube, washed it few times with water and dried it with some silica gel. The dry yield was only 3.5gr.
Due to the low yield, I decided to do the same workup(i.e. distillation>washing>drying) on the aqueous layer, but only got additional 0.5gr. Total overall yield was 4gr(=15.5% from HNO₃).


The product remains liquid at -13C.

Plausible reasons for the low yield:
the reaction temperature was too low.
the reaction needed more time to complete.
the excess toluene I've used was a bad idea for some reason.

Tomorrow I hope to try the mixed acid method(pTsOH + H₂SO₄ + NaNO₃ at 0C).

Good night.


[Edited on 18-6-2020 by B.D.E]

Quote: Originally posted by Tsjerk

With a bit of luck I can try this reaction tomorrow, I will let you know what happens. I'm not sure yet whether I will separate the DCM from the sulfuric acid/KNO3 before adding the toluene. The paper Chemplayer refers to in the video appears not to do so. Maybe I will extract the HNO3 three time with DCM and pool the extracts before attempting the nitration. Are you sure you distilled of everything under 105 degrees? Toluene has a boiling point of 110...

Quote: Originally posted by Tsjerk

I had such a great idea... only the execution was a bit poor. I started the reaction, everything looks fine. I will run it overnight and will report on the yield tomorrow. My great idea: I extracted the HNO3 three times with DCM from the sulfuric acid/KNO3. I know exactly how much sulfuric acid and KNO3 I used, so I can calculate how much acid would be left in the salty sulfuric acid/KHSO4/KNO3 mix when the extraction would be 100% efficient. I calculated how much NaOH would be needed to neutralize that acid. I could then measure the pH of the "neutralized" mixture which would correspond with the HNO3 not extracted with the DCM. So I dissolved the salt mix in 500 ml of water and added the amount of NaOH... Only to realize there was a bit of DCM on the bottom of the beaker which of course started to boil trowing 4/5th of the contents of the beaker all over the place... So no pH measured. But tomorrow I will quenche the reaction with a known solution of bicarbonate to see how much nitric acid is left which together with the nitrotoluene should sort of correspond with the amount of HNO3 extracted.

Quote: Originally posted by Boffis

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As for the solid that formed after adding water to the nitrated solution, here how the mixture looked like after the precipitation occurred:

(I know it doesn't really help with anything, but it definitely can't hurt ).

I struggled filtering all of the liquids out of the solid, so I settled on just filtering as much as I could(probably most of it), before adding some arbitrary amount of dH₂O directly into the sinter funnel to dissolve whatever had left. The solid dissolved quite easily to create said solution "(b)"(from my previous post). I also kept the filtrate from before adding the water(aka solution "(a)"), and ran all of the following workup steps on both solutions separately.

As for the solid that formed while neutralizing said solutions, I didn't kept it nor investigated it at all, as I was sure it was just K₂SO₄(at the time). I did however washed it out of the sinter funnel and it seemed to dissolved well in water.

As for the reduction to anthranilic acid - I'll be sure check your reference soon and maybe try adding CuSO₄ to samples of the solutions I was left with, in order to see if I can ppt any copper anthranilate. Much thanks for this info.
#Update - I added some Cu(NO₃)₂ and no green ppt had formed.

The calcium method sound a bit too messy for me. Do you really think it's necessary to isolate the sulfonated intermediate to such an extent before the desulfonation? If so, I hope that it's indeed possible to isolate it as an hydrate directly after the nitration(it's seems as if its ortho isomer does form an hydrate, so there's still hope in my heart).

As for "data about 2-nitrotoluene sulphonic acid and salts", I did looked it up on chemspider and pubchem, but couldn't find anything that seemed relevant. I also checked Ullmanns and Vogel, but couldn't find anything useful on there as well. (I only searched for the free acid).

Much thanks for the reply and the willing to help, I really do appreciate it

[Edited on 20-6-2020 by B.D.E]

@Tsjerk Great write-up man. I must admit it's a bit disappointing to hear that even though you seemed to have done everything right - you still got a rather low yield.

To be fair, the reference we all followed(ref[right?]) never really nitrated toluene. So at least as far as I know, the reaction might just not work well with toluene under those condition.
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@Boffis Thanks for all the info
Unfortunately some of the references you gave are in German. I also find it quite hard to read old papers as such(freaking 1869 man! ). It was cool though to see how much work people have put into some of these papers(especially the detailed hand drawings).

As for the self reduction/oxidation, I have found this:

ref: 978-0-470-03403-3(ISBN) page 113

Meaning that the oxidation probably requires a catalyst in order to be rapid. I didn't dag too much into it, but from what I could found it didn't seems likely that this should be an issue in my case.

As for your comment about Aryl-sulfonate salts being easier to isolate than their free acids - I would have agreed with you if pTsOH wouldn't have been so easy to isolate as an hydrate directly from its mother solution(i.e the solution in which it was prepared). After all, there isn't a real advantage in nitrating pTsONa(for instance) over simply nitrating pTsOH(obviously the salt would be converted to the free acid the moment you'll add the mixed acid).

As for this comment:

-I still haven't desolfunated the intermediate, so at least for the time being I'm yet to have checked a freezing point.

The only thing I did since my last update was to completely evaporate all water from the solutions I previously made("a" and "b"). This is what I got:

(b) - on the right ; (a) - on the left
With a bit of luck, one of those should contain 2-nitrotoluene-4-sulfonate(potassium salt).

I planing to get back into it next Sunday(28).
Hopefully I would be able desulfonate the intermediate and get the promised o-nitrotoluene.

[Edited on 23-6-2020 by B.D.E]

OK here's a translation of the most useful paper from Zeit. f. Chem.. I have only translated the bit by Bek but its pretty useful. There are a few things I wasn't sure about like what the hell is metabenzylsulphohydrate (Metabenzylsulfhydrats in the original)? There are also a few clear errors, they don't seem to have appreciated that barium was divalent and Na/K monovalent so the formulas are a bit suspect and the hydration states of the barium and lead salts are clearly wrong. For instance the writer claims that the theoretical water content of the monohydrate is 5.95% but I calculated about 3% so it looks like the salt may be a dihydrate.

Attachment: Nitrotoluene-4-sulphonic acid and derivatives Zeit.f.Chem Engelhardt & Bek 1869 EngTrans.docx (20kB)
This file has been downloaded 368 times

There is a lot of amazing chemistry in that old German literature, particularly before about 1930 since most of the chemicals and equipment they used ares now readily accessible (often from ebay with the exception of Oleum ).

The clip you posted above re-oxidation of nitrotoluene sulphonic acids refers to intermolecular reactions with external oxidation. Under certain conditions 2-nitrotoluene and its 4-sulphonic acid will undergo intramolecular oxidation where the nitro group will oxidise the methyl group. The yields are often not good enough to make these preparatory methods because there are often a lot of side reaction but you need to know about them if you are going to apply fairly brutle reaction conditions to something like 2-nitrotoluene. I'll see if I can find some of the references (probably in German too!) These reactions do appear to occur mostly in alkaline solutions though.

Quote: Originally posted by Boffis

OK here's a translation of the most useful paper from Zeit. f. Chem.. I have only translated the bit by Bek but its pretty useful. There are a few things I wasn't sure about like what the hell is metabenzylsulphohydrate (Metabenzylsulfhydrats in the original)? There are also a few clear errors, they don't seem to have appreciated that barium was divalent and Na/K monovalent so the formulas are a bit suspect and the hydration states of the barium and lead salts are clearly wrong. For instance the writer claims that the theoretical water content of the monohydrate is 5.95% but I calculated about 3% so it looks like the salt may be a dihydrate. There is a lot of amazing chemistry in that old German literature, particularly before about 1930 since most of the chemicals and equipment they used ares now readily accessible (often from ebay with the exception of Oleum ). The clip you posted above re-oxidation of nitrotoluene sulphonic acids refers to intermolecular reactions with external oxidation. Under certain conditions 2-nitrotoluene and its 4-sulphonic acid will undergo intramolecular oxidation where the nitro group will oxidise the methyl group. The yields are often not good enough to make these preparatory methods because there are often a lot of side reaction but you need to know about them if you are going to apply fairly brutle reaction conditions to something like 2-nitrotoluene. I'll see if I can find some of the references (probably in German too!) These reactions do appear to occur mostly in alkaline solutions though.

Wow man, thank you very much for translating this for me. I see now what you're mean.
Oh well, you win some and you lose some I guess "^_^

Nonetheless, just because I already got this far, I felt as it will be a waste not to at least try the reaction myself. So I made a 80% H₂SO₄(aq) solution and heated it to ~170C for around 1.5 hours with s.stirring. After letting the mixture cool, I poured it into an excess of water and carefully sniffed the dilute homogeneous solution - I couldn't identify any trace of the aromatic aroma associated with nitrotoluene(nothing at all).

Due to me being at the midst of another project, I decided not to research the product/products any further by isolation and thus poured the solution down the drain.

Thanks again boffis, you are a very nice guy and the info you sheared helped a lot