Nitration of phthalic acid

Nice write-up kmno4; I haven't tried this with phthalic acid but I did some preliminary work on nitration of terephthalic acid a little while back (when I posted all the stuff on terephthalic acid). I used similar quantities, 10g TPA in 50ml of 98% sulphuric acid and then added about 10g of dried sodium nitrate (roughly 2 fold excess). This was heated on a stirrer hotplate for 2 hrs before drowning in ice and water. The nitration of terephthalic acid has the advantage over phthalic acid that there is only on possible isomer but it appears very difficult to nitrate and initially I struggled to find a way to test the product which looked exactly like the starting material and was equally infusible. My plan now is to use the same technique that I used for the terephthalic acid and terepthalamide derivatives that I prepared, the back-titrated equivalence value, the fully nitrated acid should require less alkali to neutralize it than the partially nitrated acid per unit weight. I have yet to try this on my produc but I fear that it is mainly recovered TPA for various other reasons.

I also tried this method to dinitrate 2-chlorophenol. The target was 2,4-dinitro-6-chlorophenol and then by partial reduction 4-nitro-6-chloro-2aminophenol. Th nitric acid route works well with standard conc nitric acid (70%) and sulphuric acid and is high yielding but nitric acid is getting difficult to source now so I tied sodium nitrate again but the results were poor and the product difficult to isolate, it appears to be much more soluble in the sodium sulphate -dilute acid mixture than in dilute sulphuric acid alone.

I need 100-200 g of 3-nitrophthalic acid for my non-luminol scientific project, so I followed kmno4's procedure.

My yield was 18 %, m.p.=218-220 C.

There were 2 differences: I washed the precipitate just after the nitation and the target product with water (0-4 C). May be, I shouldn't have and these washings led to such a low yield.

So, kmno4's method really works, but I find this classical nitration unsatisfactory because of 2 reasons.

1. The yield is too small.
2. H2SO4 is a scheduled substance in a country I live in, so its usage in this synthesis is just a waste of the limited reagent. Thinking about СH3SO3H :-D.

I tried a literature search. These are the results:

1. One another classical method of 3-nitrophthalic acid preparation is via naphthalene nitration, that can be done with HNO3. Too long for me.
2. There's a nonclassical Bi(NO3)3-SiO2/THF/MW-nitration of phthalic anhydride with 75-85 % yield (see attachment). All regents are avaliable for me, but microwave reaction seems to be difficult, since I have no microwave owen. And even if I have, I cannot do this work at home.
3. MOOSAVI SEYED MOJTABA and SHAHSAVAN EBRAHIM discribed phthalic acid nitration (40 % yield) done by 65 % HNO3 (https://www.sid.ir/FileServer/SE/240E201417175.pdf), but with no details. I wrote them, but no one answerd.
4. Some information about 3- and 4-nitrophthalic acid solubilities see in attachment.
5. kmno4 wrote about H2SO4/MNO3 nitration discribed in russian forums. See attachment (taken from here: http://chemistry-chemists.com/forum/viewtopic.php?f=4&t=...), sorry for no translation.

Attachment: Bi(N03)3-SiO2-THF-MW nitration.pdf (96kB)
This file has been downloaded 503 times

Attachment: solubilities.pdf (44kB)
This file has been downloaded 471 times

Quote: Originally posted by Boffis

The problem is not the yield of nitro acid but the ratio of 3 to 4 nitro acids and their separation. [Edited on 5-12-2019 by Boffis]

Quote: Originally posted by Boffis

Attached is a patent for the separation of 3 and 4-nitrophthalic acid using an organic solvent and partial neutralisation of the mixed acids. [Edited on 5-12-2019 by Boffis]

Quote: Originally posted by Dr.Bob

What else is there to do with 3-NO2-PHA? What country are you in? I made some of that about 40 years ago towards luminol, but can't remember the details. I did find the flask of luminol recently, however. That was one of my first bits of mad science. I do have some PHA and derives, if anyone in the US needs any...

I'm going to use it as a synthetic intermediate, nothing special. And I'm far away from the USA .

Quote: Originally posted by Boffis

@Fery, and then prepared the 4-nitro isomer by oxidizing 4-nitrophthalide which presumably, though not stated, was prepared by nitration of phthalide which I believe is prepared by the reduction of phthalic anhydride. So a very complex process indeed.

@Brij-09 phthalide NOT phthalamide.

This is phthalide:

Quote: Originally posted by Boffis

@Brij-09 phthalide NOT phthalamide. This is phthalide:

Quote: Originally posted by Brij-09

I need 100-200 g of 3-nitrophthalic acid .....

Quote: Originally posted by kmno4

If basic chemicals, like H2SO4, are unavailable for you, the most economical way is just buying it. It is not very expesive, especiallly from chinese suppliers.

Quote: Originally posted by Brij-09

Quote: Originally posted by kmno4   If basic chemicals, like H2SO4, are unavailable for you, the most economical way is just buying it. It is not very expesive, especiallly from chinese suppliers. I didn't say it was unavailable. ))

Quote: Originally posted by Boffis

... a patent for the separation of 3 and 4-nitrophthalic acid using an organic solvent and partial neutralisation of the mixed acids.

Yes, I knew it earlier, but I had no appropriate pH meter to try this.
Fortuitously, I have found recently there are available very cheap, digital pH meters with glass "electrode" at ebay ( and similar sites).
I have bought something like this (foto from ebay):



I was surprised, because this device gives stable and reproducible readings (thank you, PRC !). For interested, the plastic casing is made from polystyrene (or ABS) material.

Experiments are in progress, I am going to report the effects soon.

... I am still alive, the experiments are finally finished.
From the perspective of time, I must admit that some part of them was just a waste of time, but even these failed experiments were quite informative
The results are in development, but now I only say that two solvens were tested: ethanol and isopropanol. The rest of recommended solvents are not resistant to reaction conditions (pH), or too expesive, or may damage (swelling) the casing of PH-meter.
The key factor is, besides controling pH, keeping water content at rather low concentration. In case of ethanolic solutions, increasing water content up to ~15% (value from density measurements) gives clear homogeous solution, without precipitates, at pH ~3.
It took a lot of time to me to realize how harmful is careless increasing water content However, results of precipitations in ethanol and isopropanol are very similar.
Because isopropanol is much cheaper than ethanol (especially anhydrous), the rest of my experiments were performed in this medium. More details will be given in few days.

I do not know. The pH meter I have is provided for water solutions, possibly it would give some readings in anhydrous conditions..... The theory of glass electrode is rather complicated and I forgot almost whole of it
However, in solutions containing even less than 1% of water, it behaves "as if" in pure water: readings are stable and set-in quickly (seconds). The pH meter presented above is not thermally compensated, but one can correct reading by small screwdriver (included). Two buffer powders are also included in the set, but I used tap water as standard - it was checked, many times, that it has pH=7,0 everyday
The main drawback (beside low thermal stability of readings) of this pH meter is plastic case. I am sure it is not resistant to ketones, esters and aromatic hydrocarbons, as it is made from polystyrene-like material. But for water and alcoholic solutions it is OK.

During the experiments, new improved proportions for nitration of PHA was developed.
Namely:
5 g of PHA + 12,5 g of conc. H2SO4 + 3,42 g of KNO3
Instead of KNO3, NaNO3 can be used (2,88 g). But KNO3 has better solubility properties, because under reaction
conditions, only highly soluble KHSO4 is formed, contrary to NaNO3 which gives less soluble "double salt" NaHSO4xH2SO4. However, final results are the same: the same amount of 3NPA is obtained. The semi-solid mass obtained after nitration was mixed with 18,3 g of H2O. The solid obtained (see the post at the beginning of the tread) weighs about 11 g. The yellow filtrate contains 30-40 % of formed 4NPA, but almost no 3NPA - no improved amount of 3NPA is obtained after working-up the filtrate. Prepared 10-12 g sediment is congruent for further work-up. 95% isopropanol (IPA) was used for all further preparations. More concentrated, it gives bad looking, muddy, and not well resolved sediments. Much less content of IPA may give too low amounts of the sediments. For this 11 g of post-nitration solid, 100 cm3 of the IPA solution was used. This volume seems to be appropriate for given amount of the solid, but it is not very critical parameter. An attempt was made to reduce amount of introduced water, by neutralizing the wet solid with Na2CO3 and drying.
Unfortunately, some semi-solid eutectic mixture of salts is formed. This yellow mass is very sticky and adhers to everything, playing with it is loosing the time. So, the solid is placed in some twist-off jar, IPA solution is added and mixing on mag.stirrer is started. Without delay, about 1,5-2 g of solid NaOH is added in form of powder or granoules, not pellets.
It is because, in this low-water content mixture, dissolution rate is low. NaHCO3/Na2CO3 is not recommended - its dissolution and reaction is much slower than in NaOH case, CO2 formation causes additional problems. When all NaOH is dissolved (it is important), pH of obtained solution is measured : the goal is to obtain value 0,8-1. When it is too low, small amout of NaOH is added... etc., when it is too high, few droplets of conc. H2SO4 are added. The result is yellowish-green liquid with dense, white sediment on the bottom. It is filtered off, washed with few cm3 of 98% (or better) IPA and dried (optionally). It should be completely white, yellow or orange points mark not dissolved NaOH. About ~5 g of inorganic salts mixture is obtained and it contains nothing interesting --> lavatory.
More NaOH is added, in several portions, checking pH in the meantime (stirrig, stirring !!). The next stop is pH=2,7-2,8. The sediment formed is filtered, washed and dried. About 3-4 g of white, with green shade, 3NPA salt is obtained. If it has markedly yellow color, it means that something went wrong and it contains more than expected admixture of 4NPA salt. In this case, it should be returned to the mother solution, stirred and pH is rechecked. More than 10 preparations was performed in this way and such yellow coloration is in 100% indication of NaOH overdose.
Prepared salt is dissolved in 10 g of hot water and 1,5-2 cm3 of conc. HCl is added. On cooling, some crystals of 3NPA may form, but it does not always happen.Obtained transparent, yellowish-green solution is cooled to ~5 C and kept in this temp. for several hours. After this time, white sediment should be present - 3NPA separates as crystalline dust. The liquid should be mixed several times with glass rod, to finish crystallization. It may take additional hours. Finally, it is filtered. Obtained crude 3NPA weighs ~1,8-2 g. This amount is achievable when everything was done correctly, if not, this yield may be in 1-1,5 g range. The filtrate was kept !
To obtain slightly better yields, recovery of remaining 3NPA was performed.
To the remaining IPA filtrate, NaOH is added again, but more carefully, to obtain pH=3,5-3,6. It is then cooled below 0 C (freezer) and quickly filtered. Filtration can be slower than earlier, even if amount of sediment is lower, but still it goes fast.
About 1-2 g of intermediate fraction, but still 3NPA rich, was obtained. It is deeper colored than previous fraction.
When further precipitations are performed with small amounts of NaOH, very small amounts of solids are obtained, becoming more and more yellowish-brown.
Obtained solid was added to the aqueous filtrate from 3NPA precipitation, some Na2CO3 added and evaporated to dryness.
The IPA filtrate, containing maily 4NPA, was partly distilled off, to obtain ~50 cm3 distillate. Prepared earlier solid mixture was mixed with this distillate and NaOH treated, this time without isolation of inorganics (it saves a little time), to reach pH=2,8, cool below 0 C. Precipitate was filtered... etc. It weighs ~2 g, but after dissolving in water and adding HCl, merely ~0,2 g of 3NPA is obtained.
Total weight of prepared (crude) 3NPA is then ~2,2 g : I was not able to obtain more than this, even after many modifications of given procedures. It seems that no more than 0,1-0,2 g of 3NPA is lost during all operations.

Recovery of 4NPA.
It is much hadred to perform, mainly because of very fine suspension, which is formed when pH of IPA solution is set
to ~4,5. The sediment is yellow, when suspended in mother liquid. It looks like at least 10 g and does not separate
(almost) from the liquid on standing. Filtering is very painful - it takes almost hours under vacuum, even when IPA starts boiling, the filtrate goes off slowly drop by drop. Measurable amounts of IPA evaporates during such filtration, in the end there is yellowish-brown mud in the funnel.
The mud weights ~5 g, but after drying, dissapointing ~2 g of 4NPA sals is obtained. Its colour is strongly dependant on exact conditions of precipitation and - possibly - impurities: from dirty yellowish, through "beige" (description from the patent) to reddish. However, the color of pure sample of 4NPA prepared later,surprised me : white powder, very easily soluble in water, giving yellow-orange solutions. In moist air, the powder attains canary-yellow coloration at thin surface layer. Re-drying removes this color.

Photo galery.



Another samples, with better separation of 3/4 NPA salts





A - inorganics
B - 3NPA salts
C - intermediate fraction pH=3,5
D - I do not remember, the most possibly it is fraction collected between pH 3,5-4,5
F - sample of 4NPA salts

F1-F4 - samples of 4NPA salts; F4 is residue from IPA evaporation and is not very pure
E1 - sample of rather pure 4NPA
E2 - another sample of 4NPA is slightly reddish

The colors differs markedly, depending on light source. The pictures are made under daylight.

3NPA is white powdery solid in all preparations, nothing interesting to show.

Remarks.
- in almost all cases, when amount of precipitated 3NPA was smaller (eg. 1,7 g), more 3NPA is obtained from intermediate fraction
- separation of inorganics at low pH, gives better results than collecting all solids at pH=2,8
- pH should be checked at least twice during ca. 30 minutes, before filering; it may not differ more than 0,1 unit.
- all operations are conducted at 20-30 C (exept coolig in indicated cases)
- all weights are given after at least 80 C drying (to constant weight)
- when all precipitations are finished, IPA was distilled from the solution. Remaining solid weighs less than 0,5 g and contains mostly impure, sticky 4NPA salts. Larger water content in origanl solution causes markedly larger weight of this residue.
- the distilled off IPA was 89-90% (from its density)
- composition of obtained solid 3NPA/4NPA salts does not correspond to any acidic or neutral Na salts of these acids; the patent treats them as monosodium salts, but amounts of separated acids are far too small for such composition
- amount of prepared 4NPA is slightly larger than 3NPA

Conclusions.
Unfortunately, separation of 3NPA and 4NPA is not so complete as the patent says. However, some progress is achieved comparing to water mixtures. The whole separation procedure is very time-consuming and requiers careful control.
In my opinion, it makes sense only in case of lager scale preparation. On the other hand, it is exellent exercise in such old-school separation process. The difference between pKa1's of the acids in water is very small. It seems that such composition of the solvent, containing ~10% of water, acts as differentiating solvent for these 3/4 nitroacids. Maybe ketonic cosovents act better and give better separation than alcohols, but it was not tested. The only choise seems to be acetone, because of its price and availability, but I did not try this (expected condensation issues). However, I think it is not very hard to perform, maybe in some, more or less near, future, just for fun...


[Edited on 2-10-2021 by kmno4]