But how did you make it? Such compound should crystallize without problems. Are you sure you have it in the mixture?

Can you extract the basified aqueous solution with ethyl acetate and see if it is in the organic layer?

You can try to extract with Ethyl acetate or Ethylacete-IPA (95%) after basification, maintain pH  above 11-12

Reverse-phase chromatography will both desalt and purify. Then lyophilization.

Rather than salting out, you could try “sugaring out”.  Saturate the solution with simple table sugar, and then attempt to extract with ethyl acetate or acetonitrile.

Use ion-exchange - see attachment.

Add acetonitrile and dry silica (amount depends on the amount of the substance; 1-2g) to the aqueous solution (6 times MeCN volume compared to the water volume) and remove the solvents by distillation to get a dry crude mixture (MeCN/Water forms an azeotrope). Elute the mixture over a normal phase silica column with an appropriate eluent (evaluate the eluent by TLC, Rf should be 0.2-0.3). Remove the eluent from the product fractions.

It's not clear how it was prepared? As you suspect that it is in the form of salt then remove water under reduced pressure to isolate the salt and dry it. Suspend it in saturated aqueous sodium bicarbonate and after stirring well the solid separated can be filtered, dried and recrystallized from suitable solvent. Alternately it can be suspended in some organic solvent (say benzene, toluene or dichloromethane in which compound is soluble) and treated with triethyl amine (calculated amount). After stirring well it is to be washed with brine solution, dried (anhyd. sodium sulphate) and removal of solvent may give the title compound. It can be recrystallised with organic solvents. 

The above solutions are good. I also suggest you to add excess n-hexane in order to precipitate out the salt.

Otherwise, add excess NaOH and extract repeatedly with diethyl ether or ethyl acetate. 

I would suggest basifying with NaOH to pH12, adding NaCl and extracting with nBuOH which is very effective with polar substrates.

Add  more NaOH solution and extract your compound with CHCl3 repeatedly.

You have not metioned how  you prepared it? Because pyrimidine compuunds crystallize. I think you didn't get  product.

Try to do neutralization and do extraction using methylene chloride three times (3x50 ML) followed by drying over sodium sulfate anhydrous.

Hi

First neutralize your solution using base like NaOH, then extract your product using CHCl3 or ethylacetate or diethyl ether and evaporate the solvent of extraction to get your product.

Good luck

Please see https://www.researchgate.net/publication/274779930_How_to_successfully_convert_a_water-soluble_organic_onium_salt_into_its_free_base_or_change_its_anion_by_using_an_anion-exchange_resin.

Thanks to all for your suggestions..

I am not sure why you 'suspect' that it is in the form of HCl salt... Typically you would know that, e.g. just  from the procedure, or by measuring the pH and knowing what acid was added. One word of caution: I would not recommend strongly basic conditions for the isolation protocol because of the possibility of disrupting the thiadiazole - pyridine bond. Bringing pH to about 8.5-9.0 should be sufficient to allow for efficient extraction. Also, have the aqueous solution somewhat concentrated before the extractions, EtOAc should be good as the organic component (I particularly like 2-Me-THF for extracting amines from aq. solutions). If this does not work, something else in the chemistry may have gone wrong.

If your compound (pH 9),, is somewhat insoluble in organic solvents, you might need to use a continuous liquid/liquid extrator, running overnight if necessary.

Thanks for all.

Interestingly, this reaction and isolation is proceding good in , nicotinic acid and isonicotinic acid and other aromatic acids but not for picolinic acid.

The procedure is, carboxylic acid, thiosemicarbazide is refluxed in dehydrating agents such as sulfuric acid, POCl3, PPA or SOCl for 12 hrs, then poured into crushed ice and filteration.  This is not working for picolinic acid and and shows a lot of spots in TLC while monitoring. No solid forming while pouring into ice and even neutralization at pH 8-9 or more.

Suggest some more thoughts please on this.......

1) In the presence of lot of impurities (as you mentioned), it is difficult to get solid. So I think you may need to try another condition..Like first try to prepare the acid chloride of picolinic acid and then you can treat it with your thiosemicarbazide..

May be mild conditions required.

2) secondly, are you sure that your product is solid..If not solid or low melting solid than it may be difficult to get solid product directly after work up. You may have to try crystallization..

As other thiadiazoles are solid, i expect this too as solid.  I tried that conditions too as you mentioned. But couldn't.  My wonder is why this picolinic acid only have this kind of issues?

The thiadiazole ring-closure involves the protonation of the carbonyl group of the amide (followed by the attack of the amide carbon on the sulfur atom). As the pyridine nitrogen is, most probably,  already protonated under the reaction condition, the formation of a cation at the neighbouring carbon atom does not occur. You can try another method, for example, via aldehyde semicarbazone oxidation: http://www.sciencedirect.com/science/article/pii/S0223523407001006. The aldehyde is only a bit more expensive than the acid.

Thanks Mr. Andrei. This is exactly happening as you said.

And the method aldehyde semicarbazone  you suggested is also not working for picolinic acid case.

If you do not need much of that compound, you can try cross-coupling instead of the ring-closure. For instance Aldrich 647284 with 708291 (the reference is there in the catalog). Alternatively, Aldrich sells 2-pyridylzinc bromide, which I would prefer, but it is rather expensive; although you can, naturally, make it yourself via Br/Li or Br/Mg exchange. In the last case no hexanes in the mixture, what is better for the coupling. As a catalyst, I would take Aldrich 753009 instead of what they use in the TetLett publication.

Is your product is confirmed. If yes you can extract it with 10-15% methanol in DCM or 25% IPA in chloroform. 

Hi  Sivaraman Somasundaram

You may try extract your product with diethyl ether or chloroform and precipitate it with petroleum ether.

Good luck