Precipitation and Isolation of Organic Carboxylic Acids, Sulfonic Acids and Sulfinic Acids from Solution or Reaction Media.

Arylmethylisothiuronium Salts

Ionizable acids are intermediates preferred by KiloMentor in organic synthesis schemes because they are more easily separated in pure form whether by extraction of the anions into water or precipitation of insoluble salt compounds.

Arylmethylisothiuronium salts are useful intermediates for precipitating these organic acids, particularly if (i) the molecular target contains another functionality that is sensitive to aqueous alkali or (ii) the entire target molecule is water-soluble. The arylmethylisothiuronium salt reagents themselves are decomposed by aqueous alkali to liberate arylmethylthiols, so conditions must be kept slightly acidic during all operations using them. 

Carboxylic Acids

Carboxylic acids are first converted into sodium salts by reaction with sodium alkoxide in alcohol and then mixed with a solution or slurry of the arylmethyl-isothiuronium halide in alcohol. The salt crystallizes out. It is important for carboxylic acids that the liquid be water-free and the pH not at all basic.  Salts of weak acids such as the carboxylic salts, in the presence of any water, can partially hydrolyze back to free acid and sodium hydroxide which creates a basic solution which then will degrade the isothiuronium reagent. 

The isothiuronium derivative can be formed in water so long as the formation of the carboxylic acid salt is never completely neutralized. This is accomplished by only adding alkali until methyl red changes color. Another literature citation proposes that the neutralization be done to the point of the color change of phenolphthalein followed by the readdition of acid until the color disappears.

Sulfonic and Sulfinic Acids

Salts both of sulfonic acid and sulfinic acid anions and arylmethyl-isothiuronium cation are preferably formed by mixing aqueous solutions of the reagent and the alkaline metal salt of one of these acids. These precipitations can be done in water which gives much higher yields of these crystalline products. Degradation from adventitious base is less likely because for these stronger acids there is no propensity to hydrolyze the salts to create an alkaline solution.

The regeneration of all  the purified acids is done the same way. In a mixture of an organic solvent immiscible with water and water acidified with hydrochloric acid, the isothiuronium salt is added and stirred vigorously. The strong mineral acid partially or completely protonates the organic acid whereupon it dissolves into the immiscible organic layer leaving the regenerated arylmethyl-pseudothiuronium chloride in the aqueous hydrogen chloride mixture. Heating the aqueous acid phase dissolves the regenerated reagent which then crystallizes when the solution is cooled.

The purified organic acid is recovered from the organic solution by any convenient means.

It seems likely that carboxylic acids in these isothiuronium salts can be liberated by the more acidic alkylsulfonic acids; for example by methanesulfonic acid.

It might well be that any O-acid with at least two tautamerically equivalent oxygens could form these derivatives: such as alcohol sulfonic acids, sulfamic acids, or phosphonic acids. This is something that can be explored further. I do not have any information on these.