Salts of Orotic Acid: Neutralizing excess Base without increasing the Inorganic Salt Concentration

Orotic acid is a pharmaceutically acceptable salt former. That is it is safe to use as a counter ion in drug salts.

Intuitively it seems correct to conjecture that to obtain a high melting salt it might be sensible to derivatize with the highest melting salt-former available. Although such a prediction would have no ineluctable basis, it is the way to bet. Such salt would share some substructure with the acid derivatizing agent from which it was formed. If these features contribute to the high melting property of the acid, those features, if preserved in the salt’s structure, might be anticipated to contribute to some retained high melting characteristic.

Among pharmaceutically acceptable acids for making salts, the highest melting is orotic acid at around 325 C. Its structure contains multiple hydrogen bond donors and acceptors and some of these hydrogen-bonding sites may be retained in the pharmaceutical salt formed.

 Despite their presumed special desirable property orotic acid salts are rarely prepared.

The alkali metal salts of orotic acid are poorly soluble. Orotic acid itself is also poorly soluble in water. Sodium orotate can be precipitated by adding a solution of  N,N-dimethyl-2-hydroxyethyl ammonium orotate in 80% aqueous ethanol to sodium hydroxide in water. 

That is to say, N,N-dimethyl-2-hydroxyethyl ammonium orotatecombined with a sodium halide would give a precipitate of sodium orotate,  and N,N-dimethyl-2-hydroxyethyl ammonium halide. This might be a method of removing an alkali salt from an aqueous solution of an organic compound. The sodium cation would be precipitated as an alkaline salt by orotic acid.  N,N-dimethyl-2-hydroxyethyl ammonium halide would be left in the aqueous solution but this could be removed by extraction with a neutral organic, water-immiscible solvent.

Orotic acid or a salt of orotic acid might be expected to form a complex with triphenylphosphine oxide which is a good hydrogen bond acceptor. Orotic acid has an imide NH which is a good hydrogen bond donor.

Orotic acid may be a good substance to neutralizes aqueous base since both the alkaline salt and the free acid are essentially insoluble and will precipitate.

The unusual solubility properties of orotic acid and its metal salts make it worth bearing in mind when trying to isolate organic bases, particularly since, as a pharmaceutically acceptable salt, trace residues are not as critical.

The salts of orotic acid with volatile amines such as ammonia, methylamine, ethylamine, trimethylamine, and triethylamine are all expected to be substantially more soluble than those of hard metallic elements so that these hard cations are likely to be precipitated. Heating the ammonium salts of large nonvolatile acids will likely drive the volatile amine of leaving the free acid.