kilomentor | 10 June, 2010 18:12
Intuitively it seems sensible that to obtain the highest melting derivative it might be sensible to derivatize with the highest melting derivatizing agent. Although there is no firm basis for such a prediction, there is some enhanced likelihood of this being so. The derivative will share some partial structure with the derivatizing agent and if features of that agent contribute significantly to the high melting property and if those features are preserved in the derivative’s structure, some of the high melting characteristic could be anticipated to be retained.
The highest melting pharmaceutical salt former for reaction with basic substances is orotic acid. Its melting point is around 325 C. Its structure contains multiple hydrogen bond donors and acceptors that most likely contribute the melting character and these hydrogen-bonding sites are retained in the pharmaceutical salt formed.
Despite this the orotic acid salts are rarely used.
The alkali salts of orotic acid are poorly soluble. Orotic acid is also poorly soluble in water. Thus the sodium salts can be precipitated by adding a solution of the N,N-dimethylethanol salt of orotic acid in 80% aqueous ethanol. This might be tried as a method for removing an alkali salt from an alcoholic solution of an organic compound. The alkaline cation as an alkaline salt would be precipitated with orotic acid. The residual orotic acid would also be essentially insoluble. N,N-dimethylethanol would be left in solution but this could be removed by extraction with a neutral organic solvent.
Orotic acid or a salt of orotic acid might be expected to form a complex with triphenyl phosphine 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.
The unusual solubility properties of orotic acid and its metal salts make it worth bearing in mind when trying to isolate organic bases particularly because, since it is pharmaceutically acceptable, trace residues are not too critical.