R. Gilbert, K. James
May 1, 1964
Citations
0
Influential Citations
2
Citations
Journal
Journal of Pharmacy and Pharmacology
Abstract
SIR,-In a reported method for the preparation of glycyrrhizic acid (Lythgoa & Trippett, 1950; Kuboki & Hoshizaki, 1954; Ito, Kirita & Kuroda, 1955) the precipitate produced by adding lead acetate to an aqueous solution of crude ammonium glycyrrhizate is suspended in aqueous ethanol and decomposed with hydrogen sulphide; the precipitate is removed, and the solid obtained on evaporating the filtrate recrystallised. The reaction sequence would be expected to produce lead glycyrrhizate, which is subsequently decomposed to give lead sulphide and glycyrrhizic acid, but Marsh & Levvy (1956) using the same process, claimed that mono-ammonium glycyrrhizate was the end product. Thus the lead derivative could be a mixed lead-ammonium salt, and to investigate this possibility we prepared the compound and examined it. Mono-ammonium glycyrrhizate, prepared as described previously (Gilbert & James, 1964) was dissolved in 30% ethanol and made alkaline to litmus with ammonia. Excess lead acetate solution was added giving a white precipitate which was removed, washed six times with water, and dried in vacuo at 50". Gravimetric determination as chromate gave Pb 20.00% : (C4,H,,0,,),Pb, requires Pb 27.41%; C42H58018NH4Pb requires Pb 19.83%. Ammonia distillation gave NH4 1.56%; C4,HS901,NH4Pb requires NH4 1.63%. Thus mono-ammonium glycyrrhizate is the logical product, providing the first pK, value is lower than that of hydrogen sulphide (pKa 7.04), for if hydrogen sulphite were the stronger acid it would replace the ammonium in the leadammonium salt with hydrogen. Potentiometric titration of glycyrrhizic acid with sodium hydroxide gave only one inflection, which showed that the pKa values for all three carboxyl groups lay between 3.5 and 5.0, while pH measurements of mixtures of mono-ammonium glycyrrhizate and hydrochloric acid gave a mean first pKa value of 3.74 at 25". Decomposition of the lead ammonium glycyrrhizate with hydrogen sulphide gave a product identical with monoammonium glycyrrhizate. Examination of the papers which described the products as glycyrrhizic acid revealed some support for our conclusions. Both Kuboki & Hoshizaki (1954) and Ito & others (1955) quoted the melting-point of their product as 170°, mono-ammonium glycyrrhizate turns yellow at this temperature, but the acid does not. It would therefore appear that the material these workers described as glycyrrhizic acid was the mono-ammonium salt.