Synthesis and acid–base properties of (1H-benzimidazol-2-yl-methyl)phosphonate (Bimp2−). Evidence for intramolecular hydrogen-bond formation in aqueous solution between (N-1)H and the phosphonate group

Abstract

The synthesis of (1H-benzimidazol-2-yl-methyl)phosphonic acid, H₂(Bimp)^±, is described: 2-chloromethylbenzimidazole was reacted with ethylchloroformate to give 1-carboethoxy-2-chloromethylbenzimidazole which was treated with trimethyl phosphite and after hydrolysis with aqueous HBr H₂(Bimp)^± was obtained. In H₂(Bimp)^± one proton is at the N-3 site and the other at the phosphonate group; both acidity constants were determined in aqueous solution by potentiometric pH titrations (25 °C; I = 0.1 M, NaNO₃) and this furnished the pK_a values of 5.37 ± 0.02 and 7.41 ± 0.02, respectively. The acidity constant for the release of the primary proton from the P(O)(OH)₂ group of H₃(Bimp)⁺ was estimated: pK_a = 1.5 ± 0.2. Moreover, Bimp²⁻ can be further deprotonated at its neutral (N-1/N-3)H site to give the benzimidazolate residue, but this reaction occurs only in strongly alkaline solution (KOH); application of the H₋ scale developed by G. Yagil (J. Phys. Chem., 1967, 71, 1034) together with UV spectrophotometric measurements gave pK_a = 14.65 ± 0.12. Comparisons with acidity constants taken from the literature show that this latter pK_a value is far too large and this allows the conclusion that an intramolecular hydrogen bond is formed between the (N-1/N-3)H site and the phosphonate group of Bimp²⁻; the formation degree of this hydrogen-bonded isomer is estimated to be 98 ± 2%. The general relevance of this and the other results are shortly discussed and the species distribution for the Bimp system in dependence on pH is provided.