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

The synthesis of (1H-benzimidazol-2-yl-methyl)phosphonic acid, H-2(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 H-2(Bimp)(+/-) was obtained. In H-2(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 degreesC; 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 H-3(Bimp)(+) was estimated: pK(a) = 1.5 +/- 0.2. Moreover, Bimp(2-) 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 Bimp(2-); 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.