TRANS-CYCLOHEXANE-1,2-DIPHOSPHONATES SYNTHESIS, STRUCTURAL AND NMR SPECTROSCOPIC INVESTIGATIONS

Abstract

A stereospecific addition of sodium diethylphosphite to cyclohexene-1-phosphonic acid diethyl ester 1 was used to synthesize trans-cyclohexane-1,2-diphosphonic acid tetraethyl ester 2b. Acidolysis of the ester yields the corresponding diphosphonic acid 2a. Dissociation constants pK₁-pK₄ of 2a were obtained in aqueous solutions by precision potentiometric titration. The molecular structure of solid 2a determined by X-ray diffraction shows a slightly disturbed chair form of the cyclohexane ring and a bisaxial conformation of the phosphonate groups with a P–C–C–P dihedral angle of 143°. Results of molecular modeling of 2a as well as of its anions (with and without consideration of Na⁺ cations) obtained by semi-empirical MNDO methods and by empirical force field calculations including molecular dynamics are reported. The investigation of organic solutions of 2b and of aqueous solutions of 2a by NMR spectroscopy allows conclusions concerning the conformative state via a Karplus-type relation for the vicinal coupling constant ³J_pp on the P–C–C–P dihedral angle. In 2b the preferred conformation is that with a bisaxial arrangement of the phosphonate groups, while in aqueous solutions of 2a the bisequatorial conformation dominates. By titration of 2a with a strong base the portion of the bisequatorial conformation rises to a maximum value at a degree of titration T  3. Continuation of the titration leads to stabilization of the bisaxial conformation.

Key Words:

• trans-Cyclohexane-1,2-diphosphonic acid
• trans-cyclohexane-1,2-diphosphonic acid tetracthyl ester
• crystal structure
• molecular modeling
• NMR
• conformation