Conformational preferences of trans-1,2- and cis-1,3-cyclohexanedicarboxylic acids in water and dimethyl sulfoxide as a function of the ionization state as determined from NMR spectroscopy and density functional theory quantum mechanical calculations.
The populations of diaxial (aa) and diequatorial (ee) conformers of trans-1,2- and cis-1,3-cyclohexanedicarboxylic acids (CDCAs; 1 and 2, respectively) and their salts were determined in water and dimethyl sulfoxide (DMSO) solutions from vicinal proton-proton NMR J couplings ((3)J(HH)). Optimized geometries and free energies for these compounds were obtained at the M06-2X/cc-pVTZ(-f)++ level. Although carboxylic acid groups in cyclohexane rings are generally believed to be far more stable (~2 kcal/mol) in equatorial than axial positions, this investigation demonstrated that an aa conformation (normally assumed to be completely insignificant for these compounds) can be favored depending on the medium and ionization state: strong ee preferences (>90%) were observed in water and DMSO for both diacids and their salts, except for the dianion of 1 in DMSO, which was found to be substantially aa (~57%). The possibility of intramolecular hydrogen bonding (H-bonding) was also investigated; the ratios of the ionization constants (K(1)/K(2)) indicated an absence of intramolecular H-bonding because K(1)/K(2) ≪ 10(4) (a standard criterion for non-H-bonding in dicarboxylic acids) for both 1 and 2 in water and also for 2 in DMSO. For 1, K(1)/K(2) increased drastically in DMSO (K(1)/K(2) = 4 × 10(6)), where (3)J(HH) and the ratio K(1)/K(E) = 10, K(E) being the acidity constant of the monomethyl ester of 1, indicated the formation of an intramolecular H-bond for the monoanion in this solvent. An explanation for the observation of compact dianions in solution in terms of the generalized Born equation is also provided.
Crellin Laboratory of Chemistry, California Institute of Technology, Pasadena, California 91125, USA.
Alejandro J
AJ
Garza
Mrinmoy
M
Nag
William R
WR
Carroll
William A
WA
Goddard
John D
JD
Roberts
D003509:Cyclohexanecarboxylic Acids / Q000737:chemistry*; D003998:Dicarboxylic Acids / Q000737:chemistry*; D004121:Dimethyl Sulfoxide / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D011789:Quantum Theory; D013237:Stereoisomerism; D014867:Water / Q000737:chemistry
D003509:Cyclohexanecarboxylic Acids; D003998:Dicarboxylic Acids; C534517:cyclohexane-1,2-dicarboxylic acid; D014867:Water; D004121:Dimethyl Sulfoxide