CONFORMATIONAL EQUILIBRIA OF BETA-ALANINE AND RELATED-COMPOUNDS AS STUDIED BY NMR-SPECTROSCOPY

The vicinal proton-proton couplings of the dipolar form of beta-alanin e in water, alcohol-water, and dimethyl sulfoxide-water solutions indi cate little conformational preference and are consistent with an essen tially statistical equilibrium of the gauche or trans conformations. T he position of the equilibrium is only slightly affected, over a tempe rature range of about 130 degrees, by changes in dielectric constants ranging from 30 to 80 or by massive changes in ionic strength. Quantum -mechanical calculations at the HF/6-31G* and LMP2/cc-pVTZ levels wer e found to give rather good parallels with experiment, although sugges ting the gauche conformation to be 2-3 kcal/mol more stable in water o r methanol than actually observed. A number of related compounds, such as N,N,N-trimethyl-beta-alanine and N,N-diethyl-beta-alanine, as well as the conjugate acid and conjugate base Of beta-alanine, also show n o significant conformational preference in water solution. Tn conformi ty with these results, the zwitterionic form of piperidine-3-carboxyli c acid (nipecotic acid) has about the same preference for equatorial c arboxylate as cyclohexanecarboxylic acid itself. Taurine shows no sign ificant conformational preference except in basic solution, where the couplings indicate about 53% of the gauche conformation. In contrast, N,N,N-trimethyltaurine is predominantly trans in:acidic or neutral sol ution. The conformational equilibria of the N,N,N-trimethyltaurine spe cies are most Likely governed by steric hindrance, because there are r ather large tetrahedral groups at each end of the ethano chains. Yet, even here the energy difference between gauche and trans is only about 1.2 kcal.