3.3.2. β-OH Carboxylic Acids
2-COOH phenol. Salicylic acid is the classical β-OH carboxylic acid in the aromatic series. It was already discussed in Section 3.2.3 as a phenol derivative. The primary structural difference between an aromatic and an aliphatic β-OH carboxylic acid is that the heavy atoms are coplanar for the aromatic molecule unless a neighboring substituent forces the –COOH group to rotate out of the benzene plane. In the case of a coplanar skeleton like 2-COOH phenol, both =O…H–O and O–H…O–H intramolecular H-bonds are conceivable. For the latter type, the donor hydrogen can come from either hydroxy group.
Aliphatic acids. In contrast to aromatic systems, the C(carboxylic)CCO moiety would generally adopt a (nearly) gauche or trans conformation in the aliphatic series. Unfortunately, no calculations analyzing structure were found for the simplest β-hydroxy carboxylic acid, namely β-hydroxy propionic acid. Its α-amino derivative, serine (α-amino, β-hydroxy propionic acid) was studied as an α-amino acid above. Seven low-energy conformers of l-threonine ((2S,3R)-2-amino-3-hydroxybutyric acid), the β-methyl derivative of serine, were identified in the gas phase by Alonso et al. [219]. In the lowest energy conformation, the alcohol OH is a proton donor to the NH2 group, as it was found for 2-NH2 ethanol. This bond clearly does not exist for a simple β-hydroxy acid. In the second lowest energy structure (34 cm−1, 0.4 kJ/mol above the minimum, as calculated at the MP2/6-311++G** level) the alcohol OH forms a H-bond to the carbonyl oxygen of the anti carboxylic group. Because the NH2 group also serves as a competing H-bond acceptor, it did not reveal whether an O–H…O= bond is also feasible to the syn –COOH group. Geometry results indicate, however, that this interaction could easily come into existence.
A combined spectroscopic and in-solution quantum chemical investigation was carried out by Quesada-Moreno [220] at pH = 1.00, 5.70 and 13.00 in aqueous solution, and the protonation states of the molecule were modeled theoretically under the experimental conditions. The conformational search found 9 zwitterions, 27 anions and 52 cations at the B3LYP/6-311++G(d,p) level of theory, whereas the most stable conformers were optimized at the M062X/6-311++G(d,p) and MP2/6-311++G(d,p) levels of theory, as well. The solvent effects were calculated by means of the IEF-PCM method. As the authors write: “With regard to the zwitterion, the importance of the analysis of the low frequency region (700–30 cm−1) in the Far-IR spectra should be noted, because it provides relevant information that can be used to determine the presence of the most stable structures.”
Discussion of the large number of conformations is beyond the possibilities of this review. Regarding the possible H-bonds between the carboxylic and OH groups, conformers of the protonated species may be informative. For this species the –COOH group is not ionized. The presented, low energy conformations are dominated, however, by –NH3+…O hydrogen bonds (sometimes to two oxygens at the same time) and perhaps only higher-relative-energy conformers would show H-bonds between the carboxylic and OH groups. Related geometries are not provided in the paper, and the reader is advised to turn to the authors directly.