Hydrogen bonding acceptor power

On the base of work by Gordy and Stanford, the spectroscopic criterion, related to the extent of the shift to lower frequencies of the OD infrared absorption of deuterated methanol, was selected. It provides a measure of the hydrogen-bonding acceptor power of a sol-vent. The spectrum of a deuterated methanol solution in the test solution was compared with that of a solution in benzene and the hydrogen-bonding parameter was defined as... 

The next step was made by Klebe et al. [50]. Two 3D-QSAR methods were applied to get three-dimensional quantitative structure-activity relationships using a training set of 72 inhibitors of the benzamidine type with respect to their binding affinities toward Factor Xa to yield statistically reliable models of good predictive power [51-54] the widely used CoMFA method (for steric and electrostatic properties) and the comparative molecular similarity index analysis (CoMSlA) method (for steric, electrostatic, hydrophobic, hydrogen bond donor, and hydrogen bond acceptor properties). These methods allowed the consideration of various physicochemical properties, and the resulting contribution maps could be intuitively interpreted. 

The hydrogen bond acceptor (HBA) power of a compound is called hydrogen bond basicity (or hydrogen-bond electron-acceptor power) and is denoted by Pi and P2 for solvents and solutes, respectively. 

Jprgensen s group has very recaitly d onstrated the usefulness of o,P-unsaturated acyl phosphonates as hydrogen-bond acceptors in the enantioselective Hiedel-Crafts reaction with indoles [341]. Since the acyl phosphonate moiety is a powerful ester and amide surrogate, this reaction is an interesting approach towards the synthesis of optically active p-(3-indolyl)esters and amides as represented in Scheme 2.119 for selected examples. The reaction is catalyzed by chiral thiourea-based catalyst ent-191 that activates the nucleophile and the electrophile through hydrogen-bond interactions. 

As a powerful hydrogen-bond acceptor, fluoride is understandably a poor nucleophile in protic solvents. Iodide, as the worst hydrogen-bond acceptor, is thus a much more active nucleophile in protic solvents. In the absence of hydrogen-bonding interactions with the solvent, which is the case in dry polar aprotic solvents, fluoride is the strongest nucleophile. 

The hydrogen bond donating powers of water molecules and alcohols are comparable, both for the monomers in inert solvents and for the bulk solvents. Nevertheless, our results show that the primary solvation number for hydrogen bond acceptor solutes (such as Mc2CO, MeCONMc2 or anions) is usually at a maximum for aqueous solutions, but considerably less for methanolic solutions. 

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