Strong Bases Design: Predicted Limits of Basicity

Abstract

Brønsted superbases have wide applications in organic chemistry due to their ability to activate C–H bonds. The strongest neutral bases to date are substituted aminophosphazenes developed in the late 1980s by Reinhard Schwesinger. Since then, much effort has been expended to create even stronger neutral bases. In this article, the reasons for the instability of very basic compounds are investigated by means of high-level quantum-chemical calculations. Theoretical basicity limits are suggested for solutions as well as for the gas phase. A record-breaking superbase most likely to be synthesizable and stable at ambient conditions is proposed. Hexamethylphosphoramide is considered a reliable ionizing solvent for superbases.

pH Indicators for Strong Molecular Bases: A Theoretical Approach

“…Scarce data on the experimental pK a values in HMPA 27,28 hamper direct verification of the method, although indirect verification has been performed in our earlier works. 13,16,29 ■ RESULTS AND DISCUSSION indicators 1 − 10 (Table 1), yielding a good linear correlation (R 2 = 0.988).…”

“…Table 3 contains their pK a values, while Figure 1 Trimethylenedecacyclene 15 loses its first proton nearly at the same basicity level as 9-phenylfluorene 1, changing the color from red to lemon yellow. Transition to green dianion is achievable by bases stronger than Schwesinger's tBu-P 4 (pK a (BH + ) = 35.65), 13 while the last deprotonation step to deep blue trianion is just beyond the strength of the most basic molecular superbases currently known (Chart 2).…”

“…The second transition to the deep blue dianion requires a base at least as strong as ZH, which was designed by us earlier. 13 ■ CONCLUSIONS A total of 22 transition points of 17 different pH indicators, including three newly designed ones, were theoretically studied in HMPA solution, filling the pH range from 28 to 54. The basicity of the strongest known azene, phosphine, carbene, and borylene bases was computed and compared on the same scale.…”

“…The strongest in each class approach nearly the same basicity level, although the theoretical limit was found to be much further according to our computations. 13 Thus, new efforts are expected to go beyond the current records.…”

Molecular entanglement can strongly increase basicity

“…Furthermore, due to their neutral charge, organic superbases are usually soluble in the most common organic solvents while retaining their high basicity. In contrast, ionic inorganic bases tend to form ion pairs and aggregates with reduced protophilicity 21 . Amongst the drawbacks of organic superbases, we cite their high molecular weights and their synthesis that are often arduous compared to inorganic bases, leading to low atom economy and sustainability issues.…”