CC/B–N substitution in five membered heterocycles. A computational analysis†
The concept of CC bond replacement with isoelectronic B–N bonds has received renewed interest since the synthesis of 1,2-azaborine (2008) and is being explored for pharmaceutical and material science applications. Analogous neutral five membered azaborole derivatives are possible if an additional carbon atom is replaced with a heteroatom like (X = O, N or S), thus giving X–B–N or X–N–B type of molecular framework with a potential for aromatic stabilization, novel physicochemical and pharmacological properties. These five membered azaborole have proven difficult to synthesize. In this paper a computational analysis on the viability (based on relative stability, aromaticity, electrophilic/nucleophilic reactivity, 11B and 1H NMR chemical shifts, solvent effect, proton affinity, hydrolysis, dimerization and trimerization potential of X–B–N and X–N–B azaboroles) is performed. Decomposition of isomer stabilization energy (ISE) into σ bond energy and aromatic stabilization energy was found useful in explaining differences between X–B–N and X–N–B systems. Results predict that X–B–N framework is more stable than the X–N–B, however the latter retains a considerable amount of aromatic character. Azaboroles are found to be less basic than ammonia. Stepwise hydrolysis involving protonation at N of B–N moiety followed by attack of water or hydroxide ion and liberation of hydrogen is more feasible than a concerted mechanism. Tautomers are less stable than parent azaboroles except for 1,2,3-diazaborole (3). Thus, X–N–B and X–B–N type of five membered azaboroles are viable under dry conditions, and have an unexplored potential as novel building blocks towards the synthesis of new drug-like molecules and materials.