Studies of the formation of N-substituted pyridinium mesylates: A theoretical approach

Abstract DFT computations were performed for the formation of quaternary pyridinium salts in the nucleophilic substitution of (2 S ,5 S )-1,3,4-trideoxy-2,5-andydro-6- O -mesylhexitol ( 1a ) and methyl 2,3-dideoxy-5- O -mesyl-β- d -pentofuranoside ( 2a ) with pyridine in order to describe the reaction pathway in detail. The thermodynamic parameters of the reactions were computed at the B3LYP/6-31+G ** level, whereas activation barriers were calculated at two levels: B3LYP/6-31+G ** and MPW1K/6-31+G ** . All the structures were fully optimized in the gas phase and in water. Additionally, single point calculations were carried out in chloroform, ethanol and water. All calculations in solvents were performed using the polarizable continuum model (PCM). The energy profile for the whole process in the gas phase resembles an asymmetric double-well potential with five stationary points: separated reactants R , reactant complex RC , transition state TS , ion pair IP and separated ions P . A detailed description of all stationary points is presented, and the conformational behavior of the THF ring is discussed. The overall process is extremely unfavorable in the gas phase, but in high-polarity solvents it takes place very readily. Comparison of relative energies indicates that the reactant complex → ion pair conversion is accompanied by an energy decrease in the gas phase and in all solvents. Both B3LYP/6-31+G ** and MPW1K/6-31+G ** activation barriers suggest that reaction 1 proceeds faster than 2 both in the gas phase and in solution. The activation barriers found in solution are lower than those in the gas phase by about 5–10 kcal mol −1 .