Single step mechanism for nucleophilic substitution of 2,3-dichloro naphthoquinone using nitrogen, oxygen and sulfur nucleophiles: A DFT approach

Abstract The reactivity of 2,3-dichoro-1,4-naphthoquinone with difunctional nucleophiles (2-mercaptoethanol, 1,2-ethanedithiol, 2-aminoethanol and ethylene glycol) was investigated in mild conditions. Using DFT calculations (B3LYP/6–31++G(d,p) and M11/6–31++G(d,p)), we identified intramolecular interactions in the 2-(substituted)-3-chloro-1,4-naphthoquinone derivatives, which modify the electrophilicity and reactivity of the monosubstituted species, allowing the occurrence of a second nucleophilic attack. Formation of intramolecular hydrogen bonds between the terminal group of the substituent chain and the carbonyl group in the naphthoquinone increases the electrophilicity of the substitution sites of the quinone core, resulting in lower energy barriers for this process. Furthermore, transition state structures and Intrinsic Reaction Coordinate (IRC) calculations showed that the substitution reactions may occur in a single step process, without a tetrahedral intermediate.