On the origin of the regioselective hydrolysis of a naphthoquinone diacetate: a molecular orbital study

Abstract

A seletividade observada (Nunes, R.L.; Bieber, L.W.; Longo, R.L. J. Nat. Prod. 1999, 62, 1600) na reação de hidrólise do diacetato de 2,5-dimetil-1,4-naftoidroquinona em condições reacionais brandas, meio básico, e que favorece a hidrólise do grupo 4-acetato, foi investigada utilizando métodos de ab initio e semiempíricos. Em fase gasosa (sistemas isolados) estes métodos não forneceram resultados consistentes com a seletividade observada. Com a inclusão dos efeitos do solvente (água) através do modelo de solvatação discreta no método semi-empírico AM1, foi possível estabelecer a estabilidade relativa dos intermediários tetraédricos e dos seus respectivos estados de transição como sendo a responsável pela seletividade observada. A origem da estabilidade relativa, e portanto, da seletividade está relacionada com as interação repulsivas entre o grupo substituinte 2-metil no anel do naftaleno e a metila do grupo 4-acetado, assim como o impedimento destes grupos à hidratação do grupamento iônico dos intermediários tetraédricos.The regioselectivity found in the mild basic hydrolysis of the 2,5-dimethyl-1,4-naphthohydroquinone diacetate (Nunes, R.L.; Bieber, L.W.; Longo, R.L. J. Nat. Prod. 1999, 62, 1600) has been studied with ab initio and semiempirical molecular orbital methods. In the gas phase (isolated systems), these methods were not able to provide results that could explain the observed selectivity. However, when the solvent effects were included in the AM1 method using the discrete solvation model it was possible to establish that this selectivity is due to the relative stability of the tetrahedral intermediates and their transitions states. The origin of this relative stability and thus of the observed selectivity is due to the repulsive interactions between the 2-methyl substituent in the naphthalene ring and the methyl group in the 4-acetate substituent, as well as their hindrance towards the hydration of the ionic group in the tetrahedral intermediates.

The role of nonelectrostatic solvation to chemical reactions in liquid phase

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14] Usually, the electrostatic solute-solvent interaction is the most important contribution of the solvent to the free energy of solvation ( G el ), mainly in polar media and in situations where ionic species are involved. The nonelectrostatic contribution ( G nel ) is regarded as playing a minor role, but it is important for a fine turning of the solvation process modeling.…”

Free Energy Profile of the Reaction between the Hydroxide Ion and Ethyl Acetate in Aqueous and Dimethyl Sulfoxide Solutions: A Theoretical Analysis of the Changes Induced by the Solvent on the Different Reaction Pathways

“…Theoretical studies dealing with the basic hydrolysis of esters both in the gas phase and in aqueous solution have been reported in the literature. [5][6][7][8][9][10][22][23][24][25] Jorgensen pioneered the study of the gas phase reaction of the hydroxide ion with methyl formate that resulted in a careful analysis of the reaction pathways. 25 Subsequent theoretical studies mainly emphasized the B AC 2 and S N 2 mechanisms for different esters.…”

“…This is a representative system and can provide us with quantitative insights on the activation barriers and the thermodynamic stabilities of the different reaction pathways and products. Theoretical studies dealing with the basic hydrolysis of esters both in the gas phase and in aqueous solution have been reported in the literature. − ,− Jorgensen pioneered the study of the gas phase reaction of the hydroxide ion with methyl formate that resulted in a careful analysis of the reaction pathways . Subsequent theoretical studies mainly emphasized the B AC 2 and S N 2 mechanisms for different esters. − , However, recently, an extensive study of the reaction pathways of the basic hydrolysis of methyl formate both in the gas phase and in aqueous solution was reported by Pliego and Riveros. , In that work, the authors used a hybrid discrete/continuum approach to solvation , in order to calculate the free energy profile for the reaction in aqueous solution.…”

AGOA: A Hydration Procedure and Its Application to the 1-Phenyl-beta-Carboline Molecule

“…The most appropriate positions are obtained from statistical mechanics simulations 7 , that are not only very demanding, but also require the solutesolvent and the solvent-solvent interaction potentials, which are quite cumbersome to be obtained. Another approach [8][9] consists in positioning the solvent molecules randomly around the solute and then use an optimization procedure to obtain the structure corresponding to the energy minimum. This procedure in addition to be very computationally demanding, is also highly dependent upon the starting structure, since the solute-solvent energy potential surface presents a large number of local minima.…”