Análise conformacional do 3-terc-butoxicicloexanol e 3-terc-butoxi-a-metoxicicloexano

Abstract

Conformational analysis is a fundamental tool to investigate molecular stability and the factors responsible for it. Steric repulsion is a destabilizing effect and exists because of the electronic repulsion among occupied orbitals close to each other. The hyperconjugative effect usually stabilizes the structure and it is a consequence of the electronic delocalization caused by the interaction of an occupied orbital and an unoccupied orbital. In order to analyze these effects in 3-tert-butoxy-cyclohexanol (1) and 3-tert-butoxy-1-methoxycyclohexane (2), their conformational preferences were determined by means of theoretical calculations using the level of theory LC-wPBE/6- 311+G(d,p). The interactions responsible for the preferences of 1 and 2 were analyzed using natural bond orbitals (NBO) and quantum theory of atoms in molecules (QTAIM). Experimental techniques were also used to analyze compound 1, which is reported by the first time to the best of our knowledge by reaction of 1,3-cyclohexanediol with tertbutyl chloride in a media containing triethylamine. For compound 1, the intramolecular hydrogen bond (IAHB) was confirmed by IR and the solvent effect on the conformational preference was evaluated by 1 H NMR. The theoretical level LCwPBE/6-311+G(d,p) was determined through a calibration study using 1,3- propanediol, a simpler compound but similar to 1 and 2 molecules which allowed us to test the accuracy and calculation time required for different DFT functional and basis sets, comparing their results to CCSD/aug-cc-pVTZ. The results of the conformational study for compound 1 show that the axial-axial (aa) conformer is more stable than the equatorial-equatorial (ee) one. Also, the sum of the thermal populations of aa rotamers is 98%, indicating its predominance. It is confirmed that aa higher occurrence is due to the stabilization provided by the intramolecular hydrogen bond (IAHB) and its energetic compensation towards the 1,3-diaxial steric effect. The IR spectra of 1 shows both the OH stretch of the free OH and the bonded OH involved in the IAHB. The red shift between these frequencies is 116 ±1 cm-1. The 1 H NMR study was conducted by measuring the 3 JHH of the molecule in several solvents with distinct basicity. The variety of 3 JHH values obtained expressed the competition of IAHB and intermolecular hydrogen bonds among the compound and molecules of the solvent. Therefore, higher basicity solvents favor the ee conformers. For instance, the aa molar fraction for 1 in CDCl3 obtained is 0.63 while in pyridine it is 0.17. About compound 2, absent of IAHB, higher stability is observed for the ee conformer because of the smaller steric repulsion when compared to aa, as showed in NBO. The thermal population of the ee conformers in the conformational equilibrium is 96% for this compound.