Matheus P. Freitas

Interaction in trans-2-halocyclohexanols — an infrared and theoretical study

Abstract The O–H and C–O stretching frequencies of trans -2-halocyclohexanols in CCl 4 solutions have been measured and theoretical calculations have been performed to elucidate the main interactions, which are responsible for the conformational equilibria in these systems. It can be concluded that hydrogen bonding is predominant for trans -2-fluorocyclohexanol, leading to a stabilization of the eq–eq conformation, while for the chlorine, bromine and iodine derivatives, besides hydrogen bonding, gauche and steric interactions are also present.

Halogenated six-membered rings: a theoretical approach for substituent effects in conformational analysis

Abstract Studies on the conformational equilibria of a series of dihalosubstituted cyclohexanes ( I ) and halocyclohexanones ( II ) are reported. Theoretical calculations using the B3LYP method and the 6-311+g(d,p) basis set were applied to determine the energy differences (Δ E ) between the conformers of I and II , as well Δ E between the conformers of monohalocyclohexanes, in order to obtain the intramolecular interaction energies, which govern the conformational equilibria of I and II . It is shown that while the intramolecular interactions for 1,3- and 1,4-disubstituted cyclohexanes, as well as for 3- and 4-halocyclohexanones, are due to classical effects (steric and electrostatic), for the 2-halocyclohexanones it becomes evident that orbital interactions between n halo and π ∗ CO drive the equilibria towards the axial conformers. Moreover, the gauche effect seems to be irrelevant for the trans -1,2-dihalocyclohexane equilibria, opposite to several reports from the literature on other trans -1,2-disubstituted cyclohexanes bearing electronegative substituents.

The utility of infrared spectroscopy for quantitative conformational analysis at a single temperature

The carbonyl stretching vibration of 2-bromocyclohexanone (1) has been measured in a variety of solvents. It is shown that its component intensities are not only dependent on the populations of the axial and equatorial conformers, but are also dependent on the molar absorptivities (epsilon ) which are specific for each conformer in each solvent. In CCl(4), the axial and equatorial conformers have epsilon values of 417 and 818 l mol(-1) x cm(-1), respectively, while in CH(3)CN solution, the values were 664 and 293 l mol(-1) x cm(-1). These results are supported by results of theoretical calculations of frequencies, which gave an intensity of 223.8 kM mol(-1) x(1782 cm(-1)) for the axial and 174.4 kM mol(-1) x (1802 cm(-1)) for the equatorial conformer, indicating that the axial conformer presents a larger molar absorptivity than the equatorial one in the vapor phase. Moreover, the results presented here clearly demonstrate that although infrared spectroscopy at a single temperature can be an important auxiliary technique for conformational analysis, it must not be used to quantify conformational preferences of a molecule if the absorption molar coefficients for each conformer are not known or not amenable to experimental determination.

Conformational analysis of 2-halocyclohexanones: an NMR, theoretical and solvation study

The conformational equilibria of 2-fluoro-, 2-chloro- and 2-iodo-cyclohexanone have been determined in various solvents by measurement of the J2–3 couplings. The observed couplings were analysed using theoretical and solvation calculations to give both the conformer energies in the solvents studied plus the vapour phase energies and the coupling constants in the distinct conformers. These plus previous results for the 2-bromo compound give the conformer energies and couplings of all the 2-halocyclohexanones. In the 2-fluoro compound the axial conformation is the most stable one in the vapour phase (Eeq − Eax = 0.45 kcal mol−1), while the equatorial conformer predominates in all the solvents studied. The other haloketones show similar behaviour, but the energy difference in the vapour phase is larger (Eeq − Eax = 1.05, 1.50 and 1.90 kcal mol−1, for the chloro, bromo and iodo compounds respectively) and the axial conformer is still the prevailing conformer in CCl4 solution for the chloro and bromo ketones and is the major form in all solvents for the iodo compound. The vapour state conformer energies for the fluoro and chloro compounds are in complete agreement with the ab initio calculated energies, but those for the bromo and iodo are not in such good agreement. Both the ab initio calculations and molecular mechanics are used to discuss the origins of the conformer energies. It is shown that the interaction between the C2 halogen and the CO oxygen in the equatorial conformer is strongly attractive for fluorine, much less so for chlorine, ca. zero for bromine and repulsive for iodine. Comparison of the conformer couplings obtained here with calculated values show generally good agreement.

Infrared spectroscopy and theoretical calculations as tools for the conformational analysis of 2-methoxycyclohexanone

The conformational equilibrium of 2-methoxycyclohexanone has been analyzed through infrared spectroscopy and theoretical calculations. These calculations indicate that six conformations may be present in the vapor phase, due to the rotation of the methoxy group around the O-C(2) bond, leading to axial (g(+), g(-) and anti) and equatorial (g(+), g(-) and anti) conformers. However, the infrared spectrum in CCl(4) solution shows just three carbonyl stretching bands, corresponding to the conformers of lower energies. An additional band is observed for the CH(3)CN solution, attributed to a fourth conformer stabilized by a dipole-dipole interaction between this conformer, having a high dipole moment, and the very polar solvent. An interpretation of the governing factors of 2-methoxycyclohexanone equilibria is also given.

Conformational behaviour of methyl 2-fluoroesters through theoretical calculations, NMR and IR spectroscopy

The conformational equilibrium of methyl 2-fluoropropionate (1) was studied through a combination of NMR, theoretical calculations and solvation theory. IR spectroscopy was used as an auxiliary technique for this analysis. The 1JCF couplings were analysed using theoretical and solvation calculations to give conformer energies in the solvents studied, vapour phase energies, and also the coupling constants for the distinct rotamers. The trans rotamer is more stable than the cis rotamer in the vapour phase by 0.4 kcal mol−1 and the conformers are of equal energy in CCl4. The more polar cis form is the major rotamer in the remaining solvents studied. Theoretical evaluation at the B3LYP/6-311++g(d,p) level for the α-alkyl substituent effect was carried out using methyl 2-fluorobutyrate (2), methyl 2-fluoro-tert-butylacetate (3) and methyl 2-fluorophenylacetate (4) as models, and showed the great effect of these substituents on the conformational stabilities. The governing interactions of these systems were rationalised in terms of both classical and non-classical effects, such as steric, electrostatic, O⋯H–C hydrogen bonding, gauche effect and hyperconjugative interactions.

Substituent interactions in trans-2-substituted methoxycyclohexanes: an explanation to the conformational behaviour in a chemometric and theoretical view

Abstract Principal component analysis of theoretical data [B3LYP/6-311+g(d,p)] may predict the main interactions governing the conformational equilibrium of a series of trans -2-substituted methoxycyclohexanes. The classical syn -1,3-diaxial repulsion, as well as the ‘ gauche effect’ for some substituents, explain the preference towards the eq – eq conformation, although dipolar and steric repulsions between the eq – eq substituents is also an important intramolecular interaction present in these systems favouring the ax – ax form. The intramolecular interactions were supported by theoretical variables, such as nuclear repulsion energy, hardness, charges and bond order (obtained from the density matrix of the theoretical calculations), which led to the conformers separation into ax – ax and eq – eq classes.