Conformational analysis of 5-substituted 1,3-dioxanes

Abstract

Quantum-chemical study on the potential energy surface of 5-alkyl-and 5-phenyl-1,3-dioxanes at the RHF/6-31G(d) level of theory revealed two pathways for conformational isomerizations of the equatorial and axial chair conformers. Potential barriers to this process were estimated. The Gibbs conformational energies ∆G° of substituents at C 5 in the 1,3-dioxane ring were determined on the basis of experimental ( 1 H NMR) and theoretical vicinal coupling constants, which turned out to be consistent with published data. I, R = Et; II, R = i-Pr; III, R = t-Bu; IV, R = Ph.Interest in structural studies on 1,3-dioxanes is determined by specificities of their structure and the use of these compounds as reagents in fine organic synthesis [1-3]. The main attention was generally given to stereoisomeric acetals: the structure of individual cis and trans isomers, as well as parameters of configurational equilibrium were studied with a view to estimate the Gibbs conformational energy of substituents [2, 4-6]. On the other hand, cyclic formaldehyde acetals are characterized by greater conformational mobility and are very convenient models for studying the effect of heteroatoms on conformational parameters of cyclohexane heteroanalogs [7]. Computer simulation in terms of nonempirical quantum-chemical calculations previously showed that the global minimum on the potential energy surface (PES) of unsubstituted 1,3-dioxane [8,9], as well as of 2-methyl-[10], 4-methyl-[11], 4-phenyl-[12], 5-methyl-[13], and 5-isopropyl-1,3-dioxanes [14], corresponds to chair (C) or equatorial chair conformer (C eq ). Local minima are occupied by axial chair (C ax ), 1,4-twist (1,4-T), and 2,5-twist conformers (2,5-T), while halfchair, sofa, and unsymmetrical boat conformers give rise to maxima on the potential energy surface. According to the data of microwave spectroscopy, the carbon fragment in 5-methyl-1,3-dioxane is more flattened than the heteroatom-containing fragment of the ring [15]. In the present work we studied probable paths for conformational isomerization of 5-alkyland 5-phenyl-1,3-dioxanes I-IV in terms of the RHF/6-31G(d) quantum-chemical approximation using HyperChem software [16]. According to the 1 H NMR data, conformational equilibrium of compounds I-IV at room temperature is displaced toward C eq conformer (Scheme 1) [2]. Scheme 1.We have revealed general pattern of conformational transformations and localized intermediate minima and maxima on the PESs of dioxanes I-IV. The results of calculations suggest two paths for the conformational isomerization C eq ↔ C ax , which are analogous to those found previously for unsubstituted 1,3-dioxane, as well as for 2-methyl-, 5-methyl-, and 5-isopropyl-1,3-dioxanes [9,10,13,14]. In all cases, the global minimum corresponds to equatorial chair conformer (C eq ), while conformer 1,4-T has the highest energy (Table 1). Increase in the conformational volume of the R substituent (I < II < III) is accompanied by increase in the energy difference (∆E) between conformers C eq and C ax , as well as...

Computer simulation of conformational transformations of 1,3-dioxanes and their 2-sila and 2-bora analogs

“…According to the MP2/6-31G(d)//HF/6-31G(d) calculations, the C eq and C ax conformers of III are degenerate in energy. The transition states correspond to half-chair and symmetrical and unsymmetrical boat conformers [20,22]. The obtained data indicated that the concentration of flexible conformers is quite small, and the conformational behavior of dioxanes III-VII may be represented fairly accurately as the binary equilibrium between C eq and C ax .…”

“…Conformational inversion of 5-substituted 1,3-dioxanes III-VII also involves equilibrium between two non-degenerate chair conformers through intermediate minima 2,5-T and 1,4-T (not including enantiomeric structures) [20][21][22] (Scheme 5). In all cases, the global minimum is occupied by C eq , and conformer 1,4-T has the highest energy.…”

“…The ∆G° values determined by different methods showed a satisfactory agreement with each other with account taken of no correction made for solvent effect. On the other hand, accurate experimental determination of coupling constants is important, as follows from the ∆G° values for compounds IV and VI [22].…”

“…It was impossible to estimate the free conformational energy for dioxane V because of the lack of the corresponding 1 H NMR data. For other dioxanes, experimental coupling constants from different sources were used [22,[27][28][29][30] (Table 1). The ∆G° values determined by different methods showed a satisfactory agreement with each other with account taken of no correction made for solvent effect.…”

Conformational analysis of 1,3-oxathiane

“…With the help of non-empiric quantum-chemical approximations the evaluation of stereoelectronic interactions was obtained and the presence of homoanomeric effects in the 1,3-oxathiane ring was established [20,21]. But unlike cyclohexane [22], 1,3-dioxanes [22][23][24][25][26][27][28][29][30][31][32], and 1,3-dithiane [33, 34], pathways of conformational isomerization of 1,3-oxathiane molecules were not considered. In the majority of cases "chair-chair" inversion was postulated [6,[9][10][11][12][13], and in some cases the participation of flexible forms was suggested [14][15][16]18].…”