Conformational isomerism of 3-isopropyl-1,3-dioxane

Abstract

The interest in the structure of 1,3-dioxanes is related both to unique features of these compounds and their use as reagents in fine organic synthesis [1][2][3]. The potential energy surfaces of unsubstituted dioxane and 2-methyl-1,3-dioxanes contain chair (C) (or equatorial (Ce) and axial chair conformers (Ca) for monosubstituted dioxanes) as well as flexible 1,4-twist (1,4-T) and 2,5-twist (2,5-T) forms as local minima. In the present work, we have carried out the first study of the conformational isomerization of 5-isopropyl-1,3-dioxane using the HyperChem program package [9] with nonempirical RHF//STO-3G and 6-31G(d) quantum-chemical approximations.The 1 H NMR spectral data indicate that the conformational equilibrium of these molecules at room temperature is shifted toward the Ce form [2]. O O O O Ce Ca i-Pr i-Pr ∆G 0 = 0.98-1.10 kcal/molThe present results indicate two pathways for the Ce → Ca conformational isomerization analogous to those observed for unsubstituted dioxane and 2-methyl-1,3-dioxanes [4][5][6]. In this case, conformational equilibrium is possible both between the chair and twist forms and between the two flexible forms. The major minimum corresponds to the Ce conformer. Thus, the potential energy surface of the compound studied contains the same minima as for 2-methyl-1,3-dioxane [6]. However, the difference in energy between the Ce and Ca forms in the case of the 5-isopropyl analog is significantly less. This difference using the 6-31G(d) basis corresponds to the experimental ∆G 0 value [2]. The most labile minimum in all cases corresponds to the 1,4-T conformer.

Conformational analysis of 1,3-oxathiane

“…The established transition states including two semichair forms (TS-1 and TS-4) and also slightly distorted symmetric (TS-2) and unsymmetrical (TS-3 and TS-5) boats were previously found in 1,3-dioxane [23][24][25][26][27][28][29] and 1,3-dithiane [33,34]. The maximum value of the calculated activation barrier (ΔG ≠ ) is 11.2 kcal mol -1 (PBE/3z, TS-1) exceeding the data of lowtemperature NMR experiment (9.3 kcal mol -1 ) [48].…”

“…The most labile of the conformers corresponding to minimum points on the potential energy surface within the frames of all the calculated approximations is the 1,4-T (1,4-T inv ) form. This peculiarity typical also for non-substituted [23,24], 2-, 5-, and 2,5-disubstituted 1,3-dioxanes [25][26][27][28][29], non-substituted 1,3-dithiane [33,34], 1,3,2-dioxathian-2,2-dioxide [45], complexes of 2-methyl-and 2,5-dimethyl-1,3,2-dioxaborinanes with hydroxyl anions [46,47] is probably the most general characteristic of the conformational properties of symmetrically substituted six-membered 1,3-and 1,3,2-heterocyclic compounds. Besides, all conformational chair-flexible form transformations are characterized by positive changes in entropy ΔS which is observed also for 1,3-dioxane [23] and 1,3-dithiane [33].…”

“…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].…”

“…Recently it was shown by computer simulation that for 1,3-oxathianes the unusual direct chair-chair inversion takes place avoiding the intermediate flexible forms [38,39]. Such direction of conformational isomerization is absent in the series of 1,3-dioxanes and 1,3-dithianes [24][25][26][27][28][29][30][31][32][33][34], but it is possible for 1,3-dioxa-2-sila- [40] and 2-germacyclohexanes [41]. In this study carried out by means of nonempiric HF/6-31G(d), MP2/6-31G(d)/HF/6-31G(d) approximations and density functional PBE/3z methods within the frame of HyperChem [42] and PRIRODA [43] complexes of programs all possible conforma-tional transformations of unsubstituted 1,3-oxathiane I were revealed.…”

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

“…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.…”