Structure and conformation of heterocycles. Part VI. The cis-1,4,5,8-tetraoxadecalin (hexahydro-p-dioxino [2,3-b]-p-dioxin) system: A chemical, conformational, and crystallographic study

The title system (1) (a, b, c: R = H, CH₂Br, or Me respectively) is subject of a multilateral investigation. cis-9,10-Bisbromomethyl-1,4,5,8-tetraoxadecalin (4a,8a-bisbromomethylhexahydro-p-dioxino[2,3-b]-p-dioxin) (1b) was obtained along with its bi(dioxolan-2-yl) isomer (2b) from the acid-catalysed condensation of 1,4-dibromobutane-2,3-dione with ethylene glycol. Chemical correlation between derivatives in both series, viz. (1b→ 1c) and (2b) → (2c), was achieved. Dynamic conformational analysis in solution was performed in a variable-temperature n.m.r. study of the octadeuteriated derivative, [²H₈]-(1b), which was found to exist in solution as an inverting system with ΔG‡₂₂₆ 11.2 kcal mol^-1, ΔH‡ 9.0 ± 0.9 kcal mol^-1 and ΔS‡ - 9 ± 4 e.u. Three-dimensional X-ray studies of (1a) and (1b) proved these tetraoxadecalins to be cis and to adopt a double-chair conformation. The crystal and molecular structure of (1a), analysed in greater detail [space group C2/c, Monoclinic, a = 16.003(1), b = 7.077(1), c = 11.654(1) Å, β = 92.81°, Z = 8], was solved by direct methods and was refined anisotropically by a full-matrix least-squares method to R = 0.07. The mean standard deviation of the co-ordinates of C, O, and H atoms are 0.004, 0.003, and 0.04 Å respectively. Departures from the ideal chair-chair geometry were found which did not disturb the C₂ molecular symmetry. The mean C-O distances along the C-O(1)(ax)-C-O(8)(eq)-C moiety of cis-1,4,5,8-tetraoxadecalin (1a) are 1.441. 1.429, 1.408, and 1.446 Å and the corresponding mean bond angles are C-O(8)-C 113.3° and C-O(1)-C 109.9°. These results are discussed in terms of the influence of intramolecular interactions on the conformation of (1a) and on the inversion parameters of (1b) with particular reference to the anomeric effect. The system appears to be a unique example of two adjacent anomeric moieties incorporated in a bicyclic system with C₂ symmetry.