Conformational consequence of stereoelectronic effects in seven-membered cyclic acetals: nuclear magnetic resonance investigation of 1,3-benzodioxepin and its 2-substituted derivatives

Abstract

. 62, 2830 (1984).The conformational and dynamic properties of 1,3-dioxa-4,5-benzocycloheptene (8) and several 2-substituted derivatives were investigated by 'H and "C low temperature nmr methods. The results are strikingly different from those reported for the analogous symmetrical dioxepin isomers derived from 2. The unexpectedly large preference of the 2-methoxy derivative (8c) for the C, conformation is explained in terms of deformed torsional angles in the seven-membered ring relative to those in the analogous six-membered one. These results therefore help delineate the limitations to the conformational biasing normally associated with the anomeric effect.ROBERT ST-AMOUR, M. T. PHAN VIET et MAURICE ST-JACQUES. Can. J. Chem. 62, 2830 (1984.Les propriCtCs conformationnelles et dynamiques du dioxa-1,3 benzo-4,5 cycloheptene (8) et de quelques dtrivCs en position 2 ont Ct C CtudiCes par les techniques de rmn 'H et I3C a basse tempkrature. Les rtsultats obtenus sont trks difftrents de ceux prCcCdemment rapportCs pour les isombres analogues de la benzodioxtpine symmttrique dtrivts de 2. La grande preference du derive mCthoxy-2 (8c) pour la forme C, est expliquCe par une dtformation des angles de torsion du cycle a sept chainons comparativement aux dCrivCs analogues cycliques 5 six chainons. Ces rCsultats permettent de mieux circonscrirc les consequences conformationnelles associCes a I'effet anomkre.Stereoelectronic effects ( I ) in acetals and related functions have recently brought into focus the important relationship between conformation and reactivity for several classes of molecules. Studies on the simplest acetal, dimethoxymethane (2), indicate that the g t g arrangement is most stable in conformity with observations made on carbohydrates (3) and 2-substituted tetrahydropyrans (4). This preference constitutes the basis of the anomeric and the exo-anomeric effects extensively investigated for these molecules (5). ' The relative stabilities of the various arrangements possible for a -CH2-0-CH2-0-CH?-fragment have been difficult to assess (1) and the need for a quantitative evaluation based on experimental measurements led to the recent investigation (6) of a broader range of stereochemical arrangements as exist in bicyclic acetals such as 1. By comparison, studies of the cyclic acetal 1,3-dioxane are limited because of the relatively high conformational energy of the twist-boat (TB) conformation (7) and the fact that only highly substituted derivatives have been found to exist in this form.The two possible TB forms of 1,3-dioxane (4 and 5) are characterized by -CH2-0-CH2-0-CH2-fragments in the gtgt disposition and slightly deformed gig-disposition respectively. Previous studies (7) could not clearly distinguish experimentally between these forms because they interconvert easily as a result of the low energy barrier for the pseudorotation motion involved, although calculations suggest that 5 is more stable than 4 (7). In contrast, the dioxepins 2 and 3 provided an opportunity (8, 9) to investigate experimenta...

Structural parameters for the chair or twist-boat conformations of 1,3-dioxa-5,6-benzocycloheptene and its 2-methyl and 2,2-dimethyl derivatives

“…As shown by Lambert and Vagenas (14) in carbocyclic rings, the y-effect of a methyl substituent is linearly related to the dihedral angle 0 between the methyl substituent and the y-carbon. A similar linear relationship has already been proposed (2) to explain the y-shift caused by a methyl group at C(2) on the benzylic carbons C(4) and C(7) in 2 . The average value of -2.83 ppm measured for 2 8 does not fit the linear relation, if we assume a symmetrical TB form with torsion angles taken as similar to the values of -67.7" and 170.6" determined for 3B in the solid state (Table 5).…”

“…Although not included in the least-squares planes calculations (in each of the three compounds), atoms C(4) and C(7) are found to be coplanar with the benzo group, which forms plane [I]. Atoms C(7), 0(1), 0(3), and C(4) in the chairs 1 and 2 are also coplanar; they form plane [2]. Plane [3] is the acetal function made up of atoms 0(1), 0(3), and C(2).…”

“…Whereas the presence of a methyl group on the acetal carbon, C(2), slightly stabilizes the C, form,2 2~, (96% at -115°C) (2), the addition of a second methyl on the same carbon destabilizes the C form completely in favor of the TB form, 3B (100%). This '~u t h o r s to whom correspondence may be addressed.…”

Rules for predicting the conformational behavior of saturated seven-membered heterocycles

“…In these cases, dynamic nuclear magnetic resonance has shown to be an appropriate tool in order to assess the most stable conformations and the energetic barriers shown in the equilibrium of such compounds. Several examples of benzene-fused or unsaturated sevenmembered heterocycles with one or two heteroatoms as benzoxepine, [1][2][3] 4,7-dihydro-2H-1,3-dioxepine, 4 or benzodioxepine [5][6][7][8] derivatives have been studied by means of such a technique.…”