Control of Calix[6]arene Conformations by Self-Inclusion of 1,3,5-Tri-O-alkyl Substituents: Synthesis and NMR Studies

Hexa-O-alkylated p-tert-butylcalix[6]arenes with an alternate 1,3,5-R(1)-2,4,6-R(2)-substitution pattern have been prepared and studied by NMR spectroscopy. When R(1) = CH3 and R(2) is a bulky substituent, the calix[6]arene moiety adopts predominantly a flattened cone conformation. At room temperature this conformation slowly interconverts with a 1,2,3-alternate conformation (Delta G(double dagger) = 70-88 kJ mol(-1), T = 328 K, CDCl3). The Gibbs free energy between these two conformations at T = 303 K in CDCl3 varies from 2 to 7 kJ mol(-1). From quantitative NOE data (obtained for 1,3,5-trimethoxy-2,4,6-tris[(3-nitrobenzyl)oxyl-p-tert-butylcalix[6]arene (10) three-dimensional structures of the flattened cone and the 1,2,3-alternate conformers were calculated. In both conformers the methoxy groups are accommodated in the annulus of the calix [6] arene skeleton, indicating specific interactions with the aromatic calixarene moiety. Compared to the hexasubstituted analogues, this structural feature slightly increases the activation Gibbs free energy for the interconversion process (13-21 kJ mol(-1)). Even with substituents that are too large to rotate through the annulus, there is still slow interconversion (Delta G(double dagger) = 88 kJ mol(-1), T = 328 K, CDCl3). This is attributed to a very slow transannular motion of the p-tert-butyl moiety. Also the ethoxy (16) or propoxy (17) derivatives of 2,4,6-tris(N,N-diethylacetamido)-p-tert-butylcalix[6]arene predominantly adopt flattened cone (16) and 1,2,3-alternate (17) conformations, respectively. The self-inclusion of the larger alkyl groups also contributes to the overall conformational freezing of the p-tert-butylcalix[6]arenes