Conformations and Structures of Tetra- O -alkyl-p-tert -butylcalix[4]arenes. How Is the Conformation of Calix[4]arenes Immobilized?

p-tert-Butylcalix[4]arene (1H ₄ ) was tetra-O-alkylated with alkyl halogens (RX: R = Me, Et, n-Pr, and n-Bu) in the presence of NaH as base, and the products (1R ₄ ) were analyzed by HPLC and ¹ H NMR spectroscopy. It was found that (i) ring inversion is suppressed by R greater than Et, (ii) the final conformer distribution in 1Pr ₄ and 1Bu ₄ , is governed by the kinetic control, the main products being “cone” and “partial cone” (approximately in a 1:1 ratio), (iii) 1Me ₄ mostly exists as a thermodynamically stable partial-cone conformer, and (iv) 1Et ₄ shows an intermediary behavior between 1Me ₄ and 1Pr ₄ : it mostly exists as a partial-cone conformer but slowly isomerizes to a “1,2-alternate” conformer at high temperature. The X-ray crystallographic analysis of partial-cone-1Et ₄ was investigated. To clarify where and how the conformation of 1R ₄ is immobilized, we alkylated 1H ₄ in a stepwise manner. It was shown that when NaH is used as base, the conformation of 1Et ₄ is determined at the fourth ethylation step (1HEt ₃ → 1Et ₄ ), whereas the conformation of 1Pr ₄ is determined at the third propylation step (1H ₂ PR ₂ →1HPr ₃ ). The conformer distribution was significantly affected by alkali and alkaline earth metal cations used as base; in particular, it is worthy of mentioning that (i) when Cs ₂ CO ₃ is used as base, 1,2-alternate- 1Pr ₄ is formed in addition to partial-cone-1Pr ₄ and (ii) when Ba(OH) ₂ is used as base, cone-1Pr ₄ is yielded in 100% selectivity. On the basis of these studies, we discuss how the conformation of calix[4]arenes is immobilized.