Selective O-Alkylation of the Crown Conformer of Tetra(4-hydroxyphenyl)calix[4]resorcinarene to the Corresponding Tetraalkyl Ether

Abstract

Reactions of glycidyl methacrylate with the crown and chair conformers of tetra(4-hydroxyphenyl)calix[4]resorcinarene were studied. The reactions were done over epoxide groups present in the ester, which can easily undergo an opening reaction with hydroxyl groups in the macrocyclic system. Initially, epoxidation reactions were carried out with pure conformers, and it was observed that the reaction between tetra(4-hydroxyphenyl)calix[4]resorcinarene fixed in the chair conformation does not occur, while for the molecule fixed in the crown conformation only one tetraalkylated derivative was obtained. The obtained product was characterized using IR, ¹H-NMR, ¹³C-NMR, COSY, HMQC and HMBC techniques. An exhaustive NMR study showed that the reaction is selective at the hydroxyl groups in the lower rim, without affecting the hydroxyl groups in the upper rim. In addition, the RP-HPLC analysis of the epoxidation reaction mixture, using both crown and chair conformers, showed that only the crown conformer reacted under tested conditions. Finally, a comparative study of the reactivity of tetranonylcalix[4]resorcinarene with glycidyl methacrylate showed that the reaction does not take place. Instead, the formation of the tetranonylcalix[4]resorcinarene tetrasodium salt was observed, which confirms that the hydroxyl groups in the upper rim are unreactive under these conditions.

Keywords: crown conformation; resorcinarene; ring-opening reaction; stereoselective.

Scheme 1

Synthesis of calix[4]resorcinarenes 1a, 1b and 2.

Figure 1

(A) Chromatogram of conformational isomers: crown conformation (1a), t_R = 3.3 min, chair conformation (1b), t_R = 3.8 min. (B) Chromatogram of reaction mixture. (C) Chromatogram of pure product 3, t_R = 5.8 min.

Scheme 2

Reaction of glycidyl methacrylate with calix[4]resorcinarenes 1a, 1b and 2.

Figure 2

Compound 3 carbon and hydrogen assignments.