A Simple and Convenient Strategy for the Synthesis of Novel Ten, Twelve, and Fourteen‐membered Phosphorus Macrocyclic Compounds

Abstract

Synthesis of the title compounds 4(a–i) was accomplished through a two‐step process. The synthetic route involves the cyclization of equimolar quantities of 2,2′‐methylene(methyl)bis(4,6‐di‐tert‐butyl‐phenol) (1) with tris‐(2‐chloro‐ethyl) phosphite (2a), tris‐(2‐bromo‐ethyl) phosphine (2b), and tris‐bromo methyl phosphine (2c) in the presence of sodium hydride in dry tetrahydrofuran at 45–50°C. They were further converted to the corresponding oxides, sulfides, and selenides under N2 atmosphere by reacting them with hydrogen peroxide, sulfur, and selenium, respectively (4a–c, 4d–f, and 4g–i). But the compounds 6a,b were prepared by the direct cyclocondensation of equimolar quantities of 1 with (2‐chloro‐ethyl)‐phosphonic acid dibromomethyl ester (5a) and (2‐chloro‐ethyl)‐phosphonic acid bis(2‐bromo‐ethyl) ester (5b) in the presence of sodium hydride in dry tetrahydrofuran at 45–50°C in moderate yields. All the newly synthesized compounds 4(a–i) and 6(a–b) exhibited moderate in vitro antibacterial and antifungal activities.