Intraannular functionalization of the 1,3-phenylene-19-crown-6 system via bromine-lithium exchange

In contrast to the behavior of its lower homologue 1,3-phenylene-16-crown-5 (1), the direct lithiation of 1,3-phenylene-19-crown-6 (2) with n-BuLi at the intruannular position-2 was found to be slow and not quantitative. Ther efore, (2-bromo-1,3phenylene)-19-crown-6 (8) was synthesized by the reactio n of the dicesium salt of 2-bromo-resorcinol (7) with pentaethylene glycol dibromide. The crystal structure of 8 revealed the existence of three chemi cally identical residues in the unit cell; in all cases, the bromine atom s ticks out of the crown ether ring. The bromine-lithium exchange reaction of 8 with n-BuLi to furnish the desired (2-lithio-1,3-phenylene)-19-crown-6 ( 4) was quantitative after 2 h at - 65 degrees C in THF. Derivatization of 4 with deuterium oxide, dimethyl disulfide, iodine, carbon dioxide, mercuric bromide (1 or 0.5 molar equivalents), and magnesium bromide yielded (2-deu terio-1,3-phenylene)-19-crown-6 (2a), (2methylthio-1,3-phenylene)-19-crown- 6 (10), (2-iodo-1,3-phenylene)-19-crown-6 (11), (2-carboxy-1,3-phenylene)-1 9-crown-6 (12), (2-bromomercurio-1,3-phenylene)-19-crown (13), bis[(1,3-phe nylene-19-crown-6)-2-yl]mercury (13), and (2-bromomagnesio-1,3-phenylene)-1 9-crown-6 (15), respectively. The synthesis of the Grignard reagent 15 was also carried out by the direct reaction of 8 with magnesium; contrary to th e corresponding 1,3-xylylene crown ethers, cleavage of the crown ether ring during the formation of 15 was not observed. At room temperature, the solu tion of crude 4 (prepared from 8) gave rise to ether cleavage and to the fo rmation of (2-n-butyl-1,3-phenylene)-19-crown 6 (16). (C) 1999 Elsevier Sci ence S.A. All rights reserved.