Synthesis and Highly Selective Bromination of Azacalix[4]pyrimidine Macrocycles

A number of N-substituted azacalix[4]pyrimidines were synthesized by two methods. While straightforward condensation reaction between 4,6-dichloropyrimidine and 4,6-bis(alkylamino)pyrimidines gave identically N-substituted azacalix[4]pyrimidines in low yields, a general and moderate-to-high yielding 1 + 3 macrocyclic fragment coupling reaction afforded azacalix[4]pyrimidines that contained either the same or different N-substituents. Upon treatment with N-bromosuccinimide (NBS) under controlled conditions, methylazacalix[4]pyrimidine was selectively brominated at lower rim to produce mono-, di-, and tribrominated azacalix[4]pyrimidines in good yields. While azacalix[4]pyrimidine derivatives adopted 1,3-alternate conformation in the solid state, the synthesized macrocycles were fluxional in solution, and the interconversion of various conformational structures was rapid relative to the NMR time scale.

多种N-取代的aza-calix[4]嘧啶通过两种方法合成。虽然4,6-二氯嘧啶与4,6-双(烷基氨基)嘧啶之间的简单缩合反应在低产率下产生了相同的N-取代aza-calix[4]嘧啶，但一种通用的、产率中等到高的1+3型宏环片段偶联反应提供了包含相同或不同N取代基的aza-calix[4]嘧啶。在受控条件下用N-溴代丁二酰亚胺(NBS)处理，甲基aza-calix[4]嘧啶在较低的边缘被选择性地溴化，以产生产率良好的单溴化、二溴化和三溴化的aza-calix[4]嘧啶。虽然aza-calix[4]嘧啶衍生物在固态下采用1,3-交替构象，但合成的宏环在溶液中呈流动性，各种构象结构的相互转换相对于NMR时间尺度而言是快速的。