Synthesis of Polyhalogenated 4,4′-Bipyridines via a Simple Dimerization Procedure

Polyhalogenated 4,4′-bipyridines were conveniently synthesized in a single step starting from dihalopyridines. A mechanism was proposed on the basis of experiments performed with 2-chloro-5-bromopyridine 1a. 2-Chloro-4-lithio-5-bromopyridine A1 was produced via ortholithiation of 1a by using either LDA or t-BuLi bases. When LDA was used, dimer 3a containing two chlorines and two bromine atoms was formed predominantly accompanied by several byproducts whose structure and mechanism of formation are discussed. In the case of t-BuLi, although the major product was 2-chloropyridine 7, a new pyridone product 8 was formed that is probably the result of the dihydropyridine intermediate hydrolysis. The dimerization procedure involving LDA was employed to prepare a large number of halogenated 4,4′-bipyridines in moderate to good yields. In some specific cases, halogenated 3,4′ and 2,4′-bipyridines were obtained in lower yields and their structures were unambiguously assigned by X-ray diffraction analysis.

多卤代4,4′-联吡啶可由二卤代吡啶为起始原料，通过一步法便捷合成。基于以2-氯-5-溴吡啶（1a）开展的实验，研究人员提出了该反应的机理。以二异丙基氨基锂（Lithium Diisopropylamide, LDA）或叔丁基锂（tert-butyllithium, t-BuLi）为碱，对1a进行邻位锂化，可得到中间体2-氯-4-锂-5-溴吡啶（A1）。当使用LDA时，反应主要生成含两个氯原子与两个溴原子的二聚体3a，同时伴随多种副产物，本文对这些副产物的结构及生成机理进行了讨论。若采用t-BuLi作为碱，尽管主要产物为2-氯吡啶（7），但同时生成了一种新型吡啶酮产物8，其可能源自二氢吡啶中间体的水解反应。研究人员采用基于LDA的二聚化方法，制备了大量卤代4,4′-联吡啶，产物收率可达中等至良好水平。在部分特定案例中，研究人员以较低收率得到了卤代3,4′-及2,4′-联吡啶，并通过X射线衍射分析（X-ray diffraction analysis）对其结构进行了明确确证。