White Vivienne A, Long Nicholas J, Robertson Neil
Department of Chemistry, Imperial College of Science Technology and Medicine, South Kensington, London, UK SW7 2AY.
Org Biomol Chem. 2005 Dec 7;3(23):4268-73. doi: 10.1039/b510734b. Epub 2005 Nov 2.
A series of new N4 and N8 macrocycles has been prepared, that includes cis-exogenous O2, S2 and S/O atoms to allow chelation to a metal external to the macrocyclic ring. We found that thioamide units within the macrocycles were unstable to attack by secondary amines and thus alkylated precursors containing only tertiary amines could lead to exogenous-S2 macrocycles. Cyclisation of alkylated tetraamine precursors with dimethyloxalate or dithiooxamide led to both N4 and N8 macrocycles via 1 + 1 and 2 + 2 cyclisation reactions with exogenous-O2 or S2 respectively. Alkylation of preformed exogenous-O2 macrocycles was explored and led to alkyl substitution at the secondary amine nitrogens in the ring, however synthesis of these species was overall lower yielding than cyclisation using alkylated tetraamine precursors. Thionation of an exo-O2 macrocycle using an analogue of Lawesson's Reagent led to formation of the analogous exogenous-S2 and exogenous-O,S macrocycles. Related S2N2 macrocycles with exogenous-O2 were prepared by a cyclisation route but could not be isolated free of larger ring analogues.
已经制备了一系列新的N4和N8大环化合物，其中包括顺式外源O2、S2和S/O原子，以便与大环环外的金属进行螯合。我们发现大环内的硫代酰胺单元对仲胺的攻击不稳定，因此仅含叔胺的烷基化前体可生成外源-S2大环化合物。用草酸二甲酯或二硫代草酰胺将烷基化四胺前体环化，分别通过与外源-O2或S2的1 + 1和2 + 2环化反应生成N4和N8大环化合物。对预先形成的外源-O2大环化合物的烷基化进行了探索，导致环中仲胺氮处发生烷基取代，然而这些化合物的合成总体产率低于使用烷基化四胺前体进行环化的产率。使用劳森试剂的类似物对外源-O2大环化合物进行硫代反应，导致形成类似的外源-S2和外源-O,S大环化合物。具有外源-O2的相关S2N2大环化合物通过环化路线制备，但无法分离出不含较大环类似物的产物。
