The use tetrabutylammonium fluoride to promote N- and O-11C-methylation reactions with iodo[11C]methane in DMSO
The use tetrabutylammonium fluoride to promote N- and O-11C-methylation reactions with iodo[11C]methane in DMSO
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使用四丁基氟化铵促进DMSO中碘[11C]甲烷的N-和O-11C-甲基化反应
DOI：
10.1002/jlcr.3092
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发表时间：
2013
期刊：
影响因子：
--
通讯作者：
Kato K
中科院分区：
文献类型：
--
作者：
Kikuchi T;Minegishi K;Hashimoto H;Zhang MR;Kato K
带有酰胺、苯胺或苯酚部分的化合物在碱的帮助下使用碘[11 C]甲烷（1）的N-或O-甲基化反应经常用于制备11 C标记的放射性药物。虽然氢化钠和碱金属氢氧化物通常用作这些反应中的碱，但它们在有机溶剂中的溶解性和水解活性较差，有时限制了它们的应用，并使相关的11 C-甲基化反应变得困难。与这些碱相反，四丁基氟化铵（TBAF）是中等碱性的，高度溶于有机溶剂，并且弱亲核性。尽管人们设想TBAF可以用作使用1的11 C-甲基化反应的优选碱，但关于使用TBAF促进11 C-甲基化反应的研究很少。在此，我们评估了13种模型化合物使用TBAF和1.在大多数情况下，N-11 C-甲基化在室温下通过TBAF在二甲基亚砜中有效地促进，而O-11 C-甲基化在某些情况下需要加热。比较研究表明，TBAF的11 C-甲基化反应的效率与氢化钠相当，有时甚至更高。基于这些结果，TBAF应该被认为是使用1的11 C-甲基化反应的优选碱。
TheN‐ orO‐methylation reactions of compounds bearing amide, aniline, or phenol moieties using iodo[11C]methane (1) with the aid of a base are frequently applied to the preparation of11C‐labeled radiopharmaceuticals. Although sodium hydride and alkaline metal hydroxides are commonly employed as bases in these reactions, their poor solubility properties in organic solvents and hydrolytic activities have sometimes limited their application and made the associated11C‐methylation reactions difficult. In contrast to these bases, tetrabutylammonium fluoride (TBAF) is moderately basic, highly soluble in organic solvents, and weakly nucleophilic. Although it was envisaged that TBAF could be used as the preferred base for11C‐methylation reactions using 1, studies concerning the use of TBAF to promote11C‐methylation reactions are scarce. Herein, we have evaluated the efficiency of the11C‐methylation reactions of 13 model compounds using TBAF and 1. In most cases, theN‐11C‐methylations were efficiently promoted by TBAF in dimethyl sulfoxide at ambient temperature, whereas theO‐11C‐methylations required heating in some cases. Comparison studies revealed that the efficiencies of the11C‐methylation reactions with TBAF were comparable or sometimes greater than those conducted with sodium hydride. Based on these results, TBAF should be considered as the preferred base for11C‐methylation reactions using 1.