Cai Lisheng, Xu Rong, Guo Xuelei, Pike Victor W
Molecular Imaging Branch, National Institute of Mental Health, National Institutes of Health, 10 Center Drive, Building 10, Room B3 C346A, Bethesda MD 20892, USA.
European J Org Chem. 2012 Mar;2012(7):1303-1310. doi: 10.1002/ejoc.201101499.
[C]Methyl iodide is the most widely used reagent for labeling radiotracers with carbon-11 ( = 20.4 min) for molecular imaging with positron emission tomography. However, some substrates for labeling, especially primary arylamines and pyrroles, are sluggishly reactive towards [C]methyl iodide. We found that insoluble inorganic bases, especially LiN or LiO, are effective in promoting rapid reactions (≤ 10 min) of such substrates with no-carrier-added [C]methyl iodide in DMF at room temperature to give C-methylated products in useful radiochemical yields. In particular, we discovered that some primary arylamines in LiN-DMF were converted into their formanilides, and that these were readily -methylated with [C]methyl iodide, preceding easy basic hydrolysis to the desired [C]-methyl secondary arylamines. Use of a solid base permitted selective reaction at an arylamino group and in some cases also avoided undesirable side reaction, such as ester group hydrolysis. An ultrasound device proved useful to provide remote and constant agitation of the radioactive heterogeneous reaction mixtures, but imparted no 'ultrasound-specific' chemical effect.
[C]碘甲烷是用于用碳-11（半衰期 = 20.4分钟）标记放射性示踪剂以进行正电子发射断层扫描分子成像的最广泛使用的试剂。然而，一些用于标记的底物，特别是伯芳胺和吡咯，对[C]碘甲烷的反应活性较低。我们发现不溶性无机碱，特别是LiN或LiO，可有效地促进此类底物在室温下于N，N-二甲基甲酰胺（DMF）中与无载体添加的[C]碘甲烷快速反应（≤10分钟），以有用的放射化学产率得到C-甲基化产物。特别地，我们发现LiN-DMF中的一些伯芳胺转化为它们的甲酰苯胺，并且这些甲酰苯胺很容易用[C]碘甲烷进行N-甲基化，随后易于碱性水解得到所需的[C]-甲基仲芳胺。使用固体碱可使芳氨基发生选择性反应，并且在某些情况下还避免了不希望的副反应，如酯基水解。事实证明，超声装置可有效地对放射性多相反应混合物进行远程和持续搅拌，但不会产生“超声特异性”化学效应。
