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Rapid Room‐Temperature 11 C‐Methylation of Arylamines with [ 11 C]Methyl Iodide Promoted by Solid Inorganic‐Bases in DMF
Author(s) -
Cai Lisheng,
Xu Rong,
Guo Xuelei,
Pike Victor W.
Publication year - 2012
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201101499
Subject(s) - chemistry , methyl iodide , iodide , reagent , hydrolysis , iodine , nuclear chemistry , inorganic chemistry , organic chemistry
[ 11 C]Methyl iodide is the most widely used reagent for labeling radiotracers with carbon‐11 ( t 1/2 = 20.4 min) for molecular imaging with positron emission tomography. However, some substrates for labeling, especially primary arylamines and pyrroles, are sluggishly reactive towards [ 11 C]methyl iodide. We found that insoluble inorganic bases, especially Li 3 N or Li 2 O, effectively promote rapid reactions (≤ 10 min) of such substrates with no‐carrier‐added [ 11 C]methyl iodide in N , N ‐dimethylformamide (DMF) at room temperature to give 11 C‐methylated products in useful radiochemical yields. In particular, we discovered that some primary arylamines in Li 3 N/DMF were converted into their corresponding formanilides, and that these were readily N ‐methylated with [ 11 C]methyl iodide, which preceded easy basic hydrolysis to the desired [ 11 C] N ‐methyl secondary arylamines. The use of a solid base permitted selective reaction at an arylamino group and, in some cases, avoided undesirable side reactions, 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.