B. Shen et al.
O
(Ph3P)3RhCl
-CO
(Ph3P)3RhCl
-CO
18F
18F
18F
O
O
O
CH3
CH3
CH3
O
O
D
B
A
(Ph3P)3RhCl
-CO
(Ph3P)3RhCl
-CO
O
18F
O
CH3
C
Figure 5. Two possible pathways of the decarbonylation reaction.
clearly separated. In Figure 6 the data clearly show that the
more sterically hindered formyl group is removed faster than the
other one.
100
Radioactivity on the baseline of the TLC
90
80
70
60
50
40
30
20
10
0
2-[18F]Fluoro-4-methoxyisophthalaldehyde (A)
2-[18F]Fluoro-6-methoxybenzaldehyde (B)
2-[18F]Fluoro-4-methoxybenzaldehyde (C)
1-[18F]Fluoro-3-methoxybenzene (D)
Conclusion
For the nucleophilic aromatic fluorination of o,o- and
o,p-diformylated nitro- and halogenarenes by [18F]fluoride good
radiochemical yields were found between 79 and 86%.
Compared with o- or p-formyl-substituted nitro- and halogenar-
enes, the reaction proceeded faster and often in better yields
even at room temperature. The formyl groups can efficiently be
removed by decarbonylation with Wilkinson’s catalyst. More-
over, the results of compounds (o) indicate the applicability of
SNAr to be particularly promising for a synthesis of 18F-tyrosine.
0
5
10
15
20
25
30
Time / min
References
Figure 6. Conversion of 2-[18F]fluoro-4-methoxyisophthalaldehyde in the dec-
arbonylation (1201C, 3 eq. catalyst).
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Decarbonylation
The application of two formyl groups is obviously an advantage
for performing nucleophilic aromatic substitutions at low
temperatures with short reaction times in high labelling yields.
A prerequisite, however, is the fast and efficient removal of the
two aldehydic groups from the 18F-labelled product. As shown
in Figure 4 decarbonylation was efficiently performed within
20 min both for 2-[18F]fluoro-5-methoxyisophthalaldehyde and
4-[18F]fluoro-2-methoxy-5-methylisophthalaldehyde, when at
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intermediates and the product of the reaction were monitored
by radio-TLC because the Rf-values differed so much to be
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¨
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¨
¨
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Copyright r 2010 John Wiley & Sons, Ltd.