Syntheses of meta-[18F]fluorobenzaldehyde and meta-[ 18F]fluorobenzylbromide from phenyl(3-Formylphenyl) iodonium salt precursors

Article abstract of DOI:10.1002/jlcr.1853

¹⁸F-labeled fluorobenzaldehydes and fluorobenzylbromides are useful synthons for the preparation of positron emission tomography radiopharmaceuticals. Although ortho- and para-[¹⁸F] fluorobenzaldehydes can easily be prepared with high yields, the corresponding meta-derivatives are more problematic. In order to improve the yield of meta-[¹⁸F]fluorobenzaldehyde, we used the corresponding diaryliodonium salt precursors, since diaryliodonium salts had already been used as precursors in the preparations of ¹⁸F-labeled electron-rich, as well as electron-deficient, aromatic rings. Diaryliodonium salts with different counter ions [PhIPhCHO]X (X = Cl, Br, OTs, OTf) were synthesized. ¹⁸F radiolabeling was performed using different bases at different temperatures in the presence of a radical scavenger, 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO). The best conversion (～80%) to meta-[¹⁸F] fluorobenzaldehyde was obtained using CsHCO₃ base at a reaction temperature of 110°C. To study iodonium salt counter ion effects on radiofluorination, each precursor was separately treated with Cs[ ¹⁸F]F/CsHCO₃ in DMF at 110°C for 5 min in the presence of TEMPO. Our observed reactivity order was OTs18F]fluorobenzaldehyde thus obtained was reduced to the corresponding alcohol with aqueous NaBH₄ at room temperature and then converted to meta-[¹⁸F]fluorobenzylbromide using triphenylphosphine dibromide. Formation of meta-[¹⁸F]fluorobenzylbromide was confirmed using high-performance liquid chromatography and the desired product was purified on a silica Sep-Pak plus cartridge. Copyright

Full text of DOI:10.1002/jlcr.1853

Research Article
Received 15 September 2010,
Revised 2 November 2010,
Accepted 5 November 2010
Published online 17 February 2010 in Wiley Online Library
(wileyonlinelibrary.com) DOI: 10.1002/jlcr.1853
Syntheses of meta-[18F]fluorobenzaldehyde
and meta-[18F]fluorobenzylbromide from
phenyl(3-Formylphenyl) iodonium salt
precursorsy
Ã
Falguni Basuli, Haitao Wu, and Gary L. Griffiths
18F-labeled fluorobenzaldehydes and fluorobenzylbromides are useful synthons for the preparation of positron emission
tomography radiopharmaceuticals. Although ortho- and para-[18F]fluorobenzaldehydes can easily be prepared with high
yields, the corresponding meta-derivatives are more problematic. In order to improve the yield of meta-[18F]fluor-
obenzaldehyde, we used the corresponding diaryliodonium salt precursors, since diaryliodonium salts had already been
used as precursors in the preparations of 18F-labeled electron-rich, as well as electron-deficient, aromatic rings.
Diaryliodonium salts with different counter ions [PhIPhCHO]X (X = Cl, Br, OTs, OTf) were synthesized. 18F radiolabeling was
performed using different bases at different temperatures in the presence of a radical scavenger, 2,2,6,6-tetramethylpi-
peridine-N-oxyl (TEMPO). The best conversion (ꢀ80%) to meta-[18F]fluorobenzaldehyde was obtained using CsHCO3 base
at a reaction temperature of 1101C. To study iodonium salt counter ion effects on radiofluorination, each precursor was
separately treated with Cs[18F]F/CsHCO3 in DMF at 1101C for 5 min in the presence of TEMPO. Our observed reactivity order
was OTsoCloOTfoBr. Meta-[18F]fluorobenzaldehyde thus obtained was reduced to the corresponding alcohol with
aqueous NaBH4 at room temperature and then converted to meta-[18F]fluorobenzylbromide using triphenylphosphine
dibromide. Formation of meta-[18F]fluorobenzylbromide was confirmed using high-performance liquid chromatography
and the desired product was purified on a silica Sep-Paks plus cartridge.
Keywords: fluorine-18; iodonium salt precursors; meta-[18F]fluorobenzaldehyde; meta-[18F]fluorobenzylbromide
fluorine gas as a carrier,18 so radiopharmaceuticals prepared using
Introduction
[18F]F2 have low specific activity, while only half of the activity of
[18F]F2 can be electrophilically substituted. Up until now, the most
useful route to obtain 18F-labeled compounds of high specific
Positron emission tomography (PET) is a very powerful non-invasive
in vivo molecular imaging technique, which provides not only
information on biochemical, physiological and pharmacological
processes but also offers the opportunity to study pharmacokinetics,
metabolism, and mechanisms of action of novel and established
drugs. Among the available PET radionuclides, fluorine-18 is favored
for in vivo imaging because of its most suitable nuclear and chemical
properties and its minimal perturbation to drug structure when
substituted onto low molecular weight drugs.1–4
activity is through nucleophilic fluorination by no-carrier-added
[18F]Fꢁ fluoride. However, direct nucleophilic fluorination of an
aromatic ring can be carried out successfully and in reproducibly
acceptable high yields in the presence of an appropriate leaving
group fNO2, NMe31Xꢁ, (X = OTfꢁ, TsOꢁ, ClOꢁ4 , Iꢁ)g along with an
electron withdrawing group in an ortho- or para- position (NO2,
CN, CHO, RCO, COOR). There are only a few examples of
microwave-induced 18F radiolabeling of an arene ring containing
an electron withdrawing group in the meta-position.19,20
18F-labeled fluorobenzaldehydes and fluorobenzylbromides
represent useful synthons for the preparation of PET radio-
pharmaceuticals.21–24 Although ortho- and para-[18F]fluoroben-
zaldehydes can easily be prepared with high yields by
18F-labeled aryl fluorides are widely used to prepare fluorine-18
radiolabeling synthons for the development of 18F-labeled radio-
tracers. There are several approaches available (Balz–
Schiemann reaction,5–8 Wallach reaction,9–11 electrophilic fluorina-
tion,12–14 nucleophilic displacement15–17) for the synthesis of
18F radiolabeled aryl fluorides. For the Balz–Schiemann reaction,
diazonium tetrafluoroborate is pyrolyzed in the presence of
[18F]Fꢁ. The major drawback of this method is the presence of 19
F
Imaging Probe Development Center, National Heart, Lung, and Blood Institute,
National Institutes of Health, Rockville, MD 20850, USA
in tetrafluoroborate, thus 25% labeling represents a theoretical
maximum and tetrafluoroborate ion results in isotopic carrier
reducing specific activity. The Wallach method not only uses the
decomposition of a triazene to prepare 18F-labeled compounds
but also gives a low radiochemical yield. Electron-rich aromatic
rings can also be radiolabeled by electrophilic fluorination with
[18F]Fꢁ although it is produced along with non-radioactive
*Correspondence to: Gary L. Griffiths, Imaging Probe Development Center,
National Heart, Lung, and Blood Institute, National Institutes of Health,
Rockville, MD 20850, USA.
E-mail: griffithsgl@mail.nih.gov
yThis article is a US Government work and is in the public domain in the USA.
J. Label Compd. Radiopharm 2011, 54 224–228
Published in 2011 by John Wiley & Sons, Ltd.

F. Basuli et al.
nucleophilic substitution reactions where corresponding nitro
1H NMR (400 MHz, DMSO-d6): d 10.0 (s, 1H), 8.74 (t, J = 1.5 Hz,
groups or quaternary amines are replaced by [18F]Fꢁ, the 1H), 8.53 (d, J = 8.6 Hz, 1H), 8.31 (d, J = 7.3 Hz, 2H), 8.18 (d,
corresponding meta-derivatives are more problematic. Some- J = 5.5 Hz, 1H), 7.77 (t, J = 7.8 Hz, 1H), 7.68 (t, J = 7.4 Hz, 1H), 7.55
times, meta-[18F]fluorobenzaldehyde is needed in order to (t, J = 7.82 Hz, 2H). 13C NMR (100 MHz, DMSO-d6): d 192.0, 140.7,
prepare radiopharmaceuticals with an exact molecular structure 138.8, 135.8, 135.3, 133.7, 132.9, 132.7, 132.3, 117.6, 117.1. 19F
of interest and current yields obtained for meta-[18F]fluoroben- NMR (376 MHz, DMSO-d6): d -77.76. LC-MS (ESI positive):
zaldehyde from meta-nitrobenzaldehyde are very low25–27 rt = 5.37 min, m/z 309 [M1].
because the meta-position of benzaldehyde is comparatively
electron rich. Nucleophilic [18F]Fꢁ radiolabeling of such non-
activated aromatic rings can be carried out by introducing an
activating group with its removal or modification after label-
Phenyl(3-formylphenyl)iodonium chloride (2)
Dichloromethane solution of Phenyl(3-formylphenyl)iodonium
ing.28,29 Diaryliodonium salts represent a particularly interesting
tetrafluoroborate salt obtained by the above method was
diluted with 80 mL of dichloromethane and 100 mL of saturated
approach, since they have been shown to be useful precursors
for direct nucleophilic [18F]Fꢁ introduction into both electron-
aqueous sodium chloride solution was added. After stirring for
rich and electron-deficient aromatic rings.30–37 For this reason,
30 min, the dichloromethane layer was collected. Product was
precipitated out with 50 mL of Et2O, collected by filtration and
washed with Et2O (81%).
we chose fluorination of iodonium salt precursors as a preferred
route for the radiosynthesis of meta-fluorobenzaldehyde using
1H NMR (400 MHz, DMSO-d6): d 9.98 (s, 1H), 8.64 (t, J = 1.6 Hz,
1H), 8.46–8.19 (m, 3H), 8.08 (dt, J = 7.8, 1.2 Hz, 1H), 7.68 (t,
J = 7.8 Hz, 1H), 7.60–7.44 (m, 3H). 13C NMR (100 MHz, DMSO-d6):
d 192.2, 140.5, 138.5, 135.4, 135.2, 132.7, 132.3, 131.7, 131.6,
122.1, 121.2. LC-MS (ESI positive): rt = 5.37 min, m/z 309 [M1].
n.c.a. [18F]Fꢁ.
Herein, we report the syntheses and characterization of
phenyl(3-formylphenyl)iodonium salts containing four different
counter anions (OTf, Cl, Br, OTs ) and the 18F radiolabeling of
these iodonium salts in the preparations of meta-[18F]fluoro-
benzaldehyde and meta-[18F]fluorobenzylbromide.
Phenyl(3-formylphenyl)iodonium bromide (3)
Materials and methods
Phenyl(3-formylphenyl)iodonium tetrafluoroborate obtained by
the above method was precipitated out by the addition of Et2O
(80 mL), collected and washed with Et2O. To the solution of
Phenyl(3-formylphenyl)iodonium tetrafluoroborate in methanol
(25 mL) was added 48% aq. HBr (2 mL) in methanol (25 mL) and
the solution was stirred for 45 min. The solvent was removed
and the residue was washed with acetonitrile (3 ꢂ 15 mL) to
afford Phenyl(3-formylphenyl)iodonium Bromide (3) (69%).
1H NMR (400 MHz, DMSO-d6): d 9.99 (s, 1H), 8.68 (t, J = 1.6 Hz,
1H), 8.50–8.22 (m, 3H), 8.11 (dt, J = 7.6, 1.2 Hz, 1H), 7.70 (t,
J = 7.8 Hz, 1H), 7.63–7.46 (m, 3H). 13C NMR (100 MHz, DMSO-d6):
d 192.1, 140.6, 138.6, 135.5, 135.2, 132.9, 132.5, 131.9, 131.8,
121.2, 120.3. LC-MS (ESI positive): rt = 5.37 min, m/z 309 [M1].
General
Trifluoromethane sulfonic acid and K222 were obtained from
Fluka. Tetrabutylammonium bicarbonate TBA-HCO3 was obtained
from ABX (Radeberg, Germany). 3-Chloroperoxybenzoic acid (77%
max.) from Sigma-Aldrich was dried under reduced pressure for
1 h prior to use. All other chemicals and solvents were obtained
from Sigma-Aldrich and used as received. ESI mass spectrometry
(MS) were performed on a 6130 Quadrupole LC/MS Agilent
Technologies instrument equipped with a diode array detector
using a Zorbax Stable Bond C-18 column (4.6 ꢂ 50 mm, 3.5 mm)
with a flow rate of 0.5 mL/min, 5–95% B over 10 min (B = acetoni-
trile, A = 0.5% TFA in water). Radiosynthesis was performed
manually. Formation of the product was confirmed by using
high-performance liquid chromatography (HPLC) on a Beckman
Coulter System Gold instrument equipped with multi-wavelength
detector using an Agilent Eclipse C-18, 5mm, 9.4 ꢂ 250 mm
column. All the microwave reactions were performed in a Biotage
Phenyl(3-formylphenyl) iodonium tosylate (4)
To the suspension of Phenyl(3-formylphenyl)iodonium chloride
(676 mg, 1.96 mmol) in 9:1 tetrahydrofuran, water (10 mL) was
added silver triflate (540 mg, 1.93 mmol) in THF. After stirring the
reaction mixture for 30 min, AgCl was filtered off and the filtrate
was evaporated to afford Phenyl(3-formylphenyl) iodonium
tosylate (4) (800 mg, 1.66 mmol, 85%).
1H NMR (400 MHz, DMSO-d6): d 9.97 (s, 1H), 8.73 (t, J = 1.6 Hz,
1H), 8.53–8.11 (m, 4H), 7.70 (t, J = 7.8 Hz, 1H), 7.65–7.44 (m, 5H),
7.08 (d, J = 8.8 Hz, 2H), 2.25 (s, 1H). 13C NMR (100 MHz, DMSO-d6):
d 192.0, 146.0, 140.8, 138.8, 138.2, 135.8, 135.6, 133.4, 132.8,
132.6, 132.2, 128.5, 125.9, 117.8, 117.2, 21.23. LC-MS (ESI
positive): rt = 5.37 min, m/z 309 [M1].
Initiator 2.5 using Biotage 10 mL V-shaped vials. H, 13C, 19F NMR
1
spectra were recorded with a Varian spectrometer at 400 MHz.
Chemical shifts are reported in parts per million (d) and are
referenced to tetramethylsilane (TMS). Sep-Paks plus C-18, Sep-
Paks plus silica, Sep-Pak dry cartridges were obtained from Waters.
Phenyl(3-formylphenyl)iodonium trifluoromethanesulfonate (1)
To the solution of 3-Chloroperoxybenzoic acid (815 mg,
3.64 mmol) in dry dichloromethane (20 mL) under argon was
added iodobenzene (0.4 mL, 3.52 mmol) followed by BF3.Et2O
(1.07 mL, 8.56 mmol) and the solution was stirred for 30 min at
Meta-[18F]Fluorobenzylbromide
room temperature. After cooling the reaction mixture to 01C [18F]Fꢁ (17–30 mCi) was eluted from an anion-exchange resin
solid 3-formylphenylboronic acid (555 mg, 3.7 mmol) was added (Sep-Pak light Waters Accell Plus QMA Cartridge) into
and stirred at 01C for 15 min then at room temperature for a 10-mL Biotage V-shaped vials with 0.4 mL aqueous (2.5mg/
45 min. To the reaction mixture trifluoromethanesulfonic acid mL) solution of CsHCO3 followed by 1 mL of acetonitrile and dried
(0.30 mL, 3.39 mmol) was added and stirred for 10 min. Product under nitrogen at 1101C. The residue was further azeotropically
was precipitated out with 50 mL of Et2O, collected by filtration dried with (3ꢂ 1 mL) acetonitrile. Dimethyl formamide (1 mL)
and washed with Et2O (1.2 g, 2.62 mmol, 77%).
solution of Phenyl(3-formylphenyl)iodonium Bromide (3) (1–2 mg)
J. Label Compd. Radiopharm 2011, 54 224–228
Published in 2011 by John Wiley & Sons, Ltd.
www.jlcr.org

F. Basuli et al.
and 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) (0.5–1 mg) prepared by the reaction with 48% hydrobromic acid. Salt
were added, the vial was sealed and heated at 1101C in a metathesis of phenyl(3-formylphenyl)iodonium chloride [PhIPh-
microwave for 5 min. The vial was cooled, 6 mL water was added CHO]Cl (2) with AgOTs afforded phenyl(3-formyl phenyl)iodonium
and the solution was passed through a preconditioned (5 mL tosylate [PhIPhCHO]OTs (4) (Figure 1).
ethanol, 10mL water, 20mL air) C-18 plus Sep-Paks cartridge to
In test reactions using 19F, fluorination of triflate salt (1) was
catch meta-[18F]fluorobenzaldehyde. The Sep-Pak cartridge was carried out with CsF in dimethylformamide, initially at different
washed with 4 mL of 0.2 M HCl, 4 mL water and the aldehyde was temperatures and the formation of the product was monitored by
converted to meta-[18F]fluorobenzyl alcohol on the Sep-Pak by using HPLC analysis of the reaction mixtures (Figure 2). The ratio
passing 1 mL of an aqueous (30 mg) solution of NaBH4. The of two fluorinated compound shows the general trend of more
cartridge was dried for 5 min by passing nitrogen and meta- fluorination on the electron-deficient ring. It is known from the
[18F]fluorobenzyl alcohol was eluted from the Sep-Pak cartridge literature reported by Widdowson et al.44 that radical scavenger
with 3 mL of dichloromethane, passed through a small column TEMPO increases the yield of the desired product and gives better
filled with K2CO3 and then a Sep-Pak dry cartridge (Na2SO4, reaction reproducibility. We also tried the 19F fluorination reaction
2.85g) into a sealed vial with a vent needle, containing of triflate salt (1) in the presence of different amounts of TEMPO
triphenylphosphine dibromide (90 mg). This solution was stirred (Table 1) at 1101C and obtained better yields of the product. It is
for 10min at room temperature. Meta-[18F]fluorobenzylbromide obvious from the table that the ratio of the 3-fluorobenzaldehyde
thus obtained was purified by silica plus Sep-Paks cartridge. to fluorobenzene increases from 33:6 to 59:3 upon the addition of
Formation of the product was confirmed by comparing the HPLC 20mol% of TEMPO with respect to iodonium salt and the
retention (UV detector at 254 nm) time (9.4min) with standard increased amount of TEMPO does not have any deleterious effect
meta-fluorobenzylbromide using a semi-preparative HPLC col- on the radiofluorination yield.
umn (Agilent Zorbax C-18, 5 m, 9.4 ꢂ 250 mm), mobile phase: Radiosyntheses were first carried out with compound 1 with
acetonitrile, water with 0.1 % TFA 40:60. More than 98% Cs[18F]F/Cs2CO3 in dimethylformamide at 1001C for 5 min in a
radiochemically pure product (20–40%, uncorrected, n = 6) was
obtained in a total synthesis time of 50 min.
Table 1. Effect of TEMPO on fluorination (19F) of com-
pound 1
Results and discussion
Yield (%)a (n = 2)
TEMPO (mol%)
There are several literature methods available for the prepara-
[19F]I
[19F]II
tion of diaryliodonium salts38–43 and we followed the one-pot
synthesis42 of Olofos et al., proceeding through a non-isolated
tetrafluoroborate salt, to prepare phenyl(3-formylphenyl)iodo-
nium trifluoromethanesulfonate [PhIPhCHO]OTf (1) (Figure 1).
Similarly, phenyl(3-formylphenyl)iodonium chloride [PhIPh-
CHO]Cl (2) was prepared by the anion-exchange of phenyl-
(3-formylphenyl)iodonium tetrafluoroborate with NaCl and
phenyl(3-formylphenyl)iodonium bromide [PhIPhCHO]Br (3) was
0
33
59
60
62
57
6
3
2
2
3
20
50
75
150
aYield was determined by using HPLC.
Figure 1. Syntheses of iodonium salts.
Figure 2. Fluorination reactions of Compounds 1–4.
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Published in 2011 by John Wiley & Sons, Ltd.
J. Label Compd. Radiopharm 2011, 54 224–228

F. Basuli et al.
microwave in the presence of 1 equiv. of TEMPO (Figure 2). using triphenylphosphine dibromide at room temperature in
Formation of meta-[18F]fluorobenzaldehyde was confirmed by 10min. Formation of meta-[18F]fluorobenzylbromide was con-
comparison of its retention time with cold standard meta- firmed by HPLC (Figure 4) and was purified by using silica
fluorobenzaldehyde. Radiochemical yields were determined by Sep-Paks plus. The total radiochemical yield starting from the
using radio-HPLC using an in-line radio detector. Radiolabeling elution of activity from an anion-exchange resin (Sep-Pak light
was also performed at different temperatures using cesium Waters Accell Plus QMA Cartridge) was 20–40% (uncorrected,
carbonate as base with maximum conversion to meta-[18F]fluoro- n = 6) in a 50-min synthesis.
benzaldehyde obtained at 1101C (Table 2) with a trace amount of
[18F]fluorobenzene.
The effects of different bases on the radiolabeling results were
tested at 1101C with the best conversion to [18F]-fluorobenzal-
dehyde obtained when radioactivity was eluted from an anion-
exchange resin (Sep-Pak light Waters Accell Plus QMA Cartridge)
with CsHCO3 (Figure 3 and Table 3).
To study the effects of the counter anion of the iodonium
salt on fluorination, each precursor was separately treated
with Cs[18F]F/CsHCO3 in DMF at 1101C in a microwave for 5 min
in the presence of TEMPO. The observed order of reactivity
was OTsoCloOTfoBr (Table 4), with use of the bromide
counter ion salt resulting in an 80% conversion to the desired
product.
Table 3. Effect of different bases on the radiolabeling of
compound 1
RCYa (%, nX2)
Base/amount
(mg or mL)
Temperature (1C)
[18F]I
[18F]II
Cs2CO3/1
CsHCO3/1
TBAF/30
KHCO3/K222/1/5
K2CO3/K222/1/5
110
110
110
110
110
30
60
40
50
20
3
5
4
5
6
Meta-[18F]fluorobenzaldehyde thus obtained from the reaction
of bromide salt (3) with Cs[18F]F/CsHCO3 was reduced to the
corresponding alcohol with aqueous NaBH4 at room temperature
which was then converted to meta-[18F]fluorobenzylbromide
aRadiolabeling was carried out with 3–5 mCi of activity,1–2mg
of precursor, 0.5–1 mg TEMPO in DMF (1 mL). Yield was
determined by using radio HPLC.
Table 4. Effect of counter anion on the radiolabeling of
iodonium salts 1–4
Table 2. Effect of temperature on the radiolabeling of
compound 1
RCYa
(%, nX2)
RCYa (%, n X 2)
Compound
Base
(1 mg)
Tempera-
ture (1C)
Base (1 mg)
Temperature (1C)
[18F]I
[18F]II
[18F]I 18F]II
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
100
110
120
130
24
30
10
6
2
3
1
0.3
[PhIPhCHO]OTf (1)
[PhIPhCHO]Cl (2)
[PhIPhCHO]Br(3)
[PhIPhCHO]OTs (4)
CsHCO3
CsHCO3
CsHCO3
CsHCO3
110
110
110
110
60
28
80
20
5
9
6
3
RCY, radiochemical yield.
aRadiolabeling was carried out with 3–5 mCi of activity,
1–2 mg of precursor, 0.5–1 mg TEMPO in DMF (1 mL). Yield
was determined by using radio HPLC.
aRadiolabeling was carried out with 3–5 mCi of activity,
1–2 mg of precursor, 0.5–1 mg TEMPO in DMF (1 mL). Yield
was determined by using radio HPLC.
Figure 3. HPLC analysis fColumn: Agilent Eclipse C18 5 mm, 9.4 ꢂ 250 mm; eluent:
40% B (A = 0.1% TFA in water, B = acetonitrile); flow rate = 4 mL/ming of an aliquot
taken from the crude reaction mixture of iodonium salt 1 with Cs[18F]F after 5 min
at 1101C. Solid line is for the radiodetector and the dotted line is for the UV
detector, meta-[18F] fluorobenzaldehyde rt at 9.45 min [This figure is available in
colour online at www.interscience.wiley.com/journal/jlcr].
Figure 4. HPLC analysis fColumn: Agilent Eclipse C18 5 mm, 9.4 ꢂ 250 mm; eluent:
40%
B (A = 0.1% TFA in water, B = acetonitrile); flow rate = 4 mL/ming of 3-
[
18F]fluorobenzylbromide after Sep-Pak purification. Solid line is for the radio-
detector and the dotted line is for the UV detector, meta-[18F]fluorobenzylbromide
rt at 11.68 min. [This figure is available in colour online at www.interscience.wi-
ley.com/journal/jlcr].
J. Label Compd. Radiopharm 2011, 54 224–228
Published in 2011 by John Wiley & Sons, Ltd.
www.jlcr.org

F. Basuli et al.
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Conclusions
In conclusion, the method we described can be regarded as
an efficient general procedure suitable for the preparation of
18F-labeled meta-fluorobenzaldehyde and meta-fluorobenzyl-
bromide. A diaryliodonium salt having a bromide counter ion
appears to be the preferred precursor for the radiosynthesis of
meta-[18F]fluorobenzaldehyde. As an example of the application
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