Convenient preparation of (4-iodophenyl)aryliodonium salts

Article abstract of DOI:10.1016/j.tet.2012.03.113

The (4-iodophenyl)aryliodonium salts bis(4-iodophenyl)iodonium, (4-iodophenyl)(4-methoxy-phenyl)iodonium and (4-iodophenyl)(2-thienyl)iodonium, each with three different anions, were prepared using 4-iodo-1- [hydroxy(tosyloxy)iodo]benzene. These are suita

Full text of DOI:10.1016/j.tet.2012.03.113

Tetrahedron 68 (2012) 4112e4116
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Convenient preparation of (4-iodophenyl)aryliodonium salts
*
Jens Cardinale, Johannes Ermert , Heinz H. Coenen
€
€
Institut fur Neurowissenschaften und Medizin, INM-5: Nuklearchemie, 52425 Forschungszentrum Julich GmbH, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
The (4-iodophenyl)aryliodonium salts bis(4-iodophenyl)iodonium, (4-iodophenyl)(4-methoxy-phenyl)
iodonium and (4-iodophenyl)(2-thienyl)iodonium, each with three different anions, were prepared using
4-iodo-1-[hydroxy(tosyloxy)iodo]benzene. These are suitable precursor molecules for electrophilic ra-
diofluorination and other 4-iodophenylation reactions, whose products can subsequently serve as re-
agents for transition metal catalysed cross coupling and other metal organic reactions.
Ó 2012 Elsevier Ltd. All rights reserved.
Received 22 November 2011
Received in revised form 27 March 2012
Accepted 29 March 2012
Available online 4 April 2012
Keywords:
Aryliodonium salts
Radiofluorination
4-Fluoroiodobenzene
4-Iodophenyl-moiety
Cross coupling reactions
1. Introduction
coupled by Sonogashira, Stille, Suzuki and N-arylation reactions,
yielding complex 18F-labelled molecules.10e15
Diaryliodonium salts are known for over a century. Besides their
function as cationic photo initiators and several applications as
biologically active molecules, they can serve as powerful arylating
agents. They can react with a variety of nucleophiles, including the
fluoride ion.1 This enables an elegant pathway for no-carrier-added
(n.c.a.) labelling with fluorine-18,2,3 an important radionuclide
for in vivo molecular imaging with positron emission tomography
(PET).3,4 The properties of these diaryliodonium salts, amongst
other hypervalent iodine species, have been extensively
reviewed.5e9
Today, many iodonium salts are easily accessible via a broad
range of reaction sequences including a variety of modern one-pot
procedures.9 However, several of these compounds, especially
those with functional groups sensitive to oxidative conditions and
strong acids and/or those exhibiting a complex substitution pat-
tern, require more sophisticated synthetic strategies.
(4-Halophenyl)aryliodonium salts are of special interest
since nucleophilic substitution reactions with [18F]fluoride on
these compounds deliver p-[18F]fluorohalobenzenes as products
(Scheme 1), which can be used as excellent precursors for
following metal organic and cross coupling reactions. This has been
demonstrated for n.c.a. 4-[18F]fluorobromobenzene, transferred to
lithium- and Grignard-derivatives, and 4-[18F]fluoroiodobenzene
Scheme 1. Synthesis of 1-halo-4-[18F]fluorobenzene from a diaryliodonium precursor
(Hal¼Br, I; Xꢀ¼TsOꢀ, TfOꢀ, Brꢀ, Clꢀ).
A salt of the bis(4-iodophenyl)iodonium cation 1 (Fig. 1) first
appeared in the literature in 1958, however, without an anion or
synthetic conditions specified.16 The first detailed report on the
€
synthesis of these iodonium salts was given by Wust et al. in 2003
describing two procedures.11 The first one makes use of iodyl sul-
fate, which is not stable and whose synthesis involves several
hazardous materials. The second route is the oxidation of
1,4-diiodobenzene with peracetic acid to 4-(diacetoxyiodo)-1-
iodobenzene and subsequent coupling with iodobenzene by Kita-
mura’s procedure.17 Recently, Wagner and Sanford reported the
synthesis of bis(4-iodophenyl)iodonium tetrafluoroborate18 mak-
ing use of a one-pot procedure earlier described by Bielawski et al.19
* Corresponding author. Tel.: þ49 246161 3110; fax: þ49 246161 2119; e-mail
address: j.ermert@fz-juelich.de (J. Ermert).
Fig. 1. Target structures, Xꢀ¼TsOꢀ (a); TfOꢀ (b); Brꢀ (c).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.03.113

J. Cardinale et al. / Tetrahedron 68 (2012) 4112e4116
4113
Although this procedure generally proves to be very effective, it
is not applicable for n.c.a. radiofluorination since the use of tetra-
fluoroborate could principally cause isotopic dilution of the n.c.a.
oxidation of both iodine groups is predominating. When Willgerodt
tried to obtain pI-DIB by treatment of 4-iodo-1-(dichloroiodo)-
benzene with boiling acetic acid he obtained a similar result.25 He
assumed that the product was a mixture of 1,4-bis(diacetoxyiodo)-
benzene and 4-iodo-1-iodoxybenzene, what is also consistent with
our analytical data.
[
18F]fluoride.20 Therefore, and also for reasons of general interest in
alternative methods, another reaction was developed here, making
use of 4-iodo-1-[hydroxy(tosyloxy)iodo]benzene (pI-HTIB), a de-
rivative of Koser’s reagent ([hydroxy(tosyloxy)iodo]benzene, HTIB).
This reagent was directly coupled with iodobenzene in presence of
an excess of triflic acid to yield compound 1b.
In the reaction between iodonium salts and nucleophiles the
latter will preferably be bound to the more electron deficient ring.21
Thus, salts of the (4-iodophenyl)(4-methoxyphenyl)iodonium cat-
ion 2 and the (4-iodophenyl)(2-thienyl)iodonium cation 3 are also
suitable precursor molecules for the synthesis of 4-[18F]fluo-
roiodobenzene. Additionally, this reaction is influenced by the na-
ture of the counterion and the optimal one differs in various
reactions.11,21,22 For 18F-fluorination reactions tosylate (a), triflate
(b) and bromide (c) are commonly used.2,11,22 Since it was not
possible to predict, which of the salts would deliver the best re-
action yields in given case, each of the possible salts was prepared.
An alternative oxidation procedure is offered by Koser and
Wettach in an early reference, describing the synthesis of pI-HTIB
amongst others by a ligand transfer reaction.26 This reaction can
simply be performed by stirring the appropriate iodoaryl together
with Koser’s reagent in dichloromethane (DCM). The major
drawback of this reaction is the insolubility of Koser’s reagent in
DCM, which makes the workup somewhat difficult since the
product is also insoluble. Later, Carman and Koser made use of
2-[hydroxy(tosyloxy)iodo]toluene, which is soluble in DCM.27 This
reagent proved to be superior to HTIB, since the product can be
collected by simple filtration followed by washing with DCM and
diethyl ether. Using this reagent pI-HTIB could be produced in al-
most quantitative yields (Scheme 3), however, containing residual
traces of 2-[hydroxy(tosyloxy)iodo]toluene. This can also react with
boronic acids forming iodonium compounds, why it was removed
by recrystallisation from acetonitrile/methanol 80:20, yielding ca.
68% pure pI-HTIB. Although the mother liquor was still containing
much of the desired product, the crystallization step was not fur-
ther optimised since purity was the main objective.
2. Results
In a first attempt to synthesize bis(4-iodophenyl)iodonium
tosylate, 1,4-diiodobenzene was reacted with iodobenzene in
presence of para-toluenesulfonic acid monohydrate (TsOH) and
meta-chloroperbenzoic acid (mCPBA) in a two-step one-pot pro-
cedure as described by Olofsson’s group (Scheme 2).23,24 For this
purpose, 1,4-diiodobenzene was oxidized with mCPBA and then
iodobenzene and TsOH were added to carry out the coupling step.
This sequential procedure was chosen in order to avoid an oxida-
tion of the iodobenzene that would result in the formation of (4-
iodophenyl)phenyliodonium tosylate. In spite of this precaution,
however, it was still not possible to isolate the desired compound
without this by-product (cf. Scheme 2). There are two possible
explanations for this fact. Either the oxidation of the 1,4-
diiodobenzene is incomplete and iodobenzene is oxidized by re-
sidual mCPBA, or a ligand transfer occurs between the oxidized 1,4-
diiodobenzene and iodobenzene, which would also result in an
oxidation of the latter. Since this side reaction could not be elimi-
nated by several attempts, including an elevated temperature for
the oxidation step, cooling for the coupling step, prolonged reaction
times for both steps and the choice of triflic acid instead of TsOH,
this concept was considered not suitable.
Scheme 3. Preparation of pI-HTIB by ligand exchange.
Following the method as depicted in Scheme 3, pI-HTIB was
reacted with 4-iodophenylboronic acid in DCM (Scheme 4)
according to a procedure offered by Carroll et al.28 Although the
product was formed by this reaction, a maximum achieved yield of
about 30% was considered rather low. Alternatively, reactions of pI-
HTIB with 4-methoxyphenylboronic acid or 2-thienylboronic acid
delivered the corresponding iodonium salts 2a and 3a (cf. Fig. 1) in
yields of 57% and 72%, respectively.
Scheme 4. Preparation of bis(4-iodophenyl)iodonium tosylate by reaction of pI-HTIB
with 4-iodophenylboronic acid.
According to Dohi et al. the reactivity of iodine-III species can be
promoted by the addition of 2,2,2-trifluoroethanol (TFE).29 Thus,
the latter reaction (Scheme 4) was also run in a mixture of TFE and
DCM (50:50).23 This solvent proved to be superior for the direct
reaction of pI-HTIB with anisole and thiophene, yielding the iodo-
nium salts 2a (coloured beige30) and 3a in yields of 89% and 90%,
respectively. In case of the reaction with iodobenzene, however, no
improvement was observed even if the boronic acid was used for
further promotion of reactivity. Therefore, the reaction was alter-
natively run in pure TFE. Surprisingly, this resulted not only in an
enhancement of the reaction yield, but also in the formation of a by-
product, which is proposed to be (4-iodophenyl)(4-phenylboronic
acid)iodonium tosylate due to its m/z value of 450.90 in mass
analysis (corresponding to the iodonium cation).
Scheme 2. Preparation of I as tosylate salt by a one-pot procedure.
Thus, a selective mono oxidation of 1,4-diiodobenzene seemed
rather to be the method of choice. An attempt to synthesize 4-iodo-
1-(diacetoxyiodo)benzene (pI-DIB) by an oxidation with peracetic
acid delivered the product accompanied with an unidentified by-
product. An NMR-spectrum could not be recorded due to the in-
solubility of the solid product in common NMR solvents. However,
it melted under decomposition at about 220 ꢁC and combustion
analyses delivered a higher amount of oxygen (21.33ꢂ0.04%) than
calculated (14.29%) for the target compound, meaning that the
According to Ito et al., derivatives of Koser’s reagent can oxidize
aromatic compounds in fluoroalcoholic media by a single electron

4114
J. Cardinale et al. / Tetrahedron 68 (2012) 4112e4116
transfer (SET) process.31 Since this by-product was only observed in
reactions containing 4-iodophenylboronic acid, it is supposed that
the SET process takes place on this reagent. In order to test for this,
4-iodophenylboronic acid was reacted with HTIB in pure TFE. In-
deed the by-product was formed, while (4-iodophenyl)phenyl-
iodonium tosylate (m/z¼407.00) was still found as the main
product. Alternatively, a biphenylic structure containing two iodine
substituents and one boronic acid moiety could possibly have been
formed. This is, however, not very likely due to the fact that the
product crystallizes along with the desired product and has a high
polarity (found on TLC). No steps were conducted to isolate the by-
product in a pure form.
Since TFE did improve the reactivity of pI-HTIB in an undesired
way it was tried to convert this reagent in a more specific reaction.
In fact, by reacting pI-HTIB directly with iodobenzene in presence of
triflic acid in DCM 1b could be produced with up to 85% yield
(Scheme 5). The reaction required an excess of triflic acid of
5e10 equiv.. The product can be purified by extraction with chlo-
roform and subsequent precipitation with diethyl ether.
4.2. Synthesis of 4-iodo-1-[hydroxy(tosyloxy)iodo]benzene
(pI-HTIB)
2-[Hydroxy(tosyloxy)iodo]toluene (4.88 g, 12 mmol) and 1,4-
diiodobenzene (3.96 g, 12 mmol) were dissolved in 30 mL of
DCM. It took several minutes until the components completely
dissolved. A white precipitate formed slowly. After stirring at am-
bient temperature for 7 days the white solid was collected by fil-
tration, washed with dichloromethane and diethyl ether and dried
at the air (6.1 g, 98%). The crude product was recrystallised from
acetonitrile/methanol 80:20 (4.9 g white solid, 69%).
Mp 124e125 ꢁC (dec). 1H NMR (400 MHz, DMSO-d6)
1H), 7.89 (4H), 7.41 (d, 2H, J 8.8 Hz), 7.06 (d, 2H, J 6.8 Hz), 2.23 (s,
3H). 13C NMR (400 MHz, DMSO-d6)
: 145.6, 140.2, 139.7*, 138.3,
d: 9.73 (bs,
d
136.4, 128.6, 125.9, 123.2, 100.9, 94.6*, 21.2 (*traces of unreacted
1,4-diiodobenzene). HRMS (FTMSþESI), m/z calcd for C6H5I2Oþ
([MꢀTsOꢀ]þ), 346.84243; found, 346.84248. The substance is
poorly ionisable. The sample should be dissolved immediately be-
fore analysis. Anal. calcd for C13H12I2O4S: C, 30.24; H, 2.33; S, 6.19.
Found: C, 30.23; H, 2.36; S, 6.23.
4.3. General procedure for the synthesis of iodonium
tosylates from boronic acids and pI-HTIB
To a stirred suspension of pI-HTIB in DCM (10 mL/mmol) the
corresponding boronic acid (1 equiv) was added in one portion.
After stirring for 4 h the solvent was reduced to half of its initial
volume and the product precipitated by the addition of diethyl
ether (20 mL/mmol). The solids were collected by filtration, washed
with diethyl ether and dried at the air.
Scheme 5. Preparation of bis(4-iodophenyl)iodonium triflate by direct reaction of pI-
HTIB with TfOH and iodobenzene.
The triflate salts 2b and 3b were prepared by an anion me-
tathesis starting from the corresponding tosylates 2a and 3a anal-
ogously to the in situ anion exchange reported by Zhu et al..23 The
bromide salts of 1e3 were prepared by dissolving the tosylates 2a,
3a and the triflate 1b in a water/methanol mixture (50:50) and
subsequent precipitation of the iodonium bromide by addition of
a solution of the potassium bromide in the same solvent.32
4.3.1. Bis(4-iodophenyl)iodonium tosylate (1a). White solid (27%).
Mp 190 ꢁC (dec) (Lit.11: 152e154 ꢁC). The NMR-data were consistent
with literature.11
4.3.2. (4-Iodophenyl)(4-methoxyphenyl)iodonium tosylate (2a).
White solid (57%). Mp 175e178 ꢁC 1H NMR (400 MHz, DMSO-d6)
d:
8.11 (d, 2H, J¼9.2 Hz), 7.89 (d, 2H, J¼8.4 Hz), 7.81 (d, 2H, J¼8.4 Hz),
7.42 (d, 2H, J¼8.0 Hz), 7.06 (d, 2H, J¼8.0 Hz), 7.01 (d, 2H J¼9.2 Hz),
3. Conclusions
3.74 (s, 3H), 2.23 (s, 3H).13C NMR (400 MHz, DMSO-d6)
d: 162.4,146.1,
140.6, 138.0, 137.7, 136.9, 128.5, 125.9, 117.9, 116.8, 106.0, 100.3, 56.1,
21.2. HRMS (FTMSþp ESI), m/z calcd for C13H11I2Oþ ([MꢀTsOꢀ]þ),
436.88938; found, 436.88927. HRMS (FTMSꢀp ESI), m/z calcd for
C7H7O3Sꢀ, 171.01214; found, 171.01206. Anal. calcd for C20H18I2O4S:
C, 39.49; H, 2.98; S, 5.27. Found: C, 39.16; H, 2.85; S, 5.33.
Using pI-HTIB, a derivative of Koser’s reagent, it was possible to
synthesize bis(4-iodophenyl)iodonium (1) as triflate salt in high
yields of about 90%. Furthermore, a series of unsymmetrical iodo-
nium salts of particular interest for 18F-radiochemistry could be
synthesized starting from the same reagent. Those included salts of
the (4-iodophenyl)(2-thienyl)iodonium cation 3, another versatile
precursor for 4-iodo-[18F]fluorobenzene, and further on three dif-
ferent salts of the so far not described (4-iodophenyl)(4-
methoxyphenyl)iodonium cation 2.
4.3.3. (4-Iodophenyl)(2-thienyl)iodonium tosylate (3a). White solid
(72%). Mp 150 ꢁC (dec). 1H NMR (400 MHz, DMSO-d6)
d: 8.02 (d, 1H,
J¼2.4 Hz), 7.96e7.93 (m, 3H), 7.84 (d, 2H, J¼8.4 Hz), 7.43 (d, 2H,
J¼8.0 Hz), 7.13 (t, 1H, J¼4.8 Hz), 7.07 (d, 2H, J¼7.6 Hz), 2.24 (s, 3H).
13C NMR (400 MHz, DMSO-d6)
d: 146.1, 141.0, 140.7, 138.0, 137.9,
4. Experimental
4.1. General
136.7, 130.1, 128.5, 125.9, 119.2, 101.3, 100.6, 21.2. HRMS (FTMSþp
ESI), m/z calcd for C10H7I2Sþ ([MꢀTsOꢀ]þ), 412.83578; found,
412.83518. HRMS (FTMSꢀp ESI), m/z calcd for C7H7O3Sꢀ, 171.01214;
found, 171.01205. Anal. calcd for C17H14I2O3S2: C, 34.95; H, 2.42; S,
10.98. Found: C, 34.91; H, 2.41; S, 10.90.
All chemicals were purchased from SigmaeAldrichÒ except
for triflic acid, which was acquired from Merck KGaA. 2-
[Hydroxy(tosyloxy)iodo]toluene was prepared according to
Carman and Koser.27 All reactions were run under exclusion of
light.
4.4. General procedure for the synthesis of iodonium
tosylates from arenes and pI-HTIB
NMR spectra were recorded on a Varian-Inova 400 spectrome-
ter. The chemical shifts are given in parts per million relative to the
solvent signal. Mass spectra were recorded by a Finnigan MAT 95
spectrometer and the elemental analyses were performed on
To a stirred suspension of pI-HTIB and 1 equiv. of the arene in
DCM the desired amount of TFE was added (V(DCM)þV(TFE)¼
10 mL/mmol). After stirring for 4 h the solvent was reduced to half of
its volume under reduced pressure and the product was pre-
cipitated by the addition of diethyl ether (20 mL/mmol). The product
was filtered, washed with diethyl ether and dried at the air.
€
a Vario El Cube. Melting points were determined on a Buchi B-540
melting point analyser.

J. Cardinale et al. / Tetrahedron 68 (2012) 4112e4116
4115
4.4.1. (4-Iodophenyl)(4-methoxyphenyl)iodonium tosylate (2a). In
DCM/TFE 50:50: Beige solid (90%).
quantity of the same solvent. To this the potassium bromide solu-
tion was added and the iodonium bromide immediately started
precipitating. Due to the temperature sensitivity of iodonium
compounds, this process should be performed fast. It is advisable to
cool the mixture below 50ꢁ after addition of potassium bromide.
In DCM/TFE 97:3: White solid (68%).
4.4.2. (4-Iodophenyl)(2-thienyl)iodonium tosylate (3a). In DCM/TFE
60:40: White solid (89%).
4.7.1. Bis(4-iodophenyl)iodonium bromide (1c). White solid (75%).
Mp 195e197 ꢁC. NMR: Due to low solubility in DMSO-d6 no clear
NMR-spectrum could be recorded. HRMS (FTMSþp ESI), m/z calcd
for C12H8I3 ([MꢀBrꢀ]þ), 532.77549; found, 532.77512. HRMS
(FTMSꢀp ESI), m/z calcd for Brꢀ, 80.91629; found, 80.91675. Anal.
calcd for C12H8BrI3: C, 23.52; H, 1.32. Found: C, 24.25; H, 1.46.
4.5. Synthesis of bis(4-iodophenyl)iodonium triflate (1b)
A mixture of pI-HTIB (1.04 g, 2 mmol) and iodobenzene (0.41 g,
2 mmol) in 40 mL DCM was cooled to ꢀ78 ꢁC. Subsequently triflic
acid33 (1.76 mL, 20 mmol) was added slowly and the reaction
mixture was allowed to reach ambient temperature by stirring over
night without refreshing the cooling bath. Upon addition of the
triflic acid the reaction mixture turned to a dark blue colour (io-
dine-III intermediate), which changed to red upon completion. The
product mixture was diluted with chloroform and water and the
organic components three times extracted with chloroform. The
unified organic phase was dried over MgSO4, the solvent was
largely removed under reduced pressure and the product was
precipitated as white solid by addition of diethyl ether. This was
separated by filtration, washed with diethyl ether and dried at the
air. The material could be used for labelling reactions without fur-
ther purification. 1.12 g Beige solid, (85%). Mp 142e145 ꢁC (dec)
(Lit.:11 185e187 ꢁC). The NMR-data were consistent with the
literature.11
4.7.2. (4-Iodophenyl)(4-methoxyphenyl)iodonium bromide (2c).
White solid (82%). Mp 195e196 ꢁC 1H NMR (400 MHz, DMSO-d6)
d
: 8.06 (d, 2H, J¼8.8 Hz), 7.86 (d, 2H, J¼8.4 Hz), 7.79 (d, 2H,
J¼8.4 Hz), 6.98 (d, 2H, J¼8.8 Hz), 3.73 (s, 3H). 13C NMR (400 MHz,
DMSO-d6) d: 162.1, 140.4, 137.4, 136.7, 118.9, 117.7, 108.1, 99.8, 56.1.
HRMS (FTMSþp ESI), m/z calcd for C13H11I2Oþ ([MꢀBrꢀ]þ),
436.88938; found, 436.88894. HRMS (FTMSꢀp ESI), m/z calcd for
Brꢀ, 80.91629; found, 80.91676. Anal. calcd for C13H11BrI2O: C,
30.20; H, 2.14. Found: C, 29.46; H, 2.07.
4.7.3. (4-Iodophenyl)(2-thienyl)iodonium
bromide
(3c). White
crystals (96%). Mp 186e187 (dec) (Lit.22: 162 ꢁC). The NMR-data
were consistent with literature.22
4.6. General procedure for the anion metathesis to iodonium
triflates
Acknowledgements
The authors thank Dr. S. Willbold, Dr. D. Hofmann and J. Bach-
To a stirred solution of the iodonium tosylate in methanol (2 mL/
mmol) a solution of 2 equiv of triflic acid in DCM (5 mL/mmol) was
added. After stirring for 10 min the solution was washed with
water, dried over MgSO4 and the solvent reduced to half of its initial
volume. The product was precipitated by the addition of diethyl
ether (50 mL/mmol iodonium compound), collected by filtration,
washed with diethyl ether and dried at the air.
€
hausen, all Zentralabteilung fur Chemische Analysen, For-
€
schungszentrum Julich, for recording the spectral data.
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4.6.1. (4-Iodophenyl)(4-methoxyphenyl)iodonium triflate (2b). Beige
solid (75%). Mp 240e242 ꢁC (dec). 1H NMR (400 MHz, DMSO-d6)
d:
8.12 (d, 2H, J¼8.8 Hz), 7.90 (d, 2H, J¼8.4 Hz), 7.84 (d, 2H, J¼8.4 Hz),
5. Stang, P. J. J. Org. Chem. 2003, 68, 2997e3008.
7.03 (d, 2H, J¼8.8 Hz), 3.75 (s, 3H). 13C NMR (400 MHz, DMSO-d6)
d:
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162.5, 140.7, 137.7, 136.8, 121.1 (quartet, J¼1.28 kHz), 117.9, 116.8,
105.9, 100.4, 56.1. 19F NMR (400 MHz, DMSO-d6)
d
: ꢀ77.8. HRMS
(FTMSþp ESI), m/z calcd for C13H11I2Oþ ([MꢀTfOꢀ]þ), 436.88938;
found, 436.88924. HRMS (FTMSꢀp ESI), m/z calcd for CF3O3S:
148.95257; found: 148.95250. Anal. calcd for C14H13F3I2O4S: C,
28.69; H, 1.89; S, 5.47. Found: C, 29.49; H, 1.98; S, 5.50.
€
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ꢀ
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€
4.6.2. (4-Iodophenyl)(2-thienyl)iodonium triflate (3b). White solid
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(69%). Mp 147e148 ꢁC (dec). 1H NMR (400 MHz, DMSO-d6)
d:
€
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Liberation of [19F]fluoride would, however, cause an isotopic dilution of [18F]
fluoride in solution. Since often less than nanomol amounts are aimed at for
‘no-carrier-added’ radiofluorination reactions, any trace amount of BF4 can
8.03e8.02 (m, 1H), 7.97e7.93 (m, 3H), 7.87e7.85 (m, 2H), 7.15e7.13
(m, 1H). 13C NMR (400 MHz, DMSO-d6)
d: 141.0, 140.7, 138.0, 139.6,
130.1, 121.1 (quartet, J¼1.28 kHz), 119.1, 101.2, 100.7. 19F NMR
(400 MHz, DMSO-d6)
d
: ꢀ77.8. HRMS (FTMSþp ESI), m/z calcd for
C10H7I2Sþ ([MꢀTfOꢀ]þ), 583.84737; found, 583.84737. HRMS
(FTMSꢀp ESI), m/z calcd for CF3O3S: 148.95257; found: 148.95254.
Anal. calcd for C11H7F3I2O3S2: C, 23.50; H, 1.26; S, 11.41. Found: C,
23.58; H, 1.23; S, 11.76.
cause
product.
a significant reduction of the molar activity of the final labelled
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methanolewater mixture (50:50) was prepared. The appropriate
iodonium tosylate was dissolved under heating in a minimum

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septa.
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30. The yield in radiofluorination reactions was not affected by the colorization.
When using only 3 % of TFE in the reaction solvent the product was delivered as
white solid in 68 % yield.