Journal of Fluorine Chemistry 126 (2005) 1160–1165

www.elsevier.com/locate/fluor

Fluorinated pyridine derivatives

Part 1. The synthesis of some mono- and bis-quaternary pyridine
salts of potential use in the treatment of nerve agent poisoning
Christopher M. Timperley *, Mike Bird, Suzannah C. Heard, Stuart Notman,
Robert W. Read, John E.H. Tattersall, Simon R. Turner
Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK

Received 18 February 2005; received in revised form 25 April 2005; accepted 1 May 2005
Available online 1 July 2005

Abstract

Experiments were performed to determine whether F- and CF3-substituted pyridines undergo quaternization with iodomethane (1:1 molar
ratio in THF) and 1,3-diiodopropane (2:1 molar ratio in MeCN). 2-Fluoropyridine and 2-(trifluoromethyl)pyridine did not react with MeI even
under prolonged reflux, while 3-fluoropyridine, 3,5-difluoropyridine, 3-(trifluoromethyl)pyridine and 4-(trifluoromethyl)pyridine gave
methiodide salts in 28–72% yield. 2-Fluoropyridine did not react with I(CH2)3I, 3-fluoropyridine gave the bis-quaternary salt and 3,5-
difluoropyridine yielded a mono-quaternary derivative. Both 3- and 4-(trifluoromethyl)pyridine furnished the bis-quaternary products in 53
and 55% yield, respectively. The bis-quaternary salts are potentially useful in the treatment of organophosphorus nerve agent poisoning.
# 2005 Elsevier B.V. All rights reserved.

Keywords: 2-Fluoropyridine; 3-Fluoropyridine; Nerve agent; 2-(Trifluoromethyl)pyridine; 3-(Trifluoromethyl)pyridine; 4-(Trifluoromethyl)pyridine

1. Introduction With regard to the influence of substituents in the

The formation of quaternary salts by the reaction of
pyridine and homologues with iodoethane was first observed
by Anderson [1]. All quaternizations, with the exception of a
few cases, are of the SN2 type. Pyridine was shown to react
vigorously with iodomethane [2] and early workers soon
multiplied examples of the reaction. It was noted that
primary and secondary halides participate, but that tertiary
halides are converted into alkenes [3]. Primary halides are
generally more reactive than secondary halides [4], the order
of reactivity being iodide > bromide > chloride [5,6].
Methylene dihalides X(CH2)nX react satisfactorily with
pyridine, examples with n = 2–5 and 10 having been
reported, and generally produce the bis-quaternary salts,
but in some cases both mono- and bis-quaternary salts have
been isolated [7–9].
* Corresponding author. Tel.: +44 1980 613 566; fax: +44 1980 613 834.
E-mail address: cmtimperley@dstl.gov.uk (C.M. Timperley).
pyridine ring, the effects observed are those expected from
their electronic characters, modified for C-2 (and C-6)
substituents by a steric factor. The quaternization reaction
has been observed with pyridines bearing acyl, alkyl, aryl,
amido, ester, chloro, bromo, iodo, cyano, nitro and pyridyl
substituents and combinations of these [10]. Failures to form
1-methylpyridinium compounds are rare but have been
reported for pyridines having strong electron-withdrawing
groups.
Attempts to quaternize fluorinated pyridines have
scarcely been pursued. One reason for this may be the
prejudice that such compounds are poorly basic and
therefore unlikely to enter into such a reaction. It was
claimed that 2-fluoro-3-methylpyridine and 2-fluoro-5-
methylpyridine readily form methiodides [11], while 2-
and 6-fluoronicotinamide fail to combine with iodoethane
[12]. The purpose of the present study was to compare the
reactivities of some simple fluoro- and trifluoromethyl-
substituted pyridines towards iodomethane and 1,3-diiodo-
propane.

0022-1139/$ – see front matter # 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2005.05.004
 C.M. Timperley et al. / Journal of Fluorine Chemistry 126 (2005) 1160–1165
Scheme 1.
Quaternized pyridines are of interest as similar com-
pounds, such as 2-PAM, HI-6 and TMB-4 (Scheme 1), have
been used as antidotes in human poisoning by organopho-
sphorus nerve agents [13,14]. Previous work in our
laboratory indicated that some of the therapeutic effect of
the bis-quaternary compounds may be unrelated to
cholinesterase reactivation (via the oxime groups) and
may instead be due to blockade of nicotinic ion channels at
the neuromuscular junction [15,16]. The work reported here
is part of a large programme to define molecular properties
necessary to maximise this novel therapeutic action. The
fluorinated compounds will be tested for biological activity
alongside other structurally similar analogues and the results
reported elsewhere.
2. Results and discussion
2.1. Mono-quaternary pyridinium derivatives
Polar solvents usually accelerate quaternization and for this
reason we performed methylation experiments on 2-fluor-
opyridine, 3-fluoropyridine and 3,5-difluoropyridine in tetra-
Scheme 2.
1161
hydrofuran. Introduction of electron-withdrawing groups
(EWGs) such as halogen atoms into the pyridine ring
decreases the charge on the nitrogen atom, its basicity
increasing in the order 2-EWG < 3-EWG < 4-EWG [10].
Fluorine is the most electronegative of all the halogens and the
effects it induces in the ring system are the most extreme, the 2-
fluoro substituent profoundly influencing basicity (pKa values
in water at 25 8C for pyridine, 2-fluoropyridine and 3-
fluoropyridine are 5.17, 0.44 and 2.97, respectively) [17].
We found that 2-fluoropyridine would not enter into reaction
with iodomethane even after 65 h under reflux. Only a tiny
amount of a solid identified as 2-pyridinone methiodide 1 was
isolated (Scheme 2). This product presumably arose from
slight hydrolysis of the 2-fluoropyridine during the course of
the experiment.1 Elsewhere it has been shown that 2-
fluoropyridine methiodide can be formed in low yield by
refluxing 2-fluoropyridine and iodomethane in the absence of
solvent for 12 h [11]. In contrast to 2-fluoropyridine, the more
basic 3-fluoropyridine and 3,5-difluoropyridine gave salts 2
and 3 as yellow crystalline solids.
Although a trifluoromethyl group is not as electronega-
tive as a fluorine atom [19], it is much larger and is estimated
to be at least the size of an ethyl group [20]. It was therefore
no surprise that 2-(trifluoromethyl)pyridine would not
combine with iodomethane, the combination of electron-
withdrawal and steric congestion preventing reaction
(Scheme 3). Moving the trifluoromethyl group round the
ring reduces both effects, and both 3-(trifluoromethyl)pyr-
idine and 4-(trifluoromethyl)pyridine were able to react to
give methiodides 4 and 5, respectively.
2.2. Bis-quaternary pyridinium derivatives
Previous work in our laboratory identified acetonitrile as
a particularly good solvent for the synthesis of bis-
quaternary pyridinium compounds. In this solvent, 2-
fluoropyridine failed to react with 1,3-diiodopropane
(150 h under reflux), yet 3-fluoropyridine gave the required
salt 6 in modest yield (Scheme 4). The less basic 3,5-
difluoropyridine reacted under the same conditions to yield
1
The reluctance of 2-fluoropyridine to react with iodomethane is due to
the electronic effect of fluorine. Comparable experiments with 2-bromo-
pyridine and 2-chloropyridine gave the methiodides in reasonable yield
[18].
1162 C.M. Timperley et al. / Journal of Fluorine Chemistry 126 (2005) 1160–1165
Scheme 3.
mainly mono-substituted product 7. Some bis-substituted
product was tentatively identified by thin layer chromato-
graphy, but we failed to isolate it from the reaction mixture.
The difficulty of the second substitution in this case is most
likely due to the poor reactivity of the starting pyridine.
Both 3- and 4-(trifluoromethyl)pyridine combined with
1,3-diiodopropane to yield bis-quaternary salts 8 and 9 in
moderate yield (Scheme 5).
All compounds reported in this paper were shown to be
>98% pure by 1H, 13C and 19F NMR spectroscopy. They
gave single peaks and the correct mass spectra when
analysed by liquid chromatography–mass spectrometry.
Scheme 4.
Scheme 5.
3. Conclusion
The F and CF3 substituents have a pronounced effect on
the reactivity of fluorinated pyridines towards quaternization
with alkyl iodides. No reaction was observed with these
substituents in the 2-position, due to the low basicity of the
nitrogen atom and, in the case of CF3, steric hindrance.
Reaction was observed with these substituents in other
positions, the only anomaly being 3,5-difluoropyridine,
which combined only once with 1,3-diiodopropane. From
the reflux times required for complete quaternization, it is
believed that 3-fluoropyridine is more reactive than 3,5-
difluoropyridine, and that the reactivity of the trifluoro-
methyl pyridines decreases in the order 4-CF3 > 3-
CF3  2-CF3, in line with electronic and steric effects.
4. Experimental
The fluorinated pyridines were from Apollo Chemicals
(Stockport, UK) and all other reagents from Aldrich Ltd.
(Gillingham, UK). They were used as received. Anhydrous
solvents were used throughout; tetrahydrofuran was distilled
from sodium/benzophenone. Thin layer chromatography
(TLC) was performed on MK6F silica gel 60 Å plates
(Whatman, USA) with detection by I2 vapour. Melting
points were determined on an electrothermal apparatus and
are uncorrected.
4.1. NMR spectroscopy
NMR spectra were obtained on a Jeol Lambda 300
instrument (operating at 300 MHz for 1H, 75 MHz for 13C
and 282 MHz for 19F spectra). Products were examined as
solutions in d6-dimethyl sulfoxide with SiMe4 and CFCl3 as
external references (for 1H and 19F, respectively).
4.2. Liquid chromatography–mass spectrometry
Samples were dissolved in deionised water (Milli-Q) to
give solutions of concentration of approximately 1 mg ml 1.
 C.M. Timperley et al. / Journal of Fluorine Chemistry 126 (2005) 1160–1165
Atmospheric pressure chemical ionisation (APCI) mass
spectra were acquired using a TSQ Quantum (Thermo
Finnigan) triple quadrupole instrument connected to a
Surveyor MS pump. APCI source conditions were as
follows: vaporiser temperature 400 8C, discharge current
4 mA, heated capillary 300 8C, sheath gas (nitrogen)
pressure 20 (arbitrary units) and auxiliary gas (nitrogen)
pressure 5 (arbitrary units). Source CID was set at 10 V. A
mobile phase consisting of 0.1% formic acid in water (50%)
and methanol (50%) was introduced into the APCI source at
a flow rate of 100 ml min 1. Sample solutions were infused
into this mobile phase via a T-piece, using the instrument’s
built-in syringe pump. Infusion flow rate was adjusted to
obtain an intense spectrum whilst avoiding overloading,
sample solutions being diluted with water if necessary.
4.3. General method for mono-quaternary derivatives
A 250 ml round-bottomed flask was charged with the
appropriate pyridine, tetrahydrofuran (50 ml) and a mag-
netic stirrer bar. The flask was fitted with a pressure-
equalising dropping funnel containing a solution of
iodomethane in tetrahydrofuran (25 ml). This was protected
from moisture by a guard-tube filled with anhydrous calcium
chloride. The iodomethane solution was added dropwise
over 30 min to the stirred pyridine solution at room
temperature. After addition, the progress of reaction was
monitored by TLC using 1:2 hexane–acetone.
4.4. 2-Hydroxypyridine methiodide (1)
The general method was followed starting with 2-
fluoropyridine (4.85 g, 50 mmol) and iodomethane (10.65 g,
75 mmol). TLC analysis after 12 h showed that starting
material was present and that no conversion to product had
taken place. A reflux condenser and guard-tube filled with
anhydrous calcium chloride were fitted to the flask, which
was heated under reflux for 24 h. The solution turned a wine
red colour, but no precipitate was observed. TLC analysis
confirmed that no significant reaction had occurred. After a
further 41 h of heating under reflux, a small amount of
yellow powdery precipitate had formed. Removal by
filtration and recrystallization from hot methanol yielded
the title compound as a pale yellow crystalline solid (0.1 g,
1%). Mp 120 8C. 1H NMR d = 7.72 (1H, dd, J = 7 and 2 Hz,
6-H), 7.44 (1H, ddd, J = 9, 7 and 2 Hz, 4-H), 6.41 (1H, d,
J = 9 Hz, 3-H), 6.25 (1H, td, J = 7 and 1 Hz, 5-H), 5.47 (1H,
br s, OH), 3.43 (3H, s, CH3). 13C NMR d = 161.8 (s, C–OH),
140.3 (s, 4-C), 140 (s, 6-C), 118.9 (s, 3-C), 105.7 (s, 5-C),
36.9 (s, CH3). MS m/z (rel. abundance) = 110 (M+ HI,
100), 96 (12), 95 (7), 67 (65).
4.5. 3-Fluoropyridine methiodide (2)
The general method was followed starting with 3-
fluoropyridine (4.85 g, 0.05 mol) and iodomethane (10.65 g,
1163
75 mmol). TLC analysis after 12 h showed that starting
material was present. A reflux condenser and guard-tube
filled with anhydrous calcium chloride were fitted to the
flask, which was heated under reflux for 6 h. TLC analysis
showed that all the 3-fluoropyridine had been consumed. An
immiscible orange oil was observed in the bottom of the
flask. The reaction mixture was left to stand for 12 h and the
oil solidified. The solvent was decanted and the solid
recrystallized from hot isopropanol to yield the title
compound as pale yellow needles (7.28 g, 61%). Mp
98 8C. 1H NMR d = 9.4 (1H, t, J = 3 Hz, 2-H), 8.94 (1H, d,
J = 6 Hz, 6-H), 8.71–8.56 (1H, m, 4-H), 8.32–8.16 (1H, m,
5-H), 4.36 (3H, s, CH3). 13C NMR d = 159.4 (d,
1
JCF = 251 Hz, 3-CF), 142.8 (s, 6-C), 135.9 (d,
2
JCF = 38 Hz, C-2), 132.51 (d, 2JCF = 18 Hz, 4-C), 128.9
(d, 3JCF = 8 Hz, 5-C), 48.4 (s, CH3). 19F NMR d = 118 (s,
3-CF). MS m/z (rel. abundance) = 112 (M+ I, 12), 110
(100), 98 (21).
4.6. 3,5-Difluoropyridine methiodide (3)
The general method was followed starting with 3,5-
difluoropyridine (2.3 g, 20 mmol) and iodomethane (4.26 g,
30 mmol). TLC analysis after 12 h showed that starting
material was present. A reflux condenser and guard-tube
filled with anhydrous calcium chloride were fitted to the
flask, which was heated under reflux for 32 h. After this
time, TLC analysis revealed that the starting pyridine had
been consumed. The yellow precipitate was filtered off and
recrystallized from hot isopropanol to give the title
compound as yellow-brown lustrous plates (1.43 g, 28%).
Mp 165 8C. 1H NMR d = 9.39 (2H, t, J = 2 Hz, 2- and 6-H),
8.99 (1H, tt, J = 10 and 2 Hz, 4-H), 4.36 (3H, s, CH3). 13C
NMR d = 159.6 (dd, 1JCF = 253 Hz, 3JCF = 13 Hz, 3- and 5-
CF), 133.7 (d, 2JCF = 40 Hz, 2- and 6-C), 121.6 (t,
2
JCF = 23 Hz, 3-C), 49.1 (s, CH3). 19F NMR d = 115.4
(d, 4JFF = 10 Hz, 3- and 5-F). MS m/z (rel. abundance) = 130
(M+ I, 15), 128 (100), 116 (95).
4.7. 3-(Trifluoromethyl)pyridine methiodide (4)
The general method was followed starting with 3-
(trifluoromethyl)pyridine (2.94 g, 20 mmol) and iodo-
methane (4.26 g, 30 mmol). TLC analysis after 12 h showed
that starting material was present. A reflux condenser and
guard-tube filled with anhydrous calcium chloride were
fitted to the flask, which was heated under reflux for 26 h.
TLC analysis showed that all the 3-(trifluoromethyl)pyridine
had been consumed. A creamy yellow precipitate had
formed. Filtration and recrystallization from hot ethanol
yielded the title compound as yellow crystals (4.16 g, 72%).
Mp 280 8C (dec.). 1H NMR d = 9.7 (1H, s, 2-H), 9.31 (1H, d,
J = 6 Hz, 6-H), 9.06 (1H, d, J = 8 Hz, 4-H), 8.44–8.35 (1H,
m, 5-H), 4.44 (3H, s, CH3). 13C NMR d = 149.4 (s, 6-C),
144.1 (s, 2-C), 142.1 (s, 4-C), 128.5 (s, 3-C), 128.2 (q,
2
JCF = 36 Hz, 3-C), 121.6 (q, 1JCF = 274 Hz, CF3), 48.6 (s,
1164 C.M. Timperley et al. / Journal of Fluorine Chemistry 126 (2005) 1160–1165
CH3). 19F NMR d = 61.3 (s, CF3). MS m/z (rel.
abundance) = 162 (M+ I, 27), 148 (100), 128 (16), 79 (16).
4.8. 4-(Trifluoromethyl)pyridine methiodide (5)
The general method was followed starting with 4-
(trifluoromethyl)pyridine (2.94 g, 20 mmol) and iodo-
methane (4.26 g, 30 mmol). TLC analysis after 12 h showed
that starting material was present. A reflux condenser and
guard-tube filled with anhydrous calcium chloride were
fitted to the flask, which was heated under reflux for 8 h.
TLC analysis showed that all the 4-(trifluoromethyl)pyridine
had been consumed. A bright yellow precipitate had formed.
Filtration and recrystallization yielded the title compound as
yellow crystals (2.27 g, 39%). Mp 175 8C. 1H NMR d = 9.34
(2H, d, J = 6 Hz, 2- and 6-H), 8.66 (2H, d, J = 6 Hz, 3- and 5-
H), 4.45 (3H, s, CH3). 13C NMR d = 147.8 (t, 4JCF = 8 Hz, 2-
and 6-C), 143.5–141 (m, 4-C), 124.2 (d, 3JCF = 3 Hz, 3- and
5-C), 121.3 (q, 1JCF = 275 Hz, CF3), 48.7 (s, CH3). 19F NMR
d = 63.7 (s, CF3). MS m/z (rel. abundance) = 162 (M+ I,
54), 148 (100), 143 (23), 130 (46), 124 (24).
4.9. General method for bis-quaternary derivatives
A 250 ml round-bottomed flask was charged with the
appropriate pyridine in acetonitrile (60 ml) and a magnetic
stirrer bar. The flask was fitted with a pressure-equalising
dropping funnel containing a solution of 1,3-diiodopropane
in acetonitrile (40 ml). This was protected from moisture by
a guard-tube filled with anhydrous calcium chloride. The
1,3-diiodopropane solution was added dropwise over 30 min
to the stirred pyridine solution at room temperature. After
addition, the progress of reaction was monitored by TLC
using 1:2 hexane–acetone.
4.10. Bis-1,3-(3-fluoropyridinyl)propane diiodide (6)
The general method was followed starting with 3-
fluoropyridine (7.28 g, 75 mmol) and 1,3-diiodopropane
(7.4 g, 25 mmol). TLC analysis after 12 h showed that
starting material, mono- and bis-quaternary products were
present. A reflux condenser and guard-tube filled with
anhydrous calcium chloride were fitted to the flask, which
was heated under reflux for 70 h. TLC analysis showed the
disappearance of starting material (1,3-diiodopropane Rf 0.8
and 3-fluoropyridine Rf 0.7) and the presence of mono- (Rf
0.1) and bis-quaternary products (baseline spot). No
precipitate was observed. The solvent was removed by
rotary evaporation to reveal a green solid. Recrystallization
from hot methanol (100 ml) gave the title compound as
yellow-brown crystals (4.17 g, 34%). Mp 185–186 8C. 1H
NMR d = 9.52 (2H, br s, 2-H), 9.11 (2H, d, J = 9 Hz, 6-H),
8.74 (2H, td, J = 9 and 1 Hz, 4-H), 8.35 (2H, m, 5-H), 4.8
(4H, t, J = 7 Hz, NCH2), 2.7 (2H, quintet, J = 7 Hz, CH2).
13
C NMR d = 160.4 (1JCF = 252 Hz, 3-F), 142.8 (s, 6-C),
136 (d, 2JCF = 38 Hz, 2-C), 133.9 (2JCF = 19 Hz, 4-C), 130.2
(d, 3JCF = 8 Hz, 5-C), 58.4 (s, NCH2), 31.7 (s, CH2). 19F
NMR d = 116.8 (s, CF). MS m/z (rel. abundance) = 235
(M+ I–HI, 28), 140 (10), 138 (22), 136 (28), 98 (100).
4.11. 1-(3,5-Difluoropyridinyl)-3-iodopropane
iodide (7)
The general method was followed starting with 3,5-
difluoropyridine (5.18 g, 45 mmol) and 1,3-diiodopropane
(4.44 g, 15 mmol). The mixture was heated under reflux for
92 h. After this time, TLC monitoring revealed the presence
of both mono- and (presumably) bis-quaternized product.
Removal of solvent yielded a tan coloured solid. Recrys-
tallization from hot isopropanol gave the title compound as
orange-yellow crystals (0.73 g, 12%). Mp 81 8C. 1H NMR
d = 9.47 (1H, t, J = 2 Hz, 2-H), 9.03 (1H, tt, J = 9 and 2 Hz,
4-H), 4.66 (2H, t, J = 7 Hz, NCH2), 3.33 (2H, t, J = 7 Hz,
CH2I), 2.6 2.5 (2H, br m, CH2). 13C NMR d = 160 (dd,
1
JCF = 254 Hz, 3JCF = 13 Hz, 3- and 5-CF), 133.1 (d,
2
JCF = 41 Hz, 2- and 6-C), 122.1 (t, 2JCF = 23 Hz, 4-C),
62.8 (s, NCH2), 33.6 (s, CH2), 0.8 (s, CH2I). 19F NMR
d = 114.4 (d, 4JFF = 8 Hz, 3- and 5-F). MS m/z (rel.
abundance) = 284 (M+ I, 7), 282 (23), 158 (43), 154 (95),
129 (23), 128 (30), 127 (23), 116 (100), 114 (37).
4.12. Bis-1,3-[3-(trifluoromethyl)pyridinyl]propane
diiodide (8)
The general method was followed starting with 3-
(trifluoromethyl)pyridine (3.09 g, 21 mmol) and 1,3-diio-
dopropane (2.07 g, 7 mmol). The mixture was heated under
reflux for 7 h. The solution had turned yellow but no
precipitate was evident. TLC analysis revealed a diiodo-
propane spot and further spots at Rf 0.1 and the baseline. The
mixture was heated for a further 78 h with monitoring by
TLC. After this time, the yellow precipitate was filtered off
and recrystallized from hot methanol. The title compound
was obtained as fine yellow needles (2.2 g, 53%). Mp 260 8C
(dec.). 1H NMR d = 9.75 (2H, s, 2-H), 9.43 (2H, d, J = 6 Hz,
6-H), 9.16 (2H, d, J = 8 Hz, 4-H), 8.51 (2H, dd, J = 6 and
8 Hz, 5-H), 4.85 (4H, t, J = 7 Hz, NCH2), 2.77 (2H, quintet,
J = 7 Hz, CH2). 13C NMR d = 148.7 (s, 6-C), 143.6 (q,
J = 4 Hz, 2-C), 143 (q, J = 3 Hz, 4-C), 129.2 (s, 5-C), 128.9
(q, 2JCF = 36 Hz, 3-C), 121.6 (q, 1JCF = 274 Hz, CF3), 58.1
(s, NCH2), 31.2 (s, CH2). 19F NMR d = 61.2 (s, CF3). MS
m/z (rel. abundance) = 335 (M+ I–HI, 5), 188 (7), 148
(100).
4.13. Bis-1,3-[4-(trifluoromethyl)pyridinyl]propane
diiodide (9)
The general method was followed starting with 4-
(trifluoromethyl)pyridine (6.62 g, 45 mmol) and 1,3-diio-
dopropane (4.44 g, 15 mmol). TLC analysis after 12 h
showed that starting material was present. A reflux
condenser and guard-tube filled with anhydrous calcium
 C.M. Timperley et al. / Journal of Fluorine Chemistry 126 (2005) 1160–1165
chloride were fitted to the flask, which was heated under reflux
for 42 h. TLC analysis revealed that the reaction had gone to
completion and fine needles of solid were observed in the flask.
Filtration and washing of the residue with acetonitrile gave the
title compound as fine yellow needles (4.88 g, 55%). Mp
252 8C (dec.). 1H NMR d = 9.46 (4H, d, J = 7 Hz, 2- and 6-H),
8.79 (4H, d, J = 7 Hz, 3- and 4-H), 4.84 (4H, t, J = 7 Hz,
NCH2), 2.72 (2H, quintet, J = 7 Hz, CH2). 13C NMR d = 148.1
(s, 2- and 6-C), 143.6 (d, 2JCF = 36 Hz, 4-C), 125.7 (s, 3- and 5-
C), 122.1 (m, CF3), 58.7 (s, NCH2), 32 (CH2). 19F NMR
d = 63.7 (s, CF3). MS m/z (rel. abundance) = 335 (M+ I–
HI, 47), 333 (15), 188 (40), 148 (100).
Acknowledgement
We thank the Ministry of Defence UK for funding this
work. #Crown Copyright 2005 published with the permis-
sion of the Controller HMSO.
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