Fluoroalkene chemistry: Part 3. Reactions of arylthiols with perfluoroisobutene, perfluoropropene and chlorotrifluoroethene

Article abstract of DOI:10.1016/j.jfluchem.2005.11.008

Reactions of perfluoroisobutene (PFIB), perfluoropropene (PFP) and chlorotrifluoroethene (CTFE) with benzenethiol and 2-methoxybenzenethiol in acetonitrile, with potassium carbonate as base, were compared. PFIB reacted with benzenethiol to give ketene thi

Full text of DOI:10.1016/j.jfluchem.2005.11.008

Journal of Fluorine Chemistry 127 (2006) 249–256
www.elsevier.com/locate/fluor
Fluoroalkene chemistry
Part 3. Reactions of arylthiols with perfluoroisobutene,
perfluoropropene and chlorotrifluoroethene
*
Christopher M. Timperley , Matthew J. Waters, Jackie A. Greenall
Defence Science and Technology Laboratory, Porton Down, Salisbury, Wiltshire SP4 0JQ, UK
Received 21 September 2005; received in revised form 21 November 2005; accepted 22 November 2005
Available online 27 January 2006
Dedicated to Professor R.E. Banks in honour of his enormous contribution to fluorine chemistry.
Abstract
Reactions of perfluoroisobutene (PFIB), perfluoropropene (PFP) and chlorotrifluoroethene (CTFE) with benzenethiol and 2-methoxybenze-
nethiol in acetonitrile, with potassium carbonate as base, were compared. PFIB reacted with benzenethiol to give ketene thioacetal
(
with both thiols to give the addition product CF CFHCF SAr and vinyl isomers CF CF CFSAr (6:1 E/Z ratio). CTFE reacted with several
3 2 2 3 2 3 2 2
CF ) C C(SAr) and with 2-methoxybenzenethiol to give mono- and bis-vinyl species (CF ) C CFSAr and (CF ) C C(SAr) . PFP reacted
3
2
3
methoxy-substituted arylthiols to give addition products of structure CFClHCF
2
SAr. The arylthiols used throughout the study imitate biological
thiols. Inhalation toxicities of the fluoroalkenes decrease in the order PFIB > PFP > CTFE and correlate with their reactivities towards the model
thiols, supporting the current view that their toxicity relates to their ability to react with biological thiols.
Crown Copyright # 2006 Published by Elsevier B.V. All rights reserved.
Keywords: Chlorotrifluoroethene; Perfluoroisobutene; Perfluoropropene; Thiol; Toxicity
1
. Introduction
PFIB > PFP > CTFE (Table 1) mirroring their electrophilicity
and reactivity to nucleophiles.
Interest in the reactions of fluoroalkenes with sulfur
In contrast to alkenes, polyfluorinated alkenes invite
nucleophilic attack and resist electrophilic attack because the
electronegative fluorine substituents deplete the electron-
nucleophiles was prompted by the discovery that the high
inhalation toxicities of perfluorobutenes correlated with their
reactivities towards biological thiols [1–6]. This study
compares the reactions of perfluoroisobutene (PFIB), perfluor-
opropene (PFP) and chlorotrifluoroethene (CTFE) with
selected arylthiols (Fig. 1).
1
density at the double bond. Nucleophilic attack occurs at
the difluoromethylene group – the most positive site – and three
products can arise, the first from addition of NuH to the double
bond (Fig. 2). Dehydrofluorination follows when the nucleo-
phile or conditions are appreciably basic and the interme-
diate carbanion is unstable (stability order: tertiar-
y > secondary > primary). The carbanion can eliminate
The fluoroalkenes are low-boiling colourless gases that are
TM
insoluble in water. PFIB is a by-product of Teflon
production, PFP is used in polymer synthesis and CTFE in
the manufacture of anaesthetics. Inhalation of the fluoroalkenes
in large doses can cause fatal lung damage [7–10] and small
doses of PFP [11] and CTFE [12,13] can cause kidney
damage. Acute inhalation toxicity decreases in the order
fluoride from the CF Nu group (vinyl substitution) or from
2
1
This profile determines the toxicology of alkenes and fluoroalkenes. Iso-
3 2 2
butene (CH ) C CH is excreted from the lungs, the retained portion slowly
being metabolised to the toxic epoxide, which can alkylate biological nucleo-
philes [14]. In contrast, a large proportion of inhaled perfluoroisobutene
(
3 2 2
CF ) C CF is immobilised through rapid reaction with cellular nucleophiles.
*
Corresponding author. Tel.: +44 1980 613566; fax: +44 1980 613834.
Perfluoroisobutene cannot be metabolised to an epoxide because of its low
reactivity to cytochrome oxidase enzymes present in the lung [15].
E-mail address: cmtimperley@dstl.gov.uk (C.M. Timperley).
0022-1139/$ – see front matter. Crown Copyright # 2006 Published by Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2005.11.008

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C.M. Timperley et al. / Journal of Fluorine Chemistry 127 (2006) 249–256
2
butanethiol (Triton B catalyst), 2-mercaptoacetic acid (Et N
catalyst) or 2-mercaptoethanol (NaOH catalyst) in an autoclave
3
(23–45 8C) give product E [19]. Sodium 1- and 2-propanethio-
late react similarly [20]. Sodium benzenethiolate in ethanol in
an autoclave also gives addition product E [21,22] yet sodium
n-butane- or benzene-thiolate in THF in an open vessel give
substitution product F [23].
Fig. 1. The three fluoroalkenes studied.
Table 1
Comparative toxicity data for the three fluoroalkenes [9]
a
b
LC50 rats (ppm,
Fluoroalkene
Boiling
LC100 mice (mg/l,
2 h exposure)
point (8C)
2 h exposure)
PFIB
PFP
6
ꢀ28
ꢀ28
0.015
9–20
36
<0.18
4000–4466
5040
CTFE
LC100 is the concentration that causes 100% mortality.
a
Data taken from reference 10.
b
LC50 is the lethal concentration of fluoroalkene that causes 50% mortality.
the CF group (allyl substitution). The relationship between the
3
two substitution modes depends on the nucleophile and
conditions, but has not yet been studied systematically, and
is poorly understood. Vinyl substitution predominates in
reactions of PFIB with little or no allyl product forming.
Substitution products often undergo further addition–elimina-
tion sequences to give geminal sulfides.
Fig. 3. Products from reactions of the fluoroalkenes with thiols (D and F can
exist as E- or Z-isomers) [16–27] and the structure of glutathione.
In the body, the tripeptide glutathione protects cells by
reacting with toxic electrophiles via a central cysteinyl thiol
group; the resulting sulfides are usually metabolised to less
toxic products [24]. Glutathione reacts with PFIB in neutral
phosphate buffer to give a ketene thioacetal B [25]. Glutathione
sodium salt reacts with PFP to give products C and D [26] and
with CTFE in alkaline aqueous ethanol to give addition product
E [27]. These products also form in vivo [26,27].
Selectivity of the fluoroalkenes towards thiols in preference to
other nucleophiles, such as amines, water or alcohols, governs
their interaction with biomolecules. Fluoroalkenes can be
classed as soft acids on Pearson’s scale [28] and react more
favourably with soft bases (e.g. RSH) than with hard bases (e.g.
ROH). PFP and CTFE react selectively with the thiol groups of
2-mercaptoethanol [19], N-acetylcysteine [26] and L-cysteine
[29].
Fig. 2. Carbanion from attack of a nucleophile on perfluoroisobutene (PFIB)
and perfluoropropene (PFP) and possible products from protonation or loss of
vinylic (a) or allylic (b) fluoride.
PFIB reacts with sodium ethanethiolate and butanethiolate
in ether to give mono- or bis-vinyl product A or B (Fig. 3). The
second substitution is suppressed at ꢀ30 8C, aiding isolation of
mono products [16]. Mono and bis products are also obtained
with arylthiols in THF in the presence of H u¨ nig’s base
Elsewhere it has been shown that arylthiols are good models
for biological thiols such as cysteine esters [1–4]. In this study,
reactions of PFIB, PFP and CTFE with a 10% molar excess of
benzenethiol and 2-methoxybenzenethiol were compared. The
fluoroalkene was added to a stirred solution of the thiol in
(
diisopropylethylamine) [1]. PFP gives addition or substitution
products, or a mixture of the two. Sodium methane-, ethane-
and 2-hydroxyethane-thiolate in an autoclave (130 8C) give
addition product C [17]. Lithium benzenethiolate and 4-
chlorobenzenethiolate in dioxane in an open vessel or autoclave
2
(120 8C) give addition and vinyl products C and D [18]. CTFE
yields addition or substitution products. Ethanethiol or
Triton B is a 40% aqueous solution of benzyltrimethylammonium hydro-
xide.

C.M. Timperley et al. / Journal of Fluorine Chemistry 127 (2006) 249–256
251
acetonitrile containing anhydrous potassium carbonate, and the
products separated and characterised by the usual techniques.
presumably arose from allylic then vinylic substitution, the
last dehydrofluorination yielding the E-isomer for steric
reasons. Precedent for structure 2c comes from experiments
with perfluoropropene and sodium ethanethiolate that gave in
addition to the main product CF CFHCF SEt, some bis-sulfide
2
. Results and discussion
3
2
2
.1. Perfluoroisobutene
EtSCF CFHCF SEt [17]. Formation of the latter must have
2 2
occurred by allylic substitution followed by addition of the thiol
across the newly generated double bond.
PFIB reacted with two benzenethiol molecules despite the
thiol being present in only 10% molar excess. Compound 1 was
the only significant product in the GC–MS spectrum and was
isolated in modest yield by chromatography on silica gel as a
It is interesting to compare the products from reaction of
PFIB with benzenethiol and 2-methoxybenzenethiol: the
former thiol yielded no mono-vinyl product, reacting further,
whereas the latter thiol yielded mono-vinyl product as the
major component. The difference can be rationalised by
considering the reactivity of the intermediate/product
3
low-melting white solid (Scheme 1).
(CF ) C C(SR)F towards the respective thiols. The S-phenyl
3 2
group is smaller and more electronegative than the S-(2-
methoxyphenyl) group and renders the carbon atom of the
C(SR)F group more electrophilic. Also, the small size of
benzenethiol allows it to react again, yet 2-methoxybenze-
nethiol cannot due to steric hindrance.
Scheme 1.
The threefold predominance of the 1,1-diaryl product 2b
over the 1,3-diaryl product 2c reflects the greater ease of
fluoride loss from the –CF SAr group than from the –CF group
Treatment of PFIB with 2-methoxybenzenethiol gave, from
comparison of integrals in a gas chromatogram of the reaction
mixture, a 6:3:1 mixture of mono-vinyl product 2a and bis-
vinyl products 2b and 2c (Scheme 2).
2
3
of the initial addition product (the trifluoromethyl group is
usually a chemically stable unit). This explains why vinyl
substitution dominates over allylic substitution.
2.2. Perfluoropropene
Treatment of PFP with benzenethiol gave addition product
3a and mono-vinyl product 3b in a 7:3 ratio (Scheme 3). The E
and Z diastereomers of 3b appeared as one peak by GC–MS
analysis and as one spot by TLC analysis using different solvent
systems. Column chromatography of the reaction mixture led to
apparent decomposition of compound 3a (it failed to elute) and
isolation of E/Z mixture 3b.
Scheme 2.
Whereas products 2a and 2b were isolated and charac-
terised, product 2c, whose structure is assumed, but which is
isomeric with 2b by comparison of mass spectra, was isolated
in insufficient quantity to allow full characterisation. It
Scheme 3.
Treatment of PFP with 2-methoxybenzenethiol gave
addition product 4a and diastereomeric mono-vinyl product
4
b in a 2:7 ratio (Scheme 4). Column chromatography caused
3
Compound 1 has been made before in 68% yield by treating (CF
3
)
2
C
CCl
2
apparent decomposition of compound 4a (it was however
obtained in low yield) and permitted isolation of the E/Z
mixture 4b.
with two molar equivalents of benzenethiol in THF in the presence of H u¨ nig’s
base [1] and has been detected in distillation residues after treating PFIB with
sodium benzenethiolate [30]. It has a rare structure and is related to compounds
Multinuclear NMR analysis revealed each pair of diaster-
eomers, 3b and 4b, to comprise a 6:1 E/Z mixture with the E-
isomers dominating. Diastereomers were easily differentiated
CF
CF
3
CH C(SR
2
) formed as by-products from the reactions of the fluoroalkynes
CBB CBr with sodium alkanethiolates [31]. The chemistry
3
CBB CCl and CF
3
of fluorinated alkyl (and aryl) vinyl sulfides has recently been reviewed [32].

252
C.M. Timperley et al. / Journal of Fluorine Chemistry 127 (2006) 249–256
Scheme 4.
1
by F NMR spectroscopy, the values of the F–F coupling
9
constants being particularly diagnostic (Fig. 4). For fluoroalk-
3
enes with the FC CF fragment, the trans J is usually much
Scheme 5.
FF
3
greater than the cis J , typical values being 106–148 and
FF
0
had JFF values of 146 and 3–9 Hz, respectively. For
–58 Hz, respectively [33]. The E- and Z-isomers of 3b and 4b
Schemes 3 and 4 show that the ratio of addition product to
mono-vinyl product shifts from 7:3 to 2:7 in changing the
nucleophile from benzenethiol to 2-methoxybenzenethiol. This
difference cannot be convincingly attributed to the effect of the
3
fluoroalkenes with the CF CF CF fragment, the geminal
3
3
4
3
4
JFF is typically 7–14 Hz, the cis JFF 17–25 Hz and the trans
JFF 6–13 Hz [33]. In both isomers of 3b and 4b, the geminal
SAr group on the acidity of the CF CFH proton of each addition
3
4
JFF remained constant (11 Hz) and cis J equalled 21 Hz (E-
product. Something unusual must account for the product
reversal. One possibility is dehydrofluorination assisted by the
OMe group hydrogen-bonded to the acidic proton (Scheme 6).
Such an effect would not affect the ratio of diastereomers: their
relative proportions would be the same in mono-vinyl products
derived from benzenethiol and 2-methoxybenzenethiol (as
observed).
FF
4
isomers) and trans J equalled 11 Hz (Z-isomers). Chemical
FF
shifts of the fluorine atoms connected to the double bond of the
E-isomers also differed significantly from those of the Z-
isomers (Fig. 4).
Scheme 6.
2.3. Chlorotrifluoroethene
Treatment of CTFE with benzenethiol and methoxybenze-
nethiols gave the addition products 5–8 (Scheme 7) and traces
of the diaryl disulfide (data not shown). The addition products
were isolated after chromatography as colourless liquids.
1
9
Fig. 4. F NMR assignments and coupling constants for E- and Z-isomers of
3b (top pair) and 4b (bottom pair).
The 6:1 E/Z isomer ratio found for 3b and 4b can be
rationalised by considering the transition states during the
reaction (Scheme 5). In the one leading to the E-isomer (left)
the arylthio and trifluoromethyl groups are anti, whereas in the
one leading to the Z-isomer (right) the groups are syn. The left
transition state will be lower energy than the right one where the
SAr and CF groups are aligned unfavourably, and a greater
3
proportion of the E-isomer therefore forms from dehydro-
fluorination.
Scheme 7.

C.M. Timperley et al. / Journal of Fluorine Chemistry 127 (2006) 249–256
253
3. Conclusion
In Parts 1 and 2, the toxicities of fluorocyclobutenes were
shown to correlate with the number of aliphatic thiol
molecules they could react with, supporting the contention
that toxicity was due to reaction with biological thiols in the
lung [2,3]. Fluoroalkenes were classified into groups
according to their alkylating ability. Group I fluoroalkenes
reacted with one molar equivalent of thiol, Group II
fluoroalkenes with two molar equivalents of thiol, and so
on. Members of Group I were less toxic than members of
Group II. If this system is applied to the acyclic fluoroalkenes
studied here, then CTFE belongs to Group I, PFP to Group I/
II, and PFIB to Group II. This order mirrors their relative
toxicities (refer to Table 1). A further refinement of this
classification would take into account the relative electro-
philicities of the fluoroalkenes: toxicities of fluoroalkenes in
the same groups, all other biological factors being equal,
should parallel their electrophilicity, the most electrophilic
fluoroalkene being the most toxic. An increase in electro-
philicity increases the proportion of vinyl substitution and this
results in the greatest toxicity.
1
9
1
Fig. 5. Representative F NMR (top) and H NMR (bottom) shifts for
compounds 5–8 and typical values of the F–F and H–F coupling constants.
We have demonstrated that an autoclave or an open vessel
and a large excess of fluoroalkene for aryl vinyl sulfide
preparation are unnecessary, despite being widely practised in
the past (see Section 1). In our work, mixtures of products were
quantified and the products wherever possible separated by
column chromatography and their stereochemistry deduced.
Separation of products is not easily accomplished by distillation
which is advocated in studies from other research groups, and
such an approach has led to a paucity of stereochemical
information.
1
In each case, the F NMR spectrum comprised two zones of
9
absorption: one at low field due to the CF Ar group and one at
2
3
high field due to the CHFCl group (Fig. 5). The J coupling
HF
2
was in the region of 5–8 Hz and much smaller than the J
HF
coupling (48 Hz) as expected. These NMR parameters agree
with data for related fluorinated species [34,35].
2
.4. Comparison of the reactivity of the fluoroalkenes
To summarise, PFIB gave bis-vinyl products, PFP gave
addition and mono-vinyl products and CTFE gave addition
products. These different behaviours can be rationalised by
consideration of the relative acidities of the protons in the
respective addition products (Fig. 6).
4. Experimental
PFIB was prepared at Dstl Porton Down using a known
procedure [36]. PFP and CTFE were from Apollo Scientific
Ltd. (Stockport, UK) and anhydrous solvents from Aldrich Ltd.
(
Gillingham, UK). TLC was performed on MK6F silica gel
˚
0 A plates (Whatman, USA) with detection by UV light
6
(l = 254 nm) and I vapour. Sorbsil C30 40/60 silica was used
2
for column chromatography. Melting points were determined
on an electrothermal apparatus and are uncorrected. IR spectra
were recorded on a Nicolet SP210 instrument using Omnic
software. NMR spectra were obtained on a JEOL Lambda 500
1
9
1
instrument (operating at 470 MHz for F, 500 MHz for H and
13
25 MHz for C spectra) as solutions in CDCl , with internal
Fig. 6. Products of addition of RSH to PFIB, PFP and CTFE.
1
references CFCl for F and SiMe for H spectra. Mass
3
1
9
1
3
4
The proton acidity decreases in the order G > H > I in line
with the relative electronegativities of the flanking groups
spectra were recorded on a Finnigan MAT GCQ instrument
using chemical ionisation (CI) in the presence of ammonia.
Microanalysis data were obtained from Warwick Analytical
Service Ltd. (Coventry, UK).
(
2 ꢁ CF > F + CF > F + Cl). Therefore, in the presence of
3
3
potassium carbonate, compound G loses HF readily, com-
pound H only partially, and compound I not at all. The use of a
stronger base would be expected to increase the ratio of
unsaturated products derived from PFP and CTFE, and from
the limited studies available, this appears to be the case (see
Section 1).
Caution: Owing to the high inhalation toxicities of the
fluoroalkenes, especially perfluoroisobutene, all experiments
must be performed in an efficient fume cupboard. The safest
way to handle the toxic gases is to inflate a polypropylene gas
bag with a resealing syringe port via a lecture bottle and a short

254
C.M. Timperley et al. / Journal of Fluorine Chemistry 127 (2006) 249–256
length of rubber tubing. A known volume of gas can be
removed from the bag as required using a large gas-tight
syringe. Gas bags of 1 litre capacity supplied by SKC Limited
bis(2-methoxybenzene) 2b which was isolated as mobile liquid
1
(33%). H NMR: d = 7.26 (2H, dd, J = 8 Hz, J = 2 Hz,
3
4
HH
HH
3
4-H), 6.81 (2H, dd, J = 8 Hz, J = 2 Hz, 6-H), 6.75 (2H,
4
HH
HH
3
4
3
(
Unit 11, Sunrise Park, Higher Shaftesbury Road, Blandford
dd, J = 8 Hz, J = 1 Hz, 5-H), 6.73 (2H, dd, J = 8 Hz,
HH HH HH
4
13
Forum, Dorset DT11 8ST, UK; Catalogue No. 232-01) are ideal
for the experiments described.
JHH = 2 Hz, 3-H), 3.67 (6H, s, OCH3). C NMR: d = 161.8 (1-
C), 161.7 (C-S), 158.8 (C-2), 130.5 (C-3), 127.8 (6-H), 121.3
1
q, JCF = 280 Hz, CF ), 120.5 (C-4), 117.1 (septet,
(
2
3
19
JCF = 32 Hz, C-CF ), 110.7 (C-5), 55.6 (OCH ). F NMR:
4
.1. General method
3
3
d = ꢀ54.4 (s, CF ). IR (film): n = 1583, 1523 (C C), 1479,
3
A solution of benzenethiol (1.08 g, 9.82 mmol) or 2-
1464, 1433, 1308, 1277, 1252, 1227, 1027, 1149, 1068, 1041,
ꢀ
1
methoxybenzenethiol (1.37 g, 9.82 mmol) in acetonitrile
25 ml) containing anhydrous potassium carbonate (1.36 g,
.82 mmol) and a magnetic stirrer bead was placed in a 500 ml
round-bottomed flask sealed with a rubber septum. Air
ꢂ300 ml) was removed from the flask using a gas-tight
syringe with a large bore needle. The fluoroalkene (200 ml,
.93 mmol) was transferred from a gas bag using a gas-tight
syringe and injected into the stirred contents of the flask. After
h, the septum was removed and the reaction mixture analysed
1026, 995, 910, 750, 735, 714 cm . CI–MS (m/z, %): 441
(M + 1, 40), 421 (M-HF, 38), 301 (40), 246 (100), 157 (32), 139
(18), 111 (15). Calcd. for C H F O S : C, 49.1; H, 3.2; S,
(
9
1
8 14 6 2 2
14.6. Found: C, 49.1; H, 3.1; S, 14.5%.
The third product, presumed on the basis of its chemical
(
0
ionisation mass spectrum to be 1,1 -{[(1E)-1,3,3-trifluoro-2-
(trifluoromethyl)prop-1-ene-1,3-diyl]bis(thio)}bis(2-methoxy-
8
benzene) 2c, was isolated in insufficient quantity to permit
+
accurate characterisation. CI–MS (m/z, %): 440 (M , 4), 278
(46), 171 (100), 138 (86), 107 (8), 53 (24).
2
by TLC and GC–MS. The inorganic salts were removed by
filtration, washed with acetonitrile, and the filtrate concentrated
to give a liquid. Unless otherwise stated, chromatography on
silica gel permitted separation of the major components.
4.4. Reaction of PFP with benzenethiol to give (E- and
Z-3b)
4
.2. Reaction of PFIB with benzenethiol to give (1)
Analysis of the reaction mixture by GC–MS and TLC
showed two products, the addition product 3a (Rf hexane 0.29)
and isomers 3b (Rf hexane 0.55). Chromatography on silica gel,
eluting with 16:1 hexane–acetone, gave a 6:1 mixture of {[(1E)-
1,2,3,3,3-pentafluoroprop-1-en-1-yl]thio}benzene and {[(1Z)-
1,2,3,3,3-pentafluoroprop-1-en-1-yl]thio}benzene 3b (28%).
TLC and GC–MS analysis revealed the presence of only one
product. The crude product was recrystallised from hot ether
0
and hexane to yield 1,1 -{[3,3,3-trifluoro-2-(trifluoromethyl)-
prop-1-ene-1,1-diyl]bis(thio)}dibenzene 1 as a white crystal-
line solid (36%). Mp 62–63 8C. The spectroscopic data
obtained matched those for a specimen prepared previously
under different conditions [1].
1
H NMR for isomeric mixture: d = 7.51 (2H, m, 2-H and 6-
1
H), 7.42 (3H, m, 3-H, 4-H and 5-H). C NMR of major isomer
3
3b only (CF CF CF carbon resonances were of low intensity
3
and obscured in baseline noise): d = 133.1 (2-C and 6-C), 129.8
1
9
4
.3. Reaction of PFIB with 2-methoxybenzenethiol to give
2a–2c)
(4-C), 129.6 (3-C and 5-C). F NMR for E-3b: d = ꢀ154.9 (1F,
3
3
(
dq, J = 146 and J = 11 Hz, CFCF ), ꢀ119.4 (1F, dq,
FF FF 3
3
4
4
JFF = 146 and J = 21 Hz, CFS), ꢀ67.1 (3F, dd, J = 21
FF FF
19
3
TLC analysis of the crude reaction mixture with hexane as
and J = 12 Hz, CF ). F NMR for Z-3b: d = ꢀ135.2 (1F, dq,
FF
3
3
3
4
eluent showed the presence of three products. The mixture was
chromatograped on silica gel eluting with hexane then 1:1
hexane–acetone. The first product to elute with R 0.25 was 1-
JFF = 11 and J = 3 Hz, CFCF ), ꢀ99.1 (1F, dq, J = 11
FF FF 3
FF 3 FF
3
3
and J = 3 Hz, CFS), ꢀ64.2 (3F, dd, J = each 11 Hz, CF ).
IR for E/Z-3b (film): n = 1354 (C C), 1213, 1147, 1024, 941,
f
ꢀ
1
methoxy-2-{[1,3,3,3-tetrafluoro-2-(trifluoromethyl)propen-
-yl] thio}benzene 2a which was isolated as a colourless liquid
862, 748, 719 cm . CI–MS for E/Z-3b (m/z, %): 241 (M + 1,
50), 221 (M-F, 100), 201 (M-HF , 44). Calcd. for C H F S: C,
45.0; H, 2.1; S, 13.3. Found: C, 44.9; H, 2.0; S, 13.1%.
1
2
9 5 5
1
26%). H NMR: d = 7.51 (2H, m, 4-H and 6-H), 7.02 (2H, m,
(
1
-H and 5-H), 3.94 (3H, s, OCH3). C NMR: d = 170.3 (C-S),
3
3
1
m, obscured), 121.4 (5-C), 111.6 (3-C), 102.7 (C-CF ), 55.9
59.8 (2-C), 136.5 (6-C), 133.0 (4-C), 128.1 (1-C), 121.5 (CF3,
4.5. Reaction of PFP with 2-methoxybenzenethiol to give
(4a and 4b)
3
1
9
(
OCH3). F NMR: d = ꢀ63.7 (1F, m, C-F), ꢀ56.5 (3F, dq,
4
3
4
JFF = 24 and J = 9 Hz, CF trans to SAr), ꢀ55.8 (3F, dq, J
FF 3 FF
TLC analysis of the reaction mixture with hexane as eluent
showed the presence of three products. The first two were
isolated by chromatography eluting first with hexane, then 20:1
hexane–acetone, followed by 6:1 hexane–acetone. The first
product to elute with Rf hexane 0.22 was a 6:1 mixture of 1-
methoxy-2-{[(1E)-1,2,3,3,3-pentafluoroprop-1-en-1-yl]thio}-
benzene and 1-methoxy-2-{[(1Z)-1,2,3,3,3-pentafluoroprop-1-
en-1-yl]thio}benzene 4b isolated as a colourless liquid (44%).
3
and J = 9 Hz, CF cis to SAr). IR (film): n = 1075, 1622
FF
3
(
C C), 1587, 1481, 1466, 1437, 1346, 1273, 1215, 1155, 1066,
ꢀ
1
026, 987, 910, 862, 800, 742, 705 cm . CI–MS (m/z, %): 320
1
+
M , 18), 301 (M-F, 100), 281 (M-HF , 27), 138 (14). Calcd. for
(
C H F OS: C, 41.3; H, 2.2; S, 10.0. Found: C, 41.2; H, 2.1; S,
2
1
1 7 7
9
.8%.
The second product to elute with R 0.05 was 1,1 -{[3,3,3-
trifluoro-2-(trifluoromethyl)prop-1-ene-1,1-diyl]bis(thio)}-
0
f
1
3
H NMR of isomeric mixture: d = 7.42 (2H, m, J = 8 and
HH

C.M. Timperley et al. / Journal of Fluorine Chemistry 127 (2006) 249–256
255
4
3
JHH = 2 Hz, 6-H), 7.41 (2H, m, 4-H), 7.02 (2H, J = each
1
2
19
JCF = 253 and J = 38 Hz, CHClF), 56.0 (C-1). F NMR:
CF
HH
3
Hz, 5-H), 6.94 (2H, m, J = 8 Hz, 3-H), 3.91 (6H, s,
2
3
8
d = ꢀ147.4 (dt, J = 48 and J = 18 Hz, CHClF), ꢀ90.2
HH
HF
FF
1
3
2
3
3
OCH3). C NMR of major isomer 4b only (CF CF CF carbon
resonances were of low intensity and obscured in baseline
noise): d = 158.9 (2-C), 134.1 (6-C), 132.9 (1-C), 131.4 (4-C),
(ddd, J = 222, J = 18 and J = 8 Hz, CFS), ꢀ86.0 (ddd,
3
FF FF HF
2
3
JFF = 222, J = 24 and J = 5 Hz, CFS). CI–MS (m/z, %):
3
FF HF
+
256 (M , 64), 237 (M-F, 100), 138 (25). Calcd. for
1
9
1
21.7 (5-C), 111.8 (6-C). F NMR for E-4b: d = ꢀ156.1 (1F,
C H ClF OS: C, 42.1; H, 3.1; S, 12.5. Found: C, 42.0; H,
9
8
3
3
3
dq, J = 146 and J = 11 Hz, CF CF), ꢀ120.4 (1F, dq,
3.1; S, 12.4%.
FF
FF
3
3
4
4
JFF = 146 and J = 21 Hz, CFS), ꢀ66.5 (3F, dd, J = 21
FF
FF
3
19
and J = 11 Hz, CF ). F NMR for Z-4c: d = ꢀ136.6 (1F, dq,
4.8. Reaction of CTFE with 3-methoxybenzenethiol
to give (7)
FF
3
3
3
4
JFF = 11 and J = 9 Hz, CF CF), ꢀ100.0 (1F, dq, J = 11
FF
3
FF
3
3
and J = 9 Hz, CFS), ꢀ64.2 (3F, dd, J = each 11 Hz, CF ).
FF
FF
3
IR for E/Z-4b (film): n = 1684, 1585, 1481, 1465, 1435, 1354
Chromatography on silica gel, eluting with hexane, gave 1-
[(2-chloro-1,1,2-trifluoroethyl)thio]-3-methoxybenzene 7 as a
(
C C), 1296, 1279, 1252, 1211, 1146, 1066, 1026, 939, 862,
+
ꢀ1
1
3
colourless liquid (57%). H NMR: d = 7.32 (1H, t, J = 8 Hz,
750, 719 cm . CI–MS for E/Z-4b (m/z, %): 270 (M , 54), 251
M-F, 100), 138 (38).
HH
3
5-H), 7.24 (1H, d, J = 8 Hz, 6-H), 7.19 (1H, m, fine coupling
(
HH
4
5
The second product to elute with Rf hexane 0.11 was 1-
2 Hz, 4-H), 7.02 (1H, ddd, J = 3 Hz, J = 3 and 1 Hz, 2-H),
HH HH
2
3
3
[
(1,1,2,3,3,3-hexafluoropropyl)thio]-2-methoxybenzene
1
4a
isolated as a colourless liquid (8%). H NMR: d = 7.62 (1H,
6.11 (1H, ddd, J = 48, J = 8 and J = 8 Hz, CHClF),
HF HF HF
13
3.83 (3H, s, OCH3). C NMR: d = 159.9 (C-3), 130.2 (5-C),
3
4
3
dd, J = 8 and J = 2 Hz, 6-H), 7.48 (1H, m, J = 8 and
4
1
2
129.0(1-C), 124.9 (4-C), 124.0 (td, J = 285and J = 27 Hz,
CF CF
HH
HH
HH
1
JHH = 2 Hz, 4-H), 7.01 (2H, m, 3-H and 5-H), 4.82 (1H, m,
1
CF S), 121.8 (C-2), 116.8 (C-6), 96.9 (dt, J = 252 and
2 CF
3
2
2
3
3
19
CHF), 3.9 (3H, s, OCH3). C NMR: d = 161.0 (C-2), 139.7 (C-
), 133.2 (C-4), 131.1 (C-1), 122.5 (m, CF ), 121.3 (C-5), 119.1
JCF = 38 Hz, CHClF), 55.4 (OCH ). F NMR: d = ꢀ147.4 (dt,
3
3
2
6
JHF = 50 and J = 18 Hz, CHClF), ꢀ89.6 (ddd, J = 222,
3
FF
FF
1
m, CF S), 111.8 (C-3), 85.7 (m, CHF), 56 (OCH ). F NMR:
9
3
2
J
(
JFF = 18 and
J
= 8 Hz, CFS), ꢀ84.8 (ddd,
= 222,
2
3
HF
FF
3
+
d = ꢀ203.3 (1F, m, CHF), ꢀ87.9 and ꢀ82.8 (each 1F, m, CF S),
JFF = 24 and J = 5 Hz, CFS). CI–MS (m/z, %): 256 (M ,
HF
2
+
72.6 (3F, m, CF ). CI–MS (m/z, %): 290 (M , 15), 271 (M-F,
ꢀ
66), 237 (M-F, 100), 138 (25). Calcd. for C H ClF OS: C, 42.1;
9 8 3
3
1
00), 251 (M-HF , 12), 138 (38). Calcd. for C H F OS: C,
2
H, 3.1; S, 12.5. Found: C, 42.1; H, 3.0; S, 12.5%.
.9. Reaction of CTFE with 4-methoxybenzenethiol
to give (8)
10 8 6
4
1.4; H, 2.8; S, 11.0. Found: C, 41.3; H, 2.7; S, 11.0%.
.6. Reaction of CTFE with benzenethiol to give (5)
Analysis of the reaction mixture by GC–MS showed one
4
4
Chromatography on silica gel, eluting with 49:1 hexane-
acetone, gave 1-[(2-chloro-1,1,2-trifluoroethyl)thio]-4-meth-
fluorinated product. Chromatography on silica gel, eluting with
hexane, gave [(2-chloro-1,1,2-trifluoroethyl)thio]benzene 5
1
oxybenzene 8 as a colourless liquid (68%). H NMR:
3
d = 7.56 (2H, d, J = 9 Hz, 3-H and 5-H), 6.94 (2H, d,
1
with R 0.33 as a colourless liquid (58%). H NMR: d = 7.65
HH
f
3
2
3
JHH = 8 Hz, 2-H and 6-H), 6.07 (1H, ddd, J = 48, J = 8
HF
HF
(
2H, m, 2-H and 6-H), 7.48 (1H, m, 4-H), 7.41 (2H, m, 3-H and
3
13
and J = 8 Hz, CHClF), 3.84 (1H, s, OCH ). C NMR:
2
-H), 6.11 (1H, ddd, JHF = 48, JHF = 8 and JHF = 5 Hz,
3
3
HF
3
5
CHClF). C NMR: d = 137.0 (2-C and 6-C), 130.8 (4-C), 129.5
1
d = 161.8 (4-C), 138.7 (3-C and 5-C), 123.8 (td, J = 284 and
1
3
CF
2
JCF = 27 Hz, CF S), 115.0 (2-C and 6-C), 114.4 (C-1), 96.9
2
1
(3-C and 5-C), 124.1 (m, CF S), 97.1 (td, J = 252 and
2 CF
2
1
dt, J = 248 and J = 34 Hz, CHClF), 55.4 (OCH ).
2
19
(
F
19
2
CF
CF
2
3
JCF = 34 Hz, CHClF). F NMR: d = ꢀ146.5 (1F, dt, J = 48
HF
3
NMR: d = ꢀ147.5 (dt, J = 47 and J = 18 Hz, CHClF),
3
2
2
HF
3
FF
3
and JFF = 18 Hz, CHClF), ꢀ88.6 (1F, ddd,
J
= 221,
FF
2
ꢀ
85.9 (ddd,
J
90.8 (ddd, J = 222, J = 23 and J = 5 Hz, CFS). CI–
= 222, JFF = 18 and JHF = 8 Hz, CFS),
FF
3
3
3
JFF = 18 and J = 8 Hz, CFS), ꢀ84.1 (1F, ddd, J = 221,
HF
FF
2
3
3
ꢀ
3
JFF = 18 and J = 4 Hz, CFS). CI–MS (m/z, %): 226 (M ,
+
FF
FF
HF
HF
+
MS (m/z, %): 256 (M , 66). Calcd. for C H ClF OS: C, 42.1; H,
9
8
3
4
4
2). Calcd. for C H ClF S: C, 42.4; H, 2.7; S, 14.1. Found: C,
8 6 3
3
.1; S, 12.5. Found: C, 42.1; H, 3.1; S, 12.3%.
2.5; H, 2.6; S, 14.1%.
Acknowledgements
4.7. Reaction of CTFE with 2-methoxybenzenethiol
to give (6)
We wish to thank Suzannah Heard for double-checking
some of the experimental data, Ian Holden for assistance with
interpretation of the NMR data, and the Ministry of Defence
UK for funding this work. # Crown Copyright 2005 by
permission of HMSO Controller of Stationary.
Chromatography on silica gel, eluting with hexane, gave 1-
(2-chloro-1,1,2-trifluoroethyl)thio]-2-methoxybenzene 6 as a
[
colourless liquid (64%). H NMR: d = 7.62 (1H, dd, J = 8
1
3
HH
4
and J = 2 Hz, 3-H), 7.46 (1H, td, J = 8 and J = 2 Hz,
3
4
HH
HH
HH
3
3
5
4
-H), 6.99 (1H, t, J = 7 Hz, 6-H), 6.98 (1H, t, J = 7 Hz,
HH HH
3
-H), 6.17 (1H, ddd, JHF = 48, JHF = 8 and JHF = 8 Hz,
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1
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CHClF), 3.90 (1H, s, OCH3). C NMR: d = 160.9 (C-2), 139.5
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