Thia-Fries rearrangement of aryl triflinates to trifluoromethanesulfinylphenols

Article abstract of DOI:10.1016/S0022-1139(03)00106-4

Aryl triflinates are transformed to trifluoromethanesulfinylphenols in the presence of aluminum trichloride in dichloromethane at room temperature according to a thia-Fries rearrangement process. Rigorous exclusion of oxygen is necessary in order to avoid the formation of 2,2′-dihydroxybiaryls as secondary products.

Full text of DOI:10.1016/S0022-1139(03)00106-4

Journal of Fluorine Chemistry 123 (2003) 51–56
Thia-Fries rearrangement of aryl triflinates to
trifluoromethanesulfinylphenols
Ximin Chena, Marc Tordeuxa, Jean-Roger Desmursb, Claude Wakselmana,*
a
ˆ
SIRCOB-CNRS, Batiment Lavoisier, Universite de Versailles-Saint Quentin en Yvelines, 45 Avenue des Etats-Unis, 78035 Versailles, France
´
bRhodia Perfumery Performance Agro, 190 Avenue Thiers, 69457 Lyon Cedex 06, France
Received 24 January 2003; received in revised form 20 March 2003; accepted 20 March 2003
Dedicated to Professor Ronald Eric Banks on the occasion of his 70th birthday
Abstract
Aryl triflinates are transformed to trifluoromethanesulfinylphenols in the presence of aluminum trichloride in dichloromethane at room
temperature according to a thia-Fries rearrangement process. Rigorous exclusion of oxygen is necessary in order to avoid the formation of
2,20-dihydroxybiaryls as secondary products.
# 2003 Elsevier Science B.V. All rights reserved.
Keywords: Rearrangement; Sulfinates; Sulfoxides; Dihydroxybiaryls
1. Introduction
rearrangement of aryl triflinates 1 could be used for direct
access to new trifluoromethanesulfinylphenols 2 and/or 3
(Scheme 2).
Phenyl esters can be transformed to acylphenols in the
presence of Friedel-Crafts catalysts according to a Fries
rearrangement [1] (Scheme 1). The analogous change of aryl
sulfinates into sulfinylphenols, the ‘‘thia-Fries rearrange-
ment’’, has been reported only in the case of aryl benzene-
sulfinates [2,3] (Scheme 1: Y ¼ S; R ¼ Ph). This reaction
allows the installation of a sulfinyl substituent directly onto
an aromatic nucleus.
Among the sulfinyl groups, trifluoromethanesulfinyl is
interesting because it is present in the structure of
various biologically active compounds [4–6]. Usually, these
fluorinated sulfoxides are prepared by oxidation of the
corresponding sulfides [7,8], by reaction of trifluorome-
thyltrimethylsilane with arenesulfinyl halides [9] or with
arenesulfinate esters [10]. Alternatively, aryl and heteroaryl-
trifluoromethylsulfoxides are available by direct sulfinylation
of aromatic and heterocyclic compounds by trifluorome-
thanesulfinyl chloride [11] or by triflinate (trifluoromethane-
sulfinate) salts in the presence of phosphorus oxychloride
[12] or of triflic acid [13]. In principle, the thia-Fries
2. Results
Aryl trifluoromethanesulfinates 1 were prepared from the
corresponding phenols by reaction with a mixture of potas-
sium triflinate and phosphorus oxychloride in ethyl acetate
at room temperature [12]. Because these products are not
very stable, they were used for the study of the thia-Fries
rearrangement just after their purification by column chro-
matography. Aluminum trichloride, as Lewis acid, and
usually dichloromethane, as solvent, were employed for
their transformation to trifluoromethanesulfinylphenols.
The reactions were performed at room temperature under
argon. In the first attempts, we found that secondary pro-
ducts were formed. These compounds, more polar than the
thia-Fries products on thin layer chromatography plates, are
devoided of the trifluoromethyl group as shown by 19F
NMR. Their 1H NMR and mass spectra characteristics
are in agreement with 2,20-dihydroxybiaryl structures 4
(Scheme 3). In the literature, coupling of dichloroaluminum
phenolates for synthesizing 2,20-dihydroxybiaryls is known
to be promoted by iron trichloride or by a quinone [14]. In
the absence of these additives, oxygen was supposed to be
the oxidant (see Scheme 3 for an hypothetical mechanism).
* Corresponding author. Tel.: þ33-1-39-25-44-11;
fax: þ33-1-39-25-44-11.
E-mail addresses: tordeux@chimie.uvsq.fr (M. Tordeux),
jeanroger.desmurs@eu.rhodia.com (J.-R. Desmurs),
wakselma@chimie.uvsq.fr (C. Wakselman).
0022-1139/$ – see front matter # 2003 Elsevier Science B.V. All rights reserved.
doi:10.1016/S0022-1139(03)00106-4

52
X. Chen et al. / Journal of Fluorine Chemistry 123 (2003) 51–56
Scheme 1.
Scheme 2.
Consequently, the thia-Fries rearrangement reaction was per-
formedunderargonwithamorerigorousexclusionofoxygen.
In these last conditions, coupling products 4 were avoided.
Results of the rearrangement of various phenyl trifluor-
omethanesulfinates are gathered in Table 1. The reactions
were usually performed in dichloromethane because the
yields were lower in toluene (Table 1: entries 2 and 3).
No evidence for a sulfinylation of the aromatic solvent was
found. A single sulfoxide was isolated when the phenyl ring
is para-substituted (Scheme 4).
Mixtures of isomeric sulfoxides were obtained when the
aromatic ring of the starting phenyl sulfinates is substituted
at the meta-position (Table 1: entries 9 and 10) (Scheme 5) or
not substituted (Table 1: entry 1). Incidentally, when the
meta-substituent is the electron-withdrawing trifluoromethyl
group, such a rearrangement does not happen. 2,20-Dihy-
droxybiaryl by-products were characterized in some cases
(Table 4: compounds 4b–d, f).
In the case of 1-naphtyl trifluoromethanesulfinate 1j, only
one sulfoxide 2j was isolated with a 22% yield (Scheme 6).
Scheme 3.

X. Chen et al. / Journal of Fluorine Chemistry 123 (2003) 51–56
53
Table 1
Thia-Fries rearrangement of phenyl triflinates
Entry
Sulfinate
R
Solvent
Sulfoxide
Yield (%)
Dihydroxybiaryla
1
2
1a
1b
1b
1c
1d
1e
1f
H
CH2Cl2
Toluene
CH2Cl2
Toluene
Toluene
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
2a þ 3a
2b
2b
35 þ 38
30
75
4-F
4-F
4b
3
4
4-Cl
4-Br
4-Me
4-OMe
4-Ph
3-Me
3-Ph
2c
2d
36
4c
4d
5
23
6
2e
74
72
7
2f
2g
4f
8
1g
1h
1i
45
9
10
2h þ 3h
32 þ 13
32 þ 29
2i þ 3i
a Secondary products isolated when the medium is not completely protected against oxygen.
Scheme 4.
Scheme 5.
and chemicals shifts were based on a first order analysis.
Internal reference was the residual peak of CHCl3 (7.27 ppm)
for 1H (300 MHz), central peak of CDCl3 (77 ppm) for 13
C
(75 MHz) spectra and internal CFCl3 (0 ppm) for 19F
(282 MHz) NMR spectra. GCMS were performed with
Chrompack CP Sil 19 CB chromatography column, length
30 m, diameter 0.25 mm, film thickness 0.25 mm, initial tem-
perature 50 8C over 2 min, gradient 10 8C/min, final tempera-
ture 250 8C on a HP 5989B quadrupolar mass spectrometer.
Scheme 6.
3. Conclusion
4.2. Synthesis of 4-fluorophenyl trifluoromethanesulfinate
(compound 1b): typical procedure
Grafting of a trifluoromethanesulfinyl group to an aro-
matic nucleus is efficient when the thia-Fries rearrangement
of aryltriflinates is performed in dichloromethane at room
temperature in the presence of aluminum trichloride with
rigorous exclusion of oxygen.
In a 50 ml three-necked round bottom flask, equipped
with a gas inlet and a dry tube with silica gel, was added
3.44 g (20 mmol) of potassium triflinate and 12 ml of ethyl
acetate. At room temperature, 1.53 g (10 mmol) of phos-
phorus oxychloride was introduced under argon. The result-
ing mixture was stirred for 10 min, then 1.12 g (10 mmol) of
4-fluorophenol (dissolved in 3 ml of ethyl acetate) was
added. The reaction mixture was stirred at room temperature
for 2 h. Then the solvent was removed, and the residue was
purified by column chromatography using pentane: ether
(10:1) as eluent to give 1.61 g of colorless liquid. Properties
are summarized in Table 2.
4. Experimental
4.1. General
NMR spectra were recorded as CDCl3 solutions, on a
Bruker AC-300 spectrometer. Reported coupling constants

54
X. Chen et al. / Journal of Fluorine Chemistry 123 (2003) 51–56
Table 2
Properties of phenyl trifluoromethanesulfinates 1
Starting phenol
Sulfinate 1
Yield (%)
64
1H NMR (CDCl3)
19F NMR
d (ppm), J (Hz)
(CDCl3/CFCl3) (ppm)
1a
7.43 (t, 2H, J ¼ 7.7)
7.35 (t, 1H, J ¼ 7.4)
7.28 (d, 2H, J ¼ 7.9)
ꢀ79.6
1b
1c
1d
1e
1f
71
54
47
77
71
7.2 (m, 2H)
7.1 (m, 2H)
ꢀ79.4
ꢀ114.6 (m, 1F)
7.40 (d, 2H)
ꢀ79.3
ꢀ79.3
ꢀ79.1
ꢀ79.3
7.16 (d, 2H, J ¼ 8.8)
7.56 (d, 2H)
7.10 (d, 2H, J ¼ 8.9)
7.21 (d, 2H)
7.09 (d, 2H, J ¼ 8.2)
2.35 (s, 3H)
7.16 (d, 2H)
6.89 (d, 2H, J ¼ 8.8)
3.82 (s, 3H, CH3)
1g
1h
18
51
7.60 (bd, 2H, J ¼ 8.1)
7.46 (m, 4H)
ꢀ79.58
ꢀ79.8
7.32 (m, 3H)
7.31 (dd, 1H)
7.15 (d, 1H, J ¼ 7.2)
7.00 (d, 1H, J ¼ 8)
7.04 (bs, 1H)
2.38 (s, CH3)
1i
1j
69
43
7.2–7.65 (m, 9H)
ꢀ79.6
ꢀ79.4
8.13 (m, 1H)
7.91 (m, 1H)
7.82 (d, 1H, J ¼ 8.9)
7.61 (m, 2H)
7.46 (t, 1H, J ¼ 8.5)
7.38 (d, 1H J ¼ 7.6)
Table 3
Properties of phenyl trifluoromethylsulfoxides 2 and 3
Yield
(%)
Melting
1H NMR
(ppm)
19F NMR
(ppm)
MS (m/z, %)
211 (Mþ þ 1, 100)
Analysis
point (8C)
2a
3a
35
116.4
9.4 (s, 1H, OH)
ꢀ73.95
Calcd for C7H5F3SO2 (%) C, 39.81;
H, 2.39; found: C, 40.08; H, 2.40
7.53 (dd, 1H)
7.28 (d, 1H, J ¼ 6.4)
7.02 (t, 2H, J ¼ 7.9)
38
117.7
7.74 (d, 2H, J ¼ 7.7) ꢀ75.5
7.14 (d, 2H, J ¼ 7.7)
6.7 (s, 1H, OH)
211 (Mþ þ 1, 100)
Calcd for C7H5F3SO2 (%) C, 39.81;
H, 2.39; found: C, 40.03; H, 2.37

X. Chen et al. / Journal of Fluorine Chemistry 123 (2003) 51–56
55
Table 3 (Continued )
Yield Melting
1H NMR
(ppm)
19F NMR
(ppm)
MS (m/z, %)
Analysis
(%)
point (8C)
2b
75
107.5
9.1 (s, 1H, OH)
7.2 (m, 2H)
7.0 (m, 1H)
ꢀ73.7
229 (Mþ þ 1, 100)
Calcd for C7H4F4SO2 (%) C, 36.85;
H, 1.77; found: C, 36.92; H, 1.58
ꢀ121.8 (1F)
2c
36
23
119.2
140.0
9.2 (s, 1H, OH)
7.44 (d, 1H, J ¼ 9.1)
7.27 (bs, 1H)
ꢀ73.5
ꢀ73.5
245 (Mþ þ 1, 100)
247 (Mþ þ 3, 35)
Calcd for C7H4ClF3SO2 (%) C, 34.36;
H, 1.65; found: C, 34.38; H, 1.55
6.96 (d, 1H, J ¼ 9.1)
9.0 (s, 1H, OH)
2d
289 (Mþ þ 95)
Calcd for C7H4BrF3SO2 (%) C, 29.08;
H, 1.39; found: C, 29.06; H, 1.33
7.58 (dd, 1H)
291 (Mþ þ 2, 100)
7.46 (d, 1H, J ¼ 2.0)
6.91 (d, 1H, J ¼ 9.1)
2e
2f
74
72
134.4
121.6
9.0 (s, 1H)
ꢀ73.95
ꢀ73.7
225 (Mþ þ 1, 100)
Calcd for C8H7F3SO2 (%) C, 42.86;
H, 3.15; found: C, 43.03; H, 2.95
7.33 (d, 1H, J ¼ 8.2)
7.04 (bs, 1H)
6.9 (d, 1H, J ¼ 8.2)
2.35 (s, 3H)
8.7 (s, 1H, OH)
240 (Mþ, 22.5)
171 (Mþ-CF3, 100)
Calcd for C8H7F3SO2 (%) C, 40.00;
H, 2.94; found: C, 40.03; H, 2.92
7.11 (dd, 1H, J ¼ 9.1)
6.97 (d, 1H, J ¼ 9.1)
6.78 (d, 1H, J ¼ 2.9)
3.81 (s, OCH3)
2g
2h
45
32
9.4 (s, 1H)
ꢀ73.7
ꢀ74.3
287 (Mþ þ 1, 46)
Calcd for C13H9F3SO2 (%) C, 54.54;
H, 3.17; found: C, 54.77; H, 3.31
7.76 (d, 1H, J ¼ 8.3)
7.40 (m, 6H)
7.10 (d, 1H, J ¼ 8.7)
117.2
9.3 (s, 1H, OH)
7.10 (d, 1H, J ¼ 7.9)
6.8 (m, 2H)
224 (Mþ, 16)
155 (Mþ-CF3, 100)
Calcd for C8H7F3SO2 (%) C, 42.86;
H, 3.15; found: C, 42.89; H, 3.19
2.39 (s, 3H, CH3)
3h
2i
13
32
103.0
146.5
7.87 (d, 1H, J ¼ 8.5) ꢀ74.6
6.95 (dd, 1H)
224 (Mþ, 9)
Calcd for C8H7F3SO2 (%) C, 42.86;
H, 3.15; found: C, 42.91; H, 3.05
155 (Mþ-CF3, 100)
6.79 (d, 1H, J ¼ 2.6)
6.8 (s, 1H, OH)
2.43 (s, CH3)
9.5 (s, 1H, OH)
7.60 (d, 2H, J ¼ 8.2)
7.47 (m, 3H)
ꢀ73.9
286 (Mþ, 5)
217 (Mþ-CF3, 91)
69 (CF3þ, 100)
Calcd for C13H9F3SO2 (%) C, 54.54;
H, 3.17; found: C, 54.61; H, 3.49
7.26 (m, 3H)
3i
2j
29
22
8.05 (d, 1H, J ¼ 8.7) ꢀ73.6
7.44 (m, 4H)
286 (Mþ, 2)
Calcd for C13H9F3SO2 (%) C, 54.54;
H, 3.17; found: C, 54.92; H, 3.90
69 (CF3, 42)
7.31 (m, 2H)
7.10 (dd, 1H)
6.88 (d, 1H, J ¼ 2.8)
8.36 (d, 1H, J ¼ 8.8) ꢀ74.01
8.12 (d, 2H, J ¼ 8.7)
7.64 (m, 3H)
7.06 (d, 1H, J ¼ 8.9)
Compound 3b: 13C NMR (CDCl3): 161.02, 140.81, 128.39, 125.20 (q, J ¼ 334.6), 123.34, 118.19, 115.05, 18.43 ppm.

56
X. Chen et al. / Journal of Fluorine Chemistry 123 (2003) 51–56
Table 4
Properties of dihydroxybiphenyls 4
Dihydroxybiaryl
Yield
(%)
Melting
9F NMR
(ppm)
MS (m/z, %)
Analysis
point (8C)
4b
4c
2.2
139.9
7.0 (m, 6H)
6.21 (s, 2H, OH)
ꢀ122.9
223 (Mþ þ 1, 100) Calcd for C12H8F2O2 (%): C, 64.87;
H, 3.63; found: C, 63.85; H, 3.44
28
173.4
7.31 (dd, 2H, J ¼ 8.5)
7.0 (d, 2H, J ¼ 8.5)
7.27 (d, 2H, J ¼ 2.4)
Calcd for C12H8Cl2O2 (%): C, 56.50;
H, 3.16; found: C, 54.24; H, 3.31
4d
4f
14.5
12.5
7.39 (dd, 2H, J ¼ 8.3)
6.87 (d, 2H, J ¼ 8.3)
7.40 (d, 2H, J ¼ 2.5)
124.2
6.9 (m, 6H)
246 (Mþ, 3)
Calcd for C14H14O4 (%): C, 68.28; H, 5.73;
found: C, 66.86; H, 5.60
6.42 (s, 2H, OH)
3.82 (s, 6H)
4.3. Synthesis of 2-hydroxy-5-fluorophenyl
trifluoromethylsulfoxide (compound 2b): typical procedure
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