S-Trifluoromethyl esters of thiocarboxylic acids, RC(O)SCF3

Article abstract of DOI:10.1016/j.tetlet.2004.06.073

S-Trifluoromethyl esters of different types of thiocarboxylic acids have been prepared in moderate to excellent yields from halide substitution reactions of the corresponding acid chlorides and tetramethylammonium trifluoromethylthiolate. C₆F₅C(O)SCF₃ undergoes a surprising rearrangement on attempted isolation to give 4-CF ₃SC₆F₄C(O)F, which was converted into the corresponding acid.

Full text of DOI:10.1016/j.tetlet.2004.06.073

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 6101–6104
S-Trifluoromethyl esters of thiocarboxylic acids, RC(O)SCF3
Mikhail M. Kremlev,a Wieland Tyrra,b,* Dieter Naumannb and Yurii L. Yagupolskiia
aInstitute of Organic Chemistry, National Academy of Sciences of Ukraine, Murmanskaya St. 5, UA-02094 Kiev, Ukraine
bInstitut f€ur Anorganische Chemie, Universit€at zu K€oln, Greinstr. 6, D-50939 K€oln, Germany
Received 9 June 2004; revised 16 June 2004; accepted 16 June 2004
Available online 2 July 2004
Abstract—S-Trifluoromethyl esters of different types of thiocarboxylic acids have been prepared in moderate to excellent yields
from halide substitution reactions of the corresponding acid chlorides and tetramethylammonium trifluoromethylthiolate.
C6F5C(O)SCF3 undergoes a surprising rearrangement on attempted isolation to give 4-CF3SC6F4C(O)F, which was converted into
the corresponding acid.
Ó 2004 Elsevier Ltd. All rights reserved.
The number of S-trifluoromethyl esters of thiocarb-
1
oxylicacids is limited so far to very few examples. To
Reactions6 of carboxylic acid chlorides
1
and
[NMe4]SCF3 proceed nearly selectively in MeCN to give
the corresponding S-trifluoromethyl ester 2 in good
yields (Scheme 1). The low solubility of [NMe4]Cl in
acetonitrile must be assumed to be the driving force for
these reactions since it begins to precipitate after
combining both reactants. Formation of the corre-
sponding acid fluoride as a by-product is negligibly
small in all cases. To demonstrate the general utility of
[NMe4]SCF3, we have chosen chlorides of different
kinds of carboxylic acids as reagents.
our knowledge only one publication describes the syn-
thesis of EtC(O)SCF3 and CF3C(O)SCF3 via halide
substitution of the corresponding acid chlorides with
Hg(SCF3)2.2 On the other hand, S-trifluoromethyl and
other S-perfluoroorgano esters of dialkyldithiocarbamic
acids can be easily prepared from the reactions of
perfluoroorgano silver or cadmium compounds or the
system Me3SiRf /Fꢀ and the corresponding dithiuram-
disulfides,3 while the synthesis of S-trifluoromethyl
xanthates starting from sodium O-phenethyl xanthate
and trifluoroacetic acid anhydride followed by a
decarbonylation reaction appears to be far from trivial.4
Herein we describe a convenient synthesis of different
examples of this class starting from the corresponding
acid chlorides and the newly accessible source of SCF3
nucleophiles, [NMe4]SCF3.5
Di-substitution has been achieved using the acid
chloride of 2,6-pyridine dicarboxylic acid (3) (Scheme
2).14
The reaction of pentafluorobenzoic acid chloride (1g)
and [NMe4]SCF3 proceeds in a similar manner to give
Scheme 1. R ¼ 4-NO2C6H4 (a, 82%),7 2-furan (b, 79%),8 2-thiophene (c, 69%),9 trans-cinnamic (d, 82%),10 Et2N (e, 75%),11 CH2@CH(CH2)8
(f, 82%),12 C6F5 (g).13
Keywords: S-Trifluoromethyl esters; Acid chlorides; Halide substitution.
* Corresponding author. Tel./fax: +49-221-4703276; e-mail: tyrra@uni-koeln.de
0040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.06.073

6102
M. M. Kremlev et al. / Tetrahedron Letters 45 (2004) 6101–6104
Scheme 2.
primarily the expected S-trifluoromethyl ester (2g) (cf.
Scheme 1), which could be unambiguously identified by
its characteristic 19F NMR spectrum.13
This formal HSAB directed rearrangement proceeds
selectively with exclusive formation of the para-isomer.
Not even 19F NMR spectroscopic evidence is found for
the ortho-isomer. The formation of 5 can be understood
most probably as an intermolecular rearrangement. On
the basis of the HSAB concept it seems to be logical that
the soft SCF3 moiety tends to attack the soft C-4 atom
of the aromaticring, replaicng the hard fluoride ion,
which again combines with the hard carbonyl carbon
atom. The reaction presumably proceeds by an ionic
chain mechanism as shown in Scheme 4. Further
experiments are necessary for a deeper insight into the
mechanism.
After prolonged stirring at ambient temperature or upon
working up, 2g undergoes a rearrangement with
formation of the acid fluoride of 4-trifluoromethylthio-
2,3,5,6-tetrafluorobenzoicacid ( 5) (Scheme 3).15
Compound 5 is easily converted into the corresponding
acid 6 (Scheme 5) by common procedures.16
The method described offers a convenient access to the
poorly investigated class of S-trifluoromethyl esters of
carboxylic acids.
Scheme 3.
Scheme 4.
Scheme 5.

M. M. Kremlev et al. / Tetrahedron Letters 45 (2004) 6101–6104
6103
50.4 MHz):
d
174.6 (s, C(O)S), 139.4 (q, C-2,
Acknowledgements
4JFC ꢁ 3:0 Hz), 135.7 (s, C-5), 133.1 (s, C-4), 128.5 (s, C-
1
3), 127.8 (q, SCF3, JCF ¼ 309:7 Hz). EI-MS, (20 eV): 212
This work was generously supported by the Deutsche
Forschungsgemeinschaft (436 UKR 113). We thank our
technicians Sigrid Buslei and Silke Quadt for the prep-
aration of [NMe4]SCF3.
(Mþ), 111 (Mþ)SCF3). Anal. Calcd for C6H3F3OS2: C,
33.96; H, 1.42; S, 30.22. Found: C, 34.47; H, 1.22; S, 30.75.
10. trans-Thiocinnamic acid S-trifluoromethyl ester 2d: 0.32 g
(82%), mp 33–35 °C (n-hexane). 19F NMR (188.3 MHz,
CDCl3): d )39.9 (s, SCF3). 1H NMR (200.1 MHz, CDCl3):
3
d 7.66 (d, CH@, 1H, JHH ¼ 15:6 Hz), 7.45 (overlapping
3
m, phenyl H, 5H), 6.60 (d, CH@, 1H, JHH ¼ 15:6 Hz);
13C{1H} NMR (50.4 MHz, CDCl3): d 180.7 (s, C(O)S),
145.0 (s, CH@),132.8 (s, C-1 or C-4#), 131.7 (s, C-1 or C-
4#), 129.1 (s, C-2,6 or C-3,5#), 128.8 (s, C-2,6 or C-3,5#),
References and notes
1. For example, (a) Haas, A.; Radau, G. J. Fluorine Chem.
1998, 89, 9–18; (b) Munavalli, S.; Rossman, D. I.;
Rohrbaugh, D. K.; Ferguson, C. P.; Durst, H. D.
J. Fluorine Chem. 1996, 76, 7–13; (c) Munavalli, S.;
Rossman, D. I.; Rohrbaugh, D. K.; Ferguson, C. P.;
Szafraniec, L. J. J. Fluorine Chem. 1992, 59, 91–99; (d)
Haas, A.; Lieb, M. Chem. Ber. 1978, 111, 2891–2894.
2. Man, E. H.; Coffman, D. D.; Muetterties, E. L. J. Am.
Chem. Soc. 1959, 81, 3575–3577.
3. (a) Wessel, W.; Tyrra, W.; Naumann, D. Z. Anorg. Allg.
Chem. 2001, 627, 1264–1268; (b) Tyrra, W.; Buslei, S.;
Quadt, S. Unpublished results.
4. Bertrand, F.; Pevere, V.; Quiclet-Sire, B.; Zard, S. Z. Org.
Lett. 2001, 3, 1069–1071.
1
127.9 (q, SCF3, JCF ¼ 309:4 Hz), 122.5 (q, @CHC(O)S,
4JFC ꢁ 2:4 Hz). Marked values (#) may be interchangeable.
EI-MS, (20 eV): 232 (Mþ), 131 (Mþ)SCF3), 103
(C6H5CH@CHþ). Anal. Calcd for C10H7F3OS: C, 51.72;
H, 3.03; S, 13.81. Found: C, 51.94; H, 2.92; S, 12.99.
11. N,N-Diethylthiocarbamic acid S-trifluoromethyl ester 2e:
0.30 g (75%), bp 34–36 °C (0.09 mbar). 19F NMR
(188.3 MHz, CDCl3): d )40.2 (s, SCF3). 1H NMR
(200.1 MHz, CDCl3): 3.38/3.18 (broad m, CH2, 4H),
1.20/1.16 (broad m, CH3, 6H). 13C{1H} NMR (50.4
MHz; CDCl3): d 158.0 (s, C(O)S), 128.0 (q, SCF3,
1JFC ¼ 307:3 Hz), 42.7/42.2 (s, CH2), 13.6/12.8 (s, CH3).
EI-MS, (20 eV): 100 (Mþ)SCF3). Anal. Calcd for
C6H10F3NOS: C, 35.82; H, 5.00; N, 6.96; S, 15.94. Found:
C, 35.47; H, 4.78; N, 6.63; S, 15.61.
5. Tyrra, W.; Naumann, D.; Hoge, B.; Yagupolskii, Yu. L. J.
Fluorine Chem. 2003, 119, 101–107.
6. General procedure. To a solution of the corresponding
acid chloride (2 mmol) in 5 mL acetonitrile at )30 °C, a
solution of tetramethylammonium trifluoromethanethio-
late (2 mmol) in 10 mL acetonitrile was added drop-wise
over a period of 10 min. The reaction mixture was warmed
slowly to ambient temperature under stirring within 1 h,
filtered from tetramethylammonium chloride and all
volatile materials were evaporated at reduced pressure.
The residue was extracted with diethyl ether and filtered
again. Diethyl ether was evaporated and the crude
material was purified by recrystallisation or distillation.
19F and 13C NMR (CDCl3, 21 °C) and EI mass spectro-
metricdata as well as results of elemental analyses of the
products are incorporated in the corresponding references.
1H NMR data do not significantly deviate from those
reported for the corresponding O-alkyl esters.
12. Undec-10-enoic acid S-trifluoromethyl ester 2f: 0.44 g
(82%), bp 65–67 °C (0.10 mbar). 19F NMR (188.3 MHz,
CDCl3): d )40.7 (s, SCF3). 1H NMR (200.1 MHz, CDCl3):
d 5.78 (m, CH@, 1H), 4.95 (‘d’, CH2@, 2H), 2.60 (t, CH2,
2H), 2.02 (m, CH2, 2H), 1.67 (CH2, 2H), 1.28 (overlapping
signals, CH2, 10H); 13C{1H} NMR (CDCl3; 50.4 MHz): d
190.2 (s, C(O)S), 140.0 (s, CH@), 127.7 (q, SCF3,
1JFC ¼ 309:9 Hz), 114.1 (s, CH2@), 44.5 (q, CH2C(O)S,
4JFC ꢁ 2:4 Hz), 33.7 (s), 29.1 (s), 29.0 (s), 28.9 (s), 28.8 (6),
28.6 (s), 24.6 (s). EI-MS, (20 eV): 268 (Mþ), 199
(Mþ)CF3), 167 (Mþ)SCF3), 149 (Mþ)SCF3, –H2O).
Anal. Calcd for C12H19F3OS: C, 53.71; H, 7.14; S, 11.95.
Found: C, 53.31; H, 7.97; S, 10.76.
13. Pentafluorothiobenzoicaicd
S-trifluoromethyl ester 2g:
19F NMR (188.3 MHz, MeCN/external (CD3)2CO): d
1
)40.5 (t, SCF3, 3F, JFC ¼ 310:3 Hz, JFF ꢁ 1:6 Hz),
7. 4-Nitrothiobenzoicacid S-trifluoromethyl ester 2a: 0.31 g
(82%), mp 84–86 °C (n-hexane). 19F NMR (188.3 MHz,
CDCl3): d )40.0 (s, SCF3); 1H NMR (200.1 MHz, CDCl3):
d 8.36 (m, 2H), 8.00 (m, 2H); 13C{1H} NMR (CDCl3;
50.4 MHz): d 173.8 (s, C(O)S), 151.2 (s, C-4), 132.5 (q, C-
)139.5 (m, F-2,6, 2F), )146.2 (tt, F-4, 1F), )160.3 (m,
F-3,5, 2F).
14. Pyridine 2,6-di(thiocarboxylic acid) bis(S-trifluoromethyl
ester) 4: 0.21 g (63%), mp 119–122 °C (n-hexane). 19F
1
NMR (188.3 MHz, CDCl3): d )41.4 (s, SCF3). H NMR
4
1
1, JFC ꢁ 3:5 Hz), 130.5 (q, SCF3, JFC ¼ 308:7 Hz), 128.6
(s, C-3,5), 124.3 (s, C-2,6). Anal. Calcd for C8H4F3NO3S:
C, 38.25; H, 1.61; N, 5.57; S, 12.77. Found: C, 38.18; H,
1.62; N, 5.82; S, 12.16.
(200.1 MHz, CDCl3): d 8.24 (overlapping m, 3H). 13C{1H}
NMR (CDCl3; 50.4 MHz): d 184.7 (s, C(O)S), 149.0 (q,
4
C-2,6, JFC ꢁ 2:4 Hz), 140.3 (s, C-4), 128.1 (q, SCF3,
1JFC ¼ 310:6 Hz), 125.8 (s, C-3,5). EI-MS, (20 eV): 234
(Mþ)SCF3), 206 (Mþ)COSCF3), 150 (C7H3NOSþ), 105
(C6H3NOþ). Anal. Calcd for C9H3F6NO2S2: C, 32.24; H,
0.90; N, 4.18; S, 19.13. Found: C, 32.80; H, 0.78; N, 4.35;
S, 18.87.
8. Furan 2-thiocarboxylic acid S-trifluoromethyl ester 2b:
0.31 g (79%), bp 32–34 °C (0.14 mbar). 19F NMR
(188.3 MHz, CDCl3): d )39.4 (s, SCF3). 1H NMR
(200.1 MHz, CDCl3): d 7.64 (s, H-5, 1H), 7.29 (m, H-3,
1H), 6.62 (‘d’, H-4, 1H); 13C{1H} NMR (CDCl3;
15. 4-Trifluoromethylthio-2,3,5,6-tetrafluorobenzoicacid fluo-
ride 5: 19F NMR (188.3 MHz, MeCN/external (CD3)2CO):
d +47.8 (t, C(O)F, 1F, JFF ¼ 42:6 Hz), )40.6 (t, SCF3, 3F,
JFF ¼ 4:5 Hz), )127.5 (m, F-3,5, 2F), )133.6 (m, F-2,6,
2F).
50.4 MHz):
d
171.2 (s, C(O)S), 148.5 (q, C-2,
4JFC ꢁ 3:0 Hz), 147.8 (s, C-5), 127.8 (q, SCF3,
1JFC ¼ 309:7 Hz), 118.3 (s, C-3), 113.2 (s, C-4). EI-MS,
(20 eV): 196 (Mþ), 95 (Mþ)SCF3). Anal. Calcd for
C6H3F3O2S: C, 36.74; H, 1.54; S, 16.35. Found: C,
36.59; H, 1.32; S, 16.17.
16. 4-Trifluoromethylthio-2,3,5,6-tetrafluorobenzoicaidc
6:
To a mixture of 2 mmol pentafluorobenzoyl chloride and
5 mL acetonitrile at )30 °C, a solution of 2 mmol tetra-
methylammonium trifluoromethanethiolate in 10 mL ace-
tonitrile was added dropwise. The reaction mixture was
slowly warmed to ambient temperature (3 h) and 0.2 mL of
triethylamine were added. The mixture was stirred for
9. Thiophene 2-thiocarboxylic acid S-trifluoromethyl ester
2c: 0.29 g (69%), mp 44–46 °C (n-hexane). 19F NMR
(188.3 MHz, CDCl3): d )39.4 (s, SCF3). 1H NMR
(200.1 MHz, CDCl3): d 7.78 (d, H-5, 1H), 7.74 (d, H-3,
1H), 7.17 (‘t’, H-4, 1H). 13C{1H} NMR (CDCl3;

6104
M. M. Kremlev et al. / Tetrahedron Letters 45 (2004) 6101–6104
further 30 min; then 10 mL of an aqueous KOH solution
)128.0 (m, F-3,5, 2F), )136.0 (m, F-2,6, 2F). 1H NMR
(200.1 MHz, CDCl3): d 9.4 (broad, D1=2 ꢁ 25 Hz). 13C
NMR (CDCl3; 50.4 MHz): d 162.8 (s, C(O)OH), 147.9
(dm, C-2,6, 1JFC ¼ 253 Hz), 144.7 (dm, C-3,5,
C-4, 2JFC ꢁ 15 Hz), 108.0 (t, C-1, 2JFC ꢁ 20 Hz).
EI-MS, (20 eV): 294 (Mþ), 277 (Mþ)OH), 212
(Mþ)CF2S), 195 (Mþ)CF2S, –OH). Anal. Calcd for
C8HF7O2S: C, 32.67; H, 0.34; S, 10.90. Found: C, 32.77;
H, 0.15; S, 11.16.
(3%) were added and stirring was continued for another
30 min. The aqueous solution was washed with diethyl
ether, filtered and acidified with 2% aqueous sulfuric acid
to pH 4–5. The mixture was extracted with diethyl ether,
dried over MgSO4, filtered again and all volatile compo-
nents were evaporated. 6 was obtained as a solid crystall-
ising from chloroform in colourless needles. Yield 0.43 g
(73%), mp 136–138 °C (chloroform). 19F NMR
(188.3 MHz, CDCl3): d )41.0 (t, SCF3, 3F, JFF ¼ 5:1 Hz),
1
1JFC ¼ 258 Hz), 127.8 (q, SCF3, JFC ¼ 312 Hz), 115.3 (t,