Vicarious nucleophilic substitutions of hydrogen in 1,1,1-trifluoro-N- [oxido(phenyl)(trifluoromethyl)-λ4-sulfanylidene] methanesulfonamide

Article abstract of DOI:10.1002/ejoc.200800390

1,1,1-Trifluoro-N-[oxido(phenyl)(trifluoromethyl)-λ⁴- sulfanylidene] methanesulfonamide reacts with carbanions bearing a leaving group to give vicarious nucleophilic substitution (VNS) of hydrogen products with moderate yields. This is the firs

Full text of DOI:10.1002/ejoc.200800390

FULL PAPER
DOI: 10.1002/ejoc.200800390
Vicarious Nucleophilic Substitutions of Hydrogen in 1,1,1-Trifluoro-
N-[oxido(phenyl)(trifluoromethyl)-λ4-sulfanylidene]methanesulfonamide
Tadeusz Lemek,*[a] Grazyna Groszek,[b] and Piotr Cmoch[c]
˙
Keywords: Carbanions / Fluorine / Sulfur / Nucleophilic substitution
1,1,1-Trifluoro-N-[oxido(phenyl)(trifluoromethyl)-λ4-sulfan-
ylidene]methanesulfonamide reacts with carbanions bearing
a leaving group to give vicarious nucleophilic substitution
(VNS) of hydrogen products with moderate yields. This is the
first example of the VNS process at a benzene ring activated
by an electron-withdrawing group other than a nitro group.
The orientation of the substitution is exclusively para. Find-
ings open a large possibility for exploration of the scope of
the VNS reaction on to compounds activated with sulfur-
based electron-withdrawing groups.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2008)
methylsulfonyl group and not on the aromatic ring. The
only successful example of the VNS reaction on a homo-
cyclic aromatic ring activated by a group other than nitro is
the reaction of α-chlorosulfone and sulfonamide carbanions
with phenyl azoxysulfones described by Golin´ski.[11] A dec-
ade ago, Yagupolskii et al.[12] introduced to organic chemis-
try a new super-strong electron-withdrawing substituent –
the N-trifluoromethylsulfonyl-S-trifluoromethylsulfoximid-
yl group [CF3S(O)=NSO2CF3]. The comparison of its elec-
tron-withdrawing power with the nitro and another groups
gives the Hammett constant value for this new group σp =
1.4, calculated from 19F NMR spectroscopic data, which
reflects the static molecular state. This value is even higher
than that obtained for the “super-strong” electron-
withdrawing trifluoromethylsulfonyl group.[12] Taking into
account this promising information, we synthesized
the model compound 1,1,1-trifluoro-N-[oxido(phenyl)(tri-
fluoromethyl)-λ4-sulfanylidene]methanesulfonamide (1) and
used it in reactions with a series of classical nucleophiles
for VNS. Here we present the preliminary results of our
investigations.
Introduction
Vicarious nucleophilic substitution (VNS) was discov-
ered at the end of 1970s and subsequently studied mainly
by Makosza and coworkers, and it became a powerful syn-
˛
thetic tool in organic synthesis.[1–6] This reaction was pri-
marily designed for arenes activated by a nitro group. Later,
the scope was extended to electrophilic heterocyclic com-
pounds as well as electrophilic alkenes.[7,8] Numerous C, N,
and O anions were applied as nucleophilic substrates for
VNS. The general scheme of the reaction involves nitro-
substituted arenes that form σH adducts, which then un-
dergo base-promoted 1,2-elimination of HX (Scheme 1).
Until the end of the 20th century, it was believed that such
σH adducts are “short-lived species” and could not be ob-
served.[1] In 2003, Lemek et al.[2] proved by direct spectro-
photometric (UV and NMR) observation that σH adducts
of VNS type are relatively stable compounds. Despite an
intensive search for alternative activating groups enabling
the VNS reaction, only the nitro group seemed to provide
sufficient electron-withdrawing power and charge capacity
to stabilize efficiently the intermediate σH adducts. Al-
though the trifluoromethylsulfonyl group exhibits even
higher electron-withdrawing force than the nitro group[9]
and the fact that it was successfully used in SNAr reactions,
attempts of using it for VNS failed.[10] The reason was that
the nucleophilic attack of a carbanion took place primarily
on the CF3 group or on the sulfur atom of the trifluoro-
Scheme 1. Vicarious nucleophilic substitution of hydrogen.
[a] Department of Chemistry, School of Biotechnology, Agricul-
tural University,
31-120 Cracow, Poland
Fax: +48 12 6624054
Results and Discussion
E-mail: Tadeusz.Lemek@ar.krakow.pl
[b] Faculty of Chemistry, Rzeszów University of Technology,
6 Powstanców Warszawy Ave., 35-959 Rzeszów, Poland
[c] Institute of Organic Chemistry Polish Academy of Sciences,
Kasprzaka 44/52, 01-224 Warsaw, Poland
The reaction of 1 with carbanions 2a–f (generated in situ
by adding an excess amount of tBuOK to CH acids) carried
out with an excess amount of the base yielded VNS prod-
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© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 4206–4209

Vicarious Nucleophilic Substitution of Hydrogen
Scheme 2. Vicarious nucleophilic substitution in 1,1,1-trifluoro-N-[oxido(phenyl)(trifluoromethyl)-λ4-sulfanylidene]methanesulfonamide
(1).
ucts 3a–f (Scheme 2, Table 1). Contrary to the classical
VNS reaction, orientation of this substitution was exclu-
sively para. Under preliminary, unoptimized conditions, the
yields ware moderate to low. For comparison, the yields
of the VNS reaction for nitro-activated compounds range
between 60 and 80%.[13] In our experiments, the remaining
electrophile as well as the carbanion precursors were not
recovered after workup except for 2d. The formation of
foams and emulsions during the workup could indicate that
there is competition between the VNS reaction and nucleo-
philic attack of the carbanion on the N-trifluoromethylsul-
fonyl-S-trifluoromethylsulfoximidyl group of the electro-
phile or that the VNS products undergo decomposition,
Conclusions
which leads to unidentifiable products. Isolated product 3a
after dissolving in DMSO partially dissociates (without the
The results show that the N-trifluoromethylsulfonyl-S-
trifluoromethylsulfoximidyl group activates efficiently the
benzene ring towards nucleophilic attack of carbanions.
This is the first example of the VNS reaction in a homocy-
clic aromatic ring activated by a group other than a nitro
group. The orientation of the substitution is para. Presum-
ably, this is because of the steric effect caused by the bulky
N-trifluoromethylsulfonyl-S-trifluoromethylsulfoximidyl
group and because of competitive nucleophilic attack at this
electron-withdrawing group. The yields under the chosen
reaction conditions are moderate to low. One can expect
that compounds similar to 1, for example, trifluoro-N-
[phenyl(trifluoromethyl){[(trifluoromethyl)sulfonyl]imino}-
λ6-sulfanylidene]methanesulfonamide (A), would also enter
the VNS process.
presence of a base) with formation of a band at λmax
=
418 nm. The addition of tBuOK causes total deprotonation
of 3a (log ε = 4.7). The carbanion generated by this way
showed limited stability, and the UV absorption disap-
peared completely after 1 h. In the case of carbanion 2d,
oxidative nucleophilic substitution of hydrogen (ONSH)
was observed as a side process (product 4d was isolated).
The reason for the competition between the ONSH and
VNS reactions is a result of slow 1,2-elimination of HCl
from the σH adduct caused by steric hindrance. The reac-
tion of CHCl3 as a carbanion precursor with electrophile 1
yielded only trace amounts of the VNS product. The reac-
tion of (4-chlorophenoxy)acetonitrile with 1 gave exclu-
sively the product of the Thorpe condensation: 3-amino-
2,3-bis(4-chlorophenoxy)acrylonitrile.[13]
Table 1. The VNS reaction of electrophile 1 with carbanions 2a–g.
Entry
Carbanion
Product
No
X
Y
R
No
Yield
[%]
Experimental Section
1
2
2a
2b
2c
2d
2e
2f
Cl
Cl
Br
Cl
Cl
Br
Cl
4-Ts
CO2Me
CN
H
Me
Me
Et
H
H
Cl
3a
3b
3c
3d
3e
3f
28
22
38
9
31
5
Instruments and Materials: Chemical shifts in the 1H and 13C NMR
spectra are expressed in ppm and are reported relative to Me4Si
(δH = 0.00 ppm, δC = 0.00 ppm). Chemical shifts in the 19F NMR
spectra are expressed in ppm and are reported relative to CFCl3
(δF = 0.00 ppm). Coupling constants are in Hz. Melting points are
uncorrected. The yields refer to isolated products without optimi-
zation of the procedures. DMF was dried with CaH2 and distilled
under reduced pressure. Compound 1 and carbanion precursors
3
4[a]
5
4-Ts
COOtBu
SO2Ph
SO2Ph
6
7
2g
3g
very low
[a] ONSH product 4d was isolated (9%), and carbanion precursor
2d was recovered (20%).
Eur. J. Org. Chem. 2008, 4206–4209
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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T. Lemek, G. Groszek, P. Cmoch
FULL PAPER
2a–g were prepared according to literature procedures or were com-
mercially available. Substrates were commercially available. Silica
gel (230–400 mesh) was used for column chromatography.
131.6, 148.0 ppm. 19F NMR (376.4 MHz, CDCl3): δ = –78.9,
–75.5 ppm. MS (EI, 70 eV): m/z (%) = 395 (1) [M]+, 325 (100), 378
(12), 146 (10), 130 (16), 103 (12).
1,1,1-Trifluoro-N-[oxido(phenyl)(trifluoromethyl)-λ4-sulfanylidene]-
methanesulfonamide (1): Oil. 1H NMR (500 MHz, CDCl3): δ =
7.79–7.82 (m, 2 H, CH-meta), 7.97–8.00 (m, 1 H, CH-para), 8.15
(d, J = 7.9 Hz, 2 H9, CH-ortho) ppm. 13C NMR (125.8 MHz,
CDCl3): δ = 118.9 (q, J = 320.6 Hz), 119.9 (q, J = 328.4 Hz), 128.8,
130.5, 130.7, 138.1 ppm. 19F NMR (376.4 MHz, CDCl3): δ = –79.2,
–75.9 ppm. Compound 1 was obtained from [S-(trifluoromethyl)-
sulfonimidoyl]benzene in 45% yield by using procedure described
for substituted [S-(trifluoromethyl)sulfonimidoyl]benzenes.[14] [S-
(Trifluoromethyl)sulfonimidoyl]benzene [1H NMR (200 MHz,
CDCl3): δ = 3.6 (s, 1 H, NH, flat), 7.57–7.67 (m, 2 H, CH-meta),
7.73–7.81 (m, 1 H, CH-para), 8.11–8.16 (m, 2 H, CH-ortho) ppm]
was prepared from phenyl trifluoromethyl sulfoxide by the reaction
with NaN3 in oleum.[15]
1,1,1-Trifluoro-N-[(4-{1-[(4-methylphenyl)sulfonyl]propyl}phenyl)-
(oxido)(trifluoromethyl)-λ6-sulfanylidene]methanesulfonamide (3d):
Oil (59 mg, 11%). IR (film): ν = 2930, 1592, 1376, 1288, 1201,
˜
1
1046 cm–1. H NMR (500.1 MHz, CDCl3): δ = 0.88–0.93 (m, 3 H,
CH3), 2.20–2.26 (m, 1 H, CH2), 2.399 and 2.404 (2ϫs, 3 H, CH3),
2.46–2.57 (m, 1 H, CH2), 4.09–4.14 (2ϫdd, 1 H, CH), 7.21 (d, J
= 8.1 Hz, 2 H), 7.37–7.41 (m, 2 H), 7.52–7.54 (m, 2 H), 8.00–8.02
(m, 2 H) ppm. 13C NMR (125.8 MHz, CDCl3): δ = 11.47 and 11.50
(CH3CH2), 21.22 and 21.38 (CH3CH2), 21.55 and 21.59 (CH3C),
72.83 and 72.87 (CH), 118.9 (q, J = 320.3 Hz), 119.8 (q, J =
328.7 Hz), 128.83 and 128.93 (CH arom.), 129.02 and 129.08 (C
arom.), 129.70 and 129.75 (CH arom.), 130.47 (CH arom.), 132.02
and 132.03 (CH arom.), 133.63 and 133.67 (C arom.), 144.27 and
144.34 (C arom.), 145.54 and 145.59 (C arom.) ppm. 19F NMR
(376.4 MHz, CDCl3): δ = –79.0, –78.9, –75.7, –75.6 ppm. MS (EI,
70 eV): m/z (%) = 468 (2), 382 (100), 305 (35), 160 (60), 115 (30).
Reactions of 1 and 2a–f: To a stirred solution of tBuOK (337 mg,
3 mmol) in DMF (2 mL) at –30 °C and under an argon atmosphere
was added, by cannula, a solution of CH acid 2a–g (1 mmol) in
DMF (2 mL) and a solution of electrophile 1 (341 mg, 1 mmol) in
DMF (1 mL). After 10 min stirring, the mixture was poured into
cooled 3% aqueous HCl (100 mL). The precipitate was filtered off,
washed with water, and dried in the air, or in case of oil was ex-
tracted with AcOEt, washed with brine, and dried with Na2SO4.
Crude products 3a–g were isolated as oils, or as powders, and puri-
fied by column chromatography (hexane/ethyl acetate) and recrys-
tallized.
N-[(4-{1-Chloro-1-[(4-methylphenyl)sulfonyl]propyl}phenyl)oxido-
(trifluoromethyl)-λ4-sulfanylidene]trifluoromethanesulfonamide (4d):
Oil (50 mg, 9%). IR (film): ν = 2980, 1595, 1318, 1146, 1070 cm–1.
˜
1H NMR (500.1 MHz, CDCl3): δ = 0.97 (2ϫd, J = 7.25, 7.25 Hz,
3 H, CH3), 2.39 (s, 3 H, CH3), 2.53 (dq, J = 14.6, 7.3 Hz, 1 H,
CH2), 2.98 (dq, J = 14.4, 7.2 Hz, 1 H, CH2), 7.14 (d, J = 8.2 Hz,
2 H), 7.28–7.31 (m, 2 H), 7.35–7.37 (m, 2 H), 7.46–7.47 (m, 2 H)
ppm. 13C NMR (125.8 MHz, CDCl3): δ = 8.2 (CH3CH2), 21.6
(CH3C), 28.4 (CH3CH2), 118.9 (q, J = 320.5 Hz), 119.9 (q, J =
331.9 Hz), 92.6 (CCl), 127.9 (CH arom.), 128.8 (CH arom.), 129. 5
(CH arom.), 131.3 (CH arom.), 130.0 (C arom.), 130.6 (C arom.),
132.0 (C arom.), 145.2 (C arom.) ppm. 19F NMR (376.4 MHz,
CDCl3): δ = –78.9, –75.6 ppm. MS (EI, 70 eV): m/z (%) = 382 (1),
348 (4), 153 (100), 117 (56), 91 (50).
1,1,1-Trifluoro-N-[(4-{[(4-methylphenyl)sulfonyl]methyl}phenyl)-
(oxido)(trifluoromethyl)-λ6-sulfanylidene]methanesulfonamide (3a):
M.p. 127–128 °C (143 mg, 28%, acetonitrile/petroleum ether). IR
(KBr): ν = 3098, 2997, 2929, 1595, 1378, 1297, 1223, 1207, 1133,
˜
1095, 1052, 602 cm–1. 1H NMR (300.1 MHz, [D6]acetone): δ = 2.42
(s, 3 H, CH3), 4.85 (s, 2 H, CH2), 7.38 (d, J = 8.0 Hz, 2 H7), 7.59
(d, J = 8.2 Hz, 2 H8), 7.82 (d, J = 8.6 Hz, 2 H4), 8.25 (d, J =
8.5 Hz, 2 H2) ppm. 13C NMR (75.5 MHz, [D6]acetone): δ = 21.0,
61.6, 119.9 (q, J = 319.9 Hz), 120.8 (q, J = 327.7 Hz), 128.0, 128.8,
130.1, 131.0, 134.1, 135.9, 141.8, 145.6 ppm. 19 F NMR
(376.4 MHz, CDCl3): δ = –78.8, –75.4 ppm. MS (EI, 70 eV): m/z
(%) = 509 (10) [M]+, 440 (5.3), 293 (7.5), 191 (11), 155 (90), 138
(49), 91 (100). HRMS (EI, 70 eV): calcd. for C16H13F6NO5S3
[M]+ 508.9860; found 508.9859. C16H13F6NO5S3 (509.45): calcd. C
37.72, H 2.57,N 2.75; found C 37.72, H 2.25, N 2.72.
tert-Butyl (4-{S-(Trifluoromethyl)-N-[(trifluoromethyl)sulfonyl]-
sulfonimidoyl}phenyl)acetate (3e): Oil (141 mg, 31%). IR (film): ν =
˜
2981, 1729, 1593, 1371, 1200, 1090, 1047 cm–1 1H NMR
.
(500.1 MHz, CDCl3): δ = 1.46 [s, 9 H, C(CH3)3], 3.73 (s, 2 H, CH2),
7.70 (d, J = 8.6 Hz, 2 H, CH-arom.), 8.09 (d, J = 8.5 Hz, 2 H)
ppm. 13C NMR (125.8 MHz, CDCl3): δ = 27.9 [C(CH3)3], 42.4
[C(CH3)3], 82.4 (CH2), 118.9 (q, J = 321 Hz, CF3), 119.9 (q, J =
328 Hz, CF3), 127.1 (C arom.), 130.7 (CH arom.), 131.7 (CH
arom.), 146. 3 (C arom.), 168.6 (CO) ppm. 19F NMR (376.4 MHz,
CDCl3): δ = –79.1, –75.9 ppm. MS (EI, 70 eV): m/z (%) = 440 (12)
[M – CH3]+, 386 (32), 382 (60), 355 (72), 330 (100), 152 (32).
Methyl 2-(4-{S-(Trifluoromethyl)-N-[(trifluoromethyl)sulfonyl]-
sulfonimidoyl}phenyl)propanoate (3b): Oil (94 mg, 22%). IR (film):
1,1,1-Trifluoro-N-[oxido{4-{(phenylsulfonyl)methyl}phenyl}(tri-
fluoromethyl)-λ6-sulfanylidene]methanesulfonamide (3f): M.p. 118–
ν = 3096, 1738, 1591, 1376, 1293, 1199, 1047 cm–1 1H NMR
.
˜
(500.1 MHz, CDCl3): δ = 1.59 (d, J = 7.2 Hz, 3 H, CH3-CH), 3.72
(s, 3 H, CH3O), 3.91 (q, J = 7.2 Hz, 1 H, CH3-CH), 7.72 (d, J =
8.4 Hz, 2 H), 8.09 (d, J = 8.5 Hz, 2 H) ppm. 13C NMR (125.8 MHz,
CDCl3): δ = 18.4, 45.6, 52.6, 118.9 (q, J = 320.6 Hz), 119.9 (q, J =
328.5 Hz), 127.4, 130.1, 131.0, 151.7, 172.9 ppm. 19F NMR
(376.4 MHz, CDCl3): δ = –79.0, –75.8 ppm. MS (EI, 70 eV): m/z
(%) = 427 (10) [M]+, 382 (25), 358 (100), 266 (18), 211 (10), 166
(56). HRMS (EI, 70 eV): calcd. for C12H11F6NO5S2 [M]+ 426.9983;
found 426.9965.
1
121 °C (25 mg, 5%). H NMR (500.1 MHz, CDCl3): δ = 4.48 (s, 2
H, CH2), 7.52–7.58 (m, 4 H), 7.68–7.72 (m, 3 H), 8.08 (d, J =
8.0 Hz, 2 H) ppm. 13C NMR (75.5 MHz, [D6]acetone): δ = 62.4,
118.8 (q, J = 322.0 Hz), 119.8 (q, J = 327.0 Hz), 128.5, 129.4, 130.7,
133.0, 134.6, 137.3, 139.4, 146.1 ppm. 19F NMR (376.4 MHz,
CDCl3): δ = –78.92, –75.51 ppm. MS (EI, 70 eV): m/z (%) = 495
(40) [M]+, 426 (20), 410 (6), 354 (7), 175 (19), 152 (30), 141 (100),
90 (18), 77 (42). HRMS (EI, 70 eV): calcd. for C15H11F6NO5S3
[M]+ 494.9704; found 494.9673.
N-{[4-(1-Cyanoethyl)phenyl](oxido)(trifluoromethyl)-λ6-sulfanyl-
idene}-1,1,1-trifluoromethanesulfonamide (3c): Oil (150 mg, 38%).
[1] M. Makosza, A. Kwast, J. Phys. Org. Chem. 1998, 11, 341–349.
˛
1
IR (film): ν = 3096, 1594, 1375, 1295, 1199, 1045 cm–1. H NMR
˜
[2] T. Lemek, M. Makosza, D. S. Stephenson, H. Mayr, Angew.
˛
(500.1 MHz, CDCl3): δ = 1.75 (d, J = 7.3 Hz, 3 H, CH3), 4.11 (q,
J = 7.3 Hz, 1 H, CH), 7.81 (d, J = 8.5 Hz, 2 H), 8.19 (d, J = 8.5 Hz,
2 H) ppm. 13C NMR (125.8 MHz, CDCl3): δ = 21.0, 31.5, 118.8
(q, J = 320.5 Hz), 119.4, 119.9 (q, J = 328.5 Hz), 128.9, 129.3,
Chem. 2003, 115, 2899–2901; Angew. Chem. Int. Ed. 2003, 42,
2793–2795.
[3] T. Lemek, M. Makosza, A. Kwast, F. Terrier, J. Org. Chem.
˛
2002, 67, 394–400.
4208
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© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 4206–4209

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Received: April 18, 2008
Published Online: July 9, 2008
Eur. J. Org. Chem. 2008, 4206–4209
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4209