N-sulfonylbenzotriazoles as advantageous reagents for C-sulfonylation

Article abstract of DOI:10.1021/jo051157i

Reactions of readily available N-(alkyl-, aryl-, and heteroarylsulfonyl) benzotriazoles 3a-h with diverse nitriles, reactive heteroaromatics, alkylheteroaromatics, sulfones, and esters produced α-cyanoalkyl sulfones 5a-i, sulfonylheteroaromatics 7a-e, α-(sulfonylalkyl)heterocycles 9a-f, α-sulfonylalkyl sulfones 11a-g, and esters of α-sulfonyl acids 14a-c, respectively, in synthetically useful to excellent yields. The results represent the first examples of the successful application of sulfonylazoles for C-sulfonylation.

Full text of DOI:10.1021/jo051157i

N-Sulfonylbenzotriazoles as Advantageous Reagents for
C-Sulfonylation
Alan R. Katritzky,* Ashraf A. A. Abdel-Fattah, Anatoliy V. Vakulenko, and Hui Tao
Center for Heterocyclic Compounds, Department of Chemistry, University of Florida,
Gainesville, Florida 32611-7200
katritzky@chem.ufl.edu
Received June 8, 2005
Reactions of readily available N-(alkyl-, aryl-, and heteroarylsulfonyl)benzotriazoles 3a-h with
diverse nitriles, reactive heteroaromatics, alkylheteroaromatics, sulfones, and esters produced
R-cyanoalkyl sulfones 5a-i, sulfonylheteroaromatics 7a-e, R-(sulfonylalkyl)heterocycles 9a-f,
R-sulfonylalkyl sulfones 11a-g, and esters of R-sulfonyl acids 14a-c, respectively, in synthetically
useful to excellent yields. The results represent the first examples of the successful application of
sulfonylazoles for C-sulfonylation.
Introduction
matics,11 and (iii) as effective reagents for the N-sulfo-
nylation of amines and the O-sulfonylation of phenols to
give the corresponding sulfonamides and sulfonates,
respectively.12 As a logical sequel, we now disclose
C-sulfonylations by N-sulfonylbenzotriazoles 3 of nitriles,
heterocycles, and active alkyl groups in heterocycles,
sulfones, and esters leading to a wide variety of sulfones.
Sulfones are important intermediates in organic syn-
thesis1 and additionally have a wide applicability in
diverse fields including agrochemicals,2 pharmaceuticals,3
and polymers.4 Sulfones are notable as “chemical cha-
meleons”5 due to the ability of the sulfonyl group to serve
as a temporary transformer of chemical reactivity. The
group RSO2 can function as a nucleofuge producing a
sulfinate anion6 and powerfully stabilize adjacent car-
banions.7,8 Although lacking inherent asymmetry, the
sulfonyl group can also function as a potential stereoin-
ducer.9
N-Sulfonylbenzotriazoles 3 have been previously used
in our group (i) to convert carboxylic acids into N-
acylbenzotriazoles which are especially useful when the
corresponding acid chlorides are difficult to obtain,10 (ii)
as intermediates for the benzotriazolylalkylation of aro-
Results and Discussion
Preparation of N-Sulfonylbenzotriazoles. N-Sul-
fonylbenzotriazoles 3 were prepared following literature
procedures either by the reaction of sulfonyl chloride 1
with benzotriazole in the presence of pyridine for alkyl-
and arylsulfonylbenzotriazoles 3a-c10 or by the reaction
of organolithium reagents 2 with sulfur dioxide at -78
°C to obtain sulfinic acid salts followed by the addition
of N-chlorobenzotriazole for heteroarylsulfonylbenzotria-
zoles 3d-h12b in good to excellent yields (Scheme 1).
* To whom correspondence should be addressed. Fax: (352) 392-
9199.
(7) (a) Phillips, E. D.; Warren, E. S.; Whitham, G. H. Tetrahedron
1997, 53, 307. (b) Giovannini, R.; Petrini, M. J. Chem. Soc., Chem.
Commun. 1997, 1829.
(8) (a) Parker, W. L.; Woodward, R. B. J. Org. Chem. 1969, 34, 3085.
(b) Campbell, R. V. M.; Crombie, L.; Findley, D. A. R.; King, R. W.;
Pattenden, G.; Whiting, D. A. J. Chem. Soc., Perkin Trans. 1 1975,
897.
(1) (a) Simpkins, N. S. Sulphones in Organic Synthesis; Pergamon
Press: Oxford, 1993. (b) Prilezhaeva, E. N. Russ. Chem. Rev. 2000,
69, 367. (c) Na´jera, C.; Yus, M. Tetrahedron 1999, 55, 10547. (d)
Arvanitis, E. A.; Craig, D.; Timm, A. P. ARKIVOC 2002, 9, 19. (e)
Hassner, A.; Laxer, A. Ghera, E. ARKIVOC 2002, 5, 157.
(2) Michaely, W. J.; Krattz, G. W. US Patent 4,780,127, 1988; Chem.
Abstr. 1989, 111, 129017.
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Org. Chem. 1998, 63, 3624.
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Haginoya, N.; Nagahara, T.; Horino, H. WO9916747, 1999; Chem.
Abstr. 1999, 130, 296694.
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8210.
(4) Robsein, R. L.; Straw, J. J.; Fahey, D. R. US patent 5,260,489,
1993; Chem. Abstr. 1994, 120, 165200.
(11) Katritzky, A. R.; Gupta, V.; Garot, C.; Stevens, C. V.; Gordeev,
M. F. Heterocycles 1994, 38, 345.
(5) Trost, B. M.; Ghadiri, M. R. J. Am. Chem. Soc. 1984, 106, 7260.
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Lett. 1994, 35, 6017.
(12) (a) Katritzky, A. R.; Zhang, G.; Wu, J. Synth. Commun. 1994,
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Chem. 2004, 69, 1849.
10.1021/jo051157i CCC: $30.25 © 2005 American Chemical Society
Published on Web 10/18/2005
J. Org. Chem. 2005, 70, 9191-9197
9191

Katritzky et al.
SCHEME 1
SCHEME 3a
a For designation of R, R1, and R2 in 5, see Table 1.
TABLE 1. Preparation of r-Cyanoalkyl Sulfones 5a-i
R of
R1 of
nitrile 4
R2 of
nitrile 4 method
yield (%)
of 5
compd BtSO2R 3
5a
5b
5c
5d
5e
5f
5g
5h
5i
CH3
CH3
4-tolyl
4-tolyl
Ph
4-BrC6H4
2,4-Cl2C6H3
4-BrC6H4
2,4-Cl2C6H3
Ph
H
B
B
A
B
A
A
A
A
A
82
87
93
97
76
50
90
54
73
SCHEME 2
H
H
H
H
Ph
H
H
2-thienyl 2,4-Cl2C6H3
2-pyridyl n-C6H13
3-pyridyl Ph
H
H
CH3
After the addition of 3c, the reaction mixture was stirred
overnight; aqueous workup yielded the 4-bromophenyl-
(toluene-4-sulfonyl)acetonitrile (5c) in 43% yield with
recovery of about 50% of the starting nitrile 4a. The yield
of 5c was improved to 93% by using 2 molar equiv of
n-butyllithium. To simplify the procedure, the reaction
of nitrile 4a with 3c was next examined in the presence
of 2 molar equiv of t-BuOK in DMSO at room tempera-
ture and provided R-cyano sulfone 5c in 88% yield. The
use of 2 molar equiv of either n-butyllithium in THF at
-78 °C or t-BuOK in DMSO at room temperature proved
to be appropriate for the sulfonylation of nitriles.
After this optimization of the conditions, we investi-
gated the reactions of 1-sulfonylbenzotriazoles 3a-e,g
with nitriles 4a-f. In every case, the reaction proceeded
smoothly giving the corresponding R-cyano sulfones 5a-i
(Scheme 3 and Table 1). Success with a wide range of
1-sulfonylbenzotriazoles and nitriles demonstrates the
general applicability of this procedure. It can be used
with alkylsulfonylbenzotriazoles to give R-cyanoalkyl
sulfones 5a,b in 82% and 87% yields, respectively.
Arylsulfonylbenzotriazoles were also used to convert
acetonitrile itself and arylacetonitriles into the corre-
sponding sulfonylated products 5c-f in 50-97% yields.
As heterocyclic sulfonylating reagent examples, 1-(2-
pyridyl-, 3-pyridyl-, or 2-thienyl)sulfonylbenzotriazoles
3d,e,g reacted with a range of nitriles to give the desired
products 5g-i in 54-90% yield.
Synthesis of r-Cyanoalkyl Sulfones. R-Cyanoalkyl
sulfones have extensive synthetic uses,13 e.g., for the
preparation of pyridones,14 4-aminopyrimidines,15 5,6-
dihydro-4H-pyrans,16 tetrahydrofurans,17 cyclobutanes,16
cyclopropanes,18 and biologically active compounds such
as â-amido sulfones19 and L-indospicines.20
Published routes to R-cyano sulfones (Scheme 2) in-
clude (i) oxidation of the corresponding sulfides;21 (ii)
alkyation of benzenesulfinate salts with R-halo nitriles
either under the conditions of anionic activation22 or
under solid-liquid phase-transfer catalysis without sol-
vent;23 (iii) Michael addition of Reformatsky reagents to
geminal cyanosulfonylalkenes catalyzed by Cp2TiCl2;24
and (iv) sulfonylation of nitriles with phenyl tosylate.25
However, although these synthetic approaches have
proven to be of great utility for specific classes of the title
compounds, method (i) suffers from foul-smelling starting
materials, (ii) and (iii) require the availability of R-halo
nitriles and geminal cyanosulfonylalkenes, and (iv) is
limited to the tosylation of arylacetonitriles. We herein
report a general and efficient route to such R-cyano
sulfones by reactions of nitriles 4 with 1-sulfonylbenzo-
triazoles 3 in the presence of either n-BuLi or t-BuOK
(Scheme 3).
Initially, 4-bromophenyl acetonitrile (4a) was treated
with 1.2 molar equiv of n-butyllithium at -78 °C in THF
and reacted with 1-[(4-tolyl)sulfonyl]benzotriazole (3c).
The structures of compounds 5a-i were supported by
(13) (a) Zhang, C.; Lu, X. Synlett. 1995, 645. (b) Franzone, G.; Carle,
S.; Dorizon, P.; Ollivier, J.; Salau¨n, J. Synlett. 1996, 1067. (c) Kurose,
N.; Takahashi, T.; Koizumi, T. J. Org. Chem. 1997, 62, 4562.
(14) Bondavalli, F.; Bruno, O.; Presti, E. L.; Menozzi, G.; Mosti, L.
Synthesis 1999, 1169.
NMR spectral data and elemental analyses. The 13C NMR
1
and H NMR spectra of R-cyano sulfones 5a-i showed
characteristic signals in the regions 45.7-62.5 and 4.10-
5.85 ppm which were assigned to the carbon and proton
R to the cyano group.
(15) Perez, M. A.; Soto, J. L.; Guzman, F.; Diaz, A. Synthesis 1984,
1045.
(16) Ooms, P. H. J.; Scheeren, J. W.; Nivard, R. J. F. Synthesis 1975,
260.
Synthesis of Sulfonylheterocycles. Sufonylhetero-
cycles are important in medicinal chemistry: recent
examples include HIV-1 non-nucleosides,26 nucleoside
reverse transcriptases,27 integrase inhibitors,28 potential
cardiovascular agents,29 and anti-ulcer agents.30 Previous
preparations of sulfonylheterocycles directly from the
(17) Shim, J.-G.; Yamamoto, Y. J. Org. Chem. 1998, 63, 3067.
(18) Jiang, B.; Zhang, F.; Xiong, W. Chem. Commun. 2003, 536.
(19) Pomerantz, A.; Connor, R. J. Am. Chem. Soc. 1939, 61, 3386.
(20) Feldman, P. L.; Chi, S. Bioorg. Med. Chem. Lett. 1996, 6, 111.
(21) Wro´bel, J. T.; Hejchman, E. Synthesis 1987, 452.
(22) Sepiol, J. J.; Sepiol, J. A.; Soulen, R. L. J. Org. Chem. 1984,
49, 1125.
(23) Bram, G.; Loupy, A.; Roux-Schmitt, M. C.; Sansoulet, J.;
Strzalko, T.; Seyden-Penne, J. Synthesis 1987, 56.
(24) Zhao, Z.; Ding, Y.; Zhao, G. Synth. Commun. 2001, 31, 2089.
(25) Zhao, H.; Biehl, E. R. Synth. Commun. 1995, 25, 4063.
(26) Artico, M.; Silvestri, R.; Pagnozzi, E.; Bruno, B.; Novellino, E.;
Greco, G.; Massa, S.; Ettorre, A.; Loi, A. G.; Scintu, F.; Colla, P. L. J.
Med. Chem. 2000, 43, 1886.
9192 J. Org. Chem., Vol. 70, No. 23, 2005

N-Sulfonylbenzotriazoles as Reagents for C-Sulfonylation
SCHEME 4a
SCHEME 5
a For designation of Het and R in 7, see Table 2.
TABLE 2. Preparation of Sulfonylheterocycles 7a-d
compd
Het
R
yield (%) lit. yield (%)
7a
7b
7c
7d
2-thienyl
2-ethyl-5-furyl
2-benzofuryl
Me
Ph
47
80
73
54
4-MeC6H4
3035
SCHEME 6a
1-methylpyrrole 2-pyridyl
parent heterocycles include the following: (i) oxidation
of sulfides;31 (ii) metal-mediated cross-coupling of either
sulfinic acid salts with heteroaryl halides32 or sulfonyl
chlorides with heteroaryl boronic acids;33 and (iii) Friedel-
Crafts-type sulfonylation of heterocycles with sulfonyl
chloride and diverse catalysts.34 However, method (i) is
unattractive because of the obnoxious smell of the start-
ing material, (ii) is limited by the availability of het-
eroaryl halides or heteroaryl boronic acids, and (iii)
utilizes sulfonyl chlorides which are often liquids that
are difficult to store and handle. We now report a new
method for the synthesis of sulfonyl heteroaromatics by
reactions of readily available and odorless 1-sulfonylben-
zotriazoles 3 with the metalated heterocyles (Scheme 4).
Reactions of heterocyclic lithio derivatives 6a-d (gen-
erated by lithiation of the parent heterocycle) in dry THF
at -78 °C with the appropriate 1-sulfonylbenzotriazoles
3a-d provided the corresponding C-sulfonylated hetero-
cycles 7a-d. The TLC and NMR of the crude products
show that the reactions are clean (usually benzotriazole
is the only byproduct, but occasionally, small amounts
of unreacted starting materials are detected). This ap-
proach improved the previously reported yield35 of com-
pound 7c from 30% to 73% and afforded novel sulfonyl-
heterocycles 7a,b,d in 47-80% yields (Scheme 4, Table
2). The NMR spectra of the sulfonylated products 7a-d
clearly showed the disappearance of the benzotriazolyl
signals; the NMR data for the known compound 7c35 are
consistent with those in the literature.
a For designation of Het, R, and R1 in 9, see Table 3.
possess antibacterial activity,39 are inhibitors of poly-
merase,40 and are (PPAR) γ agonists.41
R-(Sulfonylalkyl)heterocycles were previously synthe-
sized (Scheme 5) by (i) oxidation of sulfides,42 (ii) reactions
arenesulfinate salts with either R-(haloalkyl)heterocy-
cles43 or heteroalkylpyridinium salts,44 (iii) vicarious
nucleophilic substitution,45 (iv) direct sulfonylation of
alkylheterocycles with arylsulfonyl chlorides, and (v)
diverse ring syntheses, e.g., ref 47. We now report the
use of N-sulfonylbenzotriazoles in a convenient synthesis
of R-(sulfonylalkyl)heterocycles 9 (Scheme 6).
2-Picoline was treated with 2 molar equiv of LDA to
give 2-LiCH2Py 8a in situ which on treatment with
1-(phenylsulfonyl)-benzotriazole (3b) at -78 °C in THF
and aqueous workup afforded 59% of 2-(phenylsulfonyl-
methyl)pyridine (9a). Two equivalents of LDA could be
replaced by 1 equiv of n-BuLi; use of 2 molar equiv of
n-butyllithium under the same reaction conditions did
not improve the yield. Lithio derivatives 8a-e (generated
in situ by treating the corresponding alkylated hetero-
cycles with 1 equiv of n-BuLi) reacted with the appropri-
ate 1-sulfonylbenzotriazoles 3 to afford the corresponding
R-(sulfonylalkyl)heterocycles 9b-f. Our approach pro-
vided previously unreported C-sulfonylated alkylhetero-
cycles 9b-f in 43-94% yields (Scheme 6 and Table 3).
Assigned structures of 9a-f were supported by NMR
spectral data in agreement with the published data in
Synthesis of r-(Sulfonylalkyl)heterocycles. C-(R-
Sulfonylalkyl)heterocycles are useful synthons for in-
doles36 and quinolines,37 are antiinflammatory agents,38
(27) Williams, T. M.; Ciccarone, T. M.; MacTough, S. C.; Rooney, C.
S.; Balani, S. K.; Condra, J. H.; Emini, E. A.; Goldman, M. E.; Greenlee,
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Carter, G. W.; Young, P. R. J. Med. Chem. 1983, 26, 218.
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J. Org. Chem, Vol. 70, No. 23, 2005 9193

Katritzky et al.
SCHEME 7a
TABLE 3. (r-Sulfonylalkyl)heterocycles 9a-f
compd
Het
R
R1 yield (%)
9a
9b
9c
9d
9e
9f
2-pyridyl
2-pyridyl
4-pyridyl
2-pyridyl
Ph
H
59
94
53
43
61
76
Ph
Ph
Ph
CH3
H
CH3
4-MeC6H4
2-(1-methylbenzimidazolyl) 2-thienyl
2-benzothiazolyl
2-benzofuryl H
a For designation of R, R1, and R2 in 11, see Table 4.
TABLE 4. Preparation of r-Sulfonyl Sulfones 11a-g
1
the case of 9a.48 The 13C NMR and H NMR spectra of
9a-f showed characteristic signals in the regions 56.6-
73.6 and 3.90-5.66 ppm, which were assigned to the
carbon and the proton R to the hetero group.
R of
BtSO2R 3
R1 of
R2 of
yield (%)
of 11
compd
sulfone 10 sulfone 10
11a
11b
11c
11d
11e
11f
4-tolyl
C6H5
H
C6H5
C6H5
96
87
78
91
87
67
71
4-tolyl
Our synthetic sequence for the synthesis of R-(sulfo-
nylalkyl)heterocycles 9 provides a general and efficient
approach. The closest literature analogy is the direct
sulfonylation of alkylheterocyles with sulfonyl chloride46
(Scheme 3, iv) but this method is limited to three
examples of the tosylation of 4-alkylpyridines and utilizes
3.6 molar equiv of the sulfonyl chloride to give products
of type 9. The quoted yields of 40-79% (average 60%)
are based on the amount of alkylheterocycles used,
whereas recalculation based on the sulfonyl chloride used
gives yields of only 11-23% (average 17%). Our method
uses alkylated heterocycles and readily available N-
sulfonylbenzotriazoles in a 1:1 ratio and affords yields
that range from 43% to 94% (average 69%).
4-tolyl
phenyl
2-pyridinyl
2-benzenefuryl
2-thienyl
(-CH2-)3
CH3
CH3
C2H5
C2H5
(-CH2-)3
C2H5
11g
CH3
SCHEME 8
Synthesis of r-Sulfonylalkyl Sulfones. R-Sulfonyl-
alkyl sulfones are valuable intermediates for a number
of carbocycles49 and heterocycles,50 reactive synthons for
Ramberg-Backlund olefinations51 and metal-catalyzed
cross-coupling reactions52 and useful for the synthesis of
R-aryl propanoic acid ibuprofen analogues.53
The only well-known routes to R-sulfonylalkyl sulfones
involve the oxidation of the corresponding bis-sulfides54
or R-sulfonylalkyl sulfides.55 Prompted by the lack of
available methods and in order to study the generality
of our C-sulfonylation methodology, we developed a
robust, high-yielding, and general method to a diverse
range of target molecules.
Treatment of the lithio derivatives of sulfones 10a-e
(generated in situ by the lithiation of the sulfones with
n-BuLi) at -78 °C with 1-sulfonylbenzotriazoles 3b-d,f,g
gave the corresponding R-sulfonylalkyl sulfones 11a-g
in moderate to excellent yields (Scheme 7 and Table 4).
For optimum yields, the reactions of 1-sulfonylbenzo-
triazoles with sulfones required 2 molar equivalents of
n-BuLi, since the R-sulfonylalkyl sulfones formed would
rapidly be deprotonated by unreacted carbanion; this was
suggested by our previous study of the acylation of
sulfones with N-acylbenzotriazoles.56 Products 11a-g
1
were identified on the basis of their H and 13C NMR
spectra together with elemental analyses.
This new synthetic procedure for the synthesis of
R-sulfonylalkyl sulfones is tolerant of structural diversity
of both sulfonylating reagent and sulfone: aryl- and
heteroarylsulfonylbenzotriazoles convert both acyclic and
alicyclic sulfones into the corresponding bis-sulfones.
Synthesis of Esters of r-Sulfonyl Carboxylic Ac-
ids. Esters of R-sulfonyl carboxylic acids are useful for
the synthesis of metalloproteinase inhibitors R-sulfonyl-
hydroxamic acids57 and synthons for paramagnetic het-
erocycles.58 R-Sulfonyl esters have been prepared (Scheme
8) (i) by decarboxylation of R-sulfonyl malonic esters,59
(ii) by alkoxycarboxylation of arylmethyl sulfones,60 (iii)
from benzenesulfinate salts and R-halo esters,61 and (iv)
by direct sulfonylation of ester lithium enolates or silyl
ketene acetals.62 We now use our C-sulfonylation meth-
odology in a new and general method providing a range
of these target molecules.
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Oberhuber, C.; Echavarren, A. M. J. Org. Chem. 2002, 67, 5197. (c)
Nieto-Oberhuber, C.; Mun˜oz, M. P.; Bun˜uel, E.; Nevado, C.; Ca´rdenas,
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2003, 68, 1443.
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Marzorati, L. Synth. Commun. 1998, 28, 4179.
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9194 J. Org. Chem., Vol. 70, No. 23, 2005

N-Sulfonylbenzotriazoles as Reagents for C-Sulfonylation
SCHEME 9a
N-Sulfonylbenzotriazoles 3 were prepared according to
previously published procedures.10,12b
General Procedure for Preparation of 3f,h. A solution
of benzofuran (4.1 g, 35 mmol) in anhydrous THF (120 mL)
was cooled to -78 °C under nitrogen and then treated dropwise
with n-BuLi (21.8 mL of 1.6 M in hexane, 35 mmol) and stirred
at this temperature for 15 min and then at room temperature
for 1.0 h. Sulfur dioxide was bubbled into the reaction mixture
at -78 °C and stirred at that temperature for 15 min and then
at room temperature for 1 h. N-Chlorobenzotriazole (5.4 g, 35
mmol) was added in one portion at room temperature, and the
mixture was then stirred for 2 h. Triethylamine (5.3 mL, 40
mmol) was added followed by stirring at room temperature
for 10 h. Water (300 mL) was added to the reaction mixture,
and the product was extracted with ethyl acetate (3 × 300 mL).
The combined organic layers were washed with water and
brine and dried over MgSO4. After evaporation, the residue
was recrystallized from ethyl acetate to give pure products
3f,h.
a For designation of R, R1, and R2 in 14, see Table 5.
TABLE 5. Preparation of Ester r-Sulfonyl Carboxylic
Acids 14a-d
compd
R
R1
R2 yield (%) lit. yield (%)
14a 4-MeC6H4
14b 4-MeC6H4
Ph
Et
60
62
71
47
3662
1-naphthyl Me
14c
2-benzofuryl
Bz
Et
Me
14d 5-ethyl-2-furyl Et
Ester enolates 13a-d (prepared by treating the cor-
responding ester 12 with LDA in THF at rt for 13a,b,d
or at -78 °C for 13c) were treated with N-sulfonylben-
zotriazole 3c,f,h in THF at -78 °C. The reaction mixture
was allowed to warm to room temperature while stirring
overnight and afforded, after workup, R-sulfonyl esters
14a-d in 60-71% isolated yields (Scheme 9 and Table
5).
C-Sulfonylation of esters with N-sulfonylbenzotriazoles
provides a convenient synthetic methodology for the
synthesis of R-sulfonyl esters 14 in comparison with
reported direct sulfonylation of esters (Scheme 8, iv),
which is limited to tosylation and requires the use of
moisture-sensitive p-tolylsulfonyl fluoride62 since the use
of p-tolylsulfonyl chloride gave R-chloro esters with no
sulfonylation.
In summary, novel and advantageous methods for the
syntheses of several classes of C-sulfonylated products
have been developed using 1-sulfonylbenzotriazoles. These
approaches broaden the range of available sulfone de-
rivatives, which are compounds of major synthetic,
biological, and medicinal importance. Advantages of our
procedures include the following: (i) the use of sulfonyl
chloride and foul-smelling sulfides is avoided; (ii) 1-sul-
fonylbenzotriazoles are neutral and odorless crystalline
compounds, easily accessible, and stable to storage over
years; and (iii) the C-sulfonylated products are generally
obtained in synthetically useful yields. Our results
represent the first examples of the successful use of
sulfonamides as C-sulfonylating reagents and suggest
that few limitations are to be expected for the sulfony-
lation of nitriles, heterocycles, alkylated heterocycles,
sulfones, and esters using benzotriazole methodology.
The present procedures require only simple manipula-
tions and low-priced reagents; thus, they should be
appropriate for providing highly demanded sulfone de-
rivatives. The present work provides additional evidence
for the good leaving ability of a benzotriazole group.
1-(Benzofuran-2-ylsulfonyl)-1H-1,2,3-benzotriazole (3f):
colorless microcrystals (81%); mp 147-148 °C; 1H NMR δ 8.16
(d, J ) 8.4 Hz, 1H), 8.12 (d, J ) 8.4 Hz, 1H), 7.86 (s, 1H),
7.70-7.75 (m, 2H), 7.46-7.56 (m, 3H), 7.32-7.38 (m, 1H); 13
C
NMR δ 156.5, 145.5, 131.6, 130.7, 129.4, 126.2, 125.2, 124.9,
123.6, 120.7, 116.9, 112.7, 112.2. Anal. Calcd for C14H9N3O3S:
C, 56.18; H, 3.03; N, 14.04. Found: C, 56.4; H, 2.83; N, 14.12.
1-(5-Ethylfuran-2-yl-sulfonyl)-1H-1,2,3-benzotriazole
(3h): colorless prisms (66%); mp 147-148 °C; 1H NMR δ 8.09
(d, J ) 8.4 Hz, 1H), 8.13 (d, J ) 8.4 Hz, 1H), 7.66-7.72
(m, 1H), 7.49-7.54 (m, 1H), 7.43 (d, J ) 3.7 Hz, 1H), 6.20 (d,
J ) 3.7 Hz, 1H), 2.64 (q, J ) 7.6 Hz, 2H), 1.18 (t, J ) 7.6 Hz,
3H); 13C NMR δ 166.2, 145.5, 142.5, 131.6, 130.3, 126.0,
122.8, 120.6, 112.2, 107.5, 21.7, 21.7, 11.2. Anal. Calcd for
C12H11N3O3S: C, 51.98; H, 4.00; N, 15.15. Found: C, 52.19;
H, 3.83; N, 15.22.
General Procedures for the Preparation of r-Cyano
Sulfones 5a-i. Method A. A solution of the nitrile 4 (2 mmol)
in anhydrous THF (15 mL) was cooled to -78 °C under
nitrogen and then treated dropwise with n-BuLi (2.6 mL of
1.55 M in hexane 4 mmol) to afford a clear solution, which
was stirred at this temperature for 1 h. N-Sulfonylbenzotria-
zole 3 (dissolved in 10 mL of anhydrous THF) was then added
dropwise. The reaction mixture was allowed to warm to room
temperature while stirring overnight. After the reaction was
quenched by addition of saturated NH4Cl, the mixture was
extracted with EtOAc. The organic extracts were combined,
washed with aqueous Na2CO3 10% solution and brine, and
dried over MgSO4. After evaporation under vacuum, the
residue was purified by flash chromatography (hexanes/EtOAc,
5:1) to afford the pure 5.
Method B. A mixture of nitrile 4 (2 mmol) and potassium
tert-butoxide (0.45 g, 4 mmol) in DMSO (10 mL) was stirrred
below 10 °C for 10 min. After addition of 1-sulfonylbenzotria-
zole 3 (2 mmol) in DMSO (5 mL), the mixture was allowed to
warm to room temperature and stirred for 8 h. The mixture
was poured into water (40 mL), acidified with ammonium
chloride, and then extracted with ethyl acetate (3 × 30). The
extracts were washed with water and dried over Na2SO4, and
the solvent was removed under reduced pressure. The residue
was chromatographed on a silica gel column using hexanes/
EtOAc 10:1 as elutent to give the pure product 5.
4-Bromophenylmethanesulfonylacetonitrile (5a): col-
1
orless plates (82%); mp 111-113 °C; H NMR δ 7.64 (d, J )
Experimental Section
7.6 Hz, 2H), 7.43 (d, J ) 7.7 Hz, 2H), 5.07 (s, 1H), 3.07 (s,
3H); 13C NMR δ 132.8, 131.1, 125.7, 123.4, 113.0, 60.5, 38.1.
Anal. Calcd for C9H8BrNO2S: C, 39.43; H, 2.94; N, 5.11.
Found: C, 39.60; H, 2.84; N, 5.00.
Melting points were uncorrected. NMR spectra were re-
corded in CDCl3 with tetramethylsilanes as internal standard
1
for H (300 MHz) or solvent as the internal standard for 13C
(75 MHz). Microanalyses were performed on an elemental
analyzer. THF was distilled from sodium benzophenone ketyl,
and DMSO was dried over molecular sieves prior to use.
Column chromatography was performed on silica gel 200-245
mesh.
2,4-Dichlorophenylmethanesulfonylacetonitrile (5b):
1
colorless prisms (87%); mp 155-157 °C; H NMR δ 7.73 (d, J
) 8.5 Hz, 1H), 7.55 (d, J ) 1.9 Hz, 1H), 7.45 (dd, J ) 8.5, 1,9
Hz, 1H), 5.75 (s, 1H), 3.17 (s, 3H); 13C NMR δ 138.2, 135.4,
132.0, 130.4, 128.6, 121.7, 112.7, 56.6, 39.5. Anal. Calcd for
J. Org. Chem, Vol. 70, No. 23, 2005 9195

Katritzky et al.
C9H7Cl2NO2S: C, 40.93; H, 2.67; N, 5.30. Found: C, 41.01; H,
2.56; N, 5.11.
2-Ethyl-5-(phenylsulfonyl)furan (7b): yellowish oil (80%);
1H NMR δ 7.97-8.00 (m, 2H), 7.50-7.63 (m, 3H), 1.21 (t, J )
7.6 Hz, 3H), 7.12 (d, J ) 3.4 Hz, 1H), 6.12 (d, J ) 3.4 Hz, 1H),
2.66 (q, J ) 7.6 Hz, 2H), 1.21 (t, J ) 7.6 Hz, 3H); 13C NMR δ
164.1, 147.4, 140.4, 133.4, 133.4, 129.2, 127.6, 118.8, 106.5,
21.6, 11.5. Anal. Calcd For C12H12O3S: C, 61.00; H, 5.12.
Found: 61.03; H, 5.17.
2-[(4-Methylphenyl)sulfonyl]benzofuran (7c): colorless
microcrystals (73%); mp 95-96 °C (lit.35 mp 95-95 °C); 1H
NMR δ 7.96 (d, J ) 8.2 Hz, 2H), 7.67 (d, J ) 7.8 Hz, 1H), 7.53
(d, J ) 0.6 Hz, 1H), 7.50 (d, J ) 8.4 Hz, 1H), 7.42 (td, J ) 7.0
Hz, J ) 1.1 Hz, 1H), 7.35 (d, J ) 8.2 Hz, 2H), 7.29 (dd, J )
8.0, 1.0 Hz, 1H), 2.42 (s, 3H).13C NMR δ 151.9, 145.3, 136.3,
130.0, 128.3, 127.9, 125.9, 124.2, 123.1, 112.8, 112.4, 21.6.
Anal. Calcd for C15H12O3S: C, 66.16; H, 4.44. Found: C, 65.97;
H, 4.33.
4-Bromophenyltoluene-4-sulfonylacetonitrile (5c): col-
1
orless microcrystals (93%); mp 138-139 °C; H NMR δ 7.62
(d, J ) 8.4 Hz, 2H), 7.52 (d, J ) 8.5 Hz, 2H), 7.35 (d, J ) 8.5
Hz, 2H), 7.17 (d, J ) 8.5 Hz, 2H), 5.06 (s, 1H), 2.48 (s, 3H);
13C NMR δ 147.0, 132.3, 131.2, 131.1, 130.1, 130.0, 125.2,
124.5, 113.2, 62.5, 21.8. Anal. Calcd for C15H12BrNO2S: C,
51.44; H, 3.45; N, 4.00. Found: C, 51.56; H, 3.35; N, 3.92.
2,4-Dichlorophenyltoluene-4-sulfonylacetonitrile (5d):
1
colorless prisms (97%); mp 126-128 °C; H NMR δ 7.75 (d, J
) 8.0 Hz, 2H), 7.48-7.33 (m, 5H), 5.70 (s, 1H), 2.50 (s, 3H);
13C NMR δ 147.2, 137.7, 135.8, 132.0, 131.9, 130.2, 130.0,
129.9, 128.1, 122.8, 113.0, 58.4, 21.9. Anal. Calcd. for C15H11-
Cl2NO2S: C, 52.95; H, 3.26; N, 4.12. Found: C, 52.90; H, 3.16;
N, 4.04.
Benzenesulfonylphenylacetonitrile (5e): colorless crys-
tals (76%); mp 148-150 °C (lit.63 mp 147.0-148 °C); 1H NMR
δ 7.73-7.70 (m, 3H), 7.55-7.26 (m, 7H), 5.14 (s, 1H); 13C NMR
δ 135.2, 134.3, 130.5, 130.1, 129.7, 129.2, 129.0, 125.3, 113.4,
63.1. Anal. Calcd for C14H11NO2S: N, 5.44. Found: N, 5.71.
Benzenesulfonylacetonitrile (5f): colorless crystals (50%);
2-(Methyl-1H-pyrrole-2-sulfonyl)pyridine (7d): pink
prisms (54%); mp 62-63 °C; 1H NMR δ 8.67 (br d, J ) 4.7 Hz,
1H), 8.12 (d, J ) 8.0 Hz, 1H), 7.92 (td, J ) 7.7, 1.6 Hz, 1H),
7.46 (ddd, J ) 7.7, 4.8, 1.0 Hz, 1H), 7.03 (dd, J ) 4.1, 1.9 Hz,
1H), 6.85 (t, J ) 2.1 Hz, 1H), 6.18 (dd, J ) 4.1, 2.6 Hz, 1H),
4.01 (s, 3H); 13C NMR δ 159.8, 150.1, 138.1, 130.6, 126.7, 121.2,
120.1, 108.5, 36.5. Anal. Calcd for C10H10N2O2S: C, 54.04; H,
4.53; N, 12.60. Found: C, 54.42; H, 4.58; N, 12.56.
1
mp 87-88 °C (lit.64 mp 88 °C); H NMR δ 8.06-8.02 (m, 2H),
7.82-7.77 (m, 1H), 7.69-7.64 (m, 2H), 4.10 (s, 2H); 13C NMR
δ 136.6, 135.4, 129.8, 128.8, 110.4, 45.7. Anal. Calcd. for C8H7-
NO2S: C, 53.03; H, 3.89; N, 7.73. Found: C, 53.09; H, 3.81;
N, 7.62.
General Procedure for the Preparation of (r-Sulfo-
nylalkyl)heterocycles 9a-f. A solution of the appropriate
alkylheterocycles 8 (3 mmol) in THF (20 mL) was cooled to
-78 °C under nitrogen and treated with n-BuLi (2.0 mL of
1.6 M in hexane, 3.15 mmol) or LDA (2.25 mL of 2.0 M in
heptane/THF/ethylbenzene, 4.5 mmol) for 9b,c. The reaction
mixture was stirred at -78 °C for 1.5-2.5 h and N-sulfonyl-
benzotriazole 3 (3.15 mmol) in THF (10 mL) was added slowly.
The mixture was allowed to warm to room temperature while
stirring overnight, quenched with saturated NH4Cl, and
extracted with EtOAc. The combined extracts were washed
with brine and dried over MgSO4. After evaporation under
vacuum, the residue was chromatographed or recrystalized
from an appropriate solvent to give the pure products 9a-f.
2-[(Phenylsulfonyl)methyl]pyridine (9a): colorless mi-
2,4-Dichlorophenyl(thiophene-2-sulfonyl)acetoni-
trile (5g): pale yellow plates (90%); mp 142-144 °C; 1H NMR
δ 7.91 (d, J ) 4.9 Hz, 1H), 7.73 (d, J ) 3.8 Hz, 1H), 7.48 (d, J
) 8.5 Hz, 1H), 7.46 (d, J ) 1.9 Hz, 1H), 7.36 (dd, J ) 8.4, 1.9
Hz, 1H), 7.25 (dd, J ) 4.9, 3.3 Hz, 1H), 5.85 (s, 1H). 13C NMR
δ 137.9, 137.8, 137.5, 135.9, 134.6, 131.8, 130.1, 128.6, 128.1,
122.7, 112.8, 59.4. Anal. Calcd for C12H7Cl2NO2S: C, 43.38;
H, 2.12; N, 4.22. Found: C, 43.43; H, 2.01; N, 4.07.
2-Methyl-2-(2-pyridinylsulfonyl)hexanenitrile (5h): red
1
oil (54%); H NMR δ 8.82-8.80 (m, 1H), 8.19 (d, J ) 7.8 Hz,
1H), 8.06 (td, J ) 7.8, 1.6 Hz, 1H), 7.67(dd, J ) 7.7, 4.8 Hz,
1H), 4.64 (dd, J ) 10.2, 5.0 Hz, 1H), 2.25-2.13 (m, 2H), 1.76-
1
1.50 (m, 2H), 1.45-1.21 (m, 6H), 0.90 (t, J ) 6.6 Hz, 3H); 13
C
crocrystals (59%); mp 110-111 °C (lit.48 mp 111-112 °C); H
NMR δ 154.5, 150.5, 138.6, 128.5, 123.6, 113.4, 63.1, 31.0, 28.2,
26.4, 25.0, 22.2, 13.8. Anal. Calcd for C13H18N2O2S: C, 58.62;
H, 6.81; N, 10.52. Found: C, 59.39; H, 7.13; N, 10.48.
2-Phenyl-2-(3-pyridinylsulfonyl)propanenitrile (5i): col-
NMR δ 8.42 (br d, J ) 4.3 Hz, 1H), 7.59-7.78 (m, 4H), 7.44-
7.49 (m, 3H), 7.21-7.25 (m, 1H), 4.56 (s, 2H); 13C NMR δ 149.7,
149.0, 136.7, 133.7, 129.4, 129.0, 128.4, 125.7, 123.3, 64.7.
Anal. Calcd for C12H11NO2S: C, 61.78; H, 4.75; N, 6.00.
Found: C, 61.59; H, 4.72; N, 5.60.
1
orless microcrystals (73%); mp 121-122 °C; H NMR δ 8.85
(dd, J ) 4.9, 1.7 Hz, 1H), 8.57 (d, J ) 2.2 Hz, 1H), 7.95 (d, J
) 8.0 Hz, 1H), 7.46-7.37 (m, 6H), 2.28 (s, 3H); 13C NMR δ
155.1, 150.8, 138.3, 130.6, 130.1, 129.5, 129.0, 128.1, 123.4,
116.8, 67.2, 19.2. Anal. Calcd for C14H12N2O2S: C, 61.75; H,
4.44; N, 10.29. Found: C, 61.77; H, 4.44; N, 10.05.
2-[Phenyl(phenylsulfonyl)methyl]pyridine (9b): color-
1
less needless (94%); mp 163-164 °C; H NMR δ 8.53 (br d, J
) 4.7 Hz, 1H), 7.82 (d, J ) 7.8 Hz, 1H), 7.71 (td, J ) 7.7, 1.7
Hz, 1H), 7.50-7.61 (m, 5H), 7.28-7.39 (m, 5H), 7.21-7.25 (m,
1H), 5.58 (s, 1H); 13C NMR δ 153.1, 149.6, 138.0, 136.9, 133.6,
131.8, 130.4, 129.2, 128.9, 128.6, 128.6, 124.8, 123.3, 78.1.
Anal. Calcd for C18H15NO2S: C, 69.88; H, 4.89; N, 4.53.
Found: C, 69.83; H, 4.80; N, 4.50.
General Procedure for the Preparation of Sulfonyl-
heterocycles 7a-d. A solution of the appropriate heterocycle
(3 mmol) in anhydrous THF (20 mL) was cooled to -78 °C
under nitrogen and then treated dropwise with n-BuLi (1.91
mL of 1.6 M in hexane, 3.05 mmol). The mixture was stirred
at -78 °C for 15 min and then at room temperature for 1.0 h.
After the mixture was cooled to -78 °C, a solution of N-
sulfonylbenzotriazoles 3 (3.05 mmol) in THF (10 mL) was
added slowly to the reaction mixture at -78 °C. The reaction
mixture was allowed to warm to room temperature while
stirring overnight, quenched by the addition of saturated NH4-
Cl, and extracted with EtOAc. The organic extracts were
combined, washed with brine, and dried over MgSO4. After
evaporation under vacuum, the residue was chromatographed
on a silica gel eluted with hexanes/EtOAc 4:1 to give 7a-d.
2-(Methylsulfonyl)thiophene (7a): colorless oil (47%); 1H
NMR δ 7.71-7.74 (m, 2H), 7.12 (dd, J ) 4.8, 3.8 Hz, 1H), 3.2
(s, 3H); 13C NMR δ 141.7, 133.7, 133.4, 127.9, 46.1. Anal. Calcd
for C5H6O2S2: C, 37.02; H, 3.73. Found: C, 37.12; H, 3.66.
4-[(Methylsulfonyl)(phenyl)methyl]pyridine (9c): col-
orless prisms (53%); mp 86-87 °C; 1H NMR δ 8.66 (d, J ) 5.8
Hz, 2H), 7.61-7.64 (m, 2H), 7.57 (d, J ) 5.8 Hz, 2H), 7.44-
7.47 (m, 3H), 5.30 (s, 1H), 2.81 (s, 3H); 13C NMR δ 150.4, 141.1,
131.6, 129.6, 129.58, 129.4, 124.4, 73.6, 40.1. Anal. Calcd for
C13H13NO2S: C, 63.13; H, 5.30; N, 5.66. Found: C, 63.18; H,
5.34; N, 5.61.
2-{1-[(4-Methylphenyl)sulfonyl]ethyl}pyridine (9d): yel-
lowish prisms (43%); mp 69-70 °C; 1H NMR δ 8.40 (br d, J )
4.8 Hz, 1H), 7.68 (td, J ) 7.7, 1.6 Hz, 1H), 7.49 (d, J ) 8.0 Hz,
1H), 7.45 (d, J ) 8.2 Hz, 2H), 7.20-7.22 (m, 3H), 4.49 (q, J )
7.1 Hz, 1H),), 2.40 (s, 3H), 1.78 (d, J ) 7.1 Hz, 3H); 13C NMR
δ 153.7, 149.1, 144.6, 136.5, 133.9, 129.4, 129.0, 124.6, 123.3,
67.7, 21.6, 13.5. Anal. Calcd for C14H15NO2S: C, 64.34; H, 5.79;
N, 5.36. Found: 64.62; H, 5.96; N, 5.41.
1-Methyl-2-[(2-thienylsulfonyl)methyl]-1H-benzimida-
zole (9e): yellowish prisms (64%); mp 185-187 °C; 1H NMR
δ 7.69 (d, J ) 4.9 Hz, 1H), 7.65 (d, J ) 8.0 Hz, 1H), 7.49 (d, J
) 2.7 Hz, 1H), 7.34-7.40 (m, 2H), 7.25-7.31 (m, 1H), 7.08-
(63) You, J.; Verkade, J. G. J. Org. Chem. 2003, 68, 8003.
(64) Bo¨hme, H.; Fuchs, G. Chem. Ber. 1970, 103, 2775.
9196 J. Org. Chem., Vol. 70, No. 23, 2005

N-Sulfonylbenzotriazoles as Reagents for C-Sulfonylation
7.11 (m, 1H), 4.84 (s, 2H), 3.90 (s, 3H); 13C NMR δ 142.4, 142.3,
138.0, 136.1, 135.4, 135.2, 128.0, 123.6, 122.6, 120.0, 109.8,
56.6, 30.8. Anal. Calcd for C13H12N2O2S2: C, 53.40; H, 4.14;
N, 9.58. Found: C, 53.44; H, 4.00; N, 9.50.
NMR δ 7.97 (s, 1H), 7.91 (d, J ) 7.9 Hz, 1H), 7.82 (d, J ) 8.1
Hz, 1H), 7.64 (t, J ) 8.0 Hz, 1H), 7.47 (t, J ) 7.7 Hz, 1H), 5.42
(t, J ) 8.5 Hz, 1H), 3.42-3.35 (m, 1H), 3.28-3.18 (m, 1H),
2.54-2.46 (m, 2H), 2.25-2.17 (m, 1H), 2.07-1.99 (m, 1H);
13C NMR δ 155.8, 148.3, 129.1, 125.6, 124.0, 117.1, 112.6, 76.7,
52.4, 25.3, 19.0. Anal. Calcd for C12H12O5S2: C, 47.99; H, 4.03.
Found: C, 47.58; H, 4.15.
2-[(1-Benzofuran-2-ylsulfonyl)methyl]-1,3-benzothia-
1
zole (9f: yellowish microcrystals (67%); mp 176-177 °C; H
NMR δ 8.12-8.15 (m, 1H), 7.75-7.90 (m, 4H), 7.59-7.64 (m,
2H), 7.42-7.54 (m, 3H), 5.66 (s, 2H); 13C NMR δ 156.9, 155.7,
152.3, 148.5, 135.7, 128.8, 126.5, 125.9, 125.6, 124.7, 123.8,
122.9, 122.4, 116.0, 112.4, 58.2. Anal. Calcd for C16H11NO3S2:
C, 58.34; H, 3.37; N, 4.25. Found: C, 57.98; H, 3.20; N, 4.29.
General Procedures for the Preparation of r-Sulfonyl
Sulfones 11a-g. To a solution of sulfone 10 (2 mmol) in dry
THF (10 mL) was added n-BuLi (2.6 mL, 1.55 M in pentane,
4 mmol) at -78 °C. The solution was stirred at -78 °C for 1
h and a solution of 1-sulfonylbenzotriazole 3 (2 mmol) in THF
(10 mL) was added. The reaction mixture was stirred for 10 h
while the temperature was allowed to rise to 20 °C. After
quenching with water (15 mL) and extraction with EtOAc (3
× 20 mL), the combined organic layers were washed with
water (25 mL) and dried over MgSO4, and the solvent was
removed in vacuo. The resulted oil was subjected to column
chromatography (eluent: ethyl acetate/hexanes ) 1:10 then
1: 5) to give the pure 11.
Ethyl 1-(2-thienylsulfonyl)ethyl sulfone (11g): yellow
1
oil (71%); H NMR δ 7.87 (dd, J ) 4.9, 1.2 Hz, 1H), 7.83 (dd,
J ) 3.8, 1.2 Hz, 1H), 7.22 (dd, J ) 4.8, 4.0 Hz, 1H), 4.50 (q, J
) 7.3 Hz, 1H), 3.62-3.46 (m, 2H), 1.75 (d, J ) 7.3 Hz, 3H),
1.47 (t, J ) 7.4 Hz, 3H); 13C NMR δ 137.4, 136.4, 135.5, 128.0,
76.1, 48.3, 9.5, 6.0. Anal. Calcd for C8H12O4S3: C, 35.80; H,
4.51. Found: C, 35.95; H, 4.37.
General Procedure for the Preparation of r-Sulfonyl
Esters 14a-d. A solution of esters 12a-d (3 mmol) in
anhydrous THF (20 mL) was cooled to -78 °C under nitrogen
and then treated dropwise with LDA (3 mL, 2.0 M in heptane/
THF/ethylbenzene, 6 mmol). The mixture was stirred for 2.0
h at rt (for 13a,b,d) or at -78 °C (for 13c), and N-sulfonyl-
benzotriazoles 3c,f,h (3.15 mmol) in THF (10 mL) were slowly
added at -78 °C. The reaction mixture was stirred overnight
while the temperature was allowed to rise to room tempera-
ture, quenched with saturated NH4Cl, and extracted with
EtOAc. The organic extracts were washed with a saturated
solution of Na2CO3 and dried over MgSO4. The solvent was
evaporated and the resultant oil was chromatographed to give
the pure product 14a-d.
1-(Benzenesulfonylphenylsulfonyl)-4-methylben-
zene (11a): colorless prisms (96%); mp 188-189 °C; 1H NMR
δ 7.75 (d, J ) 8.0 Hz, 2H), 7.65-7.58 (m, 3H), 7.47-7.41 (m,
2H), 7.38-7.33 (m, 2H), 7.28-7.18 (m, 5H), 5.41 (s, 1H), 2.41
(s, 3H); 13C NMR δ 145.7, 138.0, 135.0, 134.4, 130.3, 129.7,
129.6, 129.4, 128.8, 128.6, 125.8, 88.4, 21.7. Anal. Calcd for
C20H18O4S2: C, 62.15; H, 4.64. Found: C, 61.96; H, 4.64.
1-Benzenesulfonylmethanesulfonyl-4-methylben-
zene (11b): colorless prisms (87%); mp 93-94 °C; 1H NMR δ
8.00-7.98 (m, 2H), 7.87 (d, J ) 8.2 Hz, 2H), 7.77-7.72 (m,
1H), 7.64-7.56 (m, 2H), 7.41 (d, J ) 8.0 Hz, 2H), 4.75 (s, 2H),
2.50 (s, 3H). 13C NMR δ 146.1, 138.4, 135.4, 134.7, 129.9, 129.3,
128.8, 128.7, 74.5, 21.7. Anal. Calcd for C14H14O4S2: C, 54.18;
H, 4.55. Found: C, 54.25; H, 4.45.
2-(Toluene-4-sulfonyl)tetrahydrothiophene-1,1-di-
one (11c): colorless plates (78%); mp 104-105 °C; 1H NMR δ
7.89 (d, J ) 8.1 Hz, 2H), 7.40 (d, J ) 8.1 Hz, 2H), 4.32 (t, J )
8.0 Hz, 1H), 3.30-3.11 (m, 2H), 2.82-2.60 (m, 2H), 2.47 (s,
3H), 2.43-2.34 (m, 1H), 2.21-2.11 (m, 1H); 13C NMR δ 146.1,
134.2, 129.9, 129.5, 77.3, 51.2, 24.3, 21.7, 18.9. Anal. Calcd
for C11H14O4S2: C, 48.16; H, 5.14. Found: C, 48.38; H, 5.20.
(1-Ethanesulfonylethanesulfonyl)benzene (11d): color-
less crystals (91%); mp 96-97 °C (lit.65 mp 93-94 °C); 1H NMR
δ 7.97 (d, J ) 7.4 Hz, 2H), 7.76-7.71 (m, 1H), 7.63-7.58 (m,
2H), 4.38 (q, J ) 7.4 Hz, 1H), 3.67-3.47 (m, 2H), 1.69 (d, J )
7.3 Hz, 3H), 1.49 (t, J ) 7.4 Hz, 3H); 13C NMR δ 135.7, 134.9,
130.1, 129.1, 76.0, 48.2, 9.5, 6.2. Anal. Calcd for C10H14O4S2:
C, 45.78; H, 5.38. Found: C, 45.73; H, 5.37.
Ethyl 2-[(4-methylphenyl)sulfonyl]-2-phenylacetate
(14a): colorless prisms (60%); mp 112-113 °C (lit.62 mp 112-
1
113 °C); H NMR δ 7.48 (d, J ) 8.2 Hz, 2H), 7.29-7.38 (m,
5H), 7.22 (d, J ) 8.2 Hz, 2H), 5.08 (s, 1H), 4.13-4.30 (m, 2H),
2.41 (s, 3H), 1.24 (t, J ) 7.1 Hz, 3H); 13C NMR δ 164.9 145.3,
133.4, 130.3, 130.0, 129.6, 129.2, 128.6, 128.0, 75.3, 62.5, 21.7,
13.9. Anal. Calcd for C17H18O4S: C, 64.13; H, 5.70. Found: C,
64.22; H, 5.75.
Methyl 2-[(4-methylphenyl)sulfonyl]-2-(1-naphthyl)-
acetate (14b): yellowish oil (62%); 1H NMR δ 8.00-7.88 (m,
3H), 7.78 (dd, J ) 7.4, 1.0 Hz, 1H), 7.56-7.51(m, 4H), 7.44 (t,
J ) 8.0 Hz, 1H), 7.19 (d, J ) 8.1 Hz, 2H), 6.13 (s, 1H), 3.81 (s,
3H), 2.42 (s, 3H); 13C NMR δ 165.9, 145.3, 133.7, 133.3, 131.8,
130.3, 130.0, 129.1, 129.0, 128.6, 127.1, 125.9, 124.9, 123.9,
122.4, 69.1, 53.2, 21.6; HRMS calcd for C20H18O4S 354.4265,
found 354.0925. Anal. Calcd for C20H18O4S: C, 67.78; H, 5.12.
Found: C, 67.42; H, 5.26.
2-(Benzofuran-2-sulfonyl)-3-phenylpropionic acid eth-
yl ester (14c): colorless prisms (71%); mp 77-78 °C; 1H NMR
δ 7.74 (d, J ) 7.8 Hz, 1H), 7.58-7.639 (m, 2H), 7.54 (td, J )
7.1, 1.2 Hz, 1H), 7.36-7.41 (m, 1H), 7.16-7.29 (m, 5H), 4.42
(dd, J ) 11.5, 3.9 Hz, 1H), 4.03 (q, J ) 7.1 Hz, 2H), 3.37-3.56
(m, 2H), 0.96 (t, J ) 7.1 Hz, 1H); 13C NMR δ 164.4, 156.5,
148.0, 135.2, 128.9, 128.8, 128.7, 127.3, 125.7, 125.7, 124.6,
123.4, 116.5, 112.6, 71.3, 62.4, 31.9, 13.6. Anal. Calcdfor
C19H18O5S: C, 63.67; H, 5.06. Found: C, 63.64; H, 5.01.
2-(5-Ethylfuran-2-sulfonyl)butyric acid methyl ester
(14d): yellowish oil (47%); 1H NMR δ 7.11 (d, J ) 3.4 Hz, 1H),
6.21 (d, J ) 3.4 Hz, 1H), 3.95 (dd, J ) 10.6, 4.5 Hz, 1H), 3.76
(s, 1H), 2.75 (q, J ) 7.6 Hz, 2H), 2.05-2.18 (m, 2H), 1.29 (t, J
) 7.6 Hz, 3H), 1.00 (t, J ) 7.4 Hz, 3H); 13C NMR δ 165.8, 164.8,
144.0, 121.8, 106.8, 71.6, 53.0, 21.7, 20.1, 11.6, 11.4. Anal.
Calcd for C10H16O5S: C, 50.76; H, 6.20. Found: C, 50.40; H,
6.25.
2-(1-Ethanesulfonylethanesulfonyl)pyridine (11e): red
microcrystals (87%); mp 118-120 °C; 1H NMR δ 8.77 (br d, J
) 4.5 Hz, 1H), 8.14 (d, J ) 7.8 Hz, 1H), 8.04-7.99 (m, 1H),
7.64-7.60 (m, 1H), 5.14 (q, J ) 7.6 Hz, 1H), 3.60-3.33 (m,
2H), 1.86 (d, J ) 7.5 Hz, 3H), 1.45 (t, J ) 7.6 Hz, 3H); 13C
NMR δ 155.8, 150.2, 138.3, 128.0, 123.4, 72.4, 46.7, 8.8, 5.5.
Anal. Calcd for C9H13NO4S2: C, 41.05; H, 4.98; N, 5.32.
Found: C, 41.20; H, 4.94; N, 5.17.
2-(1-Benzofuran-2-ylsulfonyl)tetrahydrothiophene-1,1-
dione (11f): colorless crystals (67%); mp 147-148 °C; 1H
(65) Stetter, H.; Steinbeck, K. Liebigs Ann. Chem. 1974, 1315.
JO051157I
J. Org. Chem, Vol. 70, No. 23, 2005 9197