Synthesis of new lipophilic sulfones and their use in cyclization reactions

Article abstract of DOI:10.1080/10426500902855208

Analytically pure novel dibenzylsulfanes 2a,b were synthesized by established reactions. Their oxidation by hydrogen peroxide resulted in the formation of the corresponding sulfones 3a,b, which were isolated in high yields. Analogously, the new bis-sulfon

Full text of DOI:10.1080/10426500902855208

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Phosphorus, Sulfur, and Silicon
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Synthesis of New Lipophilic
Sulfones and Their Use in
Cyclization Reactions
Gunther Buehrdel a , Eva Petrlikova a , Petra
Herzigova a , Rainer Beckert a & Helmar Goerls b
a Institute of Organic and Macromolecular Chemistry,
Friedrich Schiller University, Jena, Germany
b Institute of Inorganic and Analytical Chemistry,
Friedrich Schiller University, Jena, Germany
Published online: 28 Apr 2009.
To cite this article: Gunther Buehrdel , Eva Petrlikova , Petra Herzigova , Rainer
Beckert & Helmar Goerls (2009) Synthesis of New Lipophilic Sulfones and Their Use
in Cyclization Reactions, Phosphorus, Sulfur, and Silicon and the Related Elements,
184:5, 1161-1174, DOI: 10.1080/10426500902855208
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Phosphorus, Sulfur, and Silicon, 184:1161–1174, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500902855208
Synthesis of New Lipophilic Sulfones and Their Use
in Cyclization Reactions
Gunther Buehrdel,1 Eva Petrlikova,1 Petra Herzigova,1
Rainer Beckert,1 and Helmar Goerls2
1Institute of Organic and Macromolecular Chemistry, Friedrich Schiller
University, Jena, Germany
2Institute of Inorganic and Analytical Chemistry, Friedrich Schiller
University, Jena, Germany
Analytically pure novel dibenzylsulfanes 2a,b were synthesized by established re-
actions. Their oxidation by hydrogen peroxide resulted in the formation of the cor-
responding sulfones 3a,b, which were isolated in high yields. Analogously, the new
bis-sulfone 7 was prepared starting from bis-bromo derivative 4 via bis-sulfane 6.
The sulfones obtained reacted readily with bis-imidoylchlorides 8, yielding highly
substituted dihydrothiophene-S,S-dioxides of type 9 and 10. Due to their vicinal
amino-imino substructures, these cyclic sulfones proved to be excellent chelating
ligands, exemplified by the preparation of the palladium complex 11.
Keywords Bis-imidoyl chlorides; cyclization reaction; oxidation; sulfanes; sulfones;
thiophene-S, S-dioxides
INTRODUCTION
Among organic sulfur compounds, sulfones have become increasingly
useful and important in organic synthesis. The sulfone group, incorpo-
rated into an organic compound, efficiently stabilizes negative charges
on an adjacent carbon center. This property is especially important
in the development of new methods for the formation of C-C bonds
Received 21 December 2007; accepted 2 February 2008.
Dedicated to Professor Marian Mikolꢀajczyk, CBMiM PAN in Lꢀ o´dz´, Poland, on the
occasion of his 70th birthday.
We are grateful to the Friedrich Schiller University–Jena for financial support of the
work of G. Buehrdel by a stipend. Syngenta Crop Protection AG and Roche Diagnostics
GmbH are acknowledged for support by chemicals.
Address correspondence to Rainer Beckert, Institute of Organic and Macromolecu-
lar Chemistry, Friedrich Schiller University, Humboldtstr. 10, D-07743 Jena, Germany.
E-mail: c6bera@uni-jena.de
1161

1162
G. Buehrdel et al.
¨
(Ramberg–Backlund reaction, Julia olefination, and others). In addi-
tion, some derivatives of sulfones show biological activity: Sulfonal and
diaminodiphenyl sulfones were used as active pharmaceutical ingredi-
ents. Recently, we focused our interest towards benzyl sulfones, which
are easily accessible and can be employed as starting materials for
sulfur-containing heterocycles.1 Thus, we used the reaction between
dibenzyl sulfone and bis-electrophiles, derived from oxalic acid, for the
synthesis of highly substituted derivatives of dihydrothiophene-S,S-
dioxides.2 These derivatives show interesting acidochromism, can be
regarded as precursor molecules for diamino dienes, and, in addition,
offer good requirements for the formation of metal complexes. How-
ever, due to the low solubility of most substituted benzyl sulfones, the
cyclization reaction is restricted to only few examples.2
Therefore our aim was to involve such benzyl sulfones into this cy-
clization reaction that possess substituents leading to a better solu-
bility, easier signal sets in their NMR spectra, and, probably, higher
biological activity.
RESULTS AND DISCUSSION
As synthetic entry, we employed the oxidation of symmetric sulfanes,
which can easily be prepared starting from the corresponding ben-
zyl halides and sodium sulphide. By adapting a procedure in the
literature,1a the sulfanes 2a,b could be isolated as colorless crystals in
very good yields by the reaction of benzyl bromides 1a,b with sodium
sulfide (Scheme 1). Surprisingly, the sulfanes 2a,b are not described
in literature despite their simple structure. Alternatively, 2b can be
prepared starting from 4-trifluoromethylbenzyl tosylate 1c instead of
from bromide 1b.
H2O2
Na2S
Ar
S
Ar
Ar
X
Ar
S
2
Ar
1
O
O
3
1a, 1b: X = Br
1c: X = OTos
1a, 2a, 3a: Ar = 4-tC4H9C6H4
1b, 1c, 2b, 3b: Ar = 4-CF3C6H4
SCHEME 1
The oxidation of a thioether can yield either the correspond-
ing sulfoxide, the corresponding sulfone, or both, depending on the
method used. As standard method for the preparation of diben-
zylsulfones, the oxidation of dibenzylsulfanes with hydrogen per-
oxide was therefore used. The sulfones 3a,b could be isolated as

Synthesis of New Lipophilic Sulfones
1163
colorless crystals in very good yields (Scheme 1). Whereas the sul-
fone 3a was not previously known, 3b was already prepared earlier
by the reaction of p-trifluoromethyl benzyl bromide 1b and sodium
hydroxymethanesulfinate.3 It is noteworthy that the overall yield
for 3b following our protocol is higher than in the literature cited
above.
OC8H17
OC8H17
NaS
Ph
5
S
Ph
Br
Ph
S
Br
OC8H17
OC8H17
4
6
OC8H17
H2O2
S
Ph
O
O
O
O
Ph
S
OC8H17
7
SCHEME 2
We were also interested in the synthesis of bis-sulfone 7. With this
aim in view, the bis-benzyl bromide 44 was converted with the sodium
salt of benzyl mercaptane 5 into the sulfane 6 (Scheme 2). This bi-
functional sulfane, which forms colorless crystals, could be isolated in
excellent yield. Its oxidation with hydrogen peroxide finally resulted
in the bis-sulfone 7, which was isolated nearly quantitatively as color-
less crystals. Elemental analysis and MS data confirmed the molecular
composition for 6 and 7. The 1H and 13C NMR spectra of 6 and 7 confirm
the high symmetry of these molecules.
In order to test the reactivity of newly synthesized sulfones,
they were cyclized with bis-electrophiles of type 8. In the course
of our past work, we demonstrated that bis-arylimidoyl chlorides
2 are excellent (and selective) bis-electrophiles that can be em-
ployed in a wide range as C2-building blocks for heterocyclic as
well as for carbocyclic compounds.5 Under quite mild conditions
(THF in the presence of tBuOK at −20◦C), 3 reacted with bis-
electrophile 8. Single products (TLC) were formed and could be iso-
lated in high yields in the form of yellow crystals. Elemental analysis

1164
G. Buehrdel et al.
RHN
NR
RN
Cl
NR
Cl
Ar
Ar
S
O
O
THF/ tBuKO
8
9
Ar
S
Ar
C8H17
O
3, 7
O
O
TolN
Ph
NHTol
O
O
S
Ph
S
O
O
TolHN
C8H17
10
NTol
O
SCHEME 3
and MS data confirmed the presence of 1:1 cyclization products 9
(Scheme 3, Table I).
Evidence for the structure of amino-imino substituted 2,3-
dihydrothiophene-dioxides of type 9 is the presence of double signal
sets in the 1H and 13C NMR spectra. The NH proton of compound 9c ab-
sorbs in the 1H NMR spectra at 7.7 ppm, whereas the cyclic CH proton
could be detected as singlet at approx. 5.4 ppm. Generally, the chemical
behavior of 9 is identical to that of derivatives reported earlier.2 Due to
the presence of donor–acceptor substitution, solutions of compounds 9
are dark yellow (9a in CHCl3: λmax = 361 nm, log ε 4.0). In addition, 9
shows an amphoteric character upon treatment with acids (HCl) and
bases (tBuOK, nBuLi). In each case, the color changes reversibly to
deep red with formation of cations/anions. The neutral dihydrothio-
phene dioxide 9 is regenerated upon treatment with acid (or base). The
TABLE I Isolated Yields of the Cyclic Sulfones of Type 9
Ar
R
Yield (%)
9a
9b
9c
9d
9e
9f
4-tBuC6H4
4-tBuC6H4
4-CF3C6H4
4-Tol
4-Tol
4-BrC6H4
4-Tol
4-BrC6H4
4-Tol
4-Tol
Ph
88
79
83
67
63
72
Ph

Synthesis of New Lipophilic Sulfones
1165
bis-sulfone 7 could be successfully cyclized twice under the same condi-
tions used for the preparation of 9. The corresponding bis-heterocycle
10 was isolated after purification by column chromatography as a yel-
low solid in an acceptable yield. In the MS spectra, the molpeak at m/z
= 1134 and an additional one at m/z = 1070 [M-SO+2 ], which resulted
1
from sulfur dioxide elimination, could be observed. The H as well as
the 13C NMR spectra of derivative 10 display complex sets of signals
mainly in the part of aromatic protons/carbons. However, the NH as
well as the cyclic CH protons could be detected at about 9.2 and 5.08
ppm, respectively.
The application of this cyclization reaction to other sulfones, e.g.,
dimethyl sulfone or diethyl sulfonyldiglycolate, failed and resulted only
in the formation of complex product mixtures.
Pd
TolN
Ar
NTol
Ar
NEt3
Cl
Cl
Pd
Pd
9a
+
S
O
O
11
Ar = 4-tBuC6H4
SCHEME 4
As a result of its vicinal amino-imino substructures, compounds of
type 9 are capable of the preparation of metal complexes. Thus, 9a
reacts readily with allyl palladium chloride in the presence of triethy-
lamine with formation of a red solution in which only one product could
be detected by TLC. Upon purification by flash chromatography, the pal-
ladium complex 11 was isolated in the form of red crystals. MS data and
1H and 13C NMR spectra confirmed the molecular structure of complex
11 (Scheme 4). In the 1H NMR of 11, the signals of the cyclic CH proton
(5.32 ppm) and the signal of the methyl moiety of the tolylamino group
(2.07) are shifted to higher fields compared to the signals of the ligand
9a. Due to the oxonole-like character of the anion of 9a, the solutions of
complex 11 are dark red (THF: λmax = 478, log ε 3.7). Derivative 11 is
electrochemically active and can be oxidized reversibly. By employing
square wave measurements, one peak at 1.064 V was observed. The
quasi-reversibility of the oxidation was confirmed by cyclovoltammet-
ric measurements ꢀERED,OX = 0.090 V. The solid-state structure of 11
was established by single-crystal X-ray diffraction studies (Figure 1).

1166
G. Buehrdel et al.
FIGURE 1 ORTEP-plot (50% probability ellipsoids) of the solid state molecu-
˚
lar structure of 11, selected bond lengths in A: Pd-N1 2.106(3), Pd-N2 2.091(3),
Pd-C1 2.112(4), Pd-C2 2.114(4), Pd-C3 2.119(5), S-O1 1.451(3), S-O2 1.445(3),
S-C5 1.807(4), S-C6 1.747(4), N1-C4 1.285(5), N2-C7 1.340(5), C4-C5 1.512(5),
C4-C7 1.484(5), C6-C7 1.397(5).
Compound 11 is a monomer in the solid state, and according to our
expectation, one thiophene-S,S-dioxide molecule is coordinated at the
palladium(II) center. The second ligand, an allyl anion, is η3-bonded,
which causes a square planar environment of the palladium(II) center
(Figure 1). The new synthesized Pd complex 11 shows high stability as
a solid as well as in solution, and can be handled under normal aerobic
conditions. The bond lengths and angles for the Pd complex 11 lie in
the expected ranges.
CONCLUSIONS
The novel dibenzylsulfanes 2a,b were synthesized in high yields and
were analytically pure. Their oxidation by hydrogen peroxide resulted
in the formation of the sulfones 3a,b, which were isolated as stable crys-
talline compounds. This method has been adapted for the preparation
of the new bis-sulfone 7.
The sulfones 3a,b as well as 7 can easily be cyclized with bis-
electrophiles of type 8 forming highly substituted thiophene-S,S-
dioxides 9 and 10. Due to their vicinal amino-imino substructures,

Synthesis of New Lipophilic Sulfones
1167
these derivatives proved to be excellent chelating ligands, exemplified
by the preparation of palladium complex 11.
EXPERIMENTAL
General
The reagents described in the following section were purchased from
commercial sources and used directly unless otherwise stated in the
text. The bis-imidoyl chlorides 8,6 the sulfones 3c,d,1a and the bis-
benzyl bromide 44 were synthesized by procedures in the literature.
All solvents were reagent grade, were dried by standard practices, and
were distilled prior to use. Reactions were monitored by TLC (0.2 mm
1
Merck silica gel plates; 60, F254), and H and 13C NMR spectra were
recorded on Bruker AVANCE 250 and 400 spectrometers; shifts are
given relative to solvent signals. Melting points were measured on a
Galen III apparatus (Boetius system) and are uncorrected.
Preparation of 4-Trifluoromethylbenzyl Tosylate (1c)
To a solution of 4-trifluoromethylbenzyl alcohol (5.00 g, 28 mmol) in
dry THF (50 mL), triethylamine (3.60 g, 35 mmol) and tosyl chloride
(5.70 g, 30 mmol) were added. The reaction mixture was stirred at
70◦C for 4 h. The mixture was filtered, and the solvent was removed
under reduced pressure; the remaining oil was dissolved in chloroform,
and the solution was washed twice with saturated sodium carbonate
solution and with water. The organic phase was dried over sodium
sulphate, the solvent was removed, and the crude product was purified
by column chromatography on silica gel (chloroform/n-heptane). The
product was obtained as colorless oil. Yield: 7.95 g (84%). 1H NMR (250
MHz, CDCl3): δ = 7.92 (d, J = 8 Hz, 2H, CH-Ar), 7.79–7.30 (m, 6H, CH-
Ar), 4.62 (s, 2H, CH2), 2.49 (s, 3H, CH3). 13C NMR (63 MHz, CDCl3):
δ = 146.8, 131.3, 130.8, 128.8, 128.2 (q, 2J = 30 Hz, C-CF3), 127.0,
126.8, 125.6 (q, 3J = 4 Hz), 123.9 (q, 1J = 270 Hz, CF3), 45.1, 21.8. MS
(neg. DCI in water): m/z (%) = 329 (10) [M-H−], 172 (20) [C7H8SO3−],
171 (100) [C7H7SO−]. Elemental analysis calculated for C15H13F3O3S
3
(330.30): C 54.54, H 3.97, S 9.71, Found: C 54.12, H 3.83, S 9.28%.
Preparation of Dibenzylsulfanes 2a,b: General Procedure
To a solution of the corresponding benzyl bromides 1a,b or tosylate 1c
(50 mmol) in methanol (30 mL), a solution of sodium sulphide trihy-
drate (5.20 g, 40 mmol) in 20 mL of water was added at rt. The reaction

1168
G. Buehrdel et al.
mixture was stirred at 80◦C for 3 h. The mixture was cooled down
to rt and was then extracted with chloroform (three times). The or-
ganic phase was dried over sodium sulphate, the solvent was removed
in vacuo, and the crude product was recrystallized from pentane (at
−16◦C) to yield 2a,b as colorless crystals.
Di(4-tert-butyl)benzyl Sulfane (2a)
Colorless crystals, yield: 7.68 g (94%), mp 55◦C. 1H NMR (250 MHz,
DMSO-d6): δ = 7.32 (d, J = 8 Hz, 4H, CH-Ar), 7.22 (d, J = 8 Hz, 4H, CH-
Ar), 3.60 (s, 4H, CH2), 1.25 (s, 18H, CH3). 13C NMR (63MHz, DMSO-d6):
δ = 149.6, 135.7, 128.9, 125.6, 35.4, 34.6, 31.4. IR (ATR): νmax = 3024,
2908, 1667, 1514, 1461, 1415, 1360, 1106, 831, 707, 655 cm−1. MS
(EI): m/z(%) = 326 (60) [M+], 179 (80), 147 (100), 117 (50). Elemental
analysis calculated for C22H30S (326.55): C 80.92, H 9.26, S 9.82, Found:
C 80.96, H 9.01, S 9.75%.
Di(4-trifluoromethyl)benzyl Sulfane (2b)
Colorless crystals, yield: 7.70 g (88%, from 1b) 7.10 g (81%, from 1c),
1
mp 19◦C (pentane). H NMR (250 MHz, DMSO-d6): δ = 7.62 (d, J = 8
Hz, 4H, CH-Ar), 7.47 (d, J = 8 Hz, 4H, CH-Ar), 3.77 (s, 4H, CH2). 13C
2
NMR (63MHz, DMSO-d6): δ = 143.7, 131.2, 127.9 (q, J = 30 Hz, C-
CF3), 125.6 (q, 3J = 4 Hz), 124.6 (q, 1J = 270 Hz, CF3), 35.2. IR (ATR):
νmax = 2923, 1619, 1424, 1325, 1165, 1124, 1165, 1019, 850 cm−1. MS
(EI): m/z(%) = 350 (30) [M+], 191 (40), 159 (100), 109 (40). Elemental
analysis calculated for C16H12F6S (350.33): C 54.86, H 3.45, S 9.15,
Found: C 54.93, H 3.57, S 9.13%.
Preparation of the Bis-sulfane 6
To a solution of sodium hydroxide (1.00 g, 25 mmol) in 5 mL of water
and 40 mL of DMF, benzyl mercaptan (3.00 g, 24 mmol) was added. The
mixture was stirred at rt for 10 min, and bis-benzyl bromide 5 (5.00
g, 9.6 mmol) was added. The solution was stirred at 60◦C for 3 h and
was cooled down to rt. The slurry was added into 200 mL of water; the
solid was filtered off and washed with water. The crude product was
recrystallized from ethanol to yield 6 as colorless crystals. Yield 4.92 g
(84%), mp 61◦C. 1H NMR (250 MHz, CDCl3): δ = 7.27 (m, 10H, CH-Ar),
6.79 (s, 2H, CH-Ar), 3.91 (t, J = 6,5 Hz, 4H, O-CH2), 3.71 (s, 4H, S-CH2),
3.68 (s, 4H, S-CH2), 1.8–1.7 (m, 4H,CH2), 1.5–1.3 (m, 20H, CH2), 1.0–0.9
(m, 6H, CH3). 13C NMR (63MHz, CDCl3): δ = 150.7, 138.6, 128.9, 128.4,
126.8, 126.3, 114.4, 69.1, 36.3, 31.9, 30.2, 29.5, 29.4, 29.3, 26.2, 22.7,
14.1. MS (EI): m/z(%) = 606 (5) [M+], 484 (10), 167 (10), 137 (25), 91

Synthesis of New Lipophilic Sulfones
1169
(100), 43 (60). Elemental analysis calculated for C38H54S2O2(606.90):
C 75.20, H 8.97, S 10.57, Found: C 75.17, H 8.40, S 10.96%.
Oxidation of the Sulfanes 2a,b and 6: General Procedure
For this oxidation reaction, the crude sulfanes were used. To the so-
lution of 25 mmol of sulfane 2a,b (or 9 mmol of 6) in 25–60 mL of
acetic acid at 60◦C (temperature maximum 90◦C), 7.3 mL of hydrogen
peroxide (8.30 g, 80 mmol, 35% in water) was slowly added. Then the
reaction mixture was stirred at 80◦C for 3 h. The mixture was cooled to
rt, and 200 mL of water was added; the colorless solid that formed was
filtered off and washed with water. After recrystallization from ethanol,
the products 3a,b and 7 were obtained as colorless crystals.
Di(4-tert-butyl)benzyl Sulfone (3a)
Colorless crystals, yield: 7.44 g (83%), mp 182◦C. 1H NMR (250 MHz,
DMSO-d6): δ = 7.41 (d, J = 8 Hz, 4H, CH-Ar), 7.29 (d, J = 8 Hz, 4H, CH-
Ar), 4.41 (s, 4H, CH2), 1.27 (s, 18H, CH3). 13C NMR (63MHz, DMSO-d6):
δ = 151.2, 131.3, 125.8, 125.5, 58.5, 34.8, 31.5. IR (ATR): νmax = 2959,
2903, 2866, 1508, 1396, 1310, 1252 (SO2), 1106 (SO2), 867, 839 cm−1
.
MS (EI): m/z(%) = 358 (10) [M+], 343 (20), 294 (80), 147 (100) 117 (100).
Elemental analysis calculated for C22H30SO2 (358.55): C 73.70, H 8.43,
S 8.94, Found: C 73.57, H 8.28, S 8.77%.
Di(4-trifluoromethyl)benzyl Sulfone (3b)
Colorless crystals, yield: 8.79 g (92%) mp 207◦C (chloroform, Lit.3
207◦C). 1H NMR (250 MHz, DMSO-d6): δ = 7.73 (d, J = 8 Hz, 4H, CH-
Ar), 7.60 (d, J = 8 Hz, 4H, CH-Ar), 4.67 (s, 4H, CH2). 13C NMR (63
2
MHz, DMSO-d6): δ = 133.3, 132.4, 129.4 (q, J = 30 Hz C-CF3), 125.7
(q, 3J = 4 Hz), 124.6 (q, 1J = 270 Hz, CF3), 57.8. IR (ATR): νmax = 2934,
1623, 1420, 1321, 1290 (SO2), 1162, 1117 (SO2), 1064, 1018, 830, 711
cm−. 1MS (EI): m/z(%) = 382 (10) [M+], 362 (20), 159 (100), 109 (40).
Elemental analysis calculated for C16H12F6S(382.33): C 50.27, H 3.16,
S 8.39, Found: C 50.24, H 3.12, S 8.34%.
Bis-sulfone 7
Colorless crystals, yield: 5.31 g (88%), mp 162◦C (ethanol/ chloro-
1
form). H NMR (250 MHz, CDCl3): δ = 7.37 (m, 10H, CH-Ar), 7.07 (s,
2H, CH-Ar), 4.37 (s, 4H, S-CH2), 4.16 (s, 4H, S-CH2), 3.99 (t, J = 6,5
Hz, 4H, O-CH2), 1.75 (m, 4H, CH2), 1.30 (m, 20H, CH2), 0.88 (m, 6H,
CH3). 13C NMR (63 MHz, CDCl3): δ = 150.9, 131.0, 128.9, 128.8, 127.0,
118.2, 116.0, 69.3, 58.4, 53.0, 31.8, 29.4, 29.3, 29.2, 26.1, 22.6, 14.1. MS

1170
G. Buehrdel et al.
(EI): m/z(%) = 671 (1) [M+], 452 (5), 359 (15), 137 (20), 91 (100), 43
(50). Elemental analysis calculated for C38H54S2O6(670.98): C 68.02, H
8.11, S 9.56, Found: C 67.90, H 7.99, S 9.80%.
Preparation of Cyclic Sulfones 9a–f: General Procedure
To a solution of 6 mmol of sulfone 3a or 3b in 50 mL of dry THF (for
the sulfones 3c and 3d 100 mL of dry THF), t-BuOK (3.00 g, 27 mmol)
was added and the solution was stirred for 5 min. The light yellow
solution was cooled to −20◦C and the corresponding bis-imidoylchloride
8 (6.5 mmol) was added. The deep red reaction mixture was stirred at
20◦C for 30 min and was then acidified (pH 6) by dropwise addition
of HCl/isopropanol. The mixture was concentrated in vacuo to dryness,
and the residue was treated with 100 mL of chloroform/n-heptane (1:1).
The slurry was filtered over SiO2, and upon removal of the solvent in
vacuo, the crude product was recrystallized from chloroform/n-heptane
to yield 9a–f as yellow crystals.
4-(4-Tolylamino)-3-(4-tolylimino-2,5-di(4-tert-butylphenyl)-2,3-
dihydrothiophene-1,1-dioxide (9a)
1
Yellow crystals, yield: 2.82 g (88%), mp 201◦C. H NMR (400 MHz,
DMSO-d6): δ = 8.32 (s, 1H, NH), 7.17–7.10 (m, 4H, CH-Ar), 6.93 (d, J =
8 Hz, 2H, CH-Ar), 6.87 (d, J = 8 Hz, 2H, CH-Ar), 6.76–6.66 (m, 6H, CH-
Ar), 6.54 (d, J = 8 Hz, 2H, CH-Ar), 5.45 (s, 1H, CH-ring), 2.13 (s, 3H,
CH3), 2.09 (s, 3H, CH3), 1.20 (s, 18H, CH3).13C NMR (63 MHz, DMSO-
d6): δ = 158.3 (C-3), 151.9, 151.5, 145.8, 138.5, 134.6, 134.4, 133.6, 130.1,
129.4, 129.1, 128.8, 128.5, 127.2, 125.4, 124.7, 124.0, 122.1, 119.2, 65.2
(C-2), 34.7, 34.6, 31.2, 20.8, 20.7. IR (ATR): νmax = 3312 (NH), 3024,
2952, 1633 (C=C), 1603 (C=N), 1519, 1500, 1300 + 1296 (SO2), 1169,
1130, 828, 812, 757 cm−1. MS (EI) m/z: 590 (30) [M+], 526 (15) [M-SO+2 ],
264 (30), 248 (90), 57 (100) [C4H+]. Elemental analysis calculated for
9
C38H42N2SO2(590.83): C 77.25, H 7.17, N 4.74, S 5.43, Found: C 76.89,
H 6.88, N 4.47, S 5.13%.
4-(4-Bromophenylamino)-3-(4-bromophenylimino-2,5-di(4-
tert-butylphenyl)-2,3-dihydrothiophene-1,1-dioxide (9b)
1
Yellow crystals, yield 3.41 g (79%), mp 206◦C. H NMR (250 MHz,
DMSO-d6): δ = 8.30 (s, 1H, NH), 7.18–6.89 (m, 12H, CH-Ar), 6.70–6.66
(m, 4H CH-Ar), 5.99 (s, 1H, CH-ring), 1.22; 1,21 (m, 18H, CH-tBu). 13
C
NMR (63 MHz, DMSO-d6): δ = 158.9 (C-3), 152.1, 151.2, 147.8, 139.6,
138.0, 131.3, 130.9, 130.6, 128.6, 126.3, 125.2, 124.9, 124.5, 122.2, 120.4,
117.1, 115.4, 79.6, 65.6 (C-2), 34.9, 34.6, 31.4. MS (EI) m/z: 722 (5) +

Synthesis of New Lipophilic Sulfones
1171
720 (10) + 718 (5) [M+], 656 (5) [M-SO+2 ], 520 (5), 314 (20), 57 (100)
[C4H+]. Elemental analysis calculated for C36H36Br2N2SO2(720.57): C
9
60.01, H 5.04, N 3.89, S 4.45, Found: C 59.63, H 4.93, N 3.53, S 4.14%.
4-(4-Tolylamino)-3-(4-tolylimino-2,5-di(4-
trifluoromethylphenyl)-2,3-dihydrothiophene-1,1-dioxide (9c)
1
Yellow crystals, yield: 3.04 g (83%), mp 193◦C. H NMR (400MHz,
CDCl3): δ = 7.77 (s, 1H, NH), 7.42 (d, J = 8 Hz, 2H, CH-Ar), 7.32 (s, 4H
CH-Ar), 7.36 (d, J = 8 Hz, 2H, CH-Ar), 7.09 (d, J = 8 Hz, 2H, CH-Ar),
6.92 (d, J = 8 Hz, 2H, CH-Ar), 6.78 (d, J = 8 Hz, 2H, CH-Ar), 6.66 (d,
J = 8 Hz, 2H, CH-Ar), 6.49 (d, J = 8 Hz, 2H, CH-Ar), 5.44 (s, 1H, CH-
ring), 2.23 (s, 3H, CH3), 2.17 (s, 3H, CH3). 13C NMR (100 MHz, CDCl3):
δ = 156.6 (C-3), 145.1, 139.9, 135.6, 135.4, 134.0, 133.7, 131.1, 130.6 (q,
2J = 30 Hz), 130.2, 129.8, 129.5 (q, 2J = 30 Hz), 129.0, 125.5 (q, 3J = 4
Hz), 124.6 (q, 3J = 4 Hz), 123.8 (q, 1J = 270 Hz), 123.7 (q, 1J = 270 Hz),
123.2, 119.8, 119.2, 117.5, 65.0 (C-2), 20.8, 20.6. MS (EI) m/z: 614 (30)
[M+], 550 (30) [M-SO2+], 275 (100), 91 (80) [C7H+]. Elemental analysis
calculated for C32H26F6N2SO2(614.61): C 62.54,7H 3.94, N 4.56, S 5.22,
Found: C 62.42, H 4.24, N 4.54, S 4.85%.
4-(4-Tolylamino)-3-(4-tolylimino-2,5-di(4-tolyl)-2,3-
dihydrothiophene-1,1-dioxide (9d)
1
Yellow crystals, yield: 2.06 g (67%), mp 240◦C. H NMR (250 MHz,
CDCl3): δ = 7.72 (s, 1H, NH), 7.22–6.81 (m, 12H, CH-Tol), 6.68 (d, J = 8
Hz, 2H, CH-Tol), 6.52 (d, J = 8 Hz, 2H, CH-Tol), 5.30 (s, 1H, CH-ring),
2.39 (s, 3H, CH3), 2.27 (m, 6H, CH3), 2.21 (s, 3H, CH-Tol).13C NMR
(63 MHz, CDCl3): δ = 158.0 (C-3), 145.6, 138.8, 138.6, 138.1, 135.3,
134.8, 130.4, 129.9, 129.6, 129.3, 129.2, 128.9, 128.7, 127.5, 121.6, 120.4,
119.8, 119.3, 65.1 (C-2), 21.35, 21.33, 21.23, 21.21. MS (EI) m/z: 506 (10)
[M+], 357 (10), 268 (20), 107 (100), 91 (40) [C7H+7 ]. Elemental analysis
calculated for C32H30N2SO2(506.67): C 75.86, H 5.97, N 5.53, S 6.33,
Found: C 75.46, H 5.68, N 5.41, S 6.03%.
4-(4-Phenylamino)-3-(4-phenylimino-2,5-di(4-tolyl)-2,3-
dihydrothiophene-1,1-dioxide (9e)
1
Yellow crystals, yield: 1.81 g (63%), mp 167◦C. H NMR (250 MHz,
CDCl3): δ = 7.80 (s, 1H, NH), 7.26–6.79 (m, 16H, CH-Ar), 6.62–6.59
(m, 2H, CH-Ph), 5.30 (s, 1H, CH-ring), 2.27 (s, 3H, CH3), 2.26 (s, 3H,
CH3). 13C NMR (63 MHz, CDCl3): δ = 158.5 (C-3), 148.1 (C-4), 139.1,
138.7, 137.5, 137.3, 130.0, 128.8, 128.75, 128.7, 128.2, 127.2, 125.0,
124.0, 123.8, 121.5, 119.2, 65.1 (C-2), 21.4 (CH3), 21.2 (CH3). MS (DEI)
m/z: 478 (20) [M+], 414 (10) [M-SO2+], 413 (20), [M-HSO+2 ], 207 (40), 77

1172
G. Buehrdel et al.
(100). Elemental analysis calculated for C30H26N2SO2(478.62): C 75.29,
H 5.48, N 5.85, S 6.70, Found: C 74.73, H 5.50, N 5.87, S 6.83%.
4-(4-Phenylamino)-3-(4-phenylimino-2,5-di(4-bromophenyl)-
2,3-dihydrothiophene-1,1-dioxide (9f)
1
Yellow crystals, yield: 2.63 g (72%), mp 193◦C. H NMR (400 MHz,
CDCl3): δ = 7.80 (s, 1H, NH), 7.29–7.00 (m, 12H, CH-Ar), 6.85–6.81 (m,
4H CH-Ph), 6.62–6.60 (m, 2H CH-Ph), 5.33 (s, 1H, CH-ring). 13C NMR
(63 MHz, CDCl3): δ = 157.7 (C-3), 147.9 (C-4), 138.3, 136.8, 132.4, 132.3,
131.9, 131.2, 130.4, 129.3, 128.8, 128.2, 125.7, 125.4, 124.8, 123.4, 122.2,
119.6, 119.0, 64.7 (C-2). MS (EI) m/z: 610 (10) + 608 (20) + 606 (10)
[M+], 544 (10) [M-SO+2 ], 349 (20), 77 (60), 32 (100). Elemental analysis
calculated for C28H20N2SO2(608.36): C 55.28, H 3.31, N 4.60, S 5.27,
Found: C 54.91, H 3.18, N 4.49, S 5.20%.
Preparation of Cyclic Bis-sulfone 10
To a solution of 7 (1.00 g, 1.5 mmol) in 50 mL of dry THF, t−BuOK
(1.00 g, 9 mmol) was added, and the solution was stirred for 5 min at
0◦C. The light yellow solution was cooled down to –20◦C, and the bis-
tolylimidoylchloride 8 (1.20 g, 4 mmol) was added. The deep red reaction
mixture was stirred at 20◦C for 30 min and was then acidified (pH 6)
by HCl/isopropanol. The mixture was concentrated in vacuo to dryness,
and the residue was treated with 100 mL of chloroform/n-heptane (1:1).
The slurry was filtered over SiO2, and upon removal of the solvent in
vacuo, the crude product was purified by column chromatography on
silica gel (chloroform/n-heptane) to yield 10 as yellow solid. Yield: 590
mg (35%). 1H NMR (400 MHz, CDCl3): δ = 9.23 (s, 2H, NH), 7.48–
7.05 (m, 28H, CH-Ar), 5.08 (s, 2H, CH-ring), 3.90 (m, 4H, O-CH2), 2.27
(m, 6H), 2.08 (m, 6H), 1.7–1.6 (m, 4H, CH2), 1.35–1.11 (m, 20H, CH2),
0.82–0.76 (m, 6H, CH3). 13C NMR (63 MHz, CDCl3): δ = 157.5, 135.3,
133.8, 131.1, 131.3, 130.9, 130.3, 129.7, 129.6, 129.5, 128.9, 128.8, 128.7,
128.3, 128.2, 127.9, 121.5, 121.4, 121.3, 119.7, 119.8, 69.3, 69.2, 66.7
(C-ring), 58.6, 58.4, 54.7, 53.2, 53.0, 31.8, 29.4, 29.3, 29.2, 26.1, 25.9,
22.6, 20.9, 20.7, 14.1. MS (micro-ESI in chloroform/methanol) m/z: 1173
(1) [M+K+], 1157 (1) [M+Na+], 1134 (1) [M+], 1170 (15) [M-SO+2 ], 1169
[M-HSO+2 ], 925 (60), 837 (100), 786 (60). Elemental analysis calculated
for C70H80N4S2O6(1137.55): C 73.91, H 7.09, N 4.93, S 5.64, Found: C
73.74, H 7.18, N 4.68, S 5.30%.
Preparation of Palladium Complex 11
To a solution of 9a (400 mg, 0.68 mmol) in 10 mL of dry THF, allyl
palladium chloride (130 mg, 0.71 mmol) and 0.2 mL of triethylamine

Synthesis of New Lipophilic Sulfones
1173
were added. The deep red solution was stirred for 2 h at 60◦C. The
reaction mixture was filtered over SiO2, and upon removal of the solvent
in vacuo, the crude product was purified by column chromatography on
silica gel (chloroform/n-heptane) to yield 11 as red solid. Red crystals
were obtained by recrystallization from toluene/chloroform/n-heptane
1
Yield: 380 mg (76%). H NMR (400 MHz, THF-d8): δ = 7.13–7.10 (m,
2H, CH-Ar), 6.93–6.72 (m, 10H, CH-Ar), 6.60 (d, J = 8 Hz, 2H, CH-
Tol), 6.53 (d, J = 8 Hz, 2H, CH-Tol), 5.6–5.4 (m, 1H, CH-allyl), 5.32
(s, 1H, CH-ring), 3.96–3.94 (m, 1H, CH-allyl), 2.95–2.79 (m, 3H, CH-
allyl), 2.30 (s, 3H, CH3), 2.22 (s, 3H, CH3), 1.26 (s, 9H, CH3), 1.22 (s,
9H, CH3). 13C NMR (100 MHz, THF-d8): δ = 150.9, 150.6, 150.5, 150.0,
148.0, 135.4, 129.8, 128.8, 128.7, 128.6, 127.2, 127.0, 124.6, 123.5, 123.4,
123.2, 120.9, 120.8, 117.4, 114.9, 114.8, 110.7, 67.4 (C-2), 61.4 (C-allyl),
59.5 (C-allyl), 34.1, 31.0, 20.0, 19.9. MS (EI) m/z: 734 (20) + 735 (50) +
736 (50) + 737 (30) + 738 (50) + 739 (20) + 740 (20) + 741 (10) [M+],
364 (100) calculated and measured isotope pattern for C41H46N2O2PdS
are in agreement.
Crystal Structure Determination for 11
The intensity data for the compound were collected on a Nonius Kappa
CCD diffractometer, using graphite-monochromated Mo-Kα radiation.
Data were corrected for Lorentz and polarization effects, but not for
absorption effects.8
The structure was solved by direct methods (SHELXS9) and refined
by full-matrix least squares techniques against F2o (SHELXL-9710). The
hydrogen atoms were included at calculated positions with fixed ther-
mal parameters. All non-hydrogen and non-solvent atoms were refined
anisotropically.10 XP (SIEMENS Analytical X-ray Instruments, Inc.)
was used for structure representations.
Crystal Data for 11
C41H46N2O2PdS · 0.5 C7H8, M = 783.33 g mol−1, red prism, size
0.04 × 0.04 × 0.04 mm3, triclinic, space group Pî, a = 10.8286(4),
˚
b = 12.8989(7), c = 15.4064(7) A, α = 69.731(2), β = 76.060(2), γ =
◦
3
◦
87.698(3) , V = 1957.00(16) A , T = −90 C, Z = 2, ρcalcd. = 1.329 gcm−3
,
˚
µ (Mo-Kα) = 5.66 cm−1, F(000) = 818, 13447 reflections in h(-14/14),
k(-15/16), l(-17/19), measured in the range 1.80◦ ≤ ꢁ ≤ 27.50◦, com-
pleteness ꢁmax = 97.9%, 8797 independent reflections, Rint = 0.0420,
6309 reflections with Fo > 4σ(Fo), 457 parameters, 0 restraints, R1obs
=
0.0582, wR2obs = 0.1269, R1all = 0.0953, wR2all = 0.1451, GOOF = 1.032,
−3
˚
largest difference peak and hole: 1.021 / −0.532 e A
.

1174
G. Buehrdel et al.
CCDC-670265 (11) contains the supplementary crystallographic
data for this article. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/conts/retrieving.html (or from the Cambridge
Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ,
UK; fax: (+44) 1223-336-033; or deposit@ccdc.cam.ac.uk).
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