Unexpected formation of disulfide-based biscalix[4]arenes

Article abstract of DOI:10.1016/j.tet.2015.12.037

Attempts at Pd-catalyzed bridging in sulfoxide-bearing calixarenes containing various substituents (phenyl, ethyl, pyrimidin-2-yl) gave the expected compound only in the case of the ethyl derivative. However, the reaction of sulfoxides with BuLi revealed

Full text of DOI:10.1016/j.tet.2015.12.037

Accepted Manuscript
Unexpected formation of disulfide-based biscalix[4]arenes
František Stejskal, Petra Cuřínová, Pavel Lhoták
PII:
S0040-4020(15)30285-4
10.1016/j.tet.2015.12.037
TET 27363
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 14 October 2015
Revised Date: 3 December 2015
Accepted Date: 15 December 2015
Please cite this article as: Stejskal F, Cuřínová P, Lhoták P, Unexpected formation of disulfide-based
biscalix[4]arenes, Tetrahedron (2016), doi: 10.1016/j.tet.2015.12.037.
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ACCEPTED MANUSCRIPT
Graphical Abstract
Unexpected formation of disulfide-based
biscalix[4]arenes
Leave this area blank for abstract info.
František Stejskal, Petra Cuřínová, and Pavel Lhoták

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
Unexpected formation of disulfide-based biscalix[4]arenes
František Stejskal a, Petra Cuřínová b, and Pavel Lhoták a,
a
Department of Organic Chemistry, University of Chemistry and Technology Prague (ICTP), Technická 5, 166 28 Prague 6, Czech Republic.
Institute of Chemical Process Fundamentals of the AS CR, v.v.i., Rozvojová 2/135, 16502 Prague 6, Czech Republic.
b
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Attempts at Pd-catalyzed bridging in sulfoxide-bearing calixarenes containing various
substituents (phenyl, ethyl, pyrimidin-2-yl) gave the expected compound only in the case
of the ethyl derivative. However, the reaction of sulfoxides with BuLi revealed the ability
of the pyrimidin-2-yl group to function unexpectedly as a leaving group. This enabled,
depending on the reaction conditions, preparation of unique bis-calixarenes connected
together via two sulfur atoms spacers: -S-S-, -S(O)-S- or –S(O)2-S-. As documented by 1H
NMR titrations these compounds, otherwise not easily accessible by common synthetic
methods, showed recognition ability towards selected cations of the N-methylpyridinium
type.
Available online
Keywords:
Calixarene
Bridging reaction
Dimer formation
Complexation
2009 Elsevier Ltd. All rights reserved
.
Cation-π interactions
Pyridinium guests
1. Introduction
position of the calixarene skeleton. Similarly, an oxazoline
moiety as an ortho-lithiation directing group was introduced into
calix[4]arene to allow functionalization of the upper rim at the
meta-position.6
Calix[n]arenes1 are well-known macrocyclic compounds that
have become very popular in supramolecular chemistry. Typical
features of these compounds include: (i) variability in the size of
the cavity, (ii) well established chemistry allowing for almost
limitless derivatization of the basic skeleton, (iii) multigram scale
of the synthesis, and (iv) excellent complexation properties
depending on the substitution. Moreover, the smallest member of
this family, calix[4]arene, possesses a unique three-dimensional
shape of the cavity that can be tuned by simple alkylation of the
lower rim (phenolic functions) to form four basic conformations
(atropisomers) - cone, partial cone, 1,3-alternate, and 1,2-
alternate.1 This makes calix[4]arene an especially attractive
molecular scaffold for the design of novel receptors2 and/or a
valuable building block for the construction of more
sophisticated supramolecular systems.
Scheme 1. Preparation of meta bridged calix[4]arene.
Recently, we published an alternative procedure based on the
introduction of the 2-pyridyl sulfoxide moiety into the upper rim
of calix[4]arene. The presence of the 2-pyridyl moiety
subsequently enabled Pd-catalyzed double C-H activation
offering an access to unprecedented derivatives with
intramolecular bridge between the meta positions of the two
neighboring aromatic subunits (Scheme 1).7 In this paper we
report on our attempts to expand the above bridging reaction to
install other sulfoxide-tethered substituents including ethyl,
phenyl, and pyrimidin-2-yl moieties.
Although the chemistry of calix[4]arenes is well developed
and many synthetic methods allowing for the regioselective
introduction of substituents at the para position of aromatic
subunits are known in the art,3 direct substitution at the meta
position is still very rare. In this context, meta-substitution can be
inter alia achieved using ortho-directing groups introduced into
the para position of the calixarene moiety. Thus, it was shown
that using groups with strong ortho/para directing effects like
hydroxy and/or alkoxy groups4 or amidic functionality5 aromatic
electrophilic substitution (bromination, nitration, formylation)
2. Results and discussion
We commenced the synthesis with monobromo derivative 1
can easily be used to introduce an electrophile into the meta
———
which is accessible in 95% yield by bromination7 of
Pavel Lhotak. Tel.: +420-220-445-055; fax: +420-220-444-288; e-mail: lhotakp@vscht.cz

2
Tetrahedron
ACCEPTED MANUSCRIPT
Scheme 1. Attempted bridging reaction in calixarene series.
tetrapropoxycalix[4]arene with NBS in butan-2-one at room
temperature. To avoid potential problems stemming from the
reduced reactivity of the bromine atom, compound 1 was
transformed into the corresponding iodide 2 in 94% yield by
metalation with tert-BuLi and subsequent reaction with I2. This
compound was then reacted with thiols 3a-3c in DMF in the
presence of CuI/1,10-phenanthroline/K2CO3 as the catalytic
system. Prolonged stirring (5 days) at high temperature (150-170
°C) provided the respective sulfides 4a-4c in very high yields
after column chromatography on silica gel (4a, 94%; 4b, 90%,
and 4c, 80% yields). Efficient oxidation to sulfoxides 5 was
achieved using meta-chloroperoxybenzoic acid (MCPBA) in
chloroform. While the reaction with 1 equiv of MCPBA led
selectively to high yields of phenyl and pyrimidin-2-yl sulfoxide
derivatives 5a (70%) and 5c (85%), the corresponding
ethylsulfoxide 5b was accompanied by substantial amount of
sulfone 5b’. The crude reaction mixture was separated by
chromatography on Chromatotrontm (SiO2/EtOAc) to provide 5b
and 5b’ in 51% and 33% yield, respectively.
Sulfoxides 5a-5c were bridged using literature conditions7:
Pd(OAc)2 (20 mol%), Ag2CO3 + benzoquinone (oxidants) in
DCE at 100 °C overnight. Unfortunately, unlike the pyrydin-2-yl
substituent (see Scheme 1), no bridging occurred in the case of
the phenyl or pyrimidin-2-yl derivatives. Thus, compound 5a was
entirely unreactive, while 5c led to the formation of a complex
reaction mixture where among others tetrapropoxycalix[4]arene
11, disulfide 8 and thiosulfonic derivative 9 were confirmed by
MS analysis. Reaction with ethyl derivative 5b provided the
expected bridged compound 6b in only 2% yield, accompanied
by a small amount of compounds 8 and 9. Slight modification of
the reaction conditions (addition of 0.2 equiv of p-
nitroiodobenzene, 1 equiv of Pd(OAc)2) increased the yield of 6b
to 13%. The structure of bridged product 6b was assigned by MS
ESI+ analysis which showed signals at m/z = 667.3448, 689.3269
and 705.3002, perfectly corresponding to the calculated values
667.3452 [M+H]+, 689.3271 [M+Na]+, and 705.3011 [M+K]+.
Despite this partial success, the overall results indicated, that
none of the selected substituents in the sulfoxide part of the
molecule (phenyl, ethyl, pyrimidin-2-yl) are synthetically useful
for bridging reactions. In other words, the role of 2-pyridyl
substituent seems to be irreplaceable in this reaction.
As the sulfoxide is a strong ortho-directing functional group,
it is used frequently for directed ortho-lithiation8 of aromatic
moieties. To verify the synthetic applicability of pyrimidin-2-yl
sulfoxide 5c, we attempted ortho-lithiation of this compound.
Thus, compound 5c was reacted with butyllithium in THF at -78
°C and finally quenched by acetaldehyde or butyraldehyde at the
same temperature (Scheme 3). Unfortunately, the formation of
expected meta-substituted calixarene 12 was not observed at all.
The complex reaction mixtures consisted of many products,
among which compounds 7-11 were isolated or identified. The
presence of compound 10 with a direct bond between the
pyrimidine and calixarene moiety was deduced from HRMS
spectra showing a peak at m/z = 729.4628 which is in good
accordance with the theoretical value for C48H61O4N2+H+ (m/z =
729.4626 [M+H]+. This behaviour of aromatic sulfoxides
(extrusion of SO group) is well documented in the literature7,9
and is based on a rapid ligand-exchange reaction upon treatment
with organolithium reagents.

3
ACCEPTED MANUSCRIPT
N
N
O
N
N
O
HO
N
S
N
S
1) n-BuLi/THF
-78 °C
R
2) R-CH=O, THF
-78 °C to rt
O
O
Pr
O
O
O
O
Pr
O
O
O
O
Pr
O
O
Pr
Pr
Pr Pr
Pr Pr
Pr
Pr Pr
10
12
5c
1) n-BuLi/THF
2) aq. HCl
O
O
O
O
Pr
Pr
Pr Pr
11
Pr
O
Pr
O
Pr
Pr
O
Pr
O
Pr
Pr
Pr
O
Pr
O
Pr
Pr
Pr
O
O
S
O
O
O
O
S
O
O
S
+
S
S
S
O
O
O
O
O
O
O
O
O
O
O
O
O
Pr
Pr
Pr
Pr Pr
Pr
Pr
Pr Pr
Pr
Pr Pr
7
9
8
Scheme 3. Attempted ortho-lithiation and the formation of biscalix[4]arenes 7-9.
As we found the yields of compounds 7-9 and their mutual
ratio in the reaction mixtures widely varied with different
reaction and/or quenching conditions. We carried out a series of
reactions to find the optimized conditions leading to the highest
yields of the corresponding products. Interestingly, the addition
of BuLi (3 equiv) to a THF solution of 5c at -78 °C, then stirring
the mixture for 30 minutes at the same temperature, and finally
quenching with aq. HCl gave thiosulfinate 7 in 62% yield after
radial chromatography. No isolatable amounts of 8 or 9 were
obtained under these reaction conditions.
thiosulfonate 9 were isolated in 33% and 28% yields,
respectively. Derivative 7 was not isolated at all in this case.
As the formation of the above compounds 7-9 was entirely
unexpected it brought us to the careful inspection of literature
sources. As we found the concomitant formation of these types of
compounds (disulfide, thiosulfinate and thiosulfonate) were
described for flash vacuum pyrolysis of the corresponding
sulfoxides at high temperatures10 or by the thermolysis of
sulfoxides at 110 °C in toluene.11 Low yields of all three products
were also isolated using steady-state irradiation or nanosecond
laser flash photolysis of the solutions containing aryl tert-butyl
sulfoxides in MeCN.12 The authors of these papers proposed the
initial formation of sulfenic acid (R-SOH) which is extremely
reactive and usually can be neither detected nor isolated. This
sulfenic acid rapidly dimerizes to form the thiosulfinate ester (R-
S(O)S-R), which
is unstable,13 and undergoes
a
Scheme 4. A tentative mechanism showing the formation of thiosulfinate,
thiosulfonate and disulfide from sulfenic acid (based on Ref. 10-12).
disproportionation reaction to yield an equimolar mixture of
disulfide (R-SS-R) and thiosulfonate ester (R-S(O)2S-R) (see
Scheme 4).
On the other hand, the same reaction mixture (a THF solution
of 5c, 3 equiv of BuLi at -78 °C) stirred for two hours with
gradual warming from -78 °C to room temperature (25 °C) gave
The reaction sequence shown in Scheme 4 was in accordance
with our own experiments: thiosulfinate 7 was isolated as the
kinetic product (short reaction time/low temperature = 30 min at -
78 °C) while the mixture of disulfide 8 and thiosulfonate 9
completely different products, as only disulfide
8 and

4
Tetrahedron
ACCEPTED MANUSCRIPT
represents the thermodynamic products (2 h, -78 °C to rt). As the
formation of free sulfenic acid under our basic reaction
conditions could be excluded, it seemed that the same reaction
sequence can be carried out with a salt of sulfenic acid. The
pyrimidine moiety does not induce ortho-lithiation, but rather
serves as a good leaving group to form the lithium sulfenate of
calixarene which undergoes the same reaction as the free acid
itself. To the best of our knowledge, no systematic study on
reactivity of sulfenic acid salts has been reported so far.
Nevertheless, we found a recent paper14 showing the reaction of
p-tolyl aryl sulfoxide with LDA in THF. The reaction conditions
(-78 °C, 30 min then rt, 90 min) led to isolation inter alia of
bis(p-tolyl)disulfide which indicated that dimerization is possible
even under strongly basic conditions.15 The crucial role of the
pyrimidine moiety in the formation of biscalixarenes 7-9 can be
also demonstrated by the same reaction with phenyl derivative
Figure 1. 1H NMR titration curve of 9 with 1-methylquinolinium iodide
(CDCl3: CD3CN = 4:1 v/v, 300 MHz, 298 K).
5a.
Using
otherwise
identical
reaction
conditions
tetrapropoxycalixarene 11 was isolated in 60% yield while the
presence of bis-calixarenes 7-9 was only detectable by TLC
analysis.
atom spacer: -S-S-, -S(O)-S- or –S(O)2-S-. The 1H NMR
titrations of these compounds showed their recognition ability
towards selected cations of the N-methylpyridinium type by
cation-π interactions.
Derivatives 7-9 represent unique structures otherwise
inaccessible by other synthetic methods. The cavities of both
calixarene subunits might cooperate to create a bigger cavity
which could be useful for the complexation of suitable guest
molecules. To confirm this assumption we carried out a
complexation study of 8 and 9 towards selected organic cations
which could be bound via cation-π interactions16 within the bis-
calixarene cavity. The addition of 1-methylpyridinium iodide
(NP) or 1-methylquinolinium iodide (1-MQ) to a solution of 8 or
9 in CDCl3: CD3CN = 4:1 led to reproducible downfield shifts of
the aromatic signals (complexation under fast exchange
conditions). As shown in Figure 1, a typical titration curve
corresponded to the formation of 1:1 complexes and the
appropriate complexation constants were collected in Table 1.
While MP and 1-MQ are bound by calixarenes, isoquinolinium
derivative 2-MQ showed no measurable interactions indicating
possible shape-recognition properties of the novel calixarenes.
4. Experimental
4.1. General
All chemicals were purchased from commercial sources and
used without further purification. 1,2-Dichloroethane,
dichloromethane and N,N’-dimethylformamide used for the
reactions were dried with CaH2 or MgSO4 and stored over
molecular sieves. THF was dried using sodium/benzophenone
method. Melting points were measured on Heiztisch Mikroskop-
Polytherm A (Wagner & Munz, Germany) and were not
corrected. The IR spectra were measured on FT-IR spectrometer
Nicolet 740 in KBr transmission mode. NMR spectra were
recorded on spectrometers Varian Gemini 300 (1H: 300 MHz,
13C: 75 MHz) and Agilent 400-MR DDR2 (1H: 400 MHz, 13C:
100 MHz). Chemical shifts (δ) are expressed in parts per million
and are referenced to the residual peak of solvent or TMS as an
internal standard, coupling constants (J) are in hertz. The mass
analyses were performed using ESI technique on a FT-MS (LTQ
Orbitrap Velos) spectrometer. Purity of the substances and
courses of the reactions were monitored by TLC using TLC
aluminium sheets with Silica gel 60 F254 (Merck) and analyzed at
254 or 365 nm. Preparative TLC chromatography was carried out
on a Chromatotron (Harrison Research) with plates covered by
Silica gel 60 GF254 (Merck). Starting compound 1 (5-bromo-
25,26,27,28-tetrapropoxycalix[4]arene) was prepared according
to a known procedure.7
Table 1. Binding constants of calixarenes 8 and 9 towards selected organic
cationsa)
compound 8
K [M-1]
compound 9
K [M-1]
Guest b)
MP
1-MQ
2-MQ
21.6 ± 0.5
6.1 ± 0.7
ncc)
17.6 ± 0.8
6.7 ± 0.7
nc
4.2. NMR titration experiments
NMR titration experiments were carried out on a Varian
Mercury 300 MHz spectrometer equipped with a 5 mm PFG
autoswitchable VT probe. To solubilize both the calix[4]arenes
and the pyridinium/quinolinium salts a mixture of deuterated
solvents (CDCl3:CD3CN = 4:1 v/v) was used. The measurements
were performed at 25 °C. In all the cases measured, the
complexation took place under fast exchange conditions. Thus,
the complexation constants were obtained from the dependency
of the calixarene aromatic proton chemical shifts on the
concentration of pyridinium/quinolinium salts added. During the
titration, the concentration of calixarene was kept constant to
avoid possible shift of signals due to dilution of the sample. For
the estimation of the stability constants and the corresponding
a) 1H NMR titration, 400 MHz, CDCl3: CD3CN = 4:1 v/v, 298 K; b)MP = 1-
methylpyridinium iodide, 1-MQ = 1-methylquinolinium iodide, 2-MQ = 2-
methylisoquinolinium iodide, c) no complexation observed.
3. Conclusions
Contrary to 2-pyridyl substituted calixarene sulfoxide, the
other substituents (phenyl, ethyl, pyrimidin-2-yl) gave the
expected intramolecularly bridged compound only in the case of
the ethyl derivative. Interestingly, the reaction of sulfoxides with
BuLi revealed the unique ability of pyrimidin-2-yl function to
play the role of the leaving group. This enabled, depending on
the reaction conditions, preparation of otherwise not easily
accessible bis-calixarenes connected together via a two-sulfur-

5
1
errors a self-made calculating program using orthogonal distance
regression17 was employed.
white solid, mp: 43-44 °C. H NMR (400 MHz, CDCl3, 293 K)
ACCEPTED MANUSCRIPT
δ (ppm): 6.57-6.70 (m, 11H, Ar-H); 4.45 (t, J = 13.5 Hz, 4H, Ar-
CH2-Ar); 3.80 – 3.90 (m, 8H, O-CH2); 3.17 (d, J = 13.3 Hz, 2H,
Ar-CH2-Ar); 3.12 (d, J = 13.3 Hz, 2H, Ar-CH2-Ar); 2.63 (q, J =
7.3 Hz, 2H, Ar-CH2); 1.88 – 1.99 (m, 8H, CH2); 1.12 (t, J = 7.3
Hz, 3H, CH3); 0.97 – 1.04 (m, 12H, CH3). 13C NMR (100 MHz,
CDCl3, 293 K) δ (ppm): 156.65; 156.33; 155.48; 135.46; 135.40;
135.12; 134.91; 134.77; 128.36; 128.16; 128.08; 128.01; 122.01;
121.95; 76.81; 76.74; 76.65; 30.96; 30.91; 28.91; 23.28; 23.25;
23.19; 14.61; 10.39; 10.32; 10.24. IR (KBr) ν (cm-1): 2961.2,
2927.5, 2873.7, 1455.3, 1209.9. HRMS-ESI (C42H52O4S) m/z
calcd: 653.36591 [M+H]+, 670.39246 [M+NH4]+, 675.34785
[M+Na]+, 691.32179 [M+K]+, found: 653.36603 [M+H]+,
670.39303 [M+NH4]+, 675.34819 [M+Na]+, 691.32143 [M+K]+.
4.3. Synthesis of 5-iodo-25,26,27,28-tetrapropoxy-
calix[4]arene (2)
A
250 mL flask charged with 5-bromotetrapropoxy-
calix[4]arene 1 (9.5 g, 14.1 mmol) and freshly distilled THF (60
mL) was cooled to -78 °C under a blanket of argon. t-BuLi (3 eq,
25 mL, 42.3 mmol) was added and the reaction was stirred for 30
minutes. Iodine (2 eq, 7.2 g, 28.2 mmol) was then added and the
reaction was stirred overnight during which the mixture was
slowly warmed to room temperature. The solvent was
evaporated, the residue was dissolved in CH2Cl2 (100 mL) and
rinsed with a saturated aqueous solution of Na2SO3 (200 mL).
The aqueous phase was extracted with CH2Cl2 (2 x 25 mL). The
combined organic phases were rinsed with water (50 mL), dried
over MgSO4 and solvent evaporated in vacuo. The crude residue
4.6. Synthesis of 5-(pyrimidin-2-ylsulfanyl)-25,26,27,28-
tetrapropoxycalix[4]arene (4c)
was purified
using column chromatography (SiO2,
A 250 mL double-necked flask was charged with compound 2
(1.0 g, 1.39 mmol), CuI (0.5 eq, 132 mg, 0.696 mmol), 1,10-
phenanthroline (1 eq, 250 mg, 1.39 mmol), K2CO3 (4 eq, 768 mg,
5.56 mmol), 2-sulfanylpyrimidine 3c (4 eq, 624 mg, 5.56 mmol),
and anhydrous DMF (90 mL). The flask was flushed with
nitrogen and the reaction mixture was stirred at 170 °C for 5
days. After that, the DMF was evaporated in vacuo, the crude
mixture dissolved in CH2Cl2 (30 mL) and purified using column
chromatography (silica gel, EtOAc:cyclohexane = 1:4 v/v, Rf =
EtOAc:cyclohexane = 1:15 v/v, Rf 1= 0.40) to give 9.5 g (94%) of
a white solid, mp: 129-130 °C; H-NMR (CDCl3, 400 MHz)
δ(ppm): 6.80 – 6.69 (m, 9H, Ar-H); 6.48 (m, 2H, Ar-H); 4.46 (d,
J = 13.8 Hz, 2H, Ar-CH2-Ar); 4.38 (d, J = 13.5 Hz, 2H, Ar-CH2-
Ar); 3.92 – 3.74 (m, 8H, OCH2); 3.18 (d, J = 13.8 Hz, 2H, Ar-
CH2-Ar); 3.09 (d, J = 13.5 Hz, 2H, Ar-CH2-Ar); 1.97 – 1.84 (m,
8H, CH2); 1.06 – 0.93 (m, 12H, CH3) All characterizations
including 13C NMR, IR and MS spectra are in agreement with
previously published data.7
1
0.45) to give 780 mg (80%) of a white solid, mp: 73-74 °C. H
NMR (400 MHz, CDCl3, 293 K)
δ (ppm): 8.44 (d, J = 4.7 Hz,
4.4. Synthesis of 5-phenylsulfanyl-25,26,27,28-tetrapropoxy-
calix[4]arene (4a)
2H, pyr-H); 6.90 (t, J = 4.7 Hz, 1H, pyr-H); 6.70 – 6.73 (m, 6H,
Ar-H); 6.61 – 6.65 (m, 3H, Ar-H); 6.52 (d, J = 7.3 Hz, 2H, Ar-
H); 4.46 (d, J = 13.3 Hz, 2H, Ar-CH2-Ar); 4.45 (d, J = 13.3 Hz,
2H, Ar-CH2-Ar); 3.79 – 3.93 (m, 8H, Ar-O-CH2-); 3.18 (d, J =
13.3 Hz, 2H, Ar-CH2-Ar); 3.17 (d, J = 13.3 Hz, 2H, Ar-CH2-Ar);
1.87 – 1.98 (m, 8H, CH2); 0.95 – 1.06 (m, 12H, CH3). 13C NMR
A 100 mL Schlenk flask was charged with compound 2 (500
mg, 0.696 mmol), CuI (1 eq, 133 mg, 0.696 mmol), 1,10-
phenanthroline (1 eq, 125 mg, 0.696 mmol), K2CO3 (4 eq, 385
mg, 2.78 mmol), thiophenol 3a (6 eq, 0.43 mL, 4.18 mmol), and
anhydrous DMF (42 mL). The flask was flushed with nitrogen
and stirred at 150 °C for 5 days. After that, DMF was evaporated
in vacuo and the crude mixture dissolved in CH2Cl2 (20 mL) and
(100 MHz, CDCl3, 293 K)
δ (ppm): 157.37; 156.80; 156.28;
136.09; 135.87; 135.60; 135.08; 134.94; 134.72; 128.50; 128.33;
127.99; 122.02; 121.99; 121.20; 116.43; 77.19; 76.91; 76.62;
30.99; 30.92; 23.38; 23.28; 23.16; 10.42; 10.40; 10.21. IR (KBr)
purified
using
column
chromatography
(SiO2,
ν
(cm-1): 2960.7, 2930.1, 2873.7, 1560.9, 1546.2, 1454.7,
EtOAc:cyclohexane = 1:20 v/v, Rf = 0.75) to give 460 mg (94%)
1
1379.1, 1190.4. HRMS-ESI (C44H50N2O4S) m/z calcd: 703.35641
[M+H]+, 720.38295 [M+NH4]+, 725.33835 [M+Na]+, 741.31229
[M+K]+, found: 703.35710 [M+H]+, 720.38318 [M+NH4]+,
725.33853 [M+Na]+, 741.31210 [M+K]+.
of white powder, mp: 103-105 °C. H NMR (400 MHz, CDCl3,
293 K) δ (ppm): 7.20 (t, J = 7.4 Hz, 2H, Ar-H); 7.12 (t, J = 7.4
Hz, 1H, Ar-H); 6.97 (m, 2H, Ar-H); 6.69 – 6.73 (m, 4H, Ar-H);
6.60 – 6.65 (m, 7H, Ar-H); 4.46 (t, J = 13.5 Hz, 4H, Ar-CH2-
Ar); 3.83 – 3.91 (m, 8H, O-CH2); 3.19 (d, J = 13.5 Hz, 2H, Ar-
CH2-Ar); 3.12 (d, J = 13.5 Hz, 2H, Ar-CH2-Ar); 1.90 – 1.98 (m,
8H, CH2); 0.98 – 1.06 (m, 12H, CH3). 13C NMR (100 MHz,
CDCl3, 293 K) δ (ppm) 156.71; 156.51; 156.34; 136.19; 135.44;
134.83; 134.72; 132.78; 128.73; 128.43; 128.18; 128.08; 127.95;
125.36; 122.10; 122.04; 76.90; 76.76; 30.98; 30.85; 23.30; 23.28;
23.19; 10.40; 10.38; 10.24. IR (KBr) ν (cm-1): 2961.0, 2930.7,
2873.9, 1582.7, 1455.3, 1383.7, 1247.2, 1210.1. HRMS-ESI
(C46H52O4S) m/z calcd: 723.34785 [M+Na]+, 739.32179 [M+K]+,
found: 723.34860 [M+Na]+, 739.32123 [M+K]+.
4.7. Synthesis of 5-phenylsulfinyl-25,26,27,28-tetrapropoxy-
calix[4]arene (5a)
A 100 mL flask charged with 5-phenylsulfanyl derivative 3a
(490 mg, 0.699 mmol) and anhydrous CH2Cl2 (60 ml) was
flushed with nitrogen. The mixture was cooled to 0 °C and
m-chloroperbenzoic acid (1 eq, 157 mg, 0.699 mmol) was added.
The reaction mixture was stirred for 1 hour during which time the
temperature rose to room temperature. Then, a saturated solution
of Na2SO3 (150 mL) was added and the organic phase was
washed with NaHCO3 (30 mL), water (40 mL), dried over
MgSO4 and the solvent was evaporated in vacuo. The mixture
was then subjected to Chromatotrontm (silica gel,
EtOAc:cyclohexane = 1:15 v/v, Rf = 0.15) to give 354 mg (70%)
of a white crystalline solid, mp: 145-147 °C. 1H NMR (400 MHz,
4.5. Synthesis of 5-ethylsulfanyl-25,26,27,28-tetrapropoxy-
calix[4]arene (4b)
A 100 mL Schlenk flask was charged with 5-iodo derivative 2
(500 mg, 0.696 mmol), CuI (1 eq, 133 mg, 0.696 mmol), 1,10-
phenanthroline (1 eq, 125 mg, 0.696 mmol), K2CO3 (4 eq, 385
mg, 2.78 mmol), ethanethiol 3b (4 eq, 0.20 mL, 2.78 mmol), and
anhydrous DMF (45 mL) and flushed with nitrogen. The mixture
was stirred at 170 °C for 5 days. The DMF was then removed in
vacuo, the crude residue dissolved in CH2Cl2 (30 mL) and
purified using column chromatography (silica gel, EtOAc:
cyclohexane = 1:9 v/v, Rf = 0.80) to give 410 mg (90%) of a
CDCl3, 293 K)
δ (ppm): 7.41 – 7.48 (m, 5H, Ar-H); 7.08 (d, J =
2.2 Hz, 1H, Ar-H); 6.66 – 6.71 (m, 4H, Ar-H); 6.52 – 6.60 (m,
4H, Ar-H); 6.47 (t, J = 7.4 Hz, 1H, Ar-H); 6.36 (m, 1H, Ar-H);
4.40 – 4.47 (m, 4H, Ar-CH2-Ar); 3.74 – 3.87 (m, 8H, O-CH2);
3.08 – 3.20 (m, 4H, Ar-CH2-Ar); 1.86 – 1.94 (m, 8H, CH2); 0.95
– 1.00 (m, 12H, CH3). 13C NMR (100 MHz, CDCl3, 293 K)
δ
(ppm): 159.53; 156.60; 156.23; 137.52; 137.01; 136.68; 135.28;
135.10; 135.03; 133.84; 133.77; 130.41; 128.92; 128.48; 128.39;

6
Tetrahedron
ACCEPTED MANUSCRIPT
128.08; 127.77; 125.60; 124.91; 122.30; 122.17; 121.97; 77.20;
76.92; 76.76; 30.99; 30.92; 23.22; 23.21; 10.32; 10.27; 10.19. IR
(KBr)
1248.7, 1210.1. HRMS-ESI (C46H52O5S) m/z calcd: 739.34277
[M+Na]+, 755.31670 [M+K]+, found: 739.34381 [M+Na]+,
755.31610 [M+K]+.
A 250 mL flask was charged with compound 3c (676 mg,
0.962 mmol), anhydrous CH2Cl2 (70 mL) and flushed with
nitrogen. Mixture was cooled to 0 °C and m-chloroperbenzoic
acid (1 eq, 216 mg, 0.962 mmol) was added. Reaction was stirred
for 1 hour during which temperature was raised to room
temperature. A saturated solution of Na2SO3 (150 mL) was added
and the organic phase was extracted with NaHCO3 (40 mL),
water (60 mL), dried over MgSO4 and the solvent was
evaporated. Mixture was then subjected to Chromatotrontm (SiO2,
EtOAc:CH2Cl2:cyclohexane = 1:1:7 v/v/v, Rf = 0.10) to give 582
ν
(cm-1): 2956.7, 2914.3, 2871.4, 2360.1, 2339.9, 1455.0,
4.8. Synthesis of 5-ethylsulfinyl-25,26,27,28-tetrapropoxy-
calix[4]arene (5b)
A 100 mL flask charged with compound 3b (114 mg, 0.175
1
mg (85%) of white crystalline substance, m.p.: 218-220 °C. H
mmol) and anhydrous CH2Cl2 (15 mL) was flushed with
NMR (400 MHz, CDCl3, 293 K) δ (ppm): 8.82 (d, J = 4.7 Hz,
2H, pyr-H); 7.30 – 7.33 (m, 2H, Ar-H); 7.14 (d, J = 2.4 Hz, 1H,
Ar-H); 6.69 (m, 3H, Ar-H); 6.43 – 6.51 (m, 4H, Ar-H); 6.33 –
6.37 (m, 2H, Ar-H); 4.41 – 4.45 (m, 4H, Ar-CH2-Ar); 3.79-3.91
(m, 8H, Ar-O-CH2-); 3.13 – 3.20 (m, 4H, Ar-CH2-Ar); 1.84 –
1.96 (m, 8H, CH2); 0.93 – 1.02 (m, 12H, CH3). 13C NMR (100
MHz, CDCl3, 293 K) δ (ppm): 174.38; 159.99; 158.39; 156.75;
156.11; 156.03; 137.38; 136.86; 135.49; 135.34; 134.93; 134.85;
134.71; 133.50; 133.44; 128.43; 128.35; 128.31; 128.23; 128.08;
127.75; 125.84; 124.68; 122.21; 122.09; 122.00; 121.30; 76.80;
76.76; 76.74; 76.57; 31.01; 30.95; 30.92; 23.25; 23.21; 23.15;
10.39; 10.19; 10.11. IR (KBr) ν (cm-1): 2961.4, 2929.2, 2874.5,
1557.2, 1454.8, 1380.5, 1209.5. HRMS-ESI (C44H50N2O5S) m/z
calcd: 741.33326 [M+Na]+, found: 741.33374 [M+Na]+.
nitrogen. The mixture was cooled to
0
°C and
m-chloroperbenzoic acid (1 eq, 40 mg, 0.175 mmol) was added.
The reaction was stirred for 1 h during which time the
temperature rose to room temperature. Then, a saturated solution
of Na2SO3 (50 mL) was added and the organic phase was washed
with aq. NaHCO3 (20 mL), water (30 mL), dried over MgSO4
and the solvent was evaporated in vacuo. The mixture was then
subjected to Chromatotrontm (silica gel, EtOAc:cyclohexane =
1:6 v/v, Rf = 0.20) to give 60 mg (51%) of a white crystalline
1
solid, m.p.: 57-59 °C. H NMR (400 MHz, CDCl3, 293 K)
δ
(ppm): 6.84 (d, J = 1.8 Hz, 1H, Ar-H); 6.73 – 6.79 (m, 5H, Ar-
H); 6.66 – 6.71 (m, 2H, Ar-H); 6.54(d, J = 7.5 Hz, 2H, Ar-H);
6.47 (t, J = 7.5 Hz, 1H, Ar-H); 4.50 (d, J = 13.5 Hz, 2H, Ar-
CH2-Ar); 4.44 – 4.48 (m, 2H, Ar-CH2-Ar); 3.88 – 3.98 (m, 4H,
O-CH2); 3.85 (t, J = 7.3 Hz, 2H, O-CH2); 3.80 (t, J = 7.3 Hz, 2H,
O-CH2); 3.15 – 3.24 (m, 4H, Ar-CH2-Ar); 2.35 – 2.46 (m, 2H,
Ar-CH2); 1.88 – 2.02 (m, 8H, CH2); 0.95 – 1.07 (m, 15H, CH3).
4.11. Synthesis of bridged compound 6b
A 50 mL Schlenk flask charged with 5-ethylsulfinyl derivative
5b (120 mg, 0.179 mmol), benzoquinone (0.5 eq, 10 mg, 0.09
mmol), Pd(OAc)2 (1 eq, 40 mg, 0.179 mmol), Ag2CO3 (2 eq, 99
mg, 0.358 mmol), p-nitroiodobenzene (0.2 eq, 9 mg, 0.036
mmol), anhydrous 1,2-dichloroethane (10 mL), was flushed with
argon and stirred at 90 °C overnight. The reaction mixture was
then poured onto a short silica gel column (EtOAc:cyclohexane =
1:3 v/v) to remove the inorganic materials. The eluate was
evaporated and subjected to Chromatotrontm (SiO2, EtOAc:
CH2Cl2:cyclohexane = 1:1:10 v/v/v, Rf = 0.20) to give 14 mg
13C NMR (100 MHz, CDCl3, 293 K)
156.14; 136.32; 135.86; 135.63; 134.66; 134.62; 134.50; 128.72;
128.29; 128.24; 127.95; 127.91; 124.18; 123.63; 122.37; 122.32;
121.92; 77.15; 76.96; 76.67; 50.38; 31.04; 31.01; 30.92; 23.31;
δ (ppm): 158.53; 156.63;
23.30; 23.13; 10.44; 10.40; 10.15; 6.42. IR (KBr)
ν
(cm-1):
2962.4, 2932.1, 2874.4, 1455.1, 1210.0. HRMS-ESI (C42H52O5S)
m/z calcd: 691.34277 [M+Na]+, 707.31670 [M+K]+, found:
691.34263 [M+Na]+, 707.31623 [M+K]+.
4.9. Synthesis of 5-ethylsulfonyl-25,26,27,28-tetrapropoxy-
calix[4]arene (5b’).
1
(13%) of a white crystalline solid, m.p.: 60-61 °C. H NMR (400
MHz, CDCl3, 293 K)
δ (ppm): 7.11 – 7.14 (m, 2H, Ar-H); 7.00
(m, 1H, Ar-H); 6.94 (m, 1H, Ar-H); 6.86 (m, 1H, Ar-H); 6.78 (t,
J = 7.6 Hz, 1H, Ar-H); 6.71 (s, 2H, Ar-H); 6.66 (t, J = 7.6 Hz,
1H, Ar-H); 4.39 (d, J = 12.5 Hz, 2H, Ar-CH2-Ar); 3.85-4.22 (m,
9H, Ar-CH2-Ar, O-CH2); 3.32-3.50 (m, 4H, Ar-CH2-Ar, O-CH2);
2.92 (d, J = 13.3 Hz, 1H, Ar-CH2-Ar); 1.72-1.99 (m, 8H, CH2);
1.52 – 1.57 (m, 2H, CH2); 1.12 – 1.17 (m, 6H, CH3); 0.93 – 0.98
(m, 6H, CH3); 0.16 (t, J = 7.4 Hz, 3H, CH3). 13C NMR (100
Compound was obtained as a by-product in the above
described synthesis of derivative 4b. The title compound (Rf =
0.55) was isolated (147 mg, 33% yield) as a white crystalline
1
solid, m.p.: 68-69 °C. H NMR (400 MHz, CDCl3, 293 K) δ
(ppm): 7.07 (s, 2H, Ar-H); 6.83 (t, J = 7.6 Hz, 4H, Ar-H); 6.73
(t, J = 7.6 Hz, 2H, Ar-H); 6.52 (d, J = 7.5 Hz, 2H, Ar-H); 6.41
(t, J = 7.4 Hz, 1H, Ar-H); 4.51 (d, J = 13.3 Hz, 2H, Ar-CH2-Ar);
4.46 (d, J = 13.3 Hz, 2H, Ar-CH2-Ar); 3.89 – 4.03 (m, 4H, O-
CH2); 3.86 (t, J = 7.3 Hz, 2H, O-CH2); 3.79 (t, J = 7.3 Hz, 2H,
O-CH2); 3.24 (d, J = 13.3 Hz, 2H, Ar-CH2-Ar); 3.19 (d, J = 13.3
Hz, 2H, Ar-CH2-Ar); 2.66 (q, J = 7.3 Hz, 2H, Ar-CH2); 1.90 –
2.03 (m, 8H, CH2); 1.06 (t, J = 6.9 Hz, 3H, CH3); 1.05 (t, J = 6.9
Hz, 3H, CH3); 0.99 (t, J = 6.9 Hz, 6H, CH3); 0.94 (t, J = 7.4 Hz,
3H, CH3). 13C NMR (100 MHz, CDCl3, 293 K) δ (ppm): 160.51;
156.64; 156.00; 135.98; 135.82; 134.49; 134.27; 131.40; 128.99;
128.34; 128.08; 127.87; 122.56; 121.93; 77.10; 76.70; 50.74;
30.93; 30.90; 23.35; 23.10; 10.50; 10.43; 10.10; 7.63. IR (KBr) ν
(cm-1): 2962.5, 2933.1, 2874.8, 1455.0, 1309.5, 1260.6, 1210.8,
1130.7. HRMS-ESI (C42H52O6S) m/z calcd: 707.33768 [M+Na]+,
723.31162 [M+K]+, found: 707.33769 [M+Na]+, 723.31128
[M+K]+.
MHz, CDCl3, 293 K)
δ (ppm): 156.69; 156.27; 155.66; 142.40;
138.58; 138.52; 138.03; 137.19; 134.56; 131.72; 131.21; 130.25;
129.70; 128.80; 128.61; 127.77; 127.51; 123.01; 122.58; 121.20;
77.20; 76.83; 75.90; 75.77; 50.26; 34.28; 33.71; 33.46; 25.54;
25.36; 23.64; 23.16; 10.77; 10.74; 10.08; 9.92; 7.33. IR (KBr)
ν
(cm-1): 2963.2, 2932.4, 2875.1, 2360.0, 2339.5, 1453.5, 1382.5,
1267.9, 1215.2. HRMS-ESI (C42H50O5S) m/z calcd: 667.34517
[M+H]+, 689.32712 [M+Na]+, 705.30105 [M+K]+, found:
667.34475 [M+H]+, 689.32687 [M+Na]+, 705.30024 [M+K]+.
4.12. Synthesis of thiosulfinate 7
A 50 mL Schlenk flask charged with 5-(pyrimidin-2-
ylsulfinyl)-tetrapropoxycalix[4]arene 5c (50 mg, 0.070 mmol)
and freshly distilled THF (15 mL) under an argon atmosphere
was cooled to -78 °C. n-BuLi (3 eq, 0.10 mL, 0.209 mmol) was
added and the mixture was stirred for 30 minutes at the same
temperature. Aqueous HCl (1M, 10 mL) was added to quench the
reaction and the reaction mixture was stirred at room temperature
4.10. Synthesis of 5-(pyrimidin-2-ylsulfinyl)-25,26,27,28-
tetrapropoxycalix[4]arene (5c)

7
for 1 hour. CH2Cl2 (20 mL) was added and the resulting mixture
Acknowledgments
ACCEPTED MANUSCRIPT
was washed with water (40 mL) and dried over MgSO4. After
evaporation of solvent in vacuo the mixture was subjected to
Chromatotrontm (SiO2, EtOAc: cyclohexane = 1:20 v/v, Rf =
0.35) to give 27 mg (62%) of a white crystalline solid, m.p.: 103-
The authors wish to thank the Czech Science Foundation
(grant Nu. 13-21704S).
104 °C. 1H NMR (400 MHz, CDCl3, 293 K)
δ (ppm): 6.98 (d, J =
References and notes
2.1 Hz, 1H, Ar-H); 6.45 – 6.81 (m, 21H, Ar-H); 4.40 – 4.53 (m,
8H, Ar-CH2-Ar); 3.79 – 3.94 (m, 16H, O-CH2); 3.13 – 3.26 (m,
8H, Ar-CH2-Ar2); 1.87 – 1.96 (m, 16H, CH2); 0.96 – 1.06 (m,
1. For books on calixarenes and their applications see: (a) Gutsche,
C. D. Calixarenes An introduction 2nd Edition, The Royal Society
of Chemistry, Thomas Graham House, Cambridge, 2008. (b)
Vicens, J.; Harrowfield, J.; Backlouti, L.; Eds. Calixarenes in the
Nanoworld, Springer Verlag, Dordrecht, 2007. (c) Asfari, Z.;
Böhmer, V.; Harrowfield, J.; Vicens, J.; Eds. Calixarenes 2001,
Kluwer Academic Publishers, Dordrecht, 2001. (d) Mandolini, L.;
Ungaro, R. Calixarenes in Action, Imperial College Press,
London, 2000.
2. For reviews on various calixarene-based receptors see e.g.: (a)
Siddiqui, S.; Cragg, P. J. Mini-Reviews in Org. Chem. 2009, 6,
283-299. (b) Leray, I.; Valeur, B. Eur. J. Inorg. Chem. 2009, 24,
3525-3535. (c) Matthews, S. E.; Beer, P. D. in Calixarenes 2001;
pp. 421-439 (in ref 1b). (d) Lhoták, P. Top. Curr. Chem. 2005,
255, 65-96. (e) Matthews, S. E.; Beer, P. D. Supramol. Chem.
2005, 17, 411-435. (f) Coquiere, D.; Le Gac, S.; Darbost, U.;
Seneque, O.; Jabin, I.; Reinaud, O. Org. Biomol. Chem. 2009, 7,
2485-2500. (g) Lhotak, P.; Kundrat, O. in Artificial Receptors for
Chemical Sensors, Mirsky, V.; Yatsimirsky, A. Eds.; Wiley-VCH,
Weinheim, 2011, pp. 249-272.
24H, CH3). 13C NMR (100 MHz, CDCl3, 293 K)
δ (ppm):
159.40; 158.66; 156.80; 156.74; 156.61; 156.52; 156.34; 156.30;
136.56; 136.35; 136.19; 136.16; 136.08; 135.60; 135.57; 135.50;
135.46; 135.32; 135.20; 134.88; 134.84; 134.79; 134.77; 134.72;
134.29; 128.68; 128.56; 128.38; 128.29; 128.21; 128.11; 127.96;
127.93; 127.87; 124.17; 123.78; 122.37; 122.35; 122.33; 122.17;
122.14; 122.07; 121.86; 77.19; 76.91; 76.82; 76.79; 76.76; 76.61;
31.07; 31.06; 30.99; 30.95; 30.89; 23.30; 23.26; 23.24; 23.21;
23.19; 23.16; 23.14; 10.41; 10.36; 10.33; 10.30; 10.24; 10.21;
10.20; 10.18. IR (KBr)
ν
(cm-1): 2961.6, 2931.8, 2874.5, 1454.6,
1383.9, 1291.6, 1248.1, 1209.8, 1088.3, 1037.5, 1005.6. HRMS-
ESI (C80H94O9S2) m/z calcd: 1285.62315 [M+Na]+, 1301.59708
[M+K]+, found: 1285.62391 [M+Na]+, 1301.60099 [M+K]+.
4.13. Synthesis of disulfide 8 and thiosulfonate 9
3. Kelderman, E.; Derhaeg, L., Heesink, G. J. T.; Verboom, W.;
Engbersen, J. F. J.; Hulst, N. F.; Persoons, A.; Reinhoudt, D. N.
Angew. Chem. Int. Ed. Engl. 1992, 31, 1075-1077.
4. (a) Mascal, M.; Naven, R. T.; Warmuth, R. Tetrahedron Lett.
1995, 36, 9361-9364. (b) Mascal, M.; Warmuth, R.; Naven, R. T.;
Edwards, R. A.; Hursthouse, M. B.; Hibbs, D. E. J. Chem. Soc.,
Perkin Trans. 1, 1999, 3435.
5. (a) Verboom, W.; Bodewes, P. J.; van Essen, G.; Timmerman, P.;
van Hummel, G. J.; Harkema, S.; Reinhoudt, D. N. Tetrahedron
1995, 51, 499-512. (b) Xu, Z.-X.; Zhang, C.; Zheng, Q.-Y.; Chen,
C.-F.; Huang, Z.-T. Org. Lett. 2007, 9, 4447-4450. (c) Xu, Z.-X.;
Huang, Z.-T.; Chen, C.-F. Tetrahedron Lett. 2009, 50, 5430-5433.
(d) Xu, Z.-X.; Zhang, C.; Yang, Y.; Chen, C.-F.; Huang, Z.-T.,
Org. Lett. 2008, 10, 477-479.
6. (a) Herbert, S. A.; Arnott, G. E. Org. Lett. 2009, 11, 4986-4989.
(b) Herbert, S. A.; Arnott, G. E. Org. Lett. 2010, 12, 4600-4603.
(c) Herbert, S. A.; Castell, D. C.; Clayden, J.; Arnott, G. E., Org.
Lett. 2013, 15, 3334-3337.
A 50 mL Schlenk flask charged with 5-(pyrimidin-2-
ylsulfinyl)-tetrapropoxycalix[4]arene 5c (150 mg, 0.209 mmol)
and freshly distilled THF (25 mL) under argon atmosphere was
cooled to -78 °C. n-BuLi (1.5 eq, 0.157 mL, 0.314 mmol) was
added and the reaction mixture was stirred for 2 h during which
time the reaction was gradually warmed to room temperature.
The reaction was quenched by the addition 1M HCl (aq) (15
mL), diluted by CH2Cl2 (50 mL) and washed with water (40 mL).
The mixture was then subjected to Chromatotrontm (SiO2,
EtOAc:cyclohexane = 1:20 v/v) to give 44 mg (33%) of disulfide
8 (Rf = 0.30) and 37 mg (28%) of thiosulfonate 9 (Rf = 0.45),
both in the form of a white crystalline solid.
1
Analytical data for compound 8: M.p.: 107-108 °C. H NMR
(400 MHz, CDCl3, 293 K)
δ (ppm): 6.75 (s, 4H, Ar-H); 6.54 –
6.63 (m, 18H, Ar-H); 4.41 – 4.47 (m, 8H, Ar-CH2-Ar); 3.77 –
3.89 (m, 16H, O-CH2); 3.14 (t, J = 13.5 Hz, 8H, Ar-CH2-Ar2);
1.85 – 1.97 (m, 16H, CH2); 0.97 – 1.02 (m, 24H, CH3). 13C NMR
7. Holub, J.; Eigner, V.; Vrzal, L.; Dvorakova, H.; Lhotak, P. Chem.
Commun. 2013, 49, 2798-2800.
8. For selected examples of sulfoxide-directed ortho-lithiation see:
(a) Flemming, J. P.; Berry, M. B.; Brown, J. M. Org. Biomol.
Chem., 2008, 6, 1215–1221. (b) Le Fur, N.; Mojovic, L.; Ple, N.;
Turck, A.; Reboul, V.; Metzner, P. J. Org. Chem. 2006, 71, 2609-
2616. (c) Quesnelle, C.; Iihama, T.; Aubert, T.; Perrier, H.;
Snieckus. V. Tetrahedron Lett. 1992, 33, 2625-2628.
9. Furukawa, N.; Ogawa, S.; Matsumura, K.; Fujihara, H. J. Org.
Chem., 1991, 56, 6341–6348.
(100 MHz, CDCl3, 293 K)
δ (ppm): 156.85; 156.63; 156.43;
136.13; 135.21; 135.09; 134.40; 129.67; 129.59; 128.27; 128.17;
127.95; 121.99; 121.97; 77.21; 76.79; 76.58; 30.98; 29.70; 23.25;
23.22; 10.36; 10.30; 10.27. IR (KBr)
ν
(cm-1): 2961.0, 2926.9,
2874.3, 1455.3, 1210.3. HRMS-ESI (C80H94O8S2) m/z calcd:
1269.62823 [M+Na]+, 1285.60217 [M+K]+, found: 1269.62875
[M+Na]+, 1285.60179 [M+K]+.
10. Davis, F. A.; Jenkins, Jr. R. H.; Rizvi, S. Q. A.; Yocklovich, S. G.
J. Org. Chem. 1981,46, 3467-3474.
11. Davis, F. A.; Jenkins, L. A.; Billmers, R. L. J. Org. Chem. 1986,
51, 1033-1040.
12. Cavattoni, T.; Del Giacco, T.; Lanzalunga, O.; Mazzonna, M.;
Mencarelli, P. J. Org. Chem. 2013, 78, 4886−4894.
1
Analytical data for compound 9: M.p.: 131-132 °C. H NMR
(400 MHz, CDCl3, 293 K)
δ (ppm): 7.01 (s, 2H, Ar-H); 6.74 (s,
2H, Ar-H); 6.47-6.68 (m, 16H, Ar-H); 6.31 – 6.34 (m, 2H, Ar-
H); 4.45 (t, J = 13.9 Hz, 8H, Ar-CH2-Ar); 4.07 (t, J = 7.6 Hz,
2H, O-CH2); 3.71-3.95 (m, 14H, O-CH2); 3.10 – 3.18 (m, 8H,
Ar-CH2-Ar2); 1.85 – 2.02 (m, 16H, CH2); 0.95 – 1.06 (m, 24H,
13. Kühle, E. Synthesis 1971, (11), 563-86.
14. Ruano, J. L. G.; Parra, A.; Marcos, V.; del Pozo, C.; Catalan, S.;
Monteagudo, S.; Fustero, S.; Poveda, A. J. Am. Chem. Soc. 2009,
131, 9432–9441.
CH3). 13C NMR (100 MHz, CDCl3, 293 K)
δ (ppm): 161.59;
15. The formation of a mixture of diphenyl disulfide and phenyl
benzenethiosulfonate was also reported when PhMgBr reacted
with phenyl (1-naphthyl) sulfoxide. The exact origin of phenyl
moiety (from Grignard or from sulfoxide?) in these products
remains doubtful: Baker, R. W.; Hockless, D. C. R.; Pocock, G.
R.; Sargent, M. V.; Skelton, B. W.; Sobolev, A. N.; Twiss, E.;
White, A. H. J. Chem. Soc. Perkin Trans. I 1995, 2615-2629.
16. For selected reviews on cation-π complexes of calixarenes, see
e.g.: (a) Abraham, W. J. Incl. Phenom. Macr. Chem. 2002, 43,
159–174. (b) Lhotak, P.; Shinkai, S. J. Phys. Org. Chem. 1997, 10,
273-285.
159.51; 156.84; 156.62; 156.41; 155.92; 136.63; 136.43; 136.37;
136.04; 135.55; 135.52; 134.86; 134.77; 134.43; 132.90; 128.66;
128.55; 128.47; 128.04; 128.02; 127.78; 127.62; 122.38; 122.15;
121.79; 120.14; 77.23; 76.91; 76.83; 76.82; 76.67; 76.61; 30.99;
30.93; 23.32; 23.28; 23.19; 10.48; 10.40; 10.37; 10.24; 10.18;
10.15. IR (KBr)
ν
(cm-1): 2962.3, 2932.0, 2874.9, 1455.1,
1384.1, 1326.3, 1248.8, 1209.8, 1131.4. HRMS-ESI
(C80H94O10S2) m/z calcd: 1301.61806 [M+Na]+, 1317.59200
[M+K]+, found: 1301.61877 [M+Na]+, 1317.59155 [M+K]+.

8
Tetrahedron
ACCEPTED MANUSCRIPT
17. Bernauer, M.; Bernauer, B.; Cuřínová, P.; Budka, J.: ESTAC- a
Novel Tool for Determination of Binding Constants. 29th NMR
Valtice, Abstracts, C-31, Valtice, Czech Republic, 27-30 April
2014.