One-step synthesis of rccc- and rctt-diastereomers of novel calix[4]resorcinols based on a para-thiophosphorylated derivative of benzaldehyde

Article abstract of DOI:10.1016/j.tetlet.2013.04.114

Novel calix[4]resorcinols with four 2-thioxo-1,3,2-dioxaphosphorinane fragments included in aromatic substituents have been synthesized via a one-step condensation of resorcinol and its derivatives with a new para- thiophosphorylated benzaldehyde. It has been found that the diastereomeric ratio depends substantially on the reaction conditions, in particular, the solvents and catalysts used. The macrocyclic products obtained are rctt- and/or rccc-isomers, which were isolated and the structures determined by NMR and single crystal X-ray diffraction studies.

Full text of DOI:10.1016/j.tetlet.2013.04.114

Tetrahedron Letters 54 (2013) 3538–3542
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
One-step synthesis of rccc- and rctt-diastereomers of novel
calix[4]resorcinols based on a para-thiophosphorylated derivative
of benzaldehyde
Irina R. Knyazeva a, , Victoria I. Sokolova a, Margit Gruner b, Wolf D. Habicher b, Victor V. Syakaev a,
⇑
Vera V. Khrizanforova a, Bulat M. Gabidullin a, Aidar T. Gubaidullin a, Yulia H. Budnikova a,
Alexander R. Burilov a, Michael A. Pudovik a
a A.E. Arbuzov Institute of Organic and Physical Chemistry of Kazan Scientific Center, Russian Academy of Sciences, Arbuzov Str. 8, Kazan 420088, Russia
b Institute of Organic Chemistry, Dresden University of Technology, Mommsenstr. 13, Dresden D-01062, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
Novel calix[4]resorcinols with four 2-thioxo-1,3,2-dioxaphosphorinane fragments included in aromatic
substituents have been synthesized via a one-step condensation of resorcinol and its derivatives with
a new para-thiophosphorylated benzaldehyde. It has been found that the diastereomeric ratio depends
substantially on the reaction conditions, in particular, the solvents and catalysts used. The macrocyclic
products obtained are rctt- and/or rccc-isomers, which were isolated and the structures determined by
NMR and single crystal X-ray diffraction studies.
Received 21 February 2013
Revised 18 April 2013
Accepted 26 April 2013
Available online 3 May 2013
Keywords:
Thiophosphorylated calix[4]resorcinol
Condensation
Ó 2013 Elsevier Ltd. All rights reserved.
Resorcinol
Aldehyde
Conformation
The design of phosphorus-containing macrocyclic compounds
including calixarenes is an important area of development in con-
temporary organoelement chemistry.1 The introduction of func-
tional groups with a phosphorus atom of varying coordination in
the macrocycle allows the synthesis of substances with three-
dimensional architecture. Organophosphorus fragments having
high coordination ability can enhance substantially the particular
properties of a macromolecule or give it completely new features.
For example, modification of the calix[4]arene matrix with func-
tional groups containing phosphorus and sulfur atoms allows a
remarkable improvement of the extraction ability of the deriva-
tives obtained compared to their unsubstituted precursors, with
For example, condensation of resorcinol with long-chain aliphatic
aldehydes gives predominantly the rccc-isomer in high yields,
and the use of aromatic aldehydes leads to a mixture of rccc- and
rctt-isomers.
Recently, we realized for the first time the highly effective single-
step synthesis of P = S-substituted calix[4]resorcinols containing
four diethyl thiophosphate or 2-thioxo-1,3,2-dioxaphospholane
groups on the aromatic substituents, which was based on the con-
densation of new thiophosphorylated derivatives of benzaldehyde
with resorcinol or its derivatives in acidic media.4 It was shown that
the reactions proceeded stereoselectively in moderate to high yields
with formation of only the isomer of calixarene in chair conforma-
tion with rctt-configuration of the thiophosphorylated substituents.
It should be noted that the introduction of thiophosphoryl groups on
the calixarene framework has so far been a labor-consuming
process, and involved predominantly the addition of a sulfur atom
to trivalent phosphorus atoms, which had been previously intro-
duced on the upper rim of calix[4]resorcinols or cavitands via
O-phosphorylation.2b,5
respect to soft metal ions, specifically, Ag+, Co2+, Cu2+, Zn2+, Pb2+
,
and Hg2+ 2
.
A general method for the synthesis of calix[4]resorcinols in-
volves the acid-catalyzed condensation of resorcinol or its deriva-
tives with aliphatic or aromatic aldehydes.3 The macrocyclic
compounds formed can exist as four diastereomers, namely, rccc,
rcct, rctt, and rttt, which are differentiated by the spatial orienta-
tion of the substituents of the calixarene matrix relative to the
macrocyclic cavity. The ratio of diastereomers usually depends
on the nature of the initial aldehyde and the reaction conditions.
In order to design thiophosphorylated calix[4]resorcinols as
functionalized partners in the reaction with resorcinol and its
derivatives, we used for the first time 2-(4-formylphenoxy)-2-thi-
oxa-5,5-dimethyl-1,3,2-dioxaphos-phorinane (3), which was syn-
thesized in a yield of 88% by the reaction of 2-chloro-2-thioxo-
1,3,2-dioxaphosphorinane (1), synthesized according to a known
⇑
Corresponding author. Tel.: +7 9178804234.
E-mail address: ihazieva@mail.ru (I.R. Knyazeva).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.04.114

I. R. Knyazeva et al. / Tetrahedron Letters 54 (2013) 3538–3542
3539
O
O
S
S
NaH
THF
P
Cl
P
O
CHO
HO
CHO
O
O
2
1
3
R
R
h
1
1
h
HO
OH
HO
OH
2
2
R
h
3
HO
OH
5
3
5
HO
HO
OH
HO
HO
OH
OH
v
3
R'
R'
h
R'
R'
R'
R'
4
v
4
2
v
1
v
4
R
R
R
R
CHCl3, CF3COOH
R'
R'
OH
HO
OH
HO
OH
R
R
rccc-isomer
rctt-isomer
4a-6a
4b-6b
7
8
10
O
12
11
9
6
R' =
O P
S
O
4: R = H, yield 96% (4a:4b = 1:0)
5: R = CH3, yield 89% (5a:5b = 5:1)
6: R = OH, yield 93% (6a:6b = 1:2)
Scheme 1. Synthesis of thiophosphorylated calix[4]resorcinols 4–6.
procedure,6 and 4-hydroxybenzaldehyde (2) in the presence of so-
dium hydride in anhydrous THF (Scheme 1).7 The crystal structure
of compound 3 was established by means of single crystal X-ray
diffraction.8,9
An interesting feature of compounds 4a–6a was the strong
dependence of their dynamic behavior versus solvent. As was
mentioned above, calix[4]resorcinols can exist in conformations
of various symmetries. The conformation is one of the main factors
which determines the function of these macromolecules in supra-
molecular systems.15 When a calix[4]resorcinol has small non-
bulky (e.g., aliphatic) substituents, an averaged spectrum on the
NMR time-scale is observed, which is ascribed to the cone confor-
mation; although it is the consequence of rapid boat 1–cone–boat 2
conformational interconversion (Fig. 1). When there are bulky sub-
stituents present, in some cases the frozen boat conformation is de-
tected in the NMR spectra.3a,c,16 Several reports on the effect of the
polarity of the solvent on the dynamic characteristics of
calix[4]resorcinols in solutions relate the solvent effect mainly to
its polarity and ability to break hydrogen bonds between the hy-
droxyl groups of resorcinol rings.17
Subsequent condensation of equimolar amounts of resorcinol
and aldehyde 3 in chloroform containing trifluoroacetic acid (60–
65 °C, ca. 35 h) resulted in the formation of only the rccc-isomer
of calix[4]resorcinol 4a in a yield of 96% (method A).10 Reaction
of compound 3 with 2-methylresorcinol under similar conditions
took place with the formation of a mixture of rccc- and rctt-isomers
5a and 5b, respectively, in a 5:1 ratio and a total yield of 89%.11 Fi-
nally, in an analogous reaction, pyrogallol gave a mixture of rccc-
and rctt-isomers 6a and 6b in a 1:2 ratio and a total yield of 93%;
however, the rctt-isomer 6b predominated (Scheme 1).12 It should
be noted that increasing the reaction time did not affect
substantially the ratio and total yield of the isomers, which precip-
itated from the reaction mixture. Owing to the different solubili-
ties, the isomers were isolated in pure form by means of
consecutive recrystallization from acetone and ethanol, and then
characterized.
It is interesting to note the effect of the nature of the solvents
and catalysts used on the isomeric ratios of the calix[4]resorcinols.
For example, substitution of the mixture of chloroform and triflu-
oroacetic acid for ethanol, water, and concentrated hydrochloric
acid in the reactions of resorcinol or 2-methylresorcinol with alde-
hyde 3 (not shown in Scheme 1) gave rise to stereoselective forma-
tion of only the rctt-isomers 5b and 6b, respectively, in chair
conformation, in moderate yields of up to 56% (method B).13,14
It should be noted that the rccc-isomers of thiophosphorylated
calix[4]resorcinols were synthesized for the first time in the reac-
tions with functionalized derivatives of benzaldehydes. The assign-
ments of the signals of compounds 4a–6a in the NMR spectra were
performed by means of 1H, 13C, HSQC, and HMBC experiments.
Each group of these compounds corresponds to one resonance in
the NMR spectra; this indicates the existence of highly symmetric
cone conformation in the solutions of these compounds; the multi-
plet signals of the dioxaphosphorinane fragments being the only
exception.
In our case, a large difference is observed in the 1H NMR spectra
in the two solvents, which are similar by their properties, namely,
DMSO-d6 and acetone-d6. At 303 K in acetone-d6, the observed 1H
NMR spectrum of compound 4a is characteristic of the cone confor-
mation; that is, each group of protons corresponds to one signal. In
DMSO-d6, a similar spectrum could only be obtained at 373 K,
while that at 303 K shows coalescence of the peaks due to the
H4 protons (Fig. 2).
Values of the barriers of boat 1–cone–boat 2 interconversion
(D
G#) can be calculated with the use of Eyring equations.18 Unfor-
tunately, it is impossible to determine directly from conducted
R
R
R
R
R
R
R
R
R
R
R
R
cone
boat 1
boat 2
Figure 1. Boat 1–cone–boat 2 interconversion.

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I. R. Knyazeva et al. / Tetrahedron Letters 54 (2013) 3538–3542
Figure 2. Temperature-dependent 1H NMR spectra of the aromatic protons signals of 4a at 600 MHz in acetone-d6 (a) and DMSO-d6 (b). The peak of H4 is marked by asterisk.
experiments the difference of chemical shifts d for the states being
It is interesting to note that thiophosphorylated calix[4]resor-
cinols 4a and 5a adopt a boat conformation in the crystal state
(Fig. 3a, b).8,20,21 It should be mentioned that the conformation of
molecule 5a is highly distorted.
m
in chemical exchange. In compound 4a, this is the difference of
chemical shifts of H4 protons for two opposite resorcinol rings ori-
ented vertically relative to macrocyclic cavity and two other oppo-
site resorcinol rings oriented horizontally. And H4 protons oriented
horizontally to resorcinol rings undergo the deshielding effect of
aromatic currents of two opposite resorcinol rings oriented verti-
cally. The magnitude of deshielding effect determines the differ-
ence of chemical shifts and is related to the value of aromatic
currents of resorcinol rings. As the spectrum corresponding to
the completely frozen boat conformation was not obtained in any
of the solvents used, the difference in the chemical shifts for this
conformation was considered to be 1 ppm = 600 Hz, as in earlier
work,5 where NMR structural data were given for calix[4]resorcin-
ols in boat configuration. The barriers for the boat 1–cone–boat 2
interconversion for 4a calculated from the temperatures of coales-
The 1H NMR spectra of compounds 4b–6b in the chair confor-
mation display doubling of their proton and carbon signals for
the resorcinol fragments; this attests to the different, vertical (v)
and horizontal (h), arrangements of opposite resorcinol rings with
respect to the macrocyclic plane as was the case for analogous thi-
ophosphorylated calix[4]resorcinols in our previous publications.4
The chair conformation of calixarene 6b was confirmed by single
crystal X-ray diffraction (Fig. 3c).8,22
The crystal and molecular structures of the obtained com-
pounds are of interest considering that classical hydrogen bonding
takes part in their formation. The results of structure analysis and
the relationship between their instability and the features of the
molecular packing will be reported in due course.
In conclusion, we have demonstrated that new benzaldehyde 3
is a useful starting material for the one-step preparation of novel
calix[4]resorcinols with four 2-thioxo-1,3,2-dioxaphosphorinane
fragments attached to the aromatic substituents. The syntheses
proceed with moderate to high yields enabling intentionally de-
sired rccc- and/or rctt-isomers to be prepared depending on the
experimental conditions. An interesting feature of the synthesized
compounds is the strong dependence of their dynamic behavior
on NMR time-scale versus the solvent used.
cence correspond to
G = 44.4 kJ/mol for TC = 223 K (acetone-d6).
The large difference observed for the barrier of boat 1–cone–
DG = 59.5 kJ/mol for TC = 303 K (DMSO-d6) and
D
boat 2 interconversion depending on the used solvent, more specif-
ically, DMSO-d6 or acetone-d6 (DDG = 15 kJ/mol), can be related to
the nature of DMSO, particularly its large dipole moment and abil-
ity to form hydrogen bonds with proton donor compounds. It is
known that cone conformation in calixresorcinol is stabilized by
the cyclic intramolecular hydrogen bond. While some hydroxyl
groups of resorcinol fragments are involved in it, others are free
and directed out of the calixresorcinol cavity and, consequently,
can form additional hydrogen bonds. The system is dynamic and
all hydroxyl groups are involved in flip–flop exchange between
bonded and free state.19 DMSO molecules, while solvating calixres-
orcinol, are embedded in the system of hydrogen bonds stabilizing
the existing equilibrium forms of conformers, thus increasing the
barrier of boat 1–cone–boat 2 interconversion.
Acknowledgments
We wish to thank the Russian Foundation for Basic Research
(Grants Nos. 12-03-31002, 13-03-97073).

I. R. Knyazeva et al. / Tetrahedron Letters 54 (2013) 3538–3542
3541
Figure 3. Two projections of the calix[4]resorcinol molecules in the crystals of 4a (a), 5a (b), and 6b (c). Hydrogen atoms (excluding H-atoms of the hydroxyl groups) and
solvent molecules are omitted for clarity.
of 2-chloro-2-thioxo-1,3,2-dioxaphosphorinane (1) (13.70 g, 68.3 mmol) in
THF (70 mL) was added and the resulting suspension was stirred with heating
References and notes
(ꢀ65 °C) under
a nitrogen atmosphere. The progress of the reaction was
1. (a) Antipin, I. S.; Kasakova, E. Kh.; Habicher, W. D.; Konovalov, A. I. Russ. Chem.
Rev. 1998, 67, 905; (b) Cherenok, S.; Kalchenko, V. Top. Heterocycl. Chem. 2009,
20, 229; (c) Dutasta, J.-P. Top. Curr. Chem. 2004, 232, 55; (d) Pinalli, R.;
Dalcanale, E. Acc. Chem. Res. 2013, 46, 399; (e) Knyazeva, I. R.; Burilov, A. R.;
Pudovik, M. A.; Habicher, W. D. Russ. Chem. Rev. 2013, 82, 150.
2. (a) Wang, H.; Li, Z.; Liu, Y. Sci. Chin. B Chem. 2007, 50, 654; (b) Bibal, B.;
Declercq, J.-P.; Dutasta, J.-P.; Tinantb, B.; Valad, A.-G. Tetrahedron 2003, 59,
5849.
3. (a) Tunstad, L. M.; Tucker, J. A.; Dalcanale, E.; Weiser, J.; Bryant, J. A.; Sherman, J.
C.; Helgeson, R. C.; Knobler, C. B.; Cram, D. J. J. Org. Chem. 1989, 54, 1305; (b)
Thoden van Velzen, E. U.; Engbersen, J. F.; Reinhoudt, D. N. J. Am. Chem. Soc.
1994, 116, 3597; (c) Högberg, A. G. S. J. Org. Chem. 1980, 45, 4498; (d)
Yamakawa, Y.; Ueda, M.; Nagahata, R.; Takeuchi, T.; Asai, M. J. Chem. Soc., Perkin
Trans. 1 1998, 4135; (e) Prosvirkin, A. V.; Kazakova, E. Kh.; Gubaidullin, A. T.;
Litvinov, I. A.; Gruner, M.; Habicher, W. D.; Konovalov, A. I. Russ. Chem. Bull., Int.
Ed. 2005, 54, 2550.
monitored by TLC. After 6 h, the precipitate was filtered and washed with
benzene. The solvent was evaporated and the crude residue was purified by
column chromatography using dichloromethane as eluent. The pure compound
3 was obtained as a white solid (17.11 g, 88% yield, Rf = 0.58), mp 103–104 °C.
31P NMR (166.9 MHz, CDCl3): d = 53.2 ppm. 1H NMR (600.1 MHz, CDCl3):
d = 0.94 (s, 3H, CH3), 1.35 (s, 3H, CH3), 4.04 (m, 2H, OCH2), 4.32 (m, 2H, OCH2),
3
4
3
7.38 (d, JHH = 8.49 Hz, JPH = 1.3 Hz, 2H, P–O–Car–CHar), 7.92 (d, JHH = 8.49 Hz,
2H, CHar–Car–CHO), 9.99 (s, 1H, CHO) ppm. IR (film)
m
max: 820 cmÀ1 (P@S). Anal.
Calcd for C12H15O4PS: C, 50.35; H, 5.24; P, 10.84; S, 11.19. Found: C, 50.63; H,
5.21; P, 10.70; S, 11.44. ESI-MS: m/z = 287 [M+H]+ (calcd M = 286).
8. Crystals of compound 3, suitable for X-ray analysis, were obtained by slow
evaporation of a CHCl3 solution. Suitable monocrystals of compounds 4a, 5a,
and 6b were grown in acetone/EtOH/DMSO solution. The X-ray diffraction data
for 3, 4a, 5a, and 6b were collected on
diffractometer in the -scan mode using graphite monochromated Mo K
a Bruker Smart APEX II CCD
x
a
(k = 0.71073 Å) radiation. The crystals of compounds 4a, 5a, and 6b
decomposed rapidly when exposed to air. Therefore specimens of 4a and 5a
were subjected to a nitrogen gas cooling stream immediately after being
mounted and were kept at a temperature of 150 K during the experiment. The
single crystal of 6b was loaded into a thin-walled capillary, partially filled with
supernatant solution and the experiment was carried out at 296(2) K. Crystals
of 3 were stable, the experiment was performed at 296(2) K. All non-hydrogen
atoms were refined anisotropically. The hydrogen atoms were inserted at
calculated positions and refined as riding atoms, except those of the hydroxyl
groups, which were located from difference maps and refined using a riding
model. Crystallographic data (except structure factors) reported in this paper
have been deposited at the Cambridge Crystallographic Data Centre with
supplementary publication numbers CCDC 908161, 908159, 908160, and
908162 for 3, 4a, 5a, and 6b, respectively. Copies of these data can be
4. (a) Knyazeva, I. R.; Burilov, A. R.; Fazleeva, G. M.; Nuretdinov, I. A.; Gryaznova,
T. V.; Budnikova, Yu G.; Khrisanforova, V. V.; Gubaidullin, A. T.; Gabidullin, B.
M.; Syakaev, V. V.; Pudovik, M. A.; Konovalov, A. I. Phosphorus, Sulfur Silicon
Relat. Elem. 2011, 186, 1972; (b) Knyazeva, I. R.; Sokolova, V. I.; Gruner, M.;
Habicher, W. D.; Voronina, J. K.; Burilov, A. R.; Pudovik, M. A. J. Incl. Phenom.
Macrocycl. Chem. 2012. http://dx.doi.org/10.1007/s10847-012-0190-0.
5. Maslennikova, V. I.; Serkova, O. S.; Gruner, M.; Goutal, S.; Bauer, I.; Habicher, W.
D.; Lyssenko, K. A.; Antipin, M. Yu; Nifantyev, E. E. Eur. J. Org. Chem. 2004, 4884.
6. Ren, J.-L.; Cheng, B.-W.; Zhang, J.-S. h.; Zang, H.-J.; Kang, W.-M.; Ding, Ch.-K.
Jiegou Huaxue 2008, 27, 70.
7. Experimental procedure for the preparation of and spectroscopic data of compound
3: A solution of 4-hydroxybenzaldehyde (2) (8.34 g, 68.3 mmol) in THF (60 mL)
was added dropwise to
a suspension of NaH (1.64 g, 68.3 mmol) in THF
(120 mL) at 10 °C and the mixture was stirred at rt for 60 min. Then, a solution

3542
I. R. Knyazeva et al. / Tetrahedron Letters 54 (2013) 3538–3542
obtained free of charge upon application to the CCDC (12 Union Road,
Cambridge CB2 1EZ, UK. Fax: (internat.) +44 1223/336 033; E-mail:
deposit@ccdc.cam.ac.uk).
0.21 g (15%), mp >200 °C (dec). 31P NMR (166.9 MHz, DMSO-d6): d = 55.8 ppm.
1H NMR (600.1 MHz, DMSO-d6): d = 1.01 (s, 12H, H12), 1.33 (s, 12H, H12), 4.11
(m, 8H, H10), 4.52 (m, 8H, H10), 5.84 (s, 4H, H5), 6.02 (s, 4H, H4), 6.87 (d,
3
4
9. Crystallographic data for 3: C12H15O4PS, M = 286.27, monoclinic, a = 12.109(3) Å,
3JHH = 7.86 Hz, 8H, H7), 7.08 (d, JHH = 7.86 Hz, JPH = 1.3 Hz, 8H, H8) ppm. IR
b = 16.653(4) Å, c = 6.7274(15) Å, b = 96.401(3)°, V = 1348.2(5) Å3, T = 296(2) K,
m
max: 828 (P@S); 968, 1002 (P–O–C); 3100–3600 (OH) cmÀ1. Anal. Calcd for
C72H76O24P4S4: C, 54.82; H, 4.82; P, 7.87; S, 8.12. Found: C, 54.63; H, 4.90; P,
space group Cc, Z = 4,
l
= 0.362 mmÀ1
,
7388 reflections measured
(R = 0.0338), 3037 independent reflections (Rint = 0.0298), R1 = 0.0752 (all
r
7.81; S, 8.13. ESI-MS: m/z = 1577 [M+H]+ (calcd M = 1576).
data), wR2 = 0.1973 (all data), R1 = 0.0688 (I >2
GoF = 1.345.
r
I), wR2 = 0.1925 (I >2
r
I),
13. Experimental procedure for the preparation of and spectroscopic data of compound
4b (Method B): a mixture of resorcinol (0.19 g, 1.75 mmol) and aldehyde 3
(0.50 g, 1.75 mmol) in EtOH (6.5 mL), H2O (6.5 mL), and concentrated HCl
(3 mL) was stirred under heating at 60–65 °C for 18 h. The precipitate was
filtered and washed sequentially with EtOH and Et2O. After drying in vacuo
(40 °C, 0.06 Torr) pure 4b as the rctt-isomer in chair conformation was obtained
(0.35 g, 54%) as a cream powder, mp >200 °C (dec). 31P NMR (166.9 MHz,
acetone-d6): d = 54.2 ppm. 1H NMR (600.1 MHz, DMSO-d6): 0.90 (s, 12H, H12),
1.20 (s, 12H, H12), 4.02 (m, 8H, H10), 4.35 (m, 8H, H10), 5.56 (s, 2H, H4h), 5.59
(s, 4H, H5), 6.16 (s, 2H, H1v), 6.31 (s, 2H, H4v), 6.34 (s, 2H, H1h), 6.63 (d,
10. Experimental procedure for the preparation of and spectroscopic data of compound
4a (Method A): a mixture of resorcinol (0.38 g, 3.50 mmol) and aldehyde 3 (1 g,
3.50 mmol) in CHCl3 (26 mL) and trifluoroacetic acid (3 mL) was stirred under
heating at 60–65 °C for 35 h under a nitrogen atmosphere. The precipitate
formed was filtered, washed sequentially with CHCl3 and Et2O. The washing
procedure was repeated until only a colorless filtrate was observed. After
drying in vacuo (40 °C, 0.06 Torr) pure 4a as its rccc-isomer in cone
conformation was obtained (1.27 g, 96%) as
a pale yellow powder, mp
>190 °C (dec). 31P NMR (166.9 MHz, acetone-d6): d = 54.3 ppm. 1H NMR
(600.1 MHz, acetone-d6): d = 1.02 (s, 12H, H12), 1.34 (s, 12H, H12), 4.14 (m,
8H, H10), 4.55 (m, 8H, H10), 5.87 (s, 4H, H5), 6.31 (s, 4H, H1), 6.47 (s, 4H, H4),
3JHH = 7.89 Hz, 8H, H7), 6.82 (d, JHH = 7.89 Hz, 8H, H8), 8.56 (s, 4H, OHv), 8.64
3
(s, 4H, OHh). IR max: 828 (P@S); 969, 1003 (P–O–C); 3100–3600 (OH) cmÀ1
m .
Anal. Calcd for C72H76O20P4S4: C, 57.14; H, 5.03; P, 8.20; S, 8.47. Found: C,
57.30; H, 5.07; P, 8.37; S, 8.26. ESI-MS: m/z = 1513 [M+H]+ (calcd M = 1512).
14. Experimental procedure for the preparation of and spectroscopic data of compound
5b: calix[4]resorcinol 5b, chair conformation was obtained according to
3
3
4
6.90 (d, JHH = 8.80 Hz, 8H, H7), 7.11 (d, JHH = 8.80 Hz, JPH = 1.3 Hz, 8H, H8),
7.61(s, 8H, OH) ppm. 13C NMR (150.9 MHz, acetone-d6): d = 21.4 (s, C12), 22.6
(s, C12), 33.6 (s, C11), 43.2 (s, C5), 79.3 (s, C10), 104.2 (s, C1), 121.3 (s,
3JPC = 4.3 Hz, C8), 122.4 (s, C6), 131.3 (s, C7), 133.1 (s, C4), 144.2 (s, C3), 149.9 (s,
method
aldehyde 3 (0.40 g, 1.40 mmol). Pure 5b was obtained (0.31 g, 56%) as
white powder, mp >240 °C. NMR (31P, 1H) data of compound 5b synthesized by
B by treatment of 2-methylresorcinol (0.17 g, 1.40 mmol) and
3JPC = 6.5 Hz, C9), 154.8 (s, C2) ppm. IR
m
max: 828 (P@S); 969, 1002 (P–O–C);
a
3100–3600 (OH) cmÀ1. Anal. Calcd for C72H76O20P4S4: C, 57.14; H, 5.03; P, 8.20;
S, 8.47. Found: C, 57.15; H, 4.93; P, 8.22; S, 8.50. ESI-MS: m/z = 1513 [M+H]+
(calcd M = 1512).
methods A and B were identical. IR mmax: 829 (P@S); 967, 1001 (P–O–C); 3100–
3600 (OH) cmÀ1. Anal. Calcd for C76H84O20P4S4: C, 58.16; H, 5.36; P, 7.91; S,
8.16. Found: C, 58.10; H, 5.45; P, 7.83; S, 8.15. ESI-MS: m/z = 1569 [M+H]+
(calcd M = 1568).
11. Experimental procedure for the preparation of and spectroscopic data of
compounds 5a and 5b: a mixture of 5a and 5b in a 5:1 ratio (by 31P NMR
spectroscopy) and combined yield of 0.59 g (89%) were obtained according to
the method A by treatment of 2-methylresorcinol (0.22 g, 1.75 mmol) with
aldehyde 3 (0.50 g, 1.75 mmol). Sequential recrystallization from acetone and
EtOH gave pure rctt- and rccc-isomers. Rctt-isomer 5b, chair conformation:
white powder, yield 0.10 g (15%), mp >240 °C (dec). 31P NMR (166.9 MHz,
DMSO-d6): d = 55.3 ppm. 1H NMR (600.1 MHz, DMSO-d6): d = 0.91 (s, 12H,
H12), 1.22 (s, 12H, H12), 1.93 (s, 6H, C1-CH3h), 2.08 (s, 6H, C1-CH3v), 4.03 (m,
8H, H10), 4.36 (m, 8H, H10), 5.35 (s, 2H, H4h), 5.67 (s, 4H, H5), 6.15 (s, 2H, H4v),
15. Vysotsky, M.; Schmidt, C.; Boehmer, V. In Advances in Supramolecular
Chemistry; Gokel, W., Ed.; JAI Press: Greenwich, 2000; Vol. 7, pp 139–233.
16. (a) Abis, L.; Dalcanale, E.; Du vosel, S.; Spera, S. J. Org. Chem. 1988, 53, 5475; (b)
Abis, L.; Dalcanale, E.; Duvosel, A.; Spera, S. J. Chem. Soc., Perkin Trans. 2 1990,
2075; (c) Kaminsky, J.; Dvorakova, H.; Stursa, J.; Moravcova, J. Czech. Chem.
Commun. 2011, 76, 1199.
17. (a) Schiel, Ch.; Hembury, G. A.; Borovkov, V. V.; Klaes, M.; Agena, C.; Wada, T.;
Grimme, S.; Inoue, Y.; Mattay, J. J. Org. Chem. 2006, 71, 976; (b) Roncucci, P.;
Pirondini, L.; Paderni, G.; Massera, Ch.; Dalcanale, E.; Azov, V. A.; Diederich, F.
Chem. Eur. J. 2006, 12, 4775.
3
3
6.67 (d, JHH = 8.01 Hz, 8H, H7), 6.83 (d, JHH = 8.01 Hz, 8H, H8), 7.46 (s, 4H,
OHv), 7.68 (s, 4H, OHh) ppm. IR
m
max: 829 (P@S); 965, 1001 (P–O–C); 3050–
3600 (OH) cmÀ1. Anal. Calcd for C76H84O20P4S4: C, 58.16; H, 5.36; P, 7.91; S,
8.16. Found: C, 58.12; H, 5.34; P, 7.83; S, 7.92. ESI-MS: m/z = 1569 [M+H]+
(calcd. M = 1568). Rccc-isomer 5a, cone conformation: pale yellow powder,
yield 0.43 g (65%), mp >195 °C (dec). 31P NMR (166.9 MHz, DMSO-d6):
d = 55.3 ppm. 1H NMR (600.1 MHz, DMSO-d6): d = 0.92 (s, 12H, H12), 1.23 (s,
12H, H12), 1.92 (s, 12H, C1-CH3), 4.07 (m, 8H, H10), 4.39 (m, 8H, H10), 5.81 (s,
4H, H5), 6.10 (s, 4H, H4), 6.75 (d, 3JHH = 7.86 Hz, 8H, H7), 6.95 (d, 3JHH = 7.86 Hz,
18. Activation free energies (D
G#) were determined using Eyring equations
(
D
G
# = 19.14 TCÁ(9.97 + log (TC/d )), J/mol, where, TC-is the coalescence
v
temperature and
d
is the chemical shift difference of the exchanging
m
resonances in the absence of chemical exchange.
19. (a) Schneider, H.-J.; Schneider, U. J. Incl. Phenom. Mol. Recog. Chem. 1994, 19, 67;
(b) Mäkinen, M.; Jalkanen, J.-P.; Vainiotalo, P. Tetrahedron 2002, 58, 8591.
20. Crystallographic data for 4a: C72H76O20P4S4ÁC2H6OS, M = 1591.58, triclinic,
8H, H8), 7.52 (s, 8H, OH) ppm. IR
m
max: 828 (P@S); 968, 1002 (P–O–C); 3100–
a = 17.620(9) Å,
b = 17.810(9) Å,
c = 20.288(10) Å,
d = 65.596(7)°,
3600 (OH) cmÀ1. Anal. Calcd for C76H84O20P4S4: C, 58.16; H, 5.36; P, 7.91; S,
8.16. Found: C, 58.03; H, 5.34; P, 7.84; S, 8.13. ESI-MS: m/z = 1569 [M+H]+
(calcd M = 1568).
b = 86.321(7)°, d = 73.022(7)°, V = 5533(5) Å3, T = 150(2) K, space group P1,
Z = 2, 62221 reflections measured (R = 0.1485), 23949
= 0.213 mmÀ1
independent reflections (Rint = 0.0677), R1 = 0.2068 (all data), wR2 = 0.3105
(all data), R1 = 0.1037 (I >2 I), wR2 = 0.2711 (I >2 I), GoF = 0.901.
ꢀ
l
,
r
12. Experimental procedure for the preparation of and spectroscopic data of
compounds 6a and 6b: a mixture of 6a and 6b in a 2:1 ratio (by 31P NMR
spectroscopy) and combined yield of 1.28 g (93%) were obtained according to
method A by treatment of pyrogallol (0.44 g, 3.50 mmol) with aldehyde 3 (1 g,
3.50 mmol). Sequential recrystallization from acetone and EtOH gave pure rctt-
and rccc-isomers. Rctt-isomer 6b, chair conformation: dark-pink powder, yield
0.61 g (44%), mp >220 °C (dec). 31P NMR (166.9 MHz, DMSO-d6): d = 55.3 ppm.
1H NMR (600.1 MHz, DMSO-d6): d = 0.90 (s, 12H, H12), 1.20 (s, 12H, H12), 4.02
(m, 8H, H10), 4.35 (m, 8H, H10), 5.23 (s, 2H, H4h), 5.69 (s, 4H, H5), 6.97 (s, 2H,
r
r
21. Crystallographic data for 5a: C76H84O20P4S4, M = 1569.55, monoclinic,
a = 27.5575(18) Å, b = 24.7896(17) Å, c = 20.5926(12) Å, b = 124.420(3)°,
V = 11604.6(13) Å3, T = 150(2) K, space group
C 2/c, Z = 4, l ,
= 0.184 mmÀ1
32915 reflections measured (R = 0.0468), 12508 independent reflections
r
(Rint = 0.0298), R1 = 0.0767 (all data), wR2 = 0.1639 (all data), R1 = 0.0542 (I
>2rI), wR2 = 0.1523 (I >2rI), GoF = 1.058.
22. Crystallographic data for 6b: C72H76O24P4S4Á8C3H6O, M = 2042.07, monoclinic,
a = 21.753(5) Å, b = 22.615(6) Å, c = 11.049(3) Å, b = 103.853(3), V = 5278(2) Å3,
3
3
H4v), 6.64 (d, JHH = 8.13 Hz, 8H, H7), 6.82 (d, JHH = 8.13 Hz, 8H, H8), 7.56 (s,
T = 296(2) K, space group P21/c, Z = 2,
measured (R = 0.0300), 12068 independent reflections (Rint = 0.0311),
l , 45928 reflections
= 0.227 mmÀ1
4H, OHv), 7.67 (s, 4H, OHh) ppm. IR
mmax: 830 (P@S); 967, 1001 (P–O–C); 3100–
r
3600 (OH) cmÀ1. Anal. Calcd for C72H76O24P4S4: C, 54.82; H, 4.82; P, 7.87; S,
8.12. Found: C, 54.75; H, 4.80; P, 7.57; S, 8.16. ESI-MS: m/z = 1577 [M+H]+
(calcd M = 1576). Rccc-isomer 6a, cone conformation: dark-pink powder, yield
R1 = 0.0658 (all data), wR2 = 0.1220 (all data), R1 = 0.0428 (I >2
wR2 = 0.1043 (I >2 I), GoF = 1.028.
rI),
r