Synthesis and stereochemical configuration of diastereomeric inherently chiral calixarenes with ABCH and ABCD type of substitution at the lower rim

Article abstract of DOI:10.1134/S1070428012020200

By sulfonylation of tetra(p-tert-butyl)-27-propoxy-25-[N-(1-phenylethyl) carbamoylmethoxy]calix[4] arene diastereomeric inherently chiral calixarenes with the ABCH substitution at the lower rim were synthesized and separated by column chromatography. The

Full text of DOI:10.1134/S1070428012020200

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 2, pp. 284−292. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © O.A. Yesypenko, V.I. Boyko, O.V. Shishkin, S.V. Shishkina, V.V. Pirozhenko, V.I. Kalchenko, 2012, published in Zhurnal Organicheskoi
Khimii, 2012, Vol. 48, No. 2, pp. 292−299.
Synthesis and Stereochemical Configuration
of Diastereomeric Inherently Chiral Calixarenes
with ABCH and ABCD Type of Substitution at the Lower Rim
O. A. Yesypenkoa, V. I. Boykoa, O. V. Shishkinb, S. V. Shishkinab, V. V. Pirozhenkoa,
and V. I. Kalchenkoa
aInstitute of Organic Chemistry, National Academy of Sciences of Ukraine, Kyiv-94, 02660 Ukraine
e-mail: v_boyko@ioch.kiev.ua
bSTC “Institute of Single Crystals,” National Academy of Sciences of Ukraine, Kharkiv, Ukraine
Received July 21, 2011
Abstract—By sulfonylation of tetra(p-tert-butyl)-27-propoxy-25-[N-(1-phenylethyl)carbamoylmethoxy]calix[4]
arene diastereomeric inherently chiral calixarenes with theABCH substitution at the lower rim were synthesized and
separated by column chromatography. The alkylation of these compounds afforded the corresponding calixarenes
with the ABCD substitution type. The absolute configuration of compounds was established by XRD analysis.
DOI: 10.1134/S1070428012020200
Calixarenes due to their unique cavity-shaped structure
are capable of recognition, binding, and separation
of cations, anions, and neutral organic molecules of
similar properties [1]. Chiral calixarenes are especially
interesting in this respect. Receptors based on these
compounds can recognize and bind the optical antipodes
of chiral “guest” molecules [2]. Chiral calixarenes may
also be used as organic catalysts [3] or ligands in the
metallocomplex catalysis [4] for asymmetric synthesis,
as enantioselective sensors [5], chiral stationary phases
for column chromatography [6], chiral shift reagents for
NMR spectroscopy [7]. Inherently chiral calixarenes
whose optical activity is due to the asymmetric position
of achiral substituents on the macrocyclic matrix [8] are
worth special attention. Although many examples of the
synthesis of such compounds were described, mostly their
racemates or diastereomeric mixtures were obtained. Only
several cases were described where the optical isomers
were successfully isolated in the individual state [9, 10]
and their absolute configuration was established by X-ray
analysis [9]. Therefore the search for efficient synthetic
procedures for the preparation of individual inherently
chiral calixarenes and the study of their configuration is
a topical target.
In the preceding paper [11] we reported on the
synthesis and separation of diastereomeric derivatives
of inherently chiral calix[4]arenes by the acylation of
27-propoxy-25-[N-(1-phenylethyl)carbamoylmethoxy]
calix[4]arene without substituents on the upper rim of the
macrocycle. In this work we synthesized diasteromeric
internally chiral calix[4]arenes with tert-butyl groups at
the upper rim and ABCH or ABCD type of substitution
at the lower rin, and carried out the study of the spatial
structure of compounds obtained in solution and in the
crystal state.
Chiralые calix[4]arenes IIIa, IIIb were obtained from
25-propoxycalix[4]arene I [12] in two stages (Scheme 1).
In the first stage the alkylation of the second
(distal) hydroxy group of monopropoxycalixarene I
was performed with a chiral (S)-N-(1-phenylethyl)
bromoacetamide in boiling acetonitrile using K2CO3
as base. Tetra(p-tert-butyl)-27-propoxy-25-[N-(1-
phenylethyl)carbamoylmethoxy]calix[4]arene (II) was
isolated in spectrally pure state.
Compound II is well soluble both in polar (e.g.,
284

SYNTHESIS AND STEREOCHEMICAL CONFIGURATION
285
Scheme 1.
(S)-BrCH2CONHCHMePh
I
Py
de 20%
methanol) and nonpolar (hexane) solvents. The structure
was proved using H NMR spectroscopy. Under the
phenol group reacted giving diastereomers IIIa and IIIb
possessing two symmetry elements each: the carbon
atom of the phenylethylamide residue and the АBCН
asymmetrically substituted macrocyclic frame.
1
effect of the asymmetric carbon atom in the (S)-N-(1-
phenylethyl)amide fragment of the molecule the bridging
protons (Ar–CH2–Ar) (8 pair of doublets which partially
overlapped), and also the protons OCH2 of the propyl
group (multiplet at 3.81–3.93 ppm), methylene protons
of the residue OCH2C(O)NHCH(Me)Ph (two doublets
at 4.47 and 4.53 ppm), and the protons of the hydroxy
groups became diastereotopic. Even the protons of the
aromatic rings located on the other side of the macrocycle
became nonequivalent. They appeared as multiplets
instead of two singlets and two doublets. The values of
spin-spin coupling constants of 13.2–13.4 Hz for the
bridging protons and the difference of ~0.8 ppm between
the chemical shifts of the axial and equatorial protons
confirm the cone conformation of calixarene II [13].
The mixture of diastereomers IIIa and IIIb was
isolated in 92% yield, their ratio was determined from
the integral intensity of the signals of the methyl groups
belonging to the p-toluyl fragment at 2.19 and 2.05 ppm.
This ratio was 3 : 2 (diastereomeric excess, de 20%) and
it was independent of the reaction temperature.
The attempt to separate diastereomers IIIa and
IIIb by crystallization led only to the formation of the
racemic mixture both in the solution and in the crystalline
state. The diastereomers were separated by column
chromatography and were isolated in the yields 26%
1
(IIIа) and 38% (IIIb). The analysis of the Н NMR
spectra of the diastereomers confirmed the asymmetric
substitution of the macrocyclic frame. All the bridging
methylene protons are different and give rise to 4 pairs of
doublets.Also four singlets are observed originating from
In the next stage the sulfonylation of calix[4]arene
II was performed with p-toluenesulfonyl chloride in
anhydrous pyridine where the latter simultaneously
served as a base. Under these conditions only one
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 2 2012

YESIPENKO et al.
286
the tert-butyl groups. The prochiral protons ОСН2 of the
propyl group appear as two multiplets, and the methylene
protons of the amide residue are observed as two doublets.
The 1Н NMR spectra of different diastereomers possess
a number of distinguishing features. For instance,
the signals δ(CH3) and δ(CH2) of the propyl group of
calixarene IIIа are shifted upfield as compared with the
spectrum of calixarene IIIb (Δδ 0.3 ppm) that may be
attributed to the shielding of these protons by the benzene
ring of the phenylethylamide group.
HO, РrO, TolSO2O, Ph(Mе)CHNHC(O)СН2O are placed
clockwise (Fig. 2), in diastereomer IIIb, counterclock-
wise (Fig. 3) (view from above).
Both diastereomers in pure form and in the racemate
have the partial cone conformation. The geometrical char-
acteristics of the macrocycle are very similar. The benzene
ring with the toluenesulfoxide substituent is turned upside
down, and the aromatic ring of the substituent enters the
macrocyclic cavity. Aslight difference is observed in the
conformation of the (S)-N-(1-phenylethyl)amide residue.
In the individual structures IIIa, IIIb this substituent is
so oriented that it closes the calixarene cavity from the
bottom side. The intramolecular hydrogen bond N1–
H⋯O1 [H⋯O 2.31 Å, N–H⋯O 172° (IIIа), H⋯O 2.38
Å, N–H⋯O 173° (IIIb)] stabilizes this position of the sub-
stituent. In the crystal of racemate IIIa, IIIb containing
The NMR data show that calixarenes IIIa and IIIb are
present in the partial cone conformation. The difference
in the chemical shifts for axial and equatorial protons
in two pairs of ArCH2Ar doublets lies in the range
0.54–1.13 ppm (1.13, 1.05, 0.54, 0.55) and corresponds
to the syn-orientation of the neighboring benzene rings.
For two other pairs of doublets this difference is less than
0.5 ppm (0.44, 0.40, 0.13, 0.04), characteristic of the
anti-orientation of the adjacent benzene rings [14]. In the
13C NMR spectra of calixarenes the pairs of signals 32.72,
32.73 ppm (IIIа) and 32.36, 32.57 ppm (IIIb) correspond
to the carbon atoms of the methylene bridges between
two syn-oriented benzene rings, and the pairs of signals
38.97, 38.99 ppm (IIIа) and 38.61, 38.73 ppm (IIIb), to
the carbon atoms of the methylene bridges between two
anti-oriented benzene rings [14].
The absolute configuration of diastereomers IIIa and
IIIb was established by X-ray method. In the crystal of
the racemate both diastereomers are located in the asym-
metric part of the unit cell (Fig. 1). The diastereomers are
distinguished by the sequence of substituents location on
the macrocyclic frame. In compound IIIa the substituents
Fig. 1. Molecular structure of diastereomers in the crystal of
racemate IIIa, IIIb.
(a)
(b)
Fig. 2. Molecular structure of diastereomer IIIа (а) and numeration of nonhydrogen atoms (b).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 2 2012

SYNTHESIS AND STEREOCHEMICAL CONFIGURATION
287
(a)
(b)
Fig. 3. Molecular structure of diastereomer IIIb (а) and numeration of nonhydrogen atoms (b).
both diastereomers the amide substituent does not close
the calixarene cavity from the bottom side. The benzene
ring of this substituent is turned to the outside, and the
macrocycle cavity is closed from the bottom side by the
sulfoxide group of the contiguous molecule. Owing to
this interaction of a pair of diastereomers in the racemate
crystal endless chains form along the crysatallographic
direction [0 0 1]. Diastereomer IIIa in contrast to IIIb
exists in the crystalline phase as a solvate with methanol
in the ratio 1 : 3.
in the formation of compounds IVa, IVb respectively
(Scheme 2).
The structure of tetra-substituted calix[4]arenes IVa,
IVb was confirmed by the spectral data. In the mass
spectra of compounds IV the main peak corresponds to
the molecular ion (m/z 1118.6), and the peak of m/z 1062.4
(50%) belongs to the fragment after the elimination
of the butyl group from the amide nitrogen atom. The
large number of substituents and the presence of the
chiral and prochiral centers considerably complicates
the NMR spectra leading to the splitting and broadening
of the signals. Therefore we carried out the study of the
Individual diastereomers IIIa and IIIb were used in
the synthesis of diasteromeric calixarenes with theABCD
substitution type. In their alkylation with butyl bromide
in acetonitrile in the presence of sodium hydride as a base
not only the fourth hydroxy group of calixarene reacted,
but also the amide group of the chiral substituent resulting
1
temperature dependence of the Н NMR spectra. Only
at 100°С in DMSO the signals became sufficiently clear
for the identification. According to the spectral data,
the molecule remains in the partial cone conformation.
Scheme 2.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 2 2012

YESIPENKO et al.
288
(a)
(b)
Fig. 4. Molecular structure of compound IVа (а) and the numeration of nonhydrogen atoms (b).
The NMR spectra of diastereomers IVa, IVb have close
parameters. The difference is observed only in the signals
corresponding to the dissimilar position of the chiral
amide group with respect to the calixarene phenyl rings.
The final proof of the structure of molecules was obtained
by X-ray analysis (Fig. 4).
EXPERIMENTAL
Melting points were measured on a Boёtius heating
block. 1H NMR spectra were registered on a spectrometer
Varian VXR-300 (299.943 MHz), 13С NMR spectra, on
a spectrometer Varian Gemini-2000 (100.607 MHz),
external reference TMS. IR spectra were recorded on
a spectrophotometer M-80. The reactions were carried
out in anhydrous solvents under an argon atmosphere.
The column chromatography was performed on silica
gel purchased from Acros Organics (0.035–0.070 mm,
pore diameter 6 nm).
The molecule of compound IVa, like that of compound
III, exists in the partial cone conformation where the ben-
zene ring of the macrocycle bearing the toluenesulfoxide
substituent is turned upside down. But unlike the structure
of compound III the aromatic ring of the substituent
does not enter into the calixarene cavity. This results in
a significant change in the macrocycle conformation.
The angle between the aromatic rings neighboring to
the turned one decreases from 45–55° in molecule III to
7° in molecule IVa resulting in the deformation of the
macrocycle. The presence of substituents in all aromatic
rings causes the change in the orientation of the substitu-
ent containing the amide fragment. Its flat amide frag-
ment is turned with respect to the aromatic ring of the
macrocycle by 52.3(4)° (torsion angle C55O4C27C26). The
butyl group attached to the nitrogen atom has the anti-
conformation [torsion angles N1C69C70C71 –176.1(3)°,
C69C70C71C72 180.0(3)°]. The methyl group of this sub-
stituent is fixed in the +ac conformation with respect to
the bond C56–N1 [torsion angle C56N1C57C58 121.2(3)°],
and the phenyl ring is located in the –ac orientation with
respect to the bond C56–N1 and is turned with respect to
the bond N1–C57 [torsion angles C56N1C57C59 –110.2(3)°,
N1C57C59C60 45.4(4)°].
5,11,17,23-Tetra(p-tert-butyl)-25,27-dihydroxy
-
28-propoxy-26-[N-(1-phenylethyl)carbamoylmethoxy]
calix[4]arene (II). To a solution of 1 g (1.447 mmol)
of propoxycalix[4]arene I in 40 ml of acetonitrile was
added 0.120 g (0.868 mmol) of K2CO3 , and the mixture
was strirred for 1 h at 70°С. Then 0.368 g (1.52 mmol)
of bromoacetic acid (S)-N-(1-phenylethyl)amide was
added. The reaction mixture was boiled for 16–18 h, the
solvent was distilled off in a vacuum of a water-jet pump.
The residue was dissolved in 10 ml of chloroform and
washed with 25 ml of 1% solution of hydrochloric acid.
The water layer was extracted with chloroform (2 × 5 ml).
The organic extracts were washed with 10 ml of brine
and dried with Na2SO4. Chloroform was distilled off in
a vacuum. To remove the residual water twice 5 ml of
benzene was added, and the solvent was evaporated in a
vacuum. Yield 1.23 g (96%), mp 93–95°C. IR spectrum
(KBr), ν, сm–1: 3330 br (OH⋯OAlk), 1685 m (С=О).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 2 2012

SYNTHESIS AND STEREOCHEMICAL CONFIGURATION
289
2
1Н NMR spectrum (CDCl3), δ, ppm: 0.92 s [18Н, 2 (t-
Bu)], 0.98 t (3Н, OСН2СН2СН3, 3J 7.4 Hz), 1.30 s (9Н,
t-Bu), 1.31 s (9Н, t-Bu), 1.65 d (3Н, СНСН3, 3J 7.2 Hz),
1.79 m (2Н, OСН2СН2СН3), 3.28 d [1Н, ArСН2 (He),
4.33 d [1Н, ArCH2 (1Ha), J 16.1 Hz], 4.40 d [1Н,
ArCH2 (1Ha), J 12.4 Hz], 4.76 d [1Н, NHC(O)СН2,
2
2J 15.6 Hz], 5.08–5.20 m [1Н, CH3(Ph)CHNH], 6.24 d
(2Н, ArSO2, 3J 8.4 Hz), 6.43 d (2H, ArSO2, 3J 8.4 Hz),
2J 13.3 Hz], 3.35 d [3Н, ArСН2(3He), J 13.3 Hz],
6.81 s (2Нarom), 6.85 s (2Нarom), 7.13 d (1Нarom, 4J 2.2 Hz),
2
3.87 m (2Н, OСН2СН2СН3), 4.14 d [1Н, ArСН2 (1Ha),
2J 13.3 Hz], 4.21 d [2Н, 2ArСН2 (2Ha), 2J 13.3 Hz], 4.24 d
7.17 d (1Нarom, J 2.2 Hz), 7.20–7.32 m [7H, 2Нarom
+
4
5H, CH3(Ph)CHNH], 8.03 s (1Н, ОН), 8.66 d (1Н, NH,
3J 7.2 Hz). 13С NMR spectrum (CDCl3), δ, ppm: 10.05,
21.36, 21.89, 22.54, 30.96, 31.04, 31.71, 32.12, 32.72,
32.73, 33.86, 34.03, 34.28, 34.50, 38.97, 38.99, 49.12,
72.19, 75.60, 124.36, 125.45, 126.61, 126.21, 126.58,
126.65, 126.75, 126.93, 127.08, 127.33, 127.43, 128.24,
128.28, 128.99, 130.13, 131.68, 131.83, 132.42, 132.48,
134.38, 134.94, 135.16, 142.49, 142.71, 143.32, 143.61,
145.79, 147.23, 149.01, 149.53, 150.12, 153.59, 169.65.
Found, %: С 76.67; Н 7.25; N 1.56; S 3.30. С64Н79NО7S.
Calculated, %: С 76.38; Н 7.91; N 1.39; S 3.19.
2
[1Н, ArСН2 (1Ha), J 13.3 Hz], 4.48 d (1Н, OСН2CO,
2J 15.0 Hz), 4.53 d (1Н, OСН2CO, 2J 15.0 Hz), 5.29 m
(1Н, СН), 6.76 m (4Нarom), 7.05 m (6Нarom), 7.24 m
(3Нarom), 7.43 s (1H, OH), 7.45 s (1H, OH), 8.77 d (1Н,
3
NН, J 8.2 Hz). Found, %: С 80.07; Н 8.36; N 1.75.
С57Н73NО5. Calculated, %: С 80.34; Н 8.63; N 1.64.
According to 1Н NMR spectrum the compound was pure
for further syntheses.
The sulfonylation of calix[4]arene II with
4-toluenesulfonyl chloride. Asolution of 1 g (1.17 mmol)
of calix[4]arene II in 15 ml of anhydrous pyridine was
stirred for 1 h at room temperature, 1.3 g (6.82 mmol) of
4-toluenesulfonyl chloride was added, and the mixture
was stirred for 30 min at room temperature till complete
dissolution, then it was heated for 25 h at 90–100°С (the
solution became dark-brown). The solvent was distilled
off in a vacuum (at the bath temperature 90°С). To
the brown oily residue was added 100 ml of cold 10%
solution of hydrochloric acid, the mixture was stirred
for 15 min and left standing for 24 h at 5–10°С. The
separated precipitate was filtered off, washed with water,
and dried in air. The yield of the diastereomeric mixture
as a grey powder was 1.08 g (92%). The diastereomers
were separated by column chromatography, eluent ethyl
acetate–hexane, 1 : 6.
5,11,17,23-Tetra(p-tert-butyl)-25-hydroxy-27-
[(4-methylphenyl)sulfonyloxy]-26-propoxy-28-[N-
(1-phenylethyl)carbamoylmethoxy]calix[4]arene
(IIIb). Yield 0.45 g (38%), mp 73–75°С (MeOH–
H2O), Rf 0.08. IR spectrum (KBr), ν, cm–1: 3330 br
(OH), 1680 (С=О). Н NMR spectrum (CDCl3), δ,
ppm: 0.73 s (9H, t-Bu), 0.83 s (9H, t-Bu), 0.89 t (3Н,
СН3СН2СН2О, J 7.4 Hz), 1.30–1.44 s (9H, t-Bu) +
+ s (9H, t-Bu) + m (2Н, СН3СН2СН2О), 1.47 d [3Н,
1
3
3
CH3(Ph)CHNH, J 6.8 Hz], 2.20 d (3H, CH3ArSO2),
2
2.99 d [1Н, ArCH2 (1He), J 12.7 Hz], 3.39 d [1Н,
ArCH2 (1He), J 13.7 Hz], 3.57–3.70 d [1Н, ArCH2
2
(1He), 2J 15.8 Hz] + m (1H, СН3СН2СН2О), 3.71–3.81 d
[1Н, ArCH2 (1He), J 15.8 Hz] + d [1H, NHC(O)СН2,
2
2J 14.9 Hz], 3.83–4.00 2 d [2Н, 2ArCH2 (2Ha), 2J 13.7,
15.8 Hz] + m (1H, СН3СН2СН2О), 4.09 d [1Н,
5,11,17,23-Tetra(p-tert-butyl)-25-hydroxy-27-
[(4-methylphenyl)sulfonyloxy]-28-propoxy-26-[N-
(1-phenylethyl)carbamoylmethoxy]calix[4]arene
(IIIа). Yield 0.31 g (26%), mp 138–139°С (MeOH),
Rf 0.12. IR spectrum (KBr), ν, cm–1: 3330 br (OH), 1680
(С=О). 1H NMR spectrum (СDСl3), δ, ppm: 0.55 t (3Н,
ArCH2(1На), J 12.7 Hz], 4.25 d [1Н, ArCH2 (1На),
2J 15.8 Hz], 4.69 d [1Н, NHC(O)СН2, J 14.9 Hz],
2
2
5.07–5.19 m [1Н, CH3(Ph)CHNH], 6.53 d (2Н, ArSO2,
3J 8.0 Hz), 6.61 d (2H,ArSO2, 3J 8.0 Hz), 6.73 s (1Нarom),
6.77 s (1Нarom), 6.85 s (1Нarom), 6.92 s (1Нarom), 7.01–
7.36 m [7H, 2Нarom + 5H, CH3(Ph)CHNH], 7.54 s (1Н,
3
СН3СН2СН2О, J 7.4 Hz), 0.69 s (9H, t-Bu), 0.76 s
ОН), 8.52 d (1Н, NH, J 8.0 Hz). 13С NMR spectrum
3
(9H, t-Bu), 1.34 s (9H, t-Bu), 1.41 s (9H, t-Bu), 1.49 d
3
(CDCl3), δ, ppm: 10.21, 21.48, 22.12, 23.24, 31.05,
31.14, 31.82, 32.08, 32.36, 32.57, 33.90, 34.12, 34.24,
34.57, 38.61, 38.73, 48.83, 71.99, 75.99, 124.26, 125.48,
125.85, 126.34, 126.64, 126.75, 126.79, 126.82, 127.02,
127.11, 127.82, 128.24, 129.14, 129.93, 131.56, 131.59,
132.24, 132.26, 134.39, 134.82, 135.19, 142.51, 143.26,
143.27, 143.44, 144.02, 145.77, 147.24, 148.77, 149.53,
150.39, 153.03, 168.94. Found, %: С 76.58; Н 8.13;
[3Н, CH3(Ph)CHNH, J 6.8 Hz], 1.56–1.84 m (2Н,
СН3СН2СН2О), 2.14 s (3H, CH3ArSO2), 3.22 d [1Н,
2
ArCH2 (1He), J 12.4 Hz], 3.40 d [1Н, ArCH2 (1He),
2J 13.6 Hz] + 3.38–3.49 m (1H, СН3СН2СН2О), 3.66–
3.74 m (1H, СН3СН2СН2О), 3.74 d [1Н, ArCH2 (1He),
2J 16.1 Hz)] 3.75 d [1Н,ArCH2 (1He), 2J 15.8 Hz], 3.84 d
2
[1Н, ArCH2 (1Ha), J 13.6 Hz], 3.87 d [1H, NHC(O)
СН2, 2J 15.6 Hz], 4.15 d [1Н, ArCH2 (1Ha), 2J 15.8 Hz],
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 2 2012

YESIPENKO et al.
290
N 1.33; S 3.10. С64Н79NО7S. Calculated, %: С 76.38;
Н 7.91; N 1.39; S 3.19.
%: С 77.31; Н 8.56; N 1.25; S 2.87. M 1118.6.
5,11,17,23-Tetra(p-tert-butyl)-28-[N-butyl-(1-
phenylethyl)carbamoylmethoxy]-25-butoxy-27-
[(4-methylphenyl)sulfonyloxy]-26-propoxycalix[4]
arene (IVb). Yield 0.18 g (63%), mp 112–113°С
(MeOH–H2O), Rf 0.45. IR spectrum (KBr), ν, cm–1:
Alkylation of calix[4]arenes IIIа, IIIb with butyl
bromide. A solution of 0.25 g (0.25 mmol) of calix[4]-
arene IIIа, IIIb in 3 ml of anhydrous acetonitrile was
added dropwise to a dispersion of 0.04 g (1.00 mmol) of
sodium hydride in 4 ml of acetonitrile at room temperature
stirring with a rate preventing vigorous foaming.After the
addition of all solution the reaction mixture was stirred
for 30 min at 40°С, to the dispersion 0.17 g (0.13 ml,
1.24 mmol) of butyl bromide in 3 ml of acetonitrile was
added, and the reaction mixture was boiled over 4–5 h.
The solvent was evaporated, the residue was dissolved
in 5 ml of chloroform, the solution was washed with
10% hydrochloric acid solution till acidic reaction (2 ×
2 ml), dried with Na2SO4, and evaporated. We obtained
0.26 g (92%) of yellow solid substance that was purified
by column chromatography, eluent hexane–ethyl acetate,
6 : 1.
1
1670 (С=О). Н NMR spectrum (DMSO-d6, 90°C),
3
δ, ppm: 0.75 t (3Н, СН3СН2СН2СН2N, J 7.2 Hz),
3
0.82 t (3Н, СН3СН2СН2СН2О, J 7.4 Hz), 1.00 s (9H,
3
t-Bu), 1.006 t (3Н, СН3СН2СН2О, J 7.4 Hz), 1.007 s
(9H, t-Bu), 1.07–1.22 m (6H, СН3СН2СН2СН2N +
СН3СН2СН2СН2O), 1.33 s (9H, t-Bu), 1.42 s (9H,
3
t-Bu), 1.49 d [3Н, CH3(Ph)CHNH, J 7.0 Hz], 1.42–
1.55 m (2Н, СН3СН2СН2СН2О), 1.76–1.90 m (2Н,
СН3СН2СН2О), 2.44 s (3H, CH3ArSO2), 2.86–3.00 m
(2H, СН3СН2СН2СН2N), 3.03 d [2Н, 2ArCH2 (2Не),
2
2J 12.8 Hz], 3.30 d [1Н, 2ArCH2 (1Не), J 13.6 Hz],
3.43–3.74 m [1Н, ArCH2 (1Не) + 1Н, ArCH2 (1На) +
2H, СН3СН2СН2О + 2H, СН3СН2СН2СН2О], 3.88 d
[1Н,ArCH2 (1На), 2J 13.6 Hz], 4.05 d [1Н,ArCH2 (1На),
2J 12.8 Hz], 4.09 d [1Н,ArCH2 (1На), 2J 12.8 Hz], 4.38 d
[1Н, NHC(O)СН2, 2J 13.4 Hz], 4.45 d [1H, NHC(O)СН2,
2J 13.4 Hz], 5.33–5.48 m [1H, CH3(Ph)CHNH], 6.52 d
5,11,17,23-Tetra(p-tert-butyl)-26-[N-butyl-(1-
phenylethyl)carbamoylmethoxy]-25-butoxy-27-
[(4-methylphenyl)sulfonyloxy]-28-propoxycalix[4]
arene (IVа). Yield 0.17 g (60%), mp 140–141°С
(MeOH), Rf 0.40. IR spectrum (KBr), ν, cm–1: 1670
(С=О). 1H NMR spectrum (DMSO-d6, 100°C), δ, ppm:
4
4
(1Нarom, J 2.5 Hz), 6.53 d (1Нarom, J 2.5 Hz), 6.71 d
4
4
(1Нarom, J 2.5 Hz), 6.81 d (1Нarom, J 2.5 Hz), 7.09 s
(2Нarom), 7.23–7.32 m [6H, 2Нarom + 4H, CH3(Ph)CHNH],
7.47 d (2H,ArSO2, 3J 8.3 Hz), 7.61 d [1Н, CH3(Ph)CHNH,
3
0.74 t (3Н, СН3СН2СН2СН2N, J 7.2 Hz), 0.82 t (3Н,
СН3СН2СН2СН2О, 3J 7.4 Hz), 1.00 s (9H, t-Bu), 1.01 s
(9H, t-Bu) + t (3Н, СН3СН2СН2О, 3J7.4 Hz), 1.07–1.22 m
(6H, СН3СН2СН2СН2N + СН3СН2СН2СН2O), 1.33 s
(9H, t-Bu), 1.43 s (9H, t-Bu), 1.46 d [3Н, CH3(Ph)CHNH,
3J 7.0 Hz], 1.45–1.54 m (2Н, СН3СН2СН2СН2О), 1.76–
1.89 m (2Н, СН3СН2СН2О), 2.45 s (3H, CH3ArSO2),
2.86–3.00 m (2H, СН3СН2СН2СН2N), 3.03 d [2Н,
3J 2.5 Hz], 7.69 d (2Н, ArSO2, J 8.3 Hz). Found, %:
3
С 77.17; Н 8.37; N 1.13; S 2.52. M+ 1118.8. С72Н95NО7S.
Calculated, %: С 77.31; Н 8.56; N 1.25; S 2.87. M 1118.6.
X-ray diffraction experiment was carried out on an
automatic diffractometer Xcalibur 3 (monochromated
MoKα radiation, CCD-detector, ω-scanning). The
structures were solved by the direct method with the use
of program package SHELXTL [15]. The configuration
of diastereomers for all molecules was determined
according to the known configuration of the chiral
center on the atom C57 that did not change in the course
of reactions. The restriction of bond lengths (Csp3–Csp3
1.54, Csp3–O 1.43 Å) was introduced in the refining of
the position of the propyl and tert-butyl substituents
with respect to the solvating methanol molecules in
IIIa structure. The positions of hydrogen atoms were
revealed from the difference synthesis of the electron
2
2ArCH2 (2Не), J 12.7 Hz], 3.32 d [1Н, ArCH2 (1Не),
2J 13.6 Hz], 3.43–3.73 m [1Н,ArCH2 (1Не) + 1Н,ArCH2
(1На) + 2H, СН3СН2СН2О + 2H, СН3СН2СН2СН2О],
3.88 d [1Н,ArCH2 (1На), 2J 13.6 Hz], 4.05 d [1Н,ArCH2
(1На), 2J 12.7 Hz], 4.12 d [1Н,ArCH2 (1На), 2J 12.7 Hz],
2
4.36 d [1Н, NHC(O)СН2, J 13.6 Hz], 4.49 d
2
[1H, NHC(O)СН2, J 13.6 Hz], 5.36–5.50 m [1H,
CH3(Ph)CHNH], 6.53 br.s (2Нarom), 6.72 d (1Нarom
,
,
4
4J 2.5 Hz), 6.80 d (1Нarom, J 2.5 Hz), 7.09 d (1Нarom
4
4J 2.4 Hz), 7.10 d (1Нarom, J 2.4 Hz), 7.23–7.34 m
[6Н, 2Нarom + 4H, CH3(Ph)CHNH], 7.47 d (2H, ArSO2,
3J 8.3 Hz), 7.59 d [1Н, CH3(Ph)CHNH, 3J 2.5 Hz], 7.69 d
density and were refined in the rider model with Uiso
=
3
(2Н, ArSO2, J 8.3 Hz). Mass spectrum, m/z (Irel, %):
nUeq (n = 1.5 for methyl and hydroxy groups, 1.2 for the
other hydrogen atoms). In structure IIIb the hydrogen
atoms involved into the hydrogen bonds formation were
1118.7 (100) [M]+, 1062.6 (50) [M – Bu]+. Found, %:
С 76.97; Н 8.25; N 1.56; S 2.50. С72Н95NО7S. Calculated,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 2 2012

SYNTHESIS AND STEREOCHEMICAL CONFIGURATION
291
Parameters
IIIа, IIIb (racemate)
IIIa
IIIb
IVa
Unit cell parameters
a, Å
17.0672(6)
18.7837(6)
19.5752(8)
90
13.411(2)
15.138(2)
31.353(4)
90
13.1552(3)
15.0305(3)
28.6873(5)
90
9.8984(5)
13.6458(9)
13.9768(7)
62.279(6)
74.448(4)
82.148(5)
1609.8(2)
606
b, Å
c, Å
α, deg
β, deg
115.117(5)
90
90
90
γ, deg
V, Å3
90
90
5682.1(4)
2168
6365(1)
2384
5672.3(2)
2168
F(000)
Crystal system
Monoclinic
P21
Rhombic
P212121
4
Rhombic
P212121
4
Triclinic
P1
Space group
Z
4
1
T, K
100
100
100
100
μ, mm–1
dcalc, g cm–3
0.110
0.107
1.150
50
0.110
1.178
60
0.104
1.176
1.154
2Θmax, deg
50
60
Measured reflections
37298
19063
0.084
35710
10891
0.164
5374
34685
16227
0.060
10740
681
16847
12414
0.043
Independent reflections
Rint
Reflections with F > 4σ(F)
10523
1315
9157
Refined parameters
719
747
R1
0.065
0.094
0.178
0.907
816610
0.068
0.110
0.951
816611
0.061
wR2
0.135
0.129
S
0.911
0.983
CCDC number
816612
816613
2007, vol. 9, p. 3117; Xu, Z.-X., Li, G.-K., Chen, Ch.-F.,
and Huang, Z.-T., Tetrahedron., 2008, vol. 64, p. 8668.
refined in the isotropic approximation. Crystallographic
data and the experimental parameters are presented
in the table. The final atomic coordinates, geometric
parameters, and crystallographic data are deposited in
the Cambridge Crystallographic Data Centre, 11 Union
Road, Cambridge, CB2 1EZ, UK (e-mail: deposit@ccdc.
cam.ac.uk). The registration data are given in the table.
4. Steyer, S., Jeunesse, C., Harrowfield, J., and Matt, D.,
J. Chem. Soc., Dalton Trans., 2005, p. 1301; Gaeta, C.,
De, Rosa, M., Fruilo, M., Soriente, A., and Neri, P.,
Tetrahedron: Asymmetry., 2005, vol. 16, p. 2333.
5. Luo, J., Zheng, Q.-Y., Chen, C.-F., and Huang, Z.-T.,
Tetrahedron, 2005, vol. 61, p. 8517; Karakucuk, A.,
Durmaz, M., Sirit, A., Yilmaz, M., and Demir, A.S.,
Tetrahedron: Asymmetry., 2006, vol. 17, p. 1963.
REFERENCES
6. Narumi, F., Suzuki, T., Onodera, T., and Miyano, S.,
Enantiomer., 2000, vol. 5, p. 83; Krawinkler, K.H.,
Maier, N.M., Ungaro, R., Sansone, F., Casnati, A., and
Lindner, W., Chirality, 2003, vol. 15, p. 17.
1. Gutsche, C.D., Calixarenes: An Introduction, Cambridge:
RSCPublishing, 2008.
2. Kubo, Y., Maeda, S., Tokita, S., and Kubo, M., Nature.,
1996, vol. 382, 522; Zheng, Y.-S., Zhang, C. Org.
Lett., 2004, vol. 6, 1189; Liu, X.-X. and Zheng, Y.-S.,
Tetrahedron Lett., 2006, vol. 47, p. 6357.
7. He, Y., Xiao, Y, Meng, L., Zeng, Z., Wu, X., and Wu, C.-T.,
Tetrahedron Lett., 2002, vol. 43, p. 6249; Narumi, F.,
Hattori, T., Matsumura, N., Onodera, T., Katagiri, H.,
Kabuto, C., Kameyama, H., and Miyano, S., Tetrahedron,
3. Shirakawa, S., Moriyama, A., and Shimizu, S., Org. Lett.,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 2 2012

YESIPENKO et al.
2000, vol. 2, p. 2237; Tairov, M.A., Vysotsky, M.O.,
292
2004, vol. 60, p. 7827.
Kalchenko, O.I., Pyrozhenko, V.V., and Kalchenko, V.I.,
J. Chem. Soc., Perkin Trans. I, 2002, p. 1405; Cao, Y.-
D., Luo, J., Zheng, Q.-Y., Chen, C.-F., Wang, M.-X.,
and Huang, Z.-T., J. Org. Chem., 2004, vol. 69, p. 206;
Miao, R., Zheng, Q.-Y., Chen, C.-F., and Huang, Z.-T.,
J. Org. Chem., 2005, vol. 70, p. 7662; Talotta, C., Gaeta, C.,
Troisi, F., Monaco, G., Zanasi, R., Mazzeo, G., Rosini, C.,
and Neri, P., Org. Lett., 2010, vol. 12, p. 2912.
8. Li, S.-Y., Xu, Y.-W., Liu, J.-M., and Su, Ch.-Y., Int. J. Mol.
Sci., 2011, vol. 12, p. 429.
9. Dieleman, C., Steyer, S., Jeunesse, C., and Matt, D.,
J. Chem. Soc., Dalton Trans., 2001, p. 2508; Narumi, F.,
Hattori, T., Yamabuki, W., Kabuto, C., and Kameyama, H.,
Tetrahedron: Asymmetry, 2005, vol. 16, p. 793; Boyko, V.I.,
Shivanyuk, A., Pyrozhenko, V.V., Zubatyuk, R.I.,
Shiskin, O.V., and Kalchenko, V.I., Tetrahedron Lett.,
2006, vol. 47, p. 7775; Yakovenko, A.V., Boyko, V.I.,
Danylyuk, O., Suwinska, K., Lipkowski, J., and
Kalchenko, V.I., Org. Lett., 2007, vol. 9, p. 1183; Xu, Z.-
X., Zhang, Ch., Zheng, Q.-Y., Chen, Ch.-F., and Huang, Z.-
T., Org. Lett., 2007, vol. 9, p. 4447; Xu, Z.-X., Huang,
Z.-T., and Chen, Ch.-F., Tetrahedron Lett., 2009, vol. 50,
p. 5430; Boyko, V.I., Matvieiev, Yu.I., Klyachina, M.A.,
Yesypenko, O.A., Shishkina, S.V., Shishkin, O.V., and
Kalchenko, V.I., Tetrahedron, 2009, vol. 65, p. 4220.
11. Kliachyna, M.A., Yesypenko, O.A., Pirozhenko, V.V.,
Shishkina, S.V., Shishkin, O.V., Boyko, V.I., and
Kalchenko, V.I., Tetrahydron, 2009, vol. 65, p. 7085.
12. Esypenko, O.A., Kliachina, M.A., Boyko, V.I., and
Kalchenko, V.I., Vopr. Khim. Kkhim. Tekhnol., 2009, no. 4,
p. 10.
13. Böhmer, V., Angew. Chem., Int. Ed., 1995, vol. 34, p. 713;
Iwamoto, K., Araki, K., and Shinkai, S., J. Org. Chem.,
1991, vol. 56, p. 4955.
10. Caccamese, S., Bottino, A., Cunsolo, F., Parlato, S.,
and Neti, P., Tetrahedron: Asymmetry, 2000, vol. 11,
p. 3103; Hesek, D., Inoue, Y., Drew, M.G., Beer, P.D.,
Hembury, G.A., Ishida, H., and Aoki, F., Org. Lett.,
14. Jaime, C., de, Mendoza, J., Prados, P., Nieto, P.M., and
Sanchez, C., J. Org. Chem., 1991, vol. 56, p. 3372.
15. Sheldrick, G.M., Acta Cryst. A, 2008, vol. 64, p. 112.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 2 2012