Novel synthesis and characterization of 1,3-bis(2-dihydrothiazolyl) thiaalkoxy-p-tert-butylcalix[4]arenes

Article abstract of DOI:10.1080/00397910701555212

A novel series of 1,3-bis(2-dihydrothiazolyl)thiaalkoxy-p-tert- butylcalix[4]arenes generated by the reaction between 4,5-dihydrothiazole-2- thiol and the different dibromide calix[4]aryl groups have been synthesized and structurally characterized by IR, 1H NMR, 13C NMR, and MS. From their analytical data, it was found that compounds 8, 9, and 10 had cone conformations, whereas compound 11 existed as a mixture conformation. To verify the structure of the synthetic compounds, a single-crystal X-ray structure of compound 8 was obtained. Copyright Taylor & Francis Group, LLC.

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Novel Synthesis and Characterization of
1
,3‐Bis(2‐dihydrothiazolyl)thiaalkoxy‐p‐tert‐butyl
a a a
Bing Zhao , Ya‐Qing Feng & Sha‐Sha Zhang
a
School of Chemical Engineering and Technology, Tianjin University, Tianjin,
China
Published online: 05 Oct 2007.
To cite this article: Bing Zhao , Ya‐Qing Feng & Sha‐Sha Zhang (2007): Novel Synthesis and Characterization of
1,3‐Bis(2‐dihydrothiazolyl)thiaalkoxy‐p‐tert‐butylcalix[4]arenes, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 37:20, 3479-3484
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Synthetic Communications , 37: 3479–3484, 2007
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910701555212
Novel Synthesis and Characterization
of 1,3-Bis(2-dihydrothiazolyl)thiaalkoxy-
p-tert-butylcalix[4]arenes
Bing Zhao, Ya-Qing Feng, and Sha-Sha Zhang
School of Chemical Engineering and Technology, Tianjin University,
Tianjin, China
Abstract: A novel series of 1,3-bis(2-dihydrothiazolyl)thiaalkoxy-p-tert-butylcalix[4]-
arenes generated by the reaction between 4,5-dihydrothiazole-2-thiol and the different
dibromide calix[4]aryl groups have been synthesized and structurally characterized by
1
13
IR, H NMR, C NMR, and MS. From their analytical data, it was found that
compounds 8, 9, and 10 had cone conformations, whereas compound 11 existed as a
mixture conformation. To verify the structure of the synthetic compounds, a single-
crystal X-ray structure of compound 8 was obtained.
Keywords: calix[4]arenes, characterization, conformation, dihydrothiazolyl, synthesis,
X-ray structure
INTRODUCTION
Design, synthesis, and development of novel macrocyclic molecules are
currently receiving interest in the field of supramolecular chemistry. The
calixarene family, as the third generation of the host cyclic molecules, has
received more positive attention because their derivatives can serve as a
platform that can be modified by various potential receptors for cations and
[
1]
anions or neutral molecules.
To date, many calixarene derivatives have been synthesized. Among
them, derivatives decorated with heteroatoms both at the lower and upper
rims also have been synthesized in definite, desired conformations including
Received February 9, 2007
Address correspondence to Ya-Qing Feng, School of Chemical Engineering and
Technology, Tianjin University, Tianjin 300072, China. E-mail: yqfeng@tju.edu.cn
3
479

3
480
B. Zhao, Y.-Q. Feng, and S.-S. Zhang
[
2]
[3]
[4]
substituted amides, amide-bridged calixarene, thiacalixarene, and so on.
Recently, many of the heterocyclic groups, such as pyridyl, bipyridyl, bithiazo-
lyl, and benzothiazolyl, have been introduced into the calixarenes both at their
[
5]
lower and upper rims. It is well known that calixarene derivatives containing
nitrogen and sulfur atoms would be more sensitive to transition-metal ions and
show better complexation ability. In this present communication, we report the
synthesis and characterization of novel calix[4]arene derivatives modified by
4
,5-dihydrothiazole-2-thiol in the lower rim. 4,5-Dihydrothiazole-2-thiol,
containing two sulfur atoms and one nitrogen atom, is an important hetero-
cyclic compound. After the 4,5-dihydrothiazole-2-thiol is introduced into the
calix[4]arenes in the lower rim, the target compounds, 1,3-bis(2-dihydrothiazo-
lyl)thiaalkoxy-p-tert-butylcalix[4]arenes derivates, would exhibit better selec-
tivity of bonding to transition-metal ions over alkali metal ions. As far as
we know, the 1,3-bis(2-dihydrothiazolyl)thiaalkoxy-p-tert-butylcalix[4]arene
derivates have not been reported, and the further evaluation of their metal
ions is in progress.
RESULTS AND DISCUSSION
The synthetic pathway to the target compounds (8–11) is depicted in
Scheme 1. Compounds 1–3 were synthesized according to the literature
[
6]
procedure. Compound 4 was obtained by the reaction of p-tert-butylcalix[4]-
arene with n-BuBr in N,N-dimethylformamide (DMF) in the presence of
K CO . For the 1,3-dimethylation, compound 5 was synthesized by the
2
3
reaction of p-tert-butylcalix[4]arene with the CH I in dry acetone solution
3
Scheme 1.

Novel Synthesis and Characterization
3481
with K CO as base. In particular, the reaction was performed in a sealed vessel,
2
3
which increases the speed of the reaction and shortens the time of the reaction.
Compounds 6 and 7 can be prepared by the treatment of compounds 4 and 5
with 1,3-dibromopropane. The synthesis of the target compounds 8–11 was
achieved through the condensation of the appropriate dibromides (compounds
2
, 3, 6, and 7) with 4,5-dihydrothiazole-2-thiol and release of the HBr molecule.
1
The structures of compounds 8–11 were established by infrared (IR), H
1
NMR, C NMR, and mass spectrometer (MS). The results showed that
3
compounds 8–10 were in cone conformations. Take compound 8 as an
1
example. In the H NMR spectra in CDCl , the proton signals of ArCH Ar
3
2
appeared as two doublets at d 4.22 and 3.22 ppm, and the chemical shift differ-
ence was about 1.0, which indicates this compound exists in a cone confor-
1
mation in solution. Moreover, in the C NMR, the signal peak of the
3
methylene carbons of ArCH Ar appeared at about 31 ppm according to
2
[
7]
Mendoza rule. It is also consistent with the cone conformation. Further-
more, X-ray crystal analysis also confirmed the structure of compound 8.
The crystal structure is shown in Fig. 1. The two phenyl ring planes [C1–
C6 and C23–C28] with the alkoxyl group make an angle of 45.4(3)8,
whereas the dihedral angle of the other two opposite phenolic rings [C12–
C17 and C34–C39] is 83.9(3)8. Therefore, the calix[4]arene moiety exists
in a pinched-cone conformation in the crystals. Naturally, the two pendants,
namely the 4,5-dihydrothiazolyl-2-thiapropoxyl moieties, are located in the
same side of the calix[4]aryl cavity. The structures of compounds 9 and 10
were deduced from the similarity.
Figure 1. Crystal structure of compound 8. Hydrogen atoms have been omitted.

3
482
B. Zhao, Y.-Q. Feng, and S.-S. Zhang
In comparison with compounds 8–10, it is remarkable that there is not a
1
clear H NMR spectra of compound 11 in CDCl to be obtained, due to the
3
methylation in the lower rim. The two methyl groups in the lower rim
cannot provide enough steric hindrance to control the calix[4]arene moiety
1
into a single conformation. As shown from its H NMR, the signal peaks of
the tert-butyl groups appear as the multiple absorption because of the confor-
mational conversion of calix[4]arene, so we got only the mixture confor-
mational compound 11 in CDCl3.
EXPERIMENTAL
Melting points were measured on a Yanagimoto MP-500 apparatus (uncor-
rected). The Fourier transform-infrared (FT-IR) spectra (KBr pellets) were
1
measured on a Bio-rad FTS3000 infrared spectrometer. The H NMR and
13
C
NMR spectra were recorded in CDCl using TMS as an internal standard on
3
Bruker Av500-MHz and 75-MHz instruments at 298 K. Mass spectra were
carried out on a LCQ Advantage MAX spectrometer. X-ray data were
recorded using a Smart-1000 CCD automatic diffractometer. All reagents are
commercially available and purified by standard methods prior to use.
General Procedure for the Preparation of Compounds 8–11
To a CH CN solution (30 mL) of 4,5-dihydrothiazole-2-thiol (0.30 g,
3
2.5 mmoL), KOH (0.56 g, 10 mmoL) was added. The suspension was
stirred at 508C until the solution was clarified. Then, the appropriate calix[4]-
arene dibromides (1 mmoL) (compounds 2, 3, 6, and 7) were added.
The reaction mixture was further stirred with reflux for 8 h. The solvent
was removed under reduced pressure. The residue was taken up in CH Cl
2
2
(
anhydrous magnesium sulfate, CH Cl was removed. The crude product
50 mL) and washed with brine (60 mL) three times. After drying with
2
2
was further purified by flash chromatography, eluting with a mixture of
petroleum ether (60–908C) and ethyl acetate. After purification, the target
compounds 8–11 were characterized by the spectra.
Data
2
1
5,27-Dihydroxy-26,28-bis[3-(4,5-dihydrothiazolyl-2-thia)propoxy]-5,11,-
7,23-tetra-t-butylcalix[4]arene 8. White solid, yield 65%, mp 208–2118C;
2
1
1
IR (KBr, cm ): 3282, 3043, 2955, 2872, 1573; H NMR (CDCl ): d 7.62
3
(
s, 2H, ArOH), 7.25 (s, 4H, ArH), 6.84 (s, 4H, ArH), 4.22 (d, 4H,
J ¼ 13.0 Hz, ArCH Ar), 4.19 (t, 4H, J ¼ 8.0 Hz, SCH CH N), 4.08 (t, 4H,
2
2
2
J ¼ 6.5 Hz, ArOCH ), 3.60 (t, 4H, J ¼ 6.5 Hz, CH S), 3.22 (d, 4H,
2
2

Novel Synthesis and Characterization
3483
J ¼ 13.0 Hz, ArCH Ar), 3.20 (t, 4H, J ¼ 8.0 Hz, SCH CH N), 2.41 (m, 4H,
2
2
2
1
3
ArOCH CH CH S), 1.27 [s, 18H, C(CH ) ], 0.99 [s, 18H, C(CH ) ]; C
NMR (CDCl ): d 29.07 [2C(CH ) ], 29.84 [2C(CH ) ], 31.04 (6CH ),
2
2
2
3 3
3 3
3
3 3
3 3
3
3
3
1
1.70 (6CH ), 31.91 (4ArCH Ar), 33.8 (hetero 2C), 34.00 (hetero 2C),
3 2
5.29 (2OCH CH CH S), 64.27 (2CH S), 73.92 (2CH O), [125.13 (4C),
2
2
2
2
2
25.60 (4C), 127.60 (4C), 132.73 (4C), 141.53 (2C), 147.06 (2C), 149.46
(
(
2C), 150.69 (2C)] (aromatic 24C), 167.58 (hetero 2C). ESI-MS m/z 989.7
M þ Na) .
þ
2
2
(
5,27-Dihydroxy-26,28-bis[4-(4,5-dihydrothiazolyl-2-thia)butoxy]-5,11,17,-
3-tetra-t-butylcalix[4]arene 9. White solid, yield 60%, mp 180–1848C; IR
2
1
1
KBr, cm ): 3282, 3043, 2955, 2872, 1573; H NMR (CDCl ): d 7.56
3
(
s, 2H, ArOH), 7.05 (s, 4H, ArH), 6.82 (s, 4H, ArH), 4.26 (d, 4H, J ¼
1
3.0 Hz, ArCH Ar), 4.19 (t, 4H, J ¼ 8.0 Hz, SCH CH N), 4.00 (t, 4H,
2 2
2
2
2
J ¼ 6.5 Hz, ArOCH ), 3.35 (d, 4H, J ¼ 13.0 Hz, ArCH Ar), 3.10
(
t, 4H, J ¼ 8.0 Hz, SCH CH N), 2.13 (m, 8H, ArOCH CH CH CH S), 1.29
2
2
2
2
2
2
1
3
[s, 18H, C(CH ) ], 0.98 [s, 18H, C(CH ) ]; C NMR (CDCl ): d 26.11
3 3 3 3 3
[2C(CH ) ], 29.09 [2C(CH ) ], 31.04 (6CH ), 31.71 (6CH ), 31.83
3 3 3 3 3 3
(4ArCH Ar), 32.69 (2OCH CH CH CH S), 33.80 (hetero 2C), 33.94 (hetero
2 2 2 2 2
2C), 35.31 (2OCH CH CH CH S), 64.18 (2CH S), 75.73 (2CH O), [125.06
2 2 2 2 2 2
(4C), 125.50 (4C), 127.69 (4C), 132.65 (4C), 141.36 (2C), 146.82 (2C),
1
1
49.85 (2C), 150.74 (2C)] (aromatic 24C), 166.49 (hetero 2C). ESI-MS m/z
þ
017.5 (M þ Na) .
2
2
(
5,27-Dibutoxy-26,28-bis[3-(4,5-dihydrothiazolyl-2-thia)propoxy]-5,11,17,-
3-tetra-t-butylcalix[4]arene 10. White solid, yield 70%, mp 135–1378C; IR
2
1
1
KBr, cm ): 3032, 2958, 2868, 1571; H NMR (CDCl ): d 6.89 (s, 4H,
3
ArH), 6.68 (s, 4H, ArH), 4.36 (d, 4H, J ¼ 12.5 Hz, ArCH Ar), 4.23 (t.
2
4
H, J ¼ 8.0 Hz, SCH CH N), 4.00 (t, 4H, J ¼ 7.5 Hz, ArOCH ), 3.81 (t, 4H,
2 2 2
2
2
2
J ¼ 7.5 Hz, ArOCH ), 3.40 (t, 4H, J ¼ 8.0 Hz, SCH CH N), 3.29 (t,
4
ArOCH CH CH SPy), 1.94 (m, 4H, ArOCH CH CH CH ), 1.44 (m,
H, J ¼ 7.5 Hz, CH S), 3.14 (d, 4H, J ¼ 12.5 Hz, ArCH Ar), 2.44 (m, 4H,
2 2 2 2 2 2 3
2
2
4
H, ArOCH CH CH CH ), 1.17 [s, 18H, C(CH ) ], 1.00 [s, 18H, C(CH ) ],
2 2 2 3 3 3 3 3
1
3
0
.95 [t, 6H, J ¼ 7.5 Hz, ArOCH CH CH CH ); C NMR (CDCl ): d 14.40
2
2
2
3
3
(2ArOCH CH CH CH ), 19.62 (2ArOCH CH CH CH ), 29.95 [4C(CH ) ],
2 2 2 3 2 2 2 3 3 3
3
CH ), 33.93 (hetero 2C), 34.10 (hetero 2C), 35.58 (2OCH CH CH S), 64.45
1.28 (4ArCH Ar), 31.56 (6CH ), 31.74 (6CH ), 32.60 (2ArOCH CH CH
2 3 3 2 2 2-
3
2
2
2
(
(
(
2CH S), 73.61 (2CH O), 75.57 (2CH O), [124.99 (4C), 125.37 (4C), 133.33
2 2 2
4C), 134.51 (4C), 144.39 (2C), 144.88 (2C), 155.38 (2C), 153.80 (2C)],
aromatic 24C), 165.75 (hetero 2C). ESI-MS m/z 1101.7 (M þ Na)þ.
2
1
5,27-Dimethoxy-26,28-bis[3-(4,5-dihydrothiazolyl-2-thia)propoxy]-5,11,
7,23-tetra-t-butylcalix[4]arene 11. White solid, yield 70%, mp 135–1378C;
2
1
1
IR (KBr, cm ): 3036, 2926, 2868, 1572; H NMR (CDCl ): d 7.23–6.77
3
(
m, 8H, ArH), 4.29 (d, 4H, J ¼ 12.5 Hz, ArCH Ar), 4.21 (t, 4H,
2

3
484
B. Zhao, Y.-Q. Feng, and S.-S. Zhang
J ¼ 8.0 Hz, SCH CH N), 3.93 (br, 6H, ArOCH ), 4.19–3.15 (m, 12H), 3.39
2
2
3
(
t, 4H, J ¼ 8.0 Hz, SCH CH N), 2.31–2.27 (m, 4H, ArOCH CH CH ),
2
2
2
2
2
þ
1
.35–1.06 (m, 36H, CH ); ESI-MS m/z 1017.7 (M þ Na) .
3
ACKNOWLEDGMENTS
Thanks for the support of the National Natural Science Foundation of China
No. 20376059).
(
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7