Synthesis and structural properties of novel calixarene analogues having Schiff base units

Article abstract of DOI:10.3184/030823407X266225

Novel calixarene analogues having Schiff base units have been synthesised by condensation reaction of the bisaldehyde with ophenylenediamines in the presence of boric acid. The present calixarene analogues form hydrogen bonds between imine nitrogen and ph

Full text of DOI:10.3184/030823407X266225

JOURNAL OF CHEMICAL RESEARCH 2007
NOvEMbER, 649–652
RESEARCH PAPER 649
Synthesis and structural properties of novel calixarene analogues having
Schiff base units
Takehiko Yamatoa*, Shinpei Miyamotoa, Masashi Takimotoa and Pierre Thuéryb
aDepartment of Applied Chemistry, Faculty of Science and Engineering, Saga University, Honjo-machi 1, Saga-shi, Saga 840-8502,
Japan
bService de Chimie Moléculaire, DSM, DRECAM, CNRS URA 331, CEA Saclay, 91191 Gif-sur-Yvette, France
Novel calixarene analogues having Schiff base units have been synthesised by condensation reaction of the
bisaldehyde with o-phenylenediamines in the presence of boric acid. The present calixarene analogues form
hydrogen bonds between imine nitrogen and phenol hydrogen with 1,2-alternate conformation, confirmed by X-ray
crystallography.
Keywords: schiff base condensation reaction, calixarene analogue, hydrogen bond, conformation
Development of conjugated macrocycles is a rapidly
growing area of interest because they may form the basis of
catalytic,1 magnetic,2 liquid crystalline,3 pharmaceutical,4
and supramolecular materials.5 Aldehyde and amine repeat
formation and cleavage of Schiff base combination (imino
group) reversibly under suitable reaction conditions, finally,
reach the thermodynamic most stable state. The library of
cyclic compound with various composition ratios is formed
when there are some formyl groups and amino groups,
respectively, the specific compound obtained selectively.
Since the structure of a product depends on the structure of
the materials to be used, the correlation with the structure of
a spacer and the starting materials which connect a formyl
group or an amino group is greatly interesting. For example,
the reaction of the bis(hydroxybenzaldehyde) derivatives
with diamines in which have various spacer gave 1:1 or
2:2 macrocycles.6 In the synthesis of macrocycles which
has Schiff base unit, many researches on correlation with
the structure of a spacer7 and a product are clarified by the
construction of various libraries and calculation of molecular
orbital.8 However, there are only few reports about the
structural characteristics. We now report on the synthesis of
novel calixarene analogues and structural studies in solution
and in the solid state as well as their complexation properties
with transition metals.
Results and discussion
Synthesis
Novel calixarene analogues having Schiff base units have
been synthesised by Schiff base condensation reaction as
shown in Scheme 1. Thus, 1,3-bis(5-tert-butyl-3-formyl-2-
hydroxyphenyl)propane 2 was prepared by formylation of
1,3-bis(5-tert-butyl-2-hydroxyphenyl)popane 19 with hexa-
methylentetramine in trifluoroacetic acid followed by
hydrolysis10 in 74% yield. The attempted codensation reaction
of 2 with o-phenylenediamine (3a) under benzene reflux
failed. Only intractable mixture of products was obtained.
No formation of the cyclised products was observed. Recently,
Hisaeda and coworkers have succeeded in preparation 2:2
macrocycle by the using a boric acid template effect.11 In fact,
the condensation reaction of 2 with o-phenylenendiamine (3a)
using the boric ion template method in CH2Cl2/methanol at
room temperature afforded the desired calixarene analogue 4a
as a 2:2 macrocycle in 75% yield. Similar result was obtained
in the condensation reaction of 2 with 1,2-diamino-4,5-
dimethylbenzene (3b) under the reaction conditions described
above afforded 4b in 72% yield.
Structural properties
Since calixarene analogues 4a and 4b has phenolic hydroxyl
groups and imine nitrogens in a molecule, the formation of
intramolecular hydrogen bond is expected. First, in order
OH
OH
OH
OH
1) Hexamethylenetetramine
CF3COOH, 90°C for 24 h
CHO
OHC
2) 10% HCl aq.
0°C for 1 h
(74%)
tBu
tBu
tBu
tBu
tBu
2
1
tBu
HO
OH
N
N
N
N
H2N
R
NH2
R
R
R
B(OH)3
+
2
CH2Cl2/MeOH
room temp. for 24 h
R
R
HO
OH
3a; R= H
b; R= Me
tBu
tBu
4a; R= H (75%)
b; R= Me (72%)
Scheme 1
* Correspondent. E-mail: yamatot@cc.saga-u.ac.jp
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650 JOURNAL OF CHEMICAL RESEARCH 2007
tBu
Me
Me
1) hexamethylene
HO
HO
OH
OH
tetramine, CF3COOH,
Me
Me
CHO
3a
N
90°C for 24 h
CH2Cl2
room temp.
for 24 h
(63%)
2) 10% HCl aq.
N
0°C for 1 h
(54%)
tBu
5
tBu
6
tBu
7
Scheme 2
to check the formation of intramolecular hydrogen bond,
1H NMR spectrum of 4a and 4b were measured by two kinds
of solvents, CDCl3 and DMSO-d6. When CDCl3 was used as
solvent, the signals for the phenolic hydroxyl group protons
were observed at d 13.32 and 13.30 ppm, respectively. In order
to investigate the intramolecular hydrogen bond between the
neighbouring phenolic hydroxyl groups and imine nitrogens
of 4 in detail, a reference compound 7 was synthesised from
4-tert-butyl-2-methylphenol 5 following the similar method
in the preparation of 4.
(a)
The intramolecular hydrogen bond was formed between
neighbouring OH and imine nitrogen which induced a large
downfield shift for OH proton (d13.32 ppm, Dd = + 0.26 ppm)
and CH=N proton (d 8.68 ppm, Dd = + 0.09 ppm) in 4a
compared to compound 7 (OH proton, d 13.06 ppm; CH=N
proton, d 8.59 ppm). Similar findings were observed for
4b (d 13.30 ppm, Dd = + 0.24 ppm for OH proton). These
observations are attributable to the macrocyclic structure of
4, which might enhance the present intramolecular hydrogen
bond.
(b)
Interestingly, the chemical shift of the OH protons in 4a was
shifted to upper field to d 8.92 ppm in DMSO-d6 than that in
CDCl3 (d 13.32 ppm, Dd = –4.40 ppm) for 4a. Similar finding
was observed for 4b (d 8.99 ppm in DMSO-d6 and d13.30 ppm
in CDCl3, Dd = –4.31 ppm). These phenomena were attributed
to the intermolecular hydrogen bonding formed between
the OH proton and solvent DMSO-d6. The intramolecular
hydrogen bonding formed in compounds 4 was broken and
the new intermolecular hydrogen bonding was formed.
Therefore, it can be surmised that calixarene analogues 4 form
the intramolecular hydrogen bond between phenolic hydroxyl
group proton and nitrogen of imino group different from that
Fig. 1 Ball-and-stick diagram of the X-ray structure of 4a
excluding the two CH2Cl2 molecules: (a) top view, hydrogen
atoms except phenolic hydrogen atoms are excluded
for clarity. Hydrogen bonds are shown as dashed lines; (b)
side view.
1
for calixarenes.12 The H NMR spectrum (in CDCl3) of 4a
indicates the cyclophane ring to be extremely flexible from
the observation of no changes of methylene signals at d = 2.17
and 2.77 ppm for propane bridge (CH2CH2CH2) even at
the lower temperature (–60°C in CD2Cl2). Interestingly,
decreasing the temperature the chemical shift of OH proton
shifted to downfield from at d 13.30 ppm at 27°C to 14.00 ppm
at –40°C in CDCl3. This phenomenon seems to be attributed
to the increased intramolecular hydrogen bonding by the
much favourable conformation between phenolic hydroxyl
group proton and nitrogen of imino group.
stick diagram of the structure of 4a from the single crystal
X-ray diffraction analysis, excluding the two CH2Cl2
molecules, is shown in Fig. 1. In the solid state, it is clear that
compound 4a adopts a 1,2-alternate conformation.
The structural property of 4a had been clarified the formation
of hydrogen bonds between a phenolic hydroxyl group proton
and imino group nitrogen that forms a flat pseudo 6-membered
ring structure. In fact, X-ray structure shows the 6-membered
ring formed by the hydrogen bond (Fig. 1). Furthermore, 4a
has a symmetrical side centreing on propane bridge and both
the 1,2-bisimino benzene rings were orientated outwards with
respect to the cavity. The imine unit (C–C=N) and the phenol
rings are almost coplanar with interplanar angles of 0.22 and
4.04 (4)°, respectively, whereas on the other side, the imine
unit (C–N=C) and the phenylenediamine rings deviate from
coplanarity by 27.76 and 36.08°, respectively. The latter non-
The structure of 4a has been assigned by 1H NMR spectro-
scopy and confirmed by X-ray crystallography. The 1H NMR
spectrum of 4a shows a singlet for the tert-butyl protons at
d 1.30 ppm and a set of doublets for the aromatic protons
at d 7.20, 7.30 ppm (J = 2.4 Hz). Other signals in the 1H NMR
spectrum may correspond to both the cone, 1,2-alternate or
1,4-alternate conformer like those for dihomocalix[4]arenes.13
Fortunately, recrystallisation from MeOH and CH2Cl2
produces X-ray quality colourless crystals of 4a. The crystals
include the two molecules of dichloromethane. The ball-and-
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JOURNAL OF CHEMICAL RESEARCH 2007 651
Preparation of calixarene analogue (4b): To a solution of 2
(200 mg, 0.50 mmol) in CH2Cl2 (7 cm3) and CH3OH (7 cm3)
was added a boric acid (16 mg, 0.25 mmol) and stirred for 1 h at
room temperature. Then a mixture was added 1,2-diamino-4,5-
dimethylbenzene (3b) (69 mg, 0.50 mmol) and yellow precipitates
appeared during stirring for 24 h. The precipitates were collected by
filtration, washed by methanol and dried in vacuo. Recrystallisation
from CH2Cl2/methanol (1:2) afforded calixarene analogue 4b
(180 mg, 72%) as yellow prisms, m.p. 243–244°C (decomp.);
IR;n(Kbr)/cm-1 3743,3673,2921,2886,1732,1622,1575,1456,1393,
planalities from the phenylenediamine ring are much smaller
than that of acyclic Schiff base compound (56.2°) reported
by Yang et al.14 This finding might be attributable to the
cyclic structure of 4. Schiff base macrocycle 4 contains four
intramolecular O–H---N hydrogen bonds between the phenol
O atom and the imine N atoms (N---H–O, 1.766 and 1.829 Å).
No notable intermolecular interaction between the molecules
of 4 or interactions involving the solvent molecules were
found.
The complexation experiments of the novel calixarene
analogues 4a and 4b with transition metals such as Ni(OAc)2
or Pd(OAc)2 were carried out. Unfortunately, although the
formation of the desired complexed products were detected by
the mass spectroscopy, isolation failed due to its low solubility
in organic solvents.
1
1266, 1213, 1057, 1003, 875, 773, 646 and 478; H NMR (CDCl3)
d 1.30 (36H, s, tbu), 2.19 (4H, m, CH2CH2CH2), 2.30 (12H, s, CH3),
2.76 (8H, t, J = 8.6 Hz, CH2CH2CH2), 7.10 (4H, s, ArH), 7.20 (4H, d,
J = 2.4 Hz, ArH), 7.30 (4H, d, J = 2.4 Hz, ArH), 8.60 (4H, s,
CH=N) and 13.30 (4H, s, OH); MS: m/z M+ 992.6. Anal. calcd.
for C66H80N4O4 (992.62) C 79.80, H 8.12, N 5.64; found: C 79.72,
H 8.10, N 5.60.
Preparation of 4-tert-butyl-2-formyl-6-methylphenol (6): To a
solution of 4-tert-butyl-2-methylphenol 5 (2.19 g, 13.3 mmol) in
CF3COOH (22 cm3) was added a hexamethylenetetramine (9.35 g,
66.7 mmol) and stirred for 24 h at 90°C. Then a reaction mixture
was cooled and poured into 10% HCl aqueous solution (150 cm3).
After 1 h, the mixture was extracted with CH2Cl2. The extracts were
washed with 10% HCl aq. and distilled water, dried with Na2SO4, and
concentrated in vacuo to gave crude as a yellow oil. The residue was
treated over colum chromatography (SiO2) to afford 6 (1.38 g, 54%)
from CHCl3 eluent as yellow oil; IR; n(NaCl)/cm-1 1652 (C=O);
1H NMR (CDCl3) d 1.32 (9H, s, tbu), 2.27 (3H, s, CH3), 7.37 (1H,
d, J = 2.4 Hz, ArH), 7.44 (1H, d, J = 2.4 Hz, ArH), 9.86 (1H, s, OH)
and 11.11 (1H, s, CHO); MS: m/z M+ 192. Anal. calcd. for C12H16O2
(192.12) C 74.97, H 8.39; found: C 74.94, H 8.26.
Preparation of 7: To a solution of 6 (330 mg, 1.73 mmol)
in CH2Cl2 (5 cm3) was added o-phenylenediamine (140 mg,
1.29 mmol) and stirred for 24 h at room temperature. The reaction
mixture was condensed in vacuum to afford a residue. Although the
residue a small amount of hexane (3 cm3) and a yellow precipitate
was collected by filtration, washed by hexane and dried in vacuo.
Recrystallisation from hexane afforded 7 (248 mg, 63%) as yellow
prisms, m.p. 95–96°C. IR; n(Kbr)/cm-1 3514, 3361 (OH), 2956,
1624, 1569, 1466, 1457, 1360, 1305, 1266, 1175, 1149, 1124, 1034,
975, 924, 873, 814, 749, 668, 506 and 429. 1H NMR (CDCl3) d 1.36
(18H, s, tbu), 2.32 (6H, s, CH3), 7.04 (4H, m, ArH), 7.22 (2H, d,
J = 2.1 Hz, ArH), 7.29 (2H, d, J = 2.1 Hz, ArH), 8.59 (2H, s, CH=N)
and 13.06 (2H, broad s, OH). MS: m/z M+ 456. Anal. calcd. for
C30H36N2O2 (456.28) C 78.91, H 7.95, N 6.13; found: C 78.76, H
7.91, N 6.16.
Conclusions
We have synthesised the novel calixarene analogues 4a and
4b by a convenient method and characterised their structures.
These compounds form the strong intramolecular hydrogen
bond between phenolic hydroxyl proton and the imino group
nitrogen. However, no notable intramolecular interaction
between the neighboring OH groups was found, which might
lead strong contribution to the flexibility of these molecules.
The complexation studies of the novel calixarene analogues
4a and 4b with transition metals are now under investigation
in our laboratory.
Experimental
1
All melting points are uncorrected. H NMR spectra were recorded
at 300 MHz on a Nippon Denshi JEOL FT-300 NMR spectrometer
in deuteriochloroform with Me4Si as an internal reference. IR spectra
were measured as Kbr pellets on a Nippon Denshi JIR-AQ2OM
spectrometer. Mass spectra were obtained on a Nippon Denshi JMS-
HX110A Ultrahigh performance mass spectrometer at 75 eV using
a direct-inlet system. Elemental analyses were performed by Yanaco
MT-5 after the samples are dried in vacuum (0.1 torr) at 50°C.
Materials
Synthesis of 1,3-bis(5-tert-butyl-2-hydroxyphenyl)propane 1 was
carried out according to the reported procedure.9
Crystallographic data for 4a: Crystal data for 4a: C62H74N4O4,
2(CH2Cl2) (sum formula: C64H76Cl4N4O4), M = 1107.09, triclinic,
P–1, a = 9.6084 (12), b = 10.9452 (3), c = 14.349 (2) Å, V = 1435.1
(3) Å3, a = 91.968 (8), b = 101.050 (7), g = 103.511 (8), Z = 1,
Dc = 1.281 g cm-3, m(Mo-Ka) = 0.258 mm-1, T = 100(2) K,
translucent light orange prisms; 20128 reflections measured on a
Kappa CCD diffractometer, of which 5072 were independent, data
corrected for absorption on the basis of symmetry equivalent and
repeated data (min and max transmission factors: 0.946, 0.979) and
Lp effects, Rint = 0.0648, structure solved by direct methods (bruker
SHELXTL), F2 refinement, R1 = 0.0522 for 5072 data with F2> 2
s(F2), wR2 = 0.1196 for all data, 3869 parameters. Crystallographic
data (excluding structure factors) for the structures in this paper have
been deposited with the Cambridge Crystallographic Data Centre
as supplementary publication numbers CCDC 651077. Copies of
the data can be obtained, free of charge, on application to CCDC,
12 Union Road, Cambridge Cb2 1EZ, UK [fax: 144-1223-336033 or
e-mail: deposit@ccdc.cam.ac.uk].
Preparation of 1,3-bis(5-tert-butyl-3-formyl-2-hydroxyphenyl)
propane (2): To a solution of 1,3-bis(5-tert-butyl-2-hydroxyphenyl)
propane 1 (1.0 g, 2.94 mmol) in CF3COOH (10 cm3) was added a
hexamethylenetetramine (1.03 g, 7.34 mmol) and stirred for 24 h at
90°C. Then a reaction mixture was cooled and poured into 10% HCl
aqueous solution. After 1 h, the mixture was extracted with CH2Cl2.
The extracts were washed with 10% HCl aq. and distilled water, dried
with Na2SO4, and concentrated in vacuo to gave crude as a yellow
solid. Recrystallisation from hexane/ethylacetate (10:1) afforded
1,3-bis(5-tert-butyl-3-formyl-2-hydroxyphenyl)propane 2 (856 mg,
74%) as yellow prisms, m.p. 60–63°C; IR; n(Kbr)/cm-1 1652 (C=O);
1H NMR (CDCl3) d 1.30 (18H, s, tbu), 1.95 (2H, m, CH2CH2CH2),
2.75 (4H, t, J = 8.6 Hz, CH2CH2CH2), 7.36 (2H, d, J = 2.1 Hz, ArH),
7.48 (2H, d, J = 2.1 Hz, ArH), 9.90 (2H, s, OH) and 11.13 (2H, s,
CHO); MS: m/z M+ 396. Anal. calcd. for C25H32O4 (396.23) C 75.73,
H 8.13; found: C 75.68, H 8.17.
Preparation of calixarene analogue (4a): To a solution of 2
(100 mg, 0.25 mmol) in CH2Cl2 (30 cm3) and CH3OH (30 cm3) was
added a boric acid (8.0 mg, 0.126 mmol) and stirred for 1 h at room
temperature. Then a mixture was added o-phenylenediamine (27.3 mg,
0.25 mmol) and yellow precipitates appeared during stirring for
24 h. The precipitates were collected by filtration, washed by methanol
and dried in vacuo. Recrystallisation from CH2Cl2/methanol (1:1)
afforded calixarene analogue 4a (88 mg, 75%) as yellow prisms,
m.p. 232–233°C (decomp.); IR; n(Kbr)/cm-1 3609, 3283, 2944,
Received 12 July 2007; accepted 15 November 2007
Paper 07/4741
doi: 10.3184/030823407X266225
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