Synthesis and characterization of new symmetrical 3,6-bis[(25,26,27- tripropoxy-28-(3-(4-iodophenyl) propoxy)-p-tert-butyl calix[4]arene ethynyl]-9H-fluoren-9-one by Sonogashira coupling as a novel precursor for synthesis of quinodimethane (QDM)

Article abstract of DOI:10.3906/kim-1006-693

Novel symmetrical 3,6-bis[(25,26,27-tripropoxy-28-(3-(4-iodophenyl)propoxy) -p-tert-butyl calix[4]arene ethynyl]-9H-fluoren-9-one with a cone conformation was synthesized by palladium-catalyzed coupling of (25,26,27-tripropoxy-28-(3- (4-iodophenyl)propoxy

Full text of DOI:10.3906/kim-1006-693

Turk J Chem
35 (2011) , 455 – 462.
¨
˙
c
ꢀ TUBITAK
doi:10.3906/kim-1006-693
Synthesis and characterization of new symmetrical
3,6-bis[(25,26,27-tripropoxy-28-(3-(4-iodophenyl)
propoxy)-p-tert-butyl calix[4]arene ethynyl]-9H-
fluoren-9-one by Sonogashira coupling as a novel
precursor for synthesis of quinodimethane (QDM)
Karim Akbari DILMAGHANI∗, Fazel Nasuhi PUR
Department of Chemistry, Faculty of Science, University of Urmia,
Urmia, 57159, IRAN
e-mail: kadilmaghani@yahoo.com
Received: 18.06.2010
Novel symmetrical 3,6-bis[(25,26,27-tripropoxy-28-(3-(4-iodophenyl)propoxy)-p-tert-butyl calix[4]arene
ethynyl]-9H-fluoren-9-one with a cone conformation was synthesized by palladium-catalyzed coupling of
(25,26,27-tripropoxy-28-(3-(4-iodophenyl)propoxy)-p-tert-butyl calix[4]arene and 3,6-diethynyl-9H-fluoren-
9-one. Its structure was confirmed by FT-IR, 1 H-NMR, and 13 C-NMR spectroscopy, and elemental analysis
and positive ion FAB mass spectrometry.
Key Words: Synthesis, 3,6-diethynyl-9H-fluoren-9-one, p-tert-butyl calix[4]arene, FAB mass, palladium-
catalyzed
Introduction
The development of methods for the synthesis of macromolecules such as dendrimers, supramolecules, and
nanostructures with specific functions has increasingly become the center of attention in recent years. 1,2
Calixarenes, which are phenol-formaldehyde cyclic oligomers, are receiving increasing attention in the field
of supramolecular chemistry. Calix[4]arenes can be selectively functionalized easily, both at the phenolic OH
∗Corresponding author
455

Synthesis and characterization of new symmetrical ..., K. A. DILMAGHANI, F. N. PUR
groups (lower rim)3 and at the para positions of the phenol rings (upper rim). Consequently, they are useful
building blocks for host molecules with different properties.4 To date, various calixarenes that possess ester,5,6a
amide,7 or other functional groups have been synthesized for separation,8 recognition,9 discrimination,10 and
catalysis.11 Lower-rim ethers,6 and esters,6a,12 show strong complexation with cations. Lower-rim esters are
more effective than simple ethers in complexation with cations.6
In recent years, the chemistry of quinodimethanes (QDM) has attracted increasing interest. 13,14 The
QDM derivative assembles itself into a spherical cyclic by the 4 weak Csp3 –Csp3 bonds between the fluorene
units (compound 8) that are formed during tetramerization. The unstable and reactive QDMs are commonly
generated in situ from a suitable precursor. QDM derivatives are of considerable interest, both from a theoretical
point of view and for their potential in organic synthesis,13 as useful dienes in Diels-Alder reactions.14 The
inter- and intramolecular Diels-Alder reactions of these compounds form the basis of the synthesis of a wide
range of target molecules.13
In this work, we reported the synthesis and characterization of a novel symmetrical “double calix[4]arene”6 -
substituted bis ethynyl fluorenone. Compound 8 is the key compound for the synthesis of QDM with a
calix[4]arene substitute.
Experimental
The melting points of all compounds were recorded on a Philip Harris C4954718 apparatus (Birmingham, UK)
without calibration. IR spectra were determined on a Thermo Nicolet 610 Nexus FT-IR spectrometer (Waltham,
MA, USA) with KBr disks. Ultraviolet spectra were recorded on a Shimadzu UV-2401/PC spectrometer
(Columbia, MD, USA). 1 H-NMR (400 MHz) and 13 C-NMR (50 and 100 MHz) measurements were recorded on
a Bruker AM-400 spectrometer (Ettlingen, Germany) in CDCl3 using TMS as the internal reference. Elemental
analyses were performed using a Heraeus CHN-O-Rapid analyzer (Austin, TX, USA). Positive ion FAB mass
spectra were recorded using a JEOL AX505HA spectrometer (Tokyo, Japan) with m−nitro benzyl alcohol as
the matrix. Thin layer chromatography (TLC) analyses were carried out on silica gel plates. All chemicals were
purchased from Merck (Tehran, Iran) and used as received by standard procedures, such as compound 5. All
reactions were carried out under an argon atmosphere. All of the instruments, chemicals, and solvents were
dried according to standard methods. Freshly distilled solvents were used throughout, and anhydrous solvents
were dried according to the method of Perrin and Armarego.15
p-tert-Butyl calix[4]arene (1): prepared according to Gutsche’s method16 as white crystals.
The cone conformer of 25,26,27-tripropoxy-28-hydroxy-p-tert-butyl calix[4]arene (2): pre-
pared by the previously reported method17 as white crystals.
25,26,27-Tripropoxy-28-(3-bromopropoxy)-p-tert-butyl calix[4]arene (3): prepared with a cone
conformation according to the literature procedure.18
3,6-Bis[(trimethyl-silyl)ethynyl]-9H-fluoren-9-one (6): prepared by Sonogashira coupling proce-
dure.19
3,6-Bis ethynyl-9H-fluoren-9-one (7): prepared according to the published procedure.19
25,26,27-Tripropoxy-28-(3-(4-iodophenyl)propoxy)-p-tert-butyl calix[4]arene (4):
To a solution of 480 mg (2.4 mmol) of 4-iodophenol in DMF (35 mL), 18 mg (3 mmol) of NaH (60%
456

Synthesis and characterization of new symmetrical ..., K. A. DILMAGHANI, F. N. PUR
dispersion in oil) was added, and the reaction mixture was stirred at 55 ◦ C for 1 h. Then 0.9 g (1.05 mmol) of
compound 3 was added and the mixture was stirred for 24 h at the same temperature. The solvent was removed
under reduced pressure. The residue was dissolved in CH2 Cl2 and washed with NaOH solution (10%). The
organic layer was washed with water and dried with MgSO4 . The solvent was evaporated and the residue was
submitted to column chromatography (SiO2 , CH2 Cl2 -petrolium ether, 30-50 ◦ C, 1:5). The expanded structure
of this compound is shown in Figure 1. Yield 77% (0.8 g), mp 91-92 ◦ C. Anal. calcd. (%) for C62 H83 O5 I
(1035.0): C, 71.93, H, 8.08; found: C, 72.08, H, 8.09. 1 H-NMR (400 MHz, CDCl3)δ (ppm): 0.97 (t, 9H, J =
7.4 Hz, H-14, 17), 1.02 (s, 18H, H-6), 1.13 (s, 9H, H-1 or 11), 1.14 (s, 9H, H-11 or 1), 1.95-2.08 (m, 6H, H-13,
16), 2.25 (quint., 2H, H-19), 3.13 (d, 2H, J = 12.5 Hz, H-3 or 8), 3.14 (d, 2H, J = 12.5 Hz, H-8 or 3), 3.73-3.84
(m, 4H, H-12), 3.86 (t, 2H, J = 7.8 Hz, H-15), 4.08 (t, 2H, J = 7.3 Hz, H-18), 4.12 (t, 2H, J = 6.3 Hz, H-20),
4.40 (d, 2H, J = 12.5 Hz, H-4 or 9), 4.43 (d, 2H, J = 12.5 Hz, H-9 or 4), 6.65-6.75 (m, 6H, H-2, 10, 22), 6.85 (s,
4H, H-5, 7), 7.56 (d, 2H, J = 9 Hz, H-21); 13 C-NMR (100 MHz, CDCl3)δ (ppm): 10.26, 10.40, 23.26, 23.36,
30.06, 31.09, 31.12, 31.39, 31.51, 31.53, 33.75, 33.85, 33.88, 65.87, 71.83, 76.68, 77.31, 82.46, 116.94, 124.77,
124.89, 125.03, 125.13, 133.25, 133.42, 134.22, 138.19, 144.20, 144.30, 144.66, 153.38, 153.67, 153.94, 159.13.
Figure 1. The numbering system for 1 H-NMR spectrum of compound 4.
3,6-Bis-(25,26,27-tripropoxy-28-(3-(4-iodophenyl)propoxy)-p-tert-butyl calix[4]arene ethynyl)9H-
fluoren-9-one (8):
To a 2-necked, 250-mL flask, 228 mg (1 mmol) of compound 7, 2.2 g (2.1 mmol) of compound 4, 28 mg
(0.04 mmol) of Pd(PPh3)2 Cl2 , and 15 mg (0.08 mmol) of CuI were added. DMF (50 mL) and Et3 N (25 mL)
were then added and stirred under argon at 80 ◦ C for 24 h. Solvents were evaporated under reduced pressure.
The residue was dissolved in CH2 Cl2 (200 mL) and washed with water. The organic layer was separated and
rotary evaporated. The residue was submitted to column chromatography (SiO2 .CH2 Cl2). The expanded
structure of this compound is shown in Figure 2. Yield 58% (1.18 g), mp 170-172◦ C. Anal. calcd. (%) for
C
141 H172 O11 (2042.5): C, 82.89, H, 8.49; found: C, 82.52, H, 8.84. IR (KBr, ν , cm−1): 2206 (C ≡ C), 1714
(C=O); 1 H-NMR (400 MHz, CDCl3)δ (ppm): 0.99 (t, 18H, J = 7.5 Hz, H-14, 17), 1.02 (s, 36H, H-6), 1.14
(s, 36H, H-1, 11), 1.95-2.05 (m, 12H, H-13, 16), 2.6 (quint., 4H, H-19), 3.14 (d, 4H, J = 12.5 Hz, H-3 or 8),
457

Synthesis and characterization of new symmetrical ..., K. A. DILMAGHANI, F. N. PUR
3.16 (d, 4H, J = 12.5 Hz, H-3 or 8), 3.74-3.86 (m, 8H, H-12), 3.90 (t, 4H, J = 7.7 Hz, H-15), 4.1 (t, 4H, J =
7.2 Hz, H-18), 4.2 (t, 4H, J = 6.2 Hz, H-20), 4.41 (d, 4H, J = 12.5 Hz, H-4 or 9), 4.44 (d, 4H, J = 12.5 Hz,
H-4 or 9), 6.65-6.75 (m, 8H, H-2, 10), 6.86 (s, 8H, H-5, 7), 6.95 (d, 4H, J = 8.7 Hz, H-22), 7.46 (dd, 2H, Jorto
= 7.7 Hz, Jmeta = 1 Hz, H-24), 7.52 (d, 4H, J = 8.7 Hz, H-21), 7.66 (d, 2H, J = 7.7 Hz, H-23), 7.68 (s, 2H,
H-26); 13 C-NMR (50 MHz, CDCl3)δ (ppm): 10.44, 23.31, 23.42, 30.17, 31.20, 31.43, 33.79, 33.89, 66.01, 71.84,
76.37, 77.63, 88.00, 94.00, 114.78, 123.19, 124.83, 124.96, 125.08, 125.20, 130.34, 133.29, 133.39, 133.46, 134.25,
144.26, 144.74, 153.45, 153.98.
Figure 2. The numbering system for 1 H-NMR spectrum of compound 8.
Analytical procedure (M+ extraction)
The organic phase (5 mL of CH2 Cl2), containing compound 4 or 8 (2.50 mmol L−1), and the aqueous phase
(5 mL), containing M+ Pic− (0.25 mmol L−1), NaOH (0.10 mol L−1), and NaCl (0.50 mol L−1), were mixed
and shaken for 12 h at 25 ◦ C. Extraction percentage values were determined spectrophotometrically at 357 nm.
Blank experiments showed that no picrate extraction occurred in the absence of calixarene.
Results and discussion
It was recognized by Cornforth et al.20 that a calix[4]arene can exist in 4 main conformations: cone, partial
cone, 1,2-alternate, and 1,3-altemate. The structures of these conformers can be easily distinguished by their
characteristic 1 H-NMR patterns arising from the ArCH2 Ar methylene protons.21−23 The conformations of
458

Synthesis and characterization of new symmetrical ..., K. A. DILMAGHANI, F. N. PUR
calix[4]arenes can be deduced from the 13 C-NMR chemical shifts of the methylene groups connecting each pair
of aromatic rings.24 An inspection of the proton-decoupled l3 C-NMR spectra of all of the series revealed that
the methylene carbon chemical shifts always ranged around 2 values: δ 31 and 37 ppm. In cone conformations,
adjacent phenol rings are in a syn (δ 31 ppm) orientation only, while in the other conformations, adjacent
phenol rings are in both syn and anti (δ 37 ppm) orientations.
The cone conformer of compound 2 (1HPr3) has only one hydroxyl group in the lower rim; therefore, its
reactions with di-bromo alkyl reagents are more selective and do not produce any other by-products. Because
of the lower acidity of the proton of the OH group in compound 2, it was activated by using NaH as a strong
base; the small size of NaH is also very useful for this type of reaction.
The cone conformer of 25,26,27-tripropoxy-28-(3-iodophenyl)propoxy)-p-tert-butyl calix[4]arene 4 was
synthesized by the reaction of appropriate mono-bromo alkyl calix[4]arene derivative 3 with 2 eq of 4-iodophenol
in DMF at an elevated temperature and in the presence of NaH. Under these conditions, compound 4 was
synthesized in a yield of 77%. The sole by-product found in the reaction mixture was a mono-alkyl derivative,
the product of the β-elimination reaction of the starting –O-(CH2)3 -Br group in 3 (Scheme 1).
Scheme 1. General synthetic pathway for synthesis of compound 4.
The coupling of the terminal alkynes with aryl or alkenyl halides was reported by Sonogashira25 in 1975.
Sonogashira coupling is carried out in the presence of a catalytic amount of a palladium(II) complex as well as
copper(I) iodide by using an amine as the solvent. This coupling is one of the most straightforward methods
for the preparation of aryl alkynes and conjugated enynes. Compound 8 was synthesized by the reaction of
compound 4 with compound 7 under Sonogashira coupling conditions. The acetylenic hydrogens in compound
7 were easily substituted by the iodo-aryl in compound 4 (Scheme 2). The formation of product 8 can be
clearly followed through its 1 H-NMR spectrum. Compound 8 was treated with 1,4-di-lithiobenzene and then
converted to the QDM derivative with a calix[4]arene substitute.
The splitting pattern for ArCH2 Ar protons (a pair of doublets with a typical AX pattern)21−23 showed
that compounds 4 and 8 adopted a cone conformation (Table 1). We used the DEPT-135 technique to
distinguish signals relevant to the methylene carbons in compounds 4 and 8, which did not show a signal
at δ 37 ppm, confirming that 4 and 8 adopt a cone conformation.6 The numbering systems for the 1 H-NMR
spectra of compounds 4 and 8 are shown in Figures 1 and 2.
459

Synthesis and characterization of new symmetrical ..., K. A. DILMAGHANI, F. N. PUR
Scheme 2. General synthetic pathway for synthesis of compound 8.
Table 1. Properties of compounds 4 and 8.
1H-NMR
ArCH2Ar
CDCl3
Splitting
pattern of
ArCH2Ar
protons
FABMSa
Sample Product
J (Hz)
Conformation
cone
data (me-1)
Mp (°C) Yield (%)
no.
type
δ (ppm)
3.13
3.14
4.40
4.43
doublet
doublet
doublet
doublet
12.5
12.5
12.5
12.5
4
mono
91-92
77
58
1036
2044
3.14
3.16
4.41
4.44
doublet
doublet
doublet
doublet
12.5
12.5
12.5
12.5
8
bis
170-172
cone
a1036 = (M+1)+ and 2044 = (M+2)+
Solvent extraction of metal salts, mostly picrates, from water into an organic solvent, usually CH2 Cl2
or CHCl3 , was performed at 25 ◦ C. Compounds 4 and 8 were able to encapsulate guest cations, and better
selectivity in favor of Na+ was obtained, especially for compound 8. Although the cation selectivity of ionophoric
calix[4]arenes can be changed by conformation, the cation affinity observed for cone conformers is always the
highest among all 4 possible conformers.17b The results for the extraction ability of 4 and 8 are summarized
in Table 2. The percentage extraction value (Ex %) for 8 was higher than that for 4; this is attributed to
460

Synthesis and characterization of new symmetrical ..., K. A. DILMAGHANI, F. N. PUR
the existence of 2 bonding sites in 8. The ratio of metal to ligand for compound 4 was 1:1 in the ML system
and 2:1 for compound 8 in M2 L. The induced 3D cavity (size-fitting) of the parent calixarene platform and
the attached side arms upon complexation play an important role in cation binding ability and selectivity. A
picrate extraction experiment was performed following a modified version of Pedersen’s procedure.26
Table 2.The percentage extraction value (Ex %) of compounds 4 and 8 for cation picrates.
Sample Ex % of
Ex % of Ex % of Ex % of
Ex % of
no.
4
Li+Pic− Na+Pic− K+Pic− Cs+Pic− Ag+Pic−
5.6
26.2
53.6
19.1
38.8
4.3
6.2
18.9
37.4
8
10.7
The conditions necessary for the formation of the complexes and the factors influencing their stability
include:
1. The relative sizes of the ion and the hole in the calixarene.
2. The number of oxygen atoms in the molecule.
3. The coplanarity of the oxygen atoms (maximum in cone conformation).
4. The symmetrical placement of the oxygen atoms (maximum in cone conformation).
5. The basicity of the oxygen atoms.
6. Steric hindrance in the hole of the calixarene (minimum in cone conformation).
7. The tendency of the ion to associate with the solvent.
8. The electrical charge of the ion.
Acknowledgement
We gratefully acknowledge the University of Urmia for providing a fellowship for the present work.
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462

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