Constitutional isomers of brominated-functionalized copillar[5]arenes: Synthesis, characterization, and crystal structures

Article abstract of DOI:10.1039/c9ra02313e

We herein report the preparation of constitutional isomers of brominated-functionalized pillar[5]arenes via co-condensation of 1,4-bis(2-bromoethoxy)benzene and 1,4-dimethoxybenzene. The structures of the obtained isomers were then established using singl

Full text of DOI:10.1039/c9ra02313e

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Constitutional isomers of brominated-
functionalized copillar[5]arenes: synthesis,
Cite this: RSC Adv., 2019, 9, 13814
characterization, and crystal structures†
*
Talal F. Al-Azemi,
Mickey Vinodh, Fatemeh H. Alipour
and Abdirahman A. Mohamod
We herein report the preparation of constitutional isomers of brominated-functionalized pillar[5]arenes via
co-condensation of 1,4-bis(2-bromoethoxy)benzene and 1,4-dimethoxybenzene. The structures of the
obtained isomers were then established using single crystal X-ray diffraction. We also found that the
isomeric yield distribution of the different constitutional isomers was independent of the monomer's
mole feed ratio, as revealed by HPLC analysis of the crude mixture. Finally, further characterization of the
separated constitutional isomers indicated that they possess different melting points, NMR spectra,
crystal structures, binding constants and stacking patterns in the solid state.
Received 26th March 2019
Accepted 30th April 2019
DOI: 10.1039/c9ra02313e
rsc.li/rsc-advances
were successfully isolated and reduced to its corresponding
hydroxy-pillar[5]arenes. Different hydroxylated regioisomers were
Introduction
also synthesized by de-O-methylation of pillar[5]arene using
various stoichiometry of the deprotecting reagent (boron tri-
bromide, BBr3).21 The isolation of the hydroxylated derivatives
was carried out aer the reaction with triuoromethanesulfonic
anhydride to facilitated the chromatographic separation. Other
constitutional isomers were synthesized and isolated using the
co-cyclization approach by adjusting the feed ratio to 2 : 3 of 1,4-
bis(4-bromobutoxy)benzene and 1,4-dimethoxybenzene respec-
tively.22 The different proximity of functional groups on the
macrocycle rim inuence the physical, conformation and host–
guest properties. This is evident from the different physical,
chemical, and complexation behavior of constitutional isomer of
pillar[5]arene obtained by condensation of asymmetric hydro-
quinone derivatives.
Herein we report the synthesis of constitutional isomers of
tetra-and-hexa-bromo-functionalized pillar[5]arenes through
the co-condensation of hydroquinone derivatives of 1,4-bis(2-
bromoethoxy)benzene and 1,4-dimethoxybenzene. Separation
of the constitutional isomers and their resulting isomeric yield
distributions with respect to varying the feed ratio are also
investigated by HPLC. In addition, the obtained constitutional
isomers are characterized by NMR spectroscopy and X-ray single
crystal diffraction studies. The complexation behavior of the
isolated constitutional isomers toward a quaternary ammo-
nium salt is investigated in details.
Pillar[n]arenes are versatile macrocyclic compounds which have
gained increasing interest for their ease of formation, func-
tionalization and their excellent host–guest properties.
Different sized pillar[n]arenes have been reported, including
pillar[5]arenes (i.e., containing a 5-membered ring),1,2 pillar[6]
arenes,3 and pillar[7]arenes.4 In addition, larger pillar[n ¼ 6–15]
arenes have been synthesized recently through the ring expan-
sion of pillar[5]arenes.5 Pillar[5]arene and its derivatives have
received the most attention to date, due to their ease of
formation and functionalization. The electron-rich cavity of
pillar[5]arene and its analogs favors the binding of positively
charged or electron-decient guests,6 and have been demon-
strated to act as hosts toward a range of organic compounds,
including viologens,7 alkanediamines,8 dinitrobenzenes,9 azo-
benzene derivatives,10 and neutral molecules.11,12
Introduction of functional groups on the macrocycles struc-
ture is an important target in the receptor design and allows
further chemical and physical manipulation to the system.
Therefore, different strategies have been utilized including direct
deprotection, oxidation-followed-by-reduction and direct cycli-
zation (followed by deprotection) to introduce functional groups
such as bromo,13 amino,14 alkyne,15 and hydroxyl moieties16–20
have been reported thus far. In the synthesis of tetrahydroxy
functionalized pillar[5]arene using oxidation-followed-by-
reduction protocol,21 regioisomers of the quinones derivative
Results and discussion
Chemistry Department, Kuwait University, P. O. Box 5969, Safat 13060, Kuwait.
E-mail: t.alazemi@ku.edu.kw; Fax: +965-2481-6482; Tel: +965-2498-554
Pillararenes synthesized by co-oligomerization of two different
monomers mainly utilize the molar ratio of 1 : 4 and even more
of 1 : 16 to simplify the chromatographic separation.18 The co-
† Electronic supplementary information (ESI) available. CCDC 1880766–1880769.
For ESI and crystallographic data in CIF or other electronic format see DOI:
10.1039/c9ra02313e
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condensation of 1,4-bis(2-bromoethoxy)benzene and 1,4-dime-
thoxybenzene result in eight possible pillar[5]arenes including
regioisomers which exhibit practically identical properties
during column chromatography (Fig. 1). Therefore, most of the
literature reports of copillar[5]arenes with two repeating units
are in 1 : 4 molar ratio. However, the separation of copillarar-
enes is dependent on the chemical structure of monomers. The
syntheses of functionalized copillararenes with repeating units
other than the repetitious molar ratio of 1 : 4, offer control of
the receptor design and enhanced its recognition ability.
Based on such systems, we synthesized and separated all
eight pillar[5]arenes shown in Fig. 1 by co-cyclization procedure
of 1,4-dimethoxybenzene with1,4-bis(2-bromoethoxy)benzene
and paraformaldehyde in the presence of BF3$OEt2. Aer
30 min the reaction mixture was ush through silica gel plunge
and the total yield of all copillar[5]arenes were in range of 57–
71%. TLC analysis of the copillar[5]arenes synthesized using the
1,4-dimethoxybenzene with 1,4-bis(2-bromoethoxy)benzene
monomers produced eight spots. Column chromatography
using a dichloromethane/hexane mixture (60 : 40 v/v) was then
employed to separate the mixture, and gave the eight possible
pillar[5]arenes (i.e., Pillars-1–6) as white solids.
Fig. 2 1H NMR spectra (600 MHz, CDCl3) of the constitutional isomers
of Pillars-3a–3b and 4a–4b and insets showing the X-ray single crystal
diffraction structures. (a) The 1,3-alternate isomer, Pillar-3a, (b) the 1,2-
alternate isomer, Pillar-3b, (c) the 1,2-alternate isomer, Pillar-4a, and
(d) the 1,3-alternate isomer, Pillar-4b.
their corresponding substitution patterns (Fig. 3). To obtain
suitable crystals for analysis, single crystals of Pillars-3a, 3b, 4a,
and 4b were grown by solvent diffusion method. In the solid
state, these constitutional isomers were found to stack either in
the edge-to-edge (registered) style (i.e., Pillars-3a and 4b) or the
corner-to-edge style (i.e., Pillars-3b and 4a) (Fig. S5 and S6†).
Interestingly, the solvent molecule 1,2-dicholorethane found
encapsulate inside the Pillar-3a cavity involved in halogen–
halogen bonding with the functional bromine on the adjacent
pillar[5]arene resulting in the formation of supramolecular
dimer, whereas in Pillar-4b similar halogen–halogen bond
induced the formation supramolecular polymeric assembly.
To gain a clear insight on the copillar[5]arenes reaction,
HPLC was used to examine yield distribution when the mole
Aer separation, analysis by HRMS were conducted and
found the four spots which corresponded to Pillar-3a–3b and
Pillar-4a–4b isomers exhibit two set of signals for [M + Na]+ at m/
z 1141.0374 and at 1324.8856 respectively. However, the melting
points of the four isomers differed signicantly (i.e., Pillar-3a ¼
ꢀ
ꢀ
ꢀ
133 C; Pillar-3b ¼ 124 C; Pillar-4a ¼ 125 C; and Pillar-4b ¼
130 ꢀC), as did their 1H NMR spectra, as shown in Fig. 2.
Inspection of the 1H NMR spectra revealed the complete
assignment of their structure is particularly challenging. Even
though the relative area of the proton's peaks is similar for
Pillar-3a and Pillar-3b and for Pillar-4a and Pillar-4b, the
chemical shi and multiplicity are entirely different (Fig. 2). For
example, the signals corresponding to methylene (–CH2–Br)
shows as one triplet for Pillar-3a, Pillar-3b found to be as two set
of triplets. Similar differences also true for the signals corre-
sponding to the phenyl, methylene bridge, and methoxy
protons.
Thus, the structures of the different isomers were assigned
using single crystal X-ray diffraction, which clearly conrmed
Fig. 1 Chemical structures of all possible pillar[5]arenes from the co- Fig. 3 Crystal structures of the constitutional isomers of tetra-and
cyclization reaction of 1,4-dimethoxybenzene with1,4-bis(2-bro- hexabromo-functionalized pillar[5]arenes obtained for single crystal
moethoxy)benzene.
X-ray diffraction analysis.
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Table 1 Pillar[5]arenes relative distribution of co-cyclization reactions of 1,4-dimethoxy-and-1,4-bis(2-bromoethoxy)benzenesa
Paper
Mole feed ratio
Monomer 1b
Pillar[5]arenes relative distributionc (%)
Entry
Monomer 2b
1
2
3(a)d + 3(b)
4(a)d + 4(b)
5
6
1
2
3
4
5
6
7
4.0
3.5
3.0
2.5
2.0
1.5
1.0
1.0
1.5
2.0
2.5
3.0
3.5
4.0
53
30
30(28)
31
14
3
nde
1<(2)
2
nde
1<
1
44(47)f
31
19(11 + 7)
25
32
32(20 + 7)
30(23 + 6)
24
6(3 + 2)
10
19
26(19 + 12)
29(23 + 11)
35
17
27
4
1
11(8)f
8(6)f
3
21(15)
18(12)
10
7(14)
10(12)
19
3(5)
5(7)
9
a
b
Reactions were carried out for 30 min at room temperature in dichloroethane. Monomer 1 ¼ 1,4-dimethoxybenzene; monomer 2 ¼ 1,4-bis(2-
c
d
bromoethoxy)benzene. % relative distributions were calculated from HPLC. Ratio of 3(a) : 3(b) and 4(a) : 4(b) are 3 : 1 and 3 : 2 respectively.
e
Not detected. f % relative distributions were calculated aer separation from column chromatography.
feed ratio were varied of monomer 1 (1,4-dimethoxybenzene) for the regioisomers the separation was accomplished by
and monomer 2 (1,4-bis(2-bromoethoxy)benzene). HPLC tech- altering the solvent system to hexane : chloroform (95 : 5 v/v).
nique is ideal due to small differences between the retention
Upon inspection of results obtained for the pillar[5]arenes
factors (Rf values) of the different copillar[5]arenes especially for yield distribution in Table 1, it's clear that monomer 1 (1,4-
the constitutional isomers of Pillar-3 and Pillar-4, which is dimethoxybenzene) more reactive than monomer 2 (1,4-bis(2-
rather difficult to estimation of their yield distribution bromoethoxy)benzene) toward electrophilic aromatic substitu-
following separation by column chromatography. Control tion due to the presence of electron withdrawing group
experiments were therefore conducted using both monomers (bromine) as evidence of relative high yield distributions of the
and the results are summarized in Table 1. Prior to HPLC permethylated pillar[5]arene (Pillar-1). In addition, the low
analysis the crude reaction mixtures were passed through silica formation of Pillar-6 even with the use of higher feed ratio of
gel plugs and eluted with dichloromethane. Typical chromato- monomer 2 of 3.5 and 4.0 mole (Table 1, entry 6 and 7). When
graph is showing in Fig. 4 along with the peak assignments monomer 1 to 2 mole feed ratio was 4 : 1 respectively, Pillar-5
which were based on a comparison with the retention times of and Pillar-6 were not detected in the HPLC chromatogram
the pure isolated corresponding pillar[5]arenes.
(Table 1, entry 1). In all reactions in Table 1, the relative ratio of
In column chromatography the elution of the pillar[5]arene the constitutional isomers 1,3-alternate and 1,2-alternate kept
derivatives is reversed compare to the order shown in Fig. 4 as constant. The tetrabromo-functionalized pillar[5]arene isomers
the permethylated pillar[5]arene, Pillar-1 eluted last and Pillar-6 Pillar-3a to Pillar-3b and for the heaxbromo-functionalized
eluted rst because of the use of LC-CN HPLC based column. pillar[5]arene isomers Pillar-4a and Pillar-4b ratios were 3 : 1
The separation was achieved by using hexane: chloroform and 3 : 2 respectively.
(85 : 15 v/v) solvent system with follow rate of 0.7 mL minꢁ1. As
The noncovalent interaction of the obtained constitutional
isomers Pillar-(3a–3b) and Pillar-(4a–4b) with n-octyltrimethyl
ammonium hexauorophosphate (OMA) was investigated using
a
1H NMR titration method. OMA is widely used as a guest
species for pillar[5]arenes,19 1H NMR spectra of mixtures of
OMA (8.4 mM) and varying concentrations of Pillar-3a in CDCl3
at 25 ꢀC conrmed host–guest complexation, as evidenced by an
upeld shi of resonances for the trimethyl protons (Ha) of
OMA (Fig. S25†). At higher concentration of the host, the guest
was completely encapsulated and negative region were observed
indicating the linear guest OMA is threaded through the pil-
lararene cavity as shown in Fig. 5b. Interestingly, the terminal
methyl group (Hi) and the methylene protons (Hh) were shied
downeld due to their location in deshielding region of the
macrocyclic aromatic system (Fig. S26†). Similar effect was
observed in 1H NMR titrations carried out for all pillararene
isomers.
The stoichiometry of complexation was established by the
method of continuous variations (Job's method). All Job's plot
between the mole fraction of the guest (c) and the observed
chemical shi change of N-trimethyl protons on the OMA guest
in 1H NMR multiplied by the guest mole fraction (c) show
maxima at a mole fraction of 0.5 which indicates a 1 : 1 host-to-
Fig. 4 HPLC chromatogram for the crude reaction mixtures of the
copillar[5]arenes synthesized from monomers 1,4-dimethoxybenzene
and 1,4-bis(2-bromoethoxy)benzene and insets showing the chro-
matogram of separated constitutional isomers of Pillar-3 and Pillar-4
(Table 1, entry 6).
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MS, Thermo Scientic, Germany). Flash column chromatog-
raphy was performed using silica gel (silica gel 60, 40–60 mesh
ASTM, EMD Millipore, Merck KGaA, Germany). Dime-
thylformamide (DMF), dichloroethane, and acetonitrile were
distilled prior to use. All other reagents and solvents were of
reagent grade purity and were used without further purication.
n-Octyltrimethyl ammonium hexauorophosphate (OMA) was
synthesized according to literature procedure.19 HPLC was
carried out using a Waters HPLC system equipped with a 1525
binary pump, a 2487 dual absorbance detector, a 717 plus
autosampler, and Breeze soware (Waters, German). Pillarar-
enes were separated using a Waters SUPELCOSIL™ 5 mm LC-CN
HPLC column using hexane: chloroform (85 : 15 v/v) as the
eluent, with a run time of 30 min and a ow rate of 0.7
mL minꢁ1. The constitutional isomer Pillar-3–4(a, b) were
separated using hexane : isopropanol (94 : 6 v/v) as the eluent,
Fig. 5 1H NMR (600 MHz, CDCl3 at 298 K) spectra of (a) 8.4 mM OMA,
(b) 3.4 ꢃ 10ꢁ2M of Pillar-3a and 8.4 mM OMA, and (c) 8.4 mM of Pillar-
3a.
with a run time of 45 min and a ow rate of 0.7 mL minꢁ1
.
1,4-Bis(2-bromoethoxy)benzene.23 The compound was
synthesized according to the literature procedure as follow, 1,4-
bis(2-hydroxyethoxy)benzene (10.0 g, 50.4 mmol) and triphe-
nylphosphine (31.5 g, 120 mmol) in dry acetonitrile (250 mL)
was cooled with an ice bath under vigorous stirring. Carbon
tetra bromide (39.8 g, 120 mmol) was then slowly added to this
solution. The mixture was stirred at room temperature for 4
hours. Cold water (200 mL) was then added to the reaction
mixture to give white precipitation. The precipitate was
collected, washed with methanol/water (3 : 2 v/v, 3 ꢃ 100 mL),
recrystallized from methanol and dried under vacuum to afford
the compound as white crystals (14.5 g, 94%). 1H NMR (600
MHz, CDCl3) d: 3.62 (t, J ¼ 6.0 Hz, 4H), 4.25 (t, J ¼ 6.6 Hz, 4H),
6.88 (s, 4H). 13C NMR (150 MHz, CDCl3), d: 29.5, 68.9, 116.3,
153.0. HRMS: (m/z): calcd for C10H12O2Br2: 321.9199; found
321.9199.
Synthesis of the pillar[5]arenes 1–6. Paraformaldehyde
(0.86 g, 60 mmol) was added to a solution of 1,4-dimethox-
ybenzene (1.0 g, 8 mmol) and 1,4-dimethoxybenzene (4.0 g, 12
mmol) in dry dichloroethane (80 mL) under a nitrogen atmo-
sphere. Boron triuoride etherate [(BF3$OEt2), 2.50 mL, 20.0
mmol] was tꢀhen added to the solution and the mixture was
stirred at 40 C for 30 min. Aer this time, methanol (200 mL)
was poured into the reaction mixture and the solution was
concentrated then dissolved in dichloromethane (100 mL). The
resulting organic solution was washed with aqueous NaHCO3 (2
ꢃ 50 mL) and H2O (50 mL), then dried over anhydrous Na2SO4,
concentrated under reduced pressure, and subjected to puri-
cation by silica gel chromatography (dichloromethane/hexanes
(60 : 40 v/v)) to give a mixture of macrocycles Pillar-1–6 (2.95 g,
guest stoichiometric ratio of complexation (Fig. S23†). Further
evidence of the formation of a 1 : 1 complex were obtained for
the ESI-MS spectrum where relevant molecular peaks at m/z ¼
1294.26 and 1482.05 were found corresponding to [(Pillar-(3a–
3b) + OMA) ꢁ PF6]+ and [(Pillar-(4a–4b) + OMA) ꢁ PF6]+, in
agreement with the results obtained from 1H NMR titration
experiments (Fig. S24†). The association constant for complex-
ation for all pillar[5]arene isomers were determined from
chemical shi changes of the trimethyl groups of the guest OMA
at 3.16 ppm and the data tted to 1 : 1 binding isotherm.24 The
calculated association constant Ka were affected by the different
spatial arrangement of the pillar[5]arene substituents. The
isomer based on 1,2-alternate of tetrabromo-functionalized
Pillar-3b shows the highest Ka value of 140.4 ꢂ 9.4 Mꢁ1, which
is approximately three folds the binding constant of the 1,3-
alternate isomer (Pillar-3a) (58.9 ꢂ 2.6 Mꢁ1). On the other hand,
the constitutional isomer based on the hexa-bromo-pillar[5]
arenes, the 1,2-alternate isomer Pillar-4b displays the lowest
binding constant of 34.9 ꢂ 1.9 Mꢁ1, where the 1,3-alternate
Pillar-4a shows Ka of 50.7 ꢂ 2.2 Mꢁ1 which is 46% increased
compare to 1,2 alternate isomer. From the binding study, it is
well evident that these pillararene constitutional isomers have
different degree of affinity towards guest molecules (OMA) and
hence could effectively employed for molecular recognition by
properly tuning their peripheral motifs.
Experimental
Materials and methods
NMR spectroscopy was carried out by on Bruker Avance II 600 57%). The pillar[5]arenes are organized according to their order
MHz (Bruker, Germany). Electron impact (EI) mass spectrom- in elution from column chromatography.
etry was performed using a DFS High Resolution GC/MS
Pillar-6. The NMR and mass spectral details are consistent
(Thermo Scientic, Germany). Electrospray ionization was with those reported in the literature.24 White solid (152 mg, 5%).
carried out in high resolution mode using a Waters Xevo G2-S Mp 141–142 ꢀC. 1H NMR (600 MHz, CDCl3) d: 3.65 (t, J ¼ 5.4 Hz,
QTOF LC-MS/MS (Waters, Germany). As detailed later, single 20H), 3.86 (s, 10H), 4.23 (t, J ¼ 5.4 Hz, 20H), 6.93 (s, 10H). 13C
crystal X-ray diffraction was carried out using an R-AXIS RAPID NMR (150 MHz, CDCl3), d: 29.6, 30.9, 69.2, 116.3, 129.3, 149.9.
II diffractometer (Rigaku, Japan), and the data were collected at
Pillar-5. White solid (413 mg, 14%). Mp 134–135 ꢀC. 1H NMR
ꢁ123 ꢀC (Oxford Cryosystems, UK). LC was carried out using an (600 MHz, CDCl3) d: 3.59–3.63 (m, 16H), 3.78 (s, 6H), 3.83–3.86
instrument equipped with a photodiode array detector (LC-MS/ (m, 10H), 4.17–4.23 (m, 16H), 6.83 (s, 2H), 6.89–6.91 (m, 8H). 13
C
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NMR (150 MHz, CDCl3), d: 14.3, 22.9, 29.6, 29.9, 30.5, 30.7, 31.8, Rigaku's ‘CrystalStructure’ crystallographic soware package
56.3, 68.9, 69.2, 114.3, 115.8, 116.4, 128.3, 129.0, 129.2, 129.4, except for renement, which was performed using SHELXL-
129.6, 149.8, 150.9. HRMS (ESI/QTOF) m/z: calcd for [M + H+]: 2017/1. The crystallographic data for all structures reported in
1486.7575 (for C53H59O10Br8); found 1486.7526.
this paper have been deposited at the Cambridge Crystallo-
Pillar-4a. White solid (560 mg, 19%). Mp 125–126 ꢀC. 1H graphic Data Centre as supplementary publications (CCDC
NMR (600 MHz, CDCl3) d: 3.53 (t, J ¼ 6 Hz, 8H), 3.71–3.72 (m, 1880766–1880769).
12H), 3.75 (s, 6H), 3.81–3.82 (m, 10H), 4.11–4.15 (m, 8H), 6.78
(d, J ¼ 10.8 Hz, 4H), 6.83–6.84 (m, 6H). 13C NMR (150 MHz,
1H NMR titrations
CDCl3), d: 29.8, 30.3, 56.0, 56.3, 68.9, 114.1, 114.5, 115.9, 128.1,
A 0.5 mL sample of the OMA guest solutions was prepared at
a concentration of 8.4 mM in chloroform-d. A sample of the host
solutions (2 mL) was prepared at a concentration of 0.1 M in
a chloroform-d solvent. All titration experiments were carried
128.3, 128.7, 129.3, 129.4, 149.9, 150.9. HRMS: (m/z): calcd for
[M + Na+]: 1324.8871 (for C51H56O10Br6Na); found 1324.8835.
Pillar-4b. White solid (350 mg, 12%). Mp 130–131 ꢀC. 1H
NMR (600 MHz, CDCl3) d: 3.55–3.59 (m, 12H), 3.75–3.76 (m,
12H), 3.83–3.84 (m, 10H), 4.12–4.21 (m, 12H), 6.80 (d, J ¼ 8.4 Hz,
4H), 6.86–6.87 (m, 6H). 13C NMR (150 MHz, CDCl3), d: 29.2, 29.7,
29.9, 30.4, 30.5, 56.3, 68.9, 69.3, 114.4, 115.9, 116.6, 128.3, 128.4,
129.1, 129.4, 129.6, 149.9, 150.0, 150.9. HRMS (ESI/QTOF) m/z:
calcd for [M + Na+]: 1324.8871 (for C51H56O10Br6 Na); found
1324.8856.
1
out in an NMR tube at 298 K, and H-NMR spectra were recor-
ded upon successive addition of aliquots of the stock solution of
the appropriate host with a syringe. The 1H-NMR spectral
changes were tted to 1 : 1 binding isotherms by nonlinear
least-squares treatment using Microso Excel to determine the
association constant, Ka.24
Pillar-3a. Yield (590 mg, 20%). Mp 124–125 ꢀC. 1H NMR (600
MHz, CDCl3) d: 3.53 (t, J ¼ 6 Hz, 8H), 3.71–3.72 (m, 12H), 3.75 (s,
6H), 3.81–3.82 (m, 10H), 4.11–4.15 (m, 8H), 6.78 (d, J ¼ 10.8 Hz,
4H), 6.83–6.84 (m, 6H). 13C NMR (150 MHz, CDCl3), d: 29.8, 30.3,
56.0, 56.3, 68.9, 114.1, 114.5, 115.9, 128.1, 128.3, 128.7, 129.3,
129.4, 149.9, 150.9. HRMS: (m/z): calcd for [M + Na+]: 1141.0348
(for C49H54O10Br4 Na); found 1141.0392.
Conclusions
In conclusion, constitutional isomers of tetra-and hexabromo-
functionalized pillar[5]arenes were synthesized by co-
cyclization from hydroquinone derivatives of 1,4-dimethox-
ybenzene and 1,4-bis(2-bromoethoxy)benzene with para-
formaldehyde in presence of BF3$OEt2. Separation of the
constitutional brominated-pillar[5]arene isomers by column
chromatography was attempted, the yields of the regioisomers
dependent on nature and the monomer mole feed ratio. The
1,4-dimethoxybenzene monomer 1 is more reactive relative to
1,4-bis(2-bromoethoxy)benzene toward the electrophilic
condensation reaction. HPLC analysis of the crude pillararene
mixture, revealed that the isomeric distribution of tetra-and
hexabromo-functionalized pilla[5]arene were 3 : 1 and 3 : 2
respectively. Characterization of the prepared and isolated
constitutional isomers revealed that they exhibited different
melting points, NMR spectra, crystal structures, and stacking
patterns in the solid state. The binding study carried out for
pillar[5]arane constitutional isomers with OMA guest indicate
that the association constant of complexation was affected by
the spatial arrangement of the substituents on the pillararene
rim. Our future work will focus on the modication and appli-
cation of the synthesized brominated-functionalized pillar[5]
arenes isomers in the receptor design.
1
Pillar-3b. Yield (206 mg, 7%). Mp 133–134 ꢀC. H NMR (600
MHz, CDCl3) d: 3.48 (t, J ¼ 6 Hz, 4H), 3.54 (t, J ¼ 6 Hz, 4H), 3.71
(s, 6H), 3.74–3.75 (m, 12H), 3.80–3.83 (m, 10H), 4.07 (t, J ¼ 6 Hz,
4H), 4.16 (t, J ¼ 6 Hz, 4H), 6.77 (s, 2H), 6.83–6.84 (m, 8H). 13C
NMR (150 MHz, CDCl3), d: 29.6, 29.8, 30.2, 56.1, 56.3, 68.9, 69.3,
114.1, 114.2, 114.4, 115.9, 116.6, 127.9, 128.4, 128.7, 128.9,
129.7, 149.8, 150.1, 150.9. HRMS (ESI/QTOF) m/z: calcd for [M +
Na+]: 1141.0348 (for C49H54O10Br4Na); found 1141.0374.
1
ꢀ
Pillar-2. Yield (440 mg, 15%). Mp 117–118 C H NMR (600
MHz, CDCl3) d: 3.47 (t, J ¼ 6 Hz, 4H), 3.67 (s, 6H), 3.71–3.72 (m,
18H), 3.80–3.81 (m, 10H), 4.08 (t, J ¼ 6 Hz, 4H), 6.76–6.82 (m,
10H). 13C NMR (150 MHz, CDCl3), d: 29.7, 30.1, 53.3, 55.9, 56.3,
68.9, 114.0, 114.2, 115.9, 128.0, 128.3, 128.8, 129.3, 149.9, 150.9,
151.0.
Pillar-1. Yield (236 mg, 8%). The NMR and mass spectral
details are consistent with those reported in the literature.1 1H
NMR (600 MHz, CDCl3) d: 3.72 (s, 30H), 3.76 (s, 10H), 6.83 (s,
10H). 13C NMR (150 MHz, CDCl3), d: 29.5, 55.4, 128.1, 133.6,
150.4.
Preparation of single crystals for X-ray diffraction
Conflicts of interest
Single crystals of the synthesized pillar[5]arenes and their
inclusion complexes were grown using either the slow solvent
evaporation method or by the diffusion method using
dichloromethane and n-hexane or acetonitrile. The single
crystal data collections were made on Rigaku R-AXIS RAPID II
There are no conicts to declare.
Acknowledgements
diffractometer by ltered Mo-Ka radiation. The data were The support received from the Kuwait Foundation of Advance-
collected under liquid nitrogen (Oxford cryosystems). ‘Crystal- ment Science (KFAS), made available through research grant no.
clear’ soware package was employed to generate hkl and p4p PR17-14SC-07, in addition to the facilities of RSPU (grant no.
les. The structure was then solved by direct methods using GS01/01, GS01/03, and GS03/08) is gratefully acknowledged.
13818 | RSC Adv., 2019, 9, 13814–13819
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