Campestarenes: New building blocks with 5-fold symmetry

Article abstract of DOI:10.1039/c8ob00957k

Campestarene is a planar, shape-persistent macrocycle with 5-fold symmetry. A range of derivatives bearing peripheral functional groups suitable for generating supramolecular interactions has been designed and synthesised for potential applications in creating 2D quasicrystal molecular assemblies. The new campestarene derivatives bear ester, carboxylic acid, methoxy, bromo, 4-pyridyl, 4-cyanophenyl and 4-phenyl carboxylic acid groups, including further derivatives of the latter two bearing alkyl chains on the phenyl groups to improve solubility. The campestarene derivatives were prepared by reductive condensation of phenol precursors bearing nitro and formyl groups using Na₂S₂O₄. The target functional groups were installed either by pre-cyclisation derivatisation or by synthesis of methoxy-substituted campestarene and subsequent derivatisation. The cyclisation reaction is tolerant of the functional groups introduced. The ten new campestarene derivatives were characterised by NMR spectroscopy and MALDI-TOF MS, although the poor solubility of some examples precluded their detailed characterisation.

Full text of DOI:10.1039/c8ob00957k

Organic & Biomolecular Chemistry
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Campestarenes: new building blocks with 5-fold symmetry
Journal: Organic & Biomolecular Chemistry
Manuscript ID OB-ART-04-2018-000957.R1
Article Type: Paper
Date Submitted by the Author: 31-Jul-2018
Complete List of Authors: Nam, Seong; University of Auckland, School of Chemical Sciences
Ware, David; University of Auckland, Chemistry
Brothers, Penelope; The University of Auckland, School of Chemical
Sciences
This article can be cited before page numbers have been issued, to do this please use: S. J. Nam, D. C. Ware
and P. J. Brothers, Org. Biomol. Chem., 2018, DOI: 10.1039/C8OB00957K.

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OrPgleanaisce&dBoionmotoaledcjuulsatr mChaermgiinstsry
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DOI: 10.1039/C8OB00957K
Organic & Biomolecular Chemistry
PAPER
Campestarenes: new building blocks with 5-fold symmetry
Seong Nam,a David C. Warea and Penelope J. Brothers*a,b
Campestarene is a planar, shape-persistent macrocycle with 5-fold symmetry. A range of derivatives bearing
peripheral functional groups suitable for generating supramolecular interactions has been designed and
synthesised for potential applications in generating 2D quasicrystal molecular assemblies. The new campestarene
derivatives bear ester, carboxylic acid, methoxy, bromo, 4-pyridyl, 4-cyanophenyl and 4-phenyl carboxylic acid
groups, including further derivatives of the latter two bearing alkyl chains on the phenyl groups to improve
solubility. The campestarene derivatives were prepared by reductive condensation of phenol precursors bearing
nitro and formyl groups using Na2S2O4. The target functional groups were installed either by pre-cyclisation
derivatisation or by synthesis of methoxy-substituted campestarene and subsequent derivatisation. The cyclisation
reaction is tolerant of the functional groups introduced. The ten new campestarene derivatives were characterised
by NMR spectroscopy and MALDI-TOF MS, although the poor solubility of some examples precluded their detailed
characterisation.
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
arrays has proved much more challenging, primarily because
Introduction
the expression of 5-fold symmetry in 2D and 3D assemblies is
inherently more complex. The building blocks cannot pack
regularly, as evidenced by the particular properties of Penrose
tiling patterns in 2D and quasicrystal packing in 3D.
This challenge has received growing interest in recent times,
prompted in part by the observation that 3D quasicrystalline
Architects and builders designing and constructing houses need
supply yards full of building materials of the right size, shape
and material properties to create buildings with the desired
dimensions, features and functions. The same is true for nano-
architects and builders whose supplies of suitable molecular
building blocks need to develop to keep pace with the
metal alloys show unusual properties in
a range of
applications.9-13 However, the rational design and assembly of
2D quasicrystal packing using molecular pentagons as building
blocks remains an elusive goal. It requires an understanding of
the unique symmetry properties of 2D crystal tiling patterns
increasing
sophistication
of
their
supramolecular
nanoarchitectures. Just as the shape of an individual brick has
a relationship with the symmetry and properties of the wall it is
used to build, individual molecular building blocks also
determine the symmetry and properties of supramolecular
nanoarchitectures. For this reason, shape-persistent molecular
building blocks have proved extremely useful for the design and
construction of ordered 2D and 3D materials on the nanoscale.
Amongst these, macrocycles with full or partial conjugation
have proved especially useful. The macrocycles themselves
often contain aryl units as integral components linked by amide,
ethynyl or imine bridges which have well defined spatial
configurations and organise the overall shape of the
macrocycles.1-6 Porphyrins, with their well-defined 4-fold
symmetry and planar geometry, are quintessential examples.7,8
Shape-persistent building blocks with 2-, 3-, 4- and 6-fold
symmetry are common, with many synthetically accessible
examples available, and have been extensively studied for 2D
and 3D assemblies which typically replicate the symmetry of
their components.1,7,8 However, extending this principle to the
use of building blocks with 5-fold symmetry to generate
assemblies which demonstrate 5-fold symmetry in extended
based on
a pentagonal tile, which are ordered but
translationally aperiodic.14-18 Amongst the conceivable
experimental approaches, the most obvious is the deposition of
planar molecular pentagons on a surface. Attempts to do this
have shown that the hexagonal symmetry of the underlying
surface rather than the pentagonal shape of the molecule
determines the packing arrangement.19 In a serendipitous
discovery, regions of 2D quasicrystalline, Penrose tile ordering
of ferrocene carboxylic acid molecules on a surface were
observed in which the ordering was directed by supramolecular
interactions between the ferrocene carboxylic acid groups.20,21
This points to the need for inclusion of functional groups
suitable for generating supramolecular interactions on the
periphery of the building blocks. This approach has been shown
to play a significant role in the packing orientation in 2D self-
assembly.22
A further barrier to the exploration of quasicrystalline
packing in 2D is the paucity of synthetically available, shape-
persistent macrocyclic building blocks with 5-fold symmetry.23-
a.School of Chemical Sciences, University of Auckland, Private Bag 92019, Auckland
1142, New Zealand. E-mail: p.brothers@auckland.ac.nz
32
Examples from the recent literature are the family of
macrocyclic pentamers from Zeng’s group,31,33,34 cyanostar
reported by Flood et al.,32 and MacLachlan’s campestarene.30,35
bMacDiarmid Institute for Advanced Materials and Nanotechnology, New Zealand
Electronic Supplementary Information (ESI) available: [details of any supplementary
information available should be included here]. See DOI: 10.1039/x0xx00000x
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DOI: 10.1039/C8OB00957K
Although these molecules are planar and rigorously 5-fold
symmetric, all of them bear alkyl groups as the peripheral
substituents and so are not ideal as building blocks for 2D
supramolecular assemblies.19,30,32,34 Suitably functionalised
macrocyclic pentamers could be useful for this purpose, and
also for dendrimer design and as building blocks for metal- or
covalent-organic frameworks (MOFs or COFs).36 The goal of this
study was to elaborate the synthesis of the campestarene
framework to allow the inclusion of a range of different
functional groups on the periphery which could serve as a
supply of 5-fold symmetric building blocks for supramolecular
assemblies.
Campestarenes are cyclic pentamers comprised of imine-
linked phenol groups. Several tautomers can be envisaged, with
enol-imine and keto-enamine forms as well as a zwitterionic
structure. Overall, the regular, planar shape is reinforced by the
3-centered hydrogen bonds between the imines and hydroxy
groups (Fig 1).30 Campestarenes are prepared by sequential
formylation and nitration of the corresponding phenols,
followed by cyclisation via a Schiff base amine-aldehyde
condensation which gives a homogeneous product in high yield.
The high selectivity for the pentameric structure from the one-
pot cyclisation is accounted for based on ab initio DFT
calculations, which for both tautomers of the pentamer were in
accord with the experimentally observed planar structure,
whereas the hexamer was calculated to adopt a twisted
confirmation.30 The planar structure favours intermolecular π-π
stacking leading to aggregation in solution and in the gas
phase.37, 38 Substitution with bulky organosilyl groups improved
their solubility in both polar and non-polar solvents allowing full
Compound
1a, 2a30
1b, 2b30
1c, 2c30
1d, 2d35
1e, 2e35
1f, 2f
R
Compound
1h, 2h
1i, 2i
1j, 2j
1k, 2k
1l, 2l
1m, 2m
1n, 2n
1o, 2o
R
tert-butyl
isoamyl
OCH(CH3)COOH
OCH3
Br
4-C5H4N
4-C6H4CN
4-C6H4COOH
C6H3-3-C4H9-4-COOH
C6H3-3-C7H15-4-COOH
1,1,3,3-tetramethylbutyl
triphenylsilyl
triisopropylsilyl
OCH(CH3)COOEt
OCH2COOH
1g, 2g
Scheme 1 Synthesis of campestarenes 1.
Results and discussion
The first approach to functionalising campestarenes is pre-
cyclisation derivatisation where the target functional group is
installed in the para-position of the monomeric phenol before
the cyclisation. Scheme 2 shows three synthetic routes to the
mono-substituted hydroquinones
(5g-Et, 5g-tBu and 5f)
required to prepare the precursors 2f-2h to the ester- and
carboxylic acid-substituted campestarenes 1f-1h. Route 1 is a
single substitution on hydroquinone using bromoacetate t-butyl
ester to yield 5g-tBu. Surprisingly, if the bromoacetate ethyl
ester was used then a mixture of the di-substituted product and
unreacted hydroquinone resulted even when the reaction time,
temperature, stoichiometry and solvent were varied. In routes
2 and 3 one hydroquinone hydroxyl group is protected by benzyl
characterisation,
including
a
molecular
structure
determination.35 Experimental studies on the tautomerisation
behaviour of campestarenes concluded that the location of the
interior protons was on nitrogen (keto-enamine form) in polar
solvents and on oxygen (enol-imine form) in non-polar solvents,
in agreement with DFT calculations. Campestarene derivatives
reported to date bear tert-butyl,30 1,1-dimethyl-propyl,30
1,1,3,3-tetramethylbutyl,30 triphenylsilyl35 and triisopropylsilyl
groups35 on the periphery 1a-1e (Scheme 1). The current study
extends the synthetic routes to campestarene derivatives
containing ester, carboxylic acid, methoxy, bromo, 4-pyridyl, 4-
cyanophenyl and 4-phenyl carboxylic acid groups, 1f-1o, chosen
for their potential utility as supramolecular recognition groups
for the construction of molecular assemblies.
and sulfate groups, respectively, resulting in 5g-Et
5f after deprotection. The next steps, formylation to give 6g-Et
6g-tBu and 6f, followed by nitration, yielded the target ester-
substituted campestarene precursors, 2g-Et 2g-tBu and 2f, of
, 5g-tBu and
,
,
which only 2f was taken on directly to the cyclisation step.
Cyclisation of 2f using sodium dithionite in refluxing
ethanol/water gave the ester-substituted campestarene 1f. De-
esterification of 1f to afford the penta-carboxylic acid
campestarene 1h using 1 or 2 M NaOH at 50oC was
unsuccessful. In the presence of strong base and heat the 3-
centered hydrogen bonds in the macrocycle core were
disrupted. Under milder conditions, < 1 M NaOH with or without
heating, the ester could not be converted into the carboxylic
acid. However, the ester precursors 2g-Et and 2g-tBu could be
de-esterified to form the carboxylic acid precursors 2g and 2h
which were then successfully cyclised to produce the carboxylic
acid campestarenes 1g and 1h
.
Compound 1f was purified by flash column chromatography
on alumina using dichloromethane/methanol as eluent to give
a pure purple solid product after solvent removal. Both silica
Fig 1 The enol-imine form with a shared hydrogen bond (left), the zwitterionic structure
(centre) and the keto-enamine form (right). The major change of hydrogen bonding is
highlighted in red.
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Scheme 2 Syntheses of ester/carboxylic acid campestarenes (1f-1h): (i) NaOH, dioxane/H2O, 3 h, then HCl; (ii) K2CO3, acetone, reflux, 3 h, then HCl; (iii) Pd/C, H2, EtOH, 12 h; (iv)
K2S2O8, NaOH, H2O, 24 h, then HCl; (v) K2CO3, EtOH, reflux 6 h, then AcOH, reflux, 2 h; (vi) Et3N, MgCl2, CH2O, MeCN, reflux, 24 h, then HCl; (vii) HNO3, AcOH, 2 h; (viii) R2= Et, NaOH,
MeOH/H2O, 12 h, then HCl or R2= t-Bu, TFA/DCM, 12 h; (ix) Na2S2O4, EtOH/H2O, reflux, 2 h.
and alumina column chromatography decomposed 1g and 1h
.
1h,
13C NMR, HSQC and HMBC spectra could not be obtained
Presumably, the five polar carboxylic acid groups on the even after more than 100,000 scans. The assignments of the 1H
macrocycles were excessively adsorbed onto silica and alumina. NMR spectra for 1f-1h are based on comparison with t-butyl
However, washing 1g and 1h with 0.1 M HCl followed by 0.1 M campestarene (1a).30
NaOH removed most of the organic by-products and
chromatography on Sephadex G-10 gave solid purple products, campestarene was conceived via the synthesis of methoxy
1g and 1h campestarene, 1i, with a plan to subsequently substitute the
An alternative approach to functionalisation of
.
Compared to t-butyl campestarene (1a) which is observed methoxy groups. 4-Methoxyphenol was formylated to form 7i
to aggregate and exists as a dimer in the gas phase and in and nitrated to prepare the precursor 2i which was cyclised to
solution,30 the 1H NMR spectra for 1f-1h in DMSO-d6 show no give 1i (Scheme 3). This purple solid was insoluble in most
evidence for aggregation (Fig 2). The signals near 17 and 9 ppm organic solvents except DMSO and DMF. The crude product 1i
can be assigned to the core hydrogens and the imine protons was purified by Soxhlet extraction with multiple solvents to
(N=CH), respectively. The two aromatic protons can be remove impurities. Although aggregation of 1i with its very flat
observed near 7.2 and 7.7 ppm. Both 1g and 1h are soluble in geometry was expected, no evidence of aggregation was
methanol, although 1h is the more soluble of the two. The ester observed by 1H NMR spectroscopy in DMSO-d6 (Fig S44) or
campestarene 1f is soluble in both methanol and MALDI-TOF MS. It is noted that ESI mass spectra could not be
dichloromethane indicating that the presence of the ester recorded for the campestarene derivatives. The attempted de-
groups confers better solubility in organic solvents than the methylation of 1i to form hydroxy campestarene using boron
carboxylic acids. Compounds 1f-1h show limited solubility in tribromide did not proceed to completion, even after addition
methanol and dichloromethane. DMSO dissolved 1f-1h best of excess BBr3. As shown in Fig. S46 (b)-(c), the signals assigned
among organic solvents. Due to the poor solubility of 1f
,
1g and to the methoxy protons at 3.9 ppm could still be observed
although with diminished intensities. The same difficulty in
achieving complete de-methylation has also been reported for
another 5-fold symmetric macrocycle.39
The brominated reagent 7j was used because halogens are
useful synthons for coupling reactions. Commercially available
reagent 7j was nitrated using fuming HNO3 to yield 2j which was
then cyclised to form bromo-campestarene 1j. Post-cyclisation
substitution of bromo-campestarene, 1j, has not yet been
achieved due its poor solubility, being only very sparingly
soluble in DMSO. In addition to the poor solubility issue, the 3-
centered hydrogen bonds in the macrocycle core limits the use
of strong regents that might cleave the imine bridges. Although
Fig 2 1H NMR spectra in DMSO-d6 of a) 1f, b) 1g and c) 1h. X denotes acetic acid and
grease.
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the condensation reaction is also tolerant toDcOyaI:n10o.1a0n39d/Cp8yOriBd0y0l957K
groups. MALDI-TOF MS confirmed the presence of 1k-1m
.
Unfortunately the solubilities of 1k-1m were too poor to
complete their purification and characterisation beyond MALDI-
TOF MS measurements. Even after multiple purification
attempts with washing using the Soxhlet technique for 1k and
1l and acid-base washing followed by Sephadex G-10 column
chromatography for 1m, the 1H NMR spectra of 1k-1m in
DMSO-d6 showed broad signals at 7-8 ppm. Based on a report
that the solubility of campestarenes could be improved by
appending n-alkyl groups,30 n-butyl and n-heptyl groups were
attached to the boronic acid reagents, 10n and 10o, which were
coupled to the intermediate 2j to synthesise the precursors 2n
and 2o (which are alkyl-substituted derivatives of 2m).
Cyclisations of 2n and 2o to synthesise campestarenes 1n and
1o were carried out under the same conditions (Scheme 4) and
their presence confirmed by MALDI-TOF MS. The solubility of
the resulting purple solid products was improved: the n-butyl
campestarene, 1n, is soluble in methanol and the n-heptyl
campestarene, 1o, can even be dissolved in dichloromethane.
However, even with improved solubility, broadening of the
Scheme 3 Syntheses of campestarenes (1i-1m): (x) HNO3, AcOH, 2 h; (xi) Na2CO3,
Pd(PPh3)4, DMF/H2O, 105oC, 6 h, then HCl; (xii) Na2S2O4, EtOH/H2O, reflux, 2h.
the MALDI-TOF mass spectrum of 1j shows peaks for [M+H]+,
[M+Na]+ and [M+K]+ with the correct isotope pattern for five
bromine atoms, its poor solubility did not allow successful
purification and consequently no further reactions were
undertaken. Surprisingly, dimerised or trimerised 1j
(aggregated) species were not found in the MALDI-TOF mass
spectrum (see Supporting Infomation).
The third approach to preparing peripherally substituted
campestarenes was to begin with boronic acid reagents and
employ Suzuki cross-coupling to install the substituents on the
precursors 2k-2m (Scheme 3). The boronic acid reagents
bearing 4-pyridyl, 4-cyanophenyl and 4-carboxyphenyl groups
were coupled to 2j, catalysed by tetrakis(triphenylphosphine)-
1
signals in their H NMR spectra in DMSO-d6 (Figs. S44, S45) is
still observed even after various attempts at further purification
via silica or alumina flash column chromatography, washing
using the Soxhlet technique and acid-base washing followed by
Sephadex G-10 column chromatography. In addition to the
broadening, the NMR spectra show additional structure in the
region of the imine N=CH and aryl CH peaks, as repoted for 1a
-
1c and interpreted as evidence for aggregation.30 Aggregation
probably also causes the poor solubility of 1k-1m and for all of
1k-1o most likely arises from the presence of 10 aromatic rings
in each campestarene derivative.
palladium(0), to give 2k-2m. Cyclisation of 2k-2m to synthesise
the corresponding campestarenes was successfully achieved to
yield the distinctive purple solid products 1k-1m, indicating that
Conclusions
Campestarenes substituted with methoxy, alkyl ester and alkyl
carboxylic acid can be prepared via sequential formylation and
nitration of appropriately substituted precursor monomers
followed by cyclisation. The cyclisation method is tolerant of
several functional groups on the monomers. The products
could be purified by Soxhlet extraction or acid-base washing
followed by Sephadex G-10 column chromatography, allowing
1
characterisation by H NMR spectroscopy and MALDI-TOF MS.
Difficulties with postcyclisation substitution on some of the
campestarenes may be attributed to the lower reactivity of
campestarenes in comparison with the monomer molecules, for
example in the de-methylation reaction. Disruption of the 3-
centered hydrogen bonds in the macrocycle core by
deprotonation in strongly basic media means that such
conditions need to be avoided. The 4-bromophenyl-substiuted
campestarenes are potentially a useful synthon but suffer, as do
other derviatives, from poor solubility.
The syntheses of monomers substituted with various aryl
functional groups were carried out via Suzuki coupling, followed
by cyclisation to the long-chain alkyl-substituted campestarenes
and the resulting products were characterised by MALDI-TOF
MS. Even so, all the derivatives bearing substituted aryl rings
Scheme 4 Syntheses of campestarenes (1n and 1o): (xiii) R5MgBr, THF, N2, 17 h, then HCl;
(xiv) n-BuLi, B(O-i-Pr)3, THF, -78oC, 3 h, then HCl; (xv) Na2CO3,Pd(PPh3)4, DMF/H2O, 105oC,
6 h; (xvi) Na2S2O4, EtOH/H2O, reflux, 2 h.
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were hampered by difficulties in purification of the sparingly Two equivalents of Et3N were added dropwisDeOtoI: 1a0.m10i3x9tu/Cr8eOoBf010957K
soluble products. Presumably, the additional five aryl groups equivalent of the corresponding phenol (5g-Et or 5g-tBu), 2
result in some aggregation with evidence of peak-broadening in equivalents of MgCl2 and 2.2 equivalents of paraformaldehyde
the 1H NMR spectra of these campestarenes in DMSO-d6.
in dry THF. The reaction mixture was refluxed for 24 h, cooled
Overall, the new compounds reported here show that the to r.t. and dilute HCl was added until the remaining solid was
rational synthesis of capestarenes bearing a range of functional completely dissolved. The organic phase was removed by rotary
groups can be achieved, expanding the potential utility of this evaporation and then the aqueous phase was extracted with
5-fold symmetric building block.
CH2Cl2. The combined extracts were dried over MgSO4, filtered
and the solvent removed under vacuum. The crude products
were purified by silica gel flash column chromatography.
Experimental section
General information
Method B (2g-Et, 2g-tBu and 2f).30
1.1 Equivalents of fuming HNO3 were added dropwise to the
corresponding hydroxybenzaldehyde (6g-Et, 6g-tBu or 6f) in
glacial acetic acid. After stirring at r.t. for 2 h, water was added
to the reaction mixture and a white precipitate formed. The
crude product was collected by filtration and recrystallized from
hot EtOH by addition of cold water.
All reagents and solvents were obtained from commercial
suppliers and used as received unless otherwise noted. All dry
solvents were collected from a solvent purifier manufactured by
LC Technology Solutions Inc (www.ictechinc.com). Sephadex G-
10 gel was sourced from Amersham Bioscience. “MilliQ” water
was used in all synthetic procedures and in the preparation of
Sephadex G-10 columns.
High resolution mass spectra were recorded on a Bruker
microHTOFQ (Hybrid Quadrupole Time of Flight) mass
spectrometer in electrospray ionisation (ESI) mode. MALDI-TOF
MS analyses were performed using saturated α-cyano-4-
hydroxycinnamic acid in 30% water in methanol as matrix on a
Voyager-DE™ PRO MALDI-TOF mass spectrometer (Applied
Biosystems, Inc., Foster City, CA). Prior to data collection, a
linear external calibration was performed using the mass
Method C (1f-1o).30
Six equivalents of sodium dithionite (Na2S2O4) were added to
the corresponding 2-hydroxy-3-nitrobenzaldehyde (2f-2o) in
EtOH and water. The reaction mixture was refluxed for 2 h,
cooled to r.t. and the solvent removed under vacuum.
Method D (2k, 2l and 2o).41
One equivalent of 2j, 1.2 equivalents of the corresponding
boronic acid, 6 equivalents of sodium carbonate and 0.05
equivalents of tetrakis(triphenylphosphine)palladium(0) were
dissolved/suspended in DMF / water (1:1). The reaction mixture
was heated at 105oC under N2 for 6 h. After cooling to r.t., 1 M
NaOH was added to the reaction mixture which was then
washed with CH2Cl2. The aqueous phase was acidified with 6 M
HCl to give an orange/yellow precipitate which was washed
with water and diethyl ether and then dried under vacuum.
calibrants: bovine insulin (Mr
= 5734), Escherichia coli
thioredoxin (Mr = 11,674) and equine apomyoglobin (Mr =
16,952). For presentation, acquired ESI and MALDI mass spectra
underwent smoothing and baseline subtraction using mMass
(Version 5.5.0). The UV/Vis absorption measurements were
obtained using a Shimadzu UV-Vis-NIR Spectrophotometer UV-
3600 Plus and the software package UVProbe 2.50. Infrared
spectra were recorded on a Perkin Elmer Spectrum 100 infrared
spectrometer.
1H, 11B, 13C, COSY, HSQC, HMBC and NOESY NMR spectra
were recorded on a Bruker Avance III 300, 400 or HD 500
spectrometers. Spectra recorded in CDCl3, D2O, CD3OD, and
DMSO-d6 were referenced to TSP-d4 for D2O, or the respective
Ethyl 2-(3-formyl-4-hydroxyphenoxy) acetate, 6g-Et
Method A. 5g-Et (1.80 g, 9.17 mmol), THF (80 mL) and 5% HCl
(150 mL). Purified by flash silica column chromatography
(eluent: 10% EtOAc in CH2Cl2) to give a yellow oil product. The
first band was the product. Yield: 0.380 g, 18.5%; HRMS (ESI)
residual
solvent
peaks.
Alkylation,40
boronation,40
formylation,30, 41 nitration,30 Suzuki coupling42 and cyclisation30
were performed according to literature. Analytical grades of
[M+Na]+ = calcd 247.0582 m/z, found 247.0573 m/z; H NMR
1
(300 MHz, CDCl3): δ = 10.62 (s, 1 H), 9.77 (s, 1 H), 7.16 (dd, 1 H,
J = 9.1, 3.0 Hz), 7.00 (d, 1 H, J = 3.0 Hz), 6.89 (d, 1 H, J = 9.1 Hz),
4.56 (s, 2 H), 4.25 (q, 2 H, J = 7.1 Hz), 1.27 (t, 3 H, J = 7.1 Hz); 13
NMR (75 MHz, CDCl3): δ = 195.99, 168.70, 156.70, 151.00,
125.87, 120.06, 118.83, 117.22, 66.37, 61.44, 14.13.
precursors
3, 7j, 8, hydroquinone, phenol, reagents and
solvents were purchased and used without further purification.
C
2i 43 2j 44 2m 42 4 45 4g-Et 46 4f 46 5g-Et 45, 46 5g-tBu 47 5f45, 46 and
, , , , , , , ,
7i48 were synthesised using either reported or modified
precedures. Their characterisation data matched literature
values. 6g-Et
10n 10o 2n
this research. Compounds 6g-Et and 6g-tBu were prepared
using Method A, 2g-Et 2g-tBu and 2f using Method B, 1f-1o
using Method C and 2k 2l 2n and 2o using Method D.
,
6g-tBu
, 6f, 2g-Et, 2g-tBu, 2f, 2g, 2h, 2k, 2l, 9n, 9o,
tert-Butyl 2-(3-formyl-4-hydroxyphenoxy) acetate, 6g-tBu
Method A. 5g-tBu (0.280 g, 1.25 mmol), THF (30 mL) and 3 M
HCl (2 mL). Purified by flash silica column chromatography
(eluent: 10% EtOAc in CH2Cl2) to give the product as a yellow oil.
The first band was the product. Yield: 0.073 g, 23.2%; HRMS
,
,
, 2o, and campestarenes 1f-1o were synthesised in
,
,
,
(ESI) [M+Na]+ = calcd 275.0895 m/z, found 275.0885 m/z 1H
;
Method A (6g-Et and 6g-tBu).30
NMR (500 MHz, CDCl3): δ = 10.60 (s, 1 H), 9.76 (s, 1 H), 7.13 (dd,
1 H, J = 9.0, 3.1 Hz), 6.97 (d, 1 H, J = 3.1 Hz), 6.88 (d, 1 H, J = 9.0
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Hz), 4.46 (s, 2 H), 1.43 (s, 9 H); 13C NMR (125 MHz, CDCl3): δ = turned to dark red in colour immediately afteDrOthI:e10a.1d0d3i9t/iCo8nOoBf010957K
195.99, 167.79, 156.55, 151.07, 125.74, 120.03, 118.76, 117.20, M NaOH. The reaction mixture was stirred at r.t. overnight.
82.52, 66.60, 28.01.
MeOH was removed under reduced pressure. 1 M HCl (25 mL)
was added to the remaining solution to form a yellow solution
(pH 1) which was extracted with CH2Cl2, dried over Na2SO4 and
Ethyl 2-(3-formyl-4-hydroxyphenoxy) propanoate, 6f
A mixture of 5f (2.52 g, 12.0 mmol), MgCl2 (1.71 g, 18.0 mmol), the solvent removed under vacuum to give yellow oily solid.
Et3N (6.36 mL, 45.6 mmol) and equivalents of Yield: 0.164 g, 99.6%;
5
paraformaldehyde (1.80 g, 60.0 mmol) in MeCN (100 mL) was 2g-tBu (0.027 g, 0.091 mmol) was dissolved in CH2Cl2 (5 mL) and
refluxed for 24 h, cooled to r.t. and poured into 5% HCl (150 mL). TFA (0.02 mL, 0.272 mmol) was added at r.t. The reaction
The crude product was extracted with diethyl ether, dried over mixture was then stirred at r.t. overnight. The solvent was
MgSO4 and the solvent removed under vacuum. The yellow oil removed under vacuum and the remaining acid was co-
residue was purified by silica gel flash column chromatography evaporated with dioxane twice to give a yellow oil. Yield: 0.021
(eluent: 10% EtOAc in n-hexane). The first band was the yellow g, 95.8%; HRMS (ESI) [M-H]- = calcd 240.0233 m/z, found
1
oil product. Yield: 0.670 g, 23.5%; HRMS (ESI) [M+Na]+ = calcd 240.0168 m/z; H NMR (500 MHz, CDCl3): δ = 11.85 (s, 1 H),
261.0739 m/z, found 261.0737 m/z; 1H NMR (400 MHz, CDCl3): 10.95 (s, 1 H), 10.45 (s, 1 H), 7.94 (d, 1 H, J = 3.4 Hz), 7.77 (d, 1
δ = 10.53 (s, 1 H), 9.69 (s, 1 H), 7.06 (dd, 1 H, J = 8.9, 3.0 Hz), 6.92 H, J = 3.4 Hz), 4.76 (s, 2 H); 13C NMR (125 MHz, CDCl3): δ =
(d, 1 H, J = 3.0 Hz), 6.79 (d, 1 H, J = 8.9 Hz), 4.62 (q, 1 H, J = 6.7 187.96, 172.38, 151.94, 150.19, 126.43, 124.29, 123.48, 117.70,
Hz), 4.13 (q, 2 H, J = 7.0 Hz), 1.51 (d, 3 H, J = 6.7 Hz), 1.15 (t, 3 H, 65.67.
J = 7.0 Hz); 13C NMR (100 MHz, CDCl3): δ = 195.916, 171.64,
156.43, 150.51, 126.23, 119.96, 118.54, 117.88, 73.66, 61.16, 2-(3-formyl-4-hydroxy-5-nitrophenoxy) propanoic acid, 2h
18.29, 13.94.
1 M NaOH (80 mL) was added to a solution of 2f (0.356 g, 1.26
mmol) in MeOH (100 mL). The yellow/orange solution turned to
dark red in colour immediately after the addition of 1 M NaOH.
Ethyl 2-(3-formyl-4-hydroxy-5-nitrophenoxy) acetate, 2g-Et
Method B. 6g-Et (0.455g, 2.03 mmol), acetic acid (2 mL) and The reaction mixture was stirred at r.t. overnight. MeOH was
water (100 mL). Purified by recrystallization from chloroform to removed under reduced pressure. 1 M HCl (50 mL) was added
give a yellow solid. Yield: 0.184 g, 40.4%; HRMS (ESI) [M+Na]+ = to the remaining solution to form a yellow solution (pH 1) which
1
calcd 292.0433 m/z, found 292.0439 m/z; H NMR (300 MHz, was extracted with CH2Cl2, dried over Na2SO4 and the solvent
CDCl3): δ = 10.91 (s, 1 H), 10.42 (s, 1 H), 7.90 (d, 1 H, J = 3.1 Hz), removed under vacuum to give yellow oily solid. Yield: 0.320 g,
7.72 (d, 1 H, J = 3.2 Hz), 4.67 (s, 2 H), 4.31 (q, 2 H, J = 7.1 Hz), 99.6%; HRMS (ESI) [M+Na]+ = calcd 278.0277 m/z, found
1.33 (t, 3 H, J = 7.1 Hz); 13C NMR (75 MHz, CDCl3): δ = 187.97, 278.0273 m/z; H NMR (500 MHz, CDCl3): δ = 10.91 (s, 1 H),
1
167.92, 151.85, 150.39, 134.75 (found in HMBC), 126.38, 10.41 (s, 1 H), 7.89 (d, 1 H, J = 3.0 Hz), 7.70 (d, 1 H, J = 3.0 Hz),
123.56, 116.97, 66.22, 61.97, 14.28.
4.85 (q, 1 H, J = 7.0 Hz), 1.70 (d, 3 H, J = 7.0 Hz); 13C NMR (125
MHz, CDCl3): δ = 188.12, 175.72, 151.94, 149.87, 135.06,
tert-Butyl 2-(3-formyl-4-hydroxy-5-nitrophenoxy) acetate, 2g- 126.36, 124.05, 117.70, 73.33, 18.37.
tBu
Method B. 6g-tBu (0.073 g, 0.089 mmol), acetic acid (1 mL) and 2-Hydroxy-3-nitro-5-(pyridin-4-yl)benzaldehyde, 2k
water (20 mL). Purified by flash silica column chromatography Method D. 4-Pyridinylboronic acid (0.148 g, 1.2 mmol), DMF (20
(eluent: 33% EtOAc in CH2Cl2) to give a yellow/orange oil. The mL) / water (20 mL), 6 M HCl (40 mL), CH2Cl2 (3 x 10 mL), 1 M
2nd band was the product. Yield: 0.027 g, 63.5%; HRMS (ESI) NaOH (60 mL) and diethyl ether (3 x 5 mL). Yield: 0.134 g, 55.7%;
1
[M+Na]+ = calcd 320.0746 m/z, found 320.0736 m/z; H NMR HRMS (ESI) [M+H]+ = calcd 245.0484 m/z, found 245.0559 m/z,
1
(400 MHz, CDCl3): δ = 10.90 (s, 1 H), 10.43 (s, 1 H), 7.88 (d, 1 H, [M+Na]+ = calcd 267.0382 m/z, found 267.0377 m/z; H NMR
J = 3.2 Hz), 7.71 (d, 1 H, J = 3.2 Hz), 4.57 (s, 2 H), 1.50 (s, 9 H).
(500 MHz, DMSO-d6): δ = 10.25 (s, 1 H), 8.47 (d, 2 H, J = 4.8 Hz),
8.30 (d, 1 H, J = 4.8 Hz), 7.95 (d, 1 H, J = 2.6 Hz), 7.55 (d, 4 H, J =
2.6 Hz); 13C NMR (125 MHz, DMSO-d6): δ = 190.56, 168.71,
Ethyl 2-(3-formyl-4-hydroxy-5-nitrophenoxy) propanoate, 2f
Method B. 6f (0.467 g, 1.96 mmol), acetic acid (2 mL) and water 149.97, 146.00, 143.11, 130.98, 130.05, 130.00, 118.96, 112.98.
(100 mL). An orange oil product. Yield: 0.251 g, 45.2%; HRMS
1
(ESI) [M+Na]+ = calcd 306.0590 m/z, found 306.0573 m/z; H 3'-Formyl-4'-hydroxy-5'-nitro-[1,1'-biphenyl]-4-carbonitrile, 2l
NMR (300 MHz, CDCl3): δ = 10.90 (s, 1 H), 10.41 (s, 1 H), 7.87 (d, Method D. 4-Cyanophenylboronic acid (0.176 g, 1.20 mmol),
1 H, J = 3.1 Hz), 7.69 (d, 1 H, J = 3.1 Hz), 4.79 (q, 1 H, J = 6.8 Hz), DMF (20 mL) / water (20 mL), 1 M NaOH (20 mL), CH2Cl2 (3 x 10
4.27 (q, 2 H, J = 7.1 Hz), 1.66 (d, 3 H, J = 6.8 Hz), 1.30 (t, 3 H, J = mL), 6 M HCl (20 mL) and diethyl ether (3 x 5 mL). Yield: 0.108
7.1 Hz); 13C NMR (75 MHz, CDCl3): δ = 188.04, 171.02, 151.75, g, 40.3%; HRMS (ESI) [M-H]- = calcd 267.0484 m/z, found
150.17, 135.31 (found in HMBC), 126.32, 124.22, 117.44, 73.93, 267.0414 m/z; 1H NMR (300 MHz, DMSO-d6): δ = 10.25 (s, 1 H),
61.93, 29.84, 18.44.
8.25 (d, 1 H, J = 2.9 Hz), 7.90 (d, 1 H, J = 2.9 Hz), 7.76 (d, 4 H, J =
2.0 Hz); 13C NMR (125 MHz, DMSO-d6): δ = 190.65, 168.46,
143.78, 142.87, 132.71, 131.77, 130.43, 130.11, 125.27, 119.19,
2-(3-formyl-4-hydroxy-5-nitrophenoxy) acetic acid, 2g
1 M NaOH (40 mL) was added to a solution of 2g-Et (0.184 g, 114.63, 107.49.
0.683 mmol) in MeOH (50 mL). The yellow/orange solution
6 | Org. Biomol.Chem., 2018, 00, 1-3
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4-Bromo-2-butylbenzoic acid, 9n
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2 H), 1.41 – 1.35 (m, 4 H), 0.95 (t, 3 H, J = 7.3DHOzI):;10.1039/C8OB00957K
13C NMR (125
1-Bromobutane (0.740 mL, 6.85 mmol) was added to MHz, MeOD): δ =171.81, 144.02, 137.43, 133.07, 131.98,
magnesium turnings (0.333 g, 13.7 mmol) in dry THF (7 mL) and 130.39, 125.46, 35.39, 35.07, 23.81, 14.28; 11B NMR (160 MHz,
the mixture was refluxed for 30 min. After cooling to r.t., the MeOD): δ = 18.54 (s, 1 B)
mixture was transferred to a solution of
8 (0.500 g, 2.28 mmol)
in dry THF (5 mL) at 0oC. The mixture was warmed to r.t. and 4-Borono-2-heptylbenzoic acid, 10o
stirred for 17 h under N2. Cold water (40 mL) was slowly added 2.5 M n-Butyllithium in n-hexane (7.31 mL, 18.3 mmol) was
to the mixture in an ice bath. The mixture was then acidified added dropwise to a solution of 9o (1.82 g, 6.10 mmol) in dry
with 6 M HCl until pH 1-2 and extracted with EtOAc (2 x 30 mL). THF (100 mL) at -78oC and the mixture was stirred at -78oC for
The combined organic layers were washed with brine, dried 10 min. Triisopropyl borate (4.22 mL, 18.3 mmol) was then
over Na2SO4 and the solvent removed under vacuum to give a added dropwise at -78oC and the mixture was then stirred at -
white solid. The crude product was purified by flash silica 78oC for 3 h. After warming to 0oC, the reaction mixture was
chromatography (eluent: CHCl3 to 30% of MeOH in CHCl3) to quenched with 2 M HCl (25 mL) and extracted with EtOAc (2 x
give a yellow solid. Yield: 0.396 g, 68.0%; HRMS (ESI) [M-H]- = 30 mL). The combined organic layers were stirred with 2.5 M
1
calcd 255.0099 m/z, found 255.0026 m/z; H NMR (500 MHz, NaOH (25 mL) for 10 min. The collected aqueous layer was
CDCl3): δ = 7.74 (t, 1 H, J = 8.0 Hz), 7.34 (m, 2 H), 2.94 (td, 2 H, J acidified to pH 3 with 6 M HCl, extracted with ethyl acetate,
= 7.3, 3.1 Hz), 1.67 (p, 2 H, J = 7.6 Hz), 1.41 – 1.32 (m, 2 H), 0.94 dried over Na2SO4 and concentrated to give a white precipitate
(t, 3 H, J = 7.3 Hz); 13C NMR (125 MHz, CDCl3): δ =197.88, 162.60, which collected by filtration, was washed with CH2Cl2 and dried
160.55, 131.93, 131.90, 128.15, 128.12, 124.94, 124.83, 120.45, under vacuum. Yield: 0.413 g, 25.7%; HRMS (ESI) [M-H]- = calcd
120.24, 43.44, 43.39, 26.12, 22.44, 14.00
263.1463 m/z, found 263.1466 m/z; 1H NMR (400 MHz, MeOD):
δ = 7.76 – 7.46 (m, 3 H), 2.96 (t, 2 H, J = 7.9 Hz), 1.60 – 1.53 (m,
2 H), 1.35 – 1.29 (m, 8 H), 0.91 (t, 3 H, J = 7.3 Hz); 13C NMR (100
4-Bromo-2-heptylbenzoic acid, 9o
1-Bromoheptane (11 mL, 68.5 mmol) was added to magnesium MHz, MeOD): δ = 162.72, 144.04, 137.09, 131.94, 131.56,
turnings (3.33 g, 137 mmol) in dry THF (50 mL) and the mixture 130.41, 35.34, 33.17, 33.01, 30.76, 30.26, 23.69, 14.41; 11B NMR
was refluxed for 30 min. After cooling to r.t., the mixture was (128 MHz, MeOD): δ = 18.76 (s, 1 B).
transferred to a solution of 8 (5.00 g, 22.8 mmol) in dry THF (50
mL) at 0oC. The mixture was warmed to r.t. and stirred for 24 h 3-Butyl-3'-formyl-4'-hydroxy-5'-nitro-[1,1'-biphenyl]-4-
under N2. Cold water (400 mL) was slowly added to the mixture carboxylic acid, 2n
in an ice bath. The mixture was then acidified with 6 M HCl until Method D. 10n (0.109 g, 0.491 mmol), DMF (10 mL) / water (10
pH 1-2 and extracted with EtOAc (2 x 200 mL). The combined mL), 1 M NaOH (10 mL), CH2Cl2 (3 x 5 mL), 6 M HCl (10 mL) and
organic layers were washed with brine, dried over Na2SO4 and washing with water only. Yield: 0.167 g, 99.0%; HRMS (ESI) [M-
1
the solvent removed under vacuum to give a white solid. The H]- = calcd 342.0983 m/z, found 342.0994 m/z; H NMR (300
crude product was purified by flash silica chromatography MHz, DMSO-d6): δ = 12.87 (s, 1 H), 10.33 (s, 1 H), 8.54 (d, 1 H, J
(eluent: CHCl3 to 30% of MeOH in CHCl3) to give a yellow solid. = 2.5 Hz), 8.34 (d, 1 H, J = 2.5 Hz), 7.88 (d, 1 H, J = 8.2 Hz), 7.68
1
Yield: 1.82 g, 26.7%; H NMR (400 MHz, CDCl3): δ = 11.59 (s, 1 (d, 1 H, J = 2.1 Hz), 7.65 (dd, 1 H, J = 8.2, 2.1 Hz), 3.03 (t, 2 H, J =
H), 7.93 (t, 1 H, J = 7.8 Hz), 7.04 (m, 2 H), 2.98 (t, 2 H, J = 7.7 Hz), 8.0 Hz), 1.60 (p, 2 H, J = 7.5 Hz), 1.38 (s, 2 H, J = 7.5 Hz), 0.93 (t,
1.64 – 1.59 (m, 2 H), 1.36 – 1.24 (m, 6 H), 0.90 (t, 3 H, J = 7.0 Hz); 3 H, J = 7.2 Hz)
13C NMR (100 MHz, CDCl3): δ = 170.07, 162.72, 161.53, 152.42,
134.13, 124.29, 116.97, 35.90, 31.84, 31.64, 30.76, 29.17, 22.76, 3'-Formyl-3-heptyl-4'-hydroxy-5'-nitro-[1,1'-biphenyl]-4-
14.16.
carboxylic acid, 2o
Method D. 10o (0.100 g, 0.379 mmol), DMF (8 mL) / water (8
mL), 1 M NaOH (8 mL), CH2Cl2 (3 x 4 mL), 6 M HCl (8 mL) and
4-Borono-2-butylbenzoic acid, 10n
2.5 M n-butyllithium in n-hexane (21.5 mL, 53.9 mmol) was washing with water alone. Yield: 0.113 g, 92.6%; HRMS (ESI)
1
added dropwise to a solution of 9n (3.96 g, 15.4 mmol) in dry [M+Na]+ = calcd 408.1418 m/z, found 408.1404 m/z; H NMR
THF (200 mL) at -78oC and the mixture was stirred at -78oC for (300 MHz, CDCl3): δ = 11.41 (s, 1 H), 10.50 (s, 1 H), 8.61 (d, 1 H,
10 min. Triisopropyl borate (12.5 mL, 53.9 mmol) was then J = 2.5 Hz), 8.39 (d, 1 H, J = 2.5 Hz), 8.16 (d, 1 H, J = 8.8 Hz), 7.52
added dropwise at -78oC and the mixture was then stirred at - (d, 1 H, J = 1.9 Hz), 7.49 (m, 1 H), 3.13 (t, 2 H, J = 7.6 Hz), 1.72 (p,
78oC for 3 h. After warmed up to 0oC, the reaction mixture was 2 H, J = 6.7 Hz), 1.45 – 1.30 (m, 8 H), 0.91 (t, 3 H, J = 6.6 Hz); 13
C
quenched with 2 M HCl (60.0 mL) and extracted with EtOAc (2 x NMR (75 MHz, CDCl3): δ = 188.99, 170.92, 156.27, 147.49,
300 mL). The combined organic layers were stirred with 2.5 M 141.11, 135.37, 132.89, 135.66, 132.45, 129.52, 129.33, 128.08,
NaOH (160 mL) for 10 min. The collected aqueous layer was 126.09, 124.13, 34.98, 32.11, 31.98, 29.92, 29.26, 22.81, 14.25.
acidified to pH 3 with 6 M HCl, extracted with EtOAc, dried over
Na2SO4 and concentrated to give a white precipitate which was Penta-ethylpropanoate(oxy)-campestarene, 1f
collected by filtration, washed with CH2Cl2 and dried under Method C. 2f (0.251 g, 0.886 mmol) in EtOH (20 mL) and water
vacuum. Yield: 1.33 g, 39.0%; HRMS (ESI) [M-H]- = calcd (3 mL). Purified twice by flash alumina column chromatography
221.0993 m/z, found 221.0988 m/z; 1H NMR (500 MHz, MeOD): (eluent: 3-10% MeOH in CH2Cl2). On column chromatography
δ = 7.87 – 7.46 (m, 3 H), 2.97 (t, 2 H, J = 8.0 Hz), 1.60 –1.54 (m, impurities were removed with 3% MeOH in CH2Cl2 and the pure
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purple product was collected with 4-10% MeOH in CH2Cl2. Yield: H, CH3). UV-vis (λmax/nm (ε/M−1 cm−1 ), DMSO): 442 (966), 303
90.0 mg, 43.2%; MALDI-TOF-MS [M+H]+ = calcd 1176.4223 m/z, (1148).
DOI: 10.1039/C8OB00957K
found 1176.9572 m/z, [M+Na]+ = calcd 1198.4121 m/z, found
1198.9564 m/z, [M+K]+
= calcd 1214.3860 m/z, found Pentabromo-campestarene, 1j
1214.9379 m/z; 1H NMR (500 MHz, DMSO-d6): δ =16.51 (s, 5 H, Method C. 2j (1 g, 4.06 mmol) in EtOH (20 mL) and water (3 mL).
OH), 9.27 (s, 5 H, HC=N), 7.67 (s, 5 H, Ar-H), 7.06 (s, 5 H, Ar-H), The purple crude product was purified twice by Soxhlet
5.01 (q, 5 H, J = 6.7 Hz, CH), 4.22 (q, 10 H, J = 6.7 Hz, CH2), 1.57 technique using CH2Cl2 and MeOH as solvents for 24 h each and
(d, 15 H, J = 6.7 Hz, CH3), 1.23 (t, 15 H, J = 6.7 Hz, CH3). UV-vis multiple washing with water using an ultra-sonic bath. Yield:
(λmax/nm (ε/M−1 cm−1 ), DMSO): 555 (1334), 440 (3016), 304 0.764 g, 94.9%; MALDI-TOF-MS [M+H]+ = calcd 989.7340 m/z,
(3408).
found 989.7634 m/z, [M+Na]+ = calcd 1011.7238 m/z, found
1011.7281 m/z, [M+K]+
calcd 1027.6977 m/z, found
1027.7227 m/z. UV-vis (λmax/nm (ε/M−1 cm−1 ), DMSO): 534
=
Pentaaceto-campestarene, 1g
Method C. 2g (0.020 g, 0.083 mmol), EtOH (2 mL) and water (0.3 (3001), 304 (2826).
mL). Purification: After addition of water (10 mL), the mixture
was acidified with 0.1 M HCl to give purple precipitate which Penta(pyridyl)-campestarene, 1k
was re-dissolved in 0.1 M NaOH (1 mL) and purified by Sephadex Method C. 2k (0.134 g, 0.549 mmol) in EtOH (20 mL) and water
G-10 column chromatography. The collected purple solution (3 mL). The purple crude product was purified twice by Soxhlet
was acidified with 0.1 M HCl to give purple precipitate which technique using CH2Cl2 and MeOH as solvents for 24 h each and
was collected by centrifuge, washed with minimum amount of multiple washing with water using an ultra-sonic bath. Yield:
water and dried under vacuum to give purple solid products. 0.062 g, 57.4%; MALDI-TOF-MS [M+H]+ = calcd 981.3183 m/z,
Yield: 2.00 mg, 12.5%; MALDI-TOF-MS [M+H]+ = calcd 966.1875 found 981.4041 m/z, [M+Na]+ = calcd 1003.3081 m/z, found
m/z, found 966.3094 m/z, [M+Na]+ = calcd 988.1773 m/z, found 1003.3911 m/z, [M+K]+
= calcd 1019.2820 m/z, found
988.2966 m/z, [M+K]+ = calcd 1004.1512 m/z, found 1004.3279 1019.3751 m/z. UV-vis (DMSO) λmax/nm: 538, 317.
1
m/z; H NMR (300 MHz, DMSO-d6): δ =16.39 (s, 5 H, OH), 9.31
(s, 5 H, HC=N), 7.66 (s, 5 H, Ar-H), 7.12 (s, 5 H, Ar-H), 4.75 (s, 10 Penta(cyanoaryl)-campestarene, 1l
H, CH2). UV-vis (λmax/nm (ε/M−1 cm−1 ), DMSO): 545 (1337), 321 Method C. 2l (0.108 g, 0.402 mmol) in EtOH (20 mL) and water
(3692).
(3 mL). The purple crude product was purified twice by Soxhlet
technique using CH2Cl2 and MeOH as solvents for 24 h each and
multiple washing with water using an ultra-sonic bath. Yield:
Pentapropionoxy-campestarene, 1h
Method C. 2h (0.320 g, 1.26 mmol) in EtOH (35 mL) and water 0.049 g, 55.1%; MALDI-TOF-MS [M+H]+ = calcd 1101.3183 m/z,
(4 mL). Purification: After addition of water (20 mL), the mixture found 1101.5008 m/z, [M+Na]+ = calcd 1123.3081 m/z, found
was acidified with 0.1 M HCl to give purple precipitate which 1123.4918 m/z, [M+K]+
= calcd 1139.2820 m/z, found
was re-dissolved in 0.1 M NaOH (1 mL) and purified by Sephadex 1139.4703 m/z. UV-vis (DMSO) λmax/nm: 537, 319.
G-10 column chromatography. The collected purple solution
was acidified with 0.1 M HCl to give purple precipitate which Penta(arylcarboxylic acid)-campestarene, 1m
was collected by centrifuge, washed with minimum amount of Method C. 2m (0.176 g, 0.612 mmol) in EtOH (20 mL) and water
water and dried under vacuum to give purple solid products. (3 mL). The purple crude product was purified twice by Soxhlet
Yield: 28.0 mg, 10.8%; MALDI-TOF-MS [M+H]+
1036.2658 m/z, found 1036.4210 m/z, [M+Na]+ = calcd multiple washing with water using an ultra-sonic bath. Yield:
= calcd technique using CH2Cl2 and MeOH as solvents for 24 h each and
1058.2556 m/z, found 1058.4048 m/z, [M+K]+
=
calcd 0.091 g, 62.3%; MALDI-TOF-MS [M+Na]+ = calcd 1218.2810 m/z,
1074.2295 m/z, found 1074.4120 m/z; 1H NMR (400 MHz, found 1218.5125 m/z. UV-vis (DMSO) λmax/nm: 538.
DMSO-d6): δ =16.49 (s, 5 H, OH), 9.30 (s, 5 H, HC=N), 7.66 (s, 5
H, Ar-H), 7.06 (s, 5 H, Ar-H), 4.90 (d, 5 H, J = 7.0 Hz, CH), 1.57 (d, Penta(n-butylarylcarboxylic acid)-campestarene, 1n
15 H, J = 7.0 Hz, CH3). UV-vis (λmax/nm (ε/M−1 cm−1 ), DMSO): 551 Method C. 2n (0.167 g, 0.486 mmol) in EtOH (17 mL) and water
(5303), 450 (4807), 319 (6429).
(2 mL). Purification: After addition of water (10 mL), the mixture
was acidified with 0.1 M HCl to give purple precipitate which
was re-dissolved in 0.1 M NaOH (0.5 mL) and purified by
Pentamethoxy-campestarene, 1i
Method C. 2i (0.182 g, 0.923 mmol) in EtOH (20 mL) and water Sephadex G-10 column chromatography. The collected purple
(3 mL). The purple crude product was purified twice by Soxhlet solution was acidified with 0.1 M HCl to give purple precipitate
technique using CH2Cl2 and MeOH as solvents for 24 h each and which was collected by centrifuge, washed with minimum
multiple washing with water using an ultra-sonic bath. Yield: amount of water and dried under vacuum to give purple solid
0.082 g, 59.4%; MALDI-TOF-MS [M+H]+ = calcd 746.2384 m/z, products. Yield: 35.1 mg, 24.5%; MALDI-TOF-MS [M+H]+ = calcd
found 746.3896 m/z, [M+Na]+ = calcd 768.2282 m/z, found 1476.6042 m/z, found 1476.7339 m/z, [M+Na]+ = calcd
768.3630 m/z, [M+K]+ = calcd 784.2021 m/z, found 784.3323 1498.5940 m/z, found 1498.8278 m/z, [M+K]+
= calcd
1
m/z; H NMR (400 MHz, DMSO-d6): δ =16.34 (s, 5 H, OH), 9.26 1514.5679 m/z, found 1514.8114 m/z. UV-vis (λmax/nm (ε/M−1
(s, 5 H, HC=N), 7.53 (s, 5 H, Ar-H), 7.51 (s, 5 H, Ar-H), 3.84 (s, 15 cm−1 ), DMSO): 544 (4342), 314 (9788).
8 | Org. Biomol.Chem., 2018, 00, 1-3
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Penta(n-heptylarylcarboxylic acid)-campestarene, 1o
Method C. 2o (0.113 g, 0.293 mmol) in EtOH (17 mL) and water
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was acidified with 0.1 M HCl to give purple precipitate which
was re-dissolved in 0.1 M NaOH (1 mL) and purified by Sephadex
G-10 column chromatography. The collected purple solution
was acidified with 0.1 M HCl to give purple precipitate which
was collected by centrifuge, washed with minimum amount of
water and dried under vacuum to give purple solid products.
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Acknowledgements
SJN is grateful to the University of Auckland, Faculty of Science
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Table of contents entry
OH
OH
=
O
O
N
O
O
Br
OH
HO
N
O
N
OH
HO
OH
N
N
R
R
N
CN
O
OH
New campestarene derivatives bear functional groups designed to facilitate the
formation of supramolecular assemblies of these 5-fold symmetric building
blocks.