Regioselective routes to disubstituted dibenzo crown ethers and their complexations

Article abstract of DOI:10.1039/b503072m

Two isomers of bis(carbomethoxybenzo)-24-crown-8 (cis-BCMB24C8, 1, and trans-BCMB24C8, 2) were synthesized regiospecifically with acceptable to excellent yields. Cyclization in the presence of a template reagent, KPF ₆, led to an essentially quantitative yield of the potassium complex of the crown ether 1; the isolated cyclization yield of pure 1 was a remarkable 89%! The methods not only avoid the very difficult separation of the isomers, but also greatly shorten the synthesis time by eliminating syringe pump usage during cyclization. The complexations of the isomeric BCMB24C8 with dibenzylammonium hexafluorophosphate (10) were studied by NMR; association constants (K_a) for 1 and 2 with the dibenzylammonium cation are 190 and 312 M^-1, respectively. The X-ray crystal structures of crown ether 2 and the complexes 1·KPF₆, 2·KPF₆ and pseudorotaxane 2·10 were determined. The Royal Society of Chemistry 2005.

Full text of DOI:10.1039/b503072m

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A R T I C L E
Regioselective routes to disubstituted dibenzo crown ethers and their
complexations†
a
a
Harry W. Gibson,*a Hong Wang,‡a Klaus Bonrad,§ Jason W. Jones,¶ Carla Slebodnick,a
Lev N. Zackharov,*b Arnold L. Rheingold,b Bradley Habenicht,††a Peter Lobue‡‡a and
a
Amy E. Ratliff§§
a Chemistry Department, Virginia Polytechnic Institute and State University, Blacksburg,
Virginia, 24061-0212, USA. E-mail: hwgibson@vt.edu; Fax: 540-231-8517; Tel: 540-231-5902
b Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla,
California, 92093-0358, USA
Received 1st March 2005, Accepted 12th April 2005
First published as an Advance Article on the web 4th May 2005
Two isomers of bis(carbomethoxybenzo)-24-crown-8 (cis-BCMB24C8, 1, and trans-BCMB24C8, 2) were synthesized
regiospecifically with acceptable to excellent yields. Cyclization in the presence of a template reagent, KPF6, led to an
essentially quantitative yield of the potassium complex of the crown ether 1; the isolated cyclization yield of pure 1
was a remarkable 89%! The methods not only avoid the very difficult separation of the isomers, but also greatly
shorten the synthesis time by eliminating syringe pump usage during cyclization. The complexations of the isomeric
BCMB24C8 with dibenzylammonium hexafluorophosphate (10) were studied by NMR; association constants (Ka)
for 1 and 2 with the dibenzylammonium cation are 190 and 312 M−1, respectively. The X-ray crystal structures of
crown ether 2 and the complexes 1·KPF6, 2·KPF6 and pseudorotaxane 2·10 were determined.
another approach using properly pre-functionalized aromatic
Introduction
precursors as starting materials to synthesize single isomers
Dibenzo-24-crown-8 (DB24C8) forms pseudorotaxanes with
of substituted crown ether macrocycles (cyclophanes). This
secondary ammonium salts driven by hydrogen bonding and
method has been successful in making di-substituted, “axi-
ion–dipole interactions in low-polarity solvents, such as chlo-
ally” symmetrical bis(m-phenylene)-(3x + 2)-crown-x ethers
using 5-functionalized resorcinols (Scheme 1) with yields
up to 50%.6–8
roform and acetonitrile.1 The dibenzo-24-crown-8 moiety has
been widely employed in the construction of pseudorotaxanes,
rotaxanes and catananes.1,2 Rotaxanes and polyrotaxanes de-
rived from mono- or di-functionalized DB24C8 have been
reported extensively.1b,3–5 However, for further development of
supramolecular chemistry, substituted crown ethers are required
to construct more complicated and delicate designs.
Though, as shown below, the method works for syntheses
of disubstituted DB24C8 using catechol analogs, control of
the regiochemistry of the product is lost due to the unsym-
metric substitution on the catechol rings. The cyclization step
produces two positional isomers, which are often difficult,
if not impossible, to separate and thus are often used as
mixtures.4e,f ,5 Due to the potential differences of the two isomers
of di(functionalized benzo) crown ethers in complexation and
other physical properties, it is desirable to study the isomers
separately. In 1997 Sachleben et al. reported syntheses of cis-
bis-(tert-butylbenzo)24C8 and cis-bis-(tert-octylbenzo)24C8 in
35% and 20% yields, respectively, using pre-linked catechols and
tri(ethylene glycol) dichloride with CsCO3 as base at unspecified
concentrations.9 Replacing the catechol rings with resorcinol
rings and making alternative crowns with the same ring size to
imitate DB24C8 are two ways that have been used to avoid the
isomer problem.10,11 In this paper, using the bis(carbomethoxy)
derivatives as examples, efficient routes for synthesis of pure
DB24C8 isomers monosubstituted on each aromatic ring are
reported. Both of the DB24C8 isomers form complexes with
dibenzylammonium hexafluorophosphate, but with different
affinities as expected.
There are two approaches for synthesis of functionalized
dibenzo crown compounds. One is the synthesis of the parent
macrocycle followed by functionalization through aromatic
electrophilic substitution. This usually consists of few steps,
but produces mixtures of regioisomers.5 Our lab has devised
† Electronic supplementary information (ESI) available: Cyclization
yields of 2 and 9 at various starting material concentrations; X-
ray crystallographic files (CIF) for trans-BCMB24C8 (2), complexes
of cis-BCMB24C8 (1) and trans-BCMB24C8 (2), respectively, with
KPF6, and the complex of trans-BCMB24C8 (2) with dibenzylam-
monium hexafluorophosphate (10); 1H NMR complexation data for
1·10 and 2·10 and analysis of Ka and Kipd; preliminary estimates of
association constants for 1 and 2 with KPF6. See http://www.rsc.org/
suppdata/ob/b5/b503072m/
‡ Present address: Eyetech Corp., 35 Hartwell Avenue, Lexington,
Massachussetts, 02421-3102, USA.
§ Present address: Schott Spezialglas AG, Hattenbergstrasse 10, 55122,
Mainz, Germany.
¶ Present address: E. I. duPont de Nemours and Company, Jackson
Laboratory, Deepwater, New Jersey, 08023, USA.
* Present address: Department of Chemistry, Texas A & M University,
College Station, Texas, 77842-3012, USA.
Results and discussion
A
Syntheses of mixed bis(carbomethoxybenzo)24C8
†† Present address: Department of Chemistry, University of Washing-
ton, Seattle, Washington, 98195, USA.
(BCMB24C8) isomers
First, we synthesized BCMB24C8 employing the traditional
method (Scheme 2) with a relatively high cyclization yield,
53%. The product obtained was a mixture of cis- and trans-
BCMB24C8 regioisomers, 1 and 2. All attempts to separate the
two isomers, including derivatization, failed. Thus we turned our
attention to other routes.
‡‡ Present address: Array Biopharma, 3200 Walnut Street, Boulder,
Colorado, 80301, USA.
§§ National Science Foundation Research Experience for Undergrad-
uates (CHE-0244068) participant, summer 2004, from Department of
Chemistry and Physics, Radford University, Radford, Virginia, 24142,
USA.
2 1 1 4
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 1 1 4 – 2 1 2 1
T h i s j o u r n a l i s
T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 5
©

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Scheme 1 General cyclization method for making disubstituted “axially” symmetrical bis-(m-phenylene)-(3x + 2)-crown-x ethers.
Scheme 2 Synthesis of a mixture of BCMB24C8 isomers 1 and 2.
Synthesis of cis-BCMB24C8 isomer 1 deprotection of 5 gave pure desired diphenolic product, 6, with
B
a yield of 87%; again we expect that optimization of this step
would make it essentially quantitative.
A method reported recently for synthesis of regio-controlled di-
formyl DB18C6 isomers12 was initially adapted. 3,4-Dihydroxy-
benzaldehyde was selectively protected at the 4-hydroxyl group
(65%) and coupled via tri(ethylene glycol) ditosylate (Scheme 3).
The deprotection of the hydroxyl groups was carried out under
H2 atmosphere as reported. However, we found that it was very
difficult to control and a mixture of aldehyde and alcohol was
always obtained.
To overcome this problem, methyl 3,4-dihydroxybenzoate
(3) was used in place of the 3,4-dihydroxybenzaldehyde. The
4-hydroxyl group in 3 was selectively protected by reaction
with benzyl bromide in DMF to give methyl 4-benzyloxy-3-
hydroxybenzoate (4) in 51% yield (Scheme 4). In this step
acetonitrile is a better solvent than DMF; it gives the same
yield, but work-up is much easier due to its lower boiling point.
Otherwise, no attempt was made to optimize this step, since
the starting materials are relatively inexpensive. The coupling
reaction of 4 with tri(ethylene glycol) ditosylate was carried out
in acetonitrile to give diprotected precursor 5 quantitatively. The
The cyclization of 6 and tri(ethylene glycol) ditosylate was
carried out in the presence of potassium hexafluorophosphate
as a template reagent. Historically, reactions to form macro-
cyclic compounds have often been performed under pseudo-
high dilution conditions via syringe pump reagent addition to
suppress the formation of acyclic oligomers.8b,13,14 It is significant
that without using a syringe pump in the cyclization step the
isolated yield for pure 1 after recrystallization is 89%. Compared
to the conventional synthesis shown in Scheme 2, this method
also saves both time and solvent. The templating effect of the
potassium cation clearly plays an important role. The initial
crude product was the complex of 1 and potassium cation,
1·K , obtained in essentially quantitative yield. Association
constants for complexation between DB24C8 and potassium
ion in acetonitrile as measured by conductivity and solubility
average 7.62 ( 1.92) × 103 M−1.15 (See the ESI for preliminary
estimates of the association constant for 1 with KPF6, which is
comparable.†) The use of templation in crown ether synthesis13
Scheme 3 DB24C8 derivatives via protection/deprotection route.
Scheme 4 Synthesis of cis-BCMB24C8 (1). a. C6H5CH2Br, K2CO3, CH3CN, 65 ◦C/12 h, 51%. b. Ts(OCH2CH2)3OTs, K2CO3, MeCN, reflux/15 h,
100%. c. H2, Pd/C, CH2Cl2, 12 h, 87%. d. Ts(OCH2CH2)3OTs, K2CO3, KPF6, MeCN, 80 ◦C/24 h, 89%.
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 1 1 4 – 2 1 2 1
2 1 1 5

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dates to their discovery by Pedersen,2a but we are unaware of
other reports of such cyclization yields for the larger (>18-
membered) crown ethers [van Eis et al. reported12a a 92% yield
of cis-bis(formylbenzo)-18-crown-6], particularly in bimolecular
processes; the highest cyclization yield (95% estimated spectro-
scopically, not isolated) known to us was reported for unimolec-
ular cyclization to form benzo-18-crown-6 in very dilute, non-
preparative conditions (0.52 mM) in the presence of NaBr.13a
1H NMR spectra of the crude product before and after
washing with water are compiled in Fig. 1. In 1H NMR signals
As with cis-BCMB24C8 (1), the trans-BCMB24C8 complex
with potassium cation (2·K+) was obtained as the crude product
before exposure to water. This complex even survives silica
gel column chromatography with ethyl acetate as eluent. (See
below for its crystal structure and the ESI for an estimate of
the association constant for 2 with KPF6, which is comparable
to that reported for DB24C8 with KPF6.15) In FAB mass
spectrometry the complex of 2 with KPF6 displayed a strong
1
peak at m/z 603.19 for [1·K]+. The H NMR spectra in Fig. 2
ꢀ
show that a- and a -proton signals are well resolved for 2·K+,
ꢀ
for a- and a -protons are well resolved in 1·K+. In FAB mass spec-
while merged in 2. All the protons except the c-protons show
downfield shifts in the complex compared to uncomplexed 2.
trometry the complex of 1 with KPF6 displayed a strong peak
at m/z 603.19 for [1·K]+. After washing with water to remove
ꢀ
K+, the signals of a- and a -protons merge in 1, while the other
signals show up- or down-field shifts relative to 1·K+. As these
spectra indicate, the cyclization yield is essentially quantitative!
The solubility of the crude product before and after washing with
water also changed greatly, from easily soluble in methanol to
slightly soluble. 1 was purified by recrystallization in methanol.
Fig. 2 400 MHz 1H NMR spectra in CDCl3: (a) crude product before
washing with water, 2·K+ PF6−, (b) crude product after washing with
water, 2.
D
Complexation of isomeric BCMB24C8 derivatives with
dibenzylammonium hexafluorophosphate (10)
For comparison with the previously reported DB24C8 results,16a
Fig. 1 400 MHz 1H NMR spectra in CDCl3: (a) crude product before
washing with water, 1·K+ PF6−, (b) crude product after washing with
water, 1.
complexation studies of BCMB24C8 isomers, 1 and 2, with 10
were carried out in 2 : 3 CD3CN : CDCl3 at 22
1
◦C. 1 is
soluble up to 30 mM, but the maximum concentration of 2 is
1
12.4 mM. In the H NMR spectra of the solutions (Fig. 3),
C
Synthesis of trans-BCMB24C8 isomer 2
just as with the model system DB24C8·10,2b,16a there are two
sets of peaks attributable to the free and complexed species of
each component, resulting from a slow-exchange complexation
based on the NMR time scale. The complexation percentages
of the crown ethers were determined by integrations of the well
resolved proton H3 signals in the complexed and free crown ether
species. Then the concentrations of each species in the samples
were calculated (see ESI: Tables S2 and S3†).
Protected phenol 4 was reacted with equimolar tri(ethylene
glycol) dichloride2a (Scheme 5) to give 7. Though it was more
reactive, tri(ethylene glycol) ditosylate gave a crude product
with complicated composition, which was difficult to separate.
With tri(ethylene glycol) dichloride the crude product can be
easily purified by column chromatography to give pure 7, which
upon deprotection by hydrogenolysis quantitatively affords
difunctional precursor 8. With potassium carbonate as the base,
8 underwent a 1 + 1 cyclization to give the expected product
2. As in the synthesis of cis-BCMB24C8, no syringe pump was
employed in the cyclization.
Intramolecular cyclization of 8 leads to the small ring product
9. We tried to minimize the contribution of the intramolecular
process by using more concentrated reaction solutions. The
results (see ESI: Table S1†) show that high concentrations do
not increase the yield of larger ring 2, although dilute conditions
do favor small ring formation. The highest yield of 2 (44%) was
obtained with an initial concentration of 23 mM of precursor 8
in the reaction solution.
The values of the apparent association constant Ka,exp
=
[complex]/([crown]o − [complex])([10]o − [complex]) varied two-
to three-fold with concentration. This result indicates we have
to take into account ion-pair dissociation effects, i.e., the fact
that the complex is not ion paired but the ammonium salt is
ion paired, meaning that it is the ammonium cation (G+) that
is the actual guest and not the salt.16 The analysis was done
Scheme 5 Synthesis of trans-BCMB24C8 (2). a. Cl(CH2CH2O)2CH2CH2Cl, K2CO3, MeCN, reflux/3 d, 75%. b. H2, Pd/C, CH2Cl2, 12 h, 100%. c.
K2CO3, KPF6, MeCN, reflux/3 d.
2 1 1 6
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 1 1 4 – 2 1 2 1

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+
˚
Table 1 Lengths (A) of ion–dipole interactions between K and ether
oxygen atoms in the complexes 1a·KPF6 and 2a·KPF6
Interaction 1a·KPF6 2a·KPF6 Interaction 1a·KPF6 2a·KPF6
a
b
c
d
e
2.94
2.75
2.81
2.93
2.97
3.00
2.74
2.81
2.94
2.92
f
2.84
2.73
2.95
2.68
2.82
2.77
2.97
2.65
g
h
i
are parallel. It resembles the solid state structure of parent
DB24C8.19
2
Solid state structures of diester crown ether complexes
20 21
with KPF6. In crystals of 1·KPF6 and 2·KPF6 the crown
molecules fold to a V-shape with a twist so that the planes
of aromatic rings have inclination angles of 120.9 and 99.4◦,
respectively (Fig. 5a,c). Potassium cations reside in the center
of the V, bound by ion–dipole interactions with all eight ether
oxygen atoms. As shown in Table 1, in both complexes the
distances between the potassium cations and the four oxygen
atoms adjacent to the c-carbons are shorter (interactions b, c, f
and g of 1·KPF6 and 2·KPF6) than those between the potassium
cation and the four phenolic oxygen atoms (interactions a,
Fig. 3 400 MHz 1H NMR spectra in 2 : 3 CD3CN : CDCl3: (a) [1]0 =
20 mM, (b) [1]0 = [10]0 = 20 mM, (c) [2]0 = 10 mM, (d) [2]0 = [10]0 =
10 mM.
1
by the method we recently developed for the parent system of
DB24C8·10.16a We found that for complexation of host 1 with
the dibenzylammonium cation (G+) Ka = 190 67 M−1, while
the ion pair dissociation constant of 10, Kipd = 6.8 ( 5.5) ×
10−3 M. For complexation of 2 with the dibenzylammonium
d, e and h of 1·KPF6 and 2·KPF6). This agrees with the H
NMR spectral results (Figs. 1 and 2) in that the c-protons
undergo upfield shifts upon complexation. Note that for 1·KPF6
interactions e and h with oxygen atoms para to the ester moieties
are longer than those meta to them, a and d; this is consistent
with the argument made above concerning the inductive and
resonance effects of the substituents. Conversely in 2·KPF6 this
correlation does not hold, perhaps because of packing forces.
cation (G+) Ka = 312
35 M−1, and the independently
determined value for Kipd of 10 was 4.4 ( 1.2) × 10−3 M. The
two values of Kipd for 10 agree with each other and our previous
determination within the error limits (see ESI for details†).
It can be understood that the association constants (Ka) of
BCMB24C8 isomers 1 and 2 with the dibenzylammonium cation
(G+) are smaller than that of unsubstituted DB24C8 (Ka = 560
60 M−1).16a The two electron-withdrawing carbomethoxy groups
reduce the electron density of the oxygen atoms in the crown
ether ring both inductively and via resonance. Thus the hydrogen
bonding of the crown ether oxygen atoms of 1 and 2 with the
acidic protons of the dibenzylammonium cation (G+) become
weaker, lowering Ka values. The different Ka values of 1 and 2
with the dibenzylammonium cation (G+) can be explained by
the different symmetry of the substitutions. In cis-crown 1, the
two tri(ethylene glycol) tethers differ from each other, because
the oxyethylene units para to both ester groups become less
basic than those meta, on account of the stronger resonance
effect,17 resulting in an unbalanced crown. In trans-crown 2 the
two tri(ethylene glycol) tethers are identically affected by the two
ester moieties. Thus the more symmetric crown ether 2 gives a
more stable complex than 1.
MALDI-TOF mass spectrometric characterization of the
complexes of 1 and 2 with 10 yielded parent ion signals at m/z
762.35 for [crown·10-PF6]+. The results corroborate the 1 : 1
complexation observed in solution and solid states (see below).
Fig. 5 Solid state structures of complexes of BCMB24C8 isomers
with K+. (gray: carbon atoms, red: oxygen atoms, blue: K+ cation): (a)
1·KPF6, (b) dimer of 1·KPF6 (p–p sta◦cking centroid–centroid distance =
E
X-Ray crystallography of DB24C8 diesters and their
complexes
˚
3.984 A, planar inclination angle = 0 ), (c) 2·KPF6, (d) dimer of 2·KPF6
˚
1
Solid state structure of trans diester crown ether 2. At-
(p–p stacking centroid–centroid distance = 3.648 A, planar inclination
angle = 9.8◦). Hydrogen atoms and PF6− groups are omitted for clarity.
tempts to grow suitable crystals of 1 failed, but crystals of 2
were readily obtained. The crystal structure of free 2 (Fig. 4)18
shows an extended molecule, in which the two aromatic rings
Both 1·KPF6 and 2·KPF6 form dimers through ion–dipole
interactions between the potassium cations residing in the
first crown molecule and the carbonyl oxygen of the second
crown molecule; these interactions have the shortest lengths
(interactions i of 1·KPF6 and 2·KPF6) among all the interactions
of the potassium cations with crown oxygen atoms (Fig. 5b,d).
Both dimers are further stabilized by p–p stacking of two of the
benzo rings.
Fig. 4 Solid state structure of 2 (gray: carbon atoms, red: oxygen
atoms). Hydrogens are omitted for clarity.
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 1 1 4 – 2 1 2 1
2 1 1 7

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Table 2 Hydrogen bond parameters for complex 2a·10
C(N)–H–O angle (◦)
˚
˚
Hydrogen bond
C(N)–O length (A)
H–O length (A)
a
b
c
d
e
f
3.07
2.82
3.25
3.59
3.30
3.29
2.15
1.90
2.60
2.64
2.47
2.32
173
179
123
163
141
165
3
Solid state structure of complex 2·10. In the crystal
ether, DB24C8, due to the electron-withdrawing carbomethoxy
groups on the crown rings. The different positions of the
carbomethoxy groups in the two isomers result in differences in
their properties, e.g., solubilities and association constants. The
carboxylate groups can be easily transformed to diverse func-
tional groups, as we have demonstrated with other crown ethers.8
Therefore, the availability of the pure isomers will inevitably
enhance the study of supramolecular systems constructed with
dibenzo crown ethers, as we will demonstrate in subsequent
publications.
structure of pseudorotaxane 2·10 (Fig. 6a),22 the crown molecule
takes on the conformation of free 2, but with a little twist so that
the two catechol rings have a planar inclination angle of 15.9◦.
The dibenzylammonium cation threads the crown ring to form
the pseudorotaxane complex, stabilized predominantly by two
N–H–O (a, b) and three N–CH–O (c, d, e, f ; c & d bifurcated) hy-
drogen bonds between the NH2+ center and the adjacent benzylic
CH2 groups, respectively, and ether oxygen atoms of 2 (Table 2).
p–p overlap between one of the catechol rings of 2 and one of the
phenyl rings of the dibenzylammonium cation further stabilizes
the pseudorotaxane complex. Though the complex of 10 with
the parent DB24C8 displays two independent conformations,2b
only one conformation is observed in 2·10, which in turn forms
a dimer, stabilized by p–p stacking interactions between phenyl
groups of neighboring dibenzylammonium ions (Fig. 6b).
Experimental
General information
All chemicals were used as received. Melting points were
measured with a Mel-Temp II device and are uncorrected.
Thin layer chromatography (TLC) was done using Whatman
1
PE SIL G/UV254. H and 13C Nuclear Magnetic Resonance
(NMR) spectra were obtained at ambient temperature on a
Varian Unity (or an Inova) 400/100 MHz spectrometer with
TMS (d = 0.00 ppm) as internal standard. High resolution
mass spectra (HR MS) were obtained on a JEOL Model
HX 110. Crystals were mounted on a nylon CryoLoopTM
R
(Hampton Research) with Krytoxꢀ Oil (DuPont) and centered
on the goniometer of an Oxford Diffraction XCalibur2TM
diffractometer equipped with a Sapphire 2TM CCD detector.
The data collection routine, unit cell refinement, and data
processing were carried out with the program CrysAlis.24 The
structure was solved by direct methods and refined using the
SHELXTL NT program package.25 The final refinement model
involved anisotropic displacement parameters for non-hydrogen
atoms and a riding model for all hydrogen atoms. The program
packages SHELXTL NT and PLATON were used to generate
crystallographic tables.25,26 The program packages SHELXTL
NT25 and Mercury were used for molecular graphics generation.
Fig. 6 Solid state structures of 2·10 (a) and its dimer (b) (gray:
carbon atoms, red: oxygen atoms, blue: N atoms). Catechol ring of 2 to
˚
phenyl ring of 10: centroid–centroid distance = 3.76 A, ring plane–ring
plane inclination = 7.5◦. In the dimer phenyl–p◦henyl centroid–centroid
˚
distance = 3.83 A, planar inclination angle = 0 .
The length of P–K+ (7.220 A) and P–NH2 (7.725 A)
+
˚
˚
separations in the solid state structures of 1·K+, 2·K+and 2·10+
˚
are in the range of reported values (7.2 to 8.4 A) for complexes
of DB24C8 with 10 and other ammonium hexafluorophosphate
derivatives.1,2b23 Thus, no tight or intimate ion pairs exist in the
solid state of these three complexes, consistent with the situation
in solution deduced from analysis of the association constant for
1·10 and 2·10 (see ESI† and reference 16).
Methyl 3,4-dihydroxybenzoate (3)
A solution of 3,4-dihydroxybenzoic acid (51.32 g, 333 mmol) and
p-toluenesulfonic acid (1.2 g, 6 mmol) in methanol (250 mL)
was refluxed for 3 days. After reaction, solvent was removed
by rotoevaporation. The solid was dissolved in ethyl acetate
and washed with 10% Na2CO3 once and saturated NaCl
solution twice. After drying over anhydrous Na2SO4, solvent was
Conclusions
Pure isomeric cis- and trans-BCMB24C8 derivatives 1 and 2
were synthesized regiospecifically, avoiding the difficult problem
of separation of the two isomers. There are three significant
advantages over the traditional synthesis route: 1) the cycliza-
tions are carried out at normal concentrations without use of
a syringe pump; 2) thus, the reaction time is shortened from
five days to one day (cis-BCMB24C8, 1) or 3 days (trans-
BCMB24C8, 2); 3) the macrocyclization templated by potassium
cation yielded the salt complex essentially quantitatively and
pure cis-BCMB24C8 (1) in high isolated yield (89%). Other
disubstituted dibenzo crown ethers can be made in this way.
For example, cyclization of precursor 6 with tetra-, penta- and
hexa-(ethylene glycol) ditosylates will afford the unsymmetrical
27-, 30- and 33-membered analogs of 1.
removed to give 51.4 g (85%) of white solid. Mp. 141.8–142.7 ◦C
◦
1
4
(lit. 138.5–139.5 C27); H NMR (CDCl3) d 7.58 (d, JHH = 2,
1H), 7.58 (dd, 4JHH = 2, 3JHH = 9, 1H), 6.91 (d, 3JHH = 9, 1H),
5.83 (s, 1H), 5.59 (s, 1H), 3.88 (s, 3H); 13C NMR (acetone-d6)
d 167.81, 151.51, 146.37, 124.08, 123.64, 117.92, 116.55, 52.63.,
52.39; HR MS m/z (FAB in NBA PEG) calc. for C8H8O4 M+
169.0501, found: 169.0508.
Methyl 3,4-bis(8ꢀ-chloro-3ꢀ,6ꢀ-dioxaoctyloxy)benzoate
To a solution of 3 (45.1 g, 268 mmol) and tri(ethylene glycol)
dichloride (340 mL, ∼2 mol) in CH3CN (350 mL) was added
K2CO3 (113.33 g, 820 mmol). The suspension was stirred at
reflux for 7 days. The solution was decanted from the salts;
CH3CN and unreacted dichloride were removed by distillation
The two new isomeric crown ether esters 1 and 2 form non-
ion paired pseudorotaxanes with dibenzylammonium hexafluo-
rophosphate, (10). Under the same conditions, these complexes
have lower association constants than that of their parent crown
2 1 1 8
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 1 1 4 – 2 1 2 1

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under reduced pressure. To remove residual salts the crude
oil was filtered through silica gel; the silica gel was washed
with CH3CN. After removal of the solvent, 90 g (72%) of a
viscous yellow oil remained. The oil was purified by column
chromatography on silica gel using ethyl acetate : n-hexane (5 : 1)
or ethyl acetate : petroleum ether (5 : 2). The pure product was
and ch◦illed in a freezer, yielding white crystals (210 g, 86%). Mp.
82–83 C (lit. 80–81 ◦C29); 1H NMR (CDCl3) d 7.79 (d, 3JHH
=
3
3
8, 4H), 7.34 (d, JHH = 8, 4H), 4.14 (t, JHH = 5, 4H), 3.65 (t,
3JHH = 5, 4H), 3.53 (s, 4H), 2.44 (s, 6H); 13C NMR (CDCl3) d
145.51, 133.53, 130.48, 128.56, 71.27, 69.85, 69.33, 22.25; HR
MS m/z (FAB in NBA PEG) calc. for C20H27O8S2 (M + H)+
459.1147, found 459.1143.
1
obtained as a light yellow oil, 69 g (55%). H NMR (acetone-
d6): d 8.47 (bs, 2H), 7.49 (d, 4JHH = 2, 1H), 7.45 (dd, 4JHH = 2,
a,x-Bis(2ꢀ-benzyloxy-5ꢀ-carbomethoxyphenoxy)-3,6-
dioxaoctane (dimethyl 4,4ꢀ-bis(benzyloxy)-3,3ꢀ-
oxytri(ethyleneoxy)dibenzoate) (5)
3
3JHH = 8, 1H), 6.91 (d, JHH = 8, 1H), 3.81 (s, 3H). 13C NMR
(acetone-d6): d 166.64, 150.31, 145.16, 122.90, 122.42, 116.72,
115.36, 51.46, 29.98, 29.80, 29.60, 29.41, 29.21, 29.02, 28.83.
Elem. anal.: calc. for C20H30Cl2O8 C 51.18, H 6.44, Cl 15.11;
found: C 51.11, H 6.34, Cl 15.08%.
A solution of 4 (11.50 g, 44.5 mmol), K2CO3 (12.30 g, 89.0 mmol)
and tri(ethylene glycol) ditosylate (9.74 g, 21.3 mmol) in CH3CN
(160 mL) was stirred at reflux for 15 h. After solvent was
removed, the residue was partitioned in water and ethyl acetate.
The water layer was extracted with ethyl acetate 5 times.
The combined ethyl acetate solution was washed with water
and saturated NaCl solution, and then dried over anhydrous
Na2SO4. After concentration in a rotoevaporator,◦14.3 g (100%)
Mixture of DB24C8 diester isomers (1 and 2)
A solution of 3 (10.38 g, 61.8 mmol) and methyl 3,4-bis(8ꢀ-
chloro-3ꢀ,6ꢀ-dioxaoctyloxy)benzoate (28.98 g, 61.8 mmol) in
CH3CN (total ∼50 mL) was added at a rate of 0.69 mL h−1
to a suspension of K2CO3 (80.60 g, 584 mmol) and catalytic
amount of tetra-n-butylammonium iodide in 3.5 L of CH3CN
at 70 ◦C. After complete addition the mixture was stirred
for six days, cooled and filtered. The solvent was removed
from the filtrate by rotoevaporation to give a gray powder. It
was recrystallized from a large amount of methanol to give
a slightly gray powder. Column chromatography with ethyl
acetate–CHCl3 (3 : 1) yielded a white solid, 17.5 g (53%, single
spot on TLC). Mp: 135–139 ◦C. 1H NMR (CDCl3): d 7.62 (dd,
1
of a white solid was obtained. Mp. 87.9–89.0 C; H NMR
(CDCl3) d 7.62 (dd, 4JHH = 2, 3JHH = 8, 2H), 7.57 (d, 4JHH = 2,
2H), 7.35 (m, 10H), 6.90 (d, 3JHH = 8, 2H), 5.15 (s, 4H), 4.19 (t,
3JHH = 5, 4H), 3.87 (t, 3JHH = 5, 4H), 3.87 (s, 6H), 3.72 (s, 4H); 13C
NMR (CDCl3) d 167.44, 153.35, 149.16, 137.22, 129.22, 128.67,
127.92, 124.53, 123.73, 115.44, 113.78, 71.70, 71.46, 70.24, 69.59,
52.64; HR MS m/z (FAB in NBA PEG) calc. for C36H38O10 M+:
630.2465, found: 630.2461.
4JHH = 2, 3JHH = 8, 2H), 7.51 (d, 4JHH = 2, 2H), 6.84 (d, 3JHH
=
a,x-Bis(2ꢀ-hydroxy-5ꢀ-carbomethoxyphenoxy)-3,6-dioxaoctane
8, 2H), 4.19 (m, 4H), 3.94 (m, 4H), 3.87 (s, 3H), 3.84 (bs, H).
13C NMR (CDCl3): d 166.74, 152.76, 148.14, 123.82, 122.78,
114.08, 111.85, 71.32, 71.39, 69.74, 69.61, 69.46, 69.41, 69.28,
69.23, 51.92. FAB MS (NBA) m/z: 603, 19%, (M + K)+; 565,
32%, (M + H)+; 533, 87%, (M − OCH3)+. Elem. anal.: calc. for
C28H36O12 C 59.57, H 6.43; found C 59.46, H 6.49%.
(dimethyl 4,4ꢀ-dihydroxy-3,3ꢀ-oxytri(ethyleneoxy)dibenzoate) (6)
To a solution of 5 (11.70 g, 18.55 mmol) in CH2Cl2 (100 mL) was
added 10% Pd/C (0.20 g). The suspension was shaken under H2
atmosphere (∼50 psi) at rt. After 12 h, TLC showed complete
conversion to product. The catalyst was removed by filtration.
The filtrate was concentrated to give a white solid, 11.58 g,
which was purified by column chromatography with a mixture
of CH2Cl2 and ethyl acetate as eluent: 7.24 g (87%) of a white
Methyl 4-benzyloxy-3-hydroxybenzoate (4)
solid. Mp. 129.0–130.1 ◦C; 1H NMR (CDCl3) d 7.66 (dd, 4JHH
=
A solution of 3 (35.0 g, 208 mmol) and K2CO3 (28.8 g,
208 mmol) in CH3CN (250 mL) was stirred at 85 ◦C for
4 h. To the suspension was added benzyl bromide (24.7 ml,
208 mmol). It was stirred at 65 ◦C for 12 h. The solid was
removed by filtration through a pad of Celite 545. The filtrate
was concentrated to give a viscous liquid. It was partitioned
in water and ethyl acetate; the water layer was extracted with
ethyl acetate 5 times. The combined ethyl acetate solution was
washed with saturated NH4Cl solution 3 times, water once and
saturated NaCl solution 3 times, and dried over anhydrous
Na2SO4. Solvent was removed in a rotoevaporator to give a
yellow solid, which was recrystallized in CHCl3 to yield 15.35 g
of 4. The filtrate solution was concentrated and separated by
silica gel column chromatography with CHCl3 as eluent to yield
an addit◦ional 12.0 g of 4 (total yield 51%). Mp. 133.7–135.0 ◦C
(lit. 128 C28); 1H NMR (CDCl3) d 7.61 (d, 4JHH = 2, 2H), 7.59
3
5
2, JHH = 9, 2H), 7.60 (d, JHH = 2, 2H), 7.50 (s, 2H), 6.96 (d,
3JHH = 9, 2H), 4.24 (t, 3JHH = 5, 4H), 3.88 (s, 6H), 3.87 (t, 3JHH
=
5, 4H), 3.79 (s, 4H); 13C NMR (CDCl3) d 167.49, 152.28, 146.22,
126.08, 122.76, 116.75, 115.97, 71.01, 70.35, 69.92, 52.62; HR
MS m/z (FAB) calc. for C22H26O10 M+ 450.1526, found 450.1521.
cis-Bis(carbomethoxybenzo)-24-crown-8 (1)
A solution of 6 (3.00 g, 6.66 mmol), K2CO3 (5.52 g, 39.9 mmol),
KPF6 (1.50 g, 8.13 mmol) and tri(ethylene glycol) ditosylate
(3.06 g, 6.67 mmol) in CH3CN (150 mL) was stirred in an
80 ◦C oil bath for 24 h. The solid was removed by filtration.
The filtrate was concentrated to give 5.20 g of off-white solid
(theoretical yield 4.99 g for 1·KPF6). MALDI MS of this KPF6
complex afforded m/z 603.1833 [1·K]+; see Fig. 1 for its 1H NMR
spectrum and Fig. 5 for the X-ray structure. The salt complex was
dissolved in CHCl3 and washed with water and saturated NaCl
solution. The solution was then dried over anhydrous Na2SO4.
After removal of solvent by rotoevaporation a white solid was
obtained. It was recrystallized in methanol to give 3.35 g (89%)
of white solid (1). Mp. 137.1–138.0 ◦C; 1H NMR (CDCl3) d 7.64
4
3
3
(dd, JHH = 2, JHH = 8, 2H), 7.41 (m, 5H), 6.94 (d, JHH = 8,
2H), 5.70 (s, 1H), 5.17 (s, 2H), 3.88 (s, 3H); 13C NMR (CDCl3)
d 167.43, 150.22, 146.12, 136.23, 129.52, 129.35, 128.57, 124.37,
123.37, 116.51, 111.86, 71.80, 52.66; HR MS m/z (FAB in NBA
PEG) calc. for C15H15O4 (M + H)+ 259.0970, found 259.0964.
4
3
4
(dd, JHH = 2, JHH = 9, 2H), 7.51 (d, JHH = 2, 2H), 6.84 (d,
3JHH = 9, 2H), 4.19 (m, 8H), 3.93 (m, 8H), 3.88 (s, 6H), 3.84
(m, 8H); 13C NMR (CDCl3) d 167.47, 153.45, 148.88, 124.53,
123.54, 114.79, 112.56, 72.22, 72.12, 70.45, 70.33, 70.13, 70.02,
52.66; HR MS m/z (FAB) calcd for C28H36O12 M+ 564.2207,
found 564.2217.
Tri(ethylene glycol) ditosylate
To an aqueous solution of NaOH (64 g, 1.6 mol, in 600 mL
of water) at 0 ◦C was added a solution of tri(ethylene glycol)
(80.04 g, 0.533 mol) in THF (150 mL) dropwise. The mixture
was stirred mechanically at 0 ◦C for 30 min and then at 0 ◦C
a solution of p-toluenesulfonyl chloride (254 g, 1.33 mol) in
THF (600 mL) was added dropwise. The mixture was stirred
at rt 2 d. The organic layer was separated and the water layer
was washed with CH2Cl2 5 times. The combined organic solution
was concentrated to give a liquid, which was dissolved in acetone
Methyl 4-benzyloxy-3-{chloroethoxy[ethoxy(ethoxy)]}benzoate
(7)
A solution of 4 (20.0 g, 77 mmol), K2CO3 (32.1 g, 232 mmol)
and tri(ethylene glycol) dichloride (36.2 g, 194 mmol) in CH3CN
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 1 1 4 – 2 1 2 1
2 1 1 9

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(250 mL) was refluxed for 3 days. The solid was removed by
filtration. The filtrate was concentrated to give a yellow oil that
was purified by column chromatography with 5 : 1 hexane : ethyl
acetate as eluent. A colorless oil (23.7 g, 75%) was obtained. 1H
filled disposable pipette before 0.500 ( 0.006 mL) mL of each
solution component (host and guest) at a specified concentration
was transferred via a to-deliver pipette to a 5.0 mm NMR
tube. NMR spectroscopic data were collected on a temperature
controlled 400 MHz spectrometer within 1 hour of mixing
the host and guest solutions. The fraction of total crown
moieties occupied by guest was determined by integration of
the complexed and uncomplexed crown signals for H3 of hosts
1 and 2; these results were corroborated by similar analyses
of H2 and Hc. Reproducibilty in fractional binding of the
host was shown to be good within 0.29% relative standard
error (100 rn/mean) using multiple (12) samples and multiple
(5) Fourier transformations/integrations for a sample with
24.2% crown bound. The major source of error in calculated
K values results from errors in weights and volumes: ∼ 2%
maximum possible relative errors in initial concentrations. The
complexation percentages’ relative error is less than 0.3%.
The error bars shown in the ESI were accumulated results
of the previously mentioned maximum possible (rather than
most probable) concentration errors. The errors for slopes and
intercepts are standard errors given by the least squares fitting
program in Origin. Though the complexation percentage of
the hosts are well controlled in the area of 20 ∼ 80%,30 our
experiments show that the complexation percentage of guest is
also an important factor influencing the quality of analysis data.
The bigger error bars shown in ESI Figure S1b† are mainly due
to the high complexation percentage (∼ 90%) of the guest in the
corresponding NMR samples (Table 2). This directly leads to
the large error for Kipd, 6.8 ( 5.5) × 10−3 M.
4
3
NMR (CDCl3) d 7.64 (dd, JHH = 2, JHH = 9, 2H), 7.51 (d,
3
3
4JHH = 2, 2H), 6.84 (d, JHH = 9, 2H), 4.19 (d, JHH = 4, 4H),
3.94 (t, 3JHH = 4, 4H), 3.93 (t, 3JHH = 4, 4H), 3.87 (s, 6H), 3.85 (s,
4H), 3.84 (s, 4H); 13C NMR (CDCl3) d 167.43, 153.37, 149.13,
137.20, 129.24, 128.71, 127.94, 124.59, 123.74, 115.53, 113.76,
72.03, 71.65, 71.48, 71.40, 70.35, 69.70, 52.66, 43.40; HR MS
m/z (FAB in NBA PEG) calc. for C21H25O6Cl (M)+ 408.1340,
found 408.1334.
Methyl 4-hydroxy-3-{chloroethoxy[ethoxy(ethoxy)]}benzoate
(8)
A suspension of 7 (3.53 g, 8.63 mmol) and 10% Pd/C (0.092 g) in
CH2Cl2 (60 mL) was shaken under H2 atmosphere (∼50 psi) at
rt. After 12 h, TLC showed complete conversion to product. The
catalyst was removed by filtration. The filtrate was concentrated
to give 2.75 g (100%) of a pure colorless oil. 1H NMR (CDCl3)
d 7.67 (dd, 5JHH = 2, 3JHH = 8, 1H), 7.62 (d, 5JHH = 2, 1H), 6.94
(d, 3JHH = 8, 1H), 4.23 (m, 2H), 3.88 (s, 3H), 3.85 (m, 2H), 3.77
(t, 3JHH = 6, 2H), 3.74 (m, 4H), 3.65 (t, 3JHH = 6, 2H); 13C NMR
(CDCl3) d 167.41, 152.61, 146.17, 126.29, 122.75, 117.54, 115.79,
72.09, 71.26, 71.11, 70.12, 52.61, 43.35; HR MS m/z (FAB in
NBA PEG) calc. for C14H19O6Cl M+ 318.0870, found: 318.0869.
trans-Bis(carbomethoxybenzo)-24-crown-8 (2) and
carbomethoxybenzo-12-crown-4 (9)
Crystal structure determinations
A solution of 8 (1.08 g, 3.39 mmol), K2CO3 (1.41 g, 10.2 mmol)
and KPF6 (0.31 g, 1.7 mmol) in CH3CN (150 mL) was stirred
at reflux 3 days. The solid was removed by filtration. The filtrate
was concentrated to give an off-white solid. It was dissolved in
CHCl3 and washed with water and saturated NaCl solution. The
solution was then dried over anhydrous Na2SO4. After removal
of solvent by rotoevaporation, the solid residue was separated
by column chromatography. Two white solids were obtained. 9:
Colorless plates of 1·KPF6 (0.35 × 0.20 × 0.03 mm3) were
formed in CHCl3 by vapor diffusion of hexane at rt. Colorless
trapezoidal crystals of 2 (0.1 × 0.3 × 0.4 mm3) and 2·KPF6
(0.15 × 0.3 × 0.3 mm3) were formed in CHCl3 by vapor
diffusion of pentane at rt. Colorless needles of 2·10 (0.8 × 0.1 ×
0.03 mm3) were formed by slow diffusion of pentane into a
mixture of CHCl3–CH3OH at rt, which were cut into smaller
crystals (0.35 × 0.084 × 0.028 mm3) before being mounted on a
nylon CryoLoopTM (Hampton Research).
◦
1
0.34 g (36%); mp. 94.2–95.0 C; H NMR (CDCl3) d 7.71 (dd,
4JHH = 2, 3JHH = 8, 1H), 7.68 (d, 4JHH = 2, 1H), 6.96 (d, 3JHH
=
Systematic absences for 1·KPF6 were consistent with the
8, 1H), 4.23 (m, 4H), 3.89 (m, 2H), 3.88 (s, 3H), 3.83 (m, 2H),
3.78 (s, 4H); 13C NMR (CDCl3) d 167.26, 150.68, 150.55, 125.95,
124.72, 120.74, 116.62, 73.32, 72.08, 71.65, 71.46, 70.43, 70.36;
HR MS m/z (FAB in NBA PEG) calc. for C14H19O6 (M + H)+
283.1182, found 283.1183. 2: 0.42 g (44%); mp. 165.3–166.5 ◦C;
1H NMR (CDCl3) d 7.64 (dd, 4JHH = 2, 3JHH = 8, 2H), 7.52 (d,
¯
triclinic space group P1 with unit cell parameters of a =
◦
˚
˚
˚
10.3429(7) A, b = 12.6823(9) A, c = 13.1381(9) A, a = 84 ,
b = 73◦, c = 78◦. Systematic absences for 2 were consistent with
the monoclinic space group P21/c with unit cell parameters
˚
˚
˚
of a = 13.8926(14) A, b = 12.4235(11) A, c = 8.2043(8) A,
b = 105.243(9)◦; the asymmetric unit of the structure comprises
0.5 crystallographically independent molecules. Systematic ab-
sences for 2·KPF6 were consistent with the monoclinic space
3
4JHH = 2, 2H), 6.84 (d, JHH = 8, 2H), 4.19 (m, 8H), 3.94 (m,
8H), 3.88 (s, 6H), 3.85 (s, 4H), 3.84 (s, 4H); 13C NMR (CDCl3)
d 167.48, 153.48, 148.86, 124.54, 123.52, 114.79, 112.56, 72.22,
72.13, 70.47, 70.34, 70.19, 69.96, 52.65; HR MS m/z (FAB in
NBA PEG) calc. for C28H36O12 M+ 564.2207, found 564.2217.
If the solid was not exposed to water before chromatography,
2·KPF6 was isolated upon elution with ethyl acetate; its 1H NMR
spectrum is shown in Fig. 2 and its crystal structure is shown in
Fig. 5.
˚
group C2/c with unit cell parameters of a = 16.840(2) A, b =
◦
˚
˚
19.447(3) A, c = 19.410(2) A, b = 91 . The asymmetric unit
of the structure comprises one crystallographically independent
•
2·KPF6 complex and two half-PF6 anions. Systematic absences
for 2·10 were consistent with the monoclinic space groups C2/c
and Cc. The centric space group C2/c was chosen with unit
˚
˚
cell parameters of a = 14.324(6) A, b = 22.806(6) A, c =
◦
˚
26.470(8) A, b = 97.20(3) . The asymmetric unit of the structure
comprises one crystallographically independent 2·10 complex
and 0.265 methanol solvate molecules. Two residual electron
density peaks were modeled as a partially occupied CH3OH
molecule disordered over two symmetrically related positions.
The occupancy in the asymmetric unit refined to 26.5%, or 53.0%
when disordered over the two sites.§§
Complexation studies
Solutions were prepared by precisely weighing a minimum of
1.00 × 10−2 g of each host and guest component by means
of an analytical balance which read to 1.0 × 10−4 g into a
5.00 ( 0.02) or 10.00 ( 0.02) mL volumetric flask equipped
with a ground glass stopper to make a moderately concentrated
(nominally 16.0 mM) master solution. This solution was then
sequentially diluted (no more than four sequential dilutions
per master solution) by transferring specific volumes of the
higher concentration solution to a clean volumetric flask via
a to-deliver volumetric pipette ( 0.006 mL) and diluting to
the mark. The fresh solutions were filtered through a cotton-
§§ CCDC reference numbers 265204–265207. See http://www.rsc.org/
suppdata/ob/b5/b503072m/ for crystallographic data in CIF or other
electronic format.
2 1 2 0
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 1 1 4 – 2 1 2 1

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11 T. Chang, A. M. Heiss, S. J. Cantrill, M. C. T. Fyfe, A. R. Pease, S. J.
Rowan, J. F. Stoddart, A. J. P. White and D. J. Williams, Org. Lett.,
2000, 2, 2947–2950.
12 (a) M. J. van Eis, L. A. Muslinkina, M. Badertscher, E. Pretsch,
F. Diederich, R. J. Alvarado, L. Echegoyen and I. P. Nunez, Helv.
Chim. Acta, 2002, 85, 2009–2055; (b) J.-P. Bourgeois, L. Echegoyen,
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Acknowledgements
This research was supported via grant DMR-0097126 from the
National Science Foundation, to whom we are grateful. We
thank the NSF (Grant CHE-0131128) for funding the purchase
of the Oxford Diffraction Xcalibur2 single crystal diffractometer
at Virginia Polytechnic Institute and State University.
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˚
18 Crystal data: C28H36O12, M = 564.57, monoclinic, a = 13.8926(14) A,
◦
˚
˚
b = 12.4235(11) A, c = 8.2043(8) A, b = 105.243(9) , V = 1366.2(2)
3
˚
A , T = 100(2) K, space group P21/c (no. 14), Z = 2, l (Mo Ka) =
0.108 mm−1, 8078 reflections measured, 3162 unique (Rint = 0.0277).
The final R values were R(F) = 0.0649 [I > 2r(I)] and wR(F2) =
0.2109 (all data).
19 I. R. Hanson, D. L. Hughes and M. R. J. Truter, Chem. Soc., Perkin
Trans. 2, 1976, 972.
20 Crystal data: C28H36O12·KPF6, M = 748.64, triclini◦c, a = 10.3429(7)
◦
¯
˚
˚
˚
A, b = 12.6823◦(9) A, c = 13.1381(9) A, a = 83.774(1) , b = 72.711(1) ,
3
˚
c = 77.938(1) , V = 1607.2(2) A , T = 100(2) K, space group P1
(no. 2), Z = 2, l (Mo Ka) = 0.312 mm−1, 13450 reflections measured,
6911 unique (Rint = 0.0176). The final R values were R(F) = 0.0392
[I > 2r(I)] and wR(F2) = 0.0988 (all data).
21 Crystal data: C28H36O12·KPF6, M = 748.64, monoclinic◦, a =
˚
3
˚
˚
16.840(2) A, b = 19.447(3) A, c = 19.410(2) A, b = 91.43(1) , V =
˚
6354(2) A , T = 100(2) K, space group C2/c (no. 15), Z = 8, l
(Mo Ka) = 0.315 mm−1, 22885 reflections measured, 9339 unique
(Rint = 0.0308). The final R values were R(F) = 0.0585 [I > 2r(I)]
and wR(F2) = 0.1926 (all data).
22 Crystal data: C28H36O12·[C14H16N][PF6]·0.265CH3OH, M = 916.31,
˚
˚
˚
monocli◦nic, a = 14.324(6) A, b = 22.806(6) A, c = 26.470(8) A, b =
3
˚
97.20(3) , V = 8579(5) A , T = 100(2) K, space group C2/c (no. 15),
Z = 8, l (Mo Ka) = 0.154 mm−1, 32751 reflections measured, 12526
unique (Rint = 0.0570). The final R values were R(F) = 0.0578 [I >
2r(I)] and wR(F2) = 0.1901 (all data).
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O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 1 1 4 – 2 1 2 1
2 1 2 1