Synthesis and alkali metal picrate extraction studies of p-tert- butylcalix[4]arene crown ethers bridged at the lower rim with pyridyl units

Article abstract of DOI:10.1016/S0040-4020(00)00160-5

The syntheses of pyridyl containing calix[4]arene receptors (4, 5, and 11) that adopt the cone conformation are reported. The complexation properties of these host molecules were estimated via the results of alkali metal picrate extraction experiments. A singly-bridged bis-calix[4]arene, i.e. 4 does not appear to be an efficient alkali metal picrate extractant. A doubly-bridged bis-calix[4]arene, i.e. 5, d splays elevated extraction avidity toward Rb⁺ and Cs⁺ picrates when compared with that of 4. A pyridyl containing calix[4]arene-crown-5, i.e. 11, shows improved avidity and selectivity toward extraction of K⁺ and Rb⁺ picrates vis-a-vis the corresponding behavior of 4 and 5. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00160-5

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 3121±3126
Synthesis and Alkali Metal Picrate Extraction Studies of
p-tert-Butylcalix[4]arene Crown Ethers Bridged at the Lower Rim
with Pyridyl Units
*
Alan P. Marchand, Hyun-Soon Chong, Mohamed Takhi and Trevor D. Power
Department of Chemistry, University of North Texas, Denton, TX 76203-5070, USA
Received 10 December 1999; accepted 17 February 2000
AbstractÐThe syntheses of pyridyl containing calix[4]arene receptors (4, 5, and 11) that adopt the cone conformation are reported. The
complexation properties of these host molecules were estimated via the results of alkali metal picrate extraction experiments. A singly-
bridged bis-calix[4]arene, i.e. 4 does not appear to be an ef®cient alkali metal picrate extractant. A doubly-bridged bis-calix[4]arene, i.e. 5,
displays elevated extraction avidity toward Rb1 and Cs1 picrates when compared with that of 4. A pyridyl containing calix[4]arene-crown-5,
i.e. 11, shows improved avidity and selectivity toward extraction of K1 and Rb1 picrates vis-a-vis the corresponding behavior of 4 and 5.
q 2000 Elsevier Science Ltd. All rights reserved.
Introduction
calix[4]arene-crown-5 (11) has been prepared, and its alkali
metal picrate extraction pro®le has been investigated.
In recent years, readily available calix[4]arenes1 have been
utilized extensively as starting materials for the synthesis of
metal selective1b ionophores. A variety of calix[4]arene-
based receptors that possess unusual cavity dimensions
have been synthesized via `upper' and `lower' rim functionali-
zation.2 The complexation properties of these molecules
appear to be highly dependent upon the nature and number
of donor atoms and also upon the conformation of the
calix[4]arene moiety.3 In particular, calix[4]arenes that
contain polyethylene glycol units attached to the lower
rim have been synthesized,4 and their behavior as alkali
metal extractants has been examined.5
The objectives of the present study are as follows: (i) to
investigate whether lower-rim pyridine-bridged bis-calix-
[4]arenes 4 and 5 display noteworthy ability to enter into
complexation with alkali metal cation guests; and (ii) to
determine the avidity and selectivity with which novel
host system 11 is able to extract alkali metal picrates from
aqueous solution into an organic phase (CHCl3).
Preparation of Host Systems 4 and 5
The methods used to prepare lower rim functionalized,
pyridine-containing bis-calix[4]arenes 4 and 5 are shown
in Schemes 1 and 2, respectively. Thus, base-promoted
reaction of p-tert-butylcalix[4]arene (1a) with 2,6-bis-
(bromomethyl)pyridine (2)9 in toluene/benzene produced
both singly-bridged (4) and doubly-bridged bis-calix[4]-
arenes (5) in 25 and 6% yield, respectively (Scheme 1).
Interestingly, when 1a was reacted with 2 in the presence
of K2CO3 as the templating base for 5 days, only 5 was
obtained in 30% yield.
The ability of pyridine-containing crown ethers to form
complexes with a variety of guests has been studied in
several laboratories.6 However, pyridine moieties have
been incorporated into the lower rim of calixarenes only
relatively recently.7 Furthermore, the complexation proper-
ties of pyridine-containing calix[4]arene crowns have not
been studied extensively.
In the present study, we report the synthesis and alkali metal
picrate extraction capabilities of novel bis-calix[4]arene8
receptors, i.e. 4 and 5, in which the lower rim of each
calix[4]arene moiety has been linked covalently with one
or more pyridine moities. In addition, a pyridine-containing
It was anticipated that monocalix[4]arene crown-3 (3) might
be formed via 1,3-bridging of 2 to 1a (Scheme 1). However,
in view of the steric strain that would become incorporated
into the resulting crown ether (3), it seems likely that 2 as a
bifunctional reagent prefers intermolecular `linking' rather
than intramolecular `bridging'.
Keywords: calixarenes; host compounds; ionophores; macrocycles;
complexation; pyridines.
* Corresponding author. Tel.: 11-940-369-7226; fax: 11-940-369-7374;
e-mail: marchand@unt.edu; e-mail: fg83@jove.acs.unt.edu
The structures of 4 and 5 were con®rmed via analysis of
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00160-5

3122
A. P. Marchand et al. / Tetrahedron 56 (2000) 3121±3126
Scheme 1.
1
their respective H NMR and 13C NMR spectra and via
HRMS analysis (see Experimental). Inspection of their
groups in 6 were protected via NaH promoted reaction
of this diol with BrCH2CH2OTHP,9 thereby affording 7.
Next, the O-tetrahydropyranyl protecting groups were
removed via treatment with p-TsOH. This procedure
afforded 8, which subsequently could be converted
into the corresponding ditosylate (9). Finally, KOt-Bu
promoted reaction of 9 with tetra-p-tert-butyl-26,28-
dimethoxycalix[4]arene5c (10) afforded 11 in 53% yield
(Scheme 2).
respective H NMR and 13C NMR spectra suggests that
1
the calix[4]arene moieties in 4 and 5 each adopt cone
conformations.10 Thus, the 1H NMR spectrum of 4 contains
overlapping AB spin systems at d 3.45, 4.24 and d 3.45,
4.52, respectively, that correspond to the two different types
1
of Ar±CH2±Ar methylene protons. In the H NMR spec-
trum of 5, a pair of doublets (d 3.33 and 4.36, Ar±CH2±Ar
methylene protons) and two singlets (d 0.93 and 1.24, tert-
butyl protons) are observed. These results suggest that the
two calix[4]arene moieties in 4 and 5 remain in the cone
conformation.10
1
The structure of 11 was con®rmed via analysis of its H
NMR and 13C NMR spectra and via HRMS analysis (see
Experimental). The 1H NMR spectrum of 11 displays an AB
spin pattern (d 3.10 and 4.23) for the Ar±CH2±Ar methyl-
ene protons and two distinct singlets (d 0.85 and 1.26) for
the the tert-butyl protons. These results suggest that the
p-tert-butylcalix[4]arene moiety in 11 preferentially adopts
the cone conformation.1a
1,3-Dimethoxy-p-tert-butylcalix[4]arene crown-5 (11),
which contains one pyridyl unit, was prepared in four
synthetic steps by starting with commercially available
2,6-bis(hydroxymethyl)pyridine (6) (Scheme 2). The OH
Scheme 2. (a) BrCH2CH2OTHP, NaH, DMF, 48 h (60%); (b) p-TsOH, MeOH (81%); (c) p-TsCl, KOH, THF (80%).

A. P. Marchand et al. / Tetrahedron 56 (2000) 3121±3126
3123
Table 1. Results of alkali metal picrate extraction experiments
Percent of picrate extracted (%)a
Results of Complexation Energy Calculations
Coordination studies of (i) 5 with Li1, Na1, K1 and Rb1 and
(ii) 11 with K1 were performed with gas-phase molecular
mechanics calculations in spartanw11 by utilizing the
Merck force ®eld (MMFF)12 and Monte Carlo confor-
mational searches. Complexation energies were determined
as the difference between the sum of the total energies of the
host molecule (ligand) and that of the complex (ligand´M1).
The lowest energy complex was arrived at by manually
docking the cation to various combinations of heteroatom
donors within the host molecule.
Host molecule
Li1
Na1
K1
Rb1
Cs1
4
0.8^0.6 6.1^0.6 8.2^0.4
3.1^0.4
1.8^0.6
5
11
1.7^0.5 6.7^0.5 7.2^0.4 13.9^0.5 11.7^0.7
3.3^0.4 8.6^0.5 40.5^0.6 32.5^0.6 6.6^0.7
a Averages and standard deviations calculated for data obtained from
three independent extraction experiments.
Alkali Metal Picrate Extraction Studies
The complexation energies thereby obtained are shown in
Table 2. The results obtained for complexation of 5 suggests
host±guest complex stability decreases in the order
K1.Rb1, Na1.Li1. By way of contrast, our experimental
picrate extraction results obtained by using 5 (Table 1) indi-
cate the following order of decreasing host±guest complex
stability: Rb1.Na1, K1.Li1. However, the signi®cantly
larger value calculated for 11´K1 complexation energy is
qualitatively consistent with the experimental results shown
in Table 1 for 11.
In an effort to investigate the complexation properties of
ligands 4, 5, and 11, a series of alkali metal picrate extrac-
tion experiments was performed. The results thereby
obtained are shown in Table 1.
Inspection of the data in Table 1 indicates that the bis-
calix[4]arenes (4 and 5) are inef®cient alkali metal picrate
extractants. Among the bis-calix[4]arenes studied, the
singly-bridged bis-calix[4]arene 4 displays slightly elevated
extraction avidity toward K1 picrate; however, 4 is an
inef®cient extractant toward Li1 and Cs1 picrates. The
doubly-bridged bis-calix[4]arene 5 displays slightly higher
extraction avidity toward all alkali metal picrates studied in
comparison with 4, with the exception of its behavior
toward K1 picrate.
Results of Molecular Modeling Studies
The appearance of the geometry-optimized structure of 5
suggests that potentially destabilizing nitrogen lone-pair
interactions which occur when the pyridine moieties lie in
a `head-to-head' (coplanar) arrangement are reduced when
the pyridine rings are mutually skewed. This `twisting'
results in minor defomation of the attached calix[4]arene
moieties, with the result that the binding sites within 5
become exposed to the approaching cation guest.
It is interesting to note that 5 displays somewhat higher
extracting ability toward Rb1 and Cs1 picrates vis-a-vis 4.
One possible rationale for this behavior is that the double-
linking of calix[4]arene moieties to pyridyl units which is
present in 5 results in a more favorable conformation for
complexation of large metal cations in 5 when compared
with that in 4.
The geometry-optimized structures that correspond to the
lowest energy conformations of complexes of 5 with Li1,
Na1, and K1, respectively, indicate the existence of M1
binding only to the pyridine ring nitrogens. Our attempts
to direct coordination of the cation guest to additional
Lewis base sites in host 5 resulted in a signi®cant increase
in complexation energy.
The data in Table 1 indicate that 1,3-dimethoxy-p-tert-
butylcalix[4]arene-pyrido-crown-5 (11) displays appreciable
extraction avidity toward K1 and Rb1 picrates. However,
this host displays much lower corresponding avidities
toward Li1, Na1 and Cs1 picrates, respectively.
In view of the improved performance of 11 as an alkali
metal picrate extractant in comparison with that of 4 and
5, we considered the possibility of converting the phenolic
hydroxyl groups in the latter two compounds into OCH3
substituents. However, KOt-Bu promoted reaction of a
di-O-methyl derivative of calix[4]arene (i.e. 1b) with 2
afforded an intractable mixture of several products from
which no single, pure compound could be isolated and
characterized. Other attempts to O-methylate the phenolic
OH groups in 5 by using standard procedures, i.e. (i)
(MeO)2SO2±K2CO3 in acetone or (ii) NaH±THF followed
by treatment with CH3I were not successful.
The energy-minized structure of 5´Rb1 is shown in Fig. 1.
This structure reveals that Rb1 is stabilized via coordination
to the two pyridine ring nitrogen atoms and also to two
hydroxyl groups in each of the two adjacent calix[4]arene
moieties. This additional coordination lowers the energy of
complex 5´Rb1 by ca. 10 kcal mol21 relative to that of the
corresponding complex in which Rb1 is stabilized only via
coordination to the two pyridine ring nitrogen atoms in 5. It
was also found that in the case of the smaller alkali metal
cations, our attempts to impose additional coordination of
M1 to calix[4]arene OH groups results in severe bending of
the calix[4]arene rings, with the result that C±H bonds
situated in the upper rim t-butyl groups become forced
into close proximity with an adjacent pyridine ring, thereby
producing signi®cant steric destabilization in the resulting
5´M1 complex. Consistent with this conclusion, for situ-
ations in which M1 is docked to six heteroatoms in the
complex 5´M1, we ®nd that the calculated total energy of
the complex decreases with increasing size of the alkali
Table 2. Calculated (MMFF Force Field)13 complexation energies for
complexes of 5 and of 11 with alkali metal cations
Host Molecule
Li1
Na1
K1
Rb1
5
11
3.3
±
11.9
±
24.0
61.5
12.8
±

3124
A. P. Marchand et al. / Tetrahedron 56 (2000) 3121±3126
1
Figure 1. Geometry-optimized structure of 5´Rb . Hydrogen atoms have been omitted for clarity. Calculated bond lengths in 5´Rb : Rb±O, 2.83 A; Rb±N,
1
Ê
Ê
2.77 A.
1
metal cation guest. Importantly, our results suggest that 5
contains a clearly de®ned cavity wherein the cation guest
resides in the 5´M1 complex.
11) were prepared. Inspection of their respective H NMR
and 13C NMR spectra suggests that calix[4]arene moieties in
4, 5, 11 occupy the cone conformation. The complexation
properties of these host molecules were estimated via the
results of alkali metal picrate extraction experiments.
The corresponding energy-minized structure of 11´K1 is
shown in Fig. 2. Here, it can be seen that K1 binds to the
pyridine ring nitrogen atom and also to both ether oxygen
atoms at the lower rim of the adjacent calix[4]arene moiety.
When coordination of K1 is restricted only to the pyridine
ring nitrogen atom in the 11´K1 complex, the calculated
complexation energy is reduced to only ca. 25 kcal mol.
Among the three host systems studied, only the doubly-
bridged bis-calix[4]arene 5 displays signi®cant avidity
toward complexation with K1 and Rb1 picrates. The
singly-bridged bis-calix[4]arene 4 is not an ef®cient host
toward alkali metal picrates, although it displays slightly
elevated extraction avidity toward K1 picrate. The results
presented herein do not provide compelling evidence that
cooperativity exists among the two calix[4]arene moieties
and the pyridyl unit(s) in 4 and 5 when they function as
donor ligands toward alkali metal cation guests.
Summary and Conclusions
Novel pyridyl containing calix[4]arene receptors (4, 5, and
Experimental
Melting points are uncorrected. Absorption intensities of
alkali metal picrate solutions were measured at lˆ374 nm
by using a Hewlett-Packard Model 84524 Diode Array UV-
visible spectrophotometer. High-resolution mass spectral
data reported herein were obtained by Professor Jennifer
S. Brodbelt at the Mass Spectrometry Facility at the Depart-
ment of Chemistry and Biochemistry, University of Texas at
Austin by using a ZAB-E double sector high-resolution
mass spectrometer (Micromass, Manchester, England) that
was operated in the chemical ionization mode.
Base promoted reaction of 1a with 2. Method A
A solution of 1a (738 mg, 1.00 mmol) and KOt-Bu (112 mg,
1.00 mmol) in dry PhCH3 (15 mL) under argon was heated
to re¯ux. To this re¯uxing solution was added dropwise
with stirring a solution of 2,6-bis(bromomethyl)pyridine
(2, 265 mg, 1.00 mmol) in dry benzene (15 mL) during
45 min. After all of this reagent had been added, the result-
ing mixture was re¯uxed during 24 h, at which time a
Figure 2. Geometry-optimized structure of 11´K1. Hydrogen atoms have
1
been omitted for clarity. Calculated bond lengths in 11´K : K±O, 2.52 A;
Ê
Ê
K±N, 2.47 A.

A. P. Marchand et al. / Tetrahedron 56 (2000) 3121±3126
3125
second portion of KOt-Bu (112 mg, 1.00 mmol) was added,
and the resulting mixture was re¯uxed for an additional
24 h. The reaction mixture was allowed to cool gradually
to ambient temperature, and H2O (10 mL) then was added.
The layers were separated, and the aqueous layer was
extracted with CHCl3 (3£30 mL). The combined organic
layers were washed with water (20 mL), dried (MgSO4),
and ®ltered, and the ®ltrate was concentrated in vacuo.
The residue was puri®ed via column chromatography on
silica gel by eluting with 10% EtOAc±hexane. Pure 4
(350 mg, 25%) was thereby obtained as a colorless micro-
crystalline solid: mp 249±2518C; IR (KBr) 3423 (br, s),
2961 (s), 1603 (m), 1489 (m), 1363 (m), 1192 (m), 1092
suspension was stirred at 08C for 10 min, at which time the
external ice±water bath was removed, and the reaction
mixture was allowed to warm gradually to ambient tempera-
ture while stirring during 2 h. The reaction mixture again
was cooled to 08C via application of an external ice±water
bath. To the cooled reaction mixture was added dropwise
with stirring a solution of 1-(O-tetrahydropyranyl)-2-
bromoethane (4.16 g, 20.0 mmol) in DMF (14 mL). The
resulting suspension was stirred at 08C for 10 min, at
which time the external cold bath was removed, and the
reaction mixture was allowed to warm gradually to ambient
temperature and was stirred at that temperature for 72 h. The
reaction mixture was concentrated in vacuo, and ice±water
(50 mL) was added to the residue. The resulting aqueous
suspension was extracted with CH2Cl2 (3£40 mL). The
combined organic layers were dried (MgSO4) and ®ltered,
and the ®ltrate was concentrated in vacuo. The residue was
puri®ed via column chromatography on silica gel by using a
10±50% EtOAc±hexane gradient elution scheme. Pure 7
(2.67 g, 67%) was thereby obtained as a colorless, viscous
oil; IR (®lm) 3028 (w), 2945 (s), 2873 (s), 1638 (s), 1448
(w), 1337 (w), 1118 (s), 1064 (m), 1027 (w), 782 (w),
1
(m), 1048 (s), 841 cm21 (m); H NMR (CDCl3) d 1.24 (s,
72H), 3.45 (d, Jˆ14.6 Hz, 8H), 4.24 (AB, JABˆ14.2 Hz,
4H), 4.52 (AB, JABˆ14.6 Hz, 4H), 5.40 (s, 4H), 6.92±7.16
(m, 16H), 8.03 (d, Jˆ7.8 Hz, 2H), 8.13 (t, Jˆ7.3 Hz, 1H),
9.43 (s, 4H), 10.12 (s, 2H); 13C NMR (CDCl3) d 31.2 (q),
31.5 (t), 32.3 (q), 33.0 (s), 33.8 (s), 34.0 (s), 34.2 (t), 78.7 (t),
122.3 (d), 125.6 (d), 126.5 (d), 127.4 (d), 128.1 (d), 128.3
(d), 133.6 (d), 138.6 (d), 143.0 (s), 143.5 (s), 147.8 (d),
148.1 (d), 148.4 (d), 149.7 (d), 155.8 (s), 158.3 (s). Exact
mass (CI HRMS) Calcd for C95H117NO8: [Mr1H]1 m/z
1399.8779. Found: [Mr1H]1 m/z 1399.8753.
1
639 cm21 (w); H NMR (CDCl3) d 1.42±1.96 (m, 12H),
3.42±4.01 (m, 12H), 4.8 (m, 6H), 7.3 (d, Jˆ8.8 Hz, 2H),
7.61 (t, Jˆ7.7 Hz, 1H); 13C NMR (CDCl3) d 19.8 (t), 25.9
(t), 31.0 (t), 62.6 (t), 67.1 (t), 70.3 (t), 74.5 (t), 99.3 (s), 120.3
(d), 137.5 (d), 158.1 (s). Exact mass (CI HRMS) Calcd for
C21H33 NO6: [Mr1H]1 m/z 396.2386. Found: [Mr1H]1 m/z
396.2392.
Continued elution of the chromatography column afforded 5
(90 mg, 6%) as a colorless microcrystalline solid: mp 241±
2448C; IR (KBr) 3354 (br, s), 2961 (s), 2870 (m), 1595 (m),
1482 (s), 1352 (m), 1205 (s), 1124 (m), 1012 (m), 879 cm21
(m); 1H NMR (CDCl3) d 0.93 (s, 36H), 1.24 (s, 36H), 3.33
(AB, JABˆ13.3 Hz, 8 H, ArCH2Ar), 4.36 (AB, JABˆ13.3 Hz,
8H, ArCH2Ar), 5.18 (s, 8H), 6.86 (s, 8H), 7.03 (s, 8H), 7.21
(s, 4H), 7.90 (t, Jˆ8.5 Hz, 2H), 8.16 (d, Jˆ8.9 Hz, 4H); 13C
NMR (CDCl3) d 31.5 (q), 32.2 (q), 34.3 (t), 34.4 (s), 78.7 (t),
120.5 (d), 125.5 (d), 126.1 (d), 128.0 (d), 128.2 (d), 132.9
(s), 139.2 (d), 142.0 (s), 147.5 (s), 150.5 (d), 151.2 (d), 157.5
(s), 158.3 (s). Exact mass (CI HRMS) Calcd for
C102H122N2O8: [Mr1H]1 m/z 1503.9280. Found: [Mr1H]1
m/z 1503.9319.
Preparation of 8
To a solution of 7 (320 mg, 0.81 mmol) in MeOH (8 mL)
was added TsOH (50 mg), and the resulting mixture was
stirred at ambient temperature during 24 h. The reaction
mixture was ®ltered, and the ®ltrate was concentrated in
vacuo. The residue was puri®ed via column chroma-
tography on basic alumina by eluting with MeOH. Pure 8
(810 mg, 81%) was thereby obtained as a colorless viscous
oil; IR (®lm) 3868 (br, s), 3029 (s), 2878 (s), 1723 (s), 1652
(s), 1591 (m), 1454 (s), 1117 (s), 1068 (s), 766 (w),
Method B
1
632 cm21 (w); H NMR (CDCl3) d 3.51±3.70 (m, 8H),
A solution of 1a (738 mg, 1.00 mmol), 2 (265 mg, 1 mmol),
and K2CO3 (550 mg, 4.00 mmol) in CH3CN (25 mL) was
re¯uxed with stirring during 4 days. The reaction mixture
was allowed to cool gradually to ambient temperature and
then was ®ltered, and the ®ltrate was concentrated in vacuo.
The residue was puri®ed via column chromatography on
silica gel by eluting with 10% EtOAc±hexane. Pure 5
(450 mg, 30%) was thereby obtained as a colorless micro-
4.50 (s, 4H), 7.16 (d, Jˆ8.7 Hz, 2H), 7.54 (t, Jˆ7.8 Hz,
1H); 13C NMR (CDCl3) d 60.6 (t), 72.5 (t), 72.7 (t), 120.1
(d), 137.2 (d), 157.5 (s). Exact mass (CI HRMS) Calcd for
C11H17NO4: [Mr1H]1 m/z 228.1236. Found: [Mr1H]1 m/z
228.1238.
Preparation of 9
crystalline solid: mp 241±2448C. The IR, 1H NMR, and 13
C
To a solution of 8 (290 mg, 1.29 mmol) in dry THF (2 mL)
was added ®nely pulverized KOH (230 mg, 3.68 mmol).
The mixture was cooled to 08C via application of an external
ice±water bath. To the resulting mixture was added drop-
wise with stirring a solution of TsCl (freshly recrystallized
from hexane, 560 mg, 2.95 mmol) in dry THF (3 mL) at 08C
under argon. The resulting mixture was stirred at 08C during
5 h, at which time the external ice±water bath was removed,
and the reaction mixture was allowed to warm gradually to
ambient temperature while stirring during 12 h. The result-
ing mixture was ®ltered, and the residue was washed with
THF (10 mL). The combined ®ltrates were concentrated in
vacuo. The residue was puri®ed via column chromatography
NMR spectra of the material thereby obtained are
essentially identical with the corresponding spectral data
reported above for authentic 5.
Preparation of 7
A suspension of NaH (60% dispersion in mineral oil,
960 mg, 20.0 mmol) in dry DMF (14 mL) under argon
was cooled to 08C via application of an external ice±
water bath. To this cooled solution was added dropwise
with stirring a solution of 2,6-pyridinedimethanol (6,
1.39 g, 10.0 mmol) in DMF (14 mL). The resulting white

3126
A. P. Marchand et al. / Tetrahedron 56 (2000) 3121±3126
on silica gel by eluting with 50% EtOAc±hexane. Pure 9
(480 mg, 80%) was thereby obtained as a colorless oil
(480 mg, 80%); IR (®lm) 3053 (m), 2898 (m), 1625 (w),
1352 (m), 1176 (s), 1029 (m), 1012 (m), 919 (m), 814 (m),
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Cantoni, M.; Graviani, E.; Pochini, A.; Secchi, A.; Sicuri, A. R.;
Ungaro, R.; Vincenti, M. Tetrahedron 1995, 51, 599.
A solution of 10 (125 mg, 0.19 mmol) and KOt±Bu (11 mg,
0.18 mmol) in dry PhCH3 (15 mL) was heated to re¯ux. To
this re¯uxing solution was added dropwise with stirring a
solution of 9 (89 mg, 0.19 mmol) in dry benzene (5 mL)
during 0.5 h. The resulting mixture was re¯uxed for 24 h,
at which time a second portion of KOt±Bu (20.7 mg,
0.19 mmol) was added, and the reaction mixture was
re¯uxed for an additional 24 h. The reaction mixture was
allowed to cool gradually to ambient temperature, and H2O
(10 mL) then was added. The layers were separated, and the
aqueous layer was extracted with CHCl3 (3£20 mL). The
combined organic layers were washed with water (20 mL),
dried (MgSO4), and ®ltered, and the ®ltrate was concen-
trated in vacuo. The residue was puri®ed via column
chromatography on silica gel by eluting with 20%
EtOAc±hexane. Pure 11 (85 mg, 53%) was thereby
obtained as a colorless, viscous oil; IR (KBr) 3423 (br, s),
2961 (s), 1653 (m), 1603 (m), 1559 (m), 1468 (m), 1363
(m), 1222 (m), 1118 (m), 1032 (s), 882 cm21 (m); 1H NMR
(CDCl3) d 0.85 (s, 18H), 1.26 (s, 18H), 3.10 (AB,
JABˆ12.3 Hz, 4H), 3.60 (s, 6 H), 3.87±4.08 (m, 8 H), 4.23
(AB, JABˆ12.3 Hz, 4 H), 4.75 (s, 4H), 6.45 (s, 4H), 7.13 (s,
4H), 7.33 (d, Jˆ8.5 Hz, 2H), 7.65 (t, Jˆ7.7 Hz, 1H); 13C
NMR (CDCl3) d(31.5 (q), 31.6 (t), 32.2 (q), 34.5 (s), 61.3
(q), 71.7 (t), 73.9 (t), 76.0 (t), 123.4 (d), 124.8 (d), 125.4 (d),
133.1 (s), 136.2 (s), 137.5 (d), 145.2 (s), 152.6 (s), 156. 3 (s),
157.7 (s, 2 C). Exact mass (CI HRMS) Calcd for C57H73O6N:
[Mr1H]1 m/z 868.5516. Found: [Mr1H]1 m/z 868.5525.
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Pappalardo, S.; Ferguson, G. J. Org. Chem. 1996, 61, 2407. (c)
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Alkali metal picrate extraction experiments
The extraction experiments were performed by using 5 mM
solutions of each compounds in CHCl3. The procedure that
was used for this purpose has been described previously.13
Acknowledgements
8. For a review, see: Asfari, Z.; Weiss, J.; Vicens, J. Synlett 1992, 719.
9. Baker, W.; Buggle, K. M.; McOmie, J. F. W.; Watkins, D. A.
M. J. Chem. Soc. 1958, 3594.
We thank the Robert A. Welch Foundation [Grants B-963
(A. P. M) and P-074 (W. H. W.)] and the U. S. Department
of Energy [Grant DE-FG07-98ER14936 (A. P. M.)], and the
Texas Advanced Technology Program [Grant 003659-0206
(A. P. M.)] for ®nancial support of this study. In addition,
we thank Prof. Jennifer S. Brodbelt (Department of
Chemistry, University of Texas at Austin) for having kindly
obtained the high-resolution chemical ionization mass
spectral data reported herein.
10. McKervey, M. A.; Owens, M.; Schulten, H.; Vogt, W.;
È
Bohmer, V. Angew. Chem., Int. Ed. Engl. 1990, 29, 280.
11. spartanw, version 5.1.3, is available from Wavefunction, Inc.,
18401 Von Karman Ave., Suite 370, Irvine, CA 92612.
12. Halgren, T. A. J. Comput. Chem. 1996, 17, 490.
13. Bartsch, R. A.; Eley, M. D.; Marchand, A. P.; Shukla, R.;
Kumar, K. A.; Reddy, G. M. Tetrahedron 1996, 52, 8979.