Convergent synthesis of p-benzylcalix[7]arene: Condensation and UHIG of p-benzylcalix[6 or 8]arenes

Article abstract of DOI:10.1021/ol9908272

(matrix presented). p-Benzylcalix[5]arene and p-benzylcalix[7]arene are formed on ultrahigh intensity grinding (UHIG) of p-benzylcalix[6 or 8]arenes in the presence of KOH and molecular sieves (4 ?), and the same calix[7]arene is also formed on condensation of p-benzylphenol and formaldehyde (15-20% yield), under more forcing conditions, along with p-benzylcalix[10]arene.

Full text of DOI:10.1021/ol9908272

ORGANIC
LETTERS
1999
Vol. 1, No. 10
1523-1526
Convergent Synthesis of
p-Benzylcalix[7]arene: Condensation
and UHIG of p-Benzylcalix[6 or 8]arenes
,‡
Jerry L. Atwood,† Michaele J. Hardie,‡ Colin L. Raston,* and
Christian A. Sandoval‡
Department of Chemistry, UniVersity of MissourisColumbia,
Columbia, Missouri 65211, and Department of Chemistry,
Monash UniVersity, Clayton, Melbourne, Victoria 3168, Australia
c.raston@sci.monash.edu.au
Received July 18, 1999
ABSTRACT
p-Benzylcalix[5]arene and p-benzylcalix[7]arene are formed on ultrahigh intensity grinding (UHIG) of p-benzylcalix[6 or 8]arenes in the presence
of KOH and molecular sieves (4 Å), and the same calix[7]arene is also formed on condensation of p-benzylphenol and formaldehyde (15−20%
yield), under more forcing conditions, along with p-benzylcalix[10]arene.
Calixarenes are an extensively studied class of compounds,
and their syntheses from p-substituted phenols (usually tert-
butylphenol) and formaldehyde in the presence of base are
well-established.1 Despite this, the reasons for the formation
of a particular calixarene are currently not well understood.1,2
Even numbers of phenol units are usually favored in one-
pot syntheses,1 although theoretical studies indicate that odd-
numbered calix[5,7]arenes are not destabilized compared
with even numbered calix[4,6]arenes.3 The base equivalent
used during the syntheses usually predetermines the ring
number, although calix[4]arenes are regarded as the ther-
modynamically favored product while calix[8]arenes are
formed under kinetic control.4
While the milling of materials has been widely used for
particle size reduction, mixing, or blending in the ceramic
and powder metallurgy industries, ultrahigh intensity grinding
(UHIG) has accomplished mechanical alloying,5 reduction
of metal chlorides,6 activation of mixed oxides,7 the trans-
formations of polymeric materials,8 and the degradation of
pesticides.9 There have been few applications of mechano-
chemistry at the molecular reaction level.10 Herein we report
the use of UHIG of p-benzylcalix[6,8]arene in a vibratory
ball-mill as a strategy to gain access to p-benzylcalix[5]-
arene in a solvent free solid-state procedure, beyond that
derived from the condensation of p-benzylphenol with
(4) (a) Gutche, C. D.; Iqbal, M.; Stewart, D. J. Org. Chem. 1986, 51,
742. (b) Dhawan, B.;.Chen, S.-I.; Gutsche, C. D. Makromol. Chem. 1987,
188, 921-950.
† University of Missouri.
‡ Monash University.
(5) Davies, R. M.; McDermot, B.; Koch, C. C. Metall. Trans. A 1988,
19A, 2867-2874.
(1) (a) Gutsche, C. D.; Calixarenes; Royal Society of Chemistry:
Cambridge, 1989. (b) A Versatile Class of Macrocyclic Compounds; Vicens,
J., Bo¨hmer, V., Eds.; Kluwer Academic Publishers: Dordrecht, 1991. (c)
Ikeda, A.; Shinkai, S. Chem. ReV. 1997, 97, 1713-1734. (d) Bo¨hmer, V.
Angew. Chem., Int. Ed. Engl. 1995, 34, 713-745.
(2) Gutsche, C. D.; Johnson, Jr., D. E.; Stewart, D. R. J. Org. Chem.
1999, 64, 3747-3750.
(6) Danielian, N. G.; Melnichenko, V. V. Phys. Lett. B 1991, 20, 1355-
1359.
(7) (a) Koch, C. C. ReV. Mater. Sci. 1989, 19, 121-143. (b) Laruelle,
S.; Figlarz, M. Solid State Ionics 1994, 111, 172-177. (c) Alonso, T.; Liu,
Y.; McCormick, P. G. Mater. Lett. 1992, 11, 164-166.
(8) Ishida, T. Mater. Lett. 1994, 13, 623-628.
(9) Rowlands S. A.; Hall, A. K.; McCormick, P. G.; Street, R.; Hart, R.
J.; Ebell, G. F.; Donecker, P. Nature 1994, 367, 223-223
(3) Harada, T.; Shinkai, S. J. Chem. Soc., Perkin Trans. 2 1995, 2231-
2242.
10.1021/ol9908272 CCC: $18.00 © 1999 American Chemical Society
Published on Web 10/28/1999

formaldehyde alone.11-13 In the course of ball-milling these
calixarenes and generating the calix[5]arene in 10-15%
yield, we noted the formation of 5-10% of a new calixarene
which was shown to be p-benzylcalix[7]arene, which was
subsequently prepared in gram quantities by the direct
reaction of p-benzylphenol with formaldehyde under more
forcing conditions. Access to additional p-benzylcalix[5]arene
alone is noteworthy as this calixarene can be used to
selectively bind C60 from fullerite mixture;12,13 this is related
to the complementarity of curvature of the calixarene with
that of C60, along with symmetry considerations.14,15 There
are only a few reports on the synthesis of calix[7]arenes.16,17
In addition, we have also isolated the corresponding calix-
[10]arene from condensation reactions, noting that the p-tert-
butylcalix[10]arene has recently been reported.18
Base-catalyzed condensation of p-benzylphenol and form-
aldehyde leads to a mixture of p-benzylcalix[5,6,8]arenes in
33%, 16%, and 12% yields, respectively, with no evidence
for formation of the calix[4 or 7]arenes.11 Following the
removal of the p-benzylcalix[5]arene, the subsequently
purified calix[6 or 8]arenes were ball-milled with paraform-
aldehyde and KOH in the presence of molecular sieves (4
Å), Scheme 1. The product mixtures were extracted and the
of the UHIG conditions described above, however, result in
only traces of the calix[5 and 7]arenes. Furthermore, calix-
arenes can be synthesized using UHIG from paraformalde-
hyde, base, molecular sieves, and p-benzylphenol, however
only in trace amounts. These findings suggest that the
products are not formed through a simple disproportonation
mechanism.
The collisions during UHIG, by means of compression,
can give rise to local temperatures well beyond 500 °C.20
It’s noteworthy that the reported syntheses of other calix[5
and 7]arenes requires high temperatures.11,16,17 Assuming a
thermally driven process, in an adapted synthesis for p-
benzylcalixarenes,21 the temperature was ramped from 80
to 205 °C in under 3 min yielding p-benzylcalix[5, 7, and
10]arenes in 18-20%, 15-20%, and <5%, respectively.
Variations of the KOH equivalents and increasing the
ramping time resulted in lower yields or an absence of
p-benzylcalix[7]arene in the reaction product mixture, sug-
gesting that the quick ramp time is necessary for the
production of p-benzylcalix[7]arene.
The solid-state structure of p-benzylcalix[7]arene was
determined by X-ray crystallography.22 The molecule adopts
a pinched conformation, Figure 1, similar to the conformation
observed for p-ethylcalix[7]arene (ignoring the benzyl and
ethyl groups respectively)23 but different from that of p-tert-
butylcalix[7]arene;24 the former has two of the seven hydroxy
groups inverted with respect to the others, appearing
Scheme 1
(19) UHIG synthesis of the p-benzylcalix[7]arene was carried out in a
stainless steel vial with a charge ratio, Cr, of 10 (mass of steel ball/mass of
powder mixture),25 under an argon atmosphere. Typically 0.6 g of a mixture
of pure p-benzylcalix[6 or 8]arene, 0.2 g of KOH, 0.6 g of 4 Å molecular
sieves, and 0.2 g of paraformaldehyde were ball milled for 4-16 h using
a Spex 8000 Mixer- Miller. The product mixture, containing unreacted
material, was extracted with CHCl3, washed with 1.0 M HCl, and water,
and then the organic fraction was dried with MgSO4. p-Benzylcalix[5 and
7]arenes were separated as white powders by chromatography (SiO2, eluent
CH2Cl2/hexane 30/70), yields 10-15% and 5-10%, respectively. Similar
yields were obtained by refluxing diphenyl ether solutions p-benzylcalix[6
or 8]arene, KOH (0.09 equiv/monomer), and paraformaldehyde (1 equiv/
monomer) for 24-36 h. p-Benzylcalix[7]arene: mp 320 °C (dec); 1H NMR
(400 MHz, CDCl3, 25 °C, TMS) δ ) 3.81 (s-br, 4H; Ar-CH2-Ar and Ph-
CH2-Ph), 6.88 (s, 2H; Ar-H), 7.21 (m, 5H; Ar-H), 10.31 (s-br, 1H; OH);
MS (ESI) m/z (%) 1413 (100) [M‚K+]; C98H84O7 (1373.8) calcd C 85.68,
H 6.16; found C 85.45, H 6.18. Crystals were grown by vapor diffusion of
MeOH into a toluene solution of p-benzylcalix[7]arene.
calix[5 and 7]arenes separated from starting material by
chromatography.19 Similar experiments with p-tert-butyl-
calix[6 and 8]arene yielded only starting materials. Variations
(10) (a) Aylmore, M. G.; Lincoln, F. J.; Cosgriff, J. E.; Deacon, G. B.;
Gatehouse, B. M.; Sandoval, C. A.; Spiccia, L. Eur. J. Solid State Inorg.
Chem. 1996, 33, 109. (b) Wang, G.-W.; Komatsu, K.; Murata, Y.; Shiro,
M. Nature 1997, 387, 583-586. (c) Komatsu, K.; Wang, G.-W.; Murata,
Y.; Tanaka, T.; Fujiwara, K. J. Org. Chem. 1998, 63, 9358-9366. (d)
Murata, Y.; Kato, N.; Fujiwara, K.; Komatsu, K. J. Org. Chem. 1999, 64,
3483-3488. (e) Yao, B.; Bassus, J.; Lamartine, R. New. J. Chem. 1996,
20, 913-915. (f) Ikeda, S.; Takata, T.; Kondo, T.; Hitoki, G.; Hara, M.;
Kondo, J. N.; Domen, K.; Hosono, H.; Kawazoe, H.; Tanaka, A. J. Chem.
Soc., Chem. Commun. 1998, 2185-2186.
(20) Schaffer, G. B.; McCormick, P. G. Metall. Trans. A 1992, 23A,
1285-1290.
(21) Synthesis of p-benzylcalix[7]arene: 9.72 g of p-benzylphenol and
4.50 g of paraformaldehyde were suspended in 65 mL of tetralin in a 250
mL RBF fitted with a Dean-Stark apparatus under N2. The mixture was
heated to 80 °C, then 0.35 mL of 14 M KOH was added, the temperature
was quickly ramped (<3 min) and maintained at 205 °C for 4 h and thenthe
solution dried with sodium sulfate, and the solvent was removed in vacuo.
Addition of warm acetone (80 mL) yielded a white precipitate of
p-benzylcalix[8]arene (12%).11 Evaporation of the solvent under vacuum,
followed by further addition of acetone (50 mL). yielded a white precipitate
of p-benzylcalix[5]arene.11 This final procedure was repeated to obtain a
second crop of p-benzylcalix[5]arene upon standing for 24-48 h (15-
20%). Further standing (1-3 days) yielded crystalline p-benzylcalix[7]arene
(15-20%). Evaporation of the solvent under vacuum, followed by addition
of acetone (40 mL) and standing at -30 °C for 2-5 days, yielded a white
precipitate of p-benzylcalix[6]arene.11 Further standing (1-2 days), after
collection of p-benzylcalix[6]arene, yielded a white precipitate consisting
of p-benzylcalix[5, 7, and 10]arenes which were separated by chromatog-
raphy (SiO2, eluent CH2Cl2/hexane 20/80), yield of p-benzylcalix[10]arene
<5%. p-Benzylcalix[10]arene: mp 280 °C (dec); 1H NMR (400 MHz, CD2-
Cl2, 25 °C, TMS) δ ) 3.78 (s, 2H; Ar-CH2-Ar), 3.79 (s, 2H; Ph-CH-Ph),
6.87 (s, 2H; Ar-H), 7.20 (m, 5H; Ar-H), 9.35 (s, 1H; OH); MS (ESI) m/z
(%) 2001 (100) [M‚K+]; C98H84O7 (1373.8) calcd C 85.68, H 6.16; found
C 85.61, H 6.19%.
(11) Souley, B.; Asfari, Z.; Vicens, J. Polish. J. Chem. 1992, 66, 959-
961.
(12) Nichols, P. J.; Raston, C. L.;.Sandoval, C. A.; Young, D. J. J. Chem.
Soc., Chem. Commun. 1997, 1839-1840.
(13) Atwood, J. L.; Barbour, L. J.; Nichols, P. J.; Raston, C. L.; Sandoval,
C. A. Chem. Eur. J. 1999, 5, 990-996.
(14) (a) Haino, T.; Yanase, M.; Fukazawa, Y. Angew. Chem., Int. Ed.
Engl. 1997, 36, 259-260. (b) Haino, T.; Yanase, M.; Fukazawa, Y.
Tetrahdron Lett. 1997, 38, 3739-3741.
(15) Ikeda, A.; Yoshimura, M.; Shinkai, S. Tetrahedron Lett. 1997, 38,
2107-2110.
(16) (a) Asfari, Z.; Vicens, J. Makromol. Chem. Rapid Commun. 1989,
10, 181-183. (b) Nakamoto, Y.; Ishida, S. Makromol. Chem. Rapid
Commun. 1982, 3, 705-707.
(17) Lubitov, I. E.; Shokova, E. A.; Kovalev, V. V. Synlett 1993, 647-
648.
(18) Stewart, D. R.; Gutsche, C. D. J. Am. Chem. Soc. 1999, 121, 4136-
4146.
1524
Org. Lett., Vol. 1, No. 10, 1999

The structure of the p-tert-butylcalix[7]arene is consistent
with the most stable conformation reported by Shinkai and
Harada from MM3(92) calculations.3 The conformation
adopted by the p-benzylcalix[7]arene and p-ethylcalix[7]-
arene, however, was reported in the same study to be
unstable, corresponding to the 19th most stable conformation.
The packing arrangement of the latter two are quite distinct,
suggesting that the adopted conformation is not necessarily
driven by crystal packing forces. Rather, the observed
pinched conformation aims at maximizing the intramolecular
hydrogen bonding network of the phenolic groups and
minimizing steric crowding between the aryl-CH2-aryl and
hydroxy groups.3 Strong intramolecular hydrogen bonding
is evident in the solid state with all O‚‚‚O distances between
2.60 and 2.74 Å. Furthermore, the IR spectra shows
ν
Ã-Η(KBr) at 3142 cm-1 (cf. 3138, 3229, and 3157 cm-1
for p-tert-butylcalix[4]arene,1 p-benzylcalix[5]arene,11 and
p-benzylcalix[6]arene, respectively) which is also consistent
with a strongly hydrogen bonded conformation.
1
The H NMR spectra for p-benzylcalix[7]arene at 20 °C
show a broad singlet at δ 10.31 ppm for the phenolic protons
with no AB-system observed for the bridging methylene
groups. At low temperature (-80 °C) the calix[7]arene
adopts C1 symmetry (cf. pseudo Cs in the solid state) which
is apparent from the appearance of seven singlets for the
hydroxy groups (δ 9.80-11.05 ppm), Figure 2, while the
methylene groups are observed to coalesce at around 0 °C.
This downfield shift is consistent with the formation of a
stronger hydrogen bonded network at the lower temperature.
Figure 1. Structure of p-benzylcalix[7]arene showing (a) the C1
symmetry (or close to Cs symmetry, ignoring the benzyl groups)
[only one of the two disordered positions are shown for the benzyl
groups] and (b) the pinched conformation (the benzyl groups have
been omitted for clarity).
relatively flat in projection, while the latter shows a full
complement of intramolecular hydrogen bonds on the same
side of the hydrocarbon macrocycle.24
(22) Crystal Structure Determination for [p-Benzylcalix[7]arene]-
[CHCl3]1.5[H2O]1.5: C99H88.5Cl4.5O8.50, Mr ) 1573.72, monoclinic, P21/c
(No. 14), a ) 16.47(9), b ) 21.8070(12), and c ) 25.4417(14) Å, γ )
103.876(1)°, V ) 8871(5) Å3, T ) 123(1) K, Fcalc ) 1.178 g cm-1, µ )
0.204 cm-1 (no correction), Z ) 4, Mo KR radiation, 15492 unique
reflections (Rint ) 0.170), 2θmax ) 50° (6378 observed, I > 2σ(I)), 1082
parameters, no restraints, R1 ) 0.1724, wR2 ) 0.4811 (all data). Data were
collected at 123(1) K on an Enraf-Nonius Kappa CCD diffractometer on a
colorless crystal of dimensions 0.25 × 0.20 × 0.20 mm. The structure was
solved by direct methods (SHELXS-97) and refined with a full matrix least-
squares refinement on F2 (SHELXL-97). The benzyl groups showed
considerable positional disorder which could not be adequately modeled
except for phenyl group C64-C69 which was modeled as being disordered
over two sites. Four of the phenyls were refined as rigid bodies. Solvent
molecules were modeled as CHCl3 or disordered water. With the exception
of the disordered phenyl group C64-C69 which was refined isotropically,
all non-hydrogen atoms were refined anisotropically. Hydrogen atoms on
the calixarene and chloroform molecules were included at calculated
positions with a riding refinement. The high residual values obtained are a
consequence of poor crystal quality, weak data (41% observed), and the
inherent disorder of the system and are in keeping with other structure
determinations of higher calixarenes.24
Figure 2. (a) 1H NMR of hydroxy region of p-benzylcalix[7]arene
and (b) p-benzylcalix[10]arene at 20 °C.
The 1H NMR of the p-benzylcalix[10]arene show a sharp
singlet at δ 9.35 ppm for the phenolic proton (20 °C) with
no AB-system observed for the bridging methylene groups.
(23) Andreetti, G. D.; Ugoozzoli, F.; Nakamoto, Y.; Ishida, S. J. Incl.
Phenom. 1991, 10, 241-253.
(24) Perrin, M.; Lecoco, S.; Asfari, Z. C. R. Acad. Sci. Ser. 2 1990, 310,
515.
(25) Maurice, D. R.; Courtney, T. H. Metall. Trans. A 1990, 21A, 289-
303.
Org. Lett., Vol. 1, No. 10, 1999
1525

At low temperature (-80 °C), however, the calix[10]arene
numbered calixarenes (5 and 7) and the formation of the
new p-benzylcalix[7 and 10]arenes which have interesting
possibilities in supramolecular chemistry.
adopts two distinct conformations, from consideration of the
1
hydroxy region of the H NMR spectrum, Figure 2. The
dominating species gives rise to five sharp peaks (δ 9.0-
9.6 ppm), each integrating for two protons, suggesting that
the adopted conformation has a mirror plain of symmetry (a
similar pattern of peaks is observed for p-tert-butylcalix-
[10]arene).18 The second conformation is considered to have
C1 symmetry by the appearance of eight equally integrating
singlets (δ 8.8-10.6 ppm), the other two hidden under two
singlets of the dominant species (from integration consid-
erations).
Acknowledgment. We thank the Australian Research
Council for support of this work.
Supporting Information Available: Crystal data, struc-
ture refinement details, and CIF file for p-benzylcalix[7]-
arene. This material is available free of charge via the Internet
at http://pubs.acs.org
Our findings demonstrate the use of UHIG in converting
two even-numbered calixarenes (either 6 or 8) into uneven-
OL9908272
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Org. Lett., Vol. 1, No. 10, 1999