The Wurtz-Fittig reaction in the preparation of C-silylated calixarenes

Article abstract of DOI:10.1021/jo070660n

(Chemical Equation Presented) The Wurtz - Fittig reaction of tetraiodo calixarene 3 with Na/Me₃SiC1 in DME gave a mixture of tetrakis- and tris-silylated calixarenes (6 and 7). Tris(silyl) calixarene 7 was assigned the flattened cone conformation. A model study using p-bromoanisole and p-iodoanisole with Na/Me₃SiC1 gave the best results with p-bromoanisole in toluene. Attempts to extend this reaction to the tetrabromo calixarene 4 resulted in slow reactions giving mixtures of products. However, the Wurtz-Fittig reaction of the bromo benzyloxycalixarene 5 was faster, giving the debenzylated silyl ether 12.

Full text of DOI:10.1021/jo070660n

for the introduction of silyl groups onto aromatic rings,6 and
few C-silylated calixarenes have been reported.4,7 We have
recently developed a convenient procedure for the preparation
of C-silylated calixarenes from bromocalixarenes by halogen-
metal exchange (using tert-BuLi) followed by treatment with
the clear supernatant from a mixture of chlorosilane and Et3N.3
We report here the use of the Wurtz-Fittig reaction for the
preparation of silylated calixarenes.
The Wurtz-Fittig Reaction in the Preparation of
C-Silylated Calixarenes
Paul F. Hudrlik,* Wondwossen D. Arasho, and
Anne M. Hudrlik
Department of Chemistry, Howard UniVersity,
Washington, D. C. 20059
The Wurtz-Fittig silylation reaction8 has been known for
many years as a method for preparing organosilicon com-
pounds,6b,9-11 and we have found it to be a useful method for
the stereospecific preparation of vinylsilanes.11 Its virtues include
ease of scale up and relatively low cost (compared to reactions,
for example, using tert-BuLi).
phudrlik@howard.edu
ReceiVed March 30, 2007
As an initial substrate for the Wurtz-Fittig reaction, the iodo
propyloxycalixarene 312 was prepared by treatment of propyl
ether 113 with I2 and CF3COOAg in CHCl313 (70-84% yields).
In some cases, a mixture of triiodo- and tetraiodocalixarenes
was obtained (based on MALDI and 1H NMR), and the mixture
was treated with additional iodine reagent to get pure 3. Other
substrates used subsequently were the bromo propyloxycalix-
arene 4,14 prepared by treatment of 1 with NBS/MEK (86-
93% yields),15a and the bromo benzyloxycalixarene 5,15b
similarly prepared by treatment of benzyl ether 216 with NBS/
MEK (78-88% yields) (Scheme 1).
In the Wurtz-Fittig silylation reaction, a silyl halide (usually
Me3SiCl) and Na are typically stirred together for several
minutes, and then an aryl or vinyl halide is introduced. In our
reactions, freshly pressed Na ribbon was used. The most
consistent results were obtained when the reaction flask was
flushed with nitrogen or argon before and immediately after
pressing the Na into it and then placed on an inert gas line.
The solvent and Me3SiCl (each recently distilled from a drying
agent) were added; the mixture was stirred for about 15 min
The Wurtz-Fittig reaction of tetraiodo calixarene 3 with Na/
Me3SiCl in DME gave a mixture of tetrakis- and tris-silylated
calixarenes (6 and 7). Tris(silyl) calixarene 7 was assigned
the flattened cone conformation. A model study using
p-bromoanisole and p-iodoanisole with Na/Me3SiCl gave the
best results with p-bromoanisole in toluene. Attempts to
extend this reaction to the tetrabromo calixarene 4 resulted
in slow reactions giving mixtures of products. However, the
Wurtz-Fittig reaction of the bromo benzyloxycalixarene 5
was faster, giving the debenzylated silyl ether 12.
Calixarenes have been widely used as building blocks in the
design and synthesis of new materials for molecular recognition
and supramolecular chemistry.1 Calixarenes substituted with silyl
groups have potential for the recognition of anionic and
nucleophilic substances,2-4 as many silicon compounds can
interact with nucleophiles to form hypervalent silicon adducts.5
Although many functional groups can be easily introduced onto
the upper (wide) rim of the calixarene skeleton by electrophilic
substitution reactions, such reactions do not appear to be useful
(6) (a) Wright, A. J. Organomet. Chem. 1978, 145, 307-314. (b) Ha¨bich,
D.; Effenberger, F. Synthesis 1979, 841-876. (c) Olah, G. A.; Bach, T.;
Prakash, G. K. S. J. Org. Chem. 1989, 54, 3770-3771. (d) Keay, B. A. In
Science of Synthesis: Houben-Weyl Methods of Molecular Transformations;
Fleming, I., Ed.; Georg Thieme Verlag: Stuttgart, 2001; Vol 4, pp 685-
712.
(7) Ihm, H.; Paek, K. Bull. Korean Chem. Soc. 1995, 16, 71-73.
(8) The term “Wurtz-Fittig reaction” is normally used for the coupling
reaction of an aryl halide with an alkyl halide in the presence of sodium.
See: Smith, M. B.; March, J. AdVanced Organic Chemistry: Reactions,
Mechanisms, and Structure, 5th ed.; McGraw-Hill: New York, 2001; p
535.
(1) (a) Gutsche, C. D. Calixarenes; The Royal Society of Chemistry:
London, 1989. (b) Bo¨hmer, V. Angew. Chem., Int. Ed. Engl. 1995, 34, 713-
745. (c) Gutsche, C. D. Calixarenes ReVisited; The Royal Society of
Chemistry: London, 1998. (d) Mandolini, L., Ungaro, R., Eds. Calixarenes
in Action; Imperial College Press: London, 2000. (e) Asfari, Z.; Bo¨hmer,
V.; Harrowfield, J., Vicens, J., Eds. Calixarenes 2001; Kluwer Academic
Publishers: Dordrecht, 2001.
(2) Anion recognition: (a) Beer, P. D.; Gale, P. A. Angew. Chem., Int.
Ed. 2001, 40, 486-516. (b) Matthews, S. E.; Beer, P. D. In ref 1e; pp
421-439.
(9) Eaborn, C.; Bott, R. W. In Organometallic compounds of group IV
metals; the bond to carbon; MacDiarmid, A. G., Ed.; Marcel Dekker, Inc.:
New York, 1968; Vol. 1, pp 105-536.
(10) (a) Nagendrappa, G. Synthesis 1980, 704-706. (b) Adam, W.;
Richter, M. J. Synthesis 1994, 176-180.
(11) Hudrlik, P. F.; Kulkarni, A. K.; Jain, S.; Hudrlik, A. M. Tetrahedron
1983, 6, 877-882.
(12) Arduini, A.; Giorgi, G.; Pochini, A.; Secchi, A.; Ugozzoli, F. J.
Org. Chem. 2001, 66, 8302-8308.
(3) (a) Hudrlik, P. F.; Hudrlik, A. M.; Arasho, W. D.; Zhang, L.; Cho,
J. Abstracts, 60th Southwest Regional Meeting of the American Chemical
Society, Fort Worth, TX, Sept 29-Oct 5, 2004. (b) Hudrlik, P. F.; Hudrlik,
A. M.; Arasho, W. D.; Butcher, R. J., submitted.
(13) Arduini, A.; Casnati, A. In Macrocycle Synthesis: A Practical
Approach; Parker, D., Ed.; Oxford University Press: Oxford, 1996; pp 145-
173.
(4) Billo, F.; Musau, R. M.; Whiting, A. ARKIVOC 2006, 199-210.
(5) (a) Chuit, C.; Corriu, R. J. P.; Reye´, C.; Young, J. C. Chem. ReV.
1993, 93, 1371-1448. (b) Chuit, C.; Corriu, R. J. P.; Reye, C. In Chemistry
of HyperValent Compounds; Akiba, K., Ed.; Wiley-VCH: New York, 1999;
pp 81-146. (c) Kira, M.; Zhang, L. C. In Chemistry of HyperValent
Compounds; Akiba, K., Ed.; Wiley-VCH: New York, 1999; pp 147-169.
(14) Larsen, M.; Jørgensen, M. J. Org. Chem. 1996, 61, 6651-6655.
(15) (a) Conner, M.; Janout, V.; Regen, S. L. J. Org. Chem. 1992, 57,
3744-3746. (b) Gutsche, C. D.; Pagoria, P. F. J. Org. Chem. 1985, 50,
5795-5802.
(16) Gutsche, C. D.; Dhawan, B.; Levine, J. A.; No, H. K.; Bauer, L. J.
Tetrahedron 1983, 39, 409-426.
10.1021/jo070660n CCC: $37.00 © 2007 American Chemical Society
Published on Web 09/12/2007
J. Org. Chem. 2007, 72, 8107-8110
8107

SCHEME 1
SCHEME 3
(27 h); THF, 22 (24 h); ether, 19 (7 h); DME, 10 (21 h); using
iodoanisole 9, ether, 25 (24 h); toluene, 19 (23 h); THF, 8 (4
h); DME, 5 (7.5 h).
SCHEME 2
The proton source for the formation of anisole (11) may be
residual HCl in the chlorosilane. We tried the more basic solvent,
Et3N, and other silylating agents, Me3SiOEt and (Me3Si)2O. All
gave inferior results. From bromoanisole 8, with Me3SiCl in
Et3N, the 10/11 ratio was 14 after 20 h; with Me3SiOEt as the
silylating agent and solvent, the 10/11 ratio was 2.9 (5 h); and
with Me3SiOEt in Et2O, or with (Me3Si)2O as both the silylating
agent and solvent, the product was almost exclusively 11.
(to remove traces of water or HCl); and then the aryl halide
was introduced.
Because the best results in the model study were obtained
using bromoanisole 8 in toluene, we studied the Wurtz-Fittig
reaction of bromo propyloxycalixarene 4 using Na and Me3-
SiCl in toluene. This reaction was attempted many times and
appeared to start much more slowly than the corresponding
reaction of bromoanisole in toluene, eventually resulting in
mixtures of products by MALDI and NMR; MALDI indicated
silylation was not complete. The reaction of bromocalixarene
4 in ether gave similar results.
Iodocalixarene 3 was subjected to the Wurtz-Fittig reaction
in DME. (We initially used DME because calixarene 3 was not
rapidly soluble in ether, the solvent in which we had run Wurtz-
Fittig reactions to prepare vinylsilanes.11) The reaction, which
turned a dark purple color, appeared to be complete (by NMR
analysis of an aliquot) after 16 h and was worked up after 21
1
h. The H NMR spectrum of the crude product suggested a
mixture of compounds. Column chromatography produced two
crystalline products assigned as the tetrakis(trimethylsilyl)-
calixarene 63b (41% yield) and the tris(trimethylsilyl)calixarene
7 (21% yield) (Scheme 2) as well as a middle fraction which
was a mixture.
To develop a procedure for preparing 6 without competition
from apparent protonation to give 7, we tried to optimize the
Wurtz-Fittig reaction conditions using 4-bromoanisole (8) and
4-iodoanisole (9) as model compounds. These reactions were
carried out in the presence of n-undecane (internal standard) in
various solvents. Aliquots were taken and analyzed by GC and
sometimes also by GC/MS. GC ratios were not corrected for
detector response, as this work was intended only to be a survey
to compare solvents and identify those most promising to pursue
with the calixarenes. In most cases, the major product was
4-trimethylsilylanisole (10) with smaller amounts of anisole (11).
When the benzyloxycalixarene 5 was treated with Na and
Me3SiCl in toluene (Scheme 3), the reaction appeared to be
considerably faster than that of the propyloxy calixarene 4.
However, it was not nearly as facile as that of bromoanisole 8,
and very vigorous stirring was needed. The reaction was
1
normally worked up in 48 h. The H NMR spectrum of the
crude product suggested the benzyl groups had been cleaved
and replaced by silyl groups. The product was assigned as
calixarene 12, which was both C-silylated and O-silylated, from
the NMR and MALDI-TOF of the purified product. Frequently,
the 1H NMR spectrum of the crude product looked remarkably
clean, but small extra peaks in the region of the bridge methylene
protons suggested the presence of another calixarene. The
integration suggested the other calixarene had one fewer silyl
group, with a ratio of 12 to the other calixarene of about 2:1.
Despite the fact that the product was a mixture, it was easily
purified by simple recrystallization from MeOH/CHCl3 (9:1)
to give calixarene 12 in 43% yield. In cases where the crude
product looked less clean, the silyl ethers were directly
hydrolyzed to the hydroxy compound 13 as described below,
and pure 13 was obtained by recrystallization, but with lower
yields.
In our work on the preparation of silylated calixarenes using
halogen-metal exchange, we found that the supernatant from
mixtures of chlorosilanes with Et3N gave purer products and
less protonation than the use of chlorosilanes alone.3 When we
used Me3SiCl/Et3N prepared in this manner in the above reaction
(5, Na, Me3SiCl/Et3N, toluene), calixarene 12 was isolated in
51% yield after recrystallization.
The highest ratios of 10/11 were found using bromoanisole
8 with toluene or benzene. These reactions appeared to start
very quickly (the reaction mixture turned blue) and were
completed within 1-2 h, faster than any of the other reactions.
The ratios of 10/11 under the most favorable conditions ranged
from about 30:1 to 70:1 for the reactions in toluene and (in
two runs) 44:1 for those in benzene.
The other solvents we tried appeared to be inferior. Typical
ratios (10/11) at a time when the reactions were substantially
complete were as follows: using bromoanisole 8, dioxane, 27
The silyl ethers in 12 were hydrolyzed using NaOMe/MeOH
and THF (rt, 5 min) to give tetrahydroxytetrakis(trimethylsilyl)-
calixarene 13 in 78% yield. As expected, silicon-carbon bond
cleavage was not a problem. The NMR spectra of calixarene
8108 J. Org. Chem., Vol. 72, No. 21, 2007

12 indicated that it was in the cone conformation.17,18 As
expected, calixarenes 1-6 and 13 were in the cone conforma-
tion, 1-6 because of the method of preparation17 and 13 because
of the stability from hydrogen bonding.
appear as one triplet at higher field and two overlapping triplets
at lower field. A DQF-COSY experiment on 7 established that
the higher-field OCH2 signal correlated to the higher-field
OCH2CH2 signal which correlated with the lower-field OCH2-
CH2CH3 signal.22 Therefore, the more atypical CH3 (lower field)
is from the same propyl group as the more atypical OCH2
(higher field).
The tris(silyl)calixarene 7 was assigned as a flattened (or
pinched) cone conformation,19 in which two of the aryl groups
are closer together (pinched) and (almost) parallel and the other
two are splayed outward. The structure of 7 was assigned from
the 1H and 13C NMR, DEPT, and IR spectra and MALDI-TOF
The separation of the multiplets for the OCH2 protons (δ 4.0
and 3.7) suggests predominantly one conformer is favored.
Jørgenson and co-workers have stated that the separation of the
signals from the OCH2 groups can be used as an estimate of
the equilibrium between the two flattened cone conformations
if they are in rapid exchange in the NMR time scale (ignoring
effects of substituents at positions 5 and 17). Identical chemical
shifts would indicate an equal mixture, whereas a difference of
ca. 0.4 ppm would indicate one conformer is clearly favored.19g,h
Calixarene 7 most certainly has the favored flattened cone
conformation with the parallel aromatic rings being those with
H and SiMe3 as p-substituents as shown in Scheme 2. The
higher-field OCH2 groups which are split into overlapping
triplets are assigned to the diastereotopic OCH2 groups on the
splayed rings. (However, a small effect of the p-SiMe3 vs H on
the chemical shift of the OCH2 of the propyls on the parallel
rings cannot be ruled out.) This assignment reinforces an earlier
assignment in a tetrapropoxythiacalix[4]arene, in which two sets
of alkoxy residues were observed, with the more highly shielded
OCH2’s assigned to those on the declined (splayed) rings by
virtue of their spatial relationship to the aromatic rings.23
p-C-Silylated calix[4]arenes have been previously prepared
by halogen-metal exchange on bromocalixarenes with tert-BuLi
1
mass spectra. The diagnostic signals in the H NMR for the
flattened cone were two separate groups of aromatic signals,
one at rather high field (δ 6.1-6.2, assigned to protons on the
parallel rings), and two equally sized sets of signals for the
propyloxy groups, in particular, signals of ca. δ 4.0 and δ 3.7
for OCH2 groups. Tetra-O-alkylated calix[4]arenes in the cone
1
conformation usually show H NMR spectra expected18 for a
symmetrical cone but are believed to undergo interconversion
in solution between flattened cone conformations, which is
usually fast on the 1H NMR time scale. Flattened cone
1
conformations have previously been observed in the H NMR
using low temperatures or with calixarenes which favor a
particular flattened conformation. This has included calixarenes
with substituents on opposite rings (5,17 positions) which are
large or which can participate in hydrogen bonding.19b-d,i
Calixarene 7 is of special interest because, in contrast to other
calix[4]arenes with flattened cone conformations which we have
seen, it has only one plane of symmetry. Consequently, the CH2
groups of two of the propyloxy groups (on the splayed rings)
have diastereotopic hydrogens. For the OCH2 protons in 7, the
lower-field signal is a multiplet having the same appearance in
7 as in other flattened cone calixarenes pictured in the literature20
and prepared in our laboratory,21 but the upper-field signal,
normally a conventional triplet, appears as two overlapping
triplets in 7.
in THF followed by treatment with silyl chlorides.3-4,7
A
tetrakis(trimethylsilyl) hexyloxy calixarene7 and tetrakis- and
tris(trimethylsilyl) methoxy calixarenes4 have been reported;
both were purified by chromatography. In the latter case,
fractional crystallization was also employed to separate the
tetrakis from the tris. A number of silylated calixarenes have
been prepared in our laboratory by halogen-metal exchange
of several p-bromocalix[4]arene ethers with tert-BuLi in THF
followed by treatment with the supernatant from mixtures of
several silyl chlorides and triethylamine.3 For example, from a
p-bromo tetrapropoxy calixarene (calixarene 4) using Me3SiCl/
Et3N, the tetrakis(trimethylsilyl)calixarene (calixarene 6) was
isolated in 79% yield. A similar reaction on a tetrabenzyloxy-
calixarene gave the tetrasilylated product in 92% yield, and
hydrogenolysis to remove the benzyl ethers gave the tetrahy-
droxy compound (calixarene 13) in 88% yield. The crude
silylation products were crystalline, and the silylated calixarenes
were purified only by a simple recrystallization.
The CH3’s of the propyl groups in flattened cone calixarenes
normally appear as two conventional triplets, but in 7, they
(17) The shapes of calix[4]arenes are usually discussed in terms of four
basic conformations: cone, partial cone, 1,2-alternate, and 1,3-alternate.
For a discussion, see ref 1c, pp 41-46, and ref 1d, pp 1-10. Introduction
of sufficiently large substituents onto the phenolic oxygens restricts
conformational interconversion. Calixarenes 6 and 7 (as well as 3-5) are
frozen in the cone conformation because of the method of preparation of
starting materials 1 and 2 (see refs 13 and: (a) Groenen, L. C.; Rue¨l, B. H.
M.; Casnati, A.; Timmerman, P.; Verboom, W.; Harkema, S.; Pochini, A.;
Ungaro, R.; Reinhoudt, D. N. Tetrahedron Lett. 1991, 32, 2675-2678. (b)
Gutsche, C. D.; Reddy, P. A. J. Org. Chem. 1991, 56, 4783-4791) and
because of the size of the substituents on the oxygens (see: Iwamoto, K.;
Araki, K.; Shinkai, S. J. Org. Chem. 1991, 56, 4955-4962).
(18) For a discussion of the NMR spectra of calix[4]arenes, see ref 16
and Ungaro, R. In ref 1d; pp 1-10.
(19) For references to pinched cone calix[4]arenes, see: (a) Grootenhuis,
P. D. J.; Kollman, P. A.; Groenen, L. C.; Reinhoudt, D. N.; van Hummel,
G. J.; Ugozzoli, F.; Andreetti, G. D. J. Am. Chem. Soc. 1990, 112, 4165-
4176. (b) Conner, M.; Janout, V.; Regen, S. L. J. Am. Chem. Soc. 1991,
113, 9670-9671. (c) Arduini, A.; Fabbi, M.; Mantovani, M.; Mirone, L.;
Pochini, A.; Secchi, A.; Ungaro, R. J. Org. Chem. 1995, 60, 1454-1457.
(d) Scheerder, J.; Vreekamp, R. H.; Engbersen, J. F. J.; Verboom, W.; van
Duynhoven, J. P. M.; Reinhoudt, D. N. J. Org. Chem. 1996, 61, 3476-
3481. (e) Jørgensen, M.; Larsen, M.; Sommer-Larsen, P.; Petersen, W. B.;
Eggert, H. J. Chem. Soc., Perkin Trans. 1 1997, 2851-2855. (f) Soi, A.;
Bauer, W.; Mauser, H.; Moll, C.; Hampel, F.; Hirsch, A. J. Chem. Soc.,
Perkin Trans. 2 1998, 1471-1478. (g) Larsen, M.; Krebs, F. C.; Harrit,
N.; Jørgensen, M. J. Chem. Soc., Perkin Trans. 2 1999, 1749-1757. (h)
Jørgensen, M.; Krebs, F. C. J. Chem. Soc., Perkin Trans. 2 2000, 1929-
1934. (i) Dondoni, A.; Kleban, M.; Hu, X.; Marra, A.; Banks, H. D. J.
Org. Chem. 2002, 67, 4722-4733.
By comparison, the Wurtz-Fittig silylation reactions using
the benzyloxycalixarene (5) gave lower yields, but the silyl
calixarenes could also be purified by simple recrystallization.
The Wurtz-Fittig procedure has the potential advantage of being
easier to scale up than the halogen-metal procedure.
In summary, the Wurtz-Fittig silylation reaction using Na
and Me3SiCl on a tetraiodo propyloxycalixarene (3) in DME
gave a mixture of tetrakis- and tris-silylated calixarenes (6 and
7). Tris(silyl) calixarene 7 was assigned the flattened cone
(22) This assignment agrees with a previous COSY spectrum of a
flattened cone calixarene in which a higher-field CH3 was assigned to the
same propyl as a lower-field OCH2 (ref 19e).
(20) Supporting Information to ref 19c.
(21) Hudrlik, P. F.; Hudrlik, A. M.; Zhang, L.; Arasho, W. D.; Cho, J.
J. Org. Chem. 2007, 72, 7858-7862.
(23) Cˇ ajan, M.; Lhota´k, P.; Lang, J.; Dvoˇra´kova´, H.; Stibor, I.; Kocˇa, J.
J. Chem. Soc., Perkin Trans. 2 2002, 1922-1929. See also ref 19h.
J. Org. Chem, Vol. 72, No. 21, 2007 8109

conformation from the 1H NMR spectrum. The effect of
conditions on the Wurtz-Fittig reaction was studied using
bromo- and iodoanisole (8 and 9) as model compounds, and
the reaction with bromoanisole proceeded efficiently in toluene
to give the silylated product 10, with little or none of the
protonated product 11. Numerous attempts to extend the reaction
to the tetrabromo calixarene 4 resulted in sluggish reactions and
mixtures of products. However, the Wurtz-Fittig reaction using
the bromo benzyloxycalixarene (5) resulted in a more rapid
reaction and a product mixture which could be purified by
recrystallization. The product (12) was that of debenzylation
as well as of silylation on both upper and lower rims; hydrolysis
produced calixarene 13. The use of benzyloxyhalo aromatic
rings as substrates in other Wurtz reactions is worthy of further
study because large-scale reactions using sodium are cheaper,
safer, and easier to run than those involving the more commonly
employed tert-BuLi.
2986, 2950, 1578, 1460, 1419, 1265, 1127, 927, 843, 733, 697
cm-1; MALDI-TOF MS (peaks of comparable size) 1024.6 (12,
[M + Na]+, calcd for C52H88O4Si8Na: 1023.5), 1000.2 (12, M+,
calcd for C52H88O4Si8: 1000.5), 952.5 (12 - Me3Si, [M + Na]+),
928.7 (12 - Me3Si, M+).
Procedure using Et3N. Na (0.85 g, 37 mmol) was pressed as
ribbon into an argon-flushed 2-neck 25 mL flask. The flask was
placed on an argon line, and 15 mL of toluene was added followed
by a 2.0 mL portion of the supernatant liquid from a mixture of
Me3SiCl/Et3N (1:1 v/v, approximately 8 mmol of chlorosilane). The
mixture was stirred for 30 min at rt, and then 0.231 g (0.210 mmol)
of benzyloxycalixarene 5 was added. The mixture was stirred for
48 h at rt (turned blue within 12 h). The reaction mixture was
filtered to remove residual Na and then washed with 15 mL of
saturated NaHCO3 followed by 15 mL of brine. The organic layer
was dried (MgSO4), concentrated, and placed under an oil pump
vacuum (2 h, 0.05 mm, rt). Addition of 10 mL of MeOH/CH2Cl2
(9:1) resulted in the formation of white solid which was filtered
and placed under an oil pump vacuum (2 h, 0.05 mm, rt) to give
0.126 g of a white powder. 1H NMR indicated a mixture of products
as above (as did MALDI-TOF). Recrystallization from MeOH/CH2-
Cl2 (9:1) gave 0.108 g (51% yield) of 12 as a white powder: mp
304-306 °C. The 1H NMR and 13C NMR spectra were essentially
the same as those reported above.
Experimental Section
5,11,17,23-Tetrakis(trimethylsilyl)-25,26,27,28-tetrakis-
(trimethylsilyloxy)calix[4]arene (12). Na (0.59 g, 26 mmol) was
pressed as ribbon into an argon-flushed 2-neck 25 mL flask. The
flask was placed on an argon line, and 15 mL of toluene was added
followed by 1.0 mL (0.85 g, 7.8 mmol) of Me3SiCl. The mixture
was stirred for 15 min at rt, and then 0.274 g (0.249 mmol) of
benzyloxycalixarene 5 was added. The mixture was stirred for 48
h at rt (turned blue within 12 h), and then the liquid was removed
by pipet and washed with 15 mL of saturated NaHCO3 followed
by 15 mL of brine. (The residual Na was more finely divided in
this reaction than in the previous reactions, and in subsequent runs,
the reaction mixture was filtered to remove the Na before
transferring to the separatory funnel.) The organic layer was then
dried (MgSO4), concentrated, and placed under an oil pump vacuum
(2 h, 0.05 mm, rt) to give 0.246 g of the crude product as a mixture
5,11,17,23-Tetrakis(trimethylsilyl)-25,26,27,28-tetrahydro-
xycalix[4]arene (13). This procedure is based on that of Cooper.24
Into a nitrogen-flushed 2-neck 25 mL flask was added 0.051 g
(0.051 mmol) of the trimethylsilyloxycalixarene (12) followed by
3.0 mL of THF. The mixture was stirred for about 2 min to dissolve
12, and then 2.5 mL of 2.0 M NaOMe in MeOH (5.0 mmol) was
added. The mixture was stirred for 5 min at rt, and then 5.0 mL of
distilled water was added. The mixture was transferred to a
separatory funnel, and 10 mL of CH2Cl2 was added. The organic
layer was separated, dried (Na2SO4), and concentrated. The product
was recrystallized from MeOH/CH2Cl2 (9:1) and placed under an
oil pump vacuum (2 h, 0.05 mm, rt) to give 0.028 g (78% yield) of
13 as white crystals: mp 263-266 °C (lit.3b mp 263.6-264.6 °C).
1
of white solid and yellowish oil. The H NMR spectrum of the
1
The H NMR, 13C NMR, and MALDI were equivalent to those
crude product indicated the disappearance of the methylene peaks
of the benzyl group of the calixarene. Two large peaks were
observed near 0.00 ppm assigned to the Me3Si protons. In addition
to the doublets at δ 4.39 and 3.04 (12), there were minor peaks at
δ 4.30 (d) and 3.0 (m). (If these were due to another calixarene
such as a compound having one fewer Me3Si group, the ratio of
12 to the other calixarene is estimated at about 2:1 based on the
integration at δ 4.39 and 4.30.) Recrystallization of the crude
product from MeOH/CHCl3 (9:1) gave a white powder which was
filtered and placed under an oil pump vacuum (2 h, 0.1 mm, rt) to
give 0.107 g (43% yield) of 12 as a white powder: mp 303-306 °C;
1H NMR (400 MHz, CHCl3 standard) δ 6.87 (s, 8 H, ArH), 4.39
(d, J ) 12.7 Hz, 4 H, ArCH2Ar), 3.04 (d, J ) 12.7 Hz, 4 H, ArCH2-
Ar), 0.27 (s, 36 H, OSiMe), 0.06 (s, 36 H, ArSiMe); 13C NMR
(100 MHz, assignments by DEPT) δ 150.9 (C), 133.1 (CH), 132.1
(C), 130.4 (C), 30.6 (CH2), 1.1 (CH3), -0.7 (CH3); IR (CHCl3)
reported.3b
Acknowledgment. Early parts of this work were supported
by the U.S. Army Research Office under contract/grant number
DAAD13-98-C-0042. We are also very grateful to the W. M.
Keck Foundation for financial support. NMR spectra were taken
on a spectrometer purchased in part with funds from NSF (CHE-
0091603). We thank Dr. Harold Banks for helpful discussions.
Supporting Information Available: Experimental for the
1
Wurtz-Fittig reaction of 3, and H and 13C NMR spectra of 6, 7,
12, and 13. This material is available free of charge via the Internet
at http://pubs.acs.org.
JO070660N
(24) Cooper, G. D. J. Org. Chem. 1961, 26, 925-929.
8110 J. Org. Chem., Vol. 72, No. 21, 2007