C3v (Trimethyl) p-(Benzyloxy)calix[6]arene: A versatile platform for the synthesis of functionalized C3v Calix[6]arenes

Article abstract of DOI:10.1002/ejoc.200901281

Partial methylation of p-(benzyloxy)calix[6]are:ne leads to the corresponding trimethylated C_3v derivative. This compound was used for the synthesis of new functional calixarenes. The presence of the p-(benzyloxy) substituent allows this new C_3v derivative to be directly oxidized to the tris(quinone), These new C_3v derivatives open the way to new supramolecular receptors, bearing easily derivatized hydroxy groups at the upper rim position.

Full text of DOI:10.1002/ejoc.200901281

FULL PAPER
DOI: 10.1002/ejoc.200901281
C3v (Trimethyl) p-(Benzyloxy)calix[6]arene: A Versatile Platform for the
Synthesis of Functionalized C3v Calix[6]arenes
Vincent Huc*[a] and Vincent Guérineau[b]
Keywords: Calixarenes / Alkylation / Quinones / Macrocycles
Partial methylation of p-(benzyloxy)calix[6]arene leads to the
corresponding trimethylated C3v derivative. This compound
was used for the synthesis of new functional calixarenes. The
presence of the p-(benzyloxy) substituent allows this new C3v
derivative to be directly oxidized to the tris(quinone). These
new C3v derivatives open the way to new supramolecular re-
ceptors, bearing easily derivatized hydroxy groups at the up-
per rim position.
Introduction
Calixarenes have received much attention during the last
decades due to the tremendous possibilities offered by these
easily accessible macrocycles.[1–4] (Let us consider, for exam-
ple, ions and/or molecule recognition phenomena,[5–13] sup-
ramolecular assemblies,[14,15] nanoparticles synthesis,[16–20]
etc.) Trimethylated C3v p-(tBu)calix[6]arene derivatives (Fig-
ure 1) were shown to be especially interesting, as they are
easily converted into conformationally rigid cone deriva-
tives, showing exceptional characteristics for the selective
formation of inclusion complexes.[21–27] In most cases, the
suitable recognition groups are introduced at the so-called
“small rim” position. “Large-rim”-functionalized C3v deriv-
atives were also described.[28–34] These new calixarene recep-
tors, functionalized at both rim positions, hold great prom-
ise for the synthesis of new supramolecular hosts (Fig-
ure 2).[27,29,30,34–37]
Up to now, these useful C3v platforms are only described
starting from the parent (p-tBu)calix[6]arene (Fig-
ure 1).[28–34] In this case, the substitution of the p-(tBu)
group is usually obtained by electrophilic cleavage. Al-
though useful, this approach often requires harsh condi-
tions and/or the use of aggressive reagents. Moreover, the
limited number of electrophilic agents able to cleave the p-
(tBu) group without altering the otherwise sensitive phen-
olic units makes this approach difficult to generalize. The
possibility to use others starting calixarene platforms
should thus be of great value for the community.
Figure 1. C3v-Symmetric calix[6]arene.
Within this frame, we wish to report here on the synthe-
sis and characterization of such a new calixarene family,
starting from p-(benzyloxy)calix[6]arene (Scheme 1).[7] We
show here that p-(benzyloxy)calix[6]arene may be converted
into the corresponding trimethylated C3v derivative on a
preparative scale. We also describe the simple and high-
yield synthesis of useful derivatives from this new C3v p-
(benzyloxy)calix[6]arene (Schemes 2–4). The presence of the
large benzyloxy groups at the para positions first allows the
simple synthesis of new receptors with a deeper hydro-
phobic cavity. Second, new possibilities are opened for easy
derivatization of these positions after Pd-catalyzed hydro-
genolysis, as already demonstrated for other p-(benzyloxy)-
functionalized calixarenes.[7,15,20,38]
Results and Discussion
[a] Institut de Chimie Moléculaire et des Matériaux d’Orsay
(ICMMO),
The starting p-(benzyloxy)calix[6]arene (2) was first ob-
tained in very low yields during the base-catalyzed conden-
sation of p-(benzyloxy)phenol (1) as a byproduct of the p-
(benzyloxy)calix[8]arene synthesis.[7] An optimized syn-
thetic procedure is provided (see the Experimental Section)
and will be detailed in a forthcoming paper.[39]
15 rue Georges Clémenceau, 91405 Orsay, France
E-mail: vincenthuc@icmo.u-psud.fr
[b] Centre de Recherche de Gif, Institut de Chimie des Substances
Naturelles, CNRS,
Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.200901281.
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Figure 2. Some already described examples of “large-rim”-functionalized calix[6]arenes.[27,29,30,34–36]
tunately, the expected trimethoxy C3v derivative is observed
as one of the main components.
The crude reaction media shows two phases (white pre-
cipitate along with a limpid supernatant). Both phases were
analyzed separately. The precipitate appears to comprise the
(1,2,4,5)-tetramethyl p-(benzyloxy)calix[6]arene derivative
(4; Scheme 1, final yield 25%). This assignment is based
on mass spectrometry (MALDI) analysis, along with the
observed symmetry of the NMR spectra (Supporting Infor-
mation, Figure S1c). The high-field region shows one sing-
4
let along with a pair of doublets, with a characteristic J
coupling constant of 4 Hz. The region around 5 ppm shows
the presence of two singlets with the expected 2:1 ratio, cor-
responding to the two benzyloxy-type methylenes. The very
low solubility of this tetraalkylated C2v-symmetric com-
pound makes this product easy to purify and readily avail-
able.
C3v-Trimethylated p-(benzyloxy)calix[6]arene (3; Scheme 1)
is recovered from the corresponding filtrate as a white solid
in 20% yield, by combining selective precipitation from ace-
tone and chromatography over deactivated alumina (see the
Experimental Section). The remaining chromatographic
fractions (probably a mixture of more highly methylated ca-
Scheme 1. Synthesis of C2v-tetramethylated 3 and C3v-trimethylated
4 p-(benzyloxy)calix[6]arenes.
Alkylation of 2 with methyl iodide {according to the pro- lix[6]arene derivatives) were not further analyzed. This
cedure already described for p-(tBu)calix[6]arene[40]} results product was fully characterized by NMR spectroscopy and
in a very complex mixture of partly alkylated products. For- mass spectrometry (Supporting Information). The 1H
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Versatile Platform for the Synthesis of Functionalized C3v Calix[6]arenes
NMR spectrum clearly shows the expected C3v symmetry, ever, the addition of a small amount of DMF was found to
as observed for the analogous p-(tBu) trimethylated C3v de- be crucial, otherwise these alkylation reactions do not pro-
rivative (Supporting Information, Figure S1a).
ceed at all, and unreacted starting products are recovered.
To the best of our knowledge, this is the first time that a
Interestingly, the NMR spectra of compound 6 are com-
partial methylation procedure is successfully applied to a pletely different from those of the corresponding p-(tBu)-
calix[6]arene not functionalized at the upper rim by tBu functionalized analog.[41,42] The expected C3v symmetry is
groups. This shows that the general behavior of the p-(tBu)- not observed. The reason for such a difference is not clear.
functionalized calixarenes is similar to that of the p-(benz- Maybe the increased bulkiness of the p-(benzyloxy) substit-
yloxy)-functionalized derivative.
uents allows some others conformations to be “frozen” dur-
In order to explore the potential of compound 3, the syn- ing the course of the alkylation reaction. This may be rein-
thesis of a representative panel of derivatives was under- forced by the fact that compound 6 is obtained at a tem-
taken (Schemes 2–4, compounds 5–10). All these new com- perature close to the ambient one (whereas the correspond-
1
pounds were fully characterized by H and 13C NMR spec- ing compound in the p-(tBu) series is obtained in refluxing
troscopy, IR spectroscopy, and mass spectrometry.
THF[41,42]). This may allow different conformations to be
It is noteworthyto mention that some ofthese new p-(benz- observed, as the conformational equilibriums are strongly
yloxy)calixarenes (although exhibiting the expected C2v or influenced by temperature. Moreover, the solvents used in
C3v symmetry) are showing broadened NMR signals rela- these two cases are different [pure ethylbromoacetate (this
tive to those of the analogously functionalized p-(tBu)ca- work) or THF]. This may also influence the conformational
lixarenes. This provides evidence that the bulkier p-(benz- equilibria.
yloxy)-functionalized phenolic subunits rotate more slowly.
The temperature needed to restore the C3v symmetry is
In the extreme cases of thioester 8 and ester 6 derivatives, so high that the product rapidly decomposes, resulting in
the conformational flexibility is reduced to such an extent the appearance of secondary peaks, and their intensity
that very broad signals are observed, probably the result rapidly increases within minutes (Supporting Information,
of the existence (on the NMR timescale) of several, slowly Figure S5b).
interconverting conformations. If necessary, variable-tem-
perature NMR experiments were used to overcome these platform for the synthesis of functionalized calixarenes. As
problems. an example, the reaction with sodium thioacetate and so-
The tris(chloroethyl) derivative 5 proved to be a versatile
Alkylation of compound 3 by 1-bromo-2-chloroethane dium azide in DMSO at ambient temperature leads to the
and ethyl bromoacetate (used as both solvents and reagents, corresponding azido and thioester derivatives in quantita-
see Experimental Section) lead to compounds 5 and 6, tive yields (compounds 7 and 8, Scheme 3).
respectively (Scheme 2). These alkylation reactions proceed
smoothly in quantitative yields with NaH as a base. How-
Scheme 3. Synthesis of the azide and thioacetyl derivatives of com-
pound 5 (compounds 7 and 8).
The MALDI mass spectrum of the tris(azide) is espe-
cially interesting. Along with the expected molecular ion,
Scheme 2. Synthesis of compounds 5 and 6.
three successive azide-to-amine reduction processes are also
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V. Huc, V. Guérineau
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observed (R-N3 Ǟ R-NH2). These reduction processes are during the analysis. Two successive two-electron/two-proton
made possible by the strongly reducing conditions associ- reductions in the case of compound 10 and three two-elec-
ated with MALDI-type mass spectrometry analyses.[43]
tron/two-proton reductions for compound 9 are observed.
An analogous tris(azido) derivative has very recently These reduction processes are probably the result of com-
been described starting from the corresponding C3v-sym- plex electron-transfer phenomena from the matrix during
metrical trimethylated p-(tBu)calix[6]arene.[44] It was shown its initial laser-induced electronic excitation. These new ca-
that this new compound is a very useful platform for the lixquinones also open interesting possibilities for the syn-
synthesis of new supramolecular receptors. Within this thesis of new supramolecular receptors, as calixquinones-
frame, the successful synthesis of the corresponding p- type macrocycles were shown to exhibit rich chemistry.[49]
(benzyloxy) derivative significantly reinforces the synthetic
potential of this new family of azido-functionalized calixar-
enes.
Along with these “classical” alkylation-based function-
Conclusions
In conclusion, alkylation of p-(benzyloxy)calix[6]arene
with methyl iodide results in a complex mixture of partly
alkylated products, from which trimethylated C3v-derivative
3 and tetramethylated derivative 4 are recovered on a pre-
parative scale. These new calixarenes were used for the syn-
thesis of new functional derivatives. Compound 3 was used
for the synthesis of a first set of derivatives by “conven-
tional” alkylation reactions of the phenolic groups. By
using the alkylating agent as a reagent and as a solvent,
these reaction proceeds in quantitative yield in the presence
of “off-the-shelf” DMF. Moreover, the presence of the p-
(benzyloxy) substituents opens the possibility to directly
convert these new C3v and C2v derivatives into tris(quinone)
9 and bis(quinone) 10, respectively.
alization strategies, the presence of the benzyloxy groups
opens the possibility to explore more specific chemistry.
Oxidation of compounds 3 and 4 with bis(trifluoroacet-
oxy)iodosobenzene results in the one-step formation of the
expected quinone derivatives in quantitative yields at ambi-
ent temperature (compounds 9 and 10, Scheme 4).
Hydrogenolysis of the p-(benzyloxy) substituents will
open the way to new calixarenes bearing easily derivatized
hydroxy groups at the upper-rim position. These new ca-
lixarene platforms are promising for the synthesis of new
supramolecular hosts. These studies are currently underway
within our group.
Experimental Section
General: All reagents were purchased from Aldrich and used as
received. All solvents were purchased from Aldrich and used as
received, without any supplementary drying or purification pro-
cedures. All the NMR spectra were collected with Bruker AMX
250, 300, and 360 MHz spectrometers. IR spectra were collected
with a Perkin–Elmer Spectrum 1000 spectrometer. HQ = hydro-
quinone.
Scheme 4. Synthesis of the oxidized C2v-tetramethylated and C3v-
trimethylated p-(benzyloxy)calix[6]arene derivatives (compounds 9
and 10).
p-(Benzyloxy)calix[6]arene (2): A solution of p-(benzyloxy)phenol
(20.93 g, 0.104 mol), aqueous RbOH (50 wt-%, 3.8 mL,
0.0323 mol), paraformaldehyde (8 g, 0.267 mol) was heated at re-
flux in of xylene (mixture of isomers, 300 mL) for 6 h. The resulting
suspension was neutralized with HCl (3 , 100 mL). The organic
phase was recovered, and the aqueous phase was washed with chlo-
roform. The combined organic phase was neutralized with
NaHCO3, and the solvents were evaporated to dryness. The re-
sulting solid was suspended in CH2Cl2 (300 mL) and filtered. The
filtrate was evaporated and suspended in ethyl acetate (200 mL).
The precipitate was filtered and suspended in acetone to yield 2 in
an almost-pure form. A second crop of 2 was recovered by column
chromatography of the evaporated acetone filtrate (SiO2, CHCl3,
Rf = 0,5). Overall yield: 40%. Spectroscopic characteristics were in
accordance with previously published ones.[7]
The simplicity and efficiency of this protocol is in con-
trast to that previously described for calixquinone synthesis
{using either multistep de-tert-butylation-based processes
or direct oxidation with toxic/unstable reagents [such as
thallium(III) salts or chlorine dioxide[45]]}. Moreover, the
yields of the calixquinones are not always satisfactory.
The NMR spectra confirm the disappearance of one type
of benzyloxy signal in both cases, while preserving the over-
all symmetry of the compounds (Supporting Information,
Figures S6a and S7).
As calixquinones are prone to undergo well-defined re-
dox processes in solution,[46–48] a rich redox behavior may
be anticipated for these new quinone derivatives. As an ex-
ample, the MALDI mass spectra of 9 and 10 show that
C3v (Trimethyl) p-(Benzyloxy)calix[6]arene (3) and C2v (Tetra-
these two polyquinones undergo a full reduction process methyl) p-(Benzyloxy)calix[6]arene (4): A suspension of p-(benzyl-
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Versatile Platform for the Synthesis of Functionalized C3v Calix[6]arenes
oxy)calix[6]arene (3 g, 2.356 mmol), K2CO3 (0.52 g, 3.77 mmol),
and methyl iodide (2.57 mL, 41.23 mmol) in acetone (120 mL) was
heated at reflux under an atmosphere of argon for 8 h. The re-
OBz) ppm. HRMS: calcd. for [C93H87Cl3O12Na]+ 1523.5160; found
1523.5210.
Calix[6]arene Tris(ethylester) (6):
A solution of 3 (490 mg,
sulting suspension was filtered and washed with acetone. The pre-
cipitate was suspended in chloroform (30 mL) and filtered. This
suspension/filtration procedure was repeated one more time with
dichloromethane (30 mL). Compound 4 (0.78 g, 25%) was reco-
vered as a white solid. 1H NMR (300 MHz, CDCl3, 293 K): δ =
3.25 (s, 12 H, OCH3), 3.78 (br. s, 8 H, ArCH2Ar), 3.88 (br. s, 4 H,
ArCH2Ar), 4.74 (s, 4 H, ArCH2O), 4.83 (s, 8 H, ArCH2O) 6.41 (s,
0.33 mmol) in ethylbromoacetate (6 mL) and off-the-shelf DMF
(0.5 mL) was prepared under an atmosphere of argon in a 100-mL
Schlenk tube. NaH (60%, 150 mg) was then added under strong
argon flushing and stirring. The resulting white suspension was left
overnight at 50 °C. A second portion of 60% NaH was added at
50 °C under an atmosphere of argon. After 3 h, the product was
precipitated with EtOH/CH3COOH (90:10, 100 mL) and washed
with ethanol. The precipitate was recovered by washing with
CH2Cl2, and the solvents were evaporated to dryness. The resulting
oil deposited onto the walls of the glassware was washed with pen-
tane (100 mL) and ethanol (100 mL). Compound 6 (0.51 g, quant.)
was recovered as a pale-yellow oil. 1H NMR (400 MHz, DMSO,
360 K): δ = 1.16 (t, 9 H, CH2CH3), 3.06 (9 H, OCH3), 3.89 (br.,
12 H, ArCH2Ar), 4.12 (q, 6 H) 4.4 [s, 6 H, CH2C(O)], 4.57 (s, 6H
ArCH2O), 5.0 (s, 6H ArCH2O) 6.31 (s, 6H ArHQH), 6.88 (s, 6H
ArHQH), 7–7.5 (m, 30 H, Ph) ppm. 13C NMR (100 MHz, CDCl3,
293 K): δ = 14.2 (CH3-C), 31 (br., ArCH2Ar), 60.4 (OCH3), 60.8
[C(O)O-CH2] 70.1, (ArCH2O), 70.5, (ArCH2O) 70.4 [OCH2C(O)-
O], 114.8 (ArHQ-H), 117.1 (ArHQ-H), 126–130 (ArC-H), 134.8
(ArHQCipso-CH2), 135.4, (ArHQCipso-CH2), 137.6 (ArC-CH2), 138
(ArC-CH2), 148.5 (ArHQCipso-O), 151.2 (ArHQCipso-O), 154.5
(ArHQCipso-OBz), 155 (ArHQCipso-OBz), 169.1 (C=O) ppm. HRMS:
calcd. for [C99H96O18Na]+ 1595.64889; found 1595.65239. IR
4
4
4 H, ArHQH), 6.60 (d, J = 4 Hz, 4 H ArHQH), 6.62 (d, J = 4 Hz,
4 H, ArHQH), 7.2–7.5 (m, 30 H, Ph) ppm. 13C NMR (100 MHz,
CDCl3, 293 K): δ = 30.6 (ArCH2Ar), 31.5 (ArCH2Ar), 60.7
(OCH3), 70.2 (ArCH2O), 70.5 (ArCH2O) 114.2 (ArHQ-H), 115.1
(ArHQ-H), 115.6 (ArHQ-H), 126–130 (ArC-H), 133.7 (ArHQCipso
CH2), 135.5 (ArHQCipso-CH2), 137 (ArCipso-CH2), 137.3 (ArCipso
CH2), 146.2 (ArHQCipso-O), 149.3 (ArHQCipso-O), 151.7 (ArHQCipso
-
-
-
OBz), 154.9 (ArHQCipso-OBz). HRMS (MALDI): calcd. for
C88H80O12K [M + K]+ 1367.52814; found 1367.53014.
The different filtrates obtained after the recovery of 4 were then
combined, evaporated to dryness, and dissolved in a minimum
amount of acetone (about 20 mL). This solution was kept at 2 °C
for two weeks. During this time, a precipitate appeared, which was
collected by filtration. C3v trimethylated p-(benzyloxy)calix[6]arene
(3; 0.62 g, 20%) was recovered by column chromatography of this
precipitate (deactivated Al2O3, CHCl3/EtOAc, 3 Ǟ 20%) as a white
solid. 1H NMR (250 MHz, CDCl3, 293 K): δ = 3.59 (s, 9 H,
OCH3), 3.86 (s, 12 H, ArCH2Ar), 4.69 (s, 6 H, PhCH2O), 4.94 (s,
6 H, PhCH2O), 6.52 (s, 6 H), 6.68 (s, 6 H, ArHQH), 7.2–Ͻ7.5 (m,
30 H, Ph) ppm. 13C NMR (100 MHz, CDCl3, 293 K): δ = 31.4
(KBr): ν = 1755 (C=O) cm–1.
˜
Calix[6]arene Tris(azido) (7): To
a solution of 5 (0.114 g,
0.076 mmol) in off-the-shelf DMSO (3 mL) in a 50-mL Schlenk
tube was added a large excess of sodium azide (30ϫ). The resulting
light-orange solution was stirred overnight at ambient temperature
(25 °C) under an argon atmosphere. The product was precipitated
with water (30 mL), filtered, and washed with water. Compound 7
(ArCH2Ar), 61.5 (OCH3), 70.1, 70.6 (ArCH2-Obz), 114, 5 (ArHQ
-
H), 115.6 (ArHQ-H), 127.6–128.5 (ArC-H), 128.4 (ArHQCipso-CH2),
134.3 (ArHQCipso-CH2), 136.9 (ArC-CH2),137.4 (ArC-CH2), 146.4
(ArHQCipso-OH), 148.52 (ArHQCipso-OCH3), 152.2 (ArHQCipso
-
1
was recovered in quantitative yield as a light-brown oil. H NMR
OCH2), 155.3 (ArHQCipso-OCH2) ppm. HRMS (MALDI): calcd.
(250 MHz, CDCl3, 293 K): δ = 3.1 (9 H, OCH3), 3.26, (br. t, 6 H,
CH2N3), 3.57 (br. t, 6 H, OCH2), 3.92 (s, 12 H, ArCH2Ar), 4.79
(s, 6 H, OCH2Ar), 4.84 (s, 6 H, OCH2Ar), 6.57 (s, 6 H, ArHQH),
6.66 (s, 6 H, ArHQH), 7.2–7.5 (m, 30 H, Ph) ppm. 13C NMR
(100 MHz, CDCl3, 293 K): δ = 30.9 (ArCH2Ar), 51.0 (CH2N3),
60.3 (OCH3), 70.1 (ArCH2O), 71.3 (ArCH2O), 114.8 (ArHQ-H),
115.4 (ArHQ-H), 127–128.5 (ArC-H), 134.8 (ArHQCipso-CH2),
135.0, (ArHQCipso-CH2), 137.2 (ArC-CH2), 137.3 (ArC-CH2), 148.3
(ArHQCipso-O), 150.4 (ArHQCipso-O), 154.5 (ArHQCipso-OBz), 154.8,
(ArHQCipso-OBz) ppm. MS: m/z = 1522.55 [M + H]+, 1494.55 [M
+ H+ – N2]+. Reduction process: m/z = 1496.55 [M + H]+ – N2 +
2H, 1468.52 {[M + H]+ – N2 + 2H} – N2. Reduction process: m/z
= 1470.51 {[M + H]+ – N2 + 2H} – N2 + 2H. HRMS (MALDI):
for C87H78O12Na [M + Na]+ 1337.53855; found 1337.54378.
Calix[6]arene Tris(chloroethyl) (5): A 100-mL Schlenk tube was
loaded with 3 (0.1 g, 0.076 mmol), bromochloroethane (6 mL), and
off-the-shelf DMF (0.3 mL) at 50 °C under an atmosphere of ar-
gon. NaH (60%, 43 mg) was added. A transient green color devel-
oped and rapidly faded. The system was left at 50 °C for 1 h. A
second portion of NaH (60%, 26 mg) was then added, and the
resulting white suspension was left overnight at 50 °C under an
atmosphere of argon. A third portion of NaH (60%, 26 mg) was
added at 50 °C. After 3 h, the system was quenched with distilled
water (50 mL) and washed with dichloromethane (3ϫ20 mL). The
organic phase was recovered, dried with MgSO4, and concentrated.
The resulting light-yellow oil on the walls of the balloon was then
washed with pentane (100 mL) under vigorous stirring (removal of
paraffin and residual bromochloroethane). The colorless pentane
supernatant was then discarded, and the light-yellow oil remaining
on the walls of the glassware was dried in vacuo to a constant
weight. Compound 5 (0.114 g, quant.) was recovered as a pale-
calcd. for [M + Na]+ 1544.63664; found 1544.63173. IR (KBr): ν
˜
= 2103.8 (R–N3) cm–1.
Calix[6]arene Tris(thioacetyl) (8): To a solution of 5 (0.114 g,
0.076 mmol) in off-the-shelf DMSO (3 mL) in a 50-mL Schlenk
tube was added a large excess (30ϫ) of potassium thioacetate. The
resulting light-orange solution was stirred overnight at ambient
yellow oil. 1H NMR (250 MHz, CDCl3, 293 K): δ = 3.1 (s, 9 H, temperature (25 °C) under an argon atmosphere. The product was
OCH3), 3.5 (br. t, CH2Cl), 3.7 (br. t, 6 H, CH2O), 3.9, (s, 12 H, precipitated with water (30 mL), filtered, and washed with water
ArCH2Ar), 4.82/4.83 (12 H, ArCH2O), 6.6 (6 H, ArHQH), 6.65 (6 and methanol. Compound 8 was recovered in quantitative yield as
H, ArHQH), 7.2–7.5 (m, 30 H, Ph) ppm. 13C NMR (100 MHz,
a light-purple oil. 1H NMR (250 MHz, DMSO, 360 K): δ = 2.74
CDCl3, 293 K): δ = 30.9 (ArCH2Ar), 53.4 (CH2Cl), 60.3 (OCH3), [s, 9 H, C(O)CH3]; 3.01 (9 H, OCH3), 3.17 (br. t, 6 H, CH2S), 3.8
70 (ArCH2O), 72.8 (ArOCH2), 114.8 (ArHQ-H), 115.1 (ArHQ-H),
127–128.5 (ArC-H), 134.8 (ArHQCipso-CH2), 135.0, (ArHQCipso
CH2), 137 (ArC-CH2), 137.2 (ArC-CH2), 148.2 (ArHQCipso-O),
150.2, (ArHQCipso-O), 154.4 (ArHQCipso-OBz), 154.8, (ArHQCipso
(br. t, 6 H, OCH2), 3.8 (br., 12 H, ArCH2Ar), 4.57 (br. s, 6 H),
4.98 (s, 6H ArCH2O), 6, 32 (s, 6H ArHQH), 6.78 (s, 6H ArHQH),
7.2–7.5 (m, 30 H, Ph) ppm. 13C NMR (100 MHz, CDCl3, 293 K):
δ = 29.2 [CH3-C(O)], 30.5 (ArCH2Ar), 53.5 (CH2S), 60.5 (OCH3),
-
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V. Huc, V. Guérineau
70.0, 70.3, 71.6 (ArCH2O), 114.1 (br., ArHQ-H), 116 (ArHQ-H), Supporting Information (see footnote on the first page of this arti-
FULL PAPER
1
126–128.5 (ArC-H), 135 (br., ArHQCipso-CH2), 135.3, (br.,
cle): H and 13C NMR, HSQC/HMBC, and variable-temperature
ArHQCipso-CH2), 137.1 (ArC-CH2), 137.4 (ArC-CH2), 147.9 NMR spectroscopic experiments.
(ArHQCipso-O), 150.8 (ArHQCipso-O), 154.3 (br., ArHQCipso-OBz),
154.8, (br., ArHQCipso-OBz), 195.3 (C=O) ppm. HRMS (MALDI):
calcd. for [C99H32S3O15Na]+ 1643,58036; found 1643,58823. IR
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(KBr): ν = 1690 (C=O) cm–1.
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Chem. Commun. 1996, 2277.
˜
(Trimethyl) Calix[6]arene Tris(quinone) (9): To solution of 3 (14 mg,
0.0106 mmol) dissolved in a mixture of CH3CN (0.4 mL), H2O
(0.2 mL), and CH2Cl2 (0.1 mL) was added a solution of bis(trifluo-
roacetoxy)iodosobenzene (0.15 g, 0.035 mmol) in CH3CN (2 mL)
at ambient temperature. The color instantly changed from colorless
to deep yellow. The solution was left for 10 min, and then quenched
with a saturated aqueous solution of NaHCO3 (10 mL). The or-
ganic phase was then recovered, filtered, and concentrated. The
product was dissolved in a mixture of CH3CN (5 mL) and water
(1 mL), and the solvents were evaporated to dryness again (removal
of benzylic alcohol). The resulting yellow oil was washed overnight
with pentane (15 mL). The pentane supernatant was then dis-
carded. After vacuuming, compound 9 (11 mg, quant.) was reco-
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Arnaud-Neu, J.-F. Dozol, R. Ungaro, J. Am. Chem. Soc. 2001,
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183.
1
vered as a yellow oil. H NMR (300 MHz, CDCl3, 293 K): δ = 3.4
[9] P. C. Leverd, I. Dumazet-Bonnamour, R. Lamartine, M. Nier-
lich, Chem. Commun. 2000, 493.
(9 H, OCH3), 3.66 (s, 12 H, ArCH2Ar), 4.93 (s, 6 H ArCH2O), 6.09
(s, 6 H ArquinoneH), 6.63 (s, 6 H ArHQH), 7.2–7.5 (m, 15 H, Ph)
ppm. 13C NMR (100 MHz, CDCl3, 293 K): δ = 30.6 (br., Ar-
CH2Ar), 60.7 (OCH3), 70.4 (ArCH2O), 114.8 (ArHQ-H), 116.1
(ArHQC-H), 126–130 (ArC-H), 132.3 (ArHQCipso-CH2), 132.5 (Ar-
quinoneC-H), 136.7 (ArCipso-CH2), 137.6 (ArHQCipso-CH2), 148.1
(ArHQCipso-O), 155.1 (ArHQCipso-OBz), 186.5 (C=O), 187.1 (C=O)
ppm. MS: m/z = 1061.32 [C66H54O12Na]+. Full reduction: m/z =
1067.35 [C66H60O12Na]+, 1077.31 [C66H54O12K]+. Full reduction:
m/z = 1083.32 [C66H60O12K]+. HRMS (MALDI): calcd. for
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valij, J. T. Davis, Angew. Chem. Int. Ed. 2006, 45, 3334.
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2394.
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Macrocycl. Chem. 2000, 36, 259.
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mun. 2005, 645.
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[C H O Na]+ 1061.35075; found 1061.34813. IR (KBr): ν = 1655
˜
66 54 12
(C=O) cm–1.
(Tetramethyl) Calix[6]arene Bis(quinone) (10): To a suspension of 9
(0.5 g, 0.38 mmol) in THF/CH3CN/H2O (1:1:1, 20 mL) was added
bis(trifluoroacetoxy)iodosobenzene (0.6 g, 1.4 mmol). The re-
sulting pale-yellow suspension was vigorously stirred overnight at
ambient temperature. Bis(trifluoroacetoxy)iodosobenzene (0.6 g,
1.4 mmol) was then added, and the resulting orange suspension
was vigorously stirred for 6 h. NaHCO3 (2 g) was then added, and
the solvents were removed under vacuum. The product was reco-
vered by washing with dichloromethane (2ϫ40 mL) and filtering,
and the resulting orange solution was evaporated to dryness. The
oil on the walls of the glassware was then washed overnight with
ethanol (100 mL) under vigorous stirring. The ethanol supernatant
was discarded. The orange solid on the walls of the glassware was
rinsed one more time with ethanol (100 mL) and dried in vacuo to
a constant weight. Compound 10 (0.43 g, quant.) was recovered as
1
an orange solid. H NMR (300 MHz, CDCl3, 293 K): δ = 3.27 (s,
12 H, OCH3), 3.66 (s, 8 H, ArCH2Ar), 3.87 (s 4 H, ArCH2Ar),
4
4.96 (s, 8 H ArCH2O), 6.2 (s, 4 H ArquinoneH), 6,63/6.64 (d, J =
4 Hz, 4 H, ArHQH), 6,67/6.68 (d, 4J = 4 Hz, 4 H, ArHQH), 7.2–7.5
(m, 20 H, Ph) ppm. 13C NMR (100 MHz, CDCl3, 293 K): δ = 30.6
(ArCH2Ar), 31.5 (ArCH2Ar), 60.5 (OCH3), 70.3 (ArCH2O) 115.4
(ArHQ-H), 116 (ArHQ-H), 126–130 (ArC-H), 131.9 (ArquinoneH),
132.5 (ArHQCipso-CH2), 137 (ArHQCipso-CH2), 137.3 (ArCipso-CH2),
148.5 (ArHQCipso-O), 154.7 (ArHQCipso-OBz), 186.6 (C=O), 187.9
(C=O). Full reduction: m/z = 1148.50 [C74H68O12 + H]+, 1167.48
[C74H64O12Na]+. Full reduction: m/z = 1171.50 [C74H68O12Na]+.
Full reduction: m/z = 1187.48 [C74H68O12K]+. HRMS (MALDI):
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calcd. for [M + Na]+ 1167.42900; found 1167.42694. IR (KBr): ν
˜
= 1654 (C=O) cm–1.
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© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 2199–2205

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Received: November 9, 2009
Published Online: March 5, 2010
Eur. J. Org. Chem. 2010, 2199–2205
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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