Preparation of calix[8]arene derivatives functionalized at a single methylene bridge

Article abstract of DOI:10.1002/ejoc.201100779

A calix[8]arene derivative substituted at the single methylene bridge by a chlorine atom reacts at the substituted bridge with O, N, and C nucleophiles under S_N1 conditions. Thiscalix[8]arene can serve as a useful starting material for the prep

Full text of DOI:10.1002/ejoc.201100779

FULL PAPER
DOI: 10.1002/ejoc.201100779
Preparation of Calix[8]arene Derivatives Functionalized at a Single Methylene
Bridge
Norbert Itzhak,[a] Katerina Kogan,[a] and Silvio E. Biali*[a]
Keywords: Macrocycles / Calixarenes / Cyclophanes / Aromatic substitution / Nucleophilic substitution
A calix[8]arene derivative substituted at the single methyl-
ene bridge by a chlorine atom reacts at the substituted bridge
with O, N, and C nucleophiles under SN1 conditions. This
calix[8]arene can serve as a useful starting material for the
preparation of calix[8]arene derivatives functionalized at a
single methylene bridge.
ethanol (TFE), hexafluoroisopropanol (HFIP), trifluoro-
acetic acid, or mixtures of these solvents with CHCl3] with-
out the need for a Lewis acid or an inert atmosphere. The
same method was recently applied to the preparation of
monofunctionalized calix[6]arene derivatives.[7] Key inter-
mediates in this route were the monohydroxy calix[6]arene
derivative 3 (obtained by photochemical bromination of
hexamethoxycalix[6]arene 1b in aqueous THF), and its
chloro derivative 4 (Scheme 1). Monofunctionalized calix[6]-
arenes incorporating alkoxy, acetylacetonyl, or aryl groups
were prepared through the reaction of 3 or 4 with nucleo-
philes under SN1 conditions.[7]
Introduction
The structural modification of the methylene bridges of
“classical” (i.e., methylene bridged) calixarenes[1] enables
the modification of the properties, preferred conformation,
and rigidity of the systems, while keeping the entire binding
groups at the lower rim intact.[2,3] The chemical modifica-
tion of a single methylene group may be of interest if a
minimal or gradual modification of the calixarene proper-
ties is desirable. A versatile method for the direct introduc-
tion of a substituent in a single bridge of the calix[4]arene
scaffold was initially reported by the group of Fantini and
is currently being developed by Weber and co-workers.[4] In
this approach (which will be referred as the lithiation
method), the calix[4]arene tetramethyl ether 1a is treated
with excess BuLi and the resulting monolithiated derivative
is reacted with an alkylating agent (an electrophile) of gene-
ral formula RX (or CO2) to yield the corresponding calix-
[4]arenes monofunctionalized at a single bridge.
We recently described the preparation of calixarenes
monofunctionalized at all bridges with identical substitu-
ents through the reaction (under SN1 conditions) of bromo-
calixarene derivatives 2[5] with a wide array of nucleo-
philes.[6] The reaction is usually conducted by simply heat-
ing a mixture of the bromocalixarene and the nucleophile
to reflux in an ionizing medium [e.g., neat 2,2,2-trifluoro-
Scheme 1. Preparation of the large-ring monohydroxy and mono-
chlorocalixarenes. NBS = N-bromosuccinimide.
The lithiation method and the SN1 route are mutually
complementary because, whereas in the first method elec-
trophiles are incorporated into a carbon bridge (formally
negatively charged), in the SN1 route the reaction proceeds
through reaction of a carbocation with nucleophilic rea-
gents. Simple alkyl groups (e.g., methyl, primary alkyls) can
be readily incorporated by the lithiation method, but are
not accessible in a single step by the SN1 route. Conversely,
[a] Institute of Chemistry, The Hebrew University of Jerusalem,
Jerusalem 91904, Israel
Fax: +972-2-6585345
E-mail: silvio@vms.huji.ac.il
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201100779.
Eur. J. Org. Chem. 2011, 6581–6585
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
6581

N. Itzhak, K. Kogan, S. E. Biali
FULL PAPER
alkoxy, azido, and aryl groups substituted with electron-do-
nating substituents can be incorporated into a methylene
bridge by the SN1 route, but are synthetically inaccessible
by the lithiation method.
Calix[8]arenes derivatives possessing two bridges substi-
tuted with alkyl groups or a single bridge substituted with
a p-nitrophenyl group have been obtained in low yield in a
[3+2] fragment condensation reaction of a linear trimer
with bis(bromomethylated) alkanediyl diphenols.[8] Taking
advantage of the synthetic availability of the monohy-
droxycalix[8]arene 5,[7] herein, we describe the preparation
of calix[8]arenes derivatives possessing a single, monofunc-
tionalized methylene bridge.
Figure 1. Top: the eight types of methylene protons (labeled a–h)
in a calix[8]arene derivative possessing a single methylene bridge
monosubstituted with the substituent R. The calix[8]arene scaffold
is schematically drawn as an octagon in which each corner repre-
sents a CH2 or CHR bridge. Bottom: 1H NMR spectrum of 9
(methylene region) displaying eight doublets for the methylene pro-
tons. Mutually coupled protons were identified by means of a
COSY spectrum.
Results and Discussion
The preparation of monohydroxycalix[8]arene 5 by pho-
tochemical bromination of 1d in a mixture of THF/water/
CaCO3 was described previously.[7,9] Calix[8]arene 5 was
converted into the chloro derivative by reaction with SOCl2
(Scheme 1). To assess whether 6 could indeed be used as a
key intermediate for the preparation of calix[8]arenes
monofunctionalized at a single bridge, we examined the re-
action of 6 with selected O, N, and C nucleophiles.
The reaction of 6 was examined with three alcohols:
TFE, HFIP, and 2-propanol. The reactions were conducted
by heating calixarene 6 and a mixture of CHCl3 and the
appropriate alcohol to reflux. In all cases, the correspond-
ing ether derivatives (7–9) were obtained in good yield.
a mixture of CHCl3 and HFIP to afford monosubstituted
derivatives 11 and 12. Both compounds displayed four sig-
nals in the NMR spectrum for the tBu and methoxy groups,
which is in agreement with the presence of monofunction-
alized calix[8]arenes with Cs symmetry. The NMR spectra
of both products displayed a doublet for the methine pro-
ton of the substituted bridge, which is consistent only with
Derivatives of 1d, which are monosubstituted at a single a structure in which the substituent at the functionalized
bridge, possess Cs symmetry when the timescale is such that bridge exists preferentially in the diketo (i.e., non-enolic)
there are fast rotations of the rings and the substituents. form.
Because pairs of protons on a given methylene group are
The product of the reaction of 6 with ethyl acetoacetate
diastereotopic, these derivatives are expected to display is of interest due to the number of chemical transformations
1
eight doublets in the H NMR spectrum (precluding acci- possible for the group. Notably, the spectrum of product 13
dental isochrony) for these protons in
a ratio of was markedly different from those of 11 and 12 and dis-
2:2:2:2:2:2:1:1. A well-resolved pattern of methylene signals played eight signals each for the tBu and methoxy groups;
1
is clearly seen in the H NMR spectrum of 9 (Figure 1).
this is probably due to the nature of the substituent at-
As a representative of an N nucleophile, the reaction of tached to the bridge. When the substituent exists in the keto
6 with aniline was examined. Although aniline can also re- (i.e., non-enolic) form, it is chiral (see Figure 2) and, since
act as a C nucleophile with electrophiles, we have shown the molecule is asymmetric (C1 symmetry), all of the tBu
previously that C–N bond formation takes place exclusively and OMe groups are inequivalent, even when the timescale
1
in the reaction of 2c with aniline.[6c] As shown in the H is such that there is fast rotations of the side chain and the
NMR spectrum of the product obtained (10), the reaction aryl rings.
with 6 proceeds with a similar regioselectivity to that of 2c,
yielding the N-functionalized bridge.
The reaction of 6 with activated aryl groups was also
conducted by heating 6 to reflux with the appropriate aro-
The formation of C(sp3)–C(sp3) bonds at the bridges matic compound in an ionizing solvent. The reaction can
through the reaction of 6 with active methylene compounds be viewed as a Friedel–Crafts reaction of the aromatic ring,
was also examined.[10] The reaction of 6 with highly enolic in which the calixarene derivative solvolytically generates
2,4-pentanedione and dibenzoylmethane was conducted in the carbocation.[11] The reaction proceeds with m-xylene
6582
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Eur. J. Org. Chem. 2011, 6581–6585

Calix[8]arene Derivatives Functionalized at a Single Methylene Bridge
(overlapping signals, 7 H), 3.78 (d, J = 15.8 Hz, 2 H), 3.44 (s, 9 H),
3.43 (s, 15 H), 1.15 (s, 18 H), 1.10 (s, 18 H), 1.08 (s, 18 H), 1.03 (s,
18 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 154.6, 154.4, 154.38,
154.36, 146.3, 146.0, 145.99, 145.94, 132.30, 133.1, 133.07, 132.9,
132.6, 131.9, 128.0, 125.8, 125.6, 125.1, 123.8, 73.7, 66.4 (q, J =
34.0 Hz), 61.2, 60.52, 60.48, 60.43, 34.33, 34.28, 34.14, 34.13, 34.10,
31.36, 31.31, 31.27, 31.24, 30.2, 30.1, 29.9, 29.7 ppm. HRMS (ESI):
calcd. for C98H133NO9F3 [M + NH4]+ 1525.9966; found 1525.9968.
Figure 2. Schematic drawing of the chiral monosubstituted calix[8]-
arene 13.
5,11,17,23,29,35,41,47-Octa-tert-butyl-49,50,51,52,53,54,55,56-octa-
methoxy-2-isopropoxycalix[8]arene (8): Yield: 45 mg (44%). M.p.
198 °C. 1H NMR (400 MHz, CDCl3): δ = 7.31 (d, J = 2.2 Hz, 2
H), 6.98 (d, J = 2.2 Hz, 2 H), 6.94 (br. s, 4 H), 6.92 (d, J = 2.2 Hz,
2 H), 6.87 (d, J = 2.2 Hz, 2 H), 6.84 (d, J = 2.3 Hz, 2 H), 6.82 (d,
and mesitylene to yield the corresponding monoarylated
derivatives 14 and 15. As shown previously for the mono-
1
mesityl derivative of 2c, the H NMR spectrum of 15 at
room temperature displays broad signals that sharpen upon J = 2.2 Hz, 2 H), 6.33 (s, 1 H), 4.30 (d, J = 15.6 Hz, 2 H), 4.21–
4.15 (overlapping signals, 5 H), 3.91–3.82 (overlapping signals, 5
H), 3.77 (d, J = 15.6 Hz, 2 H), 3.64 (h, J = 5.6 Hz, 1 H), 3.43 (s,
12 H), 3.42 (s, 6 H), 3.39 (s, 6 H), 1.26 (d, J = 6.0 Hz, 6 H), 1.12
(s, 18 H), 1.09 (s, 18 H), 1.06 (s, 18 H), 1.00 (s, 18 H) ppm. 13C
NMR (125 MHz, CDCl3): δ = 154.5, 154.4, 154.3, 145.99, 145.94,
134.0, 133.1, 133.0, 132.9, 132.8, 127.3, 125.9, 125.8, 125.7, 125.6,
124.3, 69.7, 69.5, 61.1, 60.5, 60.4, 34.3, 34.15, 34.13, 34.10, 31.37,
31.32, 31.28, 30.2, 30.1, 29.9, 29.6, 22.3 ppm. HRMS (ESI): calcd.
for C99H138NO9 [M + NH4]+ 1486.0405; found 1486.0433.
increasing the temperature. This is most likely to be due to
the increased rigidity of the calix[8]arene as a result of the
presence of the bulky substituent at the bridge.
Conclusions
We have demonstrated that monochlorocalix[8]arene de-
rivative 6 is a useful starting material for the preparation of
calixarenes with a single, monosubstituted bridge. A large
number of calix[8]arenes substituted at a single methylene
group were easily prepared by the reaction of 6 with nucleo-
philes, including aromatic rings and active methylene com-
pounds, under SN1 conditions.
Reaction of 6 with Active Methylene Compounds: A mixture of 6
(0.10 g, 0.069 mmol), chloroform (6 mL), HFIP (2 mL), and the
appropriate active methylene compound (2 mL) was heated to re-
flux for 18 h. After evaporation of the solvents, the residue was
dissolved in chloroform and washed with brine. The organic phase
was dried (Na2SO4) and the solvents evaporated. The crude prod-
uct was recrystallized from CHCl3/MeOH.
2-Acetoacetonyl-5,11,17,23,29,35,41,47-Octa-tert-butyl-
49,50,51,52,53,54,55,56-octamethoxycalix[8]arene (11): Yield:
0.03 g (29%). M.p. 172 °C. H NMR (400 MHz, CDCl3): δ = 7.17
Experimental Section
5,11,17,23,29,35,41,47-Octa-tert-butyl-2-chloro-49,50,51,52,53,
54,55,56-octamethoxycalix[8]arene (6): A mixture of 5 (1.0 g,
0.70 mmol) and thionyl chloride (6 mL) were heated at reflux for
2 h. The solvent was evaporated to dryness and the residue recrys-
tallized twice from CH2Cl2/EtOH to afford 6 (0.65 g, 65%). M.p.
265 °C. 1H NMR (400 MHz, CDCl3): δ = 7.46 (d, J = 2.3 Hz, 2 H),
7.02 (d, J = 2.3 Hz, 2 H), 6.99 (s, 1 H), 6.94 (overlapping signals, 6
H), 6.86 (overlapping doublets, 4 H), 6.80 (d, J = 2.4 Hz, 2 H),
4.25 (d, J = 16.0 Hz, 2 H), 4.17–4.13 (overlapping doublets, 5 H),
3.93–3.85 (overlapping doublets, 5 H), 3.78 (d, J = 16.0 Hz, 2 H),
3.51 (s, 6 H), 3.44 (s, 6 H), 3.41 (s, 6 H), 3.38 (s, 6 H), 1.16 (s, 18
H), 1.09 (s, 18 H), 1.06 (s, 18 H), 1.01 (s, 18 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 154.4, 154.39, 154.34, 153.2, 146.4, 146.0,
145.99, 145.93, 133.6, 133.13, 133.11, 133.07, 132.9, 132.5, 128.0,
125.9, 125.8, 125.6, 124.4, 61.17, 60.5, 60.4, 53.7, 34.4, 34.15, 34.13,
34.10, 31.4, 31.34, 31.32, 31.27, 30.3, 30.2, 29.9, 29.7 ppm. HRMS
(ESI): calcd. for C96H127ClO8 [M]+ 1443.9253; found 1443.9248.
1
(d, J = 2.0 Hz, 2 H), 6.98 (d, J = 2.0 Hz, 4 H), 6.92 (d, J = 2.0 Hz,
2 H), 6.90 (d, J = 2.0 Hz, 2 H), 6.85 (d, J = 2.0 Hz, 2 H), 6.81 (d,
J = 2.0 Hz, 2 H), 6.73 (d, J = 2.0 Hz, 2 H), 5.42 (d, J = 12.0 Hz,
1 H), 4.75 (d, J = 12.0 Hz, 1 H), 4.14–4.05 (overlapping doublets,
7 H), 3.93–3.91 (overlapping doublets, 5 H), 3.83 (d, J = 16.4 Hz,
2 H), 3.43 (s, 6 H), 3.42 (br. s, 6 H), 3.40 (s, 6 H), 3.34 (s, 6 H),
2.01 (s, 6 H), 1.15 (s, 18 H), 1.09 (s, 18 H), 1.08 (s, 18 H), 0.94 (s,
18 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 204.2, 154.4, 154.3,
154.29, 146.06, 146.01, 145.99, 145.92, 133.43, 133.2, 133.16,
133.13, 133.08, 132.9, 132.6, 127.1, 126.0, 125.9, 125.84, 125.78,
125.4, 60.7, 60.5, 60.4, 60.3, 34.3, 34.1, 34.0, 31.36, 31.33, 31.1,
30.7, 30.0, 29.9, 29.7 ppm. HRMS (ESI): calcd. for C101H134NaO10
[M + Na]+ 1530.9908; found 1530.9892.
2-Dibenzoylmethyl-5,11,17,23,29,35,41,47-octa-tert-butyl-
49,50,51,52,53,54,55,56-octamethoxycalix[8]arene (12): Yield:
0.046 g (41%). M.p. 192 °C. 1H NMR (400 MHz, CDCl3): δ = 7.88
(d, J = 8.0 Hz, 4 H), 7.84 (overlapping doublets, 2 H), 7.35 (over-
lapping doublets, 4 H), 7.10 (d, J = 2.0 Hz, 2 H), 6.97 (d, J =
2.4 Hz, 4 H), 6.89 (d, J = 2.4 Hz, 2 H), 6.85 (d, J = 2.4 Hz, 2 H),
6.80 (d, J = 2.4 Hz, 2 H), 6.62 (overlapping doublets, 5 H), 5.63
(d, J = 11.2 Hz, 1 H), 4.13–3.87 (overlapping signals, 14 H), 3.43
(s, 12 H), 3.34 (s, 6 H), 3.32 (s, 6 H), 1.07 (overlapping singlets, 36
H), 0.98 (s, 18 H), 0.94 (s, 18 H) ppm. 13C NMR (125 MHz,
General Procedure for the Preparation of Monoalkoxycalix[8]arene
Derivatives 7 and 8: A solution of monochlorocalix[8]arene (0.10 g,
0.069 mmol) in chloroform (3 mL) and the appropriate alcohol
(10 mL) was heated to reflux overnight. The solvents were evapo-
rated, affording the corresponding derivatives in quantitative yield.
A small amount was recrystallized from CHCl3/MeOH for analyti-
cal purposes.
5,11,17,23,29,35,41,47-Octa-tert-butyl-2-trifluoroethoxy-49,50, CDCl3): δ = 194.5, 154.7, 154.4, 154.3, 146.0, 145.9, 145.8, 145.6,
51,52,53,54,55,56-octamethoxycalix[8]arene (7): Yield: 55 mg
(53%). M.p. 205 °C. 1H NMR (500 MHz, 323 K, CDCl3): δ = 7.30
(br. s, 2 H), 7.07 (br. s, 2 H), 6.95 (overlapping signals, 6 H), 6.88
(overlapping signals, 4 H), 6.84 (br. s, 2 H), 6.31 (s, 1 H), 4.30 (d,
J = 15.8 Hz, 2 H), 4.16–4.11 (overlapping signals, 5 H), 3.97–3.86
137.1, 133.8, 133.2, 133.07, 133.02, 132.9, 132.8, 132.3, 128.7,
128.4, 128.3, 127.2, 126.4, 125.9, 125.8, 125.6, 60.5, 60.43, 60.40,
34.13, 34.09, 34.05, 31.34, 31.32, 31.2, 30.8, 30.0, 29.9, 29.2 ppm.
HRMS (ESI): calcd. for C111H139KO10/2 [M + H + K]2+ 836.0020;
found 836.0021.
Eur. J. Org. Chem. 2011, 6581–6585
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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6583

N. Itzhak, K. Kogan, S. E. Biali
FULL PAPER
Monoethylacetoacetyl Derivative (13): Yield: 0.035 g (33%). M.p.
(100 mg, 0.069 mmol), chloroform (8 mL), HFIP (2 mL), and m-
xylene (1 mL) was heated at reflux overnight. After evaporation of
170 °C. 1H NMR (400 MHz, CDCl3): δ = 7.26 (br. s, 1 H), 7.12 (d,
J = 2.4 Hz, 1 H), 7.00 (br. s, 2 H), 6.96 (br. s, 2 H), 6.94–6.91 the solvents, the residue was recrystallized from CHCl3/MeOH to
(overlapping doublets, 3 H), 6.88–6.86 (overlapping doublets, 3 H),
give 14 (33 mg, 31 %). M.p. 243–245 °C. 1H NMR (500 MHz,
6.84 (d, J = 2.0 Hz, 1 H), 6.80 (d, J = 2.4 Hz, 1 H), 6.77 (d, J = CDCl3): δ = 6.98–6.82 (overlapping peaks, 18 H), 6.77 (d, J =
2.4 Hz, 1 H), 6.73 (d, J = 2.4 Hz, 1 H), 5.37 (d, J = 9.2 Hz, 1 H), 7.8 Hz, 1 H), 6.35 (s, 1 H), 4.31 (d, J = 16.1 Hz, 2 H), 4.17 (overlap-
4.52 (d, J = 9.0 Hz, 1 H), 4.16–3.80 (overlapping signals, 16 H),
3.48 (br. s, 9 H), 3.41 (s, 3 H), 3.40 (s, 3 H), 3.39 (s, 3 H), 3.37 (s,
3 H), 3.32 (s, 3 H), 2.07 (s, 3 H), 1.12 (s, 9 H), 1.115 (s, 9 H), 1.112
ping doublets, 5 H), 3.92 (overlapping doublets, 5 H), 3.75 (d, J =
16.2 Hz, 2 H), 3.46 (s, 6 H), 3.44 (s, 6 H), 3.43 (s, 6 H), 3.21 (s, 6
H), 2.28 (s, 3 H), 2.16 (s, 3 H), 1.10 (s, 18 H), 1.07 (s, 18 H), 1.07
(s, 9 H), 1.10 (s, 9 H), 1.08 (s, 9 H), 1.07 (s, 9 H), 1.06 (t, J = (s, 18 H), 1.01 (s, 18 H) ppm. 13C NMR (125 MHz, CDCl3): δ =
7.2 Hz, 3 H), 0.97 (s, 9 H), 0.93 (s, 9 H) ppm. 13C NMR (125 MHz,
154.4, 154.39, 154.35, 154.2, 146.0, 145.94, 145.92, 145.6, 140.0,
CDCl3): δ = 202.9, 168.6, 154.5, 154.45, 154.43, 154.36, 154.35, 136.2, 135.2, 133.1, 133.07, 133.05, 133.0, 132.9, 132.5, 131.1,
146.02, 146.00, 145.95, 145.93, 145.7, 133.8, 133.2, 133.16, 133.13, 128.6, 126.0, 125.9, 125.6, 60.6, 60.5, 60.47, 60.4, 40.4, 34.2, 34.15,
133.12, 133.09, 133.06, 133.05, 132.99, 132.91, 132.8, 132.7, 132.6, 34.13, 34.1, 31.4, 31.36, 31.3, 31.29, 31.25, 30.2, 30.0, 29.9, 21.0,
126.9, 126.8, 126.1, 126.0, 125.9, 125.88, 125.87, 125.83, 125.7,
125.6, 125.3, 124.4, 124.0, 64.8, 61.1, 61.0, 60.7, 60.6, 60.57, 60.52,
60.49, 60.44, 60.29, 34.3, 34.2, 34.15, 34.14, 34.07, 34.04, 31.4,
31.35, 31.32, 31.25, 31.21, 31.17, 30.69, 30.06, 29.9, 29.6, 13.9 ppm.
HRMS (ESI): calcd. for C102H136NaO11 [M + Na]+ 1561.0014;
found 1561.0065.
19.7 ppm. HRMS (ESI): calcd. for C104H136NaO8 [M + Na]+
1537.0166; found 1537.0161.
5,11,17,23,29,35,41,47-Octa-tert-butyl-2-mesityl-49,50,51,52,53,54,
55,56-octamethoxycalix[8]arene (15): A mixture of 6 (100 mg,
0.069 mmol), chloroform (8 mL), HFIP (2 mL), and mesitylene
(1 mL) was heated at reflux overnight. After evaporation of the
solvents, the residue was recrystallized from CHCl3/MeOH to give
5,11,17,23,29,35,41,47-Octa-tert-butyl-49,50,51,52,53,54,55,56-octa-
methoxy-2-(1,1,1,3,3,3-hexafluoro-2-propoxy)calix[8]arene (9): A
mixture of 6 (100 mg, 0.069 mmol), chloroform (8 mL), and HFIP
(2 mL) was heated at reflux overnight. After evaporation of the
solvents, the residue was recrystallized from CHCl3/MeOH to give
1
15 (28 mg, 26%). M.p. 225–227 °C. H NMR (500 MHz, CDCl3,
328 K): δ = 7.00–6.92 (m, 16 H), 6.79 (br. s, 2 H), 6.45 (s, 1 H),
4.29 (d, J = 15.9 Hz, 2 H), 4.18 (d, J = 15.9 Hz, 2 H), 4.14 (d, J =
15.9 Hz, 2 H), 4.13 (d, J = 15.5 Hz, 1 H), 4.01 (d, J = 15.6 Hz, 1
H), 3.99 (d, J = 15.8 Hz, 2 H), 3.94 (d, J = 15.9 Hz, 2 H), 3.79 (d,
J = 16.0 Hz, 2 H), 3.50 (s, 6 H), 3.48 (s, 12 H), 3.16 (s, 6 H), 2.26
(s, 3 H), 2.11 (s, 6 H), 1.13 (s, 18 H), 1.12 (s, 18 H), 1.10 (s, 18 H),
1.07 (s, 18 H) ppm. 13C NMR (125 MHz, CDCl3, 328 K): δ =
154.8, 154.6, 154.58, 154.57, 146.0, 145.98, 145.3, 138.0, 137.2,
135.1, 133.3, 133.2, 133.18, 133.0, 132.6, 130.2, 129.4, 126.6, 126.1,
126.0, 125.9, 125.7, 60.5, 60.4, 60.41, 60.3, 41.8, 34.2, 34.17, 34.16,
31.4, 31.37, 31.3, 30.4, 30.3, 30.29, 30.2, 22.2, 20.7, 20.66 ppm.
HRMS (ESI): calcd. for C105H138NaO8 [M + Na]+ 1551.0323;
found 1551.0318.
1
8 (45 mg, 41%). M.p. 230–232 °C. H NMR (500 MHz, CDCl3): δ
= 7.36 (d, J = 2.5 Hz, 2 H), 7.06 (d, J = 2.4 Hz, 2 H), 6.95 (three
overlapping doublets, 6 H), 6.88 (two overlapping doublets, 4 H),
6.82 (d, J = 2.4 Hz, 2 H), 6.65 (s, 1 H), 4.42 (h, J = 5.8 Hz, 1 H),
4.28 (d, J = 16.1 Hz, 2 H), 4.17 (d, J = 15.9 Hz, 2 H), 4.15 (d, J =
15.8 Hz, 2 H), 4.14 (d, J = 15.6 Hz, 1 H), 3.92 (d, J = 15.9 Hz, 1
H), 3.91 (d, J = 15.8 Hz, 2 H), 3.87 (d, J = 15.9 Hz, 2 H), 3.80 (d,
J = 16.3 Hz, 2 H), 3.47 (s, 6 H), 3.44 (s, 6 H), 3.42 (s, 6 H), 3.39
(s, 6 H), 1.14 (s, 9 H), 1.09 (s, 9 H), 1.07 (s, 9 H), 1.01 (s, 9 H)
ppm. 13C NMR (125 MHz, CDCl3): δ = 154.4, 154.2, 146.5, 146.1,
146.0, 145.9, 133.1, 133.06, 133.0, 132.9, 132.5, 131.0, 128.5, 126.0,
125.9, 125.8, 125.6, 124.0, 74.2, 61.0, 60.5, 60.4, 34.3, 34.14, 34.13,
34.1, 31.4, 31.3, 31.25, 30.27, 30.1, 30.0, 29.7 ppm. 19F NMR
(470 MHz, CDCl3): δ = –72.93 (d, J = 6.1 Hz) ppm. HRMS (ESI):
calcd. for C99H128F6NaO8 [M + Na]+ 1598.9394; found 1598.9389.
Supporting Information (see footnote on the first page of this arti-
1
cle): Copies of the H and 13C NMR spectra.
Acknowledgments
2-(Anilino)-5,11,17,23,29,35,41,47-octa-tert-butyl-49,50,51,52,53,
54,55,56-octamethoxycalix[8]arene (10): A heterogeneous mixture
of 6 (50 mg, 0.035 mmol), TFE (5 mL), and aniline (0.15 mL) was
heated at reflux overnight. After evaporation of the TFE, the resi-
due was dissolved in chloroform (20 mL). The organic phase was
washed twice with water, dried (MgSO4), and the solvents evapo-
rated. Slow recrystallization from CHCl3/MeOH mixture yielded
10 (8.5 mg, 16%). M.p. 218–220 °C. 1H NMR (500 MHz, CDCl3):
δ = 7.24 (d, J = 2.5 Hz, 2 H), 7.09 (t, J = 8.4 Hz, 2 H), 6.98 (d, J
= 2.4 Hz, 2 H), 6.95 (s, 6 H), 6.88 (d, J = 2.4 Hz, 2 H), 6.84 (d, J
= 2.4 Hz, 2 H), 6.80 (d, J = 2.3 Hz, 2 H), 6.64 (t, J = 7.3 Hz, 1 H),
6.56 (d, J = 7.7 Hz, 2 H), 6.27 (s, 1 H), 4.27 (d, J = 16.3 Hz, 2 H),
This research was supported by the Israel Science Foundation
(grant no. 104/10).
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(s, 6 H), 1.10 (s, 36 H), 1.07 (s, 18 H), 0.99 (s, 18 H) ppm. 13C
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methoxy-2-(2,4-dimethylphenyl)calix[8]arene (14): A mixture of 6
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Eur. J. Org. Chem. 2011, 6581–6585

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Received: June 1, 2011
Published Online: September 16, 2011
Eur. J. Org. Chem. 2011, 6581–6585
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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