One Step Synthesis of Calix[n]quinones through the HClO4/PbO2-Mediated Oxidation of Calix[n]arenes

Article abstract of DOI:10.1002/ejoc.201600092

A procedure using HClO₄ and PbO₂ allows the straightforward oxidation of para-substituted and unsubstituted calix[n]arenes into the corresponding calix[n]quinones in approximately 82 % yield per quinone unit. These mild conditions constitute a good alternative to the classical procedure that involves highly toxic thallium(III) salts in trifluoroacetic acid.

Full text of DOI:10.1002/ejoc.201600092

DOI: 10.1002/ejoc.201600092
Communication
Calix[n]quinones Synthesis
One Step Synthesis of Calix[n]quinones through the HClO4/
PbO -Mediated Oxidation of Calix[n]arenes
2
[a,b]
[a]
[a]
[c]
Roy Lavendomme,
Ludovic Troian-Gautier, Sara Zahim, Olivia Reinaud,* and
[
a]
Ivan Jabin*
Abstract: A procedure using HClO4 and PbO2 allows the approximately 82 % yield per quinone unit. These mild condi-
straightforward oxidation of para-substituted and unsubsti- tions constitute a good alternative to the classical procedure
tuted calix[n]arenes into the corresponding calix[n]quinones in that involves highly toxic thallium(III) salts in trifluoroacetic acid.
[
7]
Introduction
PbO and 70 % aqueous HClO in acetone. This PbO /HClO -
2 4 2 4
mediated oxidation still involves a toxic heavy-metal-based
oxidant yet safer in comparison with thallium(III) salts extreme
toxicity. Herein, we show that these mild conditions can be ap-
plied to the direct oxidation of various (p-tBu-)calix[n]arenes
into the corresponding calix[n]quinones.
Calix[n]quinones have attracted considerable attention over the
last decades for their host–guest, electrochemical and photo-
[
1]
physical properties. In this regard, it was recently shown that
calix[4]quinones can be used as the cathode of rechargeable
[
2]
lithium-ion batteries. Moreover, calix[n]quinones and the cor-
responding hydroquinone derivatives constitute interesting
synthetic intermediates for the further functionalization of calix- Results and Discussion
[
3]
arenes. Nonetheless, the straightforward and efficient synthe-
sis of calix[n]quinones from the parent p-tBu-calix[n]arenes re-
mains challenging. Indeed, on the one hand, multistep synthe-
ses involving prior de-tert-butylation of the p-tBu-phenol units
proceed generally in low global yields. On the other hand, the
most efficient and popular procedure for the direct oxidation of
the p-tBu-phenol units into quinones employs extremely toxic
The PbO /HClO -mediated oxidation was evaluated on various
O-substituted and unsubstituted calix[n]arenes 1–5 (Scheme 1).
2
4
[
4]
thallium(III) salts in trifluoroacetic acid. Moreover, these harsh
conditions lead to variable yields. A similar approach involving
sodium perborate instead of a heavy-metal-based oxidant has
been reported with moderate yields but this methodology is
[
5]
applicable to de-tert-butylated calixarenes only. Anodic oxid-
ation of calixarenes into the quinone derivatives has also been
reported but this method can only be applied on relatively
[
6]
small scales and requires specific apparatus. In 1998, Omura
reported that the oxidation of o,o′,p-trisubstituted phenols into
the corresponding p-benzoquinones can be achieved by using
[
a] Laboratoire de Chimie Organique, Université libre de Bruxelles
0 avenue F. D. Roosevelt, CP160/06, 1050 Brussels, Belgium
5
E-mail: ijabin@ulb.ac.be
http://chimorg.ulb.ac.be/
[
[
b] Laboratoire de Résonance Magnétique Nucléaire Haute Résolution,
Université libre de Bruxelles
5
0 avenue F. D. Roosevelt, CP160/08, 1050 Brussels, Belgium
c] Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques
CNRS UMR 8601), Université Paris Descartes, Sorbonne Paris Cité
5 rue des Saints Pères, 75006 Paris, France
(
4
E-mail: olivia.reinaud@parisdescartes.fr
http://www.biomedicale.parisdescartes.fr/umr8601/
-
Chimie-Bioinorganique-.html
Scheme 1. PbO
ones. i) PbO (2.5 equiv./ArOH), HClO
room temp., 2 h.
2
/HClO
4
-mediated oxidation of calix[n]arenes into calix[n]quin-
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under http://dx.doi.org/10.1002/ejoc.201600092.
2
4
70 % (15 equiv./ArOH), CH Cl /acetone,
2
2
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Communication
First, preliminary experiments conducted with p-tBu-calix[4]- and 5Q, the yields are similar or higher than those previously
[
4a]
[8]
[9]
arene 1 showed that a minimum of 2 equiv. of PbO per phenol reported with thalium(III) salts (14, 79, and 19 %, respec-
2
unit are required to fully consume the starting material and tively). It is noteworthy that compound 3Q was not reported
the partially oxidized intermediates (TLC analysis). Besides, the previously. In all cases, the oxidation yield per quinone unit is
oxidation did not proceed in the absence of HClO , whereas a centered around 82 %, suggesting that the number of initial
4
large excess of HClO (> ca. 100 equiv. per phenol unit) led to phenol units as well as their position in the calix[n]arene macro-
4
degradation products. As shown below, when the oxidation of cycle has no influence on the overall yield. As no starting mate-
5
was attempted with less than 15 equiv. of HClO per phenol rial nor intermediate were observed in the crude product, the
4
unit, a lower yield was obtained (vide infra). All these results yield loss might therefore be a consequence of a polymeriza-
led us to use the conditions originally described by Omura (i.e. tion process that could arise from macrocycle opening or cova-
[
7]
2
.5 equiv. of PbO and 15 equiv. of HClO per phenol unit in lent coupling of oxidized phenol units. This hypothesis is
2
4
both cases) for the oxidation of calixarenes 1–5. However, in strengthened by the fact that, in all cases, extremely broad sig-
1
our case, the reactions were carried out in a CH Cl /acetone nals were observed in the H NMR spectrum of the crude prod-
2
2
mixture instead of acetone to improve the solubility of the uct (see the Supporting Information). To minimize the putative
starting calixarenes. It should be noted that the reaction did polymerization process, the influence of the concentration of
not proceed in CH Cl without acetone. The concentration of calixarene 5 on the reaction yield was evaluated (Table 2). In all
2
2
phenol units was set to 0.06
M to reach a combination of suffi- cases (entries 1–5), the reactions were monitored by TLC analy-
cient solubility of the starting calixarenes and rather short reac- sis and stopped after consumption of the starting material as
tion times (i.e. < 2 h). In all cases, TLC and/or ESI-MS monitoring well as of the intermediates. In comparison to the conditions
of the reactions showed that these conditions allow the oxid- used in the first set of experiments (i.e. [5] = 0.020
M
), diluted
ation to proceed smoothly at room temperature.
reaction conditions only resulted in slightly lower yields (en-
1
The yields were determined by quantitative H NMR analysis tries 2 and 3 vs. 1). It is noteworthy that raising the concentra-
of the crude reaction products or after isolation of the oxidized tion of HClO at its initial value (entry 1) led to more degrada-
4
1
products (Table 1). Their similarity shows that almost no prod- tion products (entry 4) as observed by H NMR analysis of the
uct was lost during the purification process. When performed crude material. This result indicates that the oxidation efficiency
on calix[4]arene 2 and its p-tBu-derivative 1, the PbO /HClO - depends more on the number of HClO
equiv. than on the total
mediated oxidation afforded the fully oxidized compound 1Q acid concentration of the solution. Note that the use of less
with isolated yields of 34 and 42 %, respectively. At first glance, than 15 equiv. of HClO per phenol unit also led to a lower yield
2
4
4
4
these yields can appear as moderate but the formation of 1Q (entry 5), suggesting that the conditions originally described by
from 1 and 2 required four successive oxidations and the aver- Omura for o,o′,p-trisubstituted phenols are also optimal for the
age yields per oxidized unit are actually quite good (82 and oxidation of calixarenes.
7
7 %, respectively). Reaction of 3 allowed the isolation of the
Table 2. Influence of the concentration of calixarene 5 and of HClO
oxidation yield. Reaction conditions: 2.5 equiv. of PbO in CH Cl /acetone
1:1, v/v).
4
on the
desired trisquinone 3Q with a yield of 55 % and an average
oxidation yield per quinone unit of 87 %. When performed on
calix[4]arene 4 and calix[6]arene 5, for which each phenol moi-
ety is separated by an unreactive O-substituted phenol unit, the
average oxidation yield per quinone remained in the same
range (ca. 85 %). In this case, 4Q and 5Q were purified by flash
chromatography on silica gel. This stands in contrast with quin-
ones 1Q and 3Q for which classical flash chromatography puri-
fication was precluded because of their high polarity.
2
2
2
(
Entry
[5]
[HClO
4
]
equiv. of
NMR yield
of 5Q [%]
[a]
[M]
[M]
HClO
4
/ArOH
1
2
3
4
5
0.020[b]
0.010
0.0020
0.0020
0.020
0.90
0.45
0.090
0.90
0.20
15
15
15
150
3.3
63
56
56
22
38
[
a] Determined by quantitative 1H NMR analysis of the crude product.
[b] “Usual” reaction conditions added as a reference.
Table 1. Reaction yields for the direct oxidation of calix[n]arenes 1–5 into the
corresponding calix[n]quinones [reaction conditions: PbO
2
(2.5 equiv./ArOH),
HClO 70 % (15 equiv./ArOH), CH Cl /acetone, room temp., 2 h].
4
2
2
Finally, the PbO /HClO -mediated oxidation was also carried
2 4
out on p-tBu-calix[6 and 8]arenes. Although the reaction seems
to proceed in both cases, the broad H NMR signals (attributed
Substrate
Product
NMR
yield [%]
Isolated
yield [%]
Average yield
per oxidation [%]
1
[
a]
to polymeric products) were so intense that we were unable to
purify the corresponding quinones or to determine a yield by
quantitative NMR (see the Supporting Information).
[
[
[
c]
c]
c]
1
2
3
4
5
1Q
1Q
3Q
4Q
5Q
46
36
65
n/d
63
42
34
55
72
59
82
77
87
85
86
[
b]
[d]
c]
[
1
[
a] Determined by quantitative H NMR analysis of the crude product. [b] Not Conclusions
determined because of broad and overlapping peaks. [c] Calculated on the
basis of the NMR yield. [d] Calculated on the basis of the isolated yield.
We have reported a PbO /HClO -mediated oxidation that allows
2
4
the synthesis of calix[n]quinones in a single step starting from
This first series of results shows that the PbO /HClO -medi- the corresponding (p-tBu-)calix[n]arenes. In comparison to the
2
4
ated oxidation can efficiently lead to calixquinones in one step previously reported method that involves highly toxic thal-
from (p-tBu-)calix[n]arenes. In the case of compounds 1Q, 4Q, lium(III) salts in trifluoroacetic acid, this procedure uses milder
Eur. J. Org. Chem. 2016, 1665–1668
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1666
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication
and safer conditions and proceeds in better yields. Extension spectroscopy. The remaining 45 mg of crude product were purified
by trituration (sonication) of the solid in 200 μL of acetone, centrifu-
of this oxidation method to more sophisticated calixarenes is
gation, and removal of the supernatant. This purification process
currently under investigation.
was repeated four times, affording 3Q (24 mg, 0.041 mmol). Isolated
yield: 55 %. Mp: > 180 °C (deg.). IR (ATR): ν˜ = 1657, 1300, 1199,
–
1 1
1
(
(
(
064, 919, 891 cm . H NMR (400 MHz, [D ]DMSO, 298 K): δ = 12.84
6
4
Experimental Section
s, 1 H, COOH), 6.93 (s, 2 H, ArH), 6.87 (d, J = 2.3 Hz, 2 H, QH), 6.70
d, J = 2.3 Hz, 2 H, QH), 6.50 (s, 2 H, QH), 4.40 (s, 2 H, OCH ), 3.88
d, J = 13.5 Hz, 2 H, Ar-CH -Q), 3.41–3.49 (m, 4 H, CH ), 3.24 (d, J =
3.4 Hz, 2 H, Q-CH -Q), 1.07 (s, 9 H, tBu) ppm. C{ H} NMR
4
Solvents were distilled prior to use. Silica gel (230–400 mesh) was
used for flash chromatography. NMR spectra were recorded either
at 7.0 or 9.4 Tesla. Traces of residual solvents were used as internal
2
2
2
2
2
13
1
1
2
1
(100 MHz, [D ]DMSO, 298 K): δ = 188.0, 186.8, 185.5, 184.6, 170.4,
154.0, 147.0, 146.0, 145.8, 145.7, 133.8, 133.6, 132.6, 129.5, 126.3,
standards for H (δ =7.26 ppm for CHCl , 2.05 ppm for [D ]acetone
6
3
5
1
3
and 2.50 ppm for [D ]DMSO) and C (δ =77.16 ppm for CDCl3,
5
7
0.2, 33.7, 31.6, 31.0, 29.0 ppm. HRMS (ESI+): calcd. for C H NO
2
9.84 ppm for [D ]acetone and 39.52 ppm for [D ]DMSO) chemical
34 32
9
6
6
+
[
M + NH ] 598.2072, found 598.2073.
shift referencing. Abbreviations: s: singlet, d: doublet, Q: benzoquin-
one unit. NMR yields were calculated by quantitative NMR analyses
of the crude products with added terephthalaldehyde as a refer-
ence. The high resolution mass spectra were recorded with Q-TOF
ESI+ spectrometers. Electrospray ionization (ESI) mass spectra were
recorded with an ESI-MS apparatus equipped with an ion-trap using
the following settings: ESI+, spray voltage = 5 kV, capillary tempera-
ture = 160 °C, capillary voltage = 46 V, tube lens offset voltage =
4
p-tBu-calix[4]arene-1,3-dimethyl-2,4-bisquinone 4Q: The gen-
eral procedure was used on 102 mg of 4 (0.151 mmol) to yield
98 mg of the crude product. A fraction was used for quantitative
NMR spectroscopy. The remaining 94 mg of crude product were
purified by flash chromatography [CH Cl /acetone (98:2, v/v)] af-
2
2
fording 4Q (62 mg, 0.105 mmol). Isolated yield: 72 %. Spectral data
[8]
are in accordance with the literature. R [CH Cl /acetone (98:2,
f
2
2
3
0 V. ESI-, spray voltage = 4.5 kV, capillary temperature = 160 °C,
v/v)] = 0.42.
capillary voltage = –15 V, tube lens offset voltage = –30 V. Melting
points (mp) are uncorrected. ATR-FTIR spectra were recorded at
room temperature. The starting calixarenes were either commercial
p-tBu-calix[6]arene-1,3,5-trimethyl-2,4,6-trisquinone 5Q: The
general procedure was used on 300 mg of 5 (0.295 mmol). The
crude product was purified by flash chromatography (CH Cl ) af-
2
2
(
1, 2, 5) or synthesized according to procedures described in the
fording 5Q (156 mg, 0.175 mmol). Isolated yield: 59 %. Spectral data
[10] [11]
literature (3,
4
). Aqueous phases and celite contaminated with
[
9b]
are in accordance with the literature.
R [CH Cl /acetone (98:2,
f 2 2
lead after work-up should be treated according to heavy metals
related regulations. Calix[n]quinones should be stored at low tem-
perature since darkening and slow degradation was sometime ob-
served for samples left several days at room temperature.
v/v)] = 0.29.
Acknowledgments
General Procedure for the Oxidation of Calixarenes Into Calix-
quinones 1Q-5Q: A solution or suspension of the starting calix-
This research was supported by the Fonds de la Recherche
Scientifique-FNRS (R. L. and S. Z. Ph.D. grants), the Région
Wallonne (L. T.-G. grant) and the Université libre de Bruxelles
arene in CH Cl /acetone (1:1, v/v, [ArOH] = 0.12
M) was added drop-
2
2
wise to a stirred mixture of PbO (2.5 equiv./ArOH) and HClO 70 %
2
4
(ULB).
(
15 equiv./ArOH) in CH Cl /acetone (1:1, v/v, same volume as the
2 2
calixarene solution) at room temperature. After 2 h of stirring, the
mixture was filtered through celite and the celite was rinsed with
CH Cl /acetone until all the colored solution went through it. The
solution was then extracted successively with water until the aque-
ous layer reached pH 6–7. The organic layer was concentrated un-
der vacuum. The resulting crude product (orange/brown solid) was
purified to yield a yellow solid.
2
2
Keywords: Calixarenes · Quinones · Oxidation · Synthetic
methods · Macrocycles
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Published Online: March 4, 2016
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