Table 2 Yields of calix[4]–[9]arene using microwave irradiation and
varying concentrations of tin(IV) chloride
Table 3 Chlorinated solvents utilized for calix[n]arene synthesis
Solvent
Time/h
[4]%
[5]–[6]%
[7]%
[8]%
[9]%
2 mol% SnCl4, microwave irradiation at 120 uC for 30 min
Calix[4]
5.3%
Calix[5]
4.7%
Calix[6]
14.8%
Calix[7]
25.1%
Calix[8]
24.2%
Calix[9]
12.3%
C6H5Cl
C6H5Cl
C6H5Br
C6H5Br
CCl4
1
15
1
15
1
15
1
15
1
0.9
5.6
2.8
5.7
5.0
7.0
—
5.2
—
—
9.0
18.7
9.9
18.1
4.1
4.2
6.2
14.1
1.8
10.2
12.2
12.3
14.9
5.7
8.1
6.4
8.9
3.7
19.7
43.4
20.9
46.2
7.9
11.4
12.1
52.8
57.8
58.1
46.1
51.1
5.8
9.2
6.2
10.8
1.9
2.8
3.2
11.2
28.1
32.7
24.2
36.3
10 mol% SnCl4, microwave irradiation at 75 uC for 15 min
Calix[4]
2.7%
Calix[5]
2.9%
Calix[6]
10.8%
Calix[7]
20.1%
Calix[8]
22.8%
Calix[9]
9.9%
100 mol% SnCl4, microwave irradiation at 60 uC for 1 min
CCl4
Calix[4]
4.2%
Calix[5]
0.5%
Calix[6]
7.9%
Calix[7]
5.2%
Calix[8]
54.7%
Calix[9]
17.0%
CHCl3
CHCl3
(CH2Cl)2
(CH2Cl)2
CH2Cl2
CH2Cl2
15
1
15
—
7.1
1.6
6.8
4.9
3.7
1.8
0.8
respectively, as the tin(IV) chloride increased from 10 mol% to
100 mol%. Anticipating 200 mol% of tin(IV) chloride may enhance
the yields of calix[8]- and [9]arene we were disappointed that
decomposition resulted. These preliminary results suggest that an
increase in the yield of calix[8]- and [9]arenes seems inextricably
linked to the quantity of Lewis acid employed which, in turn, may
be affording the calixarenes via a unique mechanism.
after 15 h with calix[8]arene predominating in each case (Table 3).
Interestingly, when DCM and 1,2-DCE were utilised calix[8]arene
was returned in 51.1% and 58.1% yields, respectively, whilst
calix[9]arene was afforded in an exceptionally high 36% (Fig. 1)
and 33% yields, respectively. Employing the alternative Lewis acids
mentioned above in chlorinated solvents failed to return any
substantial amounts of calixarenes.
We pondered over the possibility that increasing the tempera-
ture may not only afford a faster reaction but also a more selective
one. Following Scheme 1, utilising 2 mol% of tin(IV) chloride at
ambient temperatures, no calix[5]–[9]arene formation was observed
(Table 1). Remarkably, repeating this reaction at 120 uC under
microwave irradiation afforded an 86% yield of calix[4]–[9]arenes
(Table 2), with substantial amounts of calix[6]- to [8]arene (14.8%,
25.1% and 24.2%, respectively). As was previously observed
(Table 1), as the concentration of the tin(IV) chloride increases
so does the yield of calix[8]- and, to a more limited extent,
calix[9]arene, i.e. 24.2% to 54.7% and 12.3% to 17%, respectively.
These preliminary results indicate that the temperature/catalyst
concentration has a substantial effect on the yield of calix[8]- and
[9]arene. Interestingly, the composition of the reaction mixture
when tin(IV) chloride (2 mol%) was employed mirrors those
reported by Gutsche et al. for their acid-catalysed protocol.7
Presumably the 2 mol% of tin(IV) chloride is hydrolysed by the
para-tert-butylphenol, generating in situ HCl that subsequently
catalyses calixarene formation in a process similar to that reported
by Gutsche et al.
Separation and purification of calix[9]arene, a minor product of
the Gutsche acid catalysed procedure, is complicated and time con-
suming (the Gutsche procedure affords mixtures of calix[n]arenes
n = 9–11).7 Presumably for this reason the realisation of
calix[9]arenes’ full potential has been severely impeded. The
straightforward and uncomplicated nature of our protocol
affording excellent yields of calix[8]- and –[9]arene suggested
itself as a possible solution. Gratifyingly, quenching a reaction
performed on 3 g of para-tert-butylphenol with aqueous acid (1 M
HCl), extraction of the calixarenes into dichloromethane and
filtration of the solution through silica afforded, after solvent
removal, 2.1 g of calix[8] and [9]arenes.8 Refluxing (2 h) this pale
yellow solid with n-hexane (15 mg mL21) and cooling to ambient
temperature precipitated calix[8]arene (95% pure by HPLC, Fig. 2).
Filtering the precipitated calix[8]arene off and removal of the
n-hexane in vacuo afforded a solid significantly enriched in
calix[9]arene. Subjecting this crude calix[9]arene containing mixture
to flash chromatography afforded analytically pure calix[9]arene in
an isolated 23% yield based on 2.1 g of crude material (99% pure
by HPLC, Fig. 3). The corresponding calix[8]arene was afforded in
an isolated 55% yield (total yield 78%) with the remaining mass
We deliberated on the possibility that the tin(IV) chloride could
be acting as a macrocycle template. Following a protocol based on
that outlined in Scheme 1, anhydrous iron(III) chloride or tin(II)
chloride returned linear oligomers only. Zinc chloride and alumi-
nium trichloride, under microwave irradiation (120 uC, 30 min)
but not ambient temperature, afforded complex mixtures of
calixarenes, linear oligomers and retro-Friedal–Crafts products.
Titanium(IV) ethoxide afforded no calixarene products. With
titanium(IV) chloride the reaction went black and decomposition
took place. This again suggested that macrocycle formation was
proceeding via a unique mechanism that was intimately linked to
the Lewis acid employed, i.e., tin(IV) chloride.
A study was undertaken to probe for any solvent effects.
Employing toluene as the solvent, para-tert-butylphenol, s-trioxane
and tin(IV) chloride (all 1 eqn) at ambient temperature afforded
only linear oligomers. Interestingly, when toluene was substituted
for a more polar, potentially co-ordinating Lewis basic solvent, i.e.
acetonitrile, THF, dioxane or diglyme, no reaction was observed.
This lack of reaction contrasted sharply with that when
halogenated solvents were employed. Chloro/bromobenzene,
carbon tetrachloride and chloroform all afforded calix[n]arenes
Fig. 1 HPLC chromatogram of the reaction mixture using CH2Cl2
solvent after 15 h.
976 | Chem. Commun., 2007, 975–977
This journal is ß The Royal Society of Chemistry 2007