Cation templated improved synthesis of pillar[6]arenes

Article abstract of DOI:10.1039/c6ra07164c

Improved high yield syntheses of the larger pillar[6]arenes (P[6]) bearing different alkoxy substituents through cation templated syntheses using a series of small organic and organometallic cations is reported. Yields of P[6] up to 38% and P[6]/P[5] ratios as high as 5:1 were achieved.

Full text of DOI:10.1039/c6ra07164c

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DOI: 10.1039/C6RA07164C
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Cation Templated Improved Synthesis of Pillar[6]arenes
M. Da Pian,a O. De Lucchi,a G. Strukul,a F. Fabris,a,* A. Scarsoa,*
Received 00th January 20xx,
Accepted 00th January 20xx
Improved high yield syntheses of the larger pillar[6]arenes (P[6]) bearing different alkoxy substituents through cation
templated syntheses using a series of small organic and organometallic cations is reported. Yields of P[6] up to 38% and
P[6]/P[5] ratio as high as 5:1 were achieved
DOI: 10.1039/x0xx00000x
www.rsc.org/
In the last decade a new class of macrocyclic aromatic host ethers17 or catenanes18 based on metal ion chelates,
molecules called pillararenes has been disclosed by Ogoshi cyclotrimers19 with
a porous coordination framework,
based on the condensation reaction between para bis-alkoxy paracyclophanes20 with covalently bond template as well as
benzene derivatives and paraformaldehyde. The reaction is materials like mesoporous silica MCM-41 using surfactants. 21
catalyzed by the presence of a Lewis or Brønsted acid, leading
In the present contribution we report an improved
to the formation of macrocyclic structures containing five1 or synthesis of P[6] carried out with the templating approach
six2 arene rings. Since its discovery, this class of molecules based on the right selection of cationic guests characterized by
showed impressive host-guest properties due to the semi- proper size and shape to bind through cation-π interaction
rigid, symmetric and electron-donating cavity that promotes preferentially into the electron rich cavity of P[6] rather than
selective binding of unusual neutral molecules,3 observing P[5] (Scheme 1).
important effects due to both size and length of the alkoxy
OR
substituents. Similarly to cyclodextrins, resorcin[n]arenes and
calix[n]arenes, the recently discovered pillar[n]arenes
represent a new class of molecules with great potentialities4,5
ranging from preparation of supramolecular polymers,6
pseudorotaxanes,7 application as channel for direct methanol
fuel cells,8 inhibition of acetylcholine hydrolysis9 and other
biological applications10 to mention most recent
achievements. Therefore a great attention has been focused
OR
T1/T2/T3/T4, FeCl3
(CH2O)n
+
CH2Cl2, 25 °C
OR
OR
n = 5,6
M1: R = CH3
P1[n]: R = CH3
P2[n]: R = CH2CH3
M2: R = CH2CH3
M3: R = CH2CH2CH2CH3
on the optimization of the syntheses of pillar[5]arenes (P[5]),
11
P3[n]: R = CH2CH2CH2CH3
pillar[6]arenes (P[6]
)
and more recently on 7-15 membered
+
arenes.12 Most of the procedures reported higher yields for
-
PF6
N+
Cl-
the smaller macro-cycle, with ratios P[5]/P[6] ranging from 30
Co
to 1.5. Only few very recent examples in the literature
reported an inversion of the ratio, with the formation of higher
amounts of P[6] derivatives using i) particularly bulky para
disubstituted bis-alkoxy-benzene units with chloro-
cyclohexane as templating solvent13 or ii) polar solvents14 or iii)
solvent free conditions15 as well as iii) naphthalene diimide as
templating electron poor unit.16
T1: TMAC
T2: [CoCp2][PF6]
N+
-
Fe
PF6
N+
N
-
PF6
Templated synthesis is a common strategy to steer product
selectivity in a chemical reaction towards a particular molecule
exploiting its recognition properties towards the templating
unit. Examples of this strategy are the synthesis of crown
T4: [Bmim][PF6]
T3: [FeCp2][PF6]
Scheme 1. Synthesis of P[5] and P[6] with FeCl3 as catalyst in
the presence of different cationic templating units T1 T4
-
.
Starting from simple reagents like para-bis-alkoxy-benzene
derivatives with formaldehyde and FeCl3 as catalyst in the
a.Dipartimento di Scienze Molecolari e Nanosistemi, Università Ca' Foscari di
Venezia, via Torino 155, 30172, Mestre (VE), Italy. E-mail: fabrisfa@unive.it;
alesca@unive.it
Electronic Supplementary Information (ESI) available: experimental synthetic
procedures and NMR titrations. See DOI: 10.1039/x0xx00000x
presence of tetramethylammonium chloride
bis(cyclopentadienyl)cobalt (III) hexafluorophosphate
[CoCp2][PF6]) as templating units, P[6] was obtained as main
(TMAC) and
(
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product with isolated yields up to 38% and P[5]
/
P[6] as low as 1.2·104 M-1 (supporting information). The value observed is
indicative of a good affinity between the cationic guest and the
0.2.
In order to select possible templating guests, we larger host P2[6] and it is comparable to what observed for the
1
investigated by H NMR the interaction of a series of cationic interaction between a similar pillar[6]arene and ferrocenium.23
species like T1
,
T2,
T3,
T4, with both P2[5] and P2[6] following
In order to better investigate the contact between T2 as
the effect of the addition of the templating species on the guest and the two host structures P2[5] and P2[6] at a
resonances of the two pillararenes (see supporting semiempirical PM3 level (supporting information). According
information). We observed that T4 turned out to be a suitable to symmetry considerations it would be expected a better
guest for the smaller macrocycle P2[5] with no evidence of templating effect imparted by the pentagonal T2 on the
binding to P2[6] in agreement with recent reports for other pentagonal P2[5] rather than on the hexagonal P2[6]
similar ionic liquids.22 On the contrary, T2 and T3 turned out to analogue. Nevertheless, molecular modelling of T2@P2[5] and
bind into the cavity of P2[6] and not to that of P2[5], as T2@P2[6] show that the templating molecule T2 barely fits in
reported in Figure 1.
the cavity of P2[5] and this is further evidenced by the forced
eclipsed conformation that the cobaltocenium guest has to
assume in order to fit within the cavity. Conversely, the larger
cavity of P2[6] allows the more favoured staggered
conformation of T2, without contacts with the inner walls of
the cavity (Figure 2).
Figure 2. Minimized (semiempirical PM3) structures of
T2@P2[5] (top left: front view stick; top right: front view space
filling) and of T2@P2[6] (bottom left: front view stick; bottom
right: front view space filling).
The recent synthesis of the pillar[n]arenes24 with FeCl3 as a
low cost, environmentally friendly catalyst starting from para-
bis-alkoxy-benzene derivatives was investigated in the
presence and absence of the selected templating cationic
species T1-T4. Reactions carried out without templates with all
the para-bis-alkoxy-benzene derivative employed led to
conversions comparable to that reported in the literature but
not in terms of isolated yields (Table 1).25
Figure 1. A) Bottom to top, 1H NMR spectra of the progressive
addition of equivalent amounts of T2 to P2[6], B) Bottom to top, 1H
NMR spectrum of a progressive addition of equivalent amounts of
T3 to P2[6].
Subsequently, all the cationic guests T1-T4 were employed as
templating species in the reaction between M1-M3 derivatives and
paraformaldehyde with FeCl3. Using M1 as substrate and in the
presence of T1 the reaction led to quantitative conversion of the
aromatic substrate and formation of P1[5] and P1[6] in 30% and
13% isolated yields, respectively (Table 1, entry 4).
The affinity between T2 and P2[6] was investigated in
detail by means of 1H-NMR titration following the aromatic
resonance of host that changed from 6.47 ppm in the absence
of the guest up to 6.85 ppm under saturation conditions with
excess of guest. The fitting of the ꢀδ as a function of the ratio
between the concentration of the guest and the host was
interpolated with a 1:1 binding mode observing a Kass of
Conversion
#
Monomer Template
P[6]a/P[5]a
(%)
2 | J. Name., 2012, 00, 1-3
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In order to ascertain the scalability of the reaction, the synthesis
of P2[6] templated by T2 under conditions as in Table 2 entry 8 was
repeated on 7 mmol of M2. The reaction led to quantitative
conversion of the aromatic reagent and formation of the
corresponding P2[6] macrocycle in 38% isolated yield
corresponding to isolation of 472 mg of the host. Since the
synthesis of M2 from hydroquinone is a quantitative reaction, the
two step synthesis of P2[6] from hydroquinone is possible with an
overall yield of 38%.
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
M1
M 2
M 3
M1
-
-
-
27
29
12
100
100
27
100
100
59
100
100
8
10
94
7/3
6/3
5/traces
13/30
19/24
15/12
6/5
38/7
32/28
1/22
6/19
7/10
2/8
T1
T1
T1
T2
T2
T2
T3
T3
T3
T4
T4
T4
M 2
M 3
M 1
M 2
M 3
M 1
M 2
M 3
M 1
M 2
M 3
Conclusions
In conclusion, we reported high yielding template syntheses of
the hexameric pillararenes P[6] from 1,4-disubstituted alkoxy
benzene derivatives and paraformaldehyde with FeCl3 as Lewis acid
in the presence of templating cationic guests T1-T4. Among other
P[6] selective syntheses,13-16 our approach is rather straightforward,
it uses an economic and environmentally friendly catalyst and
requires a templating unit used in substoichiometric amount.
13/13
-
<2
Table 1. Synthesis of P[5] and P[6] with different starting
monomers (M1 methoxy-, M2 ethoxy-, M3 butoxy-) and different
templating agents: T1 and T4 15 mol%, T2 and T3 25 mol%. a)
Isolated yields.
The presence of the cationic template favored both the
reaction, since higher overall yields of macrocycles were observed
as well as the selectivity towards P1[6]. Switching from the
dimethoxy M1 to the diethoxy M2 reagent, an increase of the
amount of the corresponding P2[6] product was observed. The
longer butoxy M3 substrate displayed incomplete conversion, but
the amount of P3[6] isolated was slightly higher than that of P3[5].
The same trend was observed with the cationic species T3
observing quantitative conversions with the smaller aromatic
substrate and a P[6]/P[5] ratio that increased with the longer
substituted substrates. Nevertheless, in all cases the corresponding
P[5] was isolated as the major isomer, with a maximum 7% yield.
The use of T4 as templating unit did not provide good results, since
for all the substrates investigated the yield of the corresponding
macrocycles were rather low, in some cases due also to reduced
conversions of the reagents.
Acknowledgements
The authors acknowledge Università Ca’ Foscari di Venezia and
M.I.U.R. for financial support.
Notes and references
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When the reaction was carried out with T2, the best result was
obtained employing M2 as substrate with quantitative conversion
of the reagent and 38% and 7% yields for P2[6] and P2[5],
respectively. With the longer M3 quite good yields but with lower
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turned out to be the best templating unit to favour the synthesis of
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reaction was further investigated using M2 as substrate (Table 2). It
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Template Conversion
#
P2[6]a/P2[5]a
(mol%)
20
(%)
93
1
2
3
37/6
38/7
34/5
25
100
83
30
Table 2. Synthesis of P2[5] and P2[6] with different molar amounts
of T2. a) Isolated yields.
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Cation Templated Improved Synthesis of Pillar[6]arenes
Marta Da Pian,a Ottorino De Lucchia, Giorgio Strukul,a Fabrizio Fabrisa,* Alessandro Scarsoa,*
a) Dipartimento di Scienze Molecolari e Nanosistemi, Università Ca’Foscari di Venezia, Via Torino 155, 30172,
Mestre Venezia (ITALY)
Graphical Abstract