Pressure effects in the synthesis of isomeric rotaxanes

Article abstract of DOI:10.1039/c3cc42201a

Pressure not only influences the yield in the synthesis of a two-station [2]rotaxane, it also determines the distribution of the co-conformational isomers. At high pressure cyclobis(paraquat-p-phenylene) is preferentially assembled around a monopyrrolotetrathiafulvalene unit, while at low pressure it is preferentially assembled around a hydroquinone unit.

Full text of DOI:10.1039/c3cc42201a

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Pressure effects in the synthesis of isomeric rotaxanes†
Anne Sørensen,a Sissel S. Andersen,a Amar H. Floodb and Jan O. Jeppesen*a
Cite this: Chem. Commun., 2013,
49, 5936
Received 26th March 2013,
Accepted 14th May 2013
DOI: 10.1039/c3cc42201a
www.rsc.org/chemcomm
Pressure not only influences the yield in the synthesis of a two-station
[2]rotaxane, it also determines the distribution of the co-conformational
isomers. At high pressure cyclobis(paraquat-p-phenylene) is preferentially
assembled around a monopyrrolotetrathiafulvalene unit, while at low
pressure it is preferentially assembled around a hydroquinone unit.
Incorporating complexity into molecules in the form of stereo, regio,
constitutional, configurational and conformational isomers has long
motivated the development of new synthetic methods. Mechano-
stereochemistry1 is one of the newest branches of chemistry that is
contending with a unique form of isomerism emerging from the
interlocked character of its molecular components: co-conformational
isomerism. Consider [2]rotaxanes (Scheme 1) as an example in which a
ring component is interlocked around a dumbbell.2 When the [2]rotax-
ane has two different recognition sites along its dumbbell, as is typical
for molecular switches,3 it can exist as one of two co-conformational (or
translational4) isomers; the ring can be situated at one of the two
stations. The isomeric relationship of co-conformations is akin to the
E/Z isomerism of two functional groups substituted around an olefin.5
With that likeness in mind, being able to dictate the ring’s localisation
on one of two stations in a non-degenerate [2]rotaxane upon command
provides an opportunity to isolate one or both of the two possible co-
conformational isomers. Ultimately, such control will allow for the
creation of artificial molecular machines with enhanced complexity.6
One such outcome was demonstrated using thermodynamic control
over the relative stabilities of the two stations in a rotary molecular
motor.7 An alternative approach, which we discovered during a typical
pressure-induced reaction,8,9 was the use of pressure as a physical
parameter to access kinetic control over the ratio of co-conformational
isomers produced in the formation of a [2]rotaxane.
Scheme 1 Synthesis of the two co-conformational isomeric [2]rotaxanes
1Á4PF6ÁHQ and 1Á4PF6ÁMPTTF together with their cartoon representations.
Here, we describe how pressure not only influences the yield in the
synthesis of a two-station [2]rotaxane but that it also determines the product distribution between the two possible co-conformational iso-
mers. The [2]rotaxane 1Á4PF6 (Scheme 1) is based on a dumbbell
a Department of Physics, Chemistry, and Pharmacy, University of Southern
Denmark, Campusvej 55, DK-5230 Odense M, Denmark. E-mail: joj@sdu.dk
b Department of Chemistry, Indiana University, 800 East Kirkwood Avenue,
Bloomington, Indiana 47405, USA
containing monopyrrolotetrathiafulvalene (MPTTF) and hydroquinone
(HQ) stations for encirclement by cyclobis(paraquat-p-phenylene)
tetrakis(hexafluorophosphate) (CBPQTÁ4PF6). An S-Et group situated
between the two stations acts as an effective barrier10 to enable
measurement of the relative amount of each isomer. The synthesis
(Scheme 1) of the [2]rotaxane isomers 1Á4PF6ÁHQ and 1Á4PF6ÁMPTTF
† Electronic supplementary information (ESI) available: Experimental proce-
dures, spectral characterisation data, and description of the determination of
binding constants. See DOI: 10.1039/c3cc42201a
c
5936 Chem. Commun., 2013, 49, 5936--5938
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Table
1
Distribution of the co-conformational isomers 1Á4PF6ÁHQ and
1Á4PF6ÁMPTTF after synthesis at different pressuresa
Pressure
Yield
1Á4PF6ÁHQ : 1Á4PF6ÁMPTTFb
Colourc
1 bar
10%
31%
32%
31%
73 : 27
53 : 47
42 : 58
26 : 74
Light brown
5 kbar
10 kbar
15 kbar
k
Green
a
Syntheses were carried out with 1 equiv. dumbbell 2 (30 mM), 3 equiv.
b
3Á2PF6 and 3 equiv. dibromide 4 in anhydrous DMF at 25 1C. The
ratios were found using 1H NMR spectroscopy (ESI). The colour of the
c
mixtures of 1Á4PF6ÁHQ and 1Á4PF6ÁMPTTF in MeCN at 25 1C.
was carried out using the dumbbell compound 2 as the template for
the formation of CBPQTÁ4PF6 from 3Á2PF611 and 4. The clipping
reaction was carried out in DMF at 25 1C for three days with the effect
of pressure examined from 1 bar to 15 kbar. Following counter ion
exchange, the two isomeric [2]rotaxanes were isolated in overall yields of
10–32% in two steps. By analysing the purified product, it was observed
that 1Á4PF6 exists as a mixture of the two possible co-conformational
isomers, 1Á4PF6ÁHQ and 1Á4PF6ÁMPTTF. The solutions of these two
isomers are red and green in colour which is due to characteristic
charge-transfer (CT) UV-Vis-NIR absorption bands centred at 490 and
820 nm, respectively (ESI,† Fig. S1).
Fig. 2 Structural formulae of the [2]rotaxanes 5Á4PF6 and 6Á4PF6.
After purification, a mixture of the two possible products, 5Á4PF6 and
6Á4PF6, was observed. These two products give rise to characteristic CT
absorption bands centred at 460 and 820 nm, respectively (ESI,†
Fig. S5). The population ratio between the two products (Table 2) was
determined from the 1H NMR spectrum (ESI,† Fig. S9). As in the case of
the [2]rotaxane 1Á4PF6, the results reveal that pressure has a strong
impact on the product distribution. The amount of 6Á4PF6 increases
relative to the amount of 5Á4PF6 showing that the HQ rotaxane is
favoured as the product at ambient pressure whereas the MPTTF
rotaxane can be selectively accessed at high pressure.
It is clear that the rotaxanes with the HQ station located inside the
cavity of CBPQTÁ4PF6 are favoured at ambient pressure while those
with the MPTTF station inside the cavity of CBPQTÁ4PF6 are favoured at
high pressure. To help support this observation further, the binding
affinities of two model host–guest systems (Scheme 2) were investi-
gated. Mixing the dumbbell compounds 7 or 8 (syntheses; ESI†) with
equimolar amounts of CBPQTÁ4PF611 at 25 1C in DMF leads to the
formation of [2]pseudorotaxanes 7CCBPQTÁ4PF6 and 8CCBPQTÁ4PF6,
respectively. 7CCBPQTÁ4PF6 is formed immediately as evident by the
formation of a red solution and the concomitant appearance of a CT
band at 464 nm.13 Both observations are characteristic of superstruc-
tures in which HQ derivatives are being complexed inside the cavity of
CBPQTÁ4PF6.11 The formation of 8CCBPQTÁ4PF6 can be followed
visually over time by the slow evolution of a green solution after mixing
the components.14 A concomitant appearance of a CT absorption band
centered at 783 nm is characteristic of superstructures in which MPTTF
derivatives are complexed inside the cavity of CBPQTÁ4PF6.15 By
employing the UV/Vis dilution method (ESI†),15 the binding affinities
(Ka, DG1) at 25 1C in DMF were determined (Table 3).
The population ratios (Table 1, ESI,† Fig. S4) were determined from
1
the H NMR spectra (25 1C, CD3CN). Several protons in both the
dumbbell component and CBPQTÁ4PF6 give rise to two sets of signals,
one for each of the two isomers. Overall, the yield increases when the
pressure is increased,12 and furthermore, the amount of 1Á4PF6ÁMPTTF
increases as a function of pressure faster than the amount of 1Á4PF6Á
HQ resulting in an inversion of the ratio between the two isomeric
[2]rotaxanes. By plotting (Fig. 1) the ratio of 1Á4PF6ÁHQ : 1Á4PF6ÁMPTTF
against the pressure a linear relationship between pressure and the
distribution of the co-conformational isomers is obtained. Based on
these results, it is evident that 1Á4PF6ÁHQ is favoured at ambient
pressure whereas 1Á4PF6ÁMPTTF is favoured at high pressure.
The [2]rotaxane 1Á4PF6 contains both a HQ and a MPTTF binding
site and to get a better understanding of how these units influence the
isomeric distribution, two model [2]rotaxanes 5Á4PF6 and 6Á4PF6 (Fig. 2)
were synthesised (ESI†). The respective dumbbell compounds were
mixed together with 3Á2PF6 and the dibromide 4 to investigate the
product distribution 5Á4PF6:6Á4PF6 as a function of pressure. The
clipping reaction was carried out in DMF at 25 1C for three days with
a pressure of 1 bar or 10 kbar. Following counter ion exchange,
combined yields of 7% or 24%12 for the two steps were obtained.
The binding of 7 with CBPQTÁ4PF6 is stronger than with 8.
This result is not expected on account of the fact that MPTTF is
a stronger p-electron donor than HQ.11,15 Previous NMR studies
carried out in CD3CN on a similar MPTTF system without the
Table 2 Distribution of 5Á4PF6 and 6Á4PF6 after synthesis at different pressuresa
Colourc
b
Pressure
Yield
5Á4PF6 : 6Á4PF6
1 bar
10 kbar
7%
24%
85 : 15
39 : 61
Brown
Green
a
Syntheses were carried out with 1 equiv. dumbbell S10 (30 mM), 1 equiv.
dumbbell S13 (30 mM), 3 equiv. 3Á2PF6, and 3 equiv. dibromide 4 in anhydrous
DMF at 25 1C. b The ratios were found using 1H NMR spectroscopy (ESI). c The
colour of the mixtures of 5Á4PF6 and 6Á4PF6 in MeCN at 25 1C.
Fig. 1 A graphical representation illustrating the pressure dependency of the
isomeric distribution within [2]rotaxane 1Á4PF6.
c
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In conclusion, we have synthesised and characterised the two
different co-conformational isomers of the [2]rotaxane 1Á4PF6. By
adjusting the pressure during the synthesis, it is possible to direct
the location of the CBPQTÁ4PF6 ring to either the HQ or the MPTTF
recognition site. At high pressure, CBPQTÁ4PF6 is preferentially
assembled around the MPTTF unit, whereas at low pressure the
preference rests with the assembly around the HQ station. The findings
reported in this communication are, to the best of our knowledge, the
first example where pressure is used as a physical parameter to access
kinetic control over the ratio of co-conformational isomers produced in
the formation of a [2]rotaxane by the clipping of a macrocycle around a
two-station dumbbell.
This work has been supported by the Villum Foundation and
The Danish Natural Science Research Council (FNU, project no.
11-106744). We thank Marcel Schmidt and Gitte Sørensen for
the synthesis of some of the starting materials.
Scheme 2 Formation of the two [2]pseudorotaxanes 7CCBPQTÁ4PF6 and
8CCBPQTÁ4PF6.
Notes and references
Table 3 Comparison of binding constants (Ka values)a and derived free energies
of complexation (ÀDG1)a between CBPQTÁ4PF6 and 7 or 8
1 M. A. Olson, Y. Y. Botros and J. F. Stoddart, Pure Appl. Chem., 2010,
82, 1569.
Complex
lmax [nm]
Ka [MÀ1
b
]
ÀDG1b [kcal molÀ1
]
2 (a) F. Durola, J. Lux and J.-P. Sauvage, Chem.–Eur. J., 2009, 15, 4124;
(b) S.-Y. Hsueh, C.-T. Kuo, T.-W. Lu, C.-C. Lai, Y.-H. Liu, H.-F. Hsu,
S.-M. Peng, C.-h. Chen and S.-H. Chiu, Angew. Chem., Int. Ed., 2010,
49, 9170; (c) G. Barin, A. Coskun, D. C. Friedman, M. A. Olson,
M. T. Colvin, R. Carmielli, S. K. Dey, O. A. Bozdemir, M. R. Wasielewski
and J. F. Stoddart, Chem.–Eur. J., 2011, 17, 213; (d) T. Pierro, C. Gaeta,
C. Talotta, A. Casapullo and P. Neri, Org. Lett., 2011, 13, 2650.
3 E. R. Kay, D. A. Leigh and F. Zerbetto, Angew. Chem., Int. Ed., 2007,
46, 72.
4 Translational isomer has been advocated for rotaxanes and circum-
rotational isomer for catenanes but co-conformational isomer is a
more general term for use with any interlocked molecule2.
5 (a) D. M. Walba, Tetrahedron, 1985, 41, 3161; (b) C. O. Dietrich-
Buchecker and J.-P. Sauvage, Chem. Rev., 1987, 87, 795;
(c) J. F. Stoddart, Chem. Soc. Rev., 2009, 38, 1802.
6 (a) A. H. Flood, R. J. A. Ramirez, W.-Q. Deng, R. P. Muller,
W. A. Goddard III and J. F. Stoddart, Aust. J. Chem., 2004, 57, 301;
(b) M. S. Vickers and P. D. Beer, Chem. Soc. Rev., 2007, 36, 211.
7 J. V. Hernandez, E. R. Kay and D. A. Leigh, Science, 2004, 306, 1532.
8 (a) R. Ballardini, V. Balzani, W. Dehaen, A. Dell’Erba, F. Raymo,
J. Stoddart and M. Venturi, Eur. J. Org. Chem., 2000, 591; (b) S. Nygaard,
B. Laursen, T. Hansen, A. Bond, A. Flood and J. Jeppesen, Angew. Chem.,
Int. Ed., 2007, 46, 6093; (c) Y. Tokunaga, N. Wakamatsu, N. Ohiwa,
O. Kimizuka, A. Ohbayashi, K. Akasaka, S. Saeki, K. Hisada, T. Goda and
Y. Shimomura, J. Org. Chem., 2010, 75, 4950.
7CCBPQTÁ4PF6
8CCBPQTÁ4PF6
464
783
300 Æ 50
100 Æ 10
3.42 Æ 0.08
2.61 Æ 0.06
a
The values were determined using absorption spectroscopy at 25 1C in
b
DMF. The errors were obtained as described in ref. 16.
stopper group reveal that CBPQTÁ4PF6 is shifted a little towards the
pyrrole ring. In the present molecule, the 3,5-di-t-butyl-benzene stopper
is attached directly to the pyrrole ring making it difficult to obtain the
optimal geometry of the superstructure. We believe that this change in
geometry weakens the binding between the two components to such
a degree that the poorer HQ p-electron donor binds stronger to
CBPQTÁ4PF6. Furthermore, 7 contains two ethylene glycol chains while
8 bears only one. It has been reported previously16 that ethylene glycol
chains have a significant influence on the binding to CBPQTÁ4PF6 in
(Me)2CO, and a greater number of ethylene glycol chains enhances the
binding affinity. All these factors make the non-covalent interactions in
7CCBPQTÁ4PF6 stronger than those in 8CCBPQTÁ4PF6.
Based on prior work,9 it is reasonable to assume that the difference
between the binding affinities obtained in the two [2]pseudorotaxanes
7CCBPQTÁ4PF6 and 8CCBPQTÁ4PF6 represents the energy differences
9 J. W. Choi, A. H. Flood, D. W. Steuerman, S. Nygaard, A. B. Braunschweig,
N. N. P. Moonen, B. W. Laursen, Y. Luo, E. DeIonno, A. J. Peters, J. O.
Jeppesen, K. Xu, J. F. Stoddart and J. R. Heath, Chem.–Eur. J., 2006, 12, 26.
in [2]rotaxane 1Á4PF6. It is therefore possible to determine the theore- 10 S. Nygaard, B. W. Laursen, A. H. Flood, C. N. Hansen, J. O. Jeppesen
and J. F. Stoddart, Chem. Commun., 2006, 144.
tical thermodynamic ratio between the co-conformational isomers
11 P. L. Anelli, P. R. Ashton, R. Ballardini, V. Balzani, M. Delgado,
1Á4PF6ÁHQ and 1Á4PF6ÁMPTTF.17 At 25 1C, a KHQ/MPTTF value of 3.9 is
M. T. Gandolfi, T. T. Goodnow, A. E. Kaifer and D. Philp, J. Am.
Chem. Soc., 1992, 114, 193.
12 This pressure dependency is well known in the synthesis of ionic
obtained corresponding to a ratio of 80 : 20 between 1Á4PF6ÁHQ and
1Á4PF6ÁMPTTF, which is comparable to the ratio of 73 : 27 (Table 1)
obtained from the experiments conducted at ambient pressure. In
addition, the theoretical ratio of 80 : 20 is close to the results obtained
8,9
species of several catenanes and rotaxanes based on CBPQTÁ4PF6
.
13 As expected, the exchange between the complexed and uncomplexed
species in a 1 : 1 mixture of 7 and CBPQTÁ4PF6 occurs rapidly on the
1H NMR time scale at 25 1C.
1
for the two [2]rotaxanes 5Á4PF6 and 6Á4PF6, where H NMR spectro-
14 Due to the S-Me group on the MPTTF derivative 8, the exchange
between the complexed and uncomplexed species in a 1 : 1 mixture
of 8 and CBPQTÁ4PF6 occurs slowly on the 1H NMR time scale at
25 1C. For that reason the mixture was prepared 1 hour before use to
ensure equilibrium is established.
15 M. B. Nielsen, J. O. Jeppesen, J. Lau, C. Lomholt, D. Damgaard,
J. P. Jacobsen, J. Becher and J. F. Stoddart, J. Org. Chem., 2001,
66, 3559.
16 S. Nygaard, C. N. Hansen and J. O. Jeppesen, J. Org. Chem., 2007,
72, 1617.
17 Determined using the equation KHQ/MPTTF = exp(ÀDDG1/RT).
scopy provided a 85 : 15 ratio between 5Á4PF6 and 6Á4PF6 at 1 bar. These
findings indicate that 1Á4PF6ÁHQ is the thermodynamically most stable
product and that the clipping reaction is under kinetic control. In
addition, the experiments indicate that the rate constant for the
formation of 1Á4PF6ÁMPTTF increases faster than the rate constant
for the formation of 1Á4PF6ÁHQ when the pressure is increased, i.e., the
activation volume for the formation of 1Á4PF6ÁMPTTF is more negative
as compared to 1Á4PF6ÁHQ.
c
5938 Chem. Commun., 2013, 49, 5936--5938
This journal is The Royal Society of Chemistry 2013