The rapid synthesis and dynamic behaviour of an isophthalamide [2]catenane

Article abstract of DOI:10.1039/c5ob01770j

A serendipitous [2]catenane has been prepared in three steps from commercially available starting materials. The interlocked topology of the catenane has been confirmed by single crystal X-ray structural determination. The rings of the catenane may rotate

Full text of DOI:10.1039/c5ob01770j

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DOI: 10.1039/C5OB01770J
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The Rapid Synthesis and Dynamic Behaviour of an Isophthalamide
[2]Catenane
Calum N. Marrsa and Nicholas H. Evans*a
Received 00th January 20xx,
Accepted 00th January 20xx
A serendipitous [2]catenane has been prepared in three steps from commercially available starting materials. The
interlocked topology of the catenane has been confirmed by single crystal X-ray structural determination. The rings of the
catenane may rotate relative to one another - a process that may be controlled by varying solvent or temperature.
DOI: 10.1039/x0xx00000x
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interlocked catenane. NMR studies reveal the rings rotate
Introduction
relative to one another in
temperature, is fast on the NMR timescale in d6-DMSO, while
it is appreciably slower in chlorinated solvents.
a process that, at room
Catenanes,1 along with their interlocked counterparts
rotaxanes,2 are not only aesthetically pleasing molecules, but
are increasingly being used in nanotechnological applications3
many of which exploit the relative motion of their interlocked
components.4 Interlocked molecules have become accessible
to the synthetic chemist by the development of various
template synthesis methodologies that overcome the
entropically unfavourable association of multiple molecular
components that is required for their preparation. Templates
and templating interactions that have been used to prepare
catenanes and rotaxanes include: metal cations,5 anions,6
π-π
stacking,7 hydrogen bonding8 and (very recently) halogen
bonding.9 While a large number of synthetic strategies have
been reported to date, many involve lengthy, multi-step
procedures to obtain the precursors required for the final
reaction step that leads to covalent capture of the interlocked
molecule. This represents a considerable hurdle for a chemist
wishing to investigate the properties and possible application
of catenanes and rotaxanes, and so the discovery of new
expedient synthetic routes to these molecules has the
potential to aid future studies.
Figure 1: Schematic representation of the expedient three step synthesis of a
dynamic isophthalamide [2]catenane.
Herein we report a serendipitously discovered [2]catenane
that was prepared via a short synthetic route (Figure 1). By
reacting a bis-amine (prepared in two steps) with commercially
available isophthaloyl chloride, an isophthalamide [2]catenane
was produced – in just three reaction steps. In addition to
being characterised by NMR and IR spectroscopies and mass
spectrometry, the structure of the catenane has been
unequivocally confirmed by solid state structural
determination. The X-ray structure reveals inter-ring hydrogen
bonds which it is believed template formation of the
Results and Discussion
When attempting to prepare isophthalamide macrocycle
1
(Scheme 1) by reacting equimolar amounts of a previously
reported dimethanamine10 and isophthaloyl chloride in
dichloromethane using semi-high dilution macrocyclisation
conditions (≈ 3 mmol/L), TLC analysis of the crude reaction
mixture revealed two closely eluting compounds. Careful silica
gel column chromatography allowed for the separate isolation
of these compounds. The characterisation (NMR spectroscopy
and mass spectrometry, see ESI) of the first eluted (i.e. less
polar) species was consistent with the structure of the
a.Department of Chemistry, Lancaster University, Lancaster. LA1 4YB. UK.
anticipated macrocycle
1 (in an isolated yield of 12%). The
†
Electronic Supplementary Information (ESI) available: Additional notes on
experimental procedures; characterisation spectra of macrocycle and catenane
2; crystallographic data for macrocycle (CCDC number: 1416976) and catenane
1
growth of a single crystal allowed for solid state structure
1
2
(CCDC number: 1416977). See DOI: 10.1039/x0xx00000x
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determination, which provided conclusive proof of macrocycle
formation (see ESI).
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DOI: 10.1039/C5OB01770J
Figure 2: 1H NMR spectra of (a) macrocycle
MHz, 298 K). See Scheme 1 for atom labels.
1 and (b) catenane 2 (d6-DMSO, 400
Unequivocal evidence for the interlocked topology of catenane
was provided by single crystal X-ray structure determination
2
Scheme 1: Synthesis of Macrocycle 1 and Catenane 2.
(Figure 3). A single crystal was grown by slow evaporation of a
chloroform solution of the catenane, with the solved structure
revealing inter-ring hydrogen bonding involving each
isophthalamide cleft. As depicted in Figure 3, the
isophthalamide N-Hs of the left-hand ring are hydrogen
bonding to one of the carbonyl oxygen atoms of the right-hand
ring (N-H · · · O distances: 2.196 Å and 2.465 Å). In addition, an
N-H and the internal isophthalamide C-H of the right-hand ring
are hydrogen bonding to the central oxygen in the polyether
chain of the left-hand ring.
1
The more polar compound
2 possessed a very broad H NMR
spectrum in CDCl3 at room temperature, implying dynamic
processes that fall between the fast and slow NMR timescales,
and hinting at possible catenane formation (also isolated with
a yield of 12%). 1H NMR spectra of
1 and 2 were then recorded
in d6-DMSO, which consisted of sharp, well-resolved
resonances for both compounds (Figure 1). Comparing the
spectrum of
2 with that of 1, there are significant upfield shifts
in aromatic protons f and g, as well as the alkyl protons e, h, i
and j, which would be consistent with a freely-rotating
catenane structure, where the protons of one ring are able to
reside between the aromatic rings of the other macrocycle.
For catenane
in operation during the reaction. The presence of inter-ring
hydrogen bonding in the X-ray structure of provides evidence
to support the hypothesis that the formation of the
interlocked molecule is driven by hydrogen bond templation.
The proposed mechanism for catenane formation is that a
2 to form implies that a templating interaction is
2
Amide proton d is also significantly upfield for
2
compared to
1
. At first sight this might appear inconsistent with a catenane
structure for
2, as it is expected that in an interlocked
partially cyclized ring threads through macrocycle
by formation of the inter-component hydrogen bonds to be
found in catenane , before reaction of the remaining acid
1, templated
structure a carbonyl oxygen on one ring would hydrogen bond
to the isophthamide cleft of the other ring. However, we
rationalise the appearance of the 1H NMR spectra, by
suggesting that a DMSO solvent molecule would be able to
efficiently hydrogen bond to the isophthalamide cleft of
2
chloride and amine to close the second ring of the catenane.
At this point, it should be emphasised that other examples of
hydrogen bond templated catenanes have been discovered
1
through its highly polarised S+–O- bond, but it
serendipitously; first by Hunter8a and V gtle8b and second by
ö
macrocycle
would not be able to for the more sterically congested
Leigh8c. In contrast to these previously reported systems,
catenane possesses only one isophthalamide group per ring,
proposed catenane structure of 2.
2
rather than two, and hence represents the first example of a
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Figure 3: X-ray structure of catenane 2. Hydrogen atoms (except N-Hs and isophthalamide internal C-Hs) and disorder in one of the rings are omitted for clarity.
new class of isophthalamide containing catenane produced by proportion of the hydrogen bond accepting dimethyl sulfoxide
hydrogen bond templation. creates a solvent mixture that disrupts the inter-ring hydrogen
We have undertaken further investigations into the dynamic bonds so that ring rotation becomes fast on the NMR
behaviour of catenane
in solution by use of 1H NMR timescale.
spectroscopy. Upon varying the solvent composition from pure We also looked at the effect of temperature upon the dynamic
2
1
1
CDCl3 to 1:1 CDCl3:d6-DMSO at 298 K the H NMR spectrum of behaviour of catenane
catenane notably sharpens (Figure 4). Increasing the
2 by use of VT H NMR spectroscopy in
2
CD2Cl4 (see Figure 5). At 298 K, the spectrum is very broad,
except for the triplet attributed to proton a.
Tetrachloroethane, like chloroform, is a poor hydrogen bond
acceptor compared to dimethyl sulfoxide, and so ring rotation
is much slower than in d6-DMSO. However, heating the sample
to 318 K, results in the number of peaks reducing, and upon
continued heating to 378 K, all the peaks become sharp and
well-resolved, as the ring rotation once again becomes fast on
the NMR timescale.
Figure 4: 1H NMR spectra of catenane
mixtures (2.5 mM, 400 MHz, 298 K). See Scheme 1 for atom labels.
2 recorded in CDCl3:d6-DMSO solvent
Figure 5: 1H NMR spectra of catenane
(400 MHz). See Scheme 1 for atom labels.
2
recorded at T = 298 K to 378 K in CD2Cl4
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Conclusions
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DOI: 10.1039/C5OB01770J
In summary, a [2]catenane, where each ring possesses one
isophthalamide unit, has been synthesised in just three steps
from commercially available starting materials. The rings of the
catenane are able to rotate relative to one another; the rate of
this process may be modulated by solvent or temperature.
Further investigations into this new class of catenanes,
including the preparation of examples where the motion of the
rings may be controlled by chemical stimuli, are being
undertaken in our laboratories.
Figure 6: Carbon atom labels used in the assignment of the NMR data.
Macrocycle
2860 (C-H), 1660 (C=O), 1630 (C=O), 1530 (N-H), 1080 (C-O).
1
. Mp 198-200 °C. νmax / cm-1 (neat) 3320 (N-H),
3
4
δ
H(400 MHz; CDCl3) 7.91 (2H, dd, J = 7.7 Hz J = 1.7 Hz, C2H),
7.80 (1H, s, C4H), 7.45 (1H, t, 3J = 7.7 Hz, C1H), 7.21-7.27 (8H, m,
Acknowledgements
C8H & C9H), 6.85 (2H, t, J = 5.4 Hz, NH), 4.46-4.48 (8H, m, C6H
3
N. H. E. wishes to thank Lancaster University for financial
support. We thank Drs Fraser White, Daniel Baker and Marcus
Winter (Agilent Technologies, Yarnton, UK) and Dr Mike
Coogan (Lancaster University) for assistance with the
collection, solution and interpretation of the X-ray
& C11H), 3.58-3.68 (8H, m, C12H & C13H).
δC(100 MHz; CDCl3)
167.0 (C5), 137.6, 137.1, 134.6, 130.9, 129.5, 128.5, 128.1,
123.7 (8 Ar C environments), 72.8 (C11), 70.6, 69.4 (C12 & C13),
43.9 (C6). m/z (ES) 492.2480 ([M + NH4]+, C28H34N3O5 requires
492.2493.
crystallographic data of macrocycle
1 and catenane 2, and the
Catenane 2
. Mp 224-226 °C. νmax / cm-1 (neat) 3350 (N-H),
EPSRC UK National Mass Spectrometry facility at Swansea
University, UK.
2860 (C-H), 1650 (C=O), 1620 (C=O), 1510 (N-H), 1070 (C-O).
δ
H(400 MHz; d6-DMSO) 8.17 (2H, s, C4H), 8.04 (4H, br s, NH),
3
7.97 (4H, dd, J = 7.7 Hz 4J = 1.6 Hz, C2H), 7.59 (2H, t, 3J =
7.7 Hz, C1H), 6.92-7.04 (16H, m, C8H & C9H), 4.15-4.18 (16H, m,
C6H & C11H), 3.10 (8H, br s, OCH2CH2O), 2.93 (8H, br s,
Experimental
OCH2CH2O). δ
C(100 MHz; d6-DMSO) 165.6 (C5), 137.3, 136.2,
General Information
134.2, 130.7, 128.6, 128.5, 124.9 (8 Ar C environments), 72.2
(C11), 69.3, 68.1 (C12 & C13), 43.5 (C6). m/z (ES) 949.4374 ([M +
H]+, C56H61N4O10 requires 949.4382.
Commercially available solvents and chemicals were used
without further purification. Deionised water was used in all
cases. Analytical TLC was carried out on aluminium backed
silica gel sheets with fluorescent indicator (254 nm). Column
chromatography was carried out on silica gel with a 60 Å
particle size.
Notes and references
1
(a) N. H. Evans and P. D. Beer, Chem. Soc. Rev., 2014, 43,
4658-4683; (b) G. Gil-Ramírez, D. A. Leigh and A. J. Stephens,
Angew. Chem. Int. Ed., 2015, 54, 6110-6150.
M. Xue, Y. Yang, X. Chi, X. Yan and F. Huang, Chem. Rev.,
2015, 115, 7398-7501.
S. F. M. van Dongen, S. Cantekin, J. A. A. W. Elemans, A. E.
Rowan and R. J. M. Nolte, Chem. Soc. Rev., 2014, 43, 99-122.
E. R. Kay, D. A. Leigh and F. Zerbetto, Angew. Chem. Int. Ed.,
2007, 46, 72-191.
IR spectra were recorded on an Agilent Technologies Cary 630
FTIR spectrometer. NMR spectra were recorded on a Bruker
400 MHz Ultra Shield Plus, with the NMR data for macrocycle
and catenane reported below being assigned according to
1
2
3
4
5
2
the atom labels to be found in Figure 6. Mass spectra were
recorded on a Thermofisher LTQ Orbitrap XL at the EPSRC UK
National Mass Spectrometry Facility at Swansea University.
Melting points were recorded on a Gallenkamp capillary
melting point apparatus and are uncorrected.
(a) C.-O. Dietrich-Buchecker, J.-P. Sauvage and J.-P.
Kintzinger, Tetrahedron Lett., 1983, 24, 5095-5098; V.
Aucagne, J. Berná, J. D. Crowley, S. M. Goldup, K. D. Hänni, D.
A. Leigh, P. J. Lusby, V. E. Ronaldson, A. M. Z. Slawin, A.
Experimental Procedures
Viterisi and D. B. Walker, J. Am. Chem. Soc., 2007, 129
,
Preparation of Macrocycle 1 and Catenane 2:
11950-11963; (c) S. M. Goldup, D. A. Leigh, T. Long, P. R.
McGonigal, M. D. Symers and J. Wu, J. Am. Chem. Soc., 2009,
131, 15924-15929; (d) S.-T. Tung, C.-C. Lai, Y.-H. Liu, S.-M.
Peng and S. H. Chiu, Angew. Chem. Int. Ed., 2013, 52, 13269-
13272; (e) C. Lincheneau, B. Jean-Denis and T. Gunnlaugsson,
Chem. Commun., 2014, 50, 2857-2860; (f) J. E. Beves, B. A.
Blight, C. J. Campbell, D. A. Leigh and R. T. McBurney, Angew.
Chem. Int. Ed., 2011, 50, 9260-9327.
(a) G. M. Hübner, J. Gläser, C. Seel and F. Vögtle, Angew.
Chem. Int. Ed. 1999, 38, 383-386; (b) J. A. Wisner, P. D. Beer,
M. G. B. Drew and M. R. Sambrook, J. Am. Chem. Soc., 2002,
124, 12469-12476; (c) M. R. Sambrook, P. D. Beer, J. A.
Wisner, R. L. Paul and A. R. Cowley, J. Am. Chem. Soc., 2004,
126, 15364-15365; (d) E. Arunkumar, C. C. Forbes, B. C. Noll
and B. D. Smith, J. Am. Chem. Soc., 2005, 127, 3288-3289; (e)
Isophthaloyl chloride (242 mg, 1.19 mmol) dissolved in CH2Cl2
(100 mL) and the dimethanamine (410 mg, 1.19 mmol)
dissolved in CH2Cl2 (100 mL) were added dropwise to a
solution of NEt3 (482 mg, 0.66 mL, 4.76 mmol) in CH2Cl2 (200
mL). The reaction was stirred under an Ar(g) atmosphere for 16
h. The reaction mixture was concentrated to 100 mL, then
washed with 1M HCl(aq) (1 × 100 mL) and 1M KOH(aq) (1 × 100
mL). The organic layer was separated, dried (MgSO4), filtered
and concentrated to give a yellow oil. The crude material was
purified by silica gel column chromatography (90:10
6
EtOAc/CH2Cl2) to yield macrocycle
1 (Rf = 0.55, 68 mg, 12 %)
and catenane (Rf = 0.50, 70 mg, 12 %) as white solids.
2
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B. Q. Huang, S. M. Santos, V. Felix and P. D. Beer, Chem.
Commun., 2008, 4610-4612; (f) J.-J. Lee, J. M. Baumes, R. D.
Connell, A. G. Oliver and B. D. Smith, Chem. Commun., 2011,
47, 7188-7190; (g) M. J. Langton and P. D. Beer, Chem.
Commun., 2014, 50, 8124-8127; (h) G. T. Spence and P. D.
Beer, Acc. Chem. Res., 2013, 46, 571-586.
View Article Online
DOI: 10.1039/C5OB01770J
7
8
(a) P. R. Ashton, T. T. Goodnow, A. E. Kaifer, M. V.
Reddington, A. M. Z. Slawin, N. Spencer, J. F. Stoddart, C.
Vicent and D. J. Williams, Angew. Chem. Int. Ed. Engl., 1989,
28, 1396-1399; (b) P. L. Anelli, N. Spencer and J. F. Stoddart,
J. Am. Chem. Soc., 1991, 113, 5131-5133; (c) D. G. Hamilton,
J. K. M. Sanders, J. E. Davies, W. Clegg and S. J. Teat, Chem.
Commun., 1997, 897-898; (d) G. Barin, A. Coskun, M. M. G.
Fouda, J. F. Stoddart, ChemPlusChem, 2012, 77, 159-185.
(a) C. A. Hunter, J. Am. Chem. Soc., 1992, 114, 5303-5311; (b)
F. Vögtle, S. Meier and R. Hoss, Angew. Chem. Int. Ed. Engl.,
1992, 31, 1619-1622; (c) A. G. Johnston, D. A. Leigh, R. J.
Pritchard and M. D. Deegan, Angew. Chem. Int. Ed. Engl.,
1995, 34, 1209-1212; (d) F. G. Gatti, D. A. Leigh, S. A.
Nepogodiev, A. M. Z. Slawin, S. J. Teat and J. K. Y. Wong, J.
Am. Chem. Soc., 2001, 123, 5983-5989; (e) N. S. Simpkins, D.
F. Weske, L. Male, S. J. Coles and M. B. Pitak, Chem.
Commun., 2013, 49, 5010-5012; (f) A. Tron, P. J. Thornton,
M. Rocher, H.-P. J. de Rouville, J.-P. Desvergne, B.
Kauffmann, T. Buffeteau, D. Cavagnat, J. H. R. Tucker and N.
D. McClenaghan, Org. Lett., 2014, 16, 1358-1361.
9
L. C. Gilday, T. Lang, A. Caballero, P. J. Costa, V. Félix and P.
D. Beer, Angew. Chem. Int. Ed., 2013, 52, 4356-4360.
10 A. Vidonne and D. Philp, Tetrahedron, 2008, 64, 8464-8475.
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