Trifluoromethyl acting as stopper in [2]rotaxane

Article abstract of DOI:10.1039/c2cc31009k

A modified dumbbell obtained by replacing one of the phenyl groups of the dibenzylammonium with a strong electron-withdrawing trifluoromethyl group templated the synthesis of the smallest [2]rotaxane reported so far. The trifluoromethyl group not only enhances the templating effect of the dumbbell but also acts as the stopper to prevent dethreading of a [20]crown ether macrocycle.

Full text of DOI:10.1039/c2cc31009k

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COMMUNICATION
Trifluoromethyl acting as stopper in [2]rotaxanew
Suvankar Dasgupta,a Kuo-Wei Huangb and Jishan Wu*a
Received 11th February 2012, Accepted 23rd March 2012
DOI: 10.1039/c2cc31009k
A modified dumbbell obtained by replacing one of the phenyl
groups of the dibenzylammonium with a strong electron-
withdrawing trifluoromethyl group templated the synthesis of
the smallest [2]rotaxane reported so far. The trifluoromethyl
group not only enhances the templating effect of the dumbbell
but also acts as the stopper to prevent dethreading of a [20]crown
ether macrocycle.
Mechanically interlocked molecules (MIM)1 in addition to
being aesthetically appealing, also find potential applications
Fig. 1 Molecular structures of the dumbbells 1–4, acyclic diolefin
in molecular nanotechnology. For example, rotaxane2 based
molecular switches3 have been visioned as potential candidates
for molecular scale electronics,4 molecular actuators,5 molecular
elevators,6 smart surfaces7 and controlled drug release.8
For constructing rotaxanes, the template-directed clipping9
methodology involves self-assembly of acyclic precursors
around the recognition site of the dumbbell followed by
reversible condensation9a,b,d,f,h or metathesis9c,e,g,i to generate
the macrocycle encompassing the recognition site. The ring
closing metathesis (RCM) of an acyclic diolefin polyether, in
polyether 5, and [20]crown ether 6.
without heating. The residue, expected to be the complex
7ÁPF6 (soluble in CH2Cl2), was subjected to RCM with
Grubbs’ 2nd generation catalyst under refluxing conditions
in dry DCM for 60 h (Scheme 1).
Although the peak corresponding to the desired compound
10ÁPF6 was detected in nominal ESI-MS (Fig. S1, ESIw),
purification by column chromatography failed to isolate
10ÁPF6. Dethreading during purification may explain this
finding if 10ÁPF6 is a pseudorotaxane. However, no threading
+
the presence of the ‘‘dumbbell’’ (ArCH2)2NH2 (Ar = aryl),
is known to produce interlocked structures containing
[24]crown ether.9b–d
Very recently, using RCM we obtained a series of [2]rotaxanes
on dibenzylammonium dumbbell (1, Fig. 1) with smaller macro-
cycles such as [20], [21] and [22]crown ethers, by systematically
varying the alkyl chain length of the acyclic diolefin polyether.10
Inspired by the success with dibenzylammonium dumbbell and
knowing that [21]crown ether was the smallest crown ether to
be threaded by dialkylammonium ion (2, Fig. 1),11 one can
contemplate that clipping a [20]crown ether onto a dialkyl-
ammonium ion will give a [2]rotaxane with alkyl groups acting as
stoppers! Therefore, salt 2ÁPF612 and acyclic diolefin polyether 5
were prepared.10 A mixture of two equivalents of 5 with one
equivalent of 2ÁPF6 was stirred in CHCl3–CH3CN (3 : 1) for 24 h,
followed by removing the solvent under reduced pressure
a Department of Chemistry, National University of Singapore,
3 Science Drive 3, Singapore 117543. E-mail: chmwuj@nus.edu.sg;
Fax: (+65) 6779 1691; Tel: (+65) 6516 2677
b King Abdullah University of Science and Technology (KAUST),
Division of Chemical and Life Sciences and Engineering and KAUST
Catalysis Center, Thuwal 23955-6900, Saudi Arabia
w Electronic supplementary information (ESI) available: Synthetic
procedures, nominal ESI-MS and HR ESI-MS spectra, 2D NOESY
spectrum, stacked 1H NMR spectra, decay curve, 1H, 13C and 19F
NMR spectra. See DOI: 10.1039/c2cc31009k
Scheme 1 RCM of dumbbells 2ÁPF6, 3ÁBAr4 and 4ÁBAr4.
Chem. Commun., 2012, 48, 4821–4823 4821
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Fig. 3 1H NMR spectra (500 MHz, CD3CN) of (i) 4ÁBAr4, and
(ii) 12ÁBAr4. Dotted lines indicate the downfield shift observed
(b - d) due to the effect of H-bonding interaction.
Fig. 2 Partial 1H NMR spectra (500 MHz, CD3CN), displaying
the increase in acidity of methylene protons g - e - c in dumbbells
2 - 3 - 4. Benzylic protons a in 1 is for reference.
could be detected by 1H NMR on refluxing a mixture of 2ÁPF6
with three equivalents13 of [20]crown ether 6 (for synthesis,
see ESIw) for 7 days in CH2Cl2 followed by another 7 days in
CHCl3. 10ÁPF6 was expected to be formed in extremely low
yield (if at all), which would make it difficult to be isolated.
This may be ascribed to the weaker templating effect of the
dumbbell 2 than 1 due to the lower acidity of –CH2NH2+CH2–
protons (responsible for templating effect) in 2 (protons g
B2.9 ppm, Fig. 2(iv)) compared to 1 (protons a B4.2 ppm,
Fig. 2(i)). To increase the templating effect of the dumbbell,
N-benzylalkylammonium dumbbells 3 and 4 having electron-
withdrawing fluoromethyl (–CH2F) and trifluoromethyl
(–CF3) stopper groups were prepared. However, the dumbbell
with difluoromethyl (–CHF2) stopper group could not be
synthesized since the precursors F2CHCH2NH2 or F2CHCHO
was not easily available.
The H NMR spectrum of [2]rotaxane 12ÁBAr4 (Fig. 3(ii)),
1
displaying an –NH2+– hump (B8.6 ppm), olefinic proton
peak (protons e B6.1 ppm), and splitting of benzylic protons
(protons c B4.3 ppm), clearly indicated a [2]rotaxane structure
encircled with a [20]crown ether.10 The large downfield shift of the
methylene protons b in 4ÁBAr4 to d in 12ÁBAr4 can be explained by
the participation of protons d in hydrogen bonding with the
oxygen atoms of the [20]crown ether, substantiating an interlocked
geometry for [2]rotaxane 12ÁBAr4. The observed HR ESI-MS
result for 12ÁBAr4 showed a peak at 480.2573 (Fig. S3, ESIw) with
À1.2 ppm deviation from the calculated HRMS (480.2567)
for [M À BAr4]+, showing that pure 12ÁBAr4 can be obtained
by column chromatography. Repeated attempts to grow
suitable single crystals failed, consequently 2D NOESY
NMR (Fig. S4, ESIw) was performed in CDCl3 to reveal the
interlocked structure.
1
The electronic impact of –CH2F and –CF3 stopper groups
can be observed from the downfield chemical shifts of the
protons e (B3.4 ppm, Fig. 2(iii)) and c (B3.9 ppm, Fig. 2(ii))
in 3 and 4, respectively. The dumbbells 3 and 4 were prepared
with BAr4 counter ion because their chloride precursors (15ÁCl
and 16ÁCl, see ESIw) could not be dissolved even in hot water
and thus could not undergo a clean counter ion exchange
reaction by mixing with aqueous NH4PF6. Moreover, the BAr4
counter ion is a weakly associating ion and extremely lipo-
philic, making 3 and 4 easily dissolve in DCM.14 The salts 3Á
BAr4 and 4ÁBAr4 were then mixed with two equivalents of 5
to afford 8ÁBAr4 and 9ÁBAr4, respectively, which as for 7ÁPF6
above, were subjected to RCM with the Grubbs’ 2nd generation
catalyst under refluxing condition in dry DCM for 60 h.
The [2]rotaxane 11ÁBAr4, corresponding to the salt 3ÁBAr4,
could only be detected in nominal ESI-MS (Fig. S2, ESIw)
while [2]rotaxane 12ÁBAr4 obtained from salt 4ÁBAr4 was
isolated as a white solid in reasonably good yield (54%,
Scheme 1), reflecting the strong templating effect of 4ÁBAr4.
To ascertain the kinetic stability of 12ÁBAr4, its H NMR
spectrum was recorded in DMSO-d6, and a tiny peak (B5.75 ppm,
Fig. S5(ii), ESIw) corresponding to the free crown ether was
observed. We became suspicious of dethreading, however a
threading experiment performed with the salt 4ÁBAr4 and three
equivalents of [20]crown ether 6 failed despite refluxing the
mixture in CH2Cl2 for 7 days followed by another 7 days in
CHCl3. Moreover, in the 1H NMR spectrum of 12ÁBAr4
recorded in DMSO-d6 (Fig. S5, ESIw), the absence of peak
corresponding to the free dumbbell suggested decay of
[2]rotaxane 12ÁBAr4 was not by dethreading. Some electronic
effects, operative in the component –NH2+CH2CF3 of 12ÁBAr4,
may be responsible for the slow decomposition in polar solvent
(DMSO). A time-based concentration study of 12ÁBAr4 in
DMSO-d6 over a week suggested a first-order decay with
half-life of 26.1 h (Fig. S6, ESIw). However, the compound
12ÁBAr4 did not show any decomposition after standing in
CDCl3 over two weeks and no dethreading was observed on
heating up to 373 K in C2D2Cl4 (Fig. S7, ESIw).
c
4822 Chem. Commun., 2012, 48, 4821–4823
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Fig. 4 Capped stick (a) and space-filling (b) representation for the
calculated structure of [2]rotaxane 12ÁBAr4, showing short contact
distances (in A). (a) In capped stick structures, [C–HÁ Á ÁO] and
[N–HÁ Á ÁO] distances are shown. Hydrogen atoms not involved in
short contact distances are omitted for clarity. (b) In space-filling
representation, oxygen atoms of crown ether and fluorine atoms of the
dumbbell are represented in red and yellow, respectively. All the
hydrogen atoms are omitted for clarity.
Theoretical calculations at the B3LYP/6-31+G(d,p) level
of theory were conducted to understand the geometry of
the [2]rotaxane 12 cation.15 This method was validated by
comparing the optimized structure of an analogous [2]rotaxane
with dibenzylammonium dumbbell interlocked with a [20]crown
ether10 with its crystallographic structure, and it was confirmed
that the computed geometry was in good agreement with the
experimental observation. Similar calculations on cation 12
predict an interlocked [2]rotaxane structure involving multiple
[C–HÁ Á ÁO] and [N–HÁ Á ÁO] interactions (Fig. 4a). The space-
filling representation (Fig. 4b) gives an estimate of the cavity
size of the [20]crown ether being smaller than the volume of
the CF3 group, which is consistent with the experimental
results confirming the role of the CF3 moiety as a stopper
for the [20]crown ether.
In conclusion, the potential of alkyl or fluorinated alkyl
groups acting as stoppers has been studied in detail, with the
[20]crown ether as the encircling macrocycle. RCM has been
utilized to clip the macrocycle onto the dumbbell. Indeed, we
have obtained a very strongly interlocked [2]rotaxane on the
PhCH2NH2+CH2CF3 dumbbell encircled with a [20]crown
ether, highlighting the role of trifluoromethyl group in enhancing
the template effect (needed for clipping) along with acting as a
stopper. The [2]rotaxane 12ÁBAr4, though not stable in polar
solvents, remains extremely stable in chlorinated solvents even
at 373 K, underlying the steric resistance offered by the
trifluoromethyl group is sufficient for acting as a stopper, which
is also supported by theoretical calculations. The [2]rotaxane
12ÁBAr4 represents the smallest [2]rotaxane reported so far, in
terms of the molar mass and the total number of the atoms for
the cationic part.16
This work was financially supported by the NUS AcRF
Tier 1 grant (R-143-000-467-112) and KAUST. We thank
Han Yanhui and Ong Wei Qiang for 2D NMR analysis.
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D. A. Leigh, F. M. McMillan, H. McNab and A. M. Slawin,
J. Am. Chem. Soc., 2009, 131, 14116–14122.
15 See ESIw for computational details.
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