Covalent locking and unlocking of an atropisomeric molecular switch

Article abstract of DOI:10.1039/c2cc16511b

Demonstrated is the reversible switching and saving of a conformational molecular switch via heating in different environments followed by reversible chemical entrapment. The Royal Society of Chemistry 2012.

Full text of DOI:10.1039/c2cc16511b

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COMMUNICATION
Covalent locking and unlocking of an atropisomeric molecular switchw
Yong S. Chong, Brent E. Dial, William G. Burns and Ken D. Shimizu*
Received 19th October 2011, Accepted 21st November 2011
DOI: 10.1039/c2cc16511b
Demonstrated is the reversible switching and saving of a conforma-
tional molecular switch via heating in different environments followed
by reversible chemical entrapment.
to changes in its chemical environment. These changes in the
syn/anti ratios, however, can still be captured and chemically
‘‘locked’’ into place by alkylation of the diol 1 with benzyl bromide.6
The resulting bis(benzyl)ether 2 has a higher rotational barrier and
is conformationally stable at rt, allowing 2 to maintain its syn/anti
ratio even after removal from the conformationally biasing
environment. Finally, the covalent modification is reversible,
allowing the switch to be ‘‘unlock’’ and returned to the
conformationally malleable 1 (Scheme 1). An obvious advan-
tage is that the process has the potential to be repeated several
times due to the very mild conditions involved. This system is
envisioned as a new type of molecular information storage
featuring a write/save system with the ability to erase and
rewrite information.
The development of molecular motors, devices and switches has
been an active area of research within the fields of nanoscience
and molecular electronics.1,2 The typical requirements of a
molecular device are the abilities to: (1) adopt two or more
conformational or electronic states, (2) to switch between states,
and (3) maintain these states.3 Along these lines, we have
recently developed molecular switches and rotors based on the
atropisomeric N,N0-diaryldiimide framework (Fig. 1) that
adopts distinct syn- and anti-isomers and can be switched back
and forth.4 The conformational isomerism and dynamic write-
save properties of our systems arises from restricted rotation
about Caryl-Nimide bonds (Fig. 1).5 In diol 1 and bis(benzyl)ether 2,
the ortho-oxygens on the two N-imide rings force the aryl rings
out of plane with the central 1,4,5,8-naphthalene diimide
spacer, result in the formation of syn- and anti-isomers.
In previous studies, we tailored the N,N0-diaryldiimide
The chemical entrapment of atropisomeric 1 shares many
similarities with molecular brake systems described by Kelly and
more recently Bates in which reversible chemical modification
reactions have been used to control rotational barriers of
molecular devices.1c,7 The previously described molecular brakes
have low rotational barriers (o20 kcal molꢀ1) and thus,
rotation at room temperature is slowed but not stopped by
covalent modification. Our system based on atropisomer 1 is
differentiated in two respects. First, the rotational barrier is halted
at room temperature upon alkylation to bis(benzylether) 2.
Secondly, specific rotational isomers of 1 can be preferred via
switches to have high rotational barriers (>27 kcal molꢀ1
)
to ensure that the stimuli-induced changes in the syn/anti ratio
were ‘saved’ at rt.4 A disadvantage of this approach was that
elevated temperatures were required for the switching process,
which greatly diminished the fidelity of hydrogen bonding
guests that were used to bias the switches toward the syn-
isomers. To remedy this problem, we have developed a new
atropisomeric system (Fig. 1) that can be switched at rt and
then conformationally locked by chemical modification. Diol 1
has Caryl-Nimide bonds with lower rotational barriers and is
slowly interconverting at rt. Thus, 1 can be switched under
more mild conditions and is more sensitive and responsive
Fig. 1 Covalent locking and unlocking of a molecular system.
Scheme 1 Illustration of the chemical entrapment of a syn- and anti-
isomers of diol 1, and 1H NMR of bis(benzyl)ether 2 chemically locked
in anti- and syn-enriched states. From a mixture, either isomer can be
favored at room temperature due to an external stimulus. Enriched
diol 1 is then chemically ‘‘locked’’ into that conformation by raising
the rotational barrier. Enriched bis(benzyl)ether 2 is able to be
‘‘unlocked’’ to afford the original mixture of slowly-rotating isomers.
Department of Chemistry and Biochemistry, University of South
Carolina, Columbia, USA. E-mail: shimizu@mail.chem.sc.edu;
Fax: 803 777 9521; Tel: 803 777 6523
w Electronic supplementary information (ESI) available. CCDC
846375–846376. For ESI and crystallographic data in CIF or other
electronic format see DOI: 10.1039/c2cc16511b
c
1296 Chem. Commun., 2012, 48, 1296–1298
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Fig. 2 Ratios of isomers (syn/anti) of enriched samples of diol 1 and
bis(benzylether)-2 measured over 2 h by 1H NMR in acetone-d6 (25 1C)
and 20% acetone-d6/benene-d6 (70 1C), respectively. R is the syn/anti
ratio at a given time and Re is the syn/anti ratio at equilibrium. In this
plot, first order processes give a straight line with a rate = ꢀslope.
Fig. 3 (top) X-ray crystal structure of anti-diol 1. (bottom) X-ray
crystal structure of anti-bis(benzylether) 2.
interaction with different templating agents. The ability to
manipulate the syn/anti ratio provides an unique route to
modulating and controlling the molecular properties of the
system.
in dichloromethane and quickly running a TLC against the
original mixture of syn-/anti-1. The Rf of the neat was identical
with that of the higher Rf isomer.
Confirmation of the TLC assignments were provided by
comparisons with samples of crystals of anti-1 obtained from
acetone. The top structure in Fig. 3 shows that diol 1 adopts
the expected non-planar structure with the two N-aryl rings
perpendicular (93.11 the dihedral angle between the planes of
the phenolic aryl ring and naphthalene diimide ring) to the
central naphthalene diimide spacer.
Diol 1 was prepared in one step by the condensation of
commercially available 2-amino-4-tert-amylphenol and
1,4,5,8-naphthalene dianhydride.8 Diol 1 showed slow rotation
at room temperature. This was initially evident by the ability to
1
observe the respective syn- and anti-isomers of 1 by H NMR
and by TLC as separate species. However, the isomers were not
sufficiently stable to be isolated by column chromatography at
room temperature.9 The isomerization barrier was quantitatively
measured by monitoring the rate of isomerization of an anti-
The isomeric purity of syn- and anti-enriched samples were
estimated from trapping experiments. Alkylation raises the
rotational barrier about the Caryl-Nimide bonds in the N,N,0-
diarylimide platform and the corresponding bis(benzylether) 2
is conformationally stable at room temperature. Thus, the
higher barrier allows the syn/anti ratio to be more easily
measured at room temperature by integration of the
1H NMR spectra of bis(benzylether) 2. The anti-enriched
samples of neat diol 1 and the syn-enriched samples were
alkylated with an excess of benzyl bromide and potassium
carbonate in cold DMF (0 1C, 71% yield). The corresponding
bis(benzylether) 2 was isolated and the syn-/anti-ratio measured.y
The most clearly differentiated peaks are the benzyl CH2 protons
at 4.8 ppm. The syn- and anti-isomers of 2 show baseline
separation with the CH2 of syn-2 being more downfield
(Scheme 1). For example, alkylation of the anti-enriched samples
yielded a 1 : 4 (syn-/anti-) ratio for bis(benzylether) 2. Alkylation
of the syn-enriched samples yielded a 2 : 1 (syn-/anti-) ratio of the
bis(benzylether) 2 with 79% yield.
1
enriched sample by H NMR at 25 1C in acetone-d6 (Fig. 2).
From the isomerization rate constant (kisom), the barrier for
diol 1 was calculated to be 21.9 kcal molꢀ1 with a half-life at
25 1C of 13 min. Alkylation of the diol 1 raised the rotational
barrier sufficiently that no isomerization was observed under
similar conditions (25 1C, 2 h). Therefore, the isomerization
rate of bis(benzylether) 2 was measured at 70 1C. From the
measured isomerization rate constant, a much higher barrier of
27.5 kcal molꢀ1 was calculated, which equates to a half-life at
25 1C of 109 days.
The low rotational barrier of diol 1 allowed control over its
conformation at room temperature. Either the syn- or anti-
isomer can be preferred by treating diol 1 under different
conditions. The convergent syn-1 isomer can be preferred by
adsorbing the syn/anti-1 onto silica gel. Presumably the two
phenols of the syn-1 are better orientated than the divergent
anti-1 to interact and form hydrogen bonding interactions
with the silica gel surface.z This strategy of using silica gel to
favor the formation of syn-atropisomers appears to be a
general one. For example, Lindsey and co-workers have
reported that the adsorption of a mixture of four antropisomeric
meso-porphyrin lead to the selective formation of the all syn-
a,a,a,a-isomer.10 Conversely, anti-1 can be preferred by heating
a neat sample of syn/anti-1. Verification of the enrichment of
the neat sample in the anti-isomer was obtained by disolution
The advantage of using benzyl bromide as a trapping agent
is that it can be easily removed without involving heat, which
would subsequently equilibrate the isomers. Excellent yields
are achieved when syn-/anti-2 is subjected to H2 and Pd/C. By
removal of the benzyl ethers, a low rotational barrier is once
again achieved thereby quickly equilibrating the isomers at
ambient temperatures. This approach is a significant improve-
ment in the ‘‘erase’’ or equilibration process since extended
periods of time under high temperatures are required to achieve
c
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Chem. Commun., 2012, 48, 1296–1298 1297

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the same result with syn-/anti-2 and other ether derivatives.
Also much weaker interactions are used to control the
equilibrium ratio.
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In summary, slowly-rotating diol 1 can be chemically ‘‘trapped’’
by alkylating with benzyl bromide to favor the syn- or anti-isomer
under different equilibrium altering conditions. This is not only a
‘‘write’’ process but also a ‘‘rewritable’’ process since the benzyl
ethers can be easily removed to afford syn-/anti-1. One attractive
aspect of the system is the synthetic ease and mild manner with
which each desired isomer can be favored. Moreover, the half-life
of diol 1 at ambient temperatures is on the order of minutes as
opposed to hours with previously reported atropisomers of this
type. This greatly facilitates equilibration time.
This work was supported by the National Science Foundation
(CHE 1112431).
Notes and references
z The rate of isomerization of diol 1 adsorbed onto silica is sufficiently
slow at rt (t1/2 = 13 min) that a minimum of isomerization occurs on
the time scale of the TLC development. However, if diol 1 is left for
longer periods of time on the silica surface then isomerization occurs in
favor of the syn-isomer.
y The original isomeric enrichment of diol 1 appears to be even higher
than the observed isomeric ratios of the alkylated ether 2 samples. Thus,
some isomerization appears to be occurring during the alkylation
process. For example, crystals of pure anti-1 subjected to the alkylation
procedure resulted in a 1 : 4 (syn-/anti-) ratio of 2.
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c
1298 Chem. Commun., 2012, 48, 1296–1298
This journal is The Royal Society of Chemistry 2012