Intramolecular Diels Alder reactions in highly organized imidazolium salt-based ionic liquid crystals

Article abstract of DOI:10.1039/c4ra11693c

This paper describes the development of a new family of ionic liquid crystals based on imidazolium salts and their applications as media for intramolecular Diels Alder reactions. The use of highly organized smectic T phases was shown to be an efficient method to obtain the intramolecular Diels Alder product in high yields, without using high dilution conditions. The ionic liquid crystal media can be recycled in an easy procedure and reused up to at least five times, without loss of reactivity and selectivity.

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Intramolecular Diels Alder reactions in highly organized imidazolium
salts-based ionic liquid crystals
Tien Dat Doa and Andreea R. Schmitzer*a
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
5
DOI: 10.1039/b000000x
This paper describes the development of a new family of ionic liquid crystals based on imidazolium salts
and their applications as media for intramolecular Diels Alder reactions. The use of highly organized
smectic T phases showed to be an efficient method to obtain the intramolecular Diels Alder product in
high yields, without using high dilution conditions. The ionic liquid crystal media can be recycled in an
10 easy procedure and reused up to at least five times, without loss of reactivity and selectivity.
the transition state of the reaction. Leigh et al.9 showed that rodꢀ
Introduction
like organized LC favour the product resulting from a rodꢀlike
transition state over the product resulting from a globular
50 transition state. This effect was even more pronounced when the
liquid crystal was more organized, by reducing the diffusion rate
and the rotation of the substrate molecules.10 It is reasonable to
state that a LC state can isolate molecules dispersed into them
and that any isolation effect in obtained the isotropic phases. This
55 means that the isolation of the substrate molecules can be
controlled by the temperature.
Imidazoliumꢀbased thermotropic and lyotropic ionic liquid
crystals (ILCs) combine the selfꢀorganization properties of liquid
crystals (LC) with the unique solvent properties and ionꢀ
60 conducting properties of imidazoliumꢀbased ILs. The properties
of ILCs are significantly different from those of conventional
liquid crystals11 and change depending on the molecular
architecture of the salts and nature of the counterion used. Herein,
we report the synthesis, characterization of new ILCs and their
65 use as solvent for the intramolecular Diels Alder reaction. We
demonstrate that the organized structure of the liquid crystalline
phase favours the formation of the intramolecular DielsꢀAlder
product and the coordinating properties of the ILC accelerate the
reaction rate, compared to a classical LC.
The growing awareness of the use of environmentally benign
solvents has led to the increasing importance of ionic liquids as
alternative solvents for various organic reactions.1 Ionic liquids
15 (ILs) represent an interesting class of solvents, as they are liquid
at low temperatures, thermically and chemically stable and nonꢀ
volatile.2 Ionic liquids had shown significant advantages when
used as solvents for organic transformations, in terms of giving
similar to higher yields compared to those obtained in traditional
20 organic solvents, as well as a high recyclability.2,3,4,5 Ionic
liquids, by providing an ionic environment, may have a positive
effect on reactions possessing polar transition states. The solvent
effect is thus more pronounced in ionic liquids and some
condensation reactions, as the Diels Alder,4 Mannich5 or
25 Friedlander6 reactions have been conducted successfully in ionic
liquids. Imidazoliumꢀbased ionic liquids have been shown to
enhance the reaction rate and the stereoselectivity of the Diels
Alder reaction4 by hydrogen bonding of the most acidic hydrogen
of the imidazolium cation and the carbonyl group of the substrate.
30 However, the slow diffusion rate in ionic liquids and hence the
acceleration of the intermolecular reactions result in competitive
intermolecular products when ionic liquids are used as solvents
for the Diels Alder reaction.7 A common way to solve this
problem is the use of high dilution conditions, preventing the
35 reactant molecules to meet each other and to form intermolecular
product. However, this approach requires an important amount of
ionic liquids. Therefore, a successful strategy to obtain the
intramolecular Diels Alder (IMDA) product in high yields might
be to create a certain isolation of the reactant molecules in the
40 reaction mixture by using an organized media.
70
Results and discussion
Naphtalene core was previously reported to lower the transition
temperature of various LC.12 Recently, our group demonstrated
that dicationic ILCs based on imidazolium salts form a smectic T
75 phase.13 The transition temperatures being too high to be used as
organized solvents for an organic transformation, we decided to
replace phenyl core with a naphthalene moiety in order to reduce
the anisotropy of the mesogen and to lower the transition
temperature of the ILC (Scheme 1).
Liquid crystals (LC) are a class of compounds that can show
both unorganized and organized structures depending on the
temperature (thermotropic liquid crystals), or the composition of
the mixture (lyotropic liquid crystals).8 The highly organized
45 structure of LC has been showed to affect the outcome of organic
reactions performed in LC as reaction media, by interacting with
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up to 200oC, but the NTf2 salts were the most stable ones, up to
250oC.
X
H2n+1Cn
N
N
5
N
N
CnH2n+1
X
n = 12 (1a)
n = 12 (1b)
n = 12 (1c)
n = 12 (1d)
n = 12 (1e)
X = Br
n = 16 (2a)
X = Br
X = PF6
X = OTf
X = BF4
X = NTf2
n = 16 (2b)
n = 16 (2c)
n = 16 (2d)
n = 16 (2e)
X = PF6
X = OTf
X = BF4
X = NTf2
10
Scheme 1. Dialkyl (1,5-naphthalene)diimidazolium salts
40
The synthesis of the dialkyl (1,5ꢀnaphthalene)diimidazolium salts
from the 1,5ꢀdiimidazolenaphtalene is outlined in Scheme 2. All
Figure 1. Decomposition temperatures (based on 1% weight loss) of
dialkyl (1,5-naphthalene)diimidazolium salts
15 the compounds can be synthesized in grams scale in a fourꢀstep
procedure
from
the
commercially
available
1,5ꢀ
Liquid crystal properties
diaminonaphthalene, by a first diazotization reaction13 followed
by a copperꢀcatalyzed Ullmann reaction following the procedure
developed by Taillefer.14 The alkylation of the diimidazole
For all the compounds, their mesomorphic properties and phase
45 transition temperatures were investigated by differential scanning
calorimetry (DSC), polarizing optical microscopy (POM), and
powder Xꢀray diffractometry (PXRD). To avoid hydration of the
imidazolium salts, all the compounds were dried under vacuum
before the PXRD and DSC analyses. Only the NTf2 salts showed
50 a liquid ꢀ isotropic transition (Figure 2), also confirmed by
polarized optical microscope (POM).
20 intermediate
by
either
1ꢀbromododecane
or
1ꢀ
bromohexadodecane resulted in the desired bromide salts and
then different imidazolium salts were obtained by anion
metathesis. We decided to use fluorinated anions as NTf2, OTf,
PF6 and BF4 which generally result in nonꢀhygroscopic and more
25 acidic ionic liquids.1,15
C12H25
N
N
Br
C12H25Br
CH3CN
reflux
NaBF4
1b, 2b
1c, 2c
N
N
Br
C12H25
87%
N
N
KPF6
MeOH/H2O
1a
NH4OTf
LiNTf2
Reflux, 24h
84%-95%
C16H33
Br
1d, 2d
1e, 2e
N
N
N
N
C16H33Br
CH3CN
reflux
92%
N
N
Br
C16H33
Figure 2. DSC traces of 1e and 2e (second heating/cooling cycle).
2a
55
Scheme 2. Synthesis of dialkyl (1,5-naphthalene)diimidazolium salts
The phase transition temperatures and the corresponding enthalpy
changes derived for compounds 1e and 2e in both heating and
cooling cycles are shown in Table 1. Both compounds 1e and 2e
60 showed lancetꢀlike texture (Figure 3). The lancetꢀlike texture was
already reported in highly ordered liquid crystalline phase, for
example smectic E or smectic T phases.16 In the PXRD patterns
of both NTf2 salts, equidistant peaks were observed, showing the
lamellar structure of an ordered phase. In the wide angles region,
65 the broad hallow band was not observed, but sharp Bragg
reflections appeared, indicative of an ordered arrangement within
a smectic T phase for both compounds 1e and 2e. The unit cell
30 Thermophysical properties
The imidazolium salts were first characterized by
thermogravimetric analysis in order to study the effect of the
counterion and the length of the alkyl chain on the thermal
stability of these salts. Results presented in Figure 1 show that the
35 nature of the counterion has a higher influence on the thermal
stability of the imidazolium salts than the length of the alkyl
chains (NTf2ꢀ ≅BF4ꢀ > TfOꢀ > Brꢀ > PF6 ). All the salts were stable
ꢀ
2
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parameter a of the square lattice was 10.6 Å for both compounds
1e and 2e compounds, but the thickness of the layer was 27.7 Å
for 1e and 31.9 Å for 2e respectively, supporting the hypothesis
of a tetragonal structure of a smectic T phase. The value of 10.6
Å for parameter a is in agreement with the size of NTf2 anion
(6.6 Å). However, the thickness of the layer is smaller than the
estimated molecular length (8.4 Å). This observation suggests a
certain degree of interdigitation between two adjacent molecules.
5
10 Table 1. Phase transition temperatures and corresponding enthalpies ∆H
determined from 1st cooling and 2nd heating DSC thermograms
T/oC
Compounds
on heating
T/oC (Cr2→LC)
(∆H/J.gꢀ1)
T/oC (LC→I)
(∆H/J.gꢀ1)
(Cr1→Cr2)
(∆H/J.gꢀ1)
1e
2e
87 (33.4)
ꢀ
93 (11.6)
94 (58.3)
123 (7.5)
166 (8.2)
T/oC
(Cr1→Cr2)
(∆H/J.gꢀ1)
Compounds
on cooling
T/oC (Cr2→LC)
(∆H/J.gꢀ1)
T/oC (LC→I)
(∆H/J.gꢀ1)
1e
2e
55
ꢀ
57 (57.8)
65 (80.0)
117 (8.1)
162 (7.9)
Figure 3. PXRD pattern and POM image of 1e and 2e at 90oC.
a Abbreviations: Cr1, Cr2 for the solid crystalline phases (S in the DSC
traces), LC for liquid crystal phase, and I for isotropic phases.
40
15
ILCs as solvents for the intramolecular Diels Alder reaction
IMDA reaction is a very important reaction in organic synthesis,
as many CꢀC bonds can be formed at the same time and it can be
20 used as a tool to synthesize cyclic compounds17. Moreover,
substrates belonging to the esterꢀtethered 1,3,9ꢀdecatriene system
have low reactivity in the IMDA reaction, because their cis
conformation is not favored due to transꢀannular and nonꢀ
bonding electron pair interactions (Scheme 3).9
Figure 4. Schematic representation of the dispersion of the substrate in
the LC phase
45
25 As an alternative to the previously described high dilution
conditions in ILs for the IMDA reaction7, we decided to use ILCs
1e and 2e as solvent, hypothesising that the ILCs in the LC phase
will be able to disperse the substrate molecules and will favor the
intramolecular reaction (Figure 4).
30 We decided to perform the IMDA of various substrates at various
concentrations in both traditional bis(trifluoromethane
sulfonyl)imide 1ꢀbutylꢀ3ꢀmethylimidazolium [Bmim][NTf2] ionic
liquid and 1e, as it possess a lower transition temperature than
2e. The same procedure was applied when the traditional ionic
35 liquid was used as solvent.
O
O
H
O
O
H
Intramolecular
product
cis-conformer
O
O
O
O
O
O
trans-conformer
Intermolecular
product
Scheme 3. Intermolecular and Intramolecular Diels Alder products for
the ester-tethered 1,3,9-decatriene substrate
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As shown in Table 2, considerably less intermolecular product
conformers in the presence of 2 equivalents of IL and ILCs. First,
was obtained in the ILC 1e, compared to the traditional IL, even
the calculations correctly predict the endo selectivity for the
in high concentration conditions, for all the tested substrates. The 40 IMDA reaction in the presence of both IL and ILCs. The second
best results in terms of selectivity were obtained for the nonꢀ
substituted substrates, where no intermolecular product was
observed at 1:8, 1:16 and 1:32 substrate:ILC ratios. For substrates
presenting a substituent on the diene moiety, the intramolecular
conclusion that can be drawn when looking at the energy
difference between the cis and trans conformers, is that the cis
conformation is favored in the presence of the ILCs. The πꢀπ
between the diene unit and the naphthalene core, as well as the
5
product is the major product obtained and the intermolecular 45 additional hydrogen bond observed in this case may be
product was obtained also at less than 5%. However, all the
responsible for the higher specificity of the IMDA reactive
conformer.
The Diels Alder reactions performed in ILCs gave higher
conversions compared to the ones performed in traditional ionic
10 substrates possessing a substituent to the dienophile moiety
showed no reactivity in both IL and ILC, where no conversion
was obtained even after 36 hours. The presence of a substituent
on the dienophile moiety may cause steric hindrance in the 50 liquids. This increased reactivity is probably due to the more
transition state, preventing the reaction to take place.
acidic Hꢀ2 of the imidazolium cation in ILCs, due to its
conjugation with the naphthalene ring (Table 4). By hydrogen
bonding the carbonyl group of the substrate, the imidazolium
cation of the ILC may also lower the energy of the transition
15
Table 2. Diels Alder reactions in various dilution conditions
IL [Bmim][NTf2]
Isolated yield (%)
ILC (1e)
Isolated yield (%)
55 state.
Ratio
Substrate:
Solvent
1:4
1:8
1:16
Substrate
Inter
Intra*
Inter
Intra*
Table 4. B3LYP/6ꢀ31G(d) energy difference between conformers cis and
trans and length of hydrogen bonds of the cis conformer with IL and ILC
14
16
9
22
41
63
69
10
1
ꢀ
58
70
75
73
1:32
7
ꢀ
H bond 2
R2
O
H bond 1
O
1:4
1:8
1:16
1:32
15
12
13
8
54
48
53
68
5
3
2
2
72
75
71
73
H
H
R1
N
N
N
N
R2
R1
R1 and R2 represent the IL or ILCs substituents
1:4
1:8
1:16
1:32
8
8
7
6
52
57
54
63
6
5
5
5
71
72
71
73
Hydrogen bond 1
(Å)
Hydrogen bond 2
(Å)
ꢀE (cisꢀtrans)
(kcal/mol)
IL
2.38
ILC
5.01
IL
1.85
ILC
1.35
IL
none
ILC
1.61
*Only the endo diastereoisomer of the intramolecular product was
observed
20 The influence of the LC phase, compared to the solid phase was
studied by performing the same reaction at different
temperatures, under the same concentration (Table 3). It is not
surprising that performing the reaction in the solid state (at 50°C)
gave lower results in terms of selectivity and reactivity, compared
25 to those obtained in the LC phase.
60
Table 3. Influence of the solvent organization on the selectivity of the
Diels Alder reaction performed at 1:8 substrate:1e ratio
Isolated yields (%)
Substrate
Reaction at 50°C
Reaction at 90°C
65
Inter
Intra
Inter
Intra
20
31
1
70
30
The favoured intramolecular reaction in high concentration
conditions may be the result of the presence of the highly
organized structure of the smectic T phase around the substrate,
preventing two substrate molecules to react and give the
70 Figure 5. Optimized geometries of the 1,3,9-decatriene substrate with 2
equivalents of a) IL or b) ILCs (the NTf2 anions are not shown for clarity)
35 intermolecular product.
Table 4 and Figure 5 present data obtained for fully optimized
B3LYP/6ꢀ31G(d) geometries of cis and trans 1,3,9ꢀdecatriene
4
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55 10 (a) K. M. Lee, Y. T. Lee, J. B. Lin, J. Mater. Chem. 2003, 13, 1079;
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Recyclability of the ILC
After the reaction was completed, the reaction mixture was
extracted with diethyl ether and the ILC was directly reused for
further reactions. As shown in Table 5, the ILC can be reused up
to at least 5 catalytic runs, without loss of reactivity and
selectivity.
60
101; (e) J. M. Suisse, S. BelleminꢀLaponnaz, L. Douce, A. Maisseꢀ
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Table 5. Recycling of 1e after each Diels Alder reaction performed at 1:8
substrate:1e ratio (reaction performed at 90°C for 18 h)
Substrate
Catalytic run
Isolated yields (%)
Inter
Intra
72
70
74
74
1
2
3
4
5
1
2
1
1
1
15. S. Sowmiah, V. Srinivasadesikan, M.ꢀC. Tseng, Y.ꢀH. Chu,
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10 Conclusions
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In conclusion, we synthesized and characterized new family of
imidazolium saltsꢀbased ionic liquid crystals which exhibited
highly ordered smectic T phase, with transition temperatures
below 100oC. The use of these ILCs as reaction media in the
15 Diels Alder reaction allowed the formation of the intramolecular
products in high concentration conditions. Recycling studies
showed that the ionic liquid crystals were still active after at least
five catalytic runs without loss of reactivity or selectivity. These
new ILCs may be useful as reaction media for different
20 macrocyclization reactions, which may broaden the scope of this
methodology to other organic reactions.
Notes and references
a Département de Chimie, Université de Montréal, 2900 Édouard
Montpetit CP6128 Succursale centre ville, Montréal, H3C3J7, Qc,
25 Canada. *E-mail: ar.schmitzer@umontreal.ca
† Electronic Supplementary Information (ESI) available: general and
analytical methods, synthesis and characterization of the compounds,
TGA
curves
and
molecular
modelling
details.
See
DOI: 10.1039/b000000x/
30 ‡ We thank the Natural Sciences and Engineering Research Council of
Canada (NSERC), the Fonds Québécois pour la Recherche, la Nature et
les Technologies (FQRNT), the Centre in Green Chemistry and Catalysis
and the Université de Montréal for financial support. We thank S.
Essiembre and P. MénardꢀTremblay for assistance in PXRD and POM
35 studies.
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