Functionalized ionic liquids with highly polar polyhydroxylated appendages and their rapid synthesis via thiol-ene click chemistry

Article abstract of DOI:10.1016/j.tetlet.2011.07.126

The thiol-ene 'click' reaction of 1-thioglycerol with ionic liquids incorporating cations bearing appended vinyl- and/or allyl groups is a versatile, single-step means for their conversion into derivatives bearing up to eight hydroxyl groups per cation.

Full text of DOI:10.1016/j.tetlet.2011.07.126

Tetrahedron Letters 52 (2011) 5173–5175
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Functionalized ionic liquids with highly polar polyhydroxylated appendages
and their rapid synthesis via thiol-ene click chemistry
Richard A. O’Brien a, Arsalan Mirjafari a, Vijayakumari Jajam b, Erin N. Capley a, Alexandra C. Stenson a,
Kevin N. West b, James H. Davis Jr. a,b,
⇑
a Department of Chemistry, The University of South Alabama, Mobile, Alabama 36688, USA
b Department of Chemical & Biomolecular Engineering, The University of South Alabama, Mobile, Alabama 36688, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
The thiol-ene ‘click’ reaction of 1-thioglycerol with ionic liquids incorporating cations bearing appended
vinyl- and/or allyl groups is a versatile, single-step means for their conversion into derivatives bearing up
to eight hydroxyl groups per cation.
Received 3 March 2011
Revised 25 July 2011
Accepted 27 July 2011
Available online 3 August 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Functionalized or ‘task-specific’ ionic liquids (TSILs) have been
subjects of considerable scrutiny for the past decade.1 Distinguished
from more conventional ILs by way of incorporating ion-tethered
functional groups, these salts have proven useful in applications
ranging from separations to catalysis. However, since the functional
groups in TSILs are generally heteroatom based, their syntheses
routinely demand careful planning to minimize the formation of
undesired byproducts from competing side reactions.2 Conse-
quently, approaches which stress the assembly of molecular targets
by way of reactions orthogonal to those undergone by the targeted
functional group ought to be of great interest to those working in
the area. In this context, we recently reported3 the first express
application of the Sharpless et al.4 ‘click’ concept to the preparation
of TSILs, specifically new amine-functionalized ILs for CO2-capture.5
While the latter can be vexing to prepare by other means, our
two-step click approach involving sequential ring-opening and neu-
tralization reactions enabled us to prepare cleanly and in very high
yields a library of 70+ TSILs in a remarkably short period of time.3
Impressed by the power of the click paradigm, we have become
attentive to new developments in the area. One we find to be of par-
ticular note is the radical-based thiol-ene reaction, which has re-
cently been used to superb effect in the preparation of highly
functionalized dendrimers and related macromolecules.6 Because
of the possibility for rearrangement of these reactive intermediates,
radical-based reactions can be problematic; however, the thiol-ene
reaction is reputed to be well-behaved and to consistently produce
high yields of targeted products. Accordingly, we decided to at-
tempt thiol-ene reactions on a handful of ene-functionalized ILs to
assess its potential utility in TSIL synthesis. Here we report our
results.
Four ILs (1–4, Fig. 1) were selected as ene substrates for the
study. In each case, the IL cation was imidazolium-based and bore
an appended N-vinyl or N-allyl group. These were chosen to assess
the effect, if any, of having the alkene connected directly to the
center of cationic charge versus being separated from it. Likewise,
a variety of anions were used as elements of the substrate salts,
providing us an opportunity to observe any noticeable control ex-
erted by them over the course of the reaction. Finally, in this initial
screening we used a single thiol, 1-thioglycerol, for the photoaddi-
tion reactions. The latter has been shown by others to reliably
photoadd to alkenes, and its use in the present case allowed us
to demonstrate the incorporation of a targeted group (AOH) into
an IL by way of the orthogonal reaction of ene-bearing IL ions
and a building block bearing both the functional group of interest
and the requisite thiol moiety. Equally important, it would provide
(if successful) very direct, simple access to imidazolium ILs with
glyceryl-like vic-diol moieties. We note that such ILs have been
shown by Chiappe et al. to be ‘‘more favourable in comparison with
the ‘‘classical’’ ionic liquids such as BMIM-based ones’’ in the Heck
reaction, and that they ‘‘evidenc[e] good catalyst stability and a
high recyclability’’.7
The coupling reaction of thioglycerol to 1–4 was carried out
using an approach modeled on that used by Hawker et al. for the
thiol-ene based assembly of functionalized dendrimers.8 We found
methanol to be well-suited as the reaction solvent, but there was
no conspicuous improvement in outcomes when the reactions
were conducted under nitrogen. Also, in our hands the use of
small quantities of DMPA (2,2-dimethoxy-2-phenyl) acetophenone)
relative to alkene (mol/mol) gave erratic results under air or N2,
prompting us to significantly increase the amount of this
photoiniator used in each reaction. While the mechanistic basis
for this apparent diminution in catalyst efficiency from that
normally observed is unclear, our use of larger quantities did not
⇑
Corresponding author.
E-mail address: jdavis@jaguar1.usouthal.edu (J.H. Davis Jr.).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.07.126

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R. A. O’Brien et al. / Tetrahedron Letters 52 (2011) 5173–5175
The reactivity of the vicinal diol groups in the new ILs does
ILs 1 - 8
not appear to deviate from established norms as a consequence
of their proximity to cationic centers. For example, 3T readily
forms the new acetal-containing IL 9T when combined with
2-propanone and an acid catalyst (pTSA). However, as might be
expected, the new ILs are visibly more viscous than ILs that are
thioether-containing structural counterparts which lack the
highly polar AOH groups. Having shown in earlier work9 that
cation-tethered functional groups can profoundly affect the
solvent characteristics (Abraham parameters) of ILs, we thought
it useful to determine the temperature-dependent viscosity of a
representative IL from the present work, and to likewise deter-
mine the same property for an (otherwise) exact analog devoid
of the vic-OH groups (IL 10, Fig. 1). As anticipated, the viscosity
of 3T proved to be significantly higher than that of 10, almost
an order of magnitude so near ambient conditions, although the
density of the former is only marginally greater (Fig. 2; Table 1
[Supplementary data]). Both of these trends are consistent with
increased inter-particle interaction brought upon by the inclusion
of strongly associating hydroxyl groups, behavior anticipated by
Chiappe et al.7
1
2
Tf2N
Br
3
4
Tf2N
Br
N
N
N
N
N
5
6
7
Tf2N
I
Tf2N
Br
N
N
8
Cations of ILs 1T-8T
N
N
N
S
OH
OH
OH
N
S
OH
Given the ease with which 1–4 were functionalized, we ex-
panded the scope of the study to ILs with ions bearing more than
one ene group (Fig. 1). We did so using salts 5–8, all of which were
prepared using standard approaches. When combined with thio-
glycerol and irradiated under the same conditions as 1–4, the
anticipated polyaddition products were formed quantitatively
(NMR) and isolated in good yields. The structures of the four cation
types incorporated in ILs 1T–8T (T, thioglycerol addition product)
are shown in Figure 1.
OH
HO
S
N
N
S
OH
OH
HO
HO
S
OH
OH
Both the 1H and 13C NMR spectra of each IL 5T–8T unambigu-
ously shows complete thiolation, which is readily ascertained on
the basis of peak integration (1H) and the disappearance of the
olefinic peaks (1H, 13C) of the starting cations. However, in neither
the ESI-MS of 7T or 8 is the expected parent ion of m/z = 611 ob-
served. Instead, each produces a high-mass ion with m/z = 394,
consistent with a structure in which two of the four thioglycerol
moieties have been cleaved, leaving two intact while re-generating
two of the original N-tethered allyl moieties. This retro-thiolation
is likely promoted by severe steric crowding around the central N
of these ions, a structural attribute that is obvious upon inspection
of simple digital (ChemDraw 3D) molecular models of these
entities.
HO
S
N
S
OH
HO
S
OH
IL 9T
O
N
N
Tf2N
S
O
IL 10
Overall, the present results indicate that the construction of
functionalized ILs using the thiol-ene reaction offers considerable
promise as an easy means by which to create structurally elabo-
rated IL ions. Specifically, ILs with multiple hydroxyl and thioether
functional groups are readily prepared by the photoinitiated rad-
ical coupling of 1-thioglycerol and salts of imidazolium and qua-
ternary ammonium cations bearing tethered allyl and/or vinyl
groups. Neither the proximity of the unsaturated appendage to
the charge locus (cf., vinylic vs allylic), the nature of the cation
as aromatic (imidazolium) or nonaromatic (quaternary ammo-
nium), or the nature of the anion appears to have a material effect
on the ease with which the couplings can be accomplished. The
reactions proceed quickly and cleanly, and usually give acceptable
yields of products without optimization. The solubility character-
istics of the ionic products makes them easy to separate from
photoiniator and excess thiol by simply washing with appropriate
solvents. The incorporation of two hydroxyl groups per cation per
tethered ene moiety gives the resulting ions richly polar append-
ages with multiple H-bond donor and acceptor sites, features
which have a significant, temperature-dependent impact on the
viscosity of these ILs.
N
N
Tf2N
S
Figure 1. Structures of the ene-functionalized IL starting materials (upper left) and
the ions resulting from their photoinduced thiol-ene reaction with 1-thioglycerol
(right). The structures of the acetal derivative of IL 3T and the nonhydroxylated IL 10
are also depicted (lower left).
complicate the workup and isolation of the products. Indeed, the
photoiniator is readily removed by washing the reaction residue
(after methanol removal) with hexane, in which none of the
starting or product ILs is soluble. Likewise, in the case of the Tf2NÀ
salts, any residual/excess thioglycerol was easily removed by
washing with water, with which those ILs were immiscible. The
new ILs were isolated as yellow oils which do not appear to
undergo any visible phase transitions when cooled (3T and 10,
for example, undergo no transitions down to À50 °C [DSC]). The
1H and 13C NMR spectra of each new IL fully comport with its
proposed structure and formulation, as does its ESI-mass spectrum.

R. A. O’Brien et al. / Tetrahedron Letters 52 (2011) 5173–5175
5175
10000
1000
100
1.5
1.4
1.3
1.2
1.1
1.0
10
0
20
40
60
80
Temperature ( °C)
Figure 2. The viscosity (circles) and density (squares) for 10 (open markers) and 3T (filled markers) from 10 to 80 °C. The lines are fit models for each data set.
2. Davis, J. H., Jr.; Wasserscheid, P. Ionic Liquids in Synthesis, 2nd ed.; Wiley-VCH:
Weinheim, 2008. pp 45–55.
Acknowledgments
3. Soutullo, M. D.; Odom, C. I.; Wicker, B. F.; Henderson, C. N.; Stenson, A. C.; Davis,
J. H., Jr. Chem. Mater. 2007, 19, 3581–3583.
4. Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem., Int. Ed. 2001, 40, 2004–
2021.
5. Bates, E. D.; Mayton, R. D.; Ntai, I.; Davis, J. H., Jr. J. Am. Chem Soc. 2002, 124, 926–
927.
J.H.D. and K.N.W. thank Chevron for partial support of this
work. A.C.S. and J.H.D. thank the National Science Foundation for
an MRI Grant (1039944) used to purchase the linear ion trap mass
spectrometer used in this work.
6. (a) Franc, G.; Kakkar, A. K. Chem. Soc. Rev. 2010, 39, 1536–1544; (b) Hoyle, C. E.;
Bowman, C. N. Angew. Chem., Int. Ed. 2010, 49, 1540–1573.
7. Bellina, F.; Bertoli, A.; Melai, B.; Scalesse, F.; Signori, F.; Chiappe, C. Green Chem.
2009, 11, 622–629.
Supplementary data
8. (a) Kang, T.; Amir, R. J.; Khan, A.; Oshimizu, K.; Hunt, J. N.; Sivanandan, K.;
Montanez, M. I.; Molkoch, M.; Ueda, M.; Hawker, C. J. Chem. Commun. 2010,
1556–1558; (b) Montanez, M. I.; Campos, L. M.; Antoni, P.; Hed, Y.; Walter, M.
V.; Krull, B. T.; Khan, A.; Hult, A.; Hawker, C. J.; Malkoch, M. Macromolecules
2010, 43, 6004–6013; (c) Killops, K. L.; Campos, L. M.; Hawker, C. J. J. Am. Chem.
Soc. 2008, 130, 5062–5064.
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2011.07.126.
References and notes
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