Reversible sol-gel transition of a tris-urea gelator that responds to chemical stimuli

Article abstract of DOI:10.1016/j.tetlet.2007.10.090

Tris-urea 1 functioned as a low-molecular-weight gelator for a variety of polar organic solvents. An acetone gel of 1 became a homogeneous solution in response to the addition of anions. The minimum amount of anion necessary for the gel-sol transition was

Full text of DOI:10.1016/j.tetlet.2007.10.090

Available online at www.sciencedirect.com
Tetrahedron Letters 48 (2007) 8990–8993
Reversible sol–gel transition of a tris–urea gelator that responds
to chemical stimuli
Masamichi Yamanaka,a,* Tomohiko Nakamura,a Tomoe Nakagawaa and
Hideyuki Itagakib,c
aDepartment of Chemistry, Faculty of Science, Shizuoka University, 836 Ohya, Suruga-ku, Shizuoka 422-8529, Japan
bGraduate School of Electronic Science and Technology, Shizuoka University, Japan
cSchool of Education, Shizuoka University, Japan
Received 20 September 2007; revised 13 October 2007; accepted 18 October 2007
Available online 22 October 2007
Abstract—Tris–urea 1 functioned as a low-molecular-weight gelator for a variety of polar organic solvents. An acetone gel of 1
became a homogeneous solution in response to the addition of anions. The minimum amount of anion necessary for the gel–sol
transition was specific to the anion species. A linear relationship was demonstrated between the amount of anion required and
the total binding constant of 1 with the anion. Re-gelation occurred by addition of BF3ÆOEt2 and with ultrasound irradiation of
the acetone solution of 1 and FÀ.
Ó 2007 Elsevier Ltd. All rights reserved.
Researches on low-molecular-weight gelators have been
paid much attention in recent years.1 Reversible sol–gel
transitions in gelators responsive to various stimuli such
as light,2 redox,3 counter ions,4 and pH5 have been
achieved by various designs of gelators. Molecular rec-
ognition by designed artificial host molecules has
received much attention in recent decades.6 Tripodal
structures with binding cavities have widely investigated
as synthetic receptors for anions,7 sugars,8 and other
species.9 Sol–gel transitions responsive to chemical stim-
uli can be achieved by introduction of an artificial host
molecule into a low-molecular-weight gelator. Indeed
recently, the aggregation of urea or pyromellitamide
gelators was inhibited by anion binding.10 We report
here that a C3-symmetric tris–urea gelator 1 showed
reversible sol–gel transition in response to chemical
stimuli.
Tris–urea 1 was synthesized in three steps from 1,3,5-
tris(bromomethyl)-2,4,6-triethylbenzene (2) as shown
in Scheme 1. Trinitro compound 3 was prepared by
the reaction of 2 with 3 equiv of 3-nitrophenol. Nitro
groups of 3 were reduced with tin chloride in 1,4-diox-
Scheme 1. Synthesis of tris–urea 1.
Keywords: Gels; Host–guest chemistry; Phase transitions; Self-assembly;
Ureas.
ane solvent to afford triamine 4. The target tris–urea 1
*
was obtained by the reaction of 4 with phenyl
isocyanate.
Corresponding author. Tel.: +81 54 238 4936; fax: +81 54 237
3384; e-mail: smyaman@ipc.shizuoka.ac.jp
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.10.090

M. Yamanaka et al. / Tetrahedron Letters 48 (2007) 8990–8993
8991
Figure 1. Photographs of acetone gel of 1 responded to chemical stimuli: (a) acetone gel of 1 (2.0 wt %); (b) acetone gel of 1 (2.0 wt %) containing
(from left) 1.1 equiv of TBAF, 1.7 equiv of TBACl, and 10 equiv of TBABF4; (c) BF3ÆOEt2 (1.0 equiv for TBA salt) mixture after sonication of 1 and
TBAF (left) or TBACl (right) in acetone; (d) ZnBr2 (1.0 equiv for TBA salt) mixture after sonication of 1 and TBAF (left) or TBACl (right) in
acetone.
An acetone suspension of 1 formed a translucent gel
after brief sonication11 (critical gelation concentration:
CGC = 1.5 wt %) (Fig. 1a). Once formed the gel was
stable at ambient temperatures for at least several
months without crystallizing or melting. Cooling of a
thermally dissolved acetone solution of 1 resulted in pre-
cipitation and no gel formation. Ultrasound irradiation
may cause desolvation of 1 and trigger the gelation.
Brief sonication of mixtures of tris–urea 1 and polar
organic solvents including diethyl phthalate (CGC =
2.0 wt %), MeOH (CGC = 2.0 wt %), and THF
(CGC = 5.0 wt %) also resulted in gel formation. How-
ever, mixtures of 1 and non-polar solvents such as hex-
ane, toluene, and dichloromethane did not form gels.
Scanning electron microscopy (SEM) images of a xero-
gel prepared by freeze-drying of acetone or MeOH gels
showed intertwining nanofibers (see Supplementary
data). Fibrous aggregates would primarily form from
self-complementary hydrogen bonding of urea moieties.
Neither tris–amide (5) nor tris-N-methyl urea (6) deriv-
atives gave gels (Fig. 2). FT-IR spectroscopy of a sample
of xerogel of 1 had a peak assigned to the carbonyl
stretching at 1645 cmÀ1. Compared with the carbonyl
stretching peak of amorphous 1 (1655 cmÀ1), the peak
approximately 1.7 equiv of Me4NCl, Et4NCl, and
n-Pr4NCl were required for a complete gel–sol phase
transition similar to that with n-Bu4NCl. Addition of
1.6 equiv of AcOÀ also resulted in a homogeneous solu-
tion. AÀwhite suspension was obtained when phosphate
H2PO4 was mixed with an acetone gel of 1. It is note-
À
worthy that addition of BF4 never caused complete
À
phase transition of the gel, and 10 equiv of BF4 caused
slight melting of the gel (Fig. 1b).
The variation in the amount of anions required for com-
plete gel–sol phase transition should be based on the dif-
ferential binding constants of 1 and the anions involved.
Titration experiments of 1 with a range of anions were
1
carried out by using H NMR in acetone-d6. Data from
titration experiments were analyzed using the curve-
fitting program HypNMR.13 Titration results of halide
ions and AcOÀ were fitted with 1:anion stoichiometry
of 1:3. The total binding constant (logb13) for FÀ was
calculated at 11.61 (logK11 = 5.05, logK12 = 3.45,
logK13 = 3.11) and the estimated error was 21%. In
the case of FÀ, coexistence of deprotonation of the urea
moiety may be responsible for such a large error.14 The
other values of logb13 were calculated at 10.23, 8.81,
7.44, and 9.78 for ClÀ, BrÀ, IÀ, and AcOÀ, respectively,
with errors less than 10%. A linear correlation was dem-
onstrated between logb13 and the minimum amount of
anion required for complete gel–sol transition (Fig. 3).
was shifted to a lower wave number (mamorphous À mgel
=
10 cmÀ1) (see Supplementary data). The shift provides
evidence for the existence of intermolecular hydrogen
bonds of 1 in the gel.12
An acetone gel of 1 (2.0 wt %) formed a homogeneous
solution on addition to the gelator of FÀ (n-Bu4N+FÀ)
in excess (P1.1 equiv) (Fig. 1b). Addition of less than
1.1 equiv of FÀ caused partial disintegration of the gel.
Completion of this phase transition took 12 h at room
temperature, 2 h at 45 °C, and less than 5 min at room
temperature with sonication. Experiments on phase
transitions of an acetone gel of 1 (2.0 wt %) were
performed using a range of anions (n-Bu4N+XÀ). The
minimum amount of halide ions required for complete
gel–sol phase transition increased with the size of ionic
radius. The amounts were 1.7 equiv, 2.0 equiv, and
2.9 equiv for ClÀ, BrÀ and IÀ, respectively (Fig. 1b).
As disintegration of gel is principally caused by anions,
Figure 2. Structure of tris–amide and tris-N-methylurea 5 and 6.

8992
M. Yamanaka et al. / Tetrahedron Letters 48 (2007) 8990–8993
bility Study, Japan Science and Technology Agency.
The research was partially carried out using an instru-
ment at the Center for Instrumental Analysis of
Shizuoka University.
Supplementary data
Experimental details and spectroscopic data can be
found in the PDF format. Supplementary data associ-
ated with this article can be found, in the online version,
at doi:10.1016/j.tetlet.2007.10.090.
References and notes
Figure 3. Plot of total binding constants of 1 with anions in acetone-d6
and minimum amount of anions required for the complete gel–sol
transition.
1. (a) Terech, P.; Weiss, R. G. Chem. Rev. 1997, 97, 3133–
3159; (b) van Esch, J. H.; Feringa, B. L. Angew. Chem.,
Int. Ed. 2000, 39, 2263–2266.
2. (a) Murata, K.; Aoki, M.; Suzuki, T.; Harada, T.;
Kawabata, H.; Komori, T.; Ohseto, F.; Ueda, K.; Shinkai,
S. J. Am. Chem. Soc. 1994, 116, 6664–6676; (b) de Jong, J.
J. D.; Lucas, L. N.; Kellogg, R. M.; van Esch, J. H.;
Feringa, B. L. Science 2004, 304, 278–281; (c) Eastoe, J.;
Self-aggregation of the gel could be Àreversed by anion
recognition. Titration results for BF4 were curve-fitted
with a 1:anion stoichiometry of 1:1, and the smallest
binding constant (logK11 = 1.27) for BF4À, which could
not cause the gel–sol transition.
´
Sanchez-Dominguez, M.; Wyatt, P.; Heenan, R. K. Chem.
Commun. 2004, 2608–2609.
3. Kawano, S.; Fujita, N.; Shinkai, S. J. Am. Chem. Soc.
2004, 126, 8592–8593.
4. Kim, H.-J.; Lee, J.-H.; Lee, M. Angew. Chem., Int. Ed.
2005, 44, 5810–5814.
An additional focus was on re-gelation in solutions
where gel disintegration had occurred through the addi-
tion of anions. Specific re-gelation would enable identi-
fication of the anions involved. The reaction of a
fluoride ion with boron trifluoride gave a tetrafluorobo-
rate ion15 which did not cause disintegration of the gel.
Addition of boron trifluoride etherate (BF3ÆOEt2) to the
acetone solution of 1 and FÀ caused re-gelation after
brief sonication (Fig. 1c). This sol–gel phase transition
could be repeated at least four times.16 The other ace-
tone solution of 1 and anions were attempted to re-gel-
ate by adding BF3ÆOEt2. Re-gelation was also proceeded
in the solution including AcOÀ after sonication. Homo-
geneous solutions remained unchanged with added
BF3ÆOEt2 for the solutions involving ClÀ, BrÀ, or IÀ
(Fig. 1c). Further experiments showed that ZnBr2 acted
as a non-specific chemical stimulus for re-gelation of an
acetone solution of 1 and anions. In contrast to
BF3ÆOEt2, ZnBr2 re-gelated all solutions containing
FÀ, ClÀ, BrÀ, IÀ, or AcOÀ (Fig. 1d).
5. (a) van Bommel, K. J. C.; van der Pol, C.; Muizebelt, I.;
Friggeri, A.; Heeres, A.; Meetsma, A.; Feringa, B. L.; van
Esch, J. H. Angew. Chem., Int. Ed. 2004, 43, 1663–1667;
(b) Hwang, I.; Jeon, W. S.; Kim, H.-J.; Kim, D.; Kim, H.;
Selvapalam, N.; Fujita, N.; Shinkai, S.; Kim, K. Angew.
Chem., Int. Ed. 2007, 46, 210–213.
6. (a) Beer, P. D.; Gale, P. A. Angew. Chem., Int. Ed. 2001,
40, 486–516; (b) Lavigne, J. J.; Anslyn, E. V. Angew.
Chem., Int. Ed. 2001, 40, 3118–3130; (c) Rudkevich, D. M.
Bull. Chem. Soc. Jpn. 2002, 75, 393–413.
7. (a) Wallace, K. J.; Belcher, W. J.; Turner, D. R.; Syed, K.
F.; Steed, J. W. J. Am. Chem. Soc. 2003, 125, 9699–9715;
(b) Turner, D. R.; Paterson, M. J.; Steed, J. W. J. Org.
Chem. 2006, 71, 1598–1608; (c) Tajc, S. G.; Miller, B. L. J.
Am. Chem. Soc. 2006, 128, 2532–2533; (d) Bhattarai, K.
M.; del Amo, V.; Magro, G.; Sisson, A. L.; Joos, J. B.;
Charmant, J. P. H.; Kantacha, A.; Davis, A. P. Chem.
Commun. 2006, 2335–2337; (e) Hisaki, I.; Sasaki, S.;
Hirose, K.; Tobe, Y. Eur. J. Org. Chem. 2007, 607–
615.
In conclusion, we have demonstrated that tris–urea 1
acts as low-molecular-weight gelators for a variety of
polar organic solvents, and that reversible sol–gel transi-
tions occur in response to chemical stimuli. These find-
ings may lead to a simple and convenient anion
detection method based on the principles of molecular
recognition.
8. (a) Vacca, A.; Nativi, C.; Cacciarini, M.; Pergoli, R.;
Roelens, S. J. Am. Chem. Soc. 2004, 126, 16456–16465; (b)
Nativi, C.; Cacciarini, M.; Francesconi, O.; Vacca, A.;
Moneti, G.; Ienco, A.; Roelens, S. J. Am. Chem. Soc.
2007, 129, 4377–4385.
9. (a) Metzger, A.; Lynch, V. M.; Anslyn, E. V. Angew.
Chem., Int. Ed. 1997, 36, 862–865; (b) Niikura, K.;
Metzger, A.; Anslyn, E. V. J. Am. Chem. Soc. 1998, 120,
8533–8534; (c) Kim, S.-G.; Kim, K.-H.; Jung, J.; Shin, S.
K.; Ahn, K. H. J. Am. Chem. Soc. 2002, 124, 591–596; (d)
´
`
Ballester, P.; Capo, M.; Costa, A.; Deya, P. M.; Gomila,
R.; Decken, A.; Deslongchamps, G. J. Org. Chem. 2002,
67, 8832–8841; (e) Dai, Z.; Xu, X.; Canary, J. W. Chem.
Commun. 2002, 1414–1415; (f) Mazik, M.; Cavga, H. J.
Org. Chem. 2007, 72, 831–838.
Acknowledgments
We thank Professor Kenji Kobayashi (Shizuoka Univer-
sity) for helpful discussions. We also thank Professor
Fraser Hof (University of Victoria) for his valuable
comments. This study was supported partially by Feasi-
10. (a) Stanley, C. E.; Clarke, N.; Anderson, K. M.; Elder, J.
A.; Lenthall, J. T.; Steed, J. W. Chem. Commun. 2006,

M. Yamanaka et al. / Tetrahedron Letters 48 (2007) 8990–8993
8993
3199–3201; (b) Webb, J. E. A.; Crossley, M. J.; Turner, P.;
Thordarson, P. J. Am. Chem. Soc. 2007, 129, 7155–7162.
11. (a) Naota, T.; Koori, H. J. Am. Chem. Soc. 2005, 127,
9324–9325; (b) Isozaki, K.; Takaya, H.; Naota, T. Angew.
Chem., Int. Ed. 2007, 46, 2855–2857.
14. Wu, Y.; Peng, X.; Fan, J.; Gao, S.; Tian, M.; Zhao, J.;
Sun, S. J. Org. Chem. 2007, 72, 62–70.
15. Moss, R. A.; Shen, S.; Krogh-Jespersen, K.; Potenza, J.
A.; Schugar, H. J.; Munjal, R. C. J. Am. Chem. Soc. 1986,
108, 134–140.
12. Kiyonaka, S.; Sada, K.; Yoshimura, I.; Shinkai, S.; Kato,
N.; Hamachi, I. Nat. Mater. 2004, 3, 58–64.
13. Gans, P. HypNMR 2006, Protonic Software.
16. Five times phase transition from gel to solution by adding
fluoride ion produce a slight insoluble precipitate, but, re-
gelation by addition of BF3ÆOEt2 was achieved.