Chirality-directed organogel formation

Article abstract of DOI:10.1070/MC2005v015n04ABEH002136

New low molecular mass enantiopure organogelators (1R,4R)-1, (5)-2, (R)-3 and (R)-4 were found; racemates (R,S)-3 and (R,S)-4 have only a moderate gelating power, whereas (R,S)-1 and (R,S)-2 do not show gelating properties at all.

Full text of DOI:10.1070/MC2005v015n04ABEH002136

, 2005, 15(4), 140–141
Chirality-directed organogel formation
Remir G. Kostyanovsky,* Denis A. Lenev, Oleg N. Krutius and Andrey A. Stankevich
N. N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, 119991 Moscow, Russian Federation.
Fax: +7 095 651 2191; e-mail: kost@chph.ras.ru
DOI: 10.1070/MC2005v015n04ABEH002136
New low molecular mass enantiopure organogelators (1R,4R)-1, (S)-2, (R)-3 and (R)-4 were found; racemates (R,S)-3 and (R,S)-4
have only a moderate gelating power, whereas (R,S)-1 and (R,S)-2 do not show gelating properties at all.
Van’t Hoff1 was captivated by an interesting experiment of
O
O
Wallerant:2(a) during the cooling of the melts of malonic acid
diamide in the presence of (+) or (–)-tartaric acids, helical
crystallization with the opposite senses of helicity was observed,
whereas the racemic acid did not produce such an effect.2(b)
This observation was further developed in the whole science of
a unique state of matter, a cholesteric mesophase. The chirality-
directed formation of a cholesteric mesophase from an achiral
nematic mesophase is a sensitive test for conglomerate formation.3
Another mesophase, namely, gels formed by low molecular
mass organic compounds, have attracted a lot of attention recently
due to their ubiquity and important applications,4 such as the
binding of oil in oil/water mixtures,4(b) the use as biocompatible
soft materials,4(c) pH-sensitive fluorescent probes,4(d) and other
interesting properties, more often associated with covalent poly-
meric assemblies.5 Note that such gels also show the effects of
chiral recognition: they often consist of helically twisted fibers
with the sence of helicity determined by the relative configura-
tion of a gelator, whereas racemates form regular crystals.6
These facts may be explained by a higher kinetic stability of an
enantiomeric mesophase due to difficulties of a rearrangement
to enantiomeric crystals.6
O
NH
HN
O
O
O
(1R,4R)-(–)-1aa
R
R'
X3C
R
Me
H
H
H
H
Me
H
NH
OH
n
m
O
R'
H
Et
Pri
Et
CO2Me
H
H
H
X
F
F
F
H
F
F
F
F
F
F
F
F
n
0
0
0
0
0
1
1
2
0
0
0
0
m
1
1
1
1
1
0
0
0
1
1
1
1
(S)-(–)-2aa
(R)-(+)-3aa
(R)-(+)-4aa
(R)-(+)-5a
(S)-(–)-6a
(R)-(–)-7aa
8
9
10
11
12
13
H
Me
Me
Here we describe new chiral amidic organogelators: diketo-
piperazine (1R,4R)-(–)-1a7 and compounds (S)-(–)-2a, (R)-(+)-3a,
( )-3b, (R)-(+)-4a in the series of amidoalcohols 2–13 (Figure 1,†
Table 1). These systems are of interest as promising chiral
stimuli-responsive gels.8
CH2OH CH2OH
CH2OH Me
CH2OH Et
aRacemates: ( )-1b, ( )-2b, ( )-3b, ( )-4b, ( )-7b.
Figure 1 Compounds studied as possible gelators.
Compounds 1a–4a and 4b reversibly gelate organic solvents
(Table 1) on heating at reflux to dissolution and cooling to room
temperature at minimum concentrations of 0.003–0.5 mol dm–3.
Figure 2 shows the formation of linear micrometre-sized aggre-
gates of organogelators 1a and 2a visualised by the atomic force
microscopy (AFM) of their xerogels (dried gels)† obtained from
methylcyclopentane or cyclohexane. The visual appearance of a
typical gel of compound (R)-(+)-3a is shown in Figure 3.
Note that racemates 1b and 2b, as well as compounds 5–10,
do not form stable gels in a variety of organic solvents. Com-
pounds 2b and 10, on cooling their solutions in light petroleum
(bp 70–100 °C), give a mixture of a solid phase and a gel at
50–55 °C; however, the gel disappears at 20 °C. The behaviour
of racemates 3b and 4b is different: they also have a moderate
gelating ability.
Under the hypothesis of enantioselective precipitation, we
attempted to resolve the enantiomers of 3b to form an optically
active gel. However, unsuccessfully: in a solution of 3b (1.2 g)
in cyclohexane (240 ml) at 35 °C, the seed of 3a (20 mg) in
cyclohexane (1 ml) was added. The mixture was kept at 20 °C
for 16 h. The gel precipitate was separated and evaporated under
a reduced pressure with the volume of the solvent in the cooling
trap equal to 34 ml. For 0.337 g of dry residue [a]D +1.06 (c 6.74,
MeOH). The mother liquor was evaporated, and the residue was
identified as pure racemate 3b.
Table 1 Gelating power of compounds 1–4: (+) gel, ( ) unstable gel, (–)
no gel, (n.d.) no data. Numbers indicate the minimum concentration for the
gelation, in 10–3 mol dm–3
.
2,3,4-Tri-
C6H6 C6F6 methyl- CHCl3 Et2O CCl4
pentane
Com- Light
Cyclo-
pound petroleum hexane
1aa
2aa
3ab
3b
4a
4b
–
6
3
3
3
3
–
18
30
n.d.
18
12
n.d.
18
6
–
100
–
n.d. n.d.
12
100 12
–
(120)
(30)
(50)
30
10
–
(30) (30) 30
–
–
–
–
60
50
100
15
–
50
–
25
–
>200
–
a1b and 2b do not form gels. bForms a gel at room temperature in heptane–
ethyl acetate, 7:1(v/v); at –18 °C, the gel is destroyed.
140 Mendeleev Commun. 2005

, 2005, 15(4), 140–141
Thus, we found that optically pure low molecular mass enantio-
pure amidoalcohols are organogelators, whereas the corresponding
racemates are not, either not forming gels, or forming unstable
gels in the narrow range of organic liquids.
(a)
We are grateful to V. A. Timofeeva (N. N. Semenov Institute
of Chemical Physics, Russian Academy of Sciences) for taking
the AFM pictures. This work was supported by the Russian
Academy of Sciences and the Russian Foundation for Basic
Research (grant nos. 03-03-32019 and 03-03-04010).
†
1a and 1b were described previously.7
(S)-(–)-2a was obtained by the reaction of (S)-(–)-alaninol with CF3CO2Et
in MeCN, yield 100%, mp 80 °C (MeCN) [lit.,10 mp 80–81 °C (C6H6)],
[a]D20 –14.1 (c 0.7, MeOH), [lit.,10 [a]D20 –15.3 (c 4.0, EtOH)]. 1H NMR
(b)
3
(CDCl3) d: 1.25 (d, 3H, Me, J 6.8 Hz), 3.67 (m, 2H, CH2, AB-part of
2
3
3
ABX-spectrum, ∆n 56.0 Hz, Jab –11.2 Hz, Jax 6.8 Hz, Jbx 5.2 Hz),
4.11 (qdd, 1H, HC, 3JHCMe = 3JHCCH = 6.8 Hz, 3JHCCH 5.2 Hz), 6.92 (br. s,
a
b
1H, NH).
( )-2b: yield 100%, mp 48–50 °C.
(R)-(+)-3a: yield 100%, mp 74–77 °C, [a]D20 +14.8 (c 3.6, MeOH).
1H NMR (C6D6) d: 0.63 (t, 3H, Me, 3J 7.5 Hz), 1.13 (m, CH2Me),
1.20 (br. s, 1H, OH), 2.97 (m, 2H, CH2O, AB-part of ABX-spectrum,
2
3
3
∆n 31.7 Hz, Jab –10.8 Hz, Jax 4.5 Hz, Jbx 3.4 Hz), 3.58 (m, 1H, CH),
5.42 (br. s, 1H, NH).
( )-3b: yield 100%, mp 59–61 °C.
(R)-(+)-4a: yield 100%, mp 85–86 °C, [a]D20 +7.01 (c 13.5, MeOH).
1H NMR (CDCl3) d: 0.96 (d, 3H, A-Me, 3J 6.8 Hz), 1.00 (d, 3H, B-Me,
3J 6.8 Hz), 1.96 (d hept, 1H, CH, 3J 6.8 Hz), 3.70–3.85 (m, 3H, HCCH2),
6.62 (br. s, 1H, NH).
Figure 2 AFM micrographs of the xerogels of (a) 1a from methylcyclo-
pentane (90×90 µm) and (b) 3a from cyclohexane (5×5 µm). Scale to the
right depicts the depth of the scan (nm) by brightness of the picture.
( )-4b: yield 100%, mp 64–65 °C.
(R)-(+)-5 was obtained from (R)-(+)-2-aminobutan-1-ol and AcOMe
in MeOH, yield 55%, liquid, [a]D20 +9.43 (c 1.4, MeOH). 1H NMR (CDCl3)
3
d: 0.94 (t, 3H, MeCH2, J 7.5 Hz), 1.54 (m, 2H, CH2Me), 2.00 (s, 3H,
MeCO), 2.36 (br. s, 1H, OH), 3.60 (m, 2H, CH2O, AB-part of ABX-
spectrum, ∆n 31.7 Hz, 2Jab –11.1 Hz, 3Jax 5.5 Hz, 3Jbx 3.7 Hz), 3.83 (m,
1H, CH), 6.00 (br. s, 1H, NH).
(S)-(–)-6 was obtained from (S)-(–)-serine methyl ester, yield 100%,
oily liquid, [a]D20 –27.2 (c 4.4, MeOH). H NMR (CDCl3) d: 3.2 (br. s,
1
1H, OH), 3.80 (s, 3H, Me), 4.00 (m, 2H, CH2O, AB-part of ABX-spec-
trum, ∆n 33.0 Hz, 2Jab –11.5 Hz, 3Jax 3.2 Hz, 3Jbx 3.4 Hz), 4.66 (m, 1H,
CH), 7.60 (br. s, 1H, NH).
Figure 3 Gel of (R)-(+)-3a in cyclohexane (a penicillin flask is turned
(R)-(–)-7a was obtained by the reaction of (R)-(–)-1-aminopropan-2-ol
upside down).
with CF3CO2Et, yield 100%, mp 33–35 °C, [a]D20 –25.7 (c 7.2, MeOH).
3
1H NMR (CDCl3) d: 1.07 (d, 3H, Me, J 6.2 Hz), 3.36 (m, 2H, CH2N,
References
2
3
AB-part of ABX-spectrum, ∆n 154.8 Hz, Jab –13.8 Hz, Jax 6.6 Hz,
3Jbx 3.3 Hz), 3.98 (m, 1H, CH), 7.11 (br. s, 1H, NH).
1
2
3
4
J. H. van’t Hoff, Die Lagerung der Atome in Räume, 3 Aufl., Viewg
und Sohn, Braunschweig, 1908.
(a) F. Wallerant, Compt. Rend., 1906, 1169; (b) F. Wallerant, Compt.
Rend., 1906, 555.
J. Jacques, A. Collet and S. H. Wilen, Enantiomers, Racemates and
Resolutions, Krieger Publishing Co., Malabar, Florida, 1994, p. 54.
(a) P. Terech and R. G. Weiss, Chem. Rev., 1997, 97, 3133; (b) D. R.
Trivedi, A. Ballabh and P. Dastidar, Chem. Mater., 2003, 15, 3971;
(c) P. D. Sawant and X. Y. Liu, Chem. Mater., 2002, 14, 3793;
(d) K. Sugiyasu, N. Fujita, M. Takeuchi, S. Yamada and S. Shinkai,
Org. Biomol. Chem., 2003, 1, 895.
( )-7b was obtained analogously, mp 60–62 °C (CHCl3).
8 was described previously without characteristics,11 obtained by the
reaction of 2-aminoethanol with CF3CO2Et in MeCN, yield 100%,
mp 33–35 °C (sealed capillary). 1H NMR (CDCl3) d: 1.55 (br. s, 1H, OH),
3
3.55 (dt, 2H, CH2N, JHCNH = 3JHCCH = 5.0 Hz), 3.82 (t, 2H, CH2O,
3J 5.0 Hz), 6.53 (br. s, 1H, NH).
9 was described previously,10 obtained by the reaction of 3-amino-
propanol with CF3CO2Et. 1H NMR (CDCl3) d: 1.8 (quint., 2H, CCH2C,
3
3J 5.8 Hz), 3.51 (q, 2H, CH2N, JHCNH = 3JHCCH = 5.8 Hz), 3.78 (t, 2H,
CH2O, 3J 5.8 Hz), 7.54 (br. s, 1H, NH).
5
(a) Polymer Gels: Fundamentals and Biomedical Applications, eds.
D. Derossi, K. Kajiwara, Y. Osada and A. Yamauchi, Plenum Press,
New York, 1991; (b) J.-M. Guenet, Thermoreversible Gelation of Poly-
mers and Biopolymers, Academic Press, London, 1992; (c) B. Jeong
and A. Gutowska, Trends Biotechnol., 2002, 20, 305.
J.-H. Fuhrhop, P. Schnieder, J. Rosenberg and E. Boekema, J. Am.
Chem. Soc., 1987, 109, 3387.
K. A. Lyssenko, D. A. Lenev and R. G. Kostyanovsky, Tetrahedron,
2002, 58, 8525.
H. Goto, H. Q. Zhang and E. Yashima, J. Am. Chem. Soc., 2003, 125,
10 was obtained by the reaction of 2-amino-2-methylpropan-1-ol with
CF3CO2Et, yield 86%, mp 94–98 °C (MeCN). 1H NMR (CDCl3) d: 1.40
(s, 6H, 2Me), 2.73 (br. s, 1H, OH), 3.65 (s, 2H, CH2), 6.46 (br. s, 1H, NH).
11: yield 100%, mp 92–93 °C (MeCN). 1H NMR ([2H6]acetone) d:
3.85 (s, 6H, 3CH2), 4.53 (br. s, 3H, 3OH), 7.55 (br. s, 1H, NH).
6
7
8
9
1
12: yield 100%, mp 112–114 °C. H NMR ([2H6]acetone) d: 1.33 (s,
3H, Me), 3.74 (m, 4H, 2CH2O, AB spectrum, ∆n 19.0 Hz, 2Jab –11.1 Hz),
7.58 (br. s, 1H, NH).
13: yield 100%, mp 77–78 °C. 1H NMR ([2H6]acetone) d: 0.88 (t, 3H,
Me, 3J 7.60 Hz), 1.84 (q, 2H, CH2Me, 3J 7.60 Hz), 2.78 (br. s, 2H,
2OH), 3.73 (m, 4H, 2CH2O, AB spectrum, ∆n 43.2 Hz, 2Jab –10.8 Hz),
7.40 (br. s, 1H, NH).
2516.
T. Tachibana, S. Kitazawa and H. Takeno, Bull. Chem. Soc. Jpn., 1970,
43, 2418.
AFM sample preparation. Hot solutions of the gelators were sand-
wiched between two glass plates (1×1 cm) by capillary forces and left to
cool to room temperature, the solvents slowly evaporated at atmospheric
pressure. The top cover was removed when the surface became opaque.
AFM was done with a Smena microscope (ND MDT, Zelenograd) in a
half-contact mode at a rate of 1.2 scan s–1, cantelever NSG 11 (type B,
radius 10 nm).
10 P. I. Svirskaya, C. C. Leznoff and M. Steinman, J. Org. Chem., 1987,
52, 1362.
11 G. M. J. Slusarczuk and M. M. Joullie, J. Chem. Soc., Chem. Commun.,
1970, 469.
Received: 7th February 2005; Com. 05/2459
Mendeleev Commun. 2005 141