Highly efficient synthesis of [3]- and [5]-rotaxanes consisting of crown ether and a sec-ammonium salt

Article abstract of DOI:10.1039/b207872d

[3]- and [5]-rotaxanes consisting of crown ether and ammonium salts were synthesized in high yields by a tributylphosphine-catalyzed end-capping method which provides a simple and practical means of obtaining higher-order rotaxanes.

Full text of DOI:10.1039/b207872d

Highly efficient synthesis of [3]- and [5]-rotaxanes consisting of crown
ether and a sec-ammonium salt
Nobuhiro Watanabe, Takaya Yagi, Nobuhiro Kihara and Toshikazu Takata*
Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University,
Gakuen-cho 1-1, Sakai, Osaka 599-8531, Japan. E-mail: takata@chem.osakafu-u.ac.jp;
Fax: +81-72-254-9910; Tel: +81-72-254-9290
Received (in Cambridge, UK) 12th August 2002, Accepted 10th October 2002
First published as an Advance Article on the web 23rd October 2002
[3]- and [5]-rotaxanes consisting of crown ether and
ammonium salts were synthesized in high yields by a
tributylphosphine-catalyzed end-capping method which
provides a simple and practical means of obtaining higher-
order rotaxanes.
Table 1. [3]Rotaxane 3c was isolated in 64% yield while
[2]rotaxane 2c was also obtained in 30% yield.7 As the length of
the spacer (R) decreased, the yield of rotaxanes decreased. The
first complexation seemed to inhibit the second complexation in
the case of a shorter spacer.8 When an ethylene spacer was used
(1a), only a small percentage of [2]rotaxane was obtained. The
solubility of 1a in organic solvents was too low to form the
pseudorotaxane. Based on the above results, the reaction
condition was optimised for the preparation of [3]rotaxane 3c:
3c was obtained in 85% yield when the reaction was carried out
using six equivalents of DB24C8 in CH2Cl2–CH3CN (2+1).
The structures of the [3]rotaxanes were confirmed by both
FAB-MS and 1H NMR spectra. In the 1H NMR spectra, signals
characteristic of rotaxane structures were observed: the benzylic
protons attached to the ammonium group shifted to downfield
by intramolecular CH…O hydrogen bonding with crown ether
oxygens, and appeared as multiplet signals like other similar
systems.9 Further, the methylene protons of DB24C8 appeared
as complex multiplet signals since each face of crown ether is
diastereotopic. Finally, the rotaxane structure was fully con-
firmed by X-ray crystallographic analysis. Crystals of 3c for
analysis were obtained by recrystallization from CHCl3–EtOH.
Fig. 1 shows the crystal structure of 3c.10 Both crown ethers
were placed at each ammonium moiety to keep the hydrogen
bonding interaction between the ammonium salt and crown
ether components.
The successful synthesis of [3]rotaxane prompted us to
investigate the synthesis of a [5]rotaxane. Tetrakisammonium
salt 6, in which the ammonium moieties were connected to each
other by a hexamethylene spacer, was designed and synthesized
starting from mono-protected hexamethylenediamine 4 as
shown in Scheme 2. In the presence of 12 equiv. of DB24C8, 6
was dissolved in CH2Cl2–CH3CN (4+1) to form the correspond-
ing pseudorotaxane. End-capping of the pseudorotaxane with
DMBA was successfully achieved in the presence of trib-
utylphosphine as catalyst. Purification by preparative HPLC
generated the desired [5]rotaxane 7 in 72% yield.7 The
formation of lower-order rotaxane was not confirmed. The
extremely high yield of 7 was attributed to both the high
association constant between 6 and DB24C8, and the high
catalytic activity of tributylphosphine in the acylation. The
[5]rotaxane structure of 7 was confirmed by FAB-MS and NMR
While the synthesis of [2]rotaxanes has been well established by
a variety of approaches such as metal template, CT interaction
and hydrogen bonding,1 the synthesis of [3]- and higher-order
rotaxanes still remains a challenging task.2 So far, only very few
[5]- and higher-order rotaxanes have been prepared.3 Higher-
order rotaxanes are necessary substances to construct molecular
devices with complex functionality.4 Our previous report
described the protocol of high yielding synthesis of [2]rotaxanes
by the threading of secondary ammonium salts into crown
ethers followed by acylative end-capping.5 Rotaxanes consist-
ing of a crown ether and an ammonium salt seem quite
promising because of their potential applicability based on their
ease in structural modification.6 Herein, we report the high
yielding synthesis of [3]- and [5]-rotaxanes. This [5]rotaxane is
the first that has no steric barrier to suppress the shuttling of the
wheel on the axle.3a
The synthesis of [3]rotaxanes was achieved as shown in
Scheme 1. Primary diamines were converted to bisammonium
salt 1 via condensation with methyl 4-formylbenzoate, followed
by LiAlH4 reduction and protonation. The synthesis of the
rotaxanes was carried out in CH2Cl2–CH3CN mixed solvent
since the pseudorotaxane derived from the bisammonium salts
was insoluble in less polar solvents. Although the axles (1a–d)
were insoluble in CH2Cl2–CH3CN (1+1) at room temperature,
1b and 1c were dissolved upon the addition of DB24C8 via the
formation of pseudorotaxane. Thus, a solution of 1 and DB24C8
was treated with 3 equiv. of 3,5-dimethylbenzoic anhydride
(DMBA) and 20 mol% of tributylphosphine to end-cap the
terminal hydroxy groups.5 Both [2]rotaxane 2 and [3]rotaxane 3
formed were isolated by preparative HPLC. The preparation of
2 and 3 using various axle bisammonium salts is summarized in
Table 1 Effect of spacer on the formation of [2]- and [3]-rotaxanesa
Yield (%)
Ammonium salt
R
[2]rotaxane 2
[3]rotaxane 3
b
1a
1b
1c
(CH2)2
(CH2)4
(CH2)6
< 6c
23
30
0
51
64
1d
36
64
a All reactions were carried out in CH2Cl2–CH3CN (1+1, 0.1 M21) at room
temperature using DMBA in the presence of 2.2 equivalents of DB24C8 and
20 mol% of Bu3P. b Carrying out in heterogeneous because of low
solubility. c Determined by 1H NMR.
Scheme 1
2720
CHEM. COMMUN., 2002, 2720–2721
This journal is © The Royal Society of Chemistry 2002

Scheme 2 Reagents and conditions: (a) adipoyl chloride, CHCl3, rt, 89%, (b) trifluoroacetic acid, rt, (c) methyl 4-formylbenzoate, CHCl3, reflux, 69% in two
steps, (d) LiAlH4, THF, reflux, (e) HCl, (f) NH4PF6, 60% in three steps, (g) 12 equivalents of DB24C8, DMBA, 20 mol% of Bu3P, CH2Cl2–CH3CN (4+1),
rt, 24 h, 72%.
Aplin, T. D. W. Claridge, T. Goodson III, A. C. Maciel, G. Rumbles, J.
F. Ryan and H. L. Anderson, J. Chem, Soc., Perkin Trans. 1, 1998, 2383;
(j) M. R. Craig, T. D. W. Claridge, M. G. Hutchings and H. L. Anderson,
Chem. Commun., 1999, 1537; (k) Y. Furusho, A. Tsuboi, N. Kihara and
T. Takata, Chem. Lett., 2000, 18.
3 (a) Higher-order rotaxanes: N. Solladié, J.-C. Chambron, C. O.
Dietrich-Buchecker and J.-P. Sauvage, Angew. Chem., Int. Ed., 1996,
35, 906; (b) P. R. Ashton, R. Ballardini, V. Balzani, M. Belohradsky, M.
T. Gandolfi, D. Philp, L. Prodi, F. M. Raymo, M. V. Reddington, N.
Spencer, J. F. Stoddart, M. Venturi and D. J. Williams, J. Am Chem.
Soc., 1996, 118, 4931; (c) D. B. Amabilino, P. R. Ashton, V. Balzani, C.
L. Brown, A. Credi, J. M. J. Fréchet, J. W. Leon, F. M. Raymo, N.
Spencer. J. F. Stoddart and M. Venturi, J. Am. Chem. Soc., 1996, 118,
12012; (d) N. Solladié, J.-C. Chambron and J.-P. Sauvage, J. Am. Chem.
Soc., 1999, 121, 3684.
4 (a) M. Tamura, D. Gao and A. Ueno, Chem, Eur, J., 2001, 7, 1390; (b)
H. Shigekawa, K. Miyake, J. Sumaoka, A. Harada and M. Komiyama,
J. Am. Chem. Soc., 2000, 122, 5411.
Fig. 1 ORTEP drawing of [3]rotaxane 3c. Hydrogens, counter anions
(PF62) and solvents (CHCl3 and EtOH) are omitted for clarity.
spectra. 7 could also be simply isolated by precipitation into
MeOH in 58% yield. The simple and easy work-up is an
important feature of this method.
In summary, we have demonstrated the practical and high-
yielding synthesis of [3]- and [5]-rotaxanes consisting of crown
ether and oligoammonium salt. The method described here can
be applied to the synthesis of higher rotaxanes without
significant decrease in yield. The rotaxanes thus obtained can be
modified by neutralization of the ammonium group by acyla-
tion,6 leading to the formation of neutral rotaxanes and it is
currently under active investigation.
5 H. Kawasaki, N. Kihara and T. Takata, Chem. Lett., 1999, 1015.
6 N. Kihara, Y. Tacibana, H. Kawasaki and T. Takata, Chem Lett., 2000,
506.
7 3c: mp 174–175 °C; IR (KBr) 3164, 1713, 1505, 1253, 1213, 840 cm21
;
1H NMR (400 MHz, DMSO-d6) d 7.62 (s, 4H), 7.46 (d, J 8.4 Hz, 4H),
7.32 (s, 2H), 7.06 (br s, 4H), 6.96–6.93 (m, 8H), 6.89–6.85 (m, 8H), 5.29
(s, 4H), 4.56 (t, J 5.6 Hz, 4H), 4.19–4.15 (m, 8H), 4.07–4.03 (m, 8H),
3.81–3.71 (m, 16H), 3.59–3.55 (m, 8H), 3.42–3.37 (m, 8H), 2.83 (br s,
4H), 2.35 (s, 12H), 1.07 (br s, 4H), 0.43 (br s, 4H); FAB-MS (matrix; m-
NBA):
m/z
1664
[M 2 PF6]+.
Anal.
Calc.
for
This work is partially supported by JSPS Research Fellow-
ships for Young Scientists (N. W).
C88H114F12N2O20P2·CHCl3: C 55.41, H 6.01, N 1.45. Found: C 55.39,
H 5.95, N 1.47%. 7: mp 219–222 °C; IR (KBr) 3448, 1718, 1593, 1506,
1254, 1124, 841; 1H NMR (400 MHz, CD3CN) d 7.65 (s, 4H), 7.40 (d,
J 8.0 Hz, 4H), 7.29 (s, 2H), 7.27 (d, J 8.0 Hz, 4H), 7.06 (br s, 4H,),
6.91–6.86 (m, 32 H), 6.60 (br s, 4H), 5.21 (s, 4H), 4.57 (t, J 6.7 Hz, 4H),
4.12–4.03 (m, 32H), 3.81–3.77 (m, 32H), 3.65 (s, 16H), 3.62–3.58 (m,
16H), 3.12–3.04 (m, 12H), 2.36 (s, 12H), 1.17 (br s, 12H), 0.79 (br s,
4H), 0.68 ((br s, 8H); FAB-MS (matrix; m-NBA): m/z 3050
[M 2 PF6]+; Anal. Calc. for C148H206F24N4O36P4·H2O: C 55.29, H
6.52, N 1.74. Found: C 55.05, H 6.59, N 1.68%.
Notes and references
1 (a) Recent reviews: J.-C. Chambron and J.-P. Sauvage, Chem. Eur. J.,
1998, 4, 1362; (b) S. A. Nepogodiev and J. F. Stoddart, Chem. Rev.,
1998, 98, 1959; (c) A. Harada, Acta Polym., 1998, 49, 3; (d) Molecular
Catenanes, Rotaxanes and Knots, ed. J.-P. Sauvage and C. O. Dietrich-
Buchecker, Wiley-VCH, Weinheim, 1999; (e) V. Balzani, A. Credi, F.
M. Raymo and J. F. Stoddart, Angew. Chem., Int. Ed., 2000, 39,
3349.
2 (a) [3]rotaxanes: D. B. Amabilino, P. R. Ashton, M. Belohradsky, F. M.
Raymo and J. F. Stoddart, J. Chem. Soc., Chem. Commun., 1995, 747;
(b) D. B. Amabilino, P. R. Ashton, M. Belohradsky, F. M. Raymo and
J. F. Stoddart, J. Chem. Soc., Chem. Commun., 1995, 751; (c) F. Vögtle,
T. Dünnwald, M. Händel, R. Jäger, S. Meier and G. Harder, Chem. Eur.
J., 1996, 2, 640; (d) P. R. Ashton, P. T. Glink, J. F. Stoddart, P. A.
Tasker, A. J. P. White and D. J. Williams, Chem. Eur. J., 1996, 2, 729;
(e) P. R. Ashton, P. T. Glink, J. F. Stoddart, S. Menzer, P. A. Tasker, A.
J. P. White and D. J. Williams, Tetrahedron Lett., 1996, 34, 6217; (f) S.
Anderson and H. L. Anderson, Angew. Chem., Int. Ed., 1996, 35, 1956;
(g) A. G. Kolchinski, N. W. Alcock, R. A. Roesner and D. H. Busch,
Chem. Commun., 1998, 1437; (h) R. Schmieder, G. Hübner, C. Seel and
F. Vögtle, Angew. Chem. Int. Ed., 1999, 38, 3528; (i) S. Anderson, R. T.
8 Ka Values of this system could not be determined by NMR experiments
because the complexes could not be distinguished from each other.
9 (a) T. Takata, H. Kawasaki, S. Asai, N. Kihara and Y. Furusho, Chem.
Lett., 1999, 111; (b) T. Takata, H. Kawasaki, S. Asai, Y. Furusho and N.
Kihara, Chem. Lett., 1999, 223.
10 Crystal data for [3]rotaxane 3c: C90H118F12N2O20.50P2Cl3,
M
=
=
1952.21, monoclinic, space group C2/c, a 41.6032(9), b
=
16.1461(3), c = 32.8652(7) Å, Z = 8, V = 19740.3(6) Å3, Dc = 1.314
cm23, m(Mo-Ka) = 0.214 Å, 76981 reflections were measured, 16980
were unique. R1 = 0.097 and wR2 = 0.288 for 16950 reflection with F
> 3s(F). The structure was solved and refined on F squared using
TEXSAN programs. CCDC 191668. See http://www.rsc.org/suppdata/
cc/b2/b207872d/ for crystallographic data in CIF or other electronic
format.
CHEM. COMMUN., 2002, 2720–2721
2721