Iterative synthesis of [n]rotaxanes

Article abstract of DOI:10.1055/s-1999-2967

An iterative pathway for the synthesis of higher order [n]rotaxanes is described. Stepwise reactions with repeatedly used building blocks lead to rod-shaped axle parts which form threading hydrogen bond interactions with macrocycles. A followed stoppering enables several molecular wheels to be fixed onto an axle.

Full text of DOI:10.1055/s-1999-2967

LETTER
1887
Iterative Synthesis of [n]Rotaxanes
Amir Hossain Parham, Roland Schmieder, Fritz Vögtle*
Kekulé-Institut für Organische Chemie und Biochemie der Universität Bonn, Gerhard-Domagk-Strasse 1, D-53121 Bonn (Germany)
Fax (+49)228-735662; E-mail: voegtle@uni-bonn.de
Received 6 September 1999
of type I (n = 2) (Scheme 1), have been realized.4 Even
Abstract: An iterative pathway for the synthesis of higher order
[4]- and [5]rotaxanes (n = 3, 4) were accessible.5 Higher
[n]rotaxanes is described. Stepwise reactions with repeatedly used
building blocks lead to rod-shaped axle parts which form threading
order representatives are of the polydisperse type.6
hydrogen bond interactions with macrocycles. A followed stopper-
ing enables several molecular wheels to be fixed onto an axle.
Keywords: macrocycle, mechanical bonding, molecular recogni-
tion, rotaxane, supramolecular chemistry
The synthesis of mechanically interlocked supramolecu-
lar compounds such as rotaxanes can be performed by
threading macrocycles onto molecular axles.1 To avoid
disassembly of the molecular components, the axle must
have bulky end-groups at both sides, that prevent deslip-
Scheme 1
ping of the wheel. The assembly is usually based on a tem-
plate assistance like the preorganization of building
blocks by metal coordination, hydrophobic and donor-ac-
ceptor interactions or hydrogen bonding with neutral, cat-
ionic or anionic molecules.2
Rotaxanes of the amide type II with more than two thread-
ed macrocyclic wheels have not been described yet.4h We
report here a methodology for building up such monodis-
perse higher order rotaxanes based advantageously on an
iterative reaction sequence.
For investigations of basic questions about molecular rec-
ognition and interactions between several wheels on an
axle it would be desirable to have preparative synthetic
access to higher order [n]rotaxanes („[n]„ results from the
quantity of assembled molecules: n-1 wheels, 1 axle). Fur-
thermore, [n]rotaxanes, containing wheels with transla-
tional and rotational freedom of movement on the axle
may open the way for the future preparation of molecular
devices and machines.3 In recent years some [3]rotaxanes
It has been shown that tetralactam macrocycles of the type
2 can act as hosts for the inclusion of guest compounds
containing secondary amide groups.7 Thus, the reaction of
stopper amine 1 with the diacid dichloride 3 in the pres-
ence of macrocycle 2 should result in a semirotaxane 4
which leads to a [2]rotaxane 6 upon reaction with another
blocking group 1. In fact, we isolated [2]rotaxane 6 in
18% yield along with 20% of the free axle 5 (Scheme 2).8
Scheme 2
Synlett 1999, No. 12, 1887–1890 ISSN 0936-5214 © Thieme Stuttgart · New York

1888
A. H. Parham et al.
LETTER
To build up higher order rotaxanes in this way, semiaxles
have to be synthesized that contain more amide groups,
one for each wheel to be bound and then threaded. By the
reaction of the stopperamine 1 with the Boc-protected p-
aminobenzoyl chloride 7 and subsequent deprotection of
the carbonamide group, the elongated semiaxle amide
amine 8 is obtained (Scheme 3). Repetition of the same re-
action sequence led to the semiaxle diamide 9.9 Further it-
erative synthetic steps with 7 should lead to even higher
order tailor made stopper amines (beyond n = 2) that
would allow to obtain rotaxanes with a predetermined
maximum number of macrocycles.
Compounds 8 and 9 are semiaxles that contain one or two
amide groups and are thus enabled to complex one or two
tetralactams 2, respectively. The terminal amino group
may then serve as reactive site to be connected with the di-
acid dichloride 3 used as axle centre piece. As a matter of
fact, [2]- to [4]rotaxanes 13-15 have been isolated along
with the free axle 12. At first, the stopper amine 8 can in-
teract with one wheel to give 10. Upon the reaction with 3
another amide group is formed, which can fix a second
wheel under formation of the semi[3]rotaxane 11. This fi-
nally reacts with another semirotaxane 10 to yield [4]ro-
taxane 15 (Scheme 4).
Scheme 3
A decomplexation equilibrium of the semiaxle and the
macrocyclic lactam is responsible for the formation of the
mixture of all possible [n]rotaxanes 13-15 as well as of the
free axle 12.8 Compounds 12-15 were unequivocally char-
It should be noted that no [3]rotaxane was formed here.
The second amide group is generated with the second
bulky stopper and therefore no more macrocycle 2 can be
threaded.
1
acterized by H, 13C NMR and mass spectroscopy. The
yields (Table) decrease with the increasing number of
Scheme 4
Synlett 1999, No. 12, 1887–1890 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Iterative Synthesis of [n]Rotaxanes
1889
wheels which is also caused by the difficulty of the chro- to bind one more wheel on the axle on account of the
matographical separation of each rotaxane on account of additional amide group. The semi[4]rotaxane 17 can now
very similar retention times. Additionally, the recognition react with the semi[3]rotaxane 16 that leads even to the
sites on the axle face close together and thus some macro- formation of the [6]rotaxane 23 (Scheme 5) but in a very
cycles could have minor access to interact.
small amount.
Rotaxane 21, 22, 23 are isolated in yields of 0.8 mg 0.6
mg, and 0.4 mg, respectively and therefore only character-
ized by mass spectrometry. As mentioned above, the ster-
ical difficulties at the recognition sites and the problems
in the chromatographical separation of the rotaxanes de-
crease the yields with increasing number of wheels. By
improving the separation and enlarging the distance be-
tween the recognition sites this iterative synthetic method
will allow to obtain a variety of higher order [n]rotaxanes.
The maximum number of molecular wheels in the corre-
sponding rotaxanes is limited by the number of amide
bonds within the molecular axle. Using this type of
threading synthesis an axle containing n carbon amide
groups can lead to a rotaxane with a maximum n-1 wheels
because the last formation of an amide group leaves no
possibility for threading another wheel.
The preparative scale synthesis of [n]rotaxanes opens up
the way for complex supramolecular nano-scale architec-
tures with coexistence of mechanical and covalent ele-
ments.10 For example, the possibility of linking two
wheels covalently together in a higher order rotaxane
opens up interesting aspects about the translational and ro-
tational movement of the wheels on the axle. Furthermore,
interesting stereochemical features can be built up by us-
ing oriented wheels to give cycloenantiomerism and -dia-
stereomerism.11
The reaction of compound 9 as the iteratively even more
elongated stopper amine with 3 in the presence of the
wheel 2 leads to the [2]- to [6]rotaxanes 19-23 and the cor-
responding axle 18.8 The yields are also listed in the
Table. The semiaxle 9 is able to thread two wheels. Addi-
tionally, the reaction with the diacid dichloride 3 enables
Scheme 5
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1890
A. H. Parham et al.
LETTER
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Acknowledgement
We thank Dr. Christian Seel for help and discussion and the Deut-
sche Forschungsgemeinschaft for financial support (Vo145/47-2).
References and Notes
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(8) General Synthesis of rotaxanes. 0.4 mmol *tetralactam 2,
0.8 mmol 4-tritylaniline 1 or semiaxle 8 or 9, respectively, and
12 drops triethylamine are dissolved in 100 mL CH2Cl2 and
cooled to 0 °C. A solution of 0.4 mmol 4,4´-stilbenedi-
carboxylic acid (3) in 100 mL CH2Cl2 is added dropwise
during 4 h. After stirring for 2 h more the solvent is removed
in vacuo, and the crude product is purified by column
chromatography [SiO2; 63-100 µm, eluent: rotaxane 6, axle 5
dichloromethane : ethyl acetate, 25:1; rotaxane 13-15, axle 12
THF: petroleum ether (40-60), 6:4; rotaxane 19-23, axle 18
dichloro-methane : ethyl acetate 4:1].
*Rotaxane 13-15:1.2 mmol tetralactam, Rotaxane 19-23:2.0
mmol tetralactam.
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(9) Synthesis of semiaxles 8 and 9. To a solution of 8 drops
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respectively, in 50 mL CH2Cl2 is added dropwise during 2 h a
solution of 360 mg (1.13 mmol) N-benzyloxycarbonyl-4-
aminobenzoylchloride in 50 mL CH2Cl2. After further 2 h the
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filtration the solvent is evaporated and the residue purified by
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Article Identifier:
1437-2096,E;1999,0,12,1887,1890,ftx,en;G22399ST.pdf
Synlett 1999, No. 12, 1887–1890 ISSN 0936-5214 © Thieme Stuttgart · New York