by extracting the chloride salt of 1d (150 mg, 0.42 mmol)
with diethyl ether and water containing 1.7 equiv of
ammonium hexafluorophosphate. Once the 1d-PF6- salt was
collected and dried, pseudorotaxane 2d was created in CDCl3
(3 mL) by adding DB24C8 (190 mg, 0.84 mmol) to the
solution under argon. Formation of the pseudorotaxane and
DCC-[2]rotaxane were verified by observing changes in the
1
chemical shifts of protons of tether 1d in H NMR spectra
(Figure 1).
Pseudorotaxanes formed quickly, and after approximately
20 min, DCC-[2]rotaxane 3d was obtained by adding DCC
(100 mg, 0.50 mmol) to the solution. After 10 min, N-(2-
aminoethyl)-3,5-di-tert-butylbenzylamide (230 mg, 0.84
mmol) was added, and the reaction was stirred under argon
at room temperature for 10 h. Reaction components were
filtered and purified on silica using CHCl3/MeOH as the
eluent to give a 73% yield of rotaxane 4d.7 This reaction
was run in CDCl3 with approximately 100% bound tether;
therefore, the yields do not match the ones reported in Table
1. We should also note that the yields reported in Table 1
were obtained from reactions that were run on a ca. 0.05
mmol scale.
We have demonstrated that rotaxanes can be easily
synthesized in good yields using a DCC-activated rotaxane
in CH3CN or CHCl3 (or their deuterated counterparts). DCC-
[2]rotaxane 3d is stable to purification by HPLC and column
chromatography on silica. Gibson et al. have also isolated a
sterically hindered acylisourea via column chromatography.8
These compounds underwent rearrangement to the nitrogen-
substituted cyclohexyl urea upon heating.
Dried DCC-[2]rotaxane 3d was stored in a freezer for 1
1
week. After this time, there was no change in its H NMR
1
spectrum and it still formed rotaxane 4d. We are currently
trying to improve rotaxane yield by forcing the amine of
the blocking group to react only with the carbonyl carbon
of the DCC-[2]rotaxane by employing Lewis acid catalysts.
Another possible route involves using large mixed anhydrides
to activate the carboxylic acids.
Figure 1. The following representative H NMR spectra for the
formation of rotaxane 4d in CD3CN at room temperature are
given: (A) tether 1d, (B) tether 1d 50% bound with DB24C8, (C)
tether 1d 100% bound with DB24C8, giving 2d, (D) addition of
DCC to 2d, giving a mixture of DCC-[2]rotaxane 3d and lactam
6d, and (E) the purified rotaxane 4d. The numbers identify protons
that clearly indicate which species are formed.
Acknowledgment. The authors thank the University of
Cincinnati for their generous funding of this project.
is consistent with the dicyclohexyl guanidinium derivative
7. This compound could be formed by the amine of the
blocking group attacking the diimide carbon atom of the
DCC-[2]rotaxanes. Addition of the blocking group to DCC
does not produce compound 7. Thus, the increased steric
congestion at the carboxylic moiety of DCC-[2]rotaxane
3a-d caused by the ring makes this reaction possible.
Performing the reactions in chloroform produced yields
of rotaxanes similar to those seen in acetonitrile (Table 1).
Association constants for pseudorotaxane formation were not
measured in CDCl3 because of the low solubility of the
capped-tethers. Once the capped-tethers interact with DB24C8
in chloroform, they dissolved, allowing rotaxane formation
to proceed.
Supporting Information Available: Synthetic procedures
and characterizations of 3,5-di-tert-butylbenzyl alcohol, 3,5-
di-tert-butylbenzaldehyde, N-(2-aminoethyl)-3,5-di-tert-
butylbenzylamide, and N-3,5-di-tert-butylbenzyl-5-amino-
valeric acid. This material is available free of charge via the
OL016107O
(7) The rotaxane exists as a mixture of conformers at ambient temper-
atures due to the ring sliding on the tether. It is not very soluble in high
boiling solvents such as d6-DMSO. 1H NMR (CDCl3) δ 7.70-7.52 (3H,
m), 7.31-7.20 (3H, m), 6.88 (8H, m), 6.66 (1H, s), 6.40 (1H, s), 4.63 (1H,
s), 4.23-4.20 (4H, m), 4.07-4.00 (4H, m), 3.80-3.70 (12H, m), 3.60-
3.50 (8H, m), 3.43 (2H, br s), 3.33 (4H, br s), 3.08 (2H, br s), 1.98 (2H, br
s), 1.66 (4H, br s), 1.30 (18H, s), 1.21 (18H, s); 13C NMR (CD3OD) δ
175.3, 171.7, 170.7, 153.1, 152.3, 152.2, 148.8, 148.0, 134.7, 133.8, 132.9,
127.0, 126.5, 125.2, 124.0, 122.5, 122.4, 133.7, 79.3, 71.6, 71.1, 69.1, 55.1,
53.6, 52.2, 51.0, 43.1, 41.1, 39.9, 39.7, 35.9, 35.5, 34.7, 33.5, 32.9, 31.8,
26.8, 26.3, 26.0, 25.8, 23.4. ESI MS m/z [M + H]+.Anal. Calcd for
C61H92N3O10: 1026.68 Found: 1026.71.
The rotaxanes were constructed using a one-pot synthetic
route. As an example, rotaxane 4d was obtained using
capped-tether 1d, which was obtained from a reductive
amination reaction of 3,5-di-tert-butylbenzaldehyde and
5-amino valeric acid. To enhance pseudorotaxane formation
(8) Nagvekar, D. S.; Delaviz, Y.; Prasad, A.; Merola, J. S.; Marand, H.;
Gibson, H. W. J. Org. Chem. 1996, 61, 1211-1218.
with DB24C8, the Cl- counterion was exchanged with PF6
-
Org. Lett., Vol. 3, No. 16, 2001
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