Binding of secondary dialkylammonium salts by pyrido-21-crown-7

Article abstract of DOI:10.1016/j.tetlet.2008.09.110

Pyrido-21-crown-7 (P21C7) has been synthesized and shown to form [2]pseudorotaxanes spontaneously with secondary dialkylammonium ions. These complexes are stronger than their benzo-21-crown-7 counterparts and much stronger than their dibenzo-24-crown-8 counterparts. Based on this new P21C7/secondary dialkylammonium salt recognition motif, a [2]rotaxane terminated by phenyl groups as stoppers has been successfully constructed using the threading-followed-by-stoppering technique.

Full text of DOI:10.1016/j.tetlet.2008.09.110

Tetrahedron Letters 49 (2008) 6917–6920
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Binding of secondary dialkylammonium salts by pyrido-21-crown-7
*
Chuanju Zhang, Kelong Zhu, Shijun Li, Jinqiang Zhang, Feng Wang, Ming Liu, Ning Li, Feihe Huang
Department of Chemistry, Zhejiang University, Hangzhou 310027, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 5 July 2008
Revised 1 September 2008
Accepted 19 September 2008
Available online 23 September 2008
Pyrido-21-crown-7 (P21C7) has been synthesized and shown to form [2]pseudorotaxanes spontaneously
with secondary dialkylammonium ions. These complexes are stronger than their benzo-21-crown-7
counterparts and much stronger than their dibenzo-24-crown-8 counterparts. Based on this new
P21C7/secondary dialkylammonium salt recognition motif, a [2]rotaxane terminated by phenyl groups
as stoppers has been successfully constructed using the threading-followed-by-stoppering technique.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Crown ether
Secondary ammonium salt
Host–guest system
Pseudrotaxane
Rotaxane
Secondary dialkylammonium salts have been widely used as
guests of crown ethers and their derivatives in the construction
of pseudorotaxane-, rotaxane-, and catenane-type threaded
structures with many applications.1,2 Recently, we reported that
secondary dialkylammonium salts can thread through the cavity
of benzo-21-crown-7 (B21C7) to form [2]pseudorotaxane- and
[2]rotaxane-type threaded structures.3 We found that B21C7 can
bind dialkylammonium salts more strongly than their traditional
crown ether host dibenzo-24-crown-8 (DB24C8) and further dem-
onstrated that B21C7 is the smallest benzocrown ether, which is
capable of forming threaded structures with secondary dialkylam-
monium salts. For the construction of more complicated mechani-
cally interlocked threaded structures using the B21C7/secondary
dialkylammonium salt recognition motif, it becomes worthwhile
to functionalize B21C7. However, the use of mono- and difunction-
alized o-phenylene crown ether hosts leads inevitably to complica-
tions as a result of the formation of stereoisomeric complexes
when two or more hosts participate.4
afford dipyrido-24-crown-8 (DP24C8).4b The strategy used by the
Gibson group to solve the symmetry problem that o-phenylene
crown ethers have is to introduce m-phenylene crown ethers.6
By replacing both the catechol rings in DB24C8 or dibenzo-
30-crown-10 with resorcinol rings, they prepared bis-m-phen-
ylene-26-crown-8 (BMP26C8), bis-m-phenylene-32-crown-10
(BMP32C10), and their derivatives.6 Due to their symmetric nat-
ure, these substituted bis(m-phenylene) crown ethers can be easily
prepared as pure compounds without tedious isomer separation,
and they have simpler NMR spectra than those of their substituted
bis(o-phenylene) analogues. However, BMP26C8 and BMP32C10
were shown not to complex effectively with secondary dialkyl-
ammonium salts.6c
Usually pyridine-containing crown ethers have stronger com-
plexation to hydrogen-bonded guests than the analogous all-oxy-
gen atom-containing crown ethers, since an aromatic nitrogen
atom is a better hydrogen bond acceptor than either aliphatic or
phenolic ether oxygen atoms.4b,7 For example, the association con-
stant (Ka) value, 1100 MÀ1, of DP24C8ÁDBA-Br at 5 mM host and
guest at 25 °C in acetonitrile was determined to be two times high-
er than the corresponding value, 352 MÀ1, of DB24C8ÁDBA-Br.4b
For another example, the binding of glycine to pyrido-18-crown-
6 (Ka = 1.6 Â 104 MÀ1) was found to be four times stronger than
that of 18-crown-6 (Ka = 3.2 Â 103 MÀ1) at 25 °C in methanol.7 To
solve the symmetry problem that functionalized o-phenylene
crown ethers including benzo-21-crown-7 have, considering that
the introduction of the pyridine nitrogen atom to the 21-crown-7
cavity will increase its binding to secondary dialkylammonium
salts, and to further explore the 21-crown-7 cavity/secondary
dialkylammonium salt recognition motif in the preparation of
In order to solve this symmetry-based problem that o-pheny-
lene crown ethers have, one strategy employed by the Stoddart
group is to replace one of the two catechol rings in DB24C8 with
a
resorcinol ring to give benzo-m-phenylene-25-crown-8
(BMP25C8).5 However, BMP25C8 has much poorer binding of sec-
ondary dialkylammonium salts because it has forfeited one of the
O–C–C–O repeating units from its constitution. Another strategy
sought by the Stoddart group is to replace two –CH2OCH2– units
of the 24-crown-8 cavity by 2,6-disubstituted pyridine rings to
* Corresponding author. Tel./fax: +86 571 87953189.
E-mail address: fhuang@zju.edu.cn (F. Huang).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.09.110

6918
C. Zhang et al. / Tetrahedron Letters 49 (2008) 6917–6920
threaded structures, we prepared pyrido-21-crown-7 (P21C7),8
which not only has the 21-crown-7 cavity but also can be function-
alized at the C-4 position of its pyrido ring symmetrically,4b and
used it in the preparation of [2]pseudorotaxane- and [2]rotax-
ane-type threaded structures.
Electrospray ionization mass spectra of equimolar acetone solu-
tions of P21C7 and each of 1–3 confirmed the 1:1 stoichiometries.
A common mass fragment of [MÀPF6]+ was found: m/z 471.3 (64%)
for P21C7Á1, 505.3 (45%) for P21C7Á2, and 530.3 (37%) for P21C7Á3.
The base peak is at m/z 342.1, corresponding to [P21C7 + H]+ for
P21C7Á1, while the base peaks are at m/z 364.1, corresponding to
[P21C7 + Na]+ for both P21C7Á2 and P21C7Á3.
The ability of P21C7 to form [2]pseudorotaxanes with dialky-
lammonium salts 1–3 has been investigated by 1H NMR spectros-
copy. The 1H NMR spectrum (Fig. 1) of an equimolar solution of
P21C7 and dibutylammonium salt 1 in acetone-d6 shows three sets
of resonances for uncomplexed P21C7, uncomplexed 1, and for the
complex between P21C7 and 1, indicating the equilibrium be-
tween complexed and uncomplexed species is slow on the 1H
NMR time scale, allowing the determination of association con-
stants to be made readily using the single-point method.9 This im-
plied the threading of 1 through the cavity of P21C7 to form a
pseudorotaxane. In the same way, complexations of P21C7 with
dialkylammonium salts 2 and 3 were also found to be slow-ex-
change systems, the same to B21C7-based complexes, B21C7Á1,
B21C7Á2 and B21C7Á3,3 and DB24C8Á4,2a but in sharp contrast to
DB24C8Á1, DB24C8Á2, DB24C8Á3, and DP24C8Á4, which are fast-
exchange systems at room temperature.2a,3,4b From integrations
of all peaks, the stoichiometries of all three complexation systems
were determined to be 1:1. The Ka values10 of P21C7Á1, P21C7Á2,
We then prepared P21C7-containing [2]rotaxane using thread-
ing-followed-by-stoppering technique (Scheme 1).11 Here, two
phenyl groups were employed as the stoppers. Although 5 is quite
soluble in MeOH, Me2CO, CH3CN, and Me2SO, it is only slightly sol-
uble in CH2Cl2, while 5 becomes soluble in this solvent after the
addition of a molar equivalent of P21C7, indicating the formation
of a stable complex P21C7Á5. An equimolar dichloromethane solu-
tion of P21C7 and 5 was treated with benzoic anhydride in the
presence of trimethylphosphine as the catalyst3,12 to yield the
[2]rotaxane 7 in 62% yield (Scheme 1). Partial proton NMR spectra
of the dumbbell-shaped component 6, rotaxane 7 and P21C7 in
DMSO-d6 are shown in Figure 2. The aromatic proton H2 and eth-
yleneoxy proton H3 of P21C7 moved upfield and methylene pro-
tons Hd, Hh, and Hi on 6 moved downfield after the formation of
rotaxane 7. These chemical shift changes, which persisted even
after excess triethylamine was added (Fig. S8), in DMSO proved
that 7 is a rotaxane, since no complexation is expected in this
highly polar solvent.2a,3 The ESI mass spectrum of rotaxane 7 has
a single peak at m/z 654.4 (100%) corresponding to [7APF6]+.
The solid-state structure (Fig. 3) is established by X-ray crystal-
lography on a suitable single crystal grown by vapor diffusion of
petroleum ether into an ethyl acetate solution of 7.13 It reveals
the anticipated threading of the secondary dialkylammonium cat-
ion through the center of the P21C7 macrocycle. Three N-methy-
lene hydrogen atoms and two N-H hydrogen atoms are involved
in seven hydrogen bonds (Fig. 3) comprising N+ÀHÁÁÁN (A in Fig
3), CÀHÁÁÁOÁÁÁ(B, C and D in Fig. 3) and N+ÀHÁÁÁO (E, F, and G in
Fig. 3) with four oxygen atoms and the pyridine nitrogen atom of
P21C7. In the crystal structure of a previously reported [2]rotaxane
based on B21C7 and the same dumbbell-shaped component 6,3 all
four N-methylene hydrogens of the secondary dialkylammonium
salt dumbbell-shaped component and all seven oxygen atoms of
the 21-crown-7 cavity are involved in hydrogen bonding between
the host and the guest in the solid state, while here one N-methy-
lene hydrogen atom of the dumbbell-shaped component and two
oxygen atoms of the 21-crown-7 cavity are not involved in hydro-
gen bonding between the host and the guest in the solid state
and P21C7Á3 in acetone-d6 are 1625 ( 48) MÀ1, 6396 ( 224) MÀ1
,
and 7479 ( 299) MÀ1, respectively. These values are higher than
the corresponding Ka values,3 527 MÀ1, 615 MÀ1, and 1062 MÀ1
of B21C7-based complexes B21C7Á1, B21C7Á2, and B21C7Á3 and
much higher than the corresponding Ka values,3 135 MÀ1
,
,
155 MÀ1, and 261 MÀ1, of DB24C8-based complexes DB24C8Á1,
DB24C8Á2, and DB24C8Á3 in acetone-d6, indicating that P21C7 is
a more efficient host than B21C7 and DB24C8 for secondary dialky-
lammonium salts. The Ka increase from P21C7Á1 to P21C7Á2 to
P21C7Á3 is a result of the acidity increase of N-methylene and
ammonium hydrogens due to the increasing electron-withdrawing
ability from propyl to phenyl to p-cyanophenyl substituents.
N
O P21C7O
O
O
O
O
PF6
OH
N
5
H2
O
O
Equimolar P21C7
Me3P, CH2Cl2, rt
12 h, 62%
N
O
PF6
O
O
O
N
H
O
2 O
O
7
O
O
Figure 1. Partial 1H NMR spectra (500 MHz, acetone-d6, 22 °C) of 1.00 mM 1 (a),
1.00 mM P21C7 and 1 (b), and 1.00 mM P21C7 (c). Complexed and uncomplexed
species are denoted by ‘c’ and ‘uc’, respectively.
Scheme 1. Synthesis of [2]rotaxane 7.

C. Zhang et al. / Tetrahedron Letters 49 (2008) 6917–6920
6919
nition motif in preparing other threaded structures, and the results
will be reported in due course.
Acknowledgments
This work was supported by the National Natural Science Foun-
dation of China (20604020 and 20774086). We thank Professor
Wanzhi Chen from Department of Chemistry at Zhejiang Univer-
sity for his kind assistance with X-ray crystallography.
Supplementary data
Synthetic procedures, characterizations, determination of asso-
ciation constants of P21C7Á1, P21C7Á2, and P21C7Á3, and crystal
data for rotaxane 7. Supplementary data associated with this arti-
cle can be found, in the online version, at doi:10.1016/j.tetlet.
2008.09.110.
References and notes
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Zerbetto, F. Angew. Chem., Int. Ed. 2007, 46, 72–191; (e) Lankshear, M. D.; Beer,
P. D. Acc. Chem. Res. 2007, 40, 657–668.
Figure 2. Partial 1H NMR spectra (500 MHz, DMSO-d6, 22 °C) of dumbbell-shaped
component 6 (a), rotaxane 7 (b), and P21C7 (c).
2. Selected publications: (a) Ashton, P. R.; Chrystal, E. J. T.; Glink, P.; Menzer, T. S.;
Schiavo, C.; Spencer, N.; Stoddart, J. F.; Tasker, P. A.; White, A. J. P.; Williams, D.
J. Chem. Eur. J. 1996, 2, 709–728; (b) Ashton, P. R.; Fyfe, M. C. T.; Schiavo, C.;
Stoddart, J. F.; White, A. J. P.; Williams, D. J. Tetrahedron Lett. 1998, 39, 5455–
5458; (c) Cantrill, S. J.; Fyfe, M. C. T.; Heiss, A. M.; Stoddart, J. F.; White, A. J. P.;
Williams, D. J. Org. Lett. 2000, 2, 61–64; (d) Glink, P. T.; Oliva, A. I.; Stoddart, J.
F.; White, A. J. P.; Williams, D. J. Angew. Chem., Int. Ed. 2001, 40, 1870–1875; (e)
Huang, F.; Jones, J. W.; Slebodnick, C.; Gibson, H. W. J. Am. Chem. Soc. 2003, 125,
14458–14464; (f) Tachibana, Y.; Kihara, N.; Furusho, Y.; Takata, T. Org. Lett.
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4923–4926; (h) Dichtel, W. R.; Miljanic, O. S.; Spruell, J. M.; Heath, J. R.;
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C.; Chiu, S.-H. J. Am. Chem. Soc. 2007, 129, 3500–3501; (j) Han, T.; Zong, Q.-S.;
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M.; Guldi, D. M. Eur. J. Org. Chem. 2007, 5027–5037; (m) Huang, F.; Jones, J. W.;
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Montero, J.-L. Org. Lett. 2008, 10, 753–756; (o) Hirose, K.; Shiba, Y.; Ishibashi, K.;
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White, A. J. P.; Williams, D. J. Angew. Chem., Int. Ed. 1998, 37, 1294–1297; (b)
Chang, T.; Heiss, A. M.; Cantrill, S. J.; Fyfe, M. C. T.; Pease, A. R.; Rowan, S. J.;
Stoddart, J. F.; White, A. J. P.; Williams, D. J. Org. Lett. 2000, 2, 2947–2950; (c)
Gibson, H. W.; Wang, H.; Bonrad, K.; Jones, J. W.; Slebodnick, C.; Zackharov, L.
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2005, 3, 2114–2121; (d) Gibson, H. W.; Wang, H.; Slebodnick, C.; Merola, J.;
Kassel, W. S.; Rheingold, A. L. J. Org. Chem. 2007, 72, 3381–3393.
Figure 3. Crystal structure of the [2]rotaxane 7. A PF6 counterion, and hydrogens
except the ones involved in hydrogen bonding have been omitted for clarity. P21C7
is red, 6 is blue, hydrogens are magenta, oxygens are green, and nitrogen is black.
Hydrogen-bond parameters: HÁÁÁO distances (Å), C(N)–HÁÁÁO(N) angles (°),
C(N)ÁÁÁO(N) distances (Å) A, 2.18, 161, 3.04; B, 2.61, 140, 3.41; C, 2.51, 143, 3.33;
D, 2.37, 161, 3.30; E, 2.00, 168, 2.89; F, 2.69, 95, 2.91; G, 2.30, 124, 2.91.
5. (a) Ashton, P. R.; Bartsch, R. A.; Cantrill, S. J.; Hanes, R. E., Jr.; Hickingbottom, S.
K.; Lowe, J. N.; Preece, J. A.; Stoddart, J. F.; Talanov, V. S.; Wang, Z.-H.
Tetrahedron Lett. 1999, 40, 3661–3664; (b) Cantrill, S. J.; Fulton, D. A.; Heiss, A.
M.; Pease, A. R.; Stoddart, J. F.; White, A. J. P.; Williams, D. J. Chem. Eur. J. 2000, 6,
2274–2287; (c) Chiu, S.-H.; Rowan, S. J.; Cantrill, S. J.; Glink, P. T.; Garrell, R. L.;
Stoddart, J. F. Org. Lett. 2000, 2, 3631–3634.
6. (a) Nagvekar, D. S.; Gibson, H. W. Can. J. Chem. 1997, 75, 1375–1384; (b)
Nagvekar, D. S.; Yamaguchi, N.; Wang, F.; Bryant, W. S.; Gibson, H. W. J. Org.
Chem. 1997, 62, 4798–4803; (c) Bryant, W. S.; Guzei, I. A.; Rheingold, A. L.;
Merola, J. S.; Gibson, H. W. J. Org. Chem. 1998, 63, 7634–7639.
7. Czekalla, M.; Stephan, H.; Habermann, B.; Trepte, J.; Gloe, K.; Schmidtchen, F. P.
Thermochim. Acta 1998, 313, 137–144.
8. P21C7 was originally prepared for the purpose of studying the complexation
with guanidinium salts by using two-phase extraction experiments. See:
Uiterwijk, J. W. H. M.; Staveren, Van C. J.; Reinhoudt, D. N.; Den Hertog, H. J. Jr.;
Kruise, L.; Harkema, S. J. Org. Chem. 1986, 51, 1575–1587.
(Fig. 3), indicating that although both P21C7 and B21C7 are 21-
membered rings, P21C7 has a slightly bigger cavity than B21C7.
This is in accordance with that the cavity of DP24C8 is bigger than
that of DB24C8 so DP24C8Á4 is a fast-exchange system while
DB24C8Á4 is a slow-exchange system at room temperature.2a,3,4b
In summary, here we have demonstrated that P21C7 can bind
widely used secondary dialkylammonium salt guests more
strongly than B21C7 and much more strongly than DB24C8.
Therefore, P21C7 is an attractive alternative for DB24C8, the tradi-
tionally used host for the secondary dialkylammonium salts. Fur-
thermore, P21C7-based [2]pseudorotaxane- and [2]rotaxane-type
threaded structures have been successfully prepared. Considering
the high association constants of the complexes based on P21C7
and secondary dialkylammonium salts (such as 1–3) and the sym-
metric nature of the P21C7 derivatives resulted from the substitu-
tion at the C-4 position of its pyrido ring,4b P21C7 should be a
versatile macrocyclic host for secondary dialkylammonium salts
in the preparation of threaded structures. Currently, we are using
the pyridine-21-crown-7/secondary dialkylammonium salt recog-
9. Connors, K. A. Binding Constants; Wiley: New York, 1987.
10. The Ka values of P21C7-based complexes, slow-exchange complexation
systems, were calculated from integrations of complexed and uncomplexed
peaks. All these Ka values are at 1.00 mM host and guest in acetone-d6.
11. Rowan, S. J.; Cantrill, S. J.; Stoddart, J. F. Org. Lett. 1999, 1, 129–132.
12. Tachibana, Y.; Kawasaki, H.; Kihara, N.; Takata, T. J. Org. Chem. 2006, 71, 5093–
5104.
13. Crystal data of 7: Prism, colorless, 0.80 Â 0.56 Â 0.46 mm3, C36H51N2O8F6P, FW
784.76, monoclinic, space group P21/c, a = 11.494(2), b = 16.863(3),
c = 23.019(7) Å,
a
= 90.00°, b = 114.94(2)°,
= 0.145 mmÀ1, 30,972 measured reflections,
c
= 90.00°, V = 4045.6(16) Å3, Z = 4,
Dc = 1.288 g cmÀ3, T = 100(2) K,
l

6920
C. Zhang et al. / Tetrahedron Letters 49 (2008) 6917–6920
7107 independent reflections, 478 parameters, 0 restraints, F(000) = 1656,
R1 = 0.1130, wR2 = 0.2795 (all data), R1 = 0.0823, wR2 = 0.2544 [I > 2 (I)], max.
residual density 0.820 e ÅÀ3 and GoF (F2) = 1.126. Crystallographic data
(excluding structure factors) for the structure in this Letter have been
deposited with the Cambridge Crystallographic Data Center as
r
supplementary publication number CCDC 687760. Copies of the data can be
obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge
CB2 1EZ, UK [fax: 144-(0)1223-336033 or e-mail: deposit@ccdc.cam.ac.uk].
,