Disaggregation reaction of [2]Pseudorotaxanes composed of dibenzo[24]crown-8 and dialkylammonium having isopropyl end groups

Article abstract of DOI:10.1246/cl.2010.510

[2]Pseudorotaxanes composed of dibenzo[24]crown-8 (DB24C8) and dialkylammonium having isopropyl end groups are converted into the component molecules in C₆D₆ solution containing PF₆ ^- anion.

Full text of DOI:10.1246/cl.2010.510

doi:10.1246/cl.2010.510
510
Published on the web April 17, 2010
Disaggregation Reaction of [2]Pseudorotaxanes Composed of Dibenzo[24]crown-8
and Dialkylammonium Having Isopropyl End Groups
Yuji Suzaki, Atsuko Takagi, and Kohtaro Osakada*
Chemical Resources Laboratory R1-3, Tokyo Institute of Technology, 4259 Nagatsuta, Midori-ku, Yokohama 226-8503
(Received February 15, 2010; CL-100159; E-mail: kosakada@res.titech.ac.jp)
[2]Pseudorotaxanes composed of dibenzo[24]crown-8
X-
(DB24C8) and dialkylammonium having isopropyl end groups
are converted into the component molecules in C6D6 solution
containing PF6 anion.
O
O
O
O
O
O
+
N
H2
¹
+
O
O
[1]BARF: X = BARF
[1]PF6: X = PF6
O
O
Rotaxanes are defined as supramolecules composed of
interlocked macrocyclic molecules and axle molecules with two
bulky end groups.1,2 Pseudorotaxanes with less bulky end
groups of the axle component undergo disaggregation to the
component molecules rapidly because the end groups are smaller
than the cavity of the macrocycle.3-5 The reaction is intrinsically
reversible, and relative stability of the pseudorotaxanes and the
component molecules governs the ratio of the components in the
equilibrated mixture (Scheme 1(i)). Disaggregation of pseudo-
rotaxanes having more bulky end groups of the axle component
proceeds more slowly (t1/2 = 4-143 h)6a (Scheme 1(ii)).6-9
Stoddart named these pseudorotaxanes rotaxane-like complex,7,8
and disaggregation has been applied to a drug delivery system.10
Raising temperature, use of polar solvents, and change of
pH have been reported to enhance the disaggregation of
the rotaxane-like complexes.8-11 Elimination of BMP25C8
(BMP25C8 = benzometaphenylene[25]crown-8) with a larger
cavity than common macrocyclic components from the
rotaxane-like complex [(t-BuC6H4-4-CH2NH2CH2C6H4-4-
CH2PPh3)(BMP25C8)](PF6)2 proceeds smoothly in polar sol-
vent or by additional base.8 The rotaxane-like complex of a
macrocyclic octaoxa[22]ferrocenophane with dialkylammoni-
um [AnCH2NH2CH2C6H4-4-OCH2CH2CH=CHCOOC6H3-3,5-
Me2]BARF (An = 9-anthryl, BARF = B{C6H3-3,5-(CF3)2}4)
undergoes disaggregation in CD3CN and DMSO-d6, while
similar reaction was not observed in less polar CDCl3.9 In this
paper, we report synthesis of cationic rotaxane-like complexes,
composed of dibenzo[24]crown-8 (DB24C8) and dialkylammo-
nium with isopropyl groups, and its disaggregation enhanced by
DB24C8
O
O
O
O
X-
+
N
O
O
O
O
H2
O
O
CD3CN
25 °C
[1(DB24C8)]BARF: X = BARF
[1(DB24C8)]PF6: X = PF6
Scheme 2. Formation
(X = BARF and PF6) in CD3CN.
of
[2]pseudorotaxane
[1(DB24C8)]X
Scheme 3. Synthesis of [2(DB24C8)]X (X = BARF and PF6).
gave an equilibrated mixture with [2]pseudorotaxane
[1(DB24C8)]BARF within 10 min. 1H NMR spectroscopy of
the mixture shows a signal at ¤ 4.58 assigned to NCH2 hydrogen
of [1(DB24C8)]BARF where the molar ratio between
[1(DB24C8)]BARF and [1]BARF was 26/74. A similar reaction
of DB24C8 with [1]PF6 yielded the mixture with
[1(DB24C8)]PF6 ([[1(DB24C8)]PF6]/[[1]PF6] = 7/93). These
results indicate that formation of the [2]pseudorotaxane from
[1]BARF with DB24C8 is more favorable than that of [1]PF6.12
Scheme 3 depicts synthesis of the rotaxane-like complexes.
Cross-metathesis reaction of [1]BARF with CH2=CHCOOi-Pr
catalyzed by (H2IMes)(PCy3)Cl2RuCHPh (H2IMes = N,N-bis-
(mesityl)-4,5-dihydroimidazol-2-ylidene) for 13 h,13 in the pres-
ence of DB24C8 yielded [NH2(CH2C6H4-4-OCH2CH2CH=
¹
PF6 anion.
Scheme 2 shows preparation of [2]pseudorotaxane, which is
employed as precursors of rotaxane-like complexes. Dissolution
of DB24C8 and [NH2(CH2C6H4-4-OCH2CH2CH=CH2)2]BARF
([1]BARF) in CD3CN at 25 °C (10 mM for each compound)
fast
(i)
+
+
Pseudorotaxane
Pseudorotaxane
slow
(ii)
CHCOOi-Pr)2(DB24C8)]BARF
([2(DB24C8)]BARF)
in
50% isolated yield.5,14-16 The ESI-MS spectrum of
[2(DB24C8)]BARF showed a peak at m/z 958 assigned to
the cationic rotaxane-like complex, [2(DB24C8)]+.17 1H NMR
spectrum of [2(DB24C8)]BARF in CDCl3 contains signals at ¤
(Rotaxane-like complex)
Scheme 1. Dethreading reactions of [2]pseudorotaxane.
Chem. Lett. 2010, 39, 510-512
© 2010 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

511
Table 1. Disaggregation reaction of [2(DB24C8)]X (X = BARF and
5
PF6)a
(a)
(b)
R
init
[2(DB24C8)]X
solvent
X = BARF, PF
6
-
X
+
N
H
(c)
(d)
H
b'
Me O
O
Me
O
+ DB24C8
2
Me
O
O
O
Me
H H
a' c'
[2]X (X = BARF, PF )
6
Conversionb
/%
Rinit
/mmol min
Run X
Solvent
¹1
0
0
8
12
4
c
d
1
2
3
4
5
6
7
8
9
BARF C6D6
0
59
43
28
59
100
86
100
86
78
100
®
t /h
c,e
¹2
C6D6 + [NH2(CH2Ph)2]PF6
1.9 © 10
7.6 © 10
1.3 © 10
4.2 © 10
c,f
¹2
¹1
¹1
C6D6 + n-Bu4NPF6
C6D6 + Et3Ng
CD3CN
Figure 1. Profile
of
disaggregation
of
[1(DB24C8)]X
([[1(DB24C8)]X]0 = 5.0 mM) in C6D6. (a) X = BARF at 50 °C. (b)
X = BARF with added [NH2(CH2Ph)2]PF6 (5.0 mM). (c) X = BARF at
50 °C with added n-Bu4NPF6 (25.0 mM). (d) X = PF6 at 25 °C.
h
DMSO-d6
®
2.1 © 10
i
¹1
PF6
C6D6
C6D6 + Et3Ng
CD3CN
®
h
¹1
¹1
4.7 © 10
5.3 © 10
7.35 and 4.46, which are assigned to NH2 and NCH2 hydrogens
of the axle component, respectively. The peak positions are at
lower magnetic fields than those of uncomplexed dialkylammo-
nium, [1]BARF (¤ 6.83 (NH2) and 4.02 (NCH2)). These
1H NMR results indicate that DB24C8 is complexed with
the ammonium group of the axle component by the N-H£O
hydrogen bonds between oxygens of DB24C8 and NH2
10
11
CD3CN + HClj
DMSO-d6
h
®
a[[2(DB24C8)]X]0 = 5.0 mM at 25 °C. b100{([[2(DB24C8)]X]0 ¹
[[2(DB24C8)]X]¨)/[[2(DB24C8)]X]0}. cAt 50 °C. dDisaggregation
was not observed for
4
days. e[[NH2(CH2Ph)2]PF6]0 = 5.0 mM
(partially undissolved). f[n-Bu4NPF6]0 = 25.0 mM (partially undis-
solved). g[Et3N]0 = 10.0 mM. hThe reaction was finished within
¹
group.18 Rotaxane-like complex with PF6 counter anion,
8 min. i[2(DB24C8)]PF6 used as
([2(DB24C8)]PF6:DB24C8 = 38/62). [HCl]0 = 10.0 mM.
a
mixture with DB24C8
[2(DB24C8)]PF6, was obtained by a similar reaction for 12 h
in 45% as a mixture with uncomplexed DB24C8. The molar
ratio of [2(DB24C8)]PF6 to DB24C8 did not change in CDCl3 at
room temperature for 17 days.
Heating a C6D6 solution of [2(DB24C8)]BARF at 50 °C did
not change its NMR spectrum for 4 days (Figure 1a, Table 1
(Run 1)). Addition of [NH2(CH2Ph)2]PF6 to the solution
(5.0 mM) at 50 °C caused degradation of the rotaxane-like
complex to form a mixture of [NH2(CH2Ph)2]+, DB24C8, 2+,
[{NH2(CH2Ph)2}(DB24C8)]+, and [2(DB24C8)]+, as revealed
j
Ha
Hb
Hc
Hc
(a)
(b)
Ha Ha'
Hb Hb'
Hc'
1
by H NMR and ESI-MS spectrometry (Figure 1b, Run 2). The
1H NMR spectrum of the C6D6 solution after 47 h exhibits peaks
at ¤ 5.88 (Ha¤), 5.11 (Hb¤), 2.06 (Hc¤) assigned to the signals of 2+
as well as the corresponding signals of [2(DB24C8)]+ (¤ 5.93
(Ha), 5.10 (Hb), 2.16 (Hc)) (Figure 2). The positions of the signal
Ha, Hb, and Hc in Figure 2b were shifted from the spectrum
obtained after 17 min (¤ 5.92 (Ha), 5.08 (Hb), 2.17 (Hc))
6.0
5.0
δ
2.2 2.0
Figure 2. 1H NMR spectra of [2(DB24C8)]BARF with addition of
[NH2(CH2Ph)2]PF6 ([[2(DB24C8)]BARF]0 = 5.0 mM, [[NH2(CH2Ph)2]-
PF6]0 = 5.0 mM, in C6D6, 25 °C). a) 17 min, b) 47 h after addition. See
Scheme 3 and Table 1 for the assignment of the signals.
(Figure 2a). The observed initial rate of the disaggregation, Rinit
,
was determined to be 1.9 © 10¹2 mmol min¹1. Addition of
n-Bu4NPF6 to [2(DB24C8)]BARF ([n-Bu4NPF6]0 = 25.0 mM,
[[2(DB24C8)]BARF]0 = 5.0 mM) at 50 °C converted 43% of
[2(DB24C8)]BARF to a mixture with DB24C8 and [2]BARF
after 10.5 h (Rinit = 7.6 © 10¹2 mmol min¹1) (Figure 1c, Run 3).
The above results indicate that the disaggregation of
[2(DB24C8)] involves activation of the N-H£O hydrogen
bonds. Chart 1 depicts plausible intermediates of the reaction.
¹
Formation of an ion-pair of the ammonium and PF6 counter
anion in intermediate A assists the activation of the N-H£O
hydrogen bonds even in nonpolar C6D6.19,20 Polar P-F bonds
form a stable hydrogen bond with the ammonium group.
The reaction of [2(DB24C8)]BARF with n-Bu4NPF6 or
[NH2(CH2Ph)2]PF6 causes partial counter ion exchange forming
[2(DB24C8)]PF6 and its facile disaggregation. Activation of N-
H£O hydrogen bonds by interaction of the ammonium group
with solvent molecules forms intermediate B and contributes to
the disaggregation reaction. Intermediate B is favorable in the
polar solvents such as DMSO-d6 and CD3CN. The similar N-
H£PF6 and N-H£L (L = solvent) interactions also affect the
thermal stability of [2]X and [2(DB24C8)]X in solution which
Disaggregation of [2(DB24C8)]PF6 in C6D6 occurs smoothly
¹1
without
the
additives
(Rinit = 2.1 © 10¹1 mmol min
)
(Figure 1d, Run 7) and attains an equilibrium after 8 h at
25 °C ([[2(DB24C8)]PF6]/[[2]PF6] = 14:86). Thus, the pres-
¹
ence of PF6 in the solution induces the disaggregation
of the pseudorotaxanes. The disaggregation reactions of
[2(DB24C8)]X were enhanced also by addition of Et3N (Runs
4 and 8) or in polar solvent such as CD3CN and DMSO-d6 (Runs
5, 6, 9, and 11). Addition of HCl to the CD3CN solution of
[2(DB24C8)]PF6 affects the dethreading reaction to a limited
extent (Run 10).
Chem. Lett. 2010, 39, 510-512
© 2010 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/

512
6, 4507. b) P. R. Ashton, M. Bělohradský, D. Philp, J. F. Stoddart,
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O
O
O
O
+
Me
Me
Me
O
N
O
O
O
Me
Me
O
O
O
H
H
O
O
O
F
F5P-
A
7
O
O
O
O
+
Me
Me
Me
O
N
O
O
O
8
9
O
O
O
O
H
H
L
O
O
L
Y. Suzaki, E. Chihara, A. Takagi, K. Osakada, Dalton Trans. 2009,
9881.
B (L = solvent)
10 a) N. Yui, Supramolecular Design for Biological Applications, CRC
Press, Boca Raton, FL, 2002. b) N. Yui, T. Ooya, J. Artif. Organs
2004, 7, 62.
Chart 1. Plausible intermediates for the disaggregation.
11 a) T. D. Nguyen, K. C.-F. Leung, M. Liong, C. D. Pentecost, J. F.
Stoddart, J. I. Zink, Org. Lett. 2006, 8, 3363. b) B. Gorodetsky,
N. R. Branda, Tetrahedron Lett. 2005, 46, 6761.
controls the equilibrium position to reach in disaggregation
reactions.21,22 The N-H£O hydrogen bonds were activated also
with Et3N via neutralization of the ammonium group to form the
corresponding amine.9-11
12 ¦G° for formation of [1(DB24C8)]BARF and [1(DB24C8)]PF6 in
CD3CN are estimated as 9.5 and 5.2 kJ mol¹1, respectively.
13 T. M. Trnka, R. H. Grubbs, Acc. Chem. Res. 2001, 34, 18.
14 X.-Z. Zhu, C.-F. Chen, J. Am. Chem. Soc. 2005, 127, 13158.
15 [1]BARF (120 mg, 0.10 mmol) was dissolved in CH2Cl2 (2.0 cm3)
containing DB24C8 (45 mg, 0.10 mmol) followed by addition of
CH2=CHCOOi-Pr (53 mg, 0.40 mmol) and Ru catalyst (10 mg,
1.0 © 10¹2 mmol). The mixture was refluxed for 13 h and solvent
was removed by evaporation to form brown oil. Washing the crude
product with hexane followed by purification by preparative HPLC
(CHCl3) gives [2(DB24C8)]BARF (90 mg, 0.050 mmol, 50%).
16 Data of [2(DB24C8)]BARF. 1H NMR (300 MHz, CDCl3, rt): ¤ 1.26
(d, 12H, CH3, J = 7 Hz), 2.65 (dt, 4H, OCH2CH2, J = 6, 6 Hz), 3.32
(s, 8H, CH2-DB24C8), 3.69 (m, 8H, CH2-DB24C8), 3.97 (t, 4H,
CH2-Axle, J = 7 Hz), 4.09 (m, 8H, CH2-Axle), 4.46 (4H, NCH2),
5.07 (sept, 2H, CH(CH3)2, J = 7 Hz), 5.93 (dt, 2H, CH2CH=CH,
J = 16, 2 Hz), 6.70 (d, 4H, C6H4-Axle, J = 9 Hz), 6.79 (m, 4H,
C6H4-DB24C8), 6.91 (m, 4H, C6H4-DB24C8), 7.00 (dt, 2H,
CH2CH=CH, J = 16, 7 Hz), 7.12 (d, 4H, C6H4-Axle, J = 9 Hz),
7.35 (brs, 2H, NH2), 7.52 (s, 4H, p-C6H3(CF3)2), 7.70 (m, 8H, o-
C6H3(CF3)2). 13C NMR (100 MHz, CDCl3, rt): ¤ 21.8 (CH3), 31.8
(OCH2CH2), 52.1 (NCH2), 65.9 (OCH2-Axle), 67.8 (OCH(CH3)2),
68.2 (CH2-DB24C8), 70.2 (CH2-DB24C8), 70.6 (CH2-DB24C8),
112.8 (C6H4-DB24C8), 114.4 (C6H4-Axle), 117.4 (p-C6H3(CF3)2),
121.9 (C6H4-DB24C8), 123.8, 124.0 (CH2CH=CH), 124.5 (q, CF3,
J(CF) = 271 Hz), 128.8 (q, CCF3, J(CF) = 31 Hz), 130.5 (C6H4-
Axle), 134.7 (o-C6H3(CF3)2), 143.8 (CH2CH=CH), 147.3, 159.2,
161.6 (q, BC, J(BC) = 50 Hz), 165.7 (C=O). Anal. Calcd for
C86H84BF24NO14: C, 56.68; H, 4.65; N, 0.77%. Found: C, 56.28; H,
4.54; N, 0.88%. ESI-MS (MeCN) m/z; [2(DB24C8)]+ calcd for
C54H72NO14, 958; found, 958.
In summary, we succeeded in synthesis of a rotaxane-like
complex [2(DB24C8)]BARF whose interlocked structure is
stable in C6D6. The counter ion exchange of BARF with PF6
induces disaggregation of the rotaxane-like complex to form a
mixture of the uncomplexed component molecules. Effect of the
added anion to the reaction rate is more significant than that
expected from difference in thermodynamic stability of analo-
gous [2]pseudorotaxane depending on the counter anion. The
¹
PF6 activates the N-H£O hydrogen bond between the
component molecules, similarly to Et3N and polar solvents.
This approach using the controlled release of component
molecule from a supramolecular system may provide a new
means to design artificial transportation of molecules.
We thank our colleagues in the Center for Advanced
Materials Analysis, Technical Department, Tokyo Institute of
Technology for elemental analysis and for ESI-MS measure-
ment. This work was supported by a Grant-in-Aid for Scientific
Research for Young Scientists from the Ministry of Education,
Culture, Sports, Science and Technology, Japan (No. 21750058)
and by Global COE Program “Education and Research Center
for Emergence of New Molecular Chemistry.”
References and Notes
1
2
3
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17 ESI-MS spectrum also contains peaks (m/z = 247, 471) assigned to
2+ and [Na(DB24C8)]+ due to disaggregation of [2(DB24C8)]+
during the measurement.
18 P. R. Ashton, P. J. Campbell, P. T. Glink, D. Philp, N. Spencer, J. F.
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21 Dissolution of DB24C8 and [2]PF6 in CDCl3 at 25 °C causes partial
formation of [2(DB24C8)]PF6. See Supporting Information.23
22 Recent example of couterion controlled rotaxane based molecular
shuttle: T.-C. Lin, C.-C. Lai, S.-H. Chiu, Org. Lett. 2009, 11, 613.
23 Supporting Information is available electronically on the CSJ-
Journal Web site, http://www.csj.jp/journals/chem-lett/index.html.
4
5
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Chem. Lett. 2010, 39, 510-512
© 2010 The Chemical Society of Japan
www.csj.jp/journals/chem-lett/