Syntheses of cis- and trans-dibenzo-30-crown-10 derivatives via regioselective routes and their complexations with paraquat and diquat

Article abstract of DOI:10.1021/jo800890x

(Chemical Equation Presented) cis-Dibenzo-30-crown-10 (cis-DB30C10) diester and trans-dibenzo-30-crown-10 (trans-DB30C10) diester were synthesized regioselectively with reasonable yields. These two isomers were further reduced to cis-dibenzo-30-crown-10 d

Full text of DOI:10.1021/jo800890x

Syntheses of cis- and trans-Dibenzo-30-Crown-10 Derivatives Wia
Regioselective Routes and Their Complexations with Paraquat and
Diquat
Chunlin He, Zuming Shi,† Qizhong Zhou, Shijun Li, Ning Li, and Feihe Huang*
Department of Chemistry, Zhejiang UniVersity, Hangzhou 310027, People’s Republic of China
fhuang@zju.edu.cn
ReceiVed April 24, 2008
cis-Dibenzo-30-crown-10 (cis-DB30C10) diester and trans-dibenzo-30-crown-10 (trans-DB30C10) diester
were synthesized regioselectively with reasonable yields. These two isomers were further reduced to
cis-dibenzo-30-crown-10 diol (1) and trans-DB30C10 diol (2), respectively. The complexations of cis-
1
and trans-DB30C10 diols with paraquat (3) and diquat (4) were investigated by H NMR, mass
spectrometry, UV-vis spectroscopy, and single-crystal X-ray analysis. The reversible control of
complexations of 1 · 3 and 2 · 3 by adding small molecules (KPF6 and dibenzo-18-crown-6) was
1
demonstrated by H NMR. The addition of 2 molar equiv of KPF6 is enough to dissociate 2 · 3 and 1 · 3
completely while the subsequent addition of 2 molar equiv of DB18C6 allows the two complexes to
reform. However, 2 molar equiv of KPF6 cannot dissociate 1·4 and 2·4 completely. Because the DB30C10
cavity has a better geometry fit with paraquat 3 than with diquat 4, 4-based complexes have much higher
association constants than the corresponding 3-based complexes. In the crystal structure of 1 · 4, the two
hydroxymethyl groups of the crown ether 1 were joined by a “water bridge” to form a “supramolecular
cryptand” while this kind of supramolecular cryptand structure was not observed in the crystal structure
of 2 · 4. This is a possible reason for the increase in association constant from 2 · 4 (3.3 × 104 M-1) to
1 · 4 (5.0 × 104 M-1).
Introduction
tion of chemosensors, molecular machines, and supramolecular
polymers.2–4 In the recent three decades, several significant
recognition motifs based on crown ethers and organic cations,
especially the complexations between dibenzo-24-crown-8
(DB24C8) with secondary dialkylammonium salts,5 between
bis(p-phenylene)-34-crown-10 (BPP34C10) and paraquat de-
Since Pederson published his discovery of the alkali metal
templated syntheses of crown ethers in 1967,1 crown ethers have
attracted much attention for their interesting binding properties
with metal and organic cations and applications in the prepara-
* Address correspondence to this author. Fax: 86-571-8795-1895. Phone: 86-
571-8795-3189.
(2) Gokel, G. W.; Leevy, W. M.; Weber, M. E. Chem. ReV. 2004, 104, 2723–
2750.
† Undergraduate Research Participant. Present address: State Key Laboratory
of Bio-Organic and Natural Products Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032,
People’s Republic of China.
(3) Balzani, V.; Gomez-Lopez, M.; Stoddart, J. F. Acc. Chem. Res. 1998,
31, 405–414.
(4) (a) Huang, F.; Gibson, H. W. J. Am. Chem. Soc. 2004, 126, 14738–
14739. (b) Huang, F.; Nagvelkar, D. S.; Zhou, X.; Gibson, H. W. Macromolecules
2007, 40, 3561–3567.
(1) Pedersen, C. J. J. Am. Chem. Soc. 1967, 89, 7017–7036.
5872 J. Org. Chem. 2008, 73, 5872–5880
10.1021/jo800890x CCC: $40.75 2008 American Chemical Society
Published on Web 06/28/2008

Syntheses of cis- and trans-Dibenzo-30-Crown-10 DeriVatiVes
SCHEME 1. Synthesis of cis-DB30C10 Diol 1a
a Reagents and conditions: (a) MeOH, SOCl2, reflux, 12 h, 90%; (b) benzyl bromide, K2CO3, N2, acetone, rt, 24 h, 50%; (c) tetra(ethylene glycol)
dichloride, K2CO3, N2, CH3CN, reflux, 36 h, 87%; (d) H2, Pd/C (10%), ethyl acetate, 50 °C, 24 h, 92%; (e) tetra(ethylene glycol) ditosylate, K2CO3, KPF6,
N2, DMF, 110 °C, 7 d, 55%; (f) LiAlH4, N2, dry THF, rt, 12 h, 95%.
SCHEME 2. Synthesis of Carbomethoxybenzo-15-Crown-5 13a
a Reagents and conditions: (a) tetra(ethylene glycol) dichloride, K2CO3, N2, CH3CN, reflux, 36 h, 77%; (b) H2, Pd/C (10%), ethyl acetate, 50 °C, 24 h,
95%; (c) K2CO3, KPF6, N2, CH3CN, reflux, 36 h, 90%.
rivatives,6 and between bis(m-phenylene)-32-crown-10 (BMP32-
C10) and paraquat derivatives,7 have been discovered. These
recognition motifs have greatly impelled the development of
host-guest chemistry.8 Paraquat derivatives (N,N′-dialkyl-4,4′-
bipyridinium salts) and diquat (1,1′-ethylene-2,2′-dipyridinium
salt) have been widely used in host-guest chemistry.9,10
However, although host-guest systems based on the recognition
motif of dibenzo-30-crown-10 (DB30C10) to metal cations have
been widely studied,11 host-guest systems based on the
recognition motif of DB30C10 to organic cations have been
relatively scarcely investigated except for several based on
the recognition motif of DB30C10 to diquat.12,13 One possible
reason is the difficulty in controlling the regiochemistry of
disubstituted dibenzo-type crown ethers and related complexes.14
Herein, we report syntheses of cis- and trans-dibenzo-30-crown-
10 derivatives Via regioselective routes, their complexations with
paraquat and diquat, and the reversible control of their com-
plexations with paraquat by the addition of small molecules
(KPF6 and dibenzo-18-crown-6).
way to prepare a cis-DB24C8 diester reported by the Gibson
group17 and reduced it to the aimed diol product 1 (Scheme 1).
B. Synthesis of trans-Dibenzo-30-Crown-10 Diol 2. We
also attempted to synthesize the trans-DB30C10 diester using
a similar route to that of trans-DB24C8 diester reported by the
Gibson group (Scheme 2).17 However, only carbomethoxy-
benzo-15-crown-5 (13) was obtained.
Then we tried another method to synthesize 2 (Scheme 3).
7b, the side product obtained in the preparation of 7a, was
reacted with 11 to give 14 (90%), a regiospecific isomer of 8.
The hydrogenolysis of 14 afforded diphenolic product 15 in a
high yield (95%). Then trans-DB30C10 diester 16 was obtained
by the cyclization reaction of 15 with tetra(ethylene glycol)
dichloride in the presence of potassium hexafluorophoaphate
as a template reagent (45%). The reduction of 16 was carried
out in dry THF to afford 2 in a high yield (93%).
(5) Ashton, P. R.; Baxter, I.; Fyfe, M. C. T.; Raymo, F. M.; Spencer, N.;
Stoddart, J. F.; White, A. J. P.; Williams, D. J. J. Am. Chem. Soc. 1998, 120,
2297–2307.
(6) Anelli, P. L.; Ashton, P. R.; Ballardini, R.; Balzani, V.; Delgado, M.;
Gandolfi, M. T.; Goodnow, T. T.; Kaifer, A. E.; Philp, D.; Pietraszkiewicz, M.;
Prodi, L.; Reddington, M. V.; Slawin, A. M. Z.; Spencer, N.; Stoddart, J. F.;
Vicent, C.; Williames, D. J. J. Am. Chem. Soc. 1992, 114, 193–219.
(7) Huang, F.; Nagvekar, D. S.; Slebodnick, C.; Gibson, H. W. J. Am. Chem.
Soc. 2005, 127, 484–485.
Results and Discussion
A. Synthesis of cis-Dibenzo-30-Crown-10 Diol 1. Syntheses
of cis- and trans-DB24C8, cis- and trans-BPP34C10, and their
derivatives were reported previously.15–17 cis-DB30C10 diol was
synthesized by the Stoddart group using an aldehyde derivative
as the starting material.18,19 To avoid the difficult control of
deprotection of the benzylated aldehyde in the Stoddart’s
method,17–19 we synthesized cis-DB30C10 diester 10 in a similar
(8) (a) Pease, A. R.; Jeppesen, J. O.; Stoddart, J. F.; Luo, Y.; Collier, C. P.;
Heath, J. R. Acc. Chem. Res. 2001, 34, 433–444. (b) Credi, A.; Balzani, V.;
Langford, S. J.; Stoddart, J. F. J. Am. Chem. Soc. 1997, 119, 2679–2681. (c)
Ashton, P. R.; Ballardini, R.; Balzani, V.; Baxter, I.; Credi, A.; Stoddart, J. F.;
Williams, D. J.; Gandolfi, M. T. J. Am. Chem. Soc. 1998, 120, 11932–11942.
(d) Han, T.; Chen, C.-F. Org. Lett. 2006, 8, 1069–1072.
J. Org. Chem. Vol. 73, No. 15, 2008 5873

He et al.
SCHEME 3. Synthesis of trans-DB30C10 Diol 2a
a Reagents and conditions: (a) 7b, K2CO3, N2, CH3CN, reflux, 36 h, 90%; (b) H2, Pd/C (10%), ethyl acetate, 50 °C, 24 h, 95%; (c) tetra(ethylene glycol)
dichloride, K2CO3, KPF6, N2, DMF, 110 °C, 7 d, 45%; (d) LiAlH4, N2, dry THF, rt, 12 h, 93%.
1
FIGURE 1. Partial H NMR spectra (400 MHz, 22 °C) of 4.00 mM crown ether 1 (a), 4.00 mM crown ether 1 and paraquat 3 (b), and 4.00 mM
paraquat 3 (c) in acetone-d6.
1
C. The 1H NMR Study of the Complexation of cis-
DB30C10 Diol 1 with Paraquat. As shown in Figure 1, the
1:1 mixture of 1 and 3 in acetone-d6 at 22 °C had significant
chemical shift changes in the H NMR signals compared with
the free crown ether host and paraquat guest under the same
condition.18 The pyridinium protons (H1 and H2) on paraquat 3
and phenyl protons (He, Hf, and Hg) of crown ether 1 moved
upfield sharply (Figure 1), indicating the formation of strong
π-π stacking interaction between the two pyridinium rings of
(9) Paraquat-based host-guest systems:(a) Huang, F.; Fronczek, F. R.;
Gibson, H. W. J. Am. Chem. Soc. 2003, 125, 9272–9273. (b) Huang, F.; Gibson,
H. W.; Bryant, W. S.; Nagvekar, D. S.; Fronczek, F. R. J. Am. Chem. Soc. 2003,
125, 9367–9371. (c) Huang, F.; Jones, J. W.; Slebodnick, C.; Gibson, H. W.
J. Am. Chem. Soc. 2003, 125, 14458–14464. (d) Huang, F.; Switek, K. A.;
Zakharov, L. N.; Fronczek, F. R.; Slebodnick, C.; Lam, M.; Golen, J. A.; Bryant,
W. S.; Mason, P. E.; Rheingold, A. L.; Ashraf-Khorassani, M.; Gibson, H. W.
J. Org. Chem. 2005, 70, 3231–3241. (e) Schmidt-Scha¨ffer, S.; Grubert, L.;
Grummt, U. W.; Buck, K.; Abraham, W. Eur. J. Org. Chem. 2006, 378–398. (f)
Huang, F.; Gantzel, P.; Nagvekar, D. S.; Rheingold, A. L.; Gibson, H. W.
Tetrahedron Lett. 2006, 47, 7841–7844. (g) Zong, Q.-S.; Chen, C.-F. Org. Lett.
2006, 8, 211–214. (h) Alcalde, E.; Pe´rez-Garc´ıa, L.; Ramos, S.; Stoddart, J. F.;
White, A. J. P.; Williams, D. J. Chem. Eur. J. 2007, 13, 3964–3979. (i) Gibson,
H. W.; Wang, H.; Slebodnick, C.; Merola, J.; Kassel, W. S.; Rheingold, A. L.
J. Org. Chem. 2007, 72, 3381–3393. (j) Zhang, J.; Huang, F.; Li, N.; Wang, H.;
Gibson, H. W.; Gantzel, P.; Rheingold, A. L. J. Org. Chem. 2007, 72, 8935–
8938. (k) Reviews: Harada, A. Acta Polym. 1998, 49, 3–17. (l) Raymo, F. M.;
Stoddart, J. F. Chem. ReV. 1999, 99, 1643–1664. (m) Molecular Catenanes and
Knots; Sauvage, J.-P., ; Dietrich-Bucheker, C., Eds.; Wiley: New York, 1999.
(n) Mahan, E.; Gibson, H. W. In Cyclic Polymers, 2nd ed.; Semlyen, A. J., Ed.;
Kluwer Publishers: Dordrecht, The Netherlands, 2000; pp 415-560. (o) Hubin,
T. J.; Busch, D. H. Coord. Chem. ReV. 2000, 200-202, 5–52. (p) Panova, I. G.;
Topchieva, I. N. Russ. Chem. ReV. 2001, 70, 23–44. (q) Huang, F.; Gibson,
H. W. Prog. Polym. Sci. 2005, 30, 982–1018.
(10) Diquat-based host-guest systems:(a) Allwood, B. L.; Shahriari-Zavareh,
H.; Stoddart, J. F.; Williams, D. J. Chem. Commun. 1987, 1058–1061. (b)
Allwood, B. L.; Spencer, N.; Shahriari-Zavareh, H.; Stoddart, J. F.; Williams,
D. J. Chem. Commun. 1987, 1061–1064. (c) Anelli, P. L.; Spencer, N.; Stoddart,
J. F. Tetrahedron Lett. 1988, 29, 1569–1572. (d) Anelli, P. L.; Slawin, A. M. Z.;
Stoddart, J. F.; Williams, D. J. Tetrahedron Lett. 1988, 29, 1573–1574. (e) Gunter,
M. J.; Johnston, M. R. Tetrahedron Lett. 1992, 33, 1771–1774. (f) Gunter, M. J.;
Jeynes, T. P.; Johnston, M. R.; Turner, P.; Chen, Z. J. Chem. Soc., Perkin Trans.
1 1998, 1945–1958. (g) Huang, F.; Slebodnick, C.; Switek, K. A.; Gibson, H. W.
Chem. Commun. 2006, 1929–1931. (h) Huang, F.; Slebodnick, C.; Switek, K. A.;
Gibson, H. W. Tetrahedron 2007, 63, 2829–2839. (i) Han, T.; Zong, Q.-S.; Chen,
C.-F. J. Org. Chem. 2007, 72, 3108–3111.
(11) (a) Lu, T.; Gan, X.; Tang, N.; Tan, M. Chem. Res. Chin. UniV. 1992, 8,
319–23. (b) Willey, G. R.; Meehan, P. R.; Rudd, M. D.; Drew, M. G. B. J. Chem.
Soc., Dalton Trans. 1995, 5, 811–17. (c) Matijasic, I.; Dapporto, P.; Rossi, P.;
Tusek-Bozic, L. Supramol. Chem. 2001, 13, 193–206. (d) Steed, J. W.; Johnson,
K.; Legido, C.; Junk, P. C. Polyhedron 2003, 22, 769–774.
(12) (a) Colquhoun, H. M.; Goodings, E. P.; Maud, J. M.; Stoddart, J. F.
J. Chem. Soc., Chem. Commun. 1983, 1140–1142. (b) Colquhoun, H. M.;
Goodings, E. P. J. Chem. Soc., Perkin. Trans. II 1985, 607–623.
5874 J. Org. Chem. Vol. 73, No. 15, 2008

Syntheses of cis- and trans-Dibenzo-30-Crown-10 DeriVatiVes
1
FIGURE 2. Partial H NMR spectra (400 MHz, 22 °C) of 4.00 mM crown ether 1 (a), 4.00 mM crown ether 1 and diquat 4 (b), and 4.00 mM
diquat 4 (c) in acetone-d6.
3 and the two phenyl rings of 1. The methyl protons (H3) of 3
and methylene protons (Hh), R-ethyleneoxy protons (Ha), and
ꢀ-ethyleneoxy protons (Hb) of 1 also had upfield chemical shift
changes after complexation (Figure 1). However, γ-ethyleneoxy
protons (Hc), δ-ethyleneoxy protons (Hd), and hydroxyl protons
(Hi) of 1 had downfield chemical shift changes after complex-
ation (Figure 1).
had about the same chemical shift changes (Figure 1, spectra a
and b) after complexation of 1 with paraquat 3 while the
chemical shift changes of He and Hg were obviously bigger than
that of Hf after complexation of 1 with diquat 4 (Figure 2,
spectra a and b). Second, the signals corresponding to phenyl
protons He and Hf were together after complexation of 1 with
paraquat 3 (Figure 1, spectra a and b) while the signals
corresponding to phenyl protons He and Hg were together after
complexation of 1 with diquat 4 (Figure 2, spectra a and b).
Third, the three peaks corresponding to ꢀ- (Hb), γ- (Hc), and
δ-ethyleneoxy protons (Hd) of 1 (Figure 1a) merged to become
a multiplet peak after complexation of 1 with paraquat 3 (Figure
1b) while they were still three separate peaks after complexation
of 1 with diquat 4 (Figure 2b). Fourth, the peak corresponding
to ꢀ-ethyleneoxy protons (Hb) of 1 moved upfield after
complexation of 1 with paraquat 3 (Figure 1, spectra a and b)
while this peak moved downfield after complexation of 1 with
diquat 4 (Figure 2, spectra a and b). These differences occurred
possibly due to the difference in host-guest geometries of the
complexes between 1 and paraquat 3 and between 1 and diquat
4 since both 3 and 4 are bipyridinium salts. γ-Pyridinium protons
H5, δ-pyridinium protons H6, and ꢀ-pyridinium protons H7 of
diquat 4 moved upfield after the complexation between crown
ether 1 and diquat 4, but the peak corresponding to δ-pyridinium
protons H6 has the biggest upfield shift (Figure 2, spectra b and
c). However, R-pyridinium protons H4 and N-methylene protons
H8 of diquat 4 have no obvious chemical shift changes (Figure
2, spectra b and c).
1
D. The H NMR Study of the Complexation of trans-
DB30C10 Diol 2 with Paraquat 3. Chemical shift changes of
protons on trans-DB30C10 diol 2 and paraquat 3 after their
complexation in acetone-d6 are similar to chemical shift changes
of protons on cis-DB30C10 diol 1 and paraquat 3 after their
complexation in acetone-d6 (Figure 1, as well as Figure S40 in
the Supporting Information). Two common characteristics are
worth noting. First, either the multiplet peak corresponding to
phenyl protons He and Hf of crown ether 1 (Figure 1a) or the
multiplet peak corresponding to phenyl protons Ho and Hp of
crown ether 2 (Figure S40a, Supporting Information) merged
to become a sharp peak after host-guest complexation (Figure
1b as well as Figure S40b in the Supporting Information).
Second, either the three peaks corresponding to ꢀ- (Hb), γ- (Hc),
and δ-ethyleneoxy protons (Hd) of 1 (Figure 1a) or the three
peaks corresponding to ꢀ- (Hk), γ- (Hl), and δ-ethyleneoxy
protons (Hm) of 2 (Figure S40a, Supporting Information) merged
to become a multiplet peak after host-guest complexation
(Figure 1b as well as Figure S40b in the Supporting Informa-
tion).
E. The 1H NMR Study of the Complexation of cis-
DB30C10 Diol 1 with Diquat 4. Chemical shift changes of
protons of 1 after complexation of crown ether 1 with diquat 4
were far different from those after complexation of crown ether
1 with paraquat 3. First, phenyl protons He, Hf, and Hg of 1
1
F. The H NMR Study of the Complexation of trans-
DB30C10 Diol 2 with Diquat 4. Chemical shift changes of
protons on trans-DB30C10 diol 2 and diquat 4 after their
complexation in acetone-d6 are similar to chemical shift changes
of protons on cis-DB30C10 diol 1 and diquat 4 after their
complexation in acetone-d6 (Figure 2 as well as Figure S41 in
the Supporting Information).
G. The Determination of Stoichiometries of the Com-
plexations between Either of Hosts 1 and 2 and Either of
Guests 3 and 4. Equimolar (0.500 mM) acetone solutions of
either of two crown ethers 1 and 2 with either of two guests 3
(13) Kohnke, F. H.; Stoddart, J. F.; Allwood, B. L.; Williams, J. Tetrahedron
Lett. 1985, 16, 1681–1684.
(14) (a) Ashton, P. R.; Baxter, I.; Cantrill, S. J.; Fyfe, M. C. T.; Glink, P. T.;
Stoddart, J. F.; 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.
(15) Li, X.-Q.; Feng, D.-J; Jiang, X.-K.; Li, Z.-T. Tetrahedron 2004, 60,
8275–8284.
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He et al.
and 4 are yellow or orange due to charge transfer between the
electron-rich aromatic rings of the crown ether hosts and the
electron-poor pyridinium rings of the bipyridinium guests. Job
plots20 (Figure S39, Supporting Information) based on UV-vis
absorption spectroscopy data demonstrated that all four com-
plexes were of 1:1 stoichiometry in acetone.
H. Electrospray Ionization Mass Spectrometry. The 1:1
stoichiometries of complexations between either of hosts 1 and
2 and either of guests 3 and 4 were further confirmed by
electrospray ionization mass spectrometry in acetone. Three
relevant peaks were found for 1·3: m/z 927.2 [1·3 - PF6]+
(79%), 781.3 [1·3 - PF6 - HPF6]+ (29%), and 391.4 [1·3 -
2PF6]2+ (25%) with the base peak at m/z 619.5 for [1 + Na]+.
FIGURE 3. Stacking diagrams of (a) paraquat 3 (blue) and a part of
the DB30C10 cavity (red) and (b) diquat 4 (blue) and a part of the
DB30C10 cavity (red) showing how the DB30C10 cavity can bind
paraquat and diquat driven by π-stacking and charge transfer interac-
tions between the electron-rich catechol rings of the DB30C10 cavity
and the electron-poor pyridinium rings of paraquat 3 or diquat 4,
electrostatic interaction between electron-rich ethyleneoxy oxygens of
the DB30C10 cavity and the positive-charged nitrogen atoms of
paraquat 3 or diquat 4, and hydrogen bonding between ethyleneoxy
oxygen atoms of the DB30C10 cavity and pyridinium hydrogens of
paraquat 3 or diquat 4. Black dashed arrows show the best places for
ethylene glycol chains where the total noncovalent interaction between
the host and guest can be maximized.
Two peaks were observed for 2·3: m/z 927.2 [2·3 - PF6]+
(32%) and 391.5 [2·3 - 2PF6]2+ (25%) with the base peak at
m/z 635.4 for [2 + K]+.
One relevant peak was detected for 1·4: m/z 925.2 [1·4 -
PF6]+ (42%) with the base peak at m/z 635.2 for [1 + K]+.
R-pyridinium hydrogens of paraquat 3 together (this is allowed
based on their positions on paraquat 3, see Figure 3).
Also one relevant peak was observed for 2·4: m/z 925.2 [2·4
- PF6]+ (18%) with the base peak at m/z 635.2 for [2 + K]+.
The Ka value of 1·3 is a little lower than that of 2·3 while
the Ka value of 1·4 is a little higher than that of 2·4, indicating
that host-guest geometries of paraquat 3-based complexes are
different from those of diquat 4-based complexes, in accordance
with the notable differences between the chemical shift changes
of protons of crown ether host 1 or 2 that occurred when it
complexes 3 and those that occurred when it complexes 4
(Figures 1a, 1b, 2a, and 2b or Figures S40a, S40b, S41a, and
S41b in the Supporting Information).
No peaks were found for complexes with other stoichiometries.
I. Determination of Association Constants. The association
constants (Ka) of 1·3, 1·4, 2·3, and 2·4 were determined by
probing the charge-transfer bands of the complexes by UV-vis
spectroscopy and employing a titration method. Progressive
addition of an acetone solution with high guest salt (3 or 4)
concentration and low host (1 or 2) concentration to an acetone
solution with the same concentration of host results in an
increase of the intensity of the charge-transfer band of the
complex. Treatment of the collected absorbance data at λ )
403 nm with a nonlinear curve-fitting program afforded the
corresponding Ka values: 1.1((0.1) × 103 M-1 for 1·3,
1.7((0.1) × 103 M-1 for 2·3, 5.0((1.3) × 104 M-1 for 1·4,
and 3.3((1.0) × 104 M-1 for 2·4. The Ka value of 1·4 is about
44 times higher than that of 1·3 and the Ka value of 2·4 is
about 18 times higher than that of 2·3. Since both paraquat 3
and diquat 4 are bipyridinium salts, the obvious increase in Ka
from 3-based complexes to 4-based complexes should be due
to the better geometry fit between diquat 4 (it has a relatively
shorter N+ · · ·N+ distance) and the DB30C10 cavity (its two
ethylene glycol chains of the DB30C10 cavity are at two
neighboring positions of its phenylene rings) than that between
paraquat 3 (it has a relatively longer N+ · · ·N+ distance) and
the DB30C10 cavity (Figure 3). It should be noted that due to
the two positive charges that the two pyridinium rings of
paraquat 3 or diquat 4 have, all hydrogens of 3 and 4 are acidic
(electron-poor) so they want to form hydrogen bonds with basic
(electron-rich) ether oxygen atoms of the DB30C10 cavity. The
two ethylene glycol chains of the DB30C10 cavity are at two
neighboring positions of its phenylene rings, making it easier
for their basic aliphatic ether oxygen atoms to form hydrogen
bonds with N-methylene hydrogens and R-pyridinium hydrogens
of diquat 4 together (this is allowed based on their positions on
diquat 4, see Figure 3) than with N-methyl hydrogens and
J. Influence of the Addition of Small Molecules KPF6
and Dibenzo-18-Crown-6 (DB18C6) on the Complexations
of Either of cis- and trans-Dibenzo-30-Crown-10 Diols 1
and 2 with Either of Paraquat 3 and Diquat 4. When 1 molar
equiv of KPF6 was added to an equimolar solution of 4.00 mM
cis-DB30C10 diol 1 and paraquat 3, the chemical shifts of
protons on paraquat 3 returned to almost their uncomplexed
values (Figure 4a,b,c,f) and correspondingly the yellow color
of the solution turned very weak. When one more molar equiv
of KPF6 was added, the chemical shifts of protons on paraquat
3 returned to their uncomplexed values (Figure 4d,f) and
correspondingly the yellow color of the solution totally disap-
peared, indicating the total dissociation of complex 1·3.
However, when 2 molar equiv of DB18C6 was subsequently
added, chemical shift changes of protons on paraquat 3 were
observed again (Figure 4e,f) and correspondingly the yellow
color of the solution recovered, indicating the reformation of
complex 1·3. The same phenomena were observed for the
complexation between trans-DB30C10 diol 2 and paraquat 3
(Figure S42, Supporting Information). These demonstrated that
the complexations between cis- and trans-DB30C10 diols 1 and
2 with paraquat 3 can be reversibly controlled by adding small
molecules KPF6 and DB18C6 (Figure 5). Considering that the
stoichiometry of the complexation between the DB30C10 cavity
and KPF6 is also 1:1,21 these also indicated that the Ka value of
complex 1·3 (or 2·3) is much lower than that of complex
1·KPF6 (or 2·KPF6) and that the Ka values of complexes
1·KPF6 (or 2·KPF6) and DB18C6 ·3 are much lower than that
of complex DB18C6 ·KPF6.
(16) Feng, D.-J.; Li, X.-Q.; Wang, X.-Z.; Jiang, X.-K.; Li, Z.-T. Tetrahedron
2004, 60, 6137–6144.
(17) Gibson, H. W.; Wang, H.; Bonrad, K.; Jones, J. W.; Slebodnick, C.;
Zackharov, L. N.; Rheingold, A. L.; Habenicht, B.; Lobue, P.; Ratliff, A. E.
Org. Biomol. Chem. 2005, 3, 2114–2121.
When 1 molar equiv of KPF6 was added to an equimolar
solution of 4.00 mM cis-DB30C10 diol 1 and diquat 4, the
(18) Allwood, B. L.; Kohnke, F. H.; Slawin, A. M. Z.; Stoddart, J. F.;
Williames, D. J. J. Chem. Soc., Chem. Commun. 1985, 311–314.
(19) Kohnke, F. H.; Stoddart, J. F. J. Chem. Soc., Chem. Commun. 1985,
314–317.
(20) Job, P. Ann. Chim. 1928, 9, 113–203.
(21) Truter, M. R.; Bush, M. A. J. Chem. Soc. D: Chem. Commun. 1970,
1439–1440.
5876 J. Org. Chem. Vol. 73, No. 15, 2008

Syntheses of cis- and trans-Dibenzo-30-Crown-10 DeriVatiVes
FIGURE 4. Partial 400 MHz 1H NMR spectra of (a) 4.00 mM 1, (b) 4.00 mM 1 and 3, (c) 4.00 mM 1, 3, and KPF6, (d) 4.00 mM 1 and 3 and 8.00
mM KPF6, (e) 4.00 mM 1 and 3 and 8.00 mM KPF6 and DB18C6, and (f) 4.00 mM 3 in acetone-d6.
FIGURE 5. Reversible control of the complexation of cis-DB30C10 diol (1) with paraquat (3) brought about by displacement with the potassium
cation from KPF6 and the subsequent rebinding of 3 by 1 as K+ is bound by added DB18C6.
chemical shift changes of protons on diquat 4 caused by its
complexation with 1 decreased (Figure 6a,b,c,f) and correspond-
ingly the orange color of the solution turned weak. When one
more molar equiv of KPF6 was added, the chemical shift
changes of protons on diquat 4 decreased further (Figure 6d,f)
and correspondingly the orange color of the solution turned a
little weaker but did not disappear, indicating that the com-
plexation between 1 and 4 was not completely prohibited. When
2 molar equiv of DB18C6 was subsequently added, chemical
shift changes of protons on diquat 4 were increased but not to
the degree when neither KPF6 nor DB18C6 were added (Figure
6b,e,f) and correspondingly the orange color of the solution
became stronger, indicating the increase of the complex 1·4
concentration. The same phenomena were observed for the
J. Org. Chem. Vol. 73, No. 15, 2008 5877

He et al.
FIGURE 6. Partial 400 MHz 1H NMR spectra of (a) 4.00 mM 1, (b) 4.00 mM 1 and 4, (c) 4.00 mM 1, 4, and KPF6, (d) 4.00 mM 1 and 4 and 8.00
mM KPF6, (e) 4.00 mM 1 and 4 and 8.00 mM KPF6 and DB18C6, and (f) 4.00 mM 4 in acetone-d6.
complexation between trans-DB30C10 diol 2 and diquat 4
(Figure S43, Supporting Information). These demonstrated that
the complexations between cis- and trans-DB30C10 diols 1 and
2 with diquat 4 cannot be controlled by adding small molecules
KPF6 and DB18C6. These also indicated that the Ka value of
complex 1·4 (or 2·4) is comparable to that of complex 1·KPF6
(or 2·KPF6).
K. Crystal Structures of Complexes 2 ·4 and 1 ·4. Single
FIGURE 7. A ball-stick view of the X-ray structure of 1·4. 1 is red,
crystals of 1·4 were obtained by diffusion of isopropyl ether
4 is blue, hydrogens are pink, oxygens are green, nitrogens are black,
and the water molecule is magenta. PF6 counterions, solvent molecules,
into a solution of 1 and 4 in acetone at room temperature. The
X-ray crystal structure of complex 1·4 confirmed the 1:1
stoichiometry and demonstrated that cis-DB30C10 diol 1 and
diquat 4 formed a taco complex in the solid state (Figure 7).
Because of the formation of a so-called “supramolecular
cryptand” structure,22 complex 1·4 is stabilized by not only the
hydrogen bonding between the host and guest and π-π stacking
between the catechol rings of the crown ether host and the
pyridinium rings of the diquat guest but also the hydrogen
bonding between the “water bridge” and 1 and 4 (Figure 7).
Interestingly, the same kind of water-assisted formation of
supramolecular cryptand structure was also observed in a
previously reported complex based on an isomeric bis(m-
phenylene)-32-crown-10 diol and diquat.10h Two N-methylene
hydrogens H8 (f and j in Figure 7) and two R-pyridinium
hydrogens H4 (e, g, h, i, k, and l in Figure 7) are directly hy-
drogen bonded to ethyleneoxy oxygen atoms of the crown ether
host. Two δ-pyridinium hydrogens H6 are indirectly connected
to the two terminal alcohol groups of host 1 by a hydrogen-
bonding water bridge (a, b, c, and d in Figure 7) to form the
supramolecular cryptand structure. None of the ꢀ-pyridinium
hydrogens H7 and γ-pyridinium hydrogens H5 of 4 are involved
and hydrogens except the ones involved in hydrogen bonding between
1 and 4 were omitted for clarity. Hydrogen bond parameters: H · · ·O
distance (Å), C(O)-H · · · O angle (deg), C(O) · · · O distance (Å)sa,
1.90, 177, 2.75; b, 1.90, 177, 2.75; c, 2.70, 180, 3.63; d, 2.54, 170,
3.46; e, 2.70, 113, 3.19; f, 2.65, 141, 3.46; g, 2.63, 108, 3.04; h, 2.26,
166, 3.17; i, 2.63, 108, 3.04; j, 2.65, 141, 3.46; k, 2.70, 113, 3.19; l,
2.50, 166, 3.41. Face-to-face π-stacking parameters: centroid-centroid
distances (Å) 4.04, 4.36, 4.04, 4.36; ring plane/ring plane inclinations
(deg) 3.3, 3.3, 3.3, 3.3.
in interactions between the host and guest in complex 1·4 in
the solid state.
The two phenylene rings of 1 are not parallel to each other
but exhibit a twist angle of 6.7°. The centroid-centroid distance
(22) Supramolecular cryptands have been referred to as “pseudocryptands”.
For the first such reference see:(a) Nabeshima, T.; Inaba, T.; Sagae, T.; Furukawa,
N. Tetrahedron Lett. 1990, 31, 3919–3922. (b) Recent references: Romain, H.;
Florence, D.; Alain, M. Chemistry 2002, 8, 2438–2445. (c) Nabeshima, T.;
Yoshihira, Y.; Saiki, T.; Akine, S.; Horn, E. J. Am. Chem. Soc. 2003, 125, 28–
29. (d) Jones, J. W.; Zakharov, L. N.; Rheingold, A. L.; Gibson, H. W. J. Am.
Chem. Soc. 2002, 124, 13378–13379. (e) Huang, F.; Zakharov, L. N.; Rheingold,
A. L.; Jones, J. W.; Gibson, H. W. Chem. Commun. 2003, 2122–2123. (f) Huang,
F.; Guzei, I. A.; Jones, J. W.; Gibson, H. W. Chem. Commun. 2005, 1693–
1695. (g) A review: Nabeshima, T.; Akine, S.; Saiki, T. ReV. Heteroatom Chem.
2000, 22, 219–239.
5878 J. Org. Chem. Vol. 73, No. 15, 2008

Syntheses of cis- and trans-Dibenzo-30-Crown-10 DeriVatiVes
Conclusion
In summary, isomeric cis- and trans-DB30C10 diols 1 and 2
were successfully synthesized regiospecifically with good yields,
avoiding the difficult problem of separation of the two isomers’
precursors diesters. Because trans-DB30C10 diester has 6 more
atoms in its polyether macroring than trans-DB24C8 diester has,
the reported method for the preparation of trans-DB24C8 diester
fell in the trouble of the exclusive formation of smaller
macrocycle carbomethoxybenzo-15-crown-5 when it was used
for the synthesis of trans-DB30C10 diester. The synthetic routes
of the two hosts 1 and 2 as a whole have atomic economy
because the side product, 7b, of benzylation of methyl 3,4-
dihydroxybenzoate was used in the preparation of trans-
DB30C10 diester 16.
The big difference (44 or 18 times) between the Ka value of
the 1·3 (or 2·3) and 1·4 (or 2·4) in acetone suggested high
selectivity of 1 (or 2) to bind diquat 4 against paraquat 3. This
indicated that the DB30C10 cavity can be used for the
preparation of chemical sensors which can selectively detect
diquat against paraquat.23
FIGURE 8. A ball-stick view of the X-ray structure of 2·4. 2 is red,
4 is blue, hydrogens are pink, oxygens are green, and nitrogens are
black. PF6 counterions, solvent molecules, and hydrogens except the
ones involved in hydrogen bonding between 2 and 4 were omitted for
clarity. Hydrogen bond parameters: H · · · O distance (Å), C-H · · · O
angle (deg), C· · ·O distance (Å)sm, 2.27, 140, 3.04; n, 2.49, 146, 3.34;
o, 2.68, 130, 3.39; p, 2.40, 166, 3.35; q, 2.69, 157, 3.60; r, 2.62, 146,
3.43; s, 2.32, 140, 3.09; t, 2.49, 150, 3.36; u, 2.57, 161, 3.47. Face-
to-face π-stacking parameters: centroid-centroid distances (Å) 3.66,
4.99, 4.87, 3.65; ring plane/ring plane inclinations (deg): 8.3, 8.3, 10.2,
6.2.
between them is 6.84 Å. The two pyridium rings of diquat 4
were twisted in the solid state for all previously reported diquat-
based complexes,10a,g–i,12,18 but the crystal structure shown in
Figure 7 demonstrates that here the two pyridium rings of diquat
4 are exactly coplanar in the solid state for complex 1·4,
presumably to maximize face-to-face π-stacking and charge
transfer interactions between the electron-rich catechol rings of
crown ether 1 and electron-poor pyridinium rings of diquat 4.
Single crystals of 2·4 were obtained by diffusion of isopropyl
ether into a solution of 2 and 4 in acetonitrile at room
temperature. The X-ray crystal structure of complex 2·4 also
confirmed the 1:1 stoichiometry and demonstrated that trans-
DB30C10 diol 2 and diquat 4 also formed a taco complex in
the solid state (Figure 8). Just like complex 1·4, complex 2·4
is also stabilized by hydrogen bonds between the host and guest
and π-π stacking interactions between the two catechol rings
of the crown ether host and the two pyridinium rings of the
diquat guest (Figure 8), two R-pyridinium hydrogens H4 (m, r,
and s in Figure 8) are directly hydrogen bonded to ethyleneoxy
oxygen atoms of the crown ether host, and none of ꢀ-pyridinium
hydrogens H7 and γ-pyridinium hydrogens H5 of 4 are involved
in interactions between the host and guest in complex 2·4 in
the solid state.
However, there are some differences. First, the formation of
a supramolecular cryptand structure is not observed for complex
2·4 in the solid state (Figure 8) and one δ-pyridinium hydrogen
H6 is directly connected to a terminal alcohol group of host 2
(i in Figure 8). This is a possible reason for the increase in
association constant from 2·4 (3.3 × 104 M-1) to 1·4 (5.0 ×
104 M-1). Second, all four N-methylene hydrogens H8 are
directly hydrogen bonded to ethyleneoxy oxygen atoms of the
crown ether host (n, o, p, q, and t in Figure 8) for complex 2·4
in the solid state while only two N-methylene hydrogens H8 do
so (f and j in Figure 7) for complex 1·4 in the solid state. Third,
the two catechol rings of the crown ether host in 2·4, with a
twist angle of 2.3°, are more parallel in the solid state (Figure
8) than those in 1·4, with a twist angle of 6.7°, in the solid
state (Figure 7). Fourth, the centroid-centroid distance, 7.23
Å, between the two catechol rings of the crown ether host in
2·4 is bigger (Figure 8) than the corresponding value, 6.84 Å,
in 1·4 (Figure 7). Fifth, the two pyridium rings of diquat 4,
with a twist angle of 16.3°, are not coplanar in the crystal
structure of complex 2·4 (Figure 8).
From the investigation of the influence of the addition of small
molecules KPF6 and DB18C6 on the complexations of either
of hosts 1 and 2 with either of guests paraquat 3 and diquat 4,
we found that the addition of KPF6 could dissociate the
complexes 1·3 and 2·3 completely and the subsequent addition
of DB18C6 could reform these complexes completely. This
reversible control makes DB30C10 derivatives and paraquat
derivatives good candidate components for constructing mo-
lecular machines driven by adding small molecules.
Experimental Section
r,ω-Bis(2′-benzyloxy-5′-carbomethoxyphenoxy)-3,6,9-triox-
aundecane (Dimethyl 4,4′-Bis(benzyloxy)-3,3′-oxytetra(ethyl-
eneoxy)dibenzoate) (8). A suspension of methyl 4-benzyloxy-3-
hydroxybanzoate 7a (5.16 g, 20.0 mmol), tetra(ethylene glycol)
dichloride (1.96 g, 8.50 mmol), and K2CO3 (7.60 g, 55.0 mmol) in
CH3CN (100 mL) was heated under N2 atmosphere at reflux for
48 h. After the mixture was filtered, the solvent of the filtrate was
removed. The residue was dissolved in CH2Cl2 and washed twice
with saturated Na2CO3 solution and the organic layer was dried
over anhydrous Na2SO4. CH2Cl2 was removed. The crude product
was absorbed on silica gel and purified by flash column chroma-
tography (ethyl acetate/petroleum ether ) 2/3) to give 8 as a light
1
yellow liquid (4.98 g, 87%). H NMR (400 MHz, CDCl3, 22 °C)
δ 7.62 (dd, J1 ) 8.4 Hz, J2 ) 2.0 Hz, 2H), 7.57 (d, J ) 2.0 Hz,
2H), 7.43-7.26 (m, 10H), 6.90 (d, J ) 8.4 Hz, 2H), 5.16 (s, 4H),
4.21 (t, J ) 5.2 Hz, 4H), 3.88 (t, J ) 5.2 Hz, 10H), 3.71 (t, J )
5.2 Hz, 4H), 3.62 (t, J ) 5.2 Hz, 4H). Anal. Calcd for C38H42O11:
C, 67.64; H, 6.27. Found: C, 67.68; H, 6.28.
r,ω-Bis(2′-hydroxy-5′-carbomethoxyphenoxy)-3,6,9-trioxaun-
decane (Dimethyl 4,4′-Dihydroxy-3,3′-oxytetra(ethyleneoxy)di-
benzoate) (9). A suspension of 8 (10.0 g, 14.8 mmol) and Pd/C
(10%, 1.00 g) in ethyl acetate (200 mL) was stirred at room
temperature under H2 atmosphere for 24 h. After filtration, the
filtrate was concentrated to give 9 as a white solid (6.72 g, 92%).
1
Mp 62-63 °C. H NMR (400 MHz, CD3COCD3, 22 °C) δ 8.46
(br, 2H), 7.51 (dd, J1 ) 8.4 Hz, J2 ) 2.0 Hz, 2H), 6.86 (d, J ) 8.4
(23) (a) Mastichiadis, C.; Kakabakos, S. E.; Christofidis, I.; Koupparis, M. A.;
Willetts, C.; Misiakos, K. Anal. Chem. 2002, 74, 6064–6072. (b) Merino, F.;
Rubio, S.; Perez-Bendito, D. Anal. Chem. 2004, 76, 3878–3886. (c) Bacigalupo,
M. A.; Meroni, G.; Mirasoli, M.; Parisi, D.; Longhi, R. J. Agric. Food Chem.
2005, 53, 216–219. (d) Aliferis, K. A.; Chrysayi-Tokousbalides, M. J. Agric.
Food Chem. 2006, 54, 1687–1692. (e) Bacigalupo, M. A.; Meroni, G. J. Agric.
Food Chem. 2007, 55, 3823–3828.
J. Org. Chem. Vol. 73, No. 15, 2008 5879

He et al.
Hz, 2H), 4.17 (t, J ) 4.2 Hz, 4H), 3.80 (t, J ) 4.2 Hz, 4H), 3.77
(s, 6H), 3.65-3.58 (m, 8H). Anal. Calcd for C24H30O11: C, 58.29;
H, 6.12. Found: C, 58.30; H, 6.14.
twice with saturated Na2CO3 solution. CH2Cl2 was removed. The crude
product was absorbed on silica gel and purified by flash column
chromatography (ethyl acetate/petroleum ether ) 1/2) to give 14 as a
1
cis-Bis(carbomethoxybenzo)-30-crown-10 (10). To a suspen-
sion of tetrabutylammonium bromide (80.0 mg) and K2CO3 (20.7
g, 150 mmol) in DMF (800 mL) under N2 atomosphere at 110 °C
was added a solution of 9 (9.01 g, 18.2 mmol) and tetra(ethylene
glycol) dichloride (4.20 g, 18.2 mmol) in DMF (50 mL) with a
syringe pump at 0.80 mL/h. The mixture was further stirred at 110
°C for 5 days. After filtration, the solvent of the filtrate was removed
under reduced pressure. The residue was dissolved in CH2Cl2 and
washed twice with water. The solvent was removed to afford a
crude product, which was absorbed on silica gel and purified by
flash column chromatography (ethyl acetate/acetone )3/1) to give
10 as a light yellow solid (6.50 g, 55%). Mp 149-150 °C; 1H NMR
(400 MHz, CD3COCD3, 22 °C) δ 7.61 (dd, J1 ) 4.8 Hz, J2 ) 1.6
Hz, 2H), 7.49 (d, J ) 1.6 Hz, 2H), 7.06 (d, J ) 4.8 Hz, 2H),
4.30-4.28 (m, 4H), 4.24-4.22 (m 4H), 3.89-3.86 (m, 14H),
3.80-3.70 (m, 16H). Anal. Calcd for C32H44O14: C, 58.89; H, 6.79.
Found: C, 58.82; H, 6.79.
cis-Bis(hydroxymethylbenzo)-30-crown-10 (1). To a suspension
of LiAlH4 (76.0 mg, 2.00 mmol) in dry THF (10 mL) was added
dropwise a solution of 10 (0.650 g, 1.00 mmol) in dry THF (20.0
mL) under N2 atmosphere at 0 °C. The mixture was further stirred
for 12 h at room temperature. The excess LiAlH4 was quenched
with ethyl acetate. The resulting mixture was filtered and the filtrate
was concentrated to give a white solid, which was dissolved in
CH2Cl2 and washed with saturated NaCl solution. The solvent was
removed to give 1 as a white solid (0.57 g, 95%). Mp 89-90 °C;
1H NMR (400 MHz, CD3COCD3, 22 °C) δ 6.91 (d, J ) 2.0 H,
2H), 6.87-6.82 (m, 4H), 4.47 (d, J ) 6.0 Hz, 4H), 4.07 (t, J ) 4.4
Hz, 8H), 3.99 (t, J ) 6.0 Hz, 2H), 3.78-3.75 (m, 8H), 3.67-3.65
(m, 8H), 3.61-3.58 (m, 8H). Anal. Calcd for C30H44O12: C, 60.39;
H, 7.43. Found: C, 60.39; H, 7.43.
Methyl 4-Benzyloxy-3-(chloroethoxy{ethoxy[ethoxy(ethoxy)]})-
benzoate (11). A solution of 7a (2.00 g, 7.70 mmol), K2CO3 (3.20
g, 23.2 mmol), and tetra(ethyleneglycol) dichloride (5.50 g, 20.0
mmol) in CH3CN (250 mL) was stirred under N2 atmosphere at
reflux for 3 days. After filtration, the solvent of the filtrate was
removed under reduced pressure. The residue was dissolved in
CH2Cl2 and washed twice with water. CH2Cl2 was removed. The
crude product was absorbed on silica gel and purified by column
chromatography (ethyl acetate/petroleum ) 1/8) to give 11 as a
light yellow liquid (2.61 g, 75%). 1H NMR (400 MHz, CD3COCD3,
22 °C) δ 7.63-7.60 (m, 2H), 7.54 (d, J ) 7.2 Hz, 2H), 7.41 (t, J
) 7.2 Hz, 2H), 7.34 (t, J ) 6.8 Hz, 1H), 7.15 (d, J ) 8.4 Hz, 1H),
5.24 (s, 2H), 4.23 (t, J ) 4.8 Hz, 2H), 3.86 (t, J ) 4.8 Hz, 2H),
3.84 (s, 3H) 3.72-3.57 (m, 12H). Anal. Calcd for C23H29ClO7: C,
60.99; H, 6.45. Found: C, 60.94; H, 6.49.
Methyl 4-Hydoxy-3-(chloroethoxy{ethoxy[ethoxy(ethoxy)]})-
benzoate (12). A suspension of 11 (0.109 g, 0.240 mmol) and 10%
Pd/C (92.0 mg) in CH3OH/CHCl3 (25.0/25.0 mL) was stirred under
H2 atmosphere at 50 °C for 48 h. After filtration, the filtrate was
concentrated to give 12 as a light yellow oil (2.75 g, 100%). This
compound was used in the next step without further purification.
ESIMS (negative) m/z 361.2 [M - H]-. ESIMS (positive) m/z 385.2
[M + Na]+, 401.2 [M + K]+. 1H NMR (400 MHz, CDCl3, 22 °C)
δ 7.79 (br, 1H), 7.66 (dd, J1 ) 8.4 Hz, J2 ) 2.4 Hz, 1H), 7.59 (d,
J ) 2.4 Hz, 1H), 6.93 (d, J ) 8.4 Hz, 1H), 4.23-4.21 (m, 2H),
3.87(s, 3H), 3.86-3.84 (m, 2H), 3.78-3.62 (m, 12H). Anal. Calcd
for C16H23ClO7: C, 52.97; H, 6.39. Found: C, 52.96; H, 6.38.
r-(2′-Benzyloxy-5′-carbomethoxyphenoxy)-ω-(5′-benzyloxy-
2′-carbomethoxyphenoxy)-3,6,9-trioxaundecane (Dimethyl 3,4′-
Bis(benzyloxy)-4,3′-oxytetra(ethyleneoxy)dibenzoate) (14). A
suspension of 7b (0.517 g, 2.00 mmol), 12 (0.810 g, 1.80 mmol), and
K2CO3 (0.790 g, 5.00 mmol) in CH3CN (25.0 mL) was stirred under
N2 atmosphere at reflux for 36 h. After filtration, the solvent was
removed. The resulting residue was dissolved in CH2Cl2 and washed
yellow liquid (1.09 g, 90%). H NMR (400 MHz, CDCl3, 22 °C) δ
7.66-7.58 (m, 4H), 7.46-7.26 (m, 10H), 6.90 (d, J ) 8.4 Hz, 2H),
5.16 (s, 2H), 5.13 (s, 2H), 4.22-4.20 (m, 4H), 3.89-3.87 (m, 10H),
3.72-3.70 (m, 4H), 3.62-3.60 (m, 4H). Anal. Calcd for C38H42O11:
C, 67.64; H, 6.27. Found: C, 67.65; H, 6.31.
r-(2′-Hydroxy-5′-carbomethoxyphenoxy)-ω-(5′-hydroxy-2′-
carbomethoxyphenoxy)-3,6,9-trioxaundecane (Dimethyl 3,4′-Bis-
(hydroxy)-4,3′-oxytetra(ethyleneoxy)dibenzoate) (15). A suspen-
sion of 14 (1.00 g, 1.48 mmol) and Pd/C (0.10 g, 10%) in ethyl acetate
(20.0 mL) was stirred under H2 atmosphere at 50 °C for 24 h. After
filtration, the filtrate was concentrated to give 15 as a light yellow
liquid (0.70 g, 96%). 1H NMR (400 MHz, CD3COCD3, 22 °C) δ 7.70
(br, 1H), 7.64 (d, J ) 8.4 Hz, 1H), 7.58-7.54 (m, 3H), 7.05 (br, 1H),
6.92 (d, J ) 8.4 Hz, 1H), 6.86 (d, J ) 8.4 Hz, 1H), 4.21-4.20 (br,
4H), 3.88-3.84 (m, 10H), 3.73-3.71 (m, 8H). Anal. Calcd for
C24H30O11: C, 58.29; H, 6.12. Found: C, 58.29; H, 6.20.
trans-Bis(carbomethoxybenzo)-30-crown-10 (16). To a stirred
suspension of tetrabutylammonium bromide (60.0 mg, 0.186 mmol)
and K2CO3 (20.7 g, 150 mmol) in DMF (800 mL) at 110 °C under
N2 atmosphere was added a solution of 15 (8.00 g, 16.2 mmol)
and tetra(ethyleneglycol) dichloride (3.74 g, 16.2 mmol) in DMF
(50 mL) with a syringe pump at 0.80 mL/h. The mixture was further
stirred at 110 °C for 5 days. After filtration, the solvent of the filtrate
was removed under reduced pressure. The residue was dissolved
in CH2Cl2 and washed twice with water. The solvent was removed
to afford a crude product, which was absorbed on silica gel and
purified by flash column chromatography (ethyl/acetone ) 3/1) to
give 16 as a light yellow solid (4.75 g, 45%). Mp 170-171 °C; 1H
NMR (400 MHz, CD3COCD3, 22 °C) δ 7.62 (dd, J1 ) 4.8 Hz, J2
) 1.6 Hz, 2H), 7.48 (d, J ) 1.6 Hz, 2H), 7.08 (d, J ) 4.8 Hz, 2H),
4.32-4.30 (m, 4H), 4.22-4.20 (m, 4H), 3.92-3.90 (m, 4H), 3.85
(s, 6H), 3.83-3.80 (m, 4H), 3.78-3.70 (m, 16H). Anal. Calcd for
C32H44O14: C, 58.89; H, 6.79. Found: C, 58.84; H, 6.77.
trans-Bis(hydroxymethylbenzo)-30-crown-10 (2). To a suspen-
sion of LiAlH4 (57.0 mg, 1.50 mmol) in THF (10.0 mL) was added
a solution of 15 (0.500 g, 0.770 mmol) in dry THF (20.0 mL)
dropwise under N2 atmosphere at 0 °C. The reaction was further
stirred for 12 h at room temerature. The excess LiAlH4 was
quenched with ethyl acetate. The resulting mixture was filtered and
the filtrate was concentrated to give a solid. The solid was washed
with saturated NaCl solution and water and dried over anhydrous
Na2SO4. The solvent was removed to give 2 as a white solid (0.43
1
g, 94%). Mp 106-107 °C; H NMR (400 MHz, CD3COCD3, 22
°C) δ 6.92 (s, 2H), 6.86-6.80 (m, 4H), 4.47 (d, J ) 6.0 Hz, 4H),
4.09-4.06 (m, 8H), 3.98 (t, J ) 6.0 Hz, 2H), 3.79-3.75 (m, 8H),
3.67-3.65 (m, 8H), 3.60-3.58 (m, 8H). Anal. Calcd for C30H44O12:
C, 60.39; H, 7.43. Found: C, 60.39; H, 7.44.
Acknowledgment. This work was supported by the National
Natural Science Foundation of China (20604020 and 20774086).
We thank Professor Wanzhi Chen from the Department of
Chemistry at Zhejiang University for his kind assistance with
X-ray crystallography.
Supporting Information Available: The X-ray crystal-
lographic files (CIF) for 1·4 and 2·4, determination of associa-
tion constants of complexes 1 · 3, 1 · 4, 2 · 3, and 3 · 4, proton
NMR spectra of compounds, electrospray ionization mass
spectra of equimolar acetone solutions of either of hosts 1 and
2 with either of guests 3 and 4, and X-ray analysis data of 1·4
and 2·4, and other materials. This material is available free of
charge via the Internet at http://pubs.acs.org.
JO800890X
5880 J. Org. Chem. Vol. 73, No. 15, 2008