Efficient syntheses and complexation studies of diacetylene-containing macrocyclic polyethers

Article abstract of DOI:10.1002/ejoc.201001140

A series of novel macrocyclic polyethers, phenylene-diacetylene-containing macrocycles was synthesized in high yields by employing copper(II)-mediated Eglinton coupling as the key macrocyclization (80-92a%). As an analogue of the bisphenylene crown ether

Full text of DOI:10.1002/ejoc.201001140

FULL PAPER
DOI: 10.1002/ejoc.201001140
Efficient Syntheses and Complexation Studies of Diacetylene-Containing
Macrocyclic Polyethers
Yahui Feng,[a] Jingning Li,[a] Lasheng Jiang,*[a] Zhihong Gao,[b] Weicong Huang,[a]
Fei Jiang,[a] Nianhua Luo,[a] Shujuan Han,[a] Ronghua Zeng,[a] and Dingqiao Yang[a]
Keywords: Host-guest systems / Crown compounds / Pseudorotaxanes / Alkynes / Macrocycles
A series of novel macrocyclic polyethers, phenylene–di-
acetylene-containing macrocycles was synthesized in high
yields by employing copper(II)-mediated Eglinton coupling
as the key macrocyclization (80–92%). As an analogue of the
bisphenylene crown ether hosts, the binding behavior of
these new macrocycles was investigated by 1H NMR spec-
troscopy, mass spectrometry (ESI), and X-ray crystallography.
The results obtained indicate that macrocycles with tetraeth-
ylene glycol chains (3c–e) bind a paraquat guest to form
[2]pseudorotaxane-like complexes in solution and in the so-
lid state, whereas macrocycles with triethylene glycol chains
(i.e., 3f–h) bind a paraquat guest to form [3]pseudorotaxane-
like complexes, which implies that macrocycles 3f–h may be
able to complex to (mono)pyridinium cations in a [2]pseudo-
rotaxane-like fashion in solution.
interesting and useful optical and electronic properties,[7] In
addition, conjugated PDAs have been actively employed as
sensory materials for the detection of biologically, environ-
mentally, and chemically important target molecules.[7b,8]
Introduction
Macrocyclic polyethers are important building blocks in
supramolecular chemistry and have been widely used in ma-
terials and biological sciences for sensors and switches.[1]
Recently, bisphenylene crown ethers, such as bisparaphen-
ylene-34-crown-10 (BPP34C10) and bismetaphenylene-32-
crown-10 (BMP32C10),[2] have attracted great interest and
have been extensively used for the construction of inter-
locked molecules,[3] mechanically bonded macromole-
cules,[4] and molecular machines.[5] Their wide use is mainly
because bisphenylene crown ether hosts can form relatively
stable molecular complexes with electron-deficient paraquat
derivatives by virtue of multiple noncovalent interactions,
such as π-stacking and hydrogen-bonding and charge-trans-
fer interactions, of which the aromatic π-stackings are indis-
pensable.[6] We wondered whether one of the aromatic rings
in the bisphenylene crown ether could be replaced by a non-
aromatic π-system and whether or not it could still form
complexes with paraquat. To answer this question, we de-
signed and synthesized diacetylene-containing macrocyclic
polyethers 3 (Scheme 1). The reason for incorporating a di-
acetylene unit into the macroring is that diacetylene com-
pounds are capable of undergoing polymerization to yield
π-conjugated polymers, polydiacetylenes (PDAs), with
Scheme 1. Synthesis of diacetylene-containing macrocycles 3a–h.
However, most bisphenylene crown ethers are usually
subjected to very low synthetic efficiency, for example,
BPP34C10 and BMP32C10 were prepared by either one-
step[9] or multistep[10] methods in less than 20% total yield.
This makes their preparation costly and time consuming.
Consequently, the development of a new and high-yielding
methodology for the synthesis of macrocyclic hosts and the
exploration of their applications in host–guest chemistry are
still thrilling and challenging topics.
In a continuation of our studies concerning the explora-
tion of novel macrocyclic compounds in the construction
of threaded and interlocked structures,[11,12] we present in
this paper a highly efficient synthesis for a series of new
macrocycles, analogues of bisphenylene crown ethers, in
which one of the phenylene units is replaced by a nonaro-
matic π-system, diacetylene moiety, and the investigations
on their complexation behaviors with paraquat.
[a] School of Chemistry and Environment, South China Normal
University,
Guangzhou 510631, China
Fax: +86-20-39310187
E-mail: jianglsh@scnu.edu.cn
[b] Instrumental Analysis and Research Center, South China Nor-
mal University,
With this small structural modification, the macrocycles
can be prepared much more easily. Complexation results
showed that diacetylene-containing macrocycles are capable
Guangzhou 510631, China
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201001140.
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Eur. J. Org. Chem. 2011, 562–568

Diacetylene-Containing Macrocyclic Polyethers
of forming complexes with paraquat. Interestingly, macro- Table 1. Synthesis of macrocycles 3a–h.
cycles with tetraethylene glycol chains (i.e., 3c–e) bind the
paraquat guest to form 1:1 host–guest [2]pseudorotaxane-
like complexes in solution and in the solid state, whereas
those with triethylene glycol chains (i.e., 3f–h) bind the
paraquat guest to form 2:1 host–guest [3]pseudorotaxane-
like complexes, which implies that macrocycles 3f–h may be
capable of recognizing (mono)pyridinium cations to form
[2]pseudorotaxane-like complexes in solution. These find-
ings might provide an alternative way for the straightfor-
ward preparation of molecular rotaxanes.[13]
Results and Discussion
Diacetylene-containing macrocycles 3a–f were fully char-
1
acterized by H and 13C NMR spectroscopy, HRMS, and
Recently, we synthesized a novel bis(m-phenylene)-26- elemental analysis. Having these new macrocycles in hand,
crown-8-based cryptand in 97% yield by using the cop- we turned our attention to their application in host–guest
per(II)-mediated Eglinton coupling for the final cycliza- chemistry. Considering that paraquat derivatives (N,NЈ-di-
tion.[11] We envisaged that this high-yielding macrocycliza- alkyl-4,4Ј-bipyridinium salts) are commonly used as guests
tion approach might have generality. Thus, diacetylene-con- in the preparation of threaded structures,[17] paraquat 4 was
taining macrocyclic polyethers 3a–h were designed to be used as a model guest in this study to test the complexation
synthesized from the corresponding diols 1a–h[14] by a sim- behaviors of these newly synthesized macrocycles. We first
ple two-step procedure as depicted in Scheme 1.
used NMR spectroscopy to monitor the formation of the
Deprotonation of the hydroxy groups in diols 1a–h fol- complex between macrocycles with tetraethylene glycol
lowed by alkylation with propargyl bromide gave bisalkynes chains (i.e., 3c–e) and paraquat 4. When equimolar
2a–h in 78–96% yield; then, by performing a unimolecular amounts of 3c, 3d, or 3e and the paraquat were dissolved
macrocyclization of 2 by employing copper(II)-mediated in CD3COCD3, the color of the solution changed from col-
Eglinton coupling[15] macrocycle 3 was afforded. The orless to yellow, indicating that a charge-transfer interaction
macrocyclization process is largely dependent on the reac- had occurred. We observed significant shifts in the 1H
tion conditions. In this study, the macrocyclization of 2b by NMR spectra (295 K) of these equimolar (10 mm) mixtures
utilizing classical Eglinton coupling conditions (room tem- (see the Supporting Information). Figure 1 shows the par-
1
perature, 5 d) resulted in incomplete coupling with the for- tial H NMR spectrum of an equimolar mixture of 3c and
mation of only a marginal amount of the desired product; paraquat in CD3COCD3. After complexation, the reso-
most of the starting material was recovered. Although the nances of the aromatic protons H-1 and the α-protons H-2
reaction is generally complete in 4 d when the temperature of the alkyne in macrocycle 3c moved upfield (δ = 6.736
is raised to 45 °C under an O2 atmosphere, under these con- and 4.186 ppm) from their original positions (δ = 6.884 and
ditions macrocycle 3b was obtained in only 23% yield to- 4.271 ppm), which indicates the existence of π-stacking be-
gether with polymers or oligomers as by-products. When a tween the π-donor (hydroquinone) and π-acceptor (bipyr-
slow addition technique was used, for example, slow ad- idinium); the protons of the ethylene glycol units in 3c
dition of dialkyne 2b over 2 d to an acetonitrile solution of moved upfield, which suggests that hydrogen bonding (N+–
Cu(OAc)2 under an atmosphere of O2 at 45 °C, macrocycle CH···O) probably takes place between the host and guest.
3b was obtained in high yield (91%). This is probably be- It is noticeable that almost no changes were observed for
cause the copper(II) ion is present in large excess under the the resonances of the bipyridinium protons. This can be
pseudo-high-dilution conditions, and it can template the cy- explained by the opposite effects of the aromatic ring
clization process by complexation with the oxygen atoms shielding and the alkyne deshielding in 3c.
of the polyethylene glycol chains. This complexation was
Electrospray ionization mass spectrometry of an equi-
discovered in the workup step, where macrocycle 3b had molar solution of 3c, 3d, or 3e and paraquat in acetonitrile
formed a complex with the copper(II) ion, and it was neces- confirmed the 1:1 stoichiometry of the complexes (see the
sary to use aqueous ammonia to remove the metal ion. Supporting Information). For example, in the mass spec-
Using this strategy, we easily prepared eight new diacetyl- trum of an equimolar solution of 3c and paraquat in aceto-
ene-containing macrocyclic polyethers in good to excellent nitrile, the base peak was at m/z = 559.50 (100%), corre-
yields (Table 1) without extra templates.[16] These results sponding to [3c + Na]+; two peaks were found for complex
demonstrate that the above unimolecular macrocyclization 3c·4: m/z = 867.20 (10%) [3c·4 – PF6]+ and 361.51 (33%)
might be a general method for the preparation of diacetyl- [3c·4 – 2PF6]2+; and a peak at m/z = 331.12 (27%) corre-
ene-containing macrocycles.
sponding to [4 – PF6]+ was also observed.
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Figure 1. Partial H NMR spectrum of (a) guest 4, (b) equimolar solution of 3c and 4, and (c) host 3c (CD3COCD3, 400 MHz, 22 °C,
10 mm).
Further X-ray analysis of the crystal structure unambig-
uously confirmed the complex formation. X-ray analysis of
a red-brown crystal of 3c·4 grown by slow vapor diffusion
of diethyl ether into an acetone solution containing a 1:1
mixture of 3c and 4 revealed that the complex has a
[2]pseudorotaxane-like structure. In the crystal structure
(Figure 2), linear molecule 4 is threaded through the cavity
of the cyclic host. For this pseudorotaxane-like complex the
main stabilization interactions in the solid state are hydro-
gen bonding, face-to-face π-stacking, and charge-transfer
interactions. The butadiyne fragment is approximately par-
Figure 2. A ball-and-stick view of the X-ray crystal structure of
allel with the electron-poor inner bipyridinium unit, and the
average distance between the plane of the inner bipyrid-
inium unit and the CϵC–CϵC axis is 3.624 Å, indicating
that π-stacking between the inner bipyridinium unit and the
diacetylene moiety exist. The centroid–centroid distance be-
3c·4. Hydrogen-bonding parameters: H···O (Å), O···H–C, C···O
(Å): a: 2.537, 148.29, 3.393; b: 2.568, 132.76, 3.271; c: 2.697, 137.54,
3.467; d: 2.584, 141.70, 3.390; e: 2.634, 152.50, 3.486; f:
2.407,145.99, 3.247.
tween the electron-poor pyridinium ring of 4 and the elec- for 3c, 3d, and 3e, respectively, with paraquat from the slope
tron-rich phenylene ring of host 3c is 3.657 Å, suggesting of the lines.[19] The relatively low Ka values of these diacetyl-
possible face-to-face π-stacking of the aromatic rings be- ene-containing crown ethers as compared to that of the cor-
tween the host and the guest. In addition, one α-pyridinium responding bisphenylene crown ethers[20] may be accounted
hydrogen and one hydrogen of the methyl group in 4 are for by the decreased electron-donating ability of the π-sys-
hydrogen bonded to the oxygen atoms on the ethyleneoxy tem in the diacetylene unit.
chain of the crown ether host.
Further investigation into the complexation between
Having determined that macrocycles with tetraethylene smaller macrocycles 3f–h (with triethylene glycol chains)
glycol chains (i.e., 3c–e) and paraquat can form stable and paraquat 4 was carried out. Interestingly, the complex-
[2]pseudorotaxane-like complexes in solution and in the so- ation results are quite different from that of macrocycles
lid state, we turned our attention toward the estimation of 3c–e (with tetraethylene glycol chains). X-ray analysis of a
the association constants[18] to quantify the affinity strength crystal of the complex, obtained by slow vapor diffusion of
of these recognition systems. Figure 3a–c shows the Benesi– diethyl ether into an acetone solution containing a 1:1 mix-
Hildebrand plots that we obtained for the binding of ture of host 3f and paraquat guest 4 reveals that the solid-
macrocycles 3c–e with paraquat 4 by NMR titration experi- state structure of the complex has a [3]pseudorotaxane-like
ments in CD3COCD3. The association constants (Ka) were geometry, that is, 2:1 host–guest complex, in which one
determined to be 90.0Ϯ7.0, 104.7Ϯ8.1, and 110.3Ϯ6.7 m–1 paraquat is encapsulated by two macrocyclic 3f hosts (Fig-
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Diacetylene-Containing Macrocyclic Polyethers
spectra, we observed the same peaks at m/z = 541 corre-
sponding to 2:1 complexes that have lost two PF6– ions and
at m/z = 779 corresponding to 1:1 complexes that have each
–
lost one PF6 ion (see the Supporting Information).
To examine whether cooperativity exists between the first
and second binding events, we determined the association
constants of these complexes by using the NMR titration
method.[18,13] The Scatchard plots of the complexation are
linear (Figure 5a–c), which suggests that the two N-methyl-
pyridinium binding sites in paraquat 4 are independent (i.e.,
noncooperative) of each other during the complexation
with macrocyclic hosts 3f–h. The association constants K1
and K2 estimated from the slope of the line in the Scatchard
plots[13] are summarized in Table 2. For all three systems,
K1 = 4K2, indicating that the two identical binding sites in
guest 4 operate independently.[11,13] These findings might
suggest that in acetone macrocyclic hosts 3f–h may possibly
bind to (mono)pyridinium cations to form [2]pseudorotax-
ane-like complexes.
Figure 3. Benesi–Hildebrand plots for (a) 3c with paraquat, (b) 3d
with paraquat, and (c) 3e with paraquat based on 1H NMR ti-
tration at 295 K in [D6]acetone. [3]0 = 0.50 mm.
ure 4). As shown in the crystal structure, the two host mole-
cules are arranged in an antiparallel form, presumably be-
cause of steric factors. The two pyridinium rings of para-
quat are twisted with a dihedral angle of about 22 °. The
average distances between the planes of the inner bipyrid-
inium unit and the CϵC–CϵC axis (3.84, 3.84 Å) and that
between the pyridinium ring centroids and the hydro-
quinone ring centroids (3.79, 4.19 Å) are around 3.8 Å, im-
plying that relatively weak π–π stacking interaction may be
expected to contribute to the formation of this complex.
Instead, some hydrogen-bonding interactions can be ob-
served for the β-pyridinium hydrogen atoms of the guest
and for the hydrogen atoms of the methyl group in guest 4
and the ether oxygen atoms of the host. It is noteworthy
that one water molecule was found in the crystal structure,
which acts as a bridge to link one methyl group in guest 4
with one ether chain of the host through hydrogen bonding.
Additionally, the structure is possibly stabilized by ion–di-
pole interaction between the viologen cation and the highly
polar ether chains.[21]
Figure 5. Scatchard plots for complexation of paraquat with (a) 3f,
(b) 3g, and (c) 3h based on 1H NMR titration at 295 K in [D6]-
acetone. [3]0 = 0.50 mm.
Table 2. Association constants for complexation of 3f–h with para-
quat in CD3COCD3 at 295 K.
Macrocycle
Complex
K1 (m–1)
K2 (m–1)
3f
3g
3h
3f·4·3f
3g·4·3g
3h·4·3h
68.8Ϯ6.5
125.4Ϯ7.7
130.2Ϯ6.2
17.2Ϯ1.6
31.4Ϯ1.9
32.5Ϯ1.6
Conclusions
In summary, we have synthesized a series of new diacetyl-
ene-containing macrocyclic polyethers by employing cop-
per(II)-mediated alkyne coupling. This strategy allows
macrocyclic polyethers to be directly prepared in good to
excellent yields under mild conditions without extra tem-
plates. Moreover, the binding behaviors of these new macro-
Figure 4. Crystal structure of complex 3f·4·3f. Hydrogen-bonding
parameters: H···O (Å), O···H–C(O), C···O (Å): a: 2.690, 128.35,
3.376; b: 2.489, 158.85, 3.401; c: 2.521, 163.47, 3.422; d: 2.623,
156.44, 3.496; e: 2.497, 136.98, 3.240; f: 2.539, 129.08, 3.211; g:
2.645, 109.67, 3.049; h: 2.444, 120.46, 2.982; i: 2.194,147.89, 2.968.
1
cycles to paraquat have also been investigated by H NMR
The ESI mass spectra recorded for an equimolar mixture spectroscopy, mass spectrometry (ESI), and X-ray crystal-
of 3f, 3g, or 3h and paraquat 4 in acetonitrile confirmed lography. The results obtained indicate that macrocycles
the 2:1 stoichiometry of these complexes. In all the mass with tetraethylene glycol chains (i.e., 3c–e) bind a paraquat
Eur. J. Org. Chem. 2011, 562–568
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2d: Yield: 85% (1.830 g). Viscous yellow oil. H NMR (400 MHz,
CDCl3, 22 °C): δ = 7.17–7.13 (m, 1 H, Ar-H), 6.52–6.50 (m, 3 H,
Ar-H), 4.20 (d, J = 2.4 Hz, 4 H, α-CH2), 4.10 (t, J = 4.9 Hz, 4 H,
α-OCH2), 3.85 (t, J = 4.9 Hz, 4 H, β-OCH2), 3.74–3.67 (m, 24 H,
-OCH2), 2.43 (t, J = 2.4 Hz, 2 H, -CϵCH) ppm. 13C NMR
(100 MHz, CDCl3, 22 °C): δ = 159.84, 129.68, 106.94, 101.65,
79.62, 74.65, 70.66, 70.56, 70.48, 70.26, 69.56, 68.97, 67.28,
58.25 ppm. MS (ESI): m/z (%) = 556.61 [M + NH4]+.
guest to form 1:1 [2]pseudorotaxane-like complexes in solu-
tion and in the solid state, whereas macrocycles with trieth-
ylene glycol chains (i.e., 3f–h) bind a paraquat guest to form
2:1 [3]pseudorotaxane-like complexes, which implies that
macrocycles 3f–h may be able to complex to (mono)pyrid-
inium cations in a [2]pseudorotaxane-like fashion in solu-
tion. Considering the easy availabilities and binding ca-
pacities of these new macrocycles toward electron-deficient
motifs, as demonstrated in this paper, they are expected to
be easily extended to the construction of other supramolec-
ular threaded structures such as rotaxanes and catenanes.
Furthermore, they may potentially be used to prepare novel
threaded and π-conjugated polymer materials by utilizing
1
2e: Yield: 78% (1.688 g). Viscous yellow oil. H NMR (400 MHz,
CDCl3, 22 °C): δ = 6.94–6.89 (m, 4 H, Ar-H), 4.20 (d, J = 2.4 Hz,
4 H, α-CH2), 4.17 (t, J = 4.5 Hz, 4 H, α-OCH2), 3.86 (t, J = 4.5 Hz,
4 H, β-OCH2), 3.75–3.67 (m, 24 H, -OCH2), 2.43 (t, J = 2.4 Hz, 2
H, -CϵCH) ppm. 13C NMR (100 MHz, CDCl3, 22 °C): δ = 148.84,
121.48, 114.76, 79.60, 74.76, 70.62 70.49, 70.42, 70.21, 69.60, 68.93,
well-established diacetylene chemistry.[22] We are currently 68.70, 58.21, 58.19 ppm. MS (ESI): m/z (%) = 561.53 [M + Na]+.
focusing on these projects.
2f: Yield: 83% (1.501 g). Orange yellow solid. M.p. 42.5–43.1 °C.
1H NMR (400 MHz, CDCl3, 22 °C): δ = 6.82 (s, 4 H, Ar-H), 4.18
(d, J = 2.4 Hz, 4 H, α-CH2), 4.06 (t, J = 4.9 Hz, 4 H, α-OCH2),
Experimental Section
3.81 (t, J = 4.9 Hz, 4 H, β-OCH2), 3.71–3.66 (m, 16 H, -OCH2),
2.40 (t, J = 2.4 Hz, 2 H, -CϵCH) ppm. 13C NMR (100 MHz,
General: Unless specified otherwise, all reagents were purchased
CDCl3, 22 °C): δ = 152.97, 115.45, 79.63, 74.68, 70.64, 70.51, 70.30,
from commercial suppliers and used as received. THF was distilled
69.72, 68.98, 67.93, 58.24 ppm. MS (ESI): m/z (%) = 468.46 [M +
from sodium–acetophenone, and CH3CN was distilled from CaH2.
NH4]+.
All reactions were carried out under an atmosphere of N2. Melting
1
2g: Yield: 83% (1.493 g). Viscous yellow oil. H NMR (400 MHz,
CDCl3, 22 °C): δ = 7.17–7.13 (m, 1 H, Ar-H), 6.53–6.51 (m, 3 H,
Ar-H), 4.25 (d, J = 2.4 Hz, 4 H, α-CH2), 4.11 (t, J = 4.3 Hz, 4 H,
α-OCH2), 3.85 (t, J = 4.3 Hz, 4 H, β-OCH2), 3.75–3.68 (m, 16 H,
-OCH2), 2.43 (t, J = 2.4 Hz, 2 H, -CϵCH) ppm. 13C NMR
(100 MHz, CDCl3, 22 °C): δ = 159.91, 129.74, 107.03, 101.75,
79.63, 74.48, 70.77, 70.63, 70.42, 69.68, 67.08, 67.36, 58.37 ppm.
MS (ESI): m/z (%) = 468.39 [M + NH4]+.
points were determined with an Electrothermal x-5 melting point
apparatus. Thin-layer chromatography was performed with Qing-
Dao silica gel. NMR spectra were recorded at ambient temperature
with a Varian NMR system 400 MHz by using the deuterated sol-
vent as the lock and the residual solvent or TMS as the internal
reference. Low-resolution electrospray ionization mass spectra were
recorded with a Thermo Finnigan LCQ Deca XP Max LC/MSn.
High-resolution electrospray ionization mass spectra were recorded
with a Bruker Apex IV FTMS at Peking University. Elemental
analysis were obtained with a FlaskEA 1112 Series CHNS–O ana-
lyzer. MALDI-TOF MS were provided by Nankai University. X-
ray crystallographic were performed with a Bruker SMART APEX
II.
1
2h: Yield: 94% (1.688 g). Viscous yellow oil. H NMR (400 MHz,
CDCl3, 22 °C): δ = 6.92–6.87 (m, 4 H, Ar-H), 4.18 (d, J = 2.4 Hz,
4 H, α-CH2), 4.15 (t, J = 5.1 Hz, 4 H, α-OCH2), 3.84 (t, J = 5.1 Hz,
4 H, β-OCH2), 3.74–3.71 (m, 4 H, γ-OCH2), 3.68–3.64 (m, 14 H,
-OCH2), 2.42 (t, J = 2.4 Hz, 2 H, -CϵCH) ppm. 13C NMR
(100 MHz, CDCl3, 22 °C): δ = 148.92, 121.56, 114.85, 79.64, 74.66,
70.71, 70.60, 70.32, 69.70, 69.03, 68.77, 58.29 ppm. MS (ESI): m/z
(%) = 468.48 [M + NH4]+.
General Procedure for the Synthesis of Dialkynes 2a–h: Compound
1 (4.0 mmol) was dissolved in dry THF (10.0 mL) and treated with
NaH (60% dispersion in oil, 3.0 equiv.). After evolution of gas had
ceased (1 h), propargyl bromide (80wt.-% in PhMe, 6.0 equiv.) was
added by syringe. The mixture was stirred at 23 °C for 2 d. Water
(1 mL) was added, and THF was removed in vacuo. The residue
solution was extracted with CH2Cl2. After drying (Na2SO4) and
removing the solvent, the crude product was separated by column
chromatography on silica gel (EtOAc/light petroleum/CH2Cl2,
60:20:50) to give pure dialkynes 2a–h.
General Procedure for the Synthesis of Macrocycles 3a–h by Alkyne
Coupling: Cu(OAc)2·H2O (1.5 mmol) was dissolved in CH3CN
(60 mL) and heated to 45 °C under an atmosphere of oxygen by
using an O2 balloon. Then, a solution of dialkyne 2 (1.2 equiv.) in
CH3CN (40 mL) was added portionwise (at a rate of 1 mL/portion/
h) into the above blue solution at 45 °C. After addition, the reac-
tion mixture was stirred at the same temperature for 1 d. The sol-
vent was then removed, and the crude bluish solid was dissolved in
aqueous ammonia (0.5 mol/mL) and extracted with CH2Cl2. After
drying and removing the solvent, the crude product was separated
by column chromatography on silica gel (EtOAc/light petroleum,
50:20) to yield macrocycle 3 in pure form.
1
2a: Yield: 96% (0.867 g). Viscous yellow oil. H NMR (400 MHz,
CDCl3, 22 °C): δ = 4.21 (d, J = 2.4 Hz, 4 H, α-CH2), 3.76–3.68 (m,
12 H, -OCH2), 2.43 (t, J = 2.4 Hz, 2 H, -CϵCH) ppm. MS (ESI):
m/z (%) = 244.13 [M + NH4]+.
1
2b: Yield: 94% (1.019 g). Viscous yellow oil. H NMR (400 MHz,
3a: Yield: 84% (0.341 g). White solid. M.p. 43.6–44.2 °C. 1H NMR
(400 MHz, CDCl3, 22 °C): δ = 4.19 (s, 4 H, α-CH2), 3.82 (t, J =
2.0 Hz, 4 H, α-OCH2), 3.71–3.684 (m, 8 H, -OCH2) ppm. 13C
NMR (100 MHz, CDCl3, 22 °C): δ = 77.46, 70.83, 70.32, 69.47,
68.83, 59.04 ppm. C12H16O4 (224.26): calcd. C 64.27, H 7.19; found
C 64.35, H 7.46. MS (ESI): m/z = 247.35 [M + Na]+.
CDCl3, 22 °C): δ = 4.21 (d, J = 2.4 Hz, 4 H, α-CH2), 3.72–3.67 (m,
16 H, -OCH2), 2.43 (t, J = 2.4 Hz, 2 H, -CϵCH) ppm. MS (ESI):
m/z = 288.21 [M + NH4]+.
1
2c: Yield: 85% (1.835 g). Yellow oil. H NMR (400 MHz, CDCl3,
22 °C): δ = 6.81 (s, 4 H, Ar-H), 4.16 (d, J = 2.4 Hz, 4 H, α-CH2),
4.05 (t, J = 4.2 Hz, 4 H, α-OCH2), 3.80 (t, J = 4.2 Hz, 4 H, β-
OCH2), 3.70–3.64 (m, 24 H, -OCH2), 2.40 (t, J = 2.4 Hz, 2 H,
3b: Yield: 91% (0.439 g). Dark red brown solid. M.p. 40.8–41.7 °C.
-CϵCH) ppm. 13C NMR (100 MHz, CDCl3, 22 °C): δ = 153.05, 1H NMR (400 MHz, CDCl3, 22 °C): δ = 4.22 (s, 4 H, α-CH2), 3.76
115.52, 79.63, 74.48, 70.75, 70.59, 70.57, 70.36, 69.80, 69.07, 68.02,
(t, J = 4.0 Hz, 4 H, α-OCH2), 3.69–3.64 (m, 12 H, -OCH2) ppm.
58.35 ppm. MS (ESI): m/z (%) = 556.50 [M + NH4]+.
13C NMR (100 MHz, CDCl3, 22 °C): δ = 77.21, 75.90, 70.73, 70.55,
566
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 562–568

Diacetylene-Containing Macrocyclic Polyethers
70.28, 58.94, 69.60 ppm. C14H20O5 (268.31): calcd. C 62.67, H 7.51;
Supporting Information (see footnote on the first page of this arti-
cle): 1H NMR, 13C NMR, and mass spectra of all compounds, and
crystal data and structure refinement data of the complexes.
found C 62.34, H 7.25. MS (ESI): m/z = 286.23 [M + NH4]+.
1
3c: Yield: 90% (0.868 g). Yellow oil. H NMR (400 MHz, CDCl3,
22 °C): δ = 6.85 (s, 4 H, Ar-H), 4.23 (s, 4 H, α-CH2), 4.08 (t, J =
4.0 Hz, 4 H, α-OCH2), 3.83 (t, J = 4.0 Hz, 4 H, β-OCH2), 3.71–
3.64 (m, 24 H, -OCH2) ppm. 13C NMR (100 MHz, CDCl3, 22 °C):
δ = 153.06, 115.62, 75.45, 70.77, 70.72, 70.69, 70.54, 69.76, 69.31,
68.16, 58.83 ppm. HRMS (ESI): calcd. for C28H44NO10 [M +
NH4]+ 554.2960; found 554.2959. HRMS (ESI): calcd. for
C28H40NaO10 [M + Na]+ 559.2514; found 559.2512.
Acknowledgments
We thank the National Natural Science Foundation of China [No.
20672038] and the Natural Science Foundation of Guangdong
Province of China [No. 8151063101000015] for financial support.
[1] a) G. W. Gokel, W. M. Leevy, M. F. Weber, Chem. Rev. 2004,
104, 2723; b) F. M. Raymo, J. F. Stoddart, Chem. Rev. 1999,
99, 1643; c) F. Huang, H. W. Gibson, Prog. Polym. Sci. 2005,
30, 982; d) V. Balzani, A. Credi, F. M. Raymo, J. F. Stoddart,
Angew. Chem. Int. Ed. 2000, 39, 3348.
1
3d: Yield: 89% (0.858 g). Yellow oil. H NMR (400 MHz, CDCl3,
22 °C): δ = 7.16 (t, J = 8.4 Hz, 1 H, Ar-H), 6.53–6.51 (m, 3 H, Ar-
H), 4.27 (s, 4 H, α-CH2), 4.13 (t, J = 4.8 Hz, 4 H, α-OCH2), 3.87
(t, J = 4.8 Hz, 4 H, β-OCH2), 3.74–3.67 (m, 24 H, -OCH2) ppm.
13C NMR (100 MHz, CDCl3, 22 °C): δ = 159.89, 129.73, 106.98,
101.64, 77.49, 75.51, 70.75, 70.67, 70.62, 70.53, 70.32, 69.60, 69.21,
67.40, 58.76 ppm. HRMS (ESI): calcd. for C28H44NO10 [M +
NH4]+ 554.2960; found 554.2958. HRMS (ESI): calcd. for
C28H40NaO10 [M + Na]+ 559.2514; found 559.2511.
ˇ
[2] For recent examples, see: a) K. Patel, O. S. Miljanic´, J. F. Stod-
dart, Chem. Commun. 2008, 1853; b) N. Christinat, R. Scopel-
liti, K. Severin, Chem. Commun. 2008, 3660; c) V. Blanco, M.
Chas, D. Abella, C. Peinador, J. M. Quintela, J. Am. Chem.
Soc. 2007, 129, 13978; d) R. L. Halterman, D. E. Martyn, J.
Org. Chem. 2007, 72, 7841; e) R. L. Halterman, X. Pan, D. E.
Martyn, J. L. Moore, A. T. Long, J. Org. Chem. 2007, 72, 6454;
f) F. Huang, C. Slebodnick, A. E. Ratliff, H. W. Gibson, Tetra-
hedron Lett. 2005, 46, 6019; g) F. Huang, H. W. Gibson, Chem.
Commun. 2005, 1696; h) F. Huang, D. S. Nagvekar, C. Slebod-
nick, H. W. Gibson, J. Am. Chem. Soc. 2005, 127, 484; i) K.
Zhu, L. Wu, X. Yan, B. Zheng, M. Zhang, F. Huang, Chem.
Eur. J. 2010, 16, 6088; j) S. Li, K. Zhu, B. Zheng, X. Wen, N.
Li, F. Huang, Eur. J. Org. Chem. 2009, 1053; k) J. Zhang, C.
Zhai, F. Wang, C. Zhang, S. Li, M. Zhang, N. Li, F. Huang,
Tetrahedron Lett. 2008, 49, 5009.
3e: Yield: 92% (0.887 g). Yellow solid. M.p. 45.3–46.1 °C. 1HNMR
(400 MHz, CDCl3, 22 °C): δ = 6.92 (br., 4 H, Ar-H), 4.27 (s, 4 H,
α-CH2), 4.18 (t, J = 4.9 Hz, 4 H, α-OCH2), 3.89 (t, J = 4.9 Hz, 4
H, β-OCH2), 3.78 (t, J = 4.0 Hz, 4 H, γ-OCH2), 3.68–3.67 (m, 20
H, -OCH2) ppm. 13C NMR (100 MHz, CDCl3, 22 °C): δ = 148.95,
121.54, 114.72, 75.53, 70.83, 70.71, 70.67, 70.49, 70.41, 69.77,
69.25, 68.84, 58.89 ppm. C28H40O10 (536.62): calcd. C 62.67, H
7.51; found C 62.18, H 7.32. MS (ESI): m/z (%) = 559.57 [M +
Na]+.
[3] a) S. J. Loeb, Chem. Soc. Rev. 2007, 36, 226; b) M. S. Vickers,
P. D. Beer, Chem. Soc. Rev. 2007, 36, 211; c) F. Aricò, J. D.
Badjic, S. J. Cantrill, A. H. Flood, K. C.-F. Leung, Y. Liu, J. F.
Stoddart, Top. Curr. Chem. 2005, 249, 203; d) A.-L. Lee, D. A.
Leigh, R. T. MsBurney, Chem. Soc. Rev. 2009, 38, 1530; e)
K. M. Mullen, P. D. Beer, Chem. Soc. Rev. 2009, 38, 1701; f)
E. Coronado, P. Gavina, S. Tatay, Chem. Soc. Rev. 2009, 38,
1674.
1
3f: Yield: 80% (0.647 g). Yellow oil. H NMR (400 MHz, CDCl3,
22 °C): δ = 6.89 (s, 4 H, Ar-H), 4.27 (s, 4 H, α-CH2), 4.12 (t, J =
4.4 Hz, 4 H, α-OCH2), 3.83 (t, J = 4.4 Hz, 4 H, β-OCH2), 3.72–
3.67 (m, 16 H, -OCH2) ppm. 13C NMR (100 MHz, CDCl3, 22 °C):
δ = 153.09, 115.82, 77.52, 75.50, 70.93, 70.57, 70.49, 70.27, 69.69,
69.28, 68.27, 58.77 ppm. HRMS (ESI): calcd. for C24H36NO8 [M
+ NH4]+ 466.2435; found 466.2437. HRMS (ESI): calcd. for
C24H32NaO8 [M + Na]+ 471.1989; found 471.1990.
[4] L. Fang, M. A. Olson, D. Benítez, E. Tkatchouk, W. A. God-
dard III, J. F. Stoddart, Chem. Soc. Rev. 2010, 39, 17.
[5] a) E. R. Kay, D. A. Leigh, F. Zerbetto, Angew. Chem. Int. Ed.
2007, 46, 72; b) B. Champin, P. Mobian, J.-P. Sauvage, Chem.
Soc. Rev. 2007, 36, 358; c) S. Saha, J. F. Stoddart, Chem. Soc.
Rev. 2007, 36, 77; d) K. Konstas, S. J. Langford, M. J. Latter,
Int. J. Mol. Sci. 2010, 11, 2453.
1
3g: Yield: 89% (0.721 g). Viscous yellow oil. H NMR (400 MHz,
CDCl3, 22 °C): δ = 7.15 (t, J = 8.2 Hz, 1 H, Ar-H), 6.53–6.51 (m,
3 H, Ar-H), 4.27 (s, 4 H, α-CH2), 4.13 (t, J = 4.6 Hz, 4 H, α-
OCH2), 3.87 (t, J = 4.6 Hz, 4 H, β-OCH2), 3.74–3.69 (m, 16 H,
-OCH2) ppm. 13C NMR (100 Hz, CDCl3, 22 °C): δ = 159.92,
129.73, 107.02, 101.51, 75.42, 70.97, 70.72, 70.48, 69.67, 69.18,
67.42, 58.89 ppm. HRMS (ESI): calcd. for C24H33O8 [M + H]+
449.2170; found 449.2172; calcd. for C24H36NO8 [M + NH4]+
466.2435; found 466.2434. HRMS (ESI): calcd. for C24H32NaO8
[M + Na]+ 471.1989; found 471.1987.
[6] For some recent examples of mechanically interlocked mole-
cules using these interactions, see: a) M. R. Sambrook, P. D.
Beer, J. A. Wisner, R. L. Paul, A. R. Cowley, J. Am. Chem. Soc.
2004, 126, 15364; b) L. Wang, M. O. Vysotsky, A. Bogdan, M.
Bolte, V. Boehmer, Science 2004, 304, 1312; c) E. Arunkumar,
C. C. Forbes, B. C. Noll, B. D. Smith, J. Am. Chem. Soc. 2005,
127, 3288; d) C.-C. Hsu, N.-C. Chen, C.-C. Lai, Y.-H. Liu, S.-
M. Peng, S.-H. Chiu, Angew. Chem. Int. Ed. 2008, 47, 7475; e)
W. Zhou, J. Li, X. He, C. Li, J. Lv, Y. Li, S. Wang, H. Liu, D.
Zhu, Chem. Eur. J. 2008, 14, 754; f) Y. Tokunaga, K. Akasaka,
N. Hashimoto, S. Yamanaka, K. Hisada, Y. Shimomura, S.
Kakuchi, J. Org. Chem. 2009, 74, 2374; g) S. Nygaard, S. W.
Hansen, J. C. Huffman, F. Jensen, A. H. Flood, J. O. Jeppesen,
J. Am. Chem. Soc. 2007, 129, 7354; h) L. M. Klivansky, G.
Koshkakaryan, D. Cao, Y. Liu, Angew. Chem. Int. Ed. 2009,
48, 4185; i) S. Li, M. Liu, B. Zheng, K. Zhu, F. Wang, N. Li,
X.-L. Zhao, F. Huang, Org. Lett. 2009, 11, 3350.
1
3h: Yield: 91% (0.736 g). Yellow oil. H NMR (400 MHz, CDCl3,
22 °C): δ = 6.95–6.89 (m, 4 H, Ar-H), 4.26 (s, 4 H, α-CH2), 4.19
(t, J = 5.0 Hz, 4 H, α-OCH2), 3.89 (t, J = 5.0 Hz, 4 H, β-OCH2),
3.78–3.76 (m, 4 H, γ-OCH2), 3.69–3.71 (m, 12 H, -OCH2) ppm.
13C NMR (100 MHz, CDCl3, 22 °C): δ = 148.98, 121.56, 114.86,
75.71, 70.95, 70.56, 70.46, 70.38, 69.88, 69.29, 68.86, 58.92 ppm.
HRMS (ESI): calcd. for C24H36NO8 [M + NH4]+ 466.2435; found
466.2432. HRMS (ESI): calcd. for C24H32NaO8 [M + Na]+
471.1989; found 471.1989.
[7] a) J. W. Lauher, F. W. Fowler, N. S. Goroff, Acc. Chem. Res.
2008, 41, 1215; b) M. A. Reppy, B. A. Pindzola, Chem. Com-
mun. 2007, 4317; c) W.-D. Zhou, Y.-L. Li, D.-B. Zhu, Chem.
Asian J. 2007, 2, 222.
[8] a) Y. K. Jung, T. W. Kim, J. Kim, J.-M. Kim, H. G. Park, Adv.
Funct. Mater. 2008, 18, 701; b) R. Jelinek, S. Kolusheva, Top.
CCDC-706936 (for 3c·4) and -725168 (for 3f·4·3f) contain the sup-
plementary crystallographic data for this paper. These data can be
obtained free of charge from The Cambridge Crystallographic
Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
Eur. J. Org. Chem. 2011, 562–568
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
567

L. Jiang et al.
FULL PAPER
Curr. Chem. 2007, 277, 155; c) B. Yoon, S. Lee, J.-M. Kim,
Chem. Soc. Rev. 2009, 38, 1958.
W. R. Dichtel, S. Mortezaei, J. F. Stoddart, Org. Lett. 2006, 8,
4835.
[17] For recent examples, see: a) A. M.-P. Pederson, R. C. Vetor,
M. A. Rouser, F. Huang, C. Slebodnick, D. V. Schoonover,
H. W. Gibson, J. Org. Chem. 2008, 73, 5570; b) K. Zhu, S. Li,
F. Wang, F. Huang, J. Org. Chem. 2009, 74, 1322; c) L. M.
Klivansky, G. Koshkakaryan, D. Cao, Y. Liu, Angew. Chem.
Int. Ed. 2009, 48, 4185; d) S. Li, B. Zheng, F. Huang, L. N.
Zakharov, C. Slebodnick, A. L. Rheingold, H. W. Gibson, Sci.
China, Ser. B Chem. 2010, 53, 858; e) D. Cao, M. Amelia, L. M.
Klivansky, G. Koshkakaryan, S. I. Khan, M. Semeraro, S. Silvi,
M. Venturi, A. Credi, Y. Liu, J. Am. Chem. Soc. 2010, 132,
1110; f) C. Li, Q. Xu, J. Li, F. Yao, X. Jia, Org. Biomol. Chem.
2010, 8, 1568; g) T. B. Gasa, J. M. Spruell, W. R. Dichtel, T. J.
Sørensen, D. Philp, J. F. Stoddart, P. Kuzmic, Chem. Eur. J.
2009, 151, 106; h) Y. Jiang, J. Cao, J.-M. Zhao, J.-F. Xiang, C.-
F. Chen, J. Org. Chem. 2010, 75, 1767; i) Q. Li, W. Zhang, O. S.
Miljanic´, C. H. Sue, Y. L. Zhao, L. Liu, C. B. Knobler, J. F.
Stoddart, O. M. Yaghi, Science 2009, 325, 855; j) Y.-L. Zhao,
L. Liu, W. Zhang, C.-H. Sue, Q. Li, O. S. Miljanic, O. M.
Yaghi, J. F. Stoddart, Chem. Eur. J. 2009, 15, 13356.
[9]
a) R. C. Helgeson, J. M. Timko, D. J. Cram, J. Am. Chem. Soc.
1974, 96, 7380; b) D. B. Amabilino, P.-L. Anelli, P. R. Ashton,
G. R. Brown, E. Córdova, L. A. Godfnez, W. Hayes, A. E.
Kaifer, D. Philp, A. M. Z. Slawin, N. Spencer, J. F. Stoddart,
M. S. Tolley, D. J. Williams, J. Am. Chem. Soc. 1995, I17,
11142; c) Y. Delaviz, H. W. Gibson, J. F. Williams, Macromole-
cules 1992, 25, 18.
a) B. L. Allwood, N. Spencer, H. Shahriari-Zavareh, D. J. Stod-
dart, J. Chem. Soc., Chem. Commun. 1987, 1061; b) P. L.
Anelli, P. R. Ashton, R. Ballardini, V. Balzani, M. Delgado,
M. T. Gandolfi, T. T. Goodnow, A. E. Kaifer, D. Philp, M. Pie-
traszkiewicz, L. Prodi, M. V. Reddington, A. M. Z. Slawin, N.
Spencer, J. F. Stoddart, C. Vicent, D. J. Williams, J. Am. Chem.
Soc. 1992, 114, 193.
Z. Xu, X. Huang, J. Liang, S. Zhang, S. Zhou, M. Chen, M.
Tang, L. Jiang, Eur. J. Org. Chem. 2010, 1904.
a) M. Chen, S. Han, L. Jiang, S. Zhou, F. Jiang, Z. Xu, J.
Liang, S. Zhang, Chem. Commun. 2010, 46, 3932; b) L. Jiang,
J. Okano, A. Orita, J. Otera, Angew. Chem. Int. Ed. 2004, 43,
2121; c) A. Orita, J. Okano, Y. Tawa, L. Jiang, J. Otera, Angew.
Chem. Int. Ed. 2004, 43, 3724.
[10]
[11]
[12]
[18] a) K. A. Connors, Binding Constants, Wiley, New York, 1987;
b) K. Hirose, J. Inclusion Phenom. Macrocyclic Chem. 2001, 39,
193.
[13] P.-N. Cheng, C.-F. Lin, Y.-H. Liu, C.-C. Lai, S.-M. Peng, S.-
H. Chiu, Org. Lett. 2006, 8, 435.
[19] We calculated the errors of the association constants on the
basis of the error of the slope, see: a) C. Gong, P. B. Balanda,
H. W. Gibson, Macromolecules 1998, 31, 5278; b) F. Huang,
P. Gantzel, D. S. Nagvekar, A. L. Rheingoldc, H. W. Gibson,
Tetrahedron Lett. 2006, 47, 7841; c) ref. 13.
[14] a) P. L. Nelli, P. R. Ashton, N. Spencer, A. M. Z. Slawin, J. F.
Stoddart, D. J. Williams, Angew. Chem. Int. Ed. Engl. 1991, 30,
1036; b) I. J. A. Mertens, R. Wegh, L. W. Jenneskens, E. J. V.
Lieststra, A. V. Kerk-van Hoof, J. W. Zwikker, T. J. Cleij,
W. J. J. Smeets, N. Veldman, A. L. Spek, J. Chem. Soc. Perkin
Trans. 2 1998, 725; c) M. Orda-Zgadzaj, W. Abraham, Synthe-
sis 2007, 3345; d) S. Koizumi, K. Ito, K. Fukuda, N. Kameta,
Tetrahedron Lett. 2006, 47, 8563.
[15] For alkyne homocoupling, see: a) P. Siemsen, R. C. Livingston,
F. Diederich, Angew. Chem. Int. Ed. 2000, 39, 2632; b) T. Kur-
ita, M. Abe, T. Maegawa, Y. Monguchi, H. Sajiki, Synlett 2007,
2521; c) K. Kamata, S. Yamaguchi, M. Kotani, K. Yamaguchi,
N. Mizuno, Angew. Chem. Int. Ed. 2008, 47, 2407.
[20] The association constant (Ka) was reported to be 730 m–1 for
BPP34C10 with paraquat in acetone [M. Asakawa, P. R. Ash-
ton, R. Ballardini, V. Balzani, M. Belohradský, M. T. Gan-
˘
dolfi, O. Kocian, L. Prodi, F. M. Raymo, J. F. Stoddart, M.
Venturi, J. Am. Chem. Soc. 1997, 119, 302] and 550 m–1 for
BMP32C10 with paraquat [F. Huang, H. W. Gibson, W. S. Bry-
ant, D. S. Nagvekar, F. R. Fronczek, J. Am. Chem. Soc. 2003,
125, 9367.].
[21] K. Nikitin, H. Müller-Bunz, New J. Chem. 2009, 33, 2472.
[22] a) R. W. Carpick, D. Y. Sasaki, M. S. Marcus, M. A. Eriksson,
A. R. Burns, J. Phys.: Condens. Matter 2004, 16, R679; b)
A. W. Sun, J. W. Lauher, N. S. Goroff, Science 2006, 312, 1030;
c) see ref.[7,8]
[16] Recently, Stoddart reported a [2]catenane by utilizing alkyne
coupling for catenation based on threading 1,5-naphthalene
ˇ
bisalkyne into cyclobis(paraquat-p-phenylene), see: O. S. Mil-
janic´, W. R. Dichtel, S. I. Khan, S. Mortezaei, J. R. Heath, J. F.
Received: August 13, 2010
Published Online: November 26, 2010
ˇ
Stoddart, J. Am. Chem. Soc. 2007, 129, 8236; O. S. Miljanic´,
568
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Eur. J. Org. Chem. 2011, 562–568