A shuttle for the transport of protons based on a [2]rotaxane

Article abstract of DOI:10.1002/ejoc.201402249

A [2]rotaxane shuttle for (light-driven) proton transport has been designed and synthesized. The rotaxane contains a macrocyclic ring that carries a pyridine nitrogen atom as a basic center to bind and to transport a proton. The axis includes an amide bin

Full text of DOI:10.1002/ejoc.201402249

FULL PAPER
DOI: 10.1002/ejoc.201402249
A Shuttle for the Transport of Protons Based on a [2]Rotaxane
Britta Hesseler,[a] Melanie Zindler,[a] Rainer Herges,[a] and Ulrich Lüning*[a]
Keywords: Supramolecular chemistry / Rotaxanes / Macrocycles / Click chemistry / Hydrogen bonds
A [2]rotaxane shuttle for (light-driven) proton transport has
been designed and synthesized. The rotaxane contains a
macrocyclic ring that carries a pyridine nitrogen atom as a
basic center to bind and to transport a proton. The axis in-
cludes an amide binding site for the macrocycle and a posi-
tive charge in close vicinity. Upon protonation of the pyridine
nitrogen atom, the hydrogen bond is broken and Coulomb
repulsion between the protonated pyridine and the perma-
nent positive charge in the axis pushes the protonated
macrocycle to the other end of the axis. By variation of the
pH the ring can shuttle to and fro. Its locations on the axis
were determined by NMR spectroscopy.
Introduction
Mechanical motion not only plays a crucial role in the
macroscopic world, it is also essential for a number of natu-
ral and artificial molecular processes.[1–3] One of the proto-
types of molecular machines in nature is ATPase[4] that pro-
duces about 35 kg ATP per capita per day. The energy
source is a pH gradient,[4] which is generated by photosyn-
thesis (in green plants) or by metabolism of glucose. In
halobacteria, the pH gradient is built up across a biological
membrane by bacteriorhodopsin, a light-driven proton
pump.[5]
A rotaxane-based artificial light-driven proton pump,[6,7]
must include the following features: at one side of the mem-
brane light must generate a low pH, and to pick up the
protons and to transport them to the other side of the mem-
brane, a transport mechanism is needed. The general design
of our rotaxane shuttle aimed at performing such transport
is shown in Figure 1. Rotaxanes are mechanically inter-
locked molecules in which a ring is able to move along an
axis. Two stoppers on either end of the rotaxane prevent
the ring from slipping off the axis. Since the first synthesis
of a rotaxane,[8,9] numerous interlocked molecules have
been synthesized.[10] For the purpose of a light-driven pro-
ton pump a rotaxane with a resting station next to one
Figure 1. Schematic representation of a light-driven proton pump.
(a) A mixture of a [2]rotaxane and a photo acid A-H is irradiated
by light. The [2]rotaxane contains a ring with a basic nitrogen atom
and an axis in which a binding site for the ring exists next to a
permanent positive charge. Upon irradiation, the acidity of A-H is
increased and the photo-acid can protonate the basic nitrogen atom
in the ring of the rotaxane. (b) The resulting positively charged
macrocyclic ring is repelled by a permanent positive charge in the
axis of the rotaxane. (c) When the ring eventually releases the pro-
ton, the resulting neutral macrocycle can diffuse back to the start-
ing point.
Over the years, [2]rotaxanes with axes containing
stopper has to be synthesized. The ring of the rotaxane various binding sites have been investigated as molecular
must be able to pick up a proton on one side, and then it shuttles.[11] For a shuttle as shown in Figure 1, a ring in-
must move to the other side, release the proton, and diffuse cluding a basic center must be able to move along an axis
back.
which has a binding site on one side for the unprotonated
ring. After protonation however, the protonated ring is re-
pelled so that it moves to the other side of the rotaxane.
For this purpose the axis needs to contain a positive charge
close to the binding site.
An amide unit was chosen as the binding site for the
basic macrocycle. The macrocyclic ring contains a 2,6-di-
substituted pyridine. The 2,6-disubstitution orients the pyr-
[a] Otto-Diels-Institut für Organische Chemie,
Christian-Albrechts-Universität zu Kiel,
Olshausenstraße 40, 24098 Kiel, Germany
E-mail: luening@oc.uni-kiel.de
http://www.luening.otto-diels-institut.de/
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201402249.
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idine nitrogen atom to the inside of the macrocycle to allow
docking to the amide NH. By protonation, the hydrogen-
bond acceptor, the pyridine nitrogen atom, becomes a
hydrogen-bond donor. This would allow a hydrogen bond
to form with the carbonyl group of the amide. However, the
positive charge generated by protonation of the pyridine in
the ring and the permanent positive charge on the axis repel
each other and push the ring towards the other end of the
axis.
Results and Discussion
Synthesis of the Macrocycle
The synthesis of 29-membered pyridine macrocycles was
already known.[13] Although saturated ring 2 was obtained
by a double Williamson-ether synthesis, its unsaturated rel-
ative 1 was synthesized by a ring-closing metathesis in con-
siderably better yields. In principle, this macrocycle could
serve as the proton carrier but it is generated as a mixture
of E and Z. Therefore, 1 was hydrogenated with platinum
oxide as the catalyst to give saturated macrocycle 2 in 99%
yield (Scheme 1).
Thus, the desired [2]rotaxane must consist of a pyridine
macrocycle and a positively charged axis. Examples of both
components of the rotaxane are described in the literature.
2,6-Disubstituted pyridine macrocycles can be synthesized
in a variety of ways.[12] We have chosen a 4-substituted 2,6-
bis(bromomethyl)pyridine as starting material, substituted
the bromine atoms by alkenyl-substituted ethers, and then
used ring-closing metathesis for the macrocycle forma-
tion.[13] Axes with positive charges, such as protonated
amines, have often been used in rotaxane syntheses and
there are also examples of rotaxanes with permanent posi-
tive charges in the axis.[14–18]
.
Finally, a suitable synthetic method must be chosen for
assembly of the rotaxane. Most rotaxane syntheses exploit
strong supramolecular interaction between the components
to generate the rotaxane in good yield, for instance by
threading or clipping.[10] But in the case of the light-driven
proton pump, preferentially no additional functional
groups should be introduced because they might interfere
with the shuttling process. The macrocyclic ring contains
only one functional group, which can be incorporated in an
assembly process, the pyridine heterocycle. Macrocycles
that contain N-heterocycles have been used in trapping syn-
theses of rotaxanes.[19–21] In such a trapping process, the
axis is formed from two half axes, which are connected in-
side the macrocycle. As nitrogen atoms bind well to transi-
tion metal ions, metal-ion-catalyzed reactions can be per-
formed in the trapping mode, for instance copper(I)-cata-
lyzed 1,3-dipolar cycloaddition reactions (click chemis-
try).[19]
Scheme 1. Synthesis of the macrocycle 2. (a) H2, PtO2, CHCl3, 2 d,
room temp., 99%.
Synthesis of the Azide Half-axis
Azide half-axis 7 was prepared in three steps starting
from known tris(tert-butylphenyl)methyl stopper deriva-
tive[25] 3 (Scheme 2). With thionyl chloride, propanoic acid
derivative 3 was converted into the respective acid chloride
that was then directly reduced with lithium aluminum
hydride to yield propanol derivative 4 in 71% yield. Alcohol
4 was then treated with 6-bromohexanoic acid chloride[26]
(5) to give ester 6 in 81% yield. Finally, bromide 6 was
converted into azide 7 in 89% yield by nucleophilic substi-
tution with sodium azide.
To realize the proton shuttle depicted in Figure 1, we
therefore needed: a pyridine containing macrocycle; one
half axis terminated by an alkyne; and one half axis termin-
ated by an azide. As stoppers, tris(tert-butylphenyl)methyl
groups were chosen because they had proven to be large
enough for use with a 29-membered ring containing a pyr-
idine ring.[19]
In contrast to other rotaxanes which can be switched by
pH changes,[11] the protonatable/deprotonatable function in
our system is located on the ring and the repelling positive
charge is part of the axis.[22] Thus the protonation/depro-
tonation process is coupled with movement of the protons
along the axis as needed for a proton pump. Movement
of a macrocycle upon protonation has been observed with
related pseudorotaxanes,[23,24] but of course, these pseudo-
rotaxanes disassemble upon protonation. In this work, we
present the synthesis of a rotaxane that contains the mobile
protonatable site in the ring. The movement and its revers-
ibility have been investigated by pH titrations.
Scheme 2. Synthesis of azide half-axis 7. (a) (i). SOCl2, 2.5 h, re-
flux, (ii). LAH, diethyl ether, 2 h, reflux, 71%; (b) Et3N, CH2Cl2,
19 h, reflux, 81%; (c) NaN3, DMF, 2 d, 80 °C, 89%.
Synthesis of the Alkyne Half-Axis
The second half of the rotaxane axis, alkyne half-axis
22, was synthesized in a convergent way from pyridine 11
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A Shuttle for the Transport of Protons Based on a [2]Rotaxane
(Scheme 3) and alkyne linker 20 (Scheme 4). By converting coupling. Both reactions worked as well, but gave pyridine
aniline[27] 8 into the respective diazonium salt, iodinated 11 in lower yields.
and brominated stoppers 9 and 10 were synthesized in 68%
For the synthesis of alkyne linker 20, monobenzyl-pro-
and 52% yield, respectively. Through palladium-catalyzed tected hydroquinone 12 was treated with potassium carb-
cross-coupling reactions halogenated stoppers 9 and 10 onate and 1,6-dibromohexane to yield alkylated ether 13 in
were then coupled to a pyridine. In the case of iodide 9, 69%. The remaining bromine atom in 13 was substituted
a Stille coupling reaction with 3-(tributyltin)pyridine was by phthalimide to yield 14 in 95% yield (Gabriel synthesis).
performed to give pyridine 11 in 38% yield. Alternatively, Treatment of phthalimide 14 with hydrazine monohydrate
bromide 10 was coupled in a Suzuki–Miyaura reaction with released the corresponding amine, which was isolated as
2-(3-pyridyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane[28] to hydrochloride 15 in 82% yield. After protection of the
yield pyridine 11 in 26%. Iodide 9 was also employed in amine as carbamate 16 (quant. yield), the benzyl protecting-
the Suzuki–Miyaura coupling and bromide 10 in the Stille group was cleaved by hydrogenation to give phenol 17
quantitatively. Phenol 17 was then deprotonated with so-
dium hydride and reaction with 5-chloropentyne gave alk-
ynylated ether 18 in 78%. The tert-butyloxycarbonyl (Boc)-
protecting group was cleaved by treatment with trifluoro-
acetic acid and resulting amine 19 was treated with
chloroacetyl chloride to give amide 20 in 66% yield.
In a Menschutkin reaction, the nitrogen atom of pyridine
stopper 11 was alkylated with alkyne linker 20 to give alk-
yne half-axis 21 in 51%. In this reaction, the positive charge
needed as part of the axis in the final shuttle is generated
(Figure 1). Finally, the iodide counterion was exchanged by
using silver(I) hexafluorophosphate to avoid the reaction of
iodide ions with the copper catalyst in the rotaxane-forming
1,3-dipolar cycloaddition reaction.
Rotaxane Assembly
Finally, the rotaxane was synthesized by trapping the two
half axes 22 and 7 within macrocycle 2. Equimolar amounts
of alkyne half-axis 22, azide half-axis 7 and macrocycle 2
were dissolved in dichloromethane and Cu(CH3CN)4PF6
was added as catalyst (Scheme 5). Because of strong bind-
ing of the copper ions in pyridine macrocycle 2, the copper
catalyst was used in equimolar amounts. After two days of
stirring at room temperature, rotaxane 23 and free axis 24
were isolated in 3% and 32% yield, respectively.
Scheme 3. Synthesis of pyridine half-axis 11. (a) (i). NaNO2, acet-
one, HCl, 30 min, 0 °C, (ii). KI, 1 h, room temp., then 2 h at 60 °C,
68%; (b) (i). NaNO2, acetone, HBr solution, 1 h, 0 °C, (ii). CuBr,
3 h, room temp., 52%; (c) 2-(3-pyridyl)-4,4,5,5-tetramethyl-1,3,2-
dioxaborolane, Ba(OH)2·8H2O, Pd(OAc)2, dppp, DME/H2O (4:1),
1 d, reflux, 26% (X = I); (d) 3-(tributyltin)pyridine, (Ph3P)2PdIICl2,
CuI, DMF, 1 d, 100 °C, 38% (X = Br).
Scheme 4. Synthesis of alkyne linker 20. (a) K2CO3, 1,6-dibromohexane, acetone, 21 h, reflux, 69%; (b) potassium phthalimide, DMF,
8 h, 70 °C, 95%; (c) (i) hydrazine monohydrate, CH2Cl2, MeOH, 17 h, room temp., (ii) 1 m HCl, 82%; (d) Et3N, di-tert-butyldicarbonate,
CH2Cl2, 19 h, room temp., quant.; (e) H2, Pd/C, CHCl3/ethyl acetate (1:1), 22 h, room temp., 100%; (f) 5-chloropentyne, NaH, DMF,
22 h, room temp., 78%; (g) F3CCOOH, CH2Cl2, 21 h, room temp., 92%; (h) chloroacetyl chloride, Et3N, CH2Cl2, 2 h, –10 °C, 66%.
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Scheme 5. Synthesis of rotaxane 23 consisting of ring 2 and axis 24. (a) NaI, 1,4-dioxane, 17 h, reflux, 51%; (b) AgPF6, CH2Cl2, 1 h,
room temp., 72%; (c) macrocycle 2, azide half-axis 7, CuI(CH3CN)4PF6, CH2Cl2, 2 d, room temp., 3% rotaxane, 32% axis.
The MALDI-TOF spectrum gave a peak at m/z = 1997, capsulated part of the axis is shielded and the respective
which corresponds to the mass of rotaxane 23 without the signals are shifted upfield. The shifts clearly show that the
counterion. Figure 2 shows the NMR spectra of rotaxane preferred position of the macrocycle is close to the pyr-
23 and its components, axis 24 and macrocycle 2. By analy- idinium ion. Two supramolecular interactions favor this
sis of the chemically induced shifts in the 1H NMR spectra, orientation: (i) the formation of a hydrogen bond between
the position of the macrocycle could be determined. Owing the amide N–H in the axis and the pyridine nitrogen atom
to the presence of aromatic rings in the macrocycle, the en- in the macrocycle. (ii) π-π-interactions between the aromatic
1
Figure 2. H NMR spectra of (a) macrocycle 2, (b) rotaxane 23 and (c) axis 24 in CDCl3. Protons of the axis are numbered, protons of
the ring are labelled with letters. Chemically induced shifts in the rotaxane are indicated by dotted lines.
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A Shuttle for the Transport of Protons Based on a [2]Rotaxane
rings of the macrocycle and the electron poor pyridinium
Analogous to the formation of short half-axis 21, elon-
unit of the axis. These interactions also cause shifts of the gated alkyne 29 was coupled with pyridine 11 in a Men-
protons of the aromatic rings in the macrocycle and of a schutkin reaction. Pyridinium iodide 30 was isolated in
CH2 group (Figure 2, Label d).
66% yield. Again, the iodide counterion was exchanged by
Rotaxane syntheses by the trapping method can lead to reaction with silver(I) hexafluorophosphate and pyridinium
very good yields[19] but rotaxane 23 was isolated in only hexafluorophosphate 31 was obtained in 58% yield.
3%. Two factors may be responsible for this: (i) the high
yields of other rotaxanes formed by trapping have been
achieved by using an excess of the half axes (in many experi-
Assembly of the Longer Rotaxane
ments, a five fold excess was used[19]). In the case of rotax-
ane 23, the syntheses of the half axes need more effort.
For the synthesis of rotaxane 32, a mixture of macrocycle
Therefore, they have not been used in excess. (ii) the perma- 2, azide half-axis 7, and elongated alkyne half-axis 31 was
nent positive charges of the pyridinium unit and the copper stirred with Cu(CH3CN)4PF6 in dichloromethane for two
ion are repelling each other, which may cause a yield-dimin- days at room temperature. Also in this synthesis, macro-
ishing effect. A larger distance between the two ions might cycle 2, copper catalyst and half-axes 7 and 31 were used in
lead to a higher yield of a respective rotaxane. Moreover, equimolar concentrations. Rotaxane 32 was isolated in 7%
the total length of rotaxane 23 is quite short. In an applica- yield and the free axis was obtained in 28% yield
tion for proton transport across a membrane, the rotaxane (Scheme 7).
must be adjusted to the thickness of the membrane, i.e. 3–
The MALDI-TOF spectrum of rotaxane 32 has an inten-
4 nm for a typical biological membrane. Therefore, alkyne sive peak at m/z = 2190, corresponding to the mass of rot-
–
linker 20 was extended to yield a longer rotaxane and ex- axane 32 without counterion PF6 . The elemental composi-
tend the distance between the alkyne function and the tion of the rotaxane was confirmed by HRMS (ICR, see
pyridinium ion.
Supporting Information). As shown in Figure 3, analysis of
the NMR spectra of rotaxane 32 with macrocycle 2 and free
axis 33 confirms the interlocked structure. Furthermore, the
position of the macrocycle on the axis could be determined.
The spectra look quite similar to those depicted in Figure 2
for shorter rotaxane 23. Again, the preferred position of the
macrocycle is in the vicinity of the pyridinium ion. A 2D
NOESY spectrum of rotaxane 32 (see Supporting Infor-
mation) shows cross signals of the CH2 group 7 of the axis
with the aromatic proton b and the CH2 group next to the
pyridine (PyCH2) of the macrocycle. This supports the as-
sumption that the macrocycle is located close to the pyrid-
inium ion.
The mechanically interlocked structure of rotaxane 32
was also proven by diffusion-ordered nuclear magnetic reso-
nance spectroscopy (DOSY). The diffusion constant of a
molecule depends on the molecular mass and the solvodyn-
amic radius of the component. The spectrum in Figure 3
(d) shows that all signals from rotaxane 32 exhibit just one
diffusion constant. The diffusion constants for rotaxane 32,
its components axis 33 and ring 2, and a mixture of the two
are listed in Table 1.
Synthesis of the Elongated Alkyne Half-axis
An extended alkyne linker 29 was prepared in five steps,
starting from phenol 17 that was used for the synthesis of
shorter alkyne linker 20 (Scheme 4). Phenol 17 was depro-
tonated with sodium hydride and reaction with bromide 13
gave elongated ether 25 in 75% yield. The benzyl protect-
ing-group was cleaved by hydrogenation and free phenol 26
was obtained in 94% yield. Alkylation of the phenol with
5-chloropentyne led to alkyne 27 in 76% yield. By reaction
with trifluoroacetic acid, the Boc-protecting group in 27
was cleaved. Resulting amine 28 was treated with chlo-
roacetyl chloride to give amide 29 in 66% yield (Scheme 6).
Owing to its smaller size, the macrocycle diffuses faster
and exhibits a larger diffusion constant. Although rotaxane
32 has a larger molecular weight than free axis 33, their
diffusion constants are extremely similar. In contrast, the
diffusion constant of free axis 33 seems to be a little bit
smaller than that of rotaxane 32. But this should not be
over interpreted because the magnitude of potential errors
is not known. It must be kept in mind that diffusion con-
stants are determined not for naked molecules but for sol-
vated ones. In rotaxane 32, the positive charge of the rotax-
ane is shielded from the solvent by the macrocycle. In con-
trast in free axis 33, the pyridinium ion can be solvated.
As described in Figure 1, the rotaxane should finally
function as a light-driven proton shuttle. Therefore, the
Scheme 6. Synthesis of the elongated alkyne linker 29. (a) NaH,
DMF, 2 d, room temp., 75%; (b) H2, Pd/C, CHCl3, 22 h, room
temp., 94%; (c) 5-chloropentyne, NaH, DMF, 18 h, room
temp., 76%; (d) F3CCOOH, CH2Cl2, 19 h, room temp., 95%;
(e) chloroacetyl chloride, Et3N, CH2Cl2, 4 h, room temp., 70%.
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Scheme 7. Synthesis of rotaxane 32 consisting of ring 2 and axis 33. (a) NaI, 1,4-dioxane, 2 d, reflux, 66%; (b) AgPF6, CH2Cl2, 2 h, room
temp., 58%; (c) macrocycle 2, azide half-axis 7, CuI(CH3CN)4PF6, CH2Cl2, 2 d, room temp., 7% rotaxane, 28% axis.
1
Figure 3. H NMR spectra of (a) macrocycle 2, (b) rotaxane 32 and (c) free axis 33 in CDCl3. (d) 2D DOSY spectrum of the rotaxane
32 in CDCl3.
macrocycle has to move along the axis when the pH
changes. The addition of an acid protonates the macrocycle,
and as a result of repulsive interactions with the permanent
positive charge of the axis, the macrocycle should move
along the axis. By addition of a base, the macrocycle is de-
protonated and it may diffuse back to the starting position
(Scheme 8).
Table 1. Diffusion constants D for 32, its components 33 and 2,
and a mixture of the two determined in CDCl3.
D [10–10 m2 s–1] signals for
axis
macrocycle
rotaxane 32
axis 33
3.62
3.38
3.60
macrocycle 2
axis 33 + macrocycle 2
8.11
8.04
The pH sensitivity of rotaxane 32 was verified by NMR
spectroscopy experiments (Scheme 8 and Figure 4). Di-
3.50
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A Shuttle for the Transport of Protons Based on a [2]Rotaxane
Scheme 8. Movement of the ring along the axis in rotaxane 32 when acid or base are added.
Figure 4. 1H NMR spectra in CD2Cl2 of (c) rotaxane 32, (b) rotaxane 32 upon addition of 3.2 equiv. F2HCCOOH according to integration
and (a) neutralization by the addition of 3.2 equiv. NEt3 according to integration. Changes are marked with dashed lines. The letters and
numbers of the corresponding protons are shown in Scheme 8.
fluoroacetic acid was chosen for two reasons: (i) owing to nitrogen atom. The shifts of the ring protons b, c and d also
the remaining hydrogen atom in this fluorinated acetic acid, changed, indicating a new environment. The protons of the
its concentration can be detected in the NMR spectra, and pyridinium ion in the axis (4, 5, 6) and the neighboring
(ii) in contrast to, for instance p-toluenesulfonic acid, this aromatic ring (1, 2) are shifted downfield (see Figure 4, c
acid is available without water.
and b). These findings indicate that the macrocycle changes
Upon addition of difluoroacetic acid to rotaxane 32, the its position on the axis. The upfield shift of protons 11 to
signal of the pyridine protons of the macrocyclic ring (a) is 15 of the axis suggest that the macrocycle is now located
shifted downfield owing to the protonation of the pyridine between the aromatic ring (11, 12) and the triazol. The 2D
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NOESY spectrum of protonated rotaxane 32·H+ (see Sup-
porting Information) shows a cross signal between the aro-
matic protons (b) of the macrocycle and the aromatic pro-
tons (12) of the axis. This indicates π–π stacking of the two
aromatic rings. Another stabilizing force for this position
with a Perkin–Elmer Spectrum 100 spectrometer equipped with a
MKII Golden GateTM Single Reflection ATR unit. Elemental
analyses were carried out with a Euro EA 3000 Elemental Analyzer
from Euro Vector.
54-Methoxy-3,7,10,21-tetraoxa-1,9(1,4)-dibenzena-5(2,6)-pyridina-
may be a hydrogen bond between the proton at the nitrogen cycloheneicosaphan (2): Hydrogen was bubbled through a suspen-
sion of platinum oxide (3.8 mg, 17 μmol) in acid-free chloroform
for 30 min. A solution of macrocycle 1[13] (101 mg, 195 μmol) in
acid-free chloroform (10 mL) was added, and the mixture was
flushed with hydrogen for further 1.5 h, followed by stirring for 2 d
under hydrogen. The solvent was evaporated and the residue was
purified by column chromatography (silica gel, dichloromethane/
ethyl acetate, 1:1, Rf = 0.54) to afford compound 2 as a white solid
(101 mg, 99%); m.p. 104 °C. 1H NMR (500 MHz, CDCl3): δ = 7.22
(d, 3J = 8.6 Hz, 4 H, Ar-3,5-H), 6.90 (br. s, 2 H, Py-3,5-H), 6.80
atom of the pyridinium ion and a triazol nitrogen atom.
Addition of triethylamine leads to deprotonation of the
macrocycle (Figure 4, a). Consequently, the macrocycle
moves back to the starting position. The NMR spectrum
shows that all signals are shifting back to their original po-
sitions (see differences between parts a and c in Figure 4).
3
(d, J = 8.6 Hz, 4 H, Ar-2,6-H), 4.59 (s, 4 H, ArCH2), 4.37 (br. s,
Conclusions
4 H, PyCH2), 3.97 (t, 3J = 6.4 Hz, 4 H, ArOCH2), 3.89 (s, 3 H,
OCH3), 1.72 (quint, 3J = 6.7 Hz, 4 H, OCH2CH2), 1.45–1.37 [m, 4
H, O(CH2)2CH2], 1.32–1.24 [m, 8 H, O(CH2)3CH2CH2] ppm. 13C
NMR (125 MHz, CDCl3): δ = 167.3 (s, Py-C-4)*, 158.8 (s, Ar-C-
1), 130.1 (d, Ar-C-3,5), 129.2 (s, Ar-C-4), 114.7 (d, Ar-C-2,6), 105.9
(d, Py-C-3,5), 72.3 (t, ArCH2), 71.0 (t, PyCH2), 67.4 (t, ArOCH2),
29.4, 28.7 [2t, O(CH2)3CH2CH2], 28.6 (t, OCH2CH2), 25.7 [t,
O(CH2)2CH2] ppm. *The signal was only detected in the HMBC
spectrum. The quaternary Py-C-2,6-signal could not be detected in
the 13C NMR spectrum. MS (MALDI-TOF, Cl-CCA): m/z = 520
[M + H]+.
[2]Rotaxane 32, which can be switched by protons, has
been synthesized. As the basis for this switching process, a
permanent positive charge has been incorporated into the
axis, and a ring containing a basic center has been chosen.
NMR studies in acidic and basic milieus proved that the
ring moves along the axis upon protonation. In its unpro-
tonated state, supramolecular interactions, such as a hydro-
gen bond and π–π interactions, bind the ring on one side
of the rotaxane next to the permanent positive charge. Pro-
tonation of the ring results in repulsion by Coulomb forces
and the protonated ring moves along the axis whereby it
will eventually release the proton. Future experiments will
aim to modify the stoppers in such a way that the rotaxane
is able to span a bilayer membrane.
1-Iodo-4-[tris(4-tert-butylphenyl)methyl]benzene (9): A suspension
of 4-[tris(4-tert-butylphenyl)methyl]aniline[27] (8; 2.52 g, 5.00 mmol)
in a mixture of acetone (50 mL) and conc. hydrochloric acid
(12 mL) was cooled to 0 °C and a solution of sodium nitrite
(535 mg, 7.76 mmol) in water (3.5 mL) was added. The suspension
was stirred for 30 min at 0 °C and then potassium iodide (1.34 g,
8.10 mmol) in water (5 mL) was added. The reaction mixture was
stirred for 1 h at 0 °C, followed by 1 h at room temperature and
finally 2 h at 60 °C. The reaction mixture was treated with a 48%
aqueous sodium hydrogen sulfite solution (100 mL) and neutral-
ized with a saturated aqueous sodium hydrogen carbonate solution.
The solution was extracted with diethyl ether (3ϫ 50 mL), the com-
bined organic layers were washed with water (100 mL) and brine
(2ϫ 50 mL) and finally dried with magnesium sulfate. The solvent
was removed under reduced pressure and the residue was purified
by column chromatography (silica gel, dichloromethane/methanol,
10:1, Rf = 0.83) to give 9 as a pale yellow solid (2.09 g, 68%); m.p.
Experimental Section
General Remarks: The following chemicals were obtained commer-
cially and were used without further purification: 4-benzyloxy-
phenol (Alfa Aesar), chloroacetyl chloride (Acros), 5-chloropent-
yne (Acros), Cu(CH3CN)4PF6 (Aldrich), 1,6-dibromohexane (Ald-
rich), 3-(tributylstannyl)pyridine (Maybridge), difluoroacetic acid
(ABCR). Macrocycle 1,[13] 4-[tris(4-tert-butylphenyl)methyl]aniline
(8),[27] 3,3,3-tris(4-tert-butylphenyl)propionic acid (3),[25] and 6-
bromohexanoyl chloride (5),[26] were prepared according to litera-
ture procedures. Dry solvents were obtained with suitable desic-
cants. All reactions carried out with dry solvents were performed
under nitrogen. Column chromatography was carried out with sil-
ica gel (0.04–0.063 mm, Macherey–Nagel). 1H and 13C NMR spec-
tra were recorded with Bruker AC 200, DRX 500 or AV 600 instru-
ments. Assignments are supported by COSY, HSQC spectroscopy,
HMBC, and NOESY. Even when obtained by DEPT, the type of
13C signal is always listed as singlet, doublet, etc. All chemical shifts
are referenced to tetramethylsilane or to the residual proton or
carbon signal of the solvent. Signal assignment in NMR spectra:
if there is more than one aromatic ring in a molecule, the rings
are labeled Ar1, Ar2 and so on from left to right according to the
orientation in the schemes above. Mass spectra were recorded with
a Finnigan MAT 8200 or MAT 8230. MALDI-TOF mass spectra
were recorded with a Bruker-Daltonics Biflex III with Cl-CCA (4-
chloro-α-cyano-cinnamic acid) as matrix. ESI mass spectra were
recorded with an Applied Biosystems Mariner Spectrometry
Workstation. HRMS were recorded with an APEX 3 FT-ICR and
a 7.05 T magnet from Bruker Daltonics. IR spectra were recorded
1
3
308 °C. H NMR (500 MHz, CDCl3): δ = 7.54 (d, J = 8.7 Hz, 2
3
3
H, Ar-3,5-H), 7.23 (d, J = 8.7 Hz, 6 H, tBuAr-3,5-H), 7.06 (d, J
= 8.7 Hz, 6 H, tBuAr-2,6-H), 6.95 (d, 3J = 8.7 Hz, 2 H, Ar-2,6-H),
1.30 (s, 27 H, CH3) ppm. 13C NMR (125 MHz, CDCl3): δ = 148.6
(s, tBuAr-C-4), 147.3 (s, Ar-C-1), 143.4 (s, tBuAr-C-1), 136.3 (d,
Ar-C-3,5), 133.5 (d, Ar-C-2,6), 130.6 (d, tBuAr-C-2,6), 124.2 (d,
tBuAr-C-3,5), 91.5 (s, Ar-C-4), 63.5 [s, C(tBuAr)3], 34.3 [s,
C(CH ) ], 31.3 (q, CH ) ppm. IR (ATR): ν = 3032 (arom. C–H),
˜
3 3
3
2960, 2903, 2867 (aliph. C–H), 1505, 1479, 1460 (arom.), 843, 823
(1,4-disubstitution) cm–1. MS (EI, 70 eV): m/z (%) = 614 (45)
[M]+·, 557 (14) [M – C(CH3)3]+, 481 (100) [M – C6H4C(CH3)3]+,
411 (82) [M – C6H4I]+, 355 (26) [M – C6H4C(CH3)3 – I]+. C37H43I
(614.24): C 72.30, H 7.05. C37H43I·1CH2Cl2·2CH3OH (762.25):
calcd. C 60.20, H 6.57; found C 60.47, H 6.23.
1-Bromo-4-[tris(4-tert-butylphenyl)methyl]benzene (10): A mixture
of 4-[tris(4-tert-butylphenyl)methyl]aniline[27] (8; 1.49 g, 2.96 mmol)
and 48% aqueous hydrobromic acid (4.37 mL, 38.7 mmol) in acet-
one (50 mL) was cooled to 0 °C. A solution of sodium nitrite
3892
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© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 3885–3901

A Shuttle for the Transport of Protons Based on a [2]Rotaxane
(292 mg, 4.17 mmol) in water (4 mL) was added and the mixture
was stirred at 0 °C for 1 h. A solution of copper(I)bromide (748 mg,
5.21 mmol) in aqueous hydrobromic acid (48% ,1 mL) was added
and the reaction mixture was stirred for 3 h at room temperature.
The precipitate was filtered and washed with water (20 mL) and
dichloromethane (20 mL). After separation of the phases, the aque-
ous layer was extracted with dichloromethane (3ϫ 40 mL) and the
combined organic layer was washed with brine (50 mL) and dried
with magnesium sulfate. The solvent was removed under reduced
pressure and the crude product was purified by column chromatog-
raphy (silica gel, dichloromethane/cyclohexane, 1:1, Rf = 0.83) to
give 10 as a light orange solid (875 mg, 52%); m.p. 278 °C. 1H
tBuAr-C-2,6), 125.8 (d, PyAr-C-2,6), 124.2 (d, tBuAr-C-3,5), 123.5
(d, Py-C-5), 63.6 [s, C(tBuAr)3], 34.3 [s, C(CH3)3], 31.4 (q,
CH ) ppm. IR (ATR): ν = 2957, 2866 (aliph. C–H), 1684 (C=N),
˜
3
1505 (C=C), 824 (1,4-disubstitution), 799, 708 (monosubstitu-
tion) cm–1. MS (EI, 70 eV): m/z (%) = 565 (65) [M]+·, 508 (28) [M –
C4H9]+, 433 (100) [M – C10H12]+·, 411 (74) [M – C11H8N]+. MS
(MALDI-TOF): m/z = 566 [M + H]+. C42H47N (565.37): C 89.15,
H 8.37, N 2.48. C42H47N·0.75H2O (578.88): calcd. C 87.07, H 8.44,
N 2.42; found C 86.92, H 8.45, N 2.41.
3,3,3-Tris(4-tert-butylphenyl)propanol (4): A mixture of 3,3,3-tris(4-
tert-butylphenyl)propionic acid[25] (3, 5.64 g, 12.0 mmol) and thio-
nyl chloride (30 mL) was heated to reflux for 2 h. The excess thionyl
chloride was removed under reduced pressure and toluene
(100 mL) was added. The solvent was removed by distillation and
the residue was dissolved in anhydrous diethyl ether. A solution of
lithium aluminum hydride (912 mg, 24.0 mmol) in anhydrous di-
ethyl ether (60 mL) was added and the mixture was heated to reflux
for 2 h. The mixture was hydrolyzed by the addition of water and
hydrochloric acid (1 m). After separation of the layers, the aqueous
layer was extracted with diethyl ether (3ϫ 100 mL). The combined
organic layer was washed with saturated aqueous sodium hydrogen
carbonate solution (50 mL) and water (50 mL) and dried with mag-
nesium sulfate. The solvent was removed under reduced pressure
and the residue was purified by crystallization from cyclohexane to
obtain 4 as a white solid (3.86 g, 71%). 205 °C. 1H NMR
3
NMR (500 MHz, CDCl3): δ = 7.34 (d, J = 8.7 Hz, 2 H, Ar-2,6-
3
3
H), 7.23 (d, J = 8.7 Hz, 6 H, tBuAr-3,5-H), 7.08 (d, J = 8.7 Hz,
2 H, Ar-3,5-H), 7.06 (d, 3J = 8.7 Hz, 6 H, tBuAr-2,6-H), 1.30 [s,
27 H, C(CH3)3] ppm. 13C NMR (125 MHz, CDCl3): δ = 148.6 (s,
tBuAr-C-4), 146.6 (s, Ar-C-4), 143.4 (s, tBuAr-C-1), 133.0 (d, Ar-
C-3,5), 130.6 (d, tBuAr-C-2,6), 130.3 (d, Ar-C-2,6), 124.2 (d,
tBuAr-C-3,5), 119.8 (s, Ar-C-1), 63.4 [s, C(tBuAr)3], 34.3
[C(CH ) ], 31.4 [q, C(CH ) ] ppm. IR (ATR): ν = 2960, 2904, 2867
˜
3 3
3 3
(aliph. C–H), 1506 (C=C), 823 (1,4-disubstitution) cm–1. MS (EI,
70 eV): m/z (%) = 568, 566 (27, 25) [M]+·, 511, 509 (7, 5) [M –
CH3]+, 488 (40) [M – Br – H]+·, 435, 433 (74, 87) [M – C10H13]+,
411 (100) [M – C6H4Br]+. MS (CI, isobutane): m/z (%) = 568, 566
(9, 8) [M]+·, 435, 433 (100, 97) [M – C10H13]+.
3
(200 MHz, CDCl3): δ = 7.26 (d, J = 8.7 Hz, 6 H, tBuAr-2,6-H),
3-{4-[Tris(4-tert-butylphenyl)methyl]phenyl}pyridine (11): Method
A: A mixture of 1-iodo-4-[tris(4-tert-butylphenyl)methyl]benzene
(9, 641 mg, 1.04 mmol), 3-(tributyltin)pyridine (500 μL, 577 mg,
3
3
7.17 (d, J = 8.7 Hz, 6 H, tBuAr-3,5-H), 3.50 (t, J = 7.1 Hz, 2 H,
3
CH2CH2OH), 2.87 (t, J = 7.1 Hz, 2 H, CH2CH2OH), 1.29 [s, 27
H, C(CH3)3] ppm. 13C NMR (50 MHz, CDCl3): δ = 148.5 (s,
tBuAr-C-4), 144.2 (s, tBuAr-C-1), 128.5 (d, tBuAr-C-3,5), 124.7
(d, tBuAr-C-2,6), 60.8 (t, CH2OH), 54.1 [s, (tBuAr)3C], 43.1 (t,
CH2CH2OH), 34.3 [s, C(CH3)3], 31.4 [q, C(CH3)3] ppm. IR (ATR):
1.56 mmol),
bis(triphenylphosphine)palladium(II)chloride
(92.6 mg, 132 μmol) and copper(I)iodide (65.9 mg, 347 μmol) in
anhydrous dimethylformamide (DMF) was heated for 20 h at
100 °C. Then, the reaction mixture was cooled to room temperature
and dichloromethane (40 mL) and water (40 mL) were added. After
separation of the layers, the aqueous layer was extracted with
dichloromethane (50 mL) and the combined organic layer was
washed with water (40 mL) and brine (40 mL) and dried with mag-
nesium sulfate. The solvent was removed under reduced pressure
and the residue was purified by column chromatography (silica gel,
cyclohexane/ethyl acetate, 6:1, Rf = 0.17) to obtain 11 as a white
ν = 3326 (OH), 3032 (arom. C–H), 2959, 2927, 2903 (aliph. C–H),
˜
1507, 1459 (arom. C–H), 1015 (C–O), 841, 820 (1,4-disubstitu-
tion) cm–1. MS (ESI, MeOH): m/z (%) = 479 (25) [M + Na]+, 437
(30) [M
– C 86.79, H 9.71.
OH]+. C33H44O (456.70):
C33H44O·C6H12 (540.86): calcd. C 86.61, H 10.44; found C 86.37,
H 10.81.
[3,3,3-Tris(4-tert-butylphenyl)]propyl 6-Bromohexanoate (6): 3,3,3-
solid (222 mg, 38%). Method B: A mixture of 1-bromo-4-[tris(4- Tris(4-tert-butylphenyl)propanol (4, 1.12 g, 2.45 mmol) was dis-
tert-butylphenyl)methyl]benzene (10, 400 mg, 706 μmol), 2-(3-pyr-
idyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolan (175 mg, 853 μmol),
barium hydroxide octahydrate (495 mg, 1.57 mmol), palladium(II)-
acetate (16.4 mg, 73.1 μmol) and 1,3-bis(diphenylphosphanyl)prop-
ane (62.1 mg, 151 μmol) in 1,2-dimethoxyethane (DME; 36 mL)
and water (9 mL) was heated to reflux for 24 h. The reaction mix-
ture was cooled to room temperature and dichloromethane (50 mL)
and water (50 mL) were added. After separation of the layers, the
aqueous layer was extracted with dichloromethane (3ϫ 50 mL) and
the combined organic layer was washed with brine (70 mL) and
dried with magnesium sulfate. The solvent was removed under re-
duced pressure and the residue was purified by column chromatog-
raphy (silica gel, cyclohexane/ethyl acetate, 6:1, Rf = 0.17) to obtain
11 as a white solid (106 mg, 26%); m.p. Ͼ 330 °C. 1H NMR
solved in anhydrous dichloromethane (25 mL), and anhydrous
triethylamine (407 μL, 297 mg, 2.94 mmol) and 6-bromohexan-
oic acid chloride (5, 676 mg, 319 mmol) were added. The reaction
mixture was heated to reflux for 19 h and washed with brine (2ϫ
30 mL) afterwards. The organic layer was dried with magnesium
sulfate and the solvent was removed under reduced pressure. The
crude product was purified by column chromatography (silica gel,
cyclohexane/ethyl acetate, 6:1, Rf = 0.60) and 6 was obtained as a
white solid (1.26 g, 81%); m.p. 158 °C. 1H NMR (500 MHz,
3
3
CDCl3): δ = 7.26 (d, J = 8.7 Hz, 6 H, tBuAr-2,6-H), 7.17 (d, J =
3
8.7 Hz, 6 H, tBuAr-3,5-H), 3.91 (mc, 2 H, COOCH2), 3.40 (t, J =
3
6.8 Hz, 2 H, CH2Br), 2.89 (mc, 2 H, COOCH2CH2), 2.25 (t, J =
7.4 Hz, 2 H, CH2COOCH2), 1.87 (mc, 2 H, CH2CH2Br), 1.62 (mc,
2 H, CH2CH2COO), 1.50–1.40 [m, 2 H, CH2(CH2)2Br], 1.29 [s, 27
H, C(CH3)3] ppm. 13C NMR (125 MHz, CDCl3): δ = 173.5 (s,
3
(500 MHz, CDCl3): δ = 8.86 (mc, 1 H, Py-2-H), 8.55 (dd, J = 4.8,
4J = 1.6 Hz, 1 H, Py-6-H), 7.87 (ddd, 3J = 7.9, 4J = 2.3, 4J = COO), 148.5 (s, tBuAr-C-4), 143.8 (s, tBuAr-C-1), 128.5 (d, tBuAr-
1.6 Hz, 1 H, Py-4-H), 7.47 (d, 3J = 8.6 Hz, 2 H, PyAr-2,6-H), 7.36–
C-2,6), 124.7 (d, tBuAr-C-3,5), 62.9 (t, COOCH2), 53.7 [s,
7.33 (m, 1 H, Py-5-H), 7.32 (d, 3J = 8.6 Hz, 2 H, PyAr-3,5-H), 7.26 (tBuAr)3C], 38.8 (t, COOCH2CH2), 34.3 [s, C(CH3)3], 34.0 (t,
(d, 3J = 8.7 Hz, 6 H, tBuAr-3,5-H), 7.13 (d, 3J = 8.7 Hz, 6 H,
CH2COOCH2), 33.5 (t, CH2Br), 32.4 (t,CH2CH2Br), 31.4 [q,
C(CH3)3], 27.6 [t, CH2(CH2)2Br], 24.0 (t,CH2CH2COO) ppm. IR
tBuAr-2,6-H), 1.31 (s, 27 H, CH3) ppm. 13C NMR (125 MHz,
CDCl3): δ = 148.6 (s, tBuAr-C-4), 148.2 (d, Py-C-2, Py-C-6), 147.6 (ATR): ν = 3032 (arom. C–H), 2992, 2959, 2866 (aliph. C–H), 1733
˜
(s, PyAr-C-4), 143.7 (s, tBuAr-C-1), 136.3 (s, Py-C-3), 134.8 (s,
(C=O), 1508, 1460 (arom.), 1015 (C–O), 841, 820 (1,4-disubstitu-
PyAr-C-1), 134.1 (d, Py-C-4), 132.0 (d, PyAr-C-3,5), 130.7 (d, tion) cm–1. MS (ESI, CHCl3, MeOH): m/z = 657, 655 [M +
Eur. J. Org. Chem. 2014, 3885–3901
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3893

B. Hesseler, M. Zindler, R. Herges, U. Lüning
FULL PAPER
Na]+. C39H53BrO2 (633.74): C 73.91, H 8.43. C39H53BrO2·0.2C6H12
(650.57): calcd. C 74.22, H 8.58; found C 74.39, H 8.75.
dichloromethane. The filtrate was concentrated under reduced pres-
sure and purified by column chromatography (silica gel, dichloro-
methane, Rf = 0.56) to obtain the product 14 as a white solid
[3,3,3-Tris(4-tert-butylphenyl)]propyl 6-Azidohexanoate (7): To a
solution of bromo ester 6 (978 mg, 1.55 mmol) in DMF (50 mL),
sodium azide (503 mg, 7.73 mmol) was added and the reaction mix-
ture was heated to 80 °C for 2 d. Then, water (30 mL) was added
and the mixture was extracted with ethyl acetate (2ϫ 40 mL). The
combined organic layer was washed with water (40 mL) and brine
(2ϫ 50 mL) and dried with magnesium sulfate. The solvent was
removed under reduced pressure and the crude product was puri-
fied by column chromatography (silica gel, cyclohexane/ethyl acet-
ate, 5:1, Rf = 0.61) to give 6 as a white solid (822 mg, 89%); m.p.
1
(1.75 g, 95%); m.p. 94 °C. H NMR (500 MHz, CDCl3): δ = 7.83
(mc, 2 H, Phth-3,6-H), 7.70 (mc, 2 H, Phth-4,5-H), 7.43–7.40 (m, 2
H, Bn-2,6-H), 7.39–7.34 (m, 2 H, Bn-3,5-H), 7.33–7.28 (m, 1 H,
Bn-4-H), 6.88 (d, 3J = 9.2 Hz, 2 H, Ar-3,5-H), 6.80 (d, 3J = 9.2 Hz,
3
2 H, Ar-2,6-H), 5.00 (s, 2 H, Bn-CH2), 3.89 (t, J = 6.4 Hz, 2 H,
OCH2), 3.69 (t, 3J = 7.3 Hz, 2 H, NCH2), 1.79–1.67 (m, 4 H,
OCH2CH2, NCH2CH2), 1.54–1.46 [m, 2 H, O(CH2)2CH2], 1.45–
1.37 [m, 2 H, N(CH2)2CH2] ppm. 13C NMR (125 MHz, CDCl3): δ
= 168.4 (s, CON), 153.4 (s, Ar-C-1), 152.9 (s, Ar-C-4), 137.4 (s, Bn-
C-1), 133.8 (d, Phth-C-4,5), 132.2 (s, Phth-C-1,2), 128.5 (d, Bn-C-
3,5), 127.8 (d, Bn-C-4), 127.4 (d, Bn-C-2,6), 123.2 (d, Phth-C-3,6),
115.8 (d, Ar-C-3,5), 115.4 (d, Ar-C-2,6), 70.7 (t, Bn-CH2), 68.4 (t,
OCH2), 37.9 (t, NCH2), 29.1 (t, OCH2CH2), 28.5 (t, NCH2CH2),
1
3
137 °C. H NMR (500 MHz, CDCl3): δ = 7.26 (d, J = 8.7 Hz, 6
H, tBuAr-3,5-H), 7.17 (d, 3J = 8.7 Hz, 6 H, tBuAr-2,6-H), 3.91
(mc, 2 H, COOCH2), 3.27 (t, J = 6.9 Hz, 2 H, CH2N3), 2.89 (mc,
3
2 H, COOCH2CH2), 2.25 (t, 3J = 7.5 Hz, 2 H, CH2COO), 1.66–
1.57 (m, 4 H, CH2CH2COO, CH2CH2N3), 1.42–1.35 [m, 2 H,
CH2(CH2)2N3], 1.29 [s, 27 H, C(CH3)3] ppm. 13C NMR (125 MHz,
CDCl3): δ = 173.5 (s, COO), 148.5 (s, tBuAr-C-4), 143.8 (s, tBuAr-
C-1), 128.5 (d, tBuAr-C-2,6), 124.7 (d, tBuAr-C-3,5), 62.9 (t,
COOCH2), 53.7 [s, (tBuAr)3C], 51.2 (t, CH2N3), 38.7 (t,
COOCH2CH2), 34.3 [s, C(CH3)3], 34.1 (t, CH2COO), 31.3 [q,
C(CH3)3], 28.6 (t, CH2CH2N3), 26.2 [t, CH2(CH2)2N3], 24.4 (t,
26.6 [t, N(CH ) CH ], 25.7 [t, O(CH ) CH ] ppm. IR (ATR): ν =
˜
2 2
2
2 2
2
2937 (aliph. C–H), 1774, 1706 (imide, five membered ring, C=O),
1510 (C=C), 1231, 1043 (C–O), 817 (1,4-disubstitution), 744, 700
(monosubstitution) cm–1. MS (EI, 70 eV): m/z (%) = 429 (54)
[M]+·, 230 (34) [M – OC6H4OCH2C6H5]+, 160 (100) [C9H6NO2]+.
MS (CI, isobutane): m/z (%) = 430 (43) [M + H]+, 230 (100) [M –
OC6H4OCH2C6H5]+, 160 (31) [C9H6NO2]+. C27H27NO4 (429.19):
calcd. C 75.50, H 6.34, N 3.26; found C 75.41, H 6.34, N 3.33.
CH CH COO) ppm. IR (ATR): ν = 3031 (arom. C–H), 2959, 2925,
˜
2
2
6-(4-Benzyloxyphenyloxy)hexylamine Hydrochloride (15): Phthal-
imide 14 (1.00 g, 2.33 mmol) was dissolved in a mixture of di
chloromethane (13 mL) and methanol (13 mL), and hydrazine
monohydrate (650 μL, 670 mg, 13.4 mmol) was added dropwise.
The mixture was stirred for 17 h at room temperature and the pre-
cipitate was filtered and washed with dichloromethane (20 mL).
The solvent was removed under reduced pressure, a mixture of
chloroform (15 mL) and ethyl acetate (15 mL) was added and a
precipitate occurred. The precipitate was filtered and the solvent
was removed under reduced pressure. Chloroform (30 mL) was
added and the organic layer was washed with water (2ϫ 20 mL)
and brine (20 mL). The organic layer was concentrated under re-
duced pressure to 5 mL and hydrochloric acid (1 m) was added and
stirred until a pH of 2 was reached. The precipitate was filtered off
and washed with cold water, ethyl acetate and diethyl ether and
then dried to yield the compound 15 as a white solid (637 mg,
82%); m.p. 196 °C. 1H NMR (500 MHz, [D6]DMSO): δ = 7.98 (br.
2851 (aliph. C–H), 2094 (N3), 1735 (C=O), 1508, 1449 (arom.),
1016 (C–O), 841, 820 (1,4-disustitution) cm–1. MS (MALDI-TOF,
Cl-CCA): m/z = 634 [M + K]+, 618 [M + Na]+, 568 [M – N2
+
H]+, 411 [C31H39]+. C39H53N3O2 (595.41): calcd. C 78.61, H 8.97,
N 7.05; found C 78.56, H 8.99, N 6.54.
1-(Benzyloxy)-4-(6-bromohexyloxy)benzene (13): 1,6-Dibromohex-
ane (19.4 g, 80.0 mmol) was added to a suspension of 4-benzyloxy-
phenol (8.00 g, 40.0 mmol) and anhydrous potassium carbonate
(8.29 g, 60.0 mmol) in anhydrous acetone (80 mL), and the reaction
mixture was heated to reflux for 21 h. The mixture was cooled and
dichloromethane (100 mL) was added. The precipitate was filtered
and washed with dichloromethane (100 mL). The filtrate was con-
centrated under reduced pressure and the residue was crystallized
from n-hexane to give 13 as a white solid (10.0 g, 69%); m.p. 76 °C.
3
1H NMR (500 MHz, CDCl3): δ = 7.42 (d, J = 7.3 Hz, 2 H, Bn-
3
3
2,6-H), 7.37 (t, J = 7.3 Hz, 2 H, Bn-3,5-H), 7.31 (t, J = 7.3 Hz,
3
3
3
3
s, 3 H, NH3+), 7.42 (d, J = 7.3 Hz, 2 H, Bn-2,6-H), 7.38 (t, J =
1 H, Bn-4-H), 6.90 (d, J = 9.3 Hz, 2 H, Ar-2,6-H), 6.82 (d, J =
9.3 Hz, 2 H, Ar-3,5-H), 5.01 (s, 2 H, BnCH2), 3.90 (t, J = 6.4 Hz,
3
7.5 Hz, 2 H, Bn-3,5-H), 7.31 (t, 3J = 7.2 Hz, 1 H, Bn-4-H), 6.92
3
3
3
3
2 H, OCH2), 3.41 (t, J = 6.8 Hz, 2 H, BrCH2), 1.89 (quint, J =
(d, J = 9.1 Hz, 2 H, Ar-3,5-H), 6.84 (d, J = 9.1 Hz, 2 H, Ar-2,6-
7.0 Hz, 6.8 Hz, H,
2
H, BrCH2CH2), 1.77 (quint, 3J
=
2
3
H), 5.03 (s, 2 H, Bn-CH2), 3.88 (t, J = 6.5 Hz, 2 H, OCH2), 2.75
OCH2CH2), 1.53–1.41 [m, 4 H, O(CH2)2(CH)2] ppm. 13C NMR
(125 MHz, CDCl3): δ = 153.4 (s, Ar-C-4), 152.9 (s, Ar-C-1), 137.3
(s, Bn-C-1), 128.5 (d, Bn-C-3,5), 127.9 (d, Bn-C-4), 127.5 (d, Bn-
C-2,6), 115.8 (d, Ar-C-3,5), 115.4 (d, Ar-C-2,6), 70.7 (t, BnCH2),
68.3 (t, OCH2), 33.7 (t, BrCH2), 32.7 (t, BrCH2CH2), 29.2 (t,
OCH2CH2), 27.9 [t, (OCH2)3CH2], 25.3 [t, (OCH2)2CH2] ppm. IR
[sext, 3J = 6.8 Hz, 2 H, O(CH2)5CH2NH3+], 1.67 (quint, 3J =
3
6.8 Hz, 2 H, OCH2CH2), 1.57 [quint, J = 7.4 Hz, 2 H, O(CH2)4-
CH2], 1.45–1.31 [m,
4
H, O(CH2)2(CH2)2] ppm. 13C NMR
(125 MHz, [D6]DMSO): δ = 153.3 (s, Ar-C-1), 152.7 (s, Ar-C-4),
137.9 (s, Bn-C-1), 128.8 (d, Bn-C-3,5), 128.2 (d, Bn-C-4), 128.0 (d,
Bn-C-2,6), 116.2 (d, Ar-C-3,5), 115.7 (d, Ar-C-2,6), 70.1 (t, Bn-
CH2), 68.1 (t, OCH2), 39.1 [t, O(CH2)5CH2NH3+], 29.1 (t,
OCH2CH2), 27.3 [t, O(CH2)4CH2], 26.0, 25.5 [2t, O(CH2)2-
(ATR): ν = 3043 (arom. C–H), 2937, 2863 (aliph. C–H), 1505
˜
(C=C), 1455, 1467 (C–H), 1224 (C–O), 824 (1,4-disubstitution),
736, 693 (monosubstitution), 645 (C–Br) cm–1. MS (EI, 70 eV): m/z
(%) = 364, 362 (99, 100) [M]+·, 273, 271 (6, 9) [M – CH2C6H5]+,
165, 163, (18, 17) [C6H12Br]+. MS (CI, isobutane): m/z (%) = 365,
363 (97, 100) [M + H]+, 165, 163 (63, 69) [C6H12Br]+. C19H23BrO2
(363.29): calcd. C 62.82, H 6.38; found C 62.80, H 6.47.
(CH ) ] ppm. IR (ATR): ν = 3030 (NH +), 2934, 2866 (aliph. C–
˜
2 2
3
H), 1598, 1533, 1506 (C=C), 1239, 1012 (C–O), 821 (1,4-disubstitu-
tion), 741, 693 (monosubstitution) cm–1. MS (CI, isobutane): m/z
= 300 [M – Cl]+. MS (ESI, MeOH): m/z = 300 [M – Cl]+.
C19H26ClNO2 (335.67): calcd. C 67.94, H 7.80, N 4.17; found C
68.02, H 7.83, N 4.14.
N-[6-(4-Benzyloxyphenyloxy)hexyl]phthalimide (14): A solution of
bromide 13 (1.53 g, 4.24 mmol) and potassium phthalimide
(952 mg, 5.13 mmol) in anhydrous DMF was heated at 70 °C for
8 h. The solvent was removed under reduced pressure and dichloro-
methane was added. The precipitate was filtered and washed with
tert-Butyl-N-6-[4-(benzyloxy)phenyloxy]hexylcarbamate (16): To a
solution of amino chloride 15 (1.16 g, 3.46 mmol) in anhydrous
dichloromethane (20 mL), anhydrous triethylamine (1.23 mL,
897 mg, 8.86 mmol) was added. The solution was stirred for 20 min
3894
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 3885–3901

A Shuttle for the Transport of Protons Based on a [2]Rotaxane
at room temperature and a solution of di-tert-butyldicarbonate
(972 mg, 4.57 mmol) in anhydrous dichloromethane (6 mL) was
added. The mixture was stirred for 19 h at room temperature and
afterwards the solvent was removed under reduced pressure. The
residue was purified by column chromatography (silica gel, dichlo-
romethane, Rf = 0.28) to give 16 as a white solid (1.38 g, quant.);
m.p. 93 °C. 1H NMR (600 MHz, CDCl3): δ = 7.42 (d, 3J = 7.3 Hz,
give 18 as a white solid (891 mg, 78%); m.p. 59 °C. 1H NMR
(500 MHz, CDCl3): δ = 6.82 (mc, 4 H, Ar-2,3,5,6-H), 4.51 (br. s, 1
3
3
H, NH), 4.01 [t, J = 6.1 Hz, 2 H, OCH2(CH2)2CϵCH], 3.89 [t, J
= 6.5 Hz, 2 H, OCH2(CH2)5NH], 3.11 [mc, 2 H, O(CH2)5CH2NH],
3
4
2.39 [td, Jt = 7.1, Jd = 2.7 Hz, 2 H, O(CH2)2CH2CϵCH], 2.01–
1.94 (m, 3 H, OCH2CH2CH2CϵCH), 1.75 [mc, 2 H, OCH2CH2-
(CH2)4NH], 1.53–1.42 [m, 4 H, O(CH2)2CH2CH2CH2CH2NH],
1.44 (s, 9 H, CH3), 1.41–1.34 [m, 2 H, O(CH2)3CH2(CH2)2-
NH] ppm. 13C NMR (125 MHz, CDCl3): δ = 156.0 (s, CONH),
153.3 (s, Ar-C-1), 153.0 (s, Ar-C-4), 115.5, 115.4 (2d, Ar-C-2,3,5,6),
83.6 (s, CϵCH), 79.0 [s, C(CH3)3], 68.7 (d, CϵCH), 68.5 [t,
3
3
2 H, Bn-2,6-H), 7.37 (t, J = 7.6 Hz, 2 H, Bn-3,5-H), 7.31 (t, J =
7.3 Hz, 1 H, Bn-4-H), 6.89 (d, 3J = 9.1 Hz, 2 H, Ar-3,5-H), 6.81
3
(d, J = 9.1 Hz, 2 H, Ar-2,6-H), 5.01 (s, 2 H, Bn-CH2), 4.51 (br. s,
1 H, NH), 3.89 (t, 3J = 6.5 Hz, 2 H, OCH2), 3.12 (mc, 2 H,
NHCH2), 1.75 (quint, 3J = 7.0 Hz, 2 H, OCH2CH2), 1.53–1.45 [m, OCH2(CH2)5NH], 66.8 [t, OCH2(CH2)2CϵCH], 40.5 [t, O(CH2)5-
4 H, HNCH2CH2, O(CH2)2CH2], 1.44 (s, 9 H, CH3), 1.41–1.33 [m, CH2NH], 30.0 [t, O(CH2)4CH2CH2NH], 29.3 [t, OCH2CH2(CH2)4-
2 H, NH(CH2)2CH2] ppm. 13C NMR (150 MHz, CDCl3): δ = 156.0 NH], 28.4 (q, CH3), 28.3 (t, OCH2CH2CH2CϵCH), 26.6 [t,
(s, CONH), 153.4 (s, Ar-C-1), 152.9 (s, Ar-C-4), 137.3 (s, Bn-C-1), O(CH2)3CH2(CH2)2NH], 25.8 [t, O(CH2)2CH2(CH2)3NH], 15.2 [t,
128.5 (d, Bn-C-3,5), 127.9 (d, Bn-C-4), 127.5 (d, Bn-C-2,6), 115.8 O(CH ) CH CϵCH] ppm. IR (ATR): ν = 3390 (N–H), 3307
˜
2 2
2
(d, Ar-C-3,5), 115.4 (d, Ar-C-2,6), 79.0 [s, C(CH3)3], 70.7 (t, Bn- (CϵC–H), 2937, 2852 (aliph. C–H), 1689 (C=O), 1511 (C=C),
CH2), 68.4 (t, OCH2), 40.5 (t, NHCH2), 30.0 (t, NHCH2CH2), 29.3
1234, 1161 (C–O), 816 (1,4-disubstitution) cm–1. MS (EI, 70 eV):
(t, OCH2CH2), 28.4 (q, CH3), 26.6 [t, NH(CH2)2CH2], 25.8 [t,
m/z (%) = 375 (64) [M]+·, 302 (10) [M – C4H9O]+, 176 (89)
O(CH ) CH ] ppm. IR (ATR): ν = 3389 (N–H), 2935, 2867 (aliph. [C6H12O]+·, 110 (100) [C6H6O2]+·. MS (CI, isobutane): m/z (%) =
˜
2 2
2
C–H), 1686 (C=O), 1520 (N–H), 1510 (C=C), 1235, 1166 (C–O),
376 (5) [M + H]+, 320 (100) [M – C4H7]+, 302 (34) [M – C4H9O]+.
C22H33NO4 (375.24): calcd. C 70.37, H 8.86, N 3.73; found C
816 (1,4-disubstitution), 741, 699 (monosubstitution) cm–1. MS
(EI, 70 eV): m/z (%) = 399 (43) [M]+·, 144 (100) [C7H14NO2]+. 70.08, H 8.90, N 3.72.
C24H33NO4 (399.24): calcd. C 72.15, H 8.33, N 3.51; found C
72.15, H 8.33, N 3.49.
6-[4-(Pent-4-ynyloxy)phenyloxy]hexylamine (19): Carbamate 18
(856 mg, 2.28 mmol) was dissolved in dichloromethane (7 mL) and
a solution of trifluoroacetic acid (6.50 mL) in dichloromethane
(7 mL) was added. The mixture was stirred for 21 h at room tem-
perature and washed with sodium hydroxide solution (1 m, 2ϫ
50 mL) afterwards. The aqueous layer was extracted with dichloro-
methane (30 mL) and the combined organic layer was washed with
brine (40 mL) and dried with magnesium sulfate. The solvent was
removed under reduced pressure and the product was obtained as
a slightly yellow solid (574 mg, 92%); m.p. 91 °C. 1H NMR
(500 MHz, CDCl3): δ = 6.81 (mc, 4 H, Ar-2,3,5,6-H), 4.00 [t, 3J
= 6.1 Hz, 2 H, OCH2(CH2)2CϵCH], 3.89 [t, 3J = 6.5 Hz, 2 H,
OCH2(CH2)5NH2], 2.72 [mc, 2 H, O(CH2)5 CH2NH2], 2.54 (br. s,
2 H, NH2), 2.39 [td, 3Jt = 7.1, 4Jd = 2.6 Hz, 2 H, O(CH2)2-
tert-Butyl-N-6-(4-hydroxyphenyloxy)hexylcarbamate (17): Hydro-
gen was bubbled through a suspension of palladium on charcoal
(10%, 150 mg) in acid-free chloroform (6 mL) and ethyl acetate
(6 mL) for 30 min. Then a solution of compound 16 (595 mg,
1.49 mmol) in a mixture of acid-free chloroform (6 mL) and ethyl
acetate (6 mL) was added, and the reaction mixture was flushed
1 h with hydrogen and afterwards it was stirred for 22 h under hy-
drogen. The solvent was removed under reduced pressure and the
residue was purified by filtration through a short column of basic
aluminum oxide with chloroform. After removal of the solvent un-
der reduced pressure, product 17 was obtained as a colorless oil
1
(462 mg, 100%). H NMR (500 MHz, CDCl3): δ = 6.76 (mc, 4 H,
3
Ar-2,3,5,6-H), 5.90 (s, 1 H, OH), 4.59 (br. s, 1 H, NH), 3.86 (t, J CH2CϵCH], 2.00–1.93 (m, 3 H, OCH2CH2CH2CϵCH), 1.75 [mc,
= 6.5 Hz, 2 H, OCH2), 3.15–3.07 (m, 2 H, NHCH2), 1.72 (quint,
2 H, OCH2CH2(CH2)4NH2], 1.54–1.43 [m, 4 H, O(CH2)2-
3J = 7.0 Hz, 2 H, OCH2CH2), 1.53–1.39 [m, 4 H, NHCH2CH2, CH2CH2CH2CH2NH2], 1.42–1.34 [m, 2 H, O(CH2)3CH2(CH2)2-
O(CH2)2CH2], 1.45 (s, 9 H, CH3), 1.38–1.30 [m, 2 H, NH(CH2)2-
NH2] ppm. 13C NMR (125 MHz, CDCl3): δ = 153.3 (s, Ar-C-1),
153.0 (s, Ar-C-4), 115.5, 115.4 (2d, Ar-C-2,3,5,6), 83.6 (s, CϵCH),
CH2] ppm. 13C NMR (125 MHz, CDCl3): δ = 156.2 (s, CONH),
152.9 (s, Ar-C-1), 149.9 (s, Ar-C-4), 116.0 (d, Ar-C-3,5), 115.6 (d, 68.8 (d, CϵCH), 68.5 [t, OCH2(CH2)5NH2], 66.8 [t, OCH2(CH2)2-
Ar-C-2,6), 79.4 [s, C(CH3)3], 68.5 (t, OCH2), 40.6 (t, NHCH2), 30.0 CϵCH], 41.8 [t, O(CH2)5CH2NH2], 33.0 [t, O(CH2)4CH2-
(t, NHCH2CH2), 29.3 (t, OCH2CH2), 28.4 (q, CH3), 26.5 [t,
CH2NH2],
29.3
[t,
OCH2CH2(CH2)4NH2],
28.3
(t,
NH(CH ) CH ], 25.7 [t, O(CH ) CH ] ppm. IR (ATR): ν = 3341 OCH2CH2CH2CϵCH), 26.6 [t, O(CH2)3CH2(CH2)2NH2], 25.9 [t,
˜
2 2
2
2 2
2
(O–H), 2933, 2861 (aliph. C–H), 1678 (C=O), 1508 (C=C), 1221, O(CH2)2CH2(CH2)3NH2], 15.2 [t, O(CH2)2CH2CϵCH] ppm. IR
1164 (C–O), 825 (1,4-disubstitution) cm–1. MS (EI, 70 eV): m/z (%)
= 309 (3) [M]+·, 253 (36) [M – C4H8]+·, 110 (100) [C6H6O2]+·. MS
(CI, isobutane): m/z (%) = 310 (18) [M + H]+, 254 (100) [M –
(ATR): ν = 3283 (CϵC–H), 2931, 2861 (aliph. C–H), 1567 (NH ),
˜
2
1507 (C=C), 1224 (C–O), 826 (1,4-disubstitution) cm–1. MS (EI,
70 eV): m/z (%) = 275 (16) [M]+·, 100 (100) [C6H14N]+. MS (CI,
C4H7]+. C17H27NO4 (309.19): calcd. C 65.99, H 8.80, N 4.53; found isobutane): m/z (%) = 276 (100) [M + H]+.
C 66.13, H 9.02, N 4.56.
2-Chloro-N-{6-[4-(pent-4-ynyloxy)phenyloxy]hexyl}acetamide (20):
tert-Butyl-N-6-[4-(pent-4-ynyloxy)phenyloxy]hexylcarbamate (18): A solution of chloroacetyl chloride (67.0 μL, 839 μmol) and an-
A suspension of sodium hydride (217 mg, 5.43 mmol) in anhydrous hydrous triethylamine (69.3 μL, 500 μmol) in anhydrous dichloro-
DMF (20 mL) was cooled to 0 °C, a solution of phenol 17 in anhy- methane (4 mL) was cooled to –10 °C, and amine 19 (135 mg,
drous DMF (15 mL) was added and the mixture was stirred for
15 min at 0 °C. 5-Chloropentyne (352 mg, 3.45 mmol) in anhydrous
DMF (5 mL) was added and the reaction mixture was stirred for
22 h at room temperature. Water (70 mL) was added and the solu-
tion was extracted with diethyl ether (5ϫ 50 mL). The combined
organic layer was dried with magnesium sulfate and the solvent
was removed under reduced pressure. The residue was purified by
column chromatography (silica gel, dichloromethane, Rf = 0.35) to
490 μmol) in anhydrous dichloromethane (10 mL) was added. The
reaction mixture was stirred for 2.5 h at –10 °C and was afterwards
filtered with dichloromethane through Celite. The filtrate was
washed with brine (2ϫ 30 mL) and the combined organic layer
was dried with magnesium sulfate. The solvent was removed under
reduced pressure and the crude product was purified by column
chromatography (silica gel, cyclohexane/ethyl acetate, 2:1, Rf
=
0.21) to give 20 as a brownish solid (113 mg, 66%); m.p. 60 °C. 1H
Eur. J. Org. Chem. 2014, 3885–3901
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3895

B. Hesseler, M. Zindler, R. Herges, U. Lüning
FULL PAPER
NMR (500 MHz, CDCl3): δ = 6.82 (mc, 4 H, Ar-2,3,5,6-H), 6.59
anhydrous dichloromethane (5 mL), a solution of silver(I) hexa-
3
(br. s, 1 H, NH), 4.05 (s, 2 H, ClCH2), 4.01 [t, J = 6.1 Hz, 2 H, fluorophosphate (44.0 mg, 174 μmol) in anhydrous dichlorometh-
3
OCH2(CH2)2CϵCH], 3.90 [t, J = 6.4 Hz, 2 H, NH(CH2)5CH2O], ane (2 mL) was added. The reaction mixture was stirred for 1 h at
3
4
3.32 [mc, 2 H, NHCH2(CH2)5O], 2.40 [td, Jt = 7.01, Jd = 2.7 Hz,
2 H, O(CH2)2CH2CϵCH], 2.01–1.94 (m, 3 H, OCH2CH2CH2- under reduced pressure and purified two times by column
CϵCH), 1.77 [mc, 2 H, NH(CH2)4CH2CH2O], 1.63–1.55 [m, 2 H, chromatography (silica gel, 1. dichloromethane/methanol, 10:1, Rf
room temperature and then filtered. The filtrate was concentrated
NHCH2CH2(CH2)4O], 1.54–1.45 [m, 2 H, NH(CH2)3CH2(CH2)2- = 0.43; 2. dichloromethane/methanol, 40:1, Rf = 0.13) to give 22
O], 1.45–1.38 [m, 2 H, NH(CH2)2CH2(CH2)3O] ppm. 13C NMR as a orange solid (122 mg, 72%); m.p. 156 °C. 1H NMR (600 MHz,
3
(125 MHz, CDCl3): δ = 165.9 (s, CONH), 153.3 (s, Ar-C-1), 153.0 CDCl3): δ = 8.81 (br. s, 1 H, Py-2-H), 8.61 (d, J = 5.9 Hz, 1 H,
3
3
3
(s, Ar-C-4), 115.5, 115.4 (2d, Ar-C-2,3,5,6), 83.6 (s, CϵCH), 68.8 Py-6-H), 8.45 (d, J = 8.2 Hz, 1 H, Py-4-H), 7.92 (dd, J = 8.0, J
(d, CϵCH), 68.4 [t, NH(CH2)5CH2O], 66.8 [t, OCH2(CH2)2- = 6.1 Hz, 1 H, Py-5-H), 7.47 (d, 3J = 8.5 Hz, 2 H, PyAr-2,6-H),
3
3
CϵCH], 42.7 (t, ClCH2), 39.8 [t, NHCH2(CH2)5O], 29.3, 29.2 [2t,
7.41 (d, J = 8.5 Hz, 2 H, PyAr-3,5-H), 7.26 (d, J = 5.6 Hz, 6 H,
NHCH2CH2(CH2)2CH2CH2O], 28.3 (t, OCH2CH2CH2CϵCH), tBuAr-3,5-H), 7.15 (br. s, 1 H, NH), 7.10 (d, 3J = 5.6 Hz, 6 H,
26.6 [t, NH(CH2)2CH2(CH2)3O], 25.8 [t, NH(CH2)3CH2(CH2)2O],
tBuAr-2,6-H), 6.79 (mc, 4 H, OAr-2,3,5,6-H), 5.38 (s, 2 H, PyCH2),
3.99 [t, 3J = 6.1 Hz, 2 H, OCH2(CH2)2CϵCH], 3.86 [t, 3J = 6.5 Hz,
15.2 [t, O(CH ) CH CϵCH] ppm. IR (ATR): ν = 3333 (N–H),
˜
2 2
2
3300 (CϵC–H), 2857 (aliph. C–H), 1742 (C=O), 1642, 1510 2 H, OCH2(CH2)5NH], 3.27 [mc, 2 H, O(CH2)5CH2NH], 2.38 [mc,
(arom.), 1232 (C–O), 817 (1,4-disubstitution), 636 (C–Cl) cm–1. MS 2 H , O ( C H 2
) 2 C H 2 C ϵ C H ] , 1 . 9 9 – 1 . 9 3 ( m , 3 H ,
(EI, 70 eV): m/z (%) = 351 (49) [M]+·, 176 (76) [C11H12O2]+, 110
(100) [C6H6O2]+. MS (CI, isobutane): m/z (%) = 352 (60) [M +
OCH2CH2CH2CϵCH), 1.75–1.69 [m, 2 H, OCH2CH2(CH2)4NH],
1.61–1.54 [m, 2 H, O(CH2)4CH2CH2NH], 1.48–1.34 [m, 4 H,
H]+, 189 (100) [C12H13O2]+·. C19H26ClNO3 (351.87): calcd. C 64.85, O(CH2)2CH2CH2(CH2)2NH], 1.30 [s, 27 H, C(CH3)3] ppm. 13C
H 7.45, N 3.98; found C 64.80, H 7.44, N 4.01.
NMR (150 MHz, CDCl3): δ = 163.0 (s, CONH), 153.3 (s, OAr-C-
1), 152.9 (s, OAr-C-4), 151.0 (s, PyAr-C-4), 148.8 (s, tBuAr-C-4),
143.3 (d, Py-C-2), 143.1 (s, tBuAr-C-1), 143.0 (d, Py-C-6), 142.8
(d, Py-C-4), 141.5 (s, Py-C-3), 132.7 (d, PyAr-C-3,5), 130.6 (d,
tBuAr-C-2,6), 129.6 (s, PyAr-C-1), 127.6 (d, Py-C-5), 126.2 (d,
PyAr-C-2,6), 124.4 (d, tBuAr-C-3,5), 115.5, 115.4 (2d, OAr-C-
2,3,5,6), 83.6 (s, CϵCH), 68.8 (d, CϵCH), 68.4 [t, OCH2(CH2)5-
NH], 66.8 [t, OCH2(CH2)2CϵCH], 63.7 [s, (tBuAr)3C], 62.5 (t, Py-
CH2), 40.4 [t, O(CH2)5CH2NH], 34.3 [s, C(CH3)3], 31.4 (q, CH3),
29.1 [t, OCH2CH2(CH2)4NH], 28.8 [t, O(CH2)4CH2CH2NH], 28.3
(t, OCH2CH2CH2CϵCH), 26.5 [t, O(CH2)3CH2(CH2)2NH], 25.6
[t, O(CH2)2CH2(CH2)3NH], 15.1 [t, O(CH2)2CH2CϵCH] ppm. IR
1-(2-Oxo-2-{6-[4-(pent-4-ynyloxy)phenyloxy]hexylamino}ethyl)-3-
{4-[tris(4-tert-butylphenyl)methyl]phenyl}pyridinium Iodide (21): A
mixture of stopper 11 (71.1 mg, 126 μmol), alkyne linker 20
(50.0 mg, 142 μmol) and sodium iodide (28.4 mg, 189 μmol) in 1,4-
dioxane (12 mL) was heated at reflux for 17 h. The solvent was
removed under reduced pressure and the residue was purified by
column chromatography (silica gel, dichloromethane/methanol,
10:1, Rf = 0.40) to give 21 as a yellow solid (65.1 mg, 51%); m.p.
218 °C. 1H NMR (500 MHz, CDCl3): δ = 9.37 (s, 1 H, Py-2-H),
9.07 (d, 3J = 6.1 Hz, 1 H, Py-6-H), 8.53 (t, 3J = 5.6 Hz, 1 H,
3
3
3
CONH), 8.49 (d, J = 8.4 Hz, 1 H, Py-4-H), 7.95 (dd, J = 8.2, J
(ATR): ν = 3417 (N–H), 3292 (CϵC–H), 3091, 3043 (arom. C–H),
˜
= 6.1 Hz, 1 H, Py-5-H), 7.60 (d, 3J = 8.7 Hz, 2 H, PyAr-2,6-H),
2955, 2904, 2866 (aliph. C–H), 1684 (C=O), 1506 (C=C), 1227 (C–
O), 824 (1,4-disubstitution) cm–1. MS (MALDI-TOF, Cl-CCA):
m/z = 882 [M – PF6]+. C61H73F6N2O3P (1026.53): C 71.32, H 7.16,
N 2.73. C61H73F6N2O3P·3H2O (1080.56): calcd. C 67.76, H 7.36,
N 2.59; found C 67.53, H 7.26, N 2.67.
3
3
7.43 (d, J = 8.7 Hz, 2 H, PyAr-3,5-H), 7.26 (d, J = 8.7 Hz, 6 H,
3
tBuAr-3,5-H), 7.10 (d, J = 8.7 Hz, 6 H, tBuAr-2,6-H), 6.80 (mc,
3
4 H, OAr-2,3,5,6-H), 5.96 (s, 2 H, PyCH2), 3.99 [t, J = 6.1 Hz, 2
3
H, OCH2(CH2)2CϵCH], 3.86 [t, J = 6.5 Hz, 2 H, OCH2(CH2)5-
NH], 3.28 [mc, 2 H, O(CH2)5CH2NH], 2.38 [td, 3Jt = 7.0, 4Jd
=
2.7 Hz, 2 H, O(CH2 )2 CH2 CϵCH], 1.99–1.93 (m, 3 H,
[2]-{[(1-{2-Oxo-2-[(6-{4-[3-(1-{6-[3,3,3-tris(4-tert-butylphenyl)prop-
OCH2CH2CH2CϵCH), 1.79–1.60 [m, 4 H, OCH2CH2(CH2)2- yloxy]-6-oxohexyl}-1,2,3-triazol-4-yl)propyloxy]}phenyloxy)hexyl]-
CH2CH2NH], 1.49–1.38 [m, 4 H, O(CH2)2CH2CH2(CH2)2NH], amino}ethyl)-3-{4-[tris(4-tert-butylphenyl)methyl]phenyl}pyridinium-
1.31 [s, 27 H, C(CH3)3] ppm. 13C NMR (125 MHz, CDCl3): δ = hexafluorophosphat]-rotaxa-[54-methoxy-3,7,10,21-tetraoxa-
163.0 (s, CONH), 153.3 (s, OAr-C-1), 152.9 (s, OAr-C-4), 151.2 (s,
PyAr-C-4), 148.8 (s, tBuAr-C-4), 143.2 (d, Py-C-2), 143.1 (s,
tBuAr-C-1), 142.8 (d, Py-C-6), 142.4 (d, Py-C-4), 141.4 (s, Py-C-
3), 132.7 (d, PyAr-C-3,5), 130.6 (d, tBuAr-C-2,6), 129.4 (s, PyAr-
1,9(1,4)-dibenzena-5(2,6)-pyridina-heneicosaphan]} (23): Macrocycle
2 (27.0 mg, 52.0 μmol), alkyne half-axis 22 (53.4 mg, 52.0 μmol)
and azide half-axis 7 (32.2 mg, 54.1 μmol) were dissolved in anhy-
drous dichloromethane (5 mL), and copper(I) tetrakisacetonitrilo
C-1), 127.5 (d, Py-C-5), 126.3 (d, PyAr-C-2,6), 124.4 (d, tBuAr-C- hexafluorophosphate (20.0 mg, 53.7 μmol) was added. The reaction
3,5), 115.5 (d, OAr-C-2,3,5,6), 83.6 (s, CϵCH), 68.8 (d, CϵCH), mixture was stirred at room temperature for 2 d and afterwards it
68.4 [t, OCH2(CH2)5NH], 66.8 [t, OCH2(CH2)2CϵCH], 63.7 [s, was diluted with dichloromethane (3 mL) and methanol (5 mL).
(tBuAr)3C], 62.5 (t, Py-CH2), 40.2 [t, O(CH2)5CH2NH], 34.3 [s,
A solution of potassium cyanide (20.0 mg, 307 μmol) in methanol
C(CH3)3], 31.3 (q, CH3), 29.2 [t, OCH2CH2(CH2)4NH], 28.8 [t,
(5 mL) was added and the mixture was stirred for 1 h at room tem-
O(CH2)4CH2CH2NH], 28.3 (t, OCH2CH2CH2CϵCH), 26.7 [t, perature. The solvent was removed under reduced pressure and
O(CH2)3CH2(CH2)2NH], 25.6 [t, O(CH2)2CH2(CH2)3NH], 15.2 [t,
dichloromethane (15 mL) was added. The organic layer was washed
O(CH ) CH CϵCH] ppm. IR (ATR): ν = 3278 (N–H), 3226
with water (15 mL) and the aqueous layer was extracted with
˜
2
2
2
(CϵC–H), 3046 (arom. C–H), 2953, 2904, 2865 (aliph. C–H), 1683 dichloromethane (2 ϫ 5 mL). The combined organic layer was
(C=O), 1506 (C=C), 1224 (C–O), 823 (1,4-disubstitution) cm–1. MS
(MALDI-TOF, Cl-CCA): m/z = 882 [M – I]+. C61H73IN2O3
(1008.47): C 72.60, H 7.29, N 2.78. C61H73IN2O3·1.5H2O
(1035.48): calcd. C 70.71, H 7.39, N 2.70; found C 70.64, H 7.25,
N 2.84.
dried with magnesium sulfate and the solvent was removed under
reduced pressure. The residue was purified two times by column
chromatography (silica gel, dichloromethane/methanol, 40:1, Rf =
0.35) to afford rotaxane 23 (3.0 mg, 3%) and axis 24 (27 mg, 32%)
as yellow solids.
1
1-(2-Oxo-2-{6-[4-(pent-4-ynyloxy)phenyloxy]hexylamino}ethyl)-3-
{4-[tris(4-tert-butylphenyl)methyl]phenyl}pyridinium Hexafluoro-
phosphate (22): To a solution of iodide 21 (166 mg, 165 μmol) in
Rotaxane 23: H NMR (600 MHz, CDCl3): δ = 8.72 (s, 1 H, Py1-
3
3
2-H), 7.89 (d, J = 7.8 Hz, 1 H, Py1-4-H), 7.81 (d, J = 6.0 Hz, 1
H, Py1-6-H), 7.49 (mc, 1 H, Py1-5-H), 7.34–7.28 (m, 7 H, Ar1-3,5-
3896
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© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 3885–3901

A Shuttle for the Transport of Protons Based on a [2]Rotaxane
H, triazol-5-H), 7.28–7.23 (m, 6 H, Ar4-3,5-H), 7.21–7.15 (m, 12 C-1), 128.5 (d, Ar4-C-2,6), 127.6 (d, Py1-C-5), 126.2 (d, Ar2-C-2,6),
H, Ar1-2,6-H, Ar4-2,6-H), 7.13 (d, 3J = 8.2 Hz, 2 H, Ar2-2,6-H),
124.7 (d, Ar4-C-3,5), 124.4 (d, Ar1-C-3,5), 120.8 (d, triazol-C-5),
7.10 (d, 3J = 8.2 Hz, 2 H, Ar2-3,5-H), 6.98 (mc, 1 H, NH), 6.85 (d, 115.4, 115.4 (2d, Ar3-C-2,3,5,6), 68.4 [t, NH(CH2)5CH2OAr3], 67.4
3J = 8.2 Hz, 4 H, Ar5-2,6-H), 6.83–6.79 (m, 6 H, Ar3-2,3,5,6-H, [t, Ar3OCH2(CH2)2triazol], 63.7 [s, C(Ar1)3Ar2], 62.9 (t, COOCH2-
Py2-3,5-H), 6.30 (d, 3J = 8.5 Hz, 4 H, Ar5-3,5-H), 5.00 (s, 2 H,
Py1CH2), 4.46–4.26 [m, 10 H, Py2CH2OCH2Ar5, triazol-CH2-
CH2), 62.6 (t, Py1CH2), 53.7 [s, C(Ar4)3], 49.9 [t, triazol-CH2(CH2)4-
COO], 40.4 (t, NHCH2), 38.7 (t, COOCH2CH2), 34.3, 34.3 [2s,
(CH2)4COO], 3.98–3.85 (m, 6 H, CH2OAr3OCH2, COOCH2CH2), C(CH3)3], 33.9 [t, triazol-(CH2)4CH2COO], 31.3 [q, C(CH3)3], 30.0
3.83 (s, 3 H, Py2-OCH3), 3.72–3.66 (m, 4 H, Ar5OCH2), 3.07 (mc, [t, triazol-CH2CH2(CH2)3COO], 29.1, 29.1 (2 t, CH2CH2-
2 H, NHCH2), 2.92–2.86 [m, 4 H, Ar3O(CH2)2CH2-triazol,
OAr3OCH2CH2), 28.8 (t, NHCH2CH2), 26.4 [t, NH(CH2)2CH2],
COOCH2CH2], 2.22 [t, 3J = 7.4 Hz, 2 H, triazol-(CH2)4CH2COO], 26.0 [t, triazol-(CH2)2CH2(CH2)2COO], 25.6 [t, NH(CH2)3CH2],
2.13 (mc, 2 H, Ar3OCH2CH2CH2-triazol), 1.92–1.84 [m, 2 H, tri- 24.2 [t, triazol-(CH2)3CH2CH2COO], 22.2 [t, Ar3O(CH2)2CH2-
azol-CH2CH2(CH2)3COO], 1.71 [mc, 2 H, NH(CH2)4CH2CH2-
OAr3], 1.68–1.54 [m, 8 H, NHCH2CH2, triazol-(CH2)3CH2CH2-
COO, Ar5OCH2CH2], 1.46–1.23 [m, 18 H, NH(CH2)2CH2CH2, tri-
azol-(CH2)2CH2(CH2)2COO, Ar5O(CH2)2CH2CH2CH2], 1.31, 1.29
[2s, 54 H, C(CH3)3] ppm. 13C NMR (150 MHz, CDCl3): δ = 173.4
(s, COOCH2), 167.1 (s, Py2-C-4), 163.0 (s, CONH), 158.9 (s, Py2-
C-2,6), 158.4 (s, Ar5-C-4), 153.3 (s, Ar3-C-1), 153.0 (s, Ar3-C-4),
150.5 (s, Ar2-C-4), 148.7 (s, Ar1-C-4), 148.5 (s, Ar4-C-4), 147.4 (s,
triazol-C-4), 145.1 (d, Py1-C-2), 143.8 (s, Ar4-C-1), 143.4 (s, Ar1-
C-1), 142.0 (d, Py1-C-6), 140.7 (d, Py1-C-4), 139.8 (s, Py1-C-3),
130.6 (d, Ar2-C-3,5), 130.5 (d, Ar1-C-2,6), 130.1 (d, Ar5-C-2,6),
129.4 (s, Ar2-C-1), 129.1 (s, Ar5-C-1), 128.5 (d, Ar4-C-2,6), 126.2
(d, Ar2-C-2,6), 125.8 (d, Py1-C-5), 124.7 (d, Ar4-C-3,5), 124.5 (d,
Ar1-C-3,5), 120.8 (d, triazol-C-5), 115.4 (d, Ar3-C-2,3,5,6), 113.9
(d, Ar5-C-3,5), 107.6 (d, Py2-C-3,5), 73.0 (t, Py2CH2OCH2Ar5),
72.3 (t, Py2CH2OCH2Ar5), 68.4 [t, OCH2(CH2)5NH], 67.5 [t,
OCH2(CH2)2triazol], 67.1 (t, Ar5OCH2), 63.8 [s, C(Ar1)3Ar2], 63.0
(t, COOCH2CH2), 61.7 (t, PyCH2CONH), 55.4 (q, OCH3), 53.7 [s,
C(Ar4)3], 49.9 [t, triazol-CH2(CH2)4COO], 40.1 [t, NHCH2(CH2)5-
OAr3], 38.7 (t, COOCH2CH2), 34.4, 34.3 [2s, C(CH3)3], 33.9 [t,
triazol-(CH2)4CH2COO], 31.4 [q, C(CH3)3], 30.1 [t, triazol-
CH2CH2(CH2)3COO], 29.3 [t, Ar5O(CH2)4CH2]#*, 29.2 [t,
NH(CH2)4CH2CH2OAr3], 29.1 (t, Ar3OCH2CH2CH2triazol), 28.8
(t, NHCH2CH2), 28.6 {t, Ar5OCH2CH2, [Ar5O(CH2)3CH2]#}*,
26.6 [t, NH(CH2)2CH2]*, 26.3 [t, triazol-(CH2)2CH2(CH2)2COO]*,
25.9 [t, Ar5O(CH2)2CH2]*, 25.7 [t, NH(CH2)3CH2]*, 24.3 (t,
CH2CH2COO)*, 22.2 [t, Ar3O(CH2)2CH2triazol] ppm. *The sig-
nals were assigned by comparison with free axis 24 and free macro-
cycle 2. #The assignment may be inverted. MS (MALDI-TOF, Cl-
CCA): m/z = 1997 [M – PF6]+.
triazol] ppm. * The signal was only observed in the HMBC spec-
trum. MS (MALDI-TOF, Cl-CCA): m/z = 1477 [M – PF6]+.
tert-Butyl-N-6-(4-{6-[4-(benzyloxy)phenyloxy]hexyloxy}phenyloxy)-
hexylcarbamate (25): A suspension of sodium hydride (249 mg,
8.73 mmol) in anhydrous DMF (20 mL) was cooled to 0 °C, and
phenol 17 (1.57 g, 5.08 mmol) in anhydrous DMF (20 mL) was
added. The reaction mixture was stirred for 15 min at 0 °C and
bromide 13 (2.05 g, 5.66 mmol) in anhydrous DMF (25 mL) was
added. The solution was stirred at room temperature for 2 d and
afterwards water (50 mL) was added. The aqueous layer was ex-
tracted with dichloromethane (3ϫ 100 mL), the combined organic
layer was washed with brine (100 mL) and dried with magnesium
sulfate. The solvent was removed under reduced pressure and the
residue was purified by crystallization from n-hexane/dichloro-
1
methane to give 25 as a white solid (2.25 g, 75%); m.p. 117 °C. H
NMR (500 MHz, CDCl3): δ = 7.42–7.40 (m, 2 H, Bn-2,6-H), 7.37
(mc, 2 H, Bn-3,5-H), 7.32–7.29 (m, 1 H, Bn-4-H), 6.90 (d, 3J =
9.1 Hz, 2 H, Ar2-3,5-H), 6.84–6. 79 (m, 6 H, Ar2-2,6-H, Ar1-
3
2,3,5,6-H), 5.00 (s, 2 H, BnCH2), 4.50 (br. s, 1 H, NH), 3.91 (t, J
3
= 6.5 Hz, 2 H, OCH2)*, 3.90 (t, J = 6.5 Hz, 2 H, OCH2)*, 3.89
3
(t, J = 6.5 Hz, 2 H, OCH2)*, 3.11 (mc, 2 H, NHCH2), 1.85–1.70
(m, 6 H, OCH2CH2), 1.55–1.46 [m, 8 H, NHCH2CH2, O(CH2)2-
CH2], 1.44 (s, 9 H, CH3), 1.41–1.35 [m, 2 H, NH(CH2)2CH2] ppm.
*An exact assignment was not possible. 13C NMR (125 MHz,
CDCl3): δ = 156.0 (s, CONH), 153.5, 153.2 (2s, Ar1-C-1,4, Ar2-C-
1), 152.9 (s, Ar2-C-4), 137.4 (s, Bn-C-1), 128.5 (d, Bn-C-3,5), 127.8
(d, Bn-C-4), 127.5 (d, Bn-C-2,6), 115.8 (d, Ar2-C-3,5), 115.4 (d,
Ar2-C-2,6, Ar1-C-2,3,5,6), 79.0 [s, C(CH3)3], 70.7 (t, BnCH2), 68.5,
68.4 (2t, OCH2), 40.5 (t, NHCH2), 30.0 (t, NHCH2CH2), 29.3 (t,
OCH2CH2), 28.4 (q, CH3), 26.6 [t, NH(CH2)2CH2], 25.9, 25.8 [2t,
O(CH ) CH ] ppm. IR (ATR): ν = 3351 (N–H), 2940, 2866 (aliph.
˜
1
Axis 24: H NMR (500 MHz, CDCl3): δ = 8.89 (s, 1 H, Py1-2-H),
2 2
2
C–H), 1689 (C=O), 1507 (C=C), 1230, 1172, 1026 (C–O), 829 (1,4-
disubstitution), 737, 694 (monosubstitution) cm–1. MS (EI, 70 eV):
m/z (%) = 591 (16) [M]+·, 517 (100) [M – C4H10O]+·. MS (CI, isobu-
tane): m/z (%) = 518 (34) [M – C4H9O]+, 113 (100). C36H49NO6
(591.36): calcd. C 73.07, H 8.35, N 2.37; found C 73.29, H 8.37, N
2.36.
8.65 (d, 3J = 6.1 Hz, 1 H, Py1-6-H), 8.48 (d, 3J = 8.4 Hz, 1 H, Py1-
4-H), 7.93 (mc, 1 H, Py1-5-H), 7.48 (d, J = 8.6 Hz, 2 H, Ar2-2,6-
3
H), 7.45 (br. s, 1 H, CONH), 7.42 (d, J = 8.6 Hz, 2 H, Ar2-3,5-
3
H), 7.28–7.23 (m, 13 H, Ar1-3,5-H, Ar4-3,5-H, triazol-5-H), 7.17
(d, J = 8.6 Hz, 6 H, Ar4-2,6-H), 7.10 (d, 3J = 8.6 Hz, 6 H, Ar1-
3
2,6-H), 6.78 (s, 4 H, Ar3-2,3,5,6-H), 5.42 (s, 2 H, Py1CH2), 4.29 [t,
3J = 7.2 Hz, 2 H, triazol-CH2(CH2)4COO], 3.92 [t, 2 H, tert-Butyl-N-6-{4-[6-(4-hydroxyphenyloxy)hexyloxy]phenyloxy}-
Ar3OCH2(CH2)2triazol], 3.90–3.88 (m, 2 H, COOCH2CH2), 3.86 hexylcarbamate (26): Hydrogen was bubbled through a suspension
[t, 3J = 6.4 Hz, 2 H, NH(CH2)5CH2OAr3], 3.27 (mc, 2 H, NHCH2),
of palladium on charcoal (10%, 239 mg) in acid-free chloroform
2.91–2.85 [m, 4 H, COOCH2CH2, Ar3O(CH2)2CH2triazol], 2.22 [t, (15 mL) for 30 min. A solution of benzyl ether 25 (1.38 g,
3J = 7.4 Hz, 2 H, triazol-(CH2)4CH2COO], 2.12 (mc, 2 H, 2.34 mmol) in acid-free chloroform (40 mL) was added, and the
Ar3OCH2CH2CH2triazol), 1.88 [quint, 2 H, triazol-CH2CH2(CH2)3- mixture was flushed 1 h with hydrogen. Afterwards the reaction
COO], 1.72 [mc, 2 H, NH(CH2)4CH2CH2OAr3], 1.66–1.54 [m, 4
H, NHCH2CH2, triazol-(CH2)3CH2CH2COO], 1.49–1.32 [m, 6 H,
NH(CH2)2CH2CH2(CH2)2OAr3, triazol-(CH2)2CH2(CH2)2COO],
mixture was stirred for 22 h under hydrogen. The solvent was re-
moved under reduced pressure and the residue was filtered with
chloroform through a small column of silica gel to yield 26 as a
1.30, 1.28 [2s, 54 H, C(CH3)3] ppm. 13C NMR (125 MHz, CDCl3): white solid (1.11 g, 94 %); m.p. 102 °C. 1H NMR (500 MHz,
δ = 173.4 (s, COOCH2), 162.9 (s, CONH), 153.3 (s, Ar3-C-1), 153.0
CDCl3): δ = 6.80 (s, 4 H, Ar1-2,3,5,6-H), 6.76 (mc, 4 H, Ar2-2,3,5,6-
(s, Ar3-C-4), 151.1 (s, Ar2-C-4), 148.8 (s, Ar1-C-4), 148.5 (s, Ar4-C- H), 5.21 (br. s, 1 H, OH), 4.54 (br. s, 1 H, NH), 3.91 (t, 3J = 6.5 Hz,
4), 147.3 (s, triazol-C-4)*, 143.8 (s, Ar4-C-1), 143.3 (d, Py1-C-2), 2 H, OCH2)*, 3.90 (t, 3J = 6.5 Hz, 2 H, OCH2)*, 3.89 (t, 3J =
143.1 (s, Ar1-C-1), 142.9 (d, Py1-C-6), 142.7 (d, Py1-C-4), 141.6 (s,
6.5 Hz, 2 H, OCH2)*, 3.11 (mc, 2 H, NHCH2), 1.82–1.70 (m, 6 H,
Py1-C-3), 132.7 (d, Ar2-C-3,5), 130.6 (d, Ar1-C-2,6), 129.6 (s, Ar2- OCH2CH2), 1.54–1.46 (m, 8 H, NHCH2CH2, OCH2CH2CH2),
Eur. J. Org. Chem. 2014, 3885–3901
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3897

B. Hesseler, M. Zindler, R. Herges, U. Lüning
FULL PAPER
1.45 (s, 9 H, CH3), 1.40–1.32 [m, 2 H, NH(CH2)2CH2] ppm. *An
OCH2CH2CH2CϵCH), 1.82–1.72 (m, 6 H, OCH2CH2), 1.55–1.50
exact assignment was not possible. 13C NMR (125 MHz, CDCl3): [m, 4 H, O(CH2)2CH2], 1.50–1.43 [m, 4 H, NH2CH2CH2CH2CH2-
δ = 156.1 (s, CONH), 153.2, 153.2, 153.1 (3s, Ar1-C-1,4, Ar2-C-1),
149.7 (s, Ar2-C-4), 116.0, 115.6, 115.5, 115.4 (4d, Ar1-C-2,3,5,6,
(CH2)2O], 1.42–1.35 [m, 2 H, NH(CH2)2CH2] ppm. 13C NMR
(125 MHz, CDCl3): δ = 153.3, 153.2, 153.2, 153.0 (4s, Ar1-C-1,4,
Ar2-C-2,3,5,6), 79.2 [s, C(CH3)3], 68.5, 68.5, 68.5 (3t, OCH2), 40.5 Ar2-C-1,4), 115.5, 115.4 (2d, Ar1-C-2,3,5,6, Ar2-C-2,3,5,6), 83.6 (s,
(t, NHCH2), 30.0 (t, NHCH2CH2), 29.3, 29.3 (2t, OCH2CH2), 28.4 CϵCH), 68.7 (d, CϵCH), 68.5, 68.5 (2t, OCH2), 66.8 [t,
(q, CH3), 26.5 [t, NH(CH2)2CH2], 25.8, 25.7 [2t, O(CH2)2-
OCH2(CH2)2CϵCH], 42.2 (t, NH2CH2), 33.8 (t, NHCH2CH2),
CH ] ppm. IR (ATR): ν = 3430 (N–H), 3299 (O–H), 2940, 2908, 29.4, 29.3 (2t, OCH2CH2), 28.3 (t, OCH2CH2CH2CϵCH), 26.7 [t,
˜
2
2869 (aliph. C–H), 1660 (C=O), 1510 (C=C), 1472 (C–H), 1363
(O–H), 1235, 1221, 1031 (C–O), 829 (1,4-disubstitution) cm–1. MS
(MALDI-TOF, Cl-CCA): m/z = 524 [M + Na]+, 501 [M]+·, 402
[M – C5H9O2 + 2 H]+. C29H43NO6 (501.31): calcd. C 69.43, H 8.64,
N 2.79; found C 69.12, H 8.69, N 2.78.
NH(CH2)2CH2], 26.0 [t, NH2(CH2)3CH2(CH2)2O], 25.9 [t, O(CH2)2-
CH ], 15.2 [t, O(CH ) CH CϵCH] ppm. IR (ATR): ν = 3288 (N–
˜
2
2 2
2
H), 2940, 2911, 2866 (aliph. C–H), 1508 (C=C), 1474 (C–H), 1226,
1027 (C–O), 828 (1,4-disubstitution) cm–1. MS (MALDI-TOF, Cl-
CCA): m/z = 468 [M + H]+.
tert-Butyl-N-6-(4-{6-[4-(pent-4-ynyloxy)phenyloxy]hexyloxy}- 2-Chloro-N-[6-(4-{6-[4-(pent-4-ynyloxy)phenyloxy]hexyloxy}-
phenyloxy)hexylcarbamate (27): A suspension of sodium hydride
(381 mg, 9.53 mmol) in anhydrous DMF (4 mL) was cooled to
phenyloxy)hexyl]acetamide (29): A solution of amine 28 (208 mg,
445 μmol) and anhydrous triethylamine (100 μL, 71.0 mg,
0 °C, and phenol 26 (1.06 g, 2.11 mmol) in anhydrous DMF 752 μmol) in anhydrous dichloromethane (54 mL) was cooled to
(30 mL) was added. The mixture was stirred for 15 min at 0 °C
and 5-chloropentyne (362 mg, 3.55 mmol) was added. The reaction
mixture was stirred for 18 h at room temperature and afterwards
water (50 mL) was added and the solution was extracted with
dichloromethane (5 ϫ 70 mL). The combined organic layer was
dried with magnesium sulfate and the solvent was removed under
reduced pressure. The crude product was purified by column
chromatography (silica gel, chloroform, Rf = 0.08) to give 27 as a
white solid (916 mg, 76 %); m.p. 98 °C. 1H NMR (500 MHz,
–10 °C, and chloroacetyl chloride (50.0 μL, 71.0 mg, 629 μmol) in
anhydrous dichloromethane (1 mL) was added. The reaction mix-
ture was stirred for 4 h at room temperature and afterwards was
washed with brine (2ϫ 50 mL). The aqueous layer was extracted
with dichloromethane (2ϫ 50 mL) and the combined organic lay-
ers were dried with magnesium sulfate. The solvent was removed
under reduced pressure and the residue was purified by column
chromatography (silica gel, chloroform/ethanol, 1:1, Rf = 0.87) to
1
give 29 as a brownish solid (170 mg, 70%); m.p. 114 °C. H NMR
CDCl3): δ = 6.82 (mc, 4 H, Ar1-2,3,5,6-H or Ar2-2,3,5,6-H), 6.81 (500 MHz, CDCl3): δ = 6.82 (s, 4 H, Ar1-2,3,5,6-H or Ar2-2,3,5,6-
(s, 4 H, Ar1-2,3,5,6-H or Ar2-2,3,5,6-H), 4.50 (br. s, 1 H, NH), 4.01
H), 6.81 (s, 4 H, Ar1-2,3,5,6-H or Ar2-2,3,5,6-H), 6.57 (br. s, 1 H,
3
3
[t, J = 6.2 Hz, 2 H, OCH2(CH2)2CϵCH], 3.91 (t, J = 6.5 Hz, 2 NH), 4.04 (s, 2 H, ClCH2), 4.01 [t, 3J = 6.1 Hz, 2 H, OCH2(CH2)2-
H, OCH2)*, 3.91 (t, 3J = 6.5 Hz, 2 H, OCH2)*, 3.89 (t, 3J = 6.5 Hz, CϵCH], 3.93–3.87 (m, 6 H, OCH2), 3.32 (mc, 2 H, NHCH2), 2.40
2 H, OCH2)*, 3.12 (mc, 2 H, NHCH2), 2.40 [td, Jt = 7.0 Hz, Jd
3
4
[td, 3Jt = 7.0 Hz, 4Jd = 2.6 Hz, 2 H, O(CH2)2CH2CϵCH], 2.01–
= 2.7 Hz, 2 H, O(CH2 )2 CH2CϵCH], 2.00–1.94 (m, 3 H, 1.94 (m, 3 H, OCH2CH2CH2CϵCH), 1.83–1.71 (m, 6 H,
3
OCH2CH2CH2CϵCH), 1.83–1.71 (m, 6 H, OCH2CH2), 1.56–1.46 OCH2CH2), 1.58 (quint, J = 7.4 Hz, 2 H, NHCH2CH2) 1.55–1.45
(m, 8 H, NHCH2CH2, OCH2CH2CH2), 1.44 (s, 9 H, CH3), 1.41– [m, 6 H, O(CH2)2CH2], 1.45–1.35 [m, 2 H, NH(CH2)2CH2] ppm.
1.33 [m, 2 H, NH(CH2)2CH2] ppm. *An exact assignment was not
possible. 13C NMR (125 MHz, CDCl3): δ = 156.0 (s, CONH),
153.3, 153.2, 153.1, 153.0 (4s, Ar1-C-1,4, Ar2-C-1,4), 115.5, 115.4,
115.4, 115.4 (4d, Ar1-C-2,3,5,6, Ar2-C-2,3,5,6), 83.6 (s, CϵCH),
79.0 [s, C(CH3)3], 68.7 (d, CϵCH), 68.5, 68.5 (2t, OCH2), 66.8 [t,
13C NMR (125 MHz, CDCl3): δ = 165.7 (s, CONH), 153.3, 153.2,
153.1, 153.0 (4s, Ar1-C-1,4, Ar2-C-1,4), 115.5, 115.4, 115.4 (3d, Ar1-
C-2,3,5,6, Ar2-C-2,3,5,6), 83.6 (s, CϵCH), 68.7 (d, CϵCH), 68.5,
68.4 (2t, OCH2), 66.8 [t, OCH2(CH2)2CϵCH], 42.7 (t, NH2CH2),
39.8 (t, ClCH2), 29.3, 29.3 (2t, OCH2CH2), 29.2 (t, NHCH2CH2),
OCH2(CH2)2CϵCH], 40.5 (t, NHCH2), 30.0 (t, NHCH2CH2), 28.3 (t, OCH2CH2CH2CϵCH), 26.6 [t, NH(CH2)2CH2], 25.9 [t,
29.3, 29.3 (2t, OCH2CH2), 28.4 (q, CH3), 28.3 (t, OCH2CH2- O(CH ) CH ], 15.2 [t, O(CH ) CH CϵCH] ppm. IR (ATR): ν =
˜
2 2
2
2 2
2
CH2CϵCH), 26.6 [t, NH(CH2)2CH2], 25.9, 25.8 [2t, O(CH2)2CH2], 3291 (CϵC–H), 2940, 2867 (aliph. C–H), 1648, 1547 (C=O), 1508
15.2 [t, O(CH ) CH CϵCH] ppm. IR (ATR): ν = 3360 (N–H),
(C=C), 1474 (C–H), 1226, 1027 (C–O), 828 (1,4-disubstitution),
770 (C–Cl) cm–1. MS (MALDI-TOF, Cl-CCA): m/z = 543 [M]+·.
MS (ESI, CHCl3, MeOH): m/z = 568, 566 [M + Na]+. C31H42-
ClNO5 (543.28): C 68.43, H 7.78, N 2.57. C31H42ClNO5·0.5H2O
˜
2 2
2
3310 (CϵC–H), 2940, 2915, 2867 (aliph. C–H), 1687 (C=O), 1508
(C=C), 1474 (C–H), 1228, 1169, 1027 (C–O), 828 (1,4-disubstitu-
tion) cm–1. MS (MALDI-TOF, Cl-CCA): m/z = 590 [M + Na]+,
567 [M]+·. C34H49NO6 (567.36): calcd. C 71.93, H 8.70, N 2.47; (552.28): calcd. C 67.31, H 7.84, N 2.53; found C 67.18, H 7.57, N
found C 71.45, H 8.69, N 2.45.
2.51.
6-(4-{6-[4-(Pent-4-ynyloxy)phenyloxy]hexyloxy}phenyloxy)hexyl-
amine (28): Carbamate 27 (284 mg, 501 μmol) was dissolved in
dichloromethane (6 mL), and trifluoroacetic acid (1.4 mL) in
dichloromethane (1 mL) was added. The reaction mixture was
stirred for 19 h at room temperature and washed with aqueous so-
dium hydroxide solution (1 m, 2ϫ 25 mL). The aqueous layer was
extracted with dichloromethane (30 mL), the combined organic
layer was washed with brine (40 mL) and dried with magnesium
sulfate. The solvent was removed under reduced pressure and the
product was obtained as a white solid (222 mg, 95%); m.p. 104–
106 °C. 1H NMR (500 MHz, CDCl3): δ = 6.82 (s, 4 H, Ar1-2,3,5,6-
(1-{2-Oxo-2-[6-(4-{6-[4-(pent-4-ynyloxy)phenyloxy]hexyloxy}-
phenyloxy)hexyl]amino}ethyl)-3-{4-[tris(4-tert-butylphenyl)-
methyl]phenyl}pyridinium Iodide (30): A mixture of pyridine 11
(600 mg, 1.06 mmol), alkyne linker 29 (576 mg, 1.06 mmol) and so-
dium iodide (247 mg, 1.65 mmol) in 1,4-dioxane (70 mL) was
heated to reflux for 2 d. The solvent was removed under reduced
pressure and the residue was purified by column chromatography
(silica gel, dichloromethane/methanol, 20:1, Rf = 0.15) to obtain
30 as an orange solid (843 mg, 66 %); m.p. 184 °C. 1H NMR
(500 MHz, CDCl3): δ = 9.38 (br. s, 1 H, Py-2-H), 9.07 (d, 3J =
6.0 Hz, 1 H, Py-6-H), 8.53–8.47 (m, 2 H, Py-4-H, CONH), 7.95
3
3
3
H or Ar2-2,3,5,6-H), 6.81 (s, 4 H, Ar1-2,3,5,6-H or Ar2-2,3,5,6-H),
(dd, J = 8.2 Hz, J = 6.0 Hz, 1 H, Py-5-H), 7.60 (d, J = 8.6 Hz,
3
3
3
4.01 [t, J = 6.1 Hz, 2 H, OCH2(CH2)2CϵCH], 3.93–3.88 (m, 6 H, 2 H, Ar2-2,6-H), 7.44 (d, J = 8.6 Hz, 2 H, Ar2-3,5-H), 7.26 (d, J
OCH2), 2.70 (t, 3J = 7.0 Hz, 2 H, NH2CH2), 2.40 [td, 3Jt = 7.0 Hz,
= 8.6 Hz, 6 H, Ar1-3,5-H), 7.10 (d, J = 8.6 Hz, 6 H, Ar1-2,6-H),
3
4Jd = 2.6 Hz, 2 H, O(CH2)2CH2CϵCH], 2.01–1.94 (m, 3 H, 6.82, 6.79 (2s, 8 H, Ar3-2,3,5,6-H, Ar4-2,3,5,6-H), 5.95 (s, 2 H,
3898
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© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 3885–3901

A Shuttle for the Transport of Protons Based on a [2]Rotaxane
PyCH2), 4.01 [t, 3J = 6.0 Hz, 2 H, Ar4OCH2(CH2)2CϵCH], 3.90 (t, PyCH2), 40.3 [t, NHCH2(CH2)5OAr3], 34.3 [s, C(CH3)3], 31.4
[mc, 4 H, Ar3OCH2(CH2)4CH2OAr4], 3.86 [t, 3J = 6.4 Hz, 2 H,
[q, C(CH3)3], 29.4, 29.3 [2t, Ar3OCH2CH2(CH2)2CH2CH2OAr4],
NH(CH2)5CH2OAr3], 3.28 [mc, 2 H, NHCH2(CH2)5OAr3], 2.39 [td, 29.2 [t, NH(CH2)4CH2CH2OAr3], 28.8 [t, NHCH2CH2(CH2)4-
3Jt = 7.0, 4Jd = 2.6 Hz, 2 H, Ar4O(CH2)2CH2CϵCH], 2.00–1.94 OAr3], 28.3 (t, Ar4OCH2CH2CH2CϵCH), 26.5 [t, NH(CH2)2-
(m, 3 H, Ar4 OCH2 CH2 CH2 CϵCH), 1.81–1.75 [m, 4 H,
Ar3OCH2CH2(CH2)2CH2CH2OAr4], 1.73 [mc, 2 H, NH(CH2)4-
CH2(CH2)3OAr3], 25.9 [t, Ar3O(CH2)2CH2CH2(CH2)2OAr4], 25.6
[t, NH(CH2)3CH2(CH2)2OAr3], 15.2 [t, Ar4O(CH2)2CH2-
CH2CH2OAr3], 1.67–1.60 [m, 2 H, NHCH2CH2(CH2)4OAr3], 1.54– CϵCH] ppm. IR (ATR): ν = 3292 (CϵC–H), 2943, 2866 (aliph.
˜
1.49 [m, 4 H, Ar3O(CH2)2CH2CH2(CH2)2OAr4], 1.47–1.39 [m, 4 C–H), 1692 (C=O),1507 (C=C), 1472 (C–H), 1228, 1018 (C–O),
H, NH(CH2)2CH2CH2(CH2)2OAr3], 1.31 [s, 27 H, C(CH3)3] ppm. 824 (1,4-disubstitution) cm–1. MS (MALDI-TOF, Cl-CCA): m/z =
13C NMR (125 MHz, CDCl3): δ = 163.0 (s, CONH), 153.3, 153.2,
153.1, 153.0 (4s, Ar3-C-1,4, Ar4-C-1,4), 151.2 (s, Ar2-C-4), 148.8 (s,
1073 [M – PF6]+. C73H89F6N2O5P (1218.64): C 71.90, H 7.36, N
2.30. C73H89F6N2O5P·1.7H2O (1249.26): calcd. C 70.14, H 7.45, N
Ar1-C-4), 143.2 (d, Py-C-2), 143.1 (s, Ar1-C-1), 142.8 (d, Py-C-6), 2.24; found C 69.94, H 7.15, N 2.30.
142.5 (d, Py-C-4), 141.4 (d, Py-C-3), 132.8 (d, Ar2-C-3,5), 130.6 (d,
[2]-{[1-(2-Oxo-2-{[6-(4-{6-[4-(3-{1-[6-(3,3,3-tris)4-tert-butylphenyl]-
Ar1-C-2,6), 129.3 (s, Ar2-C-1), 127.5 (d, Py-C-5), 126.3 (d, Ar2-C-
2,6), 124.4 (d, Ar1-C-3,5), 115.5, 115.4, 115.4 (3d, Ar3-C-2,3,5,6,
Ar4-C-2,3,5,6), 83.6 (s, CϵCH), 68.8 (d, CϵCH), 68.5, 68.5 (2t,
OCH2), 66.8 [t, Ar4OCH2(CH2)2CϵCH], 63.7 [s, C(Ar1)3Ar2], 62.5
(t, PyCH2), 40.3 [t, NHCH2(CH2)5OAr3], 34.3 [s, C(CH3)3], 31.4
[q, C(CH3)3], 29.3 [t, Ar3OCH2CH2(CH2)2CH2CH2OAr4], 29.2 [t,
NH(CH2)4CH2CH2OAr3], 28.8 [t, NHCH2CH2(CH2)4OAr3], 28.3
(t, Ar4OCH2CH2CH2CϵCH), 26.7 [t, NH(CH2)3CH2(CH2)2OAr3],
25.9 [t, Ar3O(CH2)2CH2CH2(CH2)2OAr4], 25.6 [t, NH(CH2)2CH2-
propyloxy}-6-oxohexyl)-1,2,3-triazol-4-yl]propyloxy}phenyloxy)-
hexyloxy]phenyloxy}hexyl)amino]ethyl{-3-[4-(tris)4-tert-butyl-
phenyl]methyl}phenyl}pyridinium-hexafluorophosphat[-rotaxa-(54-
methoxy-3,7,10,21-tetraoxa-1,9)1,4(-dibenzena-5)2,6]-pyridina-
heneicosaphan} (32): To a solution of macrocycle 2 (101 mg,
195 μmol), alkyne half-axis 31 (237 mg, 195 μmol) and azide half-
axis 7 (116 mg, 195 μmol) in anhydrous dichloromethane (10 mL)
copper(I) tetrakisacetonitrilo hexafluorophosphate (72.7 mg,
195 μmol) was added, and the reaction mixture was stirred for 2 d
at room temperature. The mixture was diluted with dichlorometh-
ane (20 mL) and methanol (10 mL), and potassium cyanide (60 mg,
922 μmol) in methanol (10 mL) was added. After stirring for 1 h,
the solvents were removed under reduced pressure and dichloro-
methane (10 mL) was added. The solution was washed with water
(10 mL) and the aqueous layer was extracted with dichloromethane
(10 mL). The combined organic layer was dried with magnesium
sulfate and the solvent was removed under reduced pressure. The
residue was purified by column chromatography [silica gel, gradi-
ent: dichloromethane/methanol, 40:1 to 10:1, Rf = 0.13 (40:1)] to
afford rotaxane 32 (33.5 mg, 7%) and axis 33 (99.4 mg, 28%) as
orange solids.
(CH ) OAr3], 15.2 [t, Ar4O(CH ) CH CϵCH] ppm. IR (ATR): ν
˜
2 3
2 2
2
= 3296 (CϵC–H), 3220, 3054 (N–H), 2940, 2906, 2861 (aliph. C–
H), 1677 (C=O),1507 (C=C), 1472 (C–H), 1227, 1018 (C–O), 824
(1,4-disubstitution) cm–1. MS (MALDI-TOF, Cl-CCA): m/z = 1074
[M – I]+. C73H89IN2O5 (1200.58): C 72.98, H 7.47, N 2.33.
C73H89IN2O5·2.5H2O (1245.61): calcd. C 70.34, H 7.60, N 2.25;
found C 70.38, H 7.48, N 2.19.
(1-{2-Oxo-2-[6-(4-{6-[4-(pent-4-ynyloxy)phenyloxy]hexyloxy}-
phenyloxy)hexyl]amino}ethyl)-3-{4-[tris(4-tert-butylphenyl)methyl]-
phenyl}pyridinium Hexafluorophosphate (31): Pyridinium iodide 30
(843 mg, 702 μmol) was dissolved in anhydrous dichloromethane
(10 mL), and silver(I) hexafluorophosphate (195 mg, 772 μmol) in
anhydrous dichloromethane (4 mL) was added. The mixture was
stirred for 2 h at room temperature and filtered afterwards. The
filtrate was concentrated under reduced pressure and the crude
1
Rotaxane 32: H NMR (600 MHz, CDCl3): δ = 8.70 (s, 1 H, Py1-
3
3
2-H), 7.90 (d, J = 8.1 Hz, 1 H, Py1-4-H), 7.80 (d, J = 6.1 Hz, 1
H, Py1-6-H), 7.49 (dd, J = 8.1, J = 6.1 Hz, 1 H, Py1-5-H), 7.33–
3
3
product was purified by column chromatography (silica gel, dichloro- 7.28 (m, 8 H, Ar2-3,5-H, Ar1-3,5-H), 7.27–7.23 (m, 7 H, triazol-5-
methane/methanol, 20:1, Rf = 0.21) to give 31 as an orange solid
H, Ar5-3,5-H), 7.20–7.15 (m, 12 H, Ar1-2,6-H, Ar5-2,6-H), 7.14 (d,
(495 mg, 58%); m.p. 150 °C. 1H NMR (500 MHz, CDCl3): δ = 8.81 3J = 8.4 Hz, 2 H, Ar2-2,6-H), 7.01 (mc, 1 H, CONH), 6.86 (d, J
3
3
(s, 1 H, Py-2-H), 8.71 (br. s, 1 H, Py-6-H), 8.36 (d, J = 7.8 Hz, 1 = 8.5 Hz, 4 H, Ar6-3,5-H), 6.82 (s, 2 H, Py2-3,5-H), 6.81 (s, 8 H,
3
H, Py-4-H), 7.91 (br. s, 1 H, Py-5-H), 7.54 (br. s, 1 H, CONH),
7.45 (d, 3J = 8.4 Hz, 2 H, Ar2-2,6-H), 7.39 (d, 3J = 8.4 Hz, 2 H,
Ar2-3,5-H), 7.25 (d, 3J = 8.6 Hz, 6 H, Ar1-3,5-H), 7.09 (d, 3J =
Ar3-2,3,5,6-H, Ar4-2,3,5,6-H), 6.31 (d, J = 8.5 Hz, 4 H, Ar6-2,6-
H), 5.00 (s, 2 H, Py1CH2CONH), 4.43 (d, 2J = 10.6 Hz, 2 H,
Py2CH2OCHaHbAr6), 4.37 (d, 2J = 11.6 Hz, 2 H, Py2CHaHb-
8.6 Hz, 6 H, Ar1-2,6-H), 6.81 (mc, 4 H, Ar4-2,3,5,6-H)*, 6.77 (s, 4 OCH2Ar6), 4.34 (d, J = 10.6 Hz, 2 H, Py2CH2OCHaHbAr6), 4.31
2
H, Ar3-H-2,3,5,6)*, 5.43 (s, 2 H, PyCH2), 4.00 [t, 3J = 6.0 Hz, 2 H,
(d, J = 11.6 Hz, 2 H, Py2CHaHbOCH2Ar6), 4.29 [t, J = 7.1 Hz,
2
3
Ar4OCH2(CH2)2CϵCH], 3.88 [mc, 4 H, Ar3OCH2(CH2)4CH2-
2
H, triazol-CH2(CH2)4COO], 3.94 [t, 3J
=
6.1 Hz, H,
2
3
OAr4], 3.83 [t, J = 6.5 Hz, 2 H, NH(CH2)5CH2OAr3], 3.24 [mc, 2 Ar4OCH2(CH2)2triazol], 3.92–3.85 [m, 8 H, CH2OAr3OCH2(CH2)4-
3
4
H, NHCH2(CH2)5OAr3], 2.39 [td, Jt = 7.0 Hz, Jd = 2.6 Hz, 2 H, CH2OAr4, COOCH2CH2], 3.83 (s, 3 H, Py2OCH3), 3.69 (t, 3J =
Ar4O(CH2)2CH2CϵCH], 2.00–1.94 (m, 3 H, Ar4OCH2CH2CH2-
6.1 Hz, 4 H, Ar6OCH2), 3.07 (q, 3J = 6.6 Hz, 2 H, NHCH2), 2.92–
CϵCH), 1.81–1.73 [m, 4 H, Ar3OCH2CH2(CH2)2CH2CH2OAr4], 2.85 [m, 4 H, Ar4O(CH2)2CH2triazol, COOCH2CH2], 2.22 [t, J =
3
1.69 [mc, 2 H, NH(CH2)4CH2CH2OAr3], 1.60–1.52 [m, 2 H, 7.5 Hz, 2 H, triazol-(CH2)4CH2COO], 2.13 (quint, J = 7.3 Hz, 2
3
NHCH2CH2(CH2)4OAr3], 1.50 [mc, 4 H, Ar3O(CH2)2CH2CH2-
H, Ar4OCH2CH2CH2triazol), 1.87 [quint, 3J = 7.5 Hz, 2 H, triazol-
(CH2)2OAr4], 1.45–1.33 [m, 4 H, NH(CH2)2CH2CH2(CH2)2OAr3], CH2CH2(CH2)3COO], 1.81–1.75 [m, 4 H, Ar3OCH2CH2(CH2)2-
1.29 [s, 27 H, C(CH3)3] ppm. *The assignment may be inverted. 13 CH2CH2OAr4], 1.71 [quint, 2 H, NH(CH2)4CH2CH2OAr3], 1.68–
NMR (125 MHz, CDCl3): δ = 163.2 (s, CONH), 153.3, 153.2, 1.59 [m, 6 H, Ar6OCH2CH2, triazol-(CH2)3CH2CH2COO], 1.53–
153.1, 153.0 (4s, Ar3-C-1,4, Ar4-C-1,4), 150.8 (s, Ar2-C-4), 148.8 (s, 1.48 [m, 4 H, Ar3O(CH2)2CH2CH2(CH2)2OAr4], 1.45–1.34 [m, 8
Ar1-C-4), 143.3 (d, Py-C-6), 143.2 (d, Py-C-2), 143.2 (s, Ar1-C-1), H, NHCH2CH2CH2CH2 (CH2)2OAr3, Ar6O(CH2)2CH2], 1.34–
142.6 (Py-C-4), 141.2 (s, Py-C-3), 132.6 (d, Ar2-C-3,5), 130.6 (d, 1.25[m,12H,Ar6O(CH2)3CH2CH2,NH(CH2)2CH2,triazol-(CH2)2-
C
Ar1-C-2,6), 129.8 (s, Ar2-C-1), 127.7 (d, Py-C-5), 126.2 (d, Ar2-C- CH2(CH2)2COO], 1.31, 1.29 [2s, 54 H, C(CH3)3] ppm. 13C NMR
2,6), 124.4 (d, Ar1-C-3,5), 115.5, 115.4, 115.4 (3d, Ar3-C-2,3,5,6,
Ar4-C-2,3,5,6), 83.6 (s, CϵCH), 68.8 (d, CϵCH), 68.5, 68.5 (2t,
OCH2), 66.8 [t, Ar4OCH2(CH2)2CϵCH], 63.7 [s, C(Ar1)3Ar2], 62.5
(150 MHz, CDCl3): δ = 173.4 (s, COOCH2), 167.2 (s, Py2-C-4),
163.0 (s, CONH), 158.8 (s, Py2-C-2,6), 158.4 (s, Ar6-C-1), 153.3,
153.2, 153.0 (3s, Ar3-C-1,4, Ar4-C-1,4), 150.5 (s, Ar2-C-4), 148.8 (s,
Eur. J. Org. Chem. 2014, 3885–3901
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3899

B. Hesseler, M. Zindler, R. Herges, U. Lüning
FULL PAPER
Ar1-C-4), 148.5 (s, Ar5-C-4), 147.3 (s, triazol-C-4), 144.9 (d, Py1- CH2(CH2)2OAr3]*, 24.2 (t, CH2CH2COO), 22.2 [t, Ar4O(CH2)2-
C-2), 143.8 (s, Ar5-C-1), 143.4 (s, Ar1-C-1), 141.9 (d, Py1-C-6)*, CH triazol] ppm. *The assignment may be inverted. IR (ATR): ν
˜
2
140.5 (d, Py1-C-4)*, 139.6 (s, Py1-C-3)*, 131.8 (d, Ar2-C-3,5), 130.5 = 2951, 2865 (aliph. C–H), 1731, 1693 (C=O), 1604, 1506 (C=C),
(d, Ar1-C-2,6), 130.1 (d, Ar6-C-3,5), 129.1 (s, Ar2-C-1), 129.0 (s,
Ar6-C-4)*, 128.5 (d, Ar5-C-2,6), 126.2 (d, Ar2-C-2,6), 125.7 (d, Py1-
1464 (C–H), 1226, 1017 (C–O), 840 (isolated arom. H), 822 (1,4-
disubstitution) cm–1. MS (MALDI-TOF, Cl-CCA): m/z = 1670
C-5), 124.7 (d, Ar5-C-3,5), 124.5 (d, Ar1-C-3,5), 120.8 (d, triazol- [M]+. HRMS (FT-ICR): m/z calcd. for C112H142N5O7 1669.0903
+
C-5), 115.4 (d, Ar3-C-2,3,5,6, Ar4-C-2,3,5,6), 113.9 (d, Ar6-C-2,6),
[M]+, 835.0488 [M + H]2+; found 1669.0908 [M]+, 835.0493 [M +
107.7 (d, Py2-C-3,5), 73.0 (t, Ar6CH2O), 72.6 (t, Py2CH2O), 68.5 H]2+. C112H142F6N5O7P (1814.06): calcd. C 74.10, H 7.88, N 3.86;
[t, Ar3OCH2(CH2)4CH2OAr4], 68.4 [t, NH(CH2)5CH2OAr3], 67.5 found C 73.91, H 8.19, N 4.12.
[t, Ar4OCH2(CH2)2triazol], 67.1 (t, Ar6OCH2), 63.8 [s, C(Ar1)3],
Supporting Information (see footnote on the first page of this arti-
63.0 (t, COOCH2CH2), 61.7 (t, Py1CH2), 55.4 (q, Py2OCH3), 53.7
cle): 1H and 13C NMR spectra for compounds 4, 6, 7, 9–11, 13–
[s, C(Ar5)3], 49.9 [t, triazol-CH2(CH2)4COO], 40.1 (t, NHCH2),
33, HRMS of compounds 32 and 33, and 2D NOESY spectra of
38.7 (t, COOCH2CH2), 34.4, 34.3 [2s, C(CH3)3], 33.9 [t, triazol-
32 and protonated 32.
(CH2)4CH2COO], 31.4 [q, C(CH3)3], 30.1 [t, triazol-CH2CH2(CH2)3-
COO], 29.4 [t, Ar6O(CH2)3CH2CH2]#, 29.3 [t, Ar3OCH2CH2-
(CH2)2 CH2CH2OAr4]#, 29.2 [t, NH(CH2)4CH2CH2OAr3]#, 29.1 Acknowledgments
(t, Ar4OCH2CH2CH2triazol)#, 28.8 (t, NHCH2CH2)#, 28.6 (t,
Ar6OCH2CH2)#, 26.6 [t, NH(CH2)2CH2]#, 26.0 [t, triazol-(CH2)2-
CH2(CH2)2COO]#, 25.9 [t, Ar3O(CH2)2CH2CH2(CH2)2OAr4]#,
25.9 [t, Ar6O(CH2)2CH2]#, 25.7 [t, NH(CH2)3CH2(CH2)2OAr3]#,
24.2 [t, triazol-(CH2)3CH2CH2COO], 22.2 [t, Ar4O(CH2)2CH2tria-
zol] ppm. *The signal is only observed in the HMBC spectrum.
#The signals were assigned by comparison with axis 33 and macro-
cycle 2. MS (MALDI-TOF, Cl-CCA): m/z = 2190 [M – PF6]+.
Financial support by the Deutsche Forschungsgemeinschaft
(DFG) (Sonderforschungsbereich 677) is gratefully acknowledged.
The authors thank the work group of Prof. Dr. Jürgen Grotemeyer
for HRMS measurements.
[1] T. Kelly (Ed.), Molecular Machines, Top. Curr. Chem. vol. 262,
Springer-Verlag, Berlin, Heidelberg, Germany, 2005.
[2] V. Balzani, A. Credi, M. Venturi, Molecular Devices and Ma-
chines - Concepts and Perspectives for the Nanoworld, 2nd ed.,
Wiley-VCH, Weinheim, Germany, 2008.
[3] B. L. Feringa, W. R. Browne (Eds.), Molecular Switches, 2nd
ed., Wiley-VCH, Weinheim, Germany, 2011.
[4] P. D. Boyer, Biochim. Biophys. Acta Bioenerg. 1993, 1140, 215–
250.
[5] J. Baudry, E. Tajkhorshid, F. Molnar, J. Phillips, K. Schulten,
J. Phys. Chem. B 2001, 105, 915–918.
[6] G. Steinberg-Yfrach, P. A. Liddell, S.-C. Hung, A. L. Moore,
D. Gust, T. A. Moore, Nature 1997, 385, 239–241.
[7] Whilst this manuscript was being revised, a light-driven proton
pump across a macroscopic membrane was published, see: X.
Xie, G. A. Crespo, G. Mistlberger, E. Bakker, Nature Chem.
2014, 6, 202–207.
[8] W. Vetter, G. Schill, Tetrahedron 1967, 23, 3079–3093.
[9] G. Schill, Catenanes, Rotaxanes, and Knots, Academic Press,
New York, London, 1971.
HRMS (FT-ICR): m/z calcd. for C144H183N6O12 2188.3888 [M]+,
+
1094.6980 [M + H]2+; found 2188.3863 [M]+, 1094.6986 [M +
H]2+
.
1
Axis 33: M.p. 112 °C. H NMR (500 MHz, CDCl3): δ = 8.88 (br.
s, 1 H, Py1-2-H), 8.65 (d, 3J = 6.0 Hz, 1 H, Py1-6-H), 8.48 (d, 3J =
3
3
8.2 Hz, 1 H, Py1-4-H), 7.93 (dd, J = 6.0, J = 8.2 Hz, 1 H, Py1-5-
H), 7.49 (d, J = 8.7 Hz, 2 H, Ar2-2,6-H), 7.42 (d, J = 8.7 Hz, 2
3
3
H, Ar2-3,5-H), 7.37 (br. s, 1 H, CONH), 7.28–7.23 (m, 13 H, Ar1-
3,5-H, Ar5-3,5-H, triazol-5-H), 7.17 (d, J = 8.7 Hz, 6 H, Ar5-2,6-
3
H), 7.10 (d, J = 8.7 Hz, 6 H, Ar1-2,6-H), 6.80, 6.79 (2s, 8 H, Ar3-
3
2,3,5,6-H, Ar4-2,3,5,6-H), 5.40 (s, 2 H, Py1CH2), 4.29 [t, 3J =
7.2 Hz, 2 H, triazol-CH2(CH2)4COO], 3.94 [t, 3J = 6.2 Hz, 2 H,
Ar4OCH2(CH2)2triazol], 3.92–3.84 [m, 8 H, CH2OAr3OCH2(CH2)4-
CH2OAr4, COOCH2CH2], 3.28 (mc, 2 H, NHCH2), 2.88 [mc, 4 H,
3
Ar4O(CH2)2CH2triazol, COOCH2CH2], 2.23 (t, J = 7.5 Hz, 2 H,
CH2COOCH2), 2.13 (mc, 2 H, Ar4OCH2CH2CH2triazol), 1.88
[quint, 3J = 7.5 Hz, 2 H, triazol-CH2CH2(CH2)3COO], 1.82–1.70
[m, 6 H, CH2CH2OAr3OCH2CH2(CH2)2CH2CH2O], 1.68–1.56 [m,
4 H, triazol-(CH2)3CH2CH2COO, NHCH2CH2], 1.54–1.47 [m, 6
H, CH2(CH2)2OAr3O(CH2)2CH2CH2], 1.39–1.24 [m, 4 H, triazol-
(CH2)2CH2(CH2)2COO, NH(CH2)2CH2], 1.30, 1.29 [2s, 54 H,
C(CH3)3] ppm. 13C NMR (125 MHz, CDCl3): δ = 173.4 (s, CO-
OCH2), 162.9 (s, CONH), 153.3, 153.2, 153.1, 153.0 (4s, Ar3-C-1,4,
Ar4-C-1,4), 151.1 (s, Ar2-C-4), 148.8 (s, Ar1-C-4), 148.5 (s, Ar5-C-
4), 147.3 (s, triazol-C-4), 143.8 (s, Ar5-C-1), 143.3 (d, Py1-C-2),
143.1 (s, Ar1-C-1), 142.9 (d, Py1-C-6), 142.7 (d, Py1-C-4), 141.6 (s,
Py1-C-3), 132.8 (d, Ar2-C-3,5), 130.6 (d, Ar1-C-2,6), 129.5 (s, Ar2-
C-1), 128.5 (d, Ar5-C-2,6), 127.6 (d, Py1-C-5), 126.2 (d, Ar2-C-2,6),
124.7 (d, Ar5-C-3,5), 124.4 (d, Ar1-C-3,5), 120.8 (d, triazol-C-5),
115.4, 115.4 (2d, Ar3-C-2,3,5,6, Ar4-C-2,3,5,6), 68.5, 68.4 [2t,
CH2OAr3OCH2(CH2)4CH2OAr4], 67.5 [t, Ar4OCH2(CH2)2triazol],
63.7 [s, C(Ar1)3], 62.9 (t, COOCH2CH2), 62.5 (t, Py1CH2), 53.7 [s,
C(Ar5)3], 49.9 [t, triazol-CH2(CH2)4COO], 40.4 (t, NHCH2), 38.7
(t, COOCH2CH2), 34.3, 34.3 [2s, C(CH3)3], 33.9 (t, CH2COO), 31.3
[q, C(CH3)3], 30.0 [t, triazol-CH2CH2(CH2)3COO], 29.3 [t,
Ar3OCH2CH2 (CH2)2CH2CH2OAr4], 29.2 [t, NH(CH2)4CH2CH2-
OAr3], 29.0 (t, Ar4OCH2CH2CH2-triazol), 28.8 (t, NHCH2CH2),
26.5 [t, NH(CH2)2CH2], 26.0 [t, triazol-(CH2)2CH2(CH2)2COO],
25.9 [t, Ar3O(CH2)2CH2CH2(CH2)2OAr4]*, 25.6 [t, NH(CH2)3-
[10] J.-P. Sauvage, C. Dietrich-Buchecker (Eds.), Molecular Cate-
nanes, Rotaxanes and Knots – A journey through the world of
molecular topology, Wiley-VCH, Weinheim, Germany, 1999.
[11] First switchable shuttle: R. A. Bissell, E. Córdova, A. E.
Kaifer, J. F. Stoddart, Nature 1994, 369, 133–137.
[12] A.-M. L. Fuller, D. A. Leigh, P. J. Lusby, A. M. Z. Slawin,
D. B. Walker, J. Am. Chem. Soc. 2005, 127, 12612–12619.
[13] U. Lüning, E. Mak, M. Zindler, B. Hartkopf, R. Herges, Eur.
J. Org. Chem. 2010, 4932–4940.
[14] One of many examples for bipyridinium ions in the axis, see:
P. R. Ashton, R. Ballardini, V. Balzani, A. Credi, K. R. Dress,
E. Ishow, C. J. Kleverlaan, O. Kocian, J. A. Preece, N. Spencer,
J. F. Stoddart, M. Venturi, S. Wenger, Chem. Eur. J. 2000, 6,
3558–3574.
[15] A triazolium ion as part of the axis, see: V. Blanco, A. Carlone,
K. D. Hänni, D. A. Leigh, B. Lewandowski, Angew. Chem. Int.
Ed. 2012, 51, 5166–5169; Angew. Chem. 2012, 124, 5256–5259.
[16] A second example for a triazolium ion as part of the axis, see:
G. T. Spence, M. B. Pitak, P. D. Beer, Chem. Eur. J. 2012, 18,
7100–7108.
[17] A pyridinium ion as part of the axis: E. Busseron, C. Romuald,
F. Coutrot, Chem. Eur. J. 2010, 16, 10062–10073.
[18] A rotaxane with a pyridinium ion in the axis formed by a click
reaction, see: T. Ogoshi, D. Yamafuji, T. Aoki, K. Kitajima, T.
Yamagishi, Y. Hayashi, S. Kawauchi, Chem. Eur. J. 2012, 18,
7493–7500.
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© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 3885–3901

A Shuttle for the Transport of Protons Based on a [2]Rotaxane
[19] V. Aucagne, K. D. Hänni, D. A. Leigh, P. J. Lusby, D. B.
Walker, J. Am. Chem. Soc. 2006, 128, 2186–2187.
[20] K. D. Hänni, D. A. Leigh, Chem. Soc. Rev. 2010, 39, 1240–
1251.
[21] S. Durot, P. Mobian, J.-P. Collin, J.-P. Sauvage, Tetrahedron
2008, 64, 8496–8503.
[22] For a quite similar rotaxane, but with a protonatable amine in
the axis, see: H. Zheng, W. Zhou, J. Lv, X. Yin, Y. Li, H. Liu,
Y. L i , Chem. Eur. J. 2009, 15, 13253–13262.
[23] F. Huang, K. A. Switek, H. W. Gibson, Chem. Commun. 2005,
3655–3657.
[24] S.-Z. Hu, C.-F. Chen, Chem. Eur. J. 2011, 17, 5424–5431.
[25] W. Zhang, H. Yamamoto, J. Am. Chem. Soc. 2007, 129, 286–
287.
[26] J. P. Collman, S. E. Groh, J. Am. Chem. Soc. 1982, 104, 1391–
1403.
[27] H. W. Gibson, S.-H. Lee, P. T. Engen, P. Lecavalier, J. Sze, Y. X.
Shen, M. Bheda, J. Org. Chem. 1993, 58, 3748–3756.
[28] W. Li, D. P. Nelson, M. S. Jensen, R. S. Hoerrner, D. Cai, R. D.
Larsen, Org. Synth. 2005, 81, 89–97.
Received: March 12, 2014
Published Online: May 7, 2014
Eur. J. Org. Chem. 2014, 3885–3901
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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