Using Diels-Alder reactions to synthesize [2]rotaxanes under solvent-free conditions

Article abstract of DOI:10.1016/j.tet.2008.12.082

Diels-Alder reactions of the terminal alkyne units of SiO₂-supported [2]pseudorotaxanes with 1,2,4,5-tetrazine derivatives proceed efficiently through solid-to-solid contact to provide both asymmetric and symmetric [2]rotaxanes incorporating ei

Full text of DOI:10.1016/j.tet.2008.12.082

Tetrahedron 65 (2009) 2824–2829
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journal homepage: www.elsevier.com/locate/tet
Using Diels–Alder reactions to synthesize [2]rotaxanes under solvent-free
conditions
,
Chi-Chieh Hsu a, Chien-Chen Lai b, Sheng-Hsien Chiu a
*
a Department of Chemistry, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan, ROC
b Institute of Molecular Biology, National Chung Hsing University and Department of Medical Genetics, China Medical University Hospital, Taichung, Taiwan, ROC
a r t i c l e i n f o
a b s t r a c t
Article history:
Diels–Alder reactions of the terminal alkyne units of SiO2-supported [2]pseudorotaxanes with 1,2,4,5-
tetrazine derivatives proceed efficiently through solid-to-solid contact to provide both asymmetric and
symmetric [2]rotaxanes incorporating either 24- or 25-membered-ring macrocycles.
Ó 2009 Elsevier Ltd. All rights reserved.
Received 17 December 2008
Accepted 22 December 2008
Available online 4 February 2009
1. Introduction
believe is the smallest [2]rotaxane ever prepared.6 To apply this
synthetic method to the construction of functional interlocked
Several [2]rotaxanes, supermolecular compounds comprising
an interlocked macrocycle and a dumbbell-shaped thread compo-
nent, have been developed as components for molecular electronic
devices.1 Among the protocols that can be used to synthesize
rotaxanes, the ‘threading-followed-by-stoppering’ approach2 is
one of the most straightforward; it relies on weak intermolecular
interactions to position the threadlike component within the cavity
of the macrocycle and then the interlocking of the components of
the resulting pseudorotaxane is performed using a suitable stop-
pering reaction. The formation of pseudorotaxanes from crown
ethers and dibenzylammonium (DBA) ions in solution has been
studied now for almost 15 years; the application of this binding
motif has resulted in many elegant interlocked molecules and
functional materials.3 The efficiency of rotaxane syntheses from
their pseudorotaxane precursors in solution is, however, frequently
affected by factors such as the concentration of the mixture, com-
peting solvents, and the formation of interfering byproducts. Be-
cause these disturbing influences are less pronounced in the solid
state, reactions that can proceed under solvent-free conditions
would be ideal for the efficient synthesis of crown ether/DBA ion-
based rotaxanes. Because of the paucity of known stoppering
reactions that proceed efficiently under the conditions of direct
solid-to-solid contact, only a few such syntheses have been repor-
ted so far.4 Previously, we revealed that the ball-milling of terminal
alkynes and 1,2,4,5-tetrazine produces pyridazine rings, which are
sufficiently sterically bulky to interlock the small [21]crown-7
(21C7)5 macrocycle; using this approach, we synthesized what we
molecules, it was necessary for us to broaden the reaction’s scope
so that we could interlock macrocycles more sizable than 21C7.
Herein, we report a modified set of reaction conditions for this
solvent-free stoppering approach, one that allows the efficient
interlocking of 24- and 25-membered-ring macrocycles in the form
of [2]rotaxanes.
2. Results and discussion
Previously, we demonstrated that Diels–Alder reactions be-
tween terminal alkynes and 1,2,4,5-tetrazine proceed efficiently
under solid-to-solid ball-milling conditions.6
Based on the knowledge that macrocycle 1 can complex DBA
ions tightly in low-polarity solvents,7 for its use as the threadlike
component we synthesized the salt 2-H$PF6, which contains a
p-tert-butyl phenyl terminus (i.e., a stopper for 1) and a terminal
alkyne unit, from the amine 3 and the aldehyde 4 through
sequential condensation, reduction, and ion exchange processes
(Scheme 1). We calculated the association constants for the
interactions between macrocycle 1 and thread 2-H$PF6 in CD3CN
and CD3NO2 to be 350 and 8600 Mꢀ1, respectively, based on a 1H
NMR spectroscopy-based single-point method.8 Thus, we expected
that concentrating an equimolar solution of the macrocycle 1 and
the threadlike salt 2-H$PF6 would result in a solid containing pre-
dominantly the [2]pseudorotaxane complex [(1I2-H)$PF6].9
Concentrating an equimolar mixture of the macrocycle 1 and
the threadlike salt 2-H$PF6 in CH3NO2 provided a sticky liquid
rather than a solid; therefore, we added silica gel to the solution
and then evaporated the organic solvent under reduced pressure.
Because macrocycle 1 forms a [2]pseudorotaxane with DBA in low-
polarity solvents, and because unsubstituted pyridazine rings are
* Corresponding author.
E-mail address: shchiu@ntu.edu.tw (S.-H. Chiu).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.12.082

C.-C. Hsu et al. / Tetrahedron 65 (2009) 2824–2829
2825
1. toluene / Δ
2. NaBH4
3. HCl / NH4PF6
+
NH2
N
H2
3
_
PF6
.
+
2-H PF6
O
H
88%
O
4
O
O
1
O
O
O
+
O
O
N
O
/ silica gel
H2
O
_
Dissolve in MeNO2 and concentrate
PF6
.
⊃
[(1 2-H) PF6]
1.
N
N
N
O
O
O
N
+
N
/ ball mill
N
5
N
O
H2
_
2.
Δ
O
PF6
Scheme 1.
.
61%
6-H PF6
smaller than a benzene ring, we suspected that the pyridazine unit
generated from the reaction of a terminal alkyne with 1,2,4,5-tet-
razine would not be a true stopper for interlocking the macrocycle 1
within a [2]rotaxane. Thus, we applied 3,6-diphenyl-1,2,4,5-tetra-
zine (5) to the reaction with the expectation that the steric bulk of
the resulting diphenylpyridazine would be sufficient to prevent
dethreading of macrocycle 1 from the resulting [2]rotaxane. From
1H NMR spectroscopic analyses, the ball-milling of an equimolar
mixture of the SiO2-supported [2]pseudorotaxane [(1I2-H)$PF6]
and the solid diphenyltetrazine 5 for up to 12 h produced no de-
tectable signals for the desired [2]rotaxane. Because the grinding of
1,2,4,5-tetrazine with the same SiO2-supported [2]pseudorotaxane
[(1I2-H)$PF6] produced a reasonable amount of the correspond-
ing pyridazine-terminated dumbbell component within 9 h under
the same ball-milling conditions, it appeared that the problem in
our [2]rotaxane synthesis was the relatively low reactivity of 3,6-
diphenyl-1,2,4,5-tetrazine. Relative to 1,2,4,5-tetrazine, which
sublimed readily at high temperature to afford a low yield of our
‘smallest [2]rotaxane’ synthesized under thermal conditions,5 3,6-
diphenyl-1,2,4,5-tetrazine is less volatile; therefore, we suspected
that heating a well-ground solid mixture of the SiO2-supported
[2]pseudorotaxane [(1I2-H)$PF6] and the diphenyltetrazine 5 at
high temperature would allow the stoppering reaction to proceed
efficiently under the solid-to-solid contact. Thus, we ground the
SiO2-supported [2]pseudorotaxane [(1I2-H)$PF6] with the
diphenyltetrazine 5 for 1 h and then heated the mixture at 373 K
under atmosphere pressure.10 To monitor the progress of the
reaction, at various time intervals we dissolved a portion of the
solid reaction mixture in CD3CN, filtered off the SiO2, and then
recorded the 1H NMR spectrum of the filtrate. Over time, we ob-
served a new set of signals appeared with increasing intensity
(Fig. 1). After heating at 373 K for 3 days, these signals predomi-
nated the spectrum (Fig. 1d); thus, we subjected the mixture to
column chromatography (SiO2: MeOH/CH2Cl2, 2:98) and isolated
the [2]rotaxane 6-H$PF6 in 61% yield. Similar reactions performed
in solution did not proceed as efficiently as it did in the solid state;
indeed, heating an equimolar (20 mM) mixture of the macrocycle 1,
the threadlike salt 2-H$PF6, and the diphenyltetrazine 5 in CD3CN
(at 343 K) or CD3NO2 (at 353 K) gave a complicated set of products
after 3 days.
diyne 10-H$PF6 in three steps from the amine 7 (Scheme 2). Boc-
protection of 7 followed by Sonogashira coupling of the resulting
dibromide 8 with trimethylsilylacetylene afforded the diyne 9.
Removal of the silyl and Boc protecting groups of 9 under basic and
acidic conditions, respectively, with subsequent ion exchange and
column chromatography, gave the desired threadlike salt 10-H$PF6.
Concentrating a mixture of the macrocycle 1, the threadlike diyne
10-H$PF6, and SiO2 in CH3NO2 gave a solid, which we assumed
H
(a)
N
(c)
O
H
(uc)
N
H
(b)
(c)
(d)
N N
(e)
O
H
Ph
H
H
8.5
8.0
7.5
7.0
6.5
6.0
5.5
5.0
Figure 1. Partial 1H NMR spectra (400 MHz, CD3CN, 298 K) revealing the formation of
the [2]rotaxane 6-H$PF6 during the heating of a ball-milled (1 h) solid mixture of the
SiO2-supported [2]pseudorotaxane [1I2-H][PF6] and the diphenlytetrazine 5 for (a) 0,
(b) 24, (c) 48, and (d) 72 h; (e) spectrum of isolated 6-H$PF6.
To demonstrate that the same synthetic method could be ap-
plied to synthesize a symmetric [2]rotaxane, we synthesized the

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C.-C. Hsu et al. / Tetrahedron 65 (2009) 2824–2829
Pd(PPh3)4 / CuI
Boc2O
Br
Br
Br
Br
NEt3
TMS
/
N
H
N
72%
Boc
7
8
83%
1. K2CO3 / MeOH
2. TFA
3. NH4PF6 / H2O
TMS
TMS
85%
N
N
_
9
Boc
H2
.
PF6
10-H PF6
O
O
macrocycle 1
O
silica gel
N
O
O
H2
_
dissolve in MeNO2
and concentrate
PF6
.
[(1 10-H) PF ]
⊃
6
N
N
1.
N N
O
/ ball mill
5
O
N
N
N
N
2.
Δ
N
O
72%
H2
_
O
PF6
.
O
11-H PF6
Scheme 2.
contained predominantly the [2]pseudorotaxane [(1I10-H)$PF6].
Ball-milling of this solid in the presence of the diphenyltetrazine 5
(molar ratio, 1:2) for 1 h and then heating the resulting solid mix-
ture at 373 K for 3 days gave the desired symmetrical [2]rotaxane
11-H$PF6, which we isolated in 72% yield after column chroma-
tography (SiO2: MeOH/CH2Cl2, 2:98). Relative to the 1H NMR
spectra of 1 and 10-H$PF6 (Fig. 2), the significant upfield shift for
the signal of the methylene proton adjacent to the NHþ2 center in
the [2]rotaxane 11-H$PF6 and the separation of the originally
efficiently synthesized using the same solvent-free Diels–Alder
reaction, i.e., by simply heating a well-ground mixture of the
SiO2-supported alkyne-terminated [2]pseudorotaxanes and 3,6-
diphenyl-1,2,4,5-tetrazine at 373 K for a few days.
To prove the generality of this synthetic method, we mixed the
threadlike salts 2-H$PF6 and 10-H$PF6 individually with SiO2 and
dibenzo[24]crown-8 (DB24C8) in solution and concentrated the
mixtures to produce the corresponding solids coating with the
[2]pseudorotaxanes [(DB24C8I2-H)$PF6] and [(DB24C8I10-
H)$PF6], respectively (Scheme 3). Grinding these solids individually
with the diphenyltetrazine 5 for 1 h and then heating the resulting
solid mixtures at 373 K for 3 days afforded the desired asymmetric
and symmetric [2]rotaxanes 12-H$PF6 (73%) and 13-H$PF6 (72%),
respectively, after column chromatography (SiO2: MeOH/CH2Cl2,
2:98). Figure 3 reveals the gradual formation of the [2]rotaxane
overlapping signals (at
unit into separate signals at
O] and [C–H/ ] hydrogen bonds were important noncovalent
d
3.46) for the protons of the ethylene glycol
d
3.09 and 3.52, confirmed that [N–H/
p
interactions stabilizing the recognition of the macrocycle 1 by the
dumbbell-shaped salt. Thus, both asymmetric and symmetric
[2]rotaxanes featuring the 25-membered-ring macrocycle 1 were
(a)
N
N
H
H
Ph
H
OCH2CH2O
O
H
H
H
(b)
+
N CH2
H
8
9
7
6
5
4
3
2
Figure 2. 1H NMR spectra (400 MHz, CD3CN, 298 K) of (a) the symmetric [2]rotaxane 11-H$PF6 and (b) the macrocycle 1.

C.-C. Hsu et al. / Tetrahedron 65 (2009) 2824–2829
2827
5
O O
O O
ball-mill
O
O
O
O
N
R
R'
N
N
H
N
O
2 O
O
O
H2
-
PF6
O O
O O
/ SiO2
.
.
73%
72%
⊃
12-H PF6
R=
[(DB24C8 2-H) PF6]/SiO2
R' =
R' =
N N
.
13-H PF6
Ph
Ph
.
⊃
[(DB24C8 10-H) PF ]/SiO2
6
R=
Scheme 3.
N
N
N
N
(a)
H
(b)
(c)
(d)
(e)
O
O
N
N
+NH2
OCH2CH2O
H
H
+NCH2
4.5
8.5
8.0
7.5
7.0
4.0
3.5
Figure 3. Partial 1H NMR spectra (400 MHz, CD3CN, 298 K) displaying the formation of the [2]rotaxane 13-H$PF6 during the heating of a ball-milled (1 h) solid mixture of the SiO2-
supported [2]pseudorotaxane [DB24C8I10-H][PF6] and the diphenyltetrazine 5 for (a) 0, (b) 24, (c) 48, and (d) 72 h; (e) spectrum of isolated 13-H$PF6.
13-H$PF6 during this ‘grinding-followed-by-heating’ process. Thus,
the efficiency of this stoppering method was retained when
changing the nature of the macrocyclic component.
solid contact to provide both asymmetric and symmetric
[2]rotaxanes incorporating either of the macrocycles 1 or DB24C8.
We suspect that the convenience and environmentally benign na-
ture of this synthetic method will be helpful for the construction of
other complex interlocked molecules exhibiting various functions.
The presence of the pyridazine termini of these [2]rotaxanes pro-
vides the possibility of using them as building blocks for assembling
complicated molecular architectures in the presence of suitable
metal ions; such studies are under investigation in our laboratory.
3. Conclusion
We have demonstrated that the Diels–Alder reactions of the
terminal alkyne units of SiO2-supported [2]pseudorotaxanes with
1,2,4,5-tetrazine derivatives proceed efficiently through solid-to-

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C.-C. Hsu et al. / Tetrahedron 65 (2009) 2824–2829
4. Experimental
(860 mg, 8.8 mmol) were added to a degassed solution of the
dibromide 8 (1.0 g, 2.2 mmol) in triethylamine (15 mL) and then the
mixture was heated at 40 ꢁC for 12 h. After cooling to room tem-
perature, the solution was partitioned between CH2Cl2 (10 mL) and
H2O (10 mL), the aqueous phase was extracted with CH2Cl2
(2ꢂ10 mL), and the combined organic phases were dried (MgSO4),
concentrated, and purified chromatographically (SiO2: CH2Cl2/hex-
ane, 1:3) to afford the carbamate 9 as a yellow liquid (893 mg, 83%).
4.1. General
All glassware, stirrer bars, syringes, and needles were either
oven- or flame-dried prior to use. All reagents, unless otherwise
indicated, were obtained from commercial sources. Anhydrous
CH2Cl2 and MeCN were obtained through distillation from CaH2
under N2. Anhydrous THF was obtained through distillation from
Na/Ph2CO under N2. Reactions were conducted under N2 or Ar at-
mospheres. Thin layer chromatography (TLC) was performed on
Merck 0.25-mm silica gel (Merck Art. 5715). Column chromatog-
raphy was undertaken over Kieselgel 60 (Merck, 70–230 mesh).
Melting points are uncorrected. Ball-milling was performed using
a Retsch MM 200 swing-mill, containing two 5-mL stainless-steel
cells and two stainless-steel balls (diameter: 7 mm); the mill was
operated at a frequency of 22.5 Hz at room temperature. In NMR
spectra, the deuterated solvent was used as the lock; the role of the
internal standard was played by either TMS or the solvent’s residual
protons. Chemical shifts are reported in parts per million (ppm).
Multiplicities are given as s (singlet), d (doublet), t (triplet), q
(quartet), m (mutiplet), and br (broad).
1H NMR (400 MHz, CDCl3):
d
¼0.24 (s,18H),1.44 (s, 9H), 4.24 (br, 2H),
4.36 (br, 2H), 7.00–7.18 (br, 4H), 7.39 (d, J¼8 Hz, 4H); 13C NMR
(100 MHz, CDCl3):
d
¼0.4, 28.6, 49.4, 80.1, 93.9, 104.6, 121.7, 126.6,
127.3, 131.6, 137.7, 155.0; HRMS (ESI): m/z calcd for (C29H39NO2Si2)
[MþNa]: 512.2417; found: 512.2417.
4.5. Ammonium salt 10-H$PF6
K2CO3 (1 g, 7.2 mmol) was added to a solution of the carbamate
9 (890 mg, 1.8 mmol) in MeOH (20 mL). The mixture was stirred at
room temperature for 30 min and partitioned between CH2Cl2
(20 mL) and H2O (20 mL). The aqueous phase was washed with
CH2Cl2 (2ꢂ20 mL) and then the combined organic phases were
concentrated to give a yellow liquid, which was dissolved in
a mixture of MeOH (15 mL) and trifluoroacetic acid (5 mL) and
stirred at room temperature for 12 h. Saturated aqueous NH4PF6
solution (30 mL) was added to the mixture and then the organic
solvent was evaporated. The precipitate was filtered off and washed
with H2O to afford the ammonium salt 10-H$PF6 as a white solid
(610 mg, 85%). Mp¼210–211 ꢁC; 1H NMR (400 MHz, CD3CN):
4.2. [2]Rotaxane 6-H$PF6
The organic solvent was evaporated under reduced pressure
from a mixture of macrocycle 1 (100 mg, 0.24 mmol), the alkyne 2-
H$PF6 (100 mg, 0.24 mmol), and silica gel (200 mg) in CH3NO2
(10 mL) to afford a solid mixture, which was then mixed with 3,6-
diphenyl-1,2,4,5-tetrazine (61 mg, 0.26 mmol) and ball-milled at
room temperature for 1 h. The solid mixture was transferred to
a 5 mL flask, heated to 100 ꢁC for 3 days, and then purified chro-
matographically (SiO2: MeOH/CH2Cl2, 2:98) to afford the [2]rotax-
ane 6-H$PF6 as a white solid (153 mg, 61%). Mp¼173–174 ꢁC; 1H
d
¼3.50 (s, 2H), 4.23 (s, 4H), 7.44 (dd, J¼8 Hz, 4H), 7.56 (d, J¼8 Hz,
4H); 13C NMR (100 MHz, CD3CN):
d
¼51.9, 80.3, 83.1, 124.2, 131.2,
131.7, 133.2; HRMS (ESI): m/z calcd for [10-H]þ (C18H16N): 246.1277;
found: 246.1283.
4.6. [2]Rotaxane 11-H$PF6
NMR (400 MHz, CD3CN):
d
¼1.05 (t, J¼7 Hz, 2H), 1.41 (s, 9H), 2.99 (t,
J¼6 Hz, 2H), 3.02–3.09 (m, 2H), 3.26–3.31 (m, 2H), 3.55–3.60 (m,
4H), 3.80 (d, J¼9 Hz, 2H), 4.28 (d, J¼9 Hz, 2H), 5.27 (dd, J¼25, 15 Hz,
4H), 5.97–6.02 (m, 4H), 6.35 (dd, J¼8, 2 Hz, 2H), 6.95 (dd, J¼9, 3 Hz,
2H), 7.10–7.21 (m, 6H), 7.37 (s, 4H), 7.39–7.54 (m, 7H), 7.55–7.63 (m,
5H), 8.10 (s, 1H), 8.27 (dd, J¼7, 2 Hz, 2H); 13C NMR (100 MHz,
After evaporating (under reduced pressure) the solvent from
a mixture of the macrocycle 1 (108 mg, 0.25 mmol), the dialkyne
10-H$PF6 (100 mg, 0.25 mmol), and silica gel (208 mg) in CH3NO2
(10 mL), the solid obtained was mixed with 3,6-diphenyl-1,2,4,5-
tetrazine (132 mg, 0.56 mmol) and ball-milled at room tempera-
ture for 1 h. The solid mixture was transferred to a 5 mL flask,
heated at 100 ꢁC for 3 days, and then purified chromatographically
(SiO2: MeOH/CH2Cl2, 2:98) to afford the [2]rotaxane 11-H$PF6 as
a yellow solid (210 mg, 72%). Mp¼195–196 ꢁC; 1H NMR (400 MHz,
CD3CN):
d
¼31.5, 35.5, 49.1, 52.5, 68.2, 69.8, 71.3, 74.4, 115.0, 125.6,
126.6, 126.8, 127.2, 127.9, 128.0, 129.0, 129.2, 129.4, 129.9, 129.9,
130.7, 131.0, 131.3, 131.7, 132.2, 132.9, 137.0, 137.0, 138.2, 138.3, 139.8,
154.1, 158.0, 158.7; HRMS (ESI): m/z calcd for [6-H]þ (C60H62N3O5):
904.4684; found: 904.4689.
CD3CN):
d
¼2.01 (t, J¼7 Hz, 4H), 3.06–3.12 (m, 4H), 3.50–3.56 (m,
4H), 4.05 (s, 4H), 5.29 (s, 4H), 6.60–6.73 (m, 12H), 7.37–7.47 (m,
4.3. tert-Butyl bis(4-bromobenzyl)carbamate (8)
16H), 7.49–7.64 (m, 10H), 8.10 (s, 2H), 8.28 (dd, J¼7, 2 Hz, 4H); 13C
NMR (100 MHz, CD3CN):
d
¼51.1, 68.2, 69.9, 71.2, 74.4, 116.7, 125.8,
Di-tert-butyl dicarbonate (570 mg, 2.6 mmol) and triethylamine
(390 mg, 3.9 mmol) were added to a solution of the dibromide 7
(920 mg, 2.59 mmol) in MeOH (15 mL) and then the mixture was
stirred at room temperature for 24 h. The organic solvent was
evaporated under reduced pressure and the crude product purified
chromatographically (SiO2: CH2Cl2/hexane, 1:1) to yield the Boc-
protected dibromide 8 as a yellow liquid (0.84 g, 72%). 1H NMR
127.9, 128.0, 129.1, 129.1, 129.2, 129.5, 129.9, 130.4,130.7, 131.0, 131.6,
132.0, 136.9, 138.1, 138.2, 138.4, 139.5, 158.1, 158.6, 159.3; HRMS
(ESI): m/z calcd for [11-H]þ (C72H64N5O5): 1078.4902; found:
1078.4907.
4.7. [2]Rotaxane 12-H$PF6
(400 MHz, CDCl3):
d
¼1.47 (s, 9H), 4.24 (br, 2H), 4.33 (br, 2H), 6.98–
After evaporating (under reduced pressure) the solvent from
a mixture of DB24C8 (390 mg, 0.3 mmol), the alkyne 2-H$PF6
(300 mg, 0.24 mmol), and silica gel (690 mg) in CH3NO2 (10 mL),
the solid mixture obtained was mixed with 3,6-diphenyl-1,2,4,5-
tetrazine (180 mg, 0.78 mmol), ball-milled at room temperature for
1 h, transferred to a 5 mL flask, and heated at 100 ꢁC for 3 days.
After cooling to room temperature, the resulting solid mixture was
purified chromatographically (SiO2: MeOH/CH2Cl2, 2:98) to afford
the [2]rotaxane 12-H$PF6 as a white solid (560 mg, 73%). Mp¼124–
7.10 (br, 4H), 7.43 (d, J¼8 Hz, 4H); 13C NMR (100 MHz, CDCl3):
d
¼28.4, 48.7, 49.0, 80.4,121.0,128.8,129.4,131.5,136.6,155.5; HRMS
(ESI): m/z calcd for (C19H21Br2NO2) [MþNa]: 475.98367; found:
475.98367.
4.4. tert-Butyl bis{4-[(trimethylsilyl)ethynyl]-
benzyl}carbamate (9)
Tetrakis(triphenylphosphine)palladium(0) (101 mg, 0.09 mmol),
copper iodide (16.7 mg, 0.09 mmol), and trimethylsilylacetylene
125 ꢁC; 1H NMR (400 MHz, CD3CN):
d
¼1.23 (s, 9H), 3.42–3.57 (m,
8H), 3.63–3.80 (m, 8H), 3.98–4.06 (m, 8H), 4.54 (t, J¼6 Hz, 2H), 4.74

C.-C. Hsu et al. / Tetrahedron 65 (2009) 2824–2829
2829
(t, J¼6 Hz, 2H), 6.78–6.84 (m, 8H), 7.13 (dd, J¼6, 2 Hz, 2H), 7.19 (dd,
References and notes
J¼8, 4 Hz, 4H), 7.22–7.40 (m, 7H), 7.52–7.63 (m, 5H), 7.86 (s, 1H),
8.23 (dd, J¼8, 2 Hz, 2H); 13C NMR (100 MHz, CD3CN):
¼31.3, 35.0,
d
1. (a) Molecular Electronics: Science and Technology; Aviram, A., Ratner, M., Eds.;
New York Academy of Sciences: New York, NY, 1998; (b) Collier, C. P.; Matter-
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E.; Choi, J. W.; Boukai, A.; Bunimovich, Y.; Johnston-Halperin, E.; DeIonno, E.;
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52.4, 53.0, 68.5, 70.6, 71.0, 112.7, 121.4, 125.1, 125.5, 127.2, 128.3,
128.7, 129.2, 129.4, 129.5, 129.9, 130.2, 133.0, 136.2, 137.3, 137.4,
139.6, 147.4, 152.1, 157.5, 158.2 (two signals are missing, possibly
because of signal overlap); HRMS (ESI): m/z calcd for [12-H]þ
(C58H66N3O8): 932.4850; found: 932.4850.
2. For recent examples, see: (a) Alvarez-Perez, M.; Goldup, S. M.; Leigh, D. A.;
Slawin, A. M. Z. J. Am. Chem. Soc. 2008, 130, 1836–1838; (b) Frey, J.; Tock, C.;
Collin, J.-P.; Heitz, V.; Sauvage, J.-P. J. Am. Chem. Soc. 2008, 130, 4592–4593; (c)
Zhao, Y.-L.; Dichtel, W. R.; Trabolsi, A.; Saha, S.; Aprahamian, I.; Stoddart, J. F. J.
Am. Chem. Soc. 2008, 130, 11294–11296; (d) Chen, N.-C.; Lai, C.-C.; Liu, Y.-H.;
Peng, S.-M.; Chiu, S.-H. Chem.dEur. J. 2008, 14, 2904–2908.
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D.; Spencer, N.; Stoddart, J. F.; Tasker, P. A.; Williams, D. J. Angew. Chem., Int. Ed.
Engl. 1995, 34, 1865–1869; (b) Fyfe, M. C. T.; Stoddart, J. F. Adv. Supramol. Chem.
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D.; Han, J.-Y.; Cantrill, S. J.; Fang, L.; Stoddart, J. F. Angew. Chem., Int. Ed. 2008, 47,
7470–7474.
4.8. [2]Rotaxane 13-H$PF6
After evaporating (under reduced pressure) the solvent from
a mixture of DB24C8 (69 mg, 0.15 mmol), the dialkyne 10-H$PF6
(50 mg, 0.13 mmol), and silica gel (120 mg) in CH3NO2 (5 mL), the
solid obtained was mixed with 3,6-diphenyl-1,2,4,5-tetrazine
(180 mg, 0.78 mmol) and ball-milled at room temperature for 1 h.
The resulting solid mixture was transferred to a 5 mL flask, heated to
100 ꢁC for 3 days, and then purified chromatographically (SiO2:
MeOH/CH2Cl2, 2:98) to afford the [2]rotaxane 13-H$PF6 as a white
solid (115 mg, 72%). Mp¼117–118 ꢁC; 1H NMR (400 MHz, CD3CN):
4. (a) Orita, A.; Okano, J.; Tawa, Y.; Jiang, L.; Otera, J. Angew. Chem., Int. Ed. 2004, 43,
3724–3728; (b) Kihara, N.; Hinoue, K.; Takata, T. Macromolecules 2005, 38, 223–
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Chiu, S.-H. Angew. Chem., Int. Ed. 2008, 47, 4436–4439.
d
¼3.50 (s, 8H), 3.68–3.75 (m, 8H), 4.00–4.04 (m, 8H), 4.66 (t, J¼6 Hz,
4H), 6.79 (s, 8H), 7.12 (dd, J¼6, 2 Hz, 4H), 7.27–7.32 (m, 8H), 7.33–7.40
5. Yamawaki, J.; Ando, T. Chem. Lett. 1980, 533–536.
(m, 6H), 7.56–7.62 (m, 6H), 7.62–7.70 (br, 2H), 7.86 (s, 2H), 8.23 (dd,
J¼8, 2 Hz, 4H); 13C NMR (100 MHz, CD3CN):
¼53.0, 68.9, 71.0, 71.4,
d
6. After ball-milling the [2]pseudorotaxane formed from dipropargylammo-
nium tetrafluoroborate and 21C7 on SiO2 with 1,2,4,5-tetrazine, the
‘smallest [2]rotaxane’ was isolated in 81% yield; see: Hsu, C.-C.; Chen, N.-C.;
Lai, C.-C.; Liu, Y.-H.; Peng, S.-M.; Chiu, S.-H. Angew. Chem., Int. Ed. 2008, 47,
7475–7478.
7. (a) Cheng, P.-N.; Hung, W.-C.; Chiu, S.-H. Tetrahedron Lett. 2005, 46, 4239–4242;
(b) Cheng, P.-N.; Huang, P.-Y.; Li, W.-S.; Ueng, S.-H.; Hung, W.-C.; Liu, Y.-H.; Lai,
C.-C.; Peng, S.-M.; Chao, I.; Chiu, S.-H. J. Org. Chem. 2006, 71, 2373–2383; (c)
Chen, N.-C.; Huang, P.-Y.; Lai, C.-C.; Liu, Y.-H.; Peng, S.-M.; Chiu, S.-H. Chem.
Commun. 2007, 4122–4124.
113.3,122.1,125.8,127.9,128.9,129.4,129.8,130.2,130.3,130.6,130.9,
133.1, 136.9, 138.0, 138.4, 139.3, 148.1, 158.3, 159.0; HRMS (ESI): m/z
calcd for [13-H]þ (C70H68N5O8): 1106.5062; found: 1106.5068.
Acknowledgements
We thank the National Science Council for financial support
(NSC 95-2113-M-002-016-MY3).
8. For a description of the single-point method, see: (a) Ashton, P. R.; Chrystal, E.
J. T.; Glink, P. T.; Menzer, S.; Schiavo, C.; Spencer, N.; Stoddart, J. F.; Tasker, P. A.;
White, A. J. P.; Williams, D. J. Chem.dEur. J. 1996, 2, 709–728; (b) Ashton, P. R.;
Fyfe, M. C. T.; Hickingbottom, S. K.; Stoddart, J. F.; White, A. J. P.; Williams, D. J. J.
Chem. Soc., Perkin Trans. 2 1998, 2117–2124.
9. We used a similar approach to generate pseudorotaxanes on the surface of
silica gel for the efficient synthesis of our ‘smallest [2]rotaxane’; see Ref. 6.
10. A reaction temperature of 373 K was chosen because (i) the reaction proceeded
extremely slowly at temperatures below 353 K and (ii) significantly lower
yields were obtained for the reactions performed at temperatures above 383 K,
possibly because of the rapid sublimation of diphenyltetrazine 5.
Supplementary data
Spectroscopic data (1H and 13C NMR) for all purified [2]rotax-
anes. Supplementary data associated with this article can be found
in the online version, at doi:10.1016/j.tet.2008.12.082.