Synthesis of [2]- and [3]Rotaxanes by an End-Capping Approach Utilizing Urethane Formation

Article abstract of DOI:10.1246/bcsj.77.179

Several axle-shaped sec-ammonium salts having hydroxy groups at the terminal ends were allowed to react with 3,5-dimethylphenyl isocyanate in the presence of dibenzo-24-crown-8 ether (DB24C8) in CHCl₃ by the catalysis of dibutyltin dilaurate to afford the corresponding [2]rotaxanes in good yields. Several Lewis acids other than dibutyltin dilaurate were effective for the end-capping. Although N,N-dimethylacetamide was not a suitable solvent, the use of chlorobenzene and nitromethane as solvents gave the [2]rotaxane in high yields. When a C₂-chiral 26-membered crown ether, prepared from biphenyl-2,2′,6,6′-tetrol and L-tartaric acid, was employed instead of DB24C8, the corresponding optically active [2]rotaxane was isolated in 47% yield. The present method was successfully applied to the synthesis of [3]rotaxane by employing hexamethylene diisocyanate. Thus, end-capping by acid-catalyzed urethane formation from alcohol and isocyanate was demonstrated to be an effective protocol for the synthesis a variety of rotaxanes, based on the sec-ammonium salt/crown ether recognition motif.

Full text of DOI:10.1246/bcsj.77.179

ꢀ 2004 The Chemical Society of Japan
Bull. Chem. Soc. Jpn., 77, 179–185 (2004)
179
Synthesis of [2]- and [3]Rotaxanes by an End-Capping Approach
Utilizing Urethane Formation
Yoshio Furusho, Hisahiro Sasabe, Daisuke Natsui, Ken-ichi Murakawa,
y
ꢀ;
Toshikazu Takata, and Toshiro Harada1
Department of Applied Chemisty, Osaka Prefecture University, Sakai, Osaka 599-8531
1Department of Chemistry and Materials Technology, Kyoto Institute of Technology,
Matsugasaki, Sakyo-ku, Kyoto 606-8585
Received July 1, 2003; E-mail: ttakata@polymer.titech.ac.jp
Several axle-shaped sec-ammonium salts having hydroxy groups at the terminal ends were allowed to react with 3,5-
dimethylphenyl isocyanate in the presence of dibenzo-24-crown-8 ether (DB24C8) in CHCl3 by the catalysis of dibutyltin
dilaurate to afford the corresponding [2]rotaxanes in good yields. Several Lewis acids other than dibutyltin dilaurate were
effective for the end-capping. Although N,N-dimethylacetamide was not a suitable solvent, the use of chlorobenzene and
nitromethane as solvents gave the [2]rotaxane in high yields. When a C2-chiral 26-membered crown ether, prepared from
biphenyl-2,20,6,60-tetrol and L-tartaric acid, was employed instead of DB24C8, the corresponding optically active [2]ro-
taxane was isolated in 47% yield. The present method was successfully applied to the synthesis of [3]rotaxane by employ-
ing hexamethylene diisocyanate. Thus, end-capping by acid-catalyzed urethane formation from alcohol and isocyanate
was demonstrated to be an effective protocol for the synthesis a variety of rotaxanes, based on the sec-ammonium
salt/crown ether recognition motif.
Rotaxanes have recently attracted increasing attention for
the last two decades, because they are expected to be indispen-
sable motifs for nanometer-level devices or new materials with
unusual viscoelastic properties.1 Several recognition motifs that
can be exploited for rotaxane synthesis have been reported to
date. Among them, sec-ammonium salt/crown ether system
is the most versatile couple for the design of interlocked mole-
cules, because the synthetic methods of sec-ammonium salts
and crown ethers are well established and some of them are
commercially available.2 Numerous end-capping methods have
been investigated for the sec-ammonium/crown motif, includ-
ing amide formation,3a,b ester formation,3c,d 1,3-dipolar cyclo-
addition,3e Wittig reaction,3f disulfide formation by oxidation
of thiol,3g thiol–disulfide interchange reaction,3h,i radical Mi-
chael addition,3j and urea formation.3k,l The ester-forming and
disulfide-forming protocols ascertain high yields and have high
functional-group tolerance. However, from viewpoint of fur-
ther applications, ester3c,d and disulfide3g–i groups are not suffi-
ciently stable towards nucleophiles and electrophiles as well as
reducing and oxidizing agents. Although other protocols form
stable linkages, such as C=C bonds,3f the yields are often con-
siderably low.
number of them are commercially available. Therefore, syn-
thetic methods of rotaxanes by utilizing urethane formation
should be promising for the fabrication of interlocked systems
with high durability. In this paper, we report on a novel synthet-
ic procedure for [2]- and [3]rotaxanes by end-capping utilizing
urethane formation from alcohols and isocyanates (Scheme 1).
Results and Discussion
1. Synthesis of Axles. Axle-shaped sec-ammonium salts
having a hydroxy group at the end and a bulky end-capping
group at the other end (1 and 2 in Fig. 1) were synthesized as
reported previously.3c,5 Axles having a nitro group (3a) and a
carbomethoxy group (3b) were synthesized according to
Scheme 2. The treatment of 5-t-butylsalicylaldehyde (4) with
4-nitrobenzyl chloride in the presence of NaH gave the alde-
hyde (5a) in 54% yield. Reductive amination of 5a with 3-ami-
no-1-propanol afforded hydroxypropylamine (6a) in 65% yield,
which was further treated with HPF6 to produce ammonium salt
(3a) in 79% yield. Methoxycarbonyl-substituted axle (3b) was
similarly synthesized in high yield by using methyl 4-bromo-
methylbenzoate instead of 4-nitrobenzyl chloride, as shown
in Scheme 2.
Urethanes are known to be more stable than esters and disul-
fides towards chemical reagents, heating, and light irradiation.4
In general, they can be readily prepared by the addition of alco-
hols to isocyanates under mild conditions in high yields. In ad-
dition, isocyanates can be prepared from amines, and a large
2. Synthesis of Wheel. C2-Chiral 26-membered crown
ether (9) was synthesized from optically active biphenol6 (7)
which was prepared from biphenyl-2,20,6,60-tetrol and L-tarta-
ric acid (Scheme 3). Cesium ion-templated cyclization of 7
with ditosylate (8) gave 9 in 43% yield. The 1H NMR, IR,
and mass spectral data were consistent with the structure of 9.
3. Synthesis of Rotaxanes. The addition of dibenzo-24-
crown-8 ether (DB24C8) to a suspension of 1 (0.10 mmol) in
CDCl3 (0.60 mL) resulted in a colorless clear solution. The for-
y Present address: Department of Organic and Polymeric Materi-
als, Tokyo Institute of Technology, O-okayama, Meguro-ku,
Tokyo 152-8552
Published on the web January 13, 2004; DOI 10.1246/bcsj.77.179

180 Bull. Chem. Soc. Jpn., 77, No. 1 (2004)
Synthesis of [2]- and [3]Rotaxanes
O
H
H
N
H
N
2
2
+
OH
N
O C
OCN
Scheme 1. A schematic representation of the synthetic protocol for [2]rotaxanes utilizing urethane formation from alcohol and iso-
cyanate based on sec-ammonium/crown motif.
mation of the corresponding pseudorotaxane (1 DB24C8) was
ꢁ
confirmed by 1H NMR. 3,5-Dimethylphenyl isocyanate was
added, and the resulting solution was allowed to stand at ambi-
PF
PF
6
6
ent temperature for 13 h. However, no reaction proceeded un-
der these conditions. Although, in general, urethane formation
is known to proceed at higher temperature without a catalyst,
rotaxane synthesis should be conducted at low temperature, be-
cause the ratio of pseudorotaxane formation is lowered at high
temperatures.3i Upon the addition of a catalytic amount of dibu-
tyltin dilaurate (0.010 mmol), a reaction of the hydroxy group
t
Bu
N
OH
N
H
H
2
2
OH
t
Bu
1
2
Fig. 1.
of 1 DB24C8 with 3,5-dimethylphenyl isocyanate started. Af-
ter 13 h, the reaction mixture was subjected to preparative GPC
ꢁ
X
X
OH
O
O
(i)
(ii)
CHO
CHO
N
OH
H
t
t
t
Bu
Bu
Bu
6a: 65%
b: 95%
4
5a: 54%
b: 73%
X
a: X = NO
2
b: X = CO CH
2
3
PF
6
O
(iii)
N
OH
H
2
t
Bu
3a: 79%
b: 86%
ꢂ
Scheme 2. Reagents and conditions: (i) 4-nitrobenzyl chloride for 5a, methyl 4-bromomethylbenzoate for 5b, NaH/DMF, 100 C;
ꢂ
(ii) 3-amino-1-propanol/toluene, then NaBH4/MeOH; (iii) 5% HPF6aq, 0 C.
O
O
O
O
BnO
O
O
O
O
OTs
OTs
O
O
BnO
O
O
O
O
O
O
(R)
(R)
HO
HO
O
O
(S)
(R)
(R)
8
(S)
Cs CO /THF
reflux, 13 h
2
3
BnO
BnO
9
43%
7
Scheme 3. Synthesis of optically-active 26-membered crown ether (9).

Y. Furusho et al.
Bull. Chem. Soc. Jpn., 77, No. 1 (2004)
181
O
O
O
O
O
O
O
O
O
O
PF
6
PF
6
O
O
O
O
O (DB24C8)
t-Bu
N
OH
+
t-Bu
N
H
OH
2
H
2
CDCl
3
O
t-Bu
1
t-Bu
.
1 DB24C8
O
O
O
PF
6
O
O
O
O
OCN
n-Bu Sn(OCO-n-C
t-Bu
N
O
N
O
H
2
H
H )
11 23 2
2
O
CDCl , r.t., 13 h
3
t-Bu
10
80%
Scheme 4. Synthesis of [2]rotaxane (10).
Table 1. Effect of Catalyst on the Yield of [2]Rotaxane (10)
Table 2. Effect of Solvent on the Yield of [2]Rotaxane (10)
Yield of
10/%a)
Unreacted
1/%a)
Yield of
10/%a)
Unreacted
1/%a)
Entry
Catalyst
Entry
Solvent
1
2
3
4
5
n-Bu2Sn(OCO-n-C11H23)2
n-Bu2SnCl2
Et2O BF3
87
85
79
81
56
13
14
0
0
44
1
2
3
4
Chloroform
Chlorobenzene
Nitromethane
87
90
83
0
13
9
8
ꢁ
CF3SO3H
CF3CO2H
1
N,N-Dimethylacetamide
4
a) Estimated by 1H NMR.
a) Estimated by H NMR.
Table 3. Effect of Feed Ratio of DB24C8 on the Yield of
[2]Rotaxane (10)
to give [2]rotaxane (10) in 80% yield (Scheme 4). The structure
of 10 was confirmed by 1H NMR, IR, and mass spectroscopies
along with an elemental analysis.
Feed ratio of
DB24C8 to 1
Yield of
10/%a)
Unreacted
1/%a)
Entry
The effect of a catalyst on the yield of rotaxane was exam-
ined by using 1, DB24C8, and 3,5-dimethylphenyl isocyanate
as the building blocks for 10. A catalytic amount of an acid
(0.010 mmol) was added to a mixture of 1 (0.10 mmol),
DB24C8 (0.12 mmol), and 3,5-dimethylphenyl isocyanate
(0.15 mmol) in CHCl3 (0.60 mL). The reaction mixture was al-
lowed to stand at room temperature for 13 h and then evaporat-
ed to dryness. The mixture of the residue and naphthalene (0.10
mmol) was dissolved in CDCl3 (0.60 mL). The yield of 10 was
estimated by the 1H NMR, and is summarized in Table 1. In the
case of dibutyltin dilaurate, 10 was formed in 87% yield along
with 13% of unreacted 1 (entry 1). Similarly, dibutyltin dichlo-
ride gave 10 in 85% yield and 14% of unreacted 1 (entry 2). Di-
ethyl ether–boron trifluoride (1/1) and trifluoromethanesulfon-
ic acid afforded 10 in 79% and 81% yields, respectively (entries
3 and 4). However, in these cases, no unreacted 1 was observed.
In both cases, the adduct of 1 and 3,5-dimethylphenyl isocya-
nate was formed in ca. 20% yield. This means that the yields
of 10 do not increase even if the reaction times are prolonged.
The use of trifluoroacetic acid resulted in a reaction rate slower
than those of other catalysts under the same conditions (entry
5). Thus, several typical Lewis and Bronsted acids are available
for this end-capping protocol utilizing urethane formation. The
organotin reagents can be taken as the best among them from
the viewpoints of both the yield and the reaction rate.
1
2
3
1.0
1.2
2.0
81
87
89
19
13
11
a) Estimated by 1H NMR.
The effect of a solvent on the yield of rotaxane was investi-
gated under conditions similar to those employed in Table 1.
The results are summarized in Table 2. Chlorobenzene and ni-
tromethane gave good results, similarly to that obtained with
chloroform (entries 1–3). However, 10 was not yielded at all
by use of N,N-dimethylacetamide. Instead, the adduct of 1
and 3,5-dimethylphenyl isocyanate was formed in 96% yield.
This is accounted for by the fact that N,N-dimethylacetamide
prevents the hydrogen-bonding interaction, which is the main
driving force for the complexation between sec-ammonium salt
and crown ether7 (entry 4).
The effect of the feed ratio of DB24C8 to 1 on the yield of 10
was examined. As shown in Table 3, the yield of 10 increased
with an increase in the feed ratio of DB24C8. However, there
was no appreciable difference in the yield of 10 between the
feed ratios of 2.0 and 1.2.
Three axles other than 1 were employed for the synthesis of
[2]rotaxanes (Scheme 5). When axle (2), which is longer than 1,
was employed, 11 was obtained in 90% isolated yield. The high

182 Bull. Chem. Soc. Jpn., 77, No. 1 (2004)
Synthesis of [2]- and [3]Rotaxanes
O
O
O
O
O
O
O
O
O
DB24C8
PF
6
O
O
O
O
PF
6
N
H
O
O
H
2
N
H
O
N
O
2
OH
O
11
OCN
n-Bu Sn(OCO-n-C
2
H )
11 23 2
90%
2
CDCl , r.t., 48 h
3
X
X
O
O
O
O
O
O
DB24C8
PF
6
O
O
PF
O
O
6
O
t
O
t
O
O
O
O
N
H
OH
N
H
N
H
O
O
2
2
OCN
n-Bu Sn(OCO-n-C
O
O
Bu
Bu
H )
11 23 2
2
3a: X = NO
b: X = CO CH
2
2
CDCl , r.t., 20 h
3
12a: 57%
b: 64%
3
Scheme 5. Synthesis of [2]rotaxane (11 and 12).
O
O
O
O
BnO
PF
6
O
O
O
O
t-Bu
O
(R)
(R)
+
N
OH
(S)
H
O
2
BnO
t-Bu
1
9
(R)
BnO
OBn
(R)
O O
(S)
PF
6
O
O
O
O
O
t-Bu
N
OCN
n-Bu Sn(OCO-n-C
O
N
H
2
H
O
O
H )
11 23 2
2
O
O
CDCl , r.t., 13 h
3
t-Bu
47%
13
Scheme 6. Synthesis of optically-active [2]rotaxane (13).
yield suggests that the distance between the sec-ammonium salt
and hydroxy group has almost no effect on the yield of rotax-
ane. The use of 3a resulted in a lower yield (57%) of 12a, which
can be attributed to a steric repulsion between the DB24C8 ring
and the 4-nitrobenzyloxy group attached to the axle. Similarly,
under the same conditions. Thus, this protocol has high toler-
ance to the structure of the axle component, although the axles
having bulky substituents reduce the yield of rotaxane.
To examine the effect of the structure of the wheel compo-
nent, the C2-chiral 26-membered crown ether (9) was employed
for rotaxane synthesis (Scheme 6). The corresponding optically
active [2]rotaxane (13) was obtained in 47% isolated yield. The
[2]rotaxane, having
group on the axle component (12b), was obtained in 64% yield
a
4-methoxycarbonylphenylmethoxy

Y. Furusho et al.
Bull. Chem. Soc. Jpn., 77, No. 1 (2004)
183
O
O
O
O
O
O
DB24C8
PF
6
t-Bu
O
O
N
H
OH
2
OCN(CH ) NCO
2 6
n-Bu Sn(OCO-n-C
H )
t-Bu
1
2
11 23 2
CDCl , r.t., 48 h
3
PF
PF
6
6
O
O
O
O
O
O
O
(CH )
2 6
O
O
O
O
O
O
O
O
t-Bu
t-Bu
N
O
N
N
O
N
H
H
H
H
2
2
O
O
O
14
t-Bu
t-Bu
70%
Scheme 7. Synthesis of [3]rotaxane (14).
structure of 13 was confirmed by 1H NMR, IR, and FAB mass
spectroscopies. The yield of 13 was lower than those with the
24-membered crown ethers. This result is explained by the fact
that the 26-membered crown ether has much lower association
constants with sec-ammonium salts than those with the 24-
membered ones.8 In fact, the yield of 47% is comparable to that
reported for [2]rotaxane synthesis with a 26-membered crown
ether having a binaphthyl unit.3k The present end-capping pro-
tocol thus tolerates a structural modification of wheel compo-
nent. Furthermore, 9 has two benzyl ether-protected hydroxy
groups on its outer rim, which can be utilized as a scaffold
for introducing of additional functional groups.9
zyl chloride (6.87 g, 40.2 mmol) was added to the resulting yellow
suspension. The mixture was stirred at 100 ꢂC for 24 h. After being
cooled to room temperature, the mixture was poured into water
(100 mL) and extracted with ethyl acetate (200 mL ꢃ 1). The ex-
tract was washed with water (100 mL ꢃ 1) and brine (100 mL ꢃ 1),
dried over anhydrous MgSO4, filtered, and evaporated to dryness.
The residue was subjected to SiO2 column chromatography (elu-
ent: hexane/ethyl acetate (9/1)) to afford 5-t-butyl-2-(4-nitrophen-
ylmethoxy)benzaldehyde (5a) as a yellow heavy oil (1.69 g, 54%).
1H NMR (270 MHz, CDCl3) ꢁ 10.55 (s, 1H, CHO), 8.27 (d, J ¼ 9
Hz, 2H, ArH), 7.90 (d, J ¼ 3 Hz, 1H, Ar), 7.63 (d, J ¼ 9 Hz, 1H,
ArH), 7.57 (dd, J ¼ 9, 3 Hz, 1H, ArH), 6.92 (d, J ¼ 9 Hz, 1H,
ArH), 5.28 (s, 2H, ArCH2O), 1.31 (s, 9H, t-Bu). IR (NaCl) 1728
Bifunctional isocyanates can be used for [3]rotaxane synthe-
sis by this end-capping method. Hexamethylene diisocyanate
(ꢂC=O), 1520 (ꢂN=O), 1346 (ꢂN=O) cmꢄ1
.
2-(40-Methoxycarbonylphenylmethoxy)-5-t-butylbenzalde-
hyde (5b). 73% yield. A white solid. 1H NMR (270 MHz, CDCl3)
ꢁ 10.57 (s, 1H, CHO), 8.08 (d, J ¼ 8 Hz, 2H, Ar), 7.88 (d, J ¼ 2:6
Hz, 1H, ArH), 7.57–7.50 (m, 3H, ArH), 6.94 (d, J ¼ 9 Hz, 1H, Ar),
5.24 (s, 2H, ArCH2O), 3.93 (s, 3H, CH3OCO), 1.31 (s, 9H, t-Bu).
was allowed to react with the pseudorotaxane (1 DB24C8)
ꢁ
by the catalysis of dibutyltin dilaurate. The corresponding
[3]rotaxane (14) was isolated in 70% yield (Scheme 7).
In summary, the end-capping protocol utilizing acid-cata-
lyzed urethane-formating reaction was examined in the synthe-
sis of various [2]- and [3]rotaxanes. The method is based on the
sec-ammonium salt/crown ether recognition motif. Several
acids were effective for rotaxane synthesis. Furthermore, the
present protocol has a high tolerance for modifications of the
stuctures of both the axle and wheel components.
IR (NaCl) 1707 (ꢂC=O), 1684 (ꢂC=O) cmꢄ1
.
Amino Alcohol (6a). A mixture of aldehyde (5a, 2.10 g, 6.70
mmol), 3-amino-1-propanol (503 mg, 6.70 mmol), and toluene (50
mL) was refluxed for 2 h in a flask equipped with a Dean–Stark ap-
paratus. After evaporation of the solvent, NaBH4 (633 mg, 16.7
mmol) was added portionwise to a solution of the residue in meth-
anol (50 mL) with stirring. The mixture was stirred for 20 h at room
temperature. After evaporation of the solvent, the residue was
poured into water (50 mL), and extracted with CHCl3 (30 mL ꢃ
3). The extract was washed with aqueous 10% NaOH (30 mL ꢃ
1), and brine (30 mL ꢃ 1), dried over anhydrous Na2SO4, filtered
and evaporated to dryness. The residue was subjected to SiO2 col-
umn chromatography (eluent: CHCl3/methanol (9/1)) to afford
Experimental
General. The melting points were measured on a Yanagimoto
micro melting-point apparatus and were uncorrected. IR spectra
were recorded on a JASCO FT-IR model 230 spectrometer. 1H
and 13C NMR measurements were performed on JEOL JNM-
GX-270 and JNM-L-400 spectrometers in CDCl3 with tetrameth-
ylsilane as an internal reference. FAB-MS measurements were per-
formed on a Finnigan TSQ-70 instrument. For preparative HPLC, a
JAICO LC-908 system using columns JAIGEL 1 (ꢀ 20 mm ꢃ 600
mm) and JAIGEL 2 (ꢀ 20 mm ꢃ 600 mm) was used.
1
amino alcohol (6a) as a yellow heavy oil (1.61 g, 65%). H NMR
(270 MHz, CDCl3) ꢁ 8.26 (d, J ¼ 9 Hz, 2H, ArH), 7.59 (d, J ¼ 9
Hz, 2H, ArH), 7.29–7.20 (m, 2H, ArH), 6.78 (d, J ¼ 9 Hz, 1H,
ArH), 5.19 (s, 2H, ArCH2O), 3.86 (s, 2H, ArCH2N), 3.81 (t, J ¼
5 Hz, 2H, CH2OH), 2.90 (t, J ¼ 6 Hz, 2H, NCH2CH2), 2.04–
1.67 (m, 5H, NH2, OH and CH2CH2CH2), 1.30 (s, 9H, t-Bu). IR
5-t-Butyl-2-(4-nitrophenylmethoxy)benzaldehyde (5a). To a
suspension of NaH (60% in oil, 536 mg, 13.4 mmol) in DMF (20
mL) was added dropwise a solution of 5-t-butylsalicylaldehyde (4,
2.01 g, 11.2 mmol) in DMF (10 mL) at room temperature under an
Ar atmosphere. After the evolution of H2 had stopped, 4-nitroben-
(NaCl) 3306 (ꢂN{H and ꢂO{H), 1521 (ꢂN=O), 1345 (ꢂN=O) cmꢄ1
.
Amino Alcohol (6b). 95% yield. A colorless oil. 1H NMR (270
MHz, CDCl3) ꢁ 8.07 (d, J ¼ 8 Hz, 2H, ArH), 7.48 (d, J ¼ 9 Hz,
2H, ArH), 7.26–7.20 (m, 2H, ArH), 6.81 (d, J ¼ 9 Hz, 1H,

184 Bull. Chem. Soc. Jpn., 77, No. 1 (2004)
Synthesis of [2]- and [3]Rotaxanes
ArH), 5.14 (s, 2H, ArCH2O), 3.93 (s, 3H, CH3OCO), 3.85 (s, 2H,
ArCH2N), 3.81 (t, J ¼ 5 Hz, 2H, CH2OH), 2.87 (t, J ¼ 6 Hz, 2H,
NCH2CH2), 1.73–1.66 (m, 5H, NH2, OH and CH2CH2CH2), 1.30
FAB-MS (matrix: mNBA) m=z 874.1 [(M ꢄ PF6)þ]. For elemental
analysis, recrystallization was carried out by use of CHCl3/
hexane. Found: C, 60.95; H, 7.26; N, 2.38%. Calcd for
(s, 9H, t-Bu). IR (NaCl) 1722 (ꢂC=O), 1612 (ꢂC=O) cmꢄ1
.
C51H73F6N2O10P (C6H14)0:5: C, 61.06; H, 7.59; N, 2.64%.
ꢁ
Axle (3a). To a solution of amino alcohol (6a, 1.60 g, 4.30
mmol) in methanol (10 mL) was slowly added dropwise an aque-
ous 5% HPF6 solution (72 mL) at 0 ꢂC. The resulting yellow paste
was collected and dissolved in CHCl3 (50 mL). The solution was
washed with water (50 mL ꢃ 1), dried over anhydrous MgSO4, fil-
tered, and evaporated to dryness. The resulting yellow solid was re-
crystallized from hexane/ethyl acetate to affored axle (3a) as a yel-
lowish-white solid (1.76 g, 79%). Mp 131–133 ꢂC. 1H NMR (270
MHz, CD3CN) ꢁ 8.25 (d, J ¼ 9 Hz, 2H, ArH), 7.58 (d, J ¼ 8:9 Hz,
2H, ArH), 7.46–7.43 (m, 2H, Ar), 7.13 (br s, 2H, NH2), 6.97 (d,
J ¼ 9 Hz, 1H, ArH), 5.31 (s, 2H, ArCH2O), 4.24 (t, J ¼ 5:8 Hz,
2H, ArCH2N), 3.66 (t, 2H, J ¼ 6 Hz, CH2OH), 3.22–3.12 (m,
2H, NCH2CH2), 2.18 (br s, 1H, OH), 1.86–1.78 (m, 2H,
CH2CH2CH2), 1.29 (s, 9H, t-Bu). IR (KBr) 3559, 3220, and
[2]Rotaxane (11). 90% yield. A white foamy solid. Mp 75–80
ꢂC. 1H NMR (270 MHz, CDCl3) ꢁ 7.57 (br s, 2H, NH2), 7.4–6.65
(m, 18H, ArH), 5.09 (s, 2H, ArCH2O), 4.59 (m, 2H, ArCH2N),
4.41 (m, 2H, ArCH2N), 4.10 (m, 8H, CH2 of DB24C8), 3.75 (m,
8H, CH2 of DB24C8), 3.41 (m, 8H, CH2 of DB24C8), 2.26 (s,
6H, CH3), 2.14 (s, 6H, CH3). IR (NaCl) 3394 and 3151 (ꢂN{H),
1710 (ꢂC=O), 843 and 557 (ꢂP{F) cmꢄ1. FAB-MS (matrix: mNBA)
m=z 851.4 [(M ꢄ PF6)þ]. Found: C, 57.73; H, 6.35; N, 2.56%.
Calcd for C50H63F6N2O10P (H2O)2:5: C, 57.63; H, 6.58; N, 2.69%.
ꢁ
[2]Rotaxane (12a). 57% yield. A clear pale yellow film.
1H NMR (270 MHz, CD3CN) ꢁ 8.08 (d, J ¼ 9 Hz, 2H), 7.50 (d,
J ¼ 9 Hz, 1H), 7.40–7.37 (m, 2H), 7.22–7.18 (m, 2H), 6.98 (s,
2H), 6.91–6.84 (m, 9H), 6.70 (s, 1H), 6.58 (d, J ¼ 9 H, 1H),
4.96 (s, 2H), 4.66–4.61 (m, 2H), 4.13–3.97 (m, 11H), 3.86–3.80
(m, 4H), 3.72–3.61 (m, 10H), 3.57–3.49 (m, 3H), 2.23 (s, 6H),
2.04–1.96 (m, 2H), 1.18 (s, 9H). IR (KBr) 3397 (ꢂN{H), 1730
3189 (ꢂO{H), 1531 (ꢂN=O), 1346 (ꢂN=O), 851 and 559 (ꢂP{F
)
cmꢄ1. FAB-MS (matrix: mNBA) m=z 373 [(M ꢄ PF6)þ]. Found:
C, 48.96; H, 5.67; N, 5.45%. Calcd for C21H29F6N2O4P: C,
48.65; H, 5.65; N, 5.40%.
(ꢂC=O), 1506 (ꢂN=O), 1346 (ꢂN=O), 844 and 557 (ꢂP{F) cmꢄ1
.
FAB-MS (matrix: mNBA) m=z 969.9 [(M ꢄ PF6)þ]. Found: C,
Axle (3b). 86% yield. A white solid. Mp 121–124 ꢂC. 1H NMR
(270 MHz, CD3CN) ꢁ 8.02 (d, J ¼ 9 Hz, 2H, ArH), 7.59 (d, J ¼ 9
Hz, 2H, ArH), 7.44–7.41 (m, 2H, ArH), 6.97 (d, J ¼ 8:9 Hz, 1H,
ArH), 5.26 (s, 2H, ArCH2O), 4.21 (s, 2H, ArCH2N), 3.87 (s, 3H,
CH3OCO), 3.64 (t, J ¼ 6 Hz, 2H, CH2OH), 3.15 (t, J ¼ 6:1 Hz,
2H, NCH2CH2), 2.18 (br s, 1H, OH), 1.85–1.76 (m, 2H,
CH2CH2CH2), 1.28 (s, 9H, t-Bu). IR (KBr) 3228 and 3190
(ꢂO{H), 1728 (ꢂC=O), 850 and 559 (ꢂP{F) cmꢄ1. FAB-MS (matrix:
mNBA) m=z 386 [(M ꢄ PF6)þ]. Found: C, 51.87; H, 5.95; N,
2.70%. Calcd for C23H32F6NO4P: C, 51.98; H, 6.07; N, 2.64%.
26-Membered Chiral Crown Ether (9). A mixture of diol (7,
845 mg, 1.74 mmol) and cesium carbonate (2.26 g, 6.96 mmol) in
THF (44 mL) was refluxed under Ar atmosphere for 30 min. To the
resulting white suspension was added dropwise a solution of dito-
sylate (8, 1.18 g, 1.74 mmol) in THF (26 mL). The mixture was re-
fluxed for 13 h. After being cooled to room temperature, the mix-
ture was filtered. The filtrate was extracted with CHCl3 (100 mL ꢃ
1). The extract was washed with 2 M HCl (50 mL ꢃ 1) and water
(50 mL ꢃ 1), dried over anhydrous MgSO4, filtered, and evaporat-
ed to dryness. The residue was subjected to Al2O3 column chroma-
tography (eluent: hexane/ethyl acetate (1/1)) to afford crown ether
56.09; H, 5.92; N, 3.67%. Calcd for C54H70F6N3O13P (CHCl3)0:5
:
ꢁ
C, 55.77; H, 6.05; N, 3.58%.
[2]Rotaxane (12b). 64% yield. A colorless film. 1H NMR (270
MHz, CD3CN) ꢁ 7.87 (d, J ¼ 8 Hz, 2H), 7.41–7.35 (m, 4H), 7.20–
7.16 (m, 2H), 6.98 (s, 2H), 6.91–6.88 (m, 9H), 6.70 (s, 1H), 6.56 (d,
J ¼ 8:6 Hz, 1H), 4.92 (s, 2H), 4.63–4.58 (m, 2H), 4.13–3.97 (m,
11H), 3.84–3.79 (m, 7H), 3.71–3.61 (m, 10H), 3.54–3.48 (m,
3H), 2.23 (s, 6H), 2.01–1.96 (m, 2H), 1.17 (s, 9H). IR (KBr)
3391 (ꢂN{H), 1722 (ꢂC=O), 1613 (ꢂC=O), 844 and 557 (ꢂP{F
)
cmꢄ1. FAB-MS (matrix: mNBA) m=z 981.5 [(M ꢄ PF6)þ]. Found:
C, 56.91; H, 6.05; N, 2.44%. Calcd for C56H73F6N2O13P
(CHCl3)0:5: C, 57.18; H, 6.24; N, 2.36%.
ꢁ
Chiral [2]Rotaxane (13). To a solution of axle (1, 42.3 mg,
0.10 mmol), crown ether (9, 91.8 mg, 0.110 mmol), and 3,5-di-
methylphenyl isocyanate (22 mg, 0.15 mmol) in CHCl3 (0.60
mL) was added dibutyltin dilaurate (6.3 mg, 0.010 mmol). The
mixture was stirred at room temperature for 66 h. After evapora-
tion, the residue was subjected to preparative GPC (eluent: CHCl3)
to afford chiral [2]rotaxane (13) as a colorless heavy oil (66 mg,
47%). 1H NMR (270 MHz, CDCl3) ꢁ 7.42 (t, J ¼ 2 Hz, 1H,
ArH), 7.37–7.25 (m, 13H, ArH), 7.10 (t, J ¼ 7:8 Hz, 1H, ArH),
6.98–6.79 (m, 10H, ArH), 6.67 (br s, 1H, NH), 6.34 (d, J ¼ 7:8
Hz, 1H, ArH), 4.7–3.0 (m, 40H, CH2 and CH), 2.25 (s, 6H,
CH3), 1.99 (m, 2H, CH2), 1.25 (s, 18H, t-Bu). IR (KBr) 3395
1
(9) as a colorless heavy oil (620 mg, 43%). H NMR (270 MHz,
CDCl3) ꢁ 7.38–7.16 (m, 12H, ArH), 6.90 (s, 4H, ArH), 6.82 (dd,
J ¼ 7, 1 Hz, 2H, ArH), 6.72 (dd, J ¼ 7, 1 Hz, 2H, ArH), 4.55 (s,
4H, CH2Ph), 4.20–3.56 (m, 30H, CH2O and CHO). FAB-MS (ma-
trix: mNBA) m=z 822.3 [Mþ]. Found: C, 66.13; H, 5.90%. Calcd
(ꢂN{H), 1729 (ꢂC=O), 1613 (ꢂC=O), 843 and 557 (ꢂP{F) cmꢄ1
.
FAB-MS (matrix: mNBA) m=z 1247.6 [(M ꢄ PF6)þ]. Found: C,
for C48H54O12 (H2O)0:5: C, 66.00; H, 6.22%.
63.63; H, 7.04; N, 2.27%. Calcd for C75H95F6N2O14P (H2O)1:
C, 63.82; H, 6.93; N, 1.98%.
ꢁ
ꢁ
[2]Rotaxane (10). To a solution of axle (1, 0.10 mmol),
DB24C8 (54 mg, 0.12 mmol), and 3,5-dimethylphenyl isocyanate
(22 mg, 0.15 mmol) in CHCl3 (0.60 mL) was added dibutyltin di-
laurate (6.3 mg, 0.010 mmol). The mixture was stirred at room
temperature for 13 h and was evaporated to dryness. The residue
was subjected to preparative GPC (eluent: CHCl3) to afford [2]ro-
[3]Rotaxane (14). To a solution of axle (1, 85 mg, 0.20 mmol),
DB24C8 (180 mg, 0.40 mmol), and hexamethylene diisocyanate
(16 mL, 0.10 mmol) in CHCl3 (1.0 mL) was added dibutyltin dilau-
rate (12 mL, 0.020 mmol). The mixture was stirred at room temper-
ature for 48 h and was evaporated to dryness. The residue was sub-
jected to preparative GPC (eluent: CHCl3) to afford [2]rotaxane
(10) as a white solid (140 mg, 70%). 1H NMR (CDCl3, 270
MHz) ꢁ 7.35–7.27 (m, 6H, ArH), 6.87 (s, 16H, ArH of
DB24C8), 4.69–4.67 (m, 4H, ArCH2N), 4.27–3.02 (m, 60H,
CH2), 2.03–0.90 (m, 44H, CH2 and t-Bu). IR (NaCl) 3426
(ꢂN{H), 1729 (ꢂC=O), 843 and 557 (ꢂP{F) cmꢄ1. FAB-MS (matrix:
mNBA): m=z 1621.4 [(M ꢄ 2PF6)þ]. Found: C, 55.39; H, 6.94; N,
ꢂ
taxane (10) as a white foamy solid (81 mg, 80%). Mp 72–75 C.
1H NMR (270 MHz, CDCl3) ꢁ 7.41 (br s, 1H, NHCO), 7.33 (t, J ¼
2:0 Hz, 1H, ArH), 7.29 (d, J ¼ 2:0 Hz, 2H, ArH), 7.05 (s, 2H,
ArH), 6.89 (s, 8H, ArH of DB24C8), 6.65 (s, 1H, ArH), 4.71 (m,
2H, CH2), 4.4–3.3 (m, 28H, CH2 of DB24C8 and dumbbell),
2.25 (s, 6H, CH3), 1.85 (m, 2H, CH2), 1.19 (s, 18H, t-Bu). IR
(NaCl) 3304 (ꢂN{H), 1710 (ꢂC=O), 843 and 557 (ꢂP{F) cmꢄ1
.

Y. Furusho et al.
Bull. Chem. Soc. Jpn., 77, No. 1 (2004)
185
2.81%. Calcd for C92H140F12N4O20P2 (CHCl3)1: C, 54.99; H,
ꢁ
A. M. Heiss, J. F. Stoddart, A. J. P. White, and D. J. Williams,
Chem. Commun., 1999, 1251. l) S. J. Cantrill, D. A. Fulton, M.
C. T. Fyfe, J. F. Stoddart, A. J. P. White, and D. J. Williams, Tet-
rahedron Lett., 40, 3669 (1999).
7.00; N, 2.76%.
This work was financially supported by Grant-in-Aid for Sci-
entific Research on Priority Areas (A), (No. 413/14045262)
from the Ministry of Education, Culture, Sports, Science and
Technology. We are grateful to Professor K. Osakada of Tokyo
Institute of Technology for the elemental analyses.
4
‘‘Advances in Urethane Science and Technology,’’ ed by K.
C. Frisch and D. Klempner, Rapra Technology, Shrewbury (2001).
T. Takata, H. Kawasaki, N. Kihara, and Y. Furusho, Macro-
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