69451 weinheim, germany · yi-lin huang, wei-chung hong, chien-chen lai, yi-hung liu, shie-ming...

Supporting Information

© Wiley-VCH 2007

69451 Weinheim, Germany

1

Using Acetate Anions to Induce Translational Isomerization in a Neutral

Urea-Based Molecular Switch

Yi-Lin Huang, Wei-Chung Hong, Chien-Chen Lai, Yi-Hung Liu, Shie-Ming Peng, and Sheng-Hsien Chiu*

Data Page Number

Experimental procedures and characterization data for all new compounds ............. S2–S6

Dilution isotherm for macrocycle 1 and urea-based thread 4 in CDCl3....................... S7

Dilution isotherm/Job plot for macrocycle 1 and urea-based thread 3 in CDCl3......... S7–S8

1H and 13C NMR spectra of 2....................................................................................... S9–S10

1H and 13C NMR spectra of macrocycle 1 ................................................................... S11–S12


1H and 13C NMR spectra of III .................................................................................... S15–S16


1H and 13C NMR spectra of the [2]rotaxane 9 ............................................................. S19–S20

1H and 13C NMR spectra of V ...................................................................................... S21–S22


1H and 13C NMR spectra of the [2]rotaxane 6 ............................................................. S25–S26

1H, 13C, 2D COSY, and NOSY NMR spectra of the [2]rotaxane 7.............................. S27–S32

2D COSY and NOSY NMR spectra of the [2]rotaxane 7 + TMAA (5 eq).................. S33–S37

2

General Methods: 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 by distillation from

CaH2 under N2. Anhydrous THF was obtained by distillation from Na/Ph2CO under N2.

Reactions were conducted under N2 or Ar atmospheres. Thin-layer chromatography (TLC)

was performed on Merck 0.25 mm silica gel (Merck Art. 5715). Column chromatography

was undertaken over Kieselgel 60 (Merck, 70–230 mesh). Melting points are uncorrected.

In NMR spectra, the deuterated solvent was used as the lock, while either the solvent’s

residual protons or TMS was employed as the internal standard. Chemical shifts are

reported in parts per million (ppm). Mutiplicities are given as s (singlet), d (doublet), t

(triplet), q (quartet), m (mutiplet), and br (broad).

Diethylene glycol 4-cyanobenzyl ether (2): NaH (0.57 g, 14.2 mmol) was added to a DMF

solution (20 mL) of diethylene glycol (0.45 mL, 4.7 mmol) and the solution mixture was

stirred at room temperature for 1 h before added 4-cyanobenzylbromide (2.21 g 11.3 mmol).

The solution mixture was then stirred at room temperature for 16 h and the organic solvent

was evaporated under reduced pressure. The residue was then purified by column

chromatography (SiO2; CH2Cl2/hexanes, 7:3) to give compound 2 as a yellow liquid (1.42 g,

90%). 1H NMR (400 MHz, CDCl3): δ = 3.63−3.68 (m, 8H), 4.58 (s, 4H), 7.40 (d, J = 8.4

Hz, 4H), 7.56 (d, J = 8.4 Hz, 4H); 13C NMR (100 MHz, CDCl3): δ = 70.0, 70.5, 72.1, 110.8,

118.4, 127.2, 131.6, 143.3. HRMS (ESI): m/z calcd for [M + H]+ C20H21N2O3 337.1552, found

337.1559.

Macrocycle 1: LiAlH4 (0.40 g, 10.5 mmol) was added to a THF solution (40 mL) of 2 (0.56 g,

1.7 mmol) and the solution mixture was heated under reflux for 4 h. After cooled to room

temperature, the reaction was quenched by slowly added water. The precipitation was then

filtered off, and the filtrate was dried (MgSO4) and concentrated to yield the desired diamine

as a light yellow oil (0.40 g, 70%). The crude diamine was dissolved in methanol and

methyl 2,6-pyridine dicarboxylate (0.22 g, 1.1 mmol) was added. The solution mixture was

then stirred at 50 °C for 6 d and the organic solvent was evaporated under reduced pressure.

The residue was then purified by column chromatography (SiO2; CH2Cl2/methanol, 99:1) to

3

give macrocycle 1 as a white solid (0.11 g, 20%). m.p. 241−242 °C; 1H NMR (400 MHz,

CDCl3): δ = 3.70 (m, 8H), 4.57 (s, 4H), 4.63 (d, J = 5.2 Hz, 4H), 7.22 (d, J = 7.6 Hz, 4H),

7.29 (d, J = 7.6 Hz, 4H), 7.94 (br, 2H), 8.02 (t, J = 8 Hz, 1H), 8.30 (d, J = 8 Hz, 2H); 13C

NMR (100 MHz, CDCl3): δ = 43.4, 69.7, 70.9, 72.8, 124.7, 127.0, 127.8, 136.5, 137.3,

139.0, 147.9, 162.7; HRMS (ESI): m/z calcd for [M]+ C27H29N3O5 475.2107, found 475.2129.

NH2O1. Triphosgene / Et3N

2. II

O

3

ON N

O

HH

1,3-Bis(4-(hexyloxy)phenyl)urea (3): A solution of triethylamine (0.66 mL, 4.7 mmol) and

4-hexyloxyaniline (I; 0.4 g, 2.07 mmol) in benzene (25 mL) was added to a solution of

triphosgene (0.31 g, 1.05 mmol) in benzene (25 mL). The mixture was stirred at room

temperature for 6 h, filtered, and then concentrated under reduced pressure. The resulting

isocyanate was dissolved in acetone (5 mL); 4-hexyloxyaniline (0.4 g, 2.07 mmol) was added

and the mixture stirred at room temperature for 2 h. The solvent was evaporated under

reduced pressure and the residue recrystallized from ethyl alcohol to afford 3 as a white solid

(0.48 g, 56% for two steps). M.p. 184.1−184.6 °C; 1H NMR (400 MHz, CD3SOCD3): δ =

0.88 (t, J = 6.4 Hz, 6H), 1.22−1.41 (m, 12H), 1.68 (quint, J = 6.4 Hz, 4H), 3.89 (t, J = 6.4 Hz,

4H), 6.82 (d, J = 9.2 Hz, 4H), 7.30 (d, J = 9.2 Hz, 4H), 8.33 (br, 2H); 13C NMR (100 MHz,

CD3SOCD3): δ = 14.0, 22.2, 25.3, 28.8, 31.1, 67.5, 114.4, 119.7, 132.6, 152.7, 153.5;

HRMS (ESI): m/z calcd for [M + H]+ C25H37N2O3 413.2799, found 413.2804.

O

HN

HN

O OHSi

8

NH2

OSi

NH2

OH

TIPSCl

1. Triphosgene / Et3N

2. II

II

III

4-(Triisopropylsilyloxymethyl)aniline (III): A solution of 4-aminobenzyl alcohol (II; 2 g,

16 mmol) in DMF (40 mL) was treated with imidazole (1.06 g, 16 mmol) and TIPSCl (3.4

mL, 16 mmol). The resulting solution was stirred at room temperature for 12 h, diluted with

EtOAc (200 mL), washed with brine, dried (MgSO4), and concentrated. The residue was

4

purified through chromatography (SiO2; EA/Hex, 1:4) to afford compound III as a clear oil

(3.8 g, 84%). 1H NMR (400 MHz, CDCl3): δ = 1.08−1.22 (m, 21 H), 3.59 (br, 2H), 4.70 (s,

2H), 6.64 (d, J = 8.4 Hz, 2H), 7.13 (d, J = 8.4 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ =

12.4, 18.4, 64.9, 114.5, 126.7, 131.1, 144.6; HRMS (ESI): m/z calcd for [M + H]+

C16H30NOSi 280.2091, found 280.2097.

8: Triphosgene (0.28 g, 0.94 mmol), triethylamine (0.6 mL, 4.3 mmol) and III (0.5 g, 1.79

mmol) were added to benzene (50 mL) and then stirred at room temperature for 6 h. The

resulting suspension was filtered and the solvent evaporated under reduced pressure. The

crude isocyanate was dissolved in acetone (5 mL); 4-aminobenzyl alcohol (II) (0.5 g, 4.05

mmol) was added and the mixture stirred at room temperature for 2 h. The solution was

concentrated and the residue purified through chromatography (SiO2; EA/Hex, 1:1) to afford

compound 8 as a white solid (0.4 g, 52%). M.p. 158−159 °C; 1H NMR (400 MHz, CDCl3):

δ = 1.10−1.20 (m, 21H), 4.33 (s, 2H), 4.70 (s, 2H), 6.94 (m, 4H), 7.17 (m, 4H), 7.61 (s, 1H),

7.70 (s, 1H); 13C NMR (100 MHz, CDCl3): δ = 12.5, 18.5, 64.4, 64.8, 119.9, 120.3, 126.1,

127.3, 135.2, 136.3, 136.5, 137.0, 153.7; HRMS (ESI): m/z calcd for [M + Na]+

C24H36N2NaO3Si 451.2387, found 451.2393.

O

HN

HN

O

5

OH

O

HN

HN

OH

NH2

1. Triphosgene / Et3N

2. H2N

OH

Br OH

IV

V

K2CO3

1-(3,5-Di-tert-butylphenyl)-3-(4-hydroxyphenyl)urea (V): Triphosgene (0.36 g, 1.22 mmol),

triethylamine (0.8 mL, 5.69 mmol), and 3,5-di-tert-butylaniline (IV) (0.5 g, 2.43 mmol) were

added to benzene (70 mL) and the mixture stirred at room temperature for 6 h. The resulting

suspension was filtered off and the solvent evaporated under reduced pressure. The resulting

isocyanate was dissolved in acetone (5 mL); 4-aminobenzyl alcohol (0.5 g, 4.05 mmol) was

added and the mixture stirred at room temperature for 2 h. The solution was concentrated

and the residue purified through chromatography (SiO2; EA/Hex, 1:2) to afford V as a white

5

solid (0.8 g, 97%). M.p. 238.1–238.8 °C; 1H NMR (400 MHz, CD3SOCD3): δ = 1.27 (s,

18H), 6.67 (d, J = 8.8 Hz, 2H), 6.98 (s, 1H), 7.2 (d, J = 8.8 Hz, 2H), 7.26 (s, 1H), 8.2 (s, 1H),

8.43 (s, 1H), 9.05 (s, 1H); 13C NMR (100 MHz, CD3SOCD3): δ =31.3, 34.6, 112.4, 115.0,

115.2, 120.3, 131.0, 139.1, 150.4, 152.2, 152.7; HRMS (ESI): m/z calcd for [M + H]+

C21H29N2O2 341.2224, found 341.2229.

5: K2CO3 (3.25 g, 23.5 mmole) and 5-bromo-1-pentanol (0.43 ml, 3.2 mmol) were added to a

DMF (25 mL) solution of V (0.8 g, 2.35 mmol). The resulting mixture was stirred at 90 °C

for 12 h, filtered, and concentrated under reduced pressure. The residue was then partitioned

between CH2Cl2 (25 mL) and H2O (25 mL) and the organic solution was dried (MgSO4) and

concentrated. The crude product was then purified through chromatography (SiO2; EA/Hex,

1:1) to afford 5 as a white solid (0.52 g, 52%). M.p. 197.8−198.3 °C; 1H NMR (400 MHz,

CDCl3): δ = 1.26 (s, 18H), 1.51 (quint, J = 6.8 Hz, 2H), 1.62 (quint, J = 6.8 Hz, 2H), 1.77

(quint, J = 6.8 Hz, 2H), 3.65 (br, 2H), 3.88 (t, J = 6.8 Hz, 2H), 6.76−6.88 (m, 4H), 7.13−7.20

(m, 5H); 13C NMR (100 MHz, CD3SOCD3): δ = 22.3, 29.0, 31.4, 32.4, 34.9, 62.7, 68.1,

115.1, 115.9, 118.4, 123.7, 130.7, 137.4, 152.0, 154.3, 156.1; HRMS (ESI): m/z calcd for [M

+ Na]+ C26H38N2NaO3 449.2775, found 449.2780.

Rotaxane 6: Di-n-butyl dilaurate (0.03 mL, 0.045 mmol) was added to a CH2Cl2 solution (3

mL) of 5 (0.13 g, 0.3 mmol), macrocycle 1 (0.17 g, 0.36 mmol), and 4-triphenylmethylphenyl

isocyanate (0.13 g, 0.36). After the mixture had been stirred at room temperature for 24 h,

the precipitate was filtered off and the organic solution concentrated under reduced pressure.

The residue was purified by chromatography (SiO2; CH2Cl2/MeOH, 99:1) to afford rotaxane 6

as a white solid (85 mg, 23%). M.p. 126−127 °C; 1H NMR (400 MHz, CDCl3): δ = 1.27

(s, 18H), 1.53 (quint, J = 6.2 Hz, 2H), 1.63–1.80 (m, 4H), 3.52–3.65 (m, 4H), 3.68–3.73 (m,

4H), 3.82 (t, J = 6.2 Hz, 2H), 4.07–4.20 (m, 4H), 4.31 (s, 4H), 4.58–4.66 (m, 2H), 6.32 (br,

2H), 6.47 (d, J = 8.8 Hz, 2H), 6.78 (d, J = 8 Hz, 4H), 6.83 (d, J = 8 Hz, 4H), 6.90 (d, J = 8.8

Hz, 2H), 7.01 (s, 1H), 7.02 (s, 2H), 7.07–7.29 (m, 20H), 8.04 (t, J = 8 Hz, 1H), 8.43 (d, J = 8

Hz, 2H), 9.45 (br, 2H); 13C NMR (100 MHz, CDCl3): δ = 22.7, 28.8, 29.1, 31.5, 34.9, 43.7,

64.4, 65.0, 67.8, 68.4, 70.6, 73.8, 112.6, 113.9, 115.4, 117.4, 119.2, 125.0, 125.7, 127.3, 128.0,

128.9, 130.9, 131.5, 132.2, 134.9, 135.7, 137.1, 138.2, 138.6, 141.4, 146.6, 149.3, 150.7,

152.1, 153.5, 153.7, 164.0; HRMS (ESI): m/z calcd for [M + Na]+ C79H86N6NaO9 1285.6348,

found 1285.6354.

6

Rotaxane 7: Di-n-butyl dilaurate (0.02 mL, 0.03 mmol) was added to a CH2Cl2 (2 mL)

solution of 5 (92 mg, 0.22 mmol), macrocycle 1 (0.1 g, 0.21 mmol), and

3,5-di-tert-butylphenyl isocyanate (0.13 g, 0.36 mmol). After the mixture had been stirred at

room temperature for 24 h, the precipitate was filtered off and the organic solution

concentrated under reduced pressure. The residue was purified through chromatography

(SiO2; EA/Hex, 1:1) to afford rotaxane 7 as a white solid (48 mg, 20%). M.p. 100−101 °C; 1H NMR (400 MHz, CDCl3): δ = 1.27 (s, 18H), 1.30 (s, 18H), 1.56 (quint, J = 6.4 Hz, 2H),

1.70–1.82 (m, 4H), 3.56–3.68 (m, 4H), 3.71–3.74 (m, 4H), 3.84 (t, J = 6.4 Hz, 2H), 4.13–4.21

(m, 4H), 4.31 (s, 4H), 4.58–4.65 (m, 2H), 6.33 (s, 1H), 6.35 (s, 1H), 6.48 (d, J = 8.6 Hz, 2H),

6.78 (d, J = 8 Hz, 4H), 6.83 (d, J = 8 Hz, 4H), 6.90 (d, J = 8.6 Hz, 2H), 7.00 (s, 1H), 7.01 (s,

2H), 7.11 (s, 1H), 7.22–7.25 (br, 3H), 8.06 (t, J = 8 Hz, 1H), 8.43 (d, J = 8 Hz, 2H), 9.51 (br,

2H); 13C NMR (100 MHz, CDCl3): δ = 22.7, 28.9, 29.1, 31.4, 31.5, 34.9, 35.0, 43.7, 64.9,

67.8, 68.4, 70.6, 73.8, 112.5, 113.2, 113.9, 115.3, 117.3, 119.0, 124.9, 128.0, 128.9, 132.2,

134.8, 137.0, 137.2, 138.2, 138.6, 149.3, 150.6, 151.3, 152.0, 153.6, 164.1 (one signal is

missing, possibly because of signal overlapping); HRMS (ESI): m/z calcd for [M + Na]+

C68H88N6NaO9 1155.6505, found1155.6510.

Rotaxane 9: Triethylamine (0.1 mL, 0.71 mmol) and triisopropylsilyl triflate (0.2 mL, 0.74

ml) were added dropwise to a solution of the urea-derived thread 8 (0.27 g, 0.63 mmol) and

macrocycle 1 (0.3 g, 0.63 mmol) in CH2Cl2 (6 mL). The mixture was stirred at room

temperature for 12 h and the solvent evaporated under reduced pressure. The residue was

purified through chromatography (SiO2; EA/Hex, 1:2) to afford rotaxane 9 as a colorless oil

(80 mg, 12%). 1H NMR (400 MHz, CDCl3): δ = 1.00−1.20 (m, 42H), 3.55−3.62 (m, 4H),

3.70−3.75 (m, 4H), 4.32 (s, 4H), 4.47 (d, J = 5.6 Hz, 4H), 4.70 (s, 4H), 6.55 (s, 2H), 6.74 (d, J

= 7.6 Hz, 4H), 6.80 (d, J = 7.6 Hz, 4H), 6.94 (d, J = 8.4 Hz, 4H), 7.00 (d, J = 8.4 Hz, 4H),

8.08 (t, J = 8 Hz, 1H), 8.44 (d, J = 8 Hz, 2H), 9.39 ( br, 2H); 13C NMR (100 MHz, CDCl3):

δ = 12.5, 18.5, 43.7, 64.8, 68.7, 70.6, 74.0, 117.0, 124.7, 125.5, 127.8, 128.6, 134.3, 134.4,

137.1, 137.5, 138.0, 148.9, 151.3, 163.3; HRMS (ESI): m/z calcd for [M + Na]+

C60H85N5NaO8Si2 1082.5829, found 1082. 5834.

7

The Complexation of Macrocycle 1 and Thread 3 in CDCl3 Dilution Isotherm

0.0010 0.0015 0.0020 0.0025 0.0030 0.0035 0.0040 0.0045

0.04

0.05

0.06

0.07

0.08

0.09

0.10

0.11

Data: Data1_BModel: nmr 1:1 dilution Chi^2 = 5.9784E-6R^2 = 0.98889 K 177.14348 ±20.26132D 0.32883 ±0.02231

Che

mic

al S

hift

Diff

eren

ce (∆

δ)

Concentration (M)

Using the signal of free 1 at δ 4.554 as the reference

The Complexation of Macrocycle 1 and Thread 4 in CDCl3 Dilution Isotherm

0.0002 0.0004 0.0006 0.0008 0.00100.11

0.12

0.13

0.14

0.15

0.16

0.17

Data: Data1_BModel: nmr 1:1 dilution Chi^2 = 1.5063E-6R^2 = 0.99474 K 10568.07044 ±481.14205D 0.22268 ±0.00228

Che

mic

al s

hift

diffe

renc

e (∆

δ)

Concentration (M)

B


8

The Complexation of Macrocycle 1 and thread 3 in CDCl3

Job Plot

0 0.2 0.4 0.6 0.8 1

0.01

0.02

0.03

[1]/{[1]+[3]}

∆δx

[1]/{

[1]+

[3]}

([1]+[3]) = 5.0 mM


2

S10

1

S11

1

S12

S13

3

S14

3

S15

III

S16

III

S17

8

S18

8

S19

9

S20

9

S21

V

S22

V

S23

5

S24

5

S25

6

S26

6

7

S27

7

S28

S29

NHN

NH

O

O

OO

O

ON

NH

H

OO

O

H NHe'

Ha'

Hb'

Hi'

Hj'

Hc' Hd'

Hf'Hh'

Hg'

Hk'

Hl'

Hi''

Hj''

Hh'

Hc'

+ H

d'

Hg'

Hj'

+Hi''

Hj''

Hb' H

a'

Hk'

Hl'

He'H

f'

Hm

'+H

m''

OC

H2C

H2O

NN

O

H

N H

O

N H

N HO

OC

H2

Hi'

C(Hm''3)

(Hm'3)C

S30

N HNNH

O

O

OO

O

ON

NHH

O O

O

HNHe'

Ha' Hb'

Hi'Hj'

Hc'

Hd'

Hf'

Hh'Hg'

Hk' Hl'

Hi''

Hj''

Hc' + Hd'

Hj'

Hh'Hg'N

N

O

H

NH

O

NH

Hh'

N

NO

H

H

Hj''

NH

O

O

Partial 2D NOSY [500 MHz, CDCl3/CD3CN (1:1), 298K]

S31

N HNNH

O

O

OO

O

ON

NHH

O O

O

HNHe'

Ha' Hb'

Hi'Hj'

Hc'

Hd'

Hf'

Hh'Hg'

Hk' Hl'

Hi''

Hj''

NN

O

H

Hc' + Hd'

NH

O

O

Hh'

Hj'

NH

O

NH

Hj''Hg'

He'Hf'

Hh'

Hk'

CH2

OCH2CH2O

Hl'

2D NOSY [500 MHz, CDCl3/CD3CN (1:1), 298K]

S32

2D COSY (400 MHz, CD3CN/CDCl3 (1:1), 298 K)

N HNNH

O

O

OO

O

ON

NHH

O O

O

HNHe'

Ha' Hb'

Hi'Hj'

Hc'

Hd'

Hf'

Hh'Hg'

Hk' Hl'

Hi''

Hj''

NN

O

H

He'

Hk'Hl'

Hg'

Hh'

S33

Hb'

Ha'

Hg'

+Hj' Hj''

Hi''

Hi'

Hc'

+ H

d'

Hh'

He'

Hf'

Hl'

Hm

''H

m'

OC

H2C

H2O

CH

2

NN

O

H

N HN

NH

O

O

OO

O

He'

Hf'

Hc'

Hd'

Ha'

Hb'

O

ON

C(H

m'') 3

Hi''

H

O

N

O

N(H

m') 3

CH

k'H

h'

Hg'

Hj'

Hi'

CH

3 OO H

H

Hl'

Hj''

S34

Partial 2D NOSY (500 MHz, CD3CN/CDCl3 (1:1), 298 K)

Hj''

Hh'

Hg' +Hj'

Hc' + Hd'NN

O

H

N

HNNH

O

O

OO

O

He'

Hf'

Hc'Hd'

Ha'Hb'

O

ON C(Hm'')3

Hi''

H

O

N

O

N(Hm')3C

Hk'Hh'

Hg'Hj'

Hi'

CH3

OO

H H

Hl'Hj''

S35

Partial 2D NOSY (500 MHz, CD3CN/CDCl3 (1:1), 298 K)

Hm''

Hm'

Hi''

Hi'

Hg'+Hj'

Hc' + Hd'Hj''

Hh'

Hk'

N

HNNH

O

O

OO

O

He'

Hf'

Hc'Hd'

Ha'Hb'

O

ON C(Hm'')3

Hi''

H

O

N

O

N(Hm')3C

Hk'Hh'

Hg'Hj'

Hi'

CH3

OO

H H

Hl'

Hl'OCH2CH2O

Hf'

Hj''

S36

2D NOSY (500 MHz, CD3CN/CDCl3 (1:1), 298 K)

N

HNNH1

O

O

OO

O

He'

Hf'

Hc'Hd'

Ha'Hb'

OO

N

Hi''

H

O

N

O

N Hk'Hh'

Hg'Hj'

Hi'

CH3

OO

H H

NN

O

H

Hb'

Ha'

Hc' + Hd'Hg'+Hj'Hj''

Hi''

Hi'

Hh'

Hm'

Hm'

Hf'He'

Hk'

Hl'

OCH2CH2O

Hk'

CH2

(CHm''3)

(CHm'3)

S37

2D COSY (500 MHz, CD3CN/CDCl3 (1:1), 298 K)

N

HNNH1

O

O

OO

O

He'

Hf'

Hc'Hd'

Ha'Hb'

OO

N

Hi''

H

O

N

O

N Hk'Hh'

Hg'Hj'

Hi'

CH3

OO

H H

NN

O

HCH2

Hk'

Hl'

He'

Hh'

Hg' + Hj'

69451 weinheim, germany · yi-lin huang, wei-chung hong, chien-chen lai, yi-hung liu, shie-ming...

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