Supporting Information
for
Pd- and Cu-catalyzed approaches in the syntheses of new cholane
aminoanthraquinone pincer-like ligands
Nikolay V. Lukashev*, Gennadii A. Grabovyi, Dmitry A. Erzunov, Alexey V. Kazantsev, Gennadij V.
Latyshev, Alexei D. Averin and Irina P Beletskaya.
Address: Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory 1-3,
Moscow, 119991, Russia
Email: Nikolay V. Lukashev* - [email protected]
*Corresponding author
Experimental procedures, characterization data, copies
of the 1H, 13C NMR spectra, UV–vis data
General information ..................................................................................................................................S2
Experimental procedures and characterization data ..................................................................................S2
General procedure for preparation of amines 3a-c [2] ......................................................................... S3
General procedure of Cu-catalyzed amination ..................................................................................... S5
General procedure of Pd-catalyzed amination ..................................................................................... S6
Copies of the 1H and, 13C NMR spectra ..................................................................................................S10
UV–vis titration .......................................................................................................................................S26
References: ..............................................................................................................................................S33
S1
General information
1
H and
13
C-NMR spectra were recorded at 400 and 100.6 MHz respectively with a Bruker
Avance 400 and Agilent MR 400 spectrometers. Chemical shifts were measured relative to HMDS and
solvent signal in 1H and
13
C NMR spectra respectively. Only characteristic signals in 1H-NMR of
steroids are given. Column chromatography was carried out on Macherey-Nagel slilicagel 60 (0.040–
0.063 mm). All procedures associated with oxygen- and water-sensitive compounds were conducted
under dry argon atmosphere. Cs2CO3 was dried in vacuo at 120–150 °C for several hours, stored in a
Schlenk tube, and weighed in an argon-flushed vessel.
UV–vis absorption spectra of a 50 µM solution of the ligands 5c and 5d in acetonitrile (3 ml
placed into quartz cuvette with 1 cm optical path length) were recorded as a function of added
Cu(ClO4)2, Al(ClO4)3 or Cr(ClO4)3 (0.01 M in acetonitrile) at a uniform data point interval of 1 nm with
a Cary 60 (Agilent) spectrophotometer. All necessary aliquots of perchlorates (3.0 µl or 7.5 µl) were
added manually with LLG-microliter pipette (0.5 to 10 µl). The calculation of stability constants was
performed by nonlinear least-squares analysis with the Specfit program [1].
Experimental procedures and characterization data
General procedure for preparation of amides 2a–c [2]
To the suspension of bile acid (1.0 mmol) and Et3N (1.5 equiv) in THF (2.5 ml) isobutyl
chloroformate (1.1 equiv) was added at 10 °C and reaction was stirred at this temperature for 15 min.
Conc. aqueous NH3 (1.5 equiv) was added dropwise and stirring was continued for 30 min at 10 °C and
3 h at rt. Solvents were evaporated and the crude product was washed with H2O followed by washing
with Et2O. The target product was dried in vacuo at 50–60 °C to constant mass and used without further
purification.
S2
(3α,5β)-3-Hydroxycholan-24-amide (2a)
Obtained from 1.50 g (4.0 mmol) of 1a. White powder (84%, 1.26 g). M. p. 224-226 °C (lit. 214216 °C [3], 208-210 °C [2]). 1H NMR (400 MHz, DMSO-d6): 0.60 (3H, s, 18-CH3), 0.86 (6H, 19-CH3,
21-CH3), 2.01 (2H, m, 23-CH2), 3.35 (1H, m, 3β-H), 4.43 (1H, d, J 4.5 Hz, 3-OH), 6.63 (1H, s,
C(O)NH2), 7.20 (1H, s, C(O)NH2).
(3α,5β,12α)-3,12-Dihydroxycholan-24-amide (2b)
Obtained from 5.0 g (12.7 mmol) of 1b. White powder (80%, 4.0 g). M. p. 213-215 °C (lit. 213215 °C [2]). 1H NMR (400 MHz, DMSO-d6): 0.58 (3H, s, 18-CH3), 0.83 (3H, s, 19-CH3), 0.90 (3H, d, J
6.4 Hz, 21-CH3), 1.98 (2H, m, 23-CH2), 3.36 (1H, m, 3β-H), 3.59 (1H, m, 12β-H), 4.17 (1H, s, 12-OH),
4.45 (1H, s, 3-OH), 6.61 (1H, s, C(O)NH2), 7.19 (1H, s, C(O)NH2).
(3α,5β,7α,12α)-3,7,12-Trihydroxycholan-24-amide (2c)
Obtained from 5.0 g (12.2 mmol) of 1c. White powder (85%, 4.3 g). M. p. 138-140°C (lit. 135137°C [2]). 1H NMR (400 MHz, DMSO-d6): 0.57 (3H, s, 18-CH3), 0.80 (3H, s, 19-CH3), 0.91 (3H, d, J
5.4 Hz, 21-CH3), 2.15 (2H, m, 23-CH2), 3.17 (1H, m, 3β-H), 3.60 (1H, br.s, 12β-H), 3.77 (1H, br. s, 7βH), 4.01 (1H, s, 7-OH), 4.10 (1H, s, 12-OH), 4.32 (1H, s, 3-OH), 6.63 (1H, s, C(O)NH2), 7.21 (1H, s,
C(O)NH2).
General procedure for preparation of amines 3a–c [2]
To the cooled (with an ice bath) suspension of amide 2 (1.0 mmol) in THF (10 ml) LiAlH4 (3
equiv) was added in small portions (CAUTION: exothermic reaction with hydrogen evolution) under
argon atmosphere. When evolution of hydrogen ceased the mixture was refluxed for 15 h, cooled to rt,
and excess of LiAlH4 was quenched by dropwise addition of H2O (3 ml). The suspension was half
S3
concentrated and then filtered. The white solid was washed with hot THF until disappearance of the
amine 3 in the filtrate (TLC control). The filtrate was evaporated and the product was purified by
column chromatography.
(3α,5β)-3-Hydroxycholan-24-amine (3a)
Obtained from 1.26 g (3.4 mmol) of 2a. Eluent CH2Cl2:CH3OH:Et3N 100:10:5, Rf 0.5. White
powder (67%, 0.83 g). M. p. 158-160 °C (lit. 148-150 °C [2]). 1H NMR (400 MHz, DMSO-d6): 0.63
(3H, s, 18-CH3), 0.90 (6H, s, 19-CH3, 21-CH3), 1.95 (2H, m, 24-CH2), 2.64 (2H, m, NH2), 3.58 (1H, m,
3β-H).
(3α,5β,12α)-3,12-Dihydroxycholan-24-amine (3b)
Obtained from 4.0 g (10.2 mmol) of 2b. Eluent CH2Cl2:CH3OH:Et3N 100:10:5, Rf 0.3. White
powder (68%, 2.6 g). M. p. 108-110°C. 1H NMR (400 MHz, DMSO-d6): 0.58 (3H, s, 18-CH3), 0.83
(3H, s, 19-CH3), 0.91 (3H, d, J 6.5 Hz, 21-CH3), 2.45 (2H, m, NH2), 3.35 (1H, m, 3β-H), 3.78 (1H, s,
12β-H).
13
С NMR (100.6 MHz, DMSO-d6): 11.8, 12.5, 17.4, 23.1, 23.5, 26.1, 27.0, 27.4, 28.7, 30.1,
30.2, 32.9, 34.4, 34.9, 35.3, 36.3, 41.6, 42.3, 45.7, 45,9, 46.3, 47.5, 69.9, 71.0.
(3α,5β,7α,12α)-3,7,12-Trihydroxycholan-24-amine (3c)
Obtained from 4.3 g (10.4 mmol) of 2c. Eluent CH2Cl2:CH3OH:Et3N 100:10:5, Rf 0.2. White
powder (68%, 2.8 g, 7.1 mmol). M. p. 110-112°C. 1H NMR (400 MHz, DMSO-d6): 0.58 (3H, s, 18CH3), 0.80 (3H, s, 19-CH3), 0.91 (3H, d, J 7.0 Hz, 21-CH3), 3.17 (1H, m, 3β-H), 3.60 (1H, s, 12β-H),
3.78 (1H, s, 7β-H), 4.00 (1H, s, 7-OH), 4.09 (1H, s, 12-OH), 4.30 (1H, br. s, 3-OH).
13
C NMR (100.6
MHz, DMSO-d6): 11.8, 12.4, 17.4, 23.1, 23.5, 26.1, 27.0, 27.3, 28.6, 30.1, 30.2, 32.9, 33.8, 35.1, 35.3,
35.4, 41.3, 41.5, 42.3, 45.7, 46.2, 66.2, 70.3, 71.0.
S4
General procedure of Cu-catalyzed amination
A mixture of amine 3 (0.3 mmol), aryl halide (0.1 mmol), CuI (0.02 mmol), L-proline (0.04
mmol) and K2CO3 (0.4 mmol) in DMSO (1 ml) was stirred at 110 °C in a glass vial with a screw cap
under argon atmosphere for 24 h. The reaction mixture was cooled to rt, diluted with CH2Cl2 (15 ml)
and washed with H2O (3 × 10 ml). The organic layer was dried over Na2SO4, evaporated, and the
product was purified by column chromatography.
4-[(3α,5β,12α)-3,12-Dihydroxycholan-24-ylamino]toluene (4)
Obtained from 56.7 mg (0.15 mmol) of 3b, 21.8 mg (0.1 mmol) of 4-iodotoluene, 3.8 mg (0.02
mmol) of CuI, 4.6 mg (0.04 mmol) of L-proline, 27.6 mg (0.2 mmol) of K2CO3 in DMSO (1 ml). Palebrown powder (95%, 44.4 mg). 1H NMR (400 MHz, DMSO-d6): 0.59 (3H, s, 18-CH3), 0.83 (3H, s, 19CH3), 0.93 (3H, d, J 6.5 Hz, 21-CH3), 2.12 (3H, s, CH3), 3.78 (1H, s, 12β-H), 4.19 (1H, d, J 3.8 Hz, 12OH), 4.47 (1H, d, J 3.8 Hz , 3-OH), 5.22 (1H, t, J 5.6 Hz., NH), 6.43 (2H, d, J 8.2 Hz), 6.85 (2H, d, J
8.2 Hz). 13C NMR (100.6 MHz, CDCl3): 12.7, 17.6, 20.3, 23.1, 23.6, 26.1, 26.3, 27.1, 27.6, 28.5, 30.4,
33.2, 33.6, 34.1, 35.2, 35.4, 36.0, 36.4, 42.0, 44.9, 46.4, 47.5, 48.2, 71.7, 73.14, 112.9, 126.3, 129.6,
146.2
1,3-Bis[(3α,5β)-3-hydroxycholan-24-ylamino]benzene (5a)
Pale-brown powder (40%, 31.9 mg). M.p. 123-125 oC. 1H NMR (400 MHz, CDCl3): 0.63 (6H, s,
18-CH3), 0.91 (6H, s, 19-CH3), 0.92 (6H, d, J 6.4 Hz, 21-CH3), 3.03 (4H, m, 24-CH2), 3.61 (2H, m, 3βH), 5.85 (1H, t, J 1.9 Hz, 2-HAr), 5.98 (2H, dd, J 8.0 Hz, 1.9 Hz, 4-HAr and 6-HAr), 6.95 (1H, t, J 8.0 Hz,
5-HAr).
13
C NMR (100.6 MHz, CDCl3): 12.0, 18.6, 20.8, 23.3, 24.2, 26.2, 26.4, 27.2, 28.3, 30.5, 33.3,
34.5, 35.3, 35.6, 35.8, 36.4, 40.1, 40.4, 42.0, 42.7, 44.6, 56.1, 56.4, 71.8, 76.7, 77.0, 77.3, 96.9, 102.7,
129.8, 149.7.
Calculated (C54H88N2O2): C 81.35%, H 11.13%, N 3.51%.Found: C 81.47%, H 11.12%, N 3.55%.
S5
4,4’-Bis[(3α,5β)-3-hydroxycholan-24-ylamino]biphenyl (5b)
White powder (41%, 35.8 mg). M.p. 133-135 °C. 1H NMR (400 MHz, CDCl3): 0.64 (6H, s, 18CH3), 0.91 (6H, s, 19-CH3), 0.92 (6H, d, J 6.5 Hz, 21-CH3), 3.08 (4H, m., 24-CH2), 3.61 (2H, m, 3β-H),
6.64 (4H, d, J 7.6 Hz, m-HAr), 7.35 (4H, d, J 7.6 Hz, o-HAr). 13C NMR (100.6 MHz, CDCl3): 12.0, 18.7,
20.8, 23.3, 24.2, 26.2, 26.4, 27.2, 28.3, 30.5, 33.3, 34.6, 35.3, 35.6, 35.8, 36.5, 40.2, 40.4, 42.1, 42.7,
44.8, 56.2, 56.5, 71.9, 113.1, 127.1, 130.6, 146.9.
Calculated (C60H92N2O2·CH2Cl2): C 76.45%, H 9.89%, N 2.92%. Found: C 76.22%, H 9.60%, N 3.11
%.
General procedure of Pd-catalyzed amination
A mixture of amine 3 (0.3 mmol), aryl halide (0.1 mmol), Pd(dba)2 (0.012 mmol), BINAP (0.015
mmol) and Cs2CO3 (0.4 mmol) in dioxane (2 ml) was stirred at 100 °C in a glass vial with a screw cap
under argon atmosphere for 24 h. The reaction mixture was cooled to rt, diluted with CH2Cl2 (15 ml)
and washed with H2O (3 × 10 ml). The organic layer was dried over Na2SO4, evaporated, and the
product was purified by column chromatography.
1,3-bis[(3α,5β)-3-hydroxycholan-24-ylamino]benzene (5a)
Obtained from 65.1 mg (0.18 mmol) of 3a, 7.1 μl (0.06 mmol) of 1,3-dibromobenzene, 4.1 mg
(0.0072 mmol) of Pd(dba)2, 5.6 mg (0.009 mmol) of BINAP, 34.6 mg (0.36 mmol) of t-BuONa in
dioxane (1 ml). Pale-brown powder (61%, 29.2 mg).
S6
1,8-Bis[(3α,5β)-3-hydroxycholan-24-ylamino]-9,10-anthraquinone (5c)
Obtained from 108.5 mg (0.3 mmol) of 3a and 27.7 mg (0.1 mmol) of 1,8-dichloro-9,10anthraquinone. Dark-violet powder (88%, 81,6 mg). M.p. 156-158 oC. 1H NMR (400 MHz, CDCl3): 0.62
(6H, s, 18-CH3), 0.90 (6H, s, 19-CH3), 0.94 (6H, d, J 6.5 Hz, 21-CH3), 3.25 (4H, m, 24-CH2), 3.61 (2H,
m, 3β-H), 6.99 (2H, d, J 8.4 Hz, o-HAr), 7.45 (2H, t, J 8.4 Hz, m-HAr), 7.52 (2H, d, J 7.3 Hz, p-HAr),
9.66 (2H, t, J 4.9 Hz, NH). 13C NMR (100.6 MHz, CDCl3): 12.1, 18.7, 20.8, 23.4, 24.3, 25.8, 26.5, 27.2,
28.3, 30.6, 33.5, 34.6, 35.4, 35.7, 35.9, 36.5, 40.2, 40.4, 42.1, 42.7, 43.6, 56.1, 56.5, 71.8, 114.3, 114.8,
117.7, 134.1, 134.4, 151.2, 184.8, 188.9.
Calculated (C62H90N2O4): C 80.30%, H 9.78%, N 3.02%. Found: C 80.63%, H 9.60%, N 2.91 %.
1,8-bis[(3α,5β,12α)-3,12-dihydroxycholan-24-ylamino]-9,10-anthraquinone (5d)
Obtained from 108.5 mg (0.3 mmol) of 3b, 27.7 mg (0.1 mmol) of 6a, 2.3 mg (0.004 mmol) of
Pd(dba)2, 3.1 mg (0.005 mmol) of BINAP, 130.3 mg (0.4 mmol) of Cs2CO3 and 0.4 ml of dioxane.
Dark-violet powder (74%, 71 mg). M.p. 180-182 oC. 1H NMR (400 MHz, CDCl3): 0.67 (6H, s, 18-CH3),
0.89 (6H, s, 19-CH3), 1.03 (6H, d, J 6.4 Hz, 21-CH3), 3.24 (4H, m, 24-CH2), 3.59 (2H, m, 3β-H), 3.99
(2H, br. s., 12β-H), 6.98 (2H, d, J 8.4 Hz, o-HAr), 7.44 (2H, t, J 8.3 Hz, m-HAr) 7.50 (2H, d, J 7.3 Hz, pHAr), 9.61 (2H, br. s., NH). 13C NMR (100.6 MHz, CDCl3): 12.7, 17.8, 23.1, 23.7, 25.7, 26.1, 27.1, 27.6,
28.6, 30.5, 33.5, 33.6, 34.1, 35.2, 35.4, 36.0, 36.4, 42.0, 43.6, 46.5, 47.4, 48.3, 71.7, 73.2, 114.3, 114.7,
117.7, 134.0, 134.3, 151.2, 184.7, 188.9.
Calculated (C62H90N2O6·3CH2Cl2): C 65.30%, H 7.97%, N 2.31%. Found: C 65.68%, H 7.88%, N
2.27%.
S7
1,8-bis[(3α,5β,12α)-3,7,12-Trihydroxycholan-24-ylamino]-9,10-anthraquinone (5e)
Obtained from 118.1 mg (0.3 mmol) of 3c, 27.7 mg (0.1 mmol) of 6a, 2.3 mg (0.004 mmol) of
Pd(dba)2, 3.1 mg (0.005 mmol) of BINAP, 130.3 mg (0.4 mmol) of Cs2CO3 and 0.4 ml of dioxane.
Violet powder (34%, 33.7 mg). M.p. 171-173 oC. 1H NMR (400 MHz, CDCl3): 0.63 (6H, s, 18-CH3),
0.82 (6H, s, 19-CH3), 1.02 (6H, d, J 6.4 Hz, 21-CH3), 3.25 (2H, m, 3β-H), 3.35 (4H, m, 24-CH2), 3.8
(2H, br. s., 7β-H), 3.96 (2H, br. s., 12β-H), 7.01 (2H, d, J 8.4 Hz, o-HAr), 7.44 (2H, t, J 8.3 Hz, m-HAr)
7.50 (2H, d, J 7.3 Hz, p-HAr), 9.70 (2 H, br. s., NH).
13
C NMR (100.6 MHz, CDCl3): 12.3, 17.8, 22.4,
23.3, 25.1, 26.3, 28.0, 28.1, 30.5, 33.6, 34.7, 34.9, 35.3, 35.6, 39.3, 41.5, 41.70, 43.2, 46.4, 47.2, 68.5,
72.1, 73.3, 114.5, 114.9, 117.8, 134.1, 134.4, 151.1, 184.6, 188.8.
Calculated (C62H90N2O8·3CH3OH): C 71.79%, H 9.45%, N 2.58%. Found: C 71.93%, H 9.41%, N
2.45%.
1,5-bis[(3α,5β)-3-Hydroxycholan-24-ylamino]-9,10-anthraquinone (5f)
Obtained from 108.5 mg (0.3 mmol) of 3a and 27.7 mg (0.1 mmol) 6b. Dark-violet powder
(76%, 70,5 mg). M.p. 152-154 oC. 1H NMR (400 MHz, CDCl3): 0.64 (6H, s, 18-CH3), 0.91 (6H, s, 19CH3), 0.95 (6H, d, J 6.4 Hz, 21-CH3), 3.26 (4H, m, 24-CH2), 3.61 (2H, m, 3β-H), 6.94 (2H, d, J 8.1 Hz,
o-HAr), 7.51 (4H, m, m-HAr and p-HAr), 9.69 (2H, t, J 4.9 Hz, NH).
13
C NMR (100.6 MHz, CDCl3):
12.0, 18.6, 20.8, 23.4, 24.2, 25.8, 26.4, 27.2, 28.3, 30.5, 33.4, 34.5, 35.3, 35.6, 35.8, 36.4, 40.1, 40.4,
42.1, 42.7, 43.5, 56.0, 56.5, 71.8, 112.8, 114.6, 116.3, 135.1, 136.3, 151.4, 185.4.
Calculated (C62H90N2O4): C 80.30%, H 9.78%, N 3.02%. Found: C 79.97%, H 9.57%, N 2.78 %.
1,8-Bis[(3α,5β)-3-methoxycholan-24-ylamino]-9,10-anthraquinone (S1)
A mixture of 5c (46 mg, 0.05 mmol) and trimethyloxonium tetrafluoroborate (17.7 mg, 0.12
mmol) in dry CH2Cl2 (5 ml) was stirred at ambient temperature under argon atmosphere for 24 h. The
S8
reaction mixture was diluted with CH2Cl2 (15 ml) and washed with H2O (10 ml). The organic layer was
dried over Na2SO4, evaporated, and the product was purified by column chromatography. Dark-violet
powder (29%, 14 mg). 1H NMR (400 MHz, CDCl3): 0.66 (6H, s, 18-CH3), 0.92 (6H, s, 19-CH3), 0.98
(6H, d, J 6.5 Hz, 21-CH3), 3.16 (2H, m, 3β-H), 3.26 (4H, m, 24-CH2), 3.35 (6H, s, 3-OCH3), 7.00 (2H,
d, J 8.1 Hz, o-HAr), 7.46 (2H, t, J 8.1 Hz, m-HAr) 7.52 (2H, d, J 7.3 Hz, p-HAr), 9.63 (2H, t, J 4.9 Hz.,
NH).
13
C NMR (100.6 MHz, CDCl3): 12.1, 18.7, 20.8, 23.4, 24.3, 25.8, 26.4, 27.3, 28.3, 29.7, 32.7,
33.4, 34.9, 35.3, 35.6, 35.9, 40.2, 40.3, 42.0, 42.7, 43.5, 55.5, 56.1, 56.5, 80.4, 114.3, 114.7, 117.6,
134.0, 134.3, 151.2, 184.8, 188.9.
S9
Copies of the 1H and, 13C NMR spectra
0.59
0.93
0.92
0.83
2.12
2.89
2.88
2.86
3.78
4.19
4.18
4.47
4.46
5.24
5.22
5.21
6.44
6.42
H NMR spectrum of 4-[(3α,5β,12α)-3,12-dihydroxycholan-24-ylamino]toluene (4) (DMSO-d6, 400 MHz, 300 K)
6.86
6.84
1
DMSO-d6
20.20
7.5
7.0
19.41
6.5
8.19
6.0
5.5
11.36
5.0
4.5
11.84
11.38
21.19
4.0
3.5
Chemical Shift (ppm)
S10
3.0
32.38
2.5
2.0
39.03 35.68
1.5
1.0
0.5
0
13
146.21
176
168
160
152
144
12.70
20.34
126.26
46.41
77.31
77.00
76.69
73.14
71.68
48.19
Chloroform-d
17.62
44.86
42.03
36.37
35.40
33.57
33.20
28.53
27.60
27.10
26.28
26.10
23.10
129.64
112.90
C NMR spectrum of 4-[(3α,5β,12α)-3,12-dihydroxycholan-24-ylamino]toluene (4) (CDCl3, 100.6 MHz, 300 K)
136
128
120
112
104
96
88
Chemical Shift (ppm)
S11
80
72
64
56
48
40
32
24
16
8
0
H NMR spectrum of 1,3-bis[(3α,5β)-3-hydroxycholan-24-ylamino]benzene (5a) (CDCl3, 400 MHz, 300 K)
7.5
7.0
6.5
6.0
20.00
5.5
5.0
4.5
42.85
4.0
3.5
Chemical Shift (ppm)
3.0
S12
0.63
20.02
0.92
0.91
10.77
3.65
3.64
3.62
3.61
3.60
3.58
3.57
3.09
3.07
3.06
3.04
3.04
3.02
3.00
2.99
5.99
5.97
5.97
5.85
Chloroform-d
6.97
6.95
6.93
1
118.67 68.78
2.5
2.0
1.5
1.0
0.5
0
13
96.94
129.81
192
184
176
168
160
152
144
136
128
120
112
12.01
20.78
18.61
35.79
35.58
77.32
77.00
76.68
149.65
34.51
102.66
44.56
71.77
Chloroform-d
42.04
40.13
36.36
35.30
30.46
28.29
27.16
24.18 26.39
56.44
56.13
40.38
23.34
C NMR spectrum of 1,3-bis[(3α,5β)-3-hydroxycholan-24-ylamino]benzene (5a) (CDCl3, 100.6 MHz, 300 K)
104
96
Chemical Shift (ppm)
S13
88
80
72
64
56
48
40
32
24
16
8
H NMR spectrum of 4,4’-bis[(3α,5β)-3-hydroxycholan-24-ylamino]biphenyl (5b) (CDCl3, 400 MHz, 300 K)
40.87
8.0
7.5
40.00
7.0
6.5
24.64
6.0
5.5
5.0
4.5
4.0
3.5
Chemical Shift (ppm)
S14
40.35
3.0
0.64
0.93
0.91
3.08
3.65
3.64
3.62
3.61
3.60
3.59
6.65
6.63
Chloroform-d
7.36
7.34
1
137.54 68.16
2.5
2.0
1.5
1.0
0.5
0
13
C NMR spectrum of 4,4’-bis[(3α,5β)-3-hydroxycholan-24-ylamino]biphenyl (5b) (CDCl3, 100.6 MHz, 300 K)
160
152
144
136
128
120
112
104
96
88
80
Chemical Shift (ppm)
S15
72
64
56
44.8
42.7
42.1
40.4
40.2
36.4
35.8
35.6
35.3
34.6
33.3
30.5
28.3
27.2
26.4
26.2
24.2
23.3
20.8
18.6
12.0
56.5
56.2
71.9
113.1
127.1
130.6
146.9
Chloroform-d
48
40
32
24
16
8
0
H NMR spectrum of 1,8-bis[(3α,5β)-3-hydroxycholan-24-ylamino]-9,10-anthraquinone (5c) (CDCl3, 400 MHz, 300 K)
19.81
9.5
9.0
8.5
8.0
40.81
20.00
7.5
7.0
21.20
6.5
6.0
5.5
5.0
4.5
Chemical Shift (ppm)
S16
4.0
3.5
39.97
0.62
0.94
0.93
0.90
3.63
3.62
3.61
3.59
3.58
3.57
3.28
3.26
3.25
3.23
3.21
7.00
6.98
7.52
7.51
7.47
7.45
7.43
Chloroform-d
9.67
9.66
9.65
1
64.23 62.25
3.0
2.5
2.0
1.5
1.0
0.5
0
13
C NMR spectrum of 1,8-bis[(3α,5β)-3-hydroxycholan-24-ylamino]-9,10-anthraquinone (5c) (CDCl3, 100.6 MHz, 300 K)
192
184
176
168
160
152
144
136
128
120
112
104
96
88
Chemical Shift (ppm)
S17
80
72
64
56
43.6
42.6
42.1
40.4
40.1
36.4
35.8
35.3
33.5
30.5
28.3
27.2
26.4
25.8
24.2
23.3
20.8
18.7
12.0
56.5
56.1
71.8
117.7
114.8
114.3
134.3
134.0
151.2
184.8
188.9
Chloroform-d
48
40
32
24
16
8
H NMR spectrum of 1,8-bis[(3α,5β,12α)-3,12-dihydroxycholan-24-ylamino]-9,10-anthraquinone (5d) (CDCl3, 400 MHz, 300 K)
19.85
9.5
9.0
8.5
8.0
41.60
19.43
7.5
7.0
20.49
6.5
6.0
5.5
5.0
4.5
Chemical Shift (ppm)
S18
4.0
21.84
3.5
40.68
0.67
1.04
1.03
0.89
3.99
3.61
3.60
3.59
3.58
3.56
3.25
3.24
6.99
6.97
7.51
7.50
7.46
7.44
7.42
Chloroform-d
9.61
1
65.42
3.0
2.5
2.0
1.5
1.0
0.5
0
13
C NMR spectrum of 1,8-bis[(3α,5β,12α)-3,12-dihydroxycholan-24-ylamino]-9,10-anthraquinone (5d) (CDCl3, 100.6 MHz, 300 K)
208
200
192
184
176
168
160
152
144
136
128
120
112
104
Chemical Shift (ppm)
S19
96
88
80
72
64
56
43.6
42.0
36.4
36.0
35.2
33.6
33.5
30.5
28.6
27.6
27.1
26.1
25.7
23.7
23.1
17.8
12.7
48.3
47.4
73.2
71.7
117.7
114.7
114.3
134.3
134.0
151.2
184.7
Chloroform-d
48
40
32
24
16
8
H NMR spectrum of 1,8-bis[(3α,5β,12α)-3,7,12-trihydroxycholan-24-ylamino]-9,10-anthraquinone (5e) (CDCl3, 400 MHz, 300 K)
18.76
10.0
9.5
40.87
9.0
8.5
8.0
7.5
20.16
7.0
18.83
6.5
6.0
5.5
5.0
4.5
Chemical Shift (ppm)
S20
4.0
0.63
0.82
1.03
1.01
3.35
3.25
3.96
3.80
7.52
7.50
7.49
7.46
7.44
7.42
7.02
7.00
Chloroform-d
9.70
1
67.00
3.5
3.0
2.5
2.0
1.5
1.0
0.5
0
13
C NMR spectrum of 1,8-bis[(3α,5β,12α)-3,7,12-trihydroxycholan-24-ylamino]-9,10-anthraquinone (5e) (CDCl3, 100.6 MHz, 300 K)
184
176
168
160
152
144
136
128
120
112
104
96
Chemical Shift (ppm)
S21
88
80
72
64
56
48
40
32
24
16
12.3
47.2
46.4
43.2
41.7
41.5
39.3
35.6
35.3
34.9
34.7
33.5
30.5
28.1
28.0
26.3
25.1
23.3
22.4
17.8
68.5
73.3
72.0
114.9
114.4
117.8
134.4
134.0
151.1
184.6
188.8
Chloroform-d
H NMR spectrum of 1,5-bis[(3α,5β)-3-hydroxycholan-24-ylamino]-9,10-anthraquinone (5f) (CDCl3, 400 MHz, 300 K)
18.05
10.0
9.5
40.13
9.0
8.5
8.0
7.5
18.93
7.0
19.93
6.5
6.0
5.5
5.0
4.5
Chemical Shift (ppm)
S22
4.0
3.5
39.29
0.64
0.96
0.94
0.91
3.64
3.62
3.61
3.60
3.59
3.29
3.28
3.26
3.24
3.23
6.96
6.93
7.54
7.53
7.50
7.48
Chloroform-d
9.70
9.69
9.68
1
128.45
3.0
2.5
2.0
1.5
1.0
0.5
0
13
C NMR spectrum of 1,5-bis[(3α,5β)-3-hydroxycholan-24-ylamino]-9,10-anthraquinone (5f) (CDCl3, 100.6 MHz, 300 K)
192
184
176
168
160
152
144
136
128
120
112
104
96
Chemical Shift (ppm)
S23
88
80
72
64
56
48
40
33.4
30.5
28.3
27.2
26.4
25.8
24.2
23.4
20.8
18.6
12.0
43.5
42.1
40.4
40.1
36.4
35.8
35.6
35.3
56.5
56.0
71.8
116.3
114.6
112.8
136.3
135.1
151.4
185.4
Chloroform-d
32
24
16
8
H NMR spectrum of 1,8-bis[(3α,5β)-3-methoxycholan-24-ylamino]-9,10-anthraquinone (S1) (CDCl3, 400 MHz, 300 K)
0.66
0.99
0.97
0.92
3.35
3.29
3.27
3.26
3.25
3.24
3.19
3.16
3.15
7.01
6.99
7.53
7.51
7.48
7.46
7.44
Chloroform-d
9.63
1
TMS
18.24
10.0
9.5
9.0
8.5
8.0
44.47
19.80
7.5
7.0
70.24
6.5
6.0
5.5
5.0
4.5
Chemical Shift (ppm)
S24
4.0
3.5
107.95
3.0
2.5
2.0
1.5
1.0
0.5
0
13
C NMR spectrum of 1,8-bis[(3α,5β)-3-methoxycholan-24-ylamino]-9,10-anthraquinone (S1) (CDCl3, 100.6 MHz, 300 K)
192
184
176
168
160
152
144
136
128
120
112
104
96
Chemical Shift (ppm)
S25
88
80
72
64
56
42.01
40.17
35.83
35.59
35.27
34.87
33.39
32.72
28.30
27.31
26.76
26.40
25.78
24.26
23.40
20.78
18.71
12.05
43.51
56.45
56.12
55.52
80.39
114.67
114.25
117.64
134.33
134.02
151.19
184.78
188.94
Chloroform-d
48
40
32
24
16
8
UV–vis titration
Figure S1: UV–vis spectra of the ligand 5c (50 μM solution in MeCN) before and after addition of 5
equiv of metal perchlorates
0,75
Ligand
0,65
Cu(II)
Ni(II)
0,55
Pb(II)
Zn(II)
Absorbance
0,45
Ag(I)
Hg(II)
Cr(III)
0,35
Mn(II)
Fe(II)
0,25
Co(II)
Al(III)
0,15
Ga(III)
Y(III)
In(III)
0,05
-0,05
250
300
350
400
450
500
Wavelength (nm)
S26
550
600
650
700
Figure S2: Evolution of UV–vis spectrum of 5c (50 µM solution in MeCN) upon addition of Cu(ClO4)2
(0–5.0 equiv)
0.45
0.0 eq
0.4
0.2 eq
0.4 eq
0.35
0.6 eq
0.8 eq
0.3
Absorbance
1.0 eq
1.2 eq
0.25
1.4 eq
0.2
1.6 eq
1.8 eq
0.15
2.0 eq
2.5 eq
0.1
3.0 eq
3.5 eq
0.05
4.0 eq
4.5 eq
0
250
300
350
400
450
500
550
600
650
700
5.0 eq
Wavelenght, nm
Figure S3: Changes of absorbance at 550 nm plotted against [Cu(ClO4)2]/[5c]total
0,45
0,4
Absorbance
0,35
0,3
0,25
0,2
0,15
0
0,5
1
1,5
2
2,5
3
[Cu(II)]total/[5c]total
S27
3,5
4
4,5
5
Figure S4: Evolution of UV–vis spectrum of 5c (50 µM solution in MeCN) upon addition of Al(ClO4)3
(0–5.0 equiv)
0,5
0.0 eq
0,45
0.2 eq
0,4
0.4 eq
0.6 eq
0,35
0.8 eq
1.0 eq
Absorbance
0,3
1.2 eq
1.4 eq
0,25
1.6 eq
0,2
1.8 eq
2.0 eq
0,15
2.5 eq
3.0 eq
0,1
3.5 eq
4.0 eq
0,05
4.5 eq
0
250
350
450
550
650
5.0
750
Wavelength (nm)
Figure S5: Changes of absorbance at 550 nm plotted against [Al(ClO4)3]/[5c]total
0,5
Absorbance
0,45
0,4
0,35
0,3
0,25
0
1
2
3
[Al(III)]total/[5c]total
S28
4
5
Figure S6: Evolution of UV–vis spectrum of 5c (50 µM solution in MeCN) upon addition of Cr(ClO4)3
(0–5.0 equiv)
0,5
0.0 eq
0,45
0.2 eq
0,4
0.4 eq
0.6 eq
0,35
0.8 eq
1.0 eq
Absorbance
0,3
1.2 eq
1.4 eq
0,25
1.6 eq
0,2
1.8 eq
2.0 eq
0,15
2.5 eq
3.0 eq
0,1
3.5 eq
4.0 eq
0,05
4.5 eq
0
250
300
350
400
450
500
550
600
650
700
Wavelength (nm)
Figure S7: Changes of absorbance at 550 nm plotted against [Cr(ClO4)3]/[5c]total
0,5
Absorbance
0,45
0,4
0,35
0,3
0,25
0
1
2
3
[Cr(III)]total/[5c]total
S29
4
5
5.0 eq
Figure S8: Evolution of UV–vis spectrum of 5d (50 µM solution in MeCN) upon addition of Cu(ClO4)2
(0–5.0 equiv)
0,7
0.0 eq
0,6
0.2 eq
0.4 eq
0.6 eq
0,5
0.8 eq
Absorbance
1.0 eq
0,4
1.2 eq
1.4 eq
1.6 eq
0,3
1.8 eq
2.0 eq
0,2
2.5 eq
3.0 eq
3.5 eq
0,1
4.0 eq
4.5 eq
0
250
300
350
400
450
500
550
600
650
700
5.0 eq
750
Wavelength (nm)
Figure S9: Changes of absorbance at 550 nm plotted against [Cu(ClO4)2]/[5d]total
0,65
0,6
Absorbance
0,55
0,5
0,45
0,4
0,35
0,3
0,25
0
0,5
1
1,5
2
2,5
[Cu(II)]tot/[5d]tot
S30
3
3,5
4
4,5
5
Figure S10: Evolution of UV–vis spectrum of 5d (50 µM solution in MeCN) upon addition of
Al(ClO4)3 (0–5.0 equiv)
0,65
0.0 eq
0.2 eq
0.4 eq
0,55
0.6 eq
0.8 eq
Absorbance
0,45
1.0 eq
1.2 eq
0,35
1.4 eq
1.6 eq
1.8 eq
0,25
2.0 eq
2.5 eq
0,15
3.0 eq
3.5 eq
4.0 eq
0,05
4.5 eq
-0,05
250
350
450
550
650
750
5.0 eq
Wavelength (nm)
Figure S11: Changes of absorbance at 550 nm plotted against [Al(ClO4)3]/[5d]total
0,65
0,6
Absorbance
0,55
0,5
0,45
0,4
0,35
0,3
0
0,5
1
1,5
2
2,5
[Al(III)]tot/[5d]tot
S31
3
3,5
4
4,5
5
Figure S12: Evolution of UV–vis spectrum of 5d (50 µM solution in MeCN) upon addition of
Cr(ClO4)3 (0–5.0 equiv)
0,65
0.0 eq
0.2 eq
0.4 eq
0,55
0.6 eq
0.8 eq
Absorbance
0,45
1.0 eq
1.2 eq
0,35
1.4 eq
1.6 eq
1.8 eq
0,25
2.0 eq
2.5 eq
0,15
3.0 eq
3.5 eq
4.0 eq
0,05
4.5 eq
-0,05
250
350
450
550
650
750
5.0 eq
Wavelength (nm)
Figure S13: Changes of absorbance at 550 nm plotted against [Cr(ClO4)3]/[5d]total
0,65
0,6
Absorbance
0,55
0,5
0,45
0,4
0,35
0
0,5
1
1,5
2
2,5
[Cr(III)]tot/[5d]tot
S32
3
3,5
4
4,5
5
References:
1. Binstead, R.A.; Jung, B.; Zuverbuhler, A.D. SPECFIT/32, Global Analysis System, ver 3.0;
Spectrum Software Associates: Marlborough, USA, 2000.
2. Fini, A.; Fazio, G.; Roda, A.; Bellini, A.M.; Mencini, E.; Guarneri, M. J. Pharm Sci. 1992, 81,
726-730.
3. Joachimiak, R.; Piasecka, M.; Paryzek, Z. J. Chem. Res., 2008, 260-265.
S33