Isolation and Structural Determination of Non-Racemic Tertiary Cathinone Derivatives
Electronic Supplementary Information
MengJie Zhou,a Samira Bouazzaoui,a Louise E. Jones,a Peter Goodrich,a Steven J. E. Bell,a Gary N. Sheldrake,a Peter N. Horton, b Simon J. Coles,b and Nicholas C. Fletcher*a,
a: School of Chemistry and Chemical Engineering, Queen’s University of Belfast, David Keir Building, Belfast, Northern Ireland, BT9 5AG, UK.
b: University of Southampton, Chemistry Department, EPSRC National, Crystallography Service, Southampton, SO17 1BJ, UK.
c: Department of Chemistry, Lancaster University, Bailrigg, Lancaster, LA1 4YB, UKEmail: [email protected]
Contents:
Figure S1 (a) 1H NMR and (b) 13C NMR spectra of (±)-N,N-dimethylcathinone (1)Figure S2 (a) 1H NMR and (b) 13C NMR spectra of (±)-N,N-diethylcathinone (2) Figure S3 (a) 1H NMR and (b) 13C NMR spectra of (±)-2-(1-pyrrolidinyl)-propiophenone (3) Figure S4 1H NMR spectrum of (±)-N,N-dimethylcathinone D-DTT salt (1-D-DTT)Figure S5 1H NMR spectrum of (±)-N,N-dimethylcathinone D-DBT salt (1-D-DBT)Figure S61H NMR spectrum of (±)-N,N-dimethylcathinone D-DBT salt (1-L-DBT)Figure S7 1H NMR spectrum of (±)-N,N-diethylcathinone D-DTT salt (2-D-DTT)Figure S8 1H NMR spectrum of (±)-N,N-diethylcathinone D-DBT salt (2-D-DBT)Figure S9 1H NMR spectrum of (±)-N,N-diethylcathinone L-DBT salt (2-L-DBT)Figure S10 1H NMR spectrum of (±)-2-(1-pyrrolidinyl)-propiophenone D-DTT salt (3-D-DTT)Figure S11 1H NMR spectrum of (±)-2-(1-pyrrolidinyl)-propiophenone D-DBT salt (3-D-DBT)Figure S12 1H NMR spectrum of (±)-2-(1-pyrrolidinyl)-propiophenone L-DBT salt (3-L-DBT)Figure S13 1H NMR spectra of compound (a) S-1 and (b) R-1Figure S14 1H NMR spectra of compound (a) S-2 and (b) R-2Figure S15 1H NMR spectra of compound (a) S-3 and (b) R-3Figure S16 Circular Dichroism spectra of (a) S-2 (red) and R-1 (blue) and (b) S-3 (red) and R-3 (blue)
Figure S17 HPLC traces of (a) R-1 and (b) S-1
Figure S18 HPLC traces of (a) R-2 and (b) S-2
Figure S19 HPLC traces of (a) R-3 and (b) S-3
Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry.This journal is © The Royal Society of Chemistry 2015
1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)
-5000
0
5000
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20000
25000
30000
35000
40000
45000
50000
55000
60000
65000
70000
75000
80000
85000
90000
95000
3.10
6.04
1.00
1.91
0.97
1.92
O
N
CH3
CH3
CH3
2,4
6
1,5
CDCl3 DCM 9
12,13
11
1
2
4
5
6
9
12
13
11
*
-20-100102030405060708090100110120130140150160170180190200210f1 (ppm)
0
10000
20000
30000
40000
50000
60000
70000
80000
90000
1E+05
1E+05
1E+05
1E+05
1E+05
2E+05
2E+05
2E+05
2E+05
2E+05
2E+05
7
carbon atoms in aromatic ring
CDCl3
9
DCM
11
triethylaminetriethylamine
12,13
O
N
CH3
CH3
CH31
2
46
9
12
13
11
*
Figure S1 (a) 1H NMR and (b) 13C NMR spectra of (±)-N,N-dimethylcathinone (1) (CDCl3, 20 oC).
1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)
-200
0
200
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600
800
1000
1200
1400
1600
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2000
2200
2400
2600
2800
3000
3200
3400
3600
3800
4000
4200
6.01
3.22
4.15
1.00
2.06
0.99
1.98
O
CH3
N
CH3
CH3
2,4
6
1,5
CDCl3DCM
9
12,14
10
13,15
1
2
4
5
6
9
10
12
14
13
15*
0102030405060708090100110120130140150160170180190200f1 (ppm)
0
10000
20000
30000
40000
50000
60000
70000
80000
90000
1E+05
7
carbon atoms in aromatic ring
CDCl3
9 DCM
triethylamine
11 12,13
14,15
O
CH3
N
CH3
CH312
4
5
6
9
10
12
14
13
15*
Figure S2 (a) 1H NMR and (b) 13C NMR spectra of (±)-N,N-diethylcathinone (2) (CDCl3, 20 oC).
1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)
-100
0
100
200
300
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500
600
700
800
900
1000
1100
1200
3.19
4.21
3.98
1.00
1.88
1.24
1.97
O
CH3
N
2,4
6
1,5
CDCl3
DCM
9
12,15
13,14
10
1
2
4
5
6
9
10
1213
14
15*
2030405060708090100110120130140150160170180190200f1 (ppm)
0
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20000
25000
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70000
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80000
85000
7
carbon atoms in aromatic ring
CDCl3
9
11 12,15
13,14
O
CH3
N1
2
46
9
10
12
15*
Figure S3 (a) 1H NMR and (b) 13C NMR spectra of (±)-2-(1-pyrrolidinyl)-propiophenone (3) (CDCl3, 20 oC).
1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)
-100
0
100
200
300
400
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600
700
800
900
1000
1100
1200
1300
1400
1500
1600
1700
1800
1900
2.99
5.63
6.14
1.17
3.84
1.90
1.00
3.80
1.87
O
N+
CH3
CH3
H
CH3
O O
OO
O
CH3OOCH3
OH
2,4
26,30,36,40
61,5
27,29,37,39
9
DCMH2O
DMSO
31,4112,14
11
1
2
4
5
6
26
30
36
40
27
2937
39
9
31
41
12
14
11
*
Figure S4 1H NMR spectrum of (±)-N,N-dimethylcathinone D-DTT salt (1-D-DTT) (DMSO-D6, 20 oC).
CH3CH3
O
O
OHO
O
O
O
H
O
O
N+
CH3
1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)
0
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55000
2.99
5.65
1.00
5.48
2.93
3.80
1.97
35,37
14,17,23,26
33,34,38
13,15,16,22,24,25
30
39,40
28DCM
DMSO
35
37
14
1723
2633 34
38
13
15
16
22
2425
30
39
40
28
*
Figure S5 1H NMR spectrum of (±)-N,N-dimethylcathinone D-DBT salt (1-D-DBT) (DMSO-D6, 20 oC).
*
CH3CH3
O
O
OHO
O
O
O
H
O
O
N+
CH3
1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)
-10000
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90000
1E+05
1E+05
1E+05
1E+05
1E+05
2E+05
2E+05
2E+05
3.28
6.42
1.00
6.10
3.07
3.84
2.35
35,37
14,17,23,26
33,34,38
13,15,16,22,24,25
30
DCM
DMSO
39,40
28
35
37
14
17
23
26
38
3334
13
15
16
22
24
25
30
39
40
28
Figure S6 1H NMR spectrum of (±)-N,N-dimethylcathinone L-DBT salt (1-L-DBT) (DMSO-D6, 20 oC).
1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)
-50
0
50
100
150
200
250
300
350
400
450
500
550
600
650
4.08
3.27
5.98
4.68
1.10
3.71
1.88
1.00
3.73
2.01
2,4
26,30,36,40
6
1,527,29,37,39
9
H2O
12,14
DMSO
31,41
11
43,44
12
4
26
30
6
5
27
29
9
1214
31
11
43 44
*
41
3940
3637
CH3
N+
O
CH3
H
O O
O
O
CH3O OH
O
O
CH3CH3
Figure S7 1H NMR spectrum of (±)-N,N-diethylcathinone D-DTT salt (2-D-DTT) (DMSO-D6, 20 oC).
1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)
0
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10000
15000
20000
25000
30000
35000
40000
45000
6.18
3.16
4.64
1.00
6.25
3.25
4.06
2.10
O
O
OHO
O
O
O
H
O
O
N+
CH3
CH3
CH3
35,37
14,17,23,26
33,34,38
13,15,16,22,24,25DCM
3039,40
DMSO
28
41,42
35
37
14
17
23
2633
38
34
13
15
16
22
2425
30
3940
28
41
42
*
Figure S8 1H NMR spectrum of (±)-N,N-diethylcathinone D-DBT salt (2-D-DBT) (DMSO-D6, 20 oC).
1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)
-10000
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50000
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80000
90000
1E+05
1E+05
1E+05
1E+05
1E+05
2E+05
2E+05
2E+05
2E+05
5.35
2.92
4.05
1.00
5.83
3.00
3.93
1.94
O
O
OHO
O
O
O
H
O
O
N+
CH3
CH3
CH3
35,37
14,17,23,26
33,34,38
13,15,16,22,24,25
DCM
39,4030
DMSO
28
41,42
35
37
14
17
23
2633 34
38
13
15
16
22
2425
30
3940
28
41
42
*
Figure S9 1H NMR spectrum of (±)-N,N-diethylcathinone L-DBT salt (2-L-DBT) (DMSO-D6, 20 oC).
O
O
OHO CH3
O
O
OO
H
CH3
O
N+
CH3
1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)
-5000
0
5000
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60000
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70000
2.97
4.01
6.39
4.27
1.09
4.49
1.95
1.00
4.27
1.97
41,43
14,17,24,27
39
40,44
13,16,23,26 DCM
36
30,33
DMSO
18,28
31,32
34
41
43
14
17
24
2739
40
44
13
16
23
26
36
3033
18
28
32
34
*
31
Figure S10 1H NMR spectrum of (±)-2-(1-pyrrolidinyl)-propiophenone D-DTT salt (3-D-DTT)(DMSO-D6, 20 oC).
1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)
-2000
0
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2.78
3.69
3.97
1.00
4.30
1.93
1.27
3.83
1.75
O
O
OHO
O
O
OO
H
CH3
N+
O
33,34
14,17,23,26
36
35,37
13,15,16,22,24,25
DCM
42
28,31
DMSO
acetone
29,30
41
33
34
13
1723
263536
37
15
14
16
22
24
25
422831
2930
41
*
Figure S11 1H NMR spectrum of (±)-2-(1-pyrrolidinyl)-propiophenone D-DBT salt (3-D-DBT)(DMSO-D6, 20 oC).
1.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)
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50000
60000
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90000
1E+05
1E+05
1E+05
1E+05
1E+05
2.91
3.93
4.11
1.00
3.82
1.62
2.37
1.17
4.03
2.04
33,34
14,17,23,26
36
35,37
15,24
13,16,22,25
DCM
42
28,3129,30
DMSO
41
14
33
34
1723
263536
37
15
2413
16
22
25
4228
31
2930
41
*
O
O
OHO
O
O
OO
H
CH3
N+
O
Figure S12 1H NMR spectrum of (±)-2-(1-pyrrolidinyl)-propiophenone L-DBT salt (3-L-DBT)(DMSO-D6, 20 oC).
1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)
0
100
200
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900
1000
1100
1200
1300
1400
1500
O
N
CH3
CH3
CH3
1,2
5
3,4
6
8, 9
7
6
5
1
2
3
47
8
9
1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)
-20000
-10000
0
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60000
70000
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90000
1E+05
1E+05
1E+05
1E+05
1E+05
2E+05
2E+05
2E+05
2E+05
2E+05
2E+05
2E+05
2E+05
2E+05
2E+05
O
N
CH3
CH3
CH3
1,25
3,4
6
8, 9
7
5
3
4
1
2
6
8
9
7
Figure S13 1H NMR spectra of compound (a) S-N,N-dimethylcathinone (S-1) and (b) R-N,N-dimethylcathinone (R-1) (CDCl3, 20 oC).
1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)
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30000
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50000
60000
70000
80000
90000
1E+05
1E+05
1E+05
1E+05
1E+05
2E+05
2E+05
2E+05
6.33
3.75
4.54
1.09
2.12
1.00
2.02
O
N
CH3
CH3
CH3
1
2
3
4
5
6
7
8
9
10
11
1,2
5
3,4
68,9
7
10,11
DCM
Acetone
1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)
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0
10000
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30000
40000
50000
60000
70000
80000
90000
1E+05
1E+05
1E+05
3.08
1.63
2.20
0.52
1.01
0.57
1.00
O
N
CH3
CH3
CH3
1
2
3
4
5
6
7
8
9
10
11
1,2
5
3,4
6
8,9
7
10,11
DCM
Acetone
Figure S14 1H NMR spectra of compound (a) S-N,N-diethylcathinone (S-2) and (b) R-N,N-diethylcathinone (R-2) (CDCl3, 20 oC).
1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)
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1.36
2.15
2.09
0.50
0.79
0.51
1.00
O
N
CH3
1,2
5
3,4
1
2
3
4
5
6
7
8
9
10
11
6
8,9
10,11
7
DCM
Acetone
1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)
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60000
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90000
1E+05
1E+05
1.51
2.04
2.03
0.52
0.99
0.50
1.00
O
N
CH3
1
2
3
4
5
6
7
8
9
10
11
1,2
5
3,4
DCM
6
8,9
Acetone
10,11
7
Figure S15 1H NMR spectra of compound (a) S-2-(1-pyrrolidinyl)-propiophenone (S-3) and (b) R-2-(1-pyrrolidinyl)-propiophenone (R-3) (CDCl3, 20 oC).
(a)
200 220 240 260 280 300 320 340 360 380 400-2000
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/
M-1m-1
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800
Wavelength / nm
/
M-1m-1
Figure S16 Circular Dichroism spectra of (a) S-2 (red) and R-1 (blue) and (b) S-3 (red) and R-3 (blue) (approx. 4 x 10-5 mol dm-3 in methanol 293 K).
0 2 4 6 8 10 12 14 16
Retention time / min
Figure S17 HPLC traces of (a) S-1 and (b) R-1 CHIRACEL® OJ-H HPLC column, 2% 2-propanol in n-hexane, 298K)
0 2 4 6 8 10 12 14 16Retention time / min
Figure S18 HPLC traces of (a) S-2 and (b) R-2 CHIRACEL® OJ-H HPLC column, 3% 2-propanol in n-hexane, 298K)
0 2 4 6 8 10 12 14 16
Retention time / min
Figure S19 HPLC traces of (a) S-3 and (b) R-3 CHIRACEL® OJ-H HPLC column, 2% 2-propanol in n-hexane, 298K)
a)
b)
a)
b)
a)
b)
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