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TRANSCRIPT
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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
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1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)
-5000
0
5000
10000
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20000
25000
30000
35000
40000
45000
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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
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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
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).
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1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)
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800
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1200
1400
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2200
2400
2600
2800
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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)
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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).
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1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.5f1 (ppm)
-100
0
100
200
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400
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)
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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
500
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700
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900
1000
1100
1200
1300
1400
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1600
1700
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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)
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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)
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70000
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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)
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6.18
3.16
4.64
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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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90000
1E+05
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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)
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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)
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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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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
300
400
500
600
700
800
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
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0
10000
20000
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50000
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).
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1.01.52.02.53.03.54.04.55.05.56.06.57.07.58.0f1 (ppm)
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0
10000
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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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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).
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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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1E+05
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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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200
400
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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)