Synthesis and complete assignment of the 1H and 13C NMR signals of new acetamido and aminoflavonoid derivatives

Article abstract of DOI:10.1002/mrc.2638

The complete 1H and13C NMR assignment of 9 acetamidochalcones, 18 acetamidoflavones, 18 aminoflavones, 9 acetamidoflavonols and 9 aminoflavonols has been performed using one- and two-dimensional NMR techniques including COSY, HMQC and HMBC experiments. Copyright

Full text of DOI:10.1002/mrc.2638

MRC Letters
Received: 6 April 2010
Revised: 17 May 2010
Accepted: 26 May 2010
Published online in Wiley Interscience: 29 June 2010
(www.interscience.com) DOI 10.1002/mrc.2638
Synthesis and complete assignment of the 1H
and 13C NMR signals of new acetamido
and aminoflavonoid derivatives
Gilles Casano,a Maxime Robin,a∗ Pascale Barbier,b Vincent Peyrotb
and Robert Faurea
The complete 1H and 13C NMR assignment of 9 acetamidochalcones, 18 acetamidoflavones, 18 aminoflavones, 9 acetamid-
oflavonols and 9 aminoflavonols has been performed using one- and two-dimensional NMR techniques including COSY, HMQC
c
and HMBC experiments. Copyright ꢀ 2010 John Wiley & Sons, Ltd.
Keywords: NMR; 1H NMR; 13C NMR; COSY; HMQC; HMBC; chalcones; flavones; flavonols
Introduction
NMR techniques
1H and 13C NMR experiments were performed at 300 K using
a Bruker Avance DRX 300 spectrometer in a 5-mm QNP probe.
Samples were dissolved in DMSO-d6 solutions, and the central
peak of solvent[24] (δH = 2.50 ppm and δC = 39.5 ppm) was used
as internal standard. Resonance multiplicities for 13C signals were
established via the acquisition of DEPT spectra. All 2D spectra were
acquired at 300 K on a Bruker Avance DRX 500 equipped with a
Bruker CryoPlatform and a 5-mm cryo TXI probe. The temperature
of the probe and preamplifier was 30 K. For 2D experiments Bruker
microprograms using gradient selection (gs) were applied. COSY
spectra[25] were obtained with an F2 spectral width of 10 ppm and
2K data points and an F1 spectral width of 256 t1 increments with
sine-bell windows in both dimensions. The HMQC spectra (inv4gs
in the standard Bruker software) resulted from 256 × 1024 data
matrix size with 32 scans per t1, an inter-pulse delay of 3.2 ms
and a 5 : 3 : 4 gradient combination.[26] The HMBC spectra[27] were
measured using a pulse sequence (hmbcgs in the Bruker library)
optimized on 3J coupling values of 8 Hz (inter-pulse delay for the
evolution of long-range coupling: 50 ms), and the same gradient
ratio as described for the HMQC experiments. In this way direct
responses (1J couplings) were not completely removed.
Flavonoids, a family of polyphenolic compounds, are prominent
plant secondary metabolites found in dietary components in-
cluding fruits, vegetables, olive oil, tea and red wine.[1,2] Owing
to their multiple biological activities, such as leishmanicidal,[3]
anti-HIV,[4–6] antiviral,[7,8] antioxidant,[9,10] bactericidal,[11,12]
anticancer[13,14] and cardioprotective[15], flavonoids synthetic
pathways have attracted considerable attention.[16–18] In order
to evaluate the potential anti-HIV and antiplasmodial activity of
flavonoids compounds, we have started a medicinal chemistry
program to highlight an SAR study of chalcone, flavone and
flavonol derivatives with amino-substituents. Recently, synthesis
and NMR data have been reported for flavones with amino groups
in various positions of B ring.[19] In this paper, we present the syn-
thesis and structural elucidation by 1D and 2D NMR experiments
of flavonoids with acetamido or amino groups in position 6 of
A ring and fluoro, trifluoromethyl and methoxy substituents in
various positions of B ring.
Experimental
Synthesis
Chalcones (1) were obtained in 10 min with good yields (70–95%)
from a modified Claisen–Schmidt condensation[20] of substi-
tuted benzaldehydes and 2-hydroxy-5-acetamidoacetophenone
using lithium hydroxide in methanol under full-power mi-
crowave irradiation (MWI) (300 W). Chalcones were converted
to flavonols (3)[21] by treatment with alkaline hydrogen per-
oxide for 24 h (40–70%). These flavonols were methylated
using dimethyl sulphate to afforded 3-methoxyflavones (4).[22]
Flavone derivatives (2) were obtained[23] by oxidative cycli-
sation of corresponding chalcone in DMSO with catalytic io-
dine in 90–95% yields during 30 min at full-power MWI.
Deprotection of acetamido intermediates to the correspond-
ing amino compounds (5–7) was done in ethanol and con-
centrated H2SO4 (9/1) under MWI for 30 min in quantitative
yield.
Results and Discussion
The 1H and 13C assignments are presented in Tables 1–4. The
compounds were grouped in seven different series: chalcones 1,
∗
´
´
Correspondence to: Maxime Robin, UMR 6263, ISM2, Universite Paul Cezanne,
Case 552 Avenue Escadrille, Normandie-Niemen 13397 Marseille Cedex
20, France. E-mail: maxime.robin@univ-cezanne.fr
´
´
a
UMR 6263, ISM2, Universite Paul Cezanne, Case 552 Avenue Escadrille
Normandie-Niemen, 13397 Marseille Cedex 20, France
´
´
´
b
CRO2, UMR 911-INSERM, Universite de la Mediterranee, UFR de Pharmacie, 27
Bd Jean Moulin, Marseille 13005, France
c
Magn. Reson. Chem. 2010, 48, 738–744
Copyright ꢀ 2010 John Wiley & Sons, Ltd.

Synthesis and complete assignment of the 1H and 13C NMR signals
Table 1. 1H NMR chemical shiftsa,b for acetamidochalcones 1a–i
Position
1a
1b
1c
1d
1e
1f
1g
1h
1i
H-3
H-4
H-6
H-α
H-β
H-2ꢁ
H-3ꢁ
H-4ꢁ
H-5ꢁ
H-6ꢁ
CH3
NH
6.96
7.71
8.17
7.77
7.77
7.79
7.47
7.47
7.47
7.79
2.03
10.00
11.70
6.96
7.69
8.28
7.84
8.04
–
6.96
7.71
8.14
7.72
7.79
7.37
–
6.96
7.71
8.19
7.64
7.79
7.78
7.04
–
6.96
7.71
8.14
7.79
7.85
–
6.96
7.70
8.11
7.74
7.82
7.63
–
6.97
7.71
8.18
7.73
7.78
7.90
7.32
–
6.96
7.71
8.10
7.83
7.93
8.21
–
6.97
7.70
8.11
7.79
7.89
7.82
8.01
–
7.13
7.47
7.05
7.79
2.05
9.95
11.93
7.34
7.53
7.32
7.92
2.08
9.95
11.57
7.04
7.37
7.37
2.02
9.92
11.71
7.29
7.50
7.72
2.02
9.87
11.63
7.82
7.69
8.11
2.02
9.91
11.60
7.04
7.78
2.04
9.95
11.98
7.32
7.90
2.03
10.01
11.73
8.01
7.82
2.02
9.92
11.50
OH
a In ppm from TMS; DMSO-d6 as solvent.
b 1H resonances in the substituents (in ppm): 2b, OCH3 3.93; 2c, OCH3 3.81; 2d, OCH3 3.82.
Table 2. 13C NMR chemical shiftsa,b for acetamidochalcones 1a–i
Position
1a
1b
1c
1d
1e
1f
1g
1h
1i
C-1
C-2
C-3
C-4
C-5
C-6
C-βꢁ
C-α
C-β
C-1ꢁ
C-2ꢁ
C-3ꢁ
C-4ꢁ
C-5ꢁ
C-6ꢁ
CO
121.46
156.93
117.90
128.22
131.35
121.17
193.06
122.94
144.30
134.66
129.29
128.99
131.13
128.99
129.29
168.35
23.92
120.93
157.17
117.83
129.41
131.27
120.56
193.22
122.41
139.51
122.82
158.69
112.03
132.69
120.90
127.97
168.22
23.85
121.39
156.93
117.86
128.29
131.27
121.23
193.13
123.26
144.28
136.06
113.97
159.87
116.93
130.29
121.44
168.28
23.88
120.89
157.10
117.69
128.08
131.03
120.89
192.89
119.57
144.55
127.03
130.84
114.61
162.13
114.61
130.84
168.13
23.72
121.47
156.52
117.75
127.93
131.26
120.72
192.45
125.46
135.68
122.21
161.05
116.28
132.83
125.16
129.87
168.13
23.74
121.46
156.95
117.87
128.52
131.23
121.46
193.00
125.34
142.66
137.24
114.96
162.67
117.66
131.28
121.46
168.29
23.84
121.26
156.74
117.68
128.10
131.12
121.11
192.81
122.69
142.87
122.69
131.18
116.15
163.57
116.15
131.18
168.13
23.70
121.68
156.85
117.87
128.54
131.24
121.48
192.93
125.28
142.17
135.89
125.36
130.08
127.08
130.29
132.67
168.28
23.85
121.78
156.60
117.86
128.27
131.31
121.28
192.66
126.04
141.79
138.70
129.43
126.05
130.27
126.05
129.43
168.24
23.85
CH3
a In ppm from TMS; DMSO-d6 as solvent.
b 13C resonances in the substituents (in ppm) and nJC,F (in Hz): 1b, OCH3 55.83; 1c, OCH3 55.50; 1d, OCH3 55.45; 1e, 1JC−2 ,F = 252.0, 2JC−1 ,F = 11.3,
ꢁ
ꢁ
3
3
3
4
1
2
2
3
2JC−3 ,F = 21.9, JC−4 ,F = 8.3, JC−6 ,F = 2.1, JC−β,F = 3.0, JC−α,F = 6.0; 1f, JC−3 ,F = 243.0, JC−2 ,F = 21.9, JC−4 ,F = 21.1, JC−1 ,F = 7.5,
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
3JC−5 ,F = 7.5, JC−β,F = 3.0, JC−α,F = 3.0; 1g, JC−4 ,F = 249.0, JC−3 ,F = 21.9, JC−2 ,F = 9.8; 1h, CF3 124.20, JC,F = 270.0, JC−3 ,F = 31.7,
4
5
1
2
3
1
2
ꢁ
ꢁ
ꢁ
ꢁ
3JC−2 ,F = 4.2, 3JC−4 ,F = 4.2; 1i, CF3 124.09, 1JC,F = 269.0, 2J
= 32.1, 3JC−3 ,F = 3.8.
ꢁ
ꢁ
ꢁ
ꢁ
C−4 ,F
acetamidoflavones 2, acetamidoflavonols 3, methoxy-3 acetamid-
oflavonols 4, aminoflavones 5, aminoflavonols 6 and methoxy-3
aminoflavonols 7 (Fig. 1). The A ring protons, which were easily as-
signed on the basis of chemical shifts and multiplicity, enabled the
assignment by direct correlation (HMQC) of carbons to which they
are directly attached. HMBC experiments were then performed
to establish long-range H/C correlations. Based on these experi-
ments, the three quaternary carbon signals C-9 (C-2 for chalcones),
C-10 (C-1 for chalcones) and C-6 (C-5 for chalcones) could be read-
ily assigned. For the 1a–1i derivatives, the complete assignment
of the C ring protons required the unambiguous determination
of the very near H-α and H-β resonances which were assigned
based on the HMQC results, since C-β is more deshielded than
C-α.[28]
Most of the 1H and 13C chemical shift assignmentsof the B
ring resonances were achieved, in a straightforward manner, on
the basis of signal intensities, chemical shift considerations,[29]
n
n
magnitude of J (C,F) and J (H,F) coupling constants and long-
range correlation peaks (3J couplings) from the methoxy protons.
The complete assignment of the other ring B resonances was
based on the analysis of the COSY, HMQC and HMBC spectra.
Finally, some of aminoflavones or aminoflavonols (5g, 5i, 6c, 6g,
6i, 7d and7e) were studied either as chlorhydrates or as a mixture
of neutral and protonated species.
c
Magn. Reson. Chem. 2010, 48, 738–744
Copyright ꢀ 2010 John Wiley & Sons, Ltd.
www.interscience.wiley.com/journal/mrc

G. Casano et al.
Table 3. 1H NMR chemical shiftsa,b,c for acetamido-(2–4) and amino(5–7) flavonoid derivatives
Position
2a
2b
2c
2d
2e
2f
2g
2h
2i
H-3
H-5
H-7
H-8
H-2ꢁ
H-3ꢁ
H-4ꢁ
H-5ꢁ
H-6ꢁ
CH3
NH
7.00
8.34
7.96
7.75
8.10
7.60
7.58
7.60
8.10
2.09
10.27
–
6.84
8.30
7.89
7.64
–
7.03
8.33
7.95
7.75
7.58
–
6.90
8.31
7.94
7.72
8.04
7.12
–
6.70
8.31
7.93
7.65
–
7.06
8.31
7.93
7.73
7.94
–
6.97
8.31
7.94
7.71
8.14
7.40
–
7.18
8.32
7.96
7.80
8.40
–
7.15
8.35
7.97
7.78
8.31
7.94
–
7.20
7.52
7.10
7.85
2.06
10.23
–
7.42
7.62
7.40
7.97
2.07
10.26
–
7.16
7.48
7.67
2.09
10.31
–
7.43
7.61
7.92
2.09
10.27
–
7.96
7.81
8.39
2.08
10.28
–
7.12
8.04
2.08
10.27
–
7.40
8.14
2.08
10.26
–
7.94
8.31
2.09
10.30
–
NH2
OH
–
–
–
–
–
–
–
–
–
OCH3
–
–
–
–
–
–
–
–
–
Atom
3a
3b
3c
3d
3e
3f
3g
3h
3i
H-3
H-5
H-7
H-8
H-2ꢁ
H-3ꢁ
H-4ꢁ
H-5ꢁ
H-6ꢁ
CH3
NH2
NH
–
–
8.46
7.86
7.58
–
–
8.45
7.92
7.73
7.75
–
–
8.41
7.88
7.71
8.19
7.12
–
–
8.48
7.88
7.62
–
–
8.45
7.92
7.73
8.02
–
–
8.44
7.91
7.71
8.27
7.40
–
–
8.42
7.91
7.76
8.54
–
–
8.44
7.90
7.73
8.40
7.92
–
8.42
7.90
7.71
8.19
7.55
7.51
7.55
8.19
2.08
–
7.19
7.49
7.08
7.46
2.10
–
7.42
7.59
7.37
7.75
2.10
–
7.09
7.47
7.77
2.09
–
7.33
7.60
8.07
2.10
–
7.85
7.80
8.46
2.08
–
7.12
8.19
2.09
–
7.40
8.27
2.08
–
7.92
8.40
2.09
–
10.30
9.53
–
10.27
8.87
–
10.27
9.45
–
10.26
9.40
–
10.28
9.36
–
10.27
9.39
–
10.35
9.51
–
10.25
9.93
–
10.26
9.98
–
OH
OCH3
Atom
4a
4b
4c
4d
4e
4f
4g
4h
4i
H-3
H-5
H-7
H-8
H-2ꢁ
H-3ꢁ
H-4ꢁ
H-5ꢁ
H-6ꢁ
CH3
NH2
NH
–
–
8.42
7.92
7.59
–
–
8.38
7.94
7.72
7.57
–
–
8.36
7.93
7.70
8.05
7.14
–
–
8.42
7.94
7.64
–
–
8.36
7.93
7.70
7.83
–
–
8.37
7.92
7.69
8.21
7.40
–
–
8.37
7.94
7.72
8.32
–
–
8.37
7.95
7.70
8.22
7.94
–
8.37
7.94
7.67
8.02
7.56
7.58
7.56
8.02
2.08
–
7.19
7.54
7.09
7.49
2.08
–
7.43
7.63
7.40
7.73
2.10
–
7.16
7.50
7.62
2.10
–
7.41
7.62
7.89
2.08
–
7.94
7.82
8.31
2.09
–
7.14
8.05
2.09
–
7.40
8.21
2.09
–
7.94
8.22
2.08
–
10.28
–
10.29
–
10.27
–
10.29
–
10.30
–
10.26
–
10.26
–
10.28
–
10.28
–
OH
OCH3
3.81
3.81
3.82
3.79
3.77
3.83
3.81
3.84
3.83
Atom
5a
5b
5c
5d
5e
5f
5gc
5h
5ic
H-3
H-5
H-7
H-8
H-2ꢁ
H-3ꢁ
H-4ꢁ
H-5ꢁ
H-6ꢁ
CH3
6.87
7.13
7.09
7.51
8.05
7.58
7.57
7.58
8.05
–
6.76
7.14
7.08
7.45
–
6.91
7.14
7.10
7.53
7.55
–
6.78
7.08
7.06
7.47
8.00
7.10
–
6.93
7.11
7.09
7.46
–
6.95
7.11
7.07
7.52
7.91
–
7.08
7.82
7.63
7.87
8.20
7.45
–
7.06
7.13
7.11
7.57
8.35
–
7.08
7.36
7.29
7.65
8.29
7.93
–
7.22
7.54
7.12
7.84
–
7.44
7.63
7.41
7.96
–
7.12
7.47
7.62
–
7.42
7.61
7.91
–
7.94
7.80
8.36
–
7.10
8.00
–
7.45
8.20
–
7.93
8.29
–
c
www.interscience.wiley.com/journal/mrc
Copyright ꢀ 2010 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2010, 48, 738–744

Synthesis and complete assignment of the 1H and 13C NMR signals
Table 3. (Continued)
Atom
5a
5b
5c
5d
5e
5f
5gc
5h
5ic
NH2
NH
5.53
5.55
5.55
5.44
5.55
5.61
5.52
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
OH
OCH3
Atom
6a
6b
6cc
6d
6e
6f
6gc
6hc
6ic
H-3
H-5
H-7
H-8
H-2ꢁ
H-3ꢁ
H-4ꢁ
H-5ꢁ
H-6ꢁ
CH3
NH2
NH
–
–
–
–
–
–
–
–
–
7.18
7.10
7.48
8.17
7.55
7.50
7.55
8.17
–
7.18
7.05
7.33
–
7.36
7.24
7.59
7.74
–
7.12
7.06
7.45
8.15
7.10
–
7.16
7.07
7.39
–
7.15
7.10
7.50
7.98
–
7.88
7.60
7.84
8.26
7.42
–
7.39
7.27
7.63
8.52
–
7.71
7.49
7.76
8.41
7.93
–
7.16
7.49
7.06
7.44
–
7.35
7.58
7.35
7.73
–
7.08
7.47
7.78
–
7.32
7.59
8.04
–
7.85
7.80
8.45
–
7.10
8.15
–
7.42
8.26
–
7.93
8.41
–
5.55
–
5.45
–
5.44
–
5.48
–
5.53
–
–
–
–
–
OH
8.54
–
8.72
–
9.75
–
OCH3
–
–
–
–
–
–
Atom
7a
7b
7c
7dc
7e
7f
7g
7h
7i
H-3
H-5
H-7
H-8
H-2ꢁ
H-3ꢁ
H-4ꢁ
H-5ꢁ
H-6ꢁ
CH3
NH2
NH
–
–
–
–
–
–
–
–
–
7.21
7.13
7.48
8.00
7.58
7.57
7.58
8.00
–
7.06
7.01
7.44
–
7.12
7.07
7.46
7.53
–
7.40
7.27
7.59
8.03
7.13
–
7.33
7.19
7.46
–
7.12
7.08
7.48
7.81
–
7.12
7.06
7.44
8.28
7.40
–
7.14
7.09
7.51
8.30
–
7.12
7.09
7.47
8.21
7.92
–
7.28
7.46
7.03
7.42
–
7.42
7.64
7.39
7.73
–
7.12
7.47
7.57
–
7.40
7.61
7.87
–
7.93
7.82
8.30
–
7.13
8.03
–
7.40
8.28
–
7.92
8.21
–
5.53
–
5.51
–
5.51
–
–
–
5.51
–
5.51
–
5.56
–
5.54
–
–
–
OH
–
–
–
–
–
–
–
–
–
OCH3
3.78
3.83
3.78
3.78
3.78
3.80
3.77
3.82
3.80
a In ppm from TMS; DMSO-d6 as solvent.
b 1H resonances in the substituents (in ppm): 2b, OCH3 3.79; 2c, OCH3 3.82; 2d, OCH3 3.85; 3b, OCH3 3.79; 3c, OCH3 3.82; 3d, OCH3 3.85; 4b, OCH3
3.75; 4c, OCH3 3.85; 4d, OCH3 3.86; 5b, OCH3 3.90; 5c, OCH3 3.86; 5d, OCH3 3.85; 6b, OCH3 3.78; 6c, OCH3 3.83; 6d, OCH3 3.83; 7b, OCH3 3.78; 7c,
OCH3 3.82; 7d, OCH3 3.85.
c Recorded as an hydrochloride.
Table 4. 13C NMR chemical shiftsa,b,c for acetamido-(2–4) and amino(5–7) flavonoid derivatives
Position
2a
2b
2c
2d
2e
2f
2g
2h
2i
C-2
C-3
C-4
C-5
C-6
C-7
C-8
C-9
C-10
C-1ꢁ
C-2ꢁ
162.34
106.42
176.98
113.01
136.79
125.56
119.01
151.49
123.50
131.21
126.29
160.47
112.52
177.02
112.94
136.67
125.54
118.96
151.76
123.25
119.99
157.58
162.15
106.72
177.08
113.01
136.82
125.61
119.10
151.51
123.51
132.64
111.50
162.14
105.00
176.86
113.13
136.69
125.40
118.91
151.46
123.35
123.35
128.19
159.50
111.10
176.93
113.11
137.12
125.97
119.24
151.84
123.47
119.24
160.23
160.81
107.11
177.02
112.95
136.89
125.64
119.08
151.41
123.47
133.61
113.18
161.40
106.32
176.92
113.00
136.80
125.55
118.99
151.43
123.40
127.80
128.98
160.60
107.50
177.04
112.96
136.94
125.70
119.21
151.49
123.51
132.48
122.90
160.62
107.84
176.99
112.94
136.96
125.78
119.12
151.47
123.50
135.19
127.17
c
Magn. Reson. Chem. 2010, 48, 738–744
Copyright ꢀ 2010 John Wiley & Sons, Ltd.
www.interscience.wiley.com/journal/mrc

G. Casano et al.
Table 4. (Continued)
Position
2a
2b
2c
2d
2e
2f
2g
2h
2i
C-3ꢁ
C-4ꢁ
C-5ꢁ
C-6ꢁ
CO
129.11
131.74
129.11
126.29
168.55
23.98
111.09
132.86
120.76
129.15
168.58
24.01
159.73
117.59
130.31
118.60
168.64
24.02
114.61
162.50
114.61
128.19
168.61
24.01
117.10
133.89
125.37
129.75
168.80
24.18
162.44
118.50
131.21
121.42
168.59
24.00
116.21
164.11
116.21
128.98
168.56
23.98
129.99
128.08
130.33
130.33
168.61
24.01
125.95
131.27
125.95
127.17
168.61
23.99
CH3
Atom
3a
3b
3c
3d
3e
3f
3g
3h
3i
C-2
C-3
C-4
C-5
C-6
C-7
C-8
C-9
C-10
C-1ꢁ
C-2ꢁ
C-3ꢁ
C-4ꢁ
C-5ꢁ
C-6ꢁ
CO
145.25
138.87
172.96
112.77
136.05
125.74
119.08
150.76
121.48
130.02
127.75
128.68
131.34
128.68
127.75
168.84
24.09
147.00
138.81
172.56
112.71
135.89
125.26
118.89
151.05
122.06
119.94
157.13
111.96
131.75
120.15
131.06
168.56
24.02
144.86
138.97
172.94
112.71
136.09
125.76
119.05
150.68
121.37
132.65
113.46
159.25
115.31
129.77
120.10
168.82
24.05
145.65
138.05
172.62
112.81
136.06
125.43
118.98
150.62
121.26
124.43
129.53
113.22
160.58
113.22
129.53
168.70
24.17
143.36
139.22
172.61
112.72
136.08
125.57
118.95
151.05
121.96
118.97
159.18
116.17
132.48
124.40
131.22
168.61
24.03
143.39
139.32
172.97
112.59
136.10
125.81
118.99
150.58
121.31
134.05
114.24
162.03
116.65
130.55
121.31
168.67
23.99
144.28
138.66
173.00
112.63
136.01
125.55
118.90
150.55
121.37
128.00
130.37
115.62
162.60
115.62
130.37
168.62
24.00
143.11
139.44
172.95
112.57
136.07
125.73
119.04
150.59
121.36
132.45
123.96
129.33
126.03
129.78
131.10
168.55
23.98
143.41
140.04
172.65
112.76
136.32
126.02
119.21
150.82
121.53
135.58
128.31
125.59
130.50
125.59
128.31
168.76
24.19
CH3
Atom
4a
4b
4c
4d
4e
4f
4g
4h
4i
C-2
140.42
154.79
173.70
112.85
136.39
125.56
118.89
150.62
123.69
130.52
128.20
128.63
130.78
128.63
128.20
168.55
24.01
140.85
155.65
173.39
112.92
136.37
125.47
118.92
151.04
124.08
119.70
156.89
111.74
132.08
120.25
130.44
168.60
24.01
140.53
154.57
173.71
112.83
136.40
125.60
119.00
150.61
123.67
131.72
113.76
159.17
116.33
129.83
120.52
168.57
23.98
139.75
154.79
173.47
112.89
136.30
125.40
118.81
150.49
123.66
122.64
130.00
114.17
161.17
114.17
130.00
168.85
23.98
141.19
152.09
173.51
113.08
136.71
125.88
119.12
151.14
124.16
118.78
159.35
116.28
133.18
124.84
131.27
168.79
24.16
140.94
153.25
173.92
112.98
136.65
125.89
119.20
150.75
123.83
132.83
115.11
162.13
117.86
131.00
124.62
168.78
24.16
140.43
154.18
174.32
113.96
136.10
126.05
118.92
150.91
123.74
126.70
130.38
115.32
163.50
115.32
130.38
168.95
23.85
140.85
152.99
173.76
112.80
136.55
125.73
119.09
150.64
123.74
132.22
124.69
129.47
127.22
129.97
131.60
168.63
24.10
141.27
153.23
173.98
112.98
136.73
126.01
119.22
150.83
123.91
134.68
129.29
125.72
130.49
125.72
129.29
168.82
24.19
C-3
C-4
C-5
C-6
C-7
C-8
C-9
C-10
C-1ꢁ
C-2ꢁ
C-3ꢁ
C-4ꢁ
C-5ꢁ
C-6ꢁ
CO
CH3
OCH3-3
59.66
59.66
59.69
59.45
60.06
59.89
59.61
59.76
60.06
Atom
5a
5b
5c
5d
5e
5f
5gc
5h
5ic
C-2
C-3
C-4
C-5
C-6
C-7
C-8
C-9
C-10
C-1ꢁ
C-2ꢁ
161.70
105.77
177.14
105.24
146.23
121.91
119.03
148.08
124.23
131.60
126.11
159.91
112.48
177.13
105.30
145.95
121.96
118.96
148.45
123.99
120.49
157.41
161.48
106.08
177.16
105.31
145.85
122.07
119.11
148.21
124.23
133.01
111.31
161.82
105.01
177.03
104.38
146.55
121.45
118.83
147.81
124.18
123.78
127.98
157.72
110.24
176.89
104.72
146.85
121.94
119.01
148.09
124.05
120.10
159.58
160.13
106.43
177.18
104.83
146.72
121.88
119.08
147.47
124.23
134.05
112.99
161.86
106.56
176.35
115.81
133.34
127.47
120.32
153.09
123.85
127.60
129.14
160.07
106.98
177.34
105.31
146.57
122.26
119.38
148.25
124.43
133.02
122.82
160.34
107.46
176.98
108.75
142.06
124.06
119.59
149.80
124.17
135.40
130.95
c
www.interscience.wiley.com/journal/mrc
Copyright ꢀ 2010 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2010, 48, 738–744

Synthesis and complete assignment of the 1H and 13C NMR signals
Table 4. (Continued)
Atom
5a
5b
5c
5d
5e
5f
5gc
5h
5ic
C-3ꢁ
C-4ꢁ
C-5ꢁ
C-6ꢁ
129.08
131.60
129.08
126.11
110.52
132.51
120.76
129.06
159.69
117.24
130.22
118.40
114.51
161.82
114.51
127.98
116.88
132.29
125.17
129.45
162.47
118.16
131.20
122.26
116.31
164.25
116.31
129.14
130.11
127.92
130.31
130.48
125.98
129.25
125.98
130.95
Atom
6a
6b
6cc
6d
6e
6f
6gc
6hc
6ic
C-2
C-3
C-4
C-5
C-6
C-7
C-8
C-9
C-10
C-1ꢁ
C-2ꢁ
C-3ꢁ
C-4ꢁ
C-5ꢁ
C-6ꢁ
144.49
138.27
172.66
104.43
145.46
122.49
118.93
147.47
122.12
129.60
127.50
128.49
131.71
128.49
127.50
146.36
138.21
172.41
104.22
145.73
121.95
118.82
147.79
122.81
120.35
157.10
111.92
131.51
120.10
131.02
144.46
138.60
172.58
112.63
131.58
125.71
119.95
148.72
121.96
132.78
113.29
159.16
115.06
129.64
119.34
144.89
137.41
173.28
104.21
145.82
122.06
118.79
147.19
122.06
124.05
129.22
114.01
160.24
114.01
129.22
142.76
138.57
172.41
104.14
145.95
122.27
118.85
147.75
122.70
119.30
159.15
116.11
132.22
124.36
131.19
142.80
138.71
172.71
103.94
145.96
122.54
118.96
147.26
122.06
133.93
113.99
162.02
116.28
130.55
123.40
144.85
138.80
172.43
115.70
132.48
127.24
120.23
152.09
121.86
127.74
130.30
115.71
162.73
115.71
130.30
143.09
139.35
172.88
108.11
141.61
124.42
119.67
149.14
122.21
132.81
124.07
129.51
126.13
130.00
131.27
143.58
140.04
172.91
113.08
135.48
126.58
120.17
151.22
122.08
135.48
128.39
125.70
129.50
125.70
128.39
Atom
7a
7b
7c
7dc
7ec
7f
7g
7h
7i
C-2
140.04
154.33
173.62
105.55
144.91
122.56
119.00
147.69
124.46
130.56
128.11
128.62
130.85
128.62
128.11
59.61
141.06
155.64
174.48
107.06
143.93
122.30
118.80
149.25
125.06
120.25
157.04
111.22
131.60
120.17
130.39
60.13
140.27
154.14
173.85
104.55
146.50
122.24
119.13
147.32
124.66
132.31
113.84
159.31
116.22
129.95
120.58
59.78
139.59
154.58
173.33
108.96
140.91
123.95
119.31
149.03
122.83
124.32
129.94
114.17
161.10
114.17
129.94
59.44
140.68
151.58
173.20
107.19
143.47
123.43
119.19
148.74
124.69
118.85
160.60
116.07
132.84
124.58
131.03
59.83
140.48
152.69
173.83
104.55
146.45
122.41
119.16
147.32
124.64
133.22
114.98
162.12
117.56
130.93
124.47
59.81
140.00
153.48
173.81
104.59
146.54
122.24
119.07
147.30
124.68
127.60
130.90
115.92
163.31
115.92
130.90
59.76
140.37
152.41
173.68
104.28
146.48
122.25
119.08
147.19
124.56
131.97
124.55
129.41
126.97
129.65
132.11
59.72
140.81
152.66
173.91
104.49
146.67
122.53
119.17
147.69
124.75
135.07
129.16
125.69
130.19
125.69
129.16
60.01
C-3
C-4
C-5
C-6
C-7
C-8
C-9
C-10
C-1ꢁ
C-2ꢁ
C-3ꢁ
C-4ꢁ
C-5ꢁ
C-6ꢁ
OCH3-3
a In ppm from TMS; DMSO-d6 as solvent.
b 13C resonances in the substituents (in ppm) and nJC,F (in Hz): 2b, OCH3 55.98; 2c, OCH3 55.49; 2d, OCH3 55.56; 2e, 1JC−2 ,F = 248.0, 2JC−1 ,F = 14.3,
ꢁ
ꢁ
3
4
1
2
2
3
3
4
2JC−3 ,F = 22.6, JC−4 ,F = 6.8, JC−3,F = 8.3; 2f, JC−3 ,F = 246.0, JC−2 ,F = 23.4, JC−4 ,F = 21.1, JC−1 ,F = 7.5, JC−5 ,F = 8.3, JC−6 ,F = 2.1;
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
1
2
3
1
2
3
3
2g, JC−4 ,F = 250.0, JC−3 ,F = 22.6, JC−2 ,F = 9.8; 2h, CF3 123.42, JC,F = 270.0, JC−3 ,F = 31.7, JC−2 ,F = 3.8, JC−4 ,F = 3.8; 2i, CF3 124.88,
ꢁ
ꢁ
ꢁ
1JC,F = 272.0, 2JC−4 ,F = 32.4, 3JC−3 ,F = 3.8; 3b, OCH3 55.76; 3c, OCH3 55.36; 3d, OCH3 55.53; 3e, 1J
= 251.0, 2JC−1 ,F = 14.3, 2JC−3 ,F = 21.1,
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
C−2 ,F
3JC−4 ,F = 9.0; 3f, 1JC−3 ,F = 242.0, 2JC−2 ,F = 24.1, 2JC−4 ,F = 20.4, 3JC−1 ,F = 8.9, 3JC−5 ,F = 8.3; 3g, 1JC−4 ,F = 247.0, 2JC−3 ,F = 21.0, 3JC−2 ,F = 8.0;
3h, CF3 123.42, 1JC,F =ꢁ270.0, 2JC−3 ,F = 31.7, 3JC−2 ,F = 3.8, 3JC−4 ,F = ꢁ3.8; 3i, CF3 124.68, 1JC,F = 272.0, 2JC−4 ,F = 32.4, 3JC−3 ,F = 3.8; 4b, OCH3
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
1
2
2
3
1
2
55.68; 4c, OCH3 55.29; 4d, OCH3 55.41; 4e, JC−2 ,F = 249.0, JC−1 ,F = 14.3, JC−3 ,F = 21.1, JC−4 ,F = 6.8; 4f, JC−3 ,F = 243.0, JC−2 ,F = 23.4,
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
2JC−4 ,F = 21.1, JC−1 ,F = 8.3, JC−5 ,F = 7.5, JC−6 ,F = 3.0; 4g, JC−4 ,F = 252.0, JC−3 ,F = 21.9, JC−2 ,F = 9.0; 4h, CF3 123.42, JC,F = 270.0,
3
3
4
1
2
3
1
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
2JC−3 ,F = 32.4, JC−2 ,F = 3.8, JC−4 ,F = 3.8; 4i, CF3 124.81, JC,F = 272.0, JC−4 ,F = 32.4, JC−3 ,F = 3.8; 5b, OCH3 55.92; 5c, OCH3 55.43; 5d,
3
3
1
2
3
ꢁ
ꢁ
1
2
2
3
3
4
1
2
OCH3 55.49; 5e, JC−2 ,F = 253.0, JC−1 ,F = 9.8, JC−3 ,F = 21.9, JC−4 ,F = 9.1, JC−2,F = 3.0, JC−3,F = 9.0; 5f, JC−3 ,F = 242.0, JC−2 ,F = 23.3,
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
2JC−4 ,F = 20.4, JC−1 ,F = 8.9, JC−5 ,F = 8.3; 5g, JC−4 ,F = 250.0, JC−3 ,F = 22.6, JC−2 ,F = 9.0; 5h, CF3 124.05, JC,F = 270.0, JC−3 ,F = 30.2,
3
3
1
2
3
1
2
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
3JC−2 ,F = 3.8, JC−4 ,F = 3.8; 5i, CF3 124.81, JC,F = 272.0, JC−4 ,F = 32.4, JC−3 ,F = 3.8. 6b, OCH3 55.71; 6c, OCH3 55.25; 6d, OCH3 55.36; 6e,
3
1
2
3
ꢁ
ꢁ
ꢁ
1
1JC−2 ,F = 251.0, JC−1 ,F = 14.3, JC−3 ,F = 21.8, JC−4 ,F 8.6, JC−5 ,F 3.5; 6f, JC−3 ,F = 243.0, JC−2 ,F = 24.1, JC−4 ,F = 20.4, JC−1 ,F = 8.3,
2
2
3
3
2
2
3
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
3JC−5 ,F = 8.3; 6g, JC−4 ,F = 249.0, JC−3 ,F = 22.0, JC−2 ,F = 8.0, JC−1 ,F = 2.5, 6h, CF3 123.42, JC,F = 270.0, JC−3 ,F = 31.7, JC−2 ,F = 3.8,
1
2
3
4
1
2
3
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
3JC−4 ,F = 3.8; 6i, CF3 124.81, JC,F = 272.0, 2JC−4 ,F = 32.4, 3JC−3 ,F = 3.8; 7b, OCH3 55.47; 7c, OCH3 55.44; 7d, OCH3 55.43; 7e, 1JC−2 ,F = 250.0,
1
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
2JC−1 ,F = 14.3, 2JC−3 ,F = 21.1, 3JC−4 ,F = 7.5; 7f, 1JC−3 ,F = 243.0, 2JC−2 ,F = 24.1, 2JC−4 ,F = 20.3, 3JC−1 ,F = 8.3, 3JC−5 ,F = 7.5, 4JC−6 ,F = 3.0; 7g,
1JC−4 ,F = 250.0, 2JC−3 ,F = 21.9, 3JC−2 ,F = 9.0, 4JC−1 ,F = 3.0; 7h, CF3 123.42, 1JC,F = 270.0, 2JC−3 ,F = ꢁ32.4, 3JC−2 ,F = 3.8, 3JC−4 ,F = 3.8; 7i, CF3
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
124.81, 1JC,F = 272.0, 2JC−4 ,F = 32.4, 3JC−3 ,F = 3.8.
ꢁ
ꢁ
c Recorded as an hydrochloride.
c
Magn. Reson. Chem. 2010, 48, 738–744
Copyright ꢀ 2010 John Wiley & Sons, Ltd.
www.interscience.wiley.com/journal/mrc

G. Casano et al.
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3'
B
6'
R"
4'
2'
1'
3
A
6
2
OH
β'
5'
4
O
β
α
1
1
5
N
H
O
3'
B
6'
R"
4'
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2'
1'
8
A
5
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C
4
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7
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2-7
2
6
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3 R'
10
O
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R"
a
b
c
d
e
f
g
h
i
H
R
NHCOCH3
NH2
2-OCH3
3-OCH3
4-OCH3
2-F
3-F
4-F
R'
H
2
3
4
5
6
7
OH
OCH3
3-CF3
4-CF3
Figure 1. Structures of chalcone, flavone and flavonol derivatives 1–7
(numbering from Ref. [28]).
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c
www.interscience.wiley.com/journal/mrc
Copyright ꢀ 2010 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2010, 48, 738–744