Letter - spectral assignments Received: 10 April 2014
Revised: 23 June 2014
Accepted: 28 June 2014
Published online in Wiley Online Library: 22 July 2014
(wileyonlinelibrary.com) DOI 10.1002/mrc.4111
Structure elucidation of a series of fluoro2-styrylchromones and methoxy2-styrylchromones using 1D and 2D NMR spectroscopy Mehbub Momin,a Deresh Ramjugernathb and Neil A. Koorbanallya* Introduction 2-Styrylchromones (2-SCs) are a chemical family of oxygen heterocyclic compounds, similar to the flavonoids (2-phenylchromones), but with a vinyl group bridging the chromone ring to the phenyl moiety. Many derivatives of 2-SCs have been synthesized,[1] and their occurrence in nature has also been reported.[2] There have also been numerous reports on the biological activity of the synthesized derivatives of 2-SCs, which has recently been reviewed by Gomes et al.,[3] and these compounds were seen to have antioxidant,[4] antiviral,[5] anticancer,[6–8] antiallergic,[9] and hepatoprotective activity[10] and shown to be A3 adenosine receptor antagonists[11] and xanthine oxidase inhibitors.[12] Although the NMR data for 2-SCs are always reported in synthetic publications that also report the biological activity, full structural elucidation of these compounds is rare. We have only noticed one publication on the structural elucidation of this class of compounds in which the nitro derivatives were described.[13] To the best of our knowledge, there are no publications where the structural elucidation of these compounds has been discussed with substituents on the aromatic rings that donate electrons by resonance into the aromatic rings. Furthermore, the structural elucidation of fluorinated molecules is more challenging because of 19F being NMR active and coupling with both the protons and the carbon atoms. We have recently reported the synthesis and antibacterial activity of these compounds[14] and herein report the structural elucidation of seven fluorinated, two methoxylated, and a methylenedioxy derivative of 2-SC along with their cinnamoyloxyacetophenone and 3-hydroxy-2,4-pentadien-1-one intermediates. The structural elucidation and NMR data reported here can help one identify newly isolated or synthesized derivatives of 2-SCs, especially fluorinated derivatives.
and phosphorus oxychloride (POCl3) at room temperature for 4–5 h producing the cinnamoyloxyacetophenone intermediates (3a–j), which were then converted to the 3-hydroxy-2,4pentadienone intermediates (4a–j) with potassium hydroxide in dimethyl sulfoxide (DMSO) by being stirred at room temperature for 2 h. Final conversion to the 2-SC derivatives (5a–j) was carried out using p-toluenesulfonic acid in DMSO by reflux at 90–95 °C for 2–3 h. The compounds were named similarly for each of the intermediates and the 2-SC according to their substitution pattern, for example, 2-(2′-fluorocinnamoyloxy) acetophenone (3a), 3-hydroxy-1-(2-hydroxyphenyl)-5-(2-fluorophenyl)-2,4-pentadien1-one (4a) and 2′-fluoro-2-SC (5a).
NMR spectra The 1H and 13C NMR spectra were recorded at 298 K with 5–10-mg samples dissolved in 0.5 ml of CDCl3 in 5-mm NMR tubes using a Bruker Avance III 400-MHz NMR spectrometer (9.4 T; Bruker, Germany) (400.22 MHz for 1H, 100.63 MHz for 13C, and 376.58 Hz for 19F). Chemical shifts (δ) are reported in ppm and coupling constants (J) in Hz. The 1H and 13C chemical shifts of the deuterated solvent were δ 7.24 and 77.0 referenced to the internal standard, TMS, respectively. For the 19F NMR spectra, the chemical shift of trifluorotoluene (0.05% in CDCl3) was referenced at δ 62.73. For the 1H NMR analyses, 16 transients were acquired with a 1-s relaxation delay using 32-K data points. The 90° pulse duration was 10.0 μs, and the spectral width was 8223.68 Hz. The 13C NMR spectra were obtained with a spectral width of 24 038.46 Hz using 64-K data points. The 90° pulse duration was 8.40 μs. For the 19F NMR spectra, the spectral width was 89 285.71 Hz using 131-K data points, and the 90° pulse duration was 12.50 μs. For the two-dimensional (2D) experiments including COSY, NOESY, HSQC, and HMBC, all data were acquired with 4-K × 128 data points (t2 × t1). The mixing
Experimental Synthesis
Magn. Reson. Chem. 2014, 52, 521–529
a School of Chemistry, University of KwaZulu-Natal, Private Bag X54001, Durban, 4000, South Africa b School of Chemical Engineering, University of KwaZulu-Natal, Private Bag X54001, Durban, 4000, South Africa
Copyright © 2014 John Wiley & Sons, Ltd.
521
The synthesis of the 2-SCs (5a–j) along with the cinnamoyloxyacetophenone (3a–j) and 3-hydroxy-2,4-pentadienone (4a–j) intermediates was carried out using the Baker–Venkataraman rearrangement in a three-step reaction, which was reported recently.[14] Essentially, the substituted 2-hydroxyacetophenones (1) were reacted with substituted cinnamic acids (2) in pyridine
* Correspondence to: Neil A. Koorbanally, School of Chemistry, University of KwaZulu-Natal, Private Bag X54001, Durban, 4000, South Africa. E-mail: [email protected]
M. Momin, D. Ramjugernath and N. A. Koorbanally
Figure 1. Scheme for the preparation of 2-styrylchromones 5a–j.
time for the NOESY experiment was 0.3 s, and the long-range coupling time for HMBC was 65 ms. All data were analyzed using Bruker Topspin 2.1 (2008) software.
Figure 2. Selected HMBC correlations for 2′-fluoro-2-styrylchromone 5a.
522
Figure 3.
1
Results and Discussion Compounds 3–5 (Fig. 1) are fully characterized in Tables 1 through to 7 with their 1H and 13C NMR assignments unambiguously assigned using splitting patterns, chemical shifts, and 2D NMR data from HSQC, HMBC, and NOESY spectra. An extensive discussion on the splitting patterns and chemical shifts of the compounds are presented below for the intermediates and the 2-SC molecules. The discussion is divided into several parts, discussing the carbon chain linking the two aromatic units together and discussing the two aromatic rings in detail. This is performed in detail for the intermediate 3, and then, a comparison to 4 and 5 is performed, pointing out salient features and resonances that have changed as well as the proton and carbon resonances that indicate that the products have been formed.
H NMR spectrum of 2′-fluoro-2-styrylchromone (5a) depicting chemical shifts and splitting patterns.
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Copyright © 2014 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2014, 52, 521–529
Copyright © 2014 John Wiley & Sons, Ltd.
3j
3i
3h
3g
3f
3e
3d
3c
3b
523
Magn. Reson. Chem. 2014, 52, 521–529
3a
Table 1.
H-3′
7.17 (d, 8.1, 0.9) 7.16 (d, 7.9)
7.23 (dd 7.8, 3.0) 7.51 (td, 7.6, 1.6) 7.54 (td, 7.8, 1.7) 7.53 (td, 7.9, 1.6)
—
7.54 (td, 7.6, 1.6) 7.55 (td, 7.8, 1.6) 7.53 (td, 8.0, 1.5) 7.55 (td, 7.6, 1.0) —
H-4′
7.31 (td, 8.0, 0.8) 7.31 (td, 7.6, 0.9) 7.31 (td, 7.9, 0.8)
7.33 (td, 8.0, 0.7) 7.34 (td, 7.6, 0.8) 7.03 (td, 8.8, 2.5) 7.03 (td 8.6, 2.5) —
7.33 (td, 7.6, 0.8) 7.35 m
H-5′ 7.85 (dd, 7.9, 1.6) 7.83(dd, 7.6, 1.6) 7.81 (dd, 8.0, 1.6) 7.82 (dd, 7.9, 1.0) 7.87 (dd, 8.8, 6.3) 7.86 (dd 8.6, 5.4) 7.15 (dd, 8.7, 4.7) 7.80 (dd, 8.0, 1.6) 7.81 (dd, 7.8, 1.7) 7.80 (dd, 7.9, 1.6)
H-6′
6.47 (d, 15.9)
6.52 (d, 15.9)
6.52 (d, 15.9)
6.64 (d, 15.9)
6.63 (d, 15.9)
6.56 (d, 16.0)
6.64 (d, 16.0)
7.78 (d, 15.9)
7.82 (d, 15.9)
7.83 (d, 15.9)
7.88 (d, 15.9)
7.88 (d, 15.9)
7.84 (d, 16.0)
7.75 (d, 16.0)
7.84 (d, 16.0)
7.82 (d, 16.0)
6.55 (d, 16.0) 6.58 (d, 16.0)
8.00 (d, 16.2)
H-β
6.76 (d, 16.2)
H-α
H NMR chemical shifts (δ in ppm) for compounds 3a–j (J is given in Hz)
7.19 (dd, 8.0, 0.8) 7.17 (dd, 8.0, 0.7) 7.17 (dd, 8.0, 0.7) 7.16 (dd, 7.9, 0.8) 6.92 (dd, 8.9, 2.5) 6.94 (dd 8.9, 2.5) 7.49 (dd, 8.7, 3.0) 7.17 (d, 8.0)
1
H-3″
7.05 (d, 1.6)
7.10 (d, 1.9)
7.58 (dd, 8.7, 5.4) 7.58 (dd, 7.6, 3.9) 7.58 (dd, 7.4, 3.6) 7.53 (d, 8.7)
7.58 (dd, 8.6, 5.4) 7.08 m
— — —
— —
7.39 m
7.44 m
6.91 (dd, 8.7)
7.39 m
7.44 m
—
6.85 (tt, 8.7, 2.3)
— 7.10 (dd, 8.6)
—
7.10 (tt, 8.2, 2.0)
7.39 m
H-4″
7.09 (t, 8.6)
7.11 (dd, 10.3, 8.8) 7.27 (d, 9.6) —
—
H-2″
6.82 (d, 7.9)
6.87 (d, 8.2)
6.91 (dd, 8.7)
7.39 m
7.44 m
7.10 (dd, 8.6)
—
7.09 (t, 8.6)
7.33 (td, 7.7, 0.8)
7.18 (t, 7.5)
H-5″
7.16 (dd, 8.2, 1.9) 7.08 (dd, 7.9, 1.6)
7.58 (dd, 8.7, 5.4) 7.58 (dd, 7.6, 3.9) 7.58 (dd, 7.4, 3.6) 7.53 (d, 8.7)
7.58 (dd, 8.6, 5.4) 7.08 m
7.59 (td, 7.9, 1.7) 7.35 m
H-6″
2.54 s
2.55 s
2.54 s
2.53 s
2.53 s
2.53 s
2.54 s
2.54 s
2.55 s
2.55 s
CH3
6.01 s
3.91 s (6H)
3.84 s
—
—
—
—
—
—
—
OCH3/OCH2O
Structure elucidation of a series of fluoro-2-styrylchromones and methoxy-2-styrylchromones
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M. Momin, D. Ramjugernath and N. A. Koorbanally Table 2.
13
C NMR chemical shifts (δ in ppm) for compounds 3a–j (J is given in Hz)
C-1
C-2
C¼O
C-α
C-β
C-1′
C-2′
C-3′
C-4′
3a
197.7
29.8
165.1
119.4 (d, 6.9)
140.0 (d, 2.7)
131.3
149.1
123.8
133.4
3b
197.7
30.0
164.9
118.3
145.8 (d, 2.7)
131.2
149.0
123.8
133.4
3c
197.8
29.7
165.1
116.6 (d, 2.4)
146.0
131.3
149.1
123.8
133.4
3d
197.6
29.5
164.6
119.7
144.5 (t, 2.8)
131.0
148.9
123.7
133.5
3e
196.1
29.7
165.1
116.1 (d, 2.2)
146.6
127.6 (d, 3.5)
151.0 (d, 11.2)
111.7 (d, 24.0)
165.0 (d, 254.1)
3f
196.1
29.8
164.8
116.3
145.4
127.0
151.0 (d, 11.4)
113.4 (d, 21.1)
166.4 (d, 255.8)
3g
196.4
29.8
165.2
116.6
145.0
132.6 (d, 6.1)
147.8
125.4 (d, 8.0)
116.5 (d, 20.5)
3h 3i 3j
197.9 197.9 197.8
29.9 29.9 29.9
165.5 165.5 165.4
114.1 114.3 114.6
147.2 147.4 147.1
131.5 131.5 131.5
149.3 151.7 150.2
123.8 123.8 125.2
133.3 133.3 133.3
The acetyl group and the α, β unsaturated ester of the intermediate 3 In 3a, the α and β proton resonances are characteristic and occur at δH 6.76 and 8.00, respectively, as two doublets with large coupling constants of 16.2 Hz, characteristic of trans olefinic protons. Their corresponding carbon resonances were present at δC 119.4 (J = 6.9 Hz, C-α) and 140.0 (J = 2.7 Hz, C-β). The C-β resonance is more deshielded than the C-α resonance because of conjugation between the double bond and the carbonyl group; in the enolate anion resonance structure, electron density is removed from C-β. The coupling constants experienced in 3a for these two resonances are attributed to that of the fluorine atom three and four bonds away from C-β and C-α, respectively. This small coupling in the carbon resonances was also seen in 3b (3″-F) with the C-β resonance and 3c (4″-F) and 3e (4′,4″-diF) with the C-α resonance but not in 3d (3″,5″-diF), 3f (4′-F), and 3g (5′-F), the remaining fluorinated acetophenone derivatives. The 1H and 13 C chemical shifts of these resonances (C-α and C-β) were similar in all of the other cinnamoyloxyacetophenone derivatives (3b–3j). A NOESY correlation between H-α and H-6″ further confirms the assignment of these resonances. The acetophenone methyl resonance occurred at δH 2.55 as an
Table 3.
524
4a 4b 4c 4d 4e 4f 4g 4h 4i 4j
1
intense singlet, also consistent with all the other derivatives 3b–3j, and the acetophenone carbonyl resonance (C-1) was present at δC 197.7, distinguished from the other ester carbonyl resonance (C=O) at δC 165.1 because the latter showed HMBC correlations to both the α and β proton resonances.
The acetophenone aromatic ring The proton resonances of 3a–3d (the unsubstituted acetophenone ring) are all similar with H-3′ and H-6′ appearing as double doublets at δH 7.19 (J = 8.0 and 0.8 Hz) and δH 7.85 (J = 7.9 and 1.6 Hz), respectively. The H-3′ resonance ortho to the oxygenated position is more shielded because of electron donation from the oxygen atom by resonance and the H-6′ resonance more deshielded because this same electron donation by resonance results in the meta position becoming electron deficient. The H-4′ and H-5′ proton resonances both appear as triplets of doublets at δH 7.5 (J = 7.6 and 1.6 Hz) and δH 7.33 (J = 7.6 and 0.8 Hz) because they experience the same coupling constant with each of their adjacent protons resulting in the triplet, which is further split into doublets because of meta coupling, hence the second small coupling constant. Only in 3b does
H NMR chemical shifts (δ in ppm) for compounds 4a–j (J is given in Hz)
2′-OH
H-3′
12.17 s 12.15 s 12.17 s 12.10 s 12.47 s 12.55 s 11.94 s 12.24 s 12.23 s 12.21 s
6.97 (dd, 8.5, 0.7) 6.97 (dd, 7.9, 0.9) 6.97 (dd, 8.5, 0.9) 6.98 (dd, 8.5, 1.1) 6.65 (dd, 10.4, 2.5) 6.65 (dd, 10.3, 2.5) 6.93 (dd, 9.1, 4.7) 6.96 (dd, 8.5, 2.1) 6.96 (dd, 8.4, 0.7) 6.96 (dd, 8.5, 0.5)
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H-4′ 7.43 (ddd, 8.5, 7.44 (ddd, 8.5, 7.44 (ddd, 8.5, 7.45 (ddd, 8.5, — — 7.17 (ddd, 9.2, 7.42 (ddd, 8.5, 7.42 (ddd, 8.5, 7.42 (ddd, 8.5,
H-5′ 7.1, 7.1, 7.1, 7.2,
1.4) 1.5) 1.4) 1.6)
7.9, 7.5, 8.3, 8.0,
3.0) 1.6) 1.5) 1.6)
6.88 (td, 8.1, 0.8) 6.89 (ddd, 8.0, 7.1, 6.88 (ddd, 8.1, 7.1, 6.89 (ddd, 8.1, 7.2, 6.60 (ddd, 8.8, 8.2, 6.60 (td, 8.0, 2.5) — 6.89 m 6.85 (td, 8.3, 0.7) 6.87 (td, 8.0, 0.5)
0.9) 0.9) 1.1) 2.2)
Copyright © 2014 John Wiley & Sons, Ltd.
H-6′
H-2
3-OH
7.69 (dd, 8.0, 1.4) 7.68 (dd, 8.0, 2.0) 7.68 (dd, 8.1, 1.4) 7.67 (dd, 8.1, 1.4) 7.68 (dd, 9.0, 6.4) 7.68 (dd, 8.9, 6.4) 7.34 (dd, 9.0, 3.0) 7.67 (dd, 8.0, 1.6) 7.67 (dd, 8.1, 1.5) 7.66 (dd, 8.0, 1.6)
6.32 s 6.32 s 6.29 s 6.32 s 6.20 s 6.21 s 6.20 s 6.26 s 6.28 s 6.26 s
14.55 s 14.55 s 14.62 s 14.46 s 14.42 s 14.48 s 14.59 s 14.72 s 14.71 s 14.68 s
Magn. Reson. Chem. 2014, 52, 521–529
Structure elucidation of a series of fluoro-2-styrylchromones and methoxy-2-styrylchromones Table 2. (Continued) C-5′
C-6′
126.1
130.2
126.2
130.2
126.1
130.2
126.3
130.3
113.3 (d, 21.2) 111.7 (d, 24.0) 159.9 (d, 245.1) 126.0 126.0 126.0
132.2 (d, 10.1) 132.3 (d, 10.2) 120.1 (d, 23.3) 130.0 130.1 130.1
C-1″
C-2″
C-3″
C-4″
C-5″
122.2 (d, 11.6) 136.3 (d, 7.9) 130.3 (d, 3.6) 137.3 (t, 9.4) 130.2 (d, 3.4) 133.9
161.8 (d, 252.6) 114.6 (d, 21.9) 130.4 (d, 8.4) 111.0 (dd, 18.8, 7.2) 130.5 (d, 8.5) 129.0
116.3 (d, 21.7) 163.0 (d, 245.6) 116.2 (d, 21.9) 163.2 (dd, 248.3, 12.8) 116.3 (d, 21.9)
132.2 (d, 14.2) 117.7 (d, 21.3) 164.3 (d, 250.7) 105.9 (t, 25.4) 164.4 (d, 251.0) 131.1
124.6 (d, 3.6) 130.6 (d, 8.0) 116.2 (d, 21.9) 163.2 (dd, 248.3, 12.8) 116.3 (d, 21.9) 128.5
128.5
C-6″
CH3/OCH2O
129.4 (d, 2.7)
—
124.4 (d, 2.9)
—
130.4 (d, 8.4)
—
111.0 (dd, 18.8, 7.2) 130.5 (d, 8.5)
-
129.0
—
133.9
128.5
129.0
131.0
129.0
128.5
—
126.8 127.0 128.5
130.2 109.8 106.7
114.5 149.2 148.5
161.9 149.3 149.2
114.5 111.1 108.6
130.2 123.3 123.8
55.4 55.9,56.0 101.7
H-5′ appear as a multiplet because of overlap with other resonances. The C-3′ to C-6′ carbon resonances for 3a–d are all similar and occur between δC 123.8 and 130.2. The C-1′ carbon resonance occurs at δC 131.3 and was assigned because of HMBC correlations to H-3′ and H-5′. The oxygenated aromatic resonance C-2′ was assigned to δC 149.1 because of HMBC correlations to H-6′ and H-4′. In 3e and 3f, where a fluorine atom is substituted at the 4′-position, the H-3′ resonance also occurs as a double doublet as in 3a–d, but now, the meta coupling is much larger at 2.5 Hz, the first coupling constant of 8.9 Hz occurring because of H-F ortho coupling. The H-5′ resonance occurs as a triplet of doublets as for 3a–d because the H-F ortho coupling constant is similar to the H–H ortho coupling constant at J = 8.8 Hz, but as for H-3′, the meta coupling constant is larger than that for 3a–d at J = 2.5 Hz. The H-6′ resonance occurs as a double doublet but distinctly different from the double doublet in 3a–d because of the larger meta H–F coupling constant of 6.3 Hz in addition to the ortho H–H coupling constant of 8.8 Hz. The H-6′ resonance also overlaps with the H-β resonance as well in these two compounds. In the 13C NMR spectrum, C-4′ occurs as a doublet with J = 254.1 Hz at δH 165.0 in 3e. The coupling constant is so large that the two resonances that make up the doublet could easily
be mistaken for two separate resonances. The carbon resonances, however, can be identified from the HMBC spectrum where both the resonances making up the doublet show HMBC correlations to a nearby proton resonance, in the case of 3e, C-4′ to H-6′. To verify this, coupling constants of approximately 220–250 Hz are normally observed. 2JF–C coupling of 24.0 and 21.2 Hz is observed respectively at δC 111.7 and 113.3 for the two doublets assigned to C-3′ and C-5′. Their chemical shifts are more shielded than their corresponding carbon resonances in 3a–d because of electron donation by resonance from the fluorine, shielding the carbon atoms more than that of hydrogen. 3 JF–C coupling of 11.2 Hz is observed at δC 150.9 for C-2′ and 10.1 Hz at δC 132.2 for C-6′. 4JF–C coupling at δC 127.6 for C-1′ is also observed with a coupling constant of 3.5 Hz in 3e; however, this is not seen in 3f. When the fluoro group is at the 5′ position in 3g, the H-3′ resonance is now meta to the fluorine atom, which by resonance deshields the meta hydrogen resulting in it appearing at δH 7.49 in 3g as opposed to δH 6.92–6.94 in 3e and 3f. The multiplicity is retained as a double doublet with J = 8.7 and 3.0 Hz for the H–H and H–F coupling, respectively. The H-4′ proton resonance coincides with the solvent peak appearing as a triplet of doublets at δH 7.23 with J = 7.8 and 3.0 Hz, the triplet being a result of similar coupling between H-4′-F and H-4′-H-3′, similar to the
Table 3. (Continued) H-4
7.73 (d, 16.0) 7.58 (d, 15.8) 7.60 (d, 16.0) 7.51 (d, 15.7) 7.60 (d, 16.0) 7.64 (d, 15.8) 7.66 (d, 15.8) 7.61 (d, 15.8) 7.59 (d, 15.7) 7.55 (d, 15.6)
H-2″ — 7.24 m 7.52 (dd, 8.9, 5.4) 7.04 (dd, 8.2, 2.2) 7.52 (dd, 8.7, 5.4) 7.53 (dd, 8.1, 2.1) 7.54 (dd, 7.9, 2.2) 7.49 (d, 8.8) 7.06 (d, 1.8) 7.04 (d(br), 0.4)
Magn. Reson. Chem. 2014, 52, 521–529
H-3″ 7.09 (t, 8.2) — 7.08 (t, 8.9) — 7.08 (t, 8.6) 7.38 m 7.40 m 6.91 (d, 8.8) — —
H-4″ 7.32 m 7.06 m — 6.80 (tt, 8.8, 2.2) — 7.38 m 7.40 m — — —
H-5″ 7.16 (t, 7.6) 7.34 (dd, 7.9, 5.7) 7.08 (t, 8.9) — 7.08 (t, 8.6) 7.38 m 7.40 m 6.91 (d, 8.8) 6.87(d, 8.3) 6.81 (d, 8.0)
Copyright © 2014 John Wiley & Sons, Ltd.
H-6″ 7.54 (td, 7.6, 1.5) 7.30 (d, 7.8) 7.52 (dd, 8.9, 5.4) 7.04 (dd, 8.2, 2.2) 7.52 (dd, 8.7, 5.4) 7.53 (dd, 8.1, 2.1) 7.54 (dd, 7.9, 2.2) 7.49 (d, 8.8) 7.11 (dd, 8.3, 1.9) 7.02 (dd, 8.0, 1.2)
OCH3/OCH2O — — — — — — 3.83 s 3.91 s, 3.92 s 6.00 s
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525
6.70 (d, 16.0) 6.56 (d, 15.8) 6.49 (d, 16.0) 6.55 (d, 15.7) 6.51 (d, 16.0) 6.57 (d, 15.8) 6.58 (d, 15.8) 6.45 (d, 15.8) 6.45 (d, 15.7) 6.39 (d, 15.6)
H-5
M. Momin, D. Ramjugernath and N. A. Koorbanally 13
Table 4.
C NMR chemical shifts (δ in ppm) for compounds 4a–j (J is given in Hz) C-1
C-2
C-3
C-4
C-5
C-1′
C-2′
C-3′
C-4′
132.6 (d, 2.2)
119.0
162.6
118.8
136.2
138.3 (d, 2.5)
119.0
162.7
118.8
136.0
4a
196.5
97.5
174.1
4b
196.3
97.4
173.6
124.9 (d, 7.8) 123.5
4c
196.0
97.0
174.3
121.9
138.5
119.0
162.6
118.8
135.9
4d
196.4
97.9
172.8
124.8
137.0
118.9
162.7
118.9
136.2
4e
194.9
96.8
174.2
121.7
138.7
115.9
4f
194.9
96.8
174.4
122.0
140.1
116.0
4g
194.8 (d, 2.7)
96.8
175.2
121.9
140.6
4h 4i 4j
195.3 195.6 195.7
96.1 96.5 96.6
174.9 175.0 174.8
119.4 119.9 120.1
139.5 140.0 139.7
118.7 (d, 6.5) 118.9 119.1 119.1
165.2 (d, 14.1) 165.1 (d, 14.1) 158.7
105.3 (d, 23.6) 105.3 (d, 23.4) 120.0 (d, 7.4) 118.4 118.7 118.7
H-5′ resonance in 3e. Because of the fluoro group being placed adjacent to H-6′, shielding this proton through electron donation by resonance, the H-6′ proton resonance moves from being the most deshielded resonance in 3e at δH 7.87, where it was meta to both the oxygenated moiety and the fluorine atom, to the most shielded of the aromatic resonances at δH 7.15 in 3g. The resonance retains its multiplicity as a double doublet because it couples to fluorine with a similar coupling constant to that of hydrogen with J = 8.7 and 4.7 Hz. In the 13 C NMR spectrum, all the carbon resonances on the aromatic ring appear as doublets except for C-2′, which is para to the fluorinated carbon and appears at δC 147.8. The fluorinated carbon is present at δC 159.9 with J = 245.1 Hz. The carbon meta to the fluorine C-1′ occurs at δC 132.6 (J = 6.1 Hz), followed by the other meta carbon C-3′, at δC 125.4 (J = 8.0 Hz), both being more deshielded than the two ortho carbon atoms at δC 120.1 (J = 23.3, C-6′) and δC 116.5 (J = 20.5, C-4′). In the 1H and 13C NMR spectra of the methoxy and methylenedioxy derivatives 3h–3j, H-3′ to H-6′, Hα and Hβ and C-1, C-2, and C-1′ to C-6′, C-α, and C-β, and the ester C¼O were all similar to 3a–3d. 1
Table 5.
526
a
The cinnamoyl aromatic ring In the absence of any substituents on this ring as in 3f and 3g, the H-3″/4″/5″ resonances overlap at δH 7.44 and appear as a multiplet in 3f, and the H-2″/6″ resonance appears as a double doublet with J = 7.6 and 3.9 in 3f. Their carbon resonances appear between δC 128.5 and δC 133.9 with the C-2″/6″ and C-3″/5″ resonances being equivalent. For the 4″-methoxy derivative 3h, a characteristic pair of doublets is seen as for other parasubstituted aromatic compounds at δH 7.53 for H-2″/6″ and at δH 6.91 for H-3″/5″ with a coupling constant of 8.7 Hz. The H-3″/5″ resonance is more shielded than that of H-2″/6″ because of the electron donating effects of the methoxy group by resonance to the ortho positions. The carbon resonances of C-2″/6″ and C-3″/5″ occur at δC 130.2 and 114.5, the C-3″/5″ resonance being more shielded because of the resonance effects explained previously. The oxygenated C-4’″ resonance appears at δC 161.9 and C-1″ appears at δC 126.8. When the phenyl ring is substituted at both C-3″ and C-4″ with oxygenated substituents, as in 3i and 3j, meta coupling is observed for H-2″ at δH 7.10 (J = 1.9 Hz) in 3i, and ortho coupling
H NMR chemical shifts (δ in ppm) for compounds 5a–j (J in Hz)
H-3 5a 5b 5ca 5d 5e 5f 5g 5h 5ia 5j
162.3 162.5 162.6
166.4 (d, 212.1) 165.2 (d, 209.2) 123.2 (d, 23.4) 135.3 135.6 135.7
6.32 s 6.34 s 6.46 s 6.34 s 6.28 s 6.29 s 6.31 s 6.28 s 6.40 s 6.28 s
H-5 8.17 (dd, 7.9, 8.18 (dd, 7.9, 8.01 (dd, 7.9, 8.18 (dd, 7.9, 8.18 (dd, 8.8, 8.19 (dd, 8.9, 7.85 (dd, 8.2, 8.18 (dd, 8.0, 8.01 (dd, 7.9, 8.17 (d, 7.6)
1.6) 1.3) 1.4) 1.6) 6.4) 6.4) 3.2) 1.6) 1.7)
H-6
H-7
H-8
H-2′
7.37 (td, 7.9, 0.8) 7.36 m 7.47 (t, 7.4) 7.39 (td, 7.9, 0.7) 7.12 m 7.10 (td, 8.6, 2.4) — 7.36 (t, 8.0) 7.47 (ddd, 7.9, 7.2, 0.7) 7.37 (t, 7.5)
7.66 (ddd, 8.6, 7.2, 1.6) 7.68 (dt, 8.6, 1.6) 7.82 m 7.72 (ddd, 8.6, 7.2, 1.6) — — 7.40 m 7.65 (ddd, 8.6, 7.1, 1.6) 7.81 (ddd, 8.2, 7.2, 1.7) 7.65 (ddd, 8.1, 7.1, 1.0)
7.53 (d, 8.3) 7.52 (d, 8.6) 7.69 (d, 8.5) 7.51 (d, 8.3) 7.20 (dd, 9.0, 2.4) 7.21 (dd, 9.1, 2.4) 7.52 (dd, 9.1, 4.2) 7.52 (d, 8.6) 7.70 (d, 8.2) 7.51 (d, 7.8)
— 7.26 m 7.79 m 7.08 (dd, 8.1, 1.9) 7.56 (dd, 8.6, 5.6) 7.58 (dd, 8.1, 1.5) 7.56 (d, 8.0) 7.48 (d, 8.7) 7.36 (d, 1.7) 7.08 s
In DMSO
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Copyright © 2014 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2014, 52, 521–529
Structure elucidation of a series of fluoro-2-styrylchromones and methoxy-2-styrylchromones Table 4. (Continued) C-5′
C-6′
119.1
128.6
119.1
128.5
119.0
128.5
119.1
128.6
107.3 (d, 22.6) 107.3 (d, 22.7) 155.1 (d, 236.8) 118.7 119.0 119.0
130.4 (d, 10.8) 130.5 (d, 11.7) 113.5 (d, 23.5) 128.8 128.4 128.4
C-1″
C-2″
123.1 (d, 11.5) 137.3 (d, 7.8) 130.2 (d, 3.5) 138.3 (t, 9.5) 130.7 (d, 11.9) 134.9
C-3″
C-4″
C-5″
C-6″
CH3/OCH2O
161.4 (d, 253.8)
116.3 (d, 21.9)
131.4 (d, 8.8)
124.5 (d, 3.6)
129.2 (d, 3.0)
—
114.1 (d, 20.0)
164.9 (d, 247.2)
116.9 (d, 21.6)
130.5 (d, 8.2)
124.1 (d, 2.8)
—
129.8 (d, 8.2)
116.2 (d, 21.9)
163.8 (d, 250.3)
116.2 (d, 21.9)
129.8 (d, 8.2)
—
110.5 (dd, 18.5, 6.8) 129.9 (d, 8.6)
163.3 (dd, 247.8, 13.1) 116.2 (d, 21.9)
163.3 (dd, 247.8, 13.1) 116.2 (d, 21.9)
110.5 (dd, 18.5, 6.8) 129.9 (d, 8.6)
—
105.1 (t, 25.6) 163.0 (d, 252.6)
—
128.0
129.0
130.2
129.0
128.0
—
134.8
128.1
129.0
130.4
129.0
128.1
—
129.8 128.0 129.5
129.4 109.7 106.3
114.2 151.1 149.6
161.1 149.3 148.5
114.2 111.2 108.7
129.4 122.6 124.6
55.2 56.0, 55.9 101.6
is observed for H-5″ at δH 6.87 (J = 8.2 Hz) with H-6″ experiencing both ortho and meta coupling at δH 7.16 (J = 8.2, 1.9 Hz). The carbon resonances of the two carbon atoms ortho to the methoxy groups, C-2″ and C-5″, occur more shielded at δC 109.8 and δC 111.1, while C-6″ meta positioned to the 4″-methoxy substituent appears slightly more deshielded at δC 123.3. The two aromatic C–O resonances C-3″ and C-4″ occur at δC 149.2 and 149.3, respectively. The two methoxy resonances in 3i overlap at δH 3.91 with corresponding carbon resonances at δC 55.9 and 56.0. The methylenedioxy group proton resonance occurs at δH 6.01 with a corresponding carbon resonance of δC 101.7. In 3a–e, fluorination either occurred at 2″, 3″, and 4″ or was difluorinated at the 3″ and 5″ positions. For the 2″-fluoro derivative 3a, the H-5″ proton only experiences coupling from the adjacent protons and appears as a triplet at δH 7.18 with J = 7.5 Hz. This resonance overlaps with H-3′, which may account for the meta coupling with H-3″ not being observed. The H-3″ proton resonance at δH 7.11 couples with both the fluorine and the proton of H-4″ and appears as a double doublet with J = 10.3 Hz (H–F coupling) and 8.8 Hz (H–H coupling). The H-4″ proton resonance appears as a multiplet at δH 7.39 because of
coupling with all of H-3″, H-5″, H-6″, and the F. However, the only coupling constant that can be observed in this multiplet is that between H-4″ and H-6″ of 1.7 Hz. The H-6″ proton resonance is the most deshielded of these resonances at δH 7.59 appearing as a triplet of doublets with J = 7.9 and 1.7 Hz. The triplet is probably caused by the meta F atom at C-2″ and the ortho proton of H-5″ having the same coupling constant. The carbon resonances of the aromatic ring of 3a with fluorine substituted at the 2″ position result in all the carbon resonances of the ring being doublets with the largest coupling occurring on the carbon directly bonded to fluorine (C-2″) at δC 161.8 (J = 252.6 Hz), followed by ortho coupling of 21.7 Hz for C-3″ at δC 116.3. The C-1″, the other ortho carbon, has a much smaller coupling constant of 11.6 Hz at δC 122.2. It is further noticed that while C-4″ at δC 132.2 meta to the fluorine has a coupling constant of 14.2 Hz, the same is not observed for the other carbon meta to the fluorine (C-6″ at δC 129.4) that only has a coupling constant of 2.7 Hz, probably because of interference from the moiety attached to C-1″. The C-5″ carbon resonance, para to the fluorine atom, has a small coupling constant of 3.6 Hz as expected at δC 124.6.
Table 5. (Continued) H-3′
H-4′
H-5′
H-6′
H-α
H-β
OCH3/OCH2O
7.11 (ddd, 9.2, 8.2, 2.4) — 7.28 (t, 8.8) — 7.10 (t, 8.6) 7.41 m 7.40 (d, 8.0) 6.92 (d, 8.7) — —
7.32 m 7.06 (t, 8.0) — 6.81 (tt, 8.7, 2.4) — 7.39 m 7.39 m — — —
7.17 (t, 7.9) 7.36 m 7.28 (t, 8.8) — 7.10 (t, 8.6) 7.41 m 7.40 (d, 8.0) 6.92 (d, 8.7) 7.02 (d, 8.3) 6.81 (d, 8.1)
7.59 (td, 7.6, 1.5) 7.36 m 7.79 m 7.08 (dd, 8.1, 1.9) 7.56 (dd, 8.6, 5.6) 7.58 (dd, 8.1, 1.5) 7.56 (d, 8.0) 7.48 (d, 8.7) 7.27 (dd, 8.3, 1.7) 7.05 (d, 8.1)
6.87 (d, 16.2) 6.77 (d, 16.0) 7.16 (d, 16.2) 6.76 (d, 16.0) 6.67 (d, 16.0) 6.76 (d, 16.0) 6.77 (d, 16.1) 6.64 (d, 16.0) 7.11 (d, 16.0) 6.59 (d, 16.1)
7.72 (d, 16.2) 7.55 (d, 16.0) 7.70 (d, 16.2) 7.49 (d, 16.0) 7.53 (d, 16.0) 7.59 (d, 16.0) 7.60 (d, 16.1) 7.55 (d, 16.0) 7.65 (d, 16.0) 7.50 (d, 16.1)
— — — — — — — 3.84 s 3.80 s, 3.83 s 6.01
527
Magn. Reson. Chem. 2014, 52, 521–529
Copyright © 2014 John Wiley & Sons, Ltd.
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M. Momin, D. Ramjugernath and N. A. Koorbanally Table 6.
13
C NMR chemical shifts (δ in ppm) for compounds 5a–j (J is given in Hz)
C-2
C-3
C-4
C-5
C-6
C-7
C-8
C-9
C-10
5a 5b 5ca 5d
161.5 161.2 161.7 160.6
111.2 111.2 110.1 111.7
178.5 178.5 177.1 178.4
125.7 125.8 124.8 125.8
125.1 125.1 125.3 125.3
133.9 133.9 134.4 134.0
117.9 117.9 118.2 117.9
156.0 156.0 155.4 156.0
124.1 124.1 123.4 124.1
5e 5f 5g 5h 5i 5j
161.8 162.0 162.0 162.3 162.3 162.0
110.6 110.6 109.9 109.9 109.2 110.2
177.4 177.5 177.6 (d, 2.3) 178.5 177.0 178.5
128.2 (d, 10.5) 128.2 (d, 10.6) 110.7 (d, 23.4) 125.7 124.7 125.7
113.7 (d, 22.5) 113.7 (d, 22.6) 159.5 (d, 245.1) 124.9 125.2 125.0
167.1 (d, 210.1) 164.5 (d, 252.6) 121.8 (d, 25.1) 133.6 134.2 133.7
104.6 (d, 25.5) 104.6 (d, 25.4) 119.9 (d, 7.9) 117.9 118.1 117.8
156.9 157.1 (d, 13.2) 152.2 156.0 155.4 156.0
121.0 121.0 125.5 (d, 7.1) 124.2 123.4 123.3
a
In DMSO
19
Table 7. F NMR chemical shifts (δ in ppm) of compounds 3a–g, 4a–g, and 5a–g No. 3 a b c d e f g
113.57 112.27 108.54 108.75 103.81, 103.17 103.91 115.35
4 114.18 112.32 109.55 109.10 100.64, 109.57 100.72 124.33
5 115.39 108.99 110.72 109.31 102.96, 109.89 103.04 115.51
528
The same trends were observed for the 3″-fluorinated derivative 3b, but now, in the 13C NMR spectrum, all the usual coupling constants were observed for the ortho carbon resonances, C-2″ and C-4″ at δC 114.6 (J = 21.9 Hz) and 117.7 (J = 21.3 Hz), the meta carbon resonances, C-1″ and C-5″ at δC 136.3 (J = 7.9 Hz) and 130.6 (J = 8.0 Hz), and the para carbon resonance of C-6″ at δC 124.4 (J = 2.9 Hz). In the para-fluoro-substituted compounds, 3c and 3e, instead of the usual pair of doublets with a coupling constant of approximately 8 Hz being observed as for the para methoxy compound 3h, the splitting pattern is a bit more complex because of coupling to fluorine. The H-3″ and H-5″ protons are equivalent, and their resonance appears as a triplet at δH 7.09 (J = 8.6 Hz). This is because of similar coupling constants between H-2″/6″ and H-3″/5″, and H-3″/5″ and the fluorine atom. The H-2″ and H-6″ protons are also equivalent with their resonance appearing as a doublet of doublets because of a smaller coupling constant between H-2″/6″ and the fluorine atom and its occurrence at δH 7.58 (J = 8.6 and 5.4 Hz). The 13C NMR spectrum of 3c shows the fluorinated carbon resonance as a doublet at δC 164.3 (J = 250.7 Hz) and a doublet resonance for C-3″/5″ at δC 116.2 (J = 21.9 Hz) and C-2″/6″ at δC 130.4 (J = 8.37 Hz). The C-1″ resonance, also a doublet, overlaps with the C-2″/6″ resonance at δC 130.3 with a coupling constant of J = 3.6 Hz. This resonance can be seen more clearly in 3e at δC 130.2 (J = 3.4 Hz). For the 3″,5″-difluorinated compound 3d, the H-4″ resonance was split into a triplet of triplets with J = 8.7 and 2.3 Hz. This was because of H-4″ coupling to F (J = 8.7 Hz) and H-4″ coupling to the meta protons H-2″/6″ (J = 2.3 Hz). The H-2″ and H-6″ protons are equivalent and appear as a double doublet at δH 7.08 with J = 7.9 Hz for the
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H–F coupling and 1.9 Hz for the meta coupling with H-4″. The slight variation in J4″,2″/6″ is because of the coalescing and broadening of peaks for H-2″/6″; however, coupling between these two resonances was verified in the COSY spectrum. In the 13C NMR spectrum, the C-3″ and C-5″ resonances are equivalent and split into a double doublet at δC 163.24 because of coupling between the fluorine that it is attached to (J = 248.3 Hz) and the fluorine meta to it (J = 12.8 Hz). The C-2″ and C-6″ resonances are also equivalent and appear as a double doublet at δC 111.0 (J = 18.8 and 7.2 Hz) arising from coupling to the fluorine ortho to it and the fluorine para to it, respectively. The C-4″, C-1″, and C-β resonances appear as triplets at δC 105.9 (J = 25.4 Hz), δC 137.3 (J = 9.4 Hz), and δC 144.5 (J = 2.8 Hz), respectively, because these carbon atoms are in the middle of the two fluorine atoms. The substituted 3-hydroxy-2,4-pentadien-1-one intermediates (4) In these intermediates, there is a noticeable shift from the acetophenone methyl group at δH 2.59 in 3a to an olefinic resonance (H-2) at δH 6.32 in 4a. This is indicative that the cinnamoyloxyacetophenones (3) had converted to the 3-hydroxy2,4-pentadien-1-ones (4). With regard to the α,β-unsaturated double bond, both the resonances are shielded by 0.3 Hz for the β resonance in 3a to H-5 in 4a and 0.1 Hz for the α resonance in 3a to H-4 in 4a. This is because the double bond is now conjugated with the newly formed keto–enol moiety, shielding H-4 and H-5 more than the H-α and H-β protons in 3. The trans configuration of the double bond is retained as evidenced by the large coupling constant of 16.0 Hz. The H-3′ to H-6′ resonances are also more shielded by 0.22, 0.11, 0.45, and 0.16 Hz for H-3′, H-4′, H-5′ and H-6′, respectively, from 3a to 4a. This is probably because of greater electron donation by the hydroxy group as opposed to the ester group in 3a. A further characteristic trait of the 1H NMR spectra of the intermediates 4 is the two hydroxyl resonances occurring at δH 14.55 (3-OH) and 12.18 (2′-OH). Both these hydroxy groups experience hydrogen bonding resulting in these characteristic resonances, 3-OH with H-5 and 2′-OH with H-2. In the 13C NMR spectrum of 4a, the appearance of the alkene carbon resonance C-2 at δC 97.4 and an enol carbon resonance C-3 at δC 174.0 instead of the methyl carbon resonance at δC 29.8 and the ester carbonyl resonance at δC 165.1 in 3a is further evidence that 3a had converted to 4a. Because of the ester group being converted to a hydroxy group from 3a to 4a, the ortho and
Copyright © 2014 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2014, 52, 521–529
Structure elucidation of a series of fluoro-2-styrylchromones and methoxy-2-styrylchromones Table 6. (Continued) C-α
C-β
C-1′
122.7 (d, 6.5) 121.7 120.4 123.0
129.5 (d, 3.1) 135.6 (d, 2.8) 135.4 134.2 (t, 3.0)
123.1 (d, 11.7) 137.3 (d, 7.8) 131.6 (d, 3.2) 138.3 (t, 11.2)
119.7 119.9 120.0 117.9 118.0 118.4
135.8 137.2 137.4 136.7 136.9 136.7
131.2 (d, 3.6) 134.9 134.9 131.0 127.8 129.5
C-2′ 161.2 (d, 253.3) 116.7 (d, 21.6) 130.0 (d, 8.1) 110.3 (dd, 18.5, 7.2) 129.5 (d, 8.2) 127.7 127.7 129.3 109.9 106.2
C-3′ 116.2 (d, 21.8) 163.2 (d, 245.5) 116.0 (d, 24.3) 163.4 (dd, 247.8, 12.9) 116.2 (d, 21.9) 129.1 129.1 114.5 149.0 149.3
para positions of ring A are now more shielded by electron donation by resonance. As such, C-1′ shifts from δ 131.3 in 3a to δ 119.0 in 4a, C-3′ from δ 123.8 to δ 118.8, and C-5′ from δ 126.1 to δ 119.1. The C-2′ resonance that is bonded to the hydroxy group, however, is now more deshielded in the Ar–OH range at δC 162.7 in 4a from the Ar–ester resonance at δC 149.1 in 3a. The resonances on the aromatic ring adjacent to the Δ4 double bond remain relatively unchanged, and the 1H NMR spectra of 4b–4j contain the same differences as that pointed out between 3a and 4a.
C-4′ 131.3 (d, 8.7) 114.0 (d, 22.0) 162.9 (d, 240.6) 105.0 (t, 25.4) 165.0 (d, 251.6) 130.0 130.0 161.1 150.5 148.5
C-5′ 124.6 (d, 3.6) 130.5 (d, 8.3) 116.0 (d, 24.3) 163.4 (dd, 247.8, 12.9) 116.2 (d, 21.9) 129.1 129.1 114.5 111.7 108.7
C-6′ 128.4 (d, 2.7) 123.6 (d, 2.7) 130.0 (d, 8.1) 110.3 (dd, 18.5, 7.2) 129.5 (d, 8.2) 127.7 127.7 129.3 122.3 123.9
OCH3/OCH2O
55.4 55.5 101.6
in 4a at δC 174.0, 97.4, and 196.5, respectively. These three resonances can also be used as evidence that the 2-SC derivatives were prepared from the 3-hydroxy-2,4-pentadienone intermediates. All structures were confirmed, and assignments of the resonances of each of the proton and carbon atoms were made with the aid of HSQC, HMBC, and NOESY data. Selected HMBC correlations for 5a are shown in Fig. 2 in the succeeding texts, and the 1H NMR spectrum of 5a is shown in Fig. 3 depicting the splitting patterns and chemical shifts of the proton resonances. Tables 1–7 contain the 1H, 13C, and 19F NMR data for all the prepared compounds. The spectra were acquired in CDCl3 unless otherwise stated.
The substituted 2-styrylchromones
Magn. Reson. Chem. 2014, 52, 521–529
Acknowledgements This research was supported by grants from the National Research Foundation, South Africa, and was supported by the South African Research Chairs Initiative of the Department of Science and Technology.
References [1] A. M. S. Silva, D. C. G. A. Pinto, J. A. S. Cavaleiro, A. Levai, T. Patonay. Arkivoc 2004, 7, 106–123. [2] W. H. Gerwick. J. Nat. Prod. 1989, 52, 252–256. [3] A. Gomes, M. Freitas, E. Fernandes, J. L. F. C. Lima. Mini-Rev. Med. Chem. 2010, 10, 1–7. [4] P. Filipe, A. M. S. Silva, P. Morliere, C. M. Brito, L. K. Patterson, G. L. Hug, J. N. Silva, J. A. S. Cavaleiro, J.-C. Maziere, J. P. Freitas, R. Santus. Biochem. Pharmacol. 2004, 67, 2207–2218. [5] N. Desideri, C. Conti, P. Mastromarino, F. Mastropaolo. Antiviral Chem. Chemother. 2000, 11, 373–381. [6] W. H. Gerwick, European patent 237166, 1987. [7] K. Momoi, Y. Sugita, M. Ishihara, K. Satoh, H. Kikuchi, K. Hashimoto, I. Yokoe, H. Nishikawa, S. Fujisawa, H. Sakagami. In Vivo 2005, 19, 157–164. [8] J. Marinho, M. Pedro, D. C. G. A. Pinto, A. M. S. Silva, J. A. S. Cavaleiro, C. E. Sunkel, M. S. J. Nascimento. Biochem. Pharmacol. 2008, 75, 826–835. [9] G. Doria, C. Romeo, A. Forgione, P. Sberze, N. Tibolla, M. L. Corno, G. Cruzzola, G. Cadelli. Eur. J. Med. Chem. 1979, 14, 347–351. [10] E. Fernandes, M. Carvalho, F. Carvalho, A. M. S. Silva, C. M. M. Santos, D. C. G. A. Pinto, J. A. S. Cavaleiro, M. L. Bastos. Arch. Toxicol. 2003, 77, 500–505. [11] Y. Karton, J. Jiang, X. Ji, N. Melman, M. E. Olah, G. L. Stiles, K. A. Jacobson. J. Med. Chem. 1996, 39, 2293–2301. [12] E. R. Fernandes, F. Carvalho, A. M. S. Silva, C. M. M. Santos, D. C. G. A. Pinto, J. A. S. Cavaleiro, M. L. Bastos. J. Enzyme Inhib. Med. Chem. 2002, 17, 45–48. [13] A. I. R. N. A. Barros, A. M. S. Silva. Magn. Reson. Chem. 2009, 47, 885–896. [14] M. Momin, D. Ramjugernath, H. Chenia, N. A. Koorbanally. J. Chem. 2013, Article ID 436758, 1–13.
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529
In the substituted 2-SCs 5, the splitting patterns and chemical shifts of the phenyl ring in the 1H and 13C NMR spectra did not change much from that of the intermediates 3 and 4, and therefore, a discussion of this will not be repeated. There was also not much change in the C-α and C-β carbon resonances as well as the H-β resonance. However, in the formation of the chromone ring, the H-α proton experiences a slightly more deshielded shift to δH 6.87 in 5a, approximately 0.2 Hz from the corresponding resonance in 4a. All the proton resonances in the chromone ring are also deshielded in forming the chromone ring from the 3-hydroxy2,4-pentadien-1-one intermediates 4. The most characteristic and noticeable of these resonances is that of H-5 occurring at δH 8.17 in 5a from 7.69 in 4a, with the H-6, H-7, and H-8 proton resonances also being significantly deshielded by between 0.23 and 0.56 Hz, at δH 7.37, 7.66, and 7.53, respectively, in 5a from δH 6.88, 7.43, and 6.97 in 4a. These deshielded shifts must occur because of delocalization of the pi electrons within the chromone skeleton, thus reducing the electron density at these specific protons. The difference in chemical shift of the H-5 proton is also because of hydrogen bonding with the C-4 carbonyl group. This is now possible because the carbonyl group is locked into position by formation of the chromone ring. With regard to the 13C NMR spectra, there is not much change in both the C-α and C-β resonances or the aromatic resonances on the chromone ring with the exception of C-6, which is para to the oxygen substituent forming the chromone ring. This shift is slightly deshielded by approximately 7 ppm at δC 125.1 in 5a from 119.1 in 4a. The most notable shifts in the 13C NMR spectrum are that of C-2, C-3, and C-4, the carbon atoms involved in forming the chromone ring from the 3-hydroxy-2,4-pentadien-1-one. In 5a, these carbon resonances occur at δC 161.5, 111.2, and 178.5 for C-2, C-3, and C-4 as opposed to their corresponding resonances
Revised: 23 June 2014
Accepted: 28 June 2014
Published online in Wiley Online Library: 22 July 2014
(wileyonlinelibrary.com) DOI 10.1002/mrc.4111
Structure elucidation of a series of fluoro2-styrylchromones and methoxy2-styrylchromones using 1D and 2D NMR spectroscopy Mehbub Momin,a Deresh Ramjugernathb and Neil A. Koorbanallya* Introduction 2-Styrylchromones (2-SCs) are a chemical family of oxygen heterocyclic compounds, similar to the flavonoids (2-phenylchromones), but with a vinyl group bridging the chromone ring to the phenyl moiety. Many derivatives of 2-SCs have been synthesized,[1] and their occurrence in nature has also been reported.[2] There have also been numerous reports on the biological activity of the synthesized derivatives of 2-SCs, which has recently been reviewed by Gomes et al.,[3] and these compounds were seen to have antioxidant,[4] antiviral,[5] anticancer,[6–8] antiallergic,[9] and hepatoprotective activity[10] and shown to be A3 adenosine receptor antagonists[11] and xanthine oxidase inhibitors.[12] Although the NMR data for 2-SCs are always reported in synthetic publications that also report the biological activity, full structural elucidation of these compounds is rare. We have only noticed one publication on the structural elucidation of this class of compounds in which the nitro derivatives were described.[13] To the best of our knowledge, there are no publications where the structural elucidation of these compounds has been discussed with substituents on the aromatic rings that donate electrons by resonance into the aromatic rings. Furthermore, the structural elucidation of fluorinated molecules is more challenging because of 19F being NMR active and coupling with both the protons and the carbon atoms. We have recently reported the synthesis and antibacterial activity of these compounds[14] and herein report the structural elucidation of seven fluorinated, two methoxylated, and a methylenedioxy derivative of 2-SC along with their cinnamoyloxyacetophenone and 3-hydroxy-2,4-pentadien-1-one intermediates. The structural elucidation and NMR data reported here can help one identify newly isolated or synthesized derivatives of 2-SCs, especially fluorinated derivatives.
and phosphorus oxychloride (POCl3) at room temperature for 4–5 h producing the cinnamoyloxyacetophenone intermediates (3a–j), which were then converted to the 3-hydroxy-2,4pentadienone intermediates (4a–j) with potassium hydroxide in dimethyl sulfoxide (DMSO) by being stirred at room temperature for 2 h. Final conversion to the 2-SC derivatives (5a–j) was carried out using p-toluenesulfonic acid in DMSO by reflux at 90–95 °C for 2–3 h. The compounds were named similarly for each of the intermediates and the 2-SC according to their substitution pattern, for example, 2-(2′-fluorocinnamoyloxy) acetophenone (3a), 3-hydroxy-1-(2-hydroxyphenyl)-5-(2-fluorophenyl)-2,4-pentadien1-one (4a) and 2′-fluoro-2-SC (5a).
NMR spectra The 1H and 13C NMR spectra were recorded at 298 K with 5–10-mg samples dissolved in 0.5 ml of CDCl3 in 5-mm NMR tubes using a Bruker Avance III 400-MHz NMR spectrometer (9.4 T; Bruker, Germany) (400.22 MHz for 1H, 100.63 MHz for 13C, and 376.58 Hz for 19F). Chemical shifts (δ) are reported in ppm and coupling constants (J) in Hz. The 1H and 13C chemical shifts of the deuterated solvent were δ 7.24 and 77.0 referenced to the internal standard, TMS, respectively. For the 19F NMR spectra, the chemical shift of trifluorotoluene (0.05% in CDCl3) was referenced at δ 62.73. For the 1H NMR analyses, 16 transients were acquired with a 1-s relaxation delay using 32-K data points. The 90° pulse duration was 10.0 μs, and the spectral width was 8223.68 Hz. The 13C NMR spectra were obtained with a spectral width of 24 038.46 Hz using 64-K data points. The 90° pulse duration was 8.40 μs. For the 19F NMR spectra, the spectral width was 89 285.71 Hz using 131-K data points, and the 90° pulse duration was 12.50 μs. For the two-dimensional (2D) experiments including COSY, NOESY, HSQC, and HMBC, all data were acquired with 4-K × 128 data points (t2 × t1). The mixing
Experimental Synthesis
Magn. Reson. Chem. 2014, 52, 521–529
a School of Chemistry, University of KwaZulu-Natal, Private Bag X54001, Durban, 4000, South Africa b School of Chemical Engineering, University of KwaZulu-Natal, Private Bag X54001, Durban, 4000, South Africa
Copyright © 2014 John Wiley & Sons, Ltd.
521
The synthesis of the 2-SCs (5a–j) along with the cinnamoyloxyacetophenone (3a–j) and 3-hydroxy-2,4-pentadienone (4a–j) intermediates was carried out using the Baker–Venkataraman rearrangement in a three-step reaction, which was reported recently.[14] Essentially, the substituted 2-hydroxyacetophenones (1) were reacted with substituted cinnamic acids (2) in pyridine
* Correspondence to: Neil A. Koorbanally, School of Chemistry, University of KwaZulu-Natal, Private Bag X54001, Durban, 4000, South Africa. E-mail: [email protected]
M. Momin, D. Ramjugernath and N. A. Koorbanally
Figure 1. Scheme for the preparation of 2-styrylchromones 5a–j.
time for the NOESY experiment was 0.3 s, and the long-range coupling time for HMBC was 65 ms. All data were analyzed using Bruker Topspin 2.1 (2008) software.
Figure 2. Selected HMBC correlations for 2′-fluoro-2-styrylchromone 5a.
522
Figure 3.
1
Results and Discussion Compounds 3–5 (Fig. 1) are fully characterized in Tables 1 through to 7 with their 1H and 13C NMR assignments unambiguously assigned using splitting patterns, chemical shifts, and 2D NMR data from HSQC, HMBC, and NOESY spectra. An extensive discussion on the splitting patterns and chemical shifts of the compounds are presented below for the intermediates and the 2-SC molecules. The discussion is divided into several parts, discussing the carbon chain linking the two aromatic units together and discussing the two aromatic rings in detail. This is performed in detail for the intermediate 3, and then, a comparison to 4 and 5 is performed, pointing out salient features and resonances that have changed as well as the proton and carbon resonances that indicate that the products have been formed.
H NMR spectrum of 2′-fluoro-2-styrylchromone (5a) depicting chemical shifts and splitting patterns.
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Copyright © 2014 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2014, 52, 521–529
Copyright © 2014 John Wiley & Sons, Ltd.
3j
3i
3h
3g
3f
3e
3d
3c
3b
523
Magn. Reson. Chem. 2014, 52, 521–529
3a
Table 1.
H-3′
7.17 (d, 8.1, 0.9) 7.16 (d, 7.9)
7.23 (dd 7.8, 3.0) 7.51 (td, 7.6, 1.6) 7.54 (td, 7.8, 1.7) 7.53 (td, 7.9, 1.6)
—
7.54 (td, 7.6, 1.6) 7.55 (td, 7.8, 1.6) 7.53 (td, 8.0, 1.5) 7.55 (td, 7.6, 1.0) —
H-4′
7.31 (td, 8.0, 0.8) 7.31 (td, 7.6, 0.9) 7.31 (td, 7.9, 0.8)
7.33 (td, 8.0, 0.7) 7.34 (td, 7.6, 0.8) 7.03 (td, 8.8, 2.5) 7.03 (td 8.6, 2.5) —
7.33 (td, 7.6, 0.8) 7.35 m
H-5′ 7.85 (dd, 7.9, 1.6) 7.83(dd, 7.6, 1.6) 7.81 (dd, 8.0, 1.6) 7.82 (dd, 7.9, 1.0) 7.87 (dd, 8.8, 6.3) 7.86 (dd 8.6, 5.4) 7.15 (dd, 8.7, 4.7) 7.80 (dd, 8.0, 1.6) 7.81 (dd, 7.8, 1.7) 7.80 (dd, 7.9, 1.6)
H-6′
6.47 (d, 15.9)
6.52 (d, 15.9)
6.52 (d, 15.9)
6.64 (d, 15.9)
6.63 (d, 15.9)
6.56 (d, 16.0)
6.64 (d, 16.0)
7.78 (d, 15.9)
7.82 (d, 15.9)
7.83 (d, 15.9)
7.88 (d, 15.9)
7.88 (d, 15.9)
7.84 (d, 16.0)
7.75 (d, 16.0)
7.84 (d, 16.0)
7.82 (d, 16.0)
6.55 (d, 16.0) 6.58 (d, 16.0)
8.00 (d, 16.2)
H-β
6.76 (d, 16.2)
H-α
H NMR chemical shifts (δ in ppm) for compounds 3a–j (J is given in Hz)
7.19 (dd, 8.0, 0.8) 7.17 (dd, 8.0, 0.7) 7.17 (dd, 8.0, 0.7) 7.16 (dd, 7.9, 0.8) 6.92 (dd, 8.9, 2.5) 6.94 (dd 8.9, 2.5) 7.49 (dd, 8.7, 3.0) 7.17 (d, 8.0)
1
H-3″
7.05 (d, 1.6)
7.10 (d, 1.9)
7.58 (dd, 8.7, 5.4) 7.58 (dd, 7.6, 3.9) 7.58 (dd, 7.4, 3.6) 7.53 (d, 8.7)
7.58 (dd, 8.6, 5.4) 7.08 m
— — —
— —
7.39 m
7.44 m
6.91 (dd, 8.7)
7.39 m
7.44 m
—
6.85 (tt, 8.7, 2.3)
— 7.10 (dd, 8.6)
—
7.10 (tt, 8.2, 2.0)
7.39 m
H-4″
7.09 (t, 8.6)
7.11 (dd, 10.3, 8.8) 7.27 (d, 9.6) —
—
H-2″
6.82 (d, 7.9)
6.87 (d, 8.2)
6.91 (dd, 8.7)
7.39 m
7.44 m
7.10 (dd, 8.6)
—
7.09 (t, 8.6)
7.33 (td, 7.7, 0.8)
7.18 (t, 7.5)
H-5″
7.16 (dd, 8.2, 1.9) 7.08 (dd, 7.9, 1.6)
7.58 (dd, 8.7, 5.4) 7.58 (dd, 7.6, 3.9) 7.58 (dd, 7.4, 3.6) 7.53 (d, 8.7)
7.58 (dd, 8.6, 5.4) 7.08 m
7.59 (td, 7.9, 1.7) 7.35 m
H-6″
2.54 s
2.55 s
2.54 s
2.53 s
2.53 s
2.53 s
2.54 s
2.54 s
2.55 s
2.55 s
CH3
6.01 s
3.91 s (6H)
3.84 s
—
—
—
—
—
—
—
OCH3/OCH2O
Structure elucidation of a series of fluoro-2-styrylchromones and methoxy-2-styrylchromones
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M. Momin, D. Ramjugernath and N. A. Koorbanally Table 2.
13
C NMR chemical shifts (δ in ppm) for compounds 3a–j (J is given in Hz)
C-1
C-2
C¼O
C-α
C-β
C-1′
C-2′
C-3′
C-4′
3a
197.7
29.8
165.1
119.4 (d, 6.9)
140.0 (d, 2.7)
131.3
149.1
123.8
133.4
3b
197.7
30.0
164.9
118.3
145.8 (d, 2.7)
131.2
149.0
123.8
133.4
3c
197.8
29.7
165.1
116.6 (d, 2.4)
146.0
131.3
149.1
123.8
133.4
3d
197.6
29.5
164.6
119.7
144.5 (t, 2.8)
131.0
148.9
123.7
133.5
3e
196.1
29.7
165.1
116.1 (d, 2.2)
146.6
127.6 (d, 3.5)
151.0 (d, 11.2)
111.7 (d, 24.0)
165.0 (d, 254.1)
3f
196.1
29.8
164.8
116.3
145.4
127.0
151.0 (d, 11.4)
113.4 (d, 21.1)
166.4 (d, 255.8)
3g
196.4
29.8
165.2
116.6
145.0
132.6 (d, 6.1)
147.8
125.4 (d, 8.0)
116.5 (d, 20.5)
3h 3i 3j
197.9 197.9 197.8
29.9 29.9 29.9
165.5 165.5 165.4
114.1 114.3 114.6
147.2 147.4 147.1
131.5 131.5 131.5
149.3 151.7 150.2
123.8 123.8 125.2
133.3 133.3 133.3
The acetyl group and the α, β unsaturated ester of the intermediate 3 In 3a, the α and β proton resonances are characteristic and occur at δH 6.76 and 8.00, respectively, as two doublets with large coupling constants of 16.2 Hz, characteristic of trans olefinic protons. Their corresponding carbon resonances were present at δC 119.4 (J = 6.9 Hz, C-α) and 140.0 (J = 2.7 Hz, C-β). The C-β resonance is more deshielded than the C-α resonance because of conjugation between the double bond and the carbonyl group; in the enolate anion resonance structure, electron density is removed from C-β. The coupling constants experienced in 3a for these two resonances are attributed to that of the fluorine atom three and four bonds away from C-β and C-α, respectively. This small coupling in the carbon resonances was also seen in 3b (3″-F) with the C-β resonance and 3c (4″-F) and 3e (4′,4″-diF) with the C-α resonance but not in 3d (3″,5″-diF), 3f (4′-F), and 3g (5′-F), the remaining fluorinated acetophenone derivatives. The 1H and 13 C chemical shifts of these resonances (C-α and C-β) were similar in all of the other cinnamoyloxyacetophenone derivatives (3b–3j). A NOESY correlation between H-α and H-6″ further confirms the assignment of these resonances. The acetophenone methyl resonance occurred at δH 2.55 as an
Table 3.
524
4a 4b 4c 4d 4e 4f 4g 4h 4i 4j
1
intense singlet, also consistent with all the other derivatives 3b–3j, and the acetophenone carbonyl resonance (C-1) was present at δC 197.7, distinguished from the other ester carbonyl resonance (C=O) at δC 165.1 because the latter showed HMBC correlations to both the α and β proton resonances.
The acetophenone aromatic ring The proton resonances of 3a–3d (the unsubstituted acetophenone ring) are all similar with H-3′ and H-6′ appearing as double doublets at δH 7.19 (J = 8.0 and 0.8 Hz) and δH 7.85 (J = 7.9 and 1.6 Hz), respectively. The H-3′ resonance ortho to the oxygenated position is more shielded because of electron donation from the oxygen atom by resonance and the H-6′ resonance more deshielded because this same electron donation by resonance results in the meta position becoming electron deficient. The H-4′ and H-5′ proton resonances both appear as triplets of doublets at δH 7.5 (J = 7.6 and 1.6 Hz) and δH 7.33 (J = 7.6 and 0.8 Hz) because they experience the same coupling constant with each of their adjacent protons resulting in the triplet, which is further split into doublets because of meta coupling, hence the second small coupling constant. Only in 3b does
H NMR chemical shifts (δ in ppm) for compounds 4a–j (J is given in Hz)
2′-OH
H-3′
12.17 s 12.15 s 12.17 s 12.10 s 12.47 s 12.55 s 11.94 s 12.24 s 12.23 s 12.21 s
6.97 (dd, 8.5, 0.7) 6.97 (dd, 7.9, 0.9) 6.97 (dd, 8.5, 0.9) 6.98 (dd, 8.5, 1.1) 6.65 (dd, 10.4, 2.5) 6.65 (dd, 10.3, 2.5) 6.93 (dd, 9.1, 4.7) 6.96 (dd, 8.5, 2.1) 6.96 (dd, 8.4, 0.7) 6.96 (dd, 8.5, 0.5)
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H-4′ 7.43 (ddd, 8.5, 7.44 (ddd, 8.5, 7.44 (ddd, 8.5, 7.45 (ddd, 8.5, — — 7.17 (ddd, 9.2, 7.42 (ddd, 8.5, 7.42 (ddd, 8.5, 7.42 (ddd, 8.5,
H-5′ 7.1, 7.1, 7.1, 7.2,
1.4) 1.5) 1.4) 1.6)
7.9, 7.5, 8.3, 8.0,
3.0) 1.6) 1.5) 1.6)
6.88 (td, 8.1, 0.8) 6.89 (ddd, 8.0, 7.1, 6.88 (ddd, 8.1, 7.1, 6.89 (ddd, 8.1, 7.2, 6.60 (ddd, 8.8, 8.2, 6.60 (td, 8.0, 2.5) — 6.89 m 6.85 (td, 8.3, 0.7) 6.87 (td, 8.0, 0.5)
0.9) 0.9) 1.1) 2.2)
Copyright © 2014 John Wiley & Sons, Ltd.
H-6′
H-2
3-OH
7.69 (dd, 8.0, 1.4) 7.68 (dd, 8.0, 2.0) 7.68 (dd, 8.1, 1.4) 7.67 (dd, 8.1, 1.4) 7.68 (dd, 9.0, 6.4) 7.68 (dd, 8.9, 6.4) 7.34 (dd, 9.0, 3.0) 7.67 (dd, 8.0, 1.6) 7.67 (dd, 8.1, 1.5) 7.66 (dd, 8.0, 1.6)
6.32 s 6.32 s 6.29 s 6.32 s 6.20 s 6.21 s 6.20 s 6.26 s 6.28 s 6.26 s
14.55 s 14.55 s 14.62 s 14.46 s 14.42 s 14.48 s 14.59 s 14.72 s 14.71 s 14.68 s
Magn. Reson. Chem. 2014, 52, 521–529
Structure elucidation of a series of fluoro-2-styrylchromones and methoxy-2-styrylchromones Table 2. (Continued) C-5′
C-6′
126.1
130.2
126.2
130.2
126.1
130.2
126.3
130.3
113.3 (d, 21.2) 111.7 (d, 24.0) 159.9 (d, 245.1) 126.0 126.0 126.0
132.2 (d, 10.1) 132.3 (d, 10.2) 120.1 (d, 23.3) 130.0 130.1 130.1
C-1″
C-2″
C-3″
C-4″
C-5″
122.2 (d, 11.6) 136.3 (d, 7.9) 130.3 (d, 3.6) 137.3 (t, 9.4) 130.2 (d, 3.4) 133.9
161.8 (d, 252.6) 114.6 (d, 21.9) 130.4 (d, 8.4) 111.0 (dd, 18.8, 7.2) 130.5 (d, 8.5) 129.0
116.3 (d, 21.7) 163.0 (d, 245.6) 116.2 (d, 21.9) 163.2 (dd, 248.3, 12.8) 116.3 (d, 21.9)
132.2 (d, 14.2) 117.7 (d, 21.3) 164.3 (d, 250.7) 105.9 (t, 25.4) 164.4 (d, 251.0) 131.1
124.6 (d, 3.6) 130.6 (d, 8.0) 116.2 (d, 21.9) 163.2 (dd, 248.3, 12.8) 116.3 (d, 21.9) 128.5
128.5
C-6″
CH3/OCH2O
129.4 (d, 2.7)
—
124.4 (d, 2.9)
—
130.4 (d, 8.4)
—
111.0 (dd, 18.8, 7.2) 130.5 (d, 8.5)
-
129.0
—
133.9
128.5
129.0
131.0
129.0
128.5
—
126.8 127.0 128.5
130.2 109.8 106.7
114.5 149.2 148.5
161.9 149.3 149.2
114.5 111.1 108.6
130.2 123.3 123.8
55.4 55.9,56.0 101.7
H-5′ appear as a multiplet because of overlap with other resonances. The C-3′ to C-6′ carbon resonances for 3a–d are all similar and occur between δC 123.8 and 130.2. The C-1′ carbon resonance occurs at δC 131.3 and was assigned because of HMBC correlations to H-3′ and H-5′. The oxygenated aromatic resonance C-2′ was assigned to δC 149.1 because of HMBC correlations to H-6′ and H-4′. In 3e and 3f, where a fluorine atom is substituted at the 4′-position, the H-3′ resonance also occurs as a double doublet as in 3a–d, but now, the meta coupling is much larger at 2.5 Hz, the first coupling constant of 8.9 Hz occurring because of H-F ortho coupling. The H-5′ resonance occurs as a triplet of doublets as for 3a–d because the H-F ortho coupling constant is similar to the H–H ortho coupling constant at J = 8.8 Hz, but as for H-3′, the meta coupling constant is larger than that for 3a–d at J = 2.5 Hz. The H-6′ resonance occurs as a double doublet but distinctly different from the double doublet in 3a–d because of the larger meta H–F coupling constant of 6.3 Hz in addition to the ortho H–H coupling constant of 8.8 Hz. The H-6′ resonance also overlaps with the H-β resonance as well in these two compounds. In the 13C NMR spectrum, C-4′ occurs as a doublet with J = 254.1 Hz at δH 165.0 in 3e. The coupling constant is so large that the two resonances that make up the doublet could easily
be mistaken for two separate resonances. The carbon resonances, however, can be identified from the HMBC spectrum where both the resonances making up the doublet show HMBC correlations to a nearby proton resonance, in the case of 3e, C-4′ to H-6′. To verify this, coupling constants of approximately 220–250 Hz are normally observed. 2JF–C coupling of 24.0 and 21.2 Hz is observed respectively at δC 111.7 and 113.3 for the two doublets assigned to C-3′ and C-5′. Their chemical shifts are more shielded than their corresponding carbon resonances in 3a–d because of electron donation by resonance from the fluorine, shielding the carbon atoms more than that of hydrogen. 3 JF–C coupling of 11.2 Hz is observed at δC 150.9 for C-2′ and 10.1 Hz at δC 132.2 for C-6′. 4JF–C coupling at δC 127.6 for C-1′ is also observed with a coupling constant of 3.5 Hz in 3e; however, this is not seen in 3f. When the fluoro group is at the 5′ position in 3g, the H-3′ resonance is now meta to the fluorine atom, which by resonance deshields the meta hydrogen resulting in it appearing at δH 7.49 in 3g as opposed to δH 6.92–6.94 in 3e and 3f. The multiplicity is retained as a double doublet with J = 8.7 and 3.0 Hz for the H–H and H–F coupling, respectively. The H-4′ proton resonance coincides with the solvent peak appearing as a triplet of doublets at δH 7.23 with J = 7.8 and 3.0 Hz, the triplet being a result of similar coupling between H-4′-F and H-4′-H-3′, similar to the
Table 3. (Continued) H-4
7.73 (d, 16.0) 7.58 (d, 15.8) 7.60 (d, 16.0) 7.51 (d, 15.7) 7.60 (d, 16.0) 7.64 (d, 15.8) 7.66 (d, 15.8) 7.61 (d, 15.8) 7.59 (d, 15.7) 7.55 (d, 15.6)
H-2″ — 7.24 m 7.52 (dd, 8.9, 5.4) 7.04 (dd, 8.2, 2.2) 7.52 (dd, 8.7, 5.4) 7.53 (dd, 8.1, 2.1) 7.54 (dd, 7.9, 2.2) 7.49 (d, 8.8) 7.06 (d, 1.8) 7.04 (d(br), 0.4)
Magn. Reson. Chem. 2014, 52, 521–529
H-3″ 7.09 (t, 8.2) — 7.08 (t, 8.9) — 7.08 (t, 8.6) 7.38 m 7.40 m 6.91 (d, 8.8) — —
H-4″ 7.32 m 7.06 m — 6.80 (tt, 8.8, 2.2) — 7.38 m 7.40 m — — —
H-5″ 7.16 (t, 7.6) 7.34 (dd, 7.9, 5.7) 7.08 (t, 8.9) — 7.08 (t, 8.6) 7.38 m 7.40 m 6.91 (d, 8.8) 6.87(d, 8.3) 6.81 (d, 8.0)
Copyright © 2014 John Wiley & Sons, Ltd.
H-6″ 7.54 (td, 7.6, 1.5) 7.30 (d, 7.8) 7.52 (dd, 8.9, 5.4) 7.04 (dd, 8.2, 2.2) 7.52 (dd, 8.7, 5.4) 7.53 (dd, 8.1, 2.1) 7.54 (dd, 7.9, 2.2) 7.49 (d, 8.8) 7.11 (dd, 8.3, 1.9) 7.02 (dd, 8.0, 1.2)
OCH3/OCH2O — — — — — — 3.83 s 3.91 s, 3.92 s 6.00 s
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525
6.70 (d, 16.0) 6.56 (d, 15.8) 6.49 (d, 16.0) 6.55 (d, 15.7) 6.51 (d, 16.0) 6.57 (d, 15.8) 6.58 (d, 15.8) 6.45 (d, 15.8) 6.45 (d, 15.7) 6.39 (d, 15.6)
H-5
M. Momin, D. Ramjugernath and N. A. Koorbanally 13
Table 4.
C NMR chemical shifts (δ in ppm) for compounds 4a–j (J is given in Hz) C-1
C-2
C-3
C-4
C-5
C-1′
C-2′
C-3′
C-4′
132.6 (d, 2.2)
119.0
162.6
118.8
136.2
138.3 (d, 2.5)
119.0
162.7
118.8
136.0
4a
196.5
97.5
174.1
4b
196.3
97.4
173.6
124.9 (d, 7.8) 123.5
4c
196.0
97.0
174.3
121.9
138.5
119.0
162.6
118.8
135.9
4d
196.4
97.9
172.8
124.8
137.0
118.9
162.7
118.9
136.2
4e
194.9
96.8
174.2
121.7
138.7
115.9
4f
194.9
96.8
174.4
122.0
140.1
116.0
4g
194.8 (d, 2.7)
96.8
175.2
121.9
140.6
4h 4i 4j
195.3 195.6 195.7
96.1 96.5 96.6
174.9 175.0 174.8
119.4 119.9 120.1
139.5 140.0 139.7
118.7 (d, 6.5) 118.9 119.1 119.1
165.2 (d, 14.1) 165.1 (d, 14.1) 158.7
105.3 (d, 23.6) 105.3 (d, 23.4) 120.0 (d, 7.4) 118.4 118.7 118.7
H-5′ resonance in 3e. Because of the fluoro group being placed adjacent to H-6′, shielding this proton through electron donation by resonance, the H-6′ proton resonance moves from being the most deshielded resonance in 3e at δH 7.87, where it was meta to both the oxygenated moiety and the fluorine atom, to the most shielded of the aromatic resonances at δH 7.15 in 3g. The resonance retains its multiplicity as a double doublet because it couples to fluorine with a similar coupling constant to that of hydrogen with J = 8.7 and 4.7 Hz. In the 13 C NMR spectrum, all the carbon resonances on the aromatic ring appear as doublets except for C-2′, which is para to the fluorinated carbon and appears at δC 147.8. The fluorinated carbon is present at δC 159.9 with J = 245.1 Hz. The carbon meta to the fluorine C-1′ occurs at δC 132.6 (J = 6.1 Hz), followed by the other meta carbon C-3′, at δC 125.4 (J = 8.0 Hz), both being more deshielded than the two ortho carbon atoms at δC 120.1 (J = 23.3, C-6′) and δC 116.5 (J = 20.5, C-4′). In the 1H and 13C NMR spectra of the methoxy and methylenedioxy derivatives 3h–3j, H-3′ to H-6′, Hα and Hβ and C-1, C-2, and C-1′ to C-6′, C-α, and C-β, and the ester C¼O were all similar to 3a–3d. 1
Table 5.
526
a
The cinnamoyl aromatic ring In the absence of any substituents on this ring as in 3f and 3g, the H-3″/4″/5″ resonances overlap at δH 7.44 and appear as a multiplet in 3f, and the H-2″/6″ resonance appears as a double doublet with J = 7.6 and 3.9 in 3f. Their carbon resonances appear between δC 128.5 and δC 133.9 with the C-2″/6″ and C-3″/5″ resonances being equivalent. For the 4″-methoxy derivative 3h, a characteristic pair of doublets is seen as for other parasubstituted aromatic compounds at δH 7.53 for H-2″/6″ and at δH 6.91 for H-3″/5″ with a coupling constant of 8.7 Hz. The H-3″/5″ resonance is more shielded than that of H-2″/6″ because of the electron donating effects of the methoxy group by resonance to the ortho positions. The carbon resonances of C-2″/6″ and C-3″/5″ occur at δC 130.2 and 114.5, the C-3″/5″ resonance being more shielded because of the resonance effects explained previously. The oxygenated C-4’″ resonance appears at δC 161.9 and C-1″ appears at δC 126.8. When the phenyl ring is substituted at both C-3″ and C-4″ with oxygenated substituents, as in 3i and 3j, meta coupling is observed for H-2″ at δH 7.10 (J = 1.9 Hz) in 3i, and ortho coupling
H NMR chemical shifts (δ in ppm) for compounds 5a–j (J in Hz)
H-3 5a 5b 5ca 5d 5e 5f 5g 5h 5ia 5j
162.3 162.5 162.6
166.4 (d, 212.1) 165.2 (d, 209.2) 123.2 (d, 23.4) 135.3 135.6 135.7
6.32 s 6.34 s 6.46 s 6.34 s 6.28 s 6.29 s 6.31 s 6.28 s 6.40 s 6.28 s
H-5 8.17 (dd, 7.9, 8.18 (dd, 7.9, 8.01 (dd, 7.9, 8.18 (dd, 7.9, 8.18 (dd, 8.8, 8.19 (dd, 8.9, 7.85 (dd, 8.2, 8.18 (dd, 8.0, 8.01 (dd, 7.9, 8.17 (d, 7.6)
1.6) 1.3) 1.4) 1.6) 6.4) 6.4) 3.2) 1.6) 1.7)
H-6
H-7
H-8
H-2′
7.37 (td, 7.9, 0.8) 7.36 m 7.47 (t, 7.4) 7.39 (td, 7.9, 0.7) 7.12 m 7.10 (td, 8.6, 2.4) — 7.36 (t, 8.0) 7.47 (ddd, 7.9, 7.2, 0.7) 7.37 (t, 7.5)
7.66 (ddd, 8.6, 7.2, 1.6) 7.68 (dt, 8.6, 1.6) 7.82 m 7.72 (ddd, 8.6, 7.2, 1.6) — — 7.40 m 7.65 (ddd, 8.6, 7.1, 1.6) 7.81 (ddd, 8.2, 7.2, 1.7) 7.65 (ddd, 8.1, 7.1, 1.0)
7.53 (d, 8.3) 7.52 (d, 8.6) 7.69 (d, 8.5) 7.51 (d, 8.3) 7.20 (dd, 9.0, 2.4) 7.21 (dd, 9.1, 2.4) 7.52 (dd, 9.1, 4.2) 7.52 (d, 8.6) 7.70 (d, 8.2) 7.51 (d, 7.8)
— 7.26 m 7.79 m 7.08 (dd, 8.1, 1.9) 7.56 (dd, 8.6, 5.6) 7.58 (dd, 8.1, 1.5) 7.56 (d, 8.0) 7.48 (d, 8.7) 7.36 (d, 1.7) 7.08 s
In DMSO
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Copyright © 2014 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2014, 52, 521–529
Structure elucidation of a series of fluoro-2-styrylchromones and methoxy-2-styrylchromones Table 4. (Continued) C-5′
C-6′
119.1
128.6
119.1
128.5
119.0
128.5
119.1
128.6
107.3 (d, 22.6) 107.3 (d, 22.7) 155.1 (d, 236.8) 118.7 119.0 119.0
130.4 (d, 10.8) 130.5 (d, 11.7) 113.5 (d, 23.5) 128.8 128.4 128.4
C-1″
C-2″
123.1 (d, 11.5) 137.3 (d, 7.8) 130.2 (d, 3.5) 138.3 (t, 9.5) 130.7 (d, 11.9) 134.9
C-3″
C-4″
C-5″
C-6″
CH3/OCH2O
161.4 (d, 253.8)
116.3 (d, 21.9)
131.4 (d, 8.8)
124.5 (d, 3.6)
129.2 (d, 3.0)
—
114.1 (d, 20.0)
164.9 (d, 247.2)
116.9 (d, 21.6)
130.5 (d, 8.2)
124.1 (d, 2.8)
—
129.8 (d, 8.2)
116.2 (d, 21.9)
163.8 (d, 250.3)
116.2 (d, 21.9)
129.8 (d, 8.2)
—
110.5 (dd, 18.5, 6.8) 129.9 (d, 8.6)
163.3 (dd, 247.8, 13.1) 116.2 (d, 21.9)
163.3 (dd, 247.8, 13.1) 116.2 (d, 21.9)
110.5 (dd, 18.5, 6.8) 129.9 (d, 8.6)
—
105.1 (t, 25.6) 163.0 (d, 252.6)
—
128.0
129.0
130.2
129.0
128.0
—
134.8
128.1
129.0
130.4
129.0
128.1
—
129.8 128.0 129.5
129.4 109.7 106.3
114.2 151.1 149.6
161.1 149.3 148.5
114.2 111.2 108.7
129.4 122.6 124.6
55.2 56.0, 55.9 101.6
is observed for H-5″ at δH 6.87 (J = 8.2 Hz) with H-6″ experiencing both ortho and meta coupling at δH 7.16 (J = 8.2, 1.9 Hz). The carbon resonances of the two carbon atoms ortho to the methoxy groups, C-2″ and C-5″, occur more shielded at δC 109.8 and δC 111.1, while C-6″ meta positioned to the 4″-methoxy substituent appears slightly more deshielded at δC 123.3. The two aromatic C–O resonances C-3″ and C-4″ occur at δC 149.2 and 149.3, respectively. The two methoxy resonances in 3i overlap at δH 3.91 with corresponding carbon resonances at δC 55.9 and 56.0. The methylenedioxy group proton resonance occurs at δH 6.01 with a corresponding carbon resonance of δC 101.7. In 3a–e, fluorination either occurred at 2″, 3″, and 4″ or was difluorinated at the 3″ and 5″ positions. For the 2″-fluoro derivative 3a, the H-5″ proton only experiences coupling from the adjacent protons and appears as a triplet at δH 7.18 with J = 7.5 Hz. This resonance overlaps with H-3′, which may account for the meta coupling with H-3″ not being observed. The H-3″ proton resonance at δH 7.11 couples with both the fluorine and the proton of H-4″ and appears as a double doublet with J = 10.3 Hz (H–F coupling) and 8.8 Hz (H–H coupling). The H-4″ proton resonance appears as a multiplet at δH 7.39 because of
coupling with all of H-3″, H-5″, H-6″, and the F. However, the only coupling constant that can be observed in this multiplet is that between H-4″ and H-6″ of 1.7 Hz. The H-6″ proton resonance is the most deshielded of these resonances at δH 7.59 appearing as a triplet of doublets with J = 7.9 and 1.7 Hz. The triplet is probably caused by the meta F atom at C-2″ and the ortho proton of H-5″ having the same coupling constant. The carbon resonances of the aromatic ring of 3a with fluorine substituted at the 2″ position result in all the carbon resonances of the ring being doublets with the largest coupling occurring on the carbon directly bonded to fluorine (C-2″) at δC 161.8 (J = 252.6 Hz), followed by ortho coupling of 21.7 Hz for C-3″ at δC 116.3. The C-1″, the other ortho carbon, has a much smaller coupling constant of 11.6 Hz at δC 122.2. It is further noticed that while C-4″ at δC 132.2 meta to the fluorine has a coupling constant of 14.2 Hz, the same is not observed for the other carbon meta to the fluorine (C-6″ at δC 129.4) that only has a coupling constant of 2.7 Hz, probably because of interference from the moiety attached to C-1″. The C-5″ carbon resonance, para to the fluorine atom, has a small coupling constant of 3.6 Hz as expected at δC 124.6.
Table 5. (Continued) H-3′
H-4′
H-5′
H-6′
H-α
H-β
OCH3/OCH2O
7.11 (ddd, 9.2, 8.2, 2.4) — 7.28 (t, 8.8) — 7.10 (t, 8.6) 7.41 m 7.40 (d, 8.0) 6.92 (d, 8.7) — —
7.32 m 7.06 (t, 8.0) — 6.81 (tt, 8.7, 2.4) — 7.39 m 7.39 m — — —
7.17 (t, 7.9) 7.36 m 7.28 (t, 8.8) — 7.10 (t, 8.6) 7.41 m 7.40 (d, 8.0) 6.92 (d, 8.7) 7.02 (d, 8.3) 6.81 (d, 8.1)
7.59 (td, 7.6, 1.5) 7.36 m 7.79 m 7.08 (dd, 8.1, 1.9) 7.56 (dd, 8.6, 5.6) 7.58 (dd, 8.1, 1.5) 7.56 (d, 8.0) 7.48 (d, 8.7) 7.27 (dd, 8.3, 1.7) 7.05 (d, 8.1)
6.87 (d, 16.2) 6.77 (d, 16.0) 7.16 (d, 16.2) 6.76 (d, 16.0) 6.67 (d, 16.0) 6.76 (d, 16.0) 6.77 (d, 16.1) 6.64 (d, 16.0) 7.11 (d, 16.0) 6.59 (d, 16.1)
7.72 (d, 16.2) 7.55 (d, 16.0) 7.70 (d, 16.2) 7.49 (d, 16.0) 7.53 (d, 16.0) 7.59 (d, 16.0) 7.60 (d, 16.1) 7.55 (d, 16.0) 7.65 (d, 16.0) 7.50 (d, 16.1)
— — — — — — — 3.84 s 3.80 s, 3.83 s 6.01
527
Magn. Reson. Chem. 2014, 52, 521–529
Copyright © 2014 John Wiley & Sons, Ltd.
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M. Momin, D. Ramjugernath and N. A. Koorbanally Table 6.
13
C NMR chemical shifts (δ in ppm) for compounds 5a–j (J is given in Hz)
C-2
C-3
C-4
C-5
C-6
C-7
C-8
C-9
C-10
5a 5b 5ca 5d
161.5 161.2 161.7 160.6
111.2 111.2 110.1 111.7
178.5 178.5 177.1 178.4
125.7 125.8 124.8 125.8
125.1 125.1 125.3 125.3
133.9 133.9 134.4 134.0
117.9 117.9 118.2 117.9
156.0 156.0 155.4 156.0
124.1 124.1 123.4 124.1
5e 5f 5g 5h 5i 5j
161.8 162.0 162.0 162.3 162.3 162.0
110.6 110.6 109.9 109.9 109.2 110.2
177.4 177.5 177.6 (d, 2.3) 178.5 177.0 178.5
128.2 (d, 10.5) 128.2 (d, 10.6) 110.7 (d, 23.4) 125.7 124.7 125.7
113.7 (d, 22.5) 113.7 (d, 22.6) 159.5 (d, 245.1) 124.9 125.2 125.0
167.1 (d, 210.1) 164.5 (d, 252.6) 121.8 (d, 25.1) 133.6 134.2 133.7
104.6 (d, 25.5) 104.6 (d, 25.4) 119.9 (d, 7.9) 117.9 118.1 117.8
156.9 157.1 (d, 13.2) 152.2 156.0 155.4 156.0
121.0 121.0 125.5 (d, 7.1) 124.2 123.4 123.3
a
In DMSO
19
Table 7. F NMR chemical shifts (δ in ppm) of compounds 3a–g, 4a–g, and 5a–g No. 3 a b c d e f g
113.57 112.27 108.54 108.75 103.81, 103.17 103.91 115.35
4 114.18 112.32 109.55 109.10 100.64, 109.57 100.72 124.33
5 115.39 108.99 110.72 109.31 102.96, 109.89 103.04 115.51
528
The same trends were observed for the 3″-fluorinated derivative 3b, but now, in the 13C NMR spectrum, all the usual coupling constants were observed for the ortho carbon resonances, C-2″ and C-4″ at δC 114.6 (J = 21.9 Hz) and 117.7 (J = 21.3 Hz), the meta carbon resonances, C-1″ and C-5″ at δC 136.3 (J = 7.9 Hz) and 130.6 (J = 8.0 Hz), and the para carbon resonance of C-6″ at δC 124.4 (J = 2.9 Hz). In the para-fluoro-substituted compounds, 3c and 3e, instead of the usual pair of doublets with a coupling constant of approximately 8 Hz being observed as for the para methoxy compound 3h, the splitting pattern is a bit more complex because of coupling to fluorine. The H-3″ and H-5″ protons are equivalent, and their resonance appears as a triplet at δH 7.09 (J = 8.6 Hz). This is because of similar coupling constants between H-2″/6″ and H-3″/5″, and H-3″/5″ and the fluorine atom. The H-2″ and H-6″ protons are also equivalent with their resonance appearing as a doublet of doublets because of a smaller coupling constant between H-2″/6″ and the fluorine atom and its occurrence at δH 7.58 (J = 8.6 and 5.4 Hz). The 13C NMR spectrum of 3c shows the fluorinated carbon resonance as a doublet at δC 164.3 (J = 250.7 Hz) and a doublet resonance for C-3″/5″ at δC 116.2 (J = 21.9 Hz) and C-2″/6″ at δC 130.4 (J = 8.37 Hz). The C-1″ resonance, also a doublet, overlaps with the C-2″/6″ resonance at δC 130.3 with a coupling constant of J = 3.6 Hz. This resonance can be seen more clearly in 3e at δC 130.2 (J = 3.4 Hz). For the 3″,5″-difluorinated compound 3d, the H-4″ resonance was split into a triplet of triplets with J = 8.7 and 2.3 Hz. This was because of H-4″ coupling to F (J = 8.7 Hz) and H-4″ coupling to the meta protons H-2″/6″ (J = 2.3 Hz). The H-2″ and H-6″ protons are equivalent and appear as a double doublet at δH 7.08 with J = 7.9 Hz for the
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H–F coupling and 1.9 Hz for the meta coupling with H-4″. The slight variation in J4″,2″/6″ is because of the coalescing and broadening of peaks for H-2″/6″; however, coupling between these two resonances was verified in the COSY spectrum. In the 13C NMR spectrum, the C-3″ and C-5″ resonances are equivalent and split into a double doublet at δC 163.24 because of coupling between the fluorine that it is attached to (J = 248.3 Hz) and the fluorine meta to it (J = 12.8 Hz). The C-2″ and C-6″ resonances are also equivalent and appear as a double doublet at δC 111.0 (J = 18.8 and 7.2 Hz) arising from coupling to the fluorine ortho to it and the fluorine para to it, respectively. The C-4″, C-1″, and C-β resonances appear as triplets at δC 105.9 (J = 25.4 Hz), δC 137.3 (J = 9.4 Hz), and δC 144.5 (J = 2.8 Hz), respectively, because these carbon atoms are in the middle of the two fluorine atoms. The substituted 3-hydroxy-2,4-pentadien-1-one intermediates (4) In these intermediates, there is a noticeable shift from the acetophenone methyl group at δH 2.59 in 3a to an olefinic resonance (H-2) at δH 6.32 in 4a. This is indicative that the cinnamoyloxyacetophenones (3) had converted to the 3-hydroxy2,4-pentadien-1-ones (4). With regard to the α,β-unsaturated double bond, both the resonances are shielded by 0.3 Hz for the β resonance in 3a to H-5 in 4a and 0.1 Hz for the α resonance in 3a to H-4 in 4a. This is because the double bond is now conjugated with the newly formed keto–enol moiety, shielding H-4 and H-5 more than the H-α and H-β protons in 3. The trans configuration of the double bond is retained as evidenced by the large coupling constant of 16.0 Hz. The H-3′ to H-6′ resonances are also more shielded by 0.22, 0.11, 0.45, and 0.16 Hz for H-3′, H-4′, H-5′ and H-6′, respectively, from 3a to 4a. This is probably because of greater electron donation by the hydroxy group as opposed to the ester group in 3a. A further characteristic trait of the 1H NMR spectra of the intermediates 4 is the two hydroxyl resonances occurring at δH 14.55 (3-OH) and 12.18 (2′-OH). Both these hydroxy groups experience hydrogen bonding resulting in these characteristic resonances, 3-OH with H-5 and 2′-OH with H-2. In the 13C NMR spectrum of 4a, the appearance of the alkene carbon resonance C-2 at δC 97.4 and an enol carbon resonance C-3 at δC 174.0 instead of the methyl carbon resonance at δC 29.8 and the ester carbonyl resonance at δC 165.1 in 3a is further evidence that 3a had converted to 4a. Because of the ester group being converted to a hydroxy group from 3a to 4a, the ortho and
Copyright © 2014 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2014, 52, 521–529
Structure elucidation of a series of fluoro-2-styrylchromones and methoxy-2-styrylchromones Table 6. (Continued) C-α
C-β
C-1′
122.7 (d, 6.5) 121.7 120.4 123.0
129.5 (d, 3.1) 135.6 (d, 2.8) 135.4 134.2 (t, 3.0)
123.1 (d, 11.7) 137.3 (d, 7.8) 131.6 (d, 3.2) 138.3 (t, 11.2)
119.7 119.9 120.0 117.9 118.0 118.4
135.8 137.2 137.4 136.7 136.9 136.7
131.2 (d, 3.6) 134.9 134.9 131.0 127.8 129.5
C-2′ 161.2 (d, 253.3) 116.7 (d, 21.6) 130.0 (d, 8.1) 110.3 (dd, 18.5, 7.2) 129.5 (d, 8.2) 127.7 127.7 129.3 109.9 106.2
C-3′ 116.2 (d, 21.8) 163.2 (d, 245.5) 116.0 (d, 24.3) 163.4 (dd, 247.8, 12.9) 116.2 (d, 21.9) 129.1 129.1 114.5 149.0 149.3
para positions of ring A are now more shielded by electron donation by resonance. As such, C-1′ shifts from δ 131.3 in 3a to δ 119.0 in 4a, C-3′ from δ 123.8 to δ 118.8, and C-5′ from δ 126.1 to δ 119.1. The C-2′ resonance that is bonded to the hydroxy group, however, is now more deshielded in the Ar–OH range at δC 162.7 in 4a from the Ar–ester resonance at δC 149.1 in 3a. The resonances on the aromatic ring adjacent to the Δ4 double bond remain relatively unchanged, and the 1H NMR spectra of 4b–4j contain the same differences as that pointed out between 3a and 4a.
C-4′ 131.3 (d, 8.7) 114.0 (d, 22.0) 162.9 (d, 240.6) 105.0 (t, 25.4) 165.0 (d, 251.6) 130.0 130.0 161.1 150.5 148.5
C-5′ 124.6 (d, 3.6) 130.5 (d, 8.3) 116.0 (d, 24.3) 163.4 (dd, 247.8, 12.9) 116.2 (d, 21.9) 129.1 129.1 114.5 111.7 108.7
C-6′ 128.4 (d, 2.7) 123.6 (d, 2.7) 130.0 (d, 8.1) 110.3 (dd, 18.5, 7.2) 129.5 (d, 8.2) 127.7 127.7 129.3 122.3 123.9
OCH3/OCH2O
55.4 55.5 101.6
in 4a at δC 174.0, 97.4, and 196.5, respectively. These three resonances can also be used as evidence that the 2-SC derivatives were prepared from the 3-hydroxy-2,4-pentadienone intermediates. All structures were confirmed, and assignments of the resonances of each of the proton and carbon atoms were made with the aid of HSQC, HMBC, and NOESY data. Selected HMBC correlations for 5a are shown in Fig. 2 in the succeeding texts, and the 1H NMR spectrum of 5a is shown in Fig. 3 depicting the splitting patterns and chemical shifts of the proton resonances. Tables 1–7 contain the 1H, 13C, and 19F NMR data for all the prepared compounds. The spectra were acquired in CDCl3 unless otherwise stated.
The substituted 2-styrylchromones
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Acknowledgements This research was supported by grants from the National Research Foundation, South Africa, and was supported by the South African Research Chairs Initiative of the Department of Science and Technology.
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In the substituted 2-SCs 5, the splitting patterns and chemical shifts of the phenyl ring in the 1H and 13C NMR spectra did not change much from that of the intermediates 3 and 4, and therefore, a discussion of this will not be repeated. There was also not much change in the C-α and C-β carbon resonances as well as the H-β resonance. However, in the formation of the chromone ring, the H-α proton experiences a slightly more deshielded shift to δH 6.87 in 5a, approximately 0.2 Hz from the corresponding resonance in 4a. All the proton resonances in the chromone ring are also deshielded in forming the chromone ring from the 3-hydroxy2,4-pentadien-1-one intermediates 4. The most characteristic and noticeable of these resonances is that of H-5 occurring at δH 8.17 in 5a from 7.69 in 4a, with the H-6, H-7, and H-8 proton resonances also being significantly deshielded by between 0.23 and 0.56 Hz, at δH 7.37, 7.66, and 7.53, respectively, in 5a from δH 6.88, 7.43, and 6.97 in 4a. These deshielded shifts must occur because of delocalization of the pi electrons within the chromone skeleton, thus reducing the electron density at these specific protons. The difference in chemical shift of the H-5 proton is also because of hydrogen bonding with the C-4 carbonyl group. This is now possible because the carbonyl group is locked into position by formation of the chromone ring. With regard to the 13C NMR spectra, there is not much change in both the C-α and C-β resonances or the aromatic resonances on the chromone ring with the exception of C-6, which is para to the oxygen substituent forming the chromone ring. This shift is slightly deshielded by approximately 7 ppm at δC 125.1 in 5a from 119.1 in 4a. The most notable shifts in the 13C NMR spectrum are that of C-2, C-3, and C-4, the carbon atoms involved in forming the chromone ring from the 3-hydroxy-2,4-pentadien-1-one. In 5a, these carbon resonances occur at δC 161.5, 111.2, and 178.5 for C-2, C-3, and C-4 as opposed to their corresponding resonances
