Synthesis and structure elucidation of a series of pyranochromene chalcones and flavanones using 1D and 2D NMR spectroscopy and X-ray crystallography

Article abstract of DOI:10.1002/mrc.4062

A series of novel pyranochromene chalcones and corresponding flavanones were synthesized. This is the first report on the confirmation of the absolute configuration of chromene-based flavanones using X-ray crystallography. These compounds were characterized by 2D NMR spectroscopy, and their assignments are reported herein. The 3D structure of the chalcone 3b and flavanone 4g was determined by X-ray crystallography, and the structure of the flavanone was confirmed to be in the S configuration at C-2. Copyright

Full text of DOI:10.1002/mrc.4062

Research article
Received: 24 October 2013
Revised: 21 February 2014
Accepted: 24 February 2014
Published online in Wiley Online Library: 13 March 2014
(wileyonlinelibrary.com) DOI 10.1002/mrc.4062
Synthesis and structure elucidation of a series
of pyranochromene chalcones and flavanones
using 1D and 2D NMR spectroscopy and X-ray
crystallography
Sunayna S. Pawar and Neil A. Koorbanally*
A series of novel pyranochromene chalcones and corresponding flavanones were synthesized. This is the first report on the
confirmation of the absolute configuration of chromene-based flavanones using X-ray crystallography. These compounds
were characterized by 2D NMR spectroscopy, and their assignments are reported herein. The 3D structure of the chalcone
3b and flavanone 4g was determined by X-ray crystallography, and the structure of the flavanone was confirmed to be in
the S configuration at C-2. Copyright © 2014 John Wiley & Sons, Ltd.
1
Keywords: NMR; H; 13C; X-ray crystallography; pyranochromene; chalcones; flavanones
Herein, we report the NMR elucidation of these fluorinated
pyranochromene chalcones and flavanones, which is slightly
Introduction
Chalcones and flavanones form a large and important group of
naturally occurring secondary metabolites.[1] Chalcones are im-
portant intermediates for the synthesis of biologically active com-
pounds such as flavone, flavonol, flavanone, isoflavone and their
derivatives.[2] Besides having a physiological role in plants, flavo-
noids have also been reported to have a wide variety of biologi-
cal activities, including anti-inflammatory, antiviral, antiprotozoal,
antioxidant, cardiovascular and anticarcinogenic properties.[2]
A five-membered prenyl moiety on a benzene ring cyclized
with an oxygen atom on an adjacent position leads to a
benzopyran or chromene molecule with a second such cycliza-
tion leading to a pyranochromene such as the naturally occurring
octandrenolone,[3,4] O-methyloctandrenolone,[4,5] trans-3‴,4‴-
dihydro-3‴,4‴-dihydroxy-O-methyloctandrenolone,[4] trans-3″,4″-
dihydro-3″,4″-dihydroxy-O-methyloctandrenolone,[4] flemiculosin,[6]
laxichalcone,[7] 3-deoxy-MS-II[3,8,9] and MS-II.[3,8] The flavanone (4a)
3-deoxy–MS-II (Scheme 1), which incorporates pyranochromene
moieties, was isolated from the methanolic extracts of the bark and
leaf of Mundulea chapelieri and exhibited activity against a human
ovarian cancer cell line.[8] Shortly afterward, its synthesis was
reported.[3] The synthesis of six chalcones with an octandrenolone
moiety was also reported.[10] Several other pyranochromene
chalcones and flavonoids were isolated from Mundulea suberosa
and Mundulea sericea and have exhibited interesting biological
activities including antimicrobial and ornithine decarboxylase
activity.[8,11–17] A pyranochromene chalcone, (-)-rubranine with
prenyl groups on the pyran rings, was also isolated from Aniba
rosaeodora.[18] Two series of prenylated chromenochalcones were
also synthesized and tested for their antileishmanial and antimalar-
ial activity where several compounds showed good activity.[19,20]
In our ongoing study on synthesizing fluorinated pharmaceuti-
cals, we have prepared several fluorinated chalcones and
flavanones with the pyranochromene moiety.
more complicated than the oxygenated or chlorinated molecules
because of the fluorine atom being NMR active and coupling
with both hydrogen and carbon. We used X-ray crystallography
and NMR studies to provide a full structural elucidation of these
novel pyranochromene chalcones and flavanones.
Experimental
Reagents and chemicals used in this study were purchased from
Sigma-Aldrich via Capital Lab, South Africa and were reagent
grade. All organic solvents were redistilled and dried according
to standard procedures. Optical rotations were recorded using a
PerkinElmer™ Model 341 Polarimeter with a 10-cm flow tube.
Melting points were measured using a Stuart scientific melting
point apparatus SMP3. IR spectra were recorded on a PerkinElmer
Spectrum 100 FT-IR spectrometer with universal attenuated total
reflectance sampling accessory. UV spectra were obtained on a
Varian Cary UV-VIS spectrophotometer in chloroform. High-
resolution mass data were obtained using a Bruker microTOF-Q
II ESI instrument operating at ambient temperatures, with a
sample concentration of approximately 1 ppm. Thin-layer chroma-
tography was performed using Merck Kieselgel 60F254 plates. Crude
compounds were purified with column chromatography using
silica gel (60–120 mesh) as the stationary phase and varying
combinations of solvents depending on the sample to be purified.
*
Correspondence to: Neil A. Koorbanally, School of Chemistry and Physics,
University of KwaZulu-Natal, Private Bag X54001, Durban, 4000, South Africa.
E-mail: Koorbanally@ukzn.ac.za; Neil.Koorbanally@gmail.com
School of Chemistry and Physics, University of KwaZulu-Natal, Private Bag
X54001, Durban, 4000, South Africa
Magn. Reson. Chem. 2014, 52, 279–288
Copyright © 2014 John Wiley & Sons, Ltd.

S. S. Pawar and N. A. Koorbanally
Scheme 1. Synthetic scheme for the synthesis of pyranochromene flavanones 4a–h. (i) 3-methyl-2-butenal, pyridine, 110 °C, reflux; (ii) substituted
benzaldehydes, KOH, EtOH/H2O, rt; and (iii) NaOAc, EtOH, 80 °C, reflux.
The 1H and 13C NMR spectra were recorded at 298 K with 5- to
10-mg samples dissolved in 0.5 ml of CDCl3 in 5-mm NMR tubes
using a Bruker AvanceIII 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). The digital digitizer resolution was set at 22
for both the 1H and 13C NMR experiments. Chemical shifts (δ)
are reported in ppm and coupling constants (J) in Hz. The 1H
and 13C chemical shifts of the deuterated solvent were 7.24
and 77.0, respectively, referenced to the internal standard,
TMS. For the 19F NMR spectra, the chemical shift of
trifluorotoluene (0.05% in CDCl3) was referenced at À62.73.
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 of 8.40 μs. For the 19F NMR spectra, the spectral width
was 89 285.71 Hz using131 K data points, and the 90° pulse
duration was 12.50 μs. For the 2D experiments including COSY,
NOESY, HSQC and HMBC, all data were acquired with 4 K × 128
data points (t2 × t1). The mixing time for the NOESY experiment
was 0.3 s, and the long range coupling time for the HMBC
experiment was 65 ms. All data were analyzed using Bruker
TopSpin 2.1 (2008) software.
1-(5-Hydroxy-2,2,8,8-tetramethyl-2H,8H-pyrano[2,3-f]chromen-
6-yl)-3-phenylpropenone (3a)
Yield 90%; mp 99–100 °C. IR (neat) υmax = 2970, 2928, 1631, 1582,
1546 and 1132 cmÀ1
.
3-(2-Fluorophenyl)-1-(5-hydroxy-2,2,8,8-tetramethyl-2H,8H-
pyrano[2,3-f]chromen-6-yl)-propenone (3b)
Yield 64%; mp 110–111 °C. 19F NMR (376 MHz, CDCl3) δ À112.95;
IR (neat) υmax = 2963, 2923, 1627, 1583, 1539, 1339, 1181, 1137
and 1109 cmÀ1; HRMS m/z 429.1476 [M + Na]+ (calcd. for
C25H23O4FNa 429.1478).
3-(3-Fluorophenyl)-1-(5-hydroxy-2,2,8,8-tetramethyl-2H,8H-
pyrano[2,3-f]chromen-6-yl)-propenone (3c)
Yield 90%; mp 150–151 °C. 19F NMR (376 MHz, CDCl3) δ À112.63;
IR (neat)
υmax = 2971, 2928, 1630, 1584, 1451, 1135 and
1112 cmÀ1; HRMS m/z 429.1472 [M + Na]+ (calcd. for C25H23O4FNa
429.1478).
3-(4-Fluorophenyl)-1-(5-hydroxy-2,2,8,8-tetramethyl-2H,8H-
pyrano[2,3-f]chromen-6-yl)-propenone (3d)
Yield 90%; mp 143–144 °C. 19F NMR (376 MHz, CDCl3) δ À109.92;
IR (neat)
υmax = 2971, 2928, 1631, 1585, 1468, 1135 and
1113 cmÀ1; HRMS m/z 429.1477 [M + Na]+ (calcd. for C25H23O4FNa
429.1478).
Materials
3-(2,4-Difluorophenyl)-1-(5-hydroxy-2,2,8,8-tetramethyl-2H,8H-
pyrano[2,3-f] chromen-6-yl)-propenone (3e)
The prenylated flavanones (4a–h) were prepared in rather
moderate overall yields (30–55%) in a three-step reaction
(Scheme 1) where 2′,4′,6′-trihydroxyacetophenone was prenylated
at the 2′ and 4′ positions with 3-methyl-2-butenal in basic
conditions under reflux resulting in the dichromene acetophenone
intermediate 2,[21] which then underwent a Claisen–Schmidt
condensation reaction with various substituted benzaldehydes to
produce chalcones 3a–h in good yields (60–90%) before being
cyclized to their corresponding flavanones 4a–h.
Yield 74%; mp 154–155 °C. 19F NMR (376 MHz, CDCl3) δ À106.57
and À108.54; IR (neat) υmax = 2977, 2931, 1630, 1612, 1582 and
1136 cmÀ1; HRMS m/z 447.1393 [M+ Na]+ (calcd. for C25H22O4F2Na
447.1384).
1-(5-Hydroxy-2,2,8,8-tetramethyl-2H,8H-pyrano[2,3-f]chromen-
6-yl)-3-(3-methoxyphenyl)-propenone (3f)
For the synthesis of octandrenolone (1-(5-hydroxy-2,2,8,8-
tetramethyl-2H,8H-pyrano[2,3-f]chromen-6-yl)ethanone) (2), the
method in Pawar et al.[21] was followed, and the NMR data were
compared with that of an authentic sample prepared earlier.[21]
The pyranochromene chalcones 3a–3h were synthesized
Yield 77%; mp 95–96 °C. IR (neat) υmax = 2975, 2924, 1640, 1625,
1586, 1534, 1465, 1153, 1131 and 1112 cmÀ1; HRMS m/z
441.1671 [M + Na]+ (calcd. for C26H26O5Na 441.1678).
1-(5-Hydroxy-2,2,8,8-tetramethyl-2H,8H-pyrano[2,3-f]chromen-
6-yl)-3-(4-methoxyphenyl)-propenone (3g)
according to the methods reported earlier in Pawar et al.[22]
,
and the compounds were purified by flash column chromatogra-
phy to produce pure brown solids. For the 1H and 13C NMR data,
refer to Tables 1 and 2.
Yield 85%; mp 125–126 °C. IR (neat) υmax = 2977, 2968, 1602,
1578, 1532, 1509, 1145, 1131 and 1110 cmÀ1
.
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Copyright © 2014 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2014, 52, 279–288

Structural elucidation of pyranochromene chalcones
3-(2-Fluoro-3-methoxyphenyl)-1-(5-hydroxy-2,2,8,8-tetramethyl-
2H,8H-pyrano[2,3-f]chromen-6-yl)-propenone (3h)
Yield 65%; mp 122–123 °C. 19F NMR (376 MHz, CDCl3) δ À136.22;
IR (neat) υmax = 2968, 2926, 1632, 1605, 1581, 1276, 1151, 1132
and 1113 cmÀ1; HRMS m/z 459.1579 [M + Na]+ (calcd. for
C26H25O5FNa 459.1584).
General Procedure for the Synthesis of
Pyranochromene Flavanones 4a–h
To a solution of sodium acetate (188 mg, 3.0 mmol) in ethanol
(10 ml), pyranochromene chalcones 3a–h (0.3 mmol) were added
at room temperature. The reaction mixture was refluxed for 48 h
at 80 °C. The solvent was distilled off under reduced pressure, and
the residue was dissolved in water (20 ml). After acidifying with
2 M HCl (20 ml), the mixture was extracted with ethyl acetate
(3 × 30 ml), washed with water and dried over anhydrous MgSO4.
Removal of the solvent followed by flash column chromatogra-
phy on silica gel afforded the pure pyranochromene flavanones
1
as yellow solids. For the H and 13C NMR data, refer to Tables 3
and 4.
6,6,10,10-Tetramethyl-2-phenyl-2,3-dihydro-6H,10H-dipyrano
[2,3-f;2′,3′-h]chromen-4-one (4a)
Yield 55%; mp 144–145 °C. IR (neat) υmax = 2923, 2853, 1729,
1677, 1637, 1571, 1434, 1363, 1136 and 1116 cmÀ1
.
2-(2-Fluorophenyl)-6,6,10,10-tetramethyl-2,3-dihydro-6H,10H-
dipyrano[2,3-f;2′,3′-h]chromen-4-one (4b)
Yield 38%; mp 148–150 °C. 19F NMR (376 MHz, CDCl3) δ À118.38;
IR (neat) υmax = 2966, 2922, 1677, 1637, 1571, 1433, 1364, 1135
and 1117 cmÀ1; HRMS m/z 429.1476 [M + Na]+ (calcd. for
C25H23O4FNa 429.1478).
2-(3-Fluorophenyl)-6,6,10,10-tetramethyl-2,3-dihydro-6H,10H-
dipyrano[2,3-f;2′,3′-h]chromen-4-one (4c)
Yield 46%; mp 92–93 °C. 19F NMR (376 MHz, CDCl3) δ À112.06; IR
(neat) υmax = 2968, 2923, 1678, 1643, 1571, 1162, 1136 and
1118 cmÀ1; HRMS m/z 429.1471 [M + Na]+ (calcd. for C25H23O4FNa
429.1478).
2-(4-Fluorophenyl)-6,6,10,10-tetramethyl-2,3-dihydro-6H,10H-
dipyrano[2,3-f;2′,3′-h]chromen-4-one (4d)
Yield 36%; mp 112–113 °C. 19F NMR (376 MHz, CDCl3) δ À113.29;
IR (neat) υmax = 2968, 2924, 2854, 1681, 1638, 1572, 1512, 1462,
1436, 1132 and 1116 cmÀ1; HRMS m/z 429.1475 [M + Na]+ (calcd.
for C25H23O4FNa 429.1478).
2-(2,4-Difluorophenyl)-6,6,10,10-tetramethyl-2,3-dihydro-
6H,10H-dipyrano[2,3-f;2′,3′-h]chromen-4-one (4e)
Yield 31%; mp 158–159 °C. 19F NMR (376 MHz, CDCl3) δ À109.62
and À114.22; IR (neat) υmax = 2978, 2925, 1679, 1641, 1590,
1570, 1132 and 1113 cmÀ1; HRMS m/z 447.1384 [M + Na]+ (calcd.
for C25H22O4F2Na 447.1384).
Magn. Reson. Chem. 2014, 52, 279–288
Copyright © 2014 John Wiley & Sons, Ltd.
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S. S. Pawar and N. A. Koorbanally
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Copyright © 2014 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2014, 52, 279–288

Structural elucidation of pyranochromene chalcones
Magn. Reson. Chem. 2014, 52, 279–288
Copyright © 2014 John Wiley & Sons, Ltd.
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S. S. Pawar and N. A. Koorbanally
Table 4. 13C NMR shifts of pyranochromene flavanones 4a–h
δ of1H (J, Hz)
No.
4a
4b
4c
4d
4e
4f*
4g
4h
2
79.1
46.1
73.5 (d, 3.1)
45.0
78.3 (d, 1.3)
46.0
78.5
46.0
73.1 (d, 2.6)
79.0
46.2
78.9
45.9
73.4 (d, 4.28)
44.9
3
44.9
4
188.9
154.5
102.5
156.1
104.8
157.6
105.7
139.3
126.1
128.9
128.6
128.8
126.1
116.4
126.4
78.1
188.5
188.3
188.6
154.4
102.5
156.1
104.8
157.4
105.7
188.3
188.9
154.5
102.6
156.1
104.9
157.6
105.8
140.9
118.4
160.1
113.9
130.0
111.9
116.5
126.5
78.1
189.1
154.4
102.5
156.1
104.7
157.7
105.7
131.3
127.7
114.2
159.9
114.2
127.7
116.5
126.3
78.0
188.6
5
154.5
154.5
155.4
154.5
6
102.6
102.5
102.5
102.6
7
156.2
156.1
156.2
156.2
8
104.9
104.9
105.0
104.9
9
157.5
157.2
157.3
157.5
10
1′
105.7
105.6
105.6
105.7
126.7 (d, 12.9)
159.8 (d, 246.2)
115.8 (d, 21.1)
130.1 (d, 8.2)
124.6 (d, 3.6)
127.4 (d, 3.7)
116.3
141.8 (d, 7.2)
113.1 (d, 22.5)
163.1 (d, 245.0)
115.5 (d, 21.0)
130.5 (d, 8.1)
121.6 (d, 2.9)
116.3
135.1 (d, 3.3)
127.9 (d, 8.2)
115.8 (d, 21.6)
162.8 (d, 245.7)
115.8 (d, 21.6)
127.9 (d, 8.2)
116.3
122.7 (dd, 13.1, 3.8)
127.5 (d, 10.2)
149.6 (d, 246.4)
147.9 (d, 10.2)
124.5 (d, 4.9)
113.4 (d, 1.6)
118.3 (d, 2.6)
116.4
2′
163.0 (dd, 236.3, 12.0)
3′
104.3 (t, 25.3)
4′
160.0 (dd, 237.0, 12.0)
5′
111.8 (dd, 21.2, 3.6)
6′
128.5 (dd, 9.7, 5.3)
1″#
2″
3″
4″†
5″†
1‴#
2‴
3‴
4‴†
5‴†
OCH3
116.2
126.6
78.1
28.7
28.4
115.9
126.9
78.0
28.3
28.1
—
126.9
126.9
126.5
126.5
78.1
78.1
78.1
78.1
28.6
28.6
28.6
28.6
28.7
28.6
28.7
28.4
28.4
28.4
28.4
28.4
28.4
28.4
116.0
126.8
77.9
116.0
116.0
116.0
116.0
126.8
77.9
116.0
126.7
77.9
116.0
126.5
126.6
126.8
126.9
78.0
78.0
77.9
77.9
28.3
28.3
28.3
28.3
28.3
28.3
28.3
28.1
—
28.1
28.0
28.1
28.1
28.0
28.1
—
—
—
55.4
55.5
56.5
* NMR frequency at 600 MHz; # and † indicate resonances that can be interchanged.
2-(3-Methoxyphenyl)-6,6,10,10-tetramethyl-2,3-dihydro-6H,10H-
dipyrano[2,3-f;2′,3′-h]chromen-4-one (4f)
Bruker Smart APEX II diffractometer with Mo Kα radiation
(λ = 0.71073 Å). The diffractometer to crystal distance was set at
4.00 cm. The initial cell matrix was obtained from three series of
scans at different starting angles. Each series consisted of 12
frames collected at intervals of 0.5° in a 6° range with the expo-
sure time of 10 s per frame. The reflections were successfully
indexed by an automated indexing routine built in the APEX II
program suite. The final cell constants were calculated from a
set of 6460 strong reflections from the actual data collection.
Data collection method involved ω scans of width 0.5°. Data
reduction was carried out using the program System Administra-
tor’s Integrated Network Tool+. The structure was solved by
direct methods using SHELXS and refined. Non-H atoms were
first refined isotropically and then by anisotropic refinement with
full-matrix least-squares calculations based on F2 using SHELXS.
All H atoms were positioned geometrically and allowed to ride
on their respective parent atoms. All H atoms were refined
isotropically. The absorption correction was based on fitting a
function to the empirical transmission surface as sampled by
multiple equivalent measurements. The final least-squares
refinement of 286 parameters against 5126 data resulted in re-
siduals R (based on F2 for I ≥ 2σ) and wR (based on F2 for all data)
of 0.0404 and 0.1035, respectively. The final difference Fourier
map was featureless. The programs Olex-2 and Ortep-3 were
used within the WinGX software package to prepare artwork
representation. The molecular diagram is drawn with 50% prob-
ability ellipsoids.
Yield 40%; mp 80–81 °C. IR (neat) υmax = 2969, 2923, 2853, 1678,
1638, 1570, 1431, 1361, 1134 and 1115 cmÀ1; HRMS m/z 441.1672
[M+ Na]+ (calcd. for C26H26O5Na 441.1678).
2-(4-Methoxyphenyl)-6,6,10,10-tetramethyl-2,3-dihydro-6H,10H-
dipyrano[2,3-f;2′,3′-h]chromen-4-one (4g)
Yield 46%; mp 141–142 °C. IR (neat) υmax = 2975, 2923, 2853,
1684, 1634, 1613. 1592, 1571, 1245, 1136 and 1115 cmÀ1; HRMS
m/z 441.1674 [M + Na]+ (calcd. for C26H26O5Na 441.1678).
2-(2-Fluoro-3-methoxyphenyl)-6,6,10,10-tetramethyl-2,3-
dihydro-6H,10H-dipyrano[2,3-f;2′,3′-h]chromen-4-one (4h)
Yield 54%; mp 100–101 °C. 19F NMR (376 MHz, CDCl3) δ À140.91; IR
(neat) υmax = 2969, 2926, 1681, 1634, 1590, 1572, 1135, 1115 and
1088 cmÀ1; HRMS m/z 459.1576 [M + Na]+ (calcd. for C26H25O5FNa
459.1584).
Single Crystal X-ray Diffraction Analysis
A cube-shaped single crystal was selected and glued onto the tip
of a glass fiber and mounted in a stream of cold nitrogen at 100
(1) K and centered in the X-ray beam using a video camera. The
crystal evaluation and data collection were performed on a
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Structural elucidation of pyranochromene chalcones
the double bond and the carbonyl group, C-8 (δC 130.5) is
more shielded than C-7 (δC 135.4) and is therefore assigned
further upfield than C-7. This is, however, not the case for
H-7 and H-8, and HSQC correlations show that H-8 appears
more deshielded than H-7. A 3J correlation in the HMBC
spectrum can also be observed between H-7 and C-2 and C-6,
verifying the assignment of H-7. The H-8 resonance is more
deshielded because of the through space deshielding effect of
the oxygen on the nearby pyran ring.
Results and Discussion
The full characterization (1H and 13C NMR assignments) of the
pyranochromene chalcones 3a–h and flavanones 4a–h is
presented in Tables 1–4, and the H spectra of a representative
1
fluorinated chalcone and fluorinated flavanone are presented in
Figs 1 and 2. The spectra of these compounds were well resolved.
With the aid of HSQC, HMBC, COSY and NOESY data as well as
multiplicity patterns, the unambiguous chemical shift assign-
ments were made.
For the pyranochromene chalcones, typical H and 13C NMR
1
resonances can be observed for the pyran rings and the α,β-
unsaturated ketone moiety. Taking the 2-fluoro derivative
(3b) as an example, the double bond of the α,β-unsaturated
ketone moiety occurs as a distinct pair of doublets at δ 8.23
(H-7) and 7.83 (H-8) with a coupling constant of 15.9 Hz,
typical of trans olefinic protons (Fig. 1). The carbonyl
resonance (C-9) is distinctly separated from the other carbon
resonances at δ 193.1 and shows HMBC correlations to both
H-7 and H-8 (Fig. 3), confirming the assignments of the α,β-
unsaturated ketone moiety. Because of conjugation between
Figure 3. HMBC correlations of compound 3b, the 2-fluoropyranochromene
chalcone.
Figure 1. 1H NMR spectrum of 2′-fluoropyranochromene chalcone (3b).
Figure 2. 1H NMR spectrum of 2′-fluoropyranochromene flavanone (4b).
Magn. Reson. Chem. 2014, 52, 279–288
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S. S. Pawar and N. A. Koorbanally
There are four resonances between 7.10 and 7.60. These are
attributed to the aromatic proton resonances of the fluorinated
aromatic ring B. C-7 shows an HMBC correlation to the
doublet of triplets (dt) at δH 7.57 (H-6). This doublet of triplets
arises from the coalescing of the doublet of doublet of
doublets (ddd) brought about by coupling with the fluorine
atom and H-5 (JH6, F = JH6,H5 = 7.6 Hz) and the meta coupling
with H-4 (JH4,H6 = 1.4 Hz). The H-6 proton resonance shows a
COSY correlation to another triplet also arising because of
coalescing of the doublet doublet that arises by coupling with
both H-6 and H-4 with JH6,H5 = JH5,H4 = 7.5 Hz. No meta
coupling between H-5 and H-3 is observed. The other two
aromatic resonances at δH 7.32–7.36 (m) and δH 7.12 (dd,
J = 11.0 and 8.8 Hz) were assigned to H-4 and H-3, respec-
tively, and could be distinguished by HMBC correlations
between C-1 (d, J = 11.4 Hz) and H-3. C-1 also showed HMBC
correlations to H-5. JH3,F (11.0 Hz) was larger than JH3,H4
(8.8 Hz). The C-3 carbon resonance was identified by an HSQC
correlation with H-3 and was seen overlapping with C-1‴and
C-1″ as a doublet at δC 116.5 (J = 21.9 Hz). C-4, C-5 and C-6 were
all identified similarly at δC 131.4 (d, J = 8.8Hz, meta C-F coupling),
124.7 (d, J = 3.6 Hz, para C-F coupling) and 130.5 (d, J = 8.3 Hz, meta
C-F coupling), respectively. The fluorine bonded C-2 showed HMBC
correlations with H-7, H-6, H-4 and H-3 and was identified as a large
doublet at δC 162.0 (J = 252.5Hz).
For the two pyran rings on the A ring (closer to the ketone), the
H-2″/2‴ resonances overlap as a pair of doublets, with four peaks
for the two doublet resonances, the first and the third peak being
assigned to H-2″ and the second and fourth peak being assigned
to H-2‴. These doublets occur at δH 5.48 and δH 5.47 and have
coupling constants of 10.0 Hz, characteristic of cis olefinic protons
and can be interchanged. The H-1″ and H-1‴proton resonances,
although occurring close to each other, do not overlap and can
be distinguished as two separate resonances at δH 6.60 and δH
6.69 (J = 10.0 Hz). The H-1″ and H-2″ and H-1‴ and H-2‴
resonances show clear coupling in the COSY spectrum. Both H-2‴
and H-2″ show HMBC correlations to C-3′ and C-5′, respectively, at
δC 102.80 and δC 102.76. However, both these sets of resonances
can be interchanged as they occur so close to each other that it is
difficult to tell them apart. The H-1‴ resonance was distinguished
from the H-1″ resonance by an HMBC correlation between H-1‴
and C-2′ at δC 161.8. The identification of H-1‴ and H-1″ allowed
the unambiguous assignments of C-4′ (through an HMBC with
H-1‴) and C-6′ (HMBC with H-1″). The C-1′ resonance at δC
106.17 was detected by an HMBC correlation to the 2′-hydroxy
resonance at δH 14.36.
The corresponding carbon resonances of H-1‴ and H-1″ were
found at δC 116.4 (C-1‴) and δC 116.7 (C-1″) in the HSQC
spectrum. There are two methyl proton resonances for the four
methyl groups because the methyl groups on each of the pyran
rings are equivalent because of the planar nature of the
molecule. Thus, H-4″/5″ occurs at δ 1.54, and H-4‴/5‴ occurs at δ
1.46. These methyl resonances show HMBC correlations to C-2″/C-
2‴ and C-3″ and C-3‴, the latter two carbon resonances occuring
at δC 78.7 and 78.6, which can be interchanged. The C-4″/5″ and
C-4‴/5‴ resonances occur at δC 28.6 and δC 28.1. The HMBC correla-
tions of 3b are reflected in Fig. 3.
A crystal structure of 3b (Fig. 4) was solved in the monoclinic
space group P21/c, with one molecule in the asymmetric unit. The
bond length and angles are in agreement with the expected aver-
age values for related compounds.[21,22] The trans double bond is
clearly evident for C-7 and C-8, and the 2′-hydroxy group is on the
same side of the carbonyl group with weak intramolecular hydro-
gen bonds being experienced by the 2′-hydroxy and C-9 carbonyl
group. Each of the methyl groups on a particular pyran ring is in a
similar chemical environment being on different sides of the planar
molecule. The fluorine atom is seen pointing toward the angular py-
ran ring. Both pyranochromene rings exist in a half chair conforma-
tion with Φ = 0.3779 (11) Å, θ = 112.14 (18)°, Ψ = 219.32 (19)°and
Φ = 0.3460 (11) Å, θ = 113.85 (18)° and Ψ = 146.4 (2)°, respectively.
This is similar to our previous reports on similar structures.[21,22]
The cyclization of the chalcones to the flavanones is carried out
with sodium acetate under reflux at 80 °C in ethanol. The spectra
of the flavanones using 4b as an example (Fig. 2) are typified by a
doublet doublet at δH 5.69 (H-2) deshielded by the oxygen and
two double doublets at δH 2.93 (H-3a) and 2.81(H-3b), respec-
tively. The two protons at C-3 and the one proton at C-2 all
couple with each other with JH-3a,H-3b = 16.6 Hz, JH-3a,H-2 = 3.2 Hz
and JH-3b,H-2 = 12.9 Hz. These coupling constants indicate that
the H-2/H-3a dihedral angle is closer to 90° and the H-2/H-3b
dihedral angle closer to 180°. These occurrences take place with
the concomitant disappearance of the distinctive H-7 and H-8 pair
of doublets discussed previously.
Interestingly enough, the change in structure from the
pyranochromene chalcone to the flavanone led to differences
in the NMR resonances of the pyran rings. In particular, whereas
Figure 4. ORTEP diagram of 3b.
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Copyright © 2014 John Wiley & Sons, Ltd.
Magn. Reson. Chem. 2014, 52, 279–288

Structural elucidation of pyranochromene chalcones
H3b
H2
H3a
Figure 5. ORTEP diagram of 4g.
H-2″ and H-2‴ overlapped in the chalcones and H-1″ and H-1‴
could clearly be distinguished, the opposite now occurs with
the flavanones. As with the H-2″/H-2‴ resonances previously
mentioned, the H-1″/H-1‴ resonances appear as a series of four
peaks, the first and the third being the doublet of H-1″ and
the second and the fourth being the doublet of H-1‴. These
occur at δH 6.58 and δH 6.57, respectively, with JH-1″,2″ = 10.0 Hz
and JH-1‴,2‴ = 9.9 Hz. These coupling constants were used to
distinguish the olefinic methine resonances on each of the rings.
Unlike in the chalcones where there was a clear correlation
between H-1‴ and C-2′ that allowed us to assign each of the
pyran ring resonances unambiguously, there is no correlation
between H-1‴ and C-9 in the flavanones to make this distinction.
Therefore, each of the pyran ring resonances as well as C-5 and
C-7 and C-6 and C-8 may be interchangeable. Nevertheless, H-1″
shows an HMBC correlation to C-6 and H-1‴ an HMBC correlation
to C-8. Because the planarity of the molecule changes in forming
the flavanone, each of the methyl resonances in both the 1H and
Conclusion
A series of pyranochromene chalcones and flavanones were
synthesized and characterized by 1D and 2D NMR spectroscopy
and X-ray crystallography. The stereochemistry of C-2 for 4g was
shown to be in the S configuration for the flavanones, and because
the NMR spectra of all the other compounds prepared with the
same method are similar, the series of compounds is deduced to
have the S configuration for C-2. The 1H and 13C NMR assignments
of the pyranochromene chalcones and flavanones were made with
the aid of HSQC and HMBC data and will provide a reference point
for other pyranochromene chalcones synthesized or isolated.
Acknowledgement
SP thanks the College of Agriculture, Engineering and Science of
the University of KwaZulu-Natal for a doctoral bursary.
13C NMR spectra appears as separate resonances at δH 1.52, 1.50, References
1.46 and 1.44 and δC 28.7, 28.4, 28.3 and 28.1. However, it is impos-
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Magn. Reson. Chem. 2014, 52, 279–288