Synthesis and NMR of 4-Aryl-3,4-dihydrocoumarins and 4-arylcoumarins

Article abstract of DOI:10.14233/ajchem.2014.17751

This paper described the synthesis and ¹H and ¹³C NMR chemical shifts of a series of 4-aryl-3,4-dihydrocoumarin and 4-arylcoumarin derivatives based on a combination of ¹H and ¹³C NMR, HSQC and HMBC experiments.

Full text of DOI:10.14233/ajchem.2014.17751

Asian Journal of Chemistry; Vol. 26, No. 22 (2014), 7753-7758
ASIAN JOURNAL OF CHEMISTRY
http://dx.doi.org/10.14233/ajchem.2014.17751
Synthesis and NMR of 4-Aryl-3,4-dihydrocoumarins and 4-Arylcoumarins
*
JIE SUN and YANFENG WANG
Institute of Materia Medica, Shandong Academy of Medical Sciences, Jinan 250062, P.R. China
*Corresponding author: E-mail: wyfshiwoya@126.com
Received: 3 April 2014;
Accepted: 6 June 2014;
Published online: 6 November 2014;
AJC-16228
This paper described the synthesis and 1H and 13C NMR chemical shifts of a series of 4-aryl-3,4-dihydrocoumarin and 4-arylcoumarin
derivatives based on a combination of 1H and 13C NMR, HSQC and HMBC experiments.
Keywords: 1H NMR, 13C NMR, 2D NMR, 4-Aryl-3,4-dihydrocoumarins, 4-Arylcoumarins, Synthesis.
dissolved in 1 mL of CDCl3 and 0.7 mL of the solution trans-
ferred into a 5 mm Norell ST500 NMR tube. The 1H and 13C
NMR spectra of compounds were recorded on a Bruker DRX-
400 spectrometer operating at 400.13 and 100.6 MHz, respec-
tively, equipped with a 5 mm QNP 13C/1H/31P/15N probe head.
The 1H spectra were recorded with 32 scans, 3s relaxation delay,
1.36 s acquisition time, 0.367 Hz digital FID resolution, 16384
FID size, with 6009 Hz spectral width. The 13C spectra were
recorded with Waltz 16 1H broadband decoupling, 300 scans,
5s relaxation delay, 0.3 s acquisition time, 1.5 Hz digital FID
resolution, 16384 FID size, 25063 Hz spectral width. 2D
spectra were recorded on a Bruker DRX 400 spectrometer
(400.13 MHz for 1H, 100.6 MHz for 13C) equipped with QNP
probe head. Standard pulse sequences were used for 2D spectra.
Data processing was performed on a 1K × 512 data matrix.
Inverse-detected 2D heteronuclear correlated spectra were
measured over 2048 complex points in F2 and 256 increments
in F1, collecting 64 (HSQC) or 128 (HMBC) scans per incre-
ment with a relaxation delay of 2 s. The spectral widths were
4 and 22 kHz in F2 and F1 dimensions, respectively. The HSQC
experiments were optimized for C-H couplings of 145 Hz;
the HMBC experiments were optimized for long-range C-H
couplings of 3 Hz. Fourier transforms were performed on a
2048 × 512 data matrix. π/2 shifted sine-squared window
functions were used along F1 and F2 axes for all 2D spectra.
Synthesis of 5,7,4'-trimethoxy-4-phenylcoumarin (1a)
and 5,7-dimethoxy-4-phenylcoumarin (1b): Ponndorf
reaction of phenylpropiolic acid (10 mmol) with phloroglucinol
(10 mmol) in the presence of CF3COOH (7 mL) at room tempe-
rature. The reaction mixture was poured into ice water, washed
with water (150 mL) and dried to obtain hydroxylated 4-aryl-
coumarins. To a mixture of hydroxylated 4-arylcoumarins,
INTRODUCTION
The compounds 4-arylcoumarin and 4-aryl-3,4-dihydro-
coumarin constitute a specific branch of coumarin derivatives
regarded as a rare subgroup of flavonoids. In recent years,
several 4-arylcoumarins and 4-aryl-3,4-dihydrocoumarins
have been shown to possess antidiabetic1, antiinflammatory2,3,
cytotoxic4-6 and antifungal7 effects.
We have investigated the design, synthesis and potential
therapeutic properties of a series of arylcoumarins. In this
paper, to address the paucity of fully assigned NMR spectral
data for these types of compounds, a series of 4-arylcoumarin
and 4-aryl-3,4-dihydrocoumarin of varying complexity were
1
synthesized and their H and 13C NMR spectral data fully
assigned based on a combination of 1D and 2D NMR experi-
ments including HSQC and HMBC.
EXPERIMENTAL
Melting points were determined using a Thiele tube and
were uncorrected. The FT-IR spectra were recorded using an
Analect RFX-65A spectrometer with KBr pellets. Spin
multiplets are given as s (singlet), d (doublet), t (triplet), q
(quartet) and m (multiplet). Mass spectra were obtained with
a Shimadzu QP-5050A spectrometer.
NMR spectra: Chemical shifts were reported on a δ scale
(ppm) with CDCl3 or CD3COCD3 as the solvents. The 1H NMR
and 13C NMR spectra were recorded with a Bruker DRX-400
spectrometer with TMS as the external standard. Chemical
shifts are reported in ppm (δ) and referenced to TMS (δH = 0
ppm) in 1H NMR spectra or to residual CDCl3 (δH = 7.25 ppm,
δC = 77 ppm) in heteronuclear 2D spectra. Scalar couplings
are reported in hertz. Typically, 20-30 mg of sample was

7754 Sun et al.
Asian J. Chem.
potassium carbonate (45m mol) and acetone (150 mL) was
added and then refluxed for 4 h. Filtrate the reaction mixture
and dried. Crude product can be purified either by column
chromatography on silica gel or by washing with water, dried
and then crystallized from ethyl acetate and petroleum ether
for two or three times8.
gel or by crystallization from acetone and water. Physical
properties of the synthesized compounds are listed below.
( )-7,8-Dihydroxy-4-(3-hydroxy-4-methoxyphenyl)-
3,4-dihydrocoumarin (2a): White crystals, m.p. 188-190 °C,
Yield: 69.5 %; IR (KBr, νmax, cm-1): 3498 (OH), 3417, 1753
(CO), 1516, 1468, 1271, 1198, 1174 and 1126; MS m/z (%)
302 [M]+, 284 [M-H2O]+, 269 [M-CH3-H2O]+, 259, 243, 229,
194, 179.
5,7-Dimethoxy-4-phenylcoumarin (1a):White crystals;
m.p. 151-152 °C; Yield: 62.8 %; IR (KBr, νmax, cm-1): 1712,
1624, 1591, 1510, 1460, 1356, 1244, 1228, 1203, 1157, 1107;
EI-MS: m/z: 312 [M]+, 284 [M-CO]+, 269 [M-CO-Me]+, 226,
211, 167, 149.
( )-7-Hydroxy-4-(3,4,5-trimethoxyphenyl)-3,4-
dihydrocoumarin (2b): White crystals, m.p. 176-178 °C,
Yield: 70 %; IR (KBr, νmax, cm-1): 3381 (OH), 1747 (CO),
1626, 1597, 1510, 1456, 1358, 1230, 1271, 1240, 1122, 987
and 968; MS m/z (%) 330 [M]+, 315 [M-CH3]+, 297 [M-CH3-
H2O]+, 287, 273, 257, 213, 128, 107.
5,7,4'-Trimethoxy-4-phenylcoumarin (1b): Yellow
crystals; m.p. 213-215 °C;Yield: 66.2 %; IR (KBr, νmax, cm-1):
1716, 1612, 1460, 1352, 1227, 1205, 1159, 1111; EI-MS: m/z:
282 [M]+, 254 [M-CO]+, 239 [M-CO-Me]+, 211, 196, 168,
152, 139.
( )-4-(3,4-Dimethoxyphenyl)-7-hydroxy-3,4-dihydro-
coumarin (3c):Yellow crystals, m.p. 144-146 °C,Yield: 60.7
%; IR (KBr, νmax, cm-1): 3429 (OH), 1761 (CO), 1626, 1597,
1516, 1462, 1419, 1335, 1271, 1244, 1159, 1103, 1024, 991,
847 and 812; MS m/z (%) 300 [M]+, 282 [M-H2O]+, 267 [M-
CH3-H2O]+, 257, 243, 227, 190 ,163, 129.
Synthesis of 4-arylcoumarins (1c-1g):A solution of the
appropriate phenol (11 mmol) and the appropriate aryl-
propargyl acid (10 mmol) in 10 mL of CF3COOH was stirred
at room temperature for 4-8 h. The reaction mixture was poured
onto ice water. It was extracted with ethyl acetate (2 × 150
mL), washed with water (150 mL) and dried. The solvent was
removed under reduced pressure to obtain the crude product,
which was then purified by chromatography on silica gel.
4-(3,4-Dimethoxyphenyl)-7-hydroxycoumarin (1c):
( )-6-Hydroxy-4-(3,4,5-trimethoxyphenyl)-3,4-dihyd-
rocoumarin (3d): White crystals, m.p. 174-176 °C, Yield:
71.4%; IR (KBr, νmax, cm-1): 3421 (OH), 1757 (CO), 1504,
1454, 1232, 1195 and 1122; MS m/z (%) 330 [M]+, 312 [M-
H2O]+, 297 [M-H2O-CH3]+, 257, 213, 181, 128.
White crystals, m.p. 233-234 °C,Yield: 56.4 %; IR (KBr, νmax
,
( )-7-Hydroxy-4-(3-hydroxy-4-methoxyphenyl)-3,4-
dihydrocoumarin (2e): White crystals, m.p. 165-168 °C,
Yield: 55.2 %; IR (KBr, νmax, cm-1): 3513 (OH), 3334, 1733
(CO), 1627, 1597, 1513, 1450, 1300, 1273, 1223, 1151 and
815; MS m/z (%) 286 [M]+, 268 [M-H2O]+, 253 [M-CH3-H2O]+,
243, 227, 213, 176, 115.
cm-1): 3194 (OH), 1695 (CO), 1624, 1599, 1518, 1263 and
1140; MS m/z (%) 298 [M]+, 283 [M-CH3]+, 270, 255, 227,
199, 184, 113.
4-(3,4-Dimethoxyphenyl)-7,8-dihydroxycoumarin
(1d): White crystals, m.p. 271-272 °C, Yield: 58 %; IR (KBr,
νmax, cm-1): 2987, 1726 (CO), 1618, 1518, 1379, 1255, 1147
and 814; MS m/z (%) 314 [M]+, 286 [M-CO]+, 271 [M-CO-
CH3]+, 161, 133, 115, 103.
( )-4-(3,4-Dimethoxyphenyl)-7,8-dihydroxy-3,4-
dihydrocoumarin(2f): White crystals, m.p. 174-176 °C,Yield:
72.8 %; IR (KBr, νmax, cm-1): 3423 (OH), 1755 (CO), 1516,
1468, 1275, 1238, 1192, 1169 and 1020; MS m/z (%) 316
[M]+, 298 [M-H2O]+, 283 [M-CH3-H2O]+, 273, 259, 243, 190.
( )-7,8-Dihydroxy-4-(3,4,5-trimethoxyphenyl)-3,4-
dihydrocoumarin(2g): White crystals, m.p. 221-223 °C,
Yield: 52.6 %; IR (KBr, νmax, cm-1): 3471 (OH), 1751 (CO),
1597, 1512, 1466, 1311, 1246, 1122 and 1007; MS m/z (%)
346 [M]+, 328 [M-H2O]+, 313 [M-CH3-H2O]+, 273, 257, 243,
229, 181, 115.
4-(3,4-Dimethoxyphenyl)-7-methoxycoumarin(1e):
White crystals, m.p. 148-149 °C,Yield: 53.8 %; IR (KBr, νmax
,
cm-1): 3411 (CO), 1695 (CO), 1606, 1518, 1448, 1173 and
1140; MS m/z (%) 312 [M]+, 297 [M-CH3]+, 284 [M-CO-CH3]+,
269, 213, 183, 139.
7,8-Dihydroxy-4-(3-hydroxy-4-methoxyphenyl)
coumarin (1f):Yellow crystals, m.p. 176-177 °C,Yield: 53.7
%; IR (KBr, νmax, cm-1): 3371 (OH), 1695 (CO), 1653, 1599,
1448, 1240, 1178 and 1130; MS m/z (%) 300 [M]+, 272 [M-
CO]+, 257 [M-CO-CH3]+, 229, 115.
( )-7,8-Dihydroxy-4-(4-methoxyphenyl)-3,4-dihydro-
coumarin (2h): White crystals, m.p. 166-168 °C, Yield:
62.2 %; IR (KBr, νmax, cm-1): 3413 (OH), 1751 (CO), 1612,
1514, 1311, 1284, 1247, 1180, 1144 and 1007; MS m/z (%)
286 [M]+, 268 [M-H2O]+, 243, 229, 200, 115.
7-Methoxy-4-(4-methoxyphenyl)coumarin (1g): White
crystals, m.p. 155-157 °C, Yield: 69 %; IR (KBr, νmax, cm-1):
3440, 3064, 2993, 1738 (CO), 1612, 1510, 1375, 1250, 825;
MS m/z (%) 282 [M]+, 254 [M-CO]+, 239 [M-CO-CH3]+, 211,
196, 168, 152, 140, 127.
( )-6-Hydroxy-4-(4-methoxyphenyl)-3,4-dihydrocou-
marin (2i): White crystals, m.p. 170-172 °C, Yield: 52.2 %;
IR (KBr, νmax, cm-1): 3320 (OH), 1732 (CO), 1510, 1456, 1309,
1252, 1194, 1155 and 831; MS m/z (%) 270 [M]+, 252 [M-
H2O]+, 227 [M-H2O-CH3]+, 213, 197, 128.
General procedure for the synthesis of 4-aryl-3,4-dihydro-
coumarins (2a-2l): To a mixture of POCl3 (10 mmol) and
BF3-Et2O (20 mmol) at 0 °C, substituted cinnamic acid
(5 mmol) was added and the reaction mixture was stirred for
15 min at 0 ºC. Substituted phenol (5 mmol) was added and
the mixture stirred at room temperature for 4-18 h. The reaction
mixture was poured onto ice water, extracted with ethyl acetate
(2 × 150 mL), washed with water (150 mL) and dried. The
solvent was evaporated under reduced pressure to obtain the
crude product, which was purified by chromatography on silica
( )-7-Methoxy-4-(4-methoxyphenyl)-3,4-dihydrocou-
marin(2j): White crystals, m.p. 136-137 °C, Yield: 52.1 %;
IR (KBr, νmax, cm-1): 2937, 1761 (CO), 1510, 1252, 1124, 1030
and 831; MS m/z (%) 284 [M]+, 256 [M-CO]+, 241 [M-CO-
CH3]+, 227, 211, 128.
( )-7-Methoxy-4-(3,4,5-trimethoxyphenyl)-3,4-dihydro-
coumarin (2k): White crystals, m.p. 131-133 °C, Yield:

Vol. 26, No. 22 (2014)
Synthesis and NMR of 4-Aryl-3,4-dihydrocoumarins and 4-Arylcoumarins 7755
57.2 %; IR (KBr, νmax, cm-1): 3456, 1761 (CO), 1593, 1506,
1460, 1130; MS m/z (%) 344 [M]+, 329 [M-CH3]+, 311 [M-
CO-CH3]+, 271, 220, 177, 121, 77.
phenols in the presence of Friedel-Crafts catalyst BF3-Et2O
and POCl3. Twelve of the 4-aryl-3,4-dihydrocoumarins
prepared were novel compound 2a-2l, while 4-arylcoumarins
(1a-1g) were reported previously8. However, only limited
NMR data are available for the two known compounds 1a and
( )-4-(3,4-Dimethoxyphenyl)-6-hydroxy-3,4-dihydro-
coumarin(2l): White crystals, m.p. 168-170 °C, Yield: 62.3
%; IR (KBr, νmax, cm-1): 3273 (OH), 1714 (CO), 1521, 1487,
1247, 1244 and 1186; MS m/z (%) 300 [M]+, 282 [M-H2O]+,
267 [M-CH3-H2O]+, 257, 243, 227, 151, 115.
1
1b and thus their 2D-NMR spectral data, as well as the H
NMR spectral data, are reported here for the first time.
The structural and spectroscopic assignments were made
through the combined use of 1D and 2D NMR experiments
such as HMQC and HMBC. All the 1H and 13C chemical shifts
and coupling constants for compounds 1a, 1b and 2a, 2b are
given in Tables 1-4, along with the HMQC and HMBC on
which the unambiguous assignments of all carbons and protons
RESULTS AND DISCUSSION
As part of our ongoing program for the studies of bioactive
arylcoumarins, we herein report a phenylpropiolic acid via
Ponndorf reaction with corresponding polyphenols to afford
5,7-dimethoxy-4-phenylcoumarin (1a), 5,7,4'-trimethoxy-4-
phenylcoumarin (1b) as well as their analogues compound
1c-1g in mild conditions with satisfactory yields. Twelve
4-aryl-3,4-dihydrocoumarins were synthesized by the conden-
sation of substituted cinnamic acids with the corresponding
1
were made. The H and 13C chemical shifts and coupling
constants for compounds 1c-1g and 2c-2l are given in Tables
5-8.
5,7-Dimethoxy-4-phenylcoumarin (1a) was obtained as
white crystals. The IR spectrum shows characteristic vibrations
OCH3
R
R
COOH
COOH
R1
OH
c
b
a
OH
OCH3
+
R5
R4
R3
R4
R1
O
O
HO
O
O
H3CO
O
O
OCH3
R3
R
R5
1a R=H
1c R1=OCH3, R4=OH, R3=R5=H
1d R1=OCH3, R3=H, R4=OH, R5=OH
1e R1=OCH3, R4=OCH3, R3=R5=H
1f R1=R4=R5=OH, R3=H
1b R=OCH3
OCH3
R1
R2
COOH
1g R1=R3=R5=H, R4=OCH3
OH
R5
R4
d
R3
+
R1
R2
R4
O
O
OCH3
R3
R5
2g R =R =OCH , R =H, R =R =OH
1 2 3 3 4 5
2a R =R =H, R =R =R =OH
1
3
2
4
5
2b R =R =OCH , R =R =H, R =OH
1
2h R =R =R =H, R =R =OH
1 2 3 4 5
2
3
3
5
4
2c R =R =R =H, R =OCH , R =OH
4
2i R =R =R =R =H, R =OH
1 2 4 5 3
1
3
5
2
3
2d R =R =OCH , R =OH, R =R =H
4
2j
R =R =R =R =H, R =OCH
1 2 3 5 4 3
1
2
3
3
5
2e R =R =R =H, R =R =OH
1
2k R =R =R =OCH , R =R =H
1
3
5
2
4
2
4
3
3
5
2f R =R =H, R =OCH , R =R =OH
1
2l R =R =R =H, R =OCH , R =OH
1 4 5 2 3 3
3
2
3
4
5
Scheme-I: Route to preparation of 4-arylcoumarin and 4-aryl-3,4-dihydrocoumarin; (a) phloroglucinol, CF3COOH, r.t. or 60 °C, 4-12 h, (b) (CH3)2SO4,
K2CO3, (Me)2CO, reflux, 4 h, (c) CF3COOH, r.t., 4-8 h, (d) POCl3 and BF3–Et2O, 0 °C → r.t., 4-18 h
TABLE-1
HMBC AND HSQC FOR 5,7-DIMETHOXY-4 PHENYLCOUMARIN (1a)
C
δC(ppm)
160.9
112.6
157.1
158.2
95.7
H
δH(ppm)
—
Multiplicity
Coupling constant (Hz)
HMBC
HSQC
—
2
—
—
s
—
—
—
—
2.0
—
2.0
—
—
—
—
—
—
—
—
—
—
—
2-C,1’-C,9-C
—
3
3
5.99
—
3-H
—
4
—
—
—
d
5
—
—
—
—
6
6
6.21
—
4-C,7-C, 8-C,9-C
6-H
7
163.3
93.5
—
—
d
8
8
6.51
—
6-C,9-C, 10-C
8-H
—
9
103.5
155.7
139.7
127.3
127.1
127.9
127.1
127.3
55.7
—
—
—
—
m
m
m
m
m
s
—
—
10
—
—
—
1’
2’
—
—
—
—
2’
7.35
7.24
7.35
7.24
7.35
3.85
3.40
6’-C
2’-H
3’-H
4’-H
5’-H
6’-H
5-OCH3
7-OCH3
3’
3’
4’
5’-C
4’
2’-C,6’-C, 1’-C
3’-C
5’
5’
6’
6’
2’-C
5-OCH3
7-OCH3
5’-OCH3
7’-OCH3
5’-C
55.4
s
7’-C

7756 Sun et al.
Asian J. Chem.
TABLE-2
HMBC AND HSQC FOR 5,7-DIMETHOXY-4-(4 METHOXYPHENYL)COUMARIN (1b)
C
H
Multiplicity
Coupling constant (Hz)
HMBC
HSQC
δC(ppm)
160.9
112.5
159.5
158.2
95.7
δH(ppm)
—
2
—
—
s
—
—
—
—
3-H
3
3
5.97
—
9-C,1’-C,2-C
4
—
—
—
d
—
—
—
5
—
—
—
—
—
6
6
6.22
—
2.4
—
8-C,9-C
6-H
7
163.2
93.5
—
—
d
—
—
8
8
—
6.49
—
2.4
—
6-C,9-C
8-H
9
103.6
155.4
132.0
128.7
112.7
157.2
112.7
128.7
55.3
—
—
—
dd
dd
—
dd
dd
s
—
—
10
1’
—
—
—
—
—
—
—
—
—
—
2’
2’
7.20
6.87
—
6.8,2
6.8,2
—
6’-C,4-C,4’-C
3-C,1’-C,4-C
—
2’-H
3’-H
—
3’
3’
4’
—
5’
5’
6.87
7.20
3.46
3.83
3.83
6.8,2
6.8,2
—
3-C,1’-C,4-C
6’-C,4-C,4’-C
5-C
5’-H
6’-H
5-OCH3
7-OCH3
4’-OCH3
6’
6’
5-OCH3
7-OCH3
4’-OCH3
5-OCH3
7-OCH3
4’-OCH3
55.4
s
—
7-C
55.7
s
—
4’-C
TABLE-3
HMBC AND HSQC FOR 7,8-DIHYDROXY-4-(3-HYDROXY-4-METHOXYPHENYL)-3,4-DIHYDROCOUMARIN (2a)
C
H
Multiplicity
Coupling constant (Hz)
HMBC
HSQC
δC(ppm)
168.0
37.9
δH(ppm)
—
2
—
3a,3b
4
—
m
t
—
—
6.4
8
—
—
3a-H,3b-H
4-H
3
2.99
4.19
6.65
6.43
—
2-C,4-C, 5-C,1’-C
4
40.4
3-C, 6-C,7-C, 6’-C1’-C
5
119.1
118.6
141.3
146.3
119.1
133.8
135.5
115.0
147.5
147.6
111.7
112.7
56.2
5
d
6-C,8-C, 10-C
5-H
6
6
d
8
7-C, 8-C
6-H
7
—
—
—
—
—
—
d
—
—
—
—
—
2.4
—
—
8
—
—
8
—
—
—
—
9
—
—
—
—
10
—
—
—
—
1’
—
—
—
5-C,4’-C
—
—
2’
2’
6.69
—
2’-H
—
3’
—
—
—
d
4’
5’
—
—
—
—
5’
6.77
6.59
3.86
1’-C,3’-C,4’-C
3’-C,4’-C,2’-C
4’-C
5’-H
6’-H
4’-OCH3
6’
6’
dd
s
8, 2.4
—
4’-OCH3
4’-OCH3
TABLE-4
HMBC AND HSQC FOR 7-HYDROXY-4-(3,4,5-TRIMETHOXYPHENYL)-3,4-DIHYDROCOUMARIN (2b)
C
H
Multiplicity
Coupling constant (Hz)
HMBC
HSQC
δC(ppm)
167.9
37.4
δH(ppm)
—
2
3
—
—
m
t
—
—
—
4,2,9,1’
3,9,2’,6’,1’2
4,7,10
8,9
—
3a-H,3b-H
4-H
3
3.01
4.18
6.84
6.56
—
4
40.4
4
6
5
117.4
112.0
156.3
104.3
129.1
152.3
137.2
104.5
153.6
136.4
153.6
104.5
56.1
5
d
8.4
2.4,8.4
—
5-H
6
6
dd
—
d
6-H
7
—
—
—
8
8
—
6.64
—
2.4
—
—
8-H
9
—
—
—
s
—
—
10
1’
2’
3’
4’
5’
6’
—
—
—
—
—
—
—
—
—
—
2’
6.33
—
—
4,6’,9,4’5’
—
2’-H
—
—
—
—
—
s
—
—
—
—
—
—
—
—
—
—
—
6’
6.33
3.78
3.82
3.78
—
4’,2’,4’,3’
3’-C
6’-H
3’-OCH3
4’-OCH3
5’-OCH3
3’-OCH3
3’-OCH3
4’-OCH3
5’-OCH3
s
—
4’-OCH3
5’-OCH3
60.9
s
—
4’-C
56.1
s
—
5’-C

Vol. 26, No. 22 (2014)
Synthesis and NMR of 4-Aryl-3,4-dihydrocoumarins and 4-Arylcoumarins 7757
at 1712 cm-1 (CO). The H-3 proton appears as a singlet at δ5.99
TABLE-5
13C NMR CHEMICAL SHIFTS (δ, ppm) of 4-ARYLCOUMARIN
DERIVATIVES 1c–1g (100.6 MHz, CDCl3 or CD3COCD3)
ppm. The protons on carbons 3, 6, 8, 2', 3', 4', 5' and 6', which
were easily assigned on the basis of chemical shift and
multiplicity, enabled the assignment by direct correlation
(HSQC) of carbons to which they are directly attached. Proton
H-3 showed a long distance correlation with C9 and with two
carbons at 160.9 and 139.7 ppm. The latter two signals were
assigned to 2 and 1', respectively, owing to their markedly
different chemical shifts. H-8 showed correlations with carbons
6, 9 and 10 and with two quaternary carbons at 95.7 and 155.7
ppm, which were assigned as 6 and 10, respectively. H-2'/
H-6' are chemically equivalent and have a long-distance
correlation (HMBC) with each other. Similarly, chemically
equivalent protons H-3'/H-5' show a long-distance correlation
with each other.
C
1c
1d
1e
1f
1g
2
161.3
112.5
157.0
128.9
112.3
162.2
103.5
112.9
156.5
129.3
111.0
151.4
150.3
113.6
122.0
56.2
161.2
112.5
157.2
118.7
112.7
144.7
133.3
113.0
149.9
129.1
110.8
151.4
150.2
113.0
122.1
56.2
161.1
112.9
157.0
128.7
112.6
163.8
101.8
112.9
156.3
129.0
111.8
151.5
150.4
113.2
122.1
56.2
161.3
112.7
157.2
118.7
112.7
144.6
133.2
113.0
149.9
129.3
110.6
147.4
149.6
112.4
120.9
–
161.4
112.7
156.0
127.8
112.2
162.7
101.1
114.3
155.5
129.9
127.8
111.4
160.7
111.4
127.8
–
3
4
5
6
7
8
9
10
1’
2’
3’
5,7,4'-Trimethoxy-4-phenylcoumarin (1b) was obtained
as yellow crystals. In the case of the compound, protons 3, 6,
8, 2', 3', 5' and 6' and the corresponding carbon atoms were
assigned as described above. The remaining correlations are
similar to those observed for compound 1a.
4’
5’
6’
3’-OCH3
4’-OCH3
7-OCH3
56.1
56.1
56.1
56.2
55.4
7,8-Dihydroxy-4-(3-hydroxy-4-methoxyphenyl)-3,4-
dihydrocoumarin (2a) was obtained as white crystals. The IR
–
–
56.3
–
55.8
TABLE-6
1H NMR CHEMICAL SHIFTS (δ, ppm) of 4-ARYLCOUMARIN DERIVATIVES 1c-1g (400.13 MHz, CDCl3 or CD3COCD3)
H
3
1c
6.20(s)
7.45(d,8.8)
—
1d
6.07(s),
7.00(d, 8.8)
6.83(d, 8.8)
—
1e
6.14(s)
1f
6.03(s)
6.98(d,8.8)
6.83(d,8.8)
—
1g
6.18(s)
5
7.55(d,8.8)
6.90(dd,8.8,2.4)
6.94(d,2.4)
7.12(d,2.4)
—
7.43(d, 8.8)
6.78(dd,8.8, 2.4)
6.87 (1H,d, J=2.4Hz,
7.37(d,8)
7.01(d,8)
—
6
8
6.98 (d, 2)
6.91(d, 2.4)
—
2’
3’
4’
5’
6’
7.10 (d, 2)
—
6.98(d,2)
—
—
—
—
—
6.97(1d,8)
6.74(dd,2.4,8)
3.94(s)
3.90(s)
—
7.06(dd,2,8.4)
7.11(d, 8.4)
3.88(s)
3.87(s)
—
7.12(d,8.4)
7.08(dd,8.4,2)
3.89(s)
6.96(dd,8,2)
7.10(d,8)
—
7.01(d,8)
7.37(d,8)
—
3’-OCH3
4’-OCH3
7-OCH3
3.88(s)
3.91(s)
—
3.68
3.93(s)
3.68
TABLE-7
13C NMR CHEMICAL SHIFTS (δ, ppm) OF 4-ARYL-3,4-DIHYDROCOUMARIN DERIVATIVES 2c–2l (100.6 MHz, CDCl3)
C
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2
168.5
37.5
168.1
36.8
168.2
37.9
166.9
37.4
166.7
37.3
167.9
37.9
168.2
37.0
167.7
37.4
167.6
37.4
168.2
36.9
3
4
39.6
41.0
39.9
40.0
40.7
40.2
39.9
39.2
40.5
40.4
5
119.7
110.5
156.3
104.2
129.1
152.2
133.1
111.6
149.3
148.3
112.0
117.7
55.9
115.5
153.6
114.5
118.0
137.2
145.3
126.9
104.6
152.6
135.7
152.6
104.6
56.1
119.1
112.3
158.5
104.2
129.9
153.4
135.6
112.7
147.4
147.6
114.9
117.9
56.2
118.9
111.3
144.2
139.3
119.7
132.7
131.1
110.6
149.4
148.5
111.5
118.1
55.9
117.6
111.3
144.3
139.3
119.0
136.0
131.1
104.5
153.6
136.0
153.6
104.5
56.2
118.5
111.7
146.3
141.2
129.3
134.5
133.8
119.1
114.9
159.6
114.9
119.1
—
114.6
152.3
114.5
118.0
131.9
145.5
128.7
127.5
114.7
159.0
114.7
127.5
—
117.9
110.6
159.8
102.4
128.7
152.3
132.6
128.4
114.3
158.8
114.3
128.4
—
117.4
110.8
160.0
104.4
128.9
152.4
136.4
102.5
153.6
137.3
153.6
102.5
56.1
114.5
152.5
111.6
119.9
132.3
145.4
127.4
110.6
149.4
148.5
115.3
118.0
55.9
6
7
8
9
10
1’
2’
3’
4’
5’
6’
3’-OCH3
4’-OCH3
5’-OCH3
7-OCH3
55.9
60.8
—
55.9
60.9
55.4
55.3
55.2
60.8
55.9
—
56.1
—
—
56.2
—
—
—
56.1
—
—
—
—
—
—
—
—
55.4
55.5
—

7758 Sun et al.
Asian J. Chem.
TABLE-8
1H NMR CHEMICAL SHIFTS (δ, ppm) of 4-ARYL-3,4-DIHYDROCOUMARIN DERIVATIVES 2c–2l (400.13 MHz, CDCl3)
H
2c
2.98 (m)
4.20 (t, 6.0)
6.67(d,8.4)
6.56(dd, 2.4 8.4)
6.80 (d, 2.4)
6.82 (d, 2.4)
6.66(d,8.4)
6.64(dd, 2.4 8.4)
3.79(s)
2d
2.98 (m)
4.17 (t, 6.4)
6.85 (d,8.6)
6.55(dd, 2.4,8.6)
6.64(d,2.4)
6.33(s)
2e
2.98 (m)
4.16 (t, 6.4)
6.82(d,8.4)
6.54(dd, 2.4 8.4)
6.69 (d, 2.4)
6.61 (d, 2.4)
6.78(d,8.4)
6.59(dd, 2.4 8.4)
—
2f
3.03(m)
4.24 (t, 6.4)
6.66(d,8.4)
6.41(d,8.4)
—
2g
3.03(m)
4.22(dd,6,7.6)
6.67(d,8.8)
6.45(d,8.8)
—
3a,3b
4
5
6
8
2’
6.66(d,2.4)
6.8(d,8.4)
6.64(dd, 2.4,8.4)
3.81(s)
6.33(s)
5’
—
—
6’
6.33(s)
6.33(s)
3’-OCH3
3.77(s)
3.78(s)
4’-OCH3
3.84(s)
3.80(s)
3.68(s)
3.85(s)
3.82(s)
5’-OCH3
—
3.77(s)
—
—
3.78(s)
H
2h
2i
2j
2k
2l
3a,3b
3.01(m)
4.24(t,6.8)
6.65(d,8.4)
6.39(d,8.4)
—
2.96(m)
4.19(dd,6,8.4)
6.38(d,2.4)
—
3.03(m)
3.00(m)
4.19(t,7.6)
6.89(d,8.4)
6.64(dd,2.4,8.4)
—
3.00(m)
4.17(dd,6,8.4)
6.63(d,2.4)
—
4
4.37(t,6.4)
6.95(d,8.4)
6.69(dd,2.4,8.4)
—
5
6
7
8
6.71(dd,3.2,8.8)
6.96(d,8.8)
7.05(d,8.8)
6.85(d,8.8)
7.05(d,8.8)
6.85(d,8.8)
—
6.68(dd,2.4,8)
6.79(d,8)
6.41(d,2.8)
—
—
6.66(d,2.4)
7.11(d,8.8)
6.89(d,8.8)
6.89(d,8.8)
7.11(d,8.8)
—
6.66(d,2.4)
6.33(s)
2’
7.04(d,8.8)
6.85(d,8.8)
7.04(d,8.8)
6.85(d,8.8)
—
3’
—
5’
—
6.96(d,8.8)
6.72(dd,2.8,8.8)
3.79(s)
6’
6.33(s)
3’-OCH3
4’-OCH3
5’-OCH3
7-OCH3
3.78(s)
3.78(s)
3.75(s)
3.76(s)
3.79(s)
3.82(s)
—
—
—
3.78(s)
—
—
—
3.81(s)
3.81(s)
—
spectrum shows characteristic vibrations at 1753 cm-1 (CO).
The H-3a and H-3b proton appear as a multiplet at δ2.99 ppm.
The H-4 proton appear as triplet at δ4.19 ppm. The protons on
carbons 3, 4, 5, 6, 2', 5' and 6', which were easily assigned on
the basis of chemical shift and multiplicity, enabled the
assignment by direct correlation (HSQC) of carbons to which
they are directly attached.
ACKNOWLEDGEMENTS
This work was financially supported by the China Post-
doctoral Science Foundation (2013M531164).
REFERENCES
1. J. Guerrero-Analco, O. Medina-Campos, F. Brindis, R. Bye, J. Pedraza-
Chaverri, A. Navarrete and R. Mata, Phytochemistry, 68, 2087 (2007).
2. T.C. Taechowisan, P. Tuntiwachwuttikul, C.H. Lu, Y.M. Shen, S.
Lumyong and W.C. Taylor, Immun. Inv., 36, 203 (2007).
3. T.C. Taechowisan, C.H. Lu, Y.M. Shen and S. Lumyong, Nat. Prod.
Res., 21, 1104 (2007).
In the case of 7-hydroxy-4-(3,4,5-trimethoxyphenyl)-3,4-
dihydrocoumarin (2b) was obtained as white crystals. The
protons on carbons 3, 4, 5, 6, 8, 2' and 6' and the corresponding
carbon atoms were assigned as described above. H-2'/H-6' are
chemically equivalent. The remaining correlations are similar
to those observed for compound 2a.
The 1H and 13C NMR spectral data for the five other aryl-
coumarins derivatives (1c-1g) and ten 4-aryl-3,4-dihydro-
coumarins (2c-2l) were fully assigned using similar reasoning
to that described above, with the results presented in Tables
5-8.
4. C. Bailly, C. Bal, P. Barbier, S. Combes, J.P. Finet, M.P. Hildebrand, V.
Peyrot and N. Wattez, J. Med. Chem., 46, 5437 (2003).
5. E. Rizzi, S. Dallavalle, L. Merlini, G. Pratesi and F. Zunino, Synth.
Commun., 36, 1117 (2006).
6. O.G. Ganina, E. Daras, V. Bourgarel-Rey, V. Peyrot, A.N. Andresyuk,
J.-P. Finet, A.Y. Fedorov, I.P. Beletskaya and S. Combes, Bioorg. Med.
Chem., 16, 8806 (2008).
7. T.C. Taechowisan, C.H. Lu, Y.M. Shen and S. Lumyong, Microbiology,
151, 1691 (2005).
8. J. Sun, W.X. Ding, K.Y. Zhang and Y. Zou, Chin. Chem. Lett., 22, 667
(2011).