10.1002/adsc.202000892
Advanced Synthesis & Catalysis
White solid. mp: 89-91 °C. Rf = 0.80 (DCM:EtOAc 1:1).
1H-NMR (300 MHz, CDCl3): δ 6.75 (s, 1H), 6.66 (d, J =
8.4 Hz, 1H), 6.53 (s, 1H), 6.42 (d, J = 8.4 Hz, 1H), 5.25
(bs, 2H), 3.89 (s, 3H), 3.87 (s, 3H), 3.84 (s, 3H), 3.81 (s,
3H), 2.65-2.62 (m, 4H), 1.92-1.86 (m, 2H). 13C-NMR (75
MHz, CDCl3): δ 151.4, 147.4, 145.0, 142.7, 142.0, 132.6,
122.6, 122.3, 119.8, 113.9, 102.3, 97.9, 56.6, 56.5, 56.2,
56.1, 30.3, 29.4, 29.3. ESI-TOF-HRMS: [M+H]+ calcd.
for C19H25O6 349.1646; found, 349.1644.
3-(3-Methoxyphenyl)-1-(2-hydroxyphenyl)propan-1-
one (3h): 225 mg, 88% yield. White solid. mp: 45-46 °C.
Rf = 0.70 (Hex:EtOAc 3:1). 1H-NMR (300 MHz, CDCl3):
δ 12.26 (s, 1H), 7.75 (dd, J = 8.3 Hz, J = 1.4 Hz, 1H), 7.46
(td, J = 7.7 Hz, J = 1.3 Hz, 1H), 7.24 (td, J = 8.0 Hz, J =
1.7 Hz, 1H), 6.98 (dd, J = 8.3 Hz, J = 1.1. Hz, 1H), 6.89-
6.76 (m, 3H), 3.80 (s, 3H), 3.30 (t, J = 7.7 Hz, 2H), 3.05
(t, J = 7.6 Hz, 2H). 13C-NMR (75 MHz, CDCl3): δ 205.5,
162.5, 159.8, 142.3, 136.4, 132.7, 129.8, 129.6, 120.7,
118.9, 118.6, 114.3, 111.4, 55.2, 40.0, 30.1. ESI-TOF-
HRMS: [M+H]+ calcd. for C16H17O3 257.3065; found,
257.3066.
General
procedure
for
the
synthesis
of
dihydrochalcones 3a-j from chalcones 1a-j
3-(4-Methylphenyl)-1-(2-hydroxyphenyl)propan-1-
one (3j): 214 mg, 89% yield. White solid. mp: 43-44 °C.
Rf = 0.78 (Hex:EtOAc 3:1). 1H-NMR (300 MHz, CDCl3):
δ 12.41 (s, 1H), 7.81 (dd, J = 8.0 Hz, J = 1.7 Hz, 1H), 7.53
(ddd, J = 8.6 Hz, J = 7.2 Hz, J = 1.6 Hz, 1H), 7.27-7.14
(m, 4H), 7.06 (dd, J = 8.4 Hz, J = 1.2 Hz, 1H), 6.95 (ddd,
J = 8.2 Hz, J = 7.1 Hz, J = 1.2 Hz, 1H), 3.38 (t, J = 7.6 Hz,
2H), 3.09 (t, J = 7.7 Hz, 2H), 2.41 (s, 3H). 13C-NMR (75
MHz, CDCl3): δ 205.5 162.5, 137.6, 136.3,135.8, 129.9,
129.3, 128.3, 118.9, 118.6,40.2, 29.6, 21.1. ESI-TOF-
HRMS: [M+H]+ calcd. for C16H17O3 257.3065; found,
257.3068.
10% Pd/C (21 mg, 0.02 mmol Pd) was added to a
deoxygenated solution of the corresponding 2’-
hydroxychalcone 1a-j (1.0 mmol) in heptane (20 mL)
under inert atmosphere. The reaction flask was thrice
evacuated and flushed with hydrogen gas and the resulting
mixture was stirred at room temperature under hydrogen
atmosphere. After 6 h, the mixture was filtered through a
Celite® pad and the solvent was removed under reduced
pressure, to afford the corresponding dihydrochalcone 3a-
j without requiring any further purification (80-98%
yield). The physical data of new dihydrochalcones 3b-d,
3g and 3j are shown below.
General procedure for the synthesis of 1,3-
diarylpropanols 4a-f from chalcones 1a-f.
3-(2-Fluorophenyl)-1-(2-hydroxyphenyl)propan-1-
one (3b): 210 mg, 86% yield. Colorless oil. Rf = 0.76
1
(Hex:EtOAc 3:1). H-NMR (300 MHz, CDCl3): δ 12.29
(s, 1H), 7.78 (dd, J = 8.0 Hz, J = 1.6 Hz, 1H), 7.49 (ddd,
J = 8.7 Hz, J = 7.2 Hz, J = 1.6 Hz, 1H), 7.36-7.18 (m, 2H),
7.15-7.04 (m, 2H), 7.01 (dd, J = 8.4 Hz, J = 1.2 Hz, 1H),
6.90 (ddd, J = 8.3 Hz, J = 7.2 Hz, J = 1.2 Hz, 1H), 3.36 (t,
J = 7.5 Hz, 2H), 3.12 (t, J = 7.6 Hz, 2H). 13C-NMR (75
MHz, CDCl3): δ 205.1, 162.4,161.2 (d, J = 245.5 Hz),
136.4, 130.9 (d, J = 4.8 Hz), 129.8, 130.9 (d, J = 7.8 Hz),
127.5 (d, J = 15.6 Hz), 124.1 (d, J = 3.6 Hz), 119.2, 118.9,
118.5, 115.4 (d, J = 21.7 Hz), 38.5, 23.9 (d, J = 2.6 Hz).
ESI-TOF-HRMS: [M+H]+ calcd. for C15H14FO2
245.1021; found, 245.1022.
10% Pd/C (210 mg, 0.2 mmol Pd) was added to a
deoxygenated solution of the corresponding 2’-
hydroxychalcone 1a-f (1.0 mmol) in a 1:1 mixture of n-
BuOH and H2O (20 mL) under inert atmosphere. The
reaction flask was thrice evacuated and flushed with
hydrogen gas and the resulting mixture was stirred at
room temperature under hydrogen atmosphere. After 2-4
h, the mixture was filtered through a Celite® pad and the
solvent was removed under reduced pressure, to afford the
corresponding 1,3-diarylpropanols 4a-f which were
purified by flash column chromatography in
EtOAc/heptane mixtures (38-98% yield). 1,3-
diarylpropanol 4a was previously described in the
literature.[32] The data for new 1,3-diarylpropanols 4b-g
are shown below.
3-(3-Fluorophenyl)-1-(2-hydroxyphenyl)propan-1-
one (3c): 207 mg, 85% yield. Colorless oil. Rf = 0.75
1
(Hex:EtOAc 3:1). H-NMR (300 MHz, CDCl3): δ 12.27
(s, 1H), 7.77 (dd, J = 8.0 Hz, J = 1.7 Hz, 1H), 7.53-7.44
(m, 1H), 7.34-7.24 (m, 2H), 7.14-6.86 (m, 4H), 3.36 (t, J
= 7.6 Hz, 2H), 3.09 (t, J = 7.6 Hz, 2H). 13C-NMR (75 MHz,
CDCl3): δ 204.6, 162.9 (d, J = 245.9 Hz), 162.4, 143.3 (d,
J = 7.0 Hz), 136.4, 130.0 (d, J = 8.4 Hz), 129.7, 124.1 (d,
J = 2.8 Hz), 119.2, 118.9, 118.6, 115.3 (d, J = 20.8 Hz),
113.2 (d, J = 21.0 Hz), 39.6, 29.6. ESI-TOF-HRMS:
[M+H]+ calcd. for C15H14FO2 245.1021; found, 245.1021.
2-[3-(2-Fluorophenyl)-1-hydroxypropyl]phenol (4b):
120 mg, 49% yield. Colourless oil. Rf = 0.49 (Hex:EtOAc
3:1). 1H-NMR (300 MHz, CDCl3): δ 8.06 (bs, 1H), 7.24-
6.82 (m, 8H), 4.83 (dd, J = 8.5 Hz, J = 5.2 Hz, 1H), 3.14
(bs, 1H), 2.92-2.70 (m, 2H), 2.32-2.18 (m, 1H), 2.15-2.03
(m, 1H). 13C-NMR (75 MHz, CDCl3): δ 161.2 (d, J =
244.6 Hz), 155.3, 130.6 (d, J = 4.9 Hz), 129.0, 128.2 (d, J
= 15.8 Hz), 127.8 (d, J = 8.2 Hz), 127.3, 127.1, 124.1 (d,
J = 3.4 Hz), 119.9, 117.1, 115.3 (d, J = 22.3 Hz), 75.0,
37.2, 25.3 (d, J = 2.5 Hz). ESI-TOF-HRMS: [M+Na]+
calcd. for C15H16FO2Na 269.0954; found, 269.0954.
3-(4-Fluorophenyl)-1-(2-hydroxyphenyl)propan-1-
one (3d): 196 mg, 80% yield. White solid. mp: 46-47 °C.
Rf = 0.70 (Hex:EtOAc 3:1). 1H-NMR (300 MHz, CDCl3):
δ 12.29 (s, 1H), 7.76 (dd, J = 8.0 Hz, J = 1.7 Hz, 1H), 7.49
(ddd, J = 8.8 Hz, J = 7.2 Hz, J = 1.7 Hz, 1H), 7.27-7.13
(m, 2H), 7.12-6.80 (m, 4H), 3.33 (t, J = 7.5 Hz, 2H), 3.07
(t, J = 7.5 Hz, 2H). 13C-NMR (75 MHz, CDCl3): δ 205.1,
162.5, 161.5 (d, J = 244.1 Hz), 136.4, 129.8 (d, J = 8.2
Hz), 129.3, 119.2, 118.9, 118.6, 115.3 (d, J = 21.1 Hz),
114.6, 40.0, 29.1. [M+H]+ calcd. for C15H14FO2 245.1021;
found, 245.1019.
2-[3-(3-Fluorophenyl)-1-hydroxypropyl]phenol (4c):
113 mg, 46% yield. Colourless oil. Rf = 0.49 (Hex:EtOAc
3:1). 1H-NMR (300 MHz, CDCl3): δ 8.07 (bs, 1H), 7.28-
7.16 (m, 2H), 7.00-6.84 (m, 6H), 4.80 (dd, J = 8.1 Hz, J =
5.4 Hz, 1H), 3.34 (bs, 1H), 2.85-2.64 (m, 2H), 2.30-2.18
(m, 1H), 2.15-2.02 (m, 1H). 13C-NMR (75 MHz, CDCl3):
δ 162.9 (d, J = 245.3 Hz), 155.3, 144.0 (d, J = 7.1 Hz),
129.9 8 (d, J = 8.4 Hz), 129.0, 127.4, 127.2, 124.1 (d, J =
2.8 Hz), 120.0, 117.1, 115.3 (d, J = 20.8 Hz), 112.8 (d, J
= 21.0 Hz), 74.7, 38.1, 31.6. HRMS (m/z): [M+Na]+ calcd.
for C15H16FO2Na 269.0954; found, 269.0973.
3-(2-Methoxyphenyl)-1-(2-hydroxyphenyl)propan-1-
one (3g): 225 mg, 88% yield. White solid. mp: 50-52 °C;
Rf = 0.70 (Hex:EtOAc 3:1); 1H-NMR (300 MHz, CDCl3):
δ 12.42 (s, 1H), 7.80 (dd, J = 8.0 Hz, J = 1.4 Hz, 1H), 7.48
(t, J = 7.8 Hz, 1H), 7.26-7-20 (m, 1H), 7.01 (d, J = 8.4 Hz,
1H), 6.97-6.83 (m, 3H), 3.85 (s, 3H), 3.34 (dd, J = 8.7 Hz,
J = 6.5 Hz, 2H), 3.07 (dd, J = 8.6 Hz, J = 6.8 Hz, 2H);
13C-NMR (75 MHz, CDCl3): δ 206.4, 162.5, 157.9, 136.2,
130.2, 130.1, 128.9, 127.7, 120.6, 118.8, 118.4, 110.2,
55.1, 38.7, 25.9. ESI-TOF-HRMS: [M+H]+ calcd. for
C16H17O3 257.3065; found, 257.3065.
2-[3-(4-Fluorophenyl)-1-hydroxypropyl]phenol (4d):
94 mg, 38% yield. White solid. Rf = 0.47 (Hex:EtOAc
1
3:1). H-NMR (300 MHz, CDCl3): δ 7.22-7.10 (m, 3H),
7.02-6.83 (m, 5H), 4.81 (dd, J = 8.2 Hz, J = 5.4 Hz, 1H),
2.82-2.62 (m, 2H), 2.30-2.18 (m, 1H), 2.13-2.03 (m, 1H).
13C-NMR (75 MHz, CDCl3): δ 161.3 (d, J = 243.7 Hz),
155.4, 136.9 (d, J = 3.3 Hz), 129.7 (d, J = 7.8 Hz), 129.0,
127.3, 127.1, 119.9, 117.2, 115.2 (d, J = 21.0Hz), 75.0,
8
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