Int. J. Mol. Sci. 2020, 21, 1609
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MHz): δ 194.8, 162.6, 159.1, 151.5, 149.5, 144.9, 128.3, 127.6, 123.2, 112.2, 111.3, 110.3, 91.1, 56.2, 56.2,
56.1, 55.7.HRMS FAB [M + H] 359,1483.
(E)‐1‐(2,4,6‐trimethoxyphenyl)‐3‐(3,4,5‐trimethoxyphenyl)prop‐2‐en‐1‐one (16).
Procedure A has been applied using 100 mg of 2,4,6‐trimethoxyacetophenone and 93 mg of 3,4,5‐
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trimethoxybenzaldehyde leading to 125 mg of 16 as a light yellow powder (72% yield). H NMR
(CDCl3, 270 MHz): δ 7.24 (d, 1H, J = 15.9 H), 6.86 (d, 1H, J = 15.9 Hz), 6.75 (s, 2H), 6.17 (s, 2H), 3.87 (s,
13
9H), 3.86 (s, 3H), 3,77 (s, 6H). C NMR (CDCl3, 68 MHz): δ 194.6, 162.6, 159.0, 153.6, 144.6, 140.3, 130.7,
128.8, 112.0, 105.7, 90.9, 61.1, 56.3, 56.1, 55.6. HRMS FAB [M + H] 389.1589.
Procedure B: Thionyl chloride (0.5 eq) is added dropwise to a solution of acetophenone (1 eq)
and benzaldehyde (1 eq) in 3 mL of dichloromethane (DCM). After being stirred at room temperature
for 24h, the reaction mixture is quenched with 10 mL of water. Crude chalcone is collected through
filtration and could be purified by silica gel column chromatography when it is required.
(E)‐3‐(4‐hydroxyphenyl)‐1‐(2,4‐dimethoxyphenyl)prop‐2‐en‐1‐one (11).
Procedure B was applied starting from 149 mg of 2,4‐dimethoxyacetophenone and 101 mg of 4‐
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hydroxybenzaldehyde, leading to 184 mg of 11 as a greenish powder. Yield: 78%. H NMR (CDCl3,
270 MHz) : δ 7.73 (d, J = 8.5 Hz, 1H), 7.64 (d, 1H, J = 15.6 Hz, oléfine), 7.48 (d, 2H, J = 8.5 Hz, Ar), 7.37
(d, 1H, J = 15.6 Hz, oléfine), 6.88 (d, 2H, J = 8.5 Hz, Ar), 6.78 (s, 1H, OH), 6.56 (dd, 1H, J = 8.7 Hz, 2.0
Hz, Ar ), 6.49 (d, 1H, J = 2.1 Hz, Ar), 3.89 (s, 3H, ‐OMe), 3.87 (s,3H,‐OMe). 13C RMN (CDCl3, 68 MHz)
: δ 191.7, 164.5, 160.7, 158.5, 143.2, 133.1, 130.6, 128.1, 124.9, 122.6, 116.3, 105.5, 105.4, 99.0, 56.0, 55.8.
(E)‐3‐(4‐hydroxy‐3,5‐dimethoxyphenyl)‐1‐(2,4‐dimethoxyphenyl)prop‐2‐en‐1‐one (13).
Procedure B was applied starting from 250 mg of 2,4‐dimethoxyacetophenone and 250 mg of 4‐
hydroxy‐3,5‐dimethoxybenzaldehyde, leading, after column chromatography (cyclohexane – EtOAc
1
(6:4)) to 394 mg of 13 as a yellow oil. Yield: 85%. H NMR (CDCl3, 270 MHz) : δ 7.71 (d, J = 8.5 Hz,
1H), 7.57 (d, J = 15.7 Hz, 1H), 7.32 (d, J = 15.6 Hz, 1H), 6.57 (dd, J = 8.6 Hz, 2.3 Hz, 1H), 6.50 (d, J = 2.2
13
Hz, 1H), 5.79 (s, 1H), 3.93 (s, 6H), 3.90 (s, 3H), 3.88 (s, 3H). C RMN (CDCl3, 68 MHz): δ 191.0, 164.2,
160.4, 147.4, 143.1, 137.2, 132.8, 127.1, 125.6, 122.6, 105.5, 105.3, 98.9, 56.5, 55.9, 55.7.
(E)‐3‐(4‐hydroxy‐3,5‐dimethoxyphenyl)‐1‐(2,4,6‐trimethoxyphenyl)prop‐2‐en‐1‐one (17).
Procedure B was applied starting from 150 mg of 2,4,6‐trimethoxyacetophenone and 129 mg of
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4‐hydroxy‐3,5‐dimethoxybenzaldehyde, leading to 70 mg of 17 as a yellow powder. Yield: 26%. H
NMR (CDCl3, 270 MHz): δ 7.23 (d, J = 15.7 Hz, 1H), 6.83 (d, J = 15.9 Hz, 1H), 6.76 (s, 2H, Ar), 6.17 (s,
13
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2H), 5.79 (s, 1H), 3.90 (s, 6H), 3.87 (s, 3H), 3.77 (s, 6H). C NMR (CDCl , 68 MHz): δ 194.8, 162.6, 159.1,
147.5, 145.3, 137.5, 127.6, 126.8, 112.2, 105.6, 91.0, 56.6, 56.2, 55.7. HRMS FAB [M + H] 389.1589.
Procedure C: In a dry reactor, 150 mg (0,76 mmol)of 2‐hydroxy‐4,6‐dimethoxyacetophenone and
139 mg of 4‐hydroxy‐3,5‐dimethoxybenzaldehyde are dissolved in ethanol (4 mL) with 200 μL of
piperidine. The reaction mixture is then heated at 150°C for 30 minutes in a Milestone microwave.
After cooling at room temperature, the suspension is filtered under reduced pressure leading to 74
mg of the expected chalcone 18 (yield: 27%).
(E)‐3‐(4‐hydroxy‐3,5‐dimethoxyphenyl)‐1‐(2‐hydroxy‐4,6‐dimethoxyphenyl)prop‐2‐en‐1‐one
(18).
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H NMR (CDCl3, 270 MHz): δ 14.39 (s, 1H), 7.78 (d, J = 15.4 Hz, 1H), 7.71 (d, J = 15.4 Hz, 1H), 6.86
(s, 2H), 6.11 (d, J = 2.4 Hz, 1H), 5.96 (d, J = 2.4 Hz, 1H), 5.81 (s, 1H), 3,95 (s, 6H), 3,91 (s, 3H), 3,84 (s,
13
3H). C RMN (CDCl3, 68 MHz): δ 192,6, 168,6, 166,3, 162,6, 147,5, 143,2, 137,4, 127,7, 125,7, 106,5, 105,7,
94,1, 91,5, 56,5, 55,9, 55,7.
Demethylation procedure: Chalcone 13 or 15 in solution in 3 mL of dry DCM is treated with 3
eq of AlCl3 for three days at room temperature. The reaction mixture is then hydrolyzed with 6 mL
of 0.5M aqueous HCl solution and extracted with DCM (3 x 10 mL). The combined organic extracts
are dried over sodium sulfate and evaporated under reduced pressure. The phenolic chalcone is
purified through flash chromatography.
(E)‐3‐(4‐hydroxy‐3,5‐dimethoxyphenyl)‐1‐(2‐hydroxy‐4‐methoxyphenyl)prop‐2‐en‐1‐one (12).
The above procedure is applied to 200 mg of chalcone 13. The conversion rate is estimated at
75% after column chromatography with cyclohexane – EtOAc (8:2) as the mobile phase, 56 mg of 12
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as a yellow powder are obtained (brsm yield: 39%). H NMR (CDCl3, 270 MHz) : δ 13.54 (s, 1H), 7.84