4198
G. Sagrera, G. Seoane
PAPER
129.0 (C3 + C5), 128.9 (C2 + C6), 128.8 (C2,6phenyl), 128.4 (C3,5phenyl),
126.0 (C4phenyl), 121.1 (Ca), 113.7 (C3¢), 111.9 (C1¢), 109.3 (C5¢),
27.6 (CH2).
Anal. Calcd for C23H20O4: C, 76.65; H, 5.59. Found: C, 76.55; H,
5.63.
6¢-Benzyl-3¢-hydroxy-4¢-methoxyflavanone (47)
Prepared according to the general procedure. Yield: 17%; light yel-
low solid; mp 87–89 °C.
1H NMR (400 MHz, CDCl3): d = 7.93 (dd, J56 = 7.8 Hz, J57 = 1.6
Hz, 1 H, H5), 7.48 (ddd, J78 = 8.3 Hz, J76 = 7.4 Hz, J75 = 1.6 Hz, 1
H, H7), 7.26–7.21 (m, 5 H, ArH), 7.05–6.99 (m, 2 H, H6 + H8), 6.86
(s, 1 H, H5¢), 6.84 (s, 1 H, H2¢), 5.39 (dd, J2ax,3ax = 13.3 Hz,
J2ax,3eq = 2.8 Hz, 1 H, H2), 4.96 (br s, 1 H, OH), 4.04 (s, 2 H, CH2–
MS (EI, 70 eV): m/z (%) = 331 (24.4) [M + 1]+, 330 (100.0) [M]+,
329 (53.8) [M – 1]+, 253 (47.2), 226 (13.3), 198 (21.8), 197 (19.4),
149 (21.5), 103 (16.7), 91 (12.8).
Anal. Calcd for C22H18O3: C, 79.98; H, 5.49. Found: C, 80.07; H,
5.59.
5¢-Benzyl-2¢,4¢-dihydroxychalcone (44b)23
yellow solid; mp 127–129.5 °C.
Ar), 3.97 (s, 3 H, OMe), 3.10 (dd, J3ax 3eq = 16.8 Hz, J3ax,2 = 13.3 Hz,
,
1H NMR (400 MHz, CDCl3–acetone-d6): d = 13.14 (s, 1 H, 2¢-OH),
7.72 (d, Jba = 15.5 Hz, 1 H, Hb), 7.53 (s, 1 H, H6¢), 7.52–7.50 (m, 2
H, H2 + H6), 7.41 (d, Jab = 15.5 Hz, 1 H, Ha), 7.34–7.31 (m, 3 H, H3
+ H4 + H5), 7.29–7.08 (m, 5 H, ArH), 6.38 (s, 1 H, H3¢), 4.60 (s, 1
H, 4¢-OH), 3.89 (s, 2 H, CH2–Ar).
13C NMR (100 MHz, CDCl3): d = 191.8 (C=O), 166.0 (C2¢), 162.5
(C4¢), 143.9 (Cb), 140.7 (C1phenyl), 135.0 (C1), 132.2 (C4), 130.6 (C6¢),
129.0 (C2 + C6), 128.8 (C3 + C5), 128.5 (C3,5phenyl), 128.4 (C2,6phenyl),
126.0 (C4phenyl), 120.8 (Ca), 120.2 (C5¢), 113.8 (C1¢), 103.4 (C3¢), 35.4
(CH2).
1 H, H3ax), 2.84 (dd, J3eq,3ax = 16.8 Hz, J3eq,2 = 2.8 Hz, 1 H, H3eq).
13C NMR (100 MHz, CDCl3): d = 192.2 (C=O), 156.8 (C8a), 149.2
(C4¢), 146.5 (C3¢), 141.0 (C1phenyl), 136.6 (C7), 132.4 (C6¢), 129.8
(C2,6phenyl), 127.9 (C3,5phenyl), 126.9 (C5), 125.9 (C4phenyl), 124.5 (C1¢),
121.9 (C4a), 118.6 (C6), 117.0 (C8), 114.5 (C2¢), 114.0 (C5¢), 77.8
(C2), 56.0 (CH3), 44.1 (C3), 36.3 (CH2).
MS (EI): m/z (%) = 361 (24.8) [M + 1]+, 360 (100.0) [M]+, 359
(57.8) [M – 1]+, 343 (11.4), 269 (17.6), 240 (31.8), 197 (26.1), 132
(13.3), 121 (28.1), 91 (20.5).
Anal. Calcd for C23H20O4: C, 76.65; H, 5.59. Found: C, 76.90; H,
5.66.
MS (EI, 70 eV): m/z (%) = 331 (25.3) [M + 1]+, 330 (100.0) [M]+,
329 (65.9) [M – 1]+, 254 (16.0), 253 (75.8), 239 (11.5), 227 (17.0),
226 (33.6), 103 (14.0), 91 (10.1).
3-Benzyl-2,2¢-dihydroxychalcone (48b)
2-(Benzyloxy)-2¢-hydroxychalcone (37; 330 mg, 1 mmol) was re-
fluxed with TFA (2 mL) in anhyd CH2Cl2 (8 mL) for 96 h. The prod-
uct was separated by column chromatography [silica gel, hexanes
then EtOAc–hexanes (2:8)]; yield: 230 mg (70%). Compound 48a
could not be isolated in pure crystalline form and was identified by
conversion into the corresponding 2¢-hydroxychalcone (48b). To
this end, the compound 48a was dissolved in 10% ethanolic NaOH
(15 mL) and stirred at r.t. for 12 h, then poured into H2O (20 mL),
acidified with 25% aq HCl, and extracted with EtOAc (3 × 25 mL).
The combined organic layers were washed with H2O (25 mL), brine
(25 mL) and then separated and dried (MgSO4). The solvent was re-
moved under vacuum, and the mixture was separated by column
chromatography [silica gel, hexanes then EtOAc–hexanes (1:4)].
Yield: 208 mg (63%); yellow solid; mp 103–104 °C.
4¢-Hydroxy-3¢-methoxy-5¢-benzylflavanone (45)
Prepared according to the general procedure. Yield: 77%; light yel-
low solid; mp 98–99 °C.
1H NMR (400 MHz, CDCl3): d = 7.92 (dd, J56 = 8.0 Hz, J57 = 1.6
Hz, 1 H, H5), 7.68 (s, 1 H, OH), 7.51–7.29 (m, 6 H, ArH), 7.06–7.02
(m, 2 H, H6 + H8), 6.95–6.90 (m, 2 H, H2¢ + H6¢), 5.40 (dd,
J2ax,3ax = 13.2 Hz, J2ax,3eq = 2.6 Hz, 1 H, H2), 4.19 (s, 2 H, CH2–Ar),
3.92 (s, 3 H, CH3), 3.09 (dd, J3ax,3eq = 16.8 Hz, J3ax,2 = 13.3 Hz, 1 H,
H3ax), 2.86 (dd, J3eq,3ax = 16.8 Hz, J3eq,2 = 2.8 Hz, 1 H, H3eq).
13C NMR (100 MHz, CDCl3): d = 192.0 (C=O), 161.5 (C8a), 150.0
(C4¢), 148.6 (C1phenyl), 136.9 (C3¢), 136.1 (C7), 131.7 (C5¢), 128.8
(C1¢), 128.7 (C2,6phenyl), 127.9 (C5), 127.2 (C3,5phenyl), 127.0 (C4phenyl),
121.5 (C6¢), 120.9 (C4a), 118.7 (C6), 118.1 (C8), 110.1 (C2¢), 79.5
(C2), 56.1 (OCH3), 44.5 (C3), 35.9 (CH2).
MS (EI): m/z (%) = 361 (26.0) [M + 1]+, 360 (100.0) [M]+, 359
(60.3) [M – 1]+, 342 (10.5), 269 (19.5), 240 (33.2), 197 (26.3), 121
(28.3), 91 (20.1).
1H NMR (400 MHz, CDCl3): d = 12.84 (s, 1 H, 2¢-OH), 8.09 (d,
Jba = 15.6 Hz, 1 H, Hb), 7.69 (d, Jab = 15.6 Hz, 1 H, Ha), 7.63 (dd,
J6¢5¢ = 8.1 Hz, J6¢4¢ = 1.5 Hz, 1 H, H6¢), 7.48–7.45 (m, 3 H, ArH),
7.37–7.29 (m, 3 H, ArH), 7.22 (dd, J45 = 7.8 Hz, J46 = 1.4 Hz, 1 H,
H4), 7.11 (t, J56 = J54 = 8.0 Hz, 1 H, H5), 7.02–6.99 (m, 2 H, H3¢ +
H6), 6.81 (ddd, J5¢6¢ = 8.1 Hz, J5¢4¢ = 7.1 Hz, J5¢3¢ = 1.0 Hz, 1 H, H5¢),
4.09 (s, 2 H, CH2–Ar).
Anal. Calcd for C23H20O4: C, 76.65; H, 5.59. Found: C, 76.82; H,
5.54.
13C NMR (100 MHz, CDCl3): d = 194.1 (C=O), 163.5 (C2¢), 153.3
(C2), 147.8 (C1 phenyl), 141.0 (Cb), 136.4 (C4¢), 129.7 (C6¢), 129.3
(C3), 128.6, 128.5 [(C2–C6)phenyl], 128.2 (C4, C1), 124.3 (Ca), 121.9
(C5), 120.9 (C6), 120.1 (C5¢), 118.7 (C1¢), 118.4 (C3¢), 36.0 (CH2).
MS (EI): m/z (%) = 331 (20.7) [M + 1]+, 330 (100.0) [M]+, 329
(55.0) [M – 1]+, 313 (13.0), 239 (16.9), 210 (30.7), 197 (26.3), 132
(14.3), 121 (31.4), 91 (23.8).
2¢-Benzyl-3¢-hydroxy-4¢-methoxyflavanone (46)
Prepared according to the general procedure. Yield: 58%; light yel-
low solid; mp 83.5–86 °C.
1H NMR (400 MHz, CDCl3): d = 7.93 (dd, J56 = 7.8 Hz, J57 = 1.5
Hz, 1 H, H5), 7.49 (ddd, J78 = 8.3 Hz, J76 = 7.2 Hz, J75 = 1.7 Hz, 1
H, H7), 7.25–7.20 (m, 5 H, ArH), 7.06–7.00 (m, 2 H, H6 + H8), 6.88–
6.86 (m, 2 H, H5¢ + H6¢), 5.40 (dd, J2ax,3ax = 13.3 Hz, J2ax,3eq = 2.8 Hz,
1 H, H2), 4.92 (br s, 1 H, OH), 4.06 (s, 2 H, CH2–Ar), 3.94 (s, 3 H,
OMe), 3.09 (dd, J3ax,3eq = 16.8 Hz, J3ax,2 = 13.3 Hz, 1 H, H3ax), 2.83
(dd, J3eq,3ax = 16.8 Hz, J3eq,2 = 2.8 Hz, 1 H, H3eq).
Anal. Calcd for C22H18O3: C, 79.98; H, 5.49. Found: C, 80.01; H,
5.38.
13C NMR (100 MHz, CDCl3): d = 193.1 (C=O), 158.2 (C8a), 151.4
(C4¢), 148.6 (C3¢), 142.2 (C1phenyl), 134.9 (C7), 131.08 (C2,6phenyl),
128.50 (C2¢ + (C3,5phenyl), 127.4 (C5), 126.0, 125.9, (C1¢,C4phenyl),
124.6 (C4a), 121.7 (C6), 118.4 (C8), 117.0 (C6¢), 111.0 (C5¢), 78.2
(C2), 56.4 (CH3), 44.5 (C3), 34.4 (CH2).
MS (EI): m/z (%) = 361 (23.2) [M + 1]+, 360 (100.0) [M]+, 359
(55.3) [M – 1]+, 342 (13.1), 269 (18.3), 240 (30.3), 197 (25.9), 147
(10.5), 121 (28.2), 91 (25.2).
6,8-Dibenzyl-5,7-dihydroxyflavanone (49)
Prepared according to the general procedure. Yield: 72%; light yel-
low solid; mp 77.5–80 °C.
1H NMR (400 MHz, CDCl3): d = 12.20 (s, 1 H, 5-OH), 7.58–7.24
(m, 15 H, ArH), 5.41 (dd, J2ax,3ax = 13.1 Hz, J2ax,3eq = 2.9 Hz, 1 H,
H2), 4.15 (s, 2 H, CH2), 4.03 (s, 2 H, CH2), 3.03 (dd, J3ax,3eq = 16.5
Hz, J3ax,2 = 13.2 Hz, 1 H, H3ax), 2.80 (dd, J3eq,3ax = 16.5 Hz,
J3eq,2 = 3.0 Hz, 1 H, H3eq).
Synthesis 2009, No. 24, 4190–4202 © Thieme Stuttgart · New York