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10 Reaction of N,N-diethyl-O-toluamide
(7) with methyl salicylate (6)
in the presence of LDA: A solution of LDA in dry THF (200 mL) was
prepared by adding diiso-propylamine (14.7 mL, 0.10 mol) dropwise
to a 0.95 M solution of n-BuLi (95 mL,
0.10 mol) in hexane under argon at 0 °C. The ice-water
bath was replaced by a dry ice/acetone bath. The stirring
was continued for 30 min at -78 °C, and then N,N-diethyl-O-toluamide (7,
14.4 g, 75.0 mmol) in dry THF (30 mL) was added. The pale yellow
solution turned to deep red, indicating anion formation. The reaction
mixture was allowed to warm to 0 °C with an ice-water bath,
stirred for 10 min and the ice-water bath was replaced by a dry
ice/acetone bath. The stirring was continued for 1 h. A
solution of methyl salicylate (6, 11.4
g, 75.0 mmol) in dry THF (30 mL) was added slowly via syringe to
the above mixture. Stirring at this temperature was continued for
2 h and then the reaction mixture was warmed to room temperature.
2 N HCl was added and the entire mixture was stirred for 1 h. Removal
of solvent under reduced pressure gave a residue which was extracted
with CH2Cl2. The combined organic extracts
were washed with aqueous sodium carbonate solution, water and brine
solution, and dried over anhydrous sodium sulfate. After removal
of solvent, the residue was column chromatographed on silica gel
using EtOAc and hexane as eluents to provide the desired 2-(2-N,N-diethyl-carboxamidephenyl)-1-(2-hydroxyphenyl)ethan-1-one
(5) as the major adduct (13.5 g, 58%)
and 3-(2-methylphenyl) isochromen-1-one (10)
as the minor adduct (1.9 g, 11%).
11 Compound 5:
colorless crystals: mp 168-169 °C (EtOAc:hexane);
IR (KBr) 3061 (OH), 1744 (C=O), 1648 (C=O), 1628,
1603, 1486, 1272, 1215 cm-1; 1H
NMR (200 MHz, CDCl3) δ 1.03 (t, 3 H, J = 7.2 Hz), 1.09 (t, 3 H, J = 7.2 Hz), 3.15 (q, 2 H, J = 7.2 Hz), 3.45 (m, 2 H),
4.44 (br s, 2 H), 6.95 (m, 2 H), 7.30 (m, 4 H), 7.47 (dd, 1 H, J = 1.2 Hz, 7.6 Hz), 7.90 (dd,
1 H, J = 1.0 Hz, 8.1 Hz), 12.09
(s, 1 H); 13C NMR (50 MHz, CDC l3) δ 12.1,
13.7, 38.5, 42.0, 42.8, 118.3, 119.0, 119.2, 125.6, 127.0, 128.9,
130.3, 131.2, 131.3, 136.6, 137.3, 162.4, 170.3 (CON), CO not observed;
MS (EI) m/z 311 (M+,
0), 238 (68), 210 (85), 181 (100), 152 (21). HRMS (FAB) calcd for
C19H21NO3 [MH+]:
312.1560; found 312.1560.
12 Compound 10:
white solid: mp 80-82 °C (EtOH); IR (KBr) 1719
(C=O), 1648 (C=O) cm-1; 1H
NMR (200 MHz, CDCl3) δ 2.46 (s, 3 H), 6.56 (s,
1 H), 7.26 (m, 3 H), 7.46 (m, 3 H), 7.69 (dd, 1 H, J = 1.2
Hz, 7.2 Hz), 8.28 (dd, 1 H, J = 0.8
Hz, 8.0 Hz); 13C NMR (50 MHz, CDCl3) δ 20.7,
105.9, 120.3, 125.8, 126.0, 128.2, 129.2, 129.5, 129.8, 131.0, 132.7, 134.8,
136.7, 137.5, 155.5, 162.6; MS (EI) m/z 236
(M+, 100), 208 (83), 207 (39), 193 (27), 179
(43) Anal. calcd. for C16H12O2:
C, 81.34; H 5.12. Found: C, 80.94; H 4.87.
13
Hauser FM.
Rhee RP.
Prasanna S.
Weinreb SM.
Dodd JH.
Synthesis
1980,
72
14 3-(2-N,N-Diethylcarboxamidephenyl)-4H-chromen-4-one (4).
2-Hydroxydeoxybenzoin (6, 0.62 g. 2.0 mmol)
was dissolved in distilled BF3˙Et2O
(5 mL) under argon. A solution of methanesulfonyl chloride (3 mL)
in dry DMF (15 mL) was slowly added and the mixture was heated at
70 °C for 2 h. The reaction was cooled to room temperature
and poured into an ice-cold aq sodium acetate. The mixture was extracted
with ethyl acetate. The combined organic extracts were washed with
water and dried over anhydrous sodium sulfate. Solvent was removed
under vacuum and the residue was purified by preparative layer chromatography
on silica gel (elution with CH2Cl2) to give
isoflavone 4 as a white solid (0.30 g,
48%).
15 Compound 4:
mp 173-175 °C (EtOH); IR (KBr) 1639 (C=O),
1595, 1471, 1386, 1359, 1299, 1228 cm-1; 1H
NMR (200 MHz, CDCl3) δ 0.89 (m, 6 H), 3.04 (m,
4 H), 7.35 (m, 6 H), 7.63 (ddd, 1 H, J = 0.6
Hz, 1.2 Hz, 7.2 Hz), 7.57 (dd, 1 H, J = 1.2
Hz, 7.2 Hz), 7.61 (dd, 1 H, J = 1.6
Hz, 7.0 Hz, 8.6 Hz), 8.06 (s, 1 H), 8.18 (ddd, 1 H, J = 0.4 Hz, 1.6 Hz, 8.0 Hz); 13C
NMR [50(16) MHz, CDCl3] δ 12.1,
13.7, 38.5, 42.8, 118.2, 123.5, 124.2, 125.3, 126.0, 126.1, 128.3,
128.7, 131.4, 133.8, 137.5, 154.7, 156.3, 170.2, 176.2; MS (EI) m/z 321
(M+, 13), 320 (24), 249 (100), 221 (55), 192
(6), 165 (25) Anal. calcd. for C20H19NO3:
C, 74.75; H 5.96 N, 4.36. Found: C, 74.95; H 5.54 N, 4.07.
16 Compound 12:
white solid (14%): mp 183-185 °C (EtOH); IR
(KBr) 1719 (C=O), 1649 (C=O) cm-1; 1H
NMR (200 MHz, CDCl3) δ 7.19 (m, 2 H), 7.33 (m,
1 H), 7.70 (m, 2 H), 7.78 (m, 2 H), 7.92 (m, 1 H); 13C
NMR (50 MHz, CDCl3) δ 104.2, 113.7, 118.6, 122.6,
123.6, 125.8, 126.2, 127.1, 132.0, 135.2, 139.8, 142.3, 167.0, 171.3,
192.6; MS (EI)
m/z 252 (M+, 62), 224
(41), 223 (23), 196 (26), 195 (15), 180 (100), 168 (37) Anal. calcd.
for C15H8O4: C, 71.43; H 3.20. Found:
C, 71.74; H 3.10.
17
Letcher RM.
Kwok N.-C.
Lo W.-H.
Ng K.-W.
J. Chem. Soc. Perkin Trans. 1
1998,
1715
18 Wrightiadione 1:
A solution of LDA in dry THF (10 mL) was prepared as in ref.
[10]
using diisopropylamine
(0.4 mL, 2.6 mmol) and 0.7 M solution of n-BuLi
(3.0 mL, 2.5 mmol) in hexane. The LDA was stirred for 30 min at -78 °C,
and then isoflavone 4 (0.15 g, 0.5 mmol)
in dry THF (5 mL) was added. Stirring at this temperature was continued
for 2 h and then the reaction mixture was warmed to room temperature. Water
was added and the mixture was stirred for 30 min. The organic layer
was separated and washed again with water, dried over Na2SO4,
filtered, and evaporated under reduced pressure. The resulting orange
residue was purified by preparative layer chromatography on silica
gel using CH2Cl2 as eluent to give crystals
of wrightiadione 1 (0.07 g, 49%).