572 RESEARCH PAPER
OCTOBER, 572–573
JOURNAL OF CHEMICAL RESEARCH 2007
Synthesis of 2-alkylisoflavones under phase-transfer catalysis
conditions
Dai DeMing* and Weng LingLing
Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, ChengDu, Sichuan, 610041 China
2-alkyl isoflavones were synthesised with the aliphatic acid chloride and 2-hydroxydeoxybenzoins under phase-
transfer catalysis in acetone–K2CO3 medium involves the modified Baker–VenKataraman transformation
Keywords: tetrabutylammonium hydrogen sulfate, aliphatic acid chloride, 2-hydroxydeoxybenzoins, 2-alkyl isoflavone
Isoflavones are widely found in a number of natural products.
These natural products have demonstrated numerous
biological activities such as antioxidant,1 anti-inflammatory,2
anticardiovascular and anticarcinogenic activities.3
Table 1 Synthesis of 7-hydroxyl-2-methylisoflavone with the
change of amount of acetyl chloride and tetrabutylammonium
hydrogen sulfate
No.
Acetyl chloride/
equiv
TBAHSO4/
equiv
Reaction
time/h
Yield/%
Previously the synthesis of 2-alkyl isoflavones can be
achieved by adopting the Kostanecki–Robinson reaction,4,5
the method got the 2-alkyl isoflavone through the reaction of
aliphatic acid anhydrides and 2-hydroxydeoxybenzoins in the
presence of the sodium or potassium salt of the corresponding
acid under the refluxing condition, but the reaction needed
high-temperature and long reaction time. Recently the
Kostanecki–Robinson reaction was modified, and the sodium
salt of the aliphatic acid was replaced with triethylamine,6–8
the modification lowered the reaction temperature, but the
yield is not very good.
The modified Baker–VenKataraman transformation were
extensively used to synthesise the flavone compounds,9
and the 2-phenylisoflavones10 and 2-furylisoflavones11 also
were synthesised. The method use 2-hydroxydeoxybenzoins
and aromatic acid chloride to react and get isoflavones in
acetone-K2CO3 medium with refluxing, the procedure was
very simple. Recentyl 2-arylisoflavones were also acquired
with high yield under phase transfer catalysis conditions
using tetrabutylammonium hydrogen sulfate as phase
transfer catalyst, benzene as a solvent and 20% aq. potassium
carbonate as a basic catalyst.12
Initial attempts to synthesise 7-hydroxyl-2-methylisoflavone
with acetyl chloride and 2,4-dihydroxydeoxybenzoin in
acetone–K2CO3 medium involve the modified Baker–
VenKataraman transformation, but did not give the 7-
hydroxyl-2-methylisoflavone. When we added tetrabutyl-
ammonium hydrogen sulfate, we obtained the 7-hydroxyl-
2-methylisoflavone. When the acetyl chloride was
3 equivalents and tetrabutylammonium hydrogen sulfate was
0.4 equivalents, the yield reached 85% (Table 1).
This success led us to study a variety of 2-hydroxy-
deoxybenzoins and aliphatic acid chlorides. Two new
isoflavones: 7-hydroxyl-2-propylisoflavone and 7-hydroxy-2-
butylisoflavone were obtained (Table 2).
1
2
3
4
5
6
7
8
0.2
0.2
0.2
0.2
0.2
0.2
0.2
0.3
0
10
10
10
10
10
10
10
10
0
8
0.01
0.05
0.10
0.20
0.40
0.50
0.40
15
24
50
65
71
85
mild reaction condition should find a widespread use as the
method of choice to synthesise 2-alkylisoflavones.
General procedure for synthesising 2-alkyl isoflavones
1H NMR spectra were measured at 400 MHz on a Varian-Inova 400
spectrometer, 13C NMR were measured at 200 MHz on a Bruker–
ACE200 spectrometer, and chemical shifts are reported in parts per
million (ppm) (δ) relative to TMS as internal standard. Mass spectra
(ESI) were determined on API3000 spectrometer and reported
as m/z. Microanalyses were measured using a Carbo-Erba110G
microelemental analyser.
2-hydroxydeoxybenzoins (10 mmol) in acetone (45 ml),
tetrabutylammonium hydrogen sulfate (TBAHSO4, 4 mmol) and
anhydrous potassium carbonate (4.5 g) were placed in a flask
and aliphatic acid chloride (30 mmol) was added dropwise with
stirring during 15–20 min.The mixture was stirred for 2 h at room
temperature, then was refluxed for 10 h at 75˚C with stirring.
The mixture was cooled down and filtered, and solvent of the filter
was removed under reduced pressure to give a semi-solid which was
refluxed with 5% ethanolic potassium hydroxide(15 ml) for 20 min.
The crude semi-solid after removal of ethanol from solution was
diluted with water (5 ml) and acidified with dilute hydrochloric acid
(15 ml). The resulting solid was filtered, washed with 5% aq. Sodium
bicarbonate solution, dried and recrystallised. from the ethanol to
give the corresponding isoflavones.
Data for 7-hydroxy-2-propylisoflavone, m.p. 174–176˚C, 1H NMR,
d6-DMSO, δ 0.81–0.84(t, 3H), 1.59–1.69(m, 2H), 2.44–2.52(m, 2H),
6.86–6.864(d, 1H), 6.91–6.93(dd, 1H), 7.23–7.45(m, 5H arom),
7.88–7.90(d, 1H) 10.79(s, 1H, -OH). 13C NMR δ: 175.24, 165.17,
162.75, 157.36, 133.63, 130.67, 128.23, 127.25, 127.57, 122.65,
115.78, 115.00, 102.14, 33.66, 20.34, 13.84. m/z 280.1 Anal. Calcd.
for C18H16O3: C, 77.12; H, 5.75. Found C, 77.18, H, 5.71
In summary, we have described a practical, efficient and
inexpensive pathway for the synthesis of 2-alkylisoflavones in
excellent yields using tetrabutylammonium hydrogen sulfate
as phase transfer catalyst in acetone–K2CO3 medium involves
the modified Baker–VenKataraman transformation. The
availability of tetrabutylammonium hydrogen sulfate and the
Data for 7-hydroxy-2-butylisoflavone, m.p. 162–164˚C, 1H NMR,
d6-DMSO, δ 0.74–0.77(t, 3H), 1.16–1.26(m, 2H), 1.55–1.63(m,
2H), 2.44–2.53(m, 2H), 6.85–6.86(d, 1H), 6.90–6.93(dd, 1H), 7.22–
7.45(m, 5H arom), 7.88–7.90(d, 1H), 10.78(s, 1H, –OH). 13C NMR
HO
OH
HO
O
O
R
1.RCOCl,TABHSO4,K2CO3
R2
R2
2.KOH/C2H5OH
R1
O
R1
Scheme 1
* Correspondent. E-mail:dai6617@tom.com
PAPER: 07/4803
Dai, DeMing
