An efficient synthesis of bibenzylic oxygen heterocycles

Article abstract of DOI:10.3184/030823407X256091

The first total syntheses of naturally occurring 6-methoxy-4-(2- phenylethyl)benzofuran (1) and 2,2-dimethyl-7-methoxy-5-(2-phenylethyl)chroman (2) and the non-natural 7-methoxy-5-(2-phenylethyl)chromen-2-one (3) are described from 3,5-dimethoxyphenylacet

Full text of DOI:10.3184/030823407X256091

590 RESEARCH PAPER
OCTOBER, 590–593
JOURNAL OF CHEMICAL RESEARCH 2007
An efficient synthesis of bibenzylic oxygen heterocycles
Virendra B. Kumbhara, Augustine R. Josepha, Arun D. Natua, Radhika S. Kusurkarb and
Madhusudan V. Paradkara*
aDepartment of Chemistry, Post-Graduate and Research Centre, Abasaheb Garware College, Karve road, Pune 411 004.
Maharashtra, India
bDepartment of Chemistry, University of Pune, Ganeshkhind Road, Pune, India
The first total syntheses of naturally occurring 6-methoxy-4-(2-phenylethyl)benzofuran (1) and 2,2-dimethyl-7-
methoxy-5-(2-phenylethyl)chroman (2) and the non-natural 7-methoxy-5-(2-phenylethyl)chromen-2-one (3) are
described from 3,5-dimethoxyphenylacetic acid in good yields.
Keywords: bibenzylic oxygen heterocycles, Wittig reaction, Friedel–Crafts acylation
Bibenzyls and their derivatives containing oxygen
heterocyclic ring systems are of synthetic importance because
they constitute an important class of natural and non-natural
products, many of which exhibit useful biological activities.
They have been employed as 5-lipoxygenase inhibitors,1
antifungal agents,2 antimicrobial agents2 and vasopressin
antagonists.2
Owing to the natural occurrence and important biological
properties, several interesting synthetic methods have
been developed1,3-4 for bibenzyls and their oxygen hetero-
cyclic derivatives. 2,2-dimethyl-7-methoxy-5-(2-phenylethyl)
chromene,forexample,isolatedfromR.kojanawassynthesised
from 3-hydroxy-5-methoxy-2-(3-methylbutenyl)bibenzyl and
Asakawa et al. have reported1 two synthetic routes for 2,2-
ethyl bromoacetate to obtain the aryloxy derivative (9).
Saponification of (9) and treatment of the resultant acid
(10) with sodium acetate in Ac2O:AcOH (1:1) provided the
required natural product (1).
The other natural product viz. 2,2-dimethyl-7-methoxy-
5-(2-phenylethyl)chroman (2) was synthesised (Scheme 2)
by regiospecific introduction of an acetyl group into 1,3-
dimethoxy-5-(2-phenylethyl)benzene4 (6) by using glacial
acetic acid in the presence of trifluoroacetic anhydride (TFAA)
to give 2-acetyl-1,5-dimethoxy-3(-2-phenylethyl)benzene
(11). Selective demethylation of (11) by anhydrous AlCl3
in dry DCM provided 2-acetyl-1-hydroxy-5-methoxy-3-
(2-phenylethyl)benzene (12) which was reacted with an excess
of acetone in the presence of pyrrolidine and the resultant
chromone (13) was subjected to Wolf–Kishner reduction to
furnish the target chroman (2).
Finally, the non-natural coumarin derivative 7-methoxy-5-
(2-phenylethyl)chromen-2-one (3) was obtained by reacting
the previously synthesised 2,4-dimethoxy-6-(2-phenylethyl)
benzaldehyde (7) with (carbethoxymethylene)triphenylphos-
phorane in dry toluene as depicted in Scheme 3.
To conclude, we have accomplished the first total synthesis
of two natural products, 6-methoxy-4-(2-phenylethyl)
benzofuran (1) and 2,2-dimethyl-7-methoxy-5-(2-phenylethyl)
chroman (2) and the non-natural 7-methoxy-5-(2-phenylethyl)
chromen-2-one (3) in good yields by using easily accessible
starting materials and involving simple reaction conditions
and convenient workup procedures.
dimethyl-7-hydroxy-5-(2-phenylethyl)chroman.
However,
the drawbacks of these methods are the significantly low
yields of desired products and the formation of unwanted
by-products. In recent years we have initiated efforts on the
development of convenient synthetic methods for various
natural and non-natural oxygen heterocycles as well as their
biological activity screening. Our interest in bibenzylic
compounds stems from the occurrence of these systems in
biologically active oxygen heterocyclic compounds and
natural products.
Herein, we report the first total synthesis of 6-methoxy-4-
(2-phenylethyl)benzofuran (1) and 2,2-dimethyl-7-methoxy-
5-(2-phenylethyl)chroman (2), both of which are known
to occur in nature and a non-natural coumarin derivative
viz. 7-methoxy-5-(2-phenylethyl)chromen-2-one (3) for the
purpose of screening for potential bioactivity.
Experimental
Melting points were determined in capillaries and are uncorrected.
1H NMR spectra were measured in CDCl3 on a Varian Mercury 300
MHz FT-NMR spectrometer. The chemical shifts are expressed in
parts per million (ppm) using TMS as an internal standard. Coupling
constants are in Hz. IR spectra were recorded on a Perkin Elmer
spectrum BX FTIR spectrometer and are reported in wave-numbers
(cm-1). Elemental analyses were acquired using a HOSLI semi-
automatic CHN analyser.
H3CO
H3CO
O
H3CO
O
O
O
2-(3,5-Dimethoxyphenyl)-1-phenylethanone (5): A slurry of finely
powered anhydrous AlCl3 (2.5 g, 18 mmol) in dry benzene (50 ml)
was stirred at room temperature. To this mixture, a solution of 3,
5-dimethoxyphenylacetyl chloride [prepared by refluxing a mixture
of 3,5-dimethoxyphenylacetic acid (1 g, 5 mmol) and SOCl2 (1 ml,
14 mmol) in DCM (20 ml) for 1 h] in dry benzene (20 ml) was added
drop-wise under stirring over a period of 15 min. To the resultant
black-coloured mixture was added ice-cold water (50 ml) and conc.
HCl (20 ml). The organic layer was separated and the aqueous layer
was extracted with ether (2 ¥ 20 ml). Combined organic layers
were washed successively with water (2 ¥ 20 ml), satd. NaHCO3
solution (2 ¥ 20 ml), dried over anhydrous Na2SO4 and concentrated
under reduced pressure. The crude product was purified by column
chromatography over silica gel using hexane-ethyl acetate as eluent
to provide the ketone (5) (1 g) as white solid.
(1)
(2)
(3)
Initially, we focused on synthesising 6-methoxy-4-
(2-phenylethyl)benzofuran (1) starting from 3,5-dimethoxy-
phenylacetic acid (4) as depicted in Scheme 1. The acid
chloride of (4) was reacted with dry benzene in presence of
anhydrous AlCl3 and the ensuing ketone (5) was reduced
under Wolf–Kishner reduction conditions to provide 1,3-
dimethoxy-5-(2-phenylethyl)benzene4 (6). Vilsmeier–Haack
formylation of (6) followed by demethylation reaction
using anhydrous AlCl3 afforded 2-hydroxy-4-methoxy-6-
(2-phenylethyl)benzaldehyde (8), which was treated with
Yield: 77%; m.p. 66°C, (lit5. m.p. 65–66°C); IR: 1685 cm-1; 1H NMR:
d 3.74 (s, 6H), 4.18 (s, 2H), 6.40 (s, 3H), 7.46 (t, 3H), 7.98 (d, J = 8 Hz,
2H);Anal. calcd. for C16H16O3: C, 75.00; H, 6.25. Found: C, 75.0; H, 6.45.
* Correspondent. E-mail: madhusudanparadkar@yahoo.co.in
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JOURNAL OF CHEMICAL RESEARCH 2007 591
H3CO
OCH3
H3CO
OCH3
O
H3CO
OCH3
i
iii
ii
COOH
(4)
(5)
(6)
H3CO
OCH3
CHO
H3CO
OH
H3CO
OR
iv
v
vi
CHO
CHO
(7)
(8)
(9)
R = CH2COOC2H5
H3CO
OCH2COOH
CHO
H3CO
O
vii
viii
(10)
(1)
Scheme 1 Reagents and conditions: (i) SOCl2, DCM, 1 h, reflux; (ii) dry benzene, AlCl3; (iii) NH2NH2.H2O, ethylene glycol, KOH,
reflux, 3 h; (iv) DMF, POCl3, 50°C, 5 h; (v) AlCl3, DCM, 1 h, r.t.; (vi) ethyl bromoacetate, DMF, K2CO3, 1 h, r.t.; (vii) 5% aq. NaOH,
heat, 0.5 h, followed by conc. HCl; (viii) NaOAc, Ac2O–AcOH, heat, 1 h.
1,3-Dimethoxy-5-(2-phenylethyl)benzene (6): A mixture of 2-(3,5-
dimethoxyphenyl)-1-phenylethanone (5) (2 g, 7.8 mmol) and
hydrazine hydrate (4 ml) was heated on a water bath. To this
ethylene glycol (40 ml) was added and the mixture was refluxed
until a homogenous solution resulted. KOH (6 g, 107 mmol) was
carefully added into this refluxing solution in small portions over a
period of 2 h. The reaction mixture was refluxed for an additional
1 h when TLC indicated completion of reaction. After cooling
the reaction mixture to room temperature it was poured into a
beaker containing ice-cold conc. HCl (10 ml) and extracted with
ether (2 ¥ 50 ml). The ether layer was washed thoroughly with
water, dried over anhydrous Na2SO4, concentrated under
reduced pressure and the crude residue was purified by column
chromatography over silica gel using hexane as eluent to obtain
the required 1,3-dimethoxy-5-(2-phenylethyl)benzene (6) (1.46 g) as
pale yellow viscous oil.
H3CO
OCH3
H3CO
OCH3
H3CO
OH
i
ii
O
O
(6)
(11)
(12)
H3CO
O
H3CO
O
O
iii
iv
(13)
(2)
Scheme 2 Reagents and conditions: (i) glacial AcOH, TFAA, r.t. 3 h; (ii) AlCl3, DCM, R.T., 1 h; (iii) acetone, pyrrolidine,
dry benzene, reflux, 48 h; (iv) NH2NH2.H2O, ethylene glycol, KOH, reflux, 3 h.
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592 JOURNAL OF CHEMICAL RESEARCH 2007
H3CO
OH
aqueous NaHCO3 solution (5%, 10 ml), removing the insoluble
matter by filtration and acidifying the filtrate to pH 1–2 with conc.
HCl to obtain the required acid (10) (0.83 g) as off-white solid which
was sufficiently pure to be subjected to the next reaction.
Yield: 90%; m.p. 115°C.
H3CO
O
O
i
CHO
6-Methoxy-4-(2-phenylethyl) benzofuran (1):
A mixture of
2-formyl-5-methoxy-3-(2-phenylethyl)phenoxyethanoic acid (10)
(0.5 g, 1.6 mmol) and freshly fused NaOAc (0.4 g, 4.88 mmol) in
acetic acid (2.5 ml) and acetic anhydride (2.5 ml) was heated in an
oil bath at 140°C for 1 h. The reaction mixture was poured onto ice
(25 g). The resultant oil was extracted with ether (2 ¥ 20 ml).
The ether layer was washed successively with water (2 ¥ 10 ml),
satd. NaHCO3 solution (2 ¥ 10 ml), brine (2 ¥ 10 ml) and dried
over anhydrous Na2SO4. Removal of the solvent under reduced
pressure provided the crude product which was purified by column
chromatography over silica gel using hexane as eluent to obtain the
required natural product 6-methoxy-4-(2-phenylethyl)benzofuran (1)
(0.25 g) as colourless viscous oil.
(7)
(3)
Scheme 3 Reagents and conditions: (i) Ph3P =CHCOOEt,
dry toluene, reflux, 48 h.
Yield: 77%; m.p. oil, (lit4. m.p. oil); 1H NMR: d 2.86 (brs, 4H),
3.72 (s, 6H), 6.29 (m, 3H), 7.17 (m, 5H); Anal. calcd. for C16H18O2:
C, 79.65; H, 8.39. Found: C, 79.3; H, 8.1.
Yield: 63%; m.p. oil, (lit1. m.p. oil); 1H NMR: d 2.96 (m, 2H),
3.06 (m, 2H), 3.83 (s,3H), 6.67 (dd, J = 1.0, 2.2 Hz, 1H), 6.70 (d,
J = 2.2 Hz, 1H), 6.90 (brs, 1H), 7.20 (m, 5H) 7.51 (d, J = 2.2 Hz, 1H);
13C NMR: d 35.8, 38.0, 55.9, 93.6, 105.2, 110.9, 120.1, 126.0, 128.0,
128.6, 135.2, 141.5, 143.5, 156.0, 157.8; Anal. calcd. for C17H16O2:
C, 80.95; H, 6.34. Found: C, 81.2; H, 6.1.
2,4-Dimethoxy-6-(2-phenylethyl)benzaldehyde (7): To a complex
prepared from dry DMF (0.7 ml, 9.1 mmol) and POCl3 (0.9 ml,
9.62 mmol) at 0ºC was added 1,3-dimethoxy-5-(2-phenylethyl)
benzene (6) (2 g, 8.26 mmol). The mixture was stirred and heated
at 50°C for 5 h. The reaction mixture was poured into a beaker
containing a satd. solution of NaOAc (50 ml) and the resultant oil was
extracted with ethyl acetate (2 ¥ 20 ml), washed successively with
water (10 ml), satd. NaHCO3 solution (10 ml) and again with water
(10 ml). The organic layer was dried over anhydrous Na2SO4, filtered
and concentrated under reduced pressure and the crude reside was
purified by silica gel column chromatography using hexane as eluent
to afford the required compound (7) (1.34 g) as colourless solid.
Yield: 60%; m.p. 83°C; IR: 1674 cm-1; 1H NMR: d 2.81 (t,
J = 8.0 Hz, 2H), 3.22 (t, J = 8.0 Hz, 2H), 3.77 (s, 3H), 3.86 (s, 3H),
6.20 (d, J = 2.4 Hz, 1H), 6.31 (d, J = 2.4 Hz, 1H), 7.25 (m, 5H), 10.5
(s, 1H); Anal. calcd. for C17H18O3: C, 75.55; H, 6.66. Found: C, 75.9;
H, 6.4.
2-Acetyl-1,5-dimethoxy-3(-2-phenylethyl)benzene (11): To a solution
of 1,3-dimethoxy-5-(2-phenylethyl)benzene (6) (0.3 g, 1.24 mmol)
in dry DCM (6 ml), a mixture of glacial acetic acid (0.1 ml) and
trifluoroacetic anhydride (0.3 ml) was added. The reaction mixture was
stirred for 3 h at room temperature. The excess solvent was removed
under reduced pressure and the resultant residue was extracted in ether
(25 ml). The organic layer was washed with water (2 ¥ 10 ml), satd.
NaHCO3 solution (2 ¥ 10 ml) and brine (10 ml), dried over anhydrous
Na2SO4, filtered and the filtrate was concentrated under reduced
pressure. The residue was purified by column chromatography over
silica gel using hexane:ethyl acetate (9:1) as eluent to provide the
required compound (11) (0.23 g) as a light yellow oil.
2-Hydroxy-4-methoxy-6-(2-phenylethyl)benzaldehyde
(8):
A
Yield: 73%; m.p. oil; IR: 1680 cm-1; 1H NMR: d 2.43 (s, 3H), 2.76
(brs, 2H), 2.89 (brs, 2H), 3.73 (s, 3H), 3.86 (s, 3H), 6.30 (brs, 2H),
7.04–7.37 (m, 5H). Anal. calcd. for C18H20O3: C, 76.05; H, 7.04.
Found: C, 76.35; H, 7.2.
suspension of finely powered anhydrous AlCl3 (0.3 g, 2.25 mmol) in
dry DCM (10 ml) was stirred at room temperature for 20 min. To this
mixture, a solution of 2,4-dimethoxy-6-(2-phenylethyl)benzaldehyde
(7) (0.37 g, 1.37 mmol) in dry DCM (5 ml) was added under vigorous
stirring over a period of 10 min. The resultant dark green coloured
mixture was stirred at room temperature for an additional 1 h.
The excess solvent was removed under reduced pressure and the
residue was decomposed using ice cold 1:1 HCl/H2O (20 ml) and
extracted with ethyl acetate (2 ¥ 25 ml). The organic layer was
washed successively with water (2 ¥ 20 ml), satd. NaHCO3 solution
(2 ¥ 20 ml) and again with water (2 ¥ 20 ml) and dried over anhydrous
Na2SO4. Removal of organic solvent under reduced pressure followed
by column chromatographic purification of the crude product over
silica gel using hexane as eluent provided the required compound (8)
(0.3 g) as pale yellow solid.
2-Acetyl-1-hydroxy-5-methoxy-3-(2-phenylethyl)benzene
(12):
A suspension of finely powered anhydrous AlCl3 (0.3 g, 2.25 mmol)
in dry DCM (10 ml) was stirred at room temperature for 20 min.
To this mixture, a solution of (11) (0.4 g, 1.41 mmol) in dry DCM
(5 ml) was added under vigorous stirring over a period of 10 min.
The resultant dark green coloured mixture was stirred at room
temperature for an additional 1 h. Excess solvent was removed under
reduced pressure and the residue was treated with ice-cold 1:1 HCl/
H2O (20 ml) and extracted with ethyl acetate (2 ¥ 25 ml). The organic
layer was washed successively with water (2 ¥ 15 ml), satd. NaHCO3
solution (2 ¥ 15 ml), brine (20 ml) and dried over anhydrous Na2SO4.
Removal of the organic solvent under reduced pressure followed by
column chromatographic purification of the crude product over silica
gel using hexane as eluent provided (12) (0.31 g) as light yellow
viscous oil.
Yield: 87%; m.p. 50°C; IR: 1626 cm-1; 1H NMR: d 2.94 (m, 2H), 3.12
(m, 2H), 3.8 (s, 3H), 6.24 (d, J = 2.44 Hz, 1H), 6.26 (d, J = 2.44 Hz,
1H), 7.17 (m, 5H), 9.94 (s, 1H) 12.45 (s, 1H);Anal. calcd. for C16H16O3:
C, 75.00; H, 6.25. Found: C, 74.8; H, 6.5.
Yield: 82%; m.p. oil; IR: 1670 cm-1; 1H NMR: d 2.69 (s, 3H), 2.93 (m,
2H), 3.20 (m, 2H), 3.82 (s, 3H), 6.30 (m, 2H), 7.04–7.37 (m, 5H), 13.2 (s,
1H). Anal. calcd. for C17H18O3: C, 75.55; H, 6.66. Found: C, 75.8; H, 6.9.
2,2-Dimethyl-7-methoxy-5-(2-phenylethyl)chroman-4-one (13): To a
solution of 2-acetyl-1-hydroxy-5-methoxy-3-(2-phenylethyl)benzene
(12) (0.5 g, 1.85 mmol) in dry benzene (5 ml) was added freshly
distilled pyrrolidine (0.2 ml, 1.85 mmol) and dry acetone
(0.25 ml, 3.70 mmol). The resulting solution was allowed to stand
for 15 min, with intermittent swirling at room temperature and
subsequently refluxed using a Dean Stark separator for 48 h when
TLC analysis indicated completion of the reaction. The reaction
mixture was allowed to attain room temperature. Removal of excess
solvent under vacuum provided a residue which was extracted into
ethyl acetate (30 ml). The organic layer was washed successively
with water (2 ¥ 15 ml), dil. HCl (2 ¥ 15 ml), satd. NaHCO3 solution
(2 ¥ 15 ml), brine (20 ml) and dried over anhydrous Na2SO4. Removal
of the organic solvent under reduced pressure followed by column
chromatographic purification of the crude product over silica gel
using hexane as eluent yielded the required compound (13) (0.37 g)
as a colourless oil.
Ethyl 2-formyl-5-methoxy-3-(2-phenylethyl)phenoxyethanoate (9):
Toasolutionof2-hydroxy-4-methoxy-6-(2-phenylethyl)benzaldehyde
(8) (1 g, 3.9 mmol) in dry DMF (10 ml), anhydrous K2CO3 (0.8 g,
5.86 mmol) was added, followed by ethyl bromoacetate (0.65 g,
3.9 mmol). This mixture was stirred at room temperature for 1 h.
After completion of reaction, the reaction mixture was poured onto
crushed ice (50 g) and the resultant oil was extracted with ethyl
acetate (2 ¥ 20 ml). The organic layer was washed with water, dried
over anhydrous Na2SO4 and concentrated under reduced pressure.
Purification of the crude product by column chromatography over
silica gel using hexane-ethyl acetate (3:1) as eluent provided the
required ester (9) as pale yellow crystalline solid (1.14 g).
Yield: 86%; m.p. 71°C; IR: 1753.2 cm-1, 1674 cm-1; 1H NMR:
d 1.29 (t, J = 7.3 Hz, 3H), 2.84 (t, J = 8.0 Hz, 2H), 3.23 (t, J = 8.0 Hz,
2H), 3.79 (s, 3H), 4.30 (q, J = 7.3 Hz, 2H), 4.70 (s, 2H), 6.21 (d,
J = 2 Hz, 1H) 6.25 (d, J = 2 Hz, 1H), 7.26 (m, 5H), 10.62 (s, 1H);
Anal. calcd. for C20H22O5: C, 70.17; H, 6.43. Found: C, 70.4; H, 6.3.
2-Formyl-5-methoxy-3-(2-phenylethyl)phenoxyethanoic acid (10):
A 5% aqueous NaOH solution (5 ml) was added to ethyl 2-formyl-
5-methoxy-3-(2-phenylethyl)phenoxyethanoate (9) (1 g, 2.92 mmol)
and the mixture was heated on a steam bath for 30 min. The solution
was filtered over a pad of celite and the filtrate was acidified to
pH 1–2 with conc. HCl. The precipitated solid was filtered and
washed with water. The solid was further purified by dissolving in
Yield: 65%; m.p. oil; IR: 1688 cm-1; 1H NMR: d 1.40 (s, 3H), 1.60
(s, 3H), 2.6 (brs, 2H), 3.0 (t, J = 6.0 Hz, 2H), 3.5 (t, J = 6.0 Hz, 2H)
3.80 (s, 3H), 6.33 (s, 1H), 6.80 (s, 1H), 7.0–7.3 (m, 5H); Anal. calcd.
for C20H22O3: C, 77.41; H, 7.10. Found: C, 77.7; H, 6.8.
PAPER: 07/4711

JOURNAL OF CHEMICAL RESEARCH 2007 593
2,2-Dimethyl-7-methoxy-5-(2-phenylethyl)chroman (2): A mixture
of 2,2-dimethyl-7-methoxy-5-(2-phenylethyl)chroman-4-one (13)
(0.4 g, 1.29 mmol) and hydrazine hydrate (2 ml) was heated on water
bath. To this ethylene glycol (40 ml) was added and refluxed until a
homogenous solution resulted. KOH (3 g, 53.5 mmol) was carefully
added into this refluxing solution in small portions over a period of
2 h. The reaction mixture was refluxed for an additional 1 h when
TLC indicated completion of reaction. After cooling the reaction
mixture to room temperature it was poured into a beaker containing
ice-cold conc. HCl (5 ml) and extracted with ether (2 ¥ 50 ml).
The ether layer was washed thoroughly with water, dried over
anhydrous Na2SO4, concentrated under reduced pressure and the
crude residue was purified by column chromatography over silica
gel using hexane as eluent to obtain the desired natural product
2,2-dimethyl-7-methoxy-5-(2-phenylethyl)chroman (2) (0.3 g) as a
colourless oil.
Yield: 76%; m.p. oil; IR: 1730 cm-1; 1H NMR: d 2.9 (m, 2H),
3.1 (m, 2H), 3.82 (s, 3H), 6.16 (d, J = 9.1 Hz, 1H), 6.64 (brs, 1H),
6.67 (brs, 1H), 7.1–7.3 (m, 5H), 7.7 (d, J = 9.1 Hz, 1H); 13C NMR:
d 31.6, 35.8, 55.6, 102.8, 108.0, 112.0, 120.7, 126.0, 128.0, 128.6,
140.8, 141.2, 143.8, 151.5, 160.1, 160.7; Anal. calcd. for C18H16O3:
C, 77.14; H, 5.71. Found: C, 77.5; H, 5.9.
We are thankful to Dr S.N. Bhide, Principal, and Dr. H. G. Damle,
Head, Department of Chemistry, Abasaheb Garware College,
Pune, for providing the necessary facilities. We are also
thankful to the Department of Chemistry, University of Pune,
for providing spectroscopic and elemental analyses.
Received 19 June 2007; accepted 29 October 2007
Paper 07/4711 doi: 10.3184/030823407X256091
Yield: 79%; m.p. oil (lit.1. m.p. oil); 1H NMR: d 1.3 (s, 3H), 1.4 (s,
3H),1.69(brs,2H),2.52(brs,2H),2.84(brs,4H),3.80(s,3H),6.32(brs,
2H), 7.1 (m, 5H); 13C NMR: d 16.8, 27.4, 27.6, 32.2, 34.5, 37.8, 55.6,
75.8, 100.2, 105.8, 114.4, 126.0, 128.0, 128.5, 138.8, 140.8, 154.5,
159.9; Anal. calcd. for C20H24O2: C, 81.04; H, 8.16. Found: C, 81.4;
H, 8.33.
7-Methoxy-5-(2-phenylethyl)chromen-2-one (3): A solution of
2-hydroxy-4-methoxy-6-(2-phenylethyl)benzaldehyde (8) (0.3 g,
1.17 mmol) and (carbethoxymethylene)triphenylphosphorane (0.4 g,
1.17 mmol) in toluene (10 ml) was refluxed for 48 h. The excess
solvent was removed under reduced pressure to yield a residue,
which on purification by column chromatography over silica gel
using hexane as eluent provided the required coumarin (3) (0.25 g)
as light yellow oil.
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