Modified coumarins. 29. Synthesis of structural analogs of natural 6-arylfuro[3,2-g]chromen-7-ones

Article abstract of DOI:10.1007/s10600-009-9261-x

3-Substituted 6-arylfuro[3,2-g]chromen-7-ones, structural analogs of natural furocoumarins, were synthesized by linear annelation of a furan fragment to a 3-arylcoumarin system.

Full text of DOI:10.1007/s10600-009-9261-x

Chemistry of Natural Compounds, Vol. 45, No. 2, 2009
MODIFIED COUMARINS. 29. SYNTHESIS OF STRUCTURAL
ANALOGS OF NATURAL 6-ARYLFURO[3,2-g]CHROMEN-7-ONES
1*
2
1
2
M. M. Garazd, Ya. L. Garazd, A. S. Ogorodniichuk, and V. P. Khilya
UDC 547.814.5
3-Substituted 6-arylfuro[3,2-g]chromen-7-ones, structural analogs of natural furocoumarins, were synthesized
by linear annelation of a furan fragment to a 3-arylcoumarin system.
Key words: coumarins, 3-arylcoumarins, furocoumarins, psoralene.
Furocoumarins are structurally varied natural compounds that are mostly derivatives of the linear furocoumarin
psoralene [1]. The heightened interest in furocoumarins is due to the important role that they play in the life processes of
plants and animals and their high and varied biological activity [2]. In most instances furocoumarins are unsubstituted in the
2- and 3-positions of the pyran-2-one ring. However, compounds containing aryl substituents in these positions have been
isolated from natural sources. Examples of such secondary metabolites based on the 3-arylcoumarin core are pachyrrhizin {6-
(6-methoxy-1,3-benzodioxol-5-yl)furo[3,2-g]chromen-7-one}, which was isolated from the plants Pachyrrhizus erosus [3-5],
P. tuberosus [6], Neorautassenia pseudopachyrriza [7], and N. edulis [8-10]; neofolin {9-methoxy-6-(6-methoxy-1,3-
benzodioxol-5-yl)furo[3,2-g]chromen-7-one}, which was isolated from Neorautanenia ficifolia [11]; and 6-(2,4,5-
trimethoxyphenyl)furo[3,2-g]chromen-7-one, which is produced by P. tuberosus [6].
We synthesized substituted 6-arylfuro[3,2-g]chromen-7-ones, structural analogs of natural furocoumarins, based on
the 3-arylcoumarin core.
7-Acetoxycoumarins 1-5 were prepared by a Perkin—Oglialoro reaction [12] of 2,4-dihydroxybenzaldehyde and
substituted phenylacetic acids in acetic anhydride in the presence of pyridine. Acidolysis of 1-5 formed 7-hydroxy-3-
arylcoumarins 6-10 that were required for further transformations.
O
O
HO
O
O
O
O
AcO
O
O
O
c
b
a
R
R
R
R
1
1
R
3
R
3
2
2
1 - 5
6 - 10
a. EtOH, H SO ; b. R COCH Hal, K CO ; c. 1. NaOH, 2. H SO
4
11 - 24
25 - 38
2
4
3
2
2
3
2
1, 6: R = R = H; 2, 7: R = H, R = F; 3, 8: R = H, R = Cl; 4, 9: R = H, R = OMe; 5, 10: R = R = OMe
1
2
1
2
1
2
1
2
1
2
11, 25: R = R = H, R = CH ; 12, 26: R = H, R = F, R = CH ; 13, 27: R = H, R = Cl, R = CH
1
2
3
3
1
2
3
3
1
2
3
3
14, 28: R = H, R = OMe, R = CH ; 15, 29: R = R = OMe, R = CH ; 16, 30: R = R = H, R = (CH ) C
1
2
3
3
1
2
3
3
1
2
3
3 3
17, 31: R = H, R = F, R = (CH ) C; 18, 32: R = H, R = OMe, R = (CH ) C; 19, 33: R = H, R = Cl, R = Ph
1
2
3
3 3
1
2
3
3 3
1
2
3
20, 34: R = R = OMe, R = Ph, 21, 35: R = R = H, R = 4-Me-Ph; 22, 36: R = H, R = OMe, R = 4-F-Ph
1
2
3
1
2
3
1
2
3
23, 37: R = R = H, R = 3-MeO-Ph; 24, 38: R = H, R = Cl, R = 3-MeO-Ph
1
2
3
1
2
3
The reaction of hydroxycoumarins 6-10 with α-haloketones under Williamson conditions produced the corresponding
substituted oxoethers 11-24. The alkylating agents in these syntheses were chloroacetone (11-15), 1-chloropinacolone (16-
18), phenacylbromide (19 and 20), 4-methylphenacylbromide (21), 4-fluorophenacylchloride (22), and 3-methoxy-
phenacylbromide (23 and 24).
1) Institute of Bioorganic and Petroleum Chemistry, National Academy of Sciences of Ukraine, 02094, Ukraine,
Kiev, ul. Murmanskaya, 1, e-mail: gmm@i.com.ua; 1) Taras Shevchenko Kiev National University, 01033, Ukraine, Kiev, ul.
Vladimirskaya, 64. Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 140-144, March-April, 2009. Original article
submitted November 6, 2007.
©
158
0009-3130/09/4502-0158 2009 Springer Science+Business Media, Inc.

Ketones 11-24 under MacLeod cyclization conditions [13] upon heating with NaOH solution (1 N) and subsequent
acidolysis were cyclized smoothly and in high (69-89%) yields to 3-substituted-6-arylfuro[3,2-g]chromen-7-ones (25-38).
Linear annelation of the furan ring at the 6,7-positions of the 3-arylcoumarin was confirmed by PMR spectroscopy.
The PMR spectra of 25-38 showed a simplified splitting pattern for the aromatic protons compared with the starting ketones
due to decoupling of the 6-proton of the 3-arylcoumarin ring. Protons H-4 and H-9 in 3-substituted 6-arylfuro[3,2-g]chromen-
7-ones resonated as singlets at 7.82-8.34 and 7.60-7.71 ppm, respectively. Furthermore, PMR spectra of 6-arylfuro[3,2-
g]chromen-7-ones 25-38 exhibited a singlet for proton H-2, a characteristic feature of annelation of the furocoumarin ring.
The singlet of proton H-2 was located at 7.56-7.97 ppm with alkyl substituents (25-32) in the 3-position of the 6-arylfuro[3,2-
g]chromen-7-one. Aryl substituents in the 3-position (33-38) shifted the resonance of H-2 to weaker (8.37-8.48 ppm) field.
EXPERIMENTAL
The course of reactions and purity of products were monitored by TLC on Merck 60 F254 plates with CHCl :CH OH
3
3
(9:1 and 19:1) as eluents. Melting points were determined on a Kofler block. PMR spectra were recorded on Varian VXR-300
and Mercury 400 spectrometers at 300 and 400 MHz, respectively, relative to TMS (internal standard). Elemental analyses of
all compounds agreed with those calculated.
7-Acetoxy-3-arylcoumarins 1-5. A mixture of 2,4-dihydroxybenzaldehyde (13.8 g, 0.1 mol), the appropriate arylacetic
acid (0.1 mol), freshly distilled acetic anhydride (30 mL), and anhydrous pyridine (30 mL) was refluxed for 12 h and cooled.
The resulting precipitate was filtered off and crystallized from propanol-2.
7-Acetoxy-3-phenylchromen-2-one (1): yield 56%, mp 187-188°C (lit. [14] 182-183°C, [15] 182-184°C, [16] 184-
185°C, [17] 185-187°C, [18] 186°C), C H O .
17 12
4
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 2.33 (3H, s, CH COO-7), 7.18 (1H, dd, J = 2.0, 8.0, H-6), 7.32
6
3
(1H, d, J = 2.0, H-8), 7.44 (3H, m, H-3′, H-4′, H-5′), 7.72 (2H, d, J = 8.0, H-2′, H-6′), 7.82 (1H, d, J = 8.0, H-5), 8.26 (1H, s,
H-4).
3-(4-Fluorophenyl)-7-acetoxychromen-2-one (2): yield 67%, mp 203-204°C (lit. [12] 208°C), C H FO .
17 11
4
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 2.31 (3H, s, CH COO-7), 7.19 (1H, dd, J = 2.0, 8.0, H-6), 7.28-
6
3
7.33 (3H, m, H-8, H-3′, H-5′), 7.77 (2H, m, H-2′, H-6′), 7.80 (1H, d, J = 8.0, H-5), 8.26 (1H, s, H-4).
3-(4-Chlorophenyl)-7-acetoxychromen-2-one (3): yield 71%, mp 206-207°C (lit. [12] 202°C), C H ClO .
17 11
4
PMR spectrum (300 MHz, CDCl , δ, ppm, J/Hz): 2.36 (3H, s, CH COO-7), 7.08 (1H, dd, J = 2.1, 8.1, H-6), 7.16 (1H,
3
3
d, J = 2.1, H-8), 7.42 (2H, d, J = 8.1, H-3′, H-5′), 7.55 (1H, d, J = 8.1, H-5), 7.64 (2H, d, J = 8.1, H-2′, H-6′), 7.80 (1H, s,
H-4).
7-Acetoxy-3-(4-methoxyphenyl)chromen-2-one (4): yield 64%, mp 181-182°C (lit. [19] 178°C, [20] 177-178°C),
C H O .
18 14
5
PMR spectrum (300 MHz, CDCl , δ, ppm, J/Hz): 2.35 (3H, s, CH COO-7), 3.85 (3H, s, CH O-4′), 6.98 (2H, d,
3
3
3
J = 8.7, H-3′, H-5′), 7.08 (1H, dd, J = 2.1, 8.1, H-6), 7.14 (1H, d, J = 2.1, H-8), 7.52 (1H, d, J = 8.1, H-5), 7.66 (2H, d, J = 8.7,
H-2′, H-6′), 7.74 (1H, s, H-4).
7-Acetoxy-3-(3,4-dimethoxyphenyl)chromen-2-one (5): yield 68%, mp 179-180°C (lit. [17] 173-175°C), C H O .
19 16
6
PMR spectrum (300 MHz, CDCl , δ, ppm, J/Hz): 2.35 (3H, s, CH COO-7), 3.93 and 3.95 (6H, 2s, CH O-3′,
3
3
3
CH O-4′), 6.94 (1H, d, J = 8.4, H-5′), 7.07 (1H, dd, J = 2.1, 8.1, H-6), 7.15 (1H, d, J = 2.1, H-8), 7.26-7.30 (2H, m, H-2′,
3
H-6′), 7.54 (1H, d, J = 8.1, H-5), 7.77 (1H, s, H-4).
7-Hydroxy-3-arylcoumarins 6-10. A suspension of acetate 1-5 (50 mmol) in ethanol (50 mL) was treated with
H SO (20 mL, 20%), refluxed for 5-10 h (end of reaction determined by TLC), and cooled. The resulting solid was filtered
2
4
off.
7-Hydroxy-3-phenylchromen-2-one (6): yield 86%, mp 205-206°C (lit. [21] 204-205°C, [15] 206-208°C, [22]
207-208°C, [23] 209°C, [14, 18, 24] 209-210°C, [25] 211-212°C, [26] 212-213°C), C H O .
15 10
3
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 6.76 (1H, d, J = 2.0, H-8), 6.80 (1H, dd, J = 2.0, 8.0, H-6),
6
7.38-7.46 (3H, m, H-3′, H-4′, H-5′), 7.61 (1H, d, J = 8.0, H-5), 7.69 (2H, d, J = 8.0, H-2′, H-6′), 8.16 (1H, s, H-4), 10.63 (1H,
br.s, OH-7).
3-(4-Fluorophenyl)-7-hydroxychromen-2-one (7): yield 89%, mp 238-239°C (lit. [12] 245°C), C H FO .
15
9
3
159

PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 6.76 (1H, d, J = 2.0, H-8), 6.83 (1H, dd, J = 2.0, 8.0, H-6), 7.23
6
(2H, t, J = 8.8, H-3′, H-5′), 7.60 (1H, d, J = 8.0, H-5), 7.75 (2H, m, H-2′, H-6′), 8.16 (1H, s, H-4), 10.47 (1H, br.s, OH-7).
3-(4-Chlorophenyl)-7-hydroxychromen-2-one (8): yield 91%, mp 271-272°C (lit. [27] 280-282°C, [23] 289°C,
[12] 295°C), C H ClO .
15
9
3
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 6.76 (1H, d, J = 2.0, H-8), 6.84 (1H, dd, J = 2.0, 8.0, H-6), 7.50
6
(2H, d, J = 8.4, H-3′, H-5′), 7.60 (1H, d, J = 8.0, H-5), 7.74 (2H, d, J = 8.4, H-2′, H-6′), 8.20 (1H, s, H-4), 10.65 (1H, br.s,
OH-7).
7-Hydroxy-3-(4-methoxyphenyl)chromen-2-one (9): yield 82%, mp 215-216°C (lit. [28] 210-212°C, [19] 232°C,
[12] 240°C), C H O .
16 12
4
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 3.80 (3H, s, CH O-4′), 6.75 (1H, d, J = 2.0, H-8), 6.82 (1H, dd,
6
3
J = 2.0, 8.0, H-6), 7.00 (2H, d, J = 8.4, H-3′, H-5′), 7.58 (1H, d, J = 8.0, H-5), 7.66 (2H, d, J = 8.4, H-2′, H-6′), 8.08 (1H, s,
H-4), 10.55 (1H, br.s, OH-7).
7-Hydroxy-3-(3,4-dimethoxyphenyl)chromen-2-one (10): yield 87%, mp 219-220°C (lit. [17] 221-223°C),
C H O .
17 14
5
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 3.80 and 3.18 (6H, 2s, CH O-3′, CH O-4′), 6.75 (1H, d, J = 2.0,
6
3
3
H-8), 6.83 (1H, dd, J = 2.0, 8.0, H-6), 7.00 (1H, d, J = 8.4, H-5′), 7.30 (2H, m, H-2′, H-6′), 7.57 (1H, d, J = 8.0, H-5), 8.11 (1H,
s, H-4), 10.56 (1H, br.s, OH-7).
Ketones 11-24. A hot solution of coumarins 5-10 (4 mmol) in anhydrous acetone (30 mL) was treated with freshly
calcined potash (1.38 g, 10 mmol), stirred vigorously and heated (50-56°C), treated with the appropriate α-haloketone
(4.2 mmol), held for 1-5 h with heating, stirred vigorously (course of reaction monitored by TLC), and poured into H SO
2
4
solution (100 mL, 1 N). The resulting precipitate was filtered off and crystallized from propanol-2.
7-(2-Oxopropoxy)-3-phenylchromen-2-one (11): yield 78%, mp 179-180°C, C H O .
18 14
4
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 2.18 (3H, s, CH -3′′), 5.00 (2H, s, CH -1′′), 6.98 (1H, dd,
6
3
2
J = 2.0, 8.0, H-6), 7.00 (1H, d, J = 2.0, H-8), 7.37-7.46 (3H, m, H-3′, H-4′, H-5′), 7.67-7.71 (3H, m, H-5, H-2′, H-6′), 8.20 (1H,
s, H-4).
3-(4-Fluorophenyl)-7-(2-oxopropoxy)chromen-2-one (12): yield 85%, mp 193-194°C, C H FO .
18 13
4
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 2.18 (3H, s, CH -3′′), 5.00 (2H, s, CH -1′′), 6.98 (1H, dd,
6
3
2
J = 2.0, 8.0, H-6), 7.01 (1H, d, J = 2.0, H-8), 7.28 (2H, t, J = 8.8, H-3′, H-5′), 7.68 (1H, d, J = 8.0, H-5), 7.78 (2H, m, H-2′,
H-6′), 8.20 (1H, s, H-4).
3-(4-Chlorophenyl)-7-(2-oxopropoxy)chromen-2-one (13): yield 88%, mp 216-217°C, C H ClO .
18 13
4
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 2.18 (3H, s, CH -3′′), 5.01 (2H, s, CH -1′′), 6.97 (1H, dd,
6
3
2
J = 2.0, 8.0, H-6), 7.01 (1H, d, J = 2.0, H-8), 7.52 (2H, d, J = 8.8, H-3′, H-5′), 7.70 (1H, d, J = 8.0, H-5), 7.74 (2H, d, J = 8.8,
H-2′, H-6′), 8.25 (1H, s, H-4).
3-(4-Methoxyphenyl)-7-(2-oxopropoxy)chromen-2-one (14): yield 81%, mp 191-192°C, C H O .
19 16
5
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 2.18 (3H, s, CH -3′′), 4.98 (2H, s, CH -1′′), 3.18 (3H, s,
6
3
2
CH O-4′), 6.95 (2H, d, J = 8.4, H-3′, H-5′), 6.98 (1H, dd, J = 2.0, 8.0, H-6), 7.00 (1H, d, J = 2.0, H-8), 7.64 (2H, d, J = 8.4,
3
H-2′, H-6′), 7.69 (1H, d, J = 8.0, H-5), 8.21 (1H, s, H-4).
3-(3,4-Dimethoxyphenyl)-7-(2-oxopropoxy)chromen-2-one (15): yield 89%, mp 196-197°C, C H O .
20 18
6
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 2.18 (3H, s, CH -3′′), 4.98 (2H, s, CH -1′′), 3.81 and 3.82 (6H,
6
3
2
2s, CH O-3′, CH O-4′), 6.95 (1H, d, J = 8.4, H-5′), 6.97 (1H, dd, J = 2.0, 8.0, H-6), 7.00 (1H, d, J = 2.0, H-8), 7.28 (2H, m,
3
3
H-2′, H-6′), 7.70 (1H, d, J = 8.0, H-5), 8.24 (1H, s, H-4).
7-(3,3-Dimethyl-2-oxobutoxy)-3-phenylchromen-2-one (16): yield 76%, mp 185-186°C, C H O .
21 20
4
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 1.20 [9H, s, (CH ) ], 5.18 (2H, s, CH -1′′), 6.97 (1H, dd,
6
3 3
2
J = 2.0, 8.0, H-6), 7.01 (1H, d, J = 2.0, H-8), 7.37-7.46 (3H, m, H-3′, H-4′, H-5′), 7.66-7.70 (3H, m, H-5, H-2′, H-6′), 8.19 (1H,
s, H-4).
7-(3,3-Dimethyl-2-oxobutoxy)-3-(4-fluorophenyl)chromen-2-one (17): yield 87%, mp 198-199°C, C H FO .
21 19
4
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 1.19 [9H, s, (CH ) ], 5.19 (2H, s, CH -1′′), 6.98 (1H, dd,
6
3 3
2
J = 2.0, 8.0, H-6), 7.01 (1H, d, J = 2.0, H-8), 7.29 (2H, t, J = 8.8, H-3′, H-5′), 7.68 (1H, d, J = 8.0, H-5), 7.78 (2H, m, H-2′,
H-6′), 8.19 (1H, s, H-4).
160

7-(3,3-Dimethyl-2-oxobutoxy)-3-(4-methoxyphenyl)chromen-2-one (18): yield 79%, mp 187-188°C, C H O .
21 19
4
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 1.20 [9H, s, (CH ) ], 5.21 (2H, s, CH -1′′), 3.81 (3H, s,
6
3 3
2
CH O-4′), 6.95 (2H, d, J = 8.4, H-3′, H-5′), 6.97 (1H, dd, J = 2.0, 8.0, H-6), 7.00 (1H, d, J = 2.0, H-8), 7.65 (2H, d, J = 8.4,
3
H-2′, H-6′), 7.69 (1H, d, J = 8.0, H-5), 8.21 (1H, s, H-4).
3-(4-Chlorophenyl)-7-(2-oxo-2-phenylethoxy)chromen-2-one (19): yield 78%, mp 239-240°C, C H ClO .
23 15
4
PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 5.70 (2H, s, CH -1′′), 7.01 (1H, dd, J = 2.1, 8.1, H-6), 7.10 (1H,
6
2
d, J = 2.1, H-8), 7.45 (2H, d, J = 8.7, H-3′, H-5′), 7.56 (3H, t, J = 7.5, H-3′″, H-4′″, H-5′″), 7.67 (1H, d, J = 8.0, H-5), 7.73 (2H,
d, J = 8.8, H-2′, H-6′), 8.04 (2H, d, J = 8.7, H-2′″, H-5′″), 8.21 (1H, s, H-4).
3-(3,4-Dimethoxyphenyl)-7-(2-oxo-2-phenylethoxy)chromen-2-one (20): yield 87%, mp 226-227°C, C H O .
25 20
6
PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 3.82 and 3.83 (6H, 2s, CH O-3′, CH O-4′), 5.68 (2H, s,
6
3
3
CH -1′′), 6.96 (1H, d, J = 8.4, H-5′), 6.99 (1H, dd, J = 2.1, 8.1, H-6), 7.08 (1H, d, J = 2.1, H-8), 7.28 (2H, m, H-2′, H-6′), 7.56
2
(2H, t, J = 7.5, H-3′″, H-5′″), 7.63 (1H, d, J = 8.1, H-5), 7.68 (1H, m, H-4′″), 8.04 (2H, d, J = 7.2, H-2′″, H-6′″), 8.10 (1H, s,
H-4).
7-[2-(4-Methylphenyl)-2-oxoethoxy]-3-phenylchromen-2-one (21): yield 83%, mp 228-229°C, C H O .
24 18
4
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 2.40 (3H, s, Me-4′″), 5.72 (1H, s, CH -1′′), 6.98 (1H, dd,
6
2
J = 2.0, 8.0, H-6), 7.00 (1H, d, J = 2.0, H-8), 7.37-7.46 (5H, m, H-3′, H-4′, H-5′, H-3′″, H-5′″), 7.67-7.71 (3H, m, H-5, H-2′,
H-6′), 7.94 (2H, d, J = 7.6, H-2′″, H-6′″), 8.20 (1H, s, H-4).
7-[2-(4-Fluorophenyl)-2-oxoethoxy]-3-(4-methoxyphenyl)chromen-2-one (22): yield 91%, mp 233-234°C,
C H FO .
24 17
5
PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 3.81 (3H, s, CH O-4′), 5.63 (2H, s, CH -1′′), 6.95 (2H, d,
6
3
2
J = 8.7, H-3′, H-5′), 6.97 (1H, dd, J = 2.1, 8.1, H-6), 7.06 (1H, d, J = 2.1, H-8), 7.33 (2H, t, J = 8.7, H-3′″, H-5′″), 7.62 (1H, d,
J = 8.1, H-5), 7.64 (2H, d, J = 8.7, H-2′, H-6′), 8.03 (1H, s, H-4), 8.13 (2H, m, H-2′″, H-6′″).
7-[2-(3-Methoxyphenyl)-2-oxoethoxy]-3-phenylchromen-2-one (23): yield 85%, mp 241-242°C, C H O .
24 18
4
PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 3.85 (3H, s, OCH -3′″), 5.62 (2H, s, CH -1′′), 6.98 (1H, dd,
6
3
2
J = 2.1, 8.1, H-6), 7.00 (1H, d, J = 2.1, H-8), 7.22 (1H, dd, J = 2.7, 8.4, H-4′″), 7.37-7.41 (3H, m, H-3′, H-4′, H-5′), 7.45 (1H,
t, J = 8.4, H-5′″), 7.51 (1H, dd, J = 2.7, 2.7, H-2′″), 7.62 (1H, d, J = 8.4, H-6′″), 7.67-7.71 (3H, m, H-5, H-2′, H-6′), 8.20 (1H,
s, H-4).
3-(4-Chlorophenyl)-7-[2-(3-methoxyphenyl)-2-oxoethoxy]chromen-2-one (24): yield 92%, mp 248-249°C,
C H ClO .
24 17
5
PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 3.85 (3H, s, OCH -3′″), 5.62 (2H, s, CH -1′′), 6.97 (1H, dd,
6
3
2
J = 2.1, 8.1, H-6), 7.01 (1H, d, J = 2.1, H-8), 7.22 (1H, dd, J = 2.7, 8.4, H-4′″), 7.45 (1H, t, J = 8.4, H-5′″), 7.50 (1H, dd, J = 2.7,
2.7, H-2′″), 7.52 (2H, d, J = 8.7, H-3′, H-5′), 7.62 (1H, d, J = 8.4, H-6′″), 7.70 (1H, d, J = 8.1, H-5), 7.74 (2H, d, J = 8.7, H-2′,
H-6′), 8.21 (1H, s, H-4).
3-Substitited 6-Arylfuro[3,2-g]chromen-7-ones 25-38. A solution or suspension of ketones 11-24 (2 mmol) in
propanol-2 (10 mL) was treated with NaOH solution (10 mL, 1 N), heated for 3-4 h (course of reaction monitored by TLC),
and poured into H SO solution (100 mL, 1 N). The resulting precipitate was filtered off and crystallized from propanol-2.
2
4
3-Methyl-6-phenylfuro[3,2-g]chromen-7-one (25): yield 69%, mp 219-220°C, C H O .
18 12
3
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 2.25 (3H, s, CH -3), 7.47 (3H, m, H-3′, H-4′, H-5′), 7.71 (1H,
6
3
s, H-9), 7.73 (2H, d, J = 7.6, H-2′, H-6′), 7.90 (1H, s, H-2), 8.01 (1H, s, H-4), 8.37 (1H, s, H-5).
6-(4-Fluorophenyl)-3-methylfuro[3,2-g]chromen-7-one (26): yield 83%, mp 224-225°C, C H FO .
18 11
3
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 2.25 (3H, s, CH -3), 7.31 (2H, t, J = 8.0, H-3′, H-5′), 7.60 (1H,
6
3
s, H-9), 7.78 (2H, m, H-2′, H-6′), 7.94 (1H, s, H-2), 7.82 (1H, s, H-4), 8.37 (1H, s, H-5).
6-(4-Chlorophenyl)-3-methylfuro[3,2-g]chromen-7-one (27): yield 89%, mp 233-234°C, C H ClO .
18 11
3
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 2.25 (3H, s, CH -3), 7.51 (2H, d, J = 8.0, H-3′, H-5′), 7.65 (1H,
6
3
s, H-9), 7.76 (2H, d, J = 8.0, H-2′, H-6′), 7.97 (1H, s, H-2), 7.86 (1H, s, H-4), 8.36 (1H, s, H-5).
6-(4-Methoxyphenyl)-3-methylfuro[3,2-g]chromen-7-one (28): yield 78%, mp 229-230°C, C H O .
19 14
4
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 2.25 (3H, s, CH -3), 3.82 (3H, s, CH O-4′), 7.04 (2H, d, J = 8.8,
6
3
3
H-3′, H-5′), 7.69 (1H, s, H-9), 7.70 (2H, d, J = 8.8, H-2′, H-6′), 7.90 (1H, s, H-2), 7.99 (1H, s, H-4), 8.30 (1H, s, H-5).
6-(3,4-Dimethoxyphenyl)-3-methylfuro[3,2-g]chromen-7-one (29): yield 81%, mp 221-222°C, C H O .
20 16
5
161

PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 2.25 (3H, s, CH -3), 3.82 and 3.83 (6H, 2s, CH O-3′,
6
3
3
CH O-4′), 7.04 (1H, d, J = 8.8, H-5′), 7.34 (2H, m, H-2′, H-6′), 7.68 (1H, s, H-9), 7.88 (1H, s, H-2), 7.96 (1H, s, H-4), 8.33
3
(1H, s, H-5).
3-t-Butyl-6-phenylfuro[3,2-g]chromen-7-one (30): yield 75%, mp 196-197°C, C H O .
21 18
3
PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 1.44 [9H, s, (CH ) ], 7.43 (3H, m, H-3′, H-4′, H-5′), 7.58 (1H,
6
3 3
s, H-2), 7.70 (1H, s, H-9), 7.73 (2H, d, J = 7.8, H-2′, H-6′), 8.23 (1H, s, H-4), 8.37 (1H, s, H-5).
3-t-Butyl-6-(4-fluorophenyl)furo[3,2-g]chromen-7-one (31): yield 83%, mp 205-206°C, C H FO .
21 17
3
PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 1.44 [9H, s, (CH ) ], 7.24 (2H, t, J = 8.1, H-3′, H-5′), 7.58 (1H,
6
3 3
s, H-2), 7.70 (1H, s, H-9), 7.78 (2H, m, H-2′, H-6′), 8.22 (1H, s, H-4), 8.38 (1H, s, H-5).
3-t-Butyl-6-(4-methoxyphenyl)furo[3,2-g]chromen-7-one (32): yield 87%, mp 219-220°C, C H O .
22 20
4
PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 1.44 [9H, s, (CH ) ], 3.82 (3H, s, CH O-4′), 7.00 (2H, d,
6
3 3
3
J = 8.7, H-3′, H-5′), 7.56 (1H, s, H-2), 7.68 (2H, d, J = 8.7, H-2′, H-6′), 7.69 (1H, s, H-9), 8.19 (1H, s, H-4), 8.30 (1H, s, H-5).
6-(4-Chlorophenyl)-3-phenylfuro[3,2-g]chromen-7-one (33): yield 81%, mp 246-247°C, C H ClO .
23 13
3
PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 7.40-7.54 (5H, m, H-3′, H-5′, H-3′′, H-4′′, H-5′′), 7.69 (1H, s,
6
H-9), 7.76 (4H, d, J = 8.1, H-2′, H-6′, H-2′′, H-6′′), 8.32 (1H, s, H-4), 8.38 (1H, s, H-5), 8.43 (1H, s, H-2).
6-(3,4-Dimethoxyphenyl)-3-phenylfuro[3,2-g]chromen-7-one (34): yield 86%, mp 232-233°C, C H O .
25 18
5
PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 3.82 and 3.83 (6H, 2s, CH O-3′, CH O-4′), 7.00 (1H, d, J = 8.7,
6
3
3
H-5′), 7.33 (2H, m, H-2′, H-6′), 7.41 (1H, m, H-4′′), 7.52 (2H, t, J = 7.5, H-3′′, H-5′′), 7.70 (1H, s, H-9), 7.77 (2H, d, J = 7.5,
H-2′′, H-6′′), 8.31 (1H, s, H-4), 8.34 (1H, s, H-5), 8.38 (1H, s, H-2).
3-(4-Methylphenyl)-6-phenylfuro[3,2-g]chromen-7-one (35): yield 78%, mp 239-240°C, C H O .
24 16
3
PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 2.40 (3H, s, CH -4′′), 7.32 (2H, d, J = 8.1, H-3′′, H-5′′), 7.43
6
3
(3H, m, H-3′, H-4′, H-5′), 7.64 (2H, d, J = 8.1, H-2′, H-6′), 7.69 (1H, s, H-9), 7.73 (2H, d, J = 8.1, H-2′′, H-6′′), 8.31 (1H, s,
H-4), 8.33 (1H, s, H-5), 8.39 (1H, s, H-2).
3-(4-Fluorophenyl)-6-(4-methoxyphenyl)furo[3,2-g]chromen-7-one (36): yield 75%, mp 246-247°C, C H FO .
24 15
4
PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 3.82 (3H, s, CH O-4′), 7.00 (2H, d, J = 8.7, H-3′, H-5′), 7.31
6
3
(2H, t, J = 8.7, H-3′′, H-5′′), 7.68 (2H, d, J = 8.7, H-2′, H-6′), 7.71 (1H, s, H-9), 7.78 (2H, m, H-2′′, H-6′′), 8.29 (1H, s, H-4),
8.30 (1H, s, H-5), 8.37 (1H, s, H-2).
3-(3-Methoxyphenyl)-6-phenylfuro[3,2-g]chromen-7-one (37): yield 83%, mp 247-248°C, C H O .
24 16
4
PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 3.87 (3H, s, CH O-3′′), 6.96 (1H, dd, J = 2.1, 8.7, H-4′′),
6
3
7.27-7.32 (2H, m, H-2′′, H-6′′), 7.42 (1H, t, J = 8.7, H-5′′), 7.47 (3H, m, H-3′, H-4′, H-5′), 7.71 (1H, s, H-9), 7.73 (2H, d,
J = 8.7, H-2′, H-6′), 8.34 (1H, s, H-4), 8.40 (1H, s, H-5), 8.43 (1H, s, H-2).
6-(4-Chlorophenyl)-3-(3-methoxyphenyl)furo[3,2-g]chromen-7-one (38): yield 79%, mp 254-255°C, C H ClO .
24 15
4
PMR spectrum (300 MHz, DMSO-d , δ, ppm, J/Hz): 3.87 (3H, s, CH O-3′′), 6.96 (1H, dd, J = 2.1, 8.7, H-4′′),
6
3
7.27-7.32 (2H, m, H-2′′, H-6′′), 7.42 (1H, t, J = 8.7, H-5′′), 7.48 (2H, d, J = 8.7, H-3′, H-5′), 7.71 (1H, s, H-9), 7.77 (2H, d,
J = 8.7, H-2′, H-6′), 8.34 (1H, s, H-4), 8.41 (1H, s, H-5), 8.48 (1H, s, H-2).
ACKNOWLEDGMENT
We thank OAO Eximed (Kiev, Ukraine) for help in performing the work.
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