Modified coumarins. I. Synthesis of 5-phenyl-7H-furo[2,3-g]chromen-7-ones and 9-phenyl-7H-furo-[2,3-f]chromen-7-ones

Article abstract of DOI:10.1023/A:1002883305908

5-Phenyl-7H-furo[2,3-g]chromen-7-ones and 9-phenyl-7H-furo-[2,3-f]chromen-7-ones, new analogs of psoralen and allopsoralen, are synthesized from 7-hydroxy- and 5-hydroxy-4-phenylcoumarins.

Full text of DOI:10.1023/A:1002883305908

Chemistry of Natural Compounds, Vol. 36, No. 5, 2000
MODIFIED COUMARINS. I. SYNTHESIS OF
5-PHENYL-7H-FURO[2,3-g]CHROMEN-7-ONES
AND 9-PHENYL-7H-FURO-[2,3-f]CHROMEN-7-ONES
M. M. Garazd,1 Ya. L. Garazd,2
S. V. Shilin,2 and V. P. Khilya2
UDC 547.9:582.89
5-Phenyl-7H-furo[2,3-g]chromen-7-ones and 9-phenyl-7H-furo-[2,3-f]chromen-7-ones, new analogs of
psoralen and allopsoralen, are synthesized from 7-hydroxy- and 5-hydroxy-4-phenylcoumarins.
5-phenyl-7H-furo[2,3-g]chromen-7-one, 9-phenyl-7H-furo-[2,3-f]chromen-7-one, synthesis.
Key words:
Furocoumarins are an important class of natural products that are isolated mainly from higher plants belonging to the
families Rutaceae, Umbelliferae, Leguminosae, and Moraceae. These compounds are in most instances derivatives of the linear
furocoumarin psoralen (A) or its angular isomers angelicin (B) and allopsoralen (C).
O
O
O
O
O
O
O
O
O
A
B
C
The ability to bind covalently DNA and other biological macromolecules under UV irradiation stimulates interest in
the pharmacology of furocoumarins. Therefore, photosensitizing preparations of furocoumarins are widely used in the therapy
of several skin diseases [1].
Derivatives of 4-phenylcoumarin (known as neoflavones) are widely distributed in the plant kingdom, especially among
the families Dalbergia, Guttiferae, and Rubiaceae. More than 60 compounds based on the 4-phenylcoumarin framework have
been isolated from natural materials. Both natural and synthetic 4-phenylcoumarins have a broad spectrum of biological activity.
Neoflavones isolated from natural material exhibit antibactericidal and insecticidal properties [2, 3]. Synthetic derivatives of
4-phenylcoumarins possess vasodilating [4], analeptic [5], antiatherosclerotic [6], and antibacterial [7, 8] activities.
Thus, our goal was to modify the 4-phenylcoumarin structure by fusing a furan ring to it. This would possibly produce
compounds with useful biological properties.
The starting 7-hydroxy-4-phenylcoumarin ( ), 7-hydroxy-8-methyl-4-phenylcoumarin ( ), and 5-hydroxy-7-methyl-4-
1
2
phenylcoumarin ( ) were obtained in high yields via Pechmann condensation of ethylbenzoylacetate and resorcinol, 2-
3
methylresorcinol, and orcinol, respectively, in the presence of F CCO H [9]. We fused a furan ring to the 4-phenylcoumarin
3
2
using the method of MacLeod et al. [10] based upon cyclization in alkaline medium of 1-(7-coumarinyloxy)acetone derivatives.
The cyclization yields exclusively linear furocoumarins because the 6-position is strongly activated compared with the 8-position
[10].
The Williamson reaction of 7-hydroxycoumarins and with -bromoacetone or 3-chlorobutan-2-one in acetone in
1
2
the presence of K2CO3 forms the corresponding substituted 1-(4-phenyl-7-coumarinyloxy)acetones (4-7). Using
-
bromoacetophenone, -bromo-4-chloroacetophenone, -bromo-3,4-methylendioxyacetophenone, or -bromopropiophenone in
the alkylation reaction gives 2-(4-phenyl-7-coumarinyloxy)-1-phenyl-1-ethanone derivatives (8-15). Reaction of 1 and 2 with
1) Institute of Bioorganic and Petroleum Chemistry, National Academy of Sciences of Ukraine, 02094, Kiev, ul.
Murmanskaya, 1; 2) Taras Shevchenko Kiev National University, 01033, Kiev, ul. Vladimirckaya, 64. Translated from Khimiya
Prirodnykh Soedinenii, No. 5, pp. 377-382, September-October, 2000. Original article submitted November 6, 2000.
0009-3130/00/3605-0478$25.00 ©2001 Plenum Publishing Corporation
478

16
17
Williamson reaction of 5-hydroxycoumarin with -bromoacetone, 3-chlorobutan-2-one, -bromoacetophenone, -bromo-4-
2-chlorocyclohexanone in DMF in the presence of K2CO3 gives 7-(2-oxocyclohexyloxy)-4-phenylcoumarins ( and ). The
3
18 22
chloroacetophenone, and 2-chlorocyclohexanone forms ketones
-
.
R
O
O
R
O
R
1
O
Me
O
O
9
7
O
O
O
Me
2
6
Me
3
5
4
Me
25. R=H; 26. R=Me
27. R=H; 28. R=Me
23. R=H; 24. R=Me
1N NaOH
R
1N NaOH
R
1N NaOH
R
Me
Me
O
O
O
O
Me
O
O
O
O
O
O
O
O
Me
6. R=H; 7. R=Me
8. R=H; 9. R=Me
O
4. R=H; 5. R=Me
Cl
Me
O
K CO
2
3
Me
Cl
Me
O
K CO
2
3
Br
O
K CO
Me
2
3
R
HO
O
O
O
Br
Cl
R
1
R
O
R
1. R=H; 2. R=Me
K CO
O
O
O
O
O
O
2
3
K CO
3
2
O
O
O
O
Br
R
1
K CO
2
3
R
16. R=H; 17. R=Me
11. R=Me; R =H
10. R=H; R =H
1
1
O
O
O
O
13. R=Me; R =Cl
12. R=H; R =Cl
1
1
O
O
1N NaOH
1N NaOH
R
R
1
10
11
O
O
14. R=H; 15. R=Me
1N NaOH
O
O
O
O
9
2
8
4
5
R
6
7
O
O
O
R
1
35. R=H; 36. R=Me
O
29. R=H; R =H
30. R=Me; R =H
1
1
31. R=H; R =Cl
32. R=Me; R =Cl
1
1
O
33. R=H; 34. R=H
479

Heating of ketones 4-22 with 1 N NaOH smoothly cyclizes them into the corresponding 5-phenyl-7H-furo[3,2-
g]chromen-7-ones (23-36) (psoralen-type furocoumarins) and 9-phenyl-7H-furo[2,3-f]chromen-7-ones (37-41) (allopsoralen-type
furocoumarins).
6
5
Me
O
O
Me
O
O
4
Me
O
O
Me
Me
Me
O
O
7
1N NaOH
3
O
1N NaOH
Me
O
9
O
O
O1
O
Me
Me
Me
37
18
19
38
O
Cl
Me
O
K CO
2
3
Br
Br
Me
K CO
2
3
Me
O
O
O
Br
O
OH
Cl
K CO
R
1
K CO
2
3
2
3
3
4
5
3
Me
O
O
Me
O
O
O
Me
6
O
O
Me
O
O
R
1
2
7
1N NaOH
O
1
1N NaOH
O 11
O
8
O
O
9
10
R
1
41
22
20. R =H; 21. R =Cl
39. R =H; 40. R =Cl
1
1
1
1
Fusion of the furan ring to the 6,7- (23-36) or 5,6-positions (37-41) of the coumarin core was confirmed by PMR
spectroscopy. The PMR spectra of 23-36 exhibit a simplified splitting pattern in the aromatic region of coumarin owing to
decoupling to H-6 of the coumarin ring. As a result, aromatic proton H-4 of furocoumarin appears as a singlet. An analogous
situation is observed for 37-41 owing to decoupling of H-6 of the coumarin ring, causing H-5 of the furocoumarin to appear as
a singlet. Furthermore, 23, 24, 29-34, 37, 39, and 40, which do not contain substituents in the 2-position, exhibit a 1H singlet
for H-2 at 7.8-8.6 ppm. This is also characteristic of formation of a furocoumarin ring.
Thus, we prepared new psoralen and allopsoralen analogs based on 7-hydroxy- and 5-hydroxy-4-phenylcoumarins.
EXPERIMENTAL
The course of the reactions and the purity of the products were monitored using TLC on Silufol UV-254 plates and
CHCl —CH OH (9:1) and (95:5). IR spectra were recorded on a Pye Unicam SP3-300 instrument in KBr pellets. PMR spectra
3
3
were obtained on a Varian VXR-300 in DMSO-d and deuteroacetone with TMS internal standard.
6
Hydroxycoumarins 1, 2, and 3 were prepared according to the literature [8].
7-(2-Oxopropoxy)-4-phenylcoumarin (4). A hot solution of 1 (2.38 g, 10 mmol) in absolute acetone (50 ml) was
treated with freshly calcined potash (2.76 g, 20 mmol). The mixture was vigorously stirred, heated (50-56
C), and treated with
-bromoacetone (1.5 g, 11 mmol). The reaction mixture was heated and stirred vigorously for 1 h (completion of the reaction
was determined by TLC). The reaction mixture was added to 1 N H SO (300 ml). The resulting precipitate was filtered off
2
4
and crystallized from propan-2-ol (75%). Yield 85%, mp 145 C, C18H14O4. IR spectrum (KBr, cm-1): 3040, 1712, 1625, 1598,
1560, 1435, 1366, 1334, 1240, 1132, 1061, 942, 875, 796, 766. PMR spectrum (300 MHz, deuteroacetone, , ppm): 2.25 (3H,
s, CH CO), 4.95 (2H, s, COCH O), 6.16 (1H, s, H-3), 6.90 (1H, dd, J = 2.0 and 8.5 Hz, H-6), 6.95 (1H, d, J = 2.0 Hz, H-8), 7.41
3
2
(1H, d, J = 8.5 Hz, H-5), 7.56 (5H, m, Ph-4).
8-Methyl-7-(2-oxopropoxy)-4-phenylcoumarin (5) was prepared analogously to 4 using 2 (2.52 g, 10 mmol). Yield
92%, mp 159 C (75% propan-2-ol), C19H16O4. IR spectrum (KBr, cm-1): 1716, 1622, 1590, 1564, 1432, 1360, 1245, 1139,
1060, 945, 875, 785. PMR spectrum (300 MHz, deuteroacetone, , ppm): 2.25 (3H, s, CH CO), 2.36 (3H, s, CH -8), 4.91 (2H,
3
3
480

s, COCH O), 6.16 (1H, s, H-3), 6.85 (1H, d, J = 8.5 Hz, H-6), 7.25 (1H, d, J = 8.5 Hz, H-5), 7.54 (5H, m, Ph-4).
2
7-(1-Methyl-2-oxopropoxy)-4-phenylcoumarin (6) was prepared analogously to 4 using 1 (2.38 g, 10 mmol) and 3-
chloro-2-butanone (1.11 ml, 11 mmol). The reaction mixture was heated for 4 h. Yield 82%, mp 123 C (60% propan-2-ol),
C19H16O4. IR spectrum (KBr, cm-1): 3025, 1715, 1630, 1600, 1565, 1440, 1366, 1338, 1245, 1139, 1060, 942, 875, 780. PMR
spectrum (300 MHz, deuteroacetone, , ppm): 1.56 (3H, d, -CH ), 2.24 (3H, s, CH CO), 5.08 (1H, q, COCHO), 6.17 (1H, s,
3
3
H-3), 6.89 (1H, dd, J = 2.0 and 8.5 Hz, H-6), 6.95 (1H, d, J = 2.0 Hz, H-8), 7.42 (1H, d, J = 8.5 Hz, H-5), 7.58 (5H, m, Ph-4).
8-Methyl-7-(1-methyl-2-oxopropoxy)-4-phenylcoumarin (7) was prepared analogously to 4 using 2 (2.52 g, 10 mmol)
and 3-chloro-2-butanone (1.11 ml, 11 mmol). The reaction mixture was heated for 4 h. Yield 86%, mp 151 C (75% propan-2-
ol), C20H18O4. IR spectrum (KBr, cm-1): 3020, 1716, 1630, 1595, 1562, 1432, 1369, 1332, 1240, 1138, 1055, 940, 870, 786.
PMR spectrum (300 MHz, deuteroacetone, , ppm): 1.55 (3H, d, -CH ), 2.22 (3H, s, CH CO), 2.37 (3H, s, CH -8), 5.00 (1H,
3
3
3
q, COCHO), 6.17 (1H, s, H-3), 6.82 (1H, d, J = 8.5 Hz, H-6), 7.28 (1H, d, J = 8.5 Hz, H-5), 7.55 (5H, m, Ph-4).
7-(1-Methyl-2-oxo-2-phenylethoxy)-4-phenylcoumarin (8) was prepared analogously to 4 using 1 (2.38 g, 10 mmol)
and 2-bromopropiophenone (1.64 ml, 11 mmol). The reaction mixture was heated for 2 h. Yield 81%, mp 109 C (propan-2-ol),
C24H18O4. IR spectrum (KBr, cm-1): 3040, 1714, 1695, 1590, 1542, 1440, 1374, 1270, 1205, 1162, 1110, 990, 968, 835, 750.
PMR spectrum (300 MHz, deuteroacetone, , ppm): 1.70 (3H, d, -CH ), 5.99 (1H, q, COCHO), 6.17 (1H, s, H-3), 6.89 (1H,
3
dd, J = 2.0 and 8.5 Hz, H-6), 6.95 (1H, d, J = 2.0 Hz, H-8), 7.29 (1H, d, J = 8.5 Hz, H-5), 7.56 (5H, m, Ph-4), 7.60 (3H, m, H-
3,4,5 PhCO), 8.15 (2H, m, H-2,6 PhCO).
8-Methyl-7-(1-methyl-2-oxo-2-phenylethoxy)-4-phenylcoumarin (9) was prepared analogously to 4 using 2
(2.52 g, 10 mmol) and 2-bromopropiophenone (1.64 ml, 11 mmol). The reaction mixture was heated for 2 h. Yield 89%, mp
157 C (propan-2-ol), C25H20O4. IR spectrum (KBr, cm-1): 3040, 1716, 1692, 1592, 1548, 1442, 1386, 1273, 1200, 1150, 985,
840, 745. PMR spectrum (300 MHz, deuteroacetone, , ppm): 1.72 (3H, d, -CH ), 2.36 (3H, s, CH -8), 6.01 (1H, q, COCHO),
3
3
6.13 (1H, s, H-3), 6.84 (1H, d, J = 8.5 Hz, H-6), 7.21 (1H, d, J = 8.5 Hz, H-5), 7.52 (5H, m, Ph-4), 7.62 (3H, m, H-3,4,5 PhCO),
8.11 (2H, m, H-2,6 PhCO).
7-(2-Oxo-2-phenylethoxy)-4-phenylcoumarin (10) was prepared analogously to 4 using 1 (2.38 g, 10 mmol) and -
bromoacetophenone (2.19 g, 11 mmol). The reaction mixture was heated for 1 h. Yield 89%, mp 156 C (propan-2-ol),
C23H16O4. IR spectrum (KBr, cm-1): 3045, 1712, 1692, 1595, 1545, 1436, 1370, 1280, 1260, 1200, 1150, 1110, 997, 962, 830,
746. PMR spectrum (300 MHz, deuteroacetone, , ppm): 5.72 (2H, s, COCH O), 6.15 (1H, s, H-3), 6.98 (1H, dd, J = 2.0 and
2
8.5 Hz, H-6), 7.03 (1H, d, J = 2.0 Hz, H-8), 7.41 (1H, d, J = 8.5 Hz, H-5), 7.58 (5H, m, Ph-4), 7.65 (3H, m, H-3,4,5 PhCO), 8.10
(2H, m, H-2,6 PhCO).
8-Methyl-7-(2-oxo-2-phenylethoxy)-4-phenylcoumarin (11) was prepared analogously to 4 using 2 (2.52 g, 10 mmol)
and -bromoacetophenone (2.19 g, 11 mmol). The reaction mixture was heated for 1 h. Yield 95%, mp 186 C (propan-2-ol),
C24H18O4. IR spectrum (KBr, cm-1): 3040, 1716, 1690, 1600, 1550, 1435, 1377, 1275, 1262, 1210, 1130, 1005, 955, 840, 760.
PMR spectrum (300 MHz, deuteroacetone, , ppm): 2.38 (3H, s, CH -8), 5.73 (2H, s, COCH O), 6.15 (1H, s, H-3), 6.96 (1H,
3
2
d, J = 8.5 Hz, H-6), 7.25 (1H, d, J = 8.5 Hz, H-5), 7.54 (5H, m, Ph-4), 7.63 (3H, m, H-3,4,5 PhCO), 8.08 (2H, m, H-2,6 PhCO).
7-[2-(4-Chlorophenyl)-2-oxoethoxy]-4-phenylcoumarin (12) was prepared analogously to 4 using 1 (2.38 g, 10 mmol)
and -bromo-4-chloroacetophenone (2.57 g, 11 mmol). The reaction mixture was heated for 1 h. Yield 90%, mp 191 C
(propan-2-ol), C23H15ClO4. IR spectrum (KBr, cm-1): 3060, 1718, 1690, 1600, 1375, 1288, 1265, 1218, 1150, 1118, 982, 820,
765. PMR spectrum (300 MHz, DMSO-d , , ppm): 5.71 (2H, s, COCH O), 6.22 (1H, s, H-3), 6.98 (1H, dd, J = 2.0 and
6
2
8.5 Hz, H-6), 7.19 (1H, d, J = 2.0 Hz, H-8), 7.36 (1H, d, J = 8.5 Hz, H-5), 7.56 (5H, m, Ph-4), 7.64 (2H, d, J = 8 Hz, H-3,5
PhCO), 8.05 (2H, d, J = 8 Hz, H-2,6 PhCO).
7-[2-(4-Chlorophenyl)-2-oxoethoxy]-8-methyl-4-phenylcoumarin (13) was prepared analogously to 4 using 2
(2.52 g, 10 mmol) and -bromo-4-chloroacetophenone (2.57 g, 11 mmol). The reaction mixture was heated for 1 h. Yield 92%,
mp 219 C (propan-2-ol), C24H17ClO4. IR spectrum (KBr, cm-1): 3050, 1716, 1692, 1605, 1380, 1295, 1270, 1215, 1150, 1110,
980, 825, 750. PMR spectrum (300 MHz, DMSO-d , , ppm): 2.33 (3H, s, CH -8), 5.72 (2H, s, COCH O), 6.21 (1H, s, H-3),
6
3
2
6.96 (1H, d, J = 8.5 Hz, H-6), 7.18 (1H, d, J = 8.5 Hz, H-5), 7.55 (5H, m, Ph-4), 7.64 (2H, d, J = 8.5 Hz, H-3,5 PhCO), 8.04
(2H, d, J = 8.5 Hz, H-2,6 PhCO).
7-[2-(1,3-Benzodioxol-5-yl)-2-oxoethoxy]-4-phenylcoumarin (14) was prepared analogously to 4 using 1 (2.38 g,
10 mmol) and -bromo-3,4-methylenedioxyacetophenone (2.67 g, 11 mmol). The reaction mixture was heated for 1 h. Yield
86%, mp 229 C (propan-2-ol), C24H16O6. IR spectrum (KBr, cm-1): 3040, 1718, 1698, 1600, 1550, 1375, 1272, 1195, 1140,
1100, 990, 830, 755. PMR spectrum (300 MHz, DMSO-d , , ppm): 5.62 (2H, s, COCH O), 6.17 (2H, s, OCH O), 6.24 (1H,
6
2
2
481

s, H-3), 6.98 (1H, dd, J = 2.0 and 8.5 Hz, H-6), 7.10 (1H, d, J = 8.5 Hz, H-7 benzodioxol), 7.19 (1H, d, J = 2.0 Hz, H-8), 7.36
(1H, d, J = 8.5 Hz, H-5), 7.53 (1H, d, J = 2.0 Hz, H-4 benzodioxol), 7.56 (5H, m, Ph-4), 7.69 (1H, dd, J = 2.0 and 8.5 Hz, H-6
benzodioxol).
7-[2-(1,3-Benzodioxol-5-yl)-2-oxoethoxy]-8-methyl-4-phenylcoumarin (15) was prepared analogously to 4 using 2
(2.52 g, 10 mmol) and -bromo-3,4-methylenedioxyacetophenone (2.67 g, 11 mmol). The reaction mixture was heated for 1
h. Yield 88%, mp 204 C (propan-2-ol), C25H18O6. IR spectrum (KBr, cm-1): 3060, 1717, 1690, 1598, 1555, 1370, 1272, 1190,
1140, 1102, 990, 836, 760. PMR spectrum (300 MHz, DMSO-d , , ppm): 2.38 (3H, s, CH -8), 5.62 (2H, s, COCH O), 6.13
6
3
2
(2H, s, OCH O), 6.24 (1H, s, H-3), 6.96 (1H, d, J = 8.5 Hz, H-6), 7.08 (1H, d, J = 8.5 Hz, H-7 benzodioxol), 7.23 (1H, d, J =
2
8.5 Hz, H-5), 7.48 (1H, d, J = 2.0 Hz, H-4 benzodioxol), 7.55 (5H, m, Ph-4), 7.72 (1H, dd, J = 2.0 and 8.5 Hz, H-6 benzodioxol).
7-(2-Oxocyclohexyloxy)-4-phenylcoumarin (16). A solution of 1 (3.57 g, 15 mmol) in dry DMF (50 ml) was treated
with freshly calcined potash (6.2 g, 45 mmol) and 2-chlorocyclohexanone (3.43 ml, 30 mmol). The reaction mixture was stirred
vigorously and heated (75-80 C) for 24 h and then treated with 1 N H SO (300 ml). The resulting precipitate was filtered off
2
4
and crystallized from propan-2-ol. Yield 64%, mp 177 C (propan-2-ol), C21H18O4. IR spectrum (KBr, cm-1): 3055, 2935,
1710, 1688, 1590, 1545, 1440, 1368, 1272, 1200, 1150, 1105, 1064, 995, 828, 765. PMR spectrum (300 MHz, deuteroacetone,
, ppm): 1.80-2.50 [8H, m, (CH ) ], 5.16 (1H, m, -CH), 6.13 (1H, s, H-3), 6.85 (1H, dd, J = 2.0 and 8.5 Hz, H-6), 6.88 (1H,
2 4
d, J = 2.0 Hz, H-8), 7.36 (1H, d, J = 8.5 Hz, H-5), 7.55 (5H, m, Ph-4).
8-Methyl-7-(2-oxocyclohexyloxy)-4-phenylcoumarin (17) was prepared analogously to 16 using 2 (3.78 g, 15 mmol).
Yield 68%, mp 233 C (propan-2-ol), C22H20O4. IR spectrum (KBr, cm-1): 3060, 2940, 1715, 1692, 1595, 1550, 1438, 1370,
1270, 1202, 1151, 1101, 1065, 990, 830, 769. PMR spectrum (300 MHz, deuteroacetone, , ppm): 1.80-2.50 [8H, m, (CH ) )],
2 4
2.36 (3H, s, CH -8), 5.19 (1H, m, -CH), 6.21 (1H, s, H-3), 6.86 (1H, d, J = 8.5 Hz, H-6), 7.18 (1H, d, J = 8.5 Hz, H-5), 7.55
3
(5H, m, Ph-4).
7-Methyl-5-(2-oxopropoxy)-4-phenylcoumarin (18) was prepared analogously to 4 using 3 (2.52 g, 10 mmol). Yield
84%, mp 214 C (75% propan-2-ol), C19H16O4. IR spectrum (KBr, cm-1): 3050, 1716, 1620, 1590, 1445, 1364, 1245, 1130,
1065, 940, 879, 790, 770. PMR spectrum (300 MHz, deuteroacetone, , ppm): 1.70 (3H, s, CH CO), 2.40 (3H, s, CH -7), 4.43
3
3
(2H, s, COCH O), 6.04 (1H, s, H-3), 6.68 (1H, d, J = 2 Hz, H-6), 6.91 (1H, d, J = 2 Hz, H-9), 7.42 (5H, m, Ph-4).
2
7-Methyl-5-(1-methyl-2-oxopropoxy)-4-phenylcoumarin (19) was prepared analogously to 4 using 3 (2.52 g,
10 mmol) and 3-chloro-2-butanone (1.11 ml, 11 mmol). The reaction mixture was heated for 4 h. Yield 81%, mp 117 C (75%
propan-2-ol), C20H18O4. IR spectrum (KBr, cm-1): 3060, 1714, 1625, 1598, 1440, 1370, 1242, 1130, 1065, 945, 871, 791, 770.
PMR spectrum (300 MHz, deuteroacetone, , ppm): 0.86 (3H, d, -CH ), 1.86 (3H, s, CH CO), 2.37 (3H, s, CH -7), 4.66 (1H,
3
3
3
q, COCHO), 6.01 (1H, s, H-3), 6.47 (1H, d, J = 2 Hz, H-6), 6.85 (1H, d, J = 2 Hz, H-8), 7.42 (5H, m, Ph-4).
7-Methyl-5-(2-oxo-2-phenylethoxy)-4-phenylcoumarin (20) was prepared analogously to 4 using 3 (2.52 g, 10 mmol)
and -bromoacetophenone (2.19 g, 11 mmol). The reaction mixture was heated for 1 h. Yield 85%, mp 132 C (propan-2-ol),
C24H18O4. IR spectrum (KBr, cm-1): 3055, 1716, 1675, 1630, 1595, 1450, 1358, 1280, 1255, 1224, 1208, 1110, 938, 882, 865,
830, 780, 745. PMR spectrum (300 MHz, deuteroacetone, , ppm): 2.35 (3H, s, CH -7), 5.15 (2H, s, COCH O), 6.00 (1H, s,
3
2
H-3), 6.70 (1H, d, J = 2 Hz, H-6), 6.84 (1H, d, J = 2 Hz, H-8), 7.30 (5H, m, Ph-4), 7.55 (3H, m, H-3,4,5 PhCO), 7.82 (2H, m,
H-2,6 PhCO).
5-[2-(4-Chlorophenyl)-2-oxoethoxy]-7-methyl-4-phenylcoumarin (21) was prepared analogously to 4 using 3
(2.52 g, 10 mmol) and -bromo-4-chloroacetophenone (2.57 g, 11 mmol). The reaction mixture was heated for 1 h. Yield 91%,
mp 174 C (propan-1-ol), C24H17ClO4. IR spectrum (KBr, cm-1): 3050, 1716, 1685, 1605, 1462, 1370, 1282, 1265, 1220, 1150,
990, 830, 768. PMR spectrum (300 MHz, DMSO-d , , ppm): 2.33 (3H, s, CH -7), 5.13 (2H, s, COCH O), 6.03 (1H, s, H-3),
6
3
2
6.72 (1H, d, J = 2 Hz, H-6), 6.91 (1H, d, J = 2 Hz, H-8), 7.27 (5H, m, Ph-4), 7.54 (2H, d, J = 8 Hz, H-3,5 PhCO), 7.77 (2H, d,
J = 8.5 Hz, H-2,6 PhCO).
7-Methyl-5-(2-oxocyclohexyloxy)-4-phenylcoumarin (22) was prepared analogously to 16 using 3 (3.78 g, 15 mmol).
Yield 52%, mp 189 C (propan-2-ol), C22H20O4. IR spectrum (KBr, cm-1): 3060, 2945, 1714, 1695, 1591, 1550, 1440, 1375,
1270, 1195, 1150, 1105, 1075, 995, 835, 765. PMR spectrum (300 MHz, deuteroacetone, , ppm): 1.30-2.50 [8H, m, (CH ) ],
2 4
2.32 (3H, s, CH -7), 4.92 (1H, m, -CH), 6.01 (1H, s, H-3), 6.52 (1H, d, J = 2 Hz, H-6), 6.85 (1H, d, J = 2 Hz, H-8), 7.31 (5H,
3
m, Ph-4).
5-Phenyl-7H-furo[3,2-g]chromen-7-ones (23-36) and 9-phenyl-7H-furo[2,3-f]chromen-7-ones (37-41). A solution
or suspension of ketone 4-22 (6 mmol) in isopropanol (50 ml) was treated with 1 N NaOH (50 ml). The reaction mixture was
heated for 3-4 h until the ketone dissolved totally (the course of the reaction was monitored by TLC) and added to 1 N H SO
2
4
482

(300 ml). The resulting precipitate was filtered off and crystallized from propan-2-ol.
3-Methyl-5-phenyl-7H-furo[3,2-g]chromen-7-one (23): C18H12O3, yield 78%, mp 161 C. IR spectrum (KBr, cm-1):
1716, 1600, 1551, 1430, 1340, 1255, 1160, 1125, 1050, 940, 842, 760. PMR spectrum (300 MHz, DMSO-d , , ppm): 2.13
6
(3H, s, CH -3), 6.36 (1H, s, H-6), 7.54 (1H, s, H-4), 7.61 (5H, m, Ph-5), 7.76 (1H, s, H-9), 7.88 (1H, s, H-2).
3
3,9-Dimethyl-5-phenyl-7H-furo[3,2-g]chromen-7-one (24): C19H14O3, yield 82%, mp 221 C. IR spectrum (KBr,
cm-1): 1715, 1606, 1550, 1432, 1346, 1254, 1162, 1128, 1055, 941, 840, 760. PMR spectrum (300 MHz, DMSO-d , , ppm):
6
2.12 (3H, s, CH -3), 2.53 (3H, s, CH -9), 6.32 (1H, s, H-6), 7.36 (1H, s, H-4), 7.59 (5H, m, Ph-5), 7.86 (1H, s, H-2).
3
3
2,3-Dimethyl-5-phenyl-7H-furo[3,2-g]chromen-7-one (25): C19H14O3, yield 75%, mp 183 C. IR spectrum (KBr,
cm-1): 1718, 1601, 1550, 1434, 1341, 1250, 1162, 1127, 1051, 945, 840, 765. PMR spectrum (300 MHz, DMSO-d , , ppm):
6
2.03 (3H, s, CH -3), 2.37 (3H, s, CH -2), 6.27 (1H, s, H-6), 7.36 (1H, s, H-4), 7.55 (5H, m, Ph-5), 7.57 (1H, s, H-9).
3
3
2,3,9-Trimethyl-5-phenyl-7H-furo[3,2-g]chromen-7-one (26): C20H16O3, yield 72%, mp 231 C. IR spectrum (KBr,
cm-1): 1718, 1600, 1555, 1431, 1360, 1340, 1251, 1168, 1120, 1055, 941, 840, 761. PMR spectrum (300 MHz, DMSO-d , ,
6
ppm): 2.02 (3H, s, CH -3), 2.39 (3H, s, CH -2), 2.48 (3H, s, CH -9), 6.28 (1H, s, H-6), 7.20 (1H, s, H-4), 7.58 (5H, m, Ph-5).
3
3
3
2-Methyl-3,5-diphenyl-7H-furo[3,2-g]chromen-7-one (27): C24H16O3, yield 84%, mp 211 C. IR spectrum (KBr,
cm-1): 1718, 1609, 1571, 1429, 1360, 1325, 1245, 1155, 1129, 1062, 941, 830, 754. PMR spectrum (300 MHz, DMSO-d , ,
6
ppm): 2.53 (3H, s, CH -2), 6.37 (1H, s, H-6), 7.36-7.44 (5H, m, Ph-3), 7.51 (1H, s, H-4), 7.76 (1H, s, H-9).
3
2,9-Dimethyl-3,5-diphenyl-7H-furo[3,2-g]chromen-7-one (28): C25H18O3, yield 86%, mp 262 C. IR spectrum (KBr,
cm-1): 1716, 1600, 1565, 1432, 1364, 1322, 1249, 1159, 1120, 1068, 940, 835, 750. PMR spectrum (300 MHz, DMSO-d , ,
6
ppm): 2.54 (3H, s, CH -2), 2.57 (3H, s, CH -9), 6.31 (1H, s, H-6), 7.35 (1H, s, H-4), 7.40-7.45 (5H, m, Ph-3), 7.53 (1H, s, H-4).
3
3
-1
3,5-Diphenyl-7H-furo[3,2-g]chromen-7-one (29): C23H14O3, yield 83%, mp 191 C. IR spectrum (KBr, cm ): 1712,
1605, 1560, 1434, 1364, 1332, 1251, 1158, 1132, 1056, 940, 839, 758. PMR spectrum (300 MHz, DMSO-d , , ppm): 6.40
6
(1H, s, H-6), 7.36 (1H, m, H-4 of Ph-3), 7.45 (2H, m, H-3 and H-5 of Ph-3), 7.56 (2H, m, H-2 and H-6 of Ph-3), 7.60 (5H, m,
Ph-5), 7.82 (1H, s, H-4), 7.89 (1H, s, H-9), 8.43 (1H, s, H-2).
9-Methyl-3,5-diphenyl-7H-furo[3,2-g]chromen-7-one (30): C24H16O3, yield 79%, mp 248 C. IR spectrum (KBr,
cm-1): 1717, 1600, 1560, 1440, 1360, 1338, 1250, 1161, 1130, 1060, 945, 842, 762. PMR spectrum (300 MHz, DMSO-d , ,
6
ppm): 2.58 (3H, s, CH -9), 6.36 (1H, s, H-6), 7.35 (1H, m, H-4 of Ph-3), 7.43 (2H, m, H-3 and H-5 of Ph-3), 7.53 (2H, m, H-2
3
and H-6 of Ph-3), 7.56 (5H, m, Ph-5), 7.64 (1H, s, H-4), 8.41 (1H, s, H-2).
3-(4-Chlorophenyl)-5-phenyl-7H-furo[3,2-g]chromen-7-one (31): C23H13ClO3, yield 88%, mp 223 C. IR spectrum
(KBr, cm-1): 1719, 1625, 1560, 1486, 1441, 1342, 1316, 1266, 1162, 1132, 1090, 1069, 948, 860, 827, 791. PMR spectrum
(300 MHz, DMSO-d , , ppm): 6.40 (1H, s, H-6), 7.51 (2H, d, J = 9 Hz, H-3 and H-5 of Ph-3), 7.59 (2H, d, J = 9 Hz, H-2 and
6
H-6 of Ph-3), 7.61 (5H, m, Ph-5), 7.80 (1H, s, H-4), 7.90 (1H, s, H-9), 8.47 (1H, s, H-2).
3-(4-Chlorophenyl)-9-methyl-5-phenyl-7H-furo[3,2-g]chromen-7-one (32): C24H15ClO3, yield 91%, mp 267 C.
IR spectrum (KBr, cm-1): 1717, 1620, 1561, 1490, 1435, 1342, 1310, 1260, 1169, 1125, 1088, 1060, 950, 860, 790. PMR
spectrum (300 MHz, DMSO-d , , ppm): 2.58 (3H, s, CH -9), 6.38 (1H, s, H-6), 7.51 (2H, d, J = 9 Hz, H-3 and H-5 of Ph-3),
6
3
7.56 (2H, d, J = 9 Hz, H-2 and H-6 of Ph-3), 7.59 (5H, m, Ph-5), 7.60 (1H, s, H-4), 8.46 (1H, s, H-2).
3-(1,3-Benzodioxol-5-yl)-5-phenyl-7H-furo[3,2-g]chromen-7-one (33): C24H14O5, yield 76%, mp 192 C. IR
spectrum (KBr, cm-1): 1716, 1615, 1565, 1430, 1378, 1325, 1250, 1151, 1130, 1069, 968, 830, 772. PMR spectrum (300 MHz,
DMSO-d , , ppm): 6.05 (2H, s, OCH O), 6.40 (1H, s, H-6), 6.97 (1H, d, J = 8.5 Hz, H-7 of benzodioxol), 7.03 (1H, dd, J =
6
2
2.0 and 8.5 Hz, H-6 of benzodioxol), 7.14 (1H, d, J = 2.0 Hz, H-4 of benzodioxol), 7.63 (5H, m, Ph-5), 7.78 (1H, s, H-4), 7.87
(1H, s, H-9), 8.36 (1H, s, H-2).
3-(1,3-Benzodioxol-5-yl)-9-methyl-5-phenyl-7H-furo[3,2-g]chromen-7-one (34): C25H16O5, yield 83%, mp 239 C.
IR spectrum (KBr, cm-1): 1718, 1619, 1555, 1440, 1365, 1325, 1257, 1140, 1125, 1060, 961, 849, 752. PMR spectrum (300
MHz, DMSO-d , , ppm): 2.57 (3H, s, CH -9), 6.03 (2H, s, OCH O), 6.33 (1H, s, H-6), 6.96 (1H, d, J = 8.5 Hz, H-7 of
6
3
2
benzodioxol), 7.06 (1H, dd, J = 2.0 and 8.5 Hz, H-6 of benzodioxol), 7.14 (1H, d, J = 2.0 Hz, H-4 of benzodioxol), 7.58 (5H,
m, Ph-5), 7.60 (1H, s, H-4), 8.27 (1H, s, H-2).
4-Phenyl-6,7,8,9-tetrahydro-2H-benzo[4,5]furo[3,2-g]chromen-2-one (35): C21H16O3, yield 72%, mp 234 C. IR
spectrum (KBr, cm-1): 3035, 2920, 1716, 1696, 1615, 1556, 1445, 1377, 1336, 1288, 1240, 1134, 1119, 982, 949, 878, 790,
768, 709. PMR spectrum (300 MHz, DMSO-d , , ppm): 1.75 (2H, m, H-7), 1.87 (2H, m, H-8), 2.60 (2H, m, H-6), 2.73 (2H,
6
m, H-9), 6.32 (1H, s, H-3), 7.38 (1H, s, H-5), 7.59 (5H, m, Ph-4), 7.67 (1H, s, H-11).
11-Methyl-4-phenyl-6,7,8,9-tetrahydro-2H-benzo[4,5]furo[3,2-g]chromen-2-one (36): C22H18O3, yield 78%, mp
483

-1
268 C. IR spectrum (KBr, cm ): 3040, 2920, 1718, 1690, 1600, 1560, 1440, 1382, 1330, 1271, 1236, 1130, 1110, 980, 941,
880, 775. PMR spectrum (300 MHz, DMSO-d , , ppm): 1.73 (2H, m, H-7), 1.85 (2H, m, H-8), 2.46 (3H, s, CH -11), 2.60 (2H,
6
3
m, H-6), 2.73 (2H, m, H-9), 6.28 (1H, s, H-3), 7.21 (1H, s, H-5), 7.59 (5H, m, Ph-4).
3,4-Dimethyl-9-phenyl-7H-furo[2,3-f]chromen-7-one (37): C19H14O3, yield 72%, mp 186 C. IR spectrum (KBr,
cm-1): 1718, 1690, 1595, 1556, 1480, 1427, 1360, 1225, 1190, 1130, 1115, 1062, 948, 874, 755. PMR spectrum (300 MHz,
DMSO-d , , ppm): 2.32 (3H, s, CH -3), 2.70 (3H, s, CH -4), 6.26 (1H, s, H-8), 7.18 (1H, s, H-5), 7.49 (5H, m, Ph-5), 7.52
6
3
3
(1H, s, H-2).
2,3,4-Trimethyl-9-phenyl-7H-furo[2,3-f]chromen-7-one (38): C20H16O3, yield 70%, mp 162 C. IR spectrum
(KBr, cm-1): 1716, 1695, 1610, 1550, 1482, 1431, 1360, 1232, 1191, 1115, 1068, 954, 879, 755. PMR spectrum (300 MHz,
DMSO-d , , ppm): 2.02 (3H, s, CH -2), 2.24 (3H, s, CH -3), 2.66 (3H, s, CH -4), 6.25 (1H, s, H-8), 7.10 (1H, s, H-5), 7.50
6
3
3
3
(5H, m, Ph-5).
4-Methyl-3,9-diphenyl-7H-furo[2,3-f]chromen-7-one (39): C24H16O3, yield 84%, mp 216 C. IR spectrum
(KBr, cm-1): 3055, 1718, 1695, 1600, 1561, 1482, 1444, 1367, 1217, 1180, 1126, 1101, 1059, 940, 894, 865, 762. PMR
spectrum (300 MHz, DMSO-d , , ppm): 2.24 (3H, s, CH -4), 6.33 (1H, s, H-8), 7.25 (1H, s, H-5), 7.44 (5H, m, Ph-3), 7.56
6
3
(5H, m, Ph-9), 7.81 (1H, s, H-2).
3-(4-Chlorophenyl)-4-methyl-9-phenyl-7H-furo[2,3-f]chromen-7-one (40): C24H15ClO3, yield 86%, mp 225 C.
IR spectrum (KBr, cm-1): 1716, 1610, 1565, 1475, 1450, 1367, 1215, 1180, 1136, 1118, 1059, 932, 875, 755. PMR spectrum
(300 MHz, DMSO-d , , ppm): 2.26 (3H, s, CH -4), 6.32 (1H, s, H-8), 7.30 (2H, d, J = 9 Hz, H-3 and H-5 of Ph-3), 7.51 (2H,
6
3
d, J = 9 Hz, H-2 and H-6 of Ph-3), 7.54 (5H, m, Ph-9), 7.84 (1H, s, H-2).
6-Methyl-1-phenyl-7,8,9,10-tetrahydro-3H-benzo[4,5]furo[2,3-f]chromen-3-one (41): C22H18O3, yield 69%, mp
186 C. IR spectrum (KBr, cm-1): 3040, 2930, 1718, 1690, 1605, 1550, 1440, 1370, 1330, 1262, 1228, 1135, 1105, 970, 886,
779. PMR spectrum (300 MHz, DMSO-d , , ppm): 1.73 (4H, m, H-8, H-9), 2.34 (2H, m, H-10), 2.62 (3H, s, CH -6), 2.78
6
3
(2H, m, H-7), 6.26 (1H, s, H-2), 7.13 (1H, s, H-5), 7.49 (5H, m, Ph-1).
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