Modified coumarins. 15. Condensed psoralen derivatives based on substituted dibenzo[b,d]pyran-6-ones

Article abstract of DOI:10.1007/s10600-005-0030-1

Benzo[c]furo[3,2-g]chromen-5-ones, modified psoralen analogs containing a substituted benzene ring annelated at the 5,6-position of the furo[3,2-g]chromen-7-one system, were prepared by the MacLeod method. 2004 Springer Science + Business Media, Inc.

Full text of DOI:10.1007/s10600-005-0030-1

Chemistry of Natural Compounds, Vol. 40, No. 6, 2004
MODIFIED COUMARINS. 15. CONDENSED PSORALEN DERIVATIVES
BASED ON SUBSTITUTED DIBENZO[b,d]PYRAN-6-ONES
Ya. L. Garazd,1 M. M. Garazd,2 and V. P. Khilya1
UDC 547.814.5
Benzo[c]furo[3,2-g]chromen-5-ones, modified psoralen analogs containing a substituted benzene ring
annelated at the 5,6-position of the furo[3,2-g]chromen-7-one system, were prepared by the MacLeod
method.
Key words: coumarins, furocoumarins, psoralen, dibenzo[b,d]puran-6-one.
Natural and synthetic dibenzo[ , ]pyran-6-ones are known to possess a wide spectrum of biological activity, in
b d
particular, insecticidal [1], antimicrobial [2], antiviral [3], and anti-hepatitic [4], and to act as inhibitors of aldosereductase [5],
tyrosinekinase [6], and 3-phosphoglyceratekinase [7].
In continuation of the synthesis and investigation of the properties of condensed furocoumarins [8-10], we prepared
newtetracyclicpsoralen analogsbasedon 3-methoxybenzo[ ]furo[3,2- ]chromen-5-one. Modification ofthedibenzo[ , ]pyran-
b d
c
g
6-one system byadding a furan ring was expected toproduce newbiologicallyactive compounds based on natural bioregulators.
Ofthe numerous possibilities for constructing the furocoumarins [11-14], we selectedtheMacLeodmethodfor forming
the psoralen system that is based on cyclization in alkaline medium of 7-(2-oxoethyl)coumarin derivatives. In most instances
this led exclusively to linear furocoumarins (psoralen-type furocoumarins) since the 6-position of the coumarin ring is more
strongly activated than the 8-position [15, 16].
R
R
R
O
O
O
O
HO
O
O
R
R
O
O
O
O
1
2
RCOCH Hal
2
R COCHR -Hal
2 1
K CO
K CO
2 3
R
2
3
1
OMe
OMe
OMe
3 - 6, 11, 12
1, 2
7 - 10
O
1. NaOH
2. HCl
1. NaOH
2. HCl
, K CO
2
3
Cl
O
R
R
R
O
O
O
O
O
O
O
O
O
R
1
R
1
R
2
OMe
OMe
OMe
13, 14
19 - 22
15 - 18, 23, 24
3, 15: R = H, R = Me
4, 16: R = R = Me
5, 17: R = H, R = (CH )
3 3
1. NaOH
2. HCl
7, 19: R = H, R = R = Me
8, 20: R = R = R = Me
9, 21: R = H, R = Me, R = Ph
10, 22: R = R = Me, R = Ph
1
2
1
1
2
1
R
1
2
1
1
2
O
O
6, 18: R = Me, R = (CH )
3 3
O
1
11, 23: R = H, R = Ph
1
12, 24: R = Me, R = Ph
1
25, 26
OMe
1, 13, 25: R = H
2, 14, 26: R = Me
1)TarasShevchenkoKievNational University, 01033, Ukraine, Kiev, ul. Vladimirskaya, 64; 2) InstituteofBioorganic
and Petroleum Chemistry, National Academy of Sciences of Ukraine, 02094, Kiev, ul. Murmanskaya, 1, e-mail:
gmm@i.com.ua. Translated from Khimiya Prirodnykh Soedinenii, No. 6, pp. 441-445, November-December, 2004. Original
article submitted June 28, 2004.
0009-3130/04/4006-0535 ©2004 Springer Science + Business Media, Inc.
535

Thestartingmaterialsfor further conversionswere3-hydroxy-8-methoxybenzo[c]chromen-6-one(1)and3-hydroxy-8-
methoxy-4-methylbenzo[c]chromen-6-one(2),which werepreparedbyHartleycondensation [17]of5-methoxy-2-bromobenzoic
acid and resorcinol and 2-methylresorcinol, respectively, in NaOH solution using a catalyst of copper sulfate (10% solution).
The Williamson reaction of the 3-hydroxydibenzo-α-pyrones (1 and 2) with α-haloketones gave in high yields (62-
88%) the corresponding substituted 8-methoxy-3-(2-oxopropoxy)benzo[c]chromen-6-ones 3-14. The alkalyating agents in this
synthesis were chloroacetone (3, 4), 1-chloropinacolone (5, 6), 3-chlorobutan-2-one (7, 8), 2-bromopropiophenone (9, 10),
phenacylbromide (11, 12), and 2-chlorocyclohexanone (13, 14).
The PMRspectra of3-14contain signalscharacteristicofthecorrespondingalkyl substituents and benzo[c]chromen-6-
-1
one system. The IR spectra of ketones 3-14 have twoabsorption bands near 1692-1746 cm that are due to stretching vibrations
of the coumarin C=O bond and the carbonyl in the alkoxyl substituent.
Heating alcoholic solutions of oxoketones 3-14 with NaOH solution (1 N) with subsequent acidolysis of the reaction
mixtureafter thereaction wascompleteformedthecorrespondingbenzo[c]furo[3,2-g]chromen-5-ones15-26, tetracyclicanalogs
of psoralen-type furocoumarins that contain an annelated benzene ring. The structures of the furocoumarins were proved using
PMR spectroscopy. The PMR spectra of 15-26 exhibit a simplified splitting pattern for the aromatic protons compared with
the starting ketones owing to the lack of coupling for the H-2 proton of the benzo[c]chromen-6-one ring. For the
7-methylbenzo[c]furo[3,2-g]chromen-5-ones, the H-11 proton is observed as a singlet near 7.92-8.46 ppm. Protons H-7 and
H-11 resonate in the spectra of furocoumarins without a substituent in the 7-position as singlets at 7.39-7.74 and 8.17-8.51 pm,
respectively. Furthermore, furocoumarins 15-18, 23, and 24, which have no substituent at the 9-position, show a 1H singlet
for H-9. This is also typical of an annelated furocoumarin ring.
EXPERIMENTAL
The course of reactions and purity of products were monitored by TLC on Merck 60 F254 plates using CHCl :CH OH
3
3
(9:1) as eluent. Melting points were determined on a Kofler block. IR and UV spectra were measured on a Nicolet FTIR Nexus
475 spectrometer and a Specord M40 spectrophotometer, respectively. PMR spectra were recorded on a Varian Mercury 400
spectrometer at 400 MHz relative to TMS (internal standard). Elemental analyses of all compounds agreed with those
calculated.
3-Hydroxy-8-methoxybenzo[c]chromen-6-one (1). Asolution of5-methoxy-2-bromobenzoicacid(11.55g,0.05mol),
resorcinol (11.00 g, 0.1 mol), and NaOH (4.00 g, 0.1 mol) in H O (50 mL) was heated to 60°C and treated with copper sulfate
2
solution (10%, 5 mL). The reaction mixture was held at 80-90°C, stirred vigorously until it thickened, and left at room
temperature overnight. The resulting solid was filtered off, thoroughly washed with water, dried, and crystallized from glacial
acetic acid. Yield 7.51 g (62%), mp 242°C (lit. 271-280°C [18]), C H O .
14 10
4
-1
IR spectrum (KBr, cm ): 3345, 1694, 1633, 1620, 1495, 1460, 1321, 1295, 1278, 1173, 1034, 810. UV spectrum
(dioxane, λ , nm, log ε): 215 (4.43), 221 (4.46), 235 (4.39), 272 (4.11), 282 (4.21), 296 (4.07), 311 (4.03), 349 (3.75).
max
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 3.89 (3H, s, OMe-8), 6.75 (1H, d, J = 2.0, H-4), 6.83 (1H, dd,
6
J = 1.2, J = 8.8, H-2), 7.49 (1H, dd, J = 2.8, J = 8.8, H-9), 7.60 (1H, d, J = 2.8, H-7), 8.09 (1H, d, J = 8.8, H-1), 8.21 (1H, d,
J = 8.8, H-10), 10.25 (1H, s, OH-3).
3-Hydroxy-8-methoxy-4-methylbenzo[c]chromen-6-one (2) was prepared analogously to 1 from 5-methoxy-2-
bromobenzoic acid (11.55 g, 0.05 mol) and 2-methylresorcinol (12.41 g, 0.1 mol). Yield 9.35 g (73%), mp 265°C, C H O .
15 12
4
-1
IR spectrum (KBr, cm ): 3273, 1699, 1612, 1484, 1354, 1321, 1302, 1278, 1138, 1111, 1079, 1027, 815, 778.
UV spectrum (dioxane,
, nm, log ): 225 (4.68), 235 (4.57), 278 (4.32), 284 (4.38), 298 (4.21), 310 (4.21), 349 (3.96), 364
max
(3.86).
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 2.19 (3H, s, Me-4), 3.88 (3H, s, OMe-8), 6.87 (1H, d, J = 8.8,
6
H-2), 7.45 (1H, dd, J = 2.8, J = 8.8, H-9), 7.57 (1H, d, J = 2.8, H-7), 7.89 (1H, d, J = 8.8, H-1), 8.15 (1H, d, J = 8.8, H-10), 10.07
(1H, s, OH-3).
8-Methoxy-3-(2-oxopropoxy)benzo[c]chromen-6-ones (3-14). A hot solution of hydroxycoumarin 1 or 2 (4 mmol)
in absolute acetone (30 mL) was treated with freshly calcined potash (1.38 g, 10 mmol), stirred vigorously, heated (50-55°C),
and treated with the appropriate -haloketone (4.2 mmol). The reaction mixture was held for 1-3 h with heating and vigorous
stirring. The course of the reaction was monitored by TLC. The reaction mixture was poured into H SO solution (100 mL,
2
4
1 N). The resulting precipitate was filtered off and crystallized from propan-2-ol.
536

8-Methoxy-3-(2-oxopropoxy)benzo[c]chromen-6-one (3). Yield 75%, C H O , mp 174°C.
17 14
5
-1
IR spectrum (KBr, cm ): 1724, 1699, 1624, 1612, 1489, 1353, 1319, 1298, 1275, 1164, 1150, 1059, 1035.
UV spectrum (CH CN, λ , nm, log ε): 202 (4.62), 221 (4.68), 234 (4.61), 274 (4.36), 282 (4.47), 298 (4.26), 308 (4.29), 346
3
max
(3.98).
PMR spectrum (400 MHz, DMSO-d , , ppm, J/Hz): 2.18 (3H, s, CH -3′), 3.89 (3H, s, OMe-8), 4.96 (2H, s, CH -1′),
6
3
2
6.96 (1H, d, J = 2.8, H-4), 6.98 (1H, dd, J = 2.8, J = 9.2, H-2), 7.50 (1H, dd, J = 2.8, J = 8.8, H-9), 7.60 (1H, d, J = 2.8, H-7),
8.17 (1H, d, J = 9.2, H-1), 8.26 (1H, d, J = 8.8, H-10).
8-Methoxy-4-methyl-3-(2-oxopropoxy)benzo[c]chromen-6-one (4). Yield 81%, C H O , mp 158°C.
18 16
5
-1
IR spectrum (KBr, cm ): 1718, 1700, 1614, 1484, 1350, 1313, 1288, 1222, 1125, 1063, 1026, 773. UV spectrum
(CH CN,
, nm, log ): 202 (4.60), 226 (4.74), 234 (4.61), 277 (4.36), 284 (4.44), 297 (4.26), 308 (4.24), 348 (3.97).
3
max
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 2.20 (3H, s, CH -3′), 2.28 (3H, s, Me-4), 3.89 (3H, s, OMe-8),
6
3
4.95 (2H, s, CH -1′), 6.91 (1H, d, J = 9.2, H-2), 7.48 (1H, dd, J = 2.8, J = 8.8, H-9), 7.60 (1H, d, J = 2.8, H-7), 8.03 (1H, d,
2
J = 9.2, H-1), 8.26 (1H, d, J = 8.8, H-10).
3-(3,3-Dimethyl-2-oxobutoxy)-8-methoxybenzo[c]chromen-6-one (5). Yield 84%, C H O , mp 179-180°C.
20 20
5
-1
IR spectrum (KBr, cm ): 1720, 1621, 1489, 1435, 1349, 1277, 1180, 1105, 1053, 1040, 808, 774. UV spectrum
(EtOH, λ , nm, log ε): 202 (4.53), 221 (4.60), 234 (4.56), 272 (4.30), 282 (4.42), 298 (4.22), 308 (4.25), 350 (3.96).
max
PMR spectrum (400 MHz, DMSO-d , , ppm, J/Hz): 1.20 [9H, s, (CH ) ], 3.89 (3H, s, OMe-8), 5.31 (2H, s, CH -1′),
6
3 3
2
6.96 (1H, d, J = 2.8, H-4), 6.98 (1H, dd, J = 2.8, J = 9.2, H-2), 7.50 (1H, dd, J = 2.8, J = 8.8, H-9), 7.60 (1H, d, J = 2.8, H-7),
8.17 (1H, d, J = 9.2, H-1), 8.26 (1H, d, J = 8.8, H-10).
3-(3,3-Dimethyl-2-oxobutoxy)-8-methoxy-4-methylbenzo[c]chromen-6-one (6). Yield 81%, C H O , mp 194-
20 20
5
195°C.
-1
IR spectrum (KBr, cm ): 1715, 1615, 1487, 1315, 1290, 1152, 1140, 1085, 1038, 997, 808, 776. UV spectrum (EtOH,
, nm, log ): 228 (4.71), 277 (4.30), 285 (4.39), 298 (4.22), 310 (4.23), 346 (3.93).
max
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 1.20 [9H, s, (CH ) ], 2.30 (3H, s, Me-4), 3.91 (3H, s, OMe-8),
6
3 3
5.31 (2H, s, CH -1′), 6.90 (1H, d, J = 9.2, H-2), 7.50 (1H, dd, J = 2.8, J = 8.8, H-9), 7.63 (1H, d, J = 2.8, H-7), 8.06 (1H, d,
2
J = 9.2, H-1), 8.28 (1H, d, J = 8.8, H-10).
8-Methoxy-3-(1-methyl-2-oxopropoxy)benzo[c]chromen-6-one (7). Yield 73%, C H O , mp 147°C.
18 16
5
-1
IR spectrum (KBr, cm ): 1726, 1698, 1618, 1489, 1434, 1349, 1265, 1180, 1120, 1096, 1042. UV spectrum (CH CN,
3
λ
, nm, log ε): 202 (4.62), 221 (4.69), 234 (4.62), 273 (4.36), 282 (4.48), 298 (4.26), 308 (4.30), 346 (3.99).
PMR spectrum (400 MHz, DMSO-d , , ppm, J/Hz): 1.47 (3H, d, J = 6.8, CH -1′), 2.21 (3H, s, CH -3′), 3.88 (3H, s,
max
6
3
3
OMe-8), 5.12 (1H, q, J = 6.8, H-1′), 6.91 (1H, d, J = 2.8, H-4), 6.94 (1H, dd, J = 2.8, J = 8.8, H-2), 7.49 (1H, dd, J = 2.8,
J = 8.8, H-9), 7.59 (1H, d, J = 2.8, H-7), 8.16 (1H, d, J = 8.8, H-1), 8.24 (1H, d, J = 8.8, H-10).
8-Methoxy-4-methyl-3-(1-methyl-2-oxopropoxy)benzo[c]chromen-6-one (8). Yield 79%, C H O , mp 130°C.
19 18
5
-1
IR spectrum (KBr, cm ): 1716, 1699, 1613, 1482, 1311, 1287, 1153, 1134, 1117, 1098, 1026, 804, 774. UV spectrum
(CH CN,
, nm, log ): 202 (4.53), 225 (4.64), 233 (4.48), 272 (4.19), 286 (4.31), 296 (4.18), 308 (4.16), 344 (3.95).
3
max
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 1.48 (3H, d, J = 7.2, CH -1′), 2.21 (3H, s, CH -3′), 2.26 (3H, s,
6
3
3
Me-4), 3.88 (3H, s, OMe-8), 5.07 (1H, q, J = 7.2, H-1′), 6.84 (1H, d, J = 8.4, H-2), 7.45 (1H, dd, J = 2.8, J = 8.8, H-9), 7.56 (1H,
d, J = 2.8, H-7), 7.98 (1H, d, J = 8.4, H-1), 8.19 (1H, d, J = 8.8, H-10).
8-Methoxy-3-(1-methyl-2-oxo-2-phenylethoxy)benzo[c]chromen-6-one (9). Yield 85%, C H O , mp 117°C.
23 18
5
-1
IRspectrum (KBr, cm ): 1729, 1700, 1619, 1597, 1485, 1346, 1266, 1229, 1177, 1142, 1119, 1036, 823. UVspectrum
(CH CN, λ , nm, log ε): 201 (4.76), 222 (4.60), 238 (4.64), 274 (4.32), 282 (4.41), 298 (4.21), 308 (4.21), 348 (3.91).
3
max
PMR spectrum (400 MHz, DMSO-d , , ppm, J/Hz): 1.57 (3H, d, J = 6.8, CH -2′), 3.88 (3H, s, OMe-8), 6.21 (1H, q,
6
3
J = 6.8, H-2′), 6.92 (1H, d, J = 2.8, H-4), 6.95 (1H, dd, J = 2.8, J = 8.8, H-2), 7.49 (1H, dd, J = 2.8, J = 8.8, H-9), 7.60 (3H, m,
H-7, H-3″, H-5″), 7.72 (1H, m, H-4″), 8.11 (2H, d, J = 7.2, H-2″, H-6″), 8.17 (1H, d, J = 8.8, H-1), 8.23 (1H, d, J = 8.8, H-10).
8-Methoxy-4-methyl-3-(1-methyl-2-oxo-2-phenylethoxy)benzo[c]chromen-6-one (10). Yield 88%, C H O ,
24 20
5
mp 143°C.
IR spectrum (KBr, cm ): 1735, 1692, 1614, 1597, 1480, 1350, 1324, 1278, 1217, 1138, 1114, 1095, 1027.
UV spectrum (dioxane, , nm, log ): 215 (4.61), 226 (4.70), 234 (4.66), 277 (4.34), 285 (4.41), 295 (4.26), 308 (4.20), 346
-1
max
(3.95).
537

PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 1.61 (3H, d, J = 6.4, CH -2′), 2.28 (3H, s, Me-4), 3.88 (3H, s,
6
3
OMe-8), 6.17 (1H, q, J = 6.4, H-2′), 6.85 (1H, d, J = 8.4, H-2), 7.45 (1H, dd, J = 2.8, J = 8.8, H-9), 7.59 (3H, m, H-7, H-3″,
H-5″), 7.70 (1H, m, H-4″), 7.97 (1H, d, J = 8.4, H-1), 8.09 (2H, d, J = 7.2, H-2″, H-6″), 8.19 (1H, d, J = 8.8, H-10).
8-Methoxy-3-(2-oxo-2-phenylethoxy)benzo[c]chromen-6-one (11). Yield 76%, C H O , mp 191-192°C.
22 16
5
-1
IR spectrum (KBr, cm ): 1718, 1702, 1618, 1486, 1439, 1287, 1235, 1175, 1120, 1065, 1037, 968, 833. UV spectrum
(dioxane, λ , nm, log ε): 215 (4.71), 221 (4.73), 236 (4.75), 272 (4.41), 282 (4.50), 298 (4.29), 309 (4.32), 346 (4.02).
max
PMR spectrum (400 MHz, DMSO-d , , ppm, J/Hz): 3.89 (3H, s, OMe-8), 5.73 (2H, s, CH -2′), 7.05 (1H, dd, J = 2.4,
6
2
J = 8.8, H-2), 7.09 (1H, d, J = 2.4, H-4), 7.50 (1H, dd, J = 2.8, J = 8.8, H-9), 7.60 (3H, m, H-7, H-3″, H-5″), 7.71 (1H, m, H-4″),
8.05 (2H, d, J = 7.2, H-2″, H-6″), 8.19 (1H, d, J = 8.8, H-1), 8.27 (1H, d, J = 8.8, H-10).
8-Methoxy-4-methyl-3-(2-oxo-2-phenylethoxy)benzo[c]chromen-6-one (12). Yield82%, C H O , mp184-185°C.
23 18
5
-1
IR spectrum (KBr, cm ): 1712, 1699, 1616, 1485, 1434, 1358, 1314, 1280, 1224, 1133, 1070, 763. UV spectrum
(CH CN,
, nm, log ): 202 (4.86), 226 (4.82), 235 (4.77), 278 (4.48), 284 (4.55), 298 (4.31), 307 (4.21), 348 (3.95).
3
max
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 2.32 (3H, s, Me-4), 3.89 (3H, s, OMe-8), 5.75 (2H, s, CH -2′),
6
2
7.02 (1H, d, J = 8.4, H-2), 7.48 (1H, dd, J = 2.8, J = 8.8, H-9), 7.60 (3H, m, H-7, H-3″, H-5″), 7.71 (1H, m, H-4″), 8.04 (3H,
m, H-1, H-2″, H-6″), 8.26 (1H, m, J = 8.8, H-10).
8-Methoxy-3-(2-oxocyclohexyloxy)benzo[c]chromen-6-one (13). Yield 62%, C H O , mp 183-185°C.
20 18
5
-1
IR spectrum (KBr, cm ): 1746, 1728, 1719, 1621, 1599, 1486, 1470, 1433, 1343, 1316, 1267, 1181, 1110, 1064, 1034,
807. UV spectrum (EtOH, λ , nm, log ε): 204 (4.25), 221 (4.32), 235 (4.24), 272 (4.00), 282 (4.10), 299 (3.94), 308 (3.96),
max
352 (3.66).
PMR spectrum (400 MHz, DMSO-d , , ppm, J/Hz): 1.68-2.65 (8H, m, CH -3′, CH -4′, CH -5′, CH -6′), 3.88 (3H,
6
2
2
2
2
s, OMe-8), 5.10 (1H, m, H-2′), 6.91 (1H, d, J = 2.8, H-4), 6.94 (1H, dd, J = 2.8, J = 8.8, H-2), 7.49 (1H, dd, J = 2.8, J = 8.8,
H-9), 7.59 (1H, d, J = 2.8, H-7), 8.16 (1H, d, J = 8.8, H-1), 8.24 (1H, d, J = 8.8, H-10).
8-Methoxy-4-methyl-3-(2-oxocyclohexyloxy)benzo[c]chromen-6-one (14). Yield 79%, C H O , mp 184-185°C.
21 20
5
-1
IR spectrum (KBr, cm ): 1733, 1712, 1614, 1483, 1312, 1281, 1146, 1131, 1111, 1028, 798. UV spectrum (EtOH,
, nm, log ): 204 (4.37), 226 (4.53), 286 (4.30), 298 (4.17), 307 (4.12), 352 (3.83).
max
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 1.68-2.65 (8H, m, CH -3′, CH -4′, CH -5′, CH -6′), 2.29 (3H,
6
2
2
2
2
s, Me-4), 3.90 (3H, s, OMe-8), 5.10 (1H, m, H-2′), 6.82 (1H, d, J = 9.2, H-2), 7.42 (1H, dd, J = 2.8, J = 8.8, H-9), 7.59 (1H, d,
J = 2.8, H-7), 7.88 (1H, d, J = 9.2, H-1), 8.16 (1H, d, J = 8.8, H-10).
3-Methoxybenzo[c]furo[3,2-g]chromen-5-ones(15-26). Asolution or suspension ofketone3-14(2mmol)in propan-
2-ol (10 mL) was treated with NaOH solution (10 mL, 1 N). The reaction mixture was heated for 3-4 h until the starting ketone
had completely dissolved (course of reaction monitored by TLC) and then poured into HCl (50 mL, 1 N). The resulting
precipitate was filtered off and crystallized from propan-2-ol.
3-Methoxy-10-methylbenzo[c]furo[3,2-g]chromen-5-one (15). Yield 79%, C H O , mp 221-222°C.
17 12
4
-1
IR spectrum (KBr, cm ): 1722, 1700, 1615, 1517, 1460, 1354, 1344, 1298, 1269, 1141, 1047, 1033, 827. UV spectrum
(CH CN, λ , nm, log ε): 205 (4.38), 235 (4.96), 246 (4.69), 253 (4.61), 286 (4.19), 313 (4.08), 326 (4.13), 340 (4.10), 350
3
max
(4.04).
PMR spectrum (400 MHz, DMSO-d , , ppm, J/Hz): 2.25 (3H, s, Me-10), 3.88 (3H, s, OMe-3), 7.45 (1H, dd, J = 2.4,
6
J = 9.2, H-2), 7.48 (1H, s, H-7), 7.52 (1H, d, J = 2.4, H-4), 7.78 (1H, s, H-9), 8.33 (1H, s, H-11), 8.35 (1H, d, J = 9.2, H-1).
3-Methoxy-7,10-dimethylbenzo[c]furo[3,2-g]chromen-5-one (16). Yield 73%, C H O , mp 246-247°C.
18 14
4
-1
IR spectrum (KBr, cm ): 1716, 1614, 1515, 1455, 1438, 1345, 1291, 1137, 1094, 1036, 834. UV spectrum (dioxane,
, nm, log ): 215 (4.49), 237 (4.84), 250 (4.80), 255 (4.75), 278 (4.31), 289 (4.26), 314 (4.14), 326 (4.20), 340 (4.17), 353
max
(4.08).
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 2.29 (3H, s, Me-10), 2.49 (3H, s, Me-7), 3.92 (3H, s, OMe-3),
6
7.53 (1H, dd, J = 2.4, J = 8.8, H-2), 7.64 (1H, d, J = 2.4, H-4), 7.84 (1H, s, H-9), 8.35 (1H, s, H-11), 8.48 (1H, d, J = 8.8, H-1).
10-(t-Butyl)-3-methoxybenzo[c]furo[3,2-g]chromen-5-one (17). Yield 79%, C H O , mp 205-206°C.
20 18
4
-1
IR spectrum (KBr, cm ): 1720, 1615, 1512, 1479, 1464, 1350, 1270, 1251, 1134, 1078, 1014, 840. UV spectrum
(CH CN, λ , nm, log ε): 204 (4.27), 236 (4.65), 248 (4.55), 255 (4.45), 288 (3.98), 313 (3.94), 326 (4.02), 338 (3.97), 356
3
max
(3.84).
PMR spectrum (400 MHz, DMSO-d , , ppm, J/Hz): 1.48 [9H, s, (CH ) ], 3.93 (3H, s, OMe-3), 7.48 (1H, dd, J = 2.4,
6
3 3
J = 9.2, H-2), 7.55 (1H, s, H-7), 7.64 (1H, d, J = 2.4, H-4), 7.67 (1H, s, H-9), 8.51 (1H, s, H-11), 8.59 (1H, d, J = 9.2, H-1).
538

10-(t-Butyl)-3-methoxy-7-methylbenzo[c]furo[3,2-g]chromen-5-one (18). Yield 81%, C H O , mp 206-207°C.
21 20
4
-1
IR spectrum (KBr, cm ): 1721, 1615, 1513, 1461, 1439, 1365, 1343, 1277, 1256, 1137, 1087, 1031, 827. UV spectrum
(dioxane,
, nm, log ): 212 (4.33), 237 (4.67), 250 (4.57), 256 (4.47), 288 (4.00), 326 (4.08), 340 (4.01).
max
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 1.47 [9H, s, (CH ) ], 2.49 (3H, s, Me-7), 3.92 (3H, s, OMe-3),
6
3 3
7.52 (1H, dd, J = 2.4, J = 8.8, H-2), 7.64 (1H, d, J = 2.4, H-4), 7.79 (1H, s, H-9), 8.43 (1H, s, H-11), 8.66 (1H, d, J = 8.8, H-1).
3-Methoxy-9,10-dimethylbenzo[c]furo[3,2-g]chromen-5-one (19). Yield 76%, C H O , mp 214-215°C.
18 14
4
-1
IR spectrum (KBr, cm ): 1717, 1615, 1513, 1458, 1428, 1345, 1300, 1265, 1151, 1045, 841. UV spectrum (dioxane,
λ
, nm, log ε): 215 (4.53), 237 (4.80), 255 (4.80), 278 (4.27), 287 (4.25), 317 (4.20), 329 (4.27), 340 (4.23), 359 (4.06).
max
PMR spectrum (400 MHz, DMSO-d , , ppm, J/Hz): 2.19 (3H, s, Me-10), 2.37 (3H, s, Me-9), 3.90 (3H, s, OMe-3),
6
7.47 (1H, s, H-7), 7.51 (1H, dd, J = 3.2, J = 8.4, H-2), 7.59 (1H, d, J = 3.2, H-4), 8.28 (1H, s, H-11), 8.41 (1H, d, J = 8.4, H-1).
3-Methoxy-7,9,10-trimethylbenzo[c]furo[3,2-g]chromen-5-one (20). Yield 82%, C H O , mp 239°C.
19 16
4
-1
IR spectrum (KBr, cm ): 1713, 1613, 1514, 1463, 1438, 1301, 1285, 1182, 1146, 1089, 1036, 833. UV spectrum
(dioxane,
(4.04).
, nm, log ): 215 (4.72), 237 (4.86), 256 (4.84), 279 (4.40), 288 (4.36), 313 (4.24), 327 (4.27), 339 (4.23), 356
max
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 2.12 (3H, s, Me-10), 2.34 (3H, s, Me-7), 2.36 (3H, s, Me-9), 3.88
6
(3H, s, OMe-3), 7.47 (1H, dd, J = 2.8, J = 8.8, H-2), 7.64 (1H, d, J = 2.8, H-4), 8.06 (1H, s, H-11), 8.34 (1H, d, J = 8.8, H-1).
3-Methoxy-9-methyl-10-phenylbenzo[c]furo[3,2-g]chromen-5-one (21). Yield 81%, C H O , mp 233-235°C.
23 16
4
-1
IRspectrum (KBr, cm ): 1717, 1616, 1518, 1456, 1431, 1360, 1346, 1301, 1268, 1148, 1064, 1037, 834. UVspectrum
(dioxane, λ , nm, log ε): 215 (4.55), 237 (4.76), 255 (4.75), 287 (4.21), 316 (4.12), 329 (4.21), 340 (4.18), 353 (4.06).
max
PMR spectrum (400 MHz, DMSO-d , , ppm, J/Hz): 2.55 (3H, s, Me-9), 3.90 (3H, s, OMe-3), 7.45 (1H, m, H-4′), 7.47
6
(1H, dd, J = 2.4, J = 8.8, H-2), 7.59 (3H, m, H-4, H-3′, H-5′), 7.63 (2H, m, H-2′, H-6′), 7.67 (1H, s, H-7), 8.29 (1H, s, H-11),
8.42 (1H, d, J = 8.8, H-1).
3-Methoxy-7,9-dimethyl-10-phenylbenzo[c]furo[3,2-g]chromen-5-one (22). Yield74%, C H O , mp209-210°C.
24 18
4
-1
IR spectrum (KBr, cm ): 1728, 1614, 1510, 1453, 1345, 1304, 1274, 1174, 1136, 1093, 1024, 821. UV spectrum
(dioxane,
, nm, log ): 215 (4.63), 237 (4.76), 256 (4.79), 291 (4.29), 329 (4.21), 340 (4.19), 353 (4.11).
max
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 2.39 (3H, s, Me-7), 2.47 (3H, s, Me-9), 3.84 (3H, s, OMe-3), 7.36
6
(1H, dd, J = 2.8, J = 8.8, H-2), 7.46 (2H, m, H-4, H-4′), 7.56 (4H, m, H-2′, H-3′, H-5′, H-6′), 7.92 (1H, s, H-11), 8.18 (1H, d,
J = 8.8, H-1).
3-Methoxy-10-phenylbenzo[c]furo[3,2-g]chromen-5-one (23). Yield 88%, C H O , mp 195°C.
22 14
4
-1
IR spectrum (KBr, cm ): 1740, 1618, 1517, 1454, 1294, 1156, 1115, 1056, 1032, 820. UV spectrum (CH CN, λ
,
3
max
nm, log ε): 236 (4.69), 248 (4.57), 279 (4.15), 333 (4.03), 340 (4.04), 352 (3.95).
PMR spectrum (400 MHz, DMSO-d , , ppm, J/Hz): 3.90 (3H, s, OMe-3), 7.44 (1H, m, H-4′), 7.50 (1H, dd, J = 2.4,
6
J = 8.8, H-2), 7.55 (2H, m, H-3′, H-5′), 7.62 (1H, d, J = 2.4, H-4), 7.74 (1H, s, H-7), 7.85 (2H, m, H-2′, H-6′), 8.45 (1H, s, H-11),
8.54 (1H, d, J = 8.8, H-1), 8.62 (1H, s, H-9).
3-Methoxy-7-methyl-10-phenylbenzo[c]furo[3,2-g]chromen-5-one (24). Yield 91%, C H O , mp 215-217°C.
23 16
4
-1
IR spectrum (KBr, cm ): 1723, 1610, 1514, 1453, 1346, 1294, 1251, 1134, 1115, 1081, 1029, 820. UV spectrum
(dioxane,
, nm, log ): 237 (4.61), 253 (4.50), 292 (4.03), 327 (4.05), 340 (4.00).
max
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 2.53 (3H, s, Me-7), 3.91 (3H, s, OMe-3), 7.44 (1H, m, H-4′), 7.47
6
(1H, dd, J = 2.4, J = 8.8, H-2), 7.56 (2H, m, H-3′, H-5′), 7.60 (1H, d, J = 2.4, H-4), 7.85 (2H, m, H-2′, H-6′), 8.45 (1H, s, H-11),
8.46 (1H, s, H-9), 8.52 (1H, d, J = 8.8, H-1).
3-Methoxy-9,10,11,12-tetrahydrobenzo[c]benzo[4,5]furo[3,2-g]chromen-5-one (25). Yield 82%, C H O ,
20 16
4
mp 209-211°C.
-1
IRspectrum (KBr, cm ): 2930, 1722, 1619, 1512, 1454, 1438, 1346, 1311, 1287, 1265, 1143, 1042, 834. UVspectrum
(EtOH, λ , nm, log ε): 205 (4.29), 238 (4.52), 256 (4.53), 290 (3.95), 351 (3.89).
max
PMR spectrum (400 MHz, DMSO-d , , ppm, J/Hz): 1.85 (2H, m, CH -11), 1.94 (2H, m, CH -10), 2.65 (2H, m,
6
2
2
CH -12), 2.73 (2H, m, CH -9), 3.90 (3H, s, OMe-3), 7.39 (1H, s, H-7), 7.45 (1H, dd, J = 3.2, J = 8.4, H-2), 7.61 (1H, d, J = 3.2,
2
2
H-4), 8.17 (1H, d, H-13), 8.31 (1H, d, J = 8.4, H-1).
3-Methoxy-7-methyl-9,10,11,12-tetrahydrobenzo[c]benzo[4,5]furo[3,2-g]chromen-5-one (26).
C H O , mp 292-293°C.
Yield 87%,
21 18
4
539

-1
IR spectrum (KBr, cm ): 2938, 1714, 1610, 1513, 1439, 1320, 1290, 1276, 1147, 1098, 1033, 835. UV spectrum
(EtOH,
, nm, log ): 203 (4.37), 238 (4.48), 256 (4.51), 280 (4.02), 350 (3.84).
max
PMR spectrum (400 MHz, DMSO-d , δ, ppm, J/Hz): 1.80 (2H, m, CH -11), 1.94 (2H, m, CH -10), 2.50 (3H, s,
6
2
2
Me-11), 2.62 (2H, m, CH -12), 2.75 (2H, m, CH -9), 3.92 (3H, s, OMe-3), 7.46 (1H, dd, J = 2.8, J = 8.8, H-2), 7.64 (1H, d,
2
2
J = 2.8, H-4), 8.00 (1H, s, H-11), 8.31 (1H, d, J = 8.8, H-1).
REFERENCES
1.
"Montecatini" Societa Generale per l'Industria Mineraria e Chimica, Ital. Pat. No. 598913 (1959); Chem. Abstr.,
59, 10057g (1963).
2.
3.
4.
5.
6.
7.
8.
9.
J. D. Douros and E. J. McNelis, U.S. Pat. No. 3,248,286 (1966); Chem. Abstr., 65, 4578c (1966).
D. R. Meyer, A. D. Sill, and P. L. Tiernan, U.S. Pat. No. 4,169,897 (1979); Chem. Abstr., 92, P58501e (1980).
M. Ikeda, T. Sakai, et al., Jpn. Pat. No. 08268890 (1996); Chem. Abstr., 126, P74678u (1997).
H. Nakayama, M. Ishikura, et al., Jpn. Pat. No. 01250373 (1989); Chem. Abstr., 112, 178673r (1990).
R. L. Dow, WO 9,221,660 (1992); Chem. Abstr., 118, 191567c (1993).
M. Hickey, I. Coutts, L. Tsang-Tan, and C. Pogson, Biochem. Soc. Trans., 23, 6075 (1995).
Ya. L. Garazd, M. M. Garazd, S. V. Shilin, and V. P. Khilya, Khim. Prir. Soedin., 349 (2001).
Ya. L. Garazd, M. M. Garazd, S. V. Shilin, T. N. Panteleimonova, and V. P. Khilya, Khim. Prir. Soedin., 192
(2002).
10.
11.
12.
13.
14.
15.
16.
17.
18.
Ya. L. Garazd, A. S. Ogorodniichuk, M. M. Garazd, and V. P. Khilya, Khim. Prir. Soedin., 345 (2002).
E. C. Horning and D. E. Reisner, J. Am. Chem. Soc., 3619 (1948).
J. K. MacLeod and B. R. Worth, Tetrahedron Lett., 237 (1972).
R. M. Naik and V. M. Thakor, J. Org. Chem., 22, 1696 (1957).
K. D. Kaufman, F. J. Gaiser, T. D. Leth, and L. R. Worden, J. Org. Chem., 26, 2443 (1961).
F. H. Lahey and J. K. MacLeod, Aust. J. Chem., 20, 1943 (1967).
J. K. MacLeod, B. R. Worth, and R. J. Wells, Aust. J. Chem., 31, 1533 (1978).
W. R. H. Hurtley, J. Chem. Soc., 1870 (1929).
J. P. Devlin, Can. J. Chem., 53, 343 (1975).
540