HETEROCYCLES

Short Paper | Regular issue | Vol. 83, No. 7, 2011, pp. 1631-1640
Received, 30th March, 2011, Accepted, 21st April, 2011, Published online, 10th May, 2011.
DOI: 10.3987/COM-11-12223

■ A Facile Synthesis of New Troponoid-Bearing Flavonoid-Like Compounds

Mingqin Chang, Yang Li, and Wentao Gao*

Institute of Superfine Chemicals, School of Chemistry and Chemical Engineering, Bohai University, 19 Keji Road, Jinzhou 121000, China

Abstract

A facile synthesis of a series of new flavonoid-like troponoid compounds, namely 3-(3-arylacryloyl)-5-bromotropolones (2a-i) and 2-aryl-6-bromocyclohepta[b]pyran-4,9-diones (3a-i) is described, involving the Claisen-Schmidt condensation reaction of 3-acetyl-5-bromotropolone (1) with various substituted benzaldehydes followed by the intramolecular oxidation cyclization reaction through the treatment with I2/DMSO/H2SO4 system.

Flavonoids (chalcones and flavones) are an important class of naturally occurring compounds present in all vascular plants and exhibiting a wide spectrum of biological activities. The average human diet contains about 1 g of flavonoids per day, assimilated through fruits, vegetables, red wine, tea etc.1 Currently, there is considerable interest in the synthesis of chalcone and flavone derivatives due to a wide range of biological activities including anti-oxidative,2,3 anti-inflammatory,4-6 cancer suppressing7-10 and anti-viral (anti-HIV)11-13 activities. Especially, some brominated flavonoids such as 8-bromoflavonoid analogs have been reported to exhibit strong activities against human gastric adenocarcinoma cell lines (SGC-7901) and colorectal adenocarcinoma (HT-29) cells14,15 and also be used for the synthesis of biologically active natural products such as vitexin and aciculatin.16 The complex pharmacological activities together the easy synthetic reproduction and derivatization of the core structure have solicited considerable interest towards the exploitation of the unique flavonoid template for the discovery of prospective lead compounds.17-19
On the other hand, it is well known that numerous natural products and several synthetic compounds bearing troponoid nucleus exhibit remarkable pharmacological effects such as antitumor, inhibitory ribonucleotide reductase and antimalarial activities.20-25 In particular, the introduction of bromo moiety to troponoid nucleus exhibit important biological activities such as the inhibition of Hepatitis C virus.26 In addition, the troponoid moiety also plays an important role in molecular assemblies for a faster and efficient lead generation towards the new drug discovery. Despite featuring only seven ring carbon atoms and no stereocentres, the synthesis of structurally novel troponoids continues to be a considerable synthetic challenge as troponoid derivatives are scarce in nature,27 occurring only in lower plants and fungi,28 and limited information is available on these compounds.
Although the synthesis of substituted chalcones and flavones are among the most extensively reports in recent years due to their potential as valuable templates for medicinal chemistry, to the best of our knowledge, there are few reports on the synthesis of troponoid-bearing flavonoid-like compounds.29-32 In this regard, we have reported recently on the synthesis of troponoid-33 and 5,7-dibromotroponoid-bearing34 flavonoid-like compounds. Therefore, in the context of our ongoing studies on troponoid chemistry and in diversifying our work on the synthesis of new troponoid compounds,35-37 herein, we wish to report herein the synthesis of a series of monobromo-troponoid-bearing flavonoid-like compounds employing 3-acetyl-5-bromotropolone as the starting compound. As far as we know, 3-acetyl-5-bromotropolone has been synthesized conveniently for many years, but the further modification of it is very limit.38
The synthetic route for eighteen new chalcone-like (E)-3-(3-arylacryloyl)-5-bromo-2-hydroxy cyclohepta-2,4,6-trienones (2a-i) and flavone-like 2-aryl-6-bromocyclohepta[b]pyran-4,9-diones (3a-i) is illustrated in Scheme 1 and the results are summarized in Table 1. The Claisen-Schmidt condensation reaction of 3-acetyl-5-bromotropolone (1) with appropriate aromatic aldehyde (1.5 molar equv.) applying 5% aqueous KOH as catalyst in 50% aqueous methanol solvent at room temperature furnished 3-cinnamoyl-5,7-dibromotropolones (2) in high yields and high purities as well. Then the resulting chalcone-like 2 were converted to flavone-like 3 via oxidation cyclization reaction in good yields of 53-62% by treating with I2/DMSO/H2SO4 system. The oxidation cyclization reaction is performed in the presence of 10 mol% I2 as catalyst, DMSO as solvent, and concentrated H2SO4 as additive at 110 oC for 10-15 hours. In this reaction, to ensure the formation of solid a minimal amount of DMSO was used. In addition, we also attempted to conduct the oxidation cyclization reaction using the DMSO-I2 reagent in the absence of concentrated H2SO4 according to the method reported by Lokhande et al.39 The reaction also proceeds smoothly, but plagued by poor yields.

Compounds 2a-i and 3a-i are new and their structures were confirmed by spectral data and elemental analysis. For example, the IR spectrum of 2a shows a wide absorption at 3183 cm-1 for the O-H stretching, two stretching vibration bands at 1603 and 1544 cm-1 due to the carbonyl and C=C absorptions of tropolone moiety, and a typical absorption at 1646 cm-1 due to the α,β-unsaturated carbonyl group. The main features of its 1H NMR data are the resonances of the two vinylic protons appearing as two doublets at δ 7.16 and 7.69 with a coupling constant J=16.0 Hz, which indicated the E-configuration of these vinylic systems. As reported by chalcone literatures, to yield only E-stereoisomers is a prerogative of the Claisen-Schmidt condensation reaction. Further, the structure assigned for this reaction product is fully supported by its ESI-MS (positive-ion mode) spectrum, which exhibits a characteristic quasi-molecular ion peak cluster (M+H)+ at m/z 409.3, 411.3, 413.3 with a ratio of 1׃2׃1, suggesting the presence of two Br-atoms in 2a. Finally, the structure assigned for this reaction product is fully supported by its elemental analysis, which establishes its molecular formula in accordance with its suggested molecular structure. Similarly, the IR spectrum of 3a exhibits the absence of hydroxyl group at about 3183 cm-1 and the presence of two typical carbonyl absorptions for the tropone and nascent γ-pyrone moieties at 1656 and 1649 cm-1. Particularly characteristic was the presence of one C=C absorptions of γ-pyrone at 1617 cm-1. Its 1H NMR spectrum also exhibits no signals attributable to both hydroxy OH proton signal and two vinylic protons resonances. The main feature of the spectrum shows the presence of a distinct singlet, integrating for one proton resonating at δ 6.94, assignable to be the proton attached on pyrone ring moiety along with the signals for seven aromatic protons exactly matching its structure in the range of aromatic region. Further, the structure assigned for this reaction product is fully supported by its mass spectrum, which shows a characteristic quasi-molecular ion peak cluster (M+H)+ at m/z 406.9, 408.9, 410.9 and matches the expected molecular weight of 3a.
It can be concluded that the present investigation has demonstrated a facile synthesis of a series of new chalcone-like (E)-3-(3-arylacryloyl)-5-bromotropolones (2a-i) and flavone-like 2-aryl-6-bromo cyclohepta[b]pyran-4,9-dione (3a-i). The molecules we have synthesized should allow us, in the future, to investigate structure-activity relationships over various biotests. Moreover, all these synthesized molecules can be used for the synthesis of more complex troponoid compounds since a bromo group on troponoid ring can be further elaborated to a variety of other functional groups, for example, via metal-catalyzed coupling reactions.

EXPERIMENTAL
The melting points were measured on WRS-1B digital melting points apparatus and are uncorrected. The progress of the reaction was monitored by TLC. Infrared spectra were recorded on KBr pellets on an FT/IR-430 spectrophotometer. 1H NMR spectra were determined on a Bruker AVANCE 400 NMR spectrometer at 400 MHz using TMS as internal standard. Elemental analyses were estimated on an Elementar Vario EL-III element analyzer. The Mass spectra were determined using a MSD VL ESI1 spectrometer. The reaction process was monitored by thin-layer chromatography (TLC) on silica gel GF254 using EtOAc/petroleum ether (1/1).
General procedure for the synthesis of (E)-3-(3-arylacryloyl)-5-bromo-2-hydroxycyclohepta-2,4,6-trienones (2a-i). To a stirred solution of 3-acetyl-5-bromotropolone 1 (1 mmol, 0.243 g) and substituted benzaldehyde (1.5 mmol) in 50% aqueous MeOH (8 mL) was added 5 mL of 5% potassium hydroxide aqueous solution at room temperature. The resulting solution was stirred at room temperature for 24 h. The reaction mixture was then quenched by addition of 5 mL H2O and acidification with 1 N HCl. The precipitated chalcone-like tropolone 2a-i was collected and recrystallized from MeOH to yield pure product in 74-83% yields.
(E)-5-Bromo-3-[3-(2-bromophenyl)acryloyl]tropolone (2a). This compound was obtained as yellow crystals, mp 221-223 oC. IR (KBr) ν/cm-1: 3183 (OH), 1646 (C=O), 1603 (C=O), 1544 (C=C), 1451, 1379, 1298, 1222; 1H NMR (DMSO-d6) δ (ppm): 7.00 (d, 1H, J=10.4 Hz, tropolone-H), 7.16 (d, 1H, J=16.0 Hz, =CH), 7.22-7.35 (m, 2H, ArH), 7.61 (d, 1H, J=8.0 Hz, ben-H), 7.69 (d, 1H, J=16.0 Hz, =CH), 7.73-7.81 (m, 3H, ArH), 10.71 (s, br, 1H, OH); ESI-MS m/z: 409.3, 411.3, 413.3 (M+1)+. Anal. Calcd for C16H10Br2O3: C, 46.86; H, 2.46. Found: C, 46.74; H, 2.65.
(E)-5-Bromo-3-[3-(4-bromophenyl)acryloyl]tropolone (2b). This compound was obtained as yellow crystals, mp 223-224 oC. IR (KBr) ν/cm-1: 3191 (OH), 1652 (C=O), 1602 (C=O), 1545 (C=C), 1450, 1381, 1356, 1274, 1237; 1H NMR (DMSO-d6) δ (ppm): 7.01 (d, 1H, J=10.4 Hz, tropolone-H), 7.17 (d, 1H, J=16.0 Hz, =CH), 7.44 (d, 1H, J=16.0 Hz, =CH), 7.50-7.62 (m, 5H, ben-H and tropolone-H), 7.73 (d, 1H, J=10.4 Hz, tropolone-H), 10.78 (s, br, 1H, OH); ESI-MS m/z: 409.3, 411.3, 413.3 (M+1)+. Anal. Calcd for C16H10Br2O3: C, 46.86; H, 2.46. Found: C, 46.68; H, 2.52.
(E)-5-Bromo-3-[3-(2-chlorophenyl)acryloyl]tropolone (2c). This compound was obtained as orange crystals, mp 228-229 oC. IR (KBr) ν/cm-1: 3181 (OH), 1654 (C=O), 1590 (C=O), 1547 (C=C), 1424, 1344, 1262, 1219, 1195; 1H NMR (CDCl3) δ (ppm): 7.05 (d, 1H, J=10.0 Hz, tropolone-H), 7.18 (d, 1H, J=16.0 Hz, =CH), 7.30 (d, 1H, J=8.0 Hz, ben-H), 7.39 (dd, 1H, J=10.4, 2.1 Hz, tropolone-H), 7.58 (d, 1H, J=2.1 Hz, tropolone-H), 7.62-7.66 (m, 1H, ben-H), 7.71 (d, 1H, J=16.0 Hz, =CH), 7.96-8.02 (m, 2H, ben-H), 10.69 (s, br, 1H, OH); ESI-MS m/z: 364.9, 366.9, 368.9 (M+1)+. Anal. Calcd for C16H10BrClO3: C, 52.56; H, 2.76. Found: C, 52.74; H, 2.82.
(E)-5-Bromo-3-[3-(4-chlorophenyl)acryloyl]tropolone (2d). This compound was obtained as yellow crystals, mp 230-231 oC. IR (KBr) ν/cm-1: 3192 (OH), 1653 (C=O), 1637 (C=O), 1559 (C=C), 1445, 1387, 1351, 1287, 1199; 1H NMR (CDCl3) δ (ppm): 7.11 (d, 1H, J=10.4 Hz, tropolone-H), 7.21 (d, 1H, J=15.8 Hz, =CH), 7.26-7.32 (m, 2H, ben-H), 7.42 (dd, 1H, J=10.4, 2.1 Hz, tropolone-H), 7.51 (d, 1H, J=2.1 Hz, tropolone-H), 7.72 (d, 1H, J=16.0 Hz, =CH), 7.8-8.08 (m, 2H, ben-H), 10.92 (s, br, 1H, OH); ESI-MS m/z: 364.9, 366.9, 368.9 (M+1)+. Anal. Calcd for C16H10BrClO3: C, 52.56; H, 2.76. Found: C, 52.70; H, 2.67.
(E)-5-Bromo-3-[3-(4-cyanophenyl)acryloyl]tropolone (2e). This compound was obtained as orange crystals, mp 273-274 oC. IR (KBr) ν/cm-1: 3211 (OH), 2240 (CN), 1663 (C=O), 1597 (C=O), 1546 (C=C), 1454, 1382, 1303, 1252, 1220; 1H NMR (CDCl3) δ (ppm): 7.16-7.21 (m, 2H, ArH), 7.38 (d, 1H, J=16.0 Hz, =CH), 7.44 (d, 1H, J=10.0 Hz, tropolone-H), 7.52-7.57 (m, 3H, ArH), 7.67 (d, 1H, J=16.0 Hz, =CH), 7.82 (d, 1H, J=10.0 Hz, tropolone-H), 11.01 (s, br, 1H, OH); ESI-MS m/z: 356.4, 358.4 (M+1)+. Anal. Calcd for C17H10BrNO3: C, 57.33; H, 2.83. Found: C, 57.47; H, 2.89.
(E)-5-Bromo-3-[3-(2,4-dichlorophenyl)acryloyl]tropolone (2f). This compound was obtained as orange crystals, mp 233-235 oC. IR (KBr) ν/cm-1: 3190 (OH), 1642 (C=O), 1602 (C=O), 1546 (C=C), 1450, 1382, 1235, 1207; 1H NMR (DMSO-d6) δ (ppm): 7.14-7.19 (m, 1H, ArH), 7.34 (d, 1H, J=16.0 Hz, =CH), 7.36 (s, 1H, ben-H), 7.50 (d, 1H, J=10.0 Hz, tropolone-H), 7.57-7.63 (m, 2H, ArH), 7.74 (d, 1H, J=16.0 Hz, =CH), 7.97 (d, 1H, J=8.0 Hz, ben-H), 10.69 (s, br, 1H, OH); ESI-MS m/z: 398.9, 400.9, 402.9, 404.9 (M+1)+. Anal. Calcd for C16H9BrCl2O3: C, 48.04; H, 2.27. Found: C, 47.91; H, 2.34.
(E)-5-Bromo-3-[3-(2,4-dimethylphenyl)acryloyl]tropolone (2g). This compound was obtained as pale yellow crystals, mp 189-190 oC. IR (KBr) ν/cm-1: 3186 (OH), 1651 (C=O), 1607 (C=O), 1559 (C=C), 1507, 1458, 1346, 1259, 1187; 1H NMR (CDCl3) δ (ppm): 2.36 (s, 3H, Me), 2.42 (s, 3H, Me), 7.12-7.14 (m, 2H, ArH), 7.18 (d, 1H, J=16.0 Hz, =CH), 7.26-7.39 (m, 2H, ArH), 7.48 (d, 1H, J=10.0 Hz, tropolone-H), 7.61 (d, 1H, J=16.0 Hz, =CH), 7.68 (d, 1H, J=10.0 Hz, tropolone-H), 10.64 (s, br, 1H, OH); ESI-MS m/z: 359.1, 361.1 (M+1)+. Anal. Calcd for C18H15BrO3: C, 60.18; H, 4.21. Found: C, 60.09; H, 4.39.
(E)-5-Bromo-3-[3-(3,4-dimethylphenyl)acryloyl]tropolone (2h). This compound was obtained as pale yellow crystals, mp 182-184 oC. IR (KBr) ν/cm-1: 3192 (OH), 1644 (C=O), 1625 (C=O), 1545 (C=C), 1508, 1400, 1345, 1256, 1183; 1H NMR (CDCl3) δ (ppm): 2.38 (s, 3H, Me), 2.43 (s, 3H, Me), 7.12-7.26 (m, 3H, ArH and =CH), 7.40-7.52 (m, 3H, ArH), 7.64 (d, 1H, J=16.0 Hz, =CH), 7.67 (d, 1H, J=10.0 Hz, tropolone-H), 10.65 (s, br, 1H, OH); ESI-MS m/z: 359.0, 361.0 (M+1)+. Anal. Calcd for C18H15BrO3: C, 60.18; H, 4.21. Found: C, 59.93; H, 4.35.
(E)-5-Bromo-3-[3-(2,5-dimethoxylphenyl)acryloyl]tropolone (2i). This compound was obtained as yellow crystals, mp 193-194 oC. IR (KBr) ν/cm-1: 3190 (OH), 1642 (C=O), 1602 (C=O), 1545 (C=C), 1510, 1450, 1382, 1271, 1207; 1H NMR (CDCl3) δ (ppm): 3.79 (s, 3H, OMe), 3.82 (s, 3H, OMe), 6.86-6.90 (m, 2H, ArH), 7.08 (d, 1H, J=16.0 Hz, =CH), 7.18 (d, 1H, J=10.4 Hz, tropolone-H), 7.55-7.59 (m, 2H, ArH), 7.61 (d, 1H, J=16.0 Hz, =CH), 7.76 (d, 1H, J=10.0 Hz, tropolone-H), 10.88 (s, br, 1H, OH); ESI-MS m/z: 391.2, 393.2 (M+1)+. Anal. Calcd for C18H15BrO5: C, 55.26; H, 3.86. Found: C, 55.40; H, 3.77.
General procedure for the synthesis of flavone-like tropone compounds 6-Bromo-2-(2-aryl) cyclohepta[b]pyran-4,9-diones (3a-i). To a stirred solution of each 5-bromotropolone 2 in 8 mL of DMSO was added 3-4 drops of concd. H2SO4. After 15 min of magnetic stirring at 110 oC, I2 was added carefully and the resulting reaction mixture was reacted under the temperature for 10-15 h. The completion of the reaction was monitored by TLC. The reaction mixture was cooled to room temperature and added with 5 mL of H2O slowly. And then the resulting precipitate was collected by filtration and crystallized from 1,4-dioxane to give 3a-i in 53-62% yields.
6-Bromo-2-(2-bromophenyl)cyclohepta[b]pyran-4,9-dione (3a). This compound was obtained as pale yellow crystals, mp 245-246 oC. IR (KBr) ν/cm-1: 1656 (C=O), 1649 (C=O), 1617 (C=C), 1586, 1560, 1492, 1424, 1370, 1346, 1303, 1220; 1H NMR(CDCl3) δ (ppm): 6.94 (s, 1H, H-3), 7.01 (d, 1H, J=12.8 Hz, H-8), 7.38-7.41 (m, 1H, ben-H), 7.47-7.50 (m, 1H, ben-H), 7.52 (dd, 1H, J=12.8, 2.1 Hz, H-7), 7.68-7.70 (m, 1H, ben-H), 7.73-7.75 (m, 1H, ben-H), 8.41 (d, 1H, J=2.1 Hz, H-5); ESI-MS m/z: 406.9, 408.9, 410.9 (M+1)+. Anal. Calcd for C16H8Br2O3: C, 47.10; H, 1.98. Found: C, 46.94; H, 2.11.
6-Bromo-2-(4-bromophenyl)cyclohepta[b]pyran-4,9-dione (3b). This compound was obtained as yellow crystals, mp 281-282 oC. IR (KBr) ν/cm-1: 1653 (C=O), 1646 (C=O), 1615 (C=C), 1587, 1560, 1490, 1422, 1378, 1350, 1315, 1217; 1H NMR (CDCl3) δ (ppm): 6.97 (s, 1H, H-3), 7.03 (d, 1H, J=12.8 Hz, H-8), 7.53 (dd, 1H, J=12.8, 2.1 Hz, H-7), 7.68 (d, 2H, J=8.7 Hz, ben-H), 7.87 (d, 2H, J=8.7 Hz, ben-H), 8.40 (d, 1H, J=2.1 Hz, H-5); ESI-MS m/z: 407.0, 408.9, 411.0 (M+1)+. Anal. Calcd for C16H8Br2O3: C, 47.10; H, 1.98. Found: C, 47.26; H, 2.08.
6-Bromo-2-(2-chlorophenyl)cyclohepta[b]pyran-4,9-dione (3c). This compound was obtained as light yellow crystals, mp 232-233 oC. IR (KBr) ν/cm-1: 1652 (C=O), 1647 (C=O), 1617 (C=C), 1584, 1485, 1373, 1345, 1264, 1217; 1H NMR (CDCl3) δ (ppm): 7.01 (d, 1H, J=12.8 Hz, H-8), 7.05 (s, 1H, H-3), 7.43-7.55 (m, 4H, H-7 and ben-H), 7.81 (m, 1H, ben-H), 8.41 (d, 1H, J=2.0 Hz, H-5); ESI-MS m/z: 362.9, 364.9, 366.8 (M+1)+. Anal. Calcd for C16H8BrClO3: C, 52.85; H, 2.22. Found: C, 52.73; H, 2.41.
6-Bromo-2-(4-chlorophenyl)cyclohepta[b]pyran-4,9-dione (3d). This compound was obtained as yellow crystals, mp 254-255 oC. IR (KBr) ν/cm-1: 1654 (C=O), 1647 (C=O), 1618 (C=O), 1583, 1560, 1542, 1473, 1430, 1370, 1340, 1252, 1220; 1H NMR (CDCl3) δ (ppm): 6.94 (s, 1H, H-3), 7.04 (d, 1H, J=12.8 Hz, H-8), 7.23 (d, 2H, J=8.7 Hz, ben-H), 7.53 (dd, 1H, J=12.8, 2.1 Hz, H-7), 8.02 (d, 2H, J=8.7 Hz, ben-H), 8.41 (d, 1H, J=2.1 Hz, H-5); ESI-MS m/z: 362.9, 364.9, 366.9 (M+1)+. Anal. Calcd for C16H8BrClO3: C, 52.85; H, 2.22. Found: C, 52.97; H, 2.28.
6-Bromo-2-(4-cyanophenyl)cyclohepta[b]pyran-4,9-dione (3e). This compound was obtained as orange crystals, mp 227-228 oC. IR (KBr) ν/cm-1: 2210 (CN), 1667 (C=O), 1652 (C=O), 1620 (C=C), 1582, 1561, 1481, 1403, 1369, 1342, 1277, 1221; 1H NMR (CDCl3) δ (ppm): 7.07 (s, 1H, H-3), 7.13 (d, 1H, J=12.8 Hz, H-8), 7.25-7.32 (m, 2H, ben-H), 7.58 (dd, 1H, J=12.8, 2.1 Hz, H-7), 8.08-8.14 (m, 2H, ben-H), 8.49 (d, 1H, J=2.1 Hz, H-5); ESI-MS m/z: 354.1, 356.1 (M+1)+. Anal. Calcd for C17H8BrNO3: C, 57.65; H, 2.28. Found: C, 52.52; H, 2.35.
6-Bromo-2-(2,4-dichlorophenyl)cyclohepta[b]pyran-4,9-dione (3f). This compound was obtained as yellow crystals, mp 267-268 oC. IR (KBr) ν/cm-1: 1658 (C=O), 1644 (C=O), 1606 (C=C), 1584, 1559, 1490, 1431, 1374, 1346, 1186; 1H NMR (CDCl3) δ (ppm): 7.02 (d, 1H, J=12.8 Hz, H-8), 7.06 (s, 1H, H-3), 7.44 (dd, 1H, J=8.5, 2.0 Hz, ben-H), 7.53 (dd, 1H, J=12.8, 2.0 Hz, H-7), 7.57 (d, 1H, J=2.0 Hz, ben-H), 7.79 (d, 1H, J=8.5 Hz, ben-H), 8.40 (d, 1H, J=2.1 Hz, H-5); ESI-MS m/z: 396.9, 398.8, 400.9, 402.8 (M+1)+. Anal. Calcd for C16H7BrCl2O3: C, 48.28; H, 1.77. Found: C, 48.08; H, 1.81.
6-Bromo-2-(2,4-dimethylphenyl)cyclohepta[b]pyran-4,9-dione (3g). This compound was obtained as pale yellow crystals, mp 244-245 oC. IR (KBr) ν/cm-1: 1652 (C=O), 1642 (C=O), 1619 (C=C), 1583, 1560, 1489, 1412, 1370, 1343, 1317, 1289, 1187; 1H NMR (CDCl3) δ (ppm): 2.39 (s, 3H, Me), 2.54 (s, 3H, Me), 6.69 (s, 1H, H-3), 6.99 (d, 1H, J=12.8 Hz, H-8), 7.12-7.15 (m, 2H, ben-H), 7.48 (d, 1H, J=8.9 Hz, ben-H), 7.52 (dd, 1H, J=12.8, 2.0 Hz, H-7), 8.42 (d, 1H, J=2.1 Hz, H-5); ESI-MS m/z: 357.2, 359.2 (M+1)+. Anal. Calcd for C18H13BrO3: C, 60.52; H, 3.67. Found: C, 60.40; H, 3.86.
6-Bromo-2-(3,4-dimethylphenyl)cyclohepta[b]pyran-4,9-dione (3h). This compound was obtained as pale yellow crystals, mp 271-272 oC. IR (KBr) ν/cm-1: 1651 (C=O), 1640 (C=O), 1622 (C=C), 1585, 1560, 1491, 1421, 1379, 1324, 1299, 1173; 1H NMR (CDCl3) δ (ppm): 2.35 (s, 3H, Me), 2.36 (s, 3H, Me), 6.96 (s, 1H, H-3), 7.02-7.05 (m, 2H, H-8 and ben-H), 7.29-7.33 (m, 2H, ben-H), 7.52 (dd, 1H, J=12.8, 2.1 Hz, H-7), 8.41 (d, 1H, J=2.1 Hz, H-5); ESI-MS m/z: 357.1, 359.1 (M+1)+. Anal. Calcd for C18H13BrO3: C, 60.52; H, 3.67. Found: C, 60.61; H, 3.55.
6-Bromo-2-(2,5-dimethoxyphenyl)cyclohepta[b]pyran-4,9-dione (3i). This compound was obtained as golden crystals, mp 259-261 oC. IR (KBr) ν/cm-1: 1651 (C=O), 1642 (C=O), 1612 (C=O), 1566, 1491, 1451, 1379, 1300, 1250, 1184; 1H NMR (CDCl3) δ (ppm): 3.89 (s, 3H, OMe), 3.94 (s, 3H, OMe), 6.54 (d, 1H, J=2.3 Hz, ben-H), 6.68 (dd, 1H, J=8.9, 2.3 Hz, ben-H), 7.01 (d, 1H, J=12.8 Hz, H-8), 7.43 (s, 1H, H-3), 7.52 (dd, 1H, J=12.8, 2.1 Hz, H-7), 8.21 (d, 1H, J=8.9 Hz, ben-H), 8.42 (d, 1H, J=2.1 Hz, H-5); ESI-MS m/z: 389.0, 390.9 (M+1)+. Anal. Calcd for C18H13BrO5: C, 55.55; H, 3.37. Found: C, 55.75; H, 3.49.

ACKNOWLEDGEMENTS
The authors would like to thank the financial support from the Foundation of Liaoning Province Key Laboratory of Applied Chemistry (Grant No. 2008s001).

References

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