HETEROCYCLES

Paper | Regular issue | Vol. 81, No. 11, 2010, pp. 2555-2567
Received, 29th July, 2010, Accepted, 31st August, 2010, Published online, 2nd September, 2010.
DOI: 10.3987/COM-10-12029

■ Synthesis of 1-Azaxanthones and 1-Azathioxanthones by Yb(OTf)3/TfOH Co-Catalyzed Intramolecular Friedel-Crafts Reaction

Jie Li, Can Jin, and Weike Su*

Key Laboratory of Pharmaceutical Engineering of Ministry of Educations, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, China

Abstract

Intramolecular Friedel-Crafts cyclization of phenoxypyridine acids (1a-1j) and phenythiopyridine acids (3a-3i) to form 1-azaxanthones (2a-2j) and 1-azathioxanthones (4a-4i), respectively, was efficiently promoted by Yb(OTf)3/TfOH as co-catalysts. And a number of substrates could be cyclized in moderate to good yields.

INTRODUCTION
5H-[1]Benzopyrano[2,3-b]pyridine-5-one (1), referred to throughout this series, was commonly called 1-azaxanthone.1 And 5H-[1]benzothiopyrano[2,3-b]pyridine-5-one (2) was called 1-azathioxanthone.

1-Azaxanthones are of considerable pharmacological relevance.2 For example, benzopyranopyridine derivatives possess antiallergic activity.3 The photochemical and photophysical properties of 1-azaxanthone have also been studied and it is usefulness as a probe for polarity, reactivity, and/or radical pair dynamics in supramolecular systems.4 Azaxanthones and azathioxanthones are effective sensitisers for europium and terbium luminescence.5
Only a few procedures have been used to prepare 1-azaxanthones and 1-azathioxanthones. Among these methods, the most general one is intramolecular cyclization of the corresponding phenoxypyridine acids6-7 or nitriles.2 However, an excess of protic acid (often as solvent) such as sulfuric acid,8 polyphosphoric acid (PPA)6 is the reagent of choice for the intramolecular Friedel-Crafts cyclization reaction. Therefore, a large amount of acid wastes were formed after the reaction. Bromine-magnesium exchange has also been used for the synthesis of a series of 1-azaxanthone.9 However, the materials are expensive and the reactions cause some side reactions. To the best of our knowledge, no report has been made about a simple and clean methodology for the synthesis of 1-azaxanthones and 1-azathioxanthones. In this paper, we first describe the cyclization of phenoxypyridine acids and phenythiopyridine acids to form 1-azaxanthones and 1-azathioxanthones catalyzed by Yb(OTf)3/TfOH under solvent free conditions.

RESULTS AND DISCUSSION
Phenoxypridine acid 3a was chosen as a model substrate for the intramolecular cyclization reaction. Effects of various types of acids on the intramolecular cyclization of phenoxypridine acid 3a to 1-azaxanthone 1a were summarized in Table 1. As indicated, in the presence of a catalytic amount of metal triflate such as Bi(OTf)3 , Zn(OTf)2 and Yb(OTf)3, Yb(OTf)3 (5 mol%) afforded 1a in 62% yield (entry 3). Bi(OTf)3 and Zn(OTf)2 also afforded 1a but in lower yields (entries 1-2). Yield of the product 1a was slightly improved when 10 mol% of Brønsted acids such as trifluoromethanesulfonic acid (TfOH), trifluoroacetic acid (TFA) and p-toluenesulfonic acid (TsOH) were used (entries 4, 5 and 6). While lower yields were obtained in the presence of 5 mol% of Yb(OTf)3 or 10 mol% of TfOH, a 76% yield of 1a was obtained when combining 5 mol% of Yb(OTf)3 and 10 mol% of TfOH (entry 7). Further increasing the amount of the catalysts could not improve the yield (entry 8). Change of acid co-catalyst into methanesulfonic acid (MSA) led to a lower yield of 1a (entry 9). During initial studies, the effects of different solvents were examined. Only trace amount of product was detected in the solvent of PhNO2 or xylene (entries 12 and 13), while the reaction did not proceed in DMF or DMSO (entries 10 and 11). As can be seen in Table 1, 5 mol% of Yb(OTf)3 and 10 mol% of TfOH was favorable and acceptable under solvent free conditions.

The substrate scope of Yb(OTf)3/TfOH catalyzed cyclization of the phenoxypyridine acids 3a-3j was summarized in Table 2. The electronic effect of the substituents on aromatic ring of substrates was not observed (entries 2-8). When a para-substituted phenoxypyridine acid was used, the reaction gave a single product in excellent yield. However, in the meta-substituted phenoxypyridine acids, both of possible regioisomers 6- and 8-substituted 1-azaxanthones were produced (except for entry 5). In the case of 3f, the ratio of the two products (1f and 1f’) was 2:3 (entry 6). However, in the case of 3e, only 6-substituted isomer was obtained and no 8-substituted product was detected (entry 5). This could possibly due to the formation of intramolecular hydrogen bond in 1e between the hydroxyl protons (OH) with the carbonyl oxygen (CO) (Figure 1). We were very excited to find that the deactivated phenoxypyridine acid with three fluorine atoms on aromatic ring was successfully transformed to 1h in 69% yield (entry 8). And it was noteworthy that substrates 3i and 3j bearing a naphthalene group rather than a phenyl group were transformed into tetracyclic azaxanthones 1i and 1j in the yield of 74% and 87% respectively (entries 9 and 10).

Furthermore, under optimized conditions, a number of substituted phenythiopyridine acids were converted into the corresponding 1-azathioxanthones in respective yields (Table 3). The results clearly show that all the substrates participated very efficiently in the reaction to afford the cyclized products in good yields.

Phenythiopyridine acids with electron-donating groups on the aromatic ring generally afforded 1-azathioxanthones in good yields (entries 2, 3, 7, 8). The reaction of 4b and 4c bearing a methyl and bulky isopropyl group gave the corresponding 2b and 2c in 84% and 80% yields (entries 2 and 3). It should be noted that deactivated substrates, which have one or two halogen atoms on the aromatic ring, were successfully cyclized to give 1-azathioxanthones in moderate yields (entries 4, 5, 9).

Ortho- and para-substituted phenythiopyridine acids gave rise to a single product whereas a meta-substituted phenythiopyridine acid led to formation of 6- and 8-substituted isomers. In the case of 4h, the reaction afforded a 1:2 mixture of the demethylation product 2h and the desired product 2h’ in 79% total yield (Scheme 1). The formation of 2g and 2h were demethylation products (entries 7 and 8). The product 2g might form an intramolecular hydrogen bond with the sulfur atom, forming a 5-membered ring as shown in Figure 2 (or 6-membered ring in the case of the product 2h as shown in Scheme 1).10 Our group has previously developed a method for the Yb(OTf)3 catalyzed Friedel-Crafts acylation and demethylation of aryl-methyl ethers to produce hydroxyacylphenones.11
A possible mechanism is proposed according to literatures and considering Friedel-Crafts acylation.12 A very active catalyst could be produced by mixing appropriate Lewis and Brønsted acids.13-14 The synergistic effect might have been formed by combining ytterbium triflate (Yb(OTf)3) with trifluoromethanesulfonic acid (TfOH), leading to active catalytic systems for the intramolecular Friedel-Crafts reaction.
In summary, we have devised an effective protocol for the intramolecular Friedel-Crafts cyclization of phenoxypyridine acids and phenythiopyridine acids to synthesis 1-azaxanthones and 1-azathioxanthones. This approach has some advantages in term of operational simplicity, broad substrate scope and solvent-free conditions. Further research is ongoing to apply this method to other systems.

EXPERIMENTAL
Melting points were determined by Büchi B-540 melting point apparatus and are uncorrected. The IR spectra (KBr pellet) were measured on a Nicolet Avatar-370 spectrometer. 1H NMR (400 MHz) and 13C NMR (100 MHz) spectra were recorded on a Varian 400-MHz spectrometer. Mass spectra were obtained on a Thermo Finnigan LCQ-Advantage spectrometer (ESI, APCI) or a Finnigan Trace DSQ spectrometer (EI, CI). HRMS was carried out on an APEX (Bruker) mass III spectrometer.

General Procedure for Synthesis of 1-azaxanthone 1a
A mixture of Yb(OTf)3 (0.12g, 0.2mmol, 5mol%), TfOH (0.06g, 0.4mmol, 10mol%) and phenoxypridine acid 3a (0.86g, 4.0mmol) in a flask was heated in an oil bath at 160 oC for 5 h. Then the reaction mixture was dissolved in CH2Cl2 (30 mL) and washed with a saturated aqueous NaOH solution (20 mL). The organic layer was separated and the aqueous layer was extracted with CH2Cl2 (2×30 mL). The combined organic layer was dried with anhydrous Na2SO4, filtered and evaporated to give a crude product. The crude product was then charged on a small silica gel column and eluted with a mixture of EtOAc: petroleum ether (1:5) to afford the corresponding pure product 1-azaxanthone 1a (0.6g, 76% yield).

5H-Chromeno[2,3-b]pyridin-5-one (1a)
White solid. mp 178-179 °C (Lit.,6 mp 178-182 oC). IR (KBr): 3069, 1677, 1617, 1597, 1584, 1472, 1415, 1347, 1115, 1100, 760 cm-1. 1H NMR (400 MHz, CDCl3) δ: 8.78-8.77 (m, 1H), 8.74 (dd, J = 2.0, 7.6,Hz, 1H), 8.33 (dd, J = 2.0, 8.0 Hz, 1H), 7.80 (dt, J =1.6, 7.6 Hz, 1H), 7.65 (d, J = 8.0 Hz, 1H), 7.47 (t, J = 4.4, 1H), 7.44 (d, J = 6.8 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ: 177.6, 160.3, 155.7, 154.1, 137.3, 135.6, 126.6, 124.6, 121.5, 121.0, 118.5, 116.7. MS (EI): m/z (%) = 197(M+, 28), 169 (47), 113(100), 87(35).

7-tert-Butyl-5H-chromeno[2,3-b]pyridin-5-one (1c)
White solid. mp 100.3-101.8 °C (Lit.,6 mp 98-100 oC). IR (KBr): 3073, 2961, 2903, 2868, 1665, 1616, 1599, 1470, 1413, 1133, 1099, 781 cm-1. 1H NMR (400 MHz, CDCl3) δ: 8.76-8.73 (m, 2H), 8.30 (s, 1H), 7.86 (dd, J = 2.4, 8.8 Hz, 1H), 7.58 (d, J = 8.8 Hz, 1H), 7.46-7.43 (m, 1H), 1.41 (s, 9H). 13C NMR (100 MHz, CDCl3) δ: 177.8, 160.3, 153.9, 153.8, 147.9, 137.3, 133.5, 122.3, 121.3(2C), 118.1, 116.6, 34.7, 31.2(3C). MS (EI): m/z (%) = 253(M+, 25), 238 (100), 210(43), 198(32), 115(34), 77(35).

7-Methoxy-5H-chromeno[2,3-b]pyridin-5-one (1d)
White 15 mp 154-157.7 °C. IR (KBr): 3072, 3019, 2974, 2925, 2831, 1659, 1615, 1588, 1486, 1420, 1026, 781 cm-1. 1H NMR (400 MHz, CDCl3) δ: 8.77-8.73 (m, 2H), 7.68 (s, 1H), 7.58 (d, J = 8.8 Hz, 1H), 7.47-7.44 (m, 1H), 7.39 (dd, J = 3.2, 8.8 Hz, 1H), 3.94 (s, 3H). 13C NMR (100 MHz, CDCl3) δ: 177.4, 160.1, 156.4, 154.0, 150.4, 137.3, 125.5, 121.8, 120.8, 119.9, 116.0, 105.7, 55.9. MS (EI): m/z (%) = 227(M+, 100), 212 (40), 184(42), 156(84), 128(33), 101(31).

6-Hydroxy-5H-chromeno[2,3-b]pyridin-5-one (1e)
Yellow solid. mp 142.6-143.6 °C. IR (KBr): 3079, 1647, 1622, 1599, 1480, 1417, 1383, 1290, 1230, 1210, 1106, 1033, 782 cm-1. 1H NMR (400 MHz, CDCl3) δ: 12.27 (s, 1H), 8.78 (dd, J = 2.0, 7.2 Hz, 1H), 8.68 (dd, J = 1.6, 7.6 Hz, 1H), 7.66 (t, J = 8.4 Hz, 1H), 7.48-7.45 (m, 1H), 7.08 (d, J = 8.4 Hz, 1H), 6.87 (d, J = 8.4 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ: 182.6, 161.7, 160.3, 155.6, 154.9, 137.5, 136.6, 121.1, 115.6, 111.3, 108.7, 107.7. HRMS (ESI): calcd for C12H8NO3 [M+H]+: 214.0504, found: 214.0501.

6-Methyl-5H-chromeno[2,3-b]pyridin-5-one (1f)
Pale yellow solid. mp 155.5-157 °C. IR (KBr): 2968, 2929, 1664, 1611, 1596, 1565, 1476, 1426, 1411, 1030, 784 cm-1. 1H NMR (400 MHz, CDCl3) δ: 8.72 (dd, J = 2.0, 4.4 Hz, 1H), 8.67 (dd, J = 2.0, 8.0 Hz, 1H), 7.61 (t, J = 8.4 Hz, 1H), 7.47 (d, J = 8.4 Hz, 1H), 7.44-7.40 (m, 1H), 7.18 (d, J = 7.6 Hz, 1H), 2.92 (s, 3H). 13C NMR (100 MHz, CDCl3) δ: 179.0, 159.6, 156.9, 153.7, 142.0, 137.2, 134.3, 127.3, 120.7, 119.8, 117.3, 116.4, 22.9. HRMS (ESI): calcd for C13H10NO2 [M+H]+: 212.0706, found: 212.0706.

8-Methyl-5H-chromeno[2,3-b]pyridin-5-one (1f’)
Grey solid. mp 149.3-151 °C (Lit.,6 mp151-152 oC). IR (KBr): 3035, 2908, 1662, 1624, 1601, 1470, 1416, 1115, 775 cm-1. 1H NMR (400 MHz, CDCl3) δ: 8.74 (dd, J = 2.0, 4.4 Hz, 1H), 8.72 (dd, J = 2.0, 7.6 Hz, 1H), 8.20 (d, J = 8.0 Hz, 1H), 7.46-7.42 (m, 2H), 7.27 (s, 1H), 2.54 (s, 3H). 13C NMR (100 MHz, CDCl3) δ: 177.1, 160.1, 155.6, 153.7, 147.2, 137.1, 126.2, 126.0, 120.8, 119.1, 118.0, 116.6, 21.9. MS (EI): m/z (%) = 211(M+, 100), 182(83), 154(52), 127(62), 77(60).

7-Chloro-5H-chromeno[2,3-b]pyridin-5-one (1g)
White solid. mp 193.7-195.6 °C (Lit.,6 mp 198-200 oC). IR (KBr): 3098, 3066, 1667, 1596, 1475, 1434, 1417, 1130, 1105, 777 cm-1. 1H NMR (400 MHz, CDCl3) δ: 8.78 (dd, J = 2.0, 4.8 Hz, 1H), 8.73 (dd, J = 2.0, 8.0 Hz, 1H), 8.28 (s, 1H), 7.74 (dd, J = 2.8, 8.8 Hz, 1H), 7.60 (d, J = 8.8 Hz, 1H), 7.50-7.47 (m, 1H). 13C NMR (100 MHz, CDCl3) δ: 176.5, 160.1, 154.5, 154.0, 137.4, 135.7, 130.5, 125.9, 122.3, 121.2, 120.2, 116.4. MS (EI): m/z (%) = 233 ([M++2], 34), 231 (M+, 100), 203(44), 140(43).

6,7,8-Trifluoro-5H-chromeno[2,3-b]pyridin-5-one (1h)
White solid. mp 207-209 oC. IR (KBr): 3049, 1673, 1645, 1607, 1594, 1508, 1478, 1426, 1324, 1205, 1174, 1129, 1079, 778 cm-1. 1H NMR (400 MHz, CDCl3) δ: 8.76 (dd, J = 2.0, 4.4 Hz, 1H), 8.69 (dd, J = 2.0, 7.6 Hz, 1H), 7.52-7.49 (m, 1H), 7.30-7.26 (m, 1H). 13C NMR (100 MHz, CDCl3) δ: 174.3, 159.3, 154.8(d, J = 257.8 Hz, 1C), 154.2, 149.9(d, J = 261.7 Hz, 1C), 137.2, 137.1(d, J = 250.1 Hz, 1C), 121.8, 116.3, 109.6, 102.4. HRMS (ESI): calcd for C12H5F3NO2 [M+H]+: 252.0272, found: 252.0269.

7H-Benzo[7,8]chromeno[2,3-b]pyridin-7-one (1i)
Light green solid. mp 200-201.8 °C. IR (KBr): 3056, 1652, 1601, 1473, 1412, 1384, 1249, 1223, 1193, 771 cm-1. 1H NMR (400 MHz, CDCl3) δ: 8.82-8.78 (m, 3H), 8.23 (d, J = 8.4 Hz, 1H), 7.95 (dd, J = 2.0, 7.2 Hz, 1H), 7.79 (d, J = 8.8 Hz, 1H), 7.76-7.70 (m, 2H), 7.54-7.51 (m, 1H). 13C NMR (100 MHz, CDCl3) δ: 177.1, 159.9, 153.6, 153.4, 137.0, 136.7, 129.9, 127.9, 127.1, 124.7, 123.7, 123.2, 121.4, 120.8, 117.3, 117.21. HRMS (ESI): calcd for C16H10NO2 [M+H]+: 248.0706, found: 248.0703.

12H-Benzo[5,6]chromeno[2,3-b]pyridin-12-one (1j)
White solid. mp 175-176 °C. IR (KBr): 3009, 1647, 1604, 1577, 1516, 1470, 1424, 1442, 1213, 1153, 1112, 788 cm-1. 1H NMR (400 MHz, CDCl3) δ: 9.99 (d, J = 8.0 Hz, 1H), 8.81 (dd, J = 2.0, 8.0 Hz, 1H), 8.77 (dd, J = 1.6, 4.8 Hz, 1H), 8.19 (d, J = 8.0 Hz, 1H), 7.93 (d, J = 8..4 Hz, 1H), 7.80 (t, J = 8.4 Hz, 1H), 7.68 (d, J = 8.8 Hz, 1H), 7.63 (t, J = 7.6 Hz, 1H), 7.52-7.49 (m, 1H). 13C NMR (100 MHz, CDCl3) δ: 178.1, 158.5, 156.9, 152.9, 136.9, 136.9, 130.2, 129.8, 129.4, 128.0, 126.1, 126.0, 120.9, 117.6, 113.9(2C). HRMS (ESI): calcd for C16H10NO2 [M+H]+: 248.0706, found: 248.0703.

5H-Thiochromeno[2,3-b]pyridin-5-one (2a)
White solid. mp 233-234 °C (Lit.,16 mp 234 oC). IR (KBr): 3033, 1650, 1591, 1573, 1446, 1433, 1398, 1322, 1261, 1161, 1091, 739 cm-1. 1H NMR (400 MHz, CDCl3) δ: 8.82 (dd, J = 2.0, 8.0 Hz, 1H), 8.78 (dd, J = 2.0, 6.0 Hz, 1H), 8.58 (d, J = 8.0 Hz, 1H), 7.69-7.63 (m, 2H), 7.51 (t, J = 6.8 Hz, 1H), 7.45-7.42 (m, 1H). 13C NMR (100 MHz, CDCl3) δ: 180.5, 158.7, 153.4, 137.9, 137.6, 135.2, 133.1, 130.0, 128.9, 126.9, 126.6, 121.8. MS (EI): m/z (%) = 213(M+, 98), 185(100), 158(26), 140(33).

7-Methyl-5H-thiochromeno[2,3-b]pyridin-5-one (2b)
White solid. mp 147-148 °C (Lit.,17 mp 153-154 oC). IR (KBr): 3024, 2919, 1640, 1602, 1577, 1470, 1446, 1398, 1323, 1297, 1160, 1139, 1094, 760 cm-1. 1H NMR (400 MHz, CDCl3) δ: 8.81 (dd, J = 2.0, 8.0 Hz, 1H), 8.76 (dd, J = 2.0, 4.8 Hz, 1H), 8.38 (s, 1H), 7.53 (d, J = 8.4 Hz, 1H), 7.48 (dd, J = 2.0, 8.0 Hz, 1H), 7.43-7.39 (m, 1H), 2.50 (s, 3H). 13C NMR (100 MHz, CDCl3) δ: 180.3, 158.5, 152.9, 137.5, 136.7, 135.1, 134.1, 130.4, 129.4, 128.4, 126.1, 121.2, 21.2. MS (EI): m/z (%) = 227(M+, 100), 198(67), 154(16), 86(16).

7-Isopropyl-5H-thiochromeno[2,3-b]pyridin-5-one (2c)
Yellow solid. mp 66-67 °C. IR (KBr): 3062, 2954, 2952, 2866, 1643, 1601, 1576, 1474, 1450, 1397, 1319, 1135, 1077, 754 cm-1. 1H NMR (400 MHz, CDCl3) δ: 8.82 (dd, J = 2.0, 8.0 Hz, 1H), 8.77 (dd, J = 2.0, 4.4 Hz, 1H), 8.44 (s, 1H), 7.59-7.54 (m, 2H), 7.44-7.41 (m, 1H), 3.10-3.04 (m, 1H), 1.34 (s, 3H), 1.33 (s, 3H). 13C NMR (100 MHz, CDCl3) δ: 180.3, 158.5, 152.8, 147.6, 137.5, 134.4, 131.8, 128.5, 126.9, 126.2, 126.1, 121.2, 33.9, 23.8(2C). HRMS (ESI): calcd for C15H14NOS [M+H]+: 256.0796, found: 256.0793.

7-Chloro-5H-thiochromeno[2,3-b]pyridin-5-one (2d)
White solid. mp 193.5-194.6 °C (Lit.,17 mp 194-195 oC). IR (KBr): 3063, 1644, 1578, 1401, 1316, 1289, 1163, 1099, 760 cm-1. 1H NMR (400 MHz, CDCl3) δ: 8.82-8.78 (m, 2H), 8.54 (s, 1H), 7.63 (dd, J = 2.0, 8.4 Hz, 1H), 7.58 (d, J = 8.4 Hz, 1H), 7.47-7.44 (m, 1H). 13C NMR (100 MHz, CDCl3) δ: 179.2, 158.1, 153.3, 137.6, 135.4, 133.0, 129.7, 129.1, 127.6, 125.8, 121.7(2C). MS (EI): m/z (%) = 249 ([M++2], 37), 247(M+, 100), 219(48), 184(30), 140(22), 92(15).

7-Bromo-5H-thiochromeno[2,3-b]pyridin-5-one (2e)
Grey solid. mp 180-182 °C (Lit.,17 mp 190-193 oC). IR (KBr): 3061, 1645, 1577, 1398, 1311, 1289, 1127, 1091, 762 cm-1. 1H NMR (400 MHz, CDCl3) δ: 8.83-8.78 (m, 2H), 8.69 (s, 1H), 7.75 (dd, J = 2.4, 8.4 Hz, 1H), 7.52 (d, J = 8.8 Hz, 1H), 7.48-7.44 (m, 1H). 13C NMR (100 MHz, CDCl3) δ: 179.5, 158.4, 153.6, 138.0, 136.3, 136.0, 132.6, 130.2, 128.1, 126.2, 122.0, 120.9. MS (EI): m/z (%) = 294([M++3], 14), 291 (M+, 100), 265(22), 212(20), 184(60), 140(47).

9-Methyl-5H-thiochromeno[2,3-b]pyridin-5-one (2f)
Pale yellow solid. mp 160.3-161 °C (Lit.,5 mp 135-137 oC). IR (KBr): 3024, 2927, 1634, 1584, 1397, 1326, 1131, 1058, 750 cm-1. 1H NMR (400 MHz, CDCl3) δ: 8.82-8.78 (m, 2H), 8.47 (d, J = 8.0 Hz, 1H), 7.53 (d, J = 7.2 Hz, 1H), 7.46-7.44 (m, 1H), 7.43-7.41 (m, 1H), 2.58 (s, 3H). 13C NMR (100 MHz, CDCl3) δ: 180.8, 158.0, 153.1, 137.4, 136.6, 134.4, 133.9(2C), 128.9, 127.5, 125.9, 121.6, 19.6. MS (EI): m/z (%) = 227(M+, 100), 198(45), 154(15), 121(10).

9-Hydroxy-5H-thiochromeno[2,3-b]pyridin-5-one (2g)
Grey solid. mp 177-178.7 °C. IR (KBr): 3438, 2927, 1671, 1615, 1597, 1470, 1417, 1347, 1198, 760 cm-1. 1H NMR (400 MHz, CDCl3) δ: 8.74 (dd, J = 2.0, 4.8 Hz, 1H), 8.71 (dd, J = 2.0, 7.6 Hz, 1H), 8.30 (dd, J = 2.0, 8.0 Hz, 1H), 7.78 (dt, J = 1.6, 7.2 Hz, 1H), 7.62 (d, J = 8.4 Hz, 1H), 7.44 (t, J = 4.4 Hz,1H), 7.42 (s, 1H). 13C NMR (100 MHz, CDCl3) δ: 177.3, 160.1, 155.5, 154.0, 137.2, 135.5, 126.5, 124.5, 121.4, 120.9, 118.4, 116.6. HRMS (ESI): calcd for C12H8NO2S [M+H]+: 230.0270, found 230.0276.

6-Hydroxy-5H-thiochromeno[2,3-b]pyridin-5-one (2h)
Orange solid. mp 189.4-191 °C. IR (KBr): 3444, 2925, 2847, 2757, 1621, 1574, 1440, 1399, 1264, 1183, 1127, 1090, 783 cm-1. 1H NMR (400 MHz, CDCl3) δ: 13.66 (s, 1H), 8.79-8.77 (m, 2H), 7.54 (t, J = 8.0 Hz, 1H), 7.45-7.42 (m, 1H), 7.11 (d, J = 7.6 Hz, 1H), 6.95 (d, J = 8.0 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ: 186.1, 164.9, 159.0, 153.9, 138.5, 137.4, 135.6, 125.6, 121.7, 116.3, 114.9, 114.5. HRMS (ESI): calcd for C12H8NO2S [M+H]+: 230.0270, found: 230.0276.

8-Methoxy-5H-thiochromeno[2,3-b]pyridin-5-one (2h’)
Yellow solid. mp 188-190 °C. IR (KBr): 3075, 3006, 2967, 1636, 1601, 1577, 1399, 1326, 1277, 1070, 1032, 758 cm-1. 1H NMR (400 MHz, CDCl3) δ: 8.80 (dd, J = 1.6, 8.0 Hz, 1H), 8.74 (dd, J = 2.0, 4.8 Hz, 1H), 8.51 (d, J = 8.8 Hz, 1H), 7.44-7.41 (m, 1H), 7.05 (dd, J = 2.4, 4.8 Hz, 1H), 7.02 (d, J = 2.4 Hz, 1H), 3.94 (s, 3H). 13C NMR (100 MHz, CDCl3) δ: 179.5, 163.1, 158.5, 152.9, 140.0, 137.7, 132.1, 126.6, 122.7, 121.7, 115.7, 108.7, 56.1. HRMS (ESI): calcd for C13H10NO2S [M+H]+: 244.0432, found: 244.0431.

6,8-Dichloro-5H-thiochromeno[2,3-b]pyridin-5-one (2i)
Yellow solid. mp 199-201 °C. IR (KBr): 3067, 3044, 2921, 1650, 1570, 1399, 1376, 1143, 1093, 928, 857 cm-1. 1H NMR (400 MHz, CDCl3) δ: 8.74 (dd, J = 1.6, 4.4 Hz, 1H), 8.67 (dd, J = 2.0, 8.0 Hz, 1H), 7.54 (s, 1H), 7.50 (s, 1H), 7.45-7.42 (m, 1H). 13C NMR (100 MHz, CDCl3) δ: 179.3, 155.7, 153.0, 141.0, 137.9, 137.6, 133.6, 130.7, 127.8, 124.6, 122.7, 122.0. HRMS (ESI): calcd for C12H6Cl2NOS [M+]: 281.9547, found: 281.9539.

ACKNOWLEDGEMENTS
We are grateful to the National Natural Science Foundation of China (No 20876147) and Natural Science Foundation of Zhejiang Province (No Y4090346) for financial support.

References

1. F. J. Villani, J. Hannon, E. A. Wefer, and T. A. Mann, J. Org. Chem., 1975, 40, 1734. CrossRef
2. M. A. Rashid, N. Rasool, B. Appel, M. Adeel, V. Karapetyan, S. Mkrtchyan, H. Reinke, C. Fischer, and P. Langer, Tetrahedron, 2008, 64, 5416. CrossRef
3. A. Nohara, T. Ishiguro, K. Ukawa, H. Sugihara, Y. Maki, and Y. Sanno, J. Med. Chem., 1985, 28, 559. CrossRef
4. J. C. Scaiano, D. Weldon, C. N. Pliva, and L. J. Martinez, J. Phys. Chem. A., 1998, 102, 6898. CrossRef
5. P. Atkinson, K. S. Findlay, F. Fielar, R. Pal, D. P. Parker, R. A. Poole, H. Puschmann, S. L. Richardson, P. A. Stenson, A. L. Thompson, and J. H. Yu, Org. Biomol. Chem., 2006, 4, 1707. CrossRef
6. F. J. Villani, T. A. Mann, E. A. Wefer, J. Hannon, L. L. Larca, M. J. Landon, W. Spivak, and D. Vashi, J. Med. Chem., 1975, 18, 1. CrossRef
7. H. Fujiwara and K. Kitagawa, Heterocycles, 2000, 53, 409. CrossRef
8. S. J. Yang and W. A. Denny, Tetrahedron Lett., 2009, 50, 3945. CrossRef
9. F. Trécourt, G. Breton, V. Bonnet, F. Mongin, F. Marsais, and G. Quéguiner, Tetrahedron, 2000, 56, 1349. CrossRef
10. C. E. Wheelock, K. Nishi, A. Ying, P. D. Jones, M. E. Colvin, M. M. Olmstead, and B. D. Hammock, Bioorg. Med. Chem., 2008, 16, 2114. CrossRef
11. W. K. Su and C. Jin, Synth. Commun., 2004, 34, 4199. CrossRef
12. S. Kobayashi and S. Iwamoto, Tetrahedron Lett., 1998, 39, 4697. CrossRef
13. O. Mouhtady, H. G. Iloughmane, N. Roques, and C. L. Roux, Tetrahedron Lett., 2003, 44, 6379. CrossRef
14. H. C. Aspinall, J. S. Bissett, N. Greeves, and D. Levin, Tetrahedron Lett., 2002, 43, 319. CrossRef
15. F. M. Pasutto, S. Abuzar, and S. Satyamurthy, Hererocycles, 1985, 23, 2293. CrossRef
16. F. G. Mann and J. A. Reid, J. Chem. Soc., 1952, 2057. CrossRef
17. E. Jucker and A. Ebnoether, BE 19640421, 1964, CAN 62:51669