HETEROCYCLES

Short Paper | Regular issue | Vol. 85, No. 8, 2012, pp. 1997-2004
Received, 16th May, 2012, Accepted, 4th June, 2012, Published online, 8th June, 2012.
DOI: 10.3987/COM-12-12508

■ A Convenient Synthesis of 2-Arylthiochromen-4-ones (Thioflavones) by Iodine-Mediated Cyclization of 3-Aryl-1-[2-(1,1-dimethylethylsulfanyl)phenyl]prop-2-en-1-ones

Kazuhiro Kobayashi,* Akihiro Kobayashi, and Kosuke Ezaki

Division of Applied Chemistry, Department of Chemistry and Biotechnology, Graduate School of Engineering, Tottori University, 4-101 Koyama-minami, Tottori 680-8552, Japan

Abstract

A convenient two-step synthesis of 2-arylthiochromen-4-ones (thioflavones) beginning with 1-[2-(1,1-dimethylethylsulfanyl)phenyl]ethanones is described. Thus, 3-aryl-1-[2-(1,1-dimethylethylsulfanyl)phenyl]prop-2-en-1-ones were prepared by the condensation of 1-[2-(1,1- dimethylethylsulfanyl)phenyl]ethanones with aromatic aldehyde in the presence of sodium hydroxide, and were treated with iodine in refluxing N-methylpyrrolidin-2-one (NMP) or propanenitrile to afford the desired products in moderate to fair yields.

Several synthetic approaches to 2-arylthiochromen-4-ones (thioflavones) have recently been reported1 because of their biological activities.2 For example, a recent disclosure by Lee and Kim has demonstrated an elegant process based on intramolecular rearrangement of S-2-acetophenyl benzothioates.1d However this method suffers from limited scope, as it uses 1-(2-sulfanylphenyl)ethanone as the only starting substrate and therefore it cannot allow preparation of the derivatives having substituent(s) on the benzene ring of the thiochromenone structure. In this paper we wish to describe results of our investigation, which offer a new and convenient procedure for the synthesis of 2-arylthiochromen-4-ones (4), including derivatives having a substituent, such as chloro or methoxy group, at the 6-position. The method starts with 1-[2-(1,1-dimethylethylsulfanyl)phenyl]ethanones (2) and is based on the iodine-mediated cyclization reaction of 3-aryl-1-[2-(1,1-dimethylethylsulfanyl)phenyl]prop-2-en-1-ones (3), derived from 2 and aromatic aldehydes.
In our approach to 2-arylthiochromen-4-ones (4), we began with the preparation of 1-[2-(1,1-dimethylethylsulfanyl)phenyl]ethanones (2). The respective 1-(2-halophenyl)ethanones (1) were treated with sodium 2-methylpropane-2-thiolate in DMF at room temperature to afford 2 in relatively good yields as shown in Scheme 1.

Conversion of compounds (2) into 3-aryl-1-[2-(1,1-dimethylethylsulfanyl)phenyl]prop-2-en-1-ones (3) was performed by reacting 2 with aromatic aldehydes in the presence of sodium hydroxide in aqueous ethanol at room temperature (Scheme 2). The yields of the products are summarized in Table 1. It indicates that the yields are good and that naphthalene-1-carbaldehyde as well as diversely substituted benzaldehydes are usable in this step.

3-Aryl-1-[2-(1,1-dimethylethylsulfanyl)phenyl]prop-2-en-1-ones (3), thus obtained, were then subjected to cyclization on treatment with iodine to provide the desired 2-arylthiochromen-4-ones (4), as illustrated in Scheme 2. First, compound (3a) was treated with iodine in the presence of sodium hydrogencarbonate (three molar equivalents each) in acetonitrile. However, TLC analyses showed that progress of the reaction was very reluctant even at reflux temperature. When it was conducted in refluxing propanenitrile (Method A), the reaction proceeded at an allowable rate and gave, after workup with aqueous sodium thiosulfate followed by purification using column chromatography on silica gel, a somewhat complicated mixture, from which 46% yield of the desired product (4a) was isolated. Other eight 3-aryl-1-[2-(1,1-dimethylethylsulfanyl)phenyl]prop-2-en-1-ones (3b-i) gave similar results. Increasing the number of equivalents of iodine did not improve the yields of the products and shorten the reaction times. With less than three equivalents of iodine the reactions did not proceed significantly. Subsequently, we found that when the reaction of 3a, 3e, and 3f was carried out in N-methylpyrrolidin-2-one (NMP) at reflux temperature (Method B), much improved yields of the corresponding products (4a, 4e, and 4f) were obtained. Unfortunately, however, the reactions of the other substrates 3, which are carrying alkoxy or chloro substituent(s) at the 3-aryl ring or a methoxy substituent at the 1-aryl ring (i.e. 3b-d and 3g-i) in refluxing NMP gave considerably complex mixtures of the products, from which only low yields (ca. 10%) of the corresponding precuts (4) were isolated. These disappointing results are attributable to the liability of these substituents under the reaction conditions (especially higher reaction temperature). The best yield of each product is indicated in Table 1.
The probable pathway from 3 to 4 is outlined in Scheme 3. The addition of iodine to the alkene moiety of 3 generates the iodonium ion intermediate (5). The lone pair of sulfur atom attacks on the carbon atom adjacent to aryl substituent to give the thiochromanium ion intermediate (6), from which elimination of hydrogen iodide affords thiochromenium ion intermediate (7). Loss of the t-butyl moiety as 2-methylpropene and hydrogen iodide provides 4.

In conclusion, we have demonstrated that 2-arylthiochromen-4-ones can be prepared by the iodine-mediated cyclization of 3-aryl-1-[2-(1,1-dimethylethylsulfanyl)phenyl]prop-2-en-1-ones, which are prepared by an easy two-step sequence from readily available 1-(2-halophenyl)ethanones. This method can allow preparation of derivatives carrying a substituent, such as chloro or methoxy, on the thiochromenone benzene ring, which are hard to prepare by the previous methods.1 The present method may also find some value in organic synthesis because of the simplicity of operations and the ready availability of the starting materials.

EXPERIMENTAL
All melting points were obtained on a Laboratory Devices MEL-TEMP II melting apparatus and are uncorrected. IR spectra were recorded with a Shimadzu FTIR-8300 spectrophotometer. 1H NMR spectra were recorded in CDCl3 using TMS as an internal reference with a Bruker Biospin AVANCE II 600 spectrometer operating at 600 MHz, a JEOL ECP500 FT NMR spectrometer operating at 500 MHz, or a JEOL LA400FT NMR spectrometer operating at 400 MHz. 13C NMR spectra were recorded in CDCl3 using TMS as an internal reference with a Bruker Biospin AVANCE II 600 spectrometer operating at 150 MHz or a JEOL ECP500 FT NMR spectrometer operating at 125 MHz. Low-resolution MS spectra (EI, 70 eV) were measured by a JEOL JMS AX505 HA spectrometer. TLC was carried out on Merck Kieselgel 60 PF254. Column chromatography was performed using WAKO GEL C-200E. All of the organic solvents used in this study were dried over appropriate drying agents and distilled prior to use.
Starting Materials. 1-(2-Bromo-5-methoxyphenyl)ethanone (1c)3 was prepared according to the reported method. All other chemicals used in this study were commercially available.
Typical Procedure for the Preparation of 1-[2-(1,1-Dimethylethylsulfanyl)phenyl]ethanones (2). 1-[2-(1,1-Dimethylethylsulfanyl)phenyl]ethanone (2a). To a stirred suspension of NaH (60% in mineral oil; 0.66 g, 17 mmol) in DMF (20 mL) at 0 ˚C was added t-BuSH (1.5 g, 17 mmol) dropwise. After evolution of H2 gas had ceased, 1-(2-chlorophenyl)ethanone (1a) (2.3 g, 15 mmol) was added dropwise and the mixture was stirred for 1 h at the same temperature. Saturated aqueous NH4Cl (30 mL) was added and the mixture was extracted with AcOEt (3 × 25 mL). The combined extracts were washed with water three times and brine once, dried (Na2SO4), and concentrated by evaporation. The residue was purified by column chromatography on silica gel to give 2a (2.6 g, 84%); a colorless oil; Rf 0.57 (AcOEt–hexane, 1:10). The 1H NMR data of this product was identical to that reported previously.4
1-[5-Chloro-2-(1,1-dimethylethylsulfanyl)phenyl]ethanone (2b): a pale-yellow oil; Rf 0.43 (AcOEt–hexane 1:20); IR (neat) 1697 cm–1; 1H NMR (500 MHz) δ 1.23 (s, 9H), 2.62 (s, 3H), 7.35 (dd, J = 8.0, 2.9 Hz, 1H), 7.37 (d, J = 2.9 Hz, 1H), 7.49 (d, J = 8.0 Hz, 1H). Anal. Calcd for C12H15ClOS: C, 59.37; H, 6.23. Found: C, 59.40; H, 6.50.
1-[2-(1,1-Dimethylethylsulfanyl)-5-methoxyphenyl]ethanone (2c): a colorless oil; Rf 0.60 (AcOEt–hexane 1:10); IR (neat) 1697 cm–1; 1H NMR (400 MHz) δ 1.20 (s, 9H), 2.64 (s, 3H), 3.83 (s, 3H), 6.88 (d, J = 2.9 Hz, 1H), 6.92 (dd, J = 8.8, 2.9 Hz, 1H), 7.46 (d, J = 8.8 Hz, 1H). Anal. Calcd for C13H18O2S: C, 65.51; H, 7.61. Found: C, 65.48; H, 7.67.
Typical Procedure for the Preparation of 3-Aryl-1-[2-(1,1-dimethylethylsulfanyl)phenyl]prop-2-en-1-ones (3). 1-[2-(1,1-Dimethylethylsulfanyl)phenyl]-3-phenylprop-2-en-1-one (3a). To a stirred solution of 2a (0.17 g, 0.79 mmol) in EtOH–H2O (4 mL; 1:1, v/v) containing NaOH (47 mg, 1.2 mmol) at 0 ˚C was added PhCHO (84 mg, 0.79 mmol). The mixture was then stirred for 20 h at rt before saturated aqueous NH4Cl (10 mL) was added. The mixture was extracted with Et2O (3 × 10 mL), and the combined extracts were washed with brine, dried (Na2SO4), and concentrated by evaporation. The residue was purified by column chromatography on silica gel to give 3a (0.21 g, 88%); a yellow viscous oil; Rf 0.32 (CHCl3–hexane 1:1); IR (neat) 1651, 1607 cm–1; 1H NMR (500 MHz) δ 1.23 (s, 9H), 7.14 (d, J = 16.0 Hz, 1H), 7.34 (d, J = 16.0 Hz, 1H), 7.38–7.39 (m, 3H), 7.45–7.47 (m, 3H), 7.54–7.56 (m, 2H), 7.63–7.64 (m, 1H). Anal. Calcd for C19H20OS: C, 76.98; H, 6.80. Found: C, 77.14; H, 7.01.
3-(3,4-Dichlorophenyl)-1-[2-(1,1-dimethylethylsulfanyl)phenyl]prop-2-en-1-one (3b): a pale-yellow solid; mp 79–80 ˚C (hexane–Et2O); IR (KBr) 1667, 1604 cm–1; 1H NMR (500 MHz) δ 1.22 (s, 9H), 7.11 (d, J = 16.0 Hz, 1H), 7.24 (d, J = 16.0 Hz, 1H), 7.38 (dd, J = 8.0, 2.3 Hz, 1H), 7.45–7.48 (m, 4H), 7.61–7.64 (m, 2H). Anal. Calcd for C19H18Cl2OS: C, 62.47; H, 4.97. Found: C, 62.25; H, 5.06.
3-(2,5-Dimethoxyphenyl)-1-[2-(1,1-dimethylethylsulfanyl)phenyl]prop-2-en-1-one (3c): a yellow viscous oil; Rf 0.54 (CHCl3); IR (neat) 1659, 1645 cm–1; 1H NMR (500 MHz) δ 1.24 (s, 9H), 3.789 and 3.794 (2s, combined 6H), 6.83 (d, J = 8.6 Hz, 1H), 6.91 (dd, J = 8.6, 2.9 Hz, 1H), 7.10 (d, J = 2.9 Hz, 1H), 7.17 (d, J = 16.0 Hz, 1H), 7.42–7.45 (m, 3H), 7.62–7.64 (m, 1H), 7.67 (d, J = 16.0 Hz, 1H). Anal. Calcd for C21H24O3S: C, 70.75; H, 6.79. Found: C, 70.63; H, 6.76.
3-(1,3-Benzoxol-5-yl)-1-[2-(1,1-dimethylethylsulfanyl)phenyl]prop-2-en-1-one (3d): a pale-yellow solid; mp 81–83 ˚C (hexane–Et2O); IR (KBr) 1636, 1603 cm–1; 1H NMR (500 MHz) δ 1.23 (s, 9H), 6.00 (s, 2H), 6.80 (d, J = 8.0 Hz, 1H), 6.95 (d, J = 16.1 Hz, 1H), 7.00 (dd, J = 8.0, 1.8 Hz, 1H), 7.07 (d, J = 1.8 Hz, 1H), 7.24 (d, J = 16.1 Hz, 1H), 7.41–7.46 (m, 3H), 7.60–7.63 (m, 1H). Anal. Calcd for C20H20O3S: C, 70.56; H, 5.92. Found: C, 70.30; H, 6.07.
1-[2-(1,1-Dimethylethylsulfanyl)phenyl]-3-(naphthalen-1-yl)prop-2-en-1-one (3e): a yellow viscous oil; Rf 0.51 (CHCl3); IR (neat) 1659 cm–1; 1H NMR (400 MHz) δ 1.25 (s, 9H), 7.24 (d, J = 16.1 Hz, 1H),7.45–7.56 (m, 6H), 7.67 (dd, J = 8.8, 1.5 Hz, 1H), 7.83–7.90 (m, 3H), 8.10 (d, J = 8.3 Hz, 1H), 8.22 (d, J = 16.1 Hz, 1H). Anal. Calcd for C23H22OS: C, 79.73; H, 6.40. Found: C, 79.62; H, 6.42.
1-[5-Chloro-2-(1,1-dimethylethylsulfanyl)phenyl]-3-(4-methylphenyl)prop-2-en-1-one (3f): a white solid; mp 85–86 ˚C (hexane–Et2O); IR (KBr) 1638, 1607 cm–1; 1H NMR (400 MHz) δ 1.23 (s, 9H), 2.38 (s, 3H), 7.04 (d, J = 16.1 Hz, 1H), 7.20 (d, J = 7.8 Hz, 2H), 7.30 (d, J = 16.1 Hz, 1H), 7.38–7.45 (m, 4H), 7.55 (dd, J = 7.4, 0.9 Hz, 1H). Anal. Calcd for C20H21ClOS: C, 69.65; H, 6.14. Found: C, 69.60; H, 6.18.
1-[5-Chloro-2-(1,1-dimethylethylsulfanyl)phenyl]-3-(3-methoxyphenyl)prop-2-en-1-one (3g): a white solid; mp 58–60 ˚C (hexane–Et2O); IR (KBr) 1655, 1620, 1601 cm–1; 1H NMR (400 MHz) δ 1.23 (s, 9H), 3.83 (s, 3H), 6.95 (dd, J = 8.3, 2.0 Hz, 1H), 7.06 (dd, J = 2.0, 1.5 Hz, 1H), 7.07 (d, J = 16.1 Hz, 1H), 7.14 (d, J = 7.8 Hz, 1H), 7.29 (d, J = 16.1 Hz, 1H), 7.30 (dd, J = 8.3, 7.8 Hz, 1H), 7.40–7.46 (m, 2H), 7.55 (dd, J = 7.8, 1.5 Hz, 1H). Anal. Calcd for C20H21ClO2S: C, 66.56; H, 5.87. Found: C, 66.43; H, 6.02.
1-[5-Chloro-2-(1,1-dimethylethylsulfanyl)phenyl]-3-(3,4-dimethoxyphenyl)prop-2-en-1-one (3h): colorless needles; mp 132–133 ˚C (hexane–Et2O); IR (KBr) 1636, 1616 cm–1; 1H NMR (400 MHz) δ 1.24 (s, 9H), 3.915 and 3.920 (2s, combined 6H), 6.87 (d, J = 8.3 Hz, 1H), 6.95 (d, J = 16.1 Hz, 1H), 7.07 (d, J = 1.5 Hz, 1H), 7.12 (dd, J = 8.3, 1.5 Hz, 1H), 7.22 (s, 1H), 7.39–7.42 (m, 2H), 7.56 (d, J = 9.2 Hz, 1H). Anal. Calcd for C21H23ClO3S: C, 64.52; H, 5.93. Found: C, 64.46; H, 5.97.
1-[2-(1,1-Dimethylethylsulfanyl)-5-methoxyphenyl]-3-(4-methylphenyl)prop-2-en-1-one (3i): a yellow solid; mp 80–81 ˚C (hexane–Et2O); IR (KBr) 1634, 1607 cm–1; 1H NMR (400 MHz) δ 1.19 (s, 9H), 2.37 (s, 3H), 3.85 (s, 3H), 6.96–6.99 (m, 2H), 7.08 (d, J = 16.1 Hz, 1H), 7.19 (d, J = 8.3 Hz, 2H), 7.32 (d, J = 16.1 Hz, 1H), 7.44 (d, J = 8.3 Hz, 2H), 7.51 (dd, J = 8.8, 2.0 Hz, 1H). Anal. Calcd for C21H24O2S: C, 74.08; H, 7.10. Found: C, 74.03; H, 7.24.
General Procedure for the Preparation of 2-Arylthiochromen-4-ones (4). A stirred solution of 3 (0.5 mmol) in EtCN (Method A) or NMP (Method B) (4 mL) containing I2 (0.19 g, 1.5 mmol) and NaHCO3 (0.13 g, 1.5 mmol) was heated at reflux temperature until an almost complete consumption of the starting material (ca. 4 h) had been confirmed by TLC analyses. To the cooled reaction mixture was added 10% aqueous Na2S2O3 under stirring until the color of I2 had appeared. The mixture was extracted with AcOEt (3 × 10 mL), and the combined extracts were washed with saturated aqueous NaHCO3 twice, water twice, and brine once. After drying (Na2SO4), the solvent was removed by evaporation to give a residue, purification of which by column chromatography on silica gel (CHCl3–hexane 1:1) afforded 4.
2-Phenylthiochromen-4-one (4a): a beige solid; mp 120–122 ˚C (lit.,5 122–123 ˚C). The spectral (IR and 1H NMR) data of this product was identical to those reported previously.5
2-(3,4-Dichlorophenyl)thiochromen-4-one (4b): a white solid; mp 198–200 ˚C (hexane–CH2Cl2); IR (KBr) 1634 cm–1; 1H NMR (600 MHz) δ 7.19 (s, 1H), 7.53 (dd, J = 8.3, 2.2 Hz, 1H), 7.56–7.60 (m, 2H), 7.64–7.67 (m, 2H), 7.79 (d, J = 2.2 Hz, 1H), 8.54 (d, J = 7.6 Hz, 1H); 13C NMR (150 MHz) δ 123.99, 126.06, 126.52, 128.12, 128.72, 128.83, 130.82, 131.30, 131.92, 133.79, 135.27, 136.40, 137.08, 150.11, 180.58; MS m/z 306 (M+, 100). Anal. Calcd for C15H8Cl2OS: C, 58.65; H, 2.62. Found: C, 58.49; H, 2.67.
2-(2,5-Dimethoxyphenyl)thiochromen-4-one (4c): a beige solid; mp 115–117 ˚C (hexane–Et2O); IR (KBr) 1626 cm–1; 1H NMR (500 MHz) δ 3.811 and 3.814 (2s, combined 6H), 6.95 (d, J = 8.6 Hz, 1H), 6.97–7.00 (m, 2H), 7.16 (s, 1H), 7.53 (ddd, J = 8.6, 7.4, 1.7 Hz, 1H), 7.59–7.63 (m, 2H), 8.55 (d, J = 8.6, 1.1 Hz, 1H); 13C NMR (125 MHz) δ 55.87, 56.44, 113.24, 115.64, 116.60, 126.08, 126.22, 126.72, 127.48, 128.52, 130.89, 131.35, 138.68, 150.10, 150.64, 153.66, 180.76; MS m/z 298 (M+, 100). Anal. Calcd for C17H14O3S: C, 68.44; H, 4.73. Found: C, 68.45; H, 4.80.
2-(1,3-Benzoxol-5-yl)thiochromen-4-one (4d): a beige solid; mp 180–182 ˚C (hexane–CH2Cl2); IR (KBr) 1622 cm–1; 1H NMR (500 MHz) δ 6.06 (s, 2H), 6.91 (d, J = 8.0 Hz, 1H), 7.155 (s, 1H), 7.157 (d, J = 1.8 Hz, 1H), 7.23 (dd, J = 8.0, 1.8 Hz, 1H), 7.53 (ddd, J = 8.1, 7.4, 1.8 Hz, 1H), 7.57–7.65 (m, 2H), 8.52 (d, J = 8.1, 1.8 Hz, 1H); 13C NMR (125 MHz) δ 101.87, 107.16, 108.90, 121.51, 122.66, 126.36, 127.71, 128.55, 130.58, 130.89, 131.55, 137.53, 148.60, 150.00, 152.62, 180.85; MS m/z 282 (M+, 100). Anal. Calcd for C16H10O3S: C, 68.07; H, 3.57. Found: C, 67.99; H, 3.49.
2-(Naphthalen-1-yl)thiochromen-4-one (4e): a beige solid; mp 144–145 ˚C (hexane–Et2O); IR (KBr) 1624 cm–1; 1H NMR (600 MHz) δ 7.15 (s, 1H), 7.51–7.56 (m, 3H), 7.58–7.61 (m, 2H), 7.63–7.67 (m, 2H), 7.92 (dd, J = 7.5, 1.2 Hz, 1H), 7.97 (d, J = 8.1 Hz, 1H), 8.07 (d, J = 8.3 Hz, 1H), 8.63 (d, J = 7.9 Hz, 1H); 13C NMR (150 MHz) δ 124.93, 125.01, 126.23, 126.60, 127.16, 127.22, 127.38, 127.85, 128.50, 128.76, 130.43, 130.53, 131.13, 131.63, 133.72, 134.08, 138.60, 152.27, 180.38; MS m/z 288 (M+, 100). Anal. Calcd for C19H12OS: C, 79.14; H, 4.19. Found: C, 79.08; H, 4.15.
6-Chloro-2-(4-methylphenyl)thiochromen-4-one (4f): a beige solid; mp 165–167 ˚C (hexane–Et2O); IR (KBr) 1618, 1609 cm–1; 1H NMR (500 MHz) δ 2.43 (s, 3H), 7.23 (s, 1H), 7.31 (d, J = 7.4 Hz, 2H), 7.57–7.62 (m, 4H), 8.52 (d, J = 1.7 Hz, 1H); 13C NMR (125 MHz) δ 21.35, 122.59, 126.75, 127.87, 128.16, 130.02, 131.88, 132.07, 133.36, 134.21, 135.79, 141.60, 153.28, 179.66; MS m/z 286 (M+, 100). Anal. Calcd for C16H11ClOS: C, 67.01; H, 3.87. Found: C, 66.85; H, 4.04.
6-Chloro-2-(3-methoxyphenyl)thiochromen-4-one (4g): a beige solid; mp 150–151 ˚C (hexane–Et2O); IR (KBr) 1620 cm–1; 1H NMR (500 MHz) δ 3.88 (s, 3H), 7.06 (dd, J = 8.0, 1.7 Hz, 1H), 7.18 (t, J = 1.7 Hz, 1H), 7.24 (s, 1H), 7.26 (dd, J = 8.0, 1.7 Hz, 1H), 7.41 (t, J = 8.0 Hz, 1H), 7.57–7.61 (m, 2H), 8.52 (d, J = 1.7 Hz, 1H); 13C NMR (125 MHz) δ 55.47, 112.33, 116.74, 119.27, 123.25, 127.91, 128.20, 130.41, 131.99, 132.10, 134.33, 135.79, 137.56, 153.12, 160.18, 179.64; MS m/z (%) 302 (M+, 100). Anal. Calcd for C16H11ClO2S: C, 63.47; H, 3.66. Found: C, 63.45; H, 3.89.
6-Chloro-2-(3,4-dimethoxyphenyl)thiochromen-4-one (4h): a beige solid; mp 170–172 ˚C (hexane–CH2Cl2); IR (KBr) 1634 cm–1; 1H NMR (600 MHz) δ 3.96 (s, 3H), 3.97 (s, 3H), 6.97 (d, J = 8.4 Hz, 1H), 7.18 (d, J = 1.8 Hz, 1H), 7.22 (s, 1H), 7.31 (dd, J = 8.4, 1.8 Hz, 1H), 7.57–7.61 (m, 2H), 8.51 (d, J = 1.3 Hz, 1H); 13C NMR (150 MHz) δ 56.11, 56.13, 109.65, 111.47, 120.05, 122.12, 127.81, 128.21, 128.80, 131.92, 132.14, 134.27, 135.72, 149.63, 151.70, 153.06, 179.68; MS m/z 332 (M+, 100). Anal. Calcd for C17H13ClO3S: C, 61.35; H. 3.94. Found: C, 61.17; H, 3.89.
6-Methoxy-2-(4-methylphenyl)thiochromen-4-one (4i): a pale-yellow solid; mp 156–157 ˚C (hexane–Et2O); IR (KBr) 1613 cm–1; 1H NMR (500 MHz) δ 2.42 (s, 3H), 3.95 (s, 3H), 7.24 (s, 1H), 7.25 (dd, J = 8.6, 2.9 Hz, 1H), 7.30 (d, J = 8.0 Hz, 2H), 7.56 (d, J = 8.6 Hz, 1H), 7.59 (d, J = 8.0 Hz, 2H), 7.99 (d, J = 2.9 Hz, 1H); 13C NMR (125 MHz) δ 21.33, 55.73, 108.84, 122.00, 122.08, 126.78, 127.74, 129.74, 129.94, 132.33, 133.80, 141.19, 153.10, 159.54, 180.55; MS m/z 282 (M+, 100). Anal. Calcd for C17H14O2S: C, 72.31; H. 5.00. Found: C, 72.16; H, 5.08.

ACKNOWLEDGEMENTS
The assistance of Mrs. Miyuki Tanmatsu of our university in recording mass spectra and performing combustion analyses is gratefully acknowledged.

References

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