HETEROCYCLES

Short Paper | Regular issue | Vol. 85, No. 4, 2012, pp. 919-925
Received, 25th January, 2012, Accepted, 1st March, 2012, Published online, 2nd March, 2012.
DOI: 10.3987/COM-12-12435

■ A Facile Synthesis of 2-Arylthiochroman-4-ones by the Reaction of 3-Aryl-1-(2-halophenyl)prop-2-en-1-ones with Sodium Hydrogensulfide

Kazuhiro Kobayashi,* Akihiro Kobayashi, and Miyuki Tanmatsu

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

Abstract

An efficient two-step procedure for the preparation of 2-arylthiochroman-4-ones has been developed. Thus, 3-aryl-1-(2-halophenyl)prop-2-en-1-ones, prepared by the condensation between 1-(2-halophenyl)ethanones and aromatic aldehydes in ethanol at room temperature, were treated with sodium hydrogensulfide in DMF at 80 ˚C to give 2-arylthiochroman-4-ones in good overall yields.

The synthesis of thiochroman-4-ones, especially 2-aryl derivatives (thioflavanones), has recently attracted much attention, because a number of compounds having this skeleton have been reported to exhibit a variety of biological activities.1 Therefore, several efficient methods for the preparation of this class of heterocycles have been developed.2 For example, Lee has recently reported a synthesis of 2-arylthiochroman-4-ones based on the reaction of 1-(2-sulfanylphenyl)ethanone with aromatic aldehydes.2b However, this method cannot allow the preparation of derivatives carrying any substituents on the benzene ring of the thiochroman-4-one structure. Herein, we wish to report a new and facile method for the synthesis of 2-aryl- or 2-heteroaryl-thiochroman-4-ones (4), which can allow the preparation of derivatives carrying substituent(s) at the 6- and/or 7-positions of the thiochroman-4-one structure. We have found that the synthesis of these thiochroman-4-ones can be achieved by treatment of 3-aryl- or 3-hetraryl-1-(2-halophenyl)prop-2-en-1-ones (2), easily prepared by the condensation of 1-(2-halophenyl)ethanones (1) with aromatic or heteroaromatic aldehydes, with sodium hydrogensulfide.
Our preparation of 2-aryl- or 2-heteroaryl-thiochroman-4-ones (4) was conducted as illustrated in Scheme 1. 3-Aryl-1-(2-halophenyl)prop-2-en-1-ones (2a–d) and (2h–l) were readily prepared from commercially or easily available 1-(2-halophenyl)ethanones (1) by reacting with aromatic aldehydes using sodium hydroxide as a base in ethanol under the reported conditions3 in excellent yields as summarized in Table 1 (Entries 1-4 and 8-12). Similar reactions of 1 with heteroaromatic aldehydes, such as thiophene-2-carboxaldehyde, thiophene-3-carboxaldehyde, 1-methylindole-2-carboxaldehyde, and 1-methylpyrrole-2-carboxaldehyde, in place of aromatic aldehydes gave also excellent yields of the corresponding 1-(2-halophenyl)-3-heterarylprop-2-en-1-ones (2e-g) and (2m) as summarized in Table 1 (Entries 5-7 and 13) as well.

These chalcone derivatives (2a–d) and (2h–l) were then subjected to treatment with sodium hydrogensulfide. Thus, argon gas was bubbled through solutions of these precursors and sodium hydrogensulfide in DMF in order to remove oxygen, which may oxidize intermediate 3-aryl-1-(2-sulfanylphenyl)propenones (3) to the corresponding disulfides. These solutions were then heated at 80 ˚C. Substitution of the 2-halogen of 2 with a sulfanyl group giving 3 followed by intramolecular conjugate addition of the resulting 2-sulfanyl group to the enone moiety of 3 proceeded smoothly and completed within 10 min. After usual aqueous workup and subsequent purification by column chromatography on silica gel or recrystallization, the desired 2-arylthiochroman-4-ones (4a–d) and (4h–l) were obtained in good yields as summarized in Table 1 (Entries 1-4 and 8-12). Although we have no firm evidences, this order of the reaction sequence seems to be preferable to the reverse one. Treatment of heteroaryl chalcone analogues (2e-g) and (2m) with sodium hydrogensulfide in DMF was conducted in a similar manner as described for the preparation of 2-arylthiochroman-4-ones (4a–d) and (4h–l) to give also the corresponding 2-heteroarylthiochroman-4-ones (4e-g) and (4m) in yields comparable to those of (4a–d) and (4h–l) as summarized in Table 1 as well (Entries 5-7 and 13).
The results described in this paper demonstrate that 2-arylthiochroman-4-ones (thioflavanones) can be produced from readily available 1-(2-halophenyl)ethanones and aromatic aldehydes via an easy two-step sequence. This procedure has proved to be applicable to the synthesis of 2-heteroarylthiochroman-4-ones using heteroaromatic aldehydes in place of aromatic aldehydes. We believe that the present procedure is advantageous over the previous methods2 especially in the ease of operations, the readily availability of the starting materials, and the wide scope.

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. The 1H NMR spectra were recorded in CDCl3 using TMS as an internal reference with a JEOL ECP500 FT NMR spectrometer operating at 500 MHz. The 13C NMR spectra were recorded in CDCl3 using TMS as an internal reference with 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 a 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)4 and 1-(2-bromo-4,5-dimethoxyphenyl)ethanone (1d)5 were prepared by the appropriate reported procedures. All other chemicals used in this study were commercially available.
(E)-3-Aryl-1-(2-halophenyl)prop-2-en-1-ones (2). These compounds were prepared from 1-(2-halophenyl)ethanones 1 and aromatic or heteroaromatic aldehydes under the reported conditions.3 Physical, spectral, and analytical data for new compounds follow.
(E)-1-(2-Bromophenyl)-3-(3-chlorophenyl)prop-2-en-1-one (2b): a white solid; mp 95–98 ˚C (hexane); IR (KBr) 1670, 1607 cm–1; 1H NMR δ 7.10 (d, J = 16.0 Hz, 1H), 7.33–7.45 (m, 7H), 7.54 (s, 1H), 7.66 (d, J = 8.2 Hz, 1H). Anal. Calcd for C15H10BrClO: C, 56.02; H, 3.13. Found: C, 55.74; H 3.16.
(E)-1-(2-Bromophenyl)-3-(3-methoxyphenyl)prop-2-en-1-one (2c): a yellow oil; Rf 0.34 (AcOEt–hexane 1:10); IR (neat) 1651, 1603 cm–1; 1H NMR δ 3.83 (s, 3H), 6.97 (dd, J = 8.2, 2.3 Hz, 1H), 7.08 (d, J = 16.4 Hz, 1H), 7.07 (dd, J = 2.3, 1.8 Hz, 1H), 7.15 (d, J = 7.3 Hz, 1H), 7.30–7.44 (m, 5H), 7.65 (d, J = 7.8 Hz, 1H). Anal. Calcd for C16H13BrO2: C, 60.59; H, 4.13. Found: C, 60.56; H, 4.38.
(E)-1-(2,5-Dichlorophenyl)-3-phenylprop-2-en-1-one (2d): a white solid; mp 61–63 ˚C (hexane–Et2O). IR (KBr) 1668, 1607 cm–1; 1H NMR δ 7.10 (d, J = 16.5 Hz, 1H), 7.40–7.49 (m, 7H), 7.57–7.59 (m, 2H). Anal. Calcd for C15H10Cl2O: C, 65.01; H 3.64. Found: C, 65.01; H, 3.55.
(E)-1-(2,5-Dichlorophenyl)-3-(thiophen-2-yl)prop-2-en-1-one (2e): a yellow solid; mp 64–66 ˚C (hexane–Et2O); IR (KBr) 1659 cm–1; 1H NMR δ 6.89 (d, J = 16.0 Hz, 1H), 7.10 (dd, J = 5.0, 4.1 Hz, 1H), 7.34 (d, J = 4.1, 1H); 7.39 (s, 2H), 7.44 (t, J = 0.9 Hz, 1H), 7.48 (d, J = 5.0 Hz, 1H), 7.60 (d, J = 16.0 Hz, 1H). Anal. Calcd for C13H8Cl2OS: C, 55.14; H, 2.85. Found: C, 55.34; H, 2.66.
(E)-1-(2,5-Dichlorophenyl)-3-(thiophen-3-yl)prop-2-en-1-one (2f): a white solid; mp 50–52 ˚C (hexane–Et2O); IR (KBr) 1663 cm–1; 1H NMR δ 6.90 (d, J = 16.0 Hz, 1H), 7.35–7.39 (m, 4H), 7.42 (s, 1H), 7.44 (d, J = 16.0 Hz, 1H), 7.59 (t, J = 0.9 Hz, 1H). Anal. Calcd for C13H8Cl2OS: C, 55.14; H, 2.85. Found: C, 55.09; H, 2.91.
(E)-1-(2,5-Dichlorophenyl)-3-(1-methylindol-2-yl)prop-2-en-1-one (2g): a yellow solid; mp 107–108 ˚C (hexane–Et2O); IR (KBr) 1663 cm–1; 1H NMR δ 3.84 (s, 3H), 7.11 (s, 1H), 7.13 (ddd, J = 7.8, 7.3, 1.4, Hz, 1H), 7.19 (d, J = 16.0 Hz, 1H), 7.30 (ddd, J = 8.2, 7.3, 0.9 Hz, 1H), 7.33 (d, J = 7.8 Hz, 1H), 7.40–7.41 (m, 2H), 7.53 (dd, J = 1.8, 0.9 Hz, 1H), 7.62 (d, J = 8.2 Hz, 1H), 7.73 (d, J = 16.0 Hz, 1H). Anal. Calcd for C18H13Cl2NO: C, 65.47; H, 3.97; N, 4.24. Found: C, 65.27; H, 3.25; N, 4.26.
(E)-1-(2-Bromo-5-methoxyphenyl)-3-phenylprop-2-en-1-one (2h): a white solid; mp 112–114 ˚C (hexane–CH2Cl2); IR (KBr) 1651, 1620 cm–1; 1H NMR δ 3.82 (s, 3H), 6.89 (dd, J = 8.7, 3.2 Hz, 1H), 6.95 (d, J = 3.2 Hz, 1H), 7.09 (d, J = 16.0 Hz, 1H), 7.39–7.47 (m, 4H), 7.52 (d, J = 8.7 Hz, 1H), 7.56–7.58 (m, 2H). Anal. Calcd for C16H13BrO2: C, 60.59; H, 4.13. Found: C, 60.40; H, 4.14.
(E)-1-(2-Bromo-5-methoxyphenyl)-3-(4-methylphenyl)prop-2-en-1-one (2i): a white solid; mp 74–76 ˚C (hexane–Et2O); IR (KBr) 1641, 1605 cm–1; 1H NMR δ 2.39 (s, 3H), 3.82 (s, 3H), 6.89 (dd, J = 9.2, 3.2 Hz, 1H), 6.94 (d, J = 3.2 Hz, 1H), 7.04 (d, J = 16.0 Hz, 1H), 7.21 (d, J = 7.8 Hz, 2H), 7.43 (d, J = 16.0 Hz, 1H), 7.47 (d, J = 7.8 Hz, 2H), 7.51 (d, J = 9.2 Hz, 1H). Anal. Calcd for C17H15BrO2: C, 61.65; H, 4.56. Found: C, 61.58; H, 4.72.
(E)-1-(2-Bromo-5-methoxyphenyl)-3-(naphthalen-1-yl)prop-2-en-1-one (2j): a pale-yellow solid; mp 90–92 ˚C (hexane–Et2O); IR (KBr) 1647, 1609 cm–1; 1H NMR δ 3.85 (s, 3H), 6.93 (dd, J = 9.2, 3.2 Hz, 1H), 7.04 (d, J = 3.2 Hz, 1H), 7.20 (d, J = 15.6 Hz, 1H), 7.51–7.59 (m, 4H), 7.87 (dd, J = 8.2 Hz, 1H), 7.89 (d, J = 8.2 Hz, 1H), 7.94 (d, J = 8.2 Hz, 1H), 8.11 (d, J = 8.2 Hz, 1H), 8.35 (d, J = 15.6 Hz, 1H). Anal. Calcd for C20H15BrO2: C, 65.41; H, 4.12. Found: C, 65.40; H, 4.07.
(E)-1-(2-Bromo-4,5-dimethoxyphenyl)-3-phenylprop-2-en-1-one (2k): a pale-yellow solid; mp 153–155 ˚C (hexane–Et2O); IR (KBr) 1638, 1624 cm–1; 1H NMR δ 3.90 (s, 3H), 3.94 (s, 3H), 7.04 (s, 1H), 7.08 (s, 1H), 7.22 (d, J = 16.0 Hz, 1H), 7.40–7.43 (m, 3H), 7.55 (d, J = 16.0 Hz, 1H), 7.58–7.61 (m, 2H). Anal. Calcd for C17H15BrO3: C, 58.81; H, 4.35. Found: C, 58.80; H, 4.42.
(E)-3-(1,3-Benzodioxol-5yl)-1-(2-bromo-4,5-dimethoxyphenyl)prop-2-en-1-one (2l): a pale-yellow solid; mp 186–188 ˚C (hexane–CH2Cl2); IR (KBr) 1640 cm–1; 1H NMR δ 3.90 (s, 3H), 3.94 (s, 3H), 6.03 (s, 2H), 6.84 (d, J = 8.2 Hz, 1H), 7.02–7.07 (m, 4H), 7.11 (d, J = 0.9 Hz, 1H), 7.46 (d, J = 16.0 Hz, 1H). Anal. Calcd for C18H15BrO5: C, 55.26; H, 3.86. Found: C, 55.25; H, 3.86.
(E)-1-(2-Bromo-4,5-dimethoxyphenyl)-3-(1-methylpyrrol-2-yl)prop-2-en-1-one (2m): a yellow solid; mp 112–114 ˚C (hexane–Et2O); IR (KBr) 1649 cm–1; 1H NMR δ 3.74 (s, 3H), 3.90 (s, 3H), 3.93 (s, 3H), 6.22 (dd, J = 4.1, 2.3 Hz, 1H), 6.79 (dd, J = 4.1, 1.4 Hz, 1H), 6.83 (dd, J = 2.3, 1.4 Hz, 1H), 6.95 (d, J = 15.1 Hz, 1H), 7.03 (s, 1H), 7.06 (s, 1H), 7.56 (d, J = 15.1 Hz, 1H). Anal. Calcd for C16H16BrNO3: C, 54.87; H, 4.61; N, 4.00, Found: C, 54.85; H, 4.82; N, 4.00.
Typical Procedure for the Preparation of 2-Aryl- or 2-Heteroaryl-thiochromanones (4). 2-Phenylthiochroman-4-one (4a). A mixture of 2a (0.19 g, 0.65 mmol) and NaSH (70%; 52 mg, 0.65 mmol) in DMF (5 mL) was bubbled with Ar gas and was heated at 80 ˚C for 10 min. After cooling, sat. aq. NH4Cl (20 mL) was added and the mixture was extracted with AcOEt (3 × 10 mL). The combined extracts were washed with water (2 × 10 mL) and then brine (10 mL), and dried (Na2SO4). Evaporation of the solvent gave a residue, which was purified by column chromatography on silica gel (AcOEt–hexane 1:15) to give 4a (0.11 g, 71%) as a yellow solid; mp 57–59 ˚C (hexane) (lit.,2b mp 56–57 ˚C). The spectral data (IR, 1H NMR) of this product were identical to those reported previously.2b
2-(3-Chlorophenyl)thiochroman-4-one (4b): a yellow solid; mp 43–45 ˚C (pentane); IR (KBr) 1682 cm–1; 1H NMR δ 3.19 (dd, J = 16.0, 3.2 Hz, 1H), 3.28 (dd, J = 16.0, 12.8 Hz, 1H), 4.68 (dd, J = 12.8, 3.2 Hz, 1H), 7.21–7.33 (m, 5H), 7.41–7.44 (m, 2H), 8.15 (dd, J = 8.2, 1.4 Hz, 1H); 13C NMR δ 44.88, 46.40, 125.42, 125.58, 127.21, 127.70, 128.67, 129.24, 130.25, 130.31, 133.75, 134.79, 140.37, 141.47, 193.77; MS m/z 274 (M+, 100). Anal. Calcd for C15H11ClOS: C, 65.57; H, 4.04. Found: C, 65.48; H, 4.14.
2-(3-Methoxyphenyl)thiochroman-4-one (4c): a yellow solid; mp 45–47 ˚C (pentane); IR (KBr) 1678 cm–1; 1H NMR δ 3.20 (dd, J = 16.5, 3.2 Hz, 1H), 3.30 (dd, J = 16.5, 12.8 Hz, 1H), 3.82 (s, 3H), 4.69 (dd, J = 12.8, 3.2 Hz, 1H), 6.88 (dd, J = 8.2, 2.7 Hz, 1H), 6.97 (dd, J = 2.3, 1.8 Hz, 1H), 7.00 (d, J = 7.8 Hz, 1H), 7.21 (dd, J = 7.8, 7.3 Hz, 1H), 7.28–7.31 (m, 2H), 7.41 (ddd, J = 7.8, 7.3, 1.4 Hz, 1H), 8.14 (dd, J = 7.8, 1.4 Hz, 1H); 13C NMR δ 45.47, 46.71, 55.27, 113.22, 113.78, 119.61, 125.21, 127.21, 129.19, 130.03, 130.37, 133.63, 139.91, 142.03, 159.91, 194.33; MS m/z 270 (M+, 100). Anal. Calcd for C16H14O2S: C, 71.08; H, 5.22. Found: C, 68.87; H, 5.45.
6-Chloro-2-phenylthiochroman-4-one (4d): colorless needles; mp 80–83 ˚C (hexane–Et2O); IR (KBr) 1682 cm–1; 1H NMR δ 3.22 (dd, J = 16.5, 3.2 Hz, 1H), 3.31 (dd, J = 16.5, 12.8 Hz, 1H), 4.71 (dd, J = 12.8, 3.2 Hz, 1H), 7.24 (d, J = 8.2 Hz, 1H), 7.34–7.43 (m, 6H), 8.12 (d, J = 2.3 Hz, 1H); 13C NMR δ 45.46, 46.25, 127.37 (2C), 128.62, 128.80, 129.04, 131.41, 131.44, 133.59, 137.97, 140.37, 193.21; MS m/z 274 (M+, 100). Anal. Calcd for C15H11ClOS: C, 65.57; H 4.04. Found: C, 65.41; H, 4.01.
6-Chloro-2-(thiophen-2-yl)thiochroman-4-one (4e): a beige viscous oil; Rf 0.50 (THF–hexane 1:5); IR (KBr) 1682 cm–1; 1H NMR δ 3.33 (dd, J = 17.0, 10.5 Hz, 1H), 3.37 (dd, J = 17.0, 4.1 Hz, 1H), 4.96 (ddd, J = 10.5, 4.1, 0.9 Hz, 1H), 6.97 (dd, J = 5.1, 3.7 Hz, 1H), 7.06 (dt, J = 2.8, 1.3 Hz, 1H), 7.23 (d, J = 8.2 Hz, 1H), 7.27 (dd, J = 5.0, 0.9 Hz, 1H), 7.39 (dd, J = 8.2, 2.3 Hz, 1H), 8.10 (d, J = 2.3 Hz, 1H); 13C NMR δ 40.58, 47.03, 125.65, 125.99, 127.00, 128.72, 128.74, 131.38, 131.64, 133.67, 139.30, 141.59, 192.32; MS m/z 280 (M+, 100). Anal. Calcd for C13H9ClOS2: C, 55.61; H, 3.23. Found: C, 55.56; H, 3.38.
6-Chloro-2-(thiophen-3-yl)thiochroman-4-one (4f): a pale-yellow viscous oil; Rf 0.29 (CHCl3–hexane 1:2); IR (KBr) 1682 cm–1; 1H NMR δ 3.28 (dd, J = 16.5, 6.9 Hz, 1H), 3.29 (dd, J = 16.5, 8.2 Hz, 1H), 4.79 (dd, J = 8.2, 6.9 Hz, 1H), 7.14 (dd, J = 5.0, 1.4 Hz, 1H), 7.25–7.26 (m, 2H), 7.34–7.38 (m, 2H), 8.10 (d, J = 2.7 Hz, 1H); 13C NMR δ 40.59, 46.11, 122.81, 126.52, 126.87, 128.76 (2C), 131.47, 131.51, 133.61, 138.87, 139.75, 192.94; MS m/z 280 (M+, 100). Anal. Calcd for C13H9ClOS2: C, 55.61; H, 3.23. Found: C, 55.38; H, 3.18.
6-Chloro-2-(1-methylindol-2-yl)thiochroman-4-one (4g): a white solid; mp 177–180 ˚C (hexane–CH2Cl2); IR (KBr) 1682 cm–1; 1H NMR δ 3.41 (dd, J = 16.9, 3.7 Hz, 1H), 3.49 (dd, J = 16.9, 10.0 Hz, 1H), 3.81 (s, 3H), 4.84 (dd, J = 10.0, 3.7 Hz, 1H), 6.47 (s, 1H), 7.11 (ddd, J = 8.2, 7.8, 0.9 Hz, 1H), 7.20 (d, J = 8.2 Hz, 1H), 7.24 (t, J = 8.2, 7.8 Hz, 1H), 7.31 (d, J = 8.2 Hz, 1H), 7.37 (dd, J = 8.7, 2.3 Hz, 1H), 7.57 (d, J = 8.7 Hz, 1H), 8.17 (d, J = 2.3 Hz, 1H); 13C NMR δ 29.87, 37.43, 44.45, 101.32, 109.16, 120.02, 120.85, 122.49, 126.95, 128.81, 129.03, 131.60, 131.86, 133.71, 135.76, 137.83, 138.44, 192.79; MS m/z 327 (M+, 100). Anal. Calcd for C18H14ClNOS: C, 65.95; H, 4.30; N, 4.27. Found: C, 65.94; H, 4.30; N, 4.29.
6-Methoxy-2-phenylthiochroman-4-one (4h): an orange solid; mp 111–113 ˚C (hexane–Et2O); IR (KBr) 1682 cm–1; 1H NMR δ 3.21 (dd, J = 16.5, 3.2 Hz, 1H), 3.31 (dd, J = 16.5, 12.8 Hz, 1H), 3.84 (s, 3H), 4.69 (dd, J = 12.8, 3.2 Hz, 1H), 7.05 (dd, J = 8.7, 2.7 Hz, 1H), 7.20 (d, J = 8.7 Hz, 1H), 7.33 (tt, J = 7.3, 1.4 Hz, 1H), 7.38 (dd, J = 7.8, 7.3 Hz, 2H), 7.43 (dd, J = 7.8, 1.4 Hz, 2H), 7.66 (d, J = 2.7 Hz, 1H); 13C NMR δ 45.72, 46.73, 55.58, 111.30, 122.62, 127.38, 128.39, 128.52, 128.93, 131.20, 133.49, 138.52, 157.57, 194.38; MS m/z 270 (M+, 100). Anal. Calcd for C16H14O2S: C, 71.08; H 5.22. Found: C, 71.01; H, 5.31.
6-Methoxy-2-(4-methylphenyl)thiochroman-4-one (4i): pale-yellow needles; mp 104–106 ˚C (hexane–Et2O); IR (KBr) 1676 cm–1; 1H NMR δ 2.36 (s, 3H), 3.18 (dd, J = 16.5, 2.7 Hz, 1H), 3.29 (dd, J = 16.5, 13.3 Hz, 1H), 3.84 (s, 3H), 4.65 (dd, J = 13.3, 2.7 Hz, 1H), 7.04 (dd, J = 8.7, 3.2 Hz, 1H), 7.17–7.20 (m, 3H), 7.31 (d, J = 7.8 Hz, 2H), 7.65 (d, J = 3.2 Hz, 1H); 13C NMR δ 21.13, 45.44, 46.78, 55.56, 111.23, 122.59, 127.23, 128.50, 129.57 (2C), 131.17, 135.50, 138.24, 157.50, 194.56; MS m/z 284 (M+, 100). Anal. Calcd for C17H16O2S: C, 71.80; H, 5.67. Found: C, 71.75; H, 5.93.
6-Methoxy-2-(naphthalen-1-yl)thiochroman-4-one (4j): yellow needles; mp 132–134 ˚C (hexane–Et2O); IR (KBr) 1670 cm–1; 1H NMR δ 3.36 (dd, J = 16.5, 2.7 Hz, 1H), 3.52 (dd, J = 16.5, 12.8 Hz, 1H), 3.88 (s, 3H), 5.48 (dd, J = 12.8, 2.7 Hz, 1H), 7.08 (dd, J = 8.7, 2.7 Hz, 1H), 7.23 (d, J = 8.7 Hz, 1H), 7.49–7.59 (m, 3H), 7.65 (d, J = 7.3 Hz, 1H), 7.72 (d, J = 2.7 Hz, 1H), 7.85 (d, J = 7.8 Hz, 1H), 7.90 (d, J = 7.8 Hz, 1H), 8.18 (d, J = 8.2 Hz, 1H); 13C NMR δ 41.26, 46.36, 55.62, 111.41, 122.62, 122.81, 124.50, 125.35, 126.04, 126.67, 128.66, 129.03, 129.10, 130.73, 131.24, 133.75, 133.99, 134.00, 157.68, 194.83; MS m/z 320 (M+, 100). Anal. Calcd for C20H16O2S: C, 74.97; H, 5.03. Found: C, 75.01; H, 5.04.
6,7-Dimethoxy-2-phenylthiochroman-4-one (4k): a yellow solid; mp 171–174 ˚C (hexane–CH2Cl2); IR (KBr) 1653 cm–1; 1H NMR δ 3.16 (dd, J = 16.5, 3.2 Hz, 1H), 3.27 (dd, J = 16.5, 12.8 Hz, 1H), 3.92 (s, 6H), 4.70 (dd, J = 12.8, 3.2 Hz, 1H), 6.69 (s, 1H), 7.34 (tt, J = 7.3, 1.4 Hz, 1H), 7.39 (dd, J = 7.8, 7.3 Hz, 2H), 7.43 (dd, J = 7.8, 1.4 Hz, 2H), 7.65 (s, 1H); 13C NMR δ 46.09, 46.17, 56.05, 56.23, 108.58, 110.38, 123.69, 127.39, 128.38, 128.93, 135.91, 138.53, 147.35, 153.90, 193.17; MS m/z 300 (M+, 100). Anal. Calcd for C17H16O3S: C, 67.98; H, 5.37. Found: C, 67.93; H, 5.41.
2-(1,3-Benzodioxol-5-yl)-6,7-dimethoxythiochroman-4-one (4l): a yellow solid; mp 198–200 ˚C (hexane–CH2Cl2); IR (KBr) 1649 cm–1; 1H NMR δ 3.12 (dd, J = 16.5, 3.2 Hz, 1H), 3.20 (dd, J = 16.5, 12.8 Hz, 1H), 3.919 (s, 3H), 3.924 (s, 3H), 4.63 (dd, J = 12.8, 3.2 Hz, 1H), 5.99 (s, 2H), 6.68 (s, 1H), 6.79 (d, J = 7.8 Hz, 1H), 6.88 (dd, J = 7.8, 1.8 Hz, 1H), 6.93 (d, J = 1.8 Hz, 1H), 7.64 (s, 1H); 13C NMR δ 45.98, 46.49, 56.05, 56.24, 101.33, 107.76, 108.49, 108.55, 110.37, 120.95, 123.64, 132.31, 135.90, 147.35, 147.61, 147.97, 153.91, 193.16; MS m/z 344 (M+, 100). Anal. Calc for C18H16O5S: C, 62.78; H, 4.68. Found: C, 62.70; H, 4.81.
6,7-Dimethoxy-2-(1-methylpyrrol-2-yl)thiochroman-4-one (4m): a pale-yellow solid; mp 173–175 ˚C (hexane–CH2Cl2); IR (KBr) 1655 cm–1; 1H NMR δ 3.23 (dd, J = 16.9, 3.2 Hz, 1H), 3.31 (dd, J = 16.9, 11.5 Hz, 1H), 3.69 (s, 3H), 3.92 (s, 6H), 4.68 (dd, J = 11.5, 3.2 Hz, 1H), 6.09 (t, J = 2.7 Hz, 1H), 6.15 (s, 1H), 6.63 (s, 1H), 6.67 (s, 1H), 7.66 (s, 1H); 13C NMR δ 33.85, 38.11, 44.85, 56.04, 56.19, 107.27, 107.74, 108.89, 110.37, 123.50, 123.94, 129.00, 134.96, 147.43, 153.81, 193.28; MS m/z 303 (M+, 100). Anal. Calcd for C16H17NO3S: C, 63.34; H, 5.65; N, 4.62. Found: C, 63.21; H, 4.71; N, 4.82.

References

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