HETEROCYCLES

Short Paper | Regular issue | Vol. 83, No. 4, 2011, pp. 883-889
Received, 19th January, 2011, Accepted, 21st February, 2011, Published online, 2nd March, 2011.
DOI: 10.3987/COM-11-12142

■ One-Pot Synthesis of 4,5-Dihydro-3,1-benzoxazepine-2(1H)-thiones from 2-(2-Isocyanophenyl)ethanols via the Corresponding Isothiocyanates

Shuhei Fukamachi, Hisatoshi Konishi, and Kazuhiro Kobayashi*

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

Abstract

An efficient method for the preparation of 4,5-dihydro-3,1-benzoxazepine-2(1H)-thiones under mild conditions has been developed. 2-(2-Isocyanophenyl)ethanols, easily accessible by treating 1-isocyano-2-(lithiomethyl)benzenes with aldehydes or ketones, were converted into the corresponding isothiocyanates on treatment with sulfur in the presence of a catalytic amount of selenium and excess triethylamine. These isothiocyanato alcohols were then treated with sodium hydride to give 4,5-dihydro-3,1-benzoxazepine-2(1H)-thione derivatives in one pot.

Compounds having the 4,5-dihydro-3,1-benzoxazepine-2(1H)-thione structure are an important class of molecules, because this structure is found in some biologically active compounds.1 However, very few practical methods for the preparation of the 4,5-dihydro-3,1-benzoxazepine-2(1H)-thione derivatives have been reported. Suda et al. have reported on the conversion of 4,5-dihydro-3,1-benzoxazepin-2(1H)-one derivatives into the corresponding thione derivatives by the treatment with Lawesson’s reagent.1c In this paper, we describe a facile synthesis of 4,5-dihydro-3,1-benzoxazepine-2(1H)-thiones from 1-isocyano-2-methylbenzenes via a three-step procedure.
The synthesis of 4,5-dihydro-3,1-benzoxazepine-2(1H)-thione derivatives (4) from 1-isocyano-2- methylbenzenes (1), via 2-(2-isocyanophenyl)ethanols (2), is illustrated in Scheme 1. The requisite isocyano alcohols (2) were prepared by the lithiation of 1 with LDA followed by the reaction with aldehydes or ketones according to the procedure reported by Ito et al.2,3 The yields of 2 are generally good (Table 1). The reaction could be applicable to aldehydes and ketones carrying α-hydrogens, such as propanal, acetone, cyclohexanone, and acetophenone (Entries 1 and 4–6). However, as can be seen from Entries 8 and 9, the yields of the products (2j) and (2k) from 1-isocyano-2,4-dimethylbenzene are somewhat lower than those of the others. This may be ascribed to simultaneous slight lithiation of 4-methyl group

Compounds (2) thus obtained were converted into the corresponding isothiocyanates (3) on treatment with sulfur in the presence of a catalytic amount of selenium and excess Et3N in THF at reflux temperature under the same conditions as reported by Fujiwara et al.4 These isothiocyanates were then, without isolation, treated with an equimolar amount of sodium hydride at 0 ˚C to generate the corresponding sodium alkoxide intermediates, which cyclized by the attack of the alkoxide oxygen on the isothiocyanate carbon. The cyclization proceeded immediately and cleanly. The completion of each step of the sequence was monitored by TLC (silica gel) analyses. The usual aqueous workup and subsequent purification by recrystallization of the crude products afforded the desired products (4) in one pot from 2. The results are summarized in Table 1. The yields are fair to good as a whole. The 4,4-disubsutituted derivatives (4d-f) could also be obtained in generally good yields (Entries 4-6). However, in the reaction of 1-(2-isocyanophenyl)-2,2-diphenylethan-2-ol (2g) (Entry 7), its clean conversion into the corresponding isothiocyanates (3g) could be confirmed by TLC analysis, but treatment of this isothiocyanate with sodium hydride resulted in the formation of a complex mixture of products, in which only trace of the desired product (4g) was detected as a mixture with structurally undefined products by 1H NMR. This result may be ascribed to the crowdedness at the 4-position of the product due to two phenyl groups. The reaction of 2-(2-isocyanophenyl)-1-(thiophen-2-yl)ethanol (2c) was also gave a similar result (Entry 3), though the reaction for this is unclear.
In conclusion, we have demonstrated that 2-(2-isocyanophenyl)ethanols can been utilized for the one-pot synthesis of 4,5-dihydro-3,1-benzoxazepine-2(1H)-thiones. Since the method employs readily available starting materials and is experimentally simple, it may be of value in organic synthesis.

EXPERIMENTAL
The melting points were obtained on a Laboratory Devices MEL-TEMP II melting apparatus and are uncorrected. IR spectra were determined with a Shimadzu FTIR-8300 spectrophotometer. The 1H NMR spectra were determined using TMS as an internal reference with a JEOL ECP500 FT NMR spectrometer operating at 500 MHz. The 13C NMR spectra were determined using TMS as an internal reference with a JEOL ECP500 FT NMR spectrometer operating at 125 MHz. Low- and high-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-Isocyano-2-methylbenzenes (1) were prepared according to the procedure reported previously by Ito et al.5 All other chemicals used in this study were commercially available.
2-(2-Isocyanophenyl)ethanols (2). These compounds were prepared by treating the respective 1-isocyano-2-lithiomethybenzenes, generated from 1-isocyano-2-methylbenzenes (1) and LDA, with aldehydes or ketones according to the procedure reported by Ito et al.2 Physical, spectral, and analytical data for new compounds follow.
2-(2-Isocyanophenyl)-1-(thiophen-2-yl)ethanol (2c): a yellow oil; Rf 0.35 (1:4 EtOAc–hexane); IR (neat) 3412, 2120 cm-1; 1H NMR (CDCl3) δ 2.20 (d, J = 3.9 Hz, 1H), 3.12 (dd, J = 13.7, 8.3 Hz, 1H), 3.20 (dd, J = 13.7, 5.3 Hz, 1H), 5.26–5.30 (m, 1H), 6.95–6.98 (m, 2H), 7.26–7.35 (m, 4H), 7.38 (d, J = 7.8 Hz, 1H). HR-MS. Calcd for C13H11NOS: M, 229.0561. Found: m/z 229.0533.
1-[(2-Isocyanophenyl)methyl]cyclohexanol (2e): a pale-yellow oil; Rf 0.36 (1:4 THF–hexane); IR (neat) 3466, 2120 cm-1; 1H NMR (CDCl3) δ 1.27 (s, 1H), 1.53–1.63 (m, 10H), 2.93 (s, 2H), 7.26 (td, J = 7.8, 1.8 Hz, 1H), 7.34 (td, J = 7.8, 1.4 Hz, 1H), 7.38 (dd, J = 7.8, 1.8 Hz, 1H), 7.39 (dd, J = 7.8, 1.4 Hz, 1H). HR-MS. Calcd for C14H17NO: M, 215.1310. Found: m/z 215.1316.
1-(2-Isocyanophenyl)-2-phenylpropan-2-ol (2f): a pale-yellow oil; Rf 0.32 (1:5 THF–hexane); IR (neat) 3445, 2122 cm-1; 1H NMR (CDCl3) δ 1.63 (s, 3H), 1.79 (s, 1H), 3.16 (d, J = 13.7 Hz, 1H), 3.30 (d, J = 13.7 Hz, 1H), 7.14–7.16 (m, 1H), 7.24–7.36 (m, 7H), 7.44 (dd, J = 7.3, 1.4 Hz, 1H). HR-MS. Calcd for C16H15NO: M, 237.1154. Found: m/z 237.1170.
1-(2-Isocyanophenyl)-2,2-diphenylethan-2-ol (2g): a pale-yellow oil; Rf 0.33 (1:6 THF–hexane); IR (neat) 3412, 2122 cm-1; 1H NMR (CDCl3) δ 2.28 (s, 1H), 3.78 (s, 2H), 6.76 (d, J = 7.8 Hz, 1H), 7.08 (td, J = 7.8, 0.9 Hz, 1H), 7.15 (t, J = 7.8 Hz, 1H), 7.24–7.39 (m, 11H). HR-MS. Calcd for C21H17NO: M, 299.1310. Found: m/z 299.1308.
2-(2-Isocyano-5-methylphenyl)-1-phenylethanol (2h): a yellow oil; Rf 0.33 (1:5 THF–hexane); IR (neat) 3418, 2118 cm-1; 1H NMR (CDCl3) δ 1.95 (d, J = 3.2 Hz, 1H), 2.34 (s, 3H), 3.04 (dd, J = 13.7, 9.1 Hz, 1H), 3.17 (dd, J = 13.7, 4.1 Hz, 1H), 5.00–5.03 (m, 1H), 7.06 (d, J = 7.8 Hz, 1H), 7.09 (s, 1H), 7.26 (d, J = 7.8 Hz, 1H), 7.30 (tt, J = 7.3, 1.8 Hz, 1H), 7.36 (td, J = 7.3, 1.8 Hz, 2H), 7.41 (dd, J = 7.3, 1.8 Hz, 2H). HR-MS. Calcd for C16H15NO: M, 237.1154. Found: m/z 237.1129.
2-(2-Isocyano-5-methylphenyl)-1-(4-methylphenyl)ethanol (2i): colorless crystals; mp 100–102 ˚C (hexane–Et2O); IR (KBr) 3350, 2118 cm-1 ; 1H NMR (CDCl3) δ 1.87 (d, J = 3.2 Hz, 1H), 2.34 (s, 3H), 2.36 (s, 3H), 3.03 (dd, J = 13.7, 9.1 Hz, 1H), 3.15 (dd, J = 13.7, 4.1 Hz, 1H), 4.97–5.00 (m, 1H), 7.06 (d, J = 7.8 Hz, 1H), 7.12 (s, 1H), 7.17 (d, J = 7.8 Hz, 2H), 7.26 (d, J = 7.8 Hz, 1H), 7.31 (d, J = 7.8 Hz, 2H). Anal. Calcd for C17H17NO: C, 81.24; H, 6.82; N, 5.57. Found: C, 81.11; H, 6.77; N, 5.53.
2-(5-Chloro-2-isocyanophenyl)-1-(naphthalen-2-yl)ethanol (2j): a pale-yellow solid; mp 106–108 ˚C (hexane–CH2Cl2); IR (KBr) 3412, 2141 cm-1 ; 1H NMR (CDCl3) δ 2.06 (d, J = 3.4 Hz, 1H), 3.14 (dd, J = 13.7, 8.6 Hz, 1H), 3.25 (dd, J = 13.7, 4.0 Hz, 1H), 5.16–5.20 (m, 1H), 7.26 (dd, J = 8.6, 2.3 Hz, 1H), 7.31 (d, J = 8.6 Hz, 1H), 7.38 (d, J = 2.3 Hz, 1H), 7.47–7.52 (m, 2H), 7.54 (dd, J = 7.8, 1.8 Hz, 1H), 7.83–7.88 (m, 4H). Anal. Calcd for C19H14ClNO: C, 74.15; H, 4.58; N, 4.55. Found: C, 74.16; H, 4.62; N, 4.40.
2-(5-Chloro-2-isocyanophenyl)-1-(4-chlorophenyl)ethanol (2k): a yellow solid; mp 79–81 ˚C (hexane–Et2O); IR (KBr) 3354, 2124 cm-1 ; 1H NMR (CDCl3) δ 2.01 (d, J = 2.9 Hz, 1H), 3.03 (dd, J = 14.3, 9.2 Hz, 1H), 3.13 (dd, J = 14.3, 4.0 Hz, 1H), 4.97–5.00 (m, 1H), 7.26 (dd, J = 8.6, 2.3 Hz, 1H), 7.30–7.35 (m, 6H). Anal. Calcd for C15H11Cl2NO: C, 61.67; H, 3.79; N, 4.79. Found: C, 61.44; H, 3.93; N, 4.50.
2-(2-Isocyano-5-methoxyphenyl)-1-phenylethanol (2l): a pale-yellow solid; mp 62–63 ˚C (hexane–Et2O); IR (KBr) 3420, 2118 cm-1 ; 1H NMR (CDCl3) δ 2.00 (d, J = 2.9 Hz, 1H), 3.06 (dd, J = 13.7, 9.1 Hz, 1H), 3.17 (dd, J = 13.7, 4.4 Hz, 1H), 3.77 (s, 3H), 5.00–5.04 (m, 1H), 6.75 (s, 1H), 6.77 (d, J = 7.8 Hz, 1H), 7.30–7.42 (m, 6H). Anal. Calcd for C16H15NO2: C, 75.87; H, 5.97; N, 5.53. Found: C, 75.80; H, 6.06; N, 5.67.
2-(2-Isocyano-5-methoxyphenyl)-1-(3-methoxyphenyl)ethanol (2m): a yellow oil; Rf 0.26 (1:3 EtOAc–hexane); IR (neat) 3418, 2118 cm-1; 1H NMR (CDCl3) δ 1.97 (d, J = 3.4 Hz, 1H), 3.05 (dd, J = 13.7, 8.6 Hz, 1H), 3.17 (dd, J = 13.7, 4.0 Hz, 1H), 3.78 (s, 3H), 3.81 (s, 3H), 4.98–5.01 (m, 1H), 6.75–6.85 (m, 3H), 6.97 (s, 1H), 6.98 (d, J = 7.8 Hz, 1H), 7.26–7.32 (m, 2H). HR-MS. Calcd for C17H17NO3: M, 283.1208. Found: m/z 283.1183.
Typical Procedure for the Preparation of 4,5-Dihyro-3,1-benzoxazepine-2(1H)-thiones (4). 4-Ethyl-4,5-dihyro-3,1-benzoxazepine-2(1H)-thione (4a). A mixture of 2a (0.27 g, 1.5 mmol), Et3N (0.38 g, 3.8 mmol), sulfur (58 mg, 1.8 mmol), and selenium (3.6 mg, 45 µmol) in THF (5 mL) was stirred at reflux temperature for 1 h. After cooling to 0 ˚C, NaH (60% in oil; 72 mg, 1.8 mmol) was added, and stirring was continued for an additional 30 min at the same temperature. Saturated aqueous NH4Cl (10 mL) was added and organic materials were extracted with AcOEt three times (10 mL each), and the combined extracts were washed with brine, dried over anhydrous Na2SO4, and concentrated by evaporation. The residual solid was recrystallized from hexane-CH2Cl2 to give 4a (0.24 g, 78 %); a beige solid; mp 88–90 ˚C (hexane–CH2Cl2); IR (KBr) 3181, 1153 cm-1; 1H NMR (CDCl3) δ 1.09 (t, J = 7.3 Hz, 3H), 1.72–1.80 (m, 1H), 1.89–1.97 (m, 1H), 3.10 (dd, J = 16.4, 1.4 Hz, 1H), 3.21 (dd, J = 16.4, 8.2 Hz, 1H), 4.60–4.64 (m, 1H), 6.99 (dd, J = 7.8, 0.9 Hz, 1H), 7.08 (td, J = 7.8, 0.9 Hz, 1H), 7.12 (dd, J = 7.8, 1.4 Hz, 1H), 7.21 (td, J = 7.8, 1.4 Hz, 1H), 9.53 (br s, 1H); 13C NMR (CDCl3) δ 9.83, 28.19, 39.05, 86.82, 119.79, 124.93, 127.38, 127.86, 130.48, 136.44, 188.90; MS m/z 207 (M+, 17), 177 (30), 162 (100). Anal. Calcd for C11H13NOS: C, 63.74; H, 6.32; N, 6.76. Found: C, 63.70; H, 6.42; N, 6.70.
4-Phenyl-4,5-dihyro-3,1-benzoxazepine-2(1H)-thione (4b): a pale-yellow solid; mp 147–149 ˚C (hexane–EtOAc); IR (KBr) 3160, 1148 cm-1; 1H NMR (DMSO-d6) δ 3.31 (dd, J = 16.9, 2.3 Hz, 1H), 3.54 (dd, J = 16.9, 7.8 Hz, 1H), 5.80 (dd, J = 7.8, 2.3 Hz, 1H), 7.07 (td, J = 7.3, 0.9 Hz, 1H), 7.20 (d, J = 7.3, 1.4 Hz, 1H), 7.23 (td, J = 7.3, 1.4 Hz, 1H), 7.30 (dd, J = 7.3, 0.9 Hz, 1H), 7.36 (t, J = 7.3 Hz, 1H), 7.40 (t, J = 7.3 Hz, 2H), 7.47 (d, J = 7.3 Hz, 2H), 11.64 (s, 1H); 13C NMR (DMSO-d6) δ 40.47, 85.89, 120.43, 124.52, 126.37, 127.50, 128.07, 128.39, 128.45, 130.62, 137.03, 139.48, 187.83; MS m/z 255 (M+, 7.0), 225 (45), 210 (100). Anal. Calcd for C15H13NOS: C, 70.56; H, 5.13; N, 5.49. Found: C, 70.68; H, 5.17; N, 5.37.
4,4-Dimethyl-4,5-dihyro-3,1-benzoxazepine-2(1H)-thione (4d): beige crystals; mp 144–146 ˚C (hexane–CH2Cl2); IR (KBr) 3175, 1153 cm-1; 1H NMR (CDCl3) δ 1.52 (s, 6H), 3.06 (s, 2H), 7.02 (d, J = 7.8 Hz, 1H), 7.14–7.18 (m, 2H), 7.25–7.29 (m, 1H), 9.85 (br s, 1H); 13C NMR (CDCl3) δ 27.74, 44.68, 92.70, 119.99, 125.75, 128.09, 128.93, 130.49, 136.66, 188.37; MS m/z 207 (M+, 48), 132 (100). Anal. Calcd for C11H13NOS: C, 63.74; H, 6.32; N, 6.76. Found: C, 63.69; H, 6.25; N, 6.76.
Spiro[cyclohexane-1,4’-4,5-dihyro-3,1-benzoxazepine-2(1H)-thione] (4e): yellow crystals; mp 153–155 ˚C (hexane–CH2Cl2); IR (KBr) 3160, 1167 cm-1; 1H NMR (CDCl3) δ 1.31–2.04 (m, 10H), 3.04 (s, 2H), 7.02 (d, J = 7.8 Hz, 1H), 7.13–7.15 (m, 2H), 7.23–7.26 (m, 1H), 9.99 (s, 1H); 13C NMR (CDCl3) δ 22.02, 25.19, 36.04, 43.47, 93.95, 119.88, 125.58, 127.93, 128.26, 130.61, 136.66, 188.37; MS m/z 247 (M+, 20), 172 (100). Anal. Calcd for C14H17NOS: C, 67.98; H, 6.93; N, 5.66. Found: C, 67.83; H, 6.62; N, 5.49.
4-Methyl-4-phenyl-4,5-dihyro-3,1-benzoxazepine-2(1H)-thione (4f): a beige solid; mp 111–113 ˚C (hexane–CH2Cl2); IR (KBr) 3165, 1144 cm-1; 1H NMR (CDCl3) δ 1.84 (s, 3H), 3.48 (d, J = 16.0 Hz, 1H), 3.52 (d, J = 16.0 Hz, 1H), 6.88 (d, J = 7.8 Hz, 1H), 7.05–7.06 (m, 2H), 7.14–7.22 (m, 2H), 7.266 (dd, J = 7.8, 1.8 Hz, 1H), 7.273 (t, J = 7.8 Hz, 2H), 7.36 (d, J = 7.8 Hz, 1H), 9.67 (br s, 1H); 13C NMR (CDCl3) δ 30.60, 45.05, 94.31, 119.67, 124.74, 125.45, 127.58, 127.95, 128.00, 128.33, 130.74, 136.40, 142.64, 187.80; MS m/z 269 (M+, 8.5), 209 (62), 194 (100). Anal. Calcd for C16H15NOS: C, 71.34; H, 5.61; N, 5.20. Found: C, 71.25; H, 5.61; N, 5.13.
7-Methyl-4-phenyl-4,5-dihyro-3,1-benzoxazepine-2(1H)-thione (4h): a white solid; mp 126–128 ˚C (hexane–CH2Cl2); IR (KBr) 3185, 1161 cm-1; 1H NMR (CDCl3) δ 2.29 (s, 3H), 3.26 (dd, J = 16.8, 1.8 Hz, 1H), 3.59 (dd, J = 16.8, 8.7 Hz, 1H), 5.67 (dd, J = 8.7, 1.8 Hz, 1H), 6.83 (d, J = 8.4 Hz, 1H), 6.92 (d, J = 1.4 Hz, 1H), 7.04 (dd, J = 8.4, 1.4 Hz, 1H), 7.35–7.43 (m, 5H), 9.14 (s, 1H); 13C NMR (CDCl3) δ 20.57, 41.87, 86.48, 119.94, 126.04, 127.16, 128.66 (two overlapped C’s), 128.70, 131.01, 134.02, 134.96, 138.65, 188.31; MS m/z 269 (M+, 6.1), 209 (100). Anal. Calcd for C16H15NOS: C, 71.34; H, 5.61; N, 5.20. Found: C, 71.14; H, 5.50; N, 5.04.
7-Methyl-4-(4-methylphenyl)-4,5-dihyro-3,1-benzoxazepine-2(1H)-thione (4i): colorless crystals; mp 158–160 ˚C (hexane–CH2Cl2); IR (KBr) 3175, 1161 cm-1; 1H NMR (CDCl3) δ 2.28 (s, 3H), 2.36 (s, 3H), 3.24 (dd, J = 16.0, 1.8 Hz, 1H), 3.59 (dd, J = 16.0, 9.2 Hz, 1H), 5.64 (dd, J = 9.2, 1.8 Hz, 1H), 6.87 (d, J = 8.2 Hz, 1H), 6.91 (d, J = 1.8 Hz, 1H), 7.02 (dd, J = 8.2, 1.8 Hz, 1H), 7.19 (d, J = 8.2 Hz, 2H), 7.30 (d, J = 8.2 Hz, 2H), 9.41 (s, 1H); 13C NMR (CDCl3) δ 20.58, 21.15, 41.81, 86.42, 119.83, 126.05, 127.16, 128.61, 129.35, 131.08, 134.02, 134.89, 135.70, 138.56, 188.48; MS m/z 283 (M+, 5.0), 223 (100). Anal. Calcd for C17H17NOS: C, 72.05; H, 6.05; N, 5.66. Found: C, 72.06; H, 6.13; N, 5.63.
7-Chloro-4-(naphthalen-2-yl)-4,5-dihyro-3,1-benzoxazepine-2(1H)-thione (4j): a pale-yellow solid; mp 171–173 ˚C (EtOAc); IR (KBr) 3219, 1165 cm-1; 1H NMR (DMSO-d6) δ 3.43 (dd, J = 16.7, 1.7 Hz, 1H), 3.66 (dd, J = 16.7, 9.2 Hz, 1H), 5.99 (dd, J = 9.2, 1.7 Hz, 1H), 7.31–7.36 (m, 3H), 7.53–7.56 (m, 2H), 7.61 (dd, J = 8.6, 1.8 Hz, 1H), 7.91–8.00 (m, 4H), 11.77 (s, 1H); 13C NMR (DMSO-d6) δ 40.49, 85.43, 122.10, 124.27, 125.27, 126.51, 126.53, 127.39, 127.61, 128.01, 128.23, 128.25, 130.06, 130.28, 132.51, 132.73, 136.05, 136.65, 187.68; MS m/z 339 (M+, 5.0), 273 (100). Anal. Calcd for C19H14ClNOS: C, 67.15; H, 4.15; N, 4.12. Found: C, 66.87; H, 4.27; N, 3.84.
7-Chloro-4-(4-chlorophenyl)-4,5-dihyro-3,1-benzoxazepine-2(1H)-thione (4k): a yellow solid; mp 120–122 ˚C (hexane–EtOAc); IR (KBr) 3183, 1153 cm-1; 1H NMR (CDCl3) δ 3.28 (dd, J = 16.7, 2.3 Hz, 1H), 3.53 (dd, J = 16.7, 8.6 Hz, 1H), 5.69 (dd, J = 8.6, 2.3 Hz, 1H), 6.91 (d, J = 8.6 Hz, 1H), 7.11 (d, J = 2.3 Hz, 1H), 7.22 (dd, J = 8.6, 2.3 Hz, 1H), 7.34 (d, J = 8.6 Hz, 2H), 7.38 (d, J = 8.6 Hz, 2H), 9.12–9.37 (br, 1H); 13C NMR (CDCl3) δ 41.43, 85.71, 121.50, 127.52, 128.42, 128.81, 129.15, 130.47, 130.68, 134.95, 135.02, 136.70, 188.50; MS m/z 322 (M+, 8.6), 262 (100). Anal. Calcd for C15H11Cl2NOS: C, 55.57; H, 3.42; N, 4.32. Found: C, 55.66; H, 3.40; N, 4.21.
7-Methoxy-4-phenyl-4,5-dihyro-3,1-benzoxazepine-2(1H)-thione (4l): colorless needles; mp 177–178 ˚C (EtOAc); IR (KBr) 3183, 1153 cm-1; 1H NMR (CDCl3) δ 3.28 (dd, J = 16.7, 2.3 Hz, 1H), 3.56 (dd, J = 16.7, 8.6 Hz, 1H), 3.73 (s, 3H), 5.69 (dd, J = 8.6, 2.3 Hz, 1H), 6.61 (d, J = 2.7 Hz, 1H), 6.77 (dd, J = 8.6, 2.7 Hz, 1H), 6.96 (d, J = 8.6 Hz, 1H), 7.32–7.41 (m, 5H), 9.52 (s, 1H); 13C NMR (CDCl3) δ 41.97, 55.65, 86.76, 113.46, 115.58, 121.46, 126.17, 128.83 (two overlapped C’s), 129.12, 130.10, 138.75, 156.94, 188.14; MS m/z 285 (M+, 25), 225 (100). Anal. Calcd for C16H15NO2S: C, 67.34; H, 5.30; N, 4.91. Found: C, 67.29; H, 5.30; N, 4.95.
7-Methoxy-4-(3-methoxyphenyl)-4,5-dihyro-3,1-benzoxazepine-2(1H)-thione (4m): a pale-yellow solid; mp 149–150 ˚C (hexane–EtOAc); IR (KBr) 3160, 1148 cm-1; 1H NMR (DMSO-d6) δ 3.27 (dd, J = 16.7, 2.3 Hz, 1H), 3.47 (dd, J = 16.7, 8.6 Hz, 1H), 3.70 (s, 3H), 3.75 (s, 3H), 5.71 (dd, J = 8.6, 2.3 Hz, 1H), 6.82–6.84 (m, 2H), 6.92 (dd, J = 8.6, 2.3 Hz, 1H), 7.03 (d, J = 7.8 Hz, 1H), 7.06 (d, J = 2.3 Hz, 1H), 7.20 (d, J = 7.8 Hz, 1H), 7.31 (t, J = 7.8 Hz, 1H), 11.56 (s, 1H); 13C NMR (DMSO-d6) δ 40.34, 55.12, 55.31, 85.91, 112.05, 113.10, 113.76, 115.13, 118.42, 121.81, 129.54, 129.76, 130.53, 141.15, 156.02, 159.23, 186.95; MS m/z 315 (M+, 8.7), 255 (100). Anal. Calcd for C17H17NO3S: C, 64.74; H, 5.43; N, 4.44. Found: C, 64.52; H, 5.42; N, 4.33.

ACKNOWLEDGEMENT
This work was partially financial supported by a Grand-in-Aid for Scientific Research (C) 22550035 from Japan Society for the Promotion of Science. We thank Mrs. Miyuki Tanmatsu of this university for recording mass spectra and performing combustion analyses.

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