HETEROCYCLES

Paper | Regular issue | Vol. 91, No. 3, 2015, pp. 526-536
Received, 15th December, 2014, Accepted, 26th January, 2015, Published online, 3rd February, 2015.
DOI: 10.3987/COM-14-13154

■ Synthesis of N-Substituted (Z)-3-Arylbenzo[c]thiophen-1(3H)-imines by the Reaction of 1-[Aryl(methoxy)methyl]-2-lithiobenzenes with Isothiocyanates Followed by Acid-Mediated Cyclization

Kazuhiro Kobayashi,* Yuuho Shigemura, 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 simple procedure for the preparation of N-substituted (Z)-3-arylbenzo[c]thiophen-1(3H)-imines has been developed. Thus, bromine/lithium exchange between 1-[aryl(methoxy)methyl]-2-bromobenzenes and butyllithium, followed by reaction of the resulting 1-[aryl(methoxy)methyl]-2-lithiobenzenes with aliphatic and aromatic isothiocyanates, yields the corresponding N-substituted 2-[aryl(methoxy)methyl]benzothioamides. These were treated with concentrated hydrobromic acid to give the desired products.

INTRODUCTION
A number of methods for the general preparation of benzo[c]thiophen-1(3H)-imine derivatives have been reported due to their synthetic importance.1 Recently, we reported a synthesis of N-substituted (Z)-3-alkoxybenzo[c]thiophen-1(3H)-imines by the acid-catalyzed cyclization of N-substituted 2-(1,1-dialkoxymethyl)benzamides, derived from the reaction of 1-(1,1-dialkoxymethyl)-2-lithiobenzenes with isothiocyanates.1e In this paper, we wish to demonstrated a simple and general preparation of N-substituted (Z)-3-arylbenzo[c]thiophen-1(3H)-imines (3). We have found that 1-[aryl(methoxy)- methyl]-2-lithiobenzenes, generated from 1-[aryl(methoxy)methyl]-2-bromobenzenes (1) by bromine-lithium exchange with butyllithium, reacted with various isothiocyanates to give the corresponding thioamide derivatives (2), which in turn were treated with concentrated hydrobromic acid to give the desired products. Acid hydrolysis of these imines to 3-arylbenzo[c]thiophen-1(3H)-ones (4) is also described. So far, only a few methods have been known for the general preparation of benzo[c]thiophen-1(3H)-one derivatives,1e,2 while some of these derivatives have been reported to exhibit biological activities.3

RESULTS AND DISCUSSION
The preparation of 3 from 1 was conducted as illustrated in Scheme 1. Thus, the reaction of compounds (1) with butyllithium in THF at –78 ˚C generated 1-[aryl(methoxy)methyl]-2-lithiobenzenes by the bromine/lithium exchange, which were allowed to react with isothiocyanates to afford, after aqueous workup, the corresponding N-substituted benzothioamide derivatives (2). As shown in Table 1, relatively good yields were obtained in general by using aryl isothiocyanate. Although aliphatic isothiocyanates could be used for the reaction, the yields of N-alkyl derivatives (2c) and (2h) were only moderate (Entries 3 and 8, respectively).

The transformation of 2 into 3 was first attempted with a catalytic amount of p-toluenesulfonic acid monohydrate in dichloromethane at room temperature as reported for the preparation of (Z)-N-substituted 3-arylbenzo[c]thiophen-1(3H)-imines from N-aryl-2-(1,1-dialkoxymethyl)benzamides.1e However, the reaction proceeded very reluctantly even under refluxing conditions. Therefore, we felt that treatment with concentrated hydrobromic acid in acetonitrile would be suitable this transformation in view of our previous success in the preparation of N,N-disubstituted 4H-3,1-benzothiazin-2-amines from the hydroxy thiourea derivatives, derived by reduction of the adducts of aryl(2-isothiocyanatophenyl)methanones with secondary amines.4 Initially, compounds (2) were treated with a catalytic amount of hydrobromic acid. However, the reactions did not complete and resulted in the formation of the desired products 3 in rather lower yields and recovery of considerable amounts of the starting materials. Further investigation revealed that the reactions proceeded in appropriate extent by treating 2 with an equimolar amount of concentrated hydrobromic acid in acetonitrile at room temperature for a day to give 3 in satisfactory yields,5 as compiled in Table 1 as well. No stereoisomer was detected in each case. The iminobenzo[c]thiophene structure of the products (3) was confirmed by the spectral data. For example, the 13C NMR spectra for compound 3a revealed a signal assignable to the imino carbon at δ 167.78. Any signal was not observed at δ ~180 due to a thiocarbonyl carbon of the thiolactam structure. The preferable formation of 3 may be attributable to the higher nucleophilicity of sulfur atom than that of nitrogen atom.1b,c,6 The stereochemistry of the products was determined on the basis of their NOESY analyses, in which no interaction was observed between, for example, the signal at δ 8.13 assignable to 8-H and that at δ 7.22 assignable to the ortho-protons of N-phenyl group of 3a. The exclusive formation of the less crowded isomer is reasonable. Although cyclization of the N-(alkyl)thiobenzamides (2c) and (2h) was somewhat slower than that of the others, the yields of the corresponding products were comparable to those of the others (Entries 3 and 8, respectively). As can be seen in Entry 9, the yield of the product (3i) is rather lower than those of the others. The reaction proceeded rather sluggishly with extensive decomposition after prolonged reaction times. An electron-withdrawing chloro substituent on the N-aryl group may decrease the nucleophilicity of the thioamide moiety.

Transformation of 3 into 3-arylbenzo[c]thiophen-1(3H)-ones (4) by acid hydrolysis of the imino group was generally achieved in good yield on treatment with concentrated hydrochloric acid in THF at room temperature, as depicted in Scheme 2. However, hydrolysis of 3j did not occurred under these conditions at all. Therefore, hydrolysis of this compound was carried out in 1,2-dimethoxyethane (DME) at reflux temperature. Under these modified conditions, hydrolysis of 3j proceeded cleanly to give the desired product (4j) in high yield. This result may be ascribed to the less reactivity of the imino function of 3j due to the two-methoxy groups on the benzene ring of the benzo[c]thiophene structure. The results of these reactions are summarized in Table 2.

The forgoing results indicate that a convenient method for the preparation of N-substituted (Z)-3-arylbenzo[c]thiophen-1(3H)-imines has been developed using the two-step sequence starting from 1-[aryl(methoxy)methyl]-2-lithiobenzenes; the reaction of 1-[aryl(methoxy)methyl]-2-lithiobenzenes, generated from the starting materials, with isothiocyanates and the subsequent treatment with the resulting N-substituted 2-[aryl(methoxy)methyl]benzothioamides with concentrated hydrobromic acid. Hydrolysis of these imines also enables us to obtain 3-arylbenzo[c]thiophen-1(3H)-ones. The ready availability of the starting materials and the simplicity of the operations make this method attractive.

EXPERIMENTAL
All melting points were obtained on a Laboratory Devices MEL-TEMP II melting apparatus and are uncorrected. IR spectra were recorded with a Perkin–Elmer Spectrum65 FTIR spectrophotometer. 1H NMR spectra were recorded in CDCl3 using TMS as an internal reference with a JEOL ECP500 FT NMR spectrometer operating at 500 MHz. 13C NMR spectra were recorded in CDCl3 using TMS as an internal reference with a JEOL ECP500 FT NMR spectrometer operating at 125 MHz. High-resolution MS spectra (DART, positive) were measured by a Thermo Scientific Exactive spectrometer. Elemental analyses were performed with an Elementar Vario EL II instrument. 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. (2-Bromophenyl)phenylmethanol,7 (2-bromophenyl)(4-methoxyphenyl)methanol,8 (2-bromophenyl)(4-chlorophenyl)methanol,8 (2-bromo-5-chlorophenyl)phenylmethanol,9 and (2-bromo- 4,5-dimethoxyphenyl)phenylmethanol10 were prepared according to the appropriate reported procedures. n-BuLi was supplied by Asia Lithium Corporation. All other chemicals used in this study were commercially available.
Typical Procedure for the Preparation of Compounds (1). 1-Bromo-2-[methoxy(phenyl)methyl]benzene (1a).11 To a stirred suspension of NaH (60% in mineral oil; 0.37 g, 9.2 mmol) in THF (7 mL) at 0 ˚C was added a solution of (2-bromophenyl)phenylmethanol (2.4 g, 9.2 mmol) in THF (6 mL) dropwise. After evolution of H2 gas had ceased, MeI (2.6 g, 18 mmol) was added and the mixture was heated at reflux temperature for 1 h. After cooling to rt, saturated aqueous NH4Cl (20 mL) was added and the mixture was extracted with AcOEt (3 × 20 mL). The combined extracts were washed with brine, dried (Na2SO4), and concentrated by evaporation. The residue was distilled to afford 1a (2.2 g, 88%); a pale-yellow oil; bp 123–125 ˚C/0.2 mmHg; IR (neat) 1602, 1093 cm–1; 1H NMR δ 3.40 (s, 3H), 5.67 (s, 1H), 7.13 (td, J = 7.6, 1.5 Hz, 1H), 7.25 (tt, J = 7.6, 1.5 Hz, 1H), 7.30–7.34 (m, 3H), 7.39 (dd, J = 7.6, 1.5 Hz, 2H), 7.52 (dd, J = 7.6, 1.5 Hz, 1H), 7.53 (dd, J = 7.6, 1.5 Hz, 1H).
1-Bromo-2-[(4-chlorophenyl)(methoxy)methyl]benzene (1b):11 yield: 82%; a colorless oil; Rf 0.30 (CH2Cl2/hexane 1:5); IR (neat) 1488, 1091 cm–1; 1H NMR δ 3.38 (s, 3H), 5.64 (s, 1H), 7.15 (td, J =7.6, 2.3 Hz, 1H), 7.29 (d, J = 8.4 Hz, 2H), 7.32–7.35 (m, 3H), 7.49 (dd, J = 7.6, 1.5 Hz, 1H), 7.54 (d, J = 7.6 Hz, 1H).
1-Bromo-2-[(methoxy)(4-methoxyphenyl)methyl]benzene (1c): yield: 84%; a colorless oil; Rf 0.43 (CH2Cl2/hexane 1:1); IR (neat) 1610, 1511, 1249, 1090 cm–1; 1H NMR δ 3.38 (s, 3H), 3.78 (s, 3H), 5.59 (s, 1H), 6.85 (d, J = 8.4 Hz, 2H), 7.13 (td, J = 7.6, 1.5 Hz, 1H), 7.30 (d, J = 8.4 Hz, 2H), 7.34 (t, J = 7.6 Hz, 1H), 7.53 (d, J = 7.6 Hz, 1H), 7.56 (dd, J = 7.6, 1.5 Hz, 1H). Anal. Calcd for C15H15BrO2: C, 58.65; H, 4.92. Found: C, 58.38; H, 5.02.
1-Bromo-4-chloro-2-[(methoxy)(phenyl)methyl]benzene (1d): yield: 80%; a colorless oil; Rf 0.30 (CH2Cl2/hexane 1:10); IR (neat) 1454, 1095 cm–1; 1H NMR δ 3.39 (s, 3H), 5.58 (s, 1H), 7.11 (dd, J = 8.6, 2.9 Hz, 1H), 7.28 (t, J = 7.4 Hz, 1H), 7.33 (t, J = 7.4 Hz, 2H), 7.38 (d, J = 7.4 Hz, 2H), 7.45 (d, J = 8.6 Hz, 1H), 7.55 (d, J = 2.9 Hz, 1H). Anal. Calcd for C14H12BrClO: C, 53.96; H, 3.88. Found: C, 53.83; H, 4.01.
1-Bromo-4,5-dimethoxy-2-[(methoxy)(phenyl)methyl]benzene (1e): yield: 91%; a colorless oil; Rf 0.27 (CH2Cl2/hexane 1:5); IR (neat) 1602, 1502, 1258 cm–1; 1H NMR δ 3.39 (s, 3H), 3.84 (s, 3H), 3.86 (s, 3H), 5.62 (s, 1H), 7.00 (s, 1H), 7.25 (t, J = 7.4 Hz, 1H), 7.26 (s, 1H), 7.32 (t, J = 7.4 Hz, 2H), 7.37 (d, J = 7.4 Hz, 2H). Anal. Calcd for C16H17BrO3: C, 56.99; H, 5.08. Found: C, 56.74; H, 5.34.
Typical Procedure for the Preparation of Benzothioamides (2). 2-[Methoxy(phenyl)methyl]- N-phenylbenzothioamide (2a). To a stirred solution of 1a (0.55 g, 2.0 mmol) in THF (5 mL) at –78 ˚C was added dropwise n-BuLi (1.6 M in hexane, 2.0 mmol). After 15 min, PhNCS (0.27 g, 2.0 mmol) was added dropwise and stirring was continued for 1 h at the same temperature. Saturated aqueous NH4Cl (20 mL) was added, and the mixture was warmed to rt and extracted with AcOEt (3 × 20 mL). The combined extracts were washed with brine (20 mL), dried (Na2SO4), and concentrated by evaporation. The residue was purified by column chromatography on silica gel (AcOEt/hexane 1:5) to give 2a (0.54 g, 80%); a yellow solid; mp 123–125 ˚C (hexane/Et2O); IR (KBr) 3243, 1086 cm–1; 1H NMR δ 3.38 (s, 3H), 5.73 (s, 1H), 7.27–7.38 (m, 9H), 7.40 (t, J = 7.6 Hz, 2H), 7.60 (dd, J = 7.6, 2.3 Hz, 1H), 7.69 (d, J = 7.6 Hz, 2H), 9.23 (br s, 1H). Anal. Calcd for C21H19NOS: C, 75.64; H, 5.74; N, 4.20. Found: C, 75.38; 5.76; N, 4.10.
2-[Methoxy(phenyl)methyl]-N-(2-methylphenyl)benzothioamide (2b): a yellow solid; mp 81–83 ˚C (hexane/Et2O); IR (KBr) 3216, 1086 cm–1; 1H NMR δ 2.23 (s, 3H), 3.41 (s, 3H), 5.92 (s, 1H), 7.25–7.38 (m, 11H), 7.54 (d, J = 7.6, 2.3 Hz, 1H), 7.64 (dd, J = 9.2, 3.0 Hz, 1H), 9.01 (br s, 1H). Anal. Calcd for C22H21NOS: C, 76.05; H, 6.09; N, 4.03. Found: C, 76.05; 6.24; N, 3.98.
N-Butyl-2-[methoxy(phenyl)methyl]benzothioamide (2c): a yellow oil; Rf 0.23 (AcOEt/hexane 1:8); IR (neat) 3264, 1086 cm–1; 1H NMR δ 0.92 (t, J = 7.6 Hz, 3H), 1.30–1.37 (m, 2H), 1.49–1.54 (m, 2H), 3.48 (s, 3H), 3.55–3.62 (m, 1H), 3.65–3.72 (m, 1H), 5.68 (s, 1H), 7.28–7.35 (m, 8H), 7.42 (d, J = 6.9 Hz, 1H), 7.51 (br, 1H). Anal. Calcd for C19H23NOS: C, 72.80; H, 7.40; N, 4.47. Found: C, 72.62; 7.40; N, 4.32.
2-[(4-Chlorophenyl)(methoxy)methyl]-N-phenylbenzothioamide (2d): a yellow viscous oil; Rf 0.32 (AcOEt/hexane 1:1); IR (neat) 3235, 1088 cm–1; 1H NMR δ 3.37 (s, 3H), 5.73 (s, 1H), 7.27–7.30 (m, 6H), 7.35–7.37 (m, 2H), 7.42 (t, J = 7.6 Hz, 2H), 7.58 (d, J = 9.2 Hz, 1H), 7.72 (d, J = 7.6 Hz, 2H), 9.18 (br s, 1H). Anal. Calcd for C21H18ClNOS: C, 68.56; H, 4.93; N, 3.81. Found: C, 68.51; 4.93; N, 3.60.
2-[Methoxy(4-methoxyphenyl)methyl]-N-phenylbenzothioamide (2e): a yellow viscous oil; Rf 0.33 (AcOEt/hexane 1:1); IR (neat) 3260, 1610, 1084 cm–1; 1H NMR δ 3.35 (s, 3H), 3.78 (s, 3H), 5.67 (s, 1H), 6.85 (d, J = 9.2 Hz, 2H), 7.27 (t, J = 7.6 Hz, 2H), 7.36–7.41 (m, 6H), 7.59 (d, J = 7.6 Hz, 1H), 7.70 (d, J = 9.2 Hz, 2H), 9.19 (br s, 1H). Anal. Calcd for C22H21NO2S: C, 72.70; H, 5.82; N, 3.85. Found: C, 72.61; 5.80; N, 3.59.
2-[Methoxy(4-methoxyphenyl)methyl]-N-(3-methoxyphenyl)benzothioamide (2f): a yellow viscous oil; Rf 0.16 (AcOEt/hexane 1:1); IR (neat) 3262, 1609, 1084 cm–1; 1H NMR δ 3.35 (s, 3H), 3.78 (s, 3H), 3.82 (s, 3H), 5.65 (s, 1H), 6.81 (d, J = 8.6 Hz, 1H), 6.85 (d, J = 8.6 Hz, 2H), 7.10 (d, J = 8.0 Hz, 1H), 7.24–7.37 (m, 6H), 7.59 (d, J = 8.6 Hz, 2H), 9.16 (br s, 1H). Anal. Calcd for C23H23NO3S: C, 70.20; H, 5.89; N, 3.56. Found: C, 70.18; 5.91; N, 3.54.
4-Chloro-2-[methoxy(phenyl)methyl]-N-phenylbenzothioamide (2g): a yellow viscous oil; Rf 0.32 (AcOEt/hexane 1:5); IR (neat) 3227, 1075 cm–1; 1H NMR δ 3.37 (s, 3H), 5.71 (s, 1H), 7.28–7.36 (m, 9H), 7.40 (dd, J = 8.0, 7.4 Hz, 1H), 7.49 (d, J = 8.6 Hz, 1H), 7.66 (d, J = 8.0 Hz, 2H), 9.15 (br s, 1H). Anal. Calcd for C21H18ClNOS: C, 68.56; H, 4.93; N, 3.81. Found: C, 68.43; 4.92; N, 3.70.
4-Chloro-N-cyclohexyl-2-[methoxy(phenyl)methyl]benzothioamide (2h): a pale-yellow viscous oil; Rf 0.32 (AcOEt/hexane 1:8); IR (neat) 3262, 1097 cm–1; 1H NMR δ 0.99–1.06 (m, 1H), 1.12–1.19 (m, 2H), 1.35–1.46 (m, 2H), 1.64–1.73 (m, 3H), 1.92–1.94 (m, 1H), 2.15–2.18 (m, 1H), 3.38 (s, 3H), 4.37–4.42 (m, 1H), 5.76 (s, 1H), 7.25–7.36 (m, 9H). Anal. Calcd for C21H24ClNOS: C, 67.45; H, 6.47; N, 3.75. Found: C, 67.50; 6.56; N, 3.70.
4-Chloro-N-(4-chlorophenyl)-2-[methoxy(phenyl)methyl]benzothioamide (2i): a yellow solid; mp 137–139 ˚C (hexane); IR (KBr) 3226, 1092 cm–1; 1H NMR δ 3.38 (s, 3H), 5.64 (s, 1H), 7.28–7.37 (m, 9H), 7.53 (d, J = 8.0 Hz, 1H), 7.58 (d, J = 8.6 Hz, 2H), 9.14 (br s, 1H). Anal. Calcd for C21H17Cl2NOS: C, 62.69; H, 4.26; N, 3.48. Found: C, 62.41; 4.31; N, 3.19.
4,5-Dimethoxy-2-[methoxy(phenyl)methyl]-N-phenylbenzothioamide (2j): a yellow solid; mp 133–136 ˚C (hexane/CH2Cl2); IR (KBr) 3284, 1601, 1093 cm–1; 1H NMR δ 3.39 (s, 3H), 3.81 (s, 3H), 3.92 (s, 3H), 5.60 (s, 1H), 6.77 (s, 1H), 7.24–­7.40 (m, 10H), 7.66 (d, J = 8.0 Hz, 1H), 9.49 (br s, 1H). Anal. Calcd for C23H23NO3S: C, 70.20; H, 5.89; N, 3.56. Found: C, 70.17; 6.04; N, 3.52.
Typical Procedure for the Preparation of Benzo[c]thiophen-1(3H)-imines (3). (Z)-3,N- Diphenylbenzo[c]thiophen-1(3H)-imine (3a). To a stirred solution of 2a (0.50 g, 1.5 mmol) in MeCN (7 mL) at 0 ˚C was added dropwise concentrated HBr (0.26 g, 1.5 mmol). The mixture was warmed to rt and stirring was continued for a day. To the cooled (0 ˚C) mixture was added aqueous saturated NaHCO3 (20 mL) and the mixture was extracted with AcOEt (3 × 20 mL). The combined extracts were washed with brine (20 mL), dried (Na2SO4), and concentrated by evaporation. The residual solid was purified by recrystallization by hexane/Et2O to give 3a (0.39 g, 86%); a yellow solid; mp 132–133 ˚C; IR (KBr) 1625, 1591 cm–1; 1H NMR δ 5.85 (s, 1H), 7.11–7.16 (m, 4H), 7.22 (dd, J = 7.6, 1.5 Hz, 2H), 7.25–7.30 (m, 3H), 7.36 (t, J = 7.6 Hz, 2H), 7.42–7.47 (m, 2H), 8.13 (dd, J = 7.6, 1.5 Hz, 1H); 13C NMR δ 55.97, 120.34, 123.36, 124.67, 125.92, 128.02, 128.05, 128.22, 128.83, 129.11, 131.57, 137.91, 140.31, 148.14, 151.82, 167.78. HR-MS. Calcd for C20H16NS (M+H): 302.1003. Found: m/z 302.0988. Anal. Calcd for C20H15NS: C, 79.70; H, 5.02; N, 4.65. Found: C, 79.49; H, 4.96; N, 4.59.
(Z)-N-(2-Methylphenyl)-3-phenylbenzo[c]thiophen-1(3H)-imine (3b): a yellow solid; mp 134–135 ˚C (hexane/Et2O); IR (KBr) 1630, 1593 cm–1; 1H NMR δ 2.25 (s, 3H), 5.84 (s, 1H), 7.00 (d, J = 7.6 Hz, 1H), 7.04 (ddd, J = 8.0, 7.6, 1.5 Hz, 1H),7.16–7.19 (m, 2H), 7.21–7.31 (m, 6H), 7.44–7.49 (m, 2H), 8.16 (dd, J = 7.6, 1.5 Hz, 1H) 13C NMR δ 17.70, 55.82, 118.42, 123.36, 124.54, 126.01, 126.52, 128.01, 128.05, 128.20, 128.85, 128.99, 130.56, 131.52, 137.61, 140.48, 148.37, 150.87, 167.46. HR-MS. Calcd for C21H18NS (M+H): 316.1160. Found: m/z 316.1141. Anal. Calcd for C21H17NS: C, 79.96; H, 5.43; N, 4.44. Found: C, 79.66; H, 5.46; N, 4.43.
(Z)-N-Butyl-3-phenylbenzo[c]thiophen-1(3H)-imine (3c): a yellow oil; Rf 0.29 (AcOEt/hexane 1:20); IR (neat) 1634, 1601 cm–1; 1H NMR δ 0.98 (t, J = 7.4 Hz, 3H), 1.44–1.52 (m, 2H), 1.76–1.82 (m, 2H), 3.43–3.53 (m, 2H), 5.85 (s, 1H), 7.10–7.13 (m, 1H), 7.23–7.25 (m, 2H), 7.26–7.33 (m, 3H), 7.36–7.39 (m, 2H), 7.95–7.98 (m, 1H); 13C NMR δ 13.96, 20.75, 32.53, 55.64, 57.51, 122.98, 125.87, 127.84, 127.92, 128.24, 128.83, 130.77, 137.67, 141.12, 147.67, 165.27. HR-MS. Calcd for C18H20NS (M+H): 282.1316. Found: m/z 282.1304. Anal. Calcd for C18H19NS: C, 76.82; H, 6.81; N, 4.98. Found: C, 76.65; H, 6.81; N, 4.91.
(Z)-3-(4-Chlorophenyl)-N-phenylbenzo[c]thiophen-1(3H)-imine (3d): a pale-yellow solid; mp 135–137 ˚C (hexane/CH2Cl2); IR (KBr) 1626, 1590 cm–1; 1H NMR δ 5.83 (s, 1H), 7.13–7.17 (m. 6H), 7.26 (dd, J = 8.6, 6.3 Hz, 2H), 7.37 (t, J = 8.0, 7.4 Hz, 2H), 7.46–7.48 (m, 2H), 8.13 (d, J = 8.6 Hz, 1H); 13C NMR δ 55.21, 120.30, 123.54, 124.81, 125.84, 128.30, 129.07, 129.17, 129.60, 131.72, 133.90, 137.91, 139.00, 147.68, 151.74, 167.25. HR-MS. Calcd for C20H15ClNS (M+H): 336.0613. Found: m/z 336.0605. Anal. Calcd for C20H14ClNS: C, 71.53; H, 4.20; N, 4.17. Found: C, 71.43; H, 4.38; N, 4.14.
(Z)-3-(4-Methoxyphenyl)-N-phenylbenzo[c]thiophen-1(3H)-imine (3e): a yellow solid; mp 94–96 ˚C (hexane/CH2Cl2); IR (KBr) 1627, 1609 cm–1; 1H NMR δ 3.77 (s, 3H), 5.85 (s, 1H), 6.82 (d, J = 8.6 Hz, 2H), 7.12–7.18 (m, 6H), 7.37 (dd, J = 8.0, 7.4 Hz, 2H), 7.45–7.47 (m, 2H), 8.12 (d, J = 8.0 Hz, 1H); 13C NMR δ 55.27, 55.62, 114.22, 120.36, 123.30, 124.63, 125.88, 128.00, 129.11, 129.39, 131.54, 132.20, 137.89, 148.45, 151.89, 159.33, 167.93. HR-MS. Calcd for C21H18NOS (M+H): 332.1109. Found: m/z 332.1101. Anal. Calcd for C21H17NOS: C, 76.10; H, 5.17; N, 4.23; S, 9.67. Found: C, 75.80; H, 5.15; N, 4.15; S, 9.62.
(Z)-N-(3-Methoxyphenyl)-3-(4-methoxyphenyl)benzo[c]thiophen-1(3H)-imine (3f): a yellow solid; mp 112–114 ˚C (hexane/CH2Cl2); IR (KBr) 1631, 1596 cm–1; 1H NMR δ 3.78 (s, 3H), 3.80 (s, 3H), 5.85 (s, 1H), 6.68–6.92 (m, 2H), 6.75 (d, J = 8.0 Hz, 1H), 6.82 (d, J = 8.6 Hz, 2H), 7.14–7.18 (m, 3H), 7.27 (dd, J = 8.0, 7.4 Hz, 1H), 7.44–7.47 (m 2H), 8.11 (dd, J = 6.9, 2.3 Hz, 1H); 13C NMR δ 55.25, 55.28, 55.68, 105.97, 110.61, 112.60, 114.23, 123.30, 125.89, 128.00, 129.42, 129.90, 131.56, 132.17, 137.89, 148.50, 153.16, 159.35, 160.32, 168.08. HR-MS. Calcd for C22H20NO2S (M+H): 362.1214. Found: m/z 362.1208. Anal. Calcd for C22H19NO2S: C, 73.10; H, 5.30; N, 3.88. Found: C, 72.91; H, 5.27; N, 3.82.
(Z)-5-Chloro-N,3-diphenylbenzo[c]thiophen-1(3H)-imine (3g): a white solid; mp 70–78 ˚C (pentane); IR (KBr) 1620, 1591 cm–1; 1H NMR δ 5.82 (s, 1H), 7.13–7.16 (m, 4H), 7.23 (dd, J = 7.4, 1.7 Hz, 2H), 7.28–7.34 (m, 3H), 7.37 (t, J = 8.0 Hz, 2H), 7.44 (dd, J = 8.0, 1.7 Hz, 1H), 8.05 (d, J = 8.0 Hz, 1H); 13C NMR δ 55.54, 120.35, 124.38, 124.92, 126.00, 128.25, 128.36, 128.74, 129.05, 129.18, 136.62, 137.87, 139.55, 149.56, 151.51, 166.09. HR-MS. Calcd for C20H15ClNS (M+H): 336.0613. Found: m/z 336.0605. Anal. Calcd for C20H14ClNS: C, 71.53; H, 4.20; N, 4.17. Found: C, 71.49; H, 4.36; N, 4.08.
(Z)-5-Chloro-N-cyclohexyl-3-phenylbenzo[c]thiophen-1(3H)-imine (3h): a white solid; mp 121–124 ˚C (pentane); IR (KBr) 1634, 1595 cm–1; 1H NMR δ 1.24–1.41 (m, 3H), 1.49–1.60 (m, 2H), 1.65–1.67 (m, 1H), 1.81–1.92 (m, 4H), 3.14–3.20 (m, 1H), 5.79 (s, 1H), 7.09 (br s, 1H), 7.23–7.25 (m, 2H), 7.28–7.35 (m, 4H), 7.90 (d, J = 8.0 Hz, 1H); 13C NMR δ 24.74, 24.79, 25.73, 32.84, 32.95, 55.05, 67.14, 124.21, 125.87, 128.19, 128.22, 128.36, 129.00, 136.49, 136.89, 140.48, 149.04, 161.32. HR-MS. Calcd for C20H21ClNS (M+H): 342.1083. Found: m/z 342.1074. Anal. Calcd for C20H20ClNS: C, 70.26; H, 5.90; N, 4.10. Found: C, 70.16; H, 6.17; N, 3.84.
(Z)-5-Chloro-N-(4-chlorophenyl)-3-phenylbenzo[c]thiophen-1(3H)-imine (3i): a white solid; mp 116–119 ˚C (pentane); IR (KBr) 1638, 1591 cm–1; 1H NMR δ 5.84 (s, 1H), 7.09 (d, J = 8.6 Hz, 2H), 7.16 (br s, 1H), 7.23 (dd, J = 7.4, 1.7 Hz, 1H), 7.28–7.35 (m, 6H), 7.44 (dd, J = 8.0, 1.7 Hz, 1H), 8.02 (d, J = 8.0 Hz, 1H); 13C NMR δ 55.73, 121.88, 124.37, 126.04, 128.23, 128.47, 128.83, 129.11, 129.28, 130.15, 136.46, 138.11, 139.29, 149.59, 149.88, 166.80. HR-MS. Calcd for C20H14Cl2NS (M+H): 370.0224. Found: m/z 370.0218. Anal. Calcd for C20H13Cl2NS: C, 64.87; H, 3.54; N, 3.78. Found: C, 64.83; H, 3.83; N, 3.80.
(Z)-5,6-Dimethoxy-3,N-diphenylbenzo[c]thiophen-1(3H)-imine (3j): a white solid; mp 144–147 ˚C (hexane/CH2Cl2); IR (KBr) 1618, 1602, 1587 cm–1; 1H NMR δ 3.81 (s, 3H), 4.01 (s, 3H), 5.78 (s, 1H), 6.58 (s, 1H), 7.10–7.15 (m, 3H), 7.22 (dd, J = 8.0, 1.1 Hz, 2H), 7.26–7.33 (m, 3H), 7.35 (dd, J = 8.0, 7.4 Hz, 2H), 7.55 (s, 1H); 13C NMR δ 55.49, 56.16, 56.27, 104.22, 107.16, 120.48, 124.51, 128.03, 128.15, 128.91, 129.11, 130.74, 140.48, 141.66, 149.73, 152.01, 152.67, 167.53. HR-MS. Calcd for C22H20NO2S (M+H): 362.1214. Found: m/z 352.1207. Anal. Calcd for C22H19NO2S: C, 73.10; H, 5.30; N, 3.88. Found: C, 73.07; H, 5.34; N, 3.86.
Typical Procedure for the Preparation of 3-Arylbenzo[c]thiophen-1(3H)-ones (4). 3-Phenylbenzo[c]thiophen-1(3H)-one (4a).12 To a solution of 3a (0.30 g, 1.0 mmol) in THF (3 mL) at 0 ˚C was added concentrated HCl (0.5 mL). The temperature was raised to rt and stirring was continued for 2 d. Saturated aqueous NaHCO3 (10 mL) was added and the mixture was extracted with AcOEt (3 × 10 mL). The combined extracts were washed with brine, dried (Na2SO4), and concentrated by evaporation. The residual solid was purified by recrystallization to give 4a (0.19 g, 83%); a pale-yellow solid; mp 114–115 ˚C (hexane/Et2O) (lit.,12a mp 114 ˚C). The 1H NMR data for this product were identical to those reported previously.12a
3-(4-Chlorophenyl)benzo[c]thiophen-1(3H)-one (4d): a white solid; mp 113–115 ˚C (hexane/CH2Cl2); IR (KBr) 1680, 1610 cm–1; 1H NMR δ 5.88 (s, 1H), 7.19 (d, J = 8.6 Hz, 2H), 7.24 (d, J = 7.4 Hz, 1H), 7.31 (d, J = 8.6 Hz, 2H), 7.50 (t, J = 7.4 Hz, 1H), 7.58 (td, J = 7.4, 1.1 Hz, 1H), 7.86 (d, J = 7.4 Hz, 1H); 13C NMR δ 53.81, 123.71, 126.47, 128.55, 129.27, 129.63, 133.75, 134.27, 135.58, 137.41, 150.65, 196.69. HR-MS. Calcd for C14H10ClOS (M+H): 261.0141. Found: m/z 261.0134. Anal. Calcd for C14H9ClOS: C, 64.49; H, 3.48. Found: C, 64.31; H, 3.58.
3-(4-Methoxyphenyl)benzo[c]thiophen-1(3H)-one (4e): a white solid; mp 92–94 ˚C (hexane/CH2Cl2); IR (KBr) 1676, 1611 cm–1; 1H NMR δ 3.80 (s, 3H), 5.89 (s, 1H), 6.86 (d, J = 8.4 Hz, 2H), 7.17 (d, J = 8.4 Hz, 2H), 7.26 (d, J = 7.6 Hz, 1H), 7.47 (t, J = 7.6 Hz, 1H), 7.56 (td, J = 7.6, 1.5 Hz, 1H), 7.85 (d, J = 7.6 Hz, 1H); 13C NMR δ 54.26, 55.30, 114.40, 123.44, 126.49, 128.24, 129.44, 130.50, 133.53, 135.67, 151.48, 159.56, 197.31. HR MS. Calcd for C15H13O2S (M+H): 256.0636. Found: m/z 256.0628. Found: m/z 261.0134. Anal. Calcd for C15H12O2S: C, 70.29; H, 4.72. Found: C, 70.29; H, 4.73.
5-Chloro-3-phenylbenzo[c]thiophen-1(3H)-one (4g): a white solid; mp 171–173 ˚C (hexane/CH2Cl2); IR (KBr) 1671 cm–1; 1H NMR δ 5.86 (s, 1H), 7.24–7.27 (m, 3H), 7.32–7.38 (m, 3H), 7.46 (dd, J = 8.0, 1.7 Hz, 1H), 7.78 (d, J = 8.0 Hz, 1H); 13C NMR δ 54.05, 124.47, 126.69, 128.27, 128.69, 129.11, 129.23, 134.15, 137.89, 140.54, 152.58, 195.57. HR-MS. Calcd for C14H10ClOS (M+H): 261.0141. Found: m/z 261.0135. Anal. Calcd for C14H9ClOS: C, 64.49; H, 3.48. Found: C, 64.23; H, 3.43.
5,6-Dimethoxy-3-phenylbenzo[c]thiophen-1(3H)-one (4j). This compound was obtained by treating 3j with concentrated HCl in DME at reflux temperature. A pale-yellow solid; mp 114–116 ˚C (pentane); IR (KBr) 1677 cm–1; 1H NMR δ 3.81 (s, 3H), 3.96 (s, 3H), 5.80 (s, 1H), 6.63 (s, 1H), 7.23–7.26 (m, 3H), 7.31–7.36 (m, 3H); 13C NMR δ 53.89, 56.24, 56.29, 104.01, 107.54, 128.19, 128.32, 128.65, 129.06, 138.98, 145.71, 149.89, 154.35, 196.06. HR-MS. Calcd for C16H15O3S (M+H): 287.0744. Found: m/z 287.0743. Anal. Calcd for C16H14O3S: C, 67.11; H, 4.93. Found: C, 67.04; H, 4.65.
ACKNOWLEDGEMENTS
We thank Mrs. Miyuki Tanmatsu of our university for recording mass spectra and performing combustion analyses.

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