1-Chloro-4-propoxythioxanthone

(2) etherification reaction: adding 29 g of potassium carbonate to the above organic layer, 33 grams of bromopropane, heated to 80 ° C under stirring for more than 5 hours, HPLC detection was carried out until the intermediate reaction was complete and the temperature was lowered to 40 °C.(3) To the above reaction system, 340 g of water was added for washing, and the layers were allowed to stand, and the obtained organic layer was decomposed under reduced pressure. After desolvation, the temperature was lowered slightly, 250 g of ethanol was added, 10 g of activated carbon was added, and the temperature was raised to 60 ° C. After stirring for 1 hour, the mixture was filtered, and the filtrate was placed in a rotating refrigerator overnight, suction filtered, and dried in vacuo to give 55.7 g of pale yellow solid powder.The measurement result was 95.4percent based on 2-mercaptobenzoic acid, the melting point was 99-103 ° C, and the purity of the product was determined by HPLC.99.1percent.(2) etherification reaction: adding 29 g of potassium carbonate to the above organic layer, 33 grams of bromopropane, heated to 80 C under stirring for more than 5 hours, HPLC detection was carried out until the intermediate reaction was complete and the temperature was lowered to 40 C.(3) To the above reaction system, 340 g of water was added for washing, and the layers were allowed to stand, and the obtained organic layer was decomposed under reduced pressure. After desolvation, the temperature was lowered slightly, 250 g of ethanol was added, 10 g of activated carbon was added, and the temperature was raised to 60 C. After stirring for 1 hour, the mixture was filtered, and the filtrate was placed in a rotating refrigerator overnight, suction filtered, and dried in vacuo to give 55.7 g of pale yellow solid powder.The measurement result was 95.4% based on 2-mercaptobenzoic acid, the melting point was 99-103 C, and the purity of the product was determined by HPLC.99.1%.General procedure: 1-Chloro-4-propoxy-9H-thioxanthen-9-one (Tx, 450 mg, 1.48 mmol) and a suitable chiral aminoalcohol (9-16, 1.72 mmol) were dissolved in methanol (30 mL) and CuI (0.15 mmol) and K2CO3(1.92 mmol) were added. The reaction mixture was heated at 100 C in a muffle furnace for 48 h.After the completion of the reaction, the crude material was filtrated, washed with dichloromethane, and the organic solvents were evaporated under reduced pressure. Then, the obtained solid wasdissolved in 50 mL of dichloromethane and extracted with HCl 1M(3 50 mL). The aqueous layer wasbasified with NaOH 20% and extracted with dichloromethane (3 100 mL). The organic layers weregathered, washed with water (3 50 mL), dried over anhydrous sodium sulphate and the solvent wasevaporated under reduced pressure. Then, a solid phase extraction using a cation exchange cartridgeDiscovery DSC-SCX was applied to further purify the extracted material. First, an activation ofthe cartridge with dichloromethane (50 mL) was performed followed by loading the cartridge withthe sample (previously incorporated in silica). Then, elution was carried out with the followingsolvents: dichloromethane, a mixture of dichloromethane/methanol 5:5 (v/v), methanol 100% andNH3 2% in methanol. The fractions containing the chiral ATxs were gathered and the solvent wasevaporated under reduced pressure. A flash column chromatography with n-hexane/ethyl acetate ingradient and crystallization from chloroform and petroleum ether (4:1) were also performed to obtainpure compounds.General procedure: 1-Chloro-4-propoxy-9H-thioxanthen-9-one (Tx, 450 mg, 1.48 mmol) and a suitable chiral aminoalcohol (9-16, 1.72 mmol) were dissolved in methanol (30 mL) and CuI (0.15 mmol) and K2CO3(1.92 mmol) were added. The reaction mixture was heated at 100 C in a muffle furnace for 48 h.After the completion of the reaction, the crude material was filtrated, washed with dichloromethane, and the organic solvents were evaporated under reduced pressure. Then, the obtained solid wasdissolved in 50 mL of dichloromethane and extracted with HCl 1M(3 50 mL). The aqueous layer wasbasified with NaOH 20% and extracted with dichloromethane (3 100 mL). The organic layers weregathered, washed with water (3 50 mL), dried over anhydrous sodium sulphate and the solvent wasevaporated under reduced pressure. Then, a solid phase extraction using a cation exchange cartridgeDiscovery DSC-SCX was applied to further purify the extracted material. First, an activation ofthe cartridge with dichloromethane (50 mL) was performed followed by loading the cartridge withthe sample (previously incorporated in silica). Then, elution was carried out with the followingsolvents: dichloromethane, a mixture of dichloromethane/methanol 5:5 (v/v), methanol 100% andNH3 2% in methanol. The fractions containing the chiral ATxs were gathered and the solvent wasevaporated under reduced pressure. A flash column chromatography with n-hexane/ethyl acetate ingradient and crystallization from chloroform and petroleum ether (4:1) were also performed to obtainpure compounds.General procedure: 1-Chloro-4-propoxy-9H-thioxanthen-9-one (Tx, 450 mg, 1.48 mmol) and a suitable chiral aminoalcohol (9-16, 1.72 mmol) were dissolved in methanol (30 mL) and CuI (0.15 mmol) and K2CO3(1.92 mmol) were added. The reaction mixture was heated at 100 C in a muffle furnace for 48 h.After the completion of the reaction, the crude material was filtrated, washed with dichloromethane, and the organic solvents were evaporated under reduced pressure. Then, the obtained solid wasdissolved in 50 mL of dichloromethane and extracted with HCl 1M(3 50 mL). The aqueous layer wasbasified with NaOH 20% and extracted with dichloromethane (3 100 mL). The organic layers weregathered, washed with water (3 50 mL), dried over anhydrous sodium sulphate and the solvent wasevaporated under reduced pressure. Then, a solid phase extraction using a cation exchange cartridgeDiscovery DSC-SCX was applied to further purify the extracted material. First, an activation ofthe cartridge with dichloromethane (50 mL) was performed followed by loading the cartridge withthe sample (previously incorporated in silica). Then, elution was carried out with the followingsolvents: dichloromethane, a mixture of dichloromethane/methanol 5:5 (v/v), methanol 100% andNH3 2% in methanol. The fractions containing the chiral ATxs were gathered and the solvent wasevaporated under reduced pressure. A flash column chromatography with n-hexane/ethyl acetate ingradient and crystallization from chloroform and petroleum ether (4:1) were also performed to obtainpure compounds.General procedure: 1-Chloro-4-propoxy-9H-thioxanthen-9-one (Tx, 450 mg, 1.48 mmol) and a suitable chiral aminoalcohol (9-16, 1.72 mmol) were dissolved in methanol (30 mL) and CuI (0.15 mmol) and K2CO3(1.92 mmol) were added. The reaction mixture was heated at 100 C in a muffle furnace for 48 h.After the completion of the reaction, the crude material was filtrated, washed with dichloromethane, and the organic solvents were evaporated under reduced pressure. Then, the obtained solid wasdissolved in 50 mL of dichloromethane and extracted with HCl 1M(3 50 mL). The aqueous layer wasbasified with NaOH 20% and extracted with dichloromethane (3 100 mL). The organic layers weregathered, washed with water (3 50 mL), dried over anhydrous sodium sulphate and the solvent wasevaporated under reduced pressure. Then, a solid phase extraction using a cation exchange cartridgeDiscovery DSC-SCX was applied to further purify the extracted material. First, an activation ofthe cartridge with dichloromethane (50 mL) was performed followed by loading the cartridge withthe sample (previously incorporated in silica). Then, elution was carried out with the followingsolvents: dichloromethane, a mixture of dichloromethane/methanol 5:5 (v/v), methanol 100% andNH3 2% in methanol. The fractions containing the chiral ATxs were gathered and the solvent wasevaporated under reduced pressure. A flash column chromatography with n-hexane/ethyl acetate ingradient and crystallization from chloroform and petroleum ether (4:1) were also performed to obtainpure compounds.General procedure: 1-Chloro-4-propoxy-9H-thioxanthen-9-one (Tx, 450 mg, 1.48 mmol) and a suitable chiral aminoalcohol (9-16, 1.72 mmol) were dissolved in methanol (30 mL) and CuI (0.15 mmol) and K2CO3(1.92 mmol) were added. The reaction mixture was heated at 100 C in a muffle furnace for 48 h.After the completion of the reaction, the crude material was filtrated, washed with dichloromethane, and the organic solvents were evaporated under reduced pressure. Then, the obtained solid wasdissolved in 50 mL of dichloromethane and extracted with HCl 1M(3 50 mL). The aqueous layer wasbasified with NaOH 20% and extracted with dichloromethane (3 100 mL). The organic layers weregathered, washed with water (3 50 mL), dried over anhydrous sodium sulphate and the solvent wasevaporated under reduced pressure. Then, a solid phase extraction using a cation exchange cartridgeDiscovery DSC-SCX was applied to further purify the extracted material. First, an activation ofthe cartridge with dichloromethane (50 mL) was performed followed by loading the cartridge withthe sample (previously incorporated in silica). Then, elution was carried out with the followingsolvents: dichloromethane, a mixture of dichloromethane/methanol 5:5 (v/v), methanol 100% andNH3 2% in methanol. The fractions containing the chiral ATxs were gathered and the solvent wasevaporated under reduced pressure. A flash column chromatography with n-hexane/ethyl acetate ingradient and crystallization from chloroform and petroleum ether (4:1) were also performed to obtainpure compounds.General procedure: 1-Chloro-4-propoxy-9H-thioxanthen-9-one (Tx, 450 mg, 1.48 mmol) and a suitable chiral aminoalcohol (9-16, 1.72 mmol) were dissolved in methanol (30 mL) and CuI (0.15 mmol) and K2CO3(1.92 mmol) were added. The reaction mixture was heated at 100 C in a muffle furnace for 48 h.After the completion of the reaction, the crude material was filtrated, washed with dichloromethane, and the organic solvents were evaporated under reduced pressure. Then, the obtained solid wasdissolved in 50 mL of dichloromethane and extracted with HCl 1M(3 50 mL). The aqueous layer wasbasified with NaOH 20% and extracted with dichloromethane (3 100 mL). The organic layers weregathered, washed with water (3 50 mL), dried over anhydrous sodium sulphate and the solvent wasevaporated under reduced pressure. Then, a solid phase extraction using a cation exchange cartridgeDiscovery DSC-SCX was applied to further purify the extracted material. First, an activation ofthe cartridge with dichloromethane (50 mL) was performed followed by loading the cartridge withthe sample (previously incorporated in silica). Then, elution was carried out with the followingsolvents: dichloromethane, a mixture of dichloromethane/methanol 5:5 (v/v), methanol 100% andNH3 2% in methanol. The fractions containing the chiral ATxs were gathered and the solvent wasevaporated under reduced pressure. A flash column chromatography with n-hexane/ethyl acetate ingradient and crystallization from chloroform and petroleum ether (4:1) were also performed to obtainpure compounds.General procedure: 1-Chloro-4-propoxy-9H-thioxanthen-9-one (Tx, 450 mg, 1.48 mmol) and a suitable chiral aminoalcohol (9-16, 1.72 mmol) were dissolved in methanol (30 mL) and CuI (0.15 mmol) and K2CO3(1.92 mmol) were added. The reaction mixture was heated at 100 C in a muffle furnace for 48 h.After the completion of the reaction, the crude material was filtrated, washed with dichloromethane, and the organic solvents were evaporated under reduced pressure. Then, the obtained solid wasdissolved in 50 mL of dichloromethane and extracted with HCl 1M(3 50 mL). The aqueous layer wasbasified with NaOH 20% and extracted with dichloromethane (3 100 mL). The organic layers weregathered, washed with water (3 50 mL), dried over anhydrous sodium sulphate and the solvent wasevaporated under reduced pressure. Then, a solid phase extraction using a cation exchange cartridgeDiscovery DSC-SCX was applied to further purify the extracted material. First, an activation ofthe cartridge with dichloromethane (50 mL) was performed followed by loading the cartridge withthe sample (previously incorporated in silica). Then, elution was carried out with the followingsolvents: dichloromethane, a mixture of dichloromethane/methanol 5:5 (v/v), methanol 100% andNH3 2% in methanol. The fractions containing the chiral ATxs were gathered and the solvent wasevaporated under reduced pressure. A flash column chromatography with n-hexane/ethyl acetate ingradient and crystallization from chloroform and petroleum ether (4:1) were also performed to obtainpure compounds.General procedure: 1-Chloro-4-propoxy-9H-thioxanthen-9-one (Tx, 450 mg, 1.48 mmol) and a suitable chiral aminoalcohol (9-16, 1.72 mmol) were dissolved in methanol (30 mL) and CuI (0.15 mmol) and K2CO3(1.92 mmol) were added. The reaction mixture was heated at 100 C in a muffle furnace for 48 h.After the completion of the reaction, the crude material was filtrated, washed with dichloromethane, and the organic solvents were evaporated under reduced pressure. Then, the obtained solid wasdissolved in 50 mL of dichloromethane and extracted with HCl 1M(3 50 mL). The aqueous layer wasbasified with NaOH 20% and extracted with dichloromethane (3 100 mL). The organic layers weregathered, washed with water (3 50 mL), dried over anhydrous sodium sulphate and the solvent wasevaporated under reduced pressure. Then, a solid phase extraction using a cation exchange cartridgeDiscovery DSC-SCX was applied to further purify the extracted material. First, an activation ofthe cartridge with dichloromethane (50 mL) was performed followed by loading the cartridge withthe sample (previously incorporated in silica). Then, elution was carried out with the followingsolvents: dichloromethane, a mixture of dichloromethane/methanol 5:5 (v/v), methanol 100% andNH3 2% in methanol. The fractions containing the chiral ATxs were gathered and the solvent wasevaporated under reduced pressure. A flash column chromatography with n-hexane/ethyl acetate ingradient and crystallization from chloroform and petroleum ether (4:1) were also performed to obtainpure compounds.(S)-1-((1-Hydroxypropan-2-yl)amino)-4-propoxy-9H-thioxanthen-9-one (ATx 1 (+)). Yield: 1.97%. m.p.:116-118 C (dec.); [alpha]25D +112 (c = 3.4 103 g/mL in dichloromethane). IR (KBr) numax: 3419, 3270, 2962, 2925, 2873, 2359, 2341, 1618, 1568, 1507, 1435, 1293, 1269, 1252, 1225, 746 cm1. 1H-NMR(300.13 MHz, CDCl3): delta: 8.50 (1H, d, J = 8.0 Hz, H-8), : 7.56 (2H, m, H-5 and H-6), : 7.43 (1H, m, H-7), : 7.13 (1H, d, J = 9.0 Hz, H-3), : 6.85 (1H, d, J = 9.0 Hz, H-2), : 4.03 (2H, t, J = 6.5 Hz, H-a), : 3.81 (3H, m, H-10 and CH2OH), : 1.90 (2H, m, H-b), : 1.32 (3H, d, J = 6.2 Hz, H-20), : 1.12 (3H, t, J = 7.4 Hz, H-c). 13C-NMR (75.47 MHz, CDCl3): delta: 183.55 (C-9), 146.50 (C-4), 144.02 (C-1), 136.85 (C-6), 131.92(C-8a), 129.85 (C-4a), 129.24 (C-9a), 126.08 (C-8), 125.98 (C-7), 125.20 (C-5), 119.12 (C-3), 114.10 (C-10a), 109.80 (C-2), 72.48 (C-a), 65.96 (C-CH2OH), 51.91 (C-10), 22.66 (C-b), 16.86 (C-20), 10.71 (C-c). e.e. > 99%(HPLC; column: Lux Amylose-1 (250 4.6 mm i.d., 5 m), Mobile phase: n-hexane:ethanol (70:30v/v), 0.5 mL/min, max 254 nm).

Molecular Weight:304.8
XLogP3:5
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:3
Exact Mass:304.0324785
Monoisotopic Mass:304.0324785
Topological Polar Surface Area:51.6
Heavy Atom Count:20
Complexity:362
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes