2-(2-sulfanylethylsulfanyl)ethanethiol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 25.7 g (0.15 mol) of 2-mercaptoethylsulfide (purity 90%) are added to a suspension of 8.3 g (0.06 mol) of potassium carbonate in 50 ml of dimethylacetamide. A solution of 8.0 g (0.03 mol) 1-(4-chlorophenyl)-2-methyl-2-morpholin-4-yl-propan-1-one in 25 ml of dimethylacetamide is added dropwise at 85° C. over 60 min. After stirring for 5 h, the reaction mixture is cooled, diluted with ethyl acetate (100 ml), extracted with water (3×100 ml) to remove the carbonate and dimethylacetamide, dried over MgSO4, and concentrated under vacuum. The resulting yellow liquid (stench) is purified by flash chromatography on silica gel (hexane/ethyl acetate 85:15) to yield a pale yellow oil. The structure is confirmed by the 1H-NMR spectrum (CDCl3): δ [ppm] 1.31 (s, 6H), 1.750 (t, SH), 2.57 (t, 4H), 2.71-2.85 (m, 6H), 3.20 (t, 2H), 3.70 (t, 4), 7.31 (d, 2H), 8.51 (d, 2H). the reaction mixture is cooled extracted with water (3×100 ml) to remove the carbonate and dimethylacetamide dried over MgSO4 concentrated under vacuum The resulting yellow liquid (stench) is purified by flash chromatography on silica gel (hexane/ethyl acetate 85:15) to yield a pale yellow oil

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In 360 ml of methyl ethyl ketone was dissolved 27.8 g of bis(2-mercaptoethyl)sulfide, and the solution was then cooled to 5° C. Next, 32 g of a 45% aqueous sodium hydroxide solution was added dropwise thereto, followed by vigorous stirring. To this solution, 60 g of ethyl bromoacetate was added dropwise, and reaction was then carried out at room temperature for 1 hour. Afterward, 200 ml of ethyl acetate was added thereto, and the solution was washed with 50 ml of an aqueous saturated ammonium chloride solution twice, and then dried over anhydrous sodium sulfate. Afterward, the solvent was distilled off under reduced pressure to obtain 44 g of light yellow oily bis(2-ethyloxycarbonylmethylthioethyl) sulfide. This sulfide was dissolved in 70 ml of isopropanol, and 18 g of hydrazine monohydrate was added dropwise thereto, while a solution temperature of 5° C. was maintained. After 2 hours, the produced white crystalline bis(2-hydrazinocarbonylmethylthioethyl) sulfide was collected by filtration. Next, the collected crystals were washed with 20 ml of cold isopropanol twice and further washed with 10 ml of hexane. After drying, the dried material was dissolved in 150 ml of water and then cooled to 5° C., and 25 g of concentrated hydrochloric acid was then added dropwise thereto. Furthermore, a solution obtained by dissolving 16 g of sodium nitrite in 50 ml of water was added dropwise thereto. After 30 minutes, 150 ml of benzene was added thereto, and the solution was then heated up to room temperature, while vigorously stirred. Next, the resulting organic layer was separated, and then dried over anhydrous magnesium sulfate. Afterward, toluene was added thereto for dilution so as to bring the total volume to 500 ml, and the solution was then slowly heated up to 55° C. to gently carry out reaction so that nitrogen might be continuously generated. After the reaction at 70° C. for 3 hours, the solution was cooled to room temperature and then allowed to stand overnight, and the resulting white precipitate was removed by filtration. Afterward, the solvent was distilled off under reduced pressure. The obtained colorless oily product was distilled at 80° C. under a reduced pressure of 0.3 mmHg for 2 hours to remove impurities, thereby obtaining the desired bis[2-(isocyanatomethylthio)ethyl]sulfide. reaction the solution was washed with 50 ml of an aqueous saturated ammonium chloride solution twice dried over anhydrous sodium sulfate Afterward, the solvent was distilled off under reduced pressure

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In 360 ml of methyl ethyl ketone was dissolved 27.8 g of bis(2-mercaptoethyl)sulfide, and the solution was then cooled to 5° C. Next, 32 g of a 45% aqueous sodium hydroxide solution was added dropwise thereto, followed by vigorous stirring. To this solution, 60 g of ethyl bromoacetate was added dropwise, and reaction was then carried out at room temperature for 1 hour. Afterward, 200 ml of ethyl acetate was added thereto, and the solution was washed with 50 ml of an aqueous saturated ammonium chloride solution twice, and then dried over anhydrous sodium sulfate. Afterward, the solvent was distilled off under reduced pressure to obtain 44 g of light yellow oily bis(2-ethyloxycarbonylmethylthioethyl) sulfide. This sulfide was dissolved in 70 ml of isopropanol, and 18 g of hydrazine monohydrate was added dropwise thereto, while a solution temperature of 5° C. was maintained. After 2 hours, the produced white crystalline bis(2-hydrazinocarbonylmethylthioethyl) sulfide was collected by filtration. Next, the collected crystals were washed with 20 ml of cold isopropanol twice and further washed with 10 ml of hexane. After drying, the dried material was dissolved in 150 ml of water and then cooled to 5° C., and 25 g of concentrated hydrochloric acid was then added dropwise thereto. Furthermore, a solution obtained by dissolving 16 g of sodium nitrite in 50 ml of water was added dropwise thereto. After 30 minutes, 150 ml of benzene was added thereto, and the solution was then heated up to room temperature, while vigorously stirred. Next, the resulting organic layer was separated, and then dried over anhydrous magnesium sulfate. Afterward, toluene was added thereto for dilution so as to bring the total volume to 500 ml, and the solution was then slowly heated up to 55° C. to gently carry out reaction so that nitrogen might be continuously generated. After the reaction at 70° C. for 3 hours, the solution was cooled to room temperature and then allowed to stand overnight, and the resulting white precipitate was removed by filtration. Afterward, the solvent was distilled off under reduced pressure. The obtained colorless oily product was distilled at 80° C. under a reduced pressure of 0.3 mmHg for 2 hours to remove impurities, thereby obtaining the desired bis[2-(isocyanatomethylthio)ethyl]sulfide. reaction the solution was washed with 50 ml of an aqueous saturated ammonium chloride solution twice dried over anhydrous sodium sulfate Afterward, the solvent was distilled off under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixed solution of 231.48 g (1.50 mol) of bis(2-mercaptoethyl) sulfide and 1000 g of toluene was heated at 110° C. and thereinto was dropped 457.09 g (3.60 mol) of 3-chloropropano yl chloride over 2 hours. When all was dropped, the reaction mixture was further stirred for another 7 hours at 110° C., while by-product hydrogen chloride was removed out of the reaction system under nitrogen stream. Then no raw material existing in the high performance liquid chromatography (hereinafter referred to as HPLC analysis) was confirmed, and the reaction solution was cooled down to room temperature. The reaction mixture was discharged in 5000 g of 5% sodium bicarbonate aqueous solution (corresponding to 3.0 mol as sodium bicarbonate), thereto was further added 1000 g of toluene, and the reaction product was extracted. An organic layer was repeatedly washed using the ion exchange water until a drainage layer was neutralized. Then, the organic layer was taken out by separation, and then toluene was removed at 30° C. under reduced pressure and concentrated to obtain 476.54 g of a coarse composition of a colorless and transparent liquid, i.e., bis[2-(3-chloropropionylthio)ethyl]sulfide. The purity of the coarse composition was 95% (HPLC analysis by the internal standard method) and the yield was 90% (purity conversion). When all was dropped was removed out of the reaction system under nitrogen stream the reaction product was extracted An organic layer was repeatedly washed Then, the organic layer was taken out by separation toluene was removed at 30° C. under reduced pressure concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixed solution of 231.48 g (1.50 mol) of bis(2-mercaptoethyl) sulfide and 1000 g of toluene was heated at 110° C. and thereinto was dropped 457.09 g (3.60 mol) of 3-chloropropano yl chloride over 2 hours. When all was dropped, the reaction mixture was further stirred for another 7 hours at 110° C., while by-product hydrogen chloride was removed out of the reaction system under nitrogen stream. Then no raw material existing in the high performance liquid chromatography (hereinafter referred to as HPLC analysis) was confirmed, and the reaction solution was cooled down to room temperature. The reaction mixture was discharged in 5000 g of 5% sodium bicarbonate aqueous solution (corresponding to 3.0 mol as sodium bicarbonate), thereto was further added 1000 g of toluene, and the reaction product was extracted. An organic layer was repeatedly washed using the ion exchange water until a drainage layer was neutralized. Then, the organic layer was taken out by separation, and then toluene was removed at 30° C. under reduced pressure and concentrated to obtain 476.54 g of a coarse composition of a colorless and transparent liquid, i.e., bis[2-(3-chloropropionylthio)ethyl]sulfide. The purity of the coarse composition was 95% (HPLC analysis by the internal standard method) and the yield was 90% (purity conversion). When all was dropped was removed out of the reaction system under nitrogen stream the reaction product was extracted An organic layer was repeatedly washed Then, the organic layer was taken out by separation toluene was removed at 30° C. under reduced pressure concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: This compound is obtained by reacting 1,11-dichloro-3,6,9-trioxaundecane with 1,5-dimercapto-3-thiapentane in the presence of sodium carbonate in aqueous ethanol: ##STR8## This compound is obtained

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: This compound is obtained by reacting 1,11-dichloro-3,6,9-trioxaundecane with 1,5-dimercapto-3-thiapentane in the presence of sodium carbonate in aqueous ethanol: ##STR8## This compound is obtained

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: This compound is obtained by reacting 1,5-dimercapto-3-thiapentane with 1,8-dichloro-3,6-dioxaoctane in the presence of cesium carbonate in dimethylformamide (DMF): ##STR2## This compound is obtained

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: This compound is obtained by reacting 1,5-dimercapto-3-thiapentane with 1,8-dichloro-3,6-dioxaoctane in the presence of cesium carbonate in dimethylformamide (DMF): ##STR2## This compound is obtained

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 25.7 g (0.15 mol) of 2-mercaptoethylsulfide (purity 90%) are added to a suspension of 8.3 g (0.06 mol) of potassium carbonate in 50 ml of dimethylacetamide. A solution of 8.0 g (0.03 mol) 1-(4-chlorophenyl)-2-methyl-2-morpholin-4-yl-propan-1-one in 25 ml of dimethylacetamide is added dropwise at 85° C. over 60 min. After stirring for 5 h, the reaction mixture is cooled, diluted with ethyl acetate (100 ml), extracted with water (3×100 ml) to remove the carbonate and dimethylacetamide, dried over MgSO4, and concentrated under vacuum. The resulting yellow liquid (stench) is purified by flash chromatography on silica gel (hexane/ethyl acetate 85:15) to yield a pale yellow oil. The structure is confirmed by the 1H-NMR spectrum (CDCl3): δ [ppm] 1.31 (s, 6H), 1.750 (t, SH), 2.57 (t, 4H), 2.71-2.85 (m, 6H), 3.20 (t, 2H), 3.70 (t, 4), 7.31 (d, 2H), 8.51 (d, 2H). the reaction mixture is cooled extracted with water (3×100 ml) to remove the carbonate and dimethylacetamide dried over MgSO4 concentrated under vacuum The resulting yellow liquid (stench) is purified by flash chromatography on silica gel (hexane/ethyl acetate 85:15) to yield a pale yellow oil

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: In 360 ml of methyl ethyl ketone was dissolved 27.8 g of bis(2-mercaptoethyl)sulfide, and the solution was then cooled to 5° C. Next, 32 g of a 45% aqueous sodium hydroxide solution was added dropwise thereto, followed by vigorous stirring. To this solution, 60 g of ethyl bromoacetate was added dropwise, and reaction was then carried out at room temperature for 1 hour. Afterward, 200 ml of ethyl acetate was added thereto, and the solution was washed with 50 ml of an aqueous saturated ammonium chloride solution twice, and then dried over anhydrous sodium sulfate. Afterward, the solvent was distilled off under reduced pressure to obtain 44 g of light yellow oily bis(2-ethyloxycarbonylmethylthioethyl) sulfide. This sulfide was dissolved in 70 ml of isopropanol, and 18 g of hydrazine monohydrate was added dropwise thereto, while a solution temperature of 5° C. was maintained. After 2 hours, the produced white crystalline bis(2-hydrazinocarbonylmethylthioethyl) sulfide was collected by filtration. Next, the collected crystals were washed with 20 ml of cold isopropanol twice and further washed with 10 ml of hexane. After drying, the dried material was dissolved in 150 ml of water and then cooled to 5° C., and 25 g of concentrated hydrochloric acid was then added dropwise thereto. Furthermore, a solution obtained by dissolving 16 g of sodium nitrite in 50 ml of water was added dropwise thereto. After 30 minutes, 150 ml of benzene was added thereto, and the solution was then heated up to room temperature, while vigorously stirred. Next, the resulting organic layer was separated, and then dried over anhydrous magnesium sulfate. Afterward, toluene was added thereto for dilution so as to bring the total volume to 500 ml, and the solution was then slowly heated up to 55° C. to gently carry out reaction so that nitrogen might be continuously generated. After the reaction at 70° C. for 3 hours, the solution was cooled to room temperature and then allowed to stand overnight, and the resulting white precipitate was removed by filtration. Afterward, the solvent was distilled off under reduced pressure. The obtained colorless oily product was distilled at 80° C. under a reduced pressure of 0.3 mmHg for 2 hours to remove impurities, thereby obtaining the desired bis[2-(isocyanatomethylthio)ethyl]sulfide. reaction the solution was washed with 50 ml of an aqueous saturated ammonium chloride solution twice dried over anhydrous sodium sulfate Afterward, the solvent was distilled off under reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (Compound 1) of formula: ##STR11## 150 ml of absolute ethanol are introduced into a 500 ml three-necked flask, under argon, which is equipped with a thermometer, a condenser and a dropping funnel. Into it are dissolved 4.6 g of sodium (0.20 mole) and heating takes place to 45° C. This is followed by the slow addition of 15.43 g of an ethanolic 3-thia-1,5-pentane dithiol solution (0.10 mole). After stirring for 30 min., slow addition takes place of 25.58 g of an ethanolic 1-chloropentane solution (0.24 mole) and refluxing takes place for 4 hours. The reaction mixture is brought to ambient temperature, followed by filtering. This gives 28.8 g of crude product which is solubilized in 200 ml of dichloromethane and this is all washed with 2×100 ml of distilled water. Drying takes place on MgSO4, followed by filtration. After evaporating the solvent, recrystallization takes place twice in ethanol giving 18.21 g of 6,9,12-trithiaheptadecane, which corresponds to a 62% yield. The said thioether has the following characteristics: which is equipped with a thermometer, a condenser and a dropping funnel heating to 45° C slow addition refluxing for 4 hours is brought to ambient temperature by filtering all washed with 2×100 ml of distilled water Drying followed by filtration After evaporating the solvent, recrystallization