ethane-1,1-dithiol

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: 17β,19-Dihydroxy-1α-methyl-4-androsten-3-one in acetic acid is treated with ethanedithiol and p-toluenesulfonic acid. After 4 hours at room temperature, the solution is poured onto water and the mixture extracted with methylenechloride. The methylenechloride extracts are washed well with water, sodium hydroxide solution, water, dried over sodium sulfate and evaporated under reduced pressure to leave 17β,19-dihydroxy-1α-methyl-4-androsten-3-one 3-ethylenethioketal which is recrystallized once from a solution of acetone-hexane. the solution is poured onto water the mixture extracted with methylenechloride The methylenechloride extracts are washed well with water, sodium hydroxide solution, water dried over sodium sulfate evaporated under reduced pressure

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

Procedure: A mixture of ethyl {(5-methoxy-3,4-dihydro-4-oxospiro[2H-1-benzopyran-2,1'-cyclohexan]-7-yl)oxy}acetate (prepared in Preparation 49) (0.5 g, 1.44 mmol), ethanedithiol (0.149 g, 1.59 mmol), dry benzene (10 ml), and p-toluenesulfonic acid (0.013 g, 0.076 mmol) is heated to reflux for 12 hours under conditions for azeotropic dehydration. The solvent is removed under reduced pressure. The residue is applied to a silica gel column and eluted with a mixture of ethyl acetate and dichloromethane (1:9). The eluate is applied to a Lober column and eluted with a mixture of ethyl acetate and hexane (1:2) to obtain ethyl {(5-methoxy-3,4-dihydrodispiro[2H-1-benzopyran-2,1'-cyclohexan-4,2"-[1,3]dithiolan]-7-yl)oxy}acetate as an oil (0.50 g, 82.1%). A mixture of the ester (0.49 g, 1.16 mmol), 1N sodium hydroxide (1.27 ml, 1.27 mmol), and ethanol (5 ml) is stirred at room temperature for 0.5 hours. The reaction mixture is made acid with 1N HCl and distilled under reduced pressure at room temperature to remove ethanol. The residue is extracted with diethyl ether. The extract is washed with saturated brine, dried, and the solvent is removed under reduced pressure. The residue is treated with a mixture of diethyl ether and hexane to obtain the title compound as a crystalline soild (0.43 g, 93.7%). Recrystallization from ethyl acetate gives a product having a melting point of 189°-190° C. is heated to reflux for 12 hours under conditions for azeotropic dehydration The solvent is removed under reduced pressure eluted with a mixture of ethyl acetate and dichloromethane (1:9) eluted with a mixture of ethyl acetate and hexane (1:2)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 10 g of methyl rac-4,4-ethylenedioxy-1,2,3,4-tetrahydro-2-hydroxy-5,8-dimethoxynaphthalene-2-carboxylate were dissolved in 30 ml of dichloromethane and the solution was cooled to 0° C. To the solution were added 4 ml of ethanedithiol followed by 4 ml of boron trifluoride etherate. The mixture was stirred at 0° C. for 15 minutes and then poured into 200 ml of diethyl ether. The organic layer was washed with three 50 ml portions of 5% sodium hydroxide solution and evaporated to give a yellow oil which was taken up in 200 ml of methanol. 100 ml of 5% sodium hydroxide solution were added and the resulting solution was stirred at room temperature for 1.5 hours. Most of the methanol was then evaporated, the residue was diluted with 250 ml of water and washed with three 100 ml portions of ether. The aqueous layer was acidified with hydrochloric acid and the precipitated oil was left to solidfy. The product was collected by filtration, washed free from acid using water and dried. The crude acid was purified by suspension in 150 ml of ethyl acetate and heating under reflux for 30 minutes. The mixture was cooled and the product was collected by filtration after 24 hours. There were obtained 7.0 g (66.5%) of 1',2',3',4'-tetrahydro-2'-hydroxy-5',8'-dimethoxyspiro[1,3-dithiolane-2,4'-naphthalene]-2'-carboxylic acid in the form of colourless crystals of melting point 189°-189.5° C. The organic layer was washed with three 50 ml portions of 5% sodium hydroxide solution evaporated to give a yellow oil which the resulting solution was stirred at room temperature for 1.5 hours Most of the methanol was then evaporated the residue was diluted with 250 ml of water washed with three 100 ml portions of ether the precipitated oil was left The product was collected by filtration washed free from acid dried The crude acid was purified by suspension in 150 ml of ethyl acetate heating under reflux for 30 minutes The mixture was cooled the product was collected by filtration after 24 hours

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 10 g of methyl rac-4,4-ethylenedioxy-1,2,3,4-tetrahydro-2-hydroxy-5,8-dimethoxynaphthalene-2-carboxylate were dissolved in 30 ml of dichloromethane and the solution was cooled to 0° C. To the solution were added 4 ml of ethanedithiol followed by 4 ml of boron trifluoride etherate. The mixture was stirred at 0° C. for 15 minutes and then poured into 200 ml of diethyl ether. The organic layer was washed with three 50 ml portions of 5% sodium hydroxide solution and evaporated to give a yellow oil which was taken up in 200 ml of methanol. 100 ml of 5% sodium hydroxide solution were added and the resulting solution was stirred at room temperature for 1.5 hours. Most of the methanol was then evaporated, the residue was diluted with 250 ml of water and washed with three 100 ml portions of ether. The aqueous layer was acidified with hydrochloric acid and the precipitated oil was left to solidfy. The product was collected by filtration, washed free from acid using water and dried. The crude acid was purified by suspension in 150 ml of ethyl acetate and heating under reflux for 30 minutes. The mixture was cooled and the product was collected by filtration after 24 hours. There were obtained 7.0 g (66.5%) of 1',2',3',4'-tetrahydro-2'-hydroxy-5',8'-dimethoxyspiro[1,3-dithiolane-2,4'-naphthalene]-2'-carboxylic acid in the form of colourless crystals of melting point 189°-189.5° C. The organic layer was washed with three 50 ml portions of 5% sodium hydroxide solution evaporated to give a yellow oil which the resulting solution was stirred at room temperature for 1.5 hours Most of the methanol was then evaporated the residue was diluted with 250 ml of water washed with three 100 ml portions of ether the precipitated oil was left The product was collected by filtration washed free from acid dried The crude acid was purified by suspension in 150 ml of ethyl acetate heating under reflux for 30 minutes The mixture was cooled the product was collected by filtration after 24 hours

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

Procedure: Into a mixture of about 100 g of methyl levulinate and about 100 ml of ethanedithiol was slowly poured boron trifluoride etherate until reflux began. An about 500 ml portion of methanol was added followed by sufficient boron trifluoride etherate to make a total of about 100 ml of this reagent. The mixture was stirred overnight, the solvent removed and the residue poured into saturated sodium bi-carbonate. The mixture was extracted with ether. The ether extract was dried, the solvent removed and the residue distilled at about 97°-100° C., at about 0.55 mm, giving about 147 g of the desired title compound. until reflux the solvent removed the residue poured into saturated sodium bi-carbonate The mixture was extracted with ether The ether extract was dried the solvent removed the residue distilled at about 97°-100° C., at about 0.55 mm

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

Procedure: Under argon, 11.5 g (0.03 mol) of 3-(9,10-didehydro-6-methyl-8α-ergolinyl)-1,1-diethylurea is dissolved in 300 ml of chloroform. At room temperature, 105 ml of ethyl formate and 5.4 ml of ethanedithiol are added in succession. Then 13.2 ml of titanium(IV) chloride in 150 ml of chloroform is added dropwise. The mixture is agitated for 3 days at room temperature. To work up the mixture, it is cooled in an ice bath and 75 ml of methanol and 600 ml of water are added in sequence dropwise to this mixture. The solution is rendered alkaline with 60 ml of 25% ammonia solution and extracted with methylene chloride. The organic phases are washed with water and dried over magnesium sulfate. The concentrated residue is chromatographed under pressure on silica gel with ethyl acetate/methanol 95:5, thus isolating 1.7 g of 3-[9,10-didehydro-2-(1,3-dithiolan-2-yl)-6-methyl-8α-ergolinyl]-1,1-diethylurea (12% yield). is cooled in an ice bath extracted with methylene chloride The organic phases are washed with water dried over magnesium sulfate The concentrated residue is chromatographed under pressure on silica gel with ethyl acetate/methanol 95:5

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

Procedure: At room temperature under argon, 7 ml of ethyl formate and 3.6 ml (44 mmol) of ethanedithiol are added in succession to a solution of 6.8 g of 1,1-diethyl-3-(6-methyl-8α-ergolinyl)urea in 200 ml of chloroform. Thereafter 8.8 ml (80 mmol) of titanium(IV) chloride dissolved in 100 ml of chloroform is added gradually dropwise to the mixture. The latter is stirred for 20 hours at room temperature. Although the starting material is not as yet entirely converted at this point in time, the reaction mixture is worked up to avoid further formation of the disubstituted compound. For this purpose, the reaction mixture is cooled in an ice bath and combined, in sequence, dropwise with 50 ml of methanol and 40 ml of water. The mixture is then made alkaline with 25% ammonia solution and extracted with methylene chloride. The organic phases are washed with water and dried over magnesium sulfate. The evaporated residue is crystallized in boiling heat from methanol/ethyl acetate, thus obtaining 3.8 g of 1,1-diethyl-3-[2-(1,3-dithiolan-2-yl)-6-methyl-8α-ergolinyl]urea (42% yield). is added gradually dropwise to the mixture For this purpose, the reaction mixture is cooled in an ice bath extracted with methylene chloride The organic phases are washed with water dried over magnesium sulfate The evaporated residue is crystallized in boiling heat from methanol/ethyl acetate

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 10 g of methyl rac-4,4-ethylenedioxy-1,2,3,4-tetrahydro-2-hydroxy-5,8-dimethoxynaphthalene-2-carboxylate were dissolved in 30 ml of dichloromethane and the solution was cooled to 0° C. To the solution were added 4 ml of ethanedithiol followed by 4 ml of boron trifluoride etherate. The mixture was stirred at 0° C. for 15 minutes and then poured into 200 ml of diethyl ether. The organic layer was washed with three 50 ml portions of 5% sodium hydroxide solution and evaporated to give a yellow oil which was taken up in 200 ml of methanol. 100 ml of 5% sodium hydroxide solution were added and the resulting solution was stirred at room temperature for 1.5 hours. Most of the methanol was then evaporated, the residue was diluted with 250 ml of water and washed with three 100 ml portions of ether. The aqueous layer was acidified with hydrochloric acid and the precipitated oil was left to solidify. The product was collected by filtration, washed free from acid using water and dried. The crude acid was purified by suspension in 150 ml of ethyl acetate and heating under reflux for 30 minutes. The mixture was cooled and the product was collected by filtration after 24 hours. There were obtained 7.0 g (66.5%) of 1',2',3',4'-tetrahydro-2'-hydroxy-5',8'-dimethoxyspiro[1,3-dithiolane-2,4'-naphthalene]-2'-carboxylic acid in the form of colourless crystals of melting point 189°-189.5° C. The organic layer was washed with three 50 ml portions of 5% sodium hydroxide solution evaporated to give a yellow oil which the resulting solution was stirred at room temperature for 1.5 hours Most of the methanol was then evaporated the residue was diluted with 250 ml of water washed with three 100 ml portions of ether the precipitated oil was left The product was collected by filtration washed free from acid dried The crude acid was purified by suspension in 150 ml of ethyl acetate heating under reflux for 30 minutes The mixture was cooled the product was collected by filtration after 24 hours

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

Procedure: 70.7 mg of 6-(4-hydroxy-3-methoxy-phenyl)-3-oxo-2-(2-trimethylsilanyl-ethoxymethyl)-2,3-dihydro-pyridazine-4-carboxylic acid 4-chloro-benzyl amide and 60 μl ethandithiol and 60 μl water were dissolved in 750 μl TFA and stirred at room temperature for 3 h. Afterwards, the solvent was distilled off and the raw product purified by HPLC (column 125×25, PurospherStar RP18 endcapped, 5 μm; solvent: A: water (0.05% HCOOH), B: acetonitrile (0.05% HCOOH)). Afterwards, the solvent was distilled off the raw product purified by HPLC (column 125×25, PurospherStar RP18