5-iodopent-1-ynyl(trimethyl)silane

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: A suspension of 5-amino-4-cyanopyrazole (10 g) and finely ground anhydrous potassium carbonate (38 g) in dry DMF (100 ml) was treated with 5-iodo-1-trimethylsilyl-1-pentyne (25 g) and the mixture was stirred under nitrogen for two days at room temperature. The reaction mixture was then poured into water and the product extracted into ethyl acetate. The extract was washed with water and then with brine, dried over Na2SO4, and evaporated to give a semisolid brown residue. This solid was taken up in chloroform and filtered through a short plug of silica gel. Evaporation of the chloroform left a tan solid comprising a mixture of the isomeric compounds 5-amino-4-cyano-1-(5-trimethylsilyl-4-pentynyl)pyrazole and 3-amino-4-cyano-1-(5-trimethylsilyl-4-pentynyl)pyrazole. Fractional recrystallization from ethyl acetate/hexane gave 4.66 grams of the desired 5-amino-4-cyano-1-(5-trimethylsilyl-4-pentynyl)pyrazole: mp 125°-127°. the product extracted into ethyl acetate The extract was washed with water with brine, dried over Na2SO4 evaporated to give a semisolid brown residue filtered through a short plug of silica gel Evaporation of the chloroform left a tan solid comprising a mixture of the isomeric compounds 5-amino-4-cyano-1-(5-trimethylsilyl-4-pentynyl)pyrazole and 3-amino-4-cyano-1-(5-trimethylsilyl-4-pentynyl)pyrazole Fractional recrystallization from ethyl acetate/hexane

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

Procedure: n-Butyllithium (19.0 ml., 1.6M solution in hexane) was added dropwise to a stirred solution of acetone N,N-dimethylhydrazone (2.6 g.) (ref. R. H. Wiley et al J. Org. Chem. 1957, 22, 204) in dry tetrahydrofuran (40 ml.) at -70° , under a current of nitrogen. The resulting solution was stirred for 30 minutes and a solution of 5-iodo-1-trimethylsilylpent-1-yne (8.1 g.) in dry tetrahydrofuran (30 ml.) was added dropwise and the reaction mixture was stirred at -70° for 1 hour, allowed to warm to 0° and stirred for 2 hours. The reaction mixture was cooled to -70° and a second portion of n-butyllithium (19 ml. 1.6M solution in hexane) was added dropwise. The mixture was stirred at -70° for 15 minutes, allowed to warm to 0° and stirred for 30 minutes. A solution of 5-iodomethyl-2,2-dimethyl-5-n-propyl-1,3-dioxane (9.0 g. European Patent 216625) in dry tetrahydrofuran (30 ml.) was added. The mixture was stirred at 0° for 30 minutes and 48 hours at 20°. The solvent was removed in vacuo and the residue was poured into water. The aqueous mixture was extracted with diethyl ether and the ethereal extracts were washed with water, dried over anhydrous magnesium sulphate and evaporated in vacuo. Chromatography of the residue on silica, eluting with diethyl ether: hexane 1:9 gave a yellow oil which consisted of 2,2-dimethyl-5-(3-oxo9-trimethylsilylnon-8-ynyl)-5-n-propyl-1,3-dioxane and 7-oxo-1-trimethylsilyloct-1-yne in the ratio of 3:1 (1.4 g.). The above mixture in tetrahydrofuran (25 ml.) and hydrochloric acid (50 ml., 1N solution) was stirred vigorously at 20° for 1 hour. The tetrahydro- furan was removed in vacuo and the residue was extracted into diethyl ether. The ethereal extracts were dried over magnesium sulphate and the solvent was removed in vacuo. 4-n-Propyl-1-(6-trimethylsilylhex-5-ynyl)-2,6-dioxabicyclo[2.2.2]octane was obtained as a colourless oil (1.06 g.) and was used without further purification. the reaction mixture was stirred at -70° for 1 hour to warm to 0° stirred for 2 hours The reaction mixture was cooled to -70° The mixture was stirred at -70° for 15 minutes to warm to 0° stirred for 30 minutes The mixture was stirred at 0° for 30 minutes and 48 hours at 20° The solvent was removed in vacuo the residue was poured into water The aqueous mixture was extracted with diethyl ether the ethereal extracts were washed with water dried over anhydrous magnesium sulphate evaporated in vacuo Chromatography of the residue on silica, eluting with diethyl ether: hexane 1:9 gave a yellow oil which The tetrahydro- furan was removed in vacuo the residue was extracted into diethyl ether The ethereal extracts were dried over magnesium sulphate the solvent was removed in vacuo

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

Procedure: A mixture of 5-chloro-1-trimethylsilylpent-1-yne (13.5 g) and sodium iodide (29 g) in butanone (100 ml) was heated at reflux for 10 hours. After this time the solvent was removed in vacuo and the residue partitioned between diethyl ether and water. The organic phase was separated, washed with water and brine before drying over anhydrous magnesium sulphate. The solvent was removed under reduced pressure to leave 5-iodo-1-trimethylsilylpent-1-yne as a colourless oil (19.3 g). was heated at reflux for 10 hours After this time the solvent was removed in vacuo the residue partitioned between diethyl ether and water The organic phase was separated washed with water and brine before drying over anhydrous magnesium sulphate The solvent was removed under reduced pressure

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

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

Procedure: n-Butyllithium (19.0 ml., 1.6M solution in hexane) was added dropwise to a stirred solution of acetone N,N-dimethylhydrazone (2.6 g.) (ref. R. H. Wiley et al J. Org. Chem. 1957, 22, 204) in dry tetrahydrofuran (40 ml.) at -70° , under a current of nitrogen. The resulting solution was stirred for 30 minutes and a solution of 5-iodo-1-trimethylsilylpent-1-yne (8.1 g.) in dry tetrahydrofuran (30 ml.) was added dropwise and the reaction mixture was stirred at -70° for 1 hour, allowed to warm to 0° and stirred for 2 hours. The reaction mixture was cooled to -70° and a second portion of n-butyllithium (19 ml. 1.6M solution in hexane) was added dropwise. The mixture was stirred at -70° for 15 minutes, allowed to warm to 0° and stirred for 30 minutes. A solution of 5-iodomethyl-2,2-dimethyl-5-n-propyl-1,3-dioxane (9.0 g. European Patent 216625) in dry tetrahydrofuran (30 ml.) was added. The mixture was stirred at 0° for 30 minutes and 48 hours at 20°. The solvent was removed in vacuo and the residue was poured into water. The aqueous mixture was extracted with diethyl ether and the ethereal extracts were washed with water, dried over anhydrous magnesium sulphate and evaporated in vacuo. Chromatography of the residue on silica, eluting with diethyl ether: hexane 1:9 gave a yellow oil which consisted of 2,2-dimethyl-5-(3-oxo9-trimethylsilylnon-8-ynyl)-5-n-propyl-1,3-dioxane and 7-oxo-1-trimethylsilyloct-1-yne in the ratio of 3:1 (1.4 g.). The above mixture in tetrahydrofuran (25 ml.) and hydrochloric acid (50 ml., 1N solution) was stirred vigorously at 20° for 1 hour. The tetrahydro- furan was removed in vacuo and the residue was extracted into diethyl ether. The ethereal extracts were dried over magnesium sulphate and the solvent was removed in vacuo. 4-n-Propyl-1-(6-trimethylsilylhex-5-ynyl)-2,6-dioxabicyclo[2.2.2]octane was obtained as a colourless oil (1.06 g.) and was used without further purification. the reaction mixture was stirred at -70° for 1 hour to warm to 0° stirred for 2 hours The reaction mixture was cooled to -70° The mixture was stirred at -70° for 15 minutes to warm to 0° stirred for 30 minutes The mixture was stirred at 0° for 30 minutes and 48 hours at 20° The solvent was removed in vacuo the residue was poured into water The aqueous mixture was extracted with diethyl ether the ethereal extracts were washed with water dried over anhydrous magnesium sulphate evaporated in vacuo Chromatography of the residue on silica, eluting with diethyl ether: hexane 1:9 gave a yellow oil which The tetrahydro- furan was removed in vacuo the residue was extracted into diethyl ether The ethereal extracts were dried over magnesium sulphate the solvent was removed in vacuo

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

Procedure: A mixture of 5-chloro-1-trimethylsilylpent-1-yne (13.5 g) and sodium iodide (29 g) in butanone (100 ml) was heated at reflux for 10 hours. After this time the solvent was removed in vacuo and the residue partitioned between diethyl ether and water. The organic phase was separated, washed with water and brine before drying over anhydrous magnesium sulphate. The solvent was removed under reduced pressure to leave 5-iodo-1-trimethylsilylpent-1-yne as a colourless oil (19.3 g). was heated at reflux for 10 hours After this time the solvent was removed in vacuo the residue partitioned between diethyl ether and water The organic phase was separated washed with water and brine before drying over anhydrous magnesium sulphate The solvent was removed under reduced pressure

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

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

Procedure: n-Butyllithium (19.0 ml., 1.6M solution in hexane) was added dropwise to a stirred solution of acetone N,N-dimethylhydrazone (2.6 g.) (ref. R. H. Wiley at al J. Org. Chem. 1957, 22, 204) in dry tetrahydrofuran (40 ml.) at -70°, under a current of nitrogen. The resulting solution was stirred for 30 minutes and a solution of 5-iodo-1-trimethylsilylpent-1-yne (8.1 g.) in dry tetrahydrofuran (30 ml.) was added dropwise and the reaction mixture was stirred at -70° for 1 hour, allowed to warm to 0° and stirred for 2 hours. The reaction mixture was cooled to -70° and a second portion of n-butyllithium (19 ml. 1.6M solution in hexane) was added dropwise. The mixture was stirred at -70° for 15 minutes, allowed to warm to 0° and stirred for 30 minutes. A solution of 5-iodomethyl-2,2-dimethyl-5-n-propyl-1,3-dioxane (9.0 g. European Patent 216625) in dry tetrahydrofuran (30 ml.) was added. The mixture was stirred at 0° for 30 minutes and 48 hours at 20°. The solvent was removed in vacuo and the residue was poured into water. The aqueous mixture was extracted with diethyl ether and the ethereal extracts were washed with water, dried over anhydrous magnesium sulphate and evaporated in vacuo. Chromatography of the residue on silica, eluting with diethyl ether:hexane 1:9 gave a yellow oil which consisted of 2,2-dimethyl-5-(3-oxo-9-trimethylsilylnon-8-ynyl)-5-n-propyl-1,3-dioxane and 7-oxo-1-trimethylsilyloct-1-yne in the ratio of 3:1 (1.4 g.). The above mixture in tetrahydrofuran (25 ml.) and hydrochloric acid (50 ml., 1N solution) was stirred vigorously at 20° for 1 hour. The tetrahydrofuran was removed in vacuo and the residue was extracted into diethyl ether. The ethereal extracts were dried over magnesium sulphate and the solvent was removed in vacuo. 4-n-Propyl-1-(6-trimethylsilylhex-5-ynyl) 2,6-dioxabicyclo[2.2.2]octane was obtained as a colourless oil (1.06 g.) and was used without further purification. the reaction mixture was stirred at -70° for 1 hour to warm to 0° stirred for 2 hours The reaction mixture was cooled to -70° The mixture was stirred at -70° for 15 minutes to warm to 0° stirred for 30 minutes The mixture was stirred at 0° for 30 minutes and 48 hours at 20° The solvent was removed in vacuo the residue was poured into water The aqueous mixture was extracted with diethyl ether the ethereal extracts were washed with water dried over anhydrous magnesium sulphate evaporated in vacuo Chromatography of the residue on silica, eluting with diethyl ether:hexane 1:9 gave a yellow oil which The tetrahydrofuran was removed in vacuo the residue was extracted into diethyl ether The ethereal extracts were dried over magnesium sulphate the solvent was removed in vacuo

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

Procedure: A mixture of 5-chloro-1-trimethylsilylpent-1-yne (13.5 g) and sodium iodide (29 g) in butanone (100 ml) was heated at reflux for 10 hours. After this time the solvent was removed in vacuo and the residue partitioned between diethyl ether and water. The organic phase was separated, washed with water and brine before drying over anhydrous magnesium sulphate. The solvent was removed under reduced pressure to leave 5-iodo-1-trimethylsilylpent-1-yne as a colourless oil (19.3 g). was heated at reflux for 10 hours After this time the solvent was removed in vacuo the residue partitioned between diethyl ether and water The organic phase was separated washed with water and brine before drying over anhydrous magnesium sulphate The solvent was removed under reduced pressure

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

Procedure: A suspension of 5-amino-4-cyanopyrazole (10 g) and finely ground anhydrous potassium carbonate (38 g) in dry DMF (100 ml) was treated with 5-iodo-1-trimethylsilyl-1-pentyne (25 g) and the mixture was stirred under nitrogen for two days at room temperature. The reaction mixture was then poured into water and the product extracted into ethyl acetate. The extract was washed with water and then with brine, dried over Na2SO4, and evaporated to give a semisolid brown residue. This solid was taken up in chloroform and filtered through a short plug of silica gel. Evaporation of the chloroform left a tan solid comprising a mixture of the isomeric compounds 5-amino-4-cyano-1-(5-trimethylsilyl-4-pentynyl)pyrazole and 3-amino-4-cyano-1-(5-trimethylsilyl-4-pentynyl)pyrazole. Fractional recrystallization from ethyl acetate/hexane gave 4.66 grams of the desired 5-amino-4-cyano-1-(5-trimethylsilyl-4-pentynyl)pyrazole: mp 125°-127°. the product extracted into ethyl acetate The extract was washed with water with brine, dried over Na2SO4 evaporated to give a semisolid brown residue filtered through a short plug of silica gel Evaporation of the chloroform left a tan solid comprising a mixture of the isomeric compounds 5-amino-4-cyano-1-(5-trimethylsilyl-4-pentynyl)pyrazole and 3-amino-4-cyano-1-(5-trimethylsilyl-4-pentynyl)pyrazole Fractional recrystallization from ethyl acetate/hexane