1,4-dibromo-1,1,2-trifluorobutane

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Mercaptothiazole (11.7 g) in acetone (30 cm3) containing 1,4-dibromo-1,1,2-trifluorobutane (27.0 g) was treated portionwise with anhydrous potassium carbonate (13.8 g) under an atmosphere of nitrogen. The reaction was stirred for 1.5 hours, filtered and the insolubles washed with further acetone (4×25 cm3). The filtrate was evaporated under reduced pressure and the residue fractionated by chromatography (silica, eluant 10% ethyl acetate in hexane) to give 2-(4-bromo-3,4,4-trifluorobutylthio)thiazole (29.5 g). 1H NMR: δ 2.2-2.5(2H,m); 3.2-3.6(2H,m); 4.7-5.0(1H,m); 7.23(1H,d); 7.68(1H,d). filtered the insolubles washed with further acetone (4×25 cm3) The filtrate was evaporated under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Mercaptothiazole (11.7 g) in acetone (30 cm3) containing 1,4-dibromo-1,1,2-trifluorobutane (27.0 g) was treated portionwise with anhydrous potassium carbonate (13.8 g) under an atmosphere of nitrogen. The reaction was stirred for 1.5 hours, filtered and the insolubles washed with further acetone (4×25 cm3). The filtrate was evaporated under reduced pressure and the residue fractionated by chromatography (silica, eluant 10% ethyl acetate in hexane) to give 2-(4-bromo-3,4,4-trifluorobutylthio)thiazole (29.5 g). 1H NMR: δ 2.2-2.5(2H,m); 3.2-3.6(2H,m); 4.7-5.0(1H,m); 7.23(1H,d); 7.68(1H,d). filtered the insolubles washed with further acetone (4×25 cm3) The filtrate was evaporated under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To the solution of 4-bromo-1,1-difluorobut-1-ene prepared in Example 6 was added potassium carbonate (10.76 g) and 2-mercaptobenzthiazole (9.18 g). The mixture was stirred at 55° C. for 6 hours and then at room temperature overnight. Gas-liquid chromatography of a sample of the reaction mixture showed that a small amount of 4-bromo-1,1-difluorobut-1-ene remained. More potassium carbonate (1.0 g) was added and the mixture heated for another two and a half hours at 55° C., when all of the bromo compound had been consumed. The mixture was cooled to room temperature and filtered. The residue was washed with acetone and the filtrate and washings combined and evaporated under reduced pressure to give the crude product (16.18 g). This was dissolved in dichloromethane. The solution was filtered and washed with dilute sodium hydroxide (2×25 ml) and with brine (2×25 ml), dried over magnesium sulphate, filtered, the filtrate evaporated to give 2-(4,4-difluorobut-3-enyl)thiobenzthiazole, having a gas chromatographic retention time identical with that of an authentic sample. The yield was 63% based on the quantity of 1,4-dibromo-1,1,2-trifluorobutane used in step (b) of Example 1. 2-(4,4-Difluorobut-3-enyl)thiobenzoxazole was prepared in the same way, but using 2-mercapto benzoxazole instead of 2-mercapto benzthiazole.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To the solution of 4-bromo-1,1-difluorobut-1-ene prepared in Example 6 was added potassium carbonate (10.76 g) and 2-mercaptobenzthiazole (9.18 g). The mixture was stirred at 55° C. for 6 hours and then at room temperature overnight. Gas-liquid chromatography of a sample of the reaction mixture showed that a small amount of 4-bromo-1,1-difluorobut-1-ene remained. More potassium carbonate (1.0 g) was added and the mixture heated for another two and a half hours at 55° C., when all of the bromo compound had been consumed. The mixture was cooled to room temperature and filtered. The residue was washed with acetone and the filtrate and washings combined and evaporated under reduced pressure to give the crude product (16.18 g). This was dissolved in dichloromethane. The solution was filtered and washed with dilute sodium hydroxide (2×25 ml) and with brine (2×25 ml), dried over magnesium sulphate, filtered, the filtrate evaporated to give 2-(4,4-difluorobut-3-enyl)thiobenzthiazole, having a gas chromatographic retention time identical with that of an authentic sample. The yield was 63% based on the quantity of 1,4-dibromo-1,1,2-trifluorobutane used in step (b) of Example 1. 2-(4,4-Difluorobut-3-enyl)thiobenzoxazole was prepared in the same way, but using 2-mercapto benzoxazole instead of 2-mercapto benzthiazole.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 6-(2,2,2-trifluoroethoxy)-4(3H)-pyrimidinethione (see Example 1B) (3 g) and 1,4-dibromo-3,4,4-trifluorobutane (see Example 3A) (3.86 g) were added to acetone (50 cm3) containing potassium carbonate (1.97 g) and the mixture stirred at ambient temperature for 7 hours. After standing for a further 16 hours, tlc showed the reaction to be incomplete, so the mixture was heated to reflux for 5 hours. The reaction was then allowed to cool, inorganic solids were filtered off and washed with more acetone. Evaporation of the combined organic layers at reduced pressure afforded a brown oil which was chromatographed on silica gel, eluting with 1:4 ethyl acetate:hexane. This gave the title pyrimidine (3.05 g). M+ =399; 1H NMR (CDCl3): δ2.2-2.4(2H,m); 3.25-3.50(2H,m); 4.68-4.95(1H,m); 4.8(2H,q); 6.73(1H,s); 8.58(1H,s); (oil). After standing for a further 16 hours the reaction was heated to reflux for 5 hours to cool inorganic solids were filtered off washed with more acetone Evaporation of the combined organic layers at reduced pressure afforded a brown oil which was chromatographed on silica gel eluting with 1:4 ethyl acetate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To the solution of 4-bromo-1,1-difluorobut-1-ene prepared in Example 6 was added potassium carbonate (10.76 g) and 2-mercaptobenzthiazole (9.18 g). The mixture was stirred at 55° C. for 6 hours and then at room temperature overnight. Gas-liquid chromatography of a sample of the reaction mixture showed that a small amount of 4-bromo-1,1-difluorobut-1-ene remained. More potassium carbonate (1.0 g) was added and the mixture heated for another two and a half hours at 55° C., when all of the bromo compound had been consumed. The mixture was cooled to room temperature and filtered. The residue was washed with acetone and the filtrate and washings combined and evaporated under reduced pressure to give the crude product (16.18 g). This was dissolved in dichloromethane. The solution was filtered and washed with dilute sodium hydroxide (2×25 ml) and with brine (2×25 ml), dried over magnesium sulphate, filtered, the filtrate evaporated to give 2-(4,4-difluorobut-3-enyl)thiobenzthiazole, having a gas chromatographic retention time identical with that of an authentic sample. The yield was 63% based on the quantity of 1,4-dibromo-1,1,2-trifluorobutane used in step (b) of Example 1. 2-(4,4-Difluorobut-3-enyl)thiobenzoxazole was prepared in the same way, but using 2-mercapto benzoxazole instead of 2-mercapto benzthiazole.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Mercaptothiazole (11.7 g) in acetone (30 cm3) containing 1,4-dibromo-1,1,2-trifluorobutane (27.0 g) was treated portionwise with anhydrous potassium carbonate (13.8 g) under an atmosphere of nitrogen. The reaction was stirred for 1.5 hours, filtered and the insolubles washed with further acetone (4×25 cm3). The filtrate was evaporated under reduced pressure and the residue fractionated by chromatography (silica, eluant 10% ethyl acetate in hexane) to give 2-(4-bromo-3,4,4-trifluorobutylthio)thiazole (29.5 g). 1H NMR: δ 22-2.5(2H,m); 3.2-3.6(2H,m); 4.7-5.0(1H,m); 7.23(1H,d); 7.68(1H,d). filtered the insolubles washed with further acetone (4×25 cm3) The filtrate was evaporated under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Mercaptothiazole (11.7 g) in acetone (30 cm3) containing 1,4-dibromo-1,1,2-trifluorobutane (27.0 g) was treated portionwise with anhydrous potassium carbonate (13.8 g) under an atmosphere of nitrogen. The reaction was stirred for 1.5 hours, filtered and the insolubles washed with further acetone (4×25 cm3). The filtrate was evaporated under reduced pressure and the residue fractionated by chromatography (silica, eluant 10% ethyl acetate in hexane) to give 2-(4-bromo-3,4,4-trifluorobutylthio)thiazole (29.5 g). 1H NMR: δ 2.2-2.5(2H,m); 3.2-3.6(2H,m); 4.7-5.0(1H,m); 7.23(1H,d); 7.68(1H,d). filtered the insolubles washed with further acetone (4×25 cm3) The filtrate was evaporated under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 2-Mercaptothiazole (11.7 g) in acetone (30 cm3) containing 1,4-dibromo-1,1,2-trifluorobutane (27.0 g) was treated portionwise with anhydrous potassium carbonate (13.8 g) under an atmosphere of nitrogen. The reaction was stirred for 1.5 hours, filtered and the insolubles washed with further acetone (4×25 cm3). The filtrate was evaporated under reduced pressure and the residue fractionated by chromatography (silica, eluant 10% ethyl acetate in hexane) to give 2-(4-bromo-3,4,4-trifluorobutylthio)thiazole (29.5 g). 1H NMR: δ 2.2-2.5(2H,m); 3.2-3.6(2H,m); 4.7-5.0(1H,m); 7.23(1H,d); 7.68(1H,d). filtered the insolubles washed with further acetone (4×25 cm3) The filtrate was evaporated under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To the solution of 4-bromo-1,1-difluorobut-1-ene prepared in Example 6 was added potassium carbonate (10.76 g) and 2-mercaptobenzthiazole (9.18 g). The mixture was stirred at 55° C. for 6 hours and then at room temperature overnight. Gas-liquid chromatography of a sample of the reaction mixture showed that a small amount of 4-bromo-1,1-difluorobut-1-ene remained. More potassium carbonate (1.0 g) was added and the mixture heated for another two and a half hours at 55° C., when all of the bromo compound had been consumed. The mixture was cooled to room temperature and filtered. The residue was washed with acetone and the filtrate and washings combined and evaporated under reduced pressure to give the crude product (16.18 g). This was dissolved in dichloromethane. The solution was filtered and washed with dilute sodium hydroxide (2×25 ml) and with brine (2×25 ml), dried over magnesium sulphate, filtered, the filtrate evaporated to give 2-(4,4-difluorobut-3-enyl)thiobenzthiazole, having a gas chromatographic retention time identical with that of an authentic sample. The yield was 63% based on the quantity of 1,4-dibromo-1,1,2-trifluorobutane used in step (b) of Example 1. 2-(4,4-Difluorobut-3-enyl)thiobenzoxazole was prepared in the same way, but using 2-mercapto benzoxazole instead of 2-mercapto benzthiazole.