2,6-dimethoxybenzamide

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

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

Procedure: 5.0 of 2,6-dimethoxybenzoic acid suspended in 200 ml of anhydrous methylene chloride are added with 7.65 ml of triethylamine and then with 3.6 ml of oxalyl chloride. The mixture after being stirred at room temperature for three hours is concentrated under reduced pressure, cooled with ice, added with 10 ml of concentrated ammonia, then stirred for half an hour, then again evaporated under reduced pressure, taken with water and filtered. The solid so obtained, after crystallization from methanol, gives 2,6-dimethoxybenzamide with melting point 208°-209° C.; yield is 54%. is concentrated under reduced pressure cooled with ice added with 10 ml of concentrated ammonia stirred for half an hour again evaporated under reduced pressure filtered The solid so obtained after crystallization from methanol

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

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

Procedure: A solution of 300 mg of 2,6-dimethoxybenzoyl chloride in 20 ml of toluene containing 300 mg of 2-amino-5-[(2-acetoxy-1-acetoxymethyl)-1-methylethyl]-1,3,4-thiadiazole was heated at reflux for eighteen hours. The reaction mixture was cooled to room temperature and diluted with pentane. A solid precipitate which formed was collected by filtration and air dried to give N-[5-(2-acetoxy-1-acetoxymethyl)-1-methylethyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide in 3% yield. at reflux for eighteen hours A solid precipitate which formed was collected by filtration and air dried

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

Procedure: The preferred compounds of this invention are N-[5-(4-chlorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethylbenzamide, N-[5-(4-chlorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide, N-[5-(4-fluorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethylbenzamide, N-[5-(4-trifluoromethylphenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethylbenzamide, N-[5-(4-fluorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide, N-[5-(3-trifluoromethylphenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide, N-[5-(2-benxo[b]furyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide, N-[5-(3-chlorophenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide, N-[5-(3,5-bis-(trifluoromethyl)phenyl]-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide, N-[5-(4-trifluoromethylphenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide, N-[5-(5-fluoro-2-benzo[b]furyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide, N-[5-(5-chloro-2-benzo]b]furyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide and N-[5-(4-pentfluorethoxyphenyl)-1,3,4-thiadiazol-2-yl]-2,6-dimethoxybenzamide.

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

Procedure: A mixture of 2,6-dimethoxybenzamide (68 g.; prepared as described by P. Grammaticakis, Compt. rend., 1968, 267C,152), methyl fluorosulphonate (45 g.) and anhydrous methylene dichloride (1 l.) was stirred at room temperature for 3 hours. The solution was evaporated in vacuo, and the residue treated with anhydrous diethyl ether to give crude methyl 2,6-dimethoxybenzimidate fluorosulphonate as a white solid, m.p. 115°-137° C. This was dissolved in anhydrous ethanol (1 l.) and the solution was cooled to 0° C. Anhydrous ethanolic ammonia (350 ml.; prepared by saturation of anhydrous ethanol with anhydrous ammonia at 0° C.) was added, and the mixture kept at room temperature for 4 days. The solution was filtered, the filtrate was evaporated in vacuo, the residue was treated with an excess of 2N sodium hydroxide solution, and the precipitated solid was filtered off, washed with water and recrystallised from isopropanol to give 2,6-dimethoxybenzamidine (15 g.), m.p. 170°-174° C. The solution was evaporated in vacuo the residue treated with anhydrous diethyl ether to give crude methyl 2,6-dimethoxybenzimidate fluorosulphonate as a white solid, m.p. 115°-137° C the solution was cooled to 0° C the mixture kept at room temperature for 4 days The solution was filtered the filtrate was evaporated in vacuo the residue was treated with an excess of 2N sodium hydroxide solution the precipitated solid was filtered off washed with water recrystallised from isopropanol

Conditions: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 167 g. portion of 2,6-dimethoxybenzamide was slurried in 2 l. of toluene under a nitrogen atmosphere. To this solution was added 145 g. of oxalyl chloride over a one hour period. The solution was heated to 60° C. and maintained at this temperature overnight. HCl was allowed to escape while attempting to prevent water from condensing and going into the reaction mixture. Nitrogen was bubbled subsurface through a gas inlet tube while heating the reaction mixture at reflux (about 110° C.) for 11/2 hours. As stirring continued, the mixture was allowed to come to about 30° C. The solution was filtered through infusorial earth while maintaining a nitrogen atmosphere and the solvent was removed in vacuo. Yield 185 g. (97%). The oil was then stored under nitrogen. To this solution was added 145 g maintained at this temperature overnight from condensing Nitrogen was bubbled subsurface through a gas inlet tube while heating the reaction mixture at reflux (about 110° C.) for 11/2 hours to come to about 30° C The solution was filtered through infusorial earth while maintaining a nitrogen atmosphere the solvent was removed in vacuo

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

Procedure: 5.0 of 2,6-dimethoxybenzoic acid suspended in 200 ml of anhydrous methylene chloride are added with 7.65 ml of triethylamine and then with 3.6 ml of oxalyl chloride. The mixture after being stirred at room temperature for three hours is concentrated under reduced pressure, cooled with ice, added with 10 ml of concentrated ammonia, then stirred for half an hour, then again evaporated under reduced pressure, taken with water and filtered. The solid so obtained, after crystallization from methanol, gives 2,6-dimethoxybenzamide with melting point 208°-209° C.; yield is 54%. is concentrated under reduced pressure cooled with ice added with 10 ml of concentrated ammonia stirred for half an hour again evaporated under reduced pressure filtered The solid so obtained after crystallization from methanol

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