1-amino-1-methylthiourea

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

Procedure: Under anhydrous condition, 35 g of diethyloxalate is added, dropwise, to a vigorously stirred solution of 21 g of 2-methyl-3-thiosemicarbazide, 32.4 g of fresh sodium methoxide, and 750 ml of methyl alcohol. The resulting suspension is heated at 60° C. for 4 hours, stirred overnight at room teperature, and heated at 70° C. for 15 hours. The white suspension is cooled to room temperature, 200 ml of ice water is added andthe reaction concentrated in vacuo. The residue is cooled to 0° C. and made acidic with 2N hydrochloric acid. The reaction mixture is concentrated, ethyl alcohol is added and the suspension is heated to boiling. The white precipitate is collected, washed with hexane and dried to give 11 g of the crude product. Eight grams of the crude product is heated in methylene chloride and filtered while hot. The collected solid is resuspended in methyl alcohol and a solution of 4N potassium-2-ethyl hexanoate is added. The mixture is cooled to 0° C. and the precipitate collected. The solid is dissolvd in water, filtered, and 2N hydrochloric acid is added to the clear 0° C. solution. The resulting precipitate is collected and dried to give 4.1 g of the pure product. 13C NMR(CDCl3):δ 44,145, 150.115, 152.559, 169.786. heated at 70° C. for 15 hours The white suspension is cooled to room temperature concentrated in vacuo The residue is cooled to 0° C. The reaction mixture is concentrated ethyl alcohol is added the suspension is heated to boiling The white precipitate is collected washed with hexane dried to give 11 g of the crude product filtered while hot a solution of 4N potassium-2-ethyl hexanoate is added The mixture is cooled to 0° C. the precipitate collected The solid is dissolvd in water filtered 2N hydrochloric acid is added to the clear 0° C. solution The resulting precipitate is collected dried

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

Procedure: Under anhydrous condition, 35 g of diethyloxalate is added, dropwise, to a vigorously stirred solution of 21 g of 2-methyl-3-thiosemicarbazide, 32.4 g of fresh sodium methoxide, and 750 ml of methyl alcohol. The resulting suspension is heated at 60° C. for 4 hours, stirred overnight at room temperature, and heated at 70° C. for 15 hours. The white suspension is cooled to room temperature, 200 ml of ice water is added and the reaction concentrated in vacuo. The residue is cooled to 0° C. and made acidic with 2N hydrochloric acid. The reaction mixture is concentrated,ethyl alcohol is added and the suspension is heated to boiling. The white precipitate is collected, washed with hexane and dried to give 11 g of the crude product. Eight grams of the crude product is heated in methylene chloride and filtered while hot. The collected solid is resuspended in methyl alcohol and a solution of 4N potassium-2-ethyl hexanoate is added. The mixture is cooled to 0° C. and the precipitate collected. The solid is dissolved in water, filtered,and 2N hydrochloric acid is added to the clear 0° C. solution. The resulting precipitate is collected and dried to give 4.1 g of the pure product. heated at 70° C. for 15 hours The white suspension is cooled to room temperature the reaction concentrated in vacuo The residue is cooled to 0° C. is added the suspension is heated to boiling The white precipitate is collected washed with hexane dried to give 11 g of the crude product filtered while hot a solution of 4N potassium-2-ethyl hexanoate is added The mixture is cooled to 0° C. the precipitate collected The solid is dissolved in water is added to the clear 0° C. solution The resulting precipitate is collected dried

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

Procedure: Under anhydrous condition, 35 g of diethyloxalate is added, dropwise, to a vigorously stirred solution of 21 g of 2-methyl-3-thiosemicarbazide, 32.4 g of fresh sodium methoxide, and 750 ml of methyl alcohol. The resulting suspension is heated at 60° C. for 4 hours, stirred overnight at room temperature, and heated at 70° C. for 15 hours. The white suspension is cooled to room temperature, 200 ml of ice water is added and the reaction concentrated in vacuo. The residue is cooled to 0° C. and made acidic with 2N hydrochloric acid. The reaction mixture is concentrated, ethyl alcohol is added and the suspension is heated to boiling. The white precipitate is collected, washed with hexane and dried to give 11 g of the crude product. Eight grams of the crude product is heated in methylene chloride and filtered while hot. The collected solid is resuspended in methyl alcohol and a solution of 4N potassium-2-ethyl hexanoate is added. The mixture is cooled to 0° C. and the precipitate collected. The solid is dissolved in water, filtered, and 2N hydrochloric acid is added to the clear 0° C. solution. The resulting precipitate is collected and dried to give 4.1 g of the pure product. heated at 70° C. for 15 hours The white suspension is cooled to room temperature the reaction concentrated in vacuo The residue is cooled to 0° C. The reaction mixture is concentrated ethyl alcohol is added the suspension is heated to boiling The white precipitate is collected washed with hexane dried to give 11 g of the crude product filtered while hot a solution of 4N potassium-2-ethyl hexanoate is added The mixture is cooled to 0° C. the precipitate collected The solid is dissolved in water filtered 2N hydrochloric acid is added to the clear 0° C. solution The resulting precipitate is collected dried

Conditions: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 4-cyanobenzoic acid (74.8 mmol, 11 g), 2-methylthiosemicarbazide (5a) (74.8 mmol, 13.42 g) in anhydrous dioxane (110 mL) at 70° C., POCl3 (89.65 mmol, 76.76 mL) was added, and the mixture was warmed at 95° C. for 4 hours. The solvent was removed by distillation under reduced pressure to give a crude material which was basified at pH 8-7 with a saturated solution of NaHCO3. The aqueous phase was extracted with dichloromethane. The organic layer was washed with water and saturated solution of NaCl, dried over magnesium sulfate, filtered, and distilled to give a residue which was purified by silica gel chromatography (eluted with a gradient of cyclohexane/ethyl acetate finishing with the ratio 90:10) to afford 8.5 g of the title compound. Yield: 42%. The solvent was removed by distillation under reduced pressure to give a crude material which The aqueous phase was extracted with dichloromethane The organic layer was washed with water and saturated solution of NaCl dried over magnesium sulfate filtered distilled to give a residue which was purified by silica gel chromatography ( eluted with a gradient of cyclohexane/ethyl acetate finishing with the ratio 90:10)

Conditions: temp:95.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a mixture of 4-methylsulfonyl-benzoic acid (2.5 mmol, 500 mg), 2-methylthiosemicarbazide (5a) (2.5 mmol, 468 mg) in anhydrous dioxane (5 mL) at 65° C., POCl3 (3 mmol, 280 μL) was added, and the mixture was warmed at 95° C. for 5 hours. The solvent was removed by distillation under reduced pressure to give a crude material which was basified at pH 8-7 with a saturated solution of NaHCO3. The aqueous phase was extracted with dichloromethane. The organic layer was washed with saturated solution of NaCl, dried over magnesium sulfate, filtered, and distilled to give a residue which was purified by silica gel chromatography (eluted with a gradient of cyclohexane/ethyl acetate finishing with the ratio 80:20) to afford 230 mg of the title compound. Yield: 26%. The solvent was removed by distillation under reduced pressure to give a crude material which The aqueous phase was extracted with dichloromethane The organic layer was washed with saturated solution of NaCl dried over magnesium sulfate filtered distilled to give a residue which was purified by silica gel chromatography ( eluted with a gradient of cyclohexane/ethyl acetate finishing with the ratio 80:20)