1-chloro-2-isocyanato-3-methylbenzene

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: A mixture of 8.14 g (0.060 mol) of 2-amino-1,4,5,6-tetrahydropyrimidine hydrochloride, 6.0 g (0.075 mol) of 50% NaOH and 75 ml of THF was stirred for 0.5 hours at room temperature and then 15 g Na2SO4 was added. After stirring for 0.5 hours, a solution of 6.70 g (0.040 mol) of 2-chloro-6-methylphenyl isocyanate in 50 ml of THF was added over a period of 0.5 hours. After stirring for 1 hour, the reaction mixture was filtered, the filtrate evaporated in vacuo and the residue dissolved in 25 ml of 10% HCl and 25 ml of H2O with warming. After filtration through diatomaceous earth chilling in ice gave the crystalline hydrochloride which was recrystallized from cold H2O after treatment with charcoal affording 7.15 g (59%). This material was dried in vacuo (20° C., 5 mm Hg) to constant weight to give 7.11 g (59%) of pure N-(2-chloro-6-methylphenyl)-N'-(1,4,5,6-tetrahydropyrimidin-2-yl)urea monohydrochloride hemihydrate, m.p. (190) 215°-220° C. melts, then forms a new solid; m.p. 243°-245° C.; IR(CHCl3) 3224, 1713, 1677, 1641, 1543 cm-1 ; UV max. (MeOH) 236 (16,200) and 217 nm infl (21,500). After stirring for 0.5 hours After stirring for 1 hour the reaction mixture was filtered the filtrate evaporated in vacuo the residue dissolved in 25 ml of 10% HCl 25 ml of H2O with warming After filtration through diatomaceous earth chilling in ice

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 10.65 grams (0.05 mole) of 2-iminoimidazolidine hydroiodide in dimethylformamide is added dropwise with stirring over a 15 minute period to a cooled to 5° C. suspension of 397.5 milligrams (0.05 mole) of lithium hydride in 50 milliliters of dry dimethylformamide under nitrogen whereupon hydrogen evolution is observed. While stirring is continued, the mixture is allowed to gradually warm to room temperature. Thereafter, the reaction mixture is cooled to 0°-5° C. and a solution of 5.0 grams (0.03 mole) of 2-chloro-6-methylphenyl isocyanate in 25 milliliters of dry dimethylformamide is added dropwise over a two hour period. After completion of the addition, the mixture is allowed to warm gradually to room temperature while the stirring under nitrogen atmosphere is continued overnight to obtain the desired N-(2-chloro-6-methylphenyl)-N'-(2-imidazolidinylidene)urea product which remains in solution. The product is recovered from the reaction mixture by (a) adding the mixture to 300 milliliters of ice water with stirring, (b) lowering the pH below 2 with aqueous 10 percent hydrochloric acid to precipitate acid insoluble material (c) filtering, (d) basifying the filtrate to pH 8-9 with solid potassium carbonate, and (e) saturating the solution with solid sodium chloride to precipitate the desired N-(2-chloro-6-methylphenyl)-N'-(2-imidazolidinylidene)urea free base as a white solid. The product after washing thoroughly with water has a melting point of 169°-171° C. While stirring to gradually warm to room temperature Thereafter, the reaction mixture is cooled to 0°-5° C. After completion of the addition to warm gradually to room temperature while the stirring under nitrogen atmosphere is continued overnight

Conditions: temp:5.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 10.65 grams (0.05 mole) of 2-iminoimidazolidine hydroiodide in dimethylformamide is added dropwise with stirring over a 15 minute period to a cooled to 5° C. suspension of 397.5 milligrams (0.05 mole) of lithium hydride in 50 milliliters of dry dimethylformamide under nitrogen whereupon hydrogen evolution is observed. While stirring is continued, the mixture is allowed to gradually warm to room temperature. Thereafter, the reaction mixture is cooled to 0°-5° C. and a solution of 5.0 grams (0.03 mole) of 2-chloro-6-methylphenyl isocyanate in 25 milliliters of dry dimethylformamide is added dropwise over a two hour period. After completion of the addition, the mixture is allowed to warm gradually to room temperature while the stirring under nitrogen atmosphere is continued overnight to obtain the desired N-(2-chloro-6-methylphenyl)-N'-(2-imidazolidinylidene)urea product which remains in solution. The product is recovered from the reaction mixture by (a) adding the mixture to 300 milliliters of ice water with stirring, (b) lowering the pH below 2 with aqueous 10 percent hydrochloric acid to precipitate acid insoluble material (c) filtering, (d) basifying the filtrate to pH 8-9 with solid potassium carbonate, and (e) saturating the solution with solid sodium chloride to precipitate the desired N-(2-chloro-6-methylphenyl)-N'-(2-imidazolidinylidene)urea free base as a white solid. The product after washing thoroughly with water has a melting point of 169°-171° C. While stirring to gradually warm to room temperature Thereafter, the reaction mixture is cooled to 0°-5° C. After completion of the addition to warm gradually to room temperature while the stirring under nitrogen atmosphere is continued overnight

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

Procedure: A mixture of 8.14 g (0.060 mol) of 2-amino-1,4,5,6-tetrahydropyrimidine hydrochloride, 6.0 g (0.075 mol) of 50% NaOH and 75 ml of THF was stirred for 0.5 hours at room temperature and then 15 g Na2SO4 was added. After stirring for 0.5 hours, a solution of 6.70 g (0.040 mol) of 2-chloro-6-methylphenyl isocyanate in 50 ml of THF was added over a period of 0.5 hours. After stirring for 1 hour, the reaction mixture was filtered, the filtrate evaporated in vacuo and the residue dissolved in 25 ml of 10% HCl and 25 ml of H2O with warming. After filtration through diatomaceous earth chilling in ice gave the crystalline hydrochloride which was recrystallized from cold H2O after treatment with charcoal affording 7.15 g (59%). This material was dried in vacuo (20° C., 5 mm Hg) to constant weight to give 7.11 g (59%) of pure N-(2-chloro-6-methylphenyl)-N'-(1,4,5,6-tetrahydropyrimidin-2-yl)urea monohydrochloride hemihydrate, m.p. (190) 215°-220° C. melts, then forms a new solid; m.p. 243°-245° C.; IR(CHCl3) 3224, 1713, 1677, 1641, 1543 cm-1 ; UV max. (MeOH) 236 (ε16,200) and 217 nm infl (ε21,500). After stirring for 0.5 hours After stirring for 1 hour the reaction mixture was filtered the filtrate evaporated in vacuo the residue dissolved in 25 ml of 10% HCl 25 ml of H2O with warming After filtration through diatomaceous earth chilling in ice

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

Procedure: The urea was prepared from 2-hydroxy 4-nitro aniline (500 mg, 3.24 mmol) and 2-chloro 6-methyl phenyl isocyanate by general Method B. It was purified by dilution with methylene chloride and precipitation with hexane. Filtering afforded the desired compound (0.31 g, 29%). EI-MS m/z 322 (M+H)+ It was purified by dilution with methylene chloride and precipitation with hexane Filtering

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

Procedure: The urea was prepared from 2-hydroxy 4-nitro aniline (500 mg, 3.24 mmol) and 2-chloro 6-methyl phenyl isocyanate by general Method B. It was purified by dilution with methylene chloride and precipitation with hexane. Filtering afforded the desired compound (0.31 g, 29%). EI-MS m/z 322 (M+H)+ It was purified by dilution with methylene chloride and precipitation with hexane Filtering

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

Procedure: The urea was prepared from 2-hydroxy 4-nitro aniline (500 mg, 3.24 mmol) and 2-chloro 6-methyl phenylisocyanate by general Method B. It was purified by dilution with methylene chloride and precipitation with hexane. Filtering afforded the desired compound(0.31 g, 29%). EI-MS m/z 322(M+H)+. It was purified by dilution with methylene chloride and precipitation with hexane Filtering

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

Procedure: The urea was prepared from 2-hydroxy 4-nitro aniline (500 mg, 3.24 mmol) and 2-chloro 6-methyl phenylisocyanate by general Method B. It was purified by dilution with methylene chloride and precipitation with hexane. Filtering afforded the desired compound(0.31 g, 29%). EI-MS m/z 322(M+H)+. It was purified by dilution with methylene chloride and precipitation with hexane Filtering

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

Procedure: A mixture of 8.14 g (0.060 mol) of 2-amino-1,4,5,6-tetrahydropyrimidine hydrochloride, 6.0 g (0.075 mol) of 50% NaOH and 75 ml of THF was stirred for 0.5 hours at room temperature and then 15 g Na2SO4 was added. After stirring for 0.5 hours, a solution of 6.70 g (0.040 mol) of 2-chloro-6-methylphenyl isocyanate in 50 ml of THF was added over a period of 0.5 hours. After stirring for 1 hour, the reaction mixture was filtered, the filtrate evaporated in vacuo and the residue dissolved in 25 ml of 10% HCl and 25 ml of H2O with warming. After filtration through diatomaceous earth chilling in ice gave the crystalline hydrochloride which was recrystallized from cold H2O after treatment with charcoal affording 7.15 g (59%). This material was dried in vacuo (20° C., 5 mm Hg) to constant weight to give 7.11 g (59%) of pure N-(2-chloro-6-methylphenyl)-N'-(1,4,5,6-tetrahydropyrimidin-2-yl)urea monohydrochloride hemihydrate, m.p. (190) 215°-220° C. melts, then forms a new solid; m.p. 243°-245° C.; IR(CHCl3) 3224, 1713, 1677, 1641, 1543 cm-1 ; UV max. (MeOH) 236 (16,200) and 217 nm infl (21,500). After stirring for 0.5 hours After stirring for 1 hour the reaction mixture was filtered the filtrate evaporated in vacuo the residue dissolved in 25 ml of 10% HCl 25 ml of H2O with warming After filtration through diatomaceous earth chilling in ice