4,5-dimethylbenzene-1,2-diamine

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: The 2,3-dimethyl-7-trifluoromethylphenazine was prepared in a 3-step process, starting with 4,5-dimethyl-1,2-phenylenediamine and 3-nitro-4-bromobenzotrifluoride. The nucleophilic substitution product being the biarylamine was then reduced with stannous chloride in conc. HCl to the diamino diphenylamine.

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

Procedure: To a stirred solution of 4,5-dimethylphenylene-1,2-diamine (680 mg, 5 mmol) in 4N HCl (12 mL) was added chloroacetic acid (940 mg, 10 mmol). The solution was then heated to reflux for 17 hours, then cooled to room temperature. Solid sodium carbonate was then added slowly, with stirring, until the pH of the solution was approximately 9.0, at which point a beige precipitate formed. The aqueous phase was then diluted with water (10 mL) and extracted repeatedly with ethyl acetate. The combined organic fractions were then dried, concentrated and the residue was purified by column chromatography on silica gel (10% MeOH in CH2Cl2) to afford the desired 2-(chloromethyl)-5,6-dimethylbenzimidazole (530 mg, 54%). 1H NMR (CDCl3) δ 1.59 (br s, 1H), 2.31 (s, 6H), 4.83 (s, 2H), 7.42 (s, 2H). The solution was then heated to reflux for 17 hours at which point a beige precipitate formed extracted repeatedly with ethyl acetate The combined organic fractions were then dried concentrated the residue was purified by column chromatography on silica gel (10% MeOH in CH2Cl2)

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

Procedure: To a stirred solution of 4,5-dimethylphenylene-1,2-diamine (680 mg, 5 mmol) in 4N HCl (12 mL) was added chloroacetic acid (940 mg, 10 mmol). The solution was then heated to reflux for 17 hours, then cooled to room temperature. Solid sodium carbonate was then added slowly, with stirring, until the pH of the solution was approximately 9.0, at which point a beige precipitate formed. The aqueous phase was then diluted with water (10 mL) and extracted repeatedly with ethyl acetate. The combined organic fractions were then dried, concentrated and the residue was purified by column chromatography on silica gel (10% MeOH in CH2Cl2) to afford the desired 2-(chloromethyl)-5,6-dimethylbenzimidazole (530 mg, 54%). 1H NMR (CDCl3) δ 1.59 (br s, 1H), 2.31 (s, 6H), 4.83 (s, 2H), 7.42 (s, 2H). The solution was then heated to reflux for 17 hours at which point a beige precipitate formed extracted repeatedly with ethyl acetate The combined organic fractions were then dried concentrated the residue was purified by column chromatography on silica gel (10% MeOH in CH2Cl2)

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

Procedure: Using the procedure of Step A of Example 1, 2.04 g of 4,5-dimethyl-1,2-phenylene diamine and 3.73 g of ethyl pentanimidoate hydrochloride [J.A.C.S., Vol. 64, p. 1827 (1942)] were reacted to obtain 3.48 g of crude product which was chromatographed on silica (eluant: methylene chloride-methanol (9-1)) to obtain 2.27 g of the expected compound melting at 110° C. An analytical sample was prepared by crystallization of 120 mg of the product from isopropyl ether to obtain 88 mg of product melting at 110° C. were reacted to obtain 3.48 g of crude product which was chromatographed on silica (eluant: methylene chloride-methanol (9-1))

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

Procedure: Using the procedure of Step A of Example 1, 2.04 g of 4,5-dimethyl-1,2-phenylene diamine and 3.73 g of ethyl pentanimidoate hydrochloride [J.A.C.S., Vol. 64, p. 1827 (1942)] were reacted to obtain 3.48 g of crude product which was chromatographed on silica (eluant: methylene chloride-methanol (9-1)) to obtain 2.27 g of the expected compound melting at 110° C. An analytical sample was prepared by crystallization of 120 mg of the product from isopropyl ether to obtain 88 mg of product melting at 110° C. were reacted to obtain 3.48 g of crude product which was chromatographed on silica (eluant: methylene chloride-methanol (9-1))

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 4-[5-chloro-4-(1,3-dioxolan-2-yl)-2-methylimidazol-1-yl]benzoylacetate from Preparation 5 (155 mg, 0.38 mmol), and 4,5-dimethyl-1,2-diaminobenzene (55 mg, 0.4 mmol) in toluene (4 ml) was heated at reflux for 4.5 hours, then evaporated to dryness and purified by flash chromatography (eluting with ethyl acetate) to afford a pale yellow gum. 1M HCl (2 ml) was added to a solution of the residue in THF (2 ml) and the mixture was heated to 70° C. for 1 hour. The THF was evaporated and the residue was partitioned between aqueous sodium bicarbonate and dichloromethane. The organic layer was dried over magnesium sulphate and evaporated. was heated at reflux for 4.5 hours evaporated to dryness purified by flash chromatography (eluting with ethyl acetate) to afford a pale yellow gum The THF was evaporated the residue was partitioned between aqueous sodium bicarbonate and dichloromethane The organic layer was dried over magnesium sulphate evaporated

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 4-[5-chloro-4-(1,3-dioxolan-2-yl)-2-methylimidazol-1-yl]benzoylacetate from Preparation 5 (155 mg, 0.38 mmol), and 4,5-dimethyl-1,2-diaminobenzene (55 mg, 0.4 mmol) in toluene (4 ml) was heated at reflux for 4.5 hours, then evaporated to dryness and purified by flash chromatography (eluting with ethyl acetate) to afford a pale yellow gum. 1M HCl (2 ml) was added to a solution of the residue in THF (2 ml) and the mixture was heated to 70° C. for 1 hour. The THF was evaporated and the residue was partitioned between aqueous sodium bicarbonate and dichloromethane. The organic layer was dried over magnesium sulphate and evaporated. was heated at reflux for 4.5 hours evaporated to dryness purified by flash chromatography (eluting with ethyl acetate) to afford a pale yellow gum The THF was evaporated the residue was partitioned between aqueous sodium bicarbonate and dichloromethane The organic layer was dried over magnesium sulphate evaporated

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

Procedure: Reaction of 30 g (0.22 mole) of 4,5-dimethyl-1,2-phenylenediamine with potassium ethylxanthate using the method described in Example 86 yielded 19 g of 5,6-dimethyl-2-mercaptobenzimidazole, as confirmed by the nmr and infrared spectra and by elemental analysis. The title compound (3.0 g) was prepared by the method of Example 84 using 3.5 g of 5,6-dimethyl-2-mercaptobenzimidazole instead of 2-mercaptobenzimidazole. Structure assignment was supported by the nmr spectrum.

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

Procedure: A mixture of 2.72 g (2.0 mmol) of 4,5-dimethyl-1,2-phenylenediamine and 1.92 g (21.3 mmol) of oxalic acid in 30 mL of 2N HCl was refluxed for 2.5 h and cooled to room temperature. The mixture was diluted with 20 mL of H2O, filtered, washed with water, and dried to leave a pale-brown solid 3.57 g (94%); mp>250° C.; 1H NMR (DMSO-d6,2.161 (s,6), 6.869 (s,2), 11.78 (s,2). was refluxed for 2.5 h filtered washed with water dried

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

Procedure: A mixture of 4,5-dimethyl-benzene-1,2-diamine (60 g) and diethyl oxalate (600 mL) was heated under reflux for 1 h and then cooled. The precipitate of 6,7-dimethyl-1,4-dihydro-quinoxaline-2,3-dione was filtered off and washed with 96% ethanol to give 38 g of the title compound. ESI-MS: m/z 191.1 [MH+], 403.3 [2MNa+]; required MW=190.2 was heated under reflux for 1 h cooled The precipitate of 6,7-dimethyl-1,4-dihydro-quinoxaline-2,3-dione was filtered off washed with 96% ethanol