5,11-dihydrobenzo[b][1,4]benzodiazepine-6-thione

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

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

Procedure: in a 250-ml., three-neck flask fitted with a condenser, is heated to reflux 6.25 g. of 5,10-dihydro-11H-dibenzo-[b,e][1,4]diazepine-11-thione (30.0 mmol.) and 10.8 g. of aminopropionaldehyde dimethyl acetal (90.0 mmol.) in 60 ml. of n-butanol, during 2 hours. An additional 60 ml. of n-butanol is added and the mixture is refluxed overnight (22 hours). At this point, 60 ml. of n-butanol is distilled from the reaction mixture and refluxing is maintained for an additional 18 hours. On cooling, 2.0 g. of crude starting material is obtained. This is added to the reaction mixture along with an additional 5.4 g. of aminopropionaldehyde acetal (40.0 mmol.) and heating is maintained over a weekend (65 hours). On cooling and removal of the solvent in vacuo, 10 g. of brown oil is obtained. The oil is dissolved in 80 ml. of concentrated sulfuric acid and stirred at room temperature under nitrogen for 10 hours. The reaction mixture is then poured into ice and carefully neutralized with 50% aqueous sodium hydroxide solution. The basic aqueous solution is extracted thoroughly with chloroform. The combined chloroform extracts are washed with brine, dried over anhydrous potassium carbonate and concentrated in vacuo. The resulting oil is taken up in ethyl acetate, treated with activated charcoal and filtered. On concentrating and cooling the filtered solution, 3.2 g. of 2-methyl-9H-dibenzo[b,f]imidazo[1,2-d][1,4]diazepine is obtained in 2 crops (yield 40%) of melting point 232°-236° C. , three-neck flask fitted with a condenser is heated to reflux 6.25 g the mixture is refluxed overnight (22 hours) of n-butanol is distilled from the reaction mixture refluxing is maintained for an additional 18 hours On cooling is obtained This is added to the reaction mixture along with an additional 5.4 g is maintained over a weekend (65 hours) On cooling removal of the solvent in vacuo, 10 g of brown oil is obtained The oil is dissolved in 80 ml The reaction mixture is then poured into ice The basic aqueous solution is extracted thoroughly with chloroform The combined chloroform extracts are washed with brine dried over anhydrous potassium carbonate concentrated in vacuo treated with activated charcoal filtered On concentrating cooling the filtered solution, 3.2 g

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

Procedure: in a 250-ml., three-neck flask fitted with a condenser, is heated to reflux 6.25 g. of 5,10-dihydro-11H-dibenzo-[b,e][1,4]diazepine-11-thione (30.0 mmol.) and 10.8 g. of aminopropionaldehyde dimethyl acetal (90.0 mmol.) in 60 ml. of n-butanol, during 2 hours. An additional 60 ml. of n-butanol is added and the mixture is refluxed overnight (22 hours). At this point, 60 ml. of n-butanol is distilled from the reaction mixture and refluxing is maintained for an additional 18 hours. On cooling, 2.0 g. of crude starting material is obtained. This is added to the reaction mixture along with an additional 5.4 g. of aminopropionaldehyde acetal (40.0 mmol.) and heating is maintained over a weekend (65 hours). On cooling and removal of the solvent in vacuo, 10 g. of brown oil is obtained. The oil is dissolved in 80 ml. of concentrated sulfuric acid and stirred at room temperature under nitrogen for 10 hours. The reaction mixture is then poured into ice and carefully neutralized with 50% aqueous sodium hydroxide solution. The basic aqueous solution is extracted thoroughly with chloroform. The combined chloroform extracts are washed with brine, dried over anhydrous potassium carbonate and concentrated in vacuo. The resulting oil is taken up in ethyl acetate, treated with activated charcoal and filtered. On concentrating and cooling the filtered solution, 3.2 g. of 2-methyl-9H-dibenzo[b,f]imidazo[1,2-d][1,4]diazepine is obtained in 2 crops (yield 40%) of melting point 232°-236° C. , three-neck flask fitted with a condenser is heated to reflux 6.25 g the mixture is refluxed overnight (22 hours) of n-butanol is distilled from the reaction mixture refluxing is maintained for an additional 18 hours On cooling is obtained This is added to the reaction mixture along with an additional 5.4 g is maintained over a weekend (65 hours) On cooling removal of the solvent in vacuo, 10 g of brown oil is obtained The oil is dissolved in 80 ml The reaction mixture is then poured into ice The basic aqueous solution is extracted thoroughly with chloroform The combined chloroform extracts are washed with brine dried over anhydrous potassium carbonate concentrated in vacuo treated with activated charcoal filtered On concentrating cooling the filtered solution, 3.2 g

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

Procedure: 5,10-Dihydro-11H-dibenzo[b,e][1,4]diazepine-11-thione (33.75 g., 150 mmol.) is suspended in 450 ml. of n-butyl alcohol and treated with 47.25 g. (450 mmol.) of commerical aminoacetaldehyde dimethyl acetal. The reagents are heated for 5.5 hours during which time the solution turns brown. The solution is cooled to room temperature and the solvent is removed in vacuo. The residue is dissolved in 600 ml. of hot ethyl acetate, filtered, concentrated to 400 ml. and cooled to give 36.0 g. (81%) of [(5H-dibenzo[b,e][1,4]diazepin-11-yl)amio]acetaldehyde dimethyl acetal of melting point 181°-182.5° C. A second crop (2.55 g., 5.7%) of melting point 181.5°-184° C. is also collected. The reagents are heated for 5.5 hours during which time the solution the solvent is removed in vacuo The residue is dissolved in 600 ml of hot ethyl acetate, filtered concentrated to 400 ml and cooled to give 36.0 g A second crop (2.55 g., 5.7%) of melting point 181.5°-184° C. is also collected

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

Procedure: 5,10-Dihydro-11H-dibenzo[b,e][1,4]diazepine-11-thione (33.75 g., 150 mmol.) is suspended in 450 ml. of n-butyl alcohol and treated with 47.25 g. (450 mmol.) of commerical aminoacetaldehyde dimethyl acetal. The reagents are heated for 5.5 hours during which time the solution turns brown. The solution is cooled to room temperature and the solvent is removed in vacuo. The residue is dissolved in 600 ml. of hot ethyl acetate, filtered, concentrated to 400 ml. and cooled to give 36.0 g. (81%) of [(5H-dibenzo[b,e][1,4]diazepin-11-yl)amio]acetaldehyde dimethyl acetal of melting point 181°-182.5° C. A second crop (2.55 g., 5.7%) of melting point 181.5°-184° C. is also collected. The reagents are heated for 5.5 hours during which time the solution the solvent is removed in vacuo The residue is dissolved in 600 ml of hot ethyl acetate, filtered concentrated to 400 ml and cooled to give 36.0 g A second crop (2.55 g., 5.7%) of melting point 181.5°-184° C. is also collected

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

Procedure: A solution of 0.6 g (2.7 mmol) of 5,10-dihydro-dibenzo[b,e][1,4]diazepin-11-thione [German Patent, DE-2,306,762, C.A. 79:126533a (1973)] in 10 mL 2-ethoxyethanol was treated with 0.6 mL (5.4 mmol) of 3-(aminomethyl)pyridine and heated at reflux overnight. The solvent was removed under reduced pressure and the residue taken up in EtOAc and washed three times with H2O, then saturated NaHCO3 solution and saturated NaCl solution. Drying over MgSO4 and removal of the solvent under reduced pressure left the crude product. Chromatography on silica gel, eluting with CHCl3 /MeOH (95/5) gave the product. On adding CH2Cl2, the product crystallized. There was obtained 459 mg (58.1% yield) of the pure product as a yellow solid, mp 150-152° C. The structure was confirmed by NMR and mass spectroscopy. (m+H)+ =301. heated at reflux overnight The solvent was removed under reduced pressure washed three times with H2O Drying over MgSO4 and removal of the solvent under reduced pressure left the crude product Chromatography on silica gel, eluting with CHCl3 /MeOH (95/5) gave the product the product crystallized

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

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

Procedure: in a 250-ml., three-neck flask fitted with a condenser, is heated to reflux 6.25 g. of 5,10-dihydro-11H-dibenzo-[b,e][1,4]diazepine-11-thione (30.0 mmol.) and 10.8 g. of aminopropionaldehyde dimethyl acetal (90.0 mmol.) in 60 ml. of n-butanol, during 2 hours. An additional 60 ml. of n-butanol is added and the mixture is refluxed overnight (22 hours). At this point, 60 ml. of n-butanol is distilled from the reaction mixture and refluxing is maintained for an additional 18 hours. On cooling, 2.0 g. of crude starting material is obtained. This is added to the reaction mixture along with an additional 5.4 g. of aminopropionaldehyde acetal (40.0 mmol.) and heating is maintained over a weekend (65 hours). On cooling and removal of the solvent in vacuo, 10 g. of brown oil is obtained. The oil is dissolved in 80 ml. of concentrated sulfuric acid and stirred at room temperature under nitrogen for 10 hours. The reaction mixture is then poured into ice and carefully neutralized with 50% aqueous sodium hydroxide solution. The basic aqueous solution is extracted thoroughly with chloroform. The combined chloroform extracts are washed with brine, dried over anhydrous potassium carbonate and concentrated in vacuo. The resulting oil is taken up in ethyl acetate, treated with activated charcoal and filtered. On concentrating and cooling the filtered solution, 3.2 g. of 2-methyl-9H-dibenzo[b,f]imidazo[1,2-d][1,4]diazepine is obtained in 2 crops (yield 40%) of melting point 232°-236° C. , three-neck flask fitted with a condenser is heated to reflux 6.25 g the mixture is refluxed overnight (22 hours) of n-butanol is distilled from the reaction mixture refluxing is maintained for an additional 18 hours On cooling is obtained This is added to the reaction mixture along with an additional 5.4 g is maintained over a weekend (65 hours) On cooling removal of the solvent in vacuo, 10 g of brown oil is obtained The oil is dissolved in 80 ml The reaction mixture is then poured into ice The basic aqueous solution is extracted thoroughly with chloroform The combined chloroform extracts are washed with brine dried over anhydrous potassium carbonate concentrated in vacuo treated with activated charcoal filtered On concentrating cooling the filtered solution, 3.2 g

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

Procedure: 5,10-Dihydro-11H-dibenzo[b,e][1,4]diazepine-11-thione (33.75 g., 150 mmol.) is suspended in 450 ml. of n-butyl alcohol and treated with 47.25 g. (450 mmol.) of commerical aminoacetaldehyde dimethyl acetal. The reagents are heated for 5.5 hours during which time the solution turns brown. The solution is cooled to room temperature and the solvent is removed in vacuo. The residue is dissolved in 600 ml. of hot ethyl acetate, filtered, concentrated to 400 ml. and cooled to give 36.0 g. (81%) of [(5H-dibenzo[b,e][1,4]diazepin-11-yl)amio]acetaldehyde dimethyl acetal of melting point 181°-182.5° C. A second crop (2.55 g., 5.7%) of melting point 181.5°-184° C. is also collected. The reagents are heated for 5.5 hours during which time the solution the solvent is removed in vacuo The residue is dissolved in 600 ml of hot ethyl acetate, filtered concentrated to 400 ml and cooled to give 36.0 g A second crop (2.55 g., 5.7%) of melting point 181.5°-184° C. is also collected

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

Procedure: A solution of 0.6 g (2.7 mmol) of 5,10-dihydro-dibenzo[b,e][1,4]diazepin-11-thione [German Patent, DE-2,306,762, C.A. 79:126533a (1973)] in 10 mL 2-ethoxyethanol was treated with 0.6 mL (5.4 mmol) of 3-(aminomethyl)pyridine and heated at reflux overnight. The solvent was removed under reduced pressure and the residue taken up in EtOAc and washed three times with H2O, then saturated NaHCO3 solution and saturated NaCl solution. Drying over MgSO4 and removal of the solvent under reduced pressure left the crude product. Chromatography on silica gel, eluting with CHCl3 /MeOH (95/5) gave the product. On adding CH2Cl2, the product crystallized. There was obtained 459 mg (58.1% yield) of the pure product as a yellow solid, mp 150-152° C. The structure was confirmed by NMR and mass spectroscopy. (m+H)+ =301. heated at reflux overnight The solvent was removed under reduced pressure washed three times with H2O Drying over MgSO4 and removal of the solvent under reduced pressure left the crude product Chromatography on silica gel, eluting with CHCl3 /MeOH (95/5) gave the product the product crystallized