1,2-diethylhydrazine;dihydrochloride

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

Procedure: A stirred solution of 4.03 g (0.025 moles) of 1,2-diethylhydrazine dihydrochloride and 6.72 g. (0.026 moles) of 1,3-dimorpholino-2-nitropropane in a mixture of 28 ml of methanol and 16 ml of toluene was heated at reflux for 3 hours. The solvents were evaporated under reduced pressure and the residue was resuspended in 100 ml of toluene. The solid morpholine hydrochloride was removed by filtration, leaving a solution of 4-nitro-1,2-diethyl-pyrazolidine in solution. To the toluene solution was added 60 ml anhydrous ethanol and 2 g. of Raney Nickel which had been washed three times with anhydrous ethanol. The mixture was hydrogenated at about 30 psi. hydrogen pressure. The mixture was filtered carefully under nitrogen to prevent ignition. Evaporation of solvents and distillation at reduced pressure gave colorless liquid product weighing 1.95 g. (54% yield calculated on diethylhydrazine), b.p. 113°-115° C./40 mm. was heated at reflux for 3 hours The solvents were evaporated under reduced pressure The solid morpholine hydrochloride was removed by filtration

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

Procedure: A stirred solution of 4.03 g (0.025 moles) of 1,2-diethylhydrazine dihydrochloride and 6.72 g. (0.026 moles) of 1,3-dimorpholino-2-nitropropane in a mixture of 28 ml of methanol and 16 ml of toluene was heated at reflux for 3 hours. The solvents were evaporated under reduced pressure and the residue was resuspended in 100 ml of toluene. The solid morpholine hydrochloride was removed by filtration, leaving a solution of 4-nitro-1,2-diethyl-pyrazolidine in solution. To the toluene solution was added 60 ml anhydrous ethanol and 2 g. of Raney Nickel which had been washed three times with anhydrous ethanol. The mixture was hydrogenated at about 30 psi. hydrogen pressure. The mixture was filtered carefully under nitrogen to prevent ignition. Evaporation of solvents and distillation at reduced pressure gave colorless liquid product weighing 1.95 g. (54% yield calculated on diethylhydrazine), b.p. 113°-115° C./40 mm. was heated at reflux for 3 hours The solvents were evaporated under reduced pressure The solid morpholine hydrochloride was removed by filtration

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

Procedure: A stirred solution of 4.03 g. (0.025 moles) of 1,2-diethyl hydrazine dihydrochloride and 6.72 g. (0.026 moles) of 1,3-dimorpholino-2-nitropropane in a mixture of 28 ml of methanol and 16 ml of toluene was heated at reflux for 3 hours. The solvents were evaporated under reduced pressure and the residue was re-suspended in toluene. The solid (mostly morpholine hydrochloride) was removed by filtration, leaving a solution of the title compound in toluene. Evaporation of the toluene gave an oil weighing 5.1 g., the free base of the title compound with minor impurity. Column chromatography on Florisil, eluting with toluene, gave pure title compound which was obtained as an oil by evaporation of toluene under reduced pressure. The product was characterized as follows: Infra Red (CHCl3, microns) 6.46 (S), 6.94 (M), 7.27 (S) and 9.82 (M); Nuclear Magnetic Resonance (CDCL3,δ)=5.18 (m, 1H), 3.16-3.75 with weight center at 3.47 (m, 4H), 2.56 (q, 7.7HZ, 4H), 1.07 (t, 7.7 HZ, 6H); Mass Spec: M+ 173. was heated at reflux for 3 hours The solvents were evaporated under reduced pressure The solid (mostly morpholine hydrochloride) was removed by filtration

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

Procedure: A stirred solution of 4.03 g. (0.025 moles) of 1,2-diethyl hydrazine dihydrochloride and 6.72 g. (0.026 moles) of 1,3-dimorpholino-2-nitropropane in a mixture of 28 ml of methanol and 16 ml of toluene was heated at reflux for 3 hours. The solvents were evaporated under reduced pressure and the residue was re-suspended in toluene. The solid (mostly morpholine hydrochloride) was removed by filtration, leaving a solution of the title compound in toluene. Evaporation of the toluene gave an oil weighing 5.1 g., the free base of the title compound with minor impurity. Column chromatography on Florisil, eluting with toluene, gave pure title compound which was obtained as an oil by evaporation of toluene under reduced pressure. The product was characterized as follows: Infra Red (CHCl3, microns) 6.46 (S), 6.94 (M), 7.27 (S) and 9.82 (M); Nuclear Magnetic Resonance (CDCL3,δ)=5.18 (m, 1H), 3.16-3.75 with weight center at 3.47 (m, 4H), 2.56 (q, 7.7HZ, 4H), 1.07 (t, 7.7 HZ, 6H); Mass Spec: M+ 173. was heated at reflux for 3 hours The solvents were evaporated under reduced pressure The solid (mostly morpholine hydrochloride) was removed by filtration

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1,2-Diethylhydrazine dihydrochloride (1.2 equiv., 0.6 mmol, 97 mg), bromobenzene (1.0 equiv., 0.5 mmol, 0.05 mL), Pd(OAc)2 (0.05 equiv, 0.025 mmol, 6 mg), BINAP (0.05 equiv., 0.025 mmol, 16 mg), and NaOtBu (3.8 equiv., 1.9 mmol, 183 mg) and diisopropylamine (2 mL) were added to a flame dried test tube which was capped with a septum and purged briefly with argon (˜1 min.) and then heated to 80° C. for 4 hours. The reaction was then cooled to room temperature, diluted with Et2O (2 mL), filtered through Celite and concentrated under vacuum. The crude mixture was purified by flash column chromatography (2% EtOAc/Hex) to give the title product as a viscous yellow oil (27 mg, 0.16 mmol, 33% yield). dried test tube which was capped with a septum purged briefly with argon (˜1 min.) The reaction was then cooled to room temperature diluted with Et2O (2 mL) filtered through Celite concentrated under vacuum The crude mixture was purified by flash column chromatography (2% EtOAc/Hex)

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

Procedure: A suspension of tert-butyl 4-chloro-3-(chloromethyl)-2-butenoate (1.2 g, 5.3 mmol), potassium carbonate (4.0 g, 29 mmol), diethylhydrazine dihydrochloride (1.3 g, 8.0 mmol) and potassium iodide (0.86 g, 5.2 mmol) in acetonitrile was stirred at room temperature for 3 days. The mixture was filtered through celite, concentrated and purified by flash chromatography on silica gel eluting ethyl acetate:hexane (20:80, v;v) to give the tert-butyl (1,2-diethyl-4-pyrazolidinylidene)acetate (1.05 g, 82%) as an oil, MS (M+H)+=241. The mixture was filtered through celite, concentrated purified by flash chromatography on silica gel eluting ethyl acetate:hexane (20:80, v;v)

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

Procedure: A suspension of tert-butyl 4-chloro-3-(chloromethyl)-2-butenoate (1.2 g, 5.3 mmol), potassium carbonate (4.0 g, 29 mmol), diethylhydrazine dihydrochloride (1.3 g, 8.0 mmol) and potassium iodide (0.86 g, 5.2 mmol) in acetonitrile was stirred at room temperature for 3 days. The mixture was filtered through celite, concentrated and purified by flash chromatography on silica gel eluting ethyl acetate:hexane (20:80, v;v) to give the tert-butyl (1,2-diethyl-4-pyrazolidinylidene)acetate (1.05 g, 82%) as an oil, MS (M+H)+=241. The mixture was filtered through celite, concentrated purified by flash chromatography on silica gel eluting ethyl acetate:hexane (20:80, v;v)

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

Procedure: A suspension of tert-butyl 4-chloro-3-(chloromethyl)-2-butenoate (1.2 g, 5.3 mmol), potassium carbonate (4.0 g, 29 mmol), diethylhydrazine dihydrochloride (1.3 g, 8.0 mmol) and potassium iodide (0.86 g, 5.2 mmol) in acetonitrile was stirred at room temperature for 3 days. The mixture was filtered through celite, concentrated and purified by flash chromatography on silica gel eluting ethyl acetate:hexane (20:80, v;v) to give the tert-butyl (1,2-diethyl-4-pyrazolidinylidene)acetate (1.05 g, 82%) as an oil, MS (M+H)+=241. The mixture was filtered through celite, concentrated purified by flash chromatography on silica gel eluting ethyl acetate:hexane (20:80, v;v)

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

Procedure: A stirred solution of 4.03 g (0.025 moles) of 1,2-diethylhydrazine dihydrochloride and 6.72 g. (0.026 moles) of 1,3-dimorpholino-2-nitropropane in a mixture of 28 ml of methanol and 16 ml of toluene was heated at reflux for 3 hours. The solvents were evaporated under reduced pressure and the residue was resuspended in 100 ml of toluene. The solid morpholine hydrochloride was removed by filtration, leaving a solution of 4-nitro-1,2-diethyl-pyrazolidine in solution. To the toluene solution was added 60 ml anhydrous ethanol and 2 g. of Raney Nickel which had been washed three times with anhydrous ethanol. The mixture was hydrogenated at about 30 psi. hydrogen pressure. The mixture was filtered carefully under nitrogen to prevent ignition. Evaporation of solvents and distillation at reduced pressure gave colorless liquid product weighing 1.95 g. (54% yield calculated on diethylhydrazine), b.p. 113°-115° C./40 mm. was heated at reflux for 3 hours The solvents were evaporated under reduced pressure The solid morpholine hydrochloride was removed by filtration

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

Procedure: A stirred solution of 4.03 g. (0.025 moles) of 1,2-diethyl hydrazine dihydrochloride and 6.72 g. (0.026 moles) of 1,3-dimorpholino-2-nitropropane in a mixture of 28 ml of methanol and 16 ml of toluene was heated at reflux for 3 hours. The solvents were evaporated under reduced pressure and the residue was re-suspended in toluene. The solid (mostly morpholine hydrochloride) was removed by filtration, leaving a solution of the title compound in toluene. Evaporation of the toluene gave an oil weighing 5.1 g., the free base of the title compound with minor impurity. Column chromatography on Florisil, eluting with toluene, gave pure title compound which was obtained as an oil by evaporation of toluene under reduced pressure. The product was characterized as follows: Infra Red (CHCl3, microns) 6.46 (S), 6.94 (M), 7.27 (S) and 9.82 (M); Nuclear Magnetic Resonance (CDCL3, δ)=5.18 (m, 1H), 3.16-3.75 with weight center at 3.47 (m, 4H), 2.56 (q, 7.7HZ, 4H), 1.07 (t, 7.7 HZ, 6H); Mass Spec: M+ 173. was heated at reflux for 3 hours The solvents were evaporated under reduced pressure The solid (mostly morpholine hydrochloride) was removed by filtration

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1,2-Diethylhydrazine dihydrochloride (1.2 equiv., 0.6 mmol, 97 mg), bromobenzene (1.0 equiv., 0.5 mmol, 0.05 mL), Pd(OAc)2 (0.05 equiv, 0.025 mmol, 6 mg), BINAP (0.05 equiv., 0.025 mmol, 16 mg), and NaOtBu (3.8 equiv., 1.9 mmol, 183 mg) and diisopropylamine (2 mL) were added to a flame dried test tube which was capped with a septum and purged briefly with argon (˜1 min.) and then heated to 80° C. for 4 hours. The reaction was then cooled to room temperature, diluted with Et2O (2 mL), filtered through Celite and concentrated under vacuum. The crude mixture was purified by flash column chromatography (2% EtOAc/Hex) to give the title product as a viscous yellow oil (27 mg, 0.16 mmol, 33% yield). dried test tube which was capped with a septum purged briefly with argon (˜1 min.) The reaction was then cooled to room temperature diluted with Et2O (2 mL) filtered through Celite concentrated under vacuum The crude mixture was purified by flash column chromatography (2% EtOAc/Hex)

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

Procedure: A stirred solution of 4.03 g (0.025 moles) of 1,2-diethylhydrazine dihydrochloride and 6.72 g. (0.026 moles) of 1,3-dimorpholino-2-nitropropane in a mixture of 28 ml of methanol and 16 ml of toluene was heated at reflux for 3 hours. The solvents were evaporated under reduced pressure and the residue was resuspended in 100 ml of toluene. The solid morpholine hydrochloride was removed by filtration, leaving a solution of 4-nitro-1,2-diethyl-pyrazolidine in solution. To the toluene solution was added 60 ml anhydrous ethanol and 2 g. of Raney Nickel which had been washed three times with anhydrous ethanol. The mixture was hydrogenated at about 30 psi. hydrogen pressure. The mixture was filtered carefully under nitrogen to prevent ignition. Evaporation of solvents and distillation at reduced pressure gave colorless liquid product weighing 1.95 g. (54% yield calculated on diethylhydrazine), b.p. 113°-115° C./40 mm. was heated at reflux for 3 hours The solvents were evaporated under reduced pressure The solid morpholine hydrochloride was removed by filtration