N'-acetylacetohydrazide

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

Procedure: Glycolaldehyde (0.100 mmol, in dimeric form) was dissolved in 1.0 mL anhydrous hydrazine (Pierce or Aldrich Chemical Company) in a Pierce reacti-vial, and capped under nitrogen with a cap having a Pierce Tuf-bond teflon-silicone seal. The sample, after sitting at room temperature for 16 hours, was converted to the hydrazone derivative of glycolaldehyde which was evaporated to a resin-like material in a Speed-Vac concentrator. The sample was quantitatively transferred in a 1.0 mL volume of water into a 20 mL test tube, and 100 mg of sodium borohydride was added, which reduced the molecule to 2-hydrazinoethanol. After 24 hours, the sample was placed in an ice-water bath and 0.200 mL of glacial acetic acid was added, dropwise, over about a 30 second interval. The sample was diluted with 1.0 mL water. To it was added 200 mg of sodium bicarbonate and the bicarbonate was permitted to dissolve, with occasional mixing. Then, 0.100 mL acetic anhydride was added, followed by gentle swirling to dissolve all of it. After 10 minutes, another 0.100 mL acetic anhydride was added, the solution gently swirled to dissolve it, and, after an additional 50 minutes, the sample was diluted with 5.0 mL water and loaded on a column containing 10-12 mL of well-washed Dowex AG1-X8, 100-200 mesh, H+ form, to remove sodium. The column was washed with five additional washes of 10 mL water. The total eluate was rotary evaporated to near dryness, and then rotary evaporated to dryness five times with 20 mL of 1% acetic acid in methanol, and three times with 20 mL methanol alone, to remove boric acid, thereby resulting in 2-(N,N'-diacetylhydrazino)-ethanol. This sample contained some additional N,N'-diacetylhydrazine. It was either directly O-peracetylated on the free hydroxyl group as described below, or it was chromatographically purified prior to O-acetylation by high-performance liquid chromatography on a Waters GlycoPak N column (7.8×300 mm), using isocratic acetonitrile/water, at 85/15, vol/vol, at 1.0 mL/min, monitoring at a wavelength of 200 nm, giving a single product peak at 17 minutes. For O-acetylation, 1.0 μmol of 2-(N,N'-diacetylhydrazino)-ethanol, either before or after liquid chromatographic purification was dried in a Pierce reacti-vial in a Speed-Vac rotary concentrator. The dried samples were taken up in 100 μL of dry pyridine (Pierce, silylation grade) and 50 μL acetic anhydride was added. The samples were kept under argon for 24 hours at room temperature, whereupon the solvent was removed under a flow of nitrogen. The samples were solubilized in about 0.5 mL chloroform, and again concentrated under a flow of nitrogen. These data show that the product is 2-hydrazinoethanol triacetate. capped under nitrogen with a cap seal was evaporated to a resin-like material in a Speed-Vac concentrator The sample was quantitatively transferred in a 1.0 mL volume of water into a 20 mL test tube 100 mg of sodium borohydride was added After 24 hours the sample was placed in an ice-water bath 0.200 mL of glacial acetic acid was added over about a 30 second interval The sample was diluted with 1.0 mL water To it was added 200 mg of sodium bicarbonate to dissolve, with occasional mixing Then, 0.100 mL acetic anhydride was added to dissolve all of it After 10 minutes another 0.100 mL acetic anhydride was added to dissolve it after an additional 50 minutes the sample was diluted with 5.0 mL water containing 10-12 mL of well-washed Dowex AG1-X8, 100-200 mesh, H+ form to remove sodium The column was washed with five additional washes of 10 mL water The total eluate was rotary evaporated rotary evaporated to dryness five times with 20 mL of 1% acetic acid in methanol, and three times with 20 mL methanol alone to remove boric acid resulting in 2-(N,N'-diacetylhydrazino)-ethanol was chromatographically purified at 85/15, vol/vol, at 1.0 mL/min, monitoring at a wavelength of 200 nm, giving a single product peak at 17 minutes was dried in a Pierce reacti-vial in a Speed-Vac rotary concentrator 50 μL acetic anhydride was added The samples were kept under argon for 24 hours at room temperature, whereupon the solvent was removed under a flow of nitrogen again concentrated under a flow of nitrogen

Conditions: temp:20.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 35 g of diacetylhydrazine (0.3 mol), 124.4 g or 165.8 g of ground potassium carbonate (0.9 or 1.2 mol, respectively), 85.8 g of 2,2-dichlorodiethyl ether (0.6 mol) and 560 ml of solvent (see Table 2) is heated to 125° C. and maintained at 125-130° C. or 80-90° C. (in the case of DMSO) for 5 hours. The mixture is then cooled to 20° C. and filtered, and the filtration residue is washed with the solvent. The yield is given by the content of title compound in the combined filtrate. filtered the filtration residue is washed with the solvent

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

Procedure: 39.6 g of potassium hydroxide powder 85% (0.6 mol) are introduced into a mixture of 35 g of diacetylhydrazine (0.3 mol) and 560 ml of solvent (see Table 1). When the heat of reaction has died away, 85.8 g of 2,2-dichlorodiethyl ether (0.6 mol) are added; the reaction mixture is heated to 80° C. and maintained at 80-90° C. for 5 hours. The mixture is then cooled to 20° C. and filtered, and the filtration residue is washed with the solvent. The yield is given by the content of title compound in the combined filtrate. It will be seen that the solvents used according to the invention (tests 4-7) give far better yields of 4,5-diacetyl-[1,4,5]-oxadiazepine than N,N-dimethylformamide, which is known from the above prior art (DMFA, comparison test 8). When the heat of reaction maintained at 80-90° C. for 5 hours The mixture is then cooled to 20° C. filtered the filtration residue is washed with the solvent give far better

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

Procedure: 105.6 g of finely pulverised potassium hydroxide are introduced into a solution of 92.9 g of N,N′-diacetylhydrazine and 1410 g of dimethyl sulfoxide. When the heat of reaction has died away, 229.9 g of 2,2′-dichlorodiethyl ether are added and then 221.1 g of finely ground potassium carbonate are introduced. The reaction mixture is heated to 70° C. and maintained at 70 to 75° C. for 2 hours, then cooled to 20 to 25° C. and filtered, and the filtration residue is washed with dimethyl sulfoxide. Concentration of the combined filtrates by evaporation yields an oil, to which 157 g of isopropanol are added. After cooling to −10° C., filtration is carried out and the crystalline residue is washed with isopropanol. After drying of the residue, 99.4 g (65.1%) of 4,5-diacetyl-[1,4,5]-oxadiazepine are obtained in a purity of 97.6%. When the heat of reaction maintained at 70 to 75° C. for 2 hours cooled to 20 to 25° C. filtered the filtration residue is washed with dimethyl sulfoxide Concentration of the combined filtrates by evaporation yields an oil After cooling to −10° C. filtration the crystalline residue is washed with isopropanol After drying of the residue, 99.4 g (65.1%) of 4,5-diacetyl-[1,4,5]-oxadiazepine are obtained in a purity of 97.6%

Conditions: temp:82.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 10.6 g of finely pulverised 85% potassium hydroxide are introduced into a solution of 9.3 g of N,N′-diacetylhydrazine and 141 g of dimethyl sulfoxide in such a manner that a temperature of 33° C. is not exceeded. After heating to 80 to 85° C., 23 g of 2,2′-dichlorodiethyl ether are added dropwise to the reaction mixture over the course of 50 minutes. The resulting highly fluid suspension is maintained at 80 to 85° C. for 3 hours, then cooled to 20 to 25° C. and filtered, and the filtration residue is washed with dimethyl sulfoxide. 11.4 g (76.0%) of 4,5-diacetyl-[1,4,5]-oxadiazepine are obtained from the combined filtrates by concentration by evaporation. The resulting highly fluid suspension is maintained at 80 to 85° C. for 3 hours cooled to 20 to 25° C. filtered the filtration residue is washed with dimethyl sulfoxide

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

Procedure: Glycolaldehyde (0.100 mmol, in dimeric form) was dissolved in 1.0 mL anhydrous hydrazine (Pierce or Aldrich Chemical Company) in a Pierce reacti-vial, and capped under nitrogen with a cap having a Pierce Tuf-bond teflon-silicone seal. The sample, after sitting at room temperature for 16 hours, was converted to the hydrazone derivative of glycolaldehyde which was evaporated to a resin-like material in a Speed-Vac concentrator. The sample was quantitatively transferred in a 1.0 mL volume of water into a 20 mL test tube, and 100 mg of sodium borohydride was added, which reduced the molecule to 2-hydrazinoethanol. After 24 hours, the sample was placed in an ice-water bath and 0.200 mL of glacial acetic acid was added, dropwise, over about a 30 second interval. The sample was diluted with 1.0 mL water. To it was added 200 mg of sodium bicarbonate and the bicarbonate was permitted to dissolve, with occasional mixing. Then, 0.100 mL acetic anhydride was added, followed by gentle swirling to dissolve all of it. After 10 minutes, another 0.100 mL acetic anhydride was added, the solution gently swirled to dissolve it, and, after an additional 50 minutes, the sample was diluted with 5.0 mL water and loaded on a column containing 10-12 mL of well-washed Dowex AG1-X8, 100-200 mesh, H+ form, to remove sodium. The column was washed with five additional washes of 10 mL water. The total eluate was rotary evaporated to near dryness, and then rotary evaporated to dryness five times with 20 mL of 1% acetic acid in methanol, and three times with 20 mL methanol alone, to remove boric acid, thereby resulting in 2-(N,N'-diacetylhydrazino)-ethanol. This sample contained some additional N,N'-diacetylhydrazine. It was either directly O-peracetylated on the free hydroxyl group as described below, or it was chromatographically purified prior to O-acetylation by high-performance liquid chromatography on a Waters GlycoPak N column (7.8×300 mm), using isocratic acetonitrile/water, at 85/15, vol/vol, at 1.0 mL/min, monitoring at a wavelength of 200 nm, giving a single product peak at 17 minutes. For O-acetylation, 1.0 μmol of 2-(N,N'-diacetylhydrazino)-ethanol, either before or after liquid chromatographic purification was dried in a Pierce reacti-vial in a Speed-Vac rotary concentrator. The dried samples were taken up in 100 μL of dry pyridine (Pierce, silylation grade) and 50 μL acetic anhydride was added. The samples were kept under argon for 24 hours at room temperature, whereupon the solvent was removed under a flow of nitrogen. The samples were solubilized in about 0.5 mL chloroform, and again concentrated under a flow of nitrogen. These data show that the product is 2-hydrazinoethanol triacetate. capped under nitrogen with a cap seal was evaporated to a resin-like material in a Speed-Vac concentrator The sample was quantitatively transferred in a 1.0 mL volume of water into a 20 mL test tube 100 mg of sodium borohydride was added After 24 hours the sample was placed in an ice-water bath 0.200 mL of glacial acetic acid was added over about a 30 second interval The sample was diluted with 1.0 mL water To it was added 200 mg of sodium bicarbonate to dissolve, with occasional mixing Then, 0.100 mL acetic anhydride was added to dissolve all of it After 10 minutes another 0.100 mL acetic anhydride was added to dissolve it after an additional 50 minutes the sample was diluted with 5.0 mL water containing 10-12 mL of well-washed Dowex AG1-X8, 100-200 mesh, H+ form to remove sodium The column was washed with five additional washes of 10 mL water The total eluate was rotary evaporated rotary evaporated to dryness five times with 20 mL of 1% acetic acid in methanol, and three times with 20 mL methanol alone to remove boric acid resulting in 2-(N,N'-diacetylhydrazino)-ethanol was chromatographically purified at 85/15, vol/vol, at 1.0 mL/min, monitoring at a wavelength of 200 nm, giving a single product peak at 17 minutes was dried in a Pierce reacti-vial in a Speed-Vac rotary concentrator 50 μL acetic anhydride was added The samples were kept under argon for 24 hours at room temperature, whereupon the solvent was removed under a flow of nitrogen again concentrated under a flow of nitrogen