N-(3-diethoxyphosphorylpropyl)hydroxylamine

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:

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

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

Procedure: To a solution of diethyl 3-(N-hydroxyamino)propylphosphonate (2.80 g.) in chloroform (30 ml.) was added dropwise a mixture of acetic anhydride (2.04 g.) and formic acid (1.38 g.), which was prepared in the same manner as that of Example (31), under ice-cooling with stirring. The reaction mixture was stirred for half an hour at 0°-5° C. and for additional an hour at ambient temperature, and then evaporated to dryness under reduced pressure to give an oily residue, which was dissolved in a mixture of methanol (15 ml.) and water (5 ml.), adjusted to pH 8 with 1N aqueous sodium hydroxide solution and stirred for 1.5 hours at ambient temperature. The methanol was distilled off from this solution under reduced pressure to give an aqueous solution, which was adjusted to pH 5 with 10% hydrochloric acid and extracted with chloroform (once with 30 ml. portion and three times with 10 ml. portions). These combined extracts were dried over magnesium sulfate and evaporated to dryness under reduced pressure to give crude diethyl 3-(N-formyl-N-hydroxyamino)propylphosphonate (2.89 g.), which was passed through a column packed with silica gel (60 g.). The column was eluted with a mixture of chloroform and methanol (25:1 by volume), and the fractions containing an object compound were collected and evaporated to dryness under reduced pressure to give the same pure object compound (1.71 g.). was prepared in the same manner as that of Example (31) under ice-cooling The reaction mixture was stirred for half an hour at 0°-5° C. and for additional an hour at ambient temperature evaporated to dryness under reduced pressure to give an oily residue, which stirred for 1.5 hours at ambient temperature The methanol was distilled off from this solution under reduced pressure to give an aqueous solution, which extracted with chloroform (once with 30 ml These combined extracts were dried over magnesium sulfate evaporated to dryness under reduced pressure

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

Procedure: A mixture of diethyl 3-(N-hydroxyamino)propylphosphonate (12.9 g.), acetic acid (65 ml.) and 1 N hydrochloric acid (130 ml.) was heated to reflux with stirring for 8 hours and then was concentrated under reduced pressure to remove off acetic acid. The concentrate was decolorized by treating with an activated charcoal and evaporated to dryness under reduced pressure to give an oily residue (9.5 g.), which was dissolved in water (30 ml.) and adjusted to pH 4 with sodium bicarbonate (ca. 4.2 g.) to give crystals of 3-(N-hydroxyamino)propylphosphonic acid (4.80 g.), m.p. 160°-163.5° C. (decomp.). An additional crystals of the same object compound (0.91 g.) was recovered from the mother liquor after standing overnight at ambient temperature (m.p. 159°-163° C. (decomp.)). The I.R. and N.M.R. spectra of these crystals were superimposable with those of the authentic specimen (m.p. 160°-166° C. (decomp.)). was heated to reflux was concentrated under reduced pressure to remove off acetic acid by treating with an activated charcoal evaporated to dryness under reduced pressure to give an oily residue (9.5 g.), which

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

Procedure: To a solution of hydroxylamine hydrochloride (55.6 g.) in water (100 ml.) were added solution of sodium hydroxide (32.0 g.) in water (75 ml.) under ice-cooling and then methanol (75 ml.). To this solution was added dropwise diethyl 3-bromopropylphosphonate (25.5 g.), whereafter the mixture was warmed at 40°-45° C. for 3 hours with stirring. The methanol was distilled off under reduced pressure. The resultant aqueous solution was adjusted to pH 8 with sodium bicarbonate, washed three times with benzene which were discarded (once with 150 ml. and twice with 100 ml. portions) and then extracted with three 150 ml. portions of chloroform. The chloroform extracts were combined, dried over magnesium sulfate and evaporated to dryness under reduced pressure to give oily diethyl 3-(N-hydroxyamino)propylphosphonate (13.05 g.). cooling whereafter the mixture was warmed at 40°-45° C. for 3 hours The methanol was distilled off under reduced pressure washed three times with benzene which portions) and then extracted with three 150 ml dried over magnesium sulfate evaporated to dryness under reduced pressure

Conditions: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2.8 g (0.013 mol) 3-(N-hydroxyamino)-propylphosphonic acid diethylester are dissolved in 30 ml methylene chloride and added drop by drop with cooling with ice to 2.65 g (0.026 mol) acetic anhydride. The reaction mixture is stirred for 30 minutes at 0-5° C. and for a further 1.5 hours at room temperature. After concentration under reduced pressure until a yellow oily radical is achieved, this oily residue is taken up in 15 ml methanol and 5 ml water, adjusted to pH 8 with 2 n NaOH and stirred for a further 1.5 hours at room temperature. Methanol is removed under reduced pressure and the resultant solution is adjusted to pH=5 with concentrated HCl. The yellow solution is extracted repeatedly with methylene chloride (1×30 ml, 2×10 ml in each case), the combined CH2Cl2 phases are dried over MGSO4 and the solvent is removed at room temperature under reduced pressure. 3.7 g of a yellow oil are obtained which are freed from adhering volatile substances in the entire diaphragm pump vacuum. 2.78 g yellow oil remain. added drop by drop After concentration under reduced pressure until a yellow oily stirred for a further 1.5 hours at room temperature Methanol is removed under reduced pressure The yellow solution is extracted repeatedly with methylene chloride (1×30 ml, 2×10 ml in each case), the combined CH2Cl2 phases are dried over MGSO4 the solvent is removed at room temperature under reduced pressure

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

Procedure: 1.38 (0.030 mol) formic acid were added drop by drop at room temperature to 2.04 g (0.020 mol) acetic anhydride and stirred at the same temperature. This solution was added with cooling with ice to 2.8 g (0.013 mol) 3-(N-hydroxyamino)-propylphosphonic acid diethylester dissolved in chloroform. The reaction mixture is stirred for 30 minutes at 0-5° C. and for a further 1.5 hours at room temperature. After concentration under reduced pressure until an oily residue is obtained, this oily residue is taken up in 15 ml methanol and 5 ml water, adjusted to pH=8 with 2 n NaOH and stirred for a further 1.5 hours at room temperature. Methanol is removed under reduced pressure and the resultant aqueous solution is adjusted to pH=5 with concentrated HCl. The yellow solution is extracted with chloroform (1×30 ml, 2×10 ml in each case) and the CHCl3 phases are dried over MgSO4. After concentration of the solution in the entire diaphragm pump vacuum 3 g of a yellow oil are obtained. After removal of volatile constituents in the entire diaphragm pump vacuum, chromatography on 60 g SiO2 with chloroform shows: methanol in the ratio 25:1 2.65 g product as yellow oil (DE-A-27 33 658). This solution was added The reaction mixture is stirred for 30 minutes at 0-5° C. and for a further 1.5 hours at room temperature After concentration under reduced pressure until an oily residue is obtained stirred for a further 1.5 hours at room temperature Methanol is removed under reduced pressure The yellow solution is extracted with chloroform (1×30 ml, 2×10 ml in each case) and the CHCl3 phases are dried over MgSO4

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 12.9 g (0.0608 mol) 3-(N-hydroxylamino)-propylphosphonic acid diethylester and 130 ml concentrated HCl were heated for 6 hours under reflux (oil bath temperature: 150° C.). The resulting yellow/orange solution is concentrated under-reduced pressure. The remaining oil is taken up in 30 ml water, stirred with 3 spoonfuls of activated carbon for 30 minutes, filtered out from the activated carbon and the colourless solution is concentrated in the entire diaphragm pump vacuum. After take-up in 30 ml water a pH of 4.0 to 4.5 is adjusted with approximately 4.7 g (0.056 mol) NaHCO3 (from pH=1.5 the product precipitates). Suction filtering of the white solid resulted in 5.83 g 3-(hydroxyamino)-propylphosphonic acid (melting point: 160° C., decomposition). This corresponds to a yield of 61.8%. (DE-A-27 33 658, Öhler Synthesis 1995, 539-543). The resulting yellow/orange solution is concentrated under-reduced pressure filtered out from the activated carbon the colourless solution is concentrated in the entire diaphragm pump vacuum Suction filtering of the white solid resulted in 5.83 g 3-(hydroxyamino)-propylphosphonic acid (melting point: 160° C., decomposition) (DE-A-27 33 658, Öhler Synthesis 1995, 539-543)

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

Procedure: Firstly 32.0 g (0.8 mol) of sodium hydroxide dissolved in 75 ml water then 75 ml methanol, and finally 25.5 g (0.098 mol) 3-bromopropyl phosphonic acid diethylester were added drop by drop to a solution of 55.6 g (0.8 mol) hydroxylamine hydrochloride in 100 ml water with cooling with ice. This led to a clouding of the solution. After 3 hours stirring at a temperature of 40 to 45° C. methanol was removed under reduced pressure, the resulting aqueous solution was saturated with NaHCO3 (pH=8), shaken out three times with 60 ml toluene in each case (the toluene phase was discarded) and then shaken out with chloroform (1× with 90 ml, 2× with 50 ml in each case). The slightly yellowy chloroform phase was dried over MgSO4. After filtering of the dehydrating agent the solution was concentrated under reduced pressure. 15.43 g (0.0728 mol) 3-(N-hydroxyamino)-propylphosphonic acid diethylester were obtained as an almost colourless oil. This corresponds to a yield of 74.3% (DE-A-27 33 658). with cooling with ice was removed under reduced pressure then shaken out with chloroform (1× with 90 ml, 2× with 50 ml in each case) The slightly yellowy chloroform phase was dried over MgSO4 After filtering of the dehydrating agent the solution was concentrated under reduced pressure