1-[ethoxy(isothiocyanato)phosphoryl]oxyethane

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

Procedure: 0.75 ml (about 3 mmol) of N,O-bis(trimethylsilyl) acetamide was added under anhydrous conditions, to a suspension of 1.05 g (3 mmol) of D(-) 6-α-amino-benzylcarbonamidopenicillanic acid (anhydrous D(-) ampicillin) in 50 ml of dry dichloromethane and after 30 minutes stirring at about 20°C, a clear solution was obtained. Then, a solution of 0.6 g (3 mmol) of diethoxyphosphinylisothiocyanate [(C2H5O)2P(O)NCS] in 10 ml of dichloromethane was added at 0°-5°C over a period of 10 minutes and as the reaction did not cause a rise in temperature, the reaction mixture was further stirred at 5°C for 150 minutes. A small amount of precipitate was formed and according to thin-layer chromatograms, ampicillin was no longer present in the reaction mixture. The reaction mixture was poured into 75 ml of ice-water and the pH was brought to 7.0. The layers were separated and as the organic layer did contain part of the desired penicillin, the aqueous layer was extracted once with 75 ml of ethyl acetate at pH 7.0. The organic layers were combined, concentrated to some extent in vacuo in order to remove dichloromethane, and subsequently treated with n-hexane until a precipitate was formed, which was vacuum filtered off, washed with n-hexane and dried in vacuo to constant weight to obtain 0.5 g (30%) of D-6-[α-{3-diethoxyphosphinyl)-thioureido}benzylcarbonamido]-penicillanic acid. a clear solution was obtained the reaction mixture was further stirred at 5°C for 150 minutes A small amount of precipitate was formed The layers were separated and as the organic layer the aqueous layer was extracted once with 75 ml of ethyl acetate at pH 7.0 concentrated to some extent in vacuo in order to remove dichloromethane subsequently treated with n-hexane until a precipitate was formed filtered off washed with n-hexane dried in vacuo to constant weight

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

Procedure: 0.75 ml (about 3 mmol) of N,O-bis(trimethylsilyl) acetamide was added under anhydrous conditions, to a suspension of 1.05 g (3 mmol) of D(-) 6-α-amino-benzylcarbonamidopenicillanic acid (anhydrous D(-) ampicillin) in 50 ml of dry dichloromethane and after 30 minutes stirring at about 20°C, a clear solution was obtained. Then, a solution of 0.6 g (3 mmol) of diethoxyphosphinylisothiocyanate [(C2H5O)2P(O)NCS] in 10 ml of dichloromethane was added at 0°-5°C over a period of 10 minutes and as the reaction did not cause a rise in temperature, the reaction mixture was further stirred at 5°C for 150 minutes. A small amount of precipitate was formed and according to thin-layer chromatograms, ampicillin was no longer present in the reaction mixture. The reaction mixture was poured into 75 ml of ice-water and the pH was brought to 7.0. The layers were separated and as the organic layer did contain part of the desired penicillin, the aqueous layer was extracted once with 75 ml of ethyl acetate at pH 7.0. The organic layers were combined, concentrated to some extent in vacuo in order to remove dichloromethane, and subsequently treated with n-hexane until a precipitate was formed, which was vacuum filtered off, washed with n-hexane and dried in vacuo to constant weight to obtain 0.5 g (30%) of D-6-[α-{3-diethoxyphosphinyl)-thioureido}benzylcarbonamido]-penicillanic acid. a clear solution was obtained the reaction mixture was further stirred at 5°C for 150 minutes A small amount of precipitate was formed The layers were separated and as the organic layer the aqueous layer was extracted once with 75 ml of ethyl acetate at pH 7.0 concentrated to some extent in vacuo in order to remove dichloromethane subsequently treated with n-hexane until a precipitate was formed filtered off washed with n-hexane dried in vacuo to constant weight

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

Procedure: Employing the process of Example 1 in every detail except that 2-chloro-p-phenylenediamine sulfate is neutralized and allowed to react with two equivalents of diethyl phosphoroisothiocyanatidate ##STR7## in chloroform instead of methylene chloride to afford the title compound, m.p. 148°-149° C.

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

Procedure: Employing the process of Example 1 in every detail except that 2-chloro-p-phenylenediamine sulfate is neutralized and allowed to react with two equivalents of diethyl phosphoroisothiocyanatidate ##STR7## in chloroform instead of methylene chloride to afford the title compound, m.p. 148°-149° C.

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

Procedure: To a stirred slurry of 1.0 to 1.1 molar equivalent of anhydrous sodium, potassium or ammonium thiocyanate in about 50 ml to 100 ml of a solvent such as benzene, toluene, xylene, ehtylene dichloride, chloroform, methylene chloride or methylene bromide, is added one molar equivalent of diethoxyphosphoryl chloride of formula (II) at a temperature range of 5° C to 30° C and, preferably, 15° C to 25° C and the reaction mixture stirred for a period of time from 4 to 4 hours to yield diethoxyphosphinyl isothiocyanate of formula (III). The reaction is slightly exothermic and such exotherm easily is controlled by either adjusting the rate of addition of said phosphoryl chloride or by using a cooling bath, or by a combination of the two.

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

Procedure: One molar equivalent of diethoxyphosphoryl chloride of formula (II) is reacted with 1.0 to 1.2 molar equivalent of sodium-, potassium- or ammonium thiocyanate at a temperature range of 5° C to 30° C and, preferably, 15° C to 25° C for a period of time ranging from 2 to 4 hours to yield diethoxyphosphinyl isothiocyanate of formula (III). The reaction is slightly exothermic, but is easily controlled by a cooling bath.

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

Procedure: One molar equivalent of diethoxyphosphoryl chloride of formula (II) is reacted with 1.0 to 1.2 molar equivalent of sodium-, potassium- or ammonium thiocyanate at a temperature range of 5° C to 30° C and, preferably, 15° C to 25° C for a period of time ranging from 2 to 4 hours to yield diethoxyphosphinyl isothiocyanate of formula (III). The reaction is slightly exothermic, but is easily controlled by a cooling bath.