PROCESS FOR ISOLATING A (THIO)PHOSPHORIC ACID DERIVATIVE

Abstract

Provided herein is a process for isolating at least one (thio)phosphoric acid derivative, which has a boiling point of at least 70 C., from a product mixture including the at least one (thio)phosphoric acid derivative, at least one salt selected from ammonium salts and alkali metal chlorides, at least one polar solvent selected from the group consisting of ester solvents and ether solvents, and optionally at least one HCl scavenger; wherein the process is based on first dissolving the (thio)phosphoric acid derivative to be able to remove the at least one salt, and then causing solids formation of the (thio)phosphoric acid derivative.

Claims

1. A process for isolating at least one (thio)phosphoric acid derivative (1a), which has a melting point of at least 70 C., and which is selected from (i) (thio)phosphoric acid triamides according to general formula (I) ##STR00041## wherein X.sup.1 is O or S; R.sup.1 is C.sub.1-C.sub.20-alkyl, C.sub.3-C.sub.20-cycloalkyl, C.sub.6-C.sub.20-aryl, C.sub.6-C.sub.20-aryl-C.sub.1-C.sub.4-alkyl, or C.sub.1-C.sub.6-(di)alkylaminocarbonyl; R.sup.2 is H, C.sub.1-C.sub.20-alkyl, C.sub.3-C.sub.20-cycloalkyl, C.sub.6-C.sub.20-aryl, C.sub.6-C.sub.20-aryl-C.sub.1-C.sub.4-alkyl, or C.sub.1-C.sub.6-(di)alkylaminocarbonyl; or R.sup.1 and R.sup.2 together with the nitrogen atom linking them define a 5- or 6-membered saturated or unsaturated heterocyclic radical, which optionally comprises 1 or 2 further heteroatoms selected from the group consisting of N, O, and S; and R.sup.3, R.sup.4, R.sup.5, and R.sup.6 are independently of each other selected from the group consisting of H and C.sub.1-C.sub.4-alkyl; and (ii) (thio)phosphoric acid ester amides according to any one of general formula (IIa) ##STR00042## wherein X.sup.2 is O or S; R.sup.7 is C.sub.1-C.sub.20-alkyl, C.sub.3-C.sub.20-cycloalkyl, C.sub.6-C.sub.20-aryl, C.sub.6-C.sub.20-aryl-C.sub.1-C.sub.4-alkyl, or C.sub.1-C.sub.6-(di)alkylaminocarbonyl; and R.sup.8, R.sup.9, R.sup.10, and are independently of each other selected from the group consisting of H and C.sub.1-C.sub.4-alkyl; or general formula (IIb) ##STR00043## wherein X.sup.3 is O or S; R.sup.12 is C.sub.1-C.sub.20-alkyl, C.sub.3-C.sub.20-cycloalkyl, C.sub.6-C.sub.20-aryl, C.sub.6-C.sub.20-aryl-C.sub.1-C.sub.4-alkyl, or C.sub.1-C.sub.6-(di)alkylaminocarbonyl; R.sup.15 is C.sub.1-C.sub.20-alkyl, C.sub.3-C.sub.20-cycloalkyl, C.sub.6-C.sub.20-aryl, C.sub.6-C.sub.20-aryl-C.sub.1-C.sub.4-alkyl, or C.sub.1-C.sub.6-(di)alkylaminocarbonyl; and R.sup.13 and R.sup.14 are independently of each other selected from the group consisting of H and C.sub.1-C.sub.4-alkyl; from a product mixture (1) comprising (1a) the at least one (thio)phosphoric acid derivative; (1b) at least one salt selected from the group consisting of (b1) ammonium salts according to general formula H.sub.2NR.sup.16R.sup.17Cl wherein R.sup.16 and R.sup.17 are independently of each other selected from the group consisting of H and C.sub.1-C.sub.4-alkyl; and (b2) alkali metal chlorides; (1c) at least one polar solvent, which is selected from the group consisting of ester solvents and ether solvents; and (1d) optionally at least one HCl scavenger; wherein the process comprises at least-the steps of (a) heating the product mixture (1) to a temperature, which is sufficient for at least partly dissolving the at least one (thio)phosphoric acid derivative (1a); (b) separating solid material from the heated product mixture (1) to remove the at least one salt (1b) and to obtain a solution comprising the at least one (thio)phosphoric acid derivative (1a) and the at least one polar solvent (1c).sub.7 and optionally the at least one HCl scavenger (1d); (c) causing solids formation of the at least one (thio)phosphoric acid derivative (1a) from the obtained solution by partly evaporating the at least one solvent (1c) from the solution and/or cooling the solution; and (d) isolating the solid material.

2. The process of claim 1, wherein the at least one (thio)phosphoric acid derivative (1a) is N-(n-propyl)thiophosphoric acid triamide (NPPT).

3. The process according to claim 1, wherein the at least one salt (1b) is ammonium chloride (NH.sub.4Cl).

4. The process according to claim 1, wherein the at least one polar solvent (1c) is selected from tetrahydrofuran, 2-methyltetrahydrofuran, and ethyl acetate.

5. The process according to claim 1, wherein the at least one HCl scavenger (1d) is a tertiary amine.

6. The process according to claim 1, wherein, in step (a), the product mixture (1) is heated to a temperature of at least 30 C.

7. The process according to claim 1, wherein, in step (c), no additional solvent is added to the solution obtained in step (b) in order to cause solids formation.

8. The process according to claim 1, wherein, in step (c), the solution obtained in step (b) is cooled to a temperature in the range of from 20 C. to 25 C., and/or at least one tertiary amine is added to the solution obtained in step (b), wherein the at least one tertiary amine corresponds to the HCl scavenger 0 d), which is present in the solution obtained in step (b).

9. The process according to claim 1, wherein the process further comprises preparing the at least one (thio)phosphoric acid derivative (1a), wherein the (thio)phosphoric acid triamides according to general formula (I) are prepared by reacting at least one N-hydrocarbylamino(thio)phosphoryl dichloride according to general formula (III) ##STR00044## wherein X.sup.1, R.sup.1, and R.sup.2 are as defined in claim 1 with 1) at least one amine according to general formula HNR.sup.16R.sup.17, wherein R.sup.16 and R.sup.17 are independently of each other selected from the group consisting of H and C.sub.1-C.sub.4-alkyl, and/or 2) at least one amide according to general formula MNR.sup.16R.sup.17, wherein R.sup.16 and R.sup.17 are independently of each other selected from the group consisting of H and C.sub.1-C.sub.4-alkyl, and M is an alkali metal; in at least one polar solvent, which is selected from the group consisting of ester solvents and ether solvents, to obtain a product mixture (1.1) comprising (1.1a) at least one (thio)phosphoric acid triamide according to general formula (I), wherein X.sup.1, R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5, and R.sup.6 are as defined in claim 1; (1.1b) at least one salt selected from the group consisting of (b1) ammonium salts according to general formula H.sub.2NR.sup.16R.sup.17Cl wherein R.sup.16 and R.sup.17 are independently of each other selected from the group consisting of H and C.sub.1-C.sub.4-alkyl, and (b2) alkali metal chlorides; and (1.1c) at least one polar solvent, which is selected from the group consisting of ester solvents and ether solvents; and wherein the (thio)phosphoric acid ester amides according to general formula (IIa) are prepared by reacting at least one O-hydrocarbyloxy(thio)phosphoryl dichloride according to general formula (IV) ##STR00045## wherein X.sup.2 and R.sup.7 are as defined in claim 1, with 1) at least one amine according to general formula HNR.sup.16R.sup.17, wherein R.sup.16 and R.sup.17 are independently of each other selected from the group consisting of H and C.sub.1-C.sub.4-alkyl, and/or 2) at least one amide according to general formula MNR.sup.16R.sup.17, wherein R.sup.16 and R.sup.17 are independently of each other selected from the group consisting of H and C.sub.1-C.sub.4-alkyl, and M is an alkali metal; in at least one polar solvent, which is selected from the group consisting of ester solvents and ether solvents, to obtain a product mixture (1.2) comprising (1.2a) at least one (thio)phosphoric acid ester amide according to general formula (IIa), wherein X.sup.2, R.sup.7, R.sup.8, R.sup.9, R.sup.10, and R.sup.11 are as defined in claim 1; (1.2b) at least one salt selected from the group consisting of (b1) ammonium salts according to general formula H.sub.2NR.sup.16R170 wherein R.sup.16 and R.sup.17 are independently of each other selected from the group consisting of H and C.sub.1-C.sub.4-alkyl, and (b2) alkali metal chlorides; and (1.2c) at least one polar solvent, which is selected from the group consisting of ester solvents and ether solvents; and wherein the (thio)phosphoric acid ester amides according to general formula (IIb) are prepared by reacting at least one O-hydrocarbyloxy(thio)phosphoryl dichloride according to general formula (V) ##STR00046## wherein X.sup.3 and R.sup.12 are as defined in claim 1, with 1) at least one amine according to general formula HNR.sup.16R.sup.17, wherein R.sup.16 and R.sup.17 are independently of each other selected from the group consisting of H and C.sub.1-C.sub.4-alkyl, and/or 2) at least one amide according to general formula MNR.sup.16R.sup.17, wherein R.sup.16 and R.sup.17 are independently of each other selected from the group consisting of H and C.sub.1-C.sub.4-alkyl, and M is an alkali metal; and with 3) at least one alcohol according to general formula HOR.sup.15, wherein R.sup.15 is as defined in claim 1 and/or 4) at least one alcoholate according to general formula MOR.sup.15, wherein R.sup.15 is as defined in claim 1; in at least one polar solvent, which is selected from the group consisting of ester solvents and ether solvents, to obtain a product mixture (1.3) comprising (1.3a) at least one (thio)phosphoric acid ester amide according to general formula (IIb), wherein X.sup.3, R.sup.12, R.sup.13, R.sup.14, and R.sup.15 are as defined in claim 1; (1.3b) at least one salt selected from the group consisting of (b1) ammonium salts according to general formula H.sub.2NR.sup.16R.sup.17Cl wherein R.sup.16 and R.sup.17 are independently of each other selected from the group consisting of H and C.sub.1-C.sub.4-alkyl, and (b2) alkali metal chlorides; and (1.3c) at least one polar solvent, which is selected from the group consisting of ester solvents and ether solvents.

10. The process of claim 9, wherein the at least one amine HNR.sup.16R.sup.17Cl is ammonia (NH.sub.3), and wherein from 4 to 20 equivalents of ammonia are provided, when preparing the at least one (thio)phosphoric acid derivative (1a).

11. The process of claim 9, wherein the compound according to formula (III), (IV), or (V) is provided in combination with a hydrochloride salt of an HCl scavenger, so that the resulting product mixture (1.1) comprises as component (1.1d) at least one HCl scavenger, the resulting product mixture (1.2) comprises as component (1.2d) at least one HCl scavenger, and the resulting product mixture (1.3) comprises as component (1.3d) at least one HCl scavenger.

12. The process of claim 11, wherein the at least one amine HNR.sup.16R.sup.17 is ammonia (NH.sub.3), and wherein from 5 to 20 equivalents of ammonia are provided, when preparing the at least one (thio)phosphoric acid derivative.

13. The process according to claim 9, wherein the (thio)phosphoric acid derivative (1a) is a (thio)phosphoric acid triamide according to general formula (I), which is N-(n-propyl)thiophosphoric acid triamide (NPPT), the N-hydrocarbylamino(thio)phosphoryl dichloride according to general formula (III) is N-(n-propyl)amino(thio)phosphoryl dichloride, the at least one amine HNR.sup.16R.sup.17 is ammonia (NH.sub.3), the at least one polar solvent is tetrahydrofuran, 2-methyltetrahydrofuran, or ethyl acetate, and the at least one salt is ammonium chloride (NH.sub.4Cl).

14. The process according to claim 10, wherein the reaction is performed at a temperature and a pressure, which are selected such that the ammonia is present in gaseous form, and wherein the reaction is performed at a temperature of more than 30 C.

15. The process according to claim 9, wherein the reaction is performed in a reaction mixture, which comprises less than 1 wt.-% of water, based on a total weight of the reaction mixture.

Description

EXAMPLES

[0698] Characterization:

[0699] 31P-NMR Analysis was performed as follows:

[0700] Apparatus: Bruker DPX 401

[0701] Reagents: D.sub.6-DMSO (Euriso-top), tetramethylsilane (TMS, reference material no. A 0011/003/NMR3)

[0702] Sample preparation: About 130 mg of the test item was weighed in to the nearest 0.01 mg and dissolved into 0.7 ml of D.sub.6-DMSO containing a small amount of TMS

[0703] Test parameters: Sample concentration: 185.4 g/I; Measuring frequency: 162 MHz; Number of accumulated spectra: 32; Reference: TMS; Temperature: 27 C.

[0704] Chemical shift of PSCl.sub.3: (ppm)=31 (Integral: 0.134)

[0705] Chemical shift of NPPT: (ppm)=60 (Integral: 100)

[0706] HPLC Analysis was performed as follows:

[0707] Column: Kromasil 100, C 8, 2504 mm, 5 m

[0708] Flux: 1 mL/min

[0709] Injection volume: 30 l

[0710] Column temperature: 25 C.

[0711] Wavelength: 205 nm, BW 8 nm, Ref off

[0712] Peak width: >0.005 min (0.12 s)

[0713] Run time: 30 min

[0714] Eluent A: Water Milli-Q-Purity (R>18 M)

[0715] Eluent B: Acetonitrile, HPLC purity

TABLE-US-00003 Gradient: 0 min: 25% B 10 min: 25% B 11 min: 100% B 20 min: 100% B 21 min: 25% B 30 min: 25% B

Example 1

[0716] 169.4 g (1 mol) PSCl.sub.3 and 333.3 g ethyl acetate were precharged at room temperature into a reaction flask and cooled to 0 C. and a mixture of 59.7 g (1.01 mol) n-propylamine and 157.6 g (1.1 mol) tri-n-propylamine was added within 90 min. During the addition the temperature was maintained between 0-2 C. by cooling. The suspension was stirred at 0 C. for additional 60 min and afterwards heated up to dissolve the precipitated salts and obtain a homogeneous dichloride solution.

[0717] The prepared dichloride solution was added within 6 hours to a mixture of 102.2 g (6 mol) liquid ammonia and 333.3 g ethyl acetate, which were cooled to 6 C. in advance. The temperature was maintained during the addition between 5-7 C. The suspension was stirred at 5-7 C. for additional 60 min and afterwards the pressure was released.

[0718] The resulting raw product was obtained with 90% N-propyl thiophosphoryl triamide (NPPT) yield based on 31P-NMR analysis. The raw product additionally comprised ammonium chloride, ethyl acetate, and tri-n-propylamine.

Example 2

[0719] Dichloride solution prepared according to Example 1 was added to a mixture of 238.4 g (14 mol) liquid ammonia and 333.3 g ethyl acetate, which were cooled to 16 C. in advance. The temperature was maintained during the addition between 15-17 C. The suspension was stirred at 15-17 C. for additional 60 min and afterwards the pressure was released.

[0720] The resulting raw product was obtained with 93% N-propyl thiophosphoryl triamide (NPPT) yield based on 31P-NMR analysis. The raw product additionally comprised ammonium chloride, ethyl acetate, and tri-n-propylamine.

Example 3

[0721] Dichloride solution prepared according to Example 1 was added to 340.6 g (20 mol) liquid ammonia, which was cooled to 6 C. in advance. The temperature was maintained during the addition between 5-7 C. The suspension was stirred at 5-7 C. for additional 60 min and afterwards the pressure was released.

[0722] The resulting raw product was obtained with 95% N-propyl thiophosphoryl triamide (NPPT) yield based on 31P-NMR analysis. The raw product additionally comprised ammonium chloride, ethyl acetate, and tri-n-propylamine.

Example 4

[0723] 169.4 g (1 mol) PSCl.sub.3 and 333.3 g methyl-tetrahydrofuran were precharged at room temperature into a reaction flask and cooled to 0 C. and a mixture of 59.7 g (1.01 mol) n-propylamine and 157.6 g (1.1 mol) tri-n-propylamine was added within 90 min. During the addition the temperature was maintained between 0-2 C. by cooling. The suspension was stirred at 0 C. for additional 60 min and afterwards heated up to dissolve the precipitated salts and obtain a homogeneous dichloride solution.

[0724] The prepared dichloride solution was added to a mixture of 102.2 g (6 mol) liquid ammonia and 233.3 g methyl-tetrahydrofuran, which were cooled to 6 C. in advance. The temperature was maintained during the addition between 5-7 C. The suspension was stirred at 5-7 C. for additional 60 min and afterwards the pressure was released.

[0725] The resulting raw product was obtained with 91% N-propyl thiophosphoryl triamide (NPPT) yield based on 31P-NMR analysis. The raw product additionally comprised ammonium chloride, methyl-tetrahydrofuran, and tri-n-propylamine.

Example 5

[0726] Dichloride solution prepared according to Example 4 was added to 340.6 g (20 mol) liquid ammonia, which was cooled to 6 C. in advance. The temperature was maintained during the addition between 5-7 C. The suspension was stirred at 5-7 C. for additional 60 min and afterwards the pressure was released.

[0727] The resulting raw product was obtained with 93% N-propyl thiophosphoryl triamide (NPPT) yield based on 31P-NMR analysis. The raw product additionally comprised ammonium chloride, methyl-tetrahydrofuran, and tri-n-propylamine.

Example 6

[0728] 169.4 g (1 mol) PSCl.sub.3 and 333.3 g ethyl acetate were precharged at room temperature into a reaction flask and cooled to 0 C. and a mixture of 59.7 g (1.01 mol) n-propylamine and 157.6 g (1.1 mol) tri-n-propylamine was added within 90 min. During the addition the temperature was maintained between 0-2 C. by cooling. The suspension was stirred at 0 C. for additional 60 min and afterwards heated up to dissolve the precipitated salts and obtain a homogeneous dichloride solution.

[0729] The prepared dichloride solution was added parallel with 102.2 g (6 mol) gaseous ammonia (via dip pipe) to 333.3 g ethyl acetate, which was cooled to 6 C. in advance. The temperature was maintained during the addition between 5-7 C.

[0730] The resulting raw product was obtained with 88% N-propyl thiophosphoryl triamide (NPPT) yield based on 31P-NMR analysis. The raw product additionally comprised ammonium chloride, ethyl acetate, and tri-n-propylamine.

Example 7

[0731] Dichloride solution prepared according to Example 6 was added parallel with 340.6 g (20 mol) gaseous ammonia (via dip pipe) to 333.3 g ethyl acetate, which was cooled to 6 C. in advance.

[0732] The temperature was maintained during the addition between 5-7 C.

[0733] The resulting raw product was obtained with 91% N-propyl thiophosphoryl triamide (NPPT) yield based on 31P-NMR analysis. The raw product additionally comprised ammonium chloride, ethyl acetate, and tri-n-propylamine.

Example 8

[0734] Raw product prepared according to Example 6 was heated up to 50 C. and filtered at this temperature. The filter cake was washed two times with 200 g ethyl acetate at 50 C. After combining the washing solution and the filtrate approx. 600 g of the light boiler ethyl acetate was distilled off at 74-86 C. and normal pressure. A crystallization at 0 C. was followed by an isolation of the obtained solids by filtration. After drying in a cabinet at 50 C. under vacuum for 24 hours, 90 g N-propyl thiophosphoryl triamide (NPPT) was obtained at 95.9% purity based on HPLC analysis (total yield: 56%).

Example 9

[0735] Raw product prepared according to Example 6 was heated up to 50 C. and filtered at this temperature. The filter cake was washed two times with 200 g ethyl acetate at 50 C. After combining the washing solution and the filtrate approx. 680 g of the light boiler ethyl acetate was distilled off at 40-43 C. and reduced pressure. A crystallization at 0 C. was followed by an isolation of the obtained solids by filtration. After drying in a cabinet at 50 C. under vacuum for 24 hours, 111.9 g N-propyl thiophosphoryl triamide (NPPT) was obtained at 98.5% purity based on HPLC analysis (total yield: 73%).

Example 10

[0736] Raw product prepared according to Example 6 was heated up to 50 C. and filtered at this temperature. The filter cake was washed two times with 200 g ethyl acetate at 50 C.

[0737] After combining the washing solution and the filtrate approx. 260 g of the light boiler ethyl acetate was distilled off at 42-43 C. and reduced pressure. A crystallization at 0 C. was followed by an isolation of the obtained solids by filtration. After drying in a cabinet at 50 C. under vacuum for 24 hours, 101.1 g N-propyl thiophosphoryl triamide (NPPT) was obtained at 91.6% purity based on HPLC analysis (total yield: 66%).