Process for producing phosphinates

Abstract

The present invention relates primarily to a process for producing particular phosphinates (phosphonous acid monoesters) and use thereof for producing biologically active substances which may be used in the pharmaceutical or agrochemical sector, preferably for producing phosphorus-containing amino acids.

Claims

1. A process for producing a compound of formula (I) ##STR00004## comprising reacting a compound of formula (II) ##STR00005## with a compound of formula (III)
R.sup.2OH(III) wherein in each case: R.sup.1 represents (C.sub.1-C.sub.12)-alkyl, (C.sub.1-C.sub.12)-haloalkyl, (C.sub.6-C.sub.10)-aryl, (C.sub.6-C.sub.10)-haloaryl, (C.sub.7-C.sub.10)-aralkyl, (C.sub.7-C.sub.10)-haloaralkyl, (C.sub.4-C.sub.10)-cycloalkyl or (C.sub.4-C.sub.10)-halocycloalkyl, R.sup.2 represents (C.sub.3-C.sub.12)-alkyl, (C.sub.3-C.sub.12)-haloalkyl, (C.sub.6-C.sub.10)-aryl, (C.sub.6-C.sub.10)-haloaryl, (C.sub.7-C.sub.10)-aralkyl, (C.sub.7-C.sub.10)-haloaralkyl, (C.sub.4-C.sub.10)-cycloalkyl or (C.sub.4-C.sub.10)-halocycloalkyl, R.sup.3 and R.sup.4 each independently of one another represent methyl or ethyl, in the presence of an acidic catalyst and in the presence of water.

2. The process according to claim 1, wherein the total amount of water used is at least 0.8 molar equivalents, based on the total amount of compounds of formula (II) used.

3. The process according to claim 1, wherein the total amount of water used is 1 to 5 molar equivalents, based on the total amount of compounds of formula(II) used.

4. The process according to claim 1, wherein the total amount of water used is 1 to 3 molar equivalents, based on the total amount of compounds of formula (II) used.

5. The process according to claim 1, wherein the total amount of water used is 1 to 2 molar equivalents, based on the total amount of compounds of formula (II) used.

6. The process according to claim 1, wherein the total amount of compounds of formula (III) used is 1 to 25 molar equivalents, based on the total amount of compounds of formula (II) used.

7. The process according to claim 1, wherein the total amount of compounds of formula (III) used is 3 to 15 molar equivalents, based in each case on the total amount of compounds of formula (II) used.

8. The process according to claim 1, wherein the pKa of the acidic catalyst under standard conditions is less than 3.

9. The process according to claim 1, wherein the acidic catalyst is selected from the group consisting of H.sub.3PO.sub.3, H.sub.2SO.sub.4, HCl, HBr, HClO.sub.4, dichloroacetic acid, trichloroacetic acid, trifluoroacetic acid, methanesulphonic acid, trifluoromethanesulphonic acid, benzenesulphonic acid, p-toluenesulphonic acid, acidic ion exchangers, acidic polysiloxanes and acidic zeolites.

10. The process according to claim 1, wherein the reaction is carried out as a one-pot reaction.

11. The process according to claim 1, wherein the reaction is carried out at a temperature in a range from 30 to 140 C.

12. The process according to claim 1, wherein the reaction is carried out in an inert diluent or diluent-free.

13. The process according to claim 1, wherein R.sup.1 represents (C.sub.1-C.sub.6-alkyl, (C.sub.1-C.sub.6)-haloalkyl, (C.sub.6-C.sub.8-aryl, (C.sub.6-C.sub.8-haloaryl, (C.sub.7-C.sub.10)-aralkyl, (C.sub.7-C.sub.10)-haloaralkyl, (C.sub.5-C.sub.8-cycloalkyl or (C.sub.5-C.sub.8-halocycloalkyl, and R.sup.2 represents (C.sub.3-C.sub.8)-alkyl, (C.sub.3-C.sub.8)-haloalkyl, (C.sub.6-C.sub.8-aryl, (C.sub.6-C.sub.8-haloaryl, (C.sub.7-C.sub.10)-aralkyl, (C.sub.7-C.sub.10)-haloaralkyl, (C.sub.5-C.sub.8-cycloalkyl or (C.sub.5-C.sub.8-halocycloalkyl.

14. The process according to claim 1, wherein R.sup.1 represents (C.sub.1-C.sub.4)-alkyl, (C.sub.1-C.sub.4)-haloalkyl or (C.sub.6-C.sub.8-aryl R.sup.2 represents (C.sub.3-C.sub.6-alkyl or (C.sub.3-C.sub.6)-haloalkyl.

15. The process according to claim 1, wherein R.sup.1 represents methyl or ethyl, R.sup.2 represents C.sub.4-alkyl or C.sub.5-alkyl.

16. The process according to claim 1, wherein the total amount of water used is at least 0.95 molar equivalents, based on the total amount of compounds of formula (II) used.

17. The process according to claim 1, wherein the total amount of compounds of formula (III) used is 5 to 10 molar equivalents, based on the total amount of compounds of formula (II) used.

18. The process according to claim 1, wherein the pKa of the acidic catalyst under standard conditions is less than 2.

19. The process according to claim 1, wherein the reaction is carried out at a temperature in a range from 50 to 120 C.

Description

EXAMPLES

(1) All data are based on weight unless otherwise stated.

Example 1

1-Butyl methylphosphinate (methanephosphonous acid mono-n-butyl ester)

(2) 38.45 g (0.2684 mol) of diethyl methylphosphonite (purity 95%) and 1.5 g of Amberlyst 15 (strongly acidic catalyst, synthetic ion exchange resin) in 200 ml of toluene were initially charged in a stirred flask under an argon atmosphere. 4.95 g (0.275 mol) of water and 50 g (0.675 mol) of 1-butanol were added while stirring. Subsequently, the mixture was stirred at 50 C. for 30 min and then heated to reflux (initially ca. 83 C.).

(3) Low boiling components (ethanol and toluene) were then distilled off via a distillation attachment with a short Vigreux column. After 4 hours another 50 g (0.675 mol) of 1-butanol were added and further low boiling components were distilled off. Finally, at 140 C. at the bottom/113 C. at the top, a mixture of 37% 1-butanol and 63% toluene (GC analysis) was removed.

(4) After cooling and removal of the acidic catalyst, 64.3 g remained of a mixture of 55.6% 1-butyl methylphosphinate, 41.3% 1-butanol and 3.1% toluene (GC analysis against standard), corresponding to a yield of 35.75 g (0.263 mol)=97.9% of theory.

(5) By means of a fractionated fine distillation under reduced pressure, 1-butyl methylphosphinate was obtained at a purity of 98.5%.

(6) Analysis: .sup.31P-NMR (CDCl.sub.3)

(7) 1-butyl methylphosphinate 33.9 ppm

(8) diethyl methylphosphonite 177.8 ppm

Example 2

1-Pentyl methylphosphinate (methanephosphonous acid mono-n-pentyl ester)

(9) To 20 g (0.145 mol) of diethyl methylphosphonite (purity 99%) were added 2.62 g (0.145 mol) of water and 64.1 g (0.727 mol) of 1-pentanol and the mixture was reacted in the presence of 0.1 g of 96% sulphuric acid without additional solvent, wherein the mixture was stirred at the start at 50 C. for 30 minutes, and then the internal temperature was increased gradually over 3 hours up to the reflux temperature of 1-pentanol by the end. At the same time, low boiling components were distilled off, at the end only 1-pentanol (GC analysis), which was mostly distilled off.

(10) According to analysis by GC, the resulting reaction mixture no longer contained reactant.

(11) After fine distillation under reduced pressure, 21.8 g (0.139 mol) of 1-pentyl methylphosphinate (purity 96%) were obtained from the crude product, corresponding to a yield of 95.8% of theory.

(12) Analysis: .sup.31P-NMR (CDCl.sub.3): 1-pentyl methylphosphinate 34.11 ppm

Example 3

1-Butyl phenylphosphinate (phenylphosphonous acid mono-n-butyl ester)

(13) To 5.0 g (24.7 mmol) of diethyl phenylphosphonite (purity 98%) under argon were added 9.72 g (131.17 mmol) of 1-butanol, 0.445 g (24.7 mmol) of water and 0.3 g of Amberlyst 15 (strongly acidic catalyst, synthetic ion exchange resin) at 20 C. without additional diluent and the mixture was heated to reflux. Low boiling components were then distilled off via a distillation attachment with a short Vigreux column up to a bottom temperature of 117-120 C. A further 8.1 g (109.31 mmol) of 1-butanol were then added and low boiling components further distilled off at a bottom temperature of about 120 C. The overall reaction lasted in total about 5.5 hours. The profile was monitored by GC analysis. 7.95 g of crude product remained at the end (according to .sup.1H-NMR 58.3%, the residue was 1-butanol). This corresponded to a yield of 94.6% of theory.

(14) Pure 1-butyl phenylphosphinate could be obtained via a fine distillation under reduced pressure.

(15) Analysis: .sup.31P-NMR (CDCl.sub.3)

(16) 1-butyl phenylphosphinate 25.1 ppm

(17) diethyl phenylphosphonite 151.2 ppm

Example 4

2-Methylpropyl phenylphosphinate (phenylphosphonous acid mono-2-methylpropyl ester)

(18) Analogously to Example 2 above, diethyl phenylphosponite (purity 98%) was reacted with water (1 molar equivalent) and isobutanol (8 molar equivalents) in the presence of a catalytic amount of concentrated sulphuric acid (2 mol %, based on the amount of diethyl phenylphosphonite used).

(19) 2-Methylpropyl phenylphosphinate was obtained in a yield of 95.0% of theory, which had a purity of 98% after fine distillation.

(20) Analysis: .sup.31P-NMR (CDCl.sub.3): 2-methylpropyl phenylphosphinate 25.4 ppm

Example 5

2-Methylpropyl phenylphosphinate (phenylphosphonous acid mono-2-methylpropyl ester)

(21) Analogously to Example 3 above, diethyl phenylphosponite (purity 98%) was reacted with water (1 molar equivalent) and isobutanol (20 molar equivalents, which were added in two roughly equal portions) in the presence of a catalytic amount of methane sulphonic acid (1% by weight, based on the amount of diethyl phenylphosphonite used).

(22) 2-Methylpropyl phenylphosphinate was obtained in a yield of 97.0% of theory, which had a purity of 98.5% after fine distillation.

(23) Analysis: .sup.31P-NMR (CDCl.sub.3): 2-methylpropyl phenylphosphinate 25.3 ppm