Reduction of triphenylphosphine oxides with specific catalysts

Abstract

The present invention relates to an improved process for preparing triphenylphosphine (TPP) by reacting triphenylphosphine oxide (TPPO) with a specific catalyst.

Description

[0001] The present invention relates to an improved process for the preparation of triphenylphosphine (TPP), which involves reacting triphenylphosphine oxide (TPPO) using a specific catalyst and a reducing agent.

[0002] TPP is a compound of formula (I) and is used on an industrial scale for Wittig Ylide synthesis for the preparation of olefin compounds (such as vitamin A or carotenoids), as well as for the Mitsunobu reaction. TPP is used in stoichiometric amounts and is oxidized to TPPO during these reactions, which is a compound of formula (II).

[0003]

[0004] Thus, a large amount of TPPO is generated during these reactions and unfortunately only a few uses of TPPO are disclosed. Since it is an extremely stable substance and difficult to handle, numerous attempts have been made to convert it back to TPP.

[0005] A common way to handle the "TPPO-problem" is to burn TPPO so that it can be wasted in a safe manner.

[0006] Another option is to reduce TPPO to TPP via TPP dichloride so that TPP can then be reused again.

[0007] Such recycling methods are known from the prior art, for example EP 638 580A1, Heteroatom Chemistry 26(3), 2015, p. 199–205.

[0008] Recycling methods known in the prior art use catalysts which typically contain metal atoms (such as Ti or Cu). These metals cause some problems in the treatment of the waste stream after the recycling process.

[0009] Claire Laye et al., Adv. Synth. Catal. 2021, 363, 3035 - 3043 disclose the use of PhSiH3 as a reducing agent and Ph3C + [B(C6F5)4] -(=TritylBARF) serves as an initiator to reduce phosphine oxide to the corresponding phosphine. TritylBARF is a relatively new reagent and is very expensive, so it is not suitable for industrial and commercial use in the reduction of TPPO. In addition, it is not suitable or only limitedly suitable for use in combination with other silanes (especially with polymethylhydrosiloxane (PMHS)).

[0010] Surprisingly, it has been found in the present invention that the use of a combination of a specific catalyst containing no metal atoms and a reducing agent allows the conversion of TPPO to TPP in excellent yields.

[0011] The catalyst used in the process according to the invention is a catalyst of formula (III)

[0012]

[0013] wherein

[0014] A is a moiety of the following formula

[0015]

[0016]

[0017] wherein any dashed line represents the bond by which the substituent of formula A is bonded to the boron atom,

[0018] and

[0019] Y is a positively charged counterion that neutralizes the charge of the complex in square brackets.

[0020] The nature of Y is not essential for the present invention. Y can vary according to the synthesis of the compound of formula (III).

[0021] The catalyst of formula (III) is an ester of boric acid and forms a spiro compound having a boron-oxygen bond.

[0022] The catalyst (compound of formula (III)) used in the process according to the invention can be prepared according to methods disclosed in the prior art (WO02 / 068433A1 or US 5,886,196).

[0023] In this document, any dashed line in the formula represents the bond by which the substituent is bonded to the rest of the molecule.

[0024] The process according to the invention is carried out in the presence of at least one siloxane and / or silane.

[0025] Accordingly, the present invention relates to a process (P) for producing triphenylphosphine (compound of formula (I))

[0026]

[0027] in which triphenylphosphine oxide (compound of formula (II)) reacts with at least one siloxane and / or at least one silane in the presence of at least one catalyst of formula (III)

[0028]

[0029] wherein

[0030] A is a moiety of the formula

[0031]

[0032]

[0033] wherein any dashed line represents a bond by which a substituent of formula A is attached to the boron atom

[0034] and

[0035] Y is a positively charged counterion which neutralizes the charge of the complex in square brackets

[0036] Particularly suitable siloxanes are those of formula (IV)

[0037]

[0038] wherein

[0039] R1, R2, R3, R4, R5, R6, R7 and R8 are each independently H or C1-C4-alkyl, and

[0040] m is a value from 0 to 100,000;

[0041] with the proviso that at least one of the substituents R1, R2, R3, R4, R5, R6, R7 or R8 is H

[0042] Preferred siloxanes are those of formula (IV) wherein

[0043] R1, R2, R3, R4, R5, R6, R7 and R8 are each independently H or C1-C2-alkyl, and

[0044] m is a value from 0 to 100,000;

[0045] with the proviso that at least one of the substituents R1, R2, R3, R4, R5, R6, R7 or R8 is H

[0046] Preferably, R1 = H

[0047] In particular, it is preferred that R1 = H and R2 = R3 = R4 = R5 = R6 = R7 = R8, preferably R2 = R3 = R4 = R5 = R6 = R7 = R8 = ethyl or methyl, preferably methyl.

[0048] More preferred siloxanes are those of the following formulas (IV') and (IV'')

[0049]

[0050] where

[0051] m is a value of 2 and 100,000.

[0052] Preferably, m is a value from 2 to 20,000, more preferably m is a value from 2 to 12,000, and most preferably m is a value from 2 to 10,000.

[0053] The most preferred siloxane is the siloxane of formula (IV'').

[0054] Particularly suitable silanes are those compounds of formula (Va) or (Vb) or (Vc).

[0055]

[0056] where

[0057] o is a value from 3 to 10;

[0058] and R9, R 10 and R 11 are each independently H or C1-C6-alkyl or OC1-C6-alkyl or phenyl, provided that at least one of the substituents R9, R 10 and R 11 is different from H.

[0059] Particularly preferred silanes of formula (Vc) are the silanes of formula (Vc') or (Vc'') or (Vc''') or (Vc'''') preferably (Vc') or (Vc'').

[0060]

[0061]

[0062] The silanes of formulas (Vb) and (Vc') and (Vc'') are the most preferred silanes.

[0063] Accordingly, the present invention also relates to method (P1), which is method (P) wherein the at least one siloxane is selected from the group having formula (IV)

[0064]

[0065] wherein

[0066] R1, R2, R3, R4, R5, R6, R7 and R8 are each independently H or C1-C4-alkyl, and

[0067] m is a value from 0 to 100,000;

[0068] with the proviso that at least one of the substituents R1, R2, R3, R4, R5, R6, R7 or R8 is H.

[0069] Accordingly, the present invention also relates to a method (P1'), which is the method (P1), wherein the at least one siloxane is selected from the group having the formula (IV), wherein

[0070] R1, R2, R3, R4, R5, R6, R7 and R8 are each independently H or C1-C2-alkyl, and

[0071] m is a value from 0 to 100,000;

[0072] with the proviso that at least one of the substituents R1, R2, R3, R4, R5, R6, R7 or R8 is H.

[0073] Accordingly, the present invention also relates to a method (P1''), which is the method (P1), wherein the at least one siloxane is selected from the following group

[0074]

[0075] wherein

[0076] m is a value between 10 and 100,000, preferably m is a value from 100 to 20,000, more preferably m is a value from 1000 to 12,000, and most preferably m is a value from 1000 to 10,000.

[0077] Accordingly, the present invention also relates to a method (P2), which is the method (P1), (P1') or (P1''), wherein the at least one siloxane is selected from the group having the formulae (Va), (Vb) and (Vc)

[0078]

[0079] wherein

[0080] o is a value from 3 to 10;

[0081] and R9, R 10 and R 11 are each independently H or C1-C6-alkyl or OC1-C6-alkyl or phenyl, with the proviso that the substituents R9, R 10 and R 11at least one of which is different from H.

[0082] Accordingly, the present invention also relates to a method (P2'), which is the method (P1), (P1') or (P1''), wherein the at least one siloxane is a siloxane having the formula (Vb),

[0083]

[0084] In the process according to the invention, the amount of the at least one siloxane and / or the at least one silane is generally preferably 1-10 mol%, preferably 2-8 mol%, relative to the compound of formula (II).

[0085] Accordingly, the present invention relates to a method (P3), which is the method (P1), (P1'), (P1''), (P2) or (P2'), wherein the amount of the at least one siloxane and / or the at least one silane is 1-10 mol%.

[0086] Accordingly, the present invention relates to a method (P3'), which is the method (P1), (P1'), (P1''), (P2) or (P2'), wherein the amount of the at least one siloxane and / or the at least one silane is 2-8 mol%.

[0087] The process according to the invention is carried out in the presence of at least one catalyst of formula (III).

[0088] The catalyst can be added as such (as shown in formula (III)).

[0089] Alternatively, the catalyst can be generated in situ in the process. This means that: the catalyst of formula (III) is formed in the reaction mixture by adding starting materials to form the catalyst in the reaction mixture (as in US 5,886,196).

[0090] This means that: instead of the compound of formula (III), oxalic acid or malic acid (=2-hydroxy succinic acid) or citric acid and boric acid (or B2O3, B(OCH3)3 or trimethylboroxine) can be added to the reaction mixture. Oxalic acid or malic acid or citric acid and boric acid (or B2O3, B(OCH3)3 or trimethylboroxine) are added to the reaction mixture in a molar ratio of 2:1 (oxalic acid or malic acid or citric acid: boric acid).

[0091] Accordingly, the present invention also relates to a method (P4), which is the method (P1), (P1'), (P1''), (P2), (P2'), (P3) or (P3'), wherein the catalyst can be added as such (as shown in formula (III)).

[0092] Accordingly, the present invention also relates to a method (P5), which is the method (P1), (P1'), (P1''), (P2), (P2'), (P3) or (P3'), wherein the catalyst is formed in situ in the reaction mixture.

[0093] Accordingly, the present invention also relates to a method (P5'), which is the method (P5), wherein oxalic acid or malic acid or citric acid and boric acid (or B2O3, B(OCH3)3 or trimethylcyclotriboroxane) are added to the reaction mixture in a molar ratio of 2:1 (oxalic acid or malic acid or citric acid: boric acid).

[0094] In the process according to the invention, the amount of the catalyst (added as such or formed in situ) is generally preferably 0.01-1 mol%, preferably 0.05-0.8 mol%, based on the compound of formula (II).

[0095] Accordingly, the present invention relates to a method (P6), which is the method (P1), (P1'), (P1''), (P2), (P2'), (P3), (P3'), (P4), (P5) or (P5'), wherein the amount of the catalyst (added as such or formed in situ) is 0.01-1 mol%, based on the compound of formula (II).

[0096] Accordingly, the present invention relates to a method (P6'), which is the method (P1), (P1'), (P1''), (P2), (P2'), (P3), (P3'), (P4), (P5) or (P5'), wherein the amount of the catalyst (added as such or formed in situ) is 0.05-0.8 mol%, based on the compound of formula (II).

[0097] The process according to the invention is generally and preferably carried out in at least one inert solvent.

[0098] The solvent used in the process according to the invention is preferably at least one aromatic solvent, ether, carbonate and / or at least one alkane.

[0099] Suitable and preferred aromatic solvents are benzene, benzene substituted by one or more C1-C4-alkyl groups or benzene substituted by one or more OC1-C4-alkyl groups.

[0100] More preferred aromatic solvents are toluene, mesitylene, xylene and anisole. A very preferred aromatic solvent is the mixture of aromatic compounds commercially available from Exxon Mobil under the trade mark Solvesso TM , in particular Solvesso TM 100.

[0101] Suitable ethers are tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF), or cyclopentyl methyl ether (CPME). The preferred solvent is cyclopentyl methyl ether (CPME).

[0102] Suitable alkanes are C4-C 18 -alkanes, which may be straight-chain, branched-chain or cyclic.

[0103] Particularly suitable alkanes are hexane, heptane, octane, pentane, decane, undecane, dodecane or any mixture of alkanes (such as Isopar M).

[0104] Accordingly, the present invention relates to a method (P7), which is method (P1), (P1'), (P1''), (P2), (P2'), (P3), (P3'), (P4), (P5), (P5'), (P6) or (P6'), wherein the method is carried out in at least one inert solvent.

[0105] Accordingly, the present invention relates to a method (P7'), which is method (P7), wherein the solvent is selected from the group consisting of aromatic solvents, ethers, carbonates and alkanes.

[0106] Accordingly, the present invention further relates to a method (P7''), which is method (P7), wherein the solvent is selected from the group consisting of benzene, benzene substituted by one or more C1-C4-alkyl groups, and benzene substituted by one or more OC1-C4-alkyl groups.

[0107] Accordingly, the present invention further relates to a method (P7'''), which is method (P7''), wherein the solvent is selected from the group consisting of toluene, mesitylene, xylene and anisole.

[0108] Accordingly, the present invention relates to a method (P7'''') which is method (P7), wherein the solvent is selected from the group consisting of tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF) or cyclopentyl methyl ether (CPME).

[0109] Accordingly, the present invention relates to a method (P7'''''), which is method (P7), wherein the solvent is selected from the group consisting of C4-C 18 -alkanes, the C4-C 18 -alkanes may be straight-chain, branched-chain or cyclic.

[0110] Accordingly, the present invention relates to a method (P7”””), which is method (P7””'), wherein the solvent is selected from the group consisting of hexane, heptane, octane, pentane, decane, undecane, dodecane or any mixture of alkanes (such as Isopar M).

[0111] The method according to the present invention is generally and preferably carried out at an elevated temperature. Preferably, the method according to the present invention is carried out at a temperature of 80°C to 200°C, more preferably at a temperature of 90°C to 180°C.

[0112] Accordingly, the present invention relates to method (P8), which is method (P1), (P1'), (P1”), (P2), (P2'), (P3), (P3'), (P4), (P5), (P5'), (P6), (P6'), (P7), (P7'), (P7”), (P7”'), (P7””), (P7””'), (P7”””) or (P7”””'), wherein the method is carried out at a temperature of 80°C to 200°C.

[0113] Accordingly, the present invention relates to method (P8), which is method (P1), (P1'), (P1”), (P2), (P2'), (P3), (P3'), (P4), (P5), (P5'), (P6), (P6'), (P7), (P7'), (P7”), (P7”'), (P7””), (P7””'), (P7”””) or (P7”””'), wherein the method is carried out at a temperature of 90°C to 180°C.

[0114] The reaction time of the method according to the present invention is generally several hours. Generally and preferably, the reaction time of the method according to the present invention is 3 to 30 hours.

[0115] Accordingly, the present invention relates to method (P9), which is method (P1), (P1'), (P1”), (P2), (P2'), (P3), (P3'), (P4), (P5), (P5'), (P6), (P6'), (P7), (P7'), (P7”), (P7”'), (P7””), (P7””'), (P7”””), (P8) or (P8'), wherein the reaction time is 3 to 30 hours.

[0116] After this method, the reaction product (the compound of formula (I)) is separated using generally known methods. The reaction product can also be purified using known methods (when required). Examples

[0117] The following examples illustrate the present invention.

[0118] Example 1

[0119] Triphenylphosphine oxide (2.84 g, 10.0 mmol) was placed in a 100 mL flask, and CPME (50.0 ml, 99.9%, containing 50 ppm BHT as an inhibitor) was added. Oxalic acid (182.07 mg, 2.002 mmol) and boric acid (61.96 mg, 1.000 mmol) were added, and the mixture was stirred at 24 °C for 10 minutes, then PMHS (6.5 g, 6.5 ml, 2.6 equivalents, 26 mmol) was added. The mixture was heated to 105 °C for 21 h and analyzed by GC.

[0120] After phase separation, the organic phase was washed with a saturated NaHCO3 solution.

[0121] The reaction mixture was concentrated under reduced pressure (40 °C, 10 mbar) to give an oily residue of about 0.5 ml. The oily suspension was diluted with 2-propanol (25 mL) and heated to 80 °C for 1 h to give a clear solution. The reaction mixture was cooled to 25 °C and then cooled to 0 °C for 1 h. Then, the solution was cooled to -10 °C for 1 h.

[0122] The resulting precipitate was separated by filtration, washed with 2-propanol (10 mL), dried in vacuo, and the resulting colorless crystals (1.35 g) were analyzed by GC. The mother liquor was cooled to -20 °C, and the precipitated crystals were separated by filtration and washed with cold 2-propanol (5 mL). The solid was dried in vacuo, and the resulting colorless crystals (0.83 g) were analyzed by GC. The colorless crystal product triphenylphosphine (2.18 g, after GC analysis: 1.89 g, 72%) was obtained.

[0123] Additional experiments are summarized in the table below. When not otherwise listed in Table 1, the same reaction conditions as in Example 1 were used.

[0124]

[0125] Table 1: TPPO reduction experiments in the presence of silane or siloxane and catalyst

[0126] Example 11

[0127] Triphenylphosphine oxide (2.85 g, 10.0 mmol) was placed in a 100 mL sulfonation flask, and CPME (50.0 mL, 99.9%, containing 50 ppm BHT as an inhibitor), boric acid (30.97 mg, 498.4 μmol), and (S)-2-hydroxy succinic acid (134.94 mg, 996.28 μmol) were added. The reaction mixture was stirred for 10 minutes and PMHS (6.5 g, 6.5 mL, 26 mmol) was added. The mixture was heated to 105 °C for 21 hours and analyzed by GC (sampled and mixed with aqueous KOH solution (42%). After phase separation, the organic phase was washed with saturated NaHCO3, diluted with ethyl acetate, filtered, and analyzed by GC).

[0128] The reaction mixture was concentrated under reduced pressure (40 °C, 10 mbar) to give a colorless oily suspension (9.43 g). The residue was diluted with 2-propanol (5 mL) and heated to 80 °C for 5 min to obtain a clear solution. The reaction mixture was cooled to 25 °C in 1 hour and then cooled to 0 °C for 30 minutes. The resulting precipitate was separated by filtration, washed with 2-propanol (4 mL, 0 °C), dried in vacuo for 1 h, and the resulting colorless crystals (2.42 g) were analyzed by GC (solvent: ethyl acetate). The mother liquor was cooled to 0 °C for 10 min, and the precipitated crystals were separated by filtration and washed with 2-propanol (2 mL, 0 °C). The solid was dried in vacuo, and the resulting colorless crystals (0.21 g) were analyzed by GC. The colorless crystalline product triphenylphosphine (2.63 g, after GC analysis: 2.50 g, 95%) was obtained.

[0129] Example 12

[0130] Triphenylphosphine oxide (2.84 g, 10.0 mmol) was placed in a 100 mL sulfonation flask, and CPME (50.0 mL, 99.9%, containing 50 ppm BHT as an inhibitor), boric acid (31.07 mg, 500 μmol), and citric acid (192.98 mg, 999.45 μmol) were added. The reaction mixture was stirred for 10 minutes and PMHS (6.5 g, 6.5 mL, 2.6 equiv, 26 mmol) was added. The mixture was heated to 105 °C for 21 hours and analyzed by GC. (Sampled and mixed with aqueous KOH solution (42%). After phase separation, the organic phase was washed with saturated NaHCO3, concentrated by rotary evaporation (40 °C, 10 mbar), diluted with ethyl acetate, filtered, and analyzed by GC).

[0131] The reaction mixture was concentrated under reduced pressure (40 °C, 10 mbar) to give a colorless oily suspension (9.0 g). The residue was diluted with 2-propanol (6.4 mL) and heated to 70 °C for 15 min to give a clear solution. The reaction mixture was cooled to 40 °C within 30 min and then cooled to 0 °C for 15 min. The resulting precipitate was separated by filtration, washed with 2-propanol (3 x 10 mL, 0 °C), dried under vacuum for 1 h, and the resulting colorless crystals (1.70 g) were analyzed by GC (solvent: ethyl acetate). The mother liquor was cooled to 0 °C for 30 min, and the precipitated crystals were separated by filtration, dried under vacuum, and the resulting colorless crystals (0.1 g) were analyzed by GC. The colorless crystalline product triphenylphosphine (1.8 g, after GC analysis: 1.70 g, 65%) was obtained.

Claims

1. A method for preparing triphenylphosphine (a compound of formula (I)), Among them, in the presence of at least one catalyst of formula (III), triphenylphosphine oxide (a compound of formula (II)) is reacted with at least one siloxane and / or at least one silane, wherein A is a moiety of the following formula Or wherein any dashed line represents a bond by which a substituent of formula A is attached to the boron atom, and Y is a positively charged counterion that neutralizes the charge of the complex in square brackets.

2. The method according to claim 1, wherein the at least one siloxane is selected from siloxanes having the formula (IV) wherein R1, R2, R3, R4, R5, R6, R7 and R8 are each independently H or C1-C4-alkyl, and m is a value from 0 to 100,000; provided that at least one of the substituents R1, R2, R3, R4, R5, R6, R7 or R8 is H.

3. The method according to claim 1 or claim 2, wherein the at least one siloxane is selected from the group consisting of wherein m is a value between 2 and 100,000, preferably m is a value between 2 and 20,000, more preferably m is a value between 2 and 12,000, and most preferably m is a value between 2 and 10,000.

4. The method according to any one of the preceding claims, wherein the at least one silane is selected from the group having the formula (Va) and (Vb) or (Vc) or or wherein o is a value from 3 to 10; and R9, R 10 and R 11 are, independently of one another, H or C1-C6-alkyl or OC1-C6-alkyl or phenyl, with the proviso that at least one of the substituents R9, R 10 and R 11 is different from H.

5. The method according to claim 4, characterized in that the silane of formula (Vc) is the silane of (Vc') or (Vc”) or (Vc”') or (Vc””), preferably (Vc') or (Vc”) 6. The method according to any one of the preceding claims, wherein the amount of at least one siloxane and / or at least one silane is 1 - 10 mol%, preferably 2 - 8 mol%, relative to the compound of formula (II).

7. The method according to any one of the preceding claims, wherein the catalyst can be added as such.

8. The method according to any one of claims 1 to 6 of the preceding claims, wherein the catalyst is formed in situ in the reaction mixture.

9. The method according to claim 7, wherein oxalic acid or malic acid or citric acid and boric acid (or B2O3, B(OCH3)3 or trimethylcyclotriboroxane) are added to the reaction mixture in a molar ratio of 2:1 (oxalic acid or malic acid or citric acid:boric acid).

10. The method according to any one of the preceding claims, wherein the amount of the catalyst (added as such or formed in situ) is 0.01 - 1 mol% relative to the compound of formula (II).

11. The method according to any one of the preceding claims, wherein the method is carried out in at least one inert solvent.

12. The method according to claim 11, wherein the solvent is selected from aromatic solvents, ethers, carbonates and alkanes.

13. The method according to any one of the preceding claims, wherein the method is carried out at a temperature of 80°C to 200°C.

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