Reduction of triphenylphosphine oxides

Abstract

The present invention relates to an improved process for preparing triphenylphosphine (TPP) by reacting triphenylphosphine oxide (TPPO) with a catalyst in a specific solvent (or a mixture of solvents).

Description

[0001] The present invention relates to an improved method for preparing triphenylphosphine (TPP) by reacting triphenylphosphine oxide (TPPO) with a catalyst in a specific solvent (or a mixture of solvents).

[0002] TPP is a compound of the formula (I) which is used on an industrial scale in the Wittig Ylide synthesis for the preparation of olefinic compounds (eg vitamin A or carotenoids) and in the Mitsunobu reaction.

[0003]

[0004] TPP is used in stoichiometric amounts and during these reactions is oxidized to TPPO, which is a compound of formula (II)

[0005]

[0006] Therefore, large amounts of TPPO are produced during these reactions, and unfortunately only a few uses for TPPO have been disclosed. Because it is an extremely stable substance that is difficult to handle, many attempts have been made to convert it back into TPP.

[0007] A common way to deal with the "TPPO-problem" is to burn the TPPO so that it can be consumed in a safe manner.

[0008] Another option is to reduce TPPO to TPP via TPP dichloride, so that TPP can then be reused again.

[0009] Such recycling methods are known from the prior art, for example EP 638 580 A1, Heteroatom Chemistry 26(3), 2015, p. 199–205.

[0010] Most of these recycling processes are carried out in the presence of at least one siloxane and / or at least one silane.

[0011] Furthermore, in the present invention, at least one catalyst containing metal atoms is also used.

[0012] In the prior art, the reduction of TPPO is carried out in at least one inert solvent. The solvent used for the reduction of TPPO is usually an olefin or aromatic solvent.

[0013] However, it was found that the reduction of TPPO can be carried out in specific solvents, which are green solvents, and the yield of TPP is excellent.

[0014] Green solvents are environmentally friendly solvents or biosolvents (derived from the processing of agricultural crops), while other commonly used solvents (such as alkanes or aromatic solvents) are mostly petrochemical solvents. Green solvents are more environmentally friendly, less toxic and less harmful than traditional volatile organic compounds (VOCs).

[0015] Due to the importance of the reactions that produce TPPO (as a waste product) and the problems with using TPPO, there is a need for an improved way of converting TPPO to TPP, which can then be used again, and in which no petrochemical solvents are used.

[0016] It was surprisingly found that the use of specific solvents (green solvents) can allow the recovery of TPPO in excellent yields.

[0017] Therefore, the present invention relates to a process (P) for producing triphenylphosphine (compound of formula (I))

[0018]

[0019] wherein triphenylphosphine oxide (compound of formula (II)) is reacted with at least one siloxane and / or at least one silane in the presence of at least one solvent of formula (III) and in the presence of at least one metal-containing catalyst,

[0020]

[0021] R 1′ -OR 2′ (III),

[0022] in

[0023] R 1' is C1-C4-alkyl, and

[0024] R 2' is C5-cycloalkyl or C6-cycloalkyl, or

[0025] R 1' and R 2' (Together with O) it forms a 5-membered or 6-membered ring which may be substituted.

[0026] If R 1' and R 2' (Together with O) form a 5-membered ring or a 6-membered ring, preferably the ring is unsubstituted.

[0027] The process according to the invention is carried out in the presence of at least one siloxane and / or silane.

[0028] Particularly suitable siloxanes are those of formula (IV)

[0029]

[0030] in

[0031] R1, R2, R3, R4, R5, R6, R7 and R8 are independently of one another H or C1-C4-alkyl, and

[0032] m is a value from 0 to 100,000;

[0033] Provided that at least one of the substituents R1, R2, R3, R4, R5, R6, R7 or R8 is H.

[0034] Preferred siloxanes are those of formula (IV) wherein

[0035] R1, R2, R3, R4, R5, R6, R7 and R8 are independently of one another H or C1-C2-alkyl, and

[0036] m is a value from 0 to 100,000;

[0037] Provided that at least one of the substituents R1, R2, R3, R4, R5, R6, R7 or R8 is H.

[0038] Preferably, R1=H.

[0039] 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.

[0040] More preferred siloxanes are those of the following formulae (IV') and (IV")

[0041]

[0042] in

[0043] m is 2 and has a value of 100,000.

[0044] Preferably, m is a value from 2 to 20,000, more preferably m is a value from 2 to 12,000, most preferably m is a value from 2 to 10,000.

[0045] The most preferred siloxane is the siloxane of formula (IV").

[0046] Particularly suitable silanes are those of the formula (Va) or (Vb) or (Vc).

[0047] or or

[0048] in

[0049] o is a value from 3 to 10;

[0050] And R9, R 10 and R 11 are independently H or C1-C6-alkyl or OC1-C6-alkyl or phenyl, provided that the substituents R9, R 10 and R 11 At least one of them is different from H.

[0051] Particularly preferred silanes of formula (Vc) are silanes of formula (Vc′) or (Vc″) or (Vc″′) or (Vc″″), preferably (Vc′) or (Vc″),

[0052]

[0053] Silanes of formula (Vb), (Vc') and (Vc") are the most preferred silanes.

[0054] Therefore, the present invention also relates to process (P1), which is process (P), wherein the at least one siloxane is selected from the group consisting of siloxanes having formula (IV)

[0055]

[0056] in

[0057] R1, R2, R3, R4, R5, R6, R7 and R8 are independently of one another H or C1-C4-alkyl, and

[0058] m is a value from 0 to 100,000;

[0059] Provided that at least one of the substituents R1, R2, R3, R4, R5, R6, R7 or R8 is H.

[0060] Therefore, the present invention also relates to process (P1′), which is process (P1), wherein the at least one siloxane is selected from the group having formula (IV),

[0061] wherein R1, R2, R3, R4, R5, R6, R7 and R8 are independently H or C1-C2-alkyl, and

[0062] m is a value from 0 to 100,000;

[0063] Provided that at least one of the substituents R1, R2, R3, R4, R5, R6, R7 or R8 is H.

[0064] Therefore, the present invention also relates to a process (P1") which is a process (P1) wherein the at least one siloxane is selected from The group composed of

[0065] in

[0066] m is a value between 10 and 100,000, preferably m is a value between 100 and 20,000, more preferably m is a value between 1000 and 12,000, most preferably m is a value between 1000 and 10,000.

[0067] Therefore, the present invention also relates to a process (P2) which is a process (P1), (P1′) or (P1″), wherein the at least one siloxane is selected from the group consisting of siloxanes having formulae (Va) and (Vb) and (Vc).

[0068] or or

[0069] in

[0070] o is a value from 3 to 10;

[0071] And R9, R 10 and R 11 are independently H or C1-C6-alkyl or OC1-C6-alkyl or phenyl, provided that the substituents R9, R 10 and R 11 At least one of them is different from H.

[0072] Therefore, the present invention also relates to a process (P2′) which is a process (P1), (P1′) or (P1″), wherein the at least one siloxane is

[0073]

[0074] In the process according to the invention, the at least one siloxane and / or the at least one silane is generally used in an amount preferably of 1 to 10 mol %, preferably 2 to 8 mol %, relative to the compound of formula (II).

[0075] Therefore, the present invention relates to process (P3), which is process (P1), (P1′), (P1″), (P2) or (P2′), wherein the at least one siloxane and / or the at least one silane is used in an amount of 1 to 10 mol %.

[0076] Therefore, the present invention relates to process (P3') which is process (P1), (P1'), (P1"), (P2) or (P2'), wherein the at least one siloxane and / or the at least one silane is used in an amount of 2 to 8 mol %.

[0077] The method according to the invention is carried out in the presence of at least one catalyst comprising at least one metal atom. Such catalysts are known in the prior art. Suitable catalysts comprise at least one metal atom, wherein the metal is selected from the group consisting of Ti, Cu, Ni and In.

[0078] Suitable catalysts are Cu(OTf)2 or InBr3 or those of formula (VI),

[0079]

[0080] in

[0081] R 3' 、R 4' 、R 5' and R 6' Independently OR 7' ,

[0082] where R 7' is a linear or branched C1-C6 alkyl group, preferably ethyl, isopropyl, n-propyl, isobutyl or n-butyl.

[0083] Therefore, the present invention also relates to process (P4), which is process (P1), (P1'), (P1"), (P2), (P2'), (P3) or (P3'), wherein the at least one catalyst is selected from Cu(OTf)2, InBr3 and a compound of formula (VI)

[0084]

[0085] in

[0086] R 3’ 、R 4’ 、R 5’ and R 6’ Independently OR 7’ ,

[0087] where R 7’ is a linear or branched C1-C6 alkyl group, preferably R 7 It is ethyl, isopropyl, n-propyl, isobutyl or n-butyl.

[0088] In the process according to the present invention, the amount of the catalyst used is preferably generally 1 to 20 molar equivalents (relative to the amount of TPPO).

[0089] Therefore, the present invention also relates to process (P5), which is process (P1), (P1'), (P1"), (P2), (P2'), (P3), (P3') or (P4), wherein the amount of the catalyst is 1 to 20 molar equivalents (relative to the amount of TPPO).

[0090] The process according to the invention is carried out in at least one solvent of the formula (III).

[0091] Preferred are solvents of formula (III) wherein

[0092] R 1′ -OR 2′ (III),

[0093] in

[0094] R 1' is C1-C2-alkyl, and

[0095] R 2' is a C5-cycloalkyl group, or

[0096] R 1' and R 2' (Together with O) it forms a 5-membered ring which may be substituted.

[0097] Most preferred are tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF) or cyclopentyl methyl ether (CPME).The most preferred solvent of formula (III) is cyclopentyl methyl ether (CPME).

[0098] Therefore, the present invention also relates to process (P6), which is process (P1), (P1′), (P1″), (P2), (P2′), (P3), (P3′), (P4) or (P5), wherein the at least one solvent is a compound of formula (III),

[0099] R 1′ -OR 2′ (III),

[0100] in

[0101] R 1' is C1-C2-alkyl, and

[0102] R 2' is a C5-cycloalkyl group, or

[0103] R 1' and R 2' (Together with O) it forms a 5-membered ring which may be substituted.

[0104] Therefore, the present invention relates to a process (P6') which is process (P1), (P1'), (P1"), (P2), (P2'), (P3), (P3'), (P4) or (P5), wherein at least one solvent is selected from the group consisting of tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF) or cyclopentyl methyl ether (CPME), preferably cyclopentyl methyl ether (CPME).

[0105] The process according to the invention is generally and preferably carried out at elevated temperature. Preferably, the process according to the invention is carried out at a temperature of 80 to 200°C, more preferably at a temperature of 90 to 180°C.

[0106] Therefore, the present invention relates to process (P7), which is process (P1), (P1'), (P1"), (P2), (P2'), (P3), (P3'), (P4), (P5), (P6) or (P6'), wherein the process is carried out at a temperature of 80°C to 200°C.

[0107] Therefore, the present invention relates to process (P7'), which is process (P1), (P1'), (P1"), (P2), (P2'), (P3), (P3'), (P4), (P5), (P6) or (P6'), wherein the process is carried out at a temperature of 90°C to 180°C.

[0108] The reaction time of the process according to the invention is generally several hours. Typically and preferably, the reaction time of the process according to the invention is from 3 to 30 hours.

[0109] Therefore, the present invention relates to method (P8), which is method (P1), (P1'), (P1"), (P2), (P2'), (P3), (P3'), (P4), (P5), (P6), (P6'), (P7) or (P7'), wherein the reaction time is 3 to 30 hours.

[0110] After this process, the reaction product (compound of formula (I)) is isolated using generally known methods. The reaction product can also be purified (when necessary) using known methods. Example

[0111] The following examples illustrate the invention.

[0112] Example 1

[0113] The reaction was carried out under nitrogen.

[0114] Phosphine trioxide (2.76 g, 9.72 mmol) was placed in a dry 50 mL tube and CPME (20 ml, 99.8%, ACS grade) was added. Titanium (IV) isopropoxide (0.29 g, 0.31 mL, 1.0 mmol) was then added, followed by phenylsilane (2.8 g, 3.2 mL, 2.6 equivalents, 25 mmol). The tube was sealed and the mixture was heated to 125° C. for 21.25 hours and analyzed by GC (a sample was taken and concentrated using a rotary evaporator (40° C., 10 mbar), diluted with ethyl acetate, and mixed with a KOH aqueous solution (42%). After phase separation, the organic phase was washed with saturated NaHCO and analyzed by GC).

[0115] The reaction mixture was cooled to 20°C and concentrated under reduced pressure (40°C, 10mbar). The oily residue was diluted with pentane (20mL) to obtain a colorless solid precipitate. A water bath was used to cool the suspension and KOH (3M solution in MeOH, 5mL) was added. After gas evaporation stopped, the pentane phase was separated and the methanol phase was extracted with pentane (3 × 20mL). The pentane phases were merged, washed with saturated NaHCO solution (5mL), dried and concentrated under reduced pressure with MgSO. A colorless product (2.35g, after GC analysis: 2.22g, 87%) was obtained.

[0116] Example 2

[0117] The reaction was carried out under nitrogen.

[0118] Phosphine trioxide (2.84 g, 10.0 mmol) was placed in a dry 50 mL tube and CPME (20 ml, 99.8%, ACS grade) was added. Titanium (IV) isopropoxide (0.29 g, 0.31 mL, 1.0 mmol) and PMHS (6.58 g, 6.50 ml, 2.58 equivalents, 25.8 mmol) were then added. The tube was sealed and the mixture was heated to 125 ° C for 21.25 hours and analyzed by GC (a sample was taken and concentrated using a rotary evaporator (40 ° C, 10 mbar), diluted with ethyl acetate, and mixed with a KOH aqueous solution (42%). After phase separation, the organic phase was washed with saturated NaHCO 3 and analyzed by GC).

[0119] The reaction mixture was cooled to 20°C and concentrated under reduced pressure (40°C, 10mbar). The oily residue was diluted with pentane (20mL) to give a colorless solid precipitate. A water bath was used to cool the suspension and KOH (3M solution in MeOH, 5mL) was added. After gas evaporation stopped, the pentane phase was separated and the methanol phase was extracted with pentane (3×20mL). The pentane phases were combined, washed with saturated NaHCO solution (5mL), dried over MgSO and concentrated under reduced pressure. A colorless product (2.35g, after GC analysis: 2.27g, 87%) was obtained.

[0120] Additional experiments are summarized in the table below. Unless otherwise specified in Table 1, the same reaction conditions as in Example 1 were used.

[0121] Table 1: TPPO reduction experiments in the presence of silanes or siloxanes and catalysts.

[0122]

[0123] Table 2: TPPO reduction experiments in the presence of silanes or siloxanes and catalysts.

[0124]

Claims

1. A method for preparing triphenylphosphine (a compound of formula (I)) in, reacting triphenylphosphine oxide (compound of formula (II)) with at least one siloxane and / or at least one silane in the presence of at least one solvent of formula (III) and in the presence of at least one metal-containing catalyst, in R 1' is C1-C4-alkyl, and R 2' is C5-cycloalkyl or C6-cycloalkyl, or R 1' and R 2' (Together with O) it forms a 5-membered or 6-membered ring which may be substituted.

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

3. The method according to claim 1 or claim 2, wherein the at least one silane is selected from the group consisting of: or or in o is a value from 3 to 10; And R9, R 10 and R 11 are independently H or C1-C6-alkyl or OC1-C6-alkyl or phenyl, provided that the substituents R9, R 10 and R 11 At least one of them is different from H.

4. The method according to claim 3, characterized in that The silane of formula (Vc) is (Vc') or (Vc") or (Vc'") or (Vc"), preferably (Vc') or (Vc") 5. The process according to any one of the preceding claims, wherein the at least one siloxane and / or the at least one silane is used in an amount of 1 to 10 mol%, preferably 2 to 8 mol%, relative to the compound of formula (II).

6. The process according to any one of the preceding claims, wherein at least one catalyst is selected from the group having formula (VI), Cu(OTf) 2 and InBr 3 , in R 3' 、R 4' 、R 5' and R 6' Independently OR 7’ , where R 7' is a linear or branched C1-C6 alkyl group, preferably R 7 It is ethyl, isopropyl, n-propyl, isobutyl or n-butyl.

7. The process according to any one of the preceding claims, wherein the catalyst is used in an amount of 1 to 20 molar equivalents relative to the amount of TPPO.

8. The process according to any one of the preceding claims, wherein at least one solvent is a compound of formula (III), R 1′ -OR 2′ (III), in R 1' is C1-C2-alkyl, and R 2' is a C5-cycloalkyl group, or R 1' and R 2' (Together with O) it forms a 5-membered ring which may be substituted.

9. The process according to any one of the preceding claims, wherein at least one solvent is selected from the group consisting of tetrahydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF) or cyclopentyl methyl ether (CPME), preferably cyclopentyl methyl ether (CPME).

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

11. The process according to any one of the preceding claims, wherein the reaction time is from 3 to 30 hours.

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