Reduction of triphenylphosphine oxide

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 mixture of solvents).

Description

[0001] Reduction of Triphenylphosphine Oxide

[0002] 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 mixture of solvents).

[0003] TPP, which is the compound of formula (I) is used on the industrial scale in the Wittig Ylide synthesis to prepare olefinic compounds such as vitamin A or carotenoids as well as in the Mitsunobu reactions.

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

[0005] Therefore, a lot of TPPO is produced during these reactions and unfortunately only few uses of TPPO have been disclosed. Since it is an extremely stable substance which can be disposed of only with difficulty, there have been numerous attempts to convert it back into TPP.

[0006] One common way to deal with the “TPPO-problem” is to burn the TPPO, so that it can be wasted in a secure way.

[0007] Another option is the reduction of TPPO via TPP dichloride to TPP, so that TPP can then be re-used again.

[0008] Such recycling processes are known from the prior art, e.g. from EP 638 580 A1 , from Heteroatom Chemistry 26(3), 2015, p.199 - 205. Most of these recycling processes are carried out in the presence of at least one siloxane and / or at least one silane.

[0009] Furthermore, in the present invention, at least one catalyst, which comprises as metal atom, is used as well.

[0010] The reduction of TPPO, in the state of the art, is carried out in at least one inert solvent. The solvents used for the reduction of TPPO are usually alkenes or aromatic solvents.

[0011] It was, however, found that the reduction of TPPO can be carried in specific solvents, which are green solvents and the yield of TPP is excellent.

[0012] Green solvents are environmentally friendly solvents, or biosolvents, which are derived from the processing of agricultural crops, while otherwise most of the commonly used solvents (such as alkanes or aromatic solvents) are petrochemical solvents. Green solvents are vastly more eco-friendly, less toxic, less hazardous than traditional volatile organic compounds (VOCs).

[0013] Due to the importance of the reaction, wherein the TPPO is produced (as a waste product) and the problems with the use of TPPO, there is a need for an improved way for transforming TPPO into TPP, which can then be used again and wherein no petrochemical solvents are used.

[0014] Surprisingly it was found that is possible that use of specific solvents (green solvents), allows to recycle TPPO in an excellent yield.

[0015] Therefore, the present invention relates to the process (P) for producing triphenylphosphine (compound of formula (I)) wherein triphenylphosphine oxide (the compound of formula (II)) is reacted with at least one siloxane and / or at least one silane, in the presence of at least one metal containing catalyst, and in the presence of at least one solvent of formula (III)

[0016] R1-O— R2(in) wherein

[0017] R1’ is Ci-C4-alkyl, and

[0018] R2’ is a C5- or a Cs-cycloalkyl, or

[0019] R1’ and R2’ form (together with the O) a 5 or 6 membered ring, which can be substituted.

[0020] If R1’ and R2’ form (together with the O) a 5 or 6 membered ring, it is preferred that said ring is not substituted.

[0021] The process according to the present invention is carried out in the presence of at least one siloxane and / or silane.

[0022] Particularly suitable siloxanes are those of formula (IV) wherein

[0023] R1, R2, R3, R4, Rs, Re, R7 and Rs are independently from each other H or a Ci-C4-alkyl, and m is a value from 0 to 100’000; with the proviso that at least one of the substituents R1, R2, R3, R4, Rs, Re, R7 or Rs is H.

[0024] Preferred siloxanes are those of formula (IV), wherein

[0025] R1, R2, R3, R4, Rs, Re, R7 and Rs are independently from each other H or a Ci-C2-alkyl, and m is a value from 0 to 100’000 with the proviso that at least one of the substituents R1, R2, R3, R4, Rs, Re, R7 or Rs is H. It is preferred that Ri=H.

[0026] Particularly, it is preferred that Ri=H and R2= Rs= R4= Rs= Re= R? = Rs, preferably R2= Rs = R4 = Rs = Re = R? = Rs = ethyl or methyl, preferably methyl.

[0027] More preferred siloxanes are those of the formulae (IV’) and (IV”)

[0028] (TMDS)and(PMHS) wherein m is a value between 2 and 100’000.

[0029] Preferably m is a value from 2 - 20’000, more preferably m is a value from 2 - 12’000, most preferably m is a value from 2 - 10’000).

[0030] Most preferred siloxane is the siloxane of the formula (IV”).

[0031] Particularly suitable silanes are those compounds of formula (Va) or (Vb) or (Vc). wherein o is a value from 3 to 10; and Rg, R and Rn are independently from each other H or a Ci-Ce-alkyl or a OCi-Ce-alkyl or a phenyl group, with the proviso that at least one of the substituents Rg, R and Rn is different from H.

[0032] Particularly preferred silanes of formula (Vc) are silanes of the formula (Vc’) or (Vc”) or (Vc’”) or (Vc””), preferably (Vc’) or (Vc”).

[0033] (DEMS) (DMMS)

[0034] The silanes of formula (Vb) and (Vc’) and (Vc”) are the most preferred silanes.

[0035] Therefore, the present invention also relates to a process (P1), which is process (P), wherein the at least one siloxane is chosen from the group having the formula (IV) wherein

[0036] Ri, R2, R3, R4, Rs, Re, R7 and Rs are independently from each other H or a Ci-C4-alkyl, and m is a value from 0 to 100’000; with the proviso that at least one of the substituents R1, R2, R3, R4, Rs, Re, R7 or Rs is H. Therefore, the present invention also relates to a process (PT), which is process (P1), wherein the at least one siloxane is chosen from the group having the formula (IV), Wherein R1, R2, R3, R4, Rs, Re, R7 and Rs are independently from each other H or a C1-C2- alkyl, and m is a value from 0 to 100’000; with the proviso that at least one of the substituents R1, R2, R3, R4, Rs, Re, R7 or Rs is H.

[0037] Therefore, the present invention also relates to a process (P1”), which is process (P1), wherein the at least one siloxane is chosen from the group consisting of

[0038] (TMDS) and (PMHS) wherein m is a value between 10 and 100’000 (preferably m is a value from 100 - 20’000, more preferably m is a value from 1000 - 12’000, most preferably m is a value from 1000 - 10’000).

[0039] Therefore, the present invention also relates to a process (P2), which is process (P1), (PT) or (P1 ”), wherein the at least one silane is chosen from the group having the formula (Va) and (Vb) and (Vc) wherein o is a value from 3 to 10; and Rg, R and Rn are independently from each other H or a Ci-Ce-alkyl or a OCi-Ce-alkyl or a phenyl group, with the proviso that at least one of the substituents Rg, R and Rn is different from H.

[0040] Therefore, the present invention also relates to a process (P2’), which is process (P1), (PT) or (P1 ”), wherein the at least one silane is

[0041] In the process according to the present invention, the at least one siloxane and / or the at least one silane is usually and preferably used in an amount of 1 - 10 mol-%, preferably 2 - 8 mol-%, in regard to the compound of formula (II).

[0042] Therefore, the present invention also relates to a process (P3), which is process (P1), (PT), (P1 ”), (P2) or (P2’), wherein the at least one siloxane and / or the at least one silane is used in an amount of 1 - 10 mol-%, in regard to the compound of formula (II).

[0043] Therefore, the present invention also relates to a process (P3’), which is process (P1), (PT), (P1 ”), (P2) or (P2’), wherein the at least one siloxane and / or the at least one silane is used in an amount of 2 - 8 mol-%, in regard to the compound of formula (II). The process according to the present invention is carried out in the presence of at least one catalyst, which comprises at least one metal atom. Such catalysts are known from the prior art. Suitable catalysts comprise at least one metal atom, wherein the metal is chosen from the group consisting of Ti, Cu, Ni and In.

[0044] Suitable catalysts are those of formula (VI)

[0045] R6'

[0046] R3'— Ti - R5' (VI)

[0047] R4' wherein

[0048] R3’, R4’, R5’ and R6’ are independently from each other OR7’, wherein R7’ is a linear or branched Ci - Ce alkyl group, preferably ethyl, iso-propyl, n-propyl, iso-butyl or n-butyl; or

[0049] Cu(OTf)2, or InBrs.

[0050] Therefore, the present invention also relates to a process (P4), which is process (P1), (PT), (P1 ”), (P2), (P2’), (P3) or (P3’), wherein the at least one catalyst is chosen from the group consisting of compounds of formula (VI)

[0051] R6'

[0052] R3'— Ti - R5' (VI)

[0053] R4' wherein

[0054] R3’, R4’, R5’ and R6’ are independently from each other OR7’, wherein R7’ is a linear or branched Ci - Ce alkyl group, preferably R7is ethyl, isopropyl, n-propyl, iso-butyl or n-butyl;

[0055] Cu(OTf)2, and InBrs.

[0056] In the process according to the present invention the catalyst is usually and preferably used in an amount of 1 - 20 mol-equivalents (in regard to the amount of TPPO).

[0057] Therefore, the present invention also relates to a process (P5), which is process (P1), (PT), (P1 ”), (P2), (P2’), (P3), (P3’) or (P4), wherein the catalyst is used in an amount of 1-20 mol- equivalents (in regard to the amount of TPPO). The process according to the present invention is carried out in at least one solvent of formula (III).

[0058] Preferred are solvents of formula (III)

[0059] R1'— 0— R2(Hi) wherein

[0060] R1’ is Ci-C2-alkyl, and

[0061] R2’ is a Cs-cycloalkyl, or

[0062] R1’ and R2’ form (together with the O) a 5 membered ring, which can be substituted.

[0063] Most preferred are tetra hydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF) or cyclopentyl methyl ether (CPME). The most preferred solvent of formula (III) is cyclopentyl methyl ether (CPME).

[0064] Therefore, the present invention also relates to a process (P6), which is process (P1), (PT), (P1 ”), (P2), (P2’), (P3), (P3’), (P4) or (P5), wherein the at least one solvent is a compound of formula (III),

[0065] R1-O— R2(in) wherein

[0066] R1’ is Ci-C2-alkyl, and

[0067] R2’ is a Cs-cycloalkyl, or

[0068] R1’ and R2’ form (together with the O) a 5 membered ring, which can be substituted.

[0069] Therefore, the present invention also relates to a process (P6’), which is process (P1), (PT), (P1 ”), (P2), (P2’), (P3), (P3’), (P4) or (P5), wherein the at least one solvent is chosen from the group consisting of tetra hydrofuran (THF), 2-methyltetrahydrofuran (2-MeTHF) or cyclopentyl methyl ether (CPME), preferably cyclopentyl methyl ether (CPME).

[0070] The process according to the present invention is usually and preferably carried out at elevated temperature. Preferably, the process according to the present invention is carried out at a temperature of 80°C to 200°C, more preferably at 90°C to 180°C.

[0071] Therefore, the present invention also relates to a process (P7), which is process (P1), (PT), (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. Therefore, the present invention also relates to a process (P7’), which is process (P1 ), (PT), (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.

[0072] The reaction time of the process according to the present invention is usually several hours. Usually and preferably the reaction time of the process according to the present invention is 3 to 30 hours.

[0073] Therefore, the present invention also relates to a process (P8), which is process (P1), (PT), (P1 ”), (P2), (P2’), (P3), (P3’), (P4), (P5), (P6), (P6’), (P7) or (P7’), wherein the reaction time is 3 to 30 hours.

[0074] After the process the reaction product (compound of formula (I)) is isolated using commonly known methods. The reaction product can also be purified (when needed) using commonly known methods.

[0075] Examples

[0076] The following examples illustrate the invention.

[0077] Example 1

[0078] The reaction was performed under nitrogen.

[0079] Triphenylphosphine oxide (2.76 g, 9.72 mmol) was placed in a dried 50 mL tube and CPME (20 mL, 99.8 %, ACS grade) was added. Then titanium(IV) isopropoxide (0.29 g, 0.31 mL, 1 .0 mmol) was added, followed by addition of phenyl silane (2.8 g, 3.2 mL, 2.6 Eq, 25 mmol). The tube was sealed, the mixture was heated to 125 °C for 21.25 h and analyzed by GC (A sample was taken and concentrated with rotavapor (40 °C, 10 mbar), diluted with ethyl acetate and mixed with aq. KOH (42 %). After phase separation, the organic phase was washed with sat. NaHCOs and analyzed by GC).

[0080] The reaction mixture was cooled to 20 °C and concentrated under reduced pressure (40 °C, 10 mbar). The oily residue was diluted with pentane (20 mL) resulting in the precipitation of a colorless solid. The suspension was cooled using a water bath and KOH (3 M in MeOH, 5 mL) was added. After gas evaporation stopped, the pentane phase was separated, and the methanolic phase was extracted with pentane (3 x 20 mL). The pentane phases were combined, washed with sat. aq. NaHCOs (5 mL), dried with MgSO4 and concentrated under reduced pressure. The product was obtained as colorless solid (2.35 g, after GC analysis: 2.22 g, 87 %). Example 2

[0081] The reaction was performed under nitrogen.

[0082] Triphenylphosphine oxide (2.84 g, 10.0 mmol) was placed in a dried 50 mL tube and CPME (20 mL, 99.8 %, ACS grade) was added. Then titanium(IV) isopropoxide (0.29 g, 0.31 mL, 1.0 mmol) and PMHS (6.58 g, 6.50 ml, 2.58 Eq, 25.8 mmol) were added. The tube was sealed, and the mixture was heated to 125 °C for 21.25 h and analyzed by GC (A sample was taken and concentrated with rotavapor (40 °C, 10 mbar), diluted with ethyl acetate and mixed with aq. KOH (42 %). After phase separation, the organic phase was washed with sat. NaHCOs and analyzed by GC).

[0083] The reaction mixture was cooled to 20 °C and concentrated under reduced pressure (40 °C, 10 mbar). The oily residue was diluted with pentane (20 mL) resulting in the precipitation of a colorless solid. The suspension was cooled using a water bath and KOH (3 M in MeOH, 5 mL) was added. After gas evaporation stopped, the pentane phase was separated, and the methanolic phase was extracted with pentane (3 x 20 mL). The pentane phases were combined, washed with sat. aq. NaHCOs (5 mL), dried with MgSO4 and concentrated under reduced pressure. The product was obtained as colorless solid (2.35 g, after GC analysis: 2.27 g, 87 %).

[0084] Additional experiments are summarized in the following table. The same reactions conditions are used as in Example 1 when not otherwise listed in the table 1 .

[0085] Table 1 : TPPO reduction experiments in presence of silanes or siloxanes and catalyst.

[0086] Table 2: TPPO reduction experiments in presence of silanes or siloxanes and catalyst.

Claims

Claims1. Process for producing triphenylphosphine (compound of formula (I))is reacted with at least one siloxane and / or at least one silane, in the presence of at least one metal containing catalyst, and in the presence of at least one solvent of formula (III)R1-O— R2(in) whereinR1’ is Ci-C4-alkyl, andR2’ is a Cs- or a Ce-cycloalkyl, orR1’ and R2’ form (together with the O) a 5 or 6 membered ring, which can be substituted.

2. Process according to claim 1 , wherein the at least one siloxane is chosen from the group consisting of(TMDS) and (PMHS) wherein m is a value between 2 and 100’000, preferably m is a value from 2 - 20’000, more preferably m is a value from 2 - 12’000, most preferably m is a value from 2 - 10’000.

3. Process according to claim 1 or claim 2, wherein the at least one silane is chosen from the group having the formula (Va) and (Vb) or (Vc)wherein o is a value from 3 to 10 and Rg, R and Rn are independently from each other H or a Ci-Ce-alkyl or a OCi-Ce-alkyl or a phenyl group, with the proviso that at least one of the substituents Rg, R and Rn is different from H.

4. Process according to claim 3, characterized in that the silane of the formula (Vc) is a silane of the (Vc’) or (Vc”) or (Vc’”) or (Vc””), preferably (Vc’) or (Vc”)5. Process according to any of the preceding claims, wherein the at least one siloxane and / or the at least one silane is used in an amount of 1 - 10 mol-%, preferably 2 - 8 mol- %, in regard to the compound of formula (II).

6. Process according to any of the preceding claims, wherein the at least one catalyst is chosen from the group consisting of compounds of formula (VI)R6'R3'— Ti - R5' (VI)R4' whereinR3’, R4’, R5’ and R6’ are independently from each other OR7’, wherein R7’ is a linear or branched Ci - Ce alkyl group, preferably R7is ethyl, isopropyl, n-propyl, iso-butyl or n-butyl;Cu(OTf)2, and InBrs.

7. Process according to any of the preceding claims, wherein the catalyst is used in an amount of 1-20 mol-equivalents, in regard to the amount of TPPO.

8. Process according to any of the preceding claims, wherein the at least one solvent is a compound of formula (III),R1'— 0— R2(Hi) whereinR1’ is Ci-C2-alkyl, andR2’ is a Cs-cycloalkyl, orR1’ and R2’ form (together with the O) a 5 membered ring, which can be substituted.

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

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

11. Process according to any of the preceding claims, wherein the reaction time is 3 to30 hours.

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