Patent Application
20250163085
This application relates to organic chemical synthesis, and more particularly to a method for preparing a phosphine compound based on pyrophosphorous acid.
Triphenylphosphine is an important fine chemical, which has been widely used in the organic synthesis and industrial production. For example, triphenylphosphine can participate in the Wittig reaction, Staudinger reaction, Mitsunobu reaction, and Appel reaction, and it also serves as a ligand in various transition metal-catalyzed homogeneous reactions. The industrial production of vitamins through the Wittig reaction involving triphenylphosphine is accompanied by the generation of a byproduct triphenylphosphine oxide (with an annual production reaching ten thousand tons). Due to its stable chemical properties and low utilization value, the triphenylphosphine oxide is often treated as solid waste or by incineration, leading to a waste of phosphorus resources and environmental pollution. As environmental concerns and the global shortage of phosphorus resources become increasingly prominent, recycling triphenylphosphine oxide has become essential.
Currently, the triphenylphosphine oxide is often converted into triphenylphosphine by reduction for recycling through the following routes.
In summary, both the traditional methods and iodine-mediated reduction methods represented below struggle with high cost of reducing agents, potential safety risks, or serious pollution.
An object of the disclosure is to provide a method for preparing a phosphine compound based on pyrophosphorous acid to overcome the defects in the prior art. The method provided herein employs inexpensive and readily-available pyrophosphorous acid (H4P2O5) as reducing agent and an extremely low amount of iodine (I2) as a catalyst, which are mixed with a phosphine oxide (sulfide) compound to produce the desired phosphine compound. Based on this, this method is cost-effective, efficient, easy to operate, and safe, and thus is particularly suitable for the large-scale industrial production.
Technical solutions of the present disclosure are described as follows.
The method for preparing the phosphine compound based on pyrophosphorous acid, comprising:
and the pyrophosphorous acid (H4P2O5) is represented by:
wherein a molar ratio of pyrophosphorous acid to a phosphine oxide group in phosphine oxide compound or a phosphine sulfide group in the phosphine sulfide compound is 1-20:1; and a molar ratio of the catalyst to the phosphine oxide group in the phosphine oxide compound or the phosphine sulfide group in the phosphine sulfide compound is 0.001-0.1:1.
In some embodiments, the elementary halogen X2 is selected from the group consisting of Cl2, Br2 and I2; and the halide MXXY is an organic or inorganic halide free of fluorine.
In some embodiments, the halide MXXY is selected from the group consisting of LiX, NaX, KX, MgX2, AlX3, FeX2, FeX3, NH4X, R3NH and R3SiX, where R is an alkyl or an aryl group.
In some embodiments, the elementary halogen X2 is I2, and the halide MXXY is an iodide compound.
In some embodiments, the phosphine oxide compound contains an aromatic group, and the phosphine sulfide compound contains an aromatic group.
In some embodiments, the phosphine oxide compound contains the aromatic group bonded to P, and the phosphine sulfide compound contains the aromatic group bonded to P.
In some embodiments, the phosphine oxide compound and the phosphine sulfide compound are each represented by
the phosphine compound Y is correspondingly represented by
and a reaction scheme is correspondingly shown as
In some embodiments, R1 and R2 are each independently an unsubstituted phenyl, or a phenyl substituted with halogen, alkoxy, trifluoromethyl, cyano, alkyl, or a combination thereof;
In some embodiments, the high-molecular group has a molecular weight of 3000-5000, e.g., polyacrylonitrile groups and polyethylene glycol group.
In some embodiments, for the pyrophosphorous acid with impurities, the impurities comprise carboxylic acid, acyl chloride, phosphorous acid, water, hydrogen chloride, or a combination thereof.
In some embodiments, the impurities account for 20% or less of a total weight of the pyrophosphorous acid.
In some embodiments, the reduction reaction is carried out under a nitrogen atmosphere or an air atmosphere.
In some embodiments, the reduction reaction is carried out at 40-120° C.
In some embodiments, the reduction reaction is carried out at 80-100° C.
In some embodiments, the method provided herein further comprising:
In some embodiments, the organic solvent is selected from the group consisting of benzene, toluene, xylene, hexane, pentane, dichloroethane, tetrachloroethylene, trichloromethane, and a combination thereof.
In some embodiments, the organic solvent is selected from the group consisting of dichloroethane, tetrachloroethylene, trichloromethane, and a combination thereof.
In some embodiments, the molar ratio of the catalyst to the phosphine oxide group in the phosphine oxide compound or the phosphine sulfide group in the phosphine sulfide compound is 0.0025-0.025:1.
In some embodiments, a final byproduct generated in the reaction is orthophosphoric acid (H3PO4), which can be easily removed by water washing and is readily recoverable.
In some embodiments, the pyrophosphorous acid (H4P2O5) is prepared through steps of:
mixing phosphorous acid (H3PO3) with phosphorus trichloride (PCl3) in a molar ratio of 5:1 under a nitrogen atmosphere at 0° C.; restoring the reaction mixture to room temperature until the reaction is completed; and removing low-boiling point substances from the reaction mixture under reduced pressure to obtain the pyrophosphorous acid (H4P2O5).
Alternatively, the pyrophosphorous acid (H4P2O5) is prepared through the following steps: mixing a carboxylic acid with phosphorus trichloride (PCl3) in a molar ratio of 3:1 under a nitrogen atmosphere at 0° C.; restoring the reaction mixture to room temperature until the reaction is completed; and removing low-boiling point substances from the reaction mixture under reduced pressure to obtain the pyrophosphorous acid (H4P2O5).
Pyrophosphorous acid (H4P2O5) can also be synthesized by other well-known methods, for example, it can be prepared through the intermolecular dehydration of phosphorous acid (H3PO3).
Compared to the prior art, the present disclosure has the following beneficial effects.
The technical solutions of the present disclosure will be described clearly and completely below in conjunction with the embodiments. It is obvious that the described embodiments are merely some embodiments of the present disclosure, instead of all embodiments. Based on the embodiments in the present disclosure, all other embodiments obtained by those of ordinary skill in the art without making creative effort shall fall within the scope of the present disclosure.
Synthesis of Pyrophosphorous Acid (H4P2O5)
Phosphorous acid (410 g, 5 mol, 5 equiv.) was added to a three-neck flask under a nitrogen atmosphere, to which phosphorus trichloride (PCl3, 137.3 g, 1 mmol, 1 equiv.) was added dropwise at 0° C. The reaction mixture was restored to room temperature and reacted overnight. After the reaction was completed, the reaction mixture was subjected to vacuum distillation to remove low-boiling point substances, so as to produce a yellow solid pyrophosphorous acid (H4P2O5, 350.3 g, 2.4 mol, 96% yield, 99% purity as determined by 31P NMR and 1H NMR).
Triphenylphosphine oxide (Ph3P(O), 1.0 g, 3.59 mmol, 1 equiv.), iodine (I2, 22.8 mg, 0.09 mmol, 0.025 equiv.), pyrophosphorous acid (H4P2O5, 5.26 g, 35.9 mmol, 10 equiv.) and toluene (5.0 mL) were added to a 50 mL Schlenk flask under a nitrogen atmosphere. The reaction mixture was heated to 100° C. and reacted at 100° C. for 5 h. After the reaction was completed, the reaction mixture was added with water (5 mL), and subjected to extraction with ethyl acetate. An organic phase was collected, concentrated and purified by silica gel column chromatography under a nitrogen atmosphere to produce triphenylphosphine (Ph3P, 867.7 mg, 3.3 mmol, 99.5% purity analyzed by gas chromatography (GC) and 92% yield).
Based on Example 1, the solvent (without solvent or with different solvents), catalyst (iodine (I2) or hydrogen iodide (HI)), the solvent volume (mL), the molar ratio of pyrophosphorous acid (H4P2O5) to triphenylphosphine oxide (Ph3P(O)), the molar ratio of iodine (I2) to triphenylphosphine oxide (Ph3P(O)), the reaction temperature and the reaction time were adjusted to obtain various triphenylphosphine (Ph3P) samples 2-24.
The reaction conditions of Examples 1-24 were shown in Table 1.
It can be concluded from the comparison between Example 1 and Examples 2-3 that under the same conditions, the reaction was essentially complete after 5 h, and extending the reaction time will not significantly increase the yield after 5 h.
It can be concluded from the comparison between Example 1 and Examples 4-5 under the same conditions, 100° C. was the optimal reaction temperature, and lowering or further increasing the temperature will not increase the yield.
The comparison between Example 1 and Examples 6-9 showed that under the same conditions, continuously reducing the amount of pyrophosphorous acid (H4P2O5) led to a decrease in the reaction yield. In the case of 1.3 equivalents of H4P2O5 were used, only 11% of triphenylphosphine (Ph3P) was reduced. Increasing the amount of pyrophosphorous acid (H4P2O5) from 10 equivalents to 15 equivalents did not further improve the yield; instead, it decreased from 92% to 90%. Therefore, it could be concluded that for the reduction reaction of phosphine oxide (sulfur) compounds in the H4P2O5/I2 system, the molar ratio of H4P2O5 to phosphine oxide (sulfur) compounds should be between 1-20:1, with a preferred ratio of 8-15:1. Considering economic cost factors, the most optimal molar ratio is 8-10:1.
The comparison between Example 1 and Examples 10-13 showed that under the same conditions, as demonstrated in Example 10, increasing the amount of iodine (I2) as a catalyst actually decreased the reaction yield. As seen in Example 11, when the iodine (I2) amount was reduced to 0.0055 mol %, the yield increased to 94%, which was higher than the result in Example 1 where 0.025 mol % iodine was used, indicating that a moderate reduction in iodine amount was more beneficial for the reduction reaction. As shown in Example 13, when the iodine (I2) amount was further reduced to 0.0025 mol %, a high yield of 91% was still maintained. Therefore, it could be concluded that for the reduction reaction of phosphine oxide (sulfur) compounds in the H4P2O5/I2 system, the molar ratio of iodine (I2) to phosphine oxide (sulfur) compounds should be between 0.001-0.1:1, with a preferred ratio of 0.0025-0.025:1.
The comparison between Example 1 and Examples 14-15 showed that under the same reaction conditions, the reaction failed to proceed without the addition of iodine (I2) as the catalyst, nor did it proceed when hydrogen iodide (HI) was used as a substitute for iodine (I2).
The comparison between Example 1 and Example 16 showed that under the same reaction conditions, the reaction can proceed efficiently even without the addition of a solvent, achieving a yield of 91% for triphenylphosphine (Ph3P).
The comparison between Example 1 and Examples 17-18 showed that under the same reaction conditions, polar solvents, such as ethanol and THE, will hinder the reaction from occurring.
The comparison between Example 1 and Examples 19-21 demonstrated that under the same reaction conditions, the reaction can also proceed in a non-polar hydrocarbon solvent such as xylene, mesitylene, and n-hexane.
Triphenylphosphine oxide (Ph3P(O), 1.0 g, 3.59 mmol, 1 equiv.), iodine (I2) (22.8 mg, 0.09 mmol, 0.025 equiv.), pyrophosphorous acid (H4P2O5, 5.26 g, 35.9 mmol, 10 equiv.) and toluene (5.0 mL) were added to a 50 mL Schlenk flask under an air atmosphere. The reaction mixture was heated to 100° C. and reacted at 100° C. for 5 h. After the reaction was completed, the reaction mixture was added with water (5 mL), and subjected to extraction with ethyl acetate. The organic phase was collected, concentrated and purified by silica gel column chromatography under a nitrogen atmosphere to produce triphenylphosphine (Ph3P, 783.7 mg, 2.99 mmol, 99.5% GC content and 83% yield).
The comparison between Example 1 and Example 25 showed that triphenylphosphine oxide (Ph3P(O)) can participate in the reduction reaction of the H4P2O5/I2 system under both air and nitrogen atmospheres, without significant loss in yield. However, it was observed that triphenylphosphine oxide (Ph3P(O)) had a higher yield under an oxygen-free condition than under an air atmosphere. Therefore, it could be concluded that the reduction reaction of phosphine oxide (sulfur) compounds in the H4P2O5/I2 system could proceed under both air and nitrogen atmosphere (under oxygen or oxygen-free conditions).
Preparation of Triphenylphosphine (Ph3P) Based on a Mixture of Pyrophosphorous Acid (H4P2O5) Containing Impurities
Triphenylphosphine oxide (Ph3P(O), 1.0 g, 3.59 mmol, 1 equiv.), iodine (I2) (22.8 mg, 0.09 mmol, 0.025 equiv.), a mixture of pyrophosphorous acid (H4P2O5, 5.3 g, containing 80 wt. % H4P2O5, 15 wt. % H3PO3, 1 wt. % i-BuCO2H, 3 wt. % i-BuCOCl, 0.5 wt. % HCl and 0.5 wt. % unidentified substances) and toluene (5.0 mL) were added to a 50 mL Schlenk flask under a nitrogen atmosphere. The reaction mixture was heated to 100° C. and reacted at 100° C. for 5 h. After the reaction was completed, the reaction mixture was added with water (5 mL), and subjected to extraction with ethyl acetate. The organic phase was collected, concentrated and purified by silica gel column chromatography under a nitrogen atmosphere to produce triphenylphosphine (Ph3P, 848.3 mg, 3.2 mmol, 99.5% GC content and 90% yield).
The comparison between Example 1 and Example 26 showed that using the mixture of pyrophosphorous acid (H4P2O5) containing impurities to prepare triphenylphosphine (Ph3P) resulted in a yield of 90%. This indicated that the waste phosphoric acid byproduct (containing 80 wt. % pyrophosphorous acid and 8 equiv. of effective pyrophosphorous acid) obtained from the industrial preparation of isobutyryl chloride using isobutyric acid and PCl3 can be used in this reduction catalytic reaction to achieve a high yield of the triphenylphosphine product.
Reduction Reactions of Different Phosphine Oxide and Phosphine Sulfide Compounds in the H4P2O5/I2 System
Based on the optimal Example 11 in Examples 1-24, 1 g of different phosphine oxide and phosphine sulfide compounds were separately selected and reacted with 0.0055 mol % iodine (I2), 10 equivalents of pyrophosphorous acid (H4P2O5) and 5 mL of toluene at 100° C. for 5 h to obtain the corresponding phosphine compounds.
The reactions of Example 11 and Examples 27-34 were shown in Table 2.
Through Example 11, Examples 27-29 and Examples 31-33, it could be seen that the yields of the different phosphine compound products were all above 85%.
It can be concluded from the comparison between Example 11 and Examples 27-34 that the phosphine oxide compound contained an aromatic group, and the phosphine sulfide compound contained an aromatic group. Furthermore, the phosphine oxide compound contained the aromatic group bonded to P, and the phosphine sulfide compound contained the aromatic group bonded to P.
R1 and R2 were each an aryl group. R3 was selected from the group consisting of cycloalkyl, alkyl, thiophenyl, ferrocenyl, and aryl. R4 was selected from the group consisting of aryl, ferrocenyl and alkyl. R1, R2 and R3 can be the same or independently different.
Furthermore, R1 and R2 were each independently an unsubstituted phenyl, or a phenyl substituted with halogen, alkoxy, trifluoromethyl, cyano, alkyl, or a combination thereof. R3 was an unsubstituted phenyl, thiophenyl, ferrocenyl, cycloalkyl, an unsubstituted alkyl, a phenyl substituted with halogen, alkoxy, trifluoromethyl, cyano, alkyl or a combination thereof, or an alkyl substituted with phenyl. R4 was selected from the group consisting of phenyl, ferrocenyl and alkyl.
Based on Examples 1 and 27-34, it can be inferred that Z can be O or S. Therefore, it could be further speculated that both phosphine oxide and phosphine sulfide compounds can produce the phosphine compounds by reduction in the H4P2O5/I2 system.
Reduction Reactions of Various Phosphine Oxide Compounds Containing Multiple Phosphine Oxide Bonds in the H4P2O5/I2 System
Based on the optimal Example 11, 1 g of various phosphine oxide compounds containing multiple phosphine oxide bonds and phosphine sulfide compounds were separately selected and reacted with 0.0055 mol % iodine (I2), 10 equivalents of pyrophosphorous acid (H4P2O5) and 5 mL of toluene at 100° C. for 5 h to obtain the corresponding phosphine compounds.
The reactions of Examples 35-38 were shown in Table 3.
From Examples 35-38, it can be observed that compounds containing two phosphine oxide bonds reacted in the H4P2O5/I2 system with yields above 97%. Therefore, it could be concluded that phosphine oxide compounds with multiple phosphine oxide groups can react in the H4P2O5/I2 system and achieve good yields.
Based on Example 1, 0.18 mmol of different halides (MXXY) were selected as catalysts and reacted under the same conditions as in Example 1 to produce various triphenylphosphine (Ph3P) samples 39-41.
The reaction conditions for Examples 39-41 were shown in Table 4.
It could be seen from Examples 39-41 that halide (MXXY) as the catalyst enabled the preparation of phosphine compounds.
From Example 41, it was observed that non-iodide catalysts can still facilitate the preparation of phosphine compounds, although the yield was only 3%. Therefore, iodide compounds were preferred catalysts for the preparation of phosphine compounds.
Preparation of Triphenylphosphine (Ph3P) Based on Phosphorous Acid (H3PO3)
Triphenylphosphine oxide (Ph3P(O), 1.0 g, 3.59 mmol, 1 equiv.), iodine (I2, 22.8 mg, 0.09 mmol, 0.025 equiv.), phosphorous acid (H3PO3, 5.9 g, 71.87 mmol, 10 equiv.) and toluene (5.0 mL) were added to a 50 mL Schlenk flask under a nitrogen atmosphere. The reaction mixture was heated to 100° C. and reacted at 100° C. for 5 h. No reaction was observed, and the yield was 0%.
Preparation of Triphenylphosphine (Ph3P) Based on Phosphorous Acid (H3PO3)
Triphenylphosphine oxide (Ph3P(O), 1.0 g, 3.59 mmol, 1 equiv.), iodine (I2, 22.8 mg, 0.09 mmol, 0.025 equiv.), phosphorous acid (H3PO3, 5.9 g, 71.87 mmol, 20 equiv.) and toluene (5.0 mL) were added to a 50 mL Schlenk flask under a nitrogen atmosphere. The reaction mixture was heated to 120° C. and reacted at 120° C. for 10 h. No reaction was observed, and the yield was 0%.
Preparation of Triphenylphosphine (Ph3P) Based on Hypophosphorous Acid (H3PO2)
Triphenylphosphine oxide (Ph3P(O), 1.0 g, 3.59 mmol, 1 equiv.), iodine (I2, 22.8 mg, 0.09 mmol, 0.025 equiv.), hypophosphorous acid (H3PO2, 4.74 g, 71.87 mmol, 20 equiv.) and toluene (5.0 mL) were added to a 50 mL Schlenk flask under a nitrogen atmosphere. The reaction mixture was heated to 100° C. and reacted at 100° C. for 5 h. No reaction was observed, and the yield was 0%.
Preparation of Triphenylphosphine (Ph3P) Based on Metaphosphoric Acid (HPO3)
Triphenylphosphine oxide (Ph3P(O), 1.0 g, 3.59 mmol, 1 equiv.), iodine (I2, 22.8 mg, 0.09 mmol, 0.025 equiv.), metaphosphoric acid (HPO3, 3.59 g, 71.87 mmol, 20 equiv.) and toluene (5.0 mL) were added to a 50 mL Schlenk flask under a nitrogen atmosphere. The reaction mixture was heated to 100° C. and reacted at 100° C. for 5 h. No reaction was observed, and the yield was 0%.
The comparison between Examples 1-38 and Comparative Examples 1˜4 showed that reducing agents such as phosphorous acid, hypophosphorous acid or metaphosphoric acid failed to catalyze the reaction of triphenylphosphine oxide (Ph3P(O)).
Triphenylphosphine oxide (Ph3P(O), 1.0 g, 3.59 mmol, 1 equiv.), pyrophosphorous acid (H4P2O5, 5.26 g, 35.9 mmol, 10 equiv.), and toluene (5.0 mL) were added to a 50 mL Schlenk flask under a nitrogen atmosphere. The reaction mixture was heated to 100° C. and reacted at 100° C. for 5 h. After the reaction was completed, the reaction mixture was added with water (5 mL), and subjected to extraction with ethyl acetate. The organic phase was collected, concentrated and purified by silica gel column chromatography under a nitrogen atmosphere to obtain triphenylphosphine (Ph3P). The yield of the triphenylphosphine (Ph3P) was less than 1%.
The comparison between Example 1 and Comparative Example 5 showed that without the addition of the elementary halogen (X2) or halide (MXXY), triphenylphosphine (Ph3P) could not be effectively obtained.
Triphenylphosphine oxide (Ph3P(O), 1.0 g, 3.59 mmol, 1 equiv.), sodium fluoride (NaF, 0.19 mmol, 7.6 mg), pyrophosphorous acid (H4P2O5, 5.26 g, 35.9 mmol, 10 equiv.) and toluene (5.0 mL) were added to a 50 mL Schlenk flask under a nitrogen atmosphere. The reaction mixture was heated to 100° C. and reacted at 100° C. for 5 h. No reaction was observed, and the yield was 0%.
It could be seen from Comparative Example 6 that fluorine or fluorides failed to catalyze the reaction of triphenylphosphine oxide (Ph3P(O)).
| Number | Date | Country | Kind |
|---|---|---|---|
| 202410018022.4 | Jan 2024 | CN | national |
This application is a continuation of International Patent Application No. PCT/CN2024/080439, filed on Mar. 7, 2024, which claims the benefit of priority from Chinese Patent Application No. 202410018022. 4, filed on Jan. 5, 2024. The content of the aforementioned application, including any intervening amendments thereto, is incorporated herein by reference in its entirety.
| Number | Date | Country | |
|---|---|---|---|
| Parent | PCT/CN2024/080439 | Mar 2024 | WO |
| Child | 19028029 | US |
