Claims:We Claim:
1. A cost-effective, commercially viable one pot process for preparing triphenylphosphine (TPP), comprising the steps of: (a) reacting triphenylphosphine oxide (TPPO) with triphosgene in the presence of a chlorinated solvent to obtain a solution comprising triphenylphosphine dichloride (TPPCl2), with a proviso that the reaction takes place in the absence of a catalyst; and (b) reducing the TPPCl2 in-situ with aluminium powder having a particle size of not more than 150 µm.
2. A process according to claim 1, wherein TPPO used has a purity of at least 95%, preferably 98%.
3. A process according to claim 1, wherein a chlorinated solvent is selected from chlorobenzene, chloroform, dichloromethane and ortho-dichlorobenzene.
4. A process according to claim 1, wherein the amount of triphosgene used is 0.35 to 0.37 mol / mol of TPPO used.
5. A process according to claim 1, wherein the aluminium powder has a particle size ranging from 45-150 µm, preferably 53 µm.
6. A process according to claim 1, wherein the amount of aluminium powder used is 0.86 mol / mol of TPPO.
7. A cost-effective, commercially viable process for preparing triphenylphosphine substantially as herein described with reference to examples.
8. A process according to claims 1-6 & claim 7, results in triphenylphosphine having not less than 84% of the yield.
, Description:Field of the Invention
The present invention relates to a cost-effective, commercially viable process for preparing triphenylphosphine from triphenylphosphine oxide resulting in high yield and high purity. Particularly, the present invention provides a process for preparing triphenylphosphine from pure as well as recovered triphenylphosphine oxide.

Background of the Invention
The present invention relates to an industrially viable, highly reproducible process for the preparation of triphenylphosphine (TPP), wherein the process comprises treating triphenylphosphine oxide (TPPO) with a chlorinating agent in a halogenated solvent, in the absence of a catalyst to form a solution containing a triphenylphosphine dichloride (TPPCl2), which is further reduced in-situ with particulate metal to yield triphenylphosphine.
Triphenylphosphine is an organophosphorous compound widely used in synthetic organic chemistry. For example, TPP has been mainly used in coupling reactions such as Heck reaction, Suzuki reaction, Mitsunobu reaction. Furthermore TPP is useful for preparing heterocyclic nitrogen compounds by the deoxygenation of nitro, nitroso compounds and N-oxides. Moreover, deoxygenation of epoxides yields olefins.
The ability of TPP to be selectively oxidized to TPPO permits its use in processes wherein a particular group must be selectively reduced. Typical of such reactions is the Wittig reaction wherein a ketone or aldehyde group may be converted into an olefin linkage, thereby useful in the preparation of compounds such as vitamin A. Other reactions are also known wherein TPP may be employed which produce TPPO as a by-product.
Very few uses of TPPO have been disclosed and may be disposed with difficulty as it is an extremely stable substance. Hence, attempts have been made to convert it back into TPP.
Although these reactions appear to possess a wide range of utility in the field of organic chemistry, commercial realization of this potential has been precluded by the high initial cost of TPP and the inability to economically convert by-product TPPO to TPP.
The following discussion of prior art is intended to present the invention in an appropriate technical context and allow its significance to be properly appreciated. Unless clearly indicated to the contrary, reference to any prior art in this specification should be construed as an admission that such art is widely known or forms part of common general knowledge in the field.
German unexamined patent publication Nos. DE 1,618,116 and DE 2,007,535 disclose a process for preparing triphenylphosphine by reacting a mixture of chlorobenzene and phosphorous trichloride with sodium. However, the reaction has been unsafe and the reaction inducing period has been long and the yield has been low in the conventional process.
In another prior art process, the TPP was recovered from TPPO, wherein the latter is chlorinated with phosgene in the presence of carbon tetrachloride (CCl4) solvent, followed by reducing the TPPCl2 using hydrogen in toluene. It was of great importance to completely remove the CCl4 solvent from the TPPCl2 obtained in the reaction with phosgene before initiating reduction. The CCl4 would otherwise react with TPP produced by the reduction, resulting in impurities and thereby decreasing the yield of the desired product.
U.S. patent No. 3,405,180 discloses a process for reducing trihydrocarbon phosphine oxides to the corresponding phosphine by reacting the phosphine oxide with halo-complexing agents, including thionyl chloride, and the pentahalides of arsenic, antimony, and phosphorus to form an adduct of the corresponding trihydrocarbon phosphorus dihalide with said agent, then heating the adduct to its decomposition temperature. The resultant trihydrocarbon phosphorus dihalide is then reacted with a metallic reducing agent exhibiting an oxidation potential of between 0.75 and 2.5 volts to obtain the trihydrocarbon phosphine. To attain the purity required for high yields using the aforementioned prior art process employing a phosphorus pentahalide would increase raw material costs to the point where the process would no longer be economically attractive. Even if it were feasible to sufficiently purify the trihydrocarbon phosphine oxide as to make it suitable for use in the prior art process, the other starting material, a phosphorus pentahalide, is considerably more expensive than the corresponding trihalide.
U.S. pat. No. 3,855,310 describes a process for preparing trihydrocarbon phosphorous dihalides comprising reacting substantially equimolar quantities of phosphorous trihalide, elemental halogen and trihydrocarbon phosphine oxide in the presence of a halobenzene diluent having a melting point of less than about 55°C and boiling point below about 250°C and in the presence of an N,N-dialkylamide catalyst.
U.S. patent No. 4,212,831 discloses a process for preparing triphenylphosphine wherein phosphorous trihalide is added to a dispersion of phenylalkali in an inert solvent selected from the group consisting of aromatic hydrocarbons, aliphatic hydrocarbons, and mixtures thereof.
U.S. patent No. 4,246,204 describes the preparation of TPP wherein triphenylphosphine dichloride (TPPCl2) is hydrogenated in an inert solvent in the presence of a catalyst selected from the platinum, palladium, rhodium, ruthenium and iridium. For preparation of compounds on large scale, hydrogenation using metal catalysts is undesirable as they are expensive.
According to United States patent No. 4,249,023, the process for preparing TPP involves reacting TPPO with phosgene in chloroform to form a TPPCl2-chloroform adduct, followed by reduction with hydrogen at a temperature of at least 130°C in the presence or absence of a solvent to yield TPP. The drawback associated with this process is that phosgene is highly toxic and not conducive to transportation.
US patent No. 5,527,966 discloses a process for preparing TPP by reducing TPPCl2 with aluminium powder having an average particle diameter of about 200-400 µm at about 130°C. However, the process for preparing TPPCl2 involves the use of phosgene, which is highly toxic.
CN 1271075 discloses a method for synthesis of TPPCl2 wherein TPPO and triphosgene or phosgene are used as raw materials and the reaction takes place in the presence of an organic solvent using a catalyst selected from N,N-dimethylformamide, triethylamine, pyridine, tetrabutylammonium chloride, and N-methylimidazole.
EP 0725073 and EP 0761676 discloses preparation of TPP by reducing TPPCl2 with base metals, particularly aluminium, wherein the particles have a diameter of from 100 to 2000 µm at temperature from about 50°C to 150°C and under pressure from 0.2 to 10 bar.
However, the above cited prior art have the following disadvantages: a) use of phosphorous which is poisonous in nature, b) use of toxic phosgene gas, c) high reaction temperature and pressure conditions, d) use of expensive metals for reduction, e) laborious removal of solvents such as CCl4, which would otherwise react with TPP, decreasing its yield, and, f) moderate to low yields of the desired product.
In the view of the drawbacks and complexity of the above methods, a simplified and inexpensive process for preparing TPP in high yields is desirable. These limitations leave an opportunity to invent new and alternative processes for the manufacture of triphenylphosphine.
The present inventors have developed a new approach for the synthesis of triphenylphosphine using a safe and easily transportable triphosgene for chlorinating the triphenylphosphine oxide having a purity greater than 90%, in a chlorinated solvent for obtaining a solution containing triphenylphosphine dichloride, reducing the latter in-situ with aluminium powder having fine particle size to yield triphenylphosphine. The use of triphosgene has lessen the burden of lethal effects associated with the use of toxic phosgene gas.
Object of the Invention
An object of the invention to provide a cost-effective process for preparing highly pure triphenylphosphine in high yield and with high reproducibility.
Another object of the invention is to provide a commercially viable process for the preparation of triphenylphosphine, which overcomes the drawbacks of the prior art.

Summary of the Invention
In one embodiment, the present invention provides an industrially viable, highly reproducible process for the preparation of triphenylphosphine (TPP), wherein the process comprises treating triphenylphosphine oxide (TPPO) with a chlorinating agent in a halogenated solvent, in the absence of a catalyst to form a solution containing a triphenylphosphine dichloride (TPPCl2), which is further reduced with particulate aluminium to yield triphenylphosphine.
In a second embodiment, the present invention relates to a cost-effective commercially viable process for the preparation of TPP, wherein the process employs TPPO having a purity of greater than about 95% as raw material for preparing triphenylphosphine dichloride. Preferably, the TPPO has a purity of about 98%.
In the present context, the process of the present invention for preparing triphenylphosphine uses pure TPPO as well as recovered TPPO obtained as a by-product from any reaction. The recovered TPPO may be further purified using techniques well known in the art.
In a third embodiment, the present invention provides an alternative, safe approach for preparing TPP, wherein the chlorinating agent used is triphosgene, thereby reducing the toxicity associated with the use of phosgene gas.
In a fourth embodiment, the present invention provides a process for preparing TPPCl2, wherein TPPO is treated with triphosgene in the presence of a chlorinated solvent to obtain TPPCl2 in a solution, with a proviso that said reaction takes place in the absence of a catalyst.
In a fifth embodiment, the present invention provides a process for preparing TPP from TPPCl2, wherein the solution containing TPPCl2 is reduced with aluminium powder having a particle size of about 45-150 µm at a temperature of about 130-150°C.
In a sixth embodiment, the present invention provides a low cost, safe process for preparing TPP, wherein the amount of triphosgene and chlorinated solvent used is 0.35 to 0.37 mol and 3 vol per mol of TPPO used respectively. The amount of aluminium powder used for reducing TPPCl2 is 0.86 mol per mol of TPPO.
Detailed Description of the Invention
The present invention relates to a cost-effective, industrially viable process for the preparation of triphenylphosphine resulting in the product with high purity and high yield.
According to an embodiment of the present invention, the process for preparing triphenylphosphine involves two steps in a single pot, preparing triphenylphosphine dichloride, followed by reduction of the latter substance with finely divided metal to yield triphenylphosphine.
The process of the present invention comprises using triphenylphosphine oxide as a starting material, which is chlorinated in the presence of a halogenated solvent to obtain a solution containing TPPCl2.
In the present context, the TPPO used has a purity of about 90% or more. Preferably, TPPO having a purity of about 95% or more is used. More preferably, TPPO having a purity of about 98% or more is used as the starting material.
In the present disclosure, the chlorinating agent used is triphosgene, which is much stable and easily transportable. In preferred embodiments, the TPPO having a purity of about 98% or more is reacted with triphosgene in the presence of a halogenated solvent to obtain a solution containing TPPCl2.
In more preferred embodiments of the invention, the halogenated solvent used is a chlorinated solvent selected from chlorobenzene, chloroform, dichloromethane and ortho-dichlorobenzene. Further, the amount of triphosgene used is 0.35 to 0.37 mol per mol of TPPO. Triphosgene is added lot-wise over a period of time during the reaction. The amount of chlorinated solvent used is 3 volumes per mol of TPPO.
In the same context, the conversion of TPPO to TPPCl2 may be carried out at a temperature from about 10°C to 25°C and in the absence of a catalyst.
In another embodiment, the TPPCl2 is reduced with a powdered metal to yield TPP. Preferably, the TPPCl2 in the reaction is not isolated and as such the solution containing the same is treated with finely divided metal. In preferred embodiments, the metal used is aluminium in the form of powder having a particle size of about 45-150 µm, for reducing TPPCl2, most preferably having a particle size of 53 µm.
The particle size of aluminium powder is critical to the conversion of TPPCl2 to TPP. The particle size is inversely related to the surface area of the particle. The reactivity of aluminium particles corresponds to the surface area. Here, it was found that when aluminium particles in the size range of 200-1000 µm were used for reduction, a decrease in reactivity was observed. Further, aluminium particles having size in the range of 45-150 µm have found to achieve higher space time yields.
In the same context, the amount of aluminium used for reduction may be in stoichiometric amounts, preferably 0.86 mol per mol of TPPO. Reduction with aluminium powder may be carried out at temperature ranging from about 120°C-150°C, more preferably at 130-140°C and at atmospheric pressure.
In another embodiment, the process of the present invention for preparing TPP involves work-up after the reduction of TPPCl2 with aluminium powder. The product may be recovered by methods well known to persons skilled in the art.
In preferred embodiments, after the completion of reaction, water is added to the reaction mixture and the pH is adjusted to acidic (i.e 1.0 - 3.0) using dilute hydrochloric acid resulting in aqueous and organic phases. The organic phase is then worked up by distillation to completely remove the solvent to give pure TPP in a yield of more than 84% and a purity by gas chromatography (GC) is more than 95%, preferably 97%, more preferably 99%.
In some embodiments, one or more solvents may be used during work-up or for purifying the crude compound, selected from methanol, isopropyl alcohol, dichloromethane, chlorobenzene or mixtures thereof.
The process of the present invention for preparing triphenylphosphine may be represented as follows:

Further the process of the present invention is illustrated in the following examples. The following specific and non-limiting examples are to be construed as merely illustrative, and do not limit the present disclosure in any way whatsoever.
Although the present invention has been described in terms of certain preferred embodiments thereof, other embodiments and modifications to preferred embodiments may be possible that are within the principles and spirit of the invention.

Thus the scope of the present disclosure is defined by the appended claims and includes both combinations and sub combinations of the various features described herein above as well as variations and modification thereof, which would occur to persons skilled in the art upon reading the foregoing description.

Without being limited by theory, the present invention may be advantageously used to make actives which can be used for administration. The process described in the present disclosure prevents the disadvantages of the prior art. It is envisaged that by providing the present invention, the desired product in higher yields might be achieved, thereby contributing to a user friendly handling of the process according to art.

Furthermore, the process disclosed in the present invention reduces the economic burden on the part of the manufacturer and increasing the shelf-space.

The systems and methods of the present invention may be embodied in other specific forms without departing from the teachings or essential characteristics of the invention.

Example 1: In a 5 KL Glass lined reactor (GLR), 2055 L of chlorobenzene and 625 Kg of triphenylphosphine oxide were charged and stirred to obtain a suspension. To the reaction mixture, 250 Kg of triphosgene was added over a time period of 7 hours at 10-25°C and stirred for 1 hour. The temperature of the reaction mixture was raised in range to 125°C- 135 °C, and 50 Kg of aluminium powder was added over a time period of 7 hours. The reaction was maintained for a period of 4 hours at the same temperature. After completion of reaction, the mass was cooled to room temperature, followed by quenching the reaction mass (RM) on to cold water. The pH was adjusted to 1.0 using dilute hydrochloric acid. The aqueous and organic layers were separated, followed by extracting the aqueous layer with chlorobenzene (1 x 685 L). The combined organic layers were washed with 5% sodium bicarbonate solution (1 x 685 L) followed by washing with water (1 x 685 L). Chlorobenzene was distilled off completely under vacuum at a temperature of 100°C to obtain a residue. The residue was charged with methanol (1370 L) at 80°C, cooled to 10-15 °C, followed by filtration to obtain the desired product, triphenylphosphine (more than 500 Kg) with a GC purity more than 99%.
Example 2: In a 5 KL Glass lined reactor (GLR), 2055 L of chlorobenzene and 685 Kg of triphenylphosphine oxide were charged and stirred to obtain a suspension. To the reaction mixture, 263 Kg of triphosgene was added over a time period of 7 hours at 10-25°C and stirred for 1 hour. The temperature of the reaction mixture was raised to not more than 140°C and 57 Kg of aluminium powder was added over a time period of 7 hours. The reaction was maintained for a period of 4 hours at the same temperature. After completion of reaction, the mass was cooled to room temperature, followed by quenching the reaction mass (RM) on to cold water. The pH was adjusted to 1.0 using dilute hydrochloric acid. The aqueous and organic layers were separated, followed by extracting the aqueous layer with chlorobenzene (1 x 685 L). The combined organic layers were washed with 5% sodium bicarbonate solution (1 x 685 L) followed by washing with water (1 x 685 L). Chlorobenzene was distilled off completely under vacuum at a temperature of 100°C to obtain a residue. The residue was charged with methanol (1370 L) at 80°C, cooled to 10-15 °C, followed by filtration to obtain the desired product, triphenylphosphine (632 Kg, that corresponds to more than 95% yield) with a GC purity of more than 99%.

Example 3: In a 5 KL GLR, 2040 L of ortho-dichlorobenzene and 680 Kg of triphenylphosphine oxide were charged and stirred to obtain a suspension. To the reaction mixture, 269 Kg of triphosgene was added over a time period of 7 hours at 10-25°C and stirred for 1 hour. The temperature of the reaction mixture was raised to not more than 160°C and 57 Kg of aluminium powder was added over a time period of 7 hours. The reaction was maintained for a period of 4 hours at the same temperature. After completion of reaction, the mass was cooled to room temperature, followed by quenching the RM on to cold water. The pH was adjusted to 1.0 using dilute hydrochloric acid. The aqueous and organic layers were separated, followed by extracting the aqueous layer with ortho-dichlorobenzene (1 x 680 L). The combined organic layers were washed with 5% sodium bicarbonate solution (1 x 680 L) followed by washing with water (1 x 680 L). Ortho-dichlorobenzene was distilled off completely under vacuum at a temperature of 130°C to obtain a residue. The residue was charged with methanol (1360 L) at 80°C, cooled to 10-15 °C, followed by filtration to obtain the desired product, triphenylphosphine (615 Kg, 96% yield) with a GC purity of 99.1%.

Example 4: In a 5 KL GLR, 1860 L of dichloromethane and 620 Kg of triphenylphosphine oxide were charged and stirred to obtain a suspension. To the reaction mixture, 238 Kg of triphosgene was added over a time period of 7 hours at 10-25°C and stirred for 1 hour. Dichloromethane was distilled off completely to obtain a residue. 1860 L of chlorobenzene was added to the residue. The temperature of the reaction mixture was raised to not more than 150°C and some low boiling solvents which were distilled off were collected. 52 Kg of aluminium powder was added over a time period of 7 hours. The reaction was maintained for a period of 4 hours at the same temperature. After completion of reaction, the mass was cooled to room temperature, followed by quenching the RM on to cold water. The pH was adjusted to 1.0 using dilute hydrochloric acid. The aqueous and organic layers were separated, followed by extracting the aqueous layer with chlorobenzene (1 x 620 L). The combined organic layers were washed with 5% sodium bicarbonate solution (1 x 620 L) followed by washing with water (1 x 620 L). Chlorobenzene was distilled off completely under vacuum at a temperature of 100°C to obtain a residue. The residue was charged with methanol (1240 L) at 80°C, cooled to 10-15 °C, followed by filtration to obtain the desired product, triphenylphosphine (557 Kg, 95.4% yield) with a GC purity of 99.4%.

Example 5: In a 5 KL GLR, 2025 L of chloroform and 675 Kg of triphenylphosphine oxide were charged and stirred to obtain a suspension. To the reaction mixture, 259 Kg of triphosgene was added over a time period of 7 hours at 10-25°C and stirred for 1 hour. Chloroform was distilled off completely to obtain a residue. 2025 L of chlorobenzene was added to the residue. The temperature of the reaction mixture was raised to not more than 140°C and some low boiling solvents which were distilled off were collected. 56 Kg of aluminium powder was added over a time period of 7 hours. The reaction was maintained for a period of 4 hours at the same temperature. After completion of reaction, the mass was cooled to room temperature, followed by quenching the RM on to cold water. The pH was adjusted to 1.0 using dilute hydrochloric acid. The aqueous and organic layers were separated, followed by extracting the aqueous layer with chlorobenzene (1 x 675 L). The combined organic layers were washed with 5% sodium bicarbonate solution (1 x 675 L) followed by washing with water (1 x 675 L). Chlorobenzene was distilled off completely under vacuum at a temperature of 100°C to obtain a residue. The residue was charged with methanol (1350 L) at 80°C, cooled to 10-15 °C, followed by filtration to obtain the desired product, triphenylphosphine (617 Kg, 97% yield) with a GC purity of 99.5%.