Restoration of triphenylphosphine using the “sulfur method”: two valuable chemicals from waste products†

Jian-Qiu Zhang ^a, Xin Wang ^a, Teng Wang ^a, Tieqiao Chen ^ab and Li-Biao Han *^ab
aZhejiang Yangfan New Materials Co., Ltd, Shangyu, Zhejiang Province 312369, China. E-mail: hlb@shoufuchem.com
^bKey Laboratory of Ministry of Education for Advanced Materials in Tropical Island Resources, Hainan Provincial Key Lab of Fine Chem, Hainan Provincial Fine Chemical Engineering Research Center, Hainan University, Haikou, 570228, China

First published on 15th September 2023

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Introduction

Triphenylphopshine sulfide Ph₃PS is a side product from the pharmaceutical industry that is generated during the preparation of intermediates of antibiotic drugs by the well-known desulphurization process of a disulfide (RS)₂ to a sulfide R₂S using triphenylphosphine Ph₃P, as represented by eqn (1):^1,2

	(1)

Although less in quantity than triphenylphosphine oxide Ph₃P(O), the well-known side product from Wittig reactions using triphenylphosphine Ph₃P as the deoxygenation reagent,³ considerably large amounts of Ph₃PS are still produced every year from the pharmaceutical industry.^1a Since triphenylphosphine sulfide currently has limited practical applications in the industry, it has to be incinerated as chemical waste. However, the incineration of Ph₃PS is not as simple as just burning off an organic chemical, because, first, since Ph₃PS is flame resistant, a large amount of oil must be added to the incinerator in order to completely burn off Ph₃PS. Second, during the incineration, corrosive components such as P₂O₅ are generated that can damage the incinerator. Therefore, rather special equipment is required. Third, and worst, it generates SO₂etc., which causes air pollution (eqn (2)):

	(2)

We are currently studying new ways for transforming Ph₃PO, the side product from the Wittig reaction etc., into more valuable phosphorus compounds,⁴ and came to know, as described above, that Ph₃PS is a more troublesome industrial chemical waste product.

Herein, we report a solution to the problem of treating Ph₃PS (and also a solution to Ph₃PO). As described in Scheme 1, by simply heating a mixture of Ph₃PS and metallic sodium in toluene, within a couple of hours, we can quantitatively convert Ph₃PS into Ph₃P. More importantly, this reaction also generates an equimolar amount of anhydrous Na₂S. Anhydrous Na₂S is a very useful chemical that is rather difficult to prepare safely by other methods, although its hydrates Na₂S_xH₂O are quite common chemicals.^5,6,8 Therefore, this process, namely the restoration of chemical waste Ph₃PS to Ph₃P, can produce two chemicals both of which are highly valuable. The two products Na₂S and Ph₃P can be easily separated by simple filtration, and the solvent toluene can be easily recovered and reused for another cycle of the reaction. Therefore, this is a reaction that leads to the production of two valuable chemicals with zero emission from a waste product (Scheme 1).

As expected, this reaction can also be used as a safe and economical method to prepare anhydrous Na₂S under mild conditions starting from metallic sodium and elemental sulfur mediated by Ph₃P via stepwise reactions as shown in Scheme 2.⁷

As shown in Scheme 3, it has been reported in the literature that Ph₃PS could be reduced to Ph₃P by iron powder at 370 °C (a) or by RANEY®-Ni.^9b The desulfuration also takes place when refluxing (EtO)₃P or n-Bu₃P with Ph₃PS. However, n-Bu₃P is a relatively expensive reagent, and (EtO)₃P produces (EtO)₃PS, which is quite toxic (b).^9a Metal hydrides are also used to reduce Ph₃PS to Ph₃P (c),¹⁰ but for the industry, they are expensive and difficult-to-handle chemicals. Ph₃PS could be reduced to Ph₃P in 89% yield under mild conditions in refluxing THF using sodium naphthalenide (d), but isolation of the product from the mixture is tedious.¹¹

Recently, we have reported that, in THF, even at room temperature, Ph₃PS can be reduced to Ph₃P by SD (sodium finely dispersed in paraffin).¹² Because sodium is a resource-rich element, and is the most economically and easily handled alkali metal widely used in the industry, and also because the two products, Ph₃P and anhydrous Na₂S, are both useful chemicals as described above,^3,13 we thought that this should be the ideal way for regenerating Ph₃P from Ph₃PS. To our disappointment, however, we soon realized that, under such conditions, the product Ph₃P can further react with sodium to generate Ph₂PNa and other compounds (eqn (3)).¹⁴ Because of this competitive reaction, it was difficult to achieve selective reduction of Ph₃PS to Ph₃P under these current conditions:¹⁴

	(3)

Fortunately, we occasionally found that the reaction of Ph₃P with sodium is an extremely solvent-dependent reaction. Thus, although in THF Ph₃P reacts with sodium to produce Ph₂PNa rapidly, even at room temperature, no reaction took place in benzene or toluene under similar conditions. This phenomenon led us to the present finding that by carrying out reaction of Ph₃PS with sodium in toluene, desulfuration can take place selectively to give Ph₃P quantitatively (Scheme 1).

Results and discussion

Reaction of Ph₃PS with sodium

To Ph₃PS (1.0 mmol) suspended in toluene (5 mL), sodium (2.0 mmol) was added under nitrogen and the glass reaction tube was sealed and heated at 110 °C. As the metallic sodium melted a brown solid was generated, and after heating for 3 h, a pale-yellow toluene solution with dark-brown solids was generated (Scheme 4). Under nitrogen, the toluene solution was then transferred to a flask, and the remaining dark-brown solids were washed twice with dry toluene. GC analysis showed the complete consumption of Ph₃PS in the combined toluene solution and a signal assignable to Ph₃P was the only signal of the products detected in the GC chart (Scheme 4); the GC yield of Ph₃P was quantitative. For the isolation and purification of Ph₃P, toluene was removed under vacuum and the remaining Ph₃P was recrystallized using EtOH to obtain pure white solid Ph₃P in 91% yield (238.7 mg). The yield could be easily increased by reusing the EtOH for the next recrystallization. On the other hand, the dark-brown solid Na₂S was dried under vacuum to remove the remaining toluene to obtain anhydrous Na₂S in 90% yield (70.3 mg, 0.9 mmol). Two equivalents of sodium are required in order to completely convert Ph₃PS into Ph₃P. For example, when one equivalent of sodium was used, nearly 50% GC yield of Ph₃P was generated and 50% Ph₃PS remained unreacted. This excludes the possibility that Na₂S will act as a reducing reagent¹⁵ to reduce Ph₃PS to Ph₃P and generate (NaS)₂. In fact, as confirmed by a separate experiment, no reaction took place between Ph₃PS and commercially purchased anhydrous Na₂S under similar conditions.

One of the big advantages of this reaction is its easy operation because it is an endothermic reaction,¹⁶ and the dangerous sudden bumping of solvent during heating, as is often observed in many chemical reactions, does not occur. This ensures an easy and safe process for converting Ph₃PS to Ph₃P using sodium on a large scale. For example, by simply heating a mixture of Ph₃PS (20 g) and sodium (3.4 g) in toluene (100 mL) for 3 h, 16.3 g of Ph₃P was obtained (92%) by simply washing out Na₂S with water after the reaction (Scheme 4; when anhydrous Na₂S is not the target product, the isolation of Ph₃P is more conveniently conducted since Na₂S can be washed out by water leaving Ph₃P as the only product).

Other R₃PS phosphine sulfides tested, having at least one phenyl group, could also be converted by sodium into the corresponding phosphines R₃P. Thus, Ph₂MePS and PhMe₂PS gave Ph₂MeP and PhMe₂P in 96% and 97% yield, respectively. However, n-Bu₃PS did not produce n-Bu₃P under similar conditions.

The preparation of anhydrous Na₂S using the reaction of Ph₃PS with sodium

As described above, although Na₂S_x·H₂O is a quite common chemical, anhydrous Na₂S is not easy to prepare safely and efficiently. The preparation of anhydrous sodium sulfide (Na₂S) from Na₂S_x·H₂O requires very high temperatures.^8a The industrial preparation of anhydrous Na₂S by the reduction of sodium sulfate with carbon also requires severe conditions that consume considerable energy.^8a In addition, Na₂S prepared by these methods usually contains a lot of impurities that are hard to remove. The use of elemental sulfur with metallic sodium is the most direct way for the preparation of Na₂S and related compounds. However, there are problems concerning safety because this is a highly exothermic reaction that can lead to severe explosion and special equipment is required (eqn (4)). This kind of reaction has been carried out in liquid ammonia^8c or in 1,2-dimethoxyethane at 70 °C in the presence of aromatic hydrocarbons and ketone catalysts:^8b

Na + S8 → Na2S	(4)

Anhydrous sodium sulfide Na₂S, and related oligosulfides Na₂S_n are key starting chemicals for the preparation of sulfur-containing silanes (Scheme 5) that are widely used as efficient coupling reagents in eco-tires.¹⁷ These tires with such sulfur-containing silanes can significantly improve vehicle fuel consumption efficiency and thus reduce CO₂ emission.¹⁸

The new strategy for the preparation of Na₂S based on the reaction of Ph₃PS with sodium is shown in Scheme 2. It consists of two reactions, i.e. the reaction of Ph₃P with sulfur, generating Ph₃PS, and the reduction of Ph₃PS with sodium producing Na₂S and regenerating Ph₃P. By repeating this cycle, anhydrous Na₂S of high quality can be easily obtained (Scheme 6).

Thus, under nitrogen, sulfur (0.122 g, 3.8 mmol) was added drop by drop to Ph₃P (1.00 g, 3.8 mmol) dissolved in dry toluene (10 mL) at room temperature. As confirmed by GC, Ph₃P was completely converted into Ph₃PS after 1 h. Metallic sodium (0.159 g, 6.9 mmol) was then added to the solution, and the mixture was heated at 110 °C for 3 h. Ph₃P was regenerated from Ph₃PS. The toluene solution containing Ph₃P and a little Ph₃PS (ca. 3.0%) was then transferred to another glass tube (ESI, Fig. 2†). A small amount of toluene was used to wash the remaining Na₂S solid, and the toluene solutions were combined. Again, sulfur (0.122 g, 3.8 mmol) was added to the toluene solution and the above processes were repeated. By carrying out three cycles of the above reactions, a total amount of 0.848 g of anhydrous Na₂S was obtained as a brown solid (average yield: 96%).

The above Na₂S was used for the preparation of useful sulfur-containing silanes.¹⁹ Below are two examples for preparing sulfur-containing silanes using anhydrous Na₂S under the optimized conditions. For example, after optimizing the reaction conditions, it was found that by conducting a reaction of Na₂S (1.0 mmol) with (EtO)₃SiCH₂CH₂CH₂Cl (1.5 mmol) in dry EtOH (2.0 mL) at 80 °C overnight, bis(triethoxysilylpropyl) sulfide was obtained in 90% yield (eqn (5)):

	(5)

In a similar way, bis[3-(triethoxysilyl)propyl] disulfide (Si-75) was also efficiently prepared. First, Na₂S (1.0 mmol) and sulfur (1.0 mmol) were mixed in DME (2.0 mL) at 50 °C for 4 h to generate Na₂S₂. Then, (EtO)₃SiCH₂CH₂CH₂Cl (1.5 mmol) was added. The mixture was stirred at 80 °C overnight to generate Si-75 highly selectively. The solid in the solution was filtered off and the volatiles were removed under reduced pressure to obtain analytically pure Si-75 as a pale-yellow oil (451.0 mg, 95% yield, 96% GC purity, see the ESI, Fig. 4†):

	(6)

Restoration of Ph₃P from Ph₃PO using “the sulfur method”

Triphenylphosphine Ph₃P is transformed into the stable phosphine oxide form Ph₃PO, from the Wittig reactions,²⁰ catalytic synthesis as ligands, and etc.²¹ The regeneration of Ph₃P from Ph₃PO is of great importance from the viewpoint of both economic and environmental conservation, and is a hot topic at the moment.²² Currently, Ph₃PO is recovered to Ph₃P using “chlorine method”, as shown in eqn (7), by converting Ph₃PO into Ph₃PCl₂ with phosgene,²³ oxalyl dichloride,²⁴ PCl₅²⁵ and other chlorine²⁶ and reductive reagents.²⁷ Ph₃PCl₂ is then reduced to Ph₃P by metallic powders on heating. This process requires the use of toxic chlorine reagents, which present potential safety risks, and generates two waste products (CO₂ and MCl_x):

	(7)

The current efficient reduction of Ph₃PS to Ph₃P by sodium convinces us that we can develop a safer and greener new approach to solve the industrial Ph₃PO waste problem, i.e. the one-pot “sulfur method” (Scheme 5). Thus, Ph₃PO is first quantitatively transformed into Ph₃PS by P₂S₅,²⁸ and then the obtained Ph₃PS is efficiently reduced to Ph₃P using sodium. When applied to an industrial process for the restoration of Ph₃PO to Ph₃P, compared to the current “chlorine method”, the “sulfur method” has advantages including: (a) reagents that are easily handled and reaction conditions that are mild, (b) no waste products are generated during the whole process and, more importantly for the industry, (c) it could be more economically operated since profits from Na₂S and H₃PO₄ may cover the costs of the reagents used during the conversion.

Although such an idea using the “sulfur method” to solve the Ph₃PO waste problem was once considered in the literature (Scheme 7, bottom reaction),^11,28 it was not practically operable at that time because the first reaction (1) used dicholoroethane that has to be carefully removed using sodium when Ph₃PS was used for the next step. Moreover, as mentioned above, reduction using sodium naphthalenide is expensive for an industrial process and the purification of the resulting products is tedious.

This continuous one-pot “sulfur method” is shown in Scheme 8, clearly demonstrating its simplicity and practical utility. Triphenylphosphine oxide (500 g, 1.795 mol, 1.0 equiv.) and toluene (3.0 L), purchased without further purification, were added to a 5 L glass reactor. Under a nitrogen atmosphere, the reactor was heated at 110 °C to distil off ca. 500 mL of toluene. The reactor was cooled down to 70 °C, and P₂S₅ (87.8 g, 0.395 mol, 0.22 equiv.) was added. The reactor was then heated again and refluxing was continued for 2 h. GC analysis showed Ph₃PS was the only new phosphorus product, and >99% Ph₃PO was converted (ESI, Fig. 5†). Heating was stopped, and at ca. 60 °C, water (500 mL) was added. The organic layer was collected and washed with water twice (250 mL × 2), and was returned to the reactor. The solution was heated under nitrogen again to reflux and ca. 500 mL of toluene distilled off. The heating was stopped and a sodium lump (94.0 g, 4.08 mol, 2.3 equiv.) was added to the solution under nitrogen. The mixture was then heated to reflux again and the heating was continued for 3 h. The reaction was monitored by GC to make sure that most of the Ph₃PS was transformed into Ph₃P (Ph₃P/Ph₃PS > 99/1, see the ESI, Fig. 6†). The heating was stopped and the mixture was cooled down to room temperature, and water (500 mL) was added. The organic layer was collected and the volatiles were pumped off to obtain crude Ph₃P as a pale-yellow solid (447.2 g; Ph₃P > 99% GC purity). Recrystallization of the crude Ph₃P using ethanol produced a white Ph₃P solid (381.4 g, 81% yield, GC purity = 99.6%).

Conclusions

In summary, we found that although Ph₃P could rapidly react with sodium in THF to give Ph₂PNa,¹⁴ a similar reaction does not take place in toluene even on heating (Ph₃P is inert to sodium in toluene). When a mixture of Ph₃PS and sodium was heated in toluene, quantitative yields of the highly valuable Ph₃P and anhydrous Na₂S were obtained. By applying this finding, anhydrous Na₂S could be safely and conveniently prepared by a novel Ph₃P-mediated reaction using sodium and sulfur. Anhydrous sodium sulfides are key chemical reagents for industrially producing highly useful sulfur-containing silanes. The green chemistry metrics (E factor and atom economy) of these reactions and their costs were calculated (ESI†), demonstrating this finding also leads to the establishment of a feasible alternative strategy (the sulfur method) for the restoration of Ph₃PO waste to Ph₃P that is greener and safer than the current “chlorine method”.

Author contributions

J.-Q. Z. completed the writing of the manuscript; X. W., T. W., and J.-Q. Z. conducted the experiments; T. C. wrote the second draft of the manuscript; L.-B. H., in charge of the project, collated the reactions from the literature and wrote the first draft of the manuscript.

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

This work was primarily funded by the Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang (2022R01021).

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Footnote

† Electronic supplementary information (ESI) available: General information, experimental procedures, characterization data of products and copies of 1H, 13C and 31P NMR spectroscopy. See DOI: https://doi.org/10.1039/d3gc03071g

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