Synthesis of Phosphine Chalcogenides Using Tetrabutylammonium Chalcogenocyanates

Abstract

The new chalcogenylation of phosphines using ⁿBu₄N‧XCN (X = S, Se) is described. The reaction in 1,2-dichloroethane at 120 °C provided the corresponding phosphine sulfides in good to high yields. The protocol could be extended to the synthesis of phosphinic acid derivatives as well as sulfurization of poly(styrene-co-4-styryldiphenylphosphine).

Introduction

Phosphine chalcogenides^1,2) have a wide range of important applications such as ligands for transition metal catalysts,^3–6) organocatalysis,^7–9) sulfurization agent for transition metal phosphides¹⁰⁾ and molecular junction units for electronic devices.¹¹⁾ Although treatment of phosphines with elemental sulfur or selenium is one of the general methods for the preparation of phosphine chalcogenides, there are major drawbacks in that the method often requires excess amounts of reagents, high reaction temperature, long reaction times and a tedious purification task. In this context, several alternatives have been reported (Chart 1a).

Chart 1. Representative Sulfurization of Phosphorus Compounds and Presented New Sulfurization of Phosphines

Miranda et al. reported a convenient alternative to prepare phosphine sulfides using sodium polysulfides¹²⁾ (Chart 1b). Arterburn and Perry demonstrated that a rhenium(V)-catalyzed sulfurization of phosphorus(III) compounds with propylene sulfide provides phosphine sulfides and phosphonothioates in high yields¹³⁾ (Chart 1c). Sulfurization reactions of trivalent phosphorus compounds using five-membered rings containing disulfide bonds, such as 1,2-dithiole-3-thiones, 1,2,4-dithiazole-3-ones, and 1,2,4-dithiazole-3-thiones, have been extensively studied^14–16) (Chart 1d). Min and Liu reported that the reaction of triphenylphosphine oxide with thiourea in the presence of trifluoromethanesulfonic anhydride in dry dichloromethane gave triphenylphosphine sulfide in 85% yield¹⁷⁾ (Chart 1e). During our study on transition metal-catalyzed transformation with thiocyanate ions, we found that some of the triphenylphosphine added as a ligand was converted to phosphine sulfide (Chart 1f). Intrigued by these results, we focused our studies on the synthesis of phosphine chalcogenides. We herein report the first examples of chalcogenation of phosphines using thiocyanates or selenocyanates as chalcogen atom transfer reagents.

Results and Discussion

At the outset of our work, we explored the sulfurization of triphenylphosphine (1a) with tetrabutylammonium thiocyanate^18,19) in toluene. The reaction at 120 °C proceeded to give triphenylphosphine sulfide (2a) in 12% yield (Table 1, entry 1). Only slight improvement of the yield of 2a was observed when the reaction temperature was raised up to 150 °C (entry 2). Screening of various transition metal complexes showed that there was no discernible change in yields of 2a, indicating that they have no catalytic activity for sulfur atom transfer to 1a (entries 3–6). A survey of solvents revealed that the use of 1,2-dichloroethane greatly improved the product yield to 99% (entry 7). Dichloromethane was also an effective solvent, though other solvents such as n-hexane, tetrahydrofuran (THF), ethyl acetate, methanol, acetonitrile, and dimethyl sulfoxide were found to be completely ineffective (entry 7 vs. entries 9–14). Furthermore, the reaction temperature in 1,2-dichloroethane could be lowered to 100 °C without compromising the product yield (entry 15).

Table 1. Sulfurization of Triphenylphosphine (1a) with ⁿBu₄NSCN^a)

Entry	Solvent	Additive	Yield (%)b)
1	Toluene	None	12
2c)	Toluene	None	24
3	Toluene	Cu(OAc)2 (5.0 mol %)	38
4	Toluene	Yb(OTf)3 (5.0 mol %)	32
5	Toluene	Sc(OTf)3 (5.0 mol %)	34
6	Toluene	PdCl2 (5.0 mol %)	48
7	(CH2Cl)2	None	99 (93d))
8	CH2Cl2	None	67
9	n-Hexane	None	7
10	THF	None	0
11	EtOAc	None	0
12	MeOH	None	4
13	MeCN	None	4
14	DMSO	None	0
15e)	(CH2Cl)2	None	92

a) Typical procedure (entry 15): A solution of triphenylphosphine (1a, 66 mg, 0.25 mmol) and ⁿBu₄NSCN (90 mg, 0.30 mmol) in 1,2-dichlroethane (1.0 mL) was stirred at 120 °C for 24 h in a sealed tube. After 24 h, the reaction mixture was concentrated and the residue was purified by column chromatography (silica gel, n-hexane/AcOEt = 10 : 1). b) Determined by ¹H-NMR yield using 1,1,2,2-tetrachloroethane as an internal standard. c) The reaction was conducted at 150 °C. d) Isolated yield. e) The reaction was conducted at 100 °C.

With optimized conditions in hand, the applicability of this process to a range of phosphines was then investigated and the results are summarized in Table 2. Various triarylphosphines 1b–1g afforded the corresponding phosphine sulfides 2b–2f in good to high yields. Although the reaction of tris(o-tolyl)phosphine (1g), a sterically hindered phosphine, required much longer reaction time to completion, the corresponding sulfide 2g could be obtained in good yield (63%). A number of functional groups such as acetyl, dimethylamino, amide, pyridyl and thienyl moieties on the benzene ring were well-tolerated under the optimized reaction conditions. Not only 5-phenyldibenzophosphole (1m), but also alkyl-substituted phosphines 1n–1t and di- or triphosphines 1u–1y were also found to be good substrates to provide corresponding sulfides 2m–2y in moderate to high yields.

Table 2. Sulfurization of Phosphines with ⁿBu₄NSCN in 1,2-Dichloroethane^a)

a) Typical procedure: A solution of phosphine (1b, 76 mg, 0.25 mmol) and ⁿBu₄NSCN (90 mg, 0.30 mmol) in 1,2-dichloroethane (1.0 mL) was stirred at 120 °C in a sealed tube. After 24 h, the reaction mixture was concentrated and the residue was purified by column chromatography (silica gel, n-hexane/AcOEt = 6 : 1). Unless otherwise stated, yields are isolated. b) Reaction time is 72 h. c) Determined by GC analysis. d) ⁿBu₄NSCN (2.4 equiv.) was used. e) ⁿBu₄NSCN (3.6 equiv.) was used.

The present protocol could also be applied to the synthesis of phosphine selenides 3a–3d using tetrabutylammonium selenocyanate as a selenation reagent²⁰⁾ (Chart 2).

Chart 2. Selenation of Phosphines with ⁿBu₄NSeCN in 1,2-Dichloroethane

Although the reaction of tri(2-furyl)phosphine (1z), an electron-poor phosphine,²¹⁾ gave no corresponding phosphine sulfide 2z, we were gratified to find that the same reaction in the presence of 0.5 equivalent (equiv.) of copper(I) iodide provided 2z in 75% yield²²⁾ (Table 3). The protocol using CuI as an additive was found to be applicable to a variety of electron-poor phosphines including tris(4-trifluoromethylphenyl)phosphine (1aa), (4-cyanophenyl)diphenylphosphine (1ab), and (4-methoxycarbonylphenyl)diphenylphosphine (1ac), as well as sterically hindered tri(1-naphthyl)phosphine (1ad).

Table 3. Sulfurization of Electron-Deficient or Sterically Hindered Phosphines^a)

a) Typical procedure: A solution of phosphine (1z, 58 mg, 0.25 mmol) and ⁿBu₄NSCN (90 mg, 0.30 mmol) and CuI (24 mg, 0.13 mmol) in 1,2-dichloroethane (1.0 mL) was stirred at 120 °C in a sealed tube. After 24 h, the reaction mixture was concentrated and the residue was purified by column chromatography (silica gel, n-hexane/AcOEt = 3 : 1). Unless otherwise stated, yields are isolated. b) Results obtained in the absence of CuI.

It is notable that the reaction of diphenylphosphine (1ae) with tetrabutylammonium thiocyanate in the presence of copper iodide in 1,2-dichloroethane provided P,P-diphenylphosphinothioic chloride (2ae) in 70% yield (eq. 1), which was easily transformed into diphenylphosphinothioic acid derivatives such as 5a or 5b by treating with 4-phenylphenol (4a) or 4-chloroaniline (4b) under basic conditions (eq. 2).²³⁾ Unfortunately, however, the present methodology was not effective for the sulfurization of ethyl diphenylphosphinite (1af), giving a complex mixture of products (eq. 3).

  

(1)

  

(2)

  

(3)

To demonstrate the efficiency of the present methodology, we then explored the preparation of poly(styrene-co-4-styryldiphenylphosphine sulfides), which could be potential materials exhibiting unique optical and/or electronic properties and flame retardancy²⁴⁾ (Table 4). As we expected, sulfurization of both low molecular weight polymer 6_LMW²⁵⁾ and high molecular weight polymer 6_HMW²⁵⁾ using 1.2 equiv. of ⁿBu₄NSCN (12 equiv. per phosphorus atom) in 1,2-dichloroethane gave polymer-supported phosphine sulfides 7_LMW and 7_HMW, respectively, in good yields with perfect incorporation of sulfur atoms into phosphine center. We were further delighted to find that the amount of ⁿBu₄NSCN could be reduced to 0.12 equiv. (1.2 equiv. per phosphorus atom) without diminishing the product yield.

Table 4. Preparation of Poly(styrene-co-4-styryldiphenylphosphine Sulfides)^a)

Polymer 6	X	Mol fraction (%)b)		Polymer 7
		Styrene	Comonomer	Yield	Mn (g/mol)c)	Mw/Mnc)
6LMW	1.2	90	10	7LMW: 28.0 mg (89%)	4140	1.18
6LMW	0.12	90	10	7LMW: 25.8 mg (82%)	4050	1.19
6HMW	1.2	90	10	7HMW: 29.8 mg (95%)	13500	1.26
6HMW	0.12	90	10	7HMW: 24.4 mg (78%)	13300	1.25

a) Typical procedure: A solution of 6 (30.7 mg, 0.25 mmol) and ⁿBu₄NSCN (90 mg, 0.30 mmol or 9.0 mg, 0.03 mmol) in 1,2-dichloroethane (1.0 mL) was stirred at 120 °C for 24 h in a sealed tube. b) Determined by ¹H-NMR. c) Determined by SEC using THF as an eluent.

We then conducted several control experiments to elucidate the reaction mechanism. The reaction of bisphosphonium salt 8²⁶⁾ with tetrabutylammonium thiocyanate in 1,2-dichloroethane gave 2a in 57% (eq. 4). The same reaction was carried out in toluene solution, and 2a was obtained with 1a (eq. 5). These results suggested that bisphosphonium salt 8, prepared from phosphine and 1,2-dichloroethane, could be an intermediate of the reaction and the release step of triphenylphosphine should be included in the reaction mechanism. When the reaction of 1a and tetrabutylammonium thiocyanate was carried out with 1,2-dichlorooctene (9)²⁷⁾ instead of 1,2-dichloroethane in acetonitrile, 2a was obtained in 65% yield and 1-octene was detected by GC analysis (eq. 6). This result suggests that the release of ethylene gas originating from 1,2-dichloroethane occurs during the reaction, which might be the driving force for the sulfurization of phosphines.

  

(4)

  

(5)

  

(6)

Based on the above results, the plausible reaction mechanism is depicted in Chart 3²⁸⁾ for sulfurization of phosphines as follows: (1) phosphine reacts with 1,2-dichloroethane to form bisphosphonium salt A, (2) attack of the thiocyanate anion to the cationic phosphine center of A gives the pentacoordinated phosphonium intermediate B, and (3) triggered by the attack of the chloride ion to intermediate B, phosphine sulfide is generated with release of cyanogen chloride,²⁹⁾ phosphine and ethylene.³⁰⁾

Chart 3. Plausible Reaction Mechanism for Sulfurization of Phosphine Using Tetrabutylammonium Thiocyanate Salt

In summary, we developed a new chalcogenylation reaction of phosphines using tetrabutylammonium chalcogenocyanates as a chalcogen atom source. It was found that the use of 1,2-dichloroethane as a solvent is crucial for this transformation. This protocol was applicable to the synthesis of various phosphine sulfides with good functional group tolerance, phosphine selenide and poly(styrene-co-4-styryldiphenylphosphine sulfides). In the case of the sulfurization of electron deficient phosphines and diphenylphosphine, the use of 0.5 equiv. of CuI as an additive was found to be effective. Several control experiments indicated that the bisphosphonium salt A, formed from 1,2-dichloroethane and phosphines, might play an important role for the present process.

Experimental

General information: All reactions were carried out in a dry solvent under an inert atmosphere. Commercially available reagents and anhydrous solvents were degassed before use. Anhydrous 1,2-dichloroethane was purchased from Sigma-Aldrich Co. (St. Louis, MO, U.S.A.). Analytical thin layer chromatography was performed on a silica gel 60 F254 plate from Merck KGaA (Darmstadt, Germany) with visualization by ultraviolet light, anisaldehyde stain solution or phosphomolybdic acid stain solution. Medium pressure liquid chromatography (MPLC) purifications were performed on a YAMAZEN EPCLC-W-Prep 2XY (Yamazen, Tokyo, Japan). All reagents were purchased from commercial suppliers and used as received. Phosphines 1a–1d, 1f, 1g, 1i, 1k, 1n–1aa, and 1ad–1af were purchased from Sigma-Aldrich Co., Kanto Kagaku Reagent Division (Tokyo, Japan), Tokyo Kasei Kogyo Co. (Tokyo, Japan), and Wako Pure Chemical Corporation (Osaka, Japan). Tetrabutylammonium thiocyanate or selenocyanate¹⁸⁾ and phosphines 1e,³¹⁾ 1h,³²⁾ 1l,³²⁾ 1m,³³⁾ 1ab,³⁴⁾ 1ac,³⁵⁾ polymer 6²⁵⁾ bisphosphonium salt 8,²⁶⁾ and 1,2-dichlorooctane (9)²⁷⁾ were prepared according to the literature methods. NMR spectra were recorded on JEOL ECZ-500 (500 MHz for ¹H-NMR, 125 MHz for ¹³C-NMR, 470 MHz for ¹⁹F-NMR, 202 MHz for ³¹P-NMR, 95 MHz for ⁷⁷Se NMR). Data are presented as follows: chemical shift (δ, ppm), multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, sept = septet, m = multiplet, br = broad), coupling constant and integration. Proton chemical shifts are reported relative to Me₄Si (CDCl₃, CD₂Cl₂ and dimethyl sulfoxide (DMSO)-d₆) at δ 0.00 ppm or residual solvent peak (CDCl₃ at δ 7.26 ppm, CD₂Cl₂ at δ 5.32 ppm and DMSO-d₆ at δ 2.50 ppm). Carbon chemical shifts are reported relative to CDCl₃ at δ 77.00 ppm, CD₂Cl₂ at δ 53.84 ppm and DMSO-d₆ at δ 39.52 ppm. Fluorine chemical shifts are reported relative to trifluoroacetic acid (TFA) (CDCl₃) at δ −76.55 ppm as an external standard. Phosphorus chemical shifts are reported relative to 85% H₃PO₄ in D₂O at δ 0.00 ppm as an external standard. Selenium chemical shifts are reported relative to KSeCN in D₂O at a specific concentration with a chemical shift of δ −316.5 ppm (4.0 mol/L) or δ −329.0 ppm (0.25 mol/L) as an external standard. Melting points were recorded on a melting point apparatus (SANSYO SMP-300, Sansyo, Tokyo, Japan) and are uncorrected. IR spectra were recorded on a JASCO FT/IR-4100 (JASCO, Tokyo, Japan). High-resolution mass spectra (HRMS) were recorded on JEOL AccuTOF (JEOL, Tokyo, Japan) and Waters Xevo G2-S QTOF (Waters, Tokyo, Japan). GC yield was obtained on SHIMADZU GC-2014AFsc (Shimadzu, Kyoto, Japan). Molecular weights of the polymers were determined using a Shimadzu Nexera CBM-40 Multi-Detector Gel Permeation Chromatography (GPC)/Size Exclusion Chromatography System through TSKgel SuperMultiPore HZ-M 3 µm columns packed with PSDVB beads. The GPC was run with THF at a flow rate of 0.35 mL min⁻¹ at 40 °C. Molecular weights were obtained using double detection (SPD-40 and RID-20A) based on a calibration prepared with narrow dispersity polystyrene standards.

Procedure for the Sulfurization of 1a with ⁿBu₄NSCN

A mixture of triphenylphosphine (1a, 65.6 mg, 0.25 mmol), and ⁿBu₄NSCN (90.2 mg, 0.30 mmol) in 1,2-dichlroethane (1.0 mL) was stirred at 120 °C for 24 h in a sealed tube. Then the reaction mixture was cooled to ambient temperature and concentrated, and the residue was purified by column chromatography (silica gel, n-hexane/EtOAc = 10 : 1) to give triphenylphosphine sulfide (2a, 68.3 mg, 93% yield). TLC Rf = 0.46 (4/1 n-hexane/EtOAc); mp 161–163 °C; ¹H-NMR (500 MHz, CDCl₃) δ: 7.72 (tdd, J = 8.6, 7.1, 2.0 Hz, 6H), 7.51 (tt, J = 7.1, 2.0 Hz, 3H), 7.45 (ddd, J = 8.0, 7.1, 7.1 Hz, 6H); ¹³C-NMR (125 MHz, CDCl₃) δ: 132.9 (d, J_CP = 84.5 Hz), 132.2 (d, J_CP = 10.9 Hz), 131.5 (d, J_CP = 2.4 Hz), 128.5 (d, J_CP = 12.1 Hz); ³¹P-NMR (202 MHz, CDCl₃) δ: 43.7; IR (attenuated total reflectance (ATR), ν/cm⁻¹) 1433, 1101, 712, 689, 636; HRMS (DART) Calcd for C₁₈H₁₆PS [M + H]⁺ 295.0710, Found 295.0712.

Acknowledgments

This work was partially supported by JSPS KAKENHI Grant JP18K05110 (S.S.) for Scientific Research (C), Inamori Foundation (S.S.), DAIGAKUTOKUBETSU KENKYUHI Grant (Musashino University) (S.S.) and JSPS KAKENHI Grant JP21K06462 (M.A.) for Scientific Research (C). M.A. thanks Musashino University for financial support. The authors thank to Dr. Kazuki Ishikawa (Musashino University) for measurement of HRMS and Dr. Takashi Kikuchi (RIGAKU Co., Ltd.) and Prof. Dr. Akiko Inagaki (Seikei University) for X-ray analysis.

Conflict of Interest

The authors declare no conflict of interest.

Supplementary Materials

This article contains supplementary materials.

References and Notes

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