Method for the generation of a hexafluorophosphate or a phosphorus-comprising organic compound

Abstract

The invention concerns a method for the generation of a tertiary phosphine, a tertiary phosphite ester, or a hexafluorophosphate, wherein the method comprises the following steps: a) providing an elemental phosphorus, an organic disulfide, a solvent and either a compound R1-X1 and an organic base, a compound R2-O-X2 and an organic base, or a fluoride anion and b) mixing the elemental phosphorus, the organic disulfide and either the compound R1-X1 and the organic base, the compound R2-O-X2 and the organic base, or the fluoride anion in the solvent for obtaining a solution or a suspension in which the tertiary phosphine, the tertiary phosphite ester, or the hexafluorophosphate is formed.

Description

[0001] Method for the generation of a hexafluorophosphate or a phosphorus- comprising organic compound

[0002] The present invention relates to a method for the generation of a hexafluorophosphate or a phosphorus-comprising organic compound.

[0003] Industrial routes to phosphorus-comprising organic compounds involve oxidation of phosphorus by chlorine gas to give phosphorus chlorides, for example PCI3, PCIs, and POCI3, as phosphine intermediates which are subsequently reacted with nucleophiles to generate phosphorus-comprising organic compounds.

[0004] Zhang et al. "Diphenyl diselenide-catalyzed synthesis of triaryl phosphites and triaryl phosphates from white phosphorus." Org. let. 2021 , 23, 5158-5163, discloses the synthesis of triaryl phosphites by a diphenyl diselenide-catalyzed one-step procedure involving white phosphorus and phenols.

[0005] Zhang et al. "Formation of N-P(O)-S Bonds from White Phosphorus via a Four- Component Reaction." Adv. Synth. Catal. 2022, 364, 2221 -2226, discloses a functionalization of white phosphorus with disulfides, amines and KOH to phosphoram idodithioates containing P-N, P-S and P=O bonds via a four- component reaction.

[0006] Hajipour et al. "Oxidation of Thiols to the Corresponding Symmetric Disulfides with Benzyltriphenylphosphonium Peroxodisulfate (BTPPD) Under Nonaqueous Conditions." Phosphorus, Sulfur, and Silicon and the Related Elements 178 (2003): 1277 - 1281 , discloses the preparation of benzyltriphenylphosphonium peroxodisulfate (BTPPD). BTPPD is a reagent for the oxidation of aromatic and aliphatic thiols to the corresponding disulfides in refluxing acetonitrile.

[0007] Wu C. "Organic Phosphorus-Sulfur Chemistry. I. A Novel Synthesis of Tertiary Trithiophosphites." J. Am. Chem. Soc. 1965, 87, 11 , 2522 discloses the preparation of tertiary trithiophosphites by the following procedure: about 1 mL of 15 N potassium hydroxide is added to a stirred mixture of 1 g.-atom of finely divided phosphorus and 1 .5 moles of disulfide in 500 mL of acetone at room temperature under nitrogen. The product is isolated by vacuum distillation in greater than 90 % yield.

[0008] The problem to be solved by the present invention is to provide an alternative method to generate a phosphorus-comprising compound. The method shall allow the direct synthesis of the phosphorus-comprising compound by use of relatively mild reagents with a relatively low amount of waste products generated in addition to the phosphorus-comprising compound.

[0009] The problem is solved by the subject-matter of claim 1 . Embodiments of the invention are subject-matter of claims 2 to 15.

[0010] According to the invention a method for the generation of a tertiary phosphine according to formula (I), a tertiary phosphite ester according to formula (II), or a hexafluorophosphate is provided. R1and R2are each selected independently from each other from a group consisting of alkyl, aryl, heterocyclyl and heteroaryl. In particular, R1and / or R2may be aryl. The method comprises the following steps: a) providing an elemental phosphorus, an organic disulfide, a solvent, and either a compound R1-X1and an organic base for obtaining the tertiary phosphine according to formula (I), a compound R2-O-X2and an organic base for obtaining the tertiary phosphite ester according to formula (II), or a fluoride anion for obtaining the hexafluorophosphate, wherein X1is selected from a group consisting of an alkali metal atom residue, a magnesium halogenide residue or a hydrogen residue, wherein X2is selected from a group consisting of an alkali metal atom residue, an earth alkali metal atom residue or a hydrogen residue, wherein the organic base is an amine, a metal amide, a guanidine, an amidine or R3-O_, wherein R3is selected from a group consisting of alkyl, aryl, heterocyclyl and heteroaryl, and b) mixing the elemental phosphorus, the organic disulfide and either the compound R1-X1and the organic base, the compound R2-O-X2and the organic base, or the fluoride anion in the solvent for obtaining a solution or a suspension in which the tertiary phosphine according to formula (I), the tertiary phosphite ester according to formula (II), or the hexafluorophosphate is formed.

[0011] In steps a) and b) the organic base may be the only base present or it may be present together with at least one other organic base. In an embodiment of the invention no inorganic base is present in steps a) and b). The counterion of R3-O_may be an alkali metal cation, in particular a lithium, sodium or potassium cation, in particular a potassium cation, an alkaline earth metal cation, in particular a magnesium cation, or a tetraalkylammonium cation, in particular a tetramethylammonium, tetraethylammonium or tetrabutylammonium cation.

[0012] Furthermore, it has to be considered that the terms defining the invention can be considered as functional terms. Though it is possible that two different terms designate two different compounds it is also possible that two different terms designate the same compound. For example, it is possible that the same amine acts as the organic base but also as the solvent or it is possible that a part of the total amount of a compound acts as organic base whereas another part of this amount acts as a reactant. For example, potassium phenolate can act as the organic base. However, in the presence of protons potassium phenolate can form the compound R2-O-X2and thus act as a reactant.

[0013] Here and in the following chemical constituents mentioned in singular forms are to be understood as a plurality of molecules of these constituents. For example, the term "an organic disulfide" means a plurality of molecules of the organic disulfide and the term "a fluoride anion" means a plurality of fluoride anions.

[0014] The term "residue" is used according to its general meaning as a unit within a molecule. A residue may refer to an atom or a group of atoms that forms part of a molecule, such as a methyl group or such as an ion, e. g., an alkali metal or alkaline earth metal cation. In the method according to the invention the term "residue" specifies X1which is part of R1-X1and X2which is part of R2-O-X2. In case X1or X2is an ion, the binding between R1and X1and R2-0 and X2in each case is an ionic binding though symbolized by a connecting line between R1and X1and R2-0 and X2.

[0015] Unless defined otherwise or used according to a term's general meaning, the following definitions apply:

[0016] As used herein, "C1-6 alkyl" is any saturated linear or branched alkyl group having 1 to 6 carbon atoms. Examples thereof include methyl, ethyl, propyl, isopropyl, n- butyl, sec-butyl, tert-butyl, pentyl and hexyl.

[0017] "C5-10 cycloalkyl" refers to any cyclic version of alkyl having 5 to 10 carbon atoms. The term "cycloalkyl" is also meant to include bicyclic, tricyclic and polycyclic versions thereof.

[0018] "C6-10 aryl" refers to any aromatic mono- or polycyclic ring containing 6 to 10 carbon atoms. Examples are phenyl or naphthyl, preferably phenyl. "5- to 10-membered heteroaryl" refers to any 5- to 10-membered aromatic ring wherein one or more of the carbon atoms in the ring has / have been replaced by one or more of the same or different heteroatoms. The heteroatoms are selected from 0, N and S. Examples of the heteroaryl group include pyrrole, furan, thiophene, imidazole, pyrazole, oxazole, thiazole, pyridine, pyridazine, pyrimidine and pyrazine.

[0019] "5- to 10-membered heterocyclyl" refers to any 5- to 10-membered non-aromatic ring wherein one or more of the carbon atoms in the ring has / have been replaced by one or more of the same or different heteroatoms. The heteroatoms are selected from 0, N and S. Examples of the heterocyclyl group include pyrrolidine, pyrroline, pyrazolidine, pyrazoline, imidazolidine, imidazoline, oxolane, dioxolane, tetrahydrothiophene, oxazolidine, piperidine, morpholine, piperazine, tetrahydropyran, pyran, dioxane, thiane and dithiane.

[0020] "Halogen" represents F, Cl, Br or I.

[0021] If a compound or moiety is referred to as being "optionally substituted", it can in each instance include one or more of the indicated substituents, whereby the substituents can be the same or different ones.

[0022] The inventors found that a common technical feature of the method according to the invention is that the organic disulfide is provided and that the organic disulfide oxidizes the phosphorus-phosphorus single bonds of the elemental phosphorus to form an organic trithiophosph ite intermediate. The formation of the organic trithiophosphite intermediate is catalyzed by either the organic base or the fluoride anion. The phosphorus-sulfur single bonds of the organic trithiophosphite intermediate can react with either the R1-X1, the R2-O-X2, or the fluoride anion in a nucleophilic substitution reaction. In the nucleophilic substitution reaction, the R1- X1, the R2-O-X2, or the fluoride anion are nucleophiles. As such, the generation of the tertiary phosphine according to formula (I), the tertiary phosphite ester according to formula (II), or the hexafluorophosphate is enabled according to the following reaction scheme: oxidant

[0023] (b elemental P) e.g.Nu for example: oxidant

[0024] As shown in the top half of the above reaction scheme, the organic disulfide R5-S-S-R5is used to oxidize the phosphorus-phosphorus bond(s) ([P]- [P] bond(s)) of the elemental phosphorus into phosphorus-sulfur bond(s) which can then be functionalized by nucleophilic substitution using a nucleophile. This involves the formation of the organic trithiophosph ite intermediate. As byproduct of the reaction, a thiolate anion (R5S_), a thiolate or a thiol may be formed. The thiolate anion, the thiolate or the thiol can be oxidized by means of an oxidant or by means of electrochemical oxidation to regenerate the initial organic disulfide. The oxidation of the thiolate anion, the thiolate or the thiol can be performed in a separate step or as part of a catalytic cycle. As shown in the bottom half of the above reaction scheme, the intermediate is the organic trithiophosphite intermediate [(R5S)sP]. By nucleophilic substitution via the nucleophile Nu hexafluorophosphates or phosphorus-comprising organic compounds can be generated. The inventors of the present invention found that the organic base provides the nucleophile with a relatively high nucleophilicity. A relatively high nucleophilicity of the nucleophile enables the nucleophilic substitution reaction of the organic trithiophosph ite intermediate and the nucleophile. Without provision of the organic base, the nucleophilicity of the R1-X1, in particular if X1is a hydrogen residue, or the R2-O-X2, in particular if X2is a hydrogen residue, is too low for an effective nucleophilic substitution reaction of the organic trith iophosphite intermediate and the nucleophile. Thus, without the provision of the organic base together with the R1-X1or the R2-O-X2the generation of the tertiary phosphine according to formula

[0025] (I) or the tertiary phosphite ester according to formula (II) is not possible in an effective way. If X1or X2is a hydrogen residue, the relatively high nucleophilicity of the nucleophile may be provided by deprotonation of the nucleophile by means of the organic base.

[0026] For example, for the generation of the tertiary phosphine according to formula (I), the organic disulfide oxidizes the phosphorus-phosphorus bonds of the elemental phosphorus into phosphorus-sulfur bonds forming the organic trithiophosphite intermediate. In this regard, the organic base catalyzes the formation of the organic trithiophosphite intermediate. Subsequently, the R1-X1acts as nucleophile by means of the organic base, in particular if X1is a hydrogen residue, to functionalize the phosphorus-sulfur bonds of the organic trithiophosphite intermediate by nucleophilic substitution. The nucleophilic substitution reaction results in the generation of the tertiary phosphine according to formula (I).

[0027] For example, for the generation of the tertiary phosphite ester according to formula

[0028] (II), the organic disulfide oxidizes the phosphorus-phosphorus bonds of the elemental phosphorus into phosphorus-sulfur bonds forming the organic trithiophosphite intermediate. In this regard, the organic base catalyzes the formation of the organic trithiophosph ite intermediate. Subsequently, the R2-O-X2acts as nucleophile by means of the organic base, in particular if X2is a hydrogen residue, to functionalize the phosphorus-sulfur bonds of the organic trithiophosphite intermediate by nucleophilic substitution. The nucleophilic substitution reaction results in the generation of the tertiary phosphite ester according to formula (II).

[0029] A further advantage of the organic base vis-a-vis an inorganic base in the specific method according to the invention is its solubility in the solvent which usually is an organic solvent. Inorganic bases commonly are insoluble in organic solvents, which increases the effort for separation of the reaction product.

[0030] For example, for the generation of the hexafluorophosphate, the organic disulfide oxidizes the phosphorus-phosphorus bonds of the elemental phosphorus into phosphorus-sulfur bonds forming the organic trithiophosphite intermediate. In this regard, the fluoride anion catalyzes the formation of the organic trithiophosph ite intermediate. Subsequently, the fluoride anion acts as a nucleophile to functionalize the phosphorus-sulfur bonds of the organic trithiophosphite intermediate by nucleophilic substitution. The nucleophilic substitution reaction results in the generation of the hexafluorophosphate.

[0031] In contrast to the industrial route involving chlorine and the phosphine chloride intermediates, the method according to the invention allows the generation of a phosphorus-comprising organic compound or a hexafluorophosphate with compounds of no or relatively low toxicity and of relatively low corrosivity. Thus, a much lower effort for ensuring occupational safety and health of production workers is required. The method according to the invention is suitable for large- scale industrial production of the phosphorus-comprising organic compound and the hexafluorophosphate. Furthermore, in contrast to the industrial route involving chlorine and the phosphine chloride intermediates, a relatively low quantity of environmentally problematic waste products is produced by the method according to the invention. Furthermore, in contrast to industrial routes involving chlorine and phosphine chloride intermediates, the organic trithiophosphite intermediate formed during mixing according to step b) does not have to be isolated for subsequent reactions, in particular for the subsequent nucleophilic substitution reaction with the respective nucleophile. Thus, the method according to the invention allows the production of the phosphorus-comprising organic compound and the hexafluorophosphate in a cost-effective, energy-efficient and resource-saving manner.

[0032] The organic disulfide may be provided directly. The organic disulfide may be alternatively provided by oxidation of a thiol or of a thiolate by means of an oxidant or by means of electrochemical oxidation. Thus, in order to generate the organic disulfide, a thiol and an oxidant or a thiolate and an oxidant may be provided in step a). The provided thiol and the oxidant may be mixed with the base and the elemental phosphorus and either the R1-X1, the R2-O-X2, or the fluoride anion in the solvent. The base mediates a deprotonation of the thiol to the thiolate. The oxidation of the thiolate by means of the oxidant or by means of electrochemical oxidation then provides the organic disulfide.

[0033] The formed organic trithiophosphite forms the tertiary phosphine, the tertiary phosphite ester or the hexafluorophosphate when brought into contact with either the R1-X1, the R2-O-X2, or the fluoride anion in the solvent. The inventors of the present invention further found that the organic trithiophosphite is thereby converted to a thiolate anion, a thiolate or a thiol which can be oxidized by means of the oxidant or by means of electrochemical oxidation to regenerate the initial organic disulfide. The oxidation of the thiolate anion, the thiolate or the thiol by means of the oxidant or by means of electrochemical oxidation may be performed after step b). Thus, it is possible to provide the organic disulfide at the beginning of the method directly and to provide it after its conversion by oxidation. In this way a continuous generation of the tertiary phosphine, the tertiary phosphite ester, or the hexafluorophosphate is enabled.

[0034] In contrast to Zhang et al. "Diphenyl diselenide-catalyzed synthesis of triaryl phosphites and triaryl phosphates from white phosphorus." Org. Lett. 2021 , 23, 5158-5163, the inventors of the present invention found that an organic trithiophosphite is formed as an intermediate by mixing the elemental phosphorus and the organic disulfide in the solvent according to step b). In this regard, the formation of the organic trithiophosph ite is catalyzed by the organic base or by the fluoride anion. Furthermore, in contrast to Zhang et al., the method according to the invention allows the generation of tertiary phosphines according to formula (I) and hexafluorophosphates. Another difference to Zhang et al. is that the method according to the invention allows the formation of a relatively high variety of tertiary phosphite esters according to formula (II) in a relatively high yield without requiring a relatively large excess of R2-O-X2. The inventors of the present invention found that this is achieved by providing the organic disulfide, the solvent and the organic base.

[0035] During the mixing according to step b), the order in which the elemental phosphorus, the organic disulfide and either the compound R1-X1and the organic base, the compound R2-O-X2and the organic base, or the fluoride anion are mixed in the solvent is arbitrary. During the mixing according to step b), a first mixing step and a second mixing step may be performed. The first mixing step may be a step of mixing for at least 1 minute, in particular at least 30 minutes, in particular at least 1 hour, and at most 30 hours, in particular at most 15 hours. Optionally, the second mixing step may be performed directly after the first mixing step. The second mixing step may be a step of mixing for at least 30 minutes, in particular at least 1 hour, and at most 72 hours, in particular at most 30 hours. The first mixing step and / or the second mixing step may be performed under inert atmosphere. In particular, the elemental phosphorus, the organic disulfide and the organic base may be mixed in the solvent in the first mixing step followed by the second mixing step of mixing either the compound R1-X1or the compound R2-O-X2with the mixture obtained in the first mixing step. The inventors of the present invention found that mixing the elemental phosphorus, the organic disulfide and the organic base in the solvent in the first mixing step enables an efficient oxidation of the phosphorus-phosphorus single bonds of the elemental phosphorus by the organic disulfide. This results in an efficient formation of the organic trithiophosphite intermediate in the first mixing step. The formation of the organic trithiophosphite intermediate is catalyzed by the organic base. The inventors of the present invention further found that mixing of either the compound R1-X1or the compound R2-O-X2in the second mixing step enables an efficient nucleophilic substitution reaction since the organic trithiophosphite intermediate has already been formed during the first mixing step.

[0036] The alkyl may be C1-6 alkyl or C5-10 cycloalkyl. The aryl may be C6-10 aryl. The heteroaryl may be 5- to 10-membered heteroaryl. The heterocyclyl may be 5- to 10-membered heterocyclyl. The C1-6 alkyl, the C5-10 cycloalkyl, the C6-10 aryl, the 5- to 10-membered heterocyclyl and / or the 5- to 10-membered heteroaryl may be independently from each other optionally substituted by halogen, C1-6 alkyl, C6-10 aryl, C5-10 cycloalkyl, 5- to 10-membered heterocyclyl, 5- to 10-membered heteroaryl, OR', COR', COOR', CONR'2 or NR'2. R' may be independently from each other selected from the group consisting of H, C1-6 alkyl, C6-10 aryl and C5-10 cycloalkyl. The alkyl carbon chain may be optionally interrupted by one or more -O-. The C5-10 cycloalkyl and 5- to 10-membered heterocyclyl may be optionally substituted by halogen, C1-6 alkyl, C6-10 aryl, C5-10 cycloalkyl, 5- to 10- membered heterocyclyl, 5- to 10-membered heteroaryl, OR", COR", COOR", CONR"2 or NR"2. R" may be independently from each other selected from the group consisting of H, C1-6 alkyl, C6-10 aryl and C5-10 cycloalkyl.

[0037] X1is selected from a group consisting of an alkali metal atom residue, a magnesium halogenide residue or a hydrogen residue. X2is selected from a group consisting of an alkali metal atom residue, an earth alkali metal atom residue or a hydrogen residue. The alkali metal atom residue may be a lithium residue, a sodium residue or a potassium residue. The magnesium halogenide residue may be a magnesium fluoride residue, a magnesium chloride residue, a magnesium bromide residue or a magnesium iodide residue. The earth alkali metal atom residue may be a magnesium residue or a calcium residue. If X1is an alkali metal atom residue or a magnesium halogenide residue, the R1-X1is an organometallic compound. In one embodiment of the invention, the tertiary phosphine according to formula (I) is an alkylphosphine, in particular tri-n-butylphosphine or tri-n-octylphosphine, or a triarylphosphine, in particular triphenylphosphine, and the tertiary phosphite ester according to formula (II) is triphenyl phosphite, tris(nonylphenyl) phosphite or tris(2,4-di-tert-butylphenyl) phosphite.

[0038] The fluoride anion may be provided by means of hydrogen fluoride or by means of a fluoride salt. The fluoride salt may be an alkali metal fluoride, an earth alkali metal fluoride, ammonium fluoride or a quaternary ammonium fluoride. The alkali metal fluoride may be lithium fluoride, sodium fluoride or potassium fluoride. The earth alkali metal fluoride may be magnesium fluoride or calcium fluoride. The quaternary ammonium fluoride may be a quaternary ammonium fluoride according to formula (IV).

[0039] R6, R7, R8and R9may each be selected independently from each other from a group consisting of alkyl and aryl. In particular, R6, R7, R8and R9may be alkyl. The alkyl may be C1-6 alkyl or C5-10 cycloalkyl. The aryl may be C6-10 aryl. The C1-6 alkyl, the C5-10 cycloalkyl and the C6-10 aryl may be optionally substituted by C1-6 alkyl, C6-10 aryl or C5-10 cycloalkyl. In particular, the quaternary ammonium fluoride may be tetramethylammonium fluoride, tetraethylammonium fluoride or tetrabutylammonium fluoride.

[0040] The hexafluorophosphate may be a hexafluorophosphate anion, an alkali metal hexafluorophosphate, an earth alkali metal hexafluorophosphate, ammonium hexafluorophosphate or a quaternary ammonium hexafluorophosphate. The alkali metal hexafluorophosphate may be lithium hexafluorophosphate, sodium hexafluorophosphate or potassium hexafluorophosphate. The earth alkali metal hexafluorophosphate may be magnesium hexafluorophosphate or calcium hexafluorophosphate. The quaternary ammonium hexafluorophosphate may be tetramethylammonium hexafluorophosphate, tetraethylammonium hexafluorophosphate or tetrabutylammonium hexafluorophosphate.

[0041] The elemental phosphorus may be white phosphorus or red phosphorus. In particular, the elemental phosphorus may be white phosphorus.

[0042] The organic disulfide may be an organic disulfide R5-S-S-R5according to formula (V), wherein R5may be selected from the group consisting of C1-6 alkyl, C5-10 cycloalkyl, 5- to 10-membered heterocyclyl and 5- to 10-membered heteroaryl. The C1-6 alkyl, the C5-10 cycloalkyl, the 5- to 10-membered heterocyclyl and the 5- to 10-membered heteroaryl may each be optionally substituted by halogen, C1-6 alkyl, C1-6 alkyl substituted by halogen, C6-10 aryl, C5-10 cycloalkyl, 5- to 10- membered heterocyclyl, 5- to 10-membered heteroaryl, OR'", COR'", COOR'", C0NR'"2 or NR'"2. R'" may be independently from each other selected from the group consisting of H, C1-6 alkyl, C6-10 aryl and C5-10 cycloalkyl. The C1-6 alkyl substituted by halogen may be a C1-6 alkyl substituted by fluorine or chlorine, in particular substituted by fluorine. The C1-6 alkyl substituted by fluorine may be for example CF3, C2F5 or CHF2.

[0043] R5may be Ce-io aryl. The Ce-io aryl may be optionally substituted by halogen, C1-6 alkyl, C1-6 alkyl substituted by halogen, Ce-io aryl, C5-10 cycloalkyl, 5- to 10- membered heterocyclyl, 5- to 10-membered heteroaryl, OR"", COR"", COOR"", CONR""2 or NR""2. R"" may be independently from each other selected from the group consisting of H, C1-6 alkyl, Ce-io aryl and C5-10 cycloalkyl. The C1-6 alkyl substituted by halogen may be a C1-6 alkyl substituted by fluorine or chlorine, in particular substituted by fluorine. The C1-6 alkyl substituted by fluorine may be for example CF3, C2F5 or CHF2. R5may be in particular phenyl or 4-chlorophenyl.

[0044] The organic trithiophosphite may be an organic trith iophosph ite according to formula (VI).

[0045] The substituent R5of the organic trithiophosphite according to formula (VI) is the substituent R5in the organic disulfide according to formula (V).

[0046] The thiolate anion may be a thiolate anion according to formula (Vila). The thiolate or the thiol may be a thiolate or a thiol according to formula (VI lb).

[0047] (Vila) (VI lb)

[0048] X4may be a hydrogen residue, X1, if X1is an alkali metal atom residue or a magnesium halogenide residue, or X2, if X2is an alkali metal atom residue or an earth alkali metal atom residue. In formula (Vllb) X4can be a hydrogen residue for providing a thiol. In formula (Vllb) X4can be an alkali metal atom residue, a magnesium halogenide residue or an earth alkali metal atom residue for providing a thiolate. A thiolate is to be understood as a derivative of a thiol in which a metal atom replaces the hydrogen attached to sulfur.

[0049] The organic trithiophosph ite formed as intermediate in the method according to the invention is to be understood to be a substance that changes due to conversion during the method according to the invention. In the method according to the invention, the organic disulfide according to formula (V) can be formed again by oxidation of the thiolate anion, the thiolate or the thiol. The oxidation of the thiolate anion, the thiolate or the thiol may be performed by means of an oxidant or by means of electrochemical oxidation. The oxidation of the thiolate anion, the thiolate or the thiol by means of the oxidant or by means of electrochemical oxidation may be performed under inert atmosphere. After the organic disulfide according to formula (V) is formed again, the organic trithiophosphite may be formed with the organic disulfide according to formula (V) and the elemental phosphorus. Thus, the organic disulfide can be recycled in the method according to the invention.

[0050] The oxidation of the thiolate anion, the thiolate or the thiol by means of an oxidant may be performed by bringing the thiolate anion, the thiolate or the thiol into contact with the oxidant. The oxidant may be a common oxidant such as oxygen, hydrogen peroxide, Fenton's reagent, peroxydisulfuric acid, peroxydisulfate sodium salt, peroxydisulfate potassium salt, peroxydisulfate ammonium salt or peroxymonosulfuric acid. In an embodiment of the invention, the oxidant is added to and mixed with the elemental phosphorus, the organic disulfide and either the R1-X1and the organic base, the R2-O-X2and the organic base, or the fluoride anion in the solvent before or during step b) or is added to the solution or to the suspension obtained in step b) after step b). In particular, the oxidant is added to the solution or to the suspension obtained after step b). The inventors of the present invention found that adding the oxidant to the solution or to the suspension obtained after step b), enables a relatively high recycling of the organic disulfide and a relatively low reaction of the oxidant with the elemental phosphorus and the R1-X1. The oxidation may be carried out continuously. If the oxidant is oxygen, the thiolate anion, the thiolate or the thiol may be continuously contacted with the oxygen. The oxygen may be oxygen gas or contained in an oxygen-containing gas mixture, such as air. For this purpose, the solution or the suspension obtained in step b) and / or the solution or the suspension obtained after step b) may be contacted with the oxygen gas or the oxygen-containing gas mixture by means of a mixing apparatus or via a liquid-impermeable, gas-permeable membrane. The oxidation applied in this method enables a very effective and continuous oxidation of the thiolate anion, the thiolate or the thiol, and thus allows a continuous and effective generation of the hexafluorophosphate, the tertiary phosphine, or the tertiary phosphite ester with a relatively low amount of waste products generated in addition to the phosphorus-comprising organic compound or the hexafluorophosphate.

[0051] The oxidation of the thiolate anion, the thiolate or the thiol by means of electrochemical oxidation may be performed by applying an electrical current to an electrolytic cell. The electrolytic cell may comprise an anode contained in an anodic chamber, a cathode contained in a cathodic chamber, a separator contained between the anode and the cathode to physically separate the anodic and cathodic chambers, the separator allowing the transport of ions between the anodic and cathodic chamber. Optionally, the electrolytic cell may comprise an anode and a cathode both contained in a single chamber. The anodic chamber or the single chamber contains the elemental phosphorus, the solvent and either the compound R1-X1and the organic base, the compound R2-O-X2and the organic base, or the fluoride anion as specified in the method according to the invention. The anodic chamber or the single chamber further contains the organic disulfide and / or the thiolate anion, the thiolate or the thiol. The anodic chamber or the single chamber further contains a first electrolyte. The cathodic chamber contains a second electrolyte. The second electrolyte contained in the cathodic chamber may be dissolved or suspended in the solvent as specified in the method according to the invention. In particular, the solvent in the single chamber, in the cathodic chamber and / or in the anodic chamber may be an organic solvent, in particular acetonitrile or tetrahydrofuran.

[0052] The first electrolyte and the second electrolyte may be selected independently from each other from a group consisting of LiBF4, LiPFe, LiCIC , LiCFsSOs, Li(CFsSO2)2N, tetrabutylammonium tetrafluoroborate, tetrabutylammonium perchlorate, tetrabutylammoniumhexafluorophosphate, tetrabutylammonium fluoride, tetrabutylammonium chloride, tetrabutylammonium bromide, tetrabutylammonium iodide, tetraethylammonium hexafluorophosphate, tetraethylammonium fluoride, tetraethylammonium perchlorate, tetraethylammonium tetrafluoroborate, NaBF4, NaPFe, trimethylsulfonylchloride, and (NH4)2SO4. The first electrolyte and the second electrolyte may be identical. In particular, the first electrolyte and the second electrolyte may be tetrabutylammonium hexafluorophosphate in each case. The electrical current applied to the electrolytic cell may have an electrical current density in the range of 1 mA / cm2to 1000 mA / cm2, in particular in the range of 5 mA / cm2to 500 mA / cm2, in particular in the range of 10 mA / cm2to 100 mA / cm2. The voltage between the anode and the cathode is the voltage that is automatically reached at the electric current density. The electrochemical oxidation applied in this method enables a very effective and continuous oxidation of the thiolate anion, the thiolate or the thiol by means of electrochemical oxidation, and thus allows a continuous and effective generation of the hexafluorophosphate, the tertiary phosphine, or the tertiary phosphite ester with a relatively low amount of waste products, in particular environmentally problematic waste products, generated in addition to the phosphorus-comprising organic compound or the hexafluorophosphate, in particular because no chemical oxidant is required.

[0053] In case the organic base is an amine, it may be a tertiary amine, in particular diisopropylethylamine (DIPEA), triethylamine or tributylamine, or triethylendiamine (DABCO). In case the organic base is a metal amide, it may be a metal bis(trimethylsilyl)am ide, lithium tetramethylpiperidide (LiTMP) or lithium diisopropylamide (LDA). In particular, the metal bis(trimethylsilyl)amide may be lithium bis(trimethylsilyl)amide (LiHMDS), sodium bis(trimethylsilyl)amide (NaHMDS) or potassium bis(trimethylsilyl)amide (KHMDS). In case the organic base is an amidine, it may be diazabicycloundecene (DBU). If the organic base is R3-O’ it may be a phenolate. The counterion of the phenolate may be a potassium cation.

[0054] The inventors of the present invention found that the organic base, in particular a tertiary amine, in particular diisopropylethylamine, or a metal amide, in particular KHMDS, provides the R1-X1, in particular if X1is a hydrogen residue, and the R2-O-X2, in particular if X2is a hydrogen residue, with a relatively high nucleophilicity. The relatively high nucleophilicity of the R1-X1and the R2-O-X2enables the R1-X1and the R2-O-X2to displace the thiolate groups of the organic trithiophosphite. Furthermore, the tertiary amine, in particular diisopropylethylamine, is not oxidized in the method according to the invention. At the same time, the tertiary amine, in particular diisopropylethylamine, is a relatively mild reagent and does not react with the elemental phosphorus. Thus, the tertiary amine, in particular diisopropylethylamine, can provide the R1-X1, in particular if X1is a hydrogen residue, and the R2-O-X2, in particular if X2is a hydrogen residue, with a relatively high nucleophilicity for a relatively long time without reacting with the reagents as specified in the method according to the invention. Furthermore, the organic base has a relatively high solubility in organic solvents. A relatively high solubility of the organic base in organic solvents enables good reaction kinetics, i.e. allows for a faster reactivity.

[0055] The solvent may be an organic solvent. The organic solvent may be an aliphatic organic solvent, an aromatic organic solvent, an ether, an alcohol, a nitrile, dimethylsulfoxide or dimethylformamide. The aliphatic organic solvent may be pentane, hexane, heptane or octane. The aromatic organic solvent may be benzene or toluene. The ether may be diethyl ether, dimethoxyethane, 1 ,4- dioxane, 2-methyltetrahydrofuran or tetrahydrofuran. The alcohol may be methanol, ethanol, 1 -propanol and isomers thereof, 1 -butanol or isomers thereof, 1 -pentanol or isomers thereof, 1 -hexanol or isomers thereof. The nitrile may be acetonitrile or benzonitrile. In particular, the solvent may be acetonitrile or tetrahydrofuran.

[0056] The elemental phosphorus, the organic disulfide, the compound R1-X1and the organic base may be mixed in the solvent at a temperature in the range of -80 °C to less than 10 °C, in particular in the range of -70 °C to 5 °C, in particular in the range of -60 °C to 0 °C, in particular in the range of -50 °C to -5 °C, in particular in the range of -40 °C to -10 °C, in particular in the range of -30 °C to -15 °C, and optionally maintained at this temperature. The elemental phosphorus, the organic disulfide, the compound R2-O-X2and the organic base may be mixed in the solvent at a temperature in the range of 25 °C to 60 °C, in particular in the range of 30 °C to 55 °C, in particular in the range of 35 °C to 50 °C, in particular in the range of 40 °C to 45 °C, and optionally maintained at this temperature. The elemental phosphorus, the organic disulfide and the fluoride anion may be mixed in the solvent at a temperature in the range of 25 °C to 80 °C, in particular in the range of 30 °C to 75 °C, in particular in the range of 35 °C to 70 °C, in particular in the range of 40 °C to 65 °C, in particular in the range of 45 °C to 60 °C, in particular in the range of 50 °C to 55 °C, and optionally maintained at this temperature. Alternatively, the elemental phosphorus, the organic disulfide and either the compound R1-X1and the organic base, the compound R2-O-X2and the organic base, or the fluoride anion may be mixed in the solvent at a temperature in the range of 10 °C to less than 25 °C, and optionally maintained at this temperature.

[0057] The solution or the suspension obtained in step b) may be adjusted to a temperature in the range of 10 °C to less than 25 °C, in particular in the range of 15 °C to 20 °C, and maintained at this temperature.

[0058] The adjusting of the solution or the suspension obtained in step b) to a temperature may be by cooling, by keeping the present temperature or by heating. The keeping of the present temperature may be performed under inert atmosphere. The cooling may be performed as an active cooling or as a passive cooling, i.e. by letting it cool down, i.e. by letting it cool down to ambient temperature. The cooling may be performed under inert atmosphere. The heating may be performed as an active heating or as a passive heating, i.e. by letting it heat up, i.e. by letting it heat up to ambient temperature. The heating may be performed under inert atmosphere.

[0059] The temperature may be maintained for at least 1 minute, in particular for at least 5 minutes, in particular for at least 15 minutes, in particular for at least 30 minutes, in particular for at least 1 hour, in particular for at least 2 hours, in particular for at least 3 hours, in particular for at least 4 hours, and for at most 240 hours, in particular for at most 168 hours, in particular for at most 72 hours, in particular for at most 48 hours, in particular for at most 24 hours, in particular for at most 12 hours, in particular for at most 8 hours.

[0060] In the method according to the invention steps a) and b) may be performed under inert atmosphere. The inert atmosphere may be provided by means of an inert gas. The inert gas may be contained in an inert gas mixture. The inert gas may be nitrogen gas, carbon dioxide gas, helium gas, neon gas or argon gas. The inert gas mixture may be a mixture of at least two of nitrogen gas, carbon dioxide gas, helium gas, neon gas and argon gas.

[0061] The solution or the suspension may be stirred during the mixing, the adjusting and / or the maintaining.

[0062] The tertiary phosphine according to formula (I), the tertiary phosphite ester according to formula (II), or the hexafluorophosphate may be obtained by purification of the tertiary phosphine according to formula (I), the tertiary phosphite ester according to formula (II), or the hexafluorophosphate in the solution or in the suspension obtained in step b), in particular after step b). The purification of the tertiary phosphine according to formula (I), the tertiary phosphite ester according to formula (II), or the hexafluorophosphate may be performed by distillation, extraction, precipitation, crystallization, sublimation or chromatography. The purification may be performed under inert atmosphere.

[0063] The invention will be explained in more detail with reference to the following embodiments:

[0064] Fig. 1 shows a schematic representation of the chemical synthesis of a phosphorus-comprising organic compound starting from white phosphorus,

[0065] Fig. 2 shows a schematic representation of the chemical synthesis of tris(4- chlorophenyl)trithiophosphite starting from white phosphorus,

[0066] Fig. 3 shows an1H NMR spectrum of the isolated tris(4-chlorophenyl) trithiophosphite,

[0067] Fig. 4 shows a31P NMR spectrum of the isolated tris(4-chlorophenyl) trithiophosphite,

[0068] Fig. 5 shows a schematic representation of the chemical synthesis of a hexafluorophosphate starting from white phosphorus,

[0069] Fig. 6 shows a schematic representation of the chemical synthesis of triphenylphosphine starting from white phosphorus,

[0070] Fig. 7 shows a schematic representation of the chemical synthesis of triethylphosphine starting from white phosphorus,

[0071] Fig. 8 shows a schematic representation of the chemical synthesis of tri-p- tolylphosphite starting from white phosphorus, Fig. 9 shows a schematic representation of the chemical synthesis of tertiary phosphite esters starting from white phosphorus using catalytic quantities of organic disulfide and

[0072] Fig. 10 shows a schematic representation of the electrochemical synthesis of triphenylphosphite starting from white phosphorus.

[0073] The method according to the invention allows the chemical synthesis of phosphorus-comprising organic compounds. An exemplary schematic representation of the chemical synthesis is shown in Fig. 1.

[0074] Fig. 1 shows that starting from white phosphorus and a diaryldisulfide, triaryltrithiophosphite can be formed in the presence of a catalytically active organic base and acetonitrile (MeCN) as solvent. The triaryltrithiophosphite can be reacted with nucleophiles, which results in the generation of phosphorus- comprising organic compounds (Pi products). For example, the reaction of the triaryltrithiophosphite with a nucleophilic organometallic compound or a nucleophilic phenol results in the generation a tertiary phosphine according to formula (I) or a tertiary phosphite ester according to formula (II), respectively. Thereby, the triaryltrithiophosphite is reduced to arylsulfide anions. The arylsulfide anion can be oxidized by an oxidant, for example by oxygen, by hydrogen peroxide or by peroxodisulfate, to form the educt diaryldisulfide. After formation of the diaryldisulfide, the triaryltrithiophosphite can again be formed in the presence of the catalytically active organic base. This indicates, that the method according to the invention enables the generation of the triaryltrithiophosphite starting from relatively cheap educts under relatively mild conditions. The triarylthiophosphite enables the generation of a variety of phosphorus-comprising organic compounds. Furthermore, the thereby reduced triaryltrithiophosphite can be oxidized to yield the educt diaryldisulfide which subsequently can form the triarylthiophosphite allowing the reaction to be carried out continuously and with a relatively low amount of waste products generated in addition to the phosphorus-comprising organic compound or the hexafluorophosphate.

[0075] Example 2: Chemical synthesis of tris(4-chlorophenyl)trithiophosphite

[0076] 0.50 mmol of white phosphorus were mixed with 3.00 mmol of bis(4- chlorophenyl)disulfide and 0.05 mmol of potassium bis(trimethylsilyl)amide in 50 mL of acetonitrile. The mixture was incubated for 18 hours. This resulted in the formation of 1 .64 mmol of tris(4-chlorophenyl) trithiophosphite, which was isolated by washing the dried reaction mixture with hexane. The isolated tris(4- chlorophenyl) trithiophosphite was detected by1H NMR spectroscopy and31P NMR spectroscopy. The NMR spectra were acquired by dissolving a sample of the isolated material in CeDe and transferring the resulting solution to an NMR tube fitted with a J. Young valve. The sample was then analyzed at room temperature using a Bruker Avance 400 NMR spectrometer, and the resulting data analyzed using the software Topspin 3.2.

[0077] A schematic representation of the chemical synthesis of tris(4- chlorophenyl)trithiophosphite starting from white phosphorus is shown in Fig. 2. An1H NMR spectrum of the isolated tris(4-chlorophenyl) trithiophosphite is shown in Fig. 3. A31P NMR spectrum of the isolated tris(4-chlorophenyl) trithiophosphite is shown in Fig. 4.

[0078] As can be seen in Fig. 3 and Fig. 4, the1H and31P chemical shifts and1H-1H coupling constant are consistent with tris(4-chlorophenyl) trithiophosphite. The coupling pattern in the1H spectrum (of two doublets roofed towards each other with identical coupling constants) is also consistent with tris(4-chlorophenyl) trithiophosphite. Example 3: Chemical synthesis of hexafluorophosphate

[0079] In a Schlenk tube, P4 (100 pL, 0.1 M in CeHe) was added to a suspension of (p-CICeH4S)2 (37.3 mg, 0.13 mmol) and tetramethylammonium fluoride (24.2 mg, 0.26 mmol) in acetonitrile (0.5 mL). The mixture was stirred at 80 °C for 2 hours. Analysis of the reaction mixture by31P{1H} NMR spectroscopy showed the formation of [Me4N][PFe] in a 30% yield, against an internal standard of triphenylphosphine oxide.

[0080] A schematic representation of the chemical synthesis of hexafluorophosphate starting from white phosphorus is shown in Fig. 5.

[0081] Example 4: Chemical synthesis of triphenylphosphine and thiol recovery

[0082] In a Schlenk tube, acetonitrile (40 mL) was added to a solid mixture of P4 (116 mg, 0.94 mmol), (p-CICeH4S)2 (1 .64 g, 5.71 mmol), and KHMDS (16 mg, 0.09 mmol; KHMDS = [K+][N(SiMe3)2)]_. The mixture was stirred overnight, giving a pale yellow solution. Volatiles were removed in vacuo and the resulting solid residues were dissolved in tetrahydrofuran (THF) (10 mL). The solution was cooled to -78 °C and phenylmagnesium bromide (13 mL, 1.0 M in THF, 13 mmol) was added. After stirring for 2 hours at room temperature, volatiles were removed in vacuo.

[0083] Triphenylphosphine was sublimed from the solid residues as a crystalline white solid (0.70 g, 2.67 mmol, 70%). The remaining residues were quenched with saturated ammonium chloride solution and extracted into diethyl ether. Volatiles were removed in vacuo and P-CIC6H4SH (0.56 g, 34%) was sublimed from the oily residues as a colourless crystalline solid.

[0084] A schematic representation of the chemical synthesis of triphenylphosphine starting from white phosphorus is shown in Fig. 6. Example 5: Chemical synthesis of triethylphosphine

[0085] In a Schlenk tube, P4 (250 pL, 0.1 M in CeHe) was added to a suspension of Ph2S2 (35.5 mg, 0.16 mmol) and KHMDS (0.5 mg, 0.003 mmol) in acetonitrile (0.5 mL).

[0086] The solution was stirred for 1 hour. Volatiles were removed in vacuo and 0.5 mL of THF was added. The solution was cooled to -78 °C and EtMgBr (110 pL, 3 M in Et20, 0.33 mmol) was added. The mixture was stirred for 18 hours at room temperature, and volatiles were removed in vacuo. Analysis of the filtrate by31P{1H} NMR spectroscopy showed the formation of triethylphosphine in a 14% yield, against an internal standard of triphenylphosphine oxide.

[0087] A schematic representation of the chemical synthesis of triethylphosphine starting from white phosphorus is shown in Fig. 7.

[0088] It is also possible to perform the first step in another solvent then acetonitrile, e.g. in THF. In this case it is not required to remove volatiles after the first step and the whole procedure is simplified. It can be performed as follows:

[0089] P4 (100 pL, 0.1 M in CeHe) was added to a suspension of Ph2S2 (18.7 mg, 0.065 mmol) and KHMDS (0.2 mg, 0.001 mmol) in THF (0.4 mL). The solution was stirred for 1 hour, followed by addition of EtMgBr (80 pL, 3 M in Et20, 0.24 mmol). The mixture was stirred for 15 minutes at room temperature. Analysis of the reaction mixture by31P{1H} NMR spectroscopy showed the formation of triethylphosphine in a 98% yield, against an internal standard of triphenylphosphine oxide.

[0090] Example 6: Chemical synthesis of trisfphenylethynvDphosphine

[0091] P4 (100 pL, 0.1 M in CeHe) was added to a suspension of Ph2S2 (18.7 mg, 0.065 mmol) and KHMDS (0.2 mg, 0.001 mmol) in THF (0.4 mL). The solution was stirred for 1 hour, followed by addition of phenylethynylmagnesium bromide (200 pL, 1 M in THF, 0.20 mmol). The mixture was stirred for 18 hours at room temperature. Analysis of the reaction mixture by31P{1H} NMR spectroscopy showed the formation of tris(phenylethynyl)phosphine in a 72% yield, against an internal standard of triphenylphosphine oxide.

[0092] Example 7: Chemical synthesis of tri-p-tolylphosphite (4.17 equivalents nucleophile for each phosphorus-sulfur bond of the intermediate)

[0093] In a Schlenk tube, P4 (100 pL, 0.1 M in CeHe) was added to a suspension of (p-CIC6H4S)2 (18.7 mg, 0.065 mmol) and KHMDS (0.2 mg, 0.001 mmol) in THF (0.5 mL). p-Cresol (52.3 pL, 0.5 mmol) was added to the mixture, which was stirred for 3 days. Provided a complete conversion of the (p-CICeH4S)2 together with the P4to the intermediate tris(4-chlorophenyl)trithiophosphite, this corresponds to 4.17 equivalents of the nucleophile p-cresol per each phosphorussulfur bond of the intermediate. Analysis of the reaction mixture by31P{1H} NMR spectroscopy showed the formation of tri-p-toly Iphosphite in a 79% yield, against an internal standard of triphenylphosphine oxide.

[0094] A schematic representation of the chemical synthesis of tri-p-tolylphosphite starting from white phosphorus is shown in Fig. 8.

[0095] Example 8: Chemical synthesis of tri-p-tolylphosphite (2.17 equivalents nucleophile for each phosphorus-sulfur bond of the intermediate)

[0096] In a Schlenk tube, P4(100 pL, 0.1 M in CeHe) was added to a suspension of (p-CICeH4S)2 (18.7 mg, 0.065 mmol) and KHMDS (0.2 mg, 0.001 mmol) in THF (0.5 mL). p-Cresol (27.4 pL, 0.26 mmol) was added to the mixture, which was stirred overnight. Provided a complete conversion of the (p-CICeH4S)2 together with the P4to the intermediate tris(4-chlorophenyl)trithiophosphite, this corresponds to 2.17 equivalents of the nucleophile p-cresol per each phosphorussulfur bond of the intermediate. Analysis of the reaction mixture by31P{1H} NMR spectroscopy showed the formation of tri-p-tolylphosphite in a 68% yield, against an internal standard of triphenylphosphine oxide. Chemical is of tri -p-i .08 for each -sulfur bond of the i

[0097] In a Schlenk tube, P4 (100 pL, 0.1 M in CeHe) was added to a suspension of (p-CIC6H4S)2 (18.7 mg, 0.065 mmol) and KHMDS (0.2 mg, 0.001 mmol) in THF (0.5 mL). p-Cresol (13.7 pL, 0.13 mmol) was added to the mixture, which was stirred for 3 days. Provided a complete conversion of the (p-CICeH4S)2 together with the P4to the intermediate tris(4-chlorophenyl)trithiophosphite, this corresponds to 1 .08 equivalents of the nucleophile p-cresol per each phosphorussulfur bond of the intermediate. Analysis of the reaction mixture by31P{1H} NMR spectroscopy showed the formation of tri-p-toly Iphosphite in a 35% yield, against an internal standard of triphenylphosphine oxide. for each

[0098] In a Schlenk tube, p-cresol (27.4 pL, 0.26 mmol) was added to a suspension of tris(4-chlorophenyl)trithiophosphite (18.5 mg, 0.04 mmol) in acetonitrile (0.5 mL), giving a colourless solution which was stirred overnight. This corresponds to 2.17 equivalents of the nucleophile p-cresol per each phosphorus-sulfur bond of the tris(4-chlorophenyl)trithiophosphite. Analysis of the reaction mixture by31P{1H} NMR spectroscopy showed the formation of tri-p-tolylphosphite in a 72% yield, against an internal standard of triphenylphosphine oxide.

[0099] The results from examples 7 to 10 show that a higher number of equivalents of the nucleophile per phosphorus-sulfur bond of the tris(4-chlorophenyl)trithiophosphite results in a higher formation of tri-p-tolylphosphite. Furthermore, the results from examples 8 and 10 show that either provision of P4, (p-CIC6H4S)2 and KHMDS or direct provision of the tris(4-chlorophenyl)trithiophosphite both result in a similarly high formation of tri-p-tolylphosphite. Provided a complete conversion of the (p-CICeH4S)2 together with the P4to the intermediate tris(4-chlorophenyl)trithiophosphite in example 8, both reactions were performed with 2.17 equivalents of the nucleophile p-cresol per each phosphorus-sulfur bond of the tris(4-chlorophenyl)trithiophosphite. Furthermore, both reactions were stirred overnight. This further indicates that the formation of tri-p-toly Iphosphite is mediated by the intermediate tris(4-chlorophenyl)trithiophosphite.

[0100] Example 11: Chemical synthesis of tertiary phosphite esters starting from white phosphorus using catalytic quantities of organic disulfide

[0101] In a photoreactor tube, P4 (100 pL, 0.1 M in CeHe) was added to a suspension of (p-CIC6H4S)2 (0.7 mg, 0.0025 mmol), Na2S2O8 (31.0 mg, 0.13 mmol), DIPEA (22.7 pL, 0.13 mmol; DIPEA = diisopropylethylamine = / Pr2NEt), and the corresponding phenol (0.13 mmol) in acetonitrile (0.5 mL). The reaction was stirred at 40 °C for 6- 8 hours. Analysis of the reaction mixture by31P{1H} NMR spectroscopy showed the percentage conversion of P4to the corresponding triaryl phosphite, against an internal standard of triphenylphosphine oxide.

[0102] Example results are given in Fig. 9. Fig. 9 shows the percentage conversion in relation to the amount of tertiary phosphite ester product formed relative to the amount of P4starting material provided.

[0103] As can be seen in Fig. 9, the reactions with the monosubstituted phenol compounds show a percentage conversion in the range of 20 % for N-acetyl-para- aminophenol to 69 % for para-methoxyphenol. The reaction with disubstituted 3,5- dimethoxyphenol shows a percentage conversion of 49 %. The reaction with 2- napthol shows a percentage conversion of 36 %. These results indicate that a variety of tertiary phosphite esters can be generated with different aromatic compounds.

[0104] As can be further seen in Fig. 9, the turnover number (TON) is indicated for each reaction. The TON is defined according to the following formula: 6 x (observed conversion) / (catalyst loading relative to P4). The factor of 6 reflects the reaction stoichiometry, in which a stoichiometric reaction would require 6 equivalents of the disulfide per P4. As can be seen in Fig. 9, the reactions with the monosubstituted phenol compounds show a turnover number (TON) in the range of 5 for N-acetyl- para-aminophenol to 17 for para-methoxyphenol. The reaction with the disubstituted phenol compound 3,5-di-methoxyphenol shows a TON of 12. The reaction with 2-napthol shows a TON of 9. These results indicate that the catalytic turnover is relatively high in the generation of tertiary phosphite esters by the method according to the invention.

[0105] Example 12: Electrochemical synthesis of triphenylphosphite

[0106] Embodiment 1

[0107] In the anodic chamber of an H-cell, P4 (400 pL, 0.1 M in CeHe) was added to a solution of (p-CIC6H4S)2 (2.9 mg, 0.01 mmol), DIPEA (90.8 pL, 0.52 mmol), PhOH (48.9 mg, 0.52 mmol), NBU4PF6 (77.5 mg, 0.2 mmol), in acetonitrile (MeCN) (2 mL). In the cathodic chamber, NBU4PF6 (77.5 mg, 0.2 mmol) was dissolved in acetonitrile (2 mL). The chambers were sealed using rubber septa pierced with wire-connected electrodes (reticulated vitreous carbon anode and platinum wire cathode) which were connected to a constant current of 1 .5 mA. Analysis of the reaction mixture by31P{1H} NMR spectroscopy showed the formation of triphenylphosphite in a 20% yield, against an internal standard of triphenylphosphine oxide.

[0108] A schematic representation of the electrochemical synthesis of triphenylphosphite starting from white phosphorus is shown in Fig. 10.

[0109] Embodiment 2

[0110] Alternatively, the electrochemical synthesis of triphenylphosphite can also be performed in an undivided cell, e. g., as follows: To an undivided cell (IKA Electrochemistry Kit, vial 10 mL) charged withnBu4NPFe (232.5 mg, 0.6 mmol) and PhOH (271 .1 mg, 2.08 mmol), a stock solution of bis(4- chlorophenyl)disulfide (800 pL, 0.025 M in MeCN, 0.02 mmol) was added, along with / Pr2NEt (181 pL, 1.04 mmol), a stock solution of P4 (500 pL, 0.16 M in CeHe, 0.08 mmol) and MeCN (4519 pL) to reach a total volume of 6 mL. The electrodes were attached to the cell cap and the sealed electrochemical cell was connected to a potentiostat / galvanostat device (IKA ElectraSyn 2.0). A galvanostatic regime of 1.5 mA was set up in the system and the reaction was run until a total charge of 12.3 F / mol of P4 was consumed. Analysis of the reaction mixture by31P{1H} NMR spectroscopy showed the formation of triphenylphosphite in a 75% yield, against an internal standard of triphenylphosphine oxide.

[0111] The electrodes were a reticulated vitreous carbon anode and a platinum foil cathode. The reticulated vitreous carbon anode consisted of reticulated vitreous carbon (RVC) foam (from Goodfellow Cambridge Limited, UK), 96.5% porosity, 24 pores / cm, 6.35 mm thick, 8 mm x 27 mm size, attached to a graphite pencil rod. The platinum foil cathode was from the IKA Electrochemistry Kit.

[0112] Embodiment 3

[0113] Alternatively, the organic base can also be potassium phenolate which forms an equilibrium with phenol in the presence of protons. Thus, in presence of protons, potassium phenolate can act both as a reactant forming the compound R2-O-X2and as the organic base. The protons can be provided, e. g., by phenol as in the following embodiment:

[0114] To an undivided cell (IKA Electrochemistry Kit, vial 10 mL) charged withnBu4NPFe (232.5 mg, 0.6 mmol) as an electrolyte, PhOH (271 .1 mg, 2.08 mmol) and potassium phenolate (137.5 mg, 1.04 mmol), a stock solution of bis(4-chlorophenyl)disulfide (800 pL, 0.025 M in MeCN, 0.02 mmol) was added, alongside a stock solution of P4 (500 pL, 0.16 M in CeHe, 0.08 mmol) and MeCN (4700 pL) to reach a total volume of 6 mL. The electrodes (reticulated vitreous carbon anode and platinum foil cathode as in the previous embodyment) were attached to the cell cap and the sealed electrochemical cell was connected to a potentiostat / galvanostat device (IKA ElectraSyn 2.0). A galvanostatic regime of 1 .5 mA was set up in the system and the reaction was run until a total charge of 12.3 F / mol of P4 was consumed. Analysis of the reaction mixture by31P{1H} NMR spectroscopy showed the formation of triphenylphosphite in a 75% yield, against an internal standard of triphenylphosphine oxide.

[0115] Embodiment 4

[0116] Alternatively, the electrochemical synthesis of triphenylphosphite can also be performed without addition of a separate electrolyte as follows:

[0117] To an undivided cell (IKA Electrochemistry Kit, vial 10 mL) charged with PhOH (451 .7 mg, 4.8 mmol), a stock solution of bis(4-chlorophenyl)disulfide (800 pL, 0.025 M in MeCN, 0.02 mmol) was added, alongside / Pr2NEt (502 pL, 2.88 mmol), a stock solution of P4 (500 pL, 0.16 M in CeHe, 0.08 mmol) and MeCN (4198 pL) to reach a total volume of 6 mL. The electrodes (reticulated vitreous carbon anode and platinum foil cathode as in the previous embodyment) were attached to the cell cap and the sealed electrochemical cell was connected to a potentiostat / galvanostat device (IKA ElectraSyn 2.0). A galvanostatic regime of 1.5 mA was set up in the system and the reaction was run until a total charge of 12.3 F / mol of P4 was consumed. Analysis of the reaction mixture by31P{1H} NMR spectroscopy showed the formation of triphenylphosphite in a 60% yield, against an internal standard of triphenylphosphine oxide.

[0118] Example 13: Chemical synthesis of triphenylphosphite

[0119] To a Schlenk tube charged with (p-CICeH4S)2 (0.75 g, 2.6 mmol, 6.5 eq.) and KHMDS (7 mg, 0.04 mmol, 0.1 eq.) was added acetonitrile (25 mL) followed by a solution of P4 (50 mg, 0.4 mmol, 1 .0 eq.) in toluene (2 mL). After stirring for 1 h, a solution of phenol (0.90 g, 9.6 mmol, 24 eq.) in acetonitrile (10 mL) was added. The resulting colourless solution was stirred overnight. Volatiles were removed in vauco, giving a colourless liquid. Thiol and excess phenol were removed by sublimation in vacuo, and triphenyl phosphite (291 mg, 0.94 mmol, 59%) was isolated as a viscous, colourless oil by distillation in vacuo at 130 °C and analysed by NMR:

[0120] 1H NMR (400 MHz, C6D6) 5 7.19 - 7.12 (m, 6H), 7.03 - 6.96 (m, 6H), 6.87 - 6.80 ppm (m, 3H).

[0121] 13C{1H} NMR (101 MHz, C6D6) 5 152.3 (d, JCP = 3.1 Hz), 130.0 (s), 124.4 (s), 121.2 ppm (d, JCP = 6.9 Hz).

[0122] 31P{1H} NMR (162 MHz, C6D6) 5 128.6 ppm (s).

[0123] The methods of all of the above examples can be performed in inert atmosphere. It has been shown that this results in slightly higher yields than without inert atmosphere.

[0124] Abbreviations:

[0125] Et: ethyl; Ph: phenyl;nBu: n-butyl; / Pr: iso-propyl; Me: methyl

Claims

Claims1 . A method for the generation of a tertiary phosphine according to formula (I), a tertiary phosphite ester according to formula (II),or a hexafluorophosphate, wherein R1and R2are each selected independently from each other from a group consisting of alkyl, aryl, heterocyclyl and heteroaryl, wherein the method comprises the following steps: a) providing an elemental phosphorus, an organic disulfide, a solvent and either a compound R1-X1and an organic base for obtaining the tertiary phosphine according to formula (I), a compound R2-O-X2and an organic base for obtaining the tertiary phosphite ester according to formula (II), or a fluoride anion for obtaining the hexafluorophosphate, wherein X1is selected from a group consisting of an alkali metal, a magnesium halogenide and hydrogen, wherein X2is selected from a group consisting of an alkali metal, an earth alkali metal and hydrogen, wherein the organic base is an amine, a metal amide, a guanidine, an amidine or R3-O wherein R3is selected from a group consisting of alkyl, aryl, heterocyclyl and heteroaryl, and b) mixing the elemental phosphorus, the organic disulfide and either the compound R1-X1and the organic base, the compound R2-O-X2and the organic base, or the fluoride anion in the solvent for obtaining a solution or aRECTIFIED SHEET (RULE 91) ISA / EPsuspension in which the tertiary phosphine according to formula (I), the tertiary phosphite ester according to formula (II) or the hexafluorophosphate is formed.

2. Method according to claim 1 , wherein the alkyl is C1-6 alkyl or C5-10 cycloalkyl, and / or wherein the aryl is C6-10 aryl, and / or wherein the heteroaryl is 5- to 10-membered heteroaryl, and / or wherein the heterocyclyl is 5- to 10-membered heterocyclyl, wherein the C1-6 alkyl, the C5-10 cycloalkyl, the C6-10 aryl, the 5- to 10-membered heterocyclyl and / or the 5- to 10-membered heteroaryl are independently from each other optionally substituted by halogen, C1-6 alkyl, C6-10 aryl, C5-10 cycloalkyl, 5- to 10- membered heterocyclyl, 5- to 10-membered heteroaryl, OR', COR', COOR', CONR'2 or NR'2, wherein R' is independently from each other selected from the group consisting of H, C1-6 alkyl, C6-10 aryl and C5-10 cycloalkyl.

3. Method according to claim 1 or 2, wherein the elemental phosphorus is white phosphorus or red phosphorus.

4. Method according to any of the preceding claims, wherein the organic disulfide is R5-S-S-R5, wherein R5is selected from the group consisting of C1-6 alkyl, C5-10 cycloalkyl, 5- to 10-membered heterocyclyl and 5- to 10- membered heteroaryl, wherein the C1-6 alkyl, the C5-10 cycloalkyl, the 5- to 10-membered heterocyclyl and the 5- to 10-membered heteroaryl are each optionally substituted by halogen, C1-6 alkyl, C1-6 alkyl substituted by halogen, C6-10 aryl, C5-10 cycloalkyl, 5- to 10-membered heterocyclyl, 5- to 10-membered heteroaryl, OR'", COR'", COOR'", CONR'"2or NR'"2, wherein R'" is independently from each other selected from the group consisting of H, C1-6 alkyl, C6-10 aryl and C5-10 cycloalkyl.

5. Method according to any of claims 1 to 3, wherein the organic disulfide is R5-S-S-R5, wherein R5is C6-10 aryl, wherein the Ce- aryl is optionally substituted by halogen, C1-6 alkyl, C1-6 alkyl substituted by halogen, C6-10aryl, C5-10 cycloalkyl, 5- to 10-membered heterocyclyl, 5- to 10-membered heteroaryl, OR"", COR"", COOR"", CONR""2or NR""2, wherein R"" is independently from each other selected from the group consisting of H, C1-6 alkyl, C6-10 aryl and C5-10 cycloalkyl.

6. Method according to any of the preceding claims, wherein the amine is a tertiary amine, in particular diisopropylethylamine (DIPEA), triethylamine, tributylamine, or triethylendiamine (DABCO) and the metal amide is a metal bis(trimethylsilyl)amide, lithium tetramethylpiperidide (LiTMP) or lithium diisopropylamide (LDA).

7. Method according to any of claims 1 to 5, wherein the amidine is diazabicycloundecen (DBU) and the R3-O_is a phenolate.

8. Method according to any of the preceding claims, wherein the solvent is an organic solvent, in particular acetonitrile or tetrahydrofuran.

9. Method according to any of the preceding claims, wherein the alkali metal is lithium, sodium or potassium, wherein the magnesium halogenide is magnesium fluoride, magnesium chloride, magnesium bromide or magnesium iodide, wherein the earth alkali metal is magnesium or calcium.

10. Method according to any of the preceding claims, wherein the elemental phosphorus, the organic disulfide, the compound R1-X1and the organic base are mixed in the solvent at a temperature in the range of -80 °C to less than 10 °C and optionally maintained at this temperature, or wherein the elemental phosphorus, the organic disulfide, the compound R2-O-X2and the organic base are mixed in the solvent at a temperature in the range of 25 °C to 60 °C and optionally maintained at this temperature, or wherein the elemental phosphorus, the organic disulfide and the fluoride anion are mixed in the solvent at a temperature in the range of 25 °C to 80 °C and optionally maintained at this temperature.11 . Method according to any of the preceding claims, wherein the solution or the suspension obtained in step b) is adjusted to a temperature in the range of 10 °C to less than 25 °C and maintained at this temperature.

12. Method according to claim 10 or 11 , wherein the temperature is maintained for at least 1 minute, in particular for at least 30 minutes, and for at most 240 hours, in particular for at most 72 hours.

13. Method according to any of the preceding claims, wherein the tertiary phosphine according to formula (I) is an alkylphosphine, in particular tri-n- butylphosphine or tri-n-octylphosphine, or a triarylphosphine, in particular triphenylphosphine, and the tertiary phosphite ester according to formula (II) is triphenyl phosphite, tris(nonylphenyl) phosphite or tris(2, 4-d i-tert- butylphenyl) phosphite.

14. Method according to any of the preceding claims, wherein the organic disulfide is provided by oxidation of a thiol or of a thiolate by means of an oxidant or by means of electrochemical oxidation.

15. Method according to any of the preceding claims, wherein an / the oxidant is added to and mixed with the elemental phosphorus, the organic disulfide and either the compound R1-X1and the organic base, the compound R2-O-X2and the organic base, or the fluoride anion in the solvent before or during step b) and / or is added to the solution or to the suspension obtained in step b) after step b).

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