Alkyl-containing phosphine compounds and methods for producing the same

Abstract

This invention provides a method for producing novel alkyl group-containing phosphine compounds useful as ligands, specifically one that produces alkyl group-containing phosphine compounds with excellent purity. [Solution] A method for producing an alkyl group-containing phosphine compound represented by formula (1), comprising a reaction step of synthesizing a compound represented by formula (1) by reacting a compound represented by formula (4) with a specific phosphine compound, and a purification step of mixing the obtained compound of formula (1) with a saturated hydrocarbon having 5 or fewer carbon atoms. JPEG2026136981000047.jpg32154 JPEG2026136981000048.jpg33154

Description

[Technical Field]

[0001] The present invention relates to a method for producing a novel alkyl group-containing phosphine compound (hereinafter also referred to as the compound represented by formula (1)). [Background technology]

[0002] Conventionally, numerous phosphines have been designed and synthesized and used in various catalytic reactions. Phosphines play a significant role in improving activity and controlling chemoselectivity or stereoselectivity. In particular, the structural design of trisubstituted alkylphosphines is important for controlling the activity of homogeneous transition metal catalysts.

[0003] In recent years, trisubstituted phosphines with bulky substituents at distant positions have been reported to exhibit high activity in cross-coupling reactions. For example, the CyTyrranoPhos ligand has bulky substituents at the 3,5-positions of the phenyl group on the phosphorus ring, giving it steric characteristics that occupy a space at a distance rather than near the metal (Non-Patent Literature 1). This allows for high catalytic reaction efficiency in Suzuki-Miyaura (SM) coupling. On the other hand, Non-Patent Literature 2 describes how N-heterocyclic carbene ligands achieve high catalytic activity by making the bulky substituent of the aryl group linked to the imidazole ring flexible (Non-Patent Literature 2). Based on the above findings, introducing flexible and bulky substituents at distant positions in phosphine ligands may be one way to dramatically improve catalytic activity. [Prior art documents] [Non-patent literature]

[0004] [Non-Patent Document 1] Newman-Stonebraker, SH et al., Science 2021, 374, pp.301-308 [Non-Patent Document 2] Altenhoff, G. et al., J. Am. Chem. Soc. 2004, 126, pp.15195-15201 [Overview of the project] [Problems that the invention aims to solve]

[0005] However, no examples of phosphines having flexible and bulky substituents at a remote position as described above have been known until now, and such phosphines are in demand.

[0006] The inventors obtained a novel alkyl group-containing phosphine compound by reacting a compound represented by formula (4) with a phosphine compound represented by formula (5). However, they found that when the product was scaled up, the purity of the alkyl group-containing phosphine compound represented by formula (1) decreased. [Means for solving the problem]

[0007] To solve the above problems, after much consideration, the inventors discovered that the purity of the novel alkyl-containing phosphine compound of the present invention can be improved by mixing the alkyl-containing phosphine compound represented by formula (1) obtained in the reaction step with a saturated hydrocarbon having 5 or fewer carbon atoms, thus completing the present invention.

[0008] Therefore, the object of the present invention is to provide a method for producing a novel alkyl group-containing phosphine compound that is useful as a ligand, and that produces an alkyl group-containing phosphine compound with excellent purity.

[0009] In other words, the present invention provides the following invention. [1] Alkyl-containing phosphine compounds represented by the following formula (1) (hereinafter also referred to as the compound of formula (1)): [ka] (In equation (1), A is the same as in equations (2) and (3) below): [ka] (In equation (2), the wavy lines indicate connections with P.) [ka] (In equation (3), the wavy lines indicate connections with P.) This shows an alkyl group represented by a chemical formula selected from the following: In formula (1), R 1 , R 2 These independently represent an optionally substituted hydrocarbon group or an optionally substituted pyridyl group. In equation (1), n1 and n2 are independent integers between 0 and 2, and the sum of n1 and n2 is between 0 and 2. A method for manufacturing, Formula (4): [ka] (In formula (4), R 3 (This represents one halogen atom selected from the group consisting of chlorine, bromine, and iodine atoms.) Compounds represented by and Formula (5): [ka] (In formula (5), R 1 , R 2 n1 and n2 are equivalent to those in equation (1). A reaction step to synthesize an alkyl group-containing phosphine compound represented by formula (1) by reacting it with a phosphine compound represented by formula (1), and A purification step comprising mixing the alkyl group-containing phosphine compound represented by formula (1) obtained in the above reaction step with a saturated hydrocarbon having 5 or fewer carbon atoms. A method for producing alkyl group-containing phosphine compounds. [2] R 1 , R 2which is a group independently selected from the group consisting of an optionally substituted alkyl group, an optionally substituted phenyl group, an optionally substituted alicyclic hydrocarbon group, and an optionally substituted adamantyl group, the production method according to [1]. [3] The production method according to [1] or [2], wherein in the reaction step, a hydrocarbon-based lithium compound further exists. [4] The production method according to any one of [1] to [3], wherein the purification step further includes allowing the mixture obtained by the mixing to stand and filtering the supernatant of the obtained mixture. [5] The production method according to any one of [1] to [4], wherein the mixing temperature in the purification step is -80 to 30°C. [6] The production method according to any one of [1] to [5], wherein the mixing time in the purification step is 0.1 to 3 hours. [7] The production method according to any one of [1] to [6], wherein an aprotic polar solvent further exists in the reaction step. [8] The production method according to [7], further including a step of treating a mixture of the alkyl group-containing phosphine compound represented by the formula (1) obtained in the reaction step and an aprotic polar solvent with a desiccant after the reaction step and before the purification step. [9] The production method according to [8], further including a step of removing the aprotic polar solvent in the reaction step after the desiccant treatment step and before the purification step.

[10] The following formula (4): [Chemical formula] (In formula (4), R 3 represents one halogen atom selected from the group consisting of a chlorine atom, a bromine atom, and an iodine atom.) A compound represented by

[11] A compound represented by the following formula (4): [Chemical formula] (In formula (4), R 3(This represents one halogen atom selected from the group consisting of chlorine, bromine, and iodine atoms.) A method for manufacturing, Formula (6): [ka] Compounds represented by and The following equations (7) to (9): [ka] (In formula (7), R 3 This is equivalent to equation (4). [ka] (In formula (8), R 3 This is equivalent to equation (4). ), and [ka] (In formula (9), R 3 This is equivalent to equation (4). A halogen-containing compound represented by a chemical formula selected from the group consisting of and By reacting them, A method for producing a compound, comprising the step of synthesizing the compound represented by formula (4) above.

[12] A method for producing the compound according to

[11] , wherein in the reaction step, if the halogen-containing compound is a compound represented by formula (7), triphenylphosphine is further present; if the halogen-containing compound is a compound represented by formula (8), pyridine is further present; and if the halogen-containing compound is a compound represented by formula (9), iodine is further present. [Effects of the Invention]

[0010] The present invention provides a method for improving the purity of novel alkyl group-containing phosphine compounds. The production method of the present invention is advantageous in that it can reduce oxides of the target alkyl group-containing phosphine compound that are produced together with the compound. Furthermore, the production method of the present invention is advantageous in that it can produce excellent yields of novel alkyl group-containing phosphine compounds. Such novel alkyl group-containing phosphine compounds are useful as ligands. Furthermore, the production method of the present invention is advantageous in that it is easier to scale up. In addition, the production method of the present invention is advantageous in that it can reduce production costs because it eliminates the need for chromatographic operations. [Brief explanation of the drawing]

[0011] [Figure 1] This is the 1H-NMR spectrum of the compound represented by formula (6) obtained in Example 1. [Figure 2] This is the 13C-NMR spectrum of the compound represented by formula (6) obtained in Example 1. [Figure 3] This is the 1H-NMR spectrum of the compound represented by formula (4-1) obtained in Example 2. [Figure 4] This is the 13C-NMR spectrum of the compound represented by formula (4-1) obtained in Example 2. [Figure 5] This is the 31P-NMR spectrum of the crude product of the alkyl group-containing phosphine compound obtained in Example 3. [Figure 6] This is the 1H-NMR spectrum of the alkyl group-containing phosphine compound obtained in Example 3. [Figure 7] This is the 13C-NMR spectrum of the alkyl group-containing phosphine compound obtained in Example 3. [Figure 8] This is the 31P-NMR spectrum of the alkyl group-containing phosphine compound obtained in Example 3. [Modes for carrying out the invention]

[0012] [Alkyl-containing phosphine compounds] The alkyl group-containing phosphine compound of the present invention is of the following formula (1): [ka] It is represented as follows.

[0013] In equation (1), A is the same as in equations (2) and (3): [ka] [ka] It is an alkyl group represented by a chemical formula selected from the following.

[0014] In this specification, "triisobutylene (hereinafter also referred to as TIB) group" refers to the trimer structure (12 carbon atoms) of isobutylene. Specific examples of TIB groups include those derived from the structures of formulas (2-1), (2-2), and (10-1) below, with the TIB group derived from the structure of formula (2-1) being preferred.

[0015] Examples of TIB groups derived from the structure of formula (2-1) below (2,2,6,6-tetramethyl-4-methyleneheptane) include the TIB group represented by formula (2) below and the TIB group represented by formula (3) below, with the TIB group represented by formula (2) below being preferred. In addition, an example of a TIB group derived from the structure of formula (2-2) below (2,2,4,6,6-pentamethyl-3-heptene) is the TIB group represented by formula (3) below. [ka] [ka]

[0016] An example of a TIB group derived from the structure of formula (10-1) below (2,4,4,6,6-pentamethylhept-1-ene) is the TIB group represented by formula (10) below. [ka] [ka]

[0017] R in equation (1) 1 , R 2 R independently represents an optionally substituted hydrocarbon group, an alkoxy group, an amide group, or an optionally substituted pyridyl group. 1 and R 2 The number of carbon atoms in the hydrocarbon group shown is not particularly limited, but examples include 1 to 36 carbon atoms, preferably 2 to 30, and more preferably 3 to 10. Examples of the hydrocarbon group include alkyl groups, alicyclic hydrocarbon groups, aromatic hydrocarbon groups, and groups formed by combining these.

[0018] R 1 and R 2 The alkyl group represented by is not particularly limited in terms of the number of carbon atoms, but examples include groups with 1 to 20 carbon atoms, preferably 1 to 12 carbon atoms, and more preferably 1 to 8 carbon atoms. The alkyl group may be either a linear or branched alkyl group, and examples include a methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, sec-butyl group, tert-butyl group, pentyl group, hexyl group, heptyl group, 2-ethylhexyl group, saturated hydrocarbon group with 8 carbon atoms (e.g., linear octyl group or branched octyl group), nonyl group, decyl group, undecyl group, saturated hydrocarbon group with 12 carbon atoms (e.g., linear dodecyl group or branched dodecyl group), and TIB (triisobutylene) group, with tert-butyl group, branched octyl group, branched dodecyl group, and TIB group being preferred.

[0019] R 1and R 2 The alkyl group shown may be substituted, and examples of substituents include halogen atoms, -P(TIB)2 groups, and alkoxy groups. Preferably, a linear or branched C such as a fluorine atom, chlorine atom, bromine atom, iodine atom, -P(TIB)2 group, methoxy group, or ethoxy group. 1-4 It is considered an alkoxy group.

[0020] R 1 and R 2 The alicyclic hydrocarbon group represented by is not particularly limited in terms of the number of carbon atoms, but examples include those with 3 to 36 carbon atoms, preferably 5 to 30, and more preferably 6 to 20. The alicyclic hydrocarbon group may be either saturated or unsaturated. The above alicyclic hydrocarbon group may be monocyclic or polycyclic, and examples of monocyclic alicyclic hydrocarbon groups include cycloalkyl groups such as cyclopropyl group, cyclobutyl group, cyclopentyl group, cyclohexyl group, methylcyclohexyl group, dimethylcyclohexyl group, cycloheptyl group, cyclooctyl group, and cyclodecyl group, with cyclopentyl group and cyclohexyl group being preferred. Examples of polycyclic alicyclic hydrocarbon groups include decahydronaphthyl group, adamantyl group, 2-alkyladamantan-2-yl group, 1-(adamantan-1-yl)alkane-1-yl group, norbornyl group, methylnorbornyl group, and isobornyl group, with adamantyl group being preferred.

[0021] R 1 and R 2 The alicyclic hydrocarbon group shown may be substituted, and examples of substituents include halogen atoms and alkoxy groups, preferably linear or branched C atoms such as fluorine atoms, chlorine atoms, bromine atoms, iodine atoms, methoxy groups, and ethoxy groups. 1-4 It is considered an alkoxy group.

[0022] According to a preferred embodiment of the present invention, R 1 and R 2The adamantyl group shown may be substituted, and examples of substituents include halogen atoms and alkoxy groups, preferably linear or branched C atoms such as fluorine atoms, chlorine atoms, bromine atoms, iodine atoms, methoxy groups, and ethoxy groups. 1-4 It is considered an alkoxy group.

[0023] R 1 and R 2 The aromatic hydrocarbon group represented is not particularly limited in terms of the number of carbon atoms, but examples include groups with 3 to 36 carbon atoms, preferably 5 to 30, and more preferably 6 to 20. Examples of the above aromatic hydrocarbon group include phenyl groups and naphthyl groups, and phenyl groups are preferred.

[0024] R 1 and R 2 The aromatic hydrocarbon group represented by may be substituted, and examples of substituents include halogen atoms, -P(TIB)2, 2-furyl groups, 2-thienyl groups, cyclopentadienyl groups, and alkoxy groups. Preferably, a linear or branched C group such as a fluorine atom, chlorine atom, bromine atom, iodine atom, -P(TIB)2, methoxy group, or ethoxy group. 1-4 It is considered an alkoxy group.

[0025] According to a preferred embodiment of the present invention, R 1 and R 2 The phenyl group shown may be substituted, and the substituents may be linear or branched C such as a methyl group (Me) or a tert-butyl group (tert-Bu). 1-4 Alkyl groups; linear or branched C groups such as methoxy groups (OMe) and tert-butoxy groups (O-tert-Bu). 1-4 Alkoxy groups; dimethylamino groups (NMe2), and halogen atoms are more preferred. Specific R 1 and R 2Examples of substituted phenyl groups include tolyl groups such as o-tolyl, m-tolyl, and p-tolyl groups; xylyl groups such as 2,4-xylyl, 2,5-xylyl, and 3,5-xylyl groups; tert-butylphenyl groups such as p-tert-butylphenyl groups; di-tert-butylphenyl groups; methoxyphenyl groups such as p-methoxyphenyl and o-methoxyphenyl groups; tert-butoxyphenyl groups such as p-tert-butoxyphenyl groups; pentafluorophenyl groups; (2,4,6-triisopropylphenyl)phenyl groups; and (TIB)2-P-phenyl groups such as o-(TIB)2-P-phenyl groups, p-(TIB)2-P-phenyl groups, and m-(TIB)2-P-phenyl groups.

[0026] R 1 and R 2 The pyridyl group shown may be substituted, and examples of substituents include halogen atoms, -P(TIB)2, and alkoxy groups, preferably linear or branched C such as fluorine atoms, chlorine atoms, bromine atoms, iodine atoms, -P(TIB)2, methoxy groups, and ethoxy groups. 1-4 It is considered an alkoxy group.

[0027] In equation (1), n1 and n2 are independent integers between 0 and 2, and the sum of n1 and n2 is between 0 and 2.

[0028] When A in formula (1) is 2 or greater, A independently represents an alkyl group represented by a chemical formula selected from formulas (2) and (3) above.

[0029] In equation (2), the wavy lines indicate connections with P.

[0030] In equation (3), the wavy lines indicate connections with P.

[0031] In formula (1), A, R 1 , R 2According to a preferred embodiment relating to the combination of n1 and n2, A is an alkyl group represented by the chemical formula (2) or (3), more preferably an alkyl group represented by the chemical formula (2), n1 is 2, n2 is 0, and R 1 Both represent a group selected from the group consisting of optionally substituted alkyl groups, optionally substituted alicyclic hydrocarbon groups, optionally substituted phenyl groups, and optionally substituted adamantyl groups, R 2 It does not exist. In equation (1), A, R 1 , R 2 According to another preferred embodiment relating to the combination of n1 and n2, A is an alkyl group represented by the chemical formula of formula (2) or formula (3), more preferably an alkyl group represented by the chemical formula of formula (2), n1 is 1, n2 is 0, and R 1 However, R represents a group selected from the group consisting of optionally substituted alkyl groups, optionally substituted alicyclic hydrocarbon groups, optionally substituted phenyl groups, and optionally substituted adamantyl groups. 2 It does not exist. In equation (1), A, R 1 , R 2 According to another preferred embodiment relating to the combination of n1 and n2, A is an alkyl group represented by the chemical formula of formula (2) or formula (3), more preferably an alkyl group represented by the chemical formula of formula (2), n1 is 0, n2 is 0, and R 1 and R 2 It does not exist.

[0032] Preferred embodiments of the alkyl group-containing phosphine compound represented by formula (1) above include the following compounds. In the following formula, tBu represents a tert-butyl group, TIB represents a triisobutylene skeleton group, and iPr represents an isopropyl group. [ka] [ka] [ka] [ka] [ka]

[0033] The ligand consisting of the alkyl group-containing phosphine compound represented by formula (1) above has two or more bulky tert-butyl groups located away from the phosphorus atom. These tert-butyl groups are thought to be able to flexibly stabilize the active metal center and improve catalytic activity.

[0034] [Method for producing alkyl group-containing phosphine compounds] The method for producing the alkyl-containing phosphine compound represented by formula (1) is not particularly limited, but for example, it includes a reaction step of synthesizing the alkyl-containing phosphine compound represented by formula (1) by reacting the compound represented by formula (4) and the phosphine compound represented by formula (5) in the presence of a hydrocarbon lithium compound. The above reaction step will be described in detail below.

[0035] (Halogenated triisobutylene compounds) Formula (4): [ka] (In formula (4), R 3 (This represents one halogen atom selected from the group consisting of chlorine, bromine, and iodine atoms.) The compound represented by is also called a halide triisobutylene compound.

[0036] In formula (4), R 3 R is preferably a bromine atom or a chlorine atom, and more preferably a bromine atom. 3The halogenated triisobutylene compound in which the atom is bromine (the compound represented by formula (4-1) described later) is 1-bromo-2-(2,2-dimethylpropyl)-4,4-dimethylpentane, and is hereafter also called the brominated triisobutylene compound or TIB-Br compound. The method for producing the halogenated triisobutylene compound will be described later.

[0037] (Phosphine compounds) The phosphine compound used in the present invention is of the following formula (5): [ka] It is a compound represented by [formula]. In formula (5), R 1 , R 2 n1 and n2 are equivalent to those in equation (1), and so are the preferred embodiments.

[0038] Preferred embodiments of the phosphine compound represented by formula (5) above include the following compounds. [ka] [ka] [ka] [ka]

[0039] The amount of the phosphine compound represented by formula (5) above is not particularly limited as long as it does not hinder the effects of the present invention, but is such that, for example, the reactive group (hydrogen group) contained in the phosphine compound is 0.1 to 2.0 equivalents, preferably 0.2 to 1.5 equivalents, and more preferably 0.95 to 1.05 equivalents, relative to 1 equivalent of the halogenated triisobutylene compound represented by formula (4). According to another embodiment of the present invention, the amount of the phosphine compound represented by formula (5) above is, for example, 0.1 to 2.0 moles, preferably 0.2 to 1.5 moles, and more preferably 0.95 to 1.05 moles, relative to 1 mole of the halogenated triisobutylene compound represented by formula (4).

[0040] According to a preferred embodiment of the present invention, the amount of the phosphine compound represented by formula (5) is not particularly limited as long as it does not hinder the effects of the present invention, but from the viewpoint of scale-up, it is 1 mmol (mmol) or more, preferably 5 mmol (mmol) or more, and more preferably 10 mmol (mmol) or more. The upper limit of the amount of the phosphine compound represented by formula (5) is not particularly limited, but it is 100 moles or less, and preferably 1 mole or less.

[0041] According to another preferred embodiment of the present invention, the amount of the phosphine compound represented by formula (5) is not particularly limited as long as it does not hinder the effects of the present invention, but from the viewpoint of scale-up, it is 0.2 mL or more, preferably 1 mL or more, and more preferably 2 mL or more. The upper limit of the amount of the phosphine compound represented by formula (5) is not particularly limited, but is 2 L or less, and is preferably 200 mL or less.

[0042] The hydrocarbon lithium compound used in the present invention is not particularly limited as long as it does not hinder the effects of the present invention, but examples include alkyl lithiums such as methyl lithium (MeLi), n-butyl lithium (n-BuLi), sec-butyl lithium (sec-BuLi), and tert-butyl lithium (tert-BuLi), as well as aromatic lithiums such as phenyl lithium (PhLi), and preferably n-butyl lithium.

[0043] (solvent) The solvent used in the above reaction step is not particularly limited, but from the viewpoint of maintaining the oxidation resistance of the trisubstituted phosphine compound, which is the target of synthesis, non-aqueous solvents or aprotic polar solvents are preferred. For example, amide solvents such as N,N-dimethylformamide (DMF) and dimethylacetamide; ether solvents such as tetrahydrofuran (THF), cyclopentyl methyl ether (CPME), dioxane, diethyl ether, glyme, and diglyme; halogen solvents such as dichloromethane, chloroform, 1,2-dichloroethane, chlorobenzene, and o-dichlorobenzene; aromatic hydrocarbon solvents such as toluene, benzene, o-,m-,p-xylene, and mesitylene; aliphatic hydrocarbon solvents such as pentane, n-hexane, and cyclohexane; and fluorine-containing organic solvents such as hexafluorobenzene, m-bis(trifluoromethyl)benzene, p-bis(trifluoromethyl)benzene, α,α,α-trifluoromethylbenzene, and dichloropentafluoropropane can be used. Among these, aprotic polar solvents are preferred from the viewpoint of improving the affinity of the added base and improving the reactivity between the compound represented by formula (4) and the phosphine compound represented by formula (5), with DMF, THF, and mixtures thereof being more preferred. Furthermore, it is preferable that the non-aqueous solvent or aprotic polar solvent is dehydrated.

[0044] According to one embodiment of the present invention, when a non-aqueous solvent or an aprotic polar solvent is used as the solvent in the above reaction step, post-treatment can be performed, for example. The post-treatment includes treating the mixture of the alkyl group-containing phosphine compound represented by formula (1) obtained in the above reaction step and the aprotic polar solvent with a desiccant. Examples of the desiccant include sodium sulfate decahydrate (Na2SO4-10H2O) and magnesium sulfate heptahydrate (MgSO4-7H2O). The post-treatment is preferably performed after the above reaction step and before the above purification step. If hydrocarbon lithium compounds are further present in the above reaction step, unwanted hydrocarbon lithium compounds (preferably n-BuLi) can be deactivated without using water by the post-treatment.

[0045] In organic synthesis, the presence of water and organic solvents in the reaction system necessitates liquid-liquid extraction, which can increase time costs and reduce yield. Therefore, by using a non-aqueous solvent or an aprotic polar solvent as the solvent and then performing post-treatment, liquid-liquid extraction can be eliminated, simplifying the experimental procedure.

[0046] According to one embodiment of the present invention, the post-treatment step (also referred to as the desiccant treatment step) and the purification step described later further include a step to remove the non-aqueous solvent or aprotic polar solvent in the reaction step.

[0047] The amount of the above solvent used is not particularly limited, but for example, it is 1 to 10,000 parts by mass, preferably 10 to 4,000 parts by mass, relative to 100 parts by mass of the total of the halide triisobutylene compound and the phosphine compound represented by formula (5) above.

[0048] (Reaction conditions) The atmosphere in which the halide triisobutylene compound and the phosphine compound represented by formula (5) are brought into contact is not particularly limited, but from the viewpoint of maintaining the oxidation resistance of the trisubstituted phosphine compound, which is the target of synthesis, an inert gas atmosphere is preferred, and a nitrogen or argon atmosphere is more preferred.

[0049] The temperature in the reaction step between the halogenated triisobutylene compound and the phosphine compound represented by formula (5) above is not particularly limited, but is, for example, -80 to 120°C, preferably 0 to 110°C, and more preferably room temperature to 105°C, from the viewpoint of shortening the reaction time. The temperature may also be in two stages, for example, -20 to -50°C followed by room temperature to 100°C. Here, room temperature is defined as 20 to 30°C.

[0050] The reaction time for the reaction step between the halide triisobutylene compound and the phosphine compound represented by formula (5) above is not particularly limited, but is, for example, 0.1 hours or more, and from the viewpoint of shortening the reaction time, is preferably 0.1 hours to 5 hours, and more preferably 0.5 hours to 4 hours.

[0051] The amount of the above-mentioned hydrocarbon lithium compound used is not particularly limited as long as it does not hinder the effects of the present invention, but is such that, for example, the amount of counteranions in the hydrocarbon lithium compound (which may also be called counteranions derived from the hydrocarbon lithium compound) is 0.5 to 5.0 equivalents, preferably 1.0 to 2.0 equivalents, per 1 equivalent of halogeno group contained in the halogenated triisobutylene compound represented by formula (4) above. Here, as the counteranion, if the hydrocarbon lithium compound is n-butyllithium, then nBu - In another embodiment of the present invention, the amount of the hydrocarbon lithium compound used is, for example, 0.5 to 5.0 moles, preferably 1.0 to 2.0 moles, relative to 1 mole of the halide triisobutylene compound represented by formula (4).

[0052] Phosphine compounds represented by formula (5), such as PHPh2 and PHCy2, are known to be unstable in air and quickly oxidize and degrade to phosphine oxides. Furthermore, if phosphine oxides are present in the reaction system, oxides of the alkyl group-containing phosphine compound represented by formula (1), which are difficult to separate from the alkyl group-containing phosphine compound represented by formula (1), are produced. Therefore, in order to obtain the alkyl group-containing phosphine compound represented by formula (1) in a pure form, it is important to prevent the generation of these phosphine oxide-derived byproducts. Here, by including a reaction step in which the alkyl group-containing phosphine compound represented by formula (1) is synthesized by reacting the compound represented by formula (4) and the phosphine compound represented by formula (5) in the presence of a hydrocarbon lithium compound, the generation of byproducts that are difficult to separate from the alkyl group-containing phosphine compound represented by formula (1) can be reduced, and preferably not generated at all, which is advantageous.

[0053] [Method for purifying alkyl group-containing phosphine compounds] According to one embodiment of the present invention, the method for producing an alkyl group-containing phosphine compound of the present invention may further include a step of purifying the alkyl group-containing phosphine compound synthesized above. The purification method is not particularly limited, and conventionally known purification methods can be applied.

[0054] According to a preferred embodiment of the present invention, the method for producing an alkyl-containing phosphine compound of the present invention may include a purification step (hereinafter also referred to as a mixing step) in which the alkyl-containing phosphine compound represented by formula (1) obtained in the above reaction step is mixed with a saturated hydrocarbon having 5 or fewer carbon atoms and / or a dielectric constant of 1.85 or less at 20°C.

[0055] According to a more preferred embodiment of the present invention, the mixing step further includes obtaining a mixture by the mixing and obtaining the supernatant of the mixture.

[0056] According to a more preferred embodiment of the present invention, the purification step further includes filtering the supernatant of the mixture obtained in the mixing step (hereinafter also referred to as the filtering step).

[0057] Examples of saturated hydrocarbons with 5 or fewer carbon atoms and / or a dielectric constant of 1.85 or less at 20°C in the mixing step include propane, n-butane, isobutane, n-pentane, isopentane, and neopentane, with n-pentane being preferred.

[0058] The amount of saturated hydrocarbon used in the mixing step is not particularly limited, but for example, it is 1 to 1000 times the mass of the alkyl group-containing phosphine compound represented by formula (1), and preferably 5 to 100 times the mass.

[0059] The temperature in the mixing step of the alkyl group-containing phosphine compound represented by formula (1) and the saturated hydrocarbon is not particularly limited, but is, for example, -80 to 30°C, preferably -60 to 20°C, and more preferably -50 to 10°C.

[0060] The mixing time in the mixing step of the alkyl group-containing phosphine compound represented by formula (1) and the saturated hydrocarbon is not particularly limited, but is, for example, 0.1 to 3 hours, preferably 0.2 to 2 hours, and more preferably 0.5 to 1 hour. Here, the mixing time includes both the mixing time and the standing time.

[0061] The above filtration process is not particularly limited, but examples include vacuum filtration of the supernatant (supernatant liquid) and natural filtration.

[0062] According to another preferred embodiment of the present invention, the purification step may be a purification step in which the alkyl-containing phosphine compound represented by formula (1) obtained in the reaction step is mixed with the saturated hydrocarbon, and then the alkyl-containing phosphine compound represented by formula (1) and the oxide of the alkyl-containing phosphine compound represented by formula (1) (hereinafter also referred to as the oxide of the compound of formula (1)) are separated. Here, the oxide of the compound of formula (1) is thought to be generated during the reaction step and / or post-processing when the process is scaled up, even if a hydrocarbon lithium compound is used in the synthesis of the compound of formula (1) as described above. This is thought to be partly due to the fact that it is difficult to create an oxygen-free atmosphere such as a glove box when scaling up, making oxygen entrainment unavoidable. The oxide is a compound in which an oxygen atom is bonded to the phosphorus atom of the compound of formula (1). If the compound of formula (1) is, for example, the compound of formula (1-1) below, then the oxide of the compound of formula (1) is the compound of formula (1-2) below. [ka] [ka]

[0063] When the alkyl-containing phosphine compound represented by formula (1) is mixed with the saturated hydrocarbon, an oxide of the compound of formula (1) precipitates, while the compound of formula (1) dissolves in the saturated hydrocarbon. Therefore, the supernatant of the mixture obtained by mixing and standing the compound of formula (1) with the saturated hydrocarbon contains the compound of formula (1). The compound of formula (1) in the supernatant of the mixture can then be concentrated by filtration.

[0064] The purity of the compound of formula (1) obtained by the purification method of the present invention using saturated hydrocarbons having 5 or fewer carbon atoms and / or a dielectric constant of 1.85 or less at 20°C is, for example, 92% or more, preferably 94% or more, and more preferably 95%. There is no particular upper limit, but 100% or less is preferred. The residual rate of the compound of formula (1) is 31 It can be measured by P-NMR. The remaining percentage (purity) (%) of the compound in formula (1) is calculated as the area percentage of the area of ​​the compound in formula (1) relative to the area of ​​the total detected peaks.

[0065] [Method for producing halogenated triisobutylene compounds] The method for producing the halide triisobutylene compound represented by formula (4) of the present invention is not particularly limited, but includes, for example, a step of synthesizing the halide triisobutylene compound represented by formula (4) by reacting a TIB-OH compound represented by formula (6) with a halogen-containing compound represented by a chemical formula selected from the group consisting of formulas (7) to (9). The above production method will be described in detail below.

[0066] (The compound represented by formula (6)) The compound represented by the following formula (6) is 2-(2,2-dimethylpropyl)-4,4-dimethyl-1-pentanol, and is hereafter also called triisobutylene hydroxide compound or TIB-OH compound. [ka] The compound represented by formula (6) above is not particularly limited, but can be synthesized, for example, in accordance with the method described in International Publication No. 2020 / 017141 (Patent Document 1).

[0067] (Halogen-containing compounds) The halogen-containing compounds used in the present invention are those of the following formulas (7) to (9): [ka] [ka] [ka] It is represented by a chemical formula selected from the group consisting of the following:

[0068] In equations (7), (8), and (9) above, R 3 This is equivalent to equation (4), and the same applies to preferred embodiments.

[0069] Preferred embodiments of the halogen-containing compound include the compound represented by formula (7) or the compound represented by formula (8), and more preferably the compound represented by formula (7).

[0070] The amount of halogen-containing compound used is not particularly limited as long as it does not hinder the effects of the present invention, but for example, 0.5 to 2.0 moles per mole of TIB-OH compound is used, and preferably 1.0 to 1.8 moles.

[0071] (solvent) The solvent used in the above reaction step is not particularly limited, but examples include halogenated solvents such as dichloromethane, chloroform, 1,2-dichloroethane, chlorobenzene, and o-dichlorobenzene; aromatic hydrocarbon solvents such as toluene, benzene, o-,m-,p-xylene, and mesitylene; aliphatic hydrocarbon solvents such as hexane and cyclohexane; ether solvents such as cyclopentyl methyl ether (hereinafter also referred to as CPME), tetrahydrofuran (hereinafter also referred to as THF), dioxane, diethyl ether, glyme, and diglyme; and fluorine-containing organic solvents such as hexafluorobenzene, m-bis(trifluoromethyl)benzene, p-bis(trifluoromethyl)benzene, α,α,α-trifluoromethylbenzene, and dichloropentafluoropropane. Among these, dichloromethane, toluene, CPME, and mixtures thereof are preferred from the viewpoint of shortening the reaction time, improving purification efficiency, and improving yield, with dichloromethane being more preferred. Preferred embodiments of the halogen-containing compound and solvent of the present invention include, when the halogen-containing compound is a compound represented by the chemical formula (7), dichloromethane and chloroform as solvents, more preferably dichloromethane; and when the halogen-containing compound is a compound represented by the chemical formula (8), toluene and CPME as solvents, more preferably toluene.

[0072] The amount of solvent used is not particularly limited, but for example, it is 0.01 to 10,000 parts by mass, preferably 0.03 to 6,000 parts by mass, per 100 parts by mass of the total of the TIB-OH compound and the halogen-containing compound. According to one embodiment of the present invention, when the halogen-containing compound is a compound represented by formula (7), the amount of solvent used is preferably 100 to 10,000 parts by mass, more preferably 400 to 6,000 parts by mass, and even more preferably 300 to 1,200 parts by mass or 4,000 to 6,000 parts by mass, per 100 parts by mass of the total of the TIB-OH compound and the halogen-containing compound. According to another embodiment of the present invention, when the halogen-containing compound is a compound represented by formula (8), the amount of solvent used is preferably 0.1 to 200 parts by mass, more preferably 1 to 70 parts by mass, per 100 parts by mass of the total of the TIB-OH compound and the halogen-containing compound.

[0073] (Reaction conditions) The temperature at which the TIB-OH compound reacts with the halogen-containing compound is not particularly limited, but for example, it is -30°C or higher, and from the viewpoint of shortening the reaction time, it is preferably -30 to 150°C. According to one embodiment of the present invention, when the halogen-containing compound is a compound represented by formula (7), the temperature at which the TIB-OH compound reacts with the halogen-containing compound is preferably -30 to 100°C, more preferably -20 to 50°C, and even more preferably room temperature or 35 to 50°C. Here, room temperature is defined as 20 to 30°C. According to another embodiment of the present invention, when the halogen-containing compound is a compound represented by formula (8), the temperature at which the TIB-OH compound reacts with the halogen-containing compound is preferably 80 to 150°C, more preferably 90 to 100°C.

[0074] The reaction time for the TIB-OH compound and the halogen-containing compound is not particularly limited, but is, for example, 0.1 hours or more, preferably 0.5 hours to 3 days, and more preferably 1 hour to 2 days, from the viewpoint of shortening the reaction time. According to one embodiment of the present invention, when the halogen-containing compound is a compound represented by formula (7), the temperature for reacting the TIB-OH compound and the halogen-containing compound is preferably 0.1 hours to 3 days, more preferably 1 hour to 2 days, and even more preferably 0.5 to 4 hours or 1 to 2 days. According to another embodiment of the present invention, when the halogen-containing compound is a compound represented by formula (8), the temperature for reacting the TIB-OH compound and the halogen-containing compound is preferably 0.5 hours to 4 hours, and more preferably 1 hour to 3 hours.

[0075] According to a preferred embodiment of the present invention, in the method for producing a halogenated triisobutylene compound represented by formula (4) of the present invention, when the halogen-containing compound is the compound represented by formula (7), the solvent used in the reaction step is dichloromethane or chloroform, preferably dichloromethane, the reaction temperature between the TIB-OH compound and the halogen-containing compound is 35 to 50°C, the reaction time is 0.5 to 4 hours, and the amount of solvent used is 300 to 1200 parts by mass per 100 parts by mass of the total of the TIB-OH compound and the halogen-containing compound. In particular, when the reaction temperature is the above temperature, it is possible to reduce the amount of solvent and shorten the reaction time.

[0076] According to one embodiment of the present invention, when the halogen-containing compound is a compound represented by formula (7), it is preferable to further include triphenylphosphine when reacting the TIB-OH compound with the halogen-containing compound. The amount of triphenylphosphine used is not particularly limited as long as it does not hinder the effects of the present invention, but for example, it is 0.5 to 2.0 moles, preferably 1.0 to 1.8 moles, per mole of the TIB-OH compound.

[0077] According to another embodiment of the present invention, when the halogen-containing compound is a compound represented by formula (8), it is preferable to further include pyridine when reacting the TIB-OH compound with the halogen-containing compound. The amount of pyridine used is not particularly limited as long as it does not hinder the effects of the present invention, but for example, it is 0.5 to 2.0 moles, preferably 1.0 to 1.8 moles, per mole of the TIB-OH compound.

[0078] According to another embodiment of the present invention, when the halogen-containing compound is a compound represented by formula (9), it is preferable to further include iodine when reacting the TIB-OH compound with the halogen-containing compound. The amount of iodine used is not particularly limited as long as it does not hinder the effects of the present invention, but for example, it is 0.5 to 2.0 moles, preferably 1.0 to 1.8 moles, per mole of the TIB-OH compound.

[0079] [Method for purifying halogenated triisobutylene compounds] According to one embodiment of the present invention, the method for producing a halide triisobutylene compound of the present invention may include a step of further purifying the halide triisobutylene compound synthesized above. The purification method is not particularly limited, and conventionally known purification methods can be applied. Examples of purification methods include filtration (e.g., silica gel filtration), preparative chromatography, vacuum filtration, recrystallization, liquid-liquid separation, solvent removal, solvent washing, and ultrasonic cleaning, and preferably filtration (e.g., silica gel filtration) or preparative chromatography.

[0080] The column used in the above chromatography method is not particularly limited, but a normal-phase column is preferred. Examples of conditions for the preparative chromatography method include the following: Developing solvent: Ethyl acetate / hexane = 10 / 90 (vol.%) mixed solvent Column: Normal-phase silica gel (preferably a universal column, size L, manufactured by Yamazen Corporation) Equipment: Smart Flash AKROS (manufactured by Yamazen Co., Ltd.) Temperature: room temperature Detection wavelength: 254nm

[0081] According to one embodiment of the invention, when the halogen-containing compound is a compound represented by formula (7), filtration (e.g., silica gel filtration) is preferred as a method for purifying the halogenated triisobutylene compound synthesized above. For example, by distilling off a polar solvent such as dichloromethane, which is the solvent used in the reaction step, after the reaction is complete, and adding a nonpolar solvent such as hexane, the difference in solubility between the target halogenated triisobutylene compound and the by-products can be utilized. By using a nonpolar solvent, by-products that are insoluble in the nonpolar solvent can be removed by silica gel filtration alone, and the target halogenated triisobutylene compound can be isolated.

[0082] According to another embodiment of the present invention, when the halogen-containing compound is a compound represented by formula (8), preparative chromatography is preferred as the purification method for the halogenated triisobutylene compound synthesized above. [Examples]

[0083] The present invention will be specifically described below with reference to examples, but the present invention is not limited to these examples.

[0084] The structural analysis of the compound represented by formula (1) obtained by the following method was performed under the following conditions: 1 H-NMR measurement, 13 CNMR measurement, and 31 P-NMR measurements were performed. [ 1 H-NMR conditions] • NMR measurement equipment: AVANCE NEO spectrometer, Ascend600 magnet (manufactured by BRUKER JAPAN) · 1 H-NMR measurement conditions: Frequency 600.03 MHz, CD2Cl2 solvent • Measurement time: Approximately 30 minutes [ 13 C-NMR conditions] • NMR measurement equipment: AVANCE NEO spectrometer, Ascend600 magnet (manufactured by BRUKER JAPAN) ·13 ¹ • Measurement time: Approximately 60 minutes [ 31 P-NMR conditions] • NMR measurement equipment: AVANCE NEO spectrometer, Ascend600 magnet (manufactured by BRUKER JAPAN) · 31 P-NMR measurement conditions: Frequency 242.97 MHz, CD2Cl2 solvent • Measurement time: Approximately 30 minutes

[0085] Structural analysis of the compound represented by formula (4-1) and the compound represented by formula (6) obtained by the following method was performed under the following conditions: 1 H-NMR measurement and 13 1C-NMR measurements were performed. [ 1 H-NMR conditions] • NMR measurement equipment: AVANCE NEO spectrometer, Ascend600 magnet (manufactured by BRUKER JAPAN) · 1 H-NMR measurement conditions: Frequency 600.03 MHz, CDCl3 solvent • Measurement time: Approximately 30 minutes [ 13 C-NMR conditions] • NMR measurement equipment: AVANCE NEO spectrometer, Ascend600 magnet (manufactured by BRUKER JAPAN) · 13 1C-NMR measurement conditions: frequency 150.89 MHz, CDCl3 solvent • Measurement time: Approximately 60 minutes

[0086] [Example 1] <Preparation of the compound represented by formula (6) (TIB-OH compound)> The compound represented by formula (6) was synthesized, referring to the description in Synthesis Example 1 of International Publication No. 2020 / 017141.

[0087] Specifically, the following procedure was followed. In a reaction vessel under a nitrogen stream, 10.00 g (59.4 mmol) of triisobutylene starting material (manufactured by TCI) containing the compound represented by formula (11-1) below (sometimes abbreviated as "compound (11-1)") and the compound represented by formula (11-2) below (sometimes abbreviated as "compound (11-2)") was added and stirred with 60 mL of anhydrous THF. 9-borabicyclo[3.3.1]nonane (9-BBN) (89.1 mmol) was then added dropwise at 0°C under ice cooling, and after 30 minutes, the temperature was raised to 35°C. (Reaction formula I). [ka]

[0088] The reaction mixture was cooled again on ice, and 79 mL (238 mmol) of 3M NaOHaq was added dropwise. Subsequently, 80 mL of 31% by mass H2O2 solution was added dropwise, and the reaction was allowed to proceed overnight. (Reaction Equation II). [ka]

[0089] After separating the organic and aqueous layers, K2CO3 was added to the organic layer to separate the water remaining in the organic solvent. After separating the aqueous layer, the same procedure was repeated two more times. The aqueous layers were combined and extracted three times with ethyl acetate. Finally, the organic layers were combined and dried over MgSO4. After filtering out the drying agent, the solvent was removed by vacuum distillation to obtain 18.22 g of a colorless, transparent, oily crude product. Unreacted internal olefin structures were removed during vacuum distillation.

[0090] The crude product was roughly purified by vacuum distillation (bath temperature: 100°C, top temperature: 45°C, vacuum: 1.3kPa), and then purified by silica gel column (Silicagel: 92.8g, eluent: Heptane / Ethyl acetate = 7 / 1) to obtain a white solid TIB-OH compound. The yield was 2.74g (14.7 mmol), with a yield of 25%.

[0091] <The compound represented by formula (6) (TIB-OH compound) 1 H-NMR measurement and13 C-NMR measurement> The obtained TIB-OH compound 1 H-NMR measurement and 13 1C NMR measurements were performed on the TIB-OH compound. 1 The H-NMR spectrum is shown in Figure 1. 13 The 1C-NMR spectrum is shown in Figure 2. Also, the following: 1 H-NMR spectral data and 13 1C-NMR spectral data was obtained. Spectral analysis confirmed that the compound was represented by formula (6). 1 H-NMR(600.03MHz,CDCl3): δ 0.93(s,18H), 1.14-1.39(d,4H), 1.64(m,1H), 3.52(d,2H), 7.26(s,OH) 13 C-NMR(150.89MHz,CDCl3): δ 67.9, 47.5, 33.9, 31.2, 30.3

[0092] <Preparation of the compound represented by formula (4-1) (TIB-Br compound) - 1> [Example 2] In a 25 mL Schlenk flask, the compound represented by formula (6) obtained in Example 1 (TIB-OH compound) (1.24 g, 6.65 mmol) and 13.3 mL of dichloromethane were added and stirred while cooling with ice water. Then, N-bromosuccinimide (NBS) (1.72 g, 9.98 mmol) was added and dissolved. Triphenylphosphine (PPh3) (2.61 g, 9.98 mmol) was added to the resulting solution and the mixture was stirred at 40°C (under reflux) for 3 hours to allow the reaction to proceed (reaction formula III). After the reaction, the dichloromethane solvent was removed by distillation, and after adding hexane, the mixture was purified by filtration using a small amount of silica gel. After distillation of the hexane solvent, the target TIB-Br compound could be isolated in an amount of 1.40 g (85%). The results are shown in Table 1. [ka]

[0093]

Table 1

[0094] The isolated TIB-Br compound was assigned its chemical structure by NMR measurement. The 1 1H-NMR spectrum of the obtained TIB-Br compound is shown in Fig. 3, 13 and the 13C-NMR spectrum is shown in Fig. 4. Also, the following 1 1H-NMR spectrum data and 13 13C-NMR spectrum data were obtained. As a result of spectral analysis, it was confirmed that the compound was the one represented by formula (4-1). 1 1H-NMR(600.03MHz,CDCl3): δ 0.94(s,18H),1.23-1.44 (dd,4H),1.85(m,1H),3.47(d,2H) 13 13C-NMR(150.89MHz,CDCl3): δ 49.1, 44.1, 33.2, 31.1, 30.2

[0095] <Production of the compound represented by formula (1) (alkyl group-containing phosphine compound; TIB-PPh2 compound) on a 5 g scale and examination of purification using pentane><000​​​​After the reaction, Na2SO4-10H2O was added until the color of the reaction solution disappeared. Na2SO4-10H2O was removed by silica gel filtration (specifically, the reaction solution with the disappeared color was filtered on filter paper thinly spread with silica gel), and the solvent was removed to obtain an oily TIB-PPh2 crude product. The 31 P-NMR purity of the TIB-PPh2 compound in this crude product was 90% (Figure 5). The purity (%) of the above compound was calculated as the area percentage of the area of the above compound with respect to the area of all detected peaks. In Figure 5, a is derived from the TIB-PPh2 compound, and b is derived from the oxide of the TIB-PPh2 compound (the compound of formula (1-2)) 31 P-NMR assigned peaks are shown.

[0096] To the TIB-PPh2 crude product obtained above, 10 times the mass of n-pentane was added and mixed, then left standing and cooled at -50 °C for 30 minutes. Then, the supernatant (supernatant) was filtered under reduced pressure and the solvent was removed to obtain the TIB-PPh2 compound (5.97 g, isolated yield 89%, colorless oil).

Chemical formula

[0097] The chemical structure of the isolated TIB-PPh2 compound was assigned by NMR measurement. The 1 1H-NMR spectrum of the obtained TIB-PPh2 compound is shown in Figure 6, 13 13C-NMR spectrum is shown in Figure 7, 31 31P-NMR spectrum is shown in Figure 8. In Figure 8, a is derived from the TIB-PPh2 compound, and b is derived from the oxide of the TIB-PPh2 compound (the compound of formula (1-2)) 31 31P-NMR assigned peaks are shown. Also, the following 1 1H-NMR spectrum data, 13 13C-NMR spectrum data and 31 31P-NMR spectrum data were obtained. As a result of spectral analysis, it was confirmed that it is the compound represented by formula (1-1). Furthermore, the 31The P-NMR purity was 96%. Therefore, it was confirmed that the purity of the TIB-PPh2 compound was improved by purification using pentane. 1 H-NMR(600.03MHz,CD2Cl2): δ 0.82(s,18H),1.2-1.5(m,4H),2.07(d,2H), 7.30-7.44 (m,10H) 13 C-NMR(150.89MHz,CD2Cl2): δ 139.7, 133.1, 128.3, 128.2, 51.5, 38.5, 31.3, 30.3, 28.2 31 P-NMR(242.97MHz,CD2Cl2): δ -19.3

Claims

1. Alkyl-containing phosphine compounds represented by the following formula (1): 【Chemistry 1】 (In equation (1), A is the same as in equations (2) and (3) below): 【Chemistry 2】 (In equation (2), the wavy lines indicate connections with P.) 【Transformation 3】 (In equation (3), the wavy lines indicate connections with P.) This shows an alkyl group represented by a chemical formula selected from the following: In formula (1), R １ , R ２ These independently represent an optionally substituted hydrocarbon group or an optionally substituted pyridyl group. In equation (1), n1 and n2 are independent integers between 0 and 2, and the sum of n1 and n2 is between 0 and 2. A method for manufacturing, The following formula (4): 【Chemistry 4】 (In formula (4), R ３ (This represents one halogen atom selected from the group consisting of chlorine, bromine, and iodine atoms.) Compounds represented by and Formula (5) below: 【Transformation 5】 (In formula (5), R １ , R ２ n1 and n2 are equivalent to those in equation (1). A reaction step to synthesize an alkyl group-containing phosphine compound represented by formula (1) by reacting it with a phosphine compound represented by formula (1), and A purification step comprising mixing the alkyl-containing phosphine compound represented by formula (1) obtained in the above reaction step with a saturated hydrocarbon having 5 or fewer carbon atoms. A method for producing alkyl group-containing phosphine compounds.

2. R １ , R ２ The manufacturing method according to claim 1, wherein the group is independently selected from the group consisting of an optionally substituted alkyl group, an optionally substituted phenyl group, an optionally substituted alicyclic hydrocarbon group, and an optionally substituted adamantyl group.

3. The manufacturing method according to claim 1 or 2, wherein a hydrocarbon lithium compound is further present in the reaction step.

4. The manufacturing method according to claim 1 or 2, wherein the purification step further comprises allowing the mixture obtained by the mixing to stand and filtering the supernatant of the resulting mixture.

5. The manufacturing method according to claim 1 or 2, wherein the mixing temperature in the purification step is -80 to 30°C.

6. The manufacturing method according to claim 1 or 2, wherein the mixing time in the purification step is 0.1 to 3 hours.

7. The manufacturing method according to claim 1 or 2, wherein an aprotic polar solvent is further present in the reaction step.

8. The manufacturing method according to claim 7, further comprising the step of treating a mixture containing the alkyl group-containing phosphine compound represented by formula (1) obtained in the reaction step and an aprotic polar solvent with a drying agent after the reaction step and before the purification step.

9. The manufacturing method according to claim 8, further comprising a step of removing the aprotic polar solvent in the reaction step after the drying step and before the purification step.

Images