JP5402286B2 - Method for producing phosphorus compound and method for producing allyl compound derivative - Google Patents

Description

  The present invention relates to a method for producing a phosphorus compound, and more particularly to a method for easily producing a phosphoramidite compound. The present invention also relates to a method for producing an allyl compound derivative in the presence of a transition metal complex having a phosphorus compound.

Phosphoramidite compounds, which are a type of phosphorus compound, are not only substances that exhibit various physiological activities because they have a characteristic skeleton, but recently they have been applied to various catalytic reactions as ligands for homogeneous catalysts. Yes. As a typical catalytic reaction, for example, there is a reaction for producing allylamines using allyl carbonate.
As a method for obtaining such a phosphoramidite compound, for example, binaphthol is added to and reacted with a toluene solution containing phosphorus trichloride and triethylamine, and the obtained reaction solution is filtered and purified by column chromatography. A method for obtaining the target product (Non-patent Document 1), or by reacting binaphthol, trisdimethylaminophosphine and ammonium chloride, adding diethyl ether to the reaction solution, and purifying by recrystallization to obtain the target product. There is a method (Non-Patent Document 2).

However, these methods have a problem that the operation for synthesizing the target phosphoramidite compound becomes complicated, so that it is difficult to apply to a large amount on an industrial scale.
Patent Document 1 describes a method for synthesizing and purifying a bidentate or tridentate phosphoramidite compound containing two or more phosphorus atoms. As a solvent used for recrystallization, dichloromethane is used. Thus, it is not an industrially advantageous method because a halogenous and highly toxic solvent is used.

JP 2006-257081 A

Tetrahedron 56 (2000), 2865-2878 Tetrahedron Asymmetry, 5 (1994), 699-708,

  In view of the above problems, an object of the present invention is to provide a method for synthesizing a phosphoramidite compound, which is a kind of phosphorus compound, more easily and safely, and industrially advantageous. To do.

As a result of intensive studies to solve the above-mentioned problems, the present inventors have mixed phosphorus halide compounds, phenols, and bases in an organic solvent, and then added amines to the obtained mixed solution. Then, a phosphorus compound represented by the general formula (I) is generated, and the reaction solution containing the phosphorus compound represented by the general formula (I) is represented by the general formula (I) using a poor solvent. The present inventors have found a method for easily synthesizing a target product with high purity without requiring complicated operations such as column chromatography and recrystallization. Furthermore, the present inventors have found that the phosphoramidite compound synthesized by this method is a useful catalyst component for the isomerization reaction of an allyl compound, thereby completing the present invention.

That is, the gist of the present invention resides in the following [1] to [ 8 ].
[1] A method for producing a phosphorus compound represented by the following general formula (I), comprising the following steps (a) to (c):
(A) A phosphorus halide compound, a phenol represented by the following general formula (III) , and a base are reacted in an organic solvent to produce a halogenated phosphoryl compound, and the produced phosphoryl halide Obtaining a solution containing the compound,
(B) A solution containing the halogenated phosphoryl compound obtained in the step (a) is mixed with an amine represented by the following general formula (II) to obtain a phosphorus compound represented by the following general formula (I). Producing a reaction solution containing the phosphorus compound represented by the general formula (I) produced,
(C) The process of collect | recovering the phosphorus compounds represented by the following general formula (I) from a reaction liquid obtained from a process (b) using a poor solvent.

(In the general formula (I), R _a and R _b are each independently a hydrogen atom, alkyl group, aryl group, alkoxy group, aryloxy group, acyl group, acyloxy group, hydroxy group, amino group, alkylthio group, and These groups are groups selected from the group consisting of arylthio groups, and these groups may further have a substituent, Ar _{1 to} Ar ₄ are each independently an aryl group which may have a substituent. Yes, Ar ₁ and Ar ₂ , and Ar ₃ and Ar ₄ may be connected to each other to form an aromatic ring containing the bonded carbon, and the formed aromatic ring may further have a substituent. . Moreover, Q is an organic group which may have a substituent group. Here, n is an integer of 1 or more.)

(In general formula (II), Ra and Rb are each independently a hydrogen atom, alkyl group, aryl group, alkoxy group, aryloxy group, acyl group, acyloxy group, hydroxy group, amino group, alkylthio group, and arylthio group. And these groups may further have a substituent, and Q is a divalent organic group which may have a substituent, where n is a group selected from the group consisting of It is an integer greater than or equal to 1. )

(In the general formula (III), R _{1 to} R ₆ are each independently a hydrogen atom, an alkyl group, an aryl group, an alkoxy group, an aryloxy group, an acyl group, an acyloxy group, a hydroxy group, an amino group, an alkylthio group, and A group selected from the group consisting of an arylthio group, which may further have a substituent, and R _{1 to} R ₆ may be linked to form a ring; May further have a substituent.)
[2] The production method of [1], wherein the phosphorus halide compound is phosphorus tribromide.
[3] The method according to [1] or [2], wherein the poor solvent is an alcohol and / or a nitrile.
[ 4 ] The method according to any one of [1] to [ 3 ], wherein the base is a trialkylamine.
[ 5 ] The method according to any one of [1] to [ 4 ], wherein the organic solvent is an aromatic hydrocarbon and / or an ether.
[ 6 ] In any one of [1] to [ 5 ], the concentration of the phosphorus compound represented by the general formula (I) in the reaction solution in the step (c) is 1 to 50% by weight. The manufacturing method as described.
[ 7 ] In the step (a), after previously mixing a halogenated phosphorus compound and a base in the organic solvent, the phenols are added in an amount of 20% or less based on the amount of the organic solvent per minute. It adds, The manufacturing method of the phosphorus compound in any one of [1]-[ 6 ] characterized by the above-mentioned.
[ 8 ] In the presence of a phosphorus compound obtained by the production method of any one of [1] to [ 7 ] and a catalyst containing a transition metal of Group 8 to Group 10 of the periodic table, it is represented by the following general formula (1). A method for producing an isomerized compound represented by the following general formula (2) by isomerizing an allyl compound derivative.

(In General Formula (1), R _{A to} R _E are each independently a hydrogen atom, alkyl group, aryl group, alkoxy group, aryloxy group, acyl group, acyloxy group, hydroxy group, amino group, alkylthio group, and These groups are groups selected from the group consisting of arylthio groups, and these groups may further have a substituent, X represents an electron withdrawing group, and in the general formula (2), R _{A to} R _E and X is synonymous with R _{A to} R _E and X in the general formula (1), provided that the allyl compound derivative represented by the general formula (1) and the isomerization represented by the general formula (2). (A compound does not represent the same compound.)

  INDUSTRIAL APPLICABILITY According to the present invention, it is possible to provide an industrially advantageous method for synthesizing a phosphoramidite compound that makes it possible to more easily synthesize a phosphoramidite compound.

The description of the constituent requirements described below is an example (representative example) of an embodiment of the present invention, and the present invention is not limited to these contents. The details will be described below.
In the method for producing the phosphorus compound of the present invention, in producing the phosphorus compound represented by the general formula (I), (a) a halogenated phosphorus compound, a phenol and a base are reacted in an organic solvent, A step of producing a phosphorylated compound and obtaining a solution containing the produced halogenated phosphoryl compound, (b) adding amines to the solution containing the halogenated phosphoryl compound obtained in step (a), A step of producing a phosphorus compound represented by the general formula (I) and obtaining a reaction solution containing the produced phosphorus compound represented by the general formula (I), (c) from the reaction solution obtained from the step (b) In addition, it is not always necessary to perform column chromatography or recrystallization by passing through the three steps of obtaining a phosphoramidite compound using a poor solvent, and phosphoramidite can be easily obtained. Characterized in that to obtain a site compound as a precipitate. In the method for producing the phosphorus compound of the present invention, the phenols used in step (a) may be monophenols or biphenols, and each may have a substituent. The substituent that the phenols may have is not particularly limited as long as it does not inhibit the effect of the present invention, and examples thereof include an alkyl group, an alkoxy group, an aryl group, an aryloxy group, an amino group, and a cyano group. Group, ester group and the like. The alkyl group also includes a branched alkyl group and a cycloalkyl group. The aryl group includes a heterocyclic aryl group that includes other elements such as nitrogen, oxygen, and sulfur in addition to carbon to form a ring. Is included. A substituent having a molecular weight of about 200 or less is usually used. Among these, biphenols are preferable, and among the biphenols, biphenols in which aromatic rings are directly bonded without interposing a substituent therebetween are preferable. Specifically, preferred are phenols represented by the structure of the following general formula (III).

(In the general formula (III), R _{1 to} R ₆ are each independently a hydrogen atom, an alkyl group, an aryl group, an alkoxy group, an aryloxy group, an acyl group, an acyloxy group, a hydroxy group, an amino group, an alkylthio group, and A group selected from the group consisting of an arylthio group, which may further have a substituent, and R _{1 to} R ₆ may be linked to form a ring; May further have a substituent.)
Moreover, among general formula (III), phenols in which R _{1 to} R ₆ in the formula are each independently any one of a hydrogen atom, an alkyl group, and an alkoxy group are preferable. At this time, the alkyl group may be linear or branched. Although carbon number of an alkyl group is not specifically limited, Usually, C1-C20 is preferable, Preferably it is C1-C10, Most preferably, it is C1-C4. Specifically, a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, and a tertiary butyl group, and an alkoxy group is a methoxy group, an ethoxy group, a propoxy group, an isopropyloxy group, a butoxy group, and an isobutoxy group. , Is a tertiary butoxy group.

In addition, the alkoxy group at this time may be linear or branched in the portion of the alkyl structure in the alkoxy group. Moreover, although carbon number is not specifically limited, Usually, it is C1-C20, Preferably it is C1-C10, Most preferably, it is C1-C4. Furthermore, in general formula (I), R ₁ and R ₆ are hydrogen atoms, R ₃ and R ₄ are methyl groups or hydrogen atoms, and R ₂ and R ₅ are methoxy groups or tertiary butyl groups. Is most preferred.

  In the method for producing the phosphorus compound of the present invention, the halogenated phosphorus compound used in step (a) may be any compound as long as one or more halogen atoms are bonded to the three bonds of the phosphorus atom. And those in which a halogen atom is bonded to all three bonds of the phosphorus atom. In this case, the halogen atoms may be the same or different, but it is preferable that all of the halogen atoms are the same for ease of reaction. Specifically, phosphorous trichloride, phosphorous trifluoride, and phosphorous tribromide are preferable, and phosphorous tribromide is particularly preferable because of its high reactivity and ease of handling.

  In the method for producing the phosphorus compound of the present invention, the base used in step (a) may be either an inorganic base or an organic base, and is not particularly limited. Inorganic bases such as potassium hydroxide, lithium hydroxide, potassium phosphate, sodium bicarbonate; trialkylamines such as trimethylamine, triethylamine, tripropylamine, tributylamine, trihexylamine, trioctylamine, tridecylamine, tridodecylamine Examples include amines; monoalkylamines such as methylamine, ethylamine, butylamine, and octylamine; and organic bases such as dialkylamines such as dimethylamine, diethylamine, dibutylamine, dioctylamine, and diazabicycloundecene. Among these bases, organic bases are preferable, and trialkylamines are more preferable. Specifically, trimethylamine, triethylamine, tripropylamine, tributylamine, trihexylamine, and trioctylamine are preferable, and trimethylamine, triethylamine, tripropylamine, and tributylamine are particularly preferable.

  The organic solvent is not particularly limited, and various solvents such as hydrocarbons, esters, ethers, and aromatic hydrocarbons can be used. Of these, one type may be used, or two or more types may be used in combination. Preferred are ethers and aromatic hydrocarbons. Specifically, toluene, benzene, xylene, tetrahydrofuran, diethyl ether, dibutyl ether, dioxane, triglyme, tetraglyme and the like are preferable. Particularly preferred are toluene, xylene, tetrahydrofuran and dioxane.

  In the method for producing the phosphorus compound of the present invention, the temperature of step (a) is preferably in the range of −100 ° C. to 300 ° C., more preferably −20 ° C. or more and 150 ° C. or less. More preferably, it is 0 degreeC or more and 100 degrees C or less. As the temperature increases, the phosphorus compound tends to decompose, and as the temperature decreases, the reaction tends to require a longer time. The reaction time is in the range of 1 minute to 200 hours, preferably 10 minutes to 48 hours. More preferably, it is the range of 30 minutes or more and 24 hours or less. As the reaction time becomes longer, impurities derived from decomposition of the phosphorus compound tend to increase, and as the reaction time becomes shorter, the raw material residue tends to increase.

  In the method for producing the phosphorus compound of the present invention, the concentration of the phenols in the organic solvent in the step (a) is 0.1% by weight to 90% by weight, preferably 1% by weight to 50% by weight. More preferably, it is 2 to 30% by weight. As this concentration increases, solid components tend to precipitate and stirring becomes difficult, and as the concentration decreases, the progress of the reaction tends to slow.

  Further, the amount of the halogenated phosphorus compound relative to the phenols in the organic solvent is 0.01 to 100 mole equivalent, preferably 0.1 to 10 mole equivalent, more preferably 0.5. ~ 3 molar equivalents. The larger the amount, the more the halogenated phosphorus compound remains and the post-treatment tends to be difficult. The smaller the amount, the more the phenol remains and the post-treatment tends to be difficult and the cost of the starting phenol tends to increase. In addition, the amount of the base relative to the phenols in the organic solvent is 0.01 to 100 mole equivalent, preferably 0.1 to 10 mole equivalent, and more preferably 0.5 to 3 mole equivalent. Molar equivalents. As this amount increases, the cost increases due to an increase in the amount of base used and the decomposition of the phosphorus halide compound tends to become remarkable, and as the amount decreases, the reaction rate and the conversion rate of the phosphorus halide compound tend to decrease.

  In the step (a) of the present invention, in reacting a phosphorus halide compound, phenols and a base in an organic solvent, the phosphorus halide compound and the base are previously mixed in the organic solvent, and the mixture It is preferable to add phenols to the mixture. Furthermore, when adding phenols, it is preferable to add at a dropping rate of 20% or less per minute with respect to the amount of organic solvent, more preferably a dropping rate of 10% or less per minute. Most preferably, the dropping rate is 5% or less per minute. Thus, by slowly dropping and reacting the phenols, the liquid temperature of the organic solvent can be maintained, and the diffusion promotion of the phenols in the organic solvent can be improved. The method for controlling the dropping rate of phenols is not particularly limited, but can be controlled using a dropping funnel, a pump, or the like.

  In the method for producing the phosphorus compound of the present invention, the halogenated phosphoryl compound produced in the step (a) is a production intermediate of the phosphorus compound represented by the general formula (I). The halogenated phosphoryl compound to be produced is determined by the type of the halogenated phosphorus compound, phenols, and base used in step (a). The amount of the halogenated phosphoryl compound in the solution is not particularly limited, but is usually 0.01 to 50% by weight, preferably 0.1 to 20% by weight, and more preferably 0.5 to 10% by weight. As the amount increases, the halogenated phosphoryl compound tends to precipitate and the subsequent reaction does not proceed. As the amount decreases, the productivity of the reaction tends to decrease.

In the method for producing the phosphorus compound of the present invention, the solution containing the halogenated phosphoryl compound in step (a) may contain a compound other than the produced halogenated phosphoryl compound. Examples thereof include unreacted phosphorus halide compounds, unreacted phenols, and unreacted bases. Moreover, decomposition products generated by decomposition of these compounds, and by-products may also be included. As by-products, there are mainly water-soluble by-products such as ammonium halide salts. These degradation products and by-products may be separated and removed as necessary when the solution is transferred to step (b). Before the solution is transferred to step (b), the amount of the organic solvent, the unreacted phosphorus halide compound, the unreacted phenols, the unreacted base, and the generated halogenated phosphoryl compound in the solution is adjusted. May be.

In the method for producing the phosphorus compound of the present invention, the amines used in step (b) may be either bidentate or multidentate (refers to tridentate or higher, hereinafter the same) amine, It may have a substituent.
The substituent which the amines may have is not particularly limited as long as it does not inhibit the effect of the present invention, and examples thereof include an alkyl group, an alkoxy group, an aryl group, an aryloxy group, an amino group, and a cyano group. Groups, ester groups, hydroxy groups, halogen atoms and the like. A substituent having a molecular weight of about 200 or less is usually used.

  Of these amines, bidentate amines are preferred. This is because a bidentate phosphorus compound can be synthesized. Further, among the bidentate amines, amines represented by the general formula (II) are preferable.

(In the general formula (II), R _a and R _b are each independently a hydrogen atom, alkyl group, aryl group, alkoxy group, aryloxy group, acyl group, acyloxy group, hydroxy group, amino group, alkylthio group, and A group selected from the group consisting of arylthio groups, these groups may further have a substituent, and Q is a divalent organic group which may have a substituent, provided that n is an integer of 1 or more.)
Specifically, diaminomethane, diaminoethane, diaminopropane, diaminobutane, diaminopentane, diaminohexane, N-methyl-diaminomethane, N-methyl-diaminoethane, N-methyl-diaminopropane, N-methyl-diaminobutane N-methyl-diaminopentane, N-methyl-diaminohexane, N, N′-dimethylaminomethane, N, N′-dimethylaminoethane, N, N′-dimethylaminopropane, N, N′-dimethylaminobutane N, N'-dimethylaminopentane, N-ethyl-diaminomethane, N-ethyl-diaminoethane, N-ethyl-diaminopropane, N-ethyl-diaminobutane, N-ethyl-diaminopentane, N-ethyl-diamino Hexane, N, N′-diethylaminomethane, N, N′-diethyl Aminoethane, N, N′-diethylaminopropane, N, N′-diethylaminobutane, N, N′-diethylaminopentane, piperidine, etc. Among them, diaminoethane, diaminopropane, diaminobutane, diaminopentane, N-methyl are preferable. -Diaminoethane, N-methyl-diaminopropane, N-methyl-diaminobutane, N, N'-dimethylaminoethane, N, N'-dimethylaminopropane, N, N'-dimethylaminobutane.

  In the method for producing the phosphorus compound of the present invention, the temperature of step (b) is preferably in the range of −100 ° C. to 300 ° C., more preferably −20 ° C. or more and 150 ° C. or less. More preferably, it is 0 degreeC or more and 100 degrees C or less. As the temperature increases, the phosphorus compound tends to decompose, and as the temperature decreases, the reaction tends to require a longer time. The reaction time ranges from 1 minute to 200 hours, preferably from 10 minutes to 48 hours. More preferably, it is the range of 30 minutes or more and 24 hours or less. As the reaction time becomes longer, impurities derived from decomposition of the phosphorus compound tend to increase, and as the reaction time becomes shorter, the raw material residue tends to increase.

  In the method for producing the phosphorus compound of the present invention, before sending the reaction solution obtained in step (b) to step (c), the reaction solution obtained in step (b) is converted into the reaction solution using a solvent. It is preferable to go through a step of extracting and removing water-soluble by-products such as ammonium halide contained therein. The solvent used for the extraction is not particularly limited, but usually an aromatic hydrocarbon, ether, ester or the like, which is an organic solvent insoluble in water, is used. Of these, toluene, xylene, benzene, ethyl acetate, and diethyl ether are preferable because they are insoluble in water and inexpensive. By going through the extraction step, there is a merit that by-products dissolved in water can be easily removed, and halides in which corrosion concerns exist can be removed.

  Moreover, in the method for producing the phosphorus compound of the present invention, before sending the reaction solution obtained in step (b) to step (c), the reaction solution obtained in step (b) is filtered to obtain impurities and by-products. It is preferable to go through a step of separating the. Although it does not specifically limit as a method to filter, Usually, it filters using a filter paper, a filter cloth, a filter, etc. from a viewpoint of cost and simplicity. By going through the filtration step, there is an advantage that solid impurities and by-products that are insoluble in the organic solvent can be easily removed.

  In the method for producing the phosphorus compound of the present invention, the poor solvent used in the step (c) is not particularly limited as long as the solubility with the phosphorus compound is low, and various solvents can be used. Alcohols, hydrocarbons, and nitriles are preferable, and alcohols, hydrocarbons, and nitriles having 1 to 8 carbon atoms are particularly preferable. Specifically, methanol, ethanol, propanol, isopropanol, butanol, isobutanol, tertiary butanol, pentanol, hexanol, octanol, pentane, hexane, heptane, octane, acetonitrile, etc., particularly methanol, ethanol, propanol, Isopropanol and acetonitrile are preferred. When the poor solvent is mixed with the reaction solution obtained in the step (b), it may be stirred or not stirred. Thereby, a phosphoramidite compound can be precipitated as a solid content. The precipitated phosphoramidite compound is separated from the filtrate by filtration or the like, and can be recovered as a highly purified phosphoramidite compound after drying.

  The temperature at the time of carrying out this step is preferably in the range of -100 ° C to 100 ° C, more preferably -20 ° C or higher and 80 ° C or lower. More preferably, it is 0 degreeC or more and 60 degrees C or less. The higher the temperature, the more the desired phosphoramidite compound dissolves in the filtrate, and the yield of the phosphoramidite compound tends to decrease. The lower the temperature, the more the impurities to be separated do not dissolve in the filtrate. It tends to be difficult to obtain a phosphoramidite compound having difficulty in separation and high purity. The standing time until the phosphoramidite compound is obtained after mixing the poor solvent in the step (c) is usually in the range of 1 minute to 200 hours, preferably 10 minutes to 48 hours. More preferably, it is the range of 30 minutes or more and 24 hours or less. The longer the standing time, the lower the productivity per hour, and the shorter the standing time, the lower the yield (recovery rate) of the phosphoramidite compound.

  Moreover, when adding the poor solvent, the concentration of the phosphorus compound represented by the general formula (I) in the reaction solution before adding the poor solvent is set to a concentration that is high enough not to precipitate solids. Solid precipitation of the phosphorus compound (phosphoramidite compound) can be performed rapidly. Specifically, 0.001 mol / L or more and 10 mol / L or less are preferable, and 0.01 mol / L or more and 2 mol / L or less are more preferable. Especially 0.1 mol / L or more and 1 mol / L or less are preferable.

  The phosphoramidite compound that can be synthesized in the present invention has a structure represented by the general formula (I).

(In general formula (I), R _a and R _b are each independently hydrogen, alkyl group, aryl group, alkoxy group, aryloxy group, acyl group, acyloxy group, hydroxy group, amino group, alkylthio group, and arylthio group. These groups may be selected from the group consisting of groups, and these groups may further have a substituent, and Ar _{1 to} Ar ₄ are each independently an aryl group which may have a substituent. , Ar ₁ and Ar ₂ , and Ar ₃ and Ar ₄ may be linked to each other to form an aromatic ring containing the bonded carbon, and the formed aromatic ring may further have a substituent. Q is a divalent organic group which may have a substituent, where n is an integer of 1 or more. The structure of the general formula (I) is determined from the structures of the above-described phenols and amines, respectively, and preferred are phosphoramidite compounds derived from the structures of the above-mentioned preferable phenols and amines. Specifically, as Ar _{1 to} Ar ₄ , phenyl group, 2-methylphenyl group, 3-methylphenyl group, 4-methylphenyl group, 2,3-dimethylphenyl group, 2,4-dimethylphenyl group, 2, 5-dimethylphenyl group, 2,6-dimethylphenyl group, 2-ethylphenyl group, 2-isopropylphenyl group, 2-t-butylphenyl group, 2,4-di-t-butylphenyl group, 2-chlorophenyl group 3-chlorophenyl group, 4-chlorophenyl group, 2,3-dichlorophenyl group, 2,4-dichlorophenyl group, 2,5-dichlorophenyl group, 3,4-dichlorophenyl group, 3,5-dichlorophenyl group, 4-trifluoro Methylphenyl group, 2-methoxyphenyl group, 3-methoxyphenyl group, 4-methoxyphenyl group, 3,5-dimethoxyphenyl Group, 4-cyanophenyl group, a 4-nitrophenyl group, a trifluoromethyl group, pentafluoroethyl group, a pentafluorophenyl group, and the following (C-1) include ~ (C-8).

Q may be a divalent organic group which may have a substituent, but is preferably a linear hydrocarbon group or a cyclic saturated hydrocarbon group, more preferably a linear chain. It is a saturated hydrocarbon group. As a specific preferred example, — (CH ₂ ) _{-, - (CH 2) 2} -, - (
_{CH 2) 3 -, - (} CH 2) 4 -, - (CH 2) 5 -, - (CH 2) 6 -, - CH 2 -
_{CH (CH 3) -, -} CH (CH 3) -CH (CH 3) -, - CH (CH 3) CH 2 CH 2 -, - CH 2 CH (CH 3) CH 2 -, - CH (CH 3 _{) CH 2 CH (CH 3)} -, - C (CH 3) 2 -C (CH 3) 2 -, - C (CH 3) 2 -CH 2 -C (CH 3) 2 -, and the like. As the substituent for Q, those having a molecular weight of 200 or less are usually used.

Specific examples of R _a and R _b include hydrogen, methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, pentyl group, hexyl group, cyclohexyl group, and phenyl group.
As specific phosphoramidite compounds, the following (L-1) to (L-22) can be exemplified, and (L-1) to (L-15) are exemplified as particularly preferred specific examples. Can do.

  The phosphoramidites synthesized according to the present invention can be used as ligands for homogeneous complex catalysts, especially in combination with transition metals, such as hydrogenation, hydroformylation, olefin isomerization, π-allyl substitution reaction, etc. Can be used for For example, it can be used in a method for producing an isomerized compound represented by the following general formula (2) by isomerizing an allyl compound derivative represented by the following general formula (1).

(In General Formula (1), R _A -R _E each independently represents a hydrogen atom, an alkyl group, an aryl group, an alkoxy group, an aryloxy group, an acyl group, an acyloxy group, a hydroxy group, an amino group, an alkylthio group, and A group selected from the group consisting of arylthio groups, and these groups may further have a substituent, X represents an electron withdrawing group, and in the above general formula (2), R _A -R _E and X has the same meaning as R _A -R _E and X in the above general formula (1), provided that the allyl compound derivative represented by the above general formula (1) and the isomerization represented by the above general formula (2). (A compound does not represent the same compound.)
The allyl compound derivative used as a raw material in the method for producing an allyl compound derivative of the present invention is represented by the above general formula (1), and the isomerized compound produced by the isomerization reaction is represented by the above general formula (2). . In General Formula (1) and General Formula (2), R _{A to} R _E are each independently a hydrogen atom, alkyl group, aryl group, alkoxy group, aryloxy group, acyl group, acyloxy group, hydroxy group, amino group. , An alkylthio group, and an arylthio group, and these groups and rings may further have a substituent. However, the compounds represented by the general formula (1) and the general formula (2) do not represent the same compound.

The alkyl skeleton portion of the substituent (alkoxy group, acyl group, acyloxy group, alkylthio group) having an alkyl group and an alkyl skeleton in R _{A to} R _E usually has 1 to 20 carbon atoms, preferably 1 to 14 carbon atoms. It is. Specific examples of the alkyl group (hereinafter including the alkyl skeleton) include, for example, methyl group, ethyl group, n-propyl group, i-propyl group, n-butyl group, i-butyl group, sec-butyl group, t -A butyl group, a pentyl group, a hexyl group, an octyl group, a decyl group, etc. are mentioned. Moreover, as a substituent which an alkyl group may have, C1-C10 alkoxy groups, such as a methoxy group, an ethoxy group, and a propoxy group; C6-C10 aryl groups, such as a phenyl group and a naphthyl group; Acetoxy group , Propionyloxy group, butyryloxy group and the like, an acyloxy group having 1 to 10 carbon atoms, an amino group, a cyano group, an ester group having 2 to 10 carbon atoms, a hydroxy group, and a halogen atom.

Moreover, the aryl skeleton part of the substituent (aryloxy group, arylthio group) having an aryl group and an aryl skeleton in R _{A to} R _E usually has 6 to 20 carbon atoms, preferably 6 to 14 carbon atoms. Specific examples of the aryl group (hereinafter including the aryl skeleton portion) include a phenyl group and a naphthyl group. Examples of the substituent that the aryl group may have include a hydrogen atom, an alkyl group having 1 to 14 carbon atoms, an alkoxy group having 1 to 10 carbon atoms, a cycloalkyl group having 3 to 20 carbon atoms, and an aryl group having 6 to 20 carbon atoms. , An aryloxy group having 6 to 20 carbon atoms, an alkylaryl group having 6 to 20 carbon atoms, an alkylaryloxy group having 6 to 20 carbon atoms, an arylalkyl group having 6 to 20 carbon atoms, an arylalkoxy group having 6 to 20 carbon atoms , A cyano group, an ester group, a hydroxy group, a halogen atom, and the like, and specific examples thereof are the same as the substituents of the alkyl group.

X represents an electron-withdrawing group, and specific examples include acyloxy groups such as acetoxy group and propionyloxy group, and halogen atoms such as hydroxy group, chlorine atom and bromine atom, and acyloxy group is preferable. More preferably, it is an acetoxy group.
Specific examples of the allyl compound derivative represented by the general formula (1) used as a raw material in the method for producing an allyl compound derivative of the present invention include, for example, crotyl acetate, crotyl phenyl ether, crotyl alcohol, crotyl dimethyl. Amine, crotyl chloride, butadiene monoxide, 2-acetoxy-5-hydroxy-2,5-dimethyl-3-hexene, 1-phenyl-1-buten-3-yl acetate, 1-cyclohexyl acetate 2-butene, 1,3-diphenyl-3-dibenzylamino-1-propene, 1- (4-bromophenyl) -3-bromo-1-propene, 2-hexenyl acetate, 2-dodecenyl Alcohol, geranyl formate, geranyl acetate, acetic acid-3-phenyl-2-propene, methyl 9-phenoxy-7-nonen-3-one, acetic acid-3 Buten-2-yl, isobutyric acid-2,4-hexadienyl, prenyl acetate, 1,4-diacetoxy-2-butene, 1-acetoxy-4-hydroxy-2-butene, 1,4-dihydroxy-2-butene, 3,4-diacetoxy-1-butene, 3-acetoxy-4-hydroxy-1-butene, 4-acetoxy-3-hydroxy-1-butene, 3,4-dihydroxy-1-butene, 3,4-diacetoxy- 2-methyl-1-butene, 3-acetoxy-4-hydroxy-2-methyl-1-butene, 4-acetoxy-3-hydroxy-2-methyl-1-butene, 3,4-diacetoxy-3-methyl- 1-butene, 3-acetoxy-4-hydroxy-3-methyl-1-butene, 4-acetoxy-3-hydroxy-3-methyl-1-butene, 3,4-dia Toxi-2,3-dimethyl-1-butene, 3,4-diacetoxy-1-cyclohexene, 3,4-diacetoxy-1-cyclopentene, 3,4-diacetoxy-1-cycloheptene, 3,4- Examples thereof include diacetoxy-1-cyclooctene, malonic acid diallyl ester, terephthalic acid diallyl ester, and phthalic acid diallyl ester.

The allyl compound derivative is isomerized to produce the corresponding isomerized compound represented by the general formula (2).
Among the above allyl compound derivatives, preferred compounds are _RA in the general formula (1).
R _E is an allyl compound derivative selected from a hydrogen atom, an alkyl group having 1 to 30 carbon atoms, and an aryl group having 6 to 30 carbon atoms, and X is a group selected from an acetoxy group and a hydroxy group. Specific examples of more preferable raw material allyl compound derivatives include, for example, 3,4-diacetoxy-1-butene, 3-acetoxy-4-hydroxy-1-butene, 4-acetoxy-
3-hydroxy-1-butene, 3,4-dihydroxy-1-butene, 3,4-diacetoxy-2-methyl-1-butene, 3-acetoxy-4-hydroxy-2-methyl-1-butene, 4- Acetoxy-3-hydroxy-2-methyl-1-butene, 3,4-diacetoxy-3-methyl-1-butene, 3-acetoxy-4-hydroxy-3-methyl-1-butene, 4-acetoxy-3- And hydroxy-3-methyl-1-butene.

Examples of the isomerized compound represented by the above general formula (2) produced by the isomerization reaction of the above preferred raw material allyl compound derivative include 1,4-diacetoxy-2-butene, 1-acetoxy-4-hydroxy 2-butene, 1,4-dihydroxy-2-butene, 1,4-diacetoxy-2-methyl-2-butene, 1-acetoxy-4-hydroxy-2-methyl-2-butene, 1,4-diacetoxy -3-methyl-2-butene, 1-acetoxy-4-hydroxy-3-methyl-2-butene, and the like. Particularly preferable raw material allyl compound derivatives represented by the general formula (1) include 3,4-diacetoxy-1-butene, 3-acetoxy-4-hydroxy-1-butene, 4-acetoxy-3-hydroxy-1- Examples of isomerized compounds represented by the general formula (2) corresponding to butene include 1,4-diacetoxy-2-butene and 1-acetoxy-4-hydroxy-2-butene.

In the method for producing an allyl compound derivative of the present invention, 3,4-diacetoxy-1-butenes which are particularly preferred raw material allyl compound derivatives used are 1,4-diacetoxy-2 by oxidative diacetoxylation reaction of conjugated dienes and the like. -A compound obtained with butene.
Methods for producing 3,4-diacetoxy-1-butenes and / or 1,4-diacetoxy-2-butenes by diacetoxy reaction of conjugated dienes are known and most commonly used are palladium-based catalysts. In the presence, butadiene, acetic acid and oxygen are reacted to produce 1,4-diacetoxy-2-butene and 3,4-diacetoxy-1-butene, which are hydrolysates of these diacetoxybutenes. 1-acetoxy-4-hydroxy-2-butene, 3-hydroxy-4-acetoxy-1-butene, 4-hydroxy-3-acetoxy-1-butene and the like are also produced.

  Suitable conjugated dienes used in the diacetoxylation reaction include, for example, butadiene, isoprene, 1,3-cyclohexadiene, 1,3-dichloropentadiene, and particularly preferably butadiene and isoprene. The catalyst used for the diacetoxylation reaction of conjugated dienes is usually a solid catalyst containing a group 8-10 transition metal of the periodic table, particularly preferably a palladium solid catalyst.

  The palladium solid catalyst is a solid catalyst carrying palladium and tellurium as active components, prepared from palladium metal or a salt thereof and bismuth, selenium, antimony, tellurium and copper, preferably a metal of tellurium or a salt thereof as a cocatalyst. Preferably there is. As the carrier for the palladium solid catalyst, silica, alumina, titania, zirconia, activated carbon, graphite, preferably silica is used.

The diacetoxylation reaction is performed in an oxygen atmosphere, and can be performed in either a gas phase or a liquid phase. The reaction temperature is 0 to 300 ° C., preferably 10 to 200 ° C., the reaction pressure is atmospheric pressure to 50 MPa, preferably atmospheric pressure to 30 MPa, particularly preferably 1 to 20 MPa. When the diacetoxylation reaction is carried out in the liquid phase, the solvent used in the reaction is not particularly limited as long as it dissolves the reaction raw material, but becomes a reaction raw material such as water, carboxylic acid such as acetic acid, or butadiene. Conjugated dienes themselves, or acetoxylation products such as 1,4-diacetoxy-2-butene, hydrocarbons such as n-hexane, n-heptane, and n-octane, tetrahydrofuran, diethyl ether, triglyme, etc. Ethers, ethyl acetate, butyric acid n
Esters such as monobutyl, ketones such as acetone and methyl isobutyl ketone, and alcohols such as 1,4-butanediol can also be used.

  When 1,4-diacetoxy-2-butene is produced by the oxidative acetoxylation reaction as described above, 3,4-diacetoxy-1-butene is inevitably produced as a by-product. When a fraction containing 4-diacetoxy-1-butene as a main component is obtained and the fraction is subjected to an isomerization reaction according to the method of the present invention, it is effectively converted to 1,4-diacetoxy-2-butene. I can do it. Thus, the process of the present invention improves the selectivity of 1,4-diacetoxy-2-butene in a process that consistently produces 1,4-butanediol from the oxidative diacetoxylation reaction of butadienes, -An effective method for improving the consistent yield of butanediol.

  The “containing liquid containing 3,4-diacetoxy-1-butene as a main component” used as a raw material in the present invention refers to the reaction liquid itself after the diacetoxylation reaction of butadiene, or 3,4-diacetoxy such as acetic acid and water. A product obtained by removing at least a part of by-products having a lighter boiling point than 1-butene by distillation, or a part or all of a by-product having a higher boiling point than 3,4-diacetoxy-1-butene is removed by distillation. And those obtained by removing a part or all of both the light-boiling byproducts and the high-boiling byproducts. Usually, this “3,4-diacetoxy-1-butene-containing liquid as the main component” also contains the corresponding 1,4-diacetoxy-2-butene, but in addition, 3,4-diacetoxy-1-butene 3-hydroxy-4-acetoxy-1-butene, 4-hydroxy-3-acetoxy-1-butene and / or 3,4-dihydroxy-1-butene, and 1,4-diacetoxy-2 -It may contain 1-acetoxy-4-hydroxy-2-butene and / or 1,4-dihydroxy-2-butene which are hydrolysates of butene.

  The “containing liquid composed mainly of 3,4-diacetoxy-1-butene” used in the present invention is usually 3,4-diacetoxy-1-butene, 1,4-diacetoxy-2-butene, and more than them. A liquid containing a light-boiling component and a high-boiling component is introduced into the distillation tower, and a 1,4-diacetoxy-2-butene-containing liquid containing a high-boiling component is extracted from the bottom of the tower, and 3,4- It can be obtained by distilling a diacetoxy-1-butene-containing liquid. At this time, the 3,4-diacetoxy-1-butene-containing liquid can be extracted together with the light-boiling components from the top of the column, and the 3,4-diacetoxy-1-butene-containing liquid is extracted from the side stream. The light boiling component may be distilled from In the present invention, the “upper column” means above the middle stage of the distillation column, and it may be a column top extraction or an upper side drain. Further, the light boiling point component may be further separated in the second column.

  Although distillation conditions in the distillation column for obtaining the 3,4-diacetoxy-1-butene-containing liquid can be arbitrarily set, the column top pressure is usually in the range of 5 to 200 mmHg, preferably 10 to 100 mmHg, The tower top temperature is usually 0 to 200 ° C, preferably 20 to 160 ° C, more preferably 40 to 140 ° C. The reflux ratio is usually 1 to 100, preferably 1 to 10.

As the distillation column, either a packed column or a plate column can be used, but multistage distillation is preferred.
In the method for producing an allyl compound derivative of the present invention, the catalyst used for the isomerization reaction is a transition metal compound of Group 8 to 10 (according to the revised IUPAC inorganic chemical nomenclature (1998)) and the phosphorus compound synthesized in the present invention. Is a transition metal complex catalyst having a ligand as a ligand. The group 8-10 transition metal compound is preferably ruthenium, rhodium, nickel, palladium, or platinum, and particularly preferably palladium. The transition metal compound is supplied in the form of acetate, sulfate, nitrate, halide salt, organic salt, inorganic salt, acetylacetonate compound, alkene coordination compound, amine coordination compound, pyridine coordination compound, carbon monoxide. Coordination compounds, phosphine coordination compounds, phosphite coordination compounds, etc. Specific palladium compounds include palladium metal, palladium acetate, palladium trifluoroacetate, palladium sulfate, palladium nitrate, palladium chloride, palladium bromide , Palladium iodide, bis (acetylacetonato) palladium, dichlorocyclooctadiene palladium, dichlorobis (triphenylphosphine) palladium, tetrakis (triphenylphosphine) palladium, bis (dibenzyliriacetone) palladium, potassium tetrachloroparada Sodium tetrachloroparadato, dichlorobis (benzonitrile) palladium, dichlorobis (acetonitrile) palladium, other carboxylate compounds, olefin-containing compounds, organic phosphine-containing compounds, allyl palladium chloride dimers, etc. In handling, palladium acetate, palladium trifluoroacetate, bis (acetylacetonato) palladium, and tetrakis (triphenylphosphine) palladium are particularly preferable.

In the method for producing an allyl compound derivative of the present invention, the form of the transition metal compound is not particularly limited, and may be a monomer, a dimer and / or a multimer. The amount of these metal compounds used is 0.001 to 1000 wtppm, preferably 0.001 to 100 wtppm, and particularly preferably 0.01 to 100 wtppm with respect to the allyl compound as the reaction raw material. If the metal concentration is too high, the catalyst cost increases, and if the metal concentration is too low, a long reactor with a low reaction rate is required.

  In the method for producing an allyl compound derivative of the present invention, the addition amount of the ligand containing the phosphorus compound is preferably such that the molar ratio of the phosphorus atom in the ligand is 0.1 to 1000 with respect to the transition metal in the complex catalyst, More preferably, it is 1-100, Most preferably, it is 1-10. The temperature for carrying out the isomerization reaction in the present invention is usually from 40 to 200 ° C, preferably from 80 to 180 ° C, particularly preferably from 100 to 160 ° C. If the reaction temperature is too high, deterioration due to metalization of the complex catalyst will proceed, loss of activity will occur, and if the reaction temperature is too low, the reaction rate will decrease and a long reactor will be required. End up.

In the present invention, the pressure for carrying out the isomerization reaction is usually 1 atm, but it may be under reduced pressure or under pressure. If the reaction pressure is too low, the catalytic activity decreases as the reaction temperature decreases, and if the reaction pressure is too high, the reactor cost increases.
In the method for producing an allyl compound derivative of the present invention, the isomerization reaction of the allyl compound is usually performed in a liquid phase. The reaction can be carried out in the presence or absence of a solvent, and is particularly characterized in that it exhibits high isomerization activity even in the absence of a solvent. When a solvent is used, it can be used as a preferable solvent as long as it dissolves the catalyst and the raw material compound, and is not particularly limited. Specific examples include ethers such as diglyme, diphenyl ether, dibenzyl ether, diallyl ether, tetrahydrofuran (THF), dioxane, N-methyl-2-pyrrolidone, N, N-dimethylformamide, N, N-dimethylacetamide and the like. Amides, ketones such as cyclohexanone, esters such as n-butyl acetate, γ-butyrolactone, di (n-octyl) phthalate, aromatic hydrocarbons such as toluene, xylene, dodecylbenzene, n-pentane, n- Removal of aliphatic hydrocarbons such as hexane, n-heptane, n-octane, by-products generated by isomerization reaction, or allyl compound derivatives themselves as raw materials, allyl compounds themselves as products, and allyl compound derivatives as raw materials Examples include compounds derived from leaving groups. Particularly preferable solvents include the allyl compound itself as a raw material and the allyl compound derivative itself as a product. The amount of the solvent to be used is not particularly limited, but since the present invention mainly proceeds by intramolecular reaction, it is desirable to carry out with a smaller amount of solvent compared to the conventional method. Usually, it is 0-10 weight times or less with respect to the total weight of the allyl compound which is a raw material, Preferably it is 0-5 weight times, Most preferably, it is 0-1 weight times or less. When the amount of the solvent is too large, the reaction rate decreases.

  In the method for producing an allyl compound derivative of the present invention, it is preferable that a Bronsted acid coexists with a catalyst in the isomerization allyl compound derivative in the isomerization reaction. The amount of Bronsted acid is preferably 0.005 times by weight or more of the allyl compound to be isomerized, and preferably 0.2 times by weight or less of the allyl compound to be isomerized. Particularly preferably, it is 0.01 weight times or more of the allyl compound to be isomerized, and particularly preferably 0.1 weight times or less of the allyl compound to be isomerized. If the amount of Bronsted acid is too small, intermolecular reaction does not occur, the reaction rate decreases, and if it is too large, the ligand is decomposed.

  In the method for producing an allyl compound derivative of the present invention, the Bronsted acid specifically includes carboxylic acids such as formic acid, acetic acid, propionic acid and butyric acid, alcohols such as methanol, n-butanol and 2-ethylhexanol, p- Examples thereof include sulfonic acids such as toluenesulfonic acid, preferably carboxylic acids such as formic acid, acetic acid, propionic acid and butyric acid, and more preferably acetic acid.

In the method for producing an allyl compound derivative of the present invention, as a reaction system for carrying out the isomerization reaction, using a stirring type complete mixing reactor or a plug flow type reactor, a continuous system, a semi-continuous system or a batch system Either can be done. The gas phase part in the reactor is preferably formed of an inert gas such as argon or nitrogen other than the vapor derived from the solvent, the raw material compound, the reaction product, the reaction byproduct, the catalyst decomposition product, and the like. In particular, oxygen contamination due to air leakage or the like causes catalyst deterioration, that is, oxidation loss of the phosphorus compound. Therefore, it is desirable to reduce the amount as much as possible.

EXAMPLES Hereinafter, although an Example demonstrates this invention further in detail, unless it exceeds the summary of this invention, it is not limited to a following example. In the following Examples, 3,4-diacetoxy-1-butene and 1,4-diacetoxy-2-butene were analyzed by gas chromatography using an internal standard method. Dodecane was used as an internal standard.
<Example 1>
[Synthesis of phosphoramidite compounds]
First, 90 cc of tetrahydrofuran and 3.79 g (14 mmol) of phosphorus tribromide were mixed and dissolved in a 200 cc glass flask. Next, 4.3 cc (30 mmol) of triethylamine was added dropwise and cooled to 0 ° C. with ice water. A tetrahydrofuran solution (50 cc) of 5.01 g (14 mmol) of separately prepared 3,3′-di-tert-butyl-5,5′-dimethoxy-2,2′-biphenol was added to this mixture of phosphorus tribromide and triethylamine. Was added dropwise at 0 ° C. The dropping speed of 3,3′-di-tert-butyl-5,5′-dimethoxy-2,2′-biphenol at this time was 45 cc / min (the dropping amount per minute was the amount of tetrahydrofuran (90 cc 50 vol%)). After 30 minutes, the temperature was raised to room temperature, and stirring was continued for 3 hours. In addition, a part of this reaction liquid was extracted, and it was confirmed by ³¹ P-NMR analysis that phosphorus tribromide had completely disappeared.

Then, 2.6 cc (18 mmol) of triethylamine was added to the obtained reaction solution at room temperature. Thereafter, a separately prepared tetrahydrofuran solution (10 cc) of 0.85 g (8.4 mmol) of N, N′-dimethyl-1,3-aminopropane was added. The mixture was heated to 60 ° C. in an oil bath and stirring was continued for 3 hours.
Then, the obtained reaction liquid was cooled to room temperature, and solid content deposited in the liquid was removed by filtration with a filter paper. 20 cc of demineralized water and 120 cc of toluene were added to the obtained filtrate, and extraction and separation were performed with a separatory funnel. Of the two layers obtained after standing, the upper toluene layer was recovered, 20 cc of a 5 wt% aqueous sodium hydroxide solution was added thereto, and extraction and separation were performed in the same manner. The recovered upper toluene layer was again added with 20 cc of demineralized water, and the same operation was performed to recover 110 cc of the toluene layer again. Next, 110 cc of the recovered toluene layer was added dropwise at room temperature while stirring 1 L of methanol. As a result, a white solid started to precipitate. After adding the whole amount of the toluene layer, stirring was stopped and the white solid precipitated after 6 hours was collected by filtration using filter paper. The white solid was dried under reduced pressure at room temperature and weighed. As a result, the target product (phosphoramidite compound represented by (L-7) above) was obtained in a yield of 56%. The product was identified by ³¹ P-NMR analysis.

<Reference Example 1>
[Preparation of catalyst for isomerization of allyl compound derivative]
Under a nitrogen gas atmosphere, 5.1 mg of palladium acetate, 40 mg of the phosphoramidite compound (L-7) prepared in Example 1 and 25 mg of triphenylphosphine were added to 8.8 cc of toluene in a glass Schlenk. This mixed solution was heated at 120 ° C. for 5 minutes to be completely dissolved. The isomerization reaction of 3,4-diacetoxy-1-butene was performed as follows using this solution as a catalyst solution.

<Example 2>
[Isomerization of allyl compound derivatives]
Under a nitrogen atmosphere, 3.0 cc of 3,4-diacetoxy-1-butene and 0.06 cc of acetic acid were mixed in a Schlenk, and the temperature was raised to 155 ° C. in an oil bath. Thereto was added 5.5 μL of the catalyst solution prepared in Reference Example 1, and the mixture was heated and stirred at 155 ° C. for 3 hours (palladium concentration in the reaction solution: 1.0 wtppm). As a result of analyzing the liquid after the reaction by gas chromatography, the weight ratio of 1,4-diacetoxy-2-butene (cis isomer and trans isomer) to 3,4-diacetoxy-2-butene was 58:42 (1, 4-body: 3,4-body). In addition, dodecane was used as an internal standard.

<Example 3>
[Synthesis of phosphoramidite compounds]
First, 90 cc of toluene and 3.79 g (14 mmol) of phosphorus tribromide were mixed and dissolved in a 200 cc glass flask. Next, 4.3 cc (30 mmol) of triethylamine was added dropwise and cooled to 0 ° C. with ice water. A toluene solution (50 cc) of 5.01 g (14 mmol) of separately prepared 3,3′-di-tert-butyl-5,5′-dimethoxy-2,2′-biphenol was added to the mixture of phosphorus tribromide and triethylamine. Was added dropwise at 0 ° C. The dropping speed of 3,3′-di-tert-butyl-5,5′-dimethoxy-2,2′-biphenol at this time was 45 cc / min (the dropping amount per minute was the amount of toluene (90 cc 50 vol%)). After 30 minutes, the temperature was raised to room temperature, and stirring was continued for 3 hours. In addition, a part of this reaction liquid was extracted, and it was confirmed by ³¹ P-NMR analysis that phosphorus tribromide had completely disappeared.

Then, 2.6 cc (18 mmol) of triethylamine was added to the obtained reaction solution at room temperature. Thereafter, a separately prepared toluene solution (10 cc) of 0.85 g (8.4 mmol) of N, N′-dimethyl-1,3-aminopropane was added. The mixture was heated to 60 ° C. in an oil bath and stirring was continued for 3 hours.
Then, the obtained reaction liquid was cooled to room temperature, and solid content deposited in the liquid was removed by filtration with a filter paper. 20 cc of demineralized water and 120 cc of toluene were added to the obtained filtrate, and extraction and separation were performed with a separatory funnel. Of the two layers obtained after standing, the upper toluene layer was recovered, 20 cc of a 5 wt% aqueous sodium hydroxide solution was added thereto, and extraction and separation were performed in the same manner. The recovered upper toluene layer was again added with 20 cc of demineralized water, and the same operation was performed to recover 110 cc of the toluene layer again. Next, 110 cc of the recovered toluene layer was added dropwise at room temperature while stirring 1 L of methanol. As a result, a white solid started to precipitate. After adding the whole amount of the toluene layer, stirring was stopped and the white solid precipitated after 6 hours was collected by filtration using filter paper. The white solid was dried under reduced pressure at room temperature and weighed. As a result, the target product (phosphoramidite compound represented by (L-7) above) was obtained in a yield of 79%. The product was identified by ³¹ P-NMR analysis.

<Example 4>
[Synthesis of phosphoramidite compounds]
In Example 3, a phosphoramidite compound was synthesized under the same conditions except that phosphorus trichloride was used instead of phosphorus tribromide. The yield of the target product (phosphoramidite compound shown by (L-7) above) was 22%.

<Example 5>
[Synthesis of phosphoramidite compounds]
In Example 3, after using phosphorus trichloride in place of phosphorus tribromide and adding a toluene solution (10 cc) of 0.85 g (8.4 mmol) of N, N′-dimethyl-1,3-aminopropane The phosphoramidite compound was synthesized under the same conditions except that the heating conditions were 100 ° C. and 10 hours. The yield of the target product (phosphoramidite compound shown by (L-7) above) was 64%.

<Example 6>
[Synthesis of phosphoramidite compounds]
In Example 3, 3,3′-di-tert-butyl-5,5′-dimethoxy-2,
When dropping a toluene solution (50 cc) of 2′-biphenol 5.01 g (14 mmol) at 0 ° C., using a dropping funnel, the dropping rate was 1 cc / min (the dropping amount per minute was the amount of toluene (90 cc The phosphoramidite compound was synthesized under the same conditions except that it was controlled to 1.1 vol%). The yield of the target product (phosphoramidite compound shown by (L-7) above) was 96%.

<Example 7>
[Synthesis of phosphoramidite compounds]
In Example 1, when a tetrahydrofuran solution (50 cc) of 5.01 g (14 mmol) of 3,3′-di-tert-butyl-5,5′-dimethoxy-2,2′-biphenol was added dropwise at 0 ° C., Using a dropping funnel, the phosphoramidite compound was synthesized under the same conditions except that the dropping speed was controlled at 1 cc / min (the amount dropped per minute was 1.1 vol% of the amount of toluene (90 cc)). It was. The yield of the target product (phosphoramidite compound shown by (L-7) above) was 87%.

Claims (8)

A method for producing a phosphorus compound represented by the following general formula (I), comprising the following steps (a) to (c):
(A) A phosphorus halide compound, a phenol represented by the following general formula (III) , and a base are reacted in an organic solvent to produce a halogenated phosphoryl compound, and the produced phosphoryl halide Obtaining a solution containing the compound,
(B) A solution containing the halogenated phosphoryl compound obtained in the step (a) is mixed with an amine represented by the following general formula (II) to obtain a phosphorus compound represented by the following general formula (I). Producing a reaction solution containing the phosphorus compound represented by the general formula (I) produced,
(C) The process of collect | recovering the phosphorus compounds represented by the following general formula (I) from a reaction liquid obtained from a process (b) using a poor solvent.

(In the general formula (I), R _a and R _b are each independently a hydrogen atom, alkyl group, aryl group, alkoxy group, aryloxy group, acyl group, acyloxy group, hydroxy group, amino group, alkylthio group, and These groups are groups selected from the group consisting of arylthio groups, and these groups may further have a substituent, Ar _{1 to} Ar ₄ are each independently an aryl group which may have a substituent. Yes, Ar ₁ and Ar ₂ , and Ar ₃ and Ar ₄ may be connected to each other to form an aromatic ring containing the bonded carbon, and the formed aromatic ring may further have a substituent. In addition, Q is a divalent organic group which may have a substituent, where n is an integer of 1 or more.

(In the general formula (II), R _a and R _b are each independently a hydrogen atom, alkyl group, aryl group, alkoxy group, aryloxy group, acyl group, acyloxy group, hydroxy group, amino group, alkylthio group, and A group selected from the group consisting of arylthio groups, these groups may further have a substituent, and Q is a divalent organic group which may have a substituent, provided that n is an integer of 1 or more.)

(In the general formula (III), R _{1 to} R ₆ are each independently a hydrogen atom, an alkyl group, an aryl group, an alkoxy group, an aryloxy group, an acyl group, an acyloxy group, a hydroxy group, an amino group, an alkylthio group, and A group selected from the group consisting of an arylthio group, which may further have a substituent, and R _{1 to} R ₆ may be linked to form a ring; May further have a substituent.)
  The method according to claim 1, wherein the phosphorus halide compound is phosphorus tribromide.   The method according to claim 1 or 2, wherein the poor solvent is an alcohol and / or a nitrile. The process according to any one of claims 1 to 3, wherein the base is an trialkylamines. The organic solvent, process according to any one of claims 1-4, characterized in that the aromatic hydrocarbons and / or ethers. The process according to any one of claims 1 to 5, the concentration of the phosphorus compound represented by the general formula (I) in a reaction solution in the step (c) is characterized in that 1 to 50 wt%. In the step (a), after previously mixing the halogenated phosphorus compound and the base in the organic solvent, the phenols are added in an amount of 20% or less per minute with respect to the amount of the organic solvent. The method for producing a phosphorus compound according to any one of claims 1 to 6 . An allyl compound derivative represented by the following general formula (1) is isomerized in the presence of a phosphorus compound obtained by the production method according to any one of claims 1 to 7 and a catalyst containing a transition metal of Group 8 to Group 10 of the periodic table. A process for producing an isomerized compound represented by the following general formula (2) by the reaction of hydration.

(In General Formula (1), R _{A to} R _E are each independently a hydrogen atom, alkyl group, aryl group, alkoxy group, aryloxy group, acyl group, acyloxy group, hydroxy group, amino group, alkylthio group, and These groups are groups selected from the group consisting of arylthio groups, and these groups may further have a substituent, X represents an electron withdrawing group, and in the general formula (2), R _{A to} R _E and X is synonymous with R _{A to} R _E and X in the general formula (1), provided that the allyl compound derivative represented by the general formula (1) and the isomerization represented by the general formula (2). (A compound does not represent the same compound.)