JP2017132731A - Double addition of phosphine oxide to alkyne with base catalyst - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a method of synthesizing a phosphorus compound by double addition of phosphine oxide to alkyne with a base catalyst.SOLUTION: The present invention provides a method comprising the step of reacting alkyne and a phosphorus compound in an ether solvent in the presence of a catalytic amount of a base. The method of production according to the present invention (1) allows a reduction in remaining metal components in the product and (2) a reduction in production cost and (3) has an expanded scope of substrates in comparison with the conventional methods of production. Moreover, the obtained compounds may be used in flame retardants, lubricant additives, pharmaceutical intermediates, and catalyst raw materials. Furthermore, phosphine compounds that are obtained by reducing the compounds obtained by this reaction are compounds useful as ligands.SELECTED DRAWING: None

Description

  The present invention relates to the base-catalyzed double addition of phosphine oxides to alkynes.

  Phosphorus compounds are frequently used particularly as electronic materials as flame retardants. When a phosphorus compound is used for an electronic material, a synthesis method with a low metal content in the phosphorus compound is required in order to ensure the electrical properties of the electronic material, and the following methods are described in the literature.

  Non-Patent Document 1 (Russ. J. Gen. Chem. 2010, 80, 232-238) and Non-Patent Document 2 (Russ. J. Org. Chem. 2004, 40, 1, 129-130) are dimethyl sulfoxide ( Disclosed is a double addition reaction of a phosphine oxide having a phenethyl group as a substituent on the phosphorus to alkyne using potassium hydroxide in DMSO).

  Non-Patent Document 3 (Mendeleev Commun. 2005, 15, 183-184) describes the use of phosphine oxide to alkynes having cyano groups as terminal substituents using potassium hydroxide 0.5 hydrate in tetrahydrofuran (THF). A double addition reaction is disclosed.

  Non-Patent Document 4 (Journal of General Chemistry of the USSR in England 1988, 58, 2197-2203) describes a phase transfer catalyst in benzene or dimethyl sulfoxide (DMSO) and aqueous potassium hydroxide. The double addition reaction of diphenylphosphine oxide to the phenylacetylene used is disclosed.

Russ. J. et al. Gen. Chem. 2010, 80, 232-238 Russ. J. et al. Org. Chem. 2004, 40, 1, 129-130 Mendeleev Commun. 2005, 15, 183-184 Journal of General Chemistry of the U. S. S. R. in English 1988, 58, 2197-2203

  As a result of intensive studies, the present inventors consider that alkynes and phosphorus compounds can be applied to various substrates by reacting in an ether solvent in the presence of a catalytic amount of a base, and are considered highly useful. It was found that the synthesis of a product into which two phosphoryl groups containing the new compound were introduced was possible. The reaction of the present invention is superior to the conventional production method in that the compound can be obtained pure because no by-product is produced.

The present invention also provides the following items.
(Item 1)
The following general formula

(Where
R ¹ and R ² are each independently hydrogen, halogen group, substituted or unsubstituted alkyl group, substituted or unsubstituted cycloalkyl group, substituted or unsubstituted alkoxy group, substituted or unsubstituted heterocyclic group, substituted Or an unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted aryloxy group, a substituted or unsubstituted thioalkoxy group, a substituted or unsubstituted alkoxycarbonyl group, a substituted or unsubstituted alkylcarbonyl Selected from the group consisting of a group and a substituted or unsubstituted aminocarbonyl group,
R ³ is selected from the group consisting of a substituted or unsubstituted alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted aryl group, and a substituted or unsubstituted heteroaryl group. Is the group selected)
A method for producing a compound represented by the formula:

And R ³ ₂ P (O) H
And in the presence of a catalytic amount of a base in an ether solvent to form the compound or a salt thereof.
(Item 2)
The following general formula

(Where
R ¹ and R ² are each independently hydrogen, halogen group, substituted or unsubstituted alkyl group, substituted or unsubstituted cycloalkyl group, substituted or unsubstituted alkoxy group, substituted or unsubstituted heterocyclic group, substituted Or an unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted aryloxy group, a substituted or unsubstituted thioalkoxy group, a substituted or unsubstituted alkoxycarbonyl group, a substituted or unsubstituted alkylcarbonyl Selected from the group consisting of a group and a substituted or unsubstituted aminocarbonyl group,
R ³ is a group other than a substituted or unsubstituted phenethyl group)
A method for producing a compound represented by the formula:

And R ³ ₂ P (O) H
And in the presence of a catalytic amount of a base to produce the compound or a salt thereof.
(Item 3)
The ether solvents include tetrahydrofuran (THF), diethyl ether, dioxane, 1,2-dimethoxyethane (DME), methyl tert-butyl ether (MTBE), cyclopentyl methyl ether (CPME), phenyl methyl ether, tetrahydropyran and diisopropyl. A method according to the preceding item, selected from the group consisting of ethers.
(Item 4)
The method according to any one of the above items, wherein the ether solvent is tetrahydrofuran (THF).
(Item 5)
The group other than the substituted or unsubstituted phenethyl group includes an unsubstituted alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted aryl group, and a substituted or unsubstituted group. The method according to any one of the preceding items, selected from the group consisting of heteroaryl groups.
(Item 6)
The method according to any one of the above items, wherein the reaction is carried out in the absence of a phase transfer catalyst.
(Item 7)
The method according to any one of the above items, wherein the reaction is carried out in a homogeneous solvent.
(Item 8)
The method according to any one of the preceding items, wherein the base is an alkoxy alkali metal or alkali metal hydroxide or a mixture thereof.
(Item 9)
The method according to any one of the preceding items, wherein the alkoxyalkali metal is sodium tert-butoxide, potassium tert-butoxide or lithium tert-butoxide.
(Item 10)
The method according to any one of the above items, wherein the alkali metal hydroxide is lithium hydroxide, sodium hydroxide, or potassium hydroxide.
(Item 11)
The method according to any one of the above items, wherein water is not contained in the reaction vessel.
(Item 12)
The following general formula

(Where
When R ¹ is a substituted or unsubstituted alkyl group, R ² is a halogen group, a substituted or unsubstituted alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted alkoxy group, substituted or unsubstituted A substituted heterocyclic group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted aryloxy group, a substituted or unsubstituted thioalkoxy group, a substituted or unsubstituted alkoxycarbonyl group, Selected from the group consisting of a substituted or unsubstituted alkylcarbonyl group and a substituted or unsubstituted aminocarbonyl group;
When R ¹ is a group that is not a substituted or unsubstituted alkyl group (confirmed) R ² is hydrogen, a halogen group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted alkoxy group, a substituted or non-substituted group A substituted heterocyclic group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted aryloxy group, a substituted or unsubstituted thioalkoxy group, a substituted or unsubstituted alkoxycarbonyl group, Selected from the group consisting of a substituted or unsubstituted alkylcarbonyl group and a substituted or unsubstituted aminocarbonyl group;
R ³ is selected from the group consisting of a substituted or unsubstituted alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted aryl group, and a substituted or unsubstituted heteroaryl group. Selected, provided that R ³ is not a phenethyl group)
Or a salt thereof, provided that the compound is

Not a compound or salt thereof.
(Item 13)
The following general formula

(Where
When R ¹ is a substituted or unsubstituted alkyl group or hydrogen, R ² is a halogen group, a substituted or unsubstituted alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted alkoxy group, a substituted Or an unsubstituted heterocyclic group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted aryloxy group, a substituted or unsubstituted thioalkoxy group, a substituted or unsubstituted alkoxycarbonyl Selected from the group consisting of a group, a substituted or unsubstituted alkylcarbonyl group and a substituted or unsubstituted aminocarbonyl group;
When R ¹ is a group that is not hydrogen and is not a substituted or unsubstituted alkyl group, R ² is a halogen group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted group Heterocyclic group, substituted or unsubstituted aryl group, substituted or unsubstituted heteroaryl group, substituted or unsubstituted aryloxy group, substituted or unsubstituted thioalkoxy group, substituted or unsubstituted alkoxycarbonyl group, substituted or Selected from the group consisting of unsubstituted alkylcarbonyl groups and substituted or unsubstituted aminocarbonyl groups;
R ³ is selected from the group consisting of a substituted or unsubstituted alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted aryl group, and a substituted or unsubstituted heteroaryl group. Selected, provided that R ³ is not a phenethyl group)
The compound or its salt as described in any one of the said items shown by these.
(Item 14)

The compound or a salt thereof according to any one of the above items, selected from the group consisting of:
(Item 15)
The flame retardant containing the compound or its salt of any one of the said items.

  In the present invention, it is contemplated that one or more of the above features may be provided in further combinations in addition to the express combinations. Still further embodiments and advantages of the invention will be recognized by those of ordinary skill in the art upon reading and understanding the following detailed description as needed.

  The production method of the present invention enables (1) reduction of residual metal components in the product, (2) reduction of production cost, and (3) expansion of the application range of the substrate compared with the conventional production method. . Moreover, the obtained compound can be used for a flame retardant, a lubricating oil additive, a pharmaceutical intermediate, and a catalyst raw material. In addition, compounds obtained by this reaction were prepared by the method of “Guide to Organophosphorus Chemistry”, Bull. By Wiley-Interscience, Louis D Quin, and Bull. Chem. Soc. Jpn. , 73, 705-712 (2000), and can be converted into a phosphine compound useful as a ligand.

FIG. 1 is the ¹ H-NMR spectrum of Example 3 entry 1. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 2 is a ³¹ P-NMR spectrum of Example 3 entry 1. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 3 is the ¹ H-NMR spectrum of Example 3 entry 2. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 4 is a ³¹ P-NMR spectrum of Example 3 entry 2. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 5 is the ¹ H-NMR spectrum of Example 3 entry 3. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 6 is a ³¹ P-NMR spectrum of Example 3 entry 3. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 7 is the ¹ H-NMR spectrum of Example 3 entry 4. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 8 is a ³¹ P-NMR spectrum of Example 3 entry 4. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 9 is the ¹ H-NMR spectrum of Example 3 entry 5. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 10 is a ³¹ P-NMR spectrum of Example 3 entry 5. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 11 is the ¹ H-NMR spectrum of Example 4 entry 2. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 12 is a ³¹ P-NMR spectrum of Example 4 entry 2. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 13 is the ¹ H-NMR spectrum of Example 4 entry 3. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 14 is a ³¹ P-NMR spectrum of Example 4 entry 3. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 15 is the ¹ H-NMR spectrum of Example 4 entry 4. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 16 is a ³¹ P-NMR spectrum of Example 4 entry 4. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 17 is the ¹ H-NMR spectrum of Example 4 entry 5. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 18 is a ³¹ P-NMR spectrum of Example 4 entry 5. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 19 is the ¹ H-NMR spectrum of Example 4, entry 6. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 20 is a ³¹ P-NMR spectrum of Example 4 entry 6. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 21 is the ¹ H-NMR spectrum of Example 4 entry 7. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 22 is the ³¹ P-NMR spectrum of Example 4 entry 7. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 23 is the ¹ H-NMR spectrum of Example 4 entry 8. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 24 is the ³¹ P-NMR spectrum of Example 4 entry 8. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 25 is the ¹ H-NMR spectrum of Example 4 entry 9. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 26 is the ³¹ P-NMR spectrum of Example 4 entry 9. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 27 is the ¹ H-NMR spectrum of Example 4 entry 10. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 28 is the ³¹ P-NMR spectrum of Example 4 entry 10. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 29 is the ¹ H-NMR spectrum of Example 4 entry 11. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 30 is the ³¹ P-NMR spectrum of Example 4 entry 11. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 31 is the ¹ H-NMR spectrum of Example 4 entry 12. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). 32 is a ³¹ P-NMR spectrum of Example 4 entry 12. FIG. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 33 is the ¹ H-NMR spectrum of Example 4 entry 13. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 34 is the ³¹ P-NMR spectrum of Example 4 entry 13. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 35 is the ¹ H-NMR spectrum of Example 4 entry 14. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 36 is the ³¹ P-NMR spectrum of Example 4 entry 14. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 37 is the ¹ H-NMR spectrum of Example 4 entry 15. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 38 is the ³¹ P-NMR spectrum of Example 4 entry 15. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 39 is the ¹ H-NMR spectrum of Example 4 entry 16. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). 40 is a ³¹ P-NMR spectrum of Example 4 entry 16. FIG. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 41 is the ¹ H-NMR spectrum of Example 4 entry 17. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 42 is the ³¹ P-NMR spectrum of Example 4 entry 17. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 43 is the ¹ H-NMR spectrum after the reaction of Example 5, entry 1. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). 44 is a ³¹ P-NMR spectrum after the reaction of Example 5 entry 1. FIG. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). FIG. 45 is the ¹ H-NMR spectrum after the reaction of Example 5 entry 2. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm). 46 is a ³¹ P-NMR spectrum after the reaction of Example 5 entry 2. FIG. The vertical axis represents the relative intensity of the signal, and the horizontal axis represents the chemical shift (δ) value (ppm).

  The present invention will be described below with reference to the best mode. Throughout this specification, it should be understood that the singular forms also include the plural concept unless specifically stated otherwise. Thus, it should be understood that singular articles (eg, “a”, “an”, “the”, etc. in the case of English) also include the plural concept unless otherwise stated. In addition, it is to be understood that the terms used in the present specification are used in the meaning normally used in the art unless otherwise specified. Thus, unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. In case of conflict, the present specification, including definitions, will control.

(Definition of terms)
Terms used in this specification will be described below.

  As used herein, “substitution” refers to replacement of a specific hydrogen atom in an organic compound with another atom or atomic group.

  In the present specification, the “substituent” refers to an atom or a functional group substituted with another in a chemical structure.

  In the present specification, unless otherwise specified, substitution is the substitution of one or more hydrogen atoms in a certain organic compound or substituent with another atom or atomic group, or a double bond or triple bond. That means. It is possible to remove one hydrogen atom and replace it with a monovalent substituent, or combine with a single bond to form a double bond, and remove two hydrogen atoms to form a divalent substituent. It can be substituted or combined with a single bond to form a triple bond.

  Examples of the substituent in the present invention include hydrogen, halogen group, thiol group, hydroxy group, cyano group, substituted or unsubstituted alkyl group, substituted or unsubstituted cycloalkyl group, substituted or unsubstituted alkoxy group, substituted or unsubstituted Substituted heterocyclic group, substituted or unsubstituted aryl group, substituted or unsubstituted aryloxy group, substituted or unsubstituted amino group, substituted or unsubstituted thioalkoxy group, substituted or unsubstituted alkoxycarbonyl group, substituted Or an unsubstituted alkylcarbonyl group or a substituted or unsubstituted aminocarbonyl group, but is not limited thereto. All the substituents may have a substituent other than hydrogen. The substituent of the “substituted A group” is preferably not the A group. Specifically, the substituent of the “substituted alkyl group” is preferably not an alkyl group.

  In the present specification, C1, C2,..., Cn represent the number of carbon atoms (where n represents an arbitrary positive integer). Therefore, C1 is used to represent a substituent having 1 carbon.

  In the present specification, the “phosphorus compound” is a compound containing phosphorus in the structure.

As used herein, “alkyne” refers to an aliphatic hydrocarbon having one triple bond in the molecule, such as acetylene, and is generally represented by C _n H _{2n− 2} (where n is 2 This is a positive integer. “Substituted alkyne” refers to an alkyne in which H of the alkyne is substituted with a substituent specified below. Specific examples include C2-C3 alkyne, C2-C4 alkyne, C2-C5 alkyne, C2-C6 alkyne, C2-C7 alkyne, C2-C8 alkyne, C2-C9 alkyne, C2-C10 alkyne, C2-C11 alkyne, C2-C20 alkyne, C2-C3 substituted alkyne, C2-C4 substituted alkyne, C2-C5 substituted alkyne, C2-C6 substituted alkyne, C2-C7 substituted alkyne, C2-C8 substituted alkyne, C2-C9 substituted alkyne, C2-C10 It can be a substituted alkyne, a C2-C11 substituted alkyne or a C2-C20 substituted alkyne. Here, for example, C2 to C10 alkyne means, for example, a linear or branched alkyne containing 2 to 10 carbon atoms, and includes acetylene (CH≡CH), propyne (CH ₃ C≡CH), 1 -Butyne (CH≡C ₃ H ₅ ), 2-butyne (CH ₃ C≡CCH ₃ ), 1-pentene (CH ₂ ≡C ₅ H ₆ ), 2-pentene (CH ₃ CH≡CC ₂ H ₄ ), etc. Is exemplified. For example, a C2-C10 substituted alkyne refers to a C2-C10 alkyne, in which one or more hydrogen atoms are substituted with a substituent.

  In the present specification, the “halogen group” is one of elements such as chlorine (Cl), bromine (Br), and iodine (I) belonging to Group 17 of the periodic table (referred to as Group 17 in the recent definition). A valent group.

In the present specification, the “alkyl group” refers to a monovalent group generated by losing one hydrogen atom from an aliphatic hydrocarbon (alkane) such as methane, ethane, or propane, and is generally represented by C _n H _{2n + 1} −. Where n is a positive integer. Alkyl can be linear or branched. In the present specification, the “substituted alkyl group” refers to a group in which alkyl hydrogen is substituted. Specific examples thereof include C1-C2 alkyl, C1-C3 alkyl, C1-C4 alkyl, C1-C5 alkyl, C1-C6 alkyl, C1-C7 alkyl, C1-C8 alkyl, C1-C9 alkyl, C1-C10 alkyl. C1-C11 alkyl or C1-C20 alkyl, C1-C2 substituted alkyl, C1-C3 substituted alkyl, C1-C4 substituted alkyl, C1-C5 substituted alkyl, C1-C6 substituted alkyl, C1-C7 substituted alkyl, C1-C8 It can be substituted alkyl, C1-C9 substituted alkyl, C1-C10 substituted alkyl, C1-C11 substituted alkyl or C1-C20 substituted alkyl. Here, for example, C1-C10 alkyl means linear or branched alkyl having 1 to 10 carbon atoms, methyl (CH _3- ), ethyl (C ₂ H _5- ), n-propyl. _{(CH 3 CH 2 CH 2 -} ), isopropyl _{((CH 3) 2 CH -} ), n- butyl _{(CH 3 CH 2 CH 2 CH} 2 -), n- pentyl _{(CH 3 CH 2 CH 2 CH} 2 CH 2 -), n-hexyl _{(CH 3 CH 2 CH 2 CH} 2 CH 2 CH 2 -), n- heptyl _{(CH 3 CH 2 CH 2 CH} 2 CH 2 CH 2 CH 2 -), n- octyl _(CH 3 CH _{2 CH 2 CH 2 CH 2 CH} 2 CH 2 CH 2 -), n- nonyl _{(CH 3 CH 2 CH 2 CH} 2 CH 2 CH 2 CH 2 CH 2 CH 2 -), n- decyl _(CH 3 CH 2 CH _{2 CH 2 CH 2 CH 2 CH 2} CH 2 CH 2 CH 2 -), - C (CH 3) 2 CH 2 CH 2 CH (CH 3) 2, -CH 2 CH (CH 3) such as ₂ are exemplified. Further, for example, C1-C10 substituted alkyl refers to C1-C10 alkyl, in which one or more hydrogen atoms are substituted with a substituent.
In addition, “a group that is not a substituted or unsubstituted alkyl group” means a hydrogen, halogen group, substituted or unsubstituted cycloalkyl group, substituted or unsubstituted alkoxy group, substituted or unsubstituted heterocyclic group, substituted or non-substituted group. A substituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted aryloxy group, a substituted or unsubstituted thioalkoxy group, a substituted or unsubstituted alkoxycarbonyl group, a substituted or unsubstituted alkylcarbonyl group, or Although it refers to a substituted or unsubstituted aminocarbonyl group, it is not limited thereto.

  In the present specification, the “cycloalkyl group” refers to an alkyl having a cyclic structure. Specific examples include C3-C4 cycloalkyl, C3-C5 cycloalkyl, C3-C6 cycloalkyl, C3-C7 cycloalkyl, C3-C8 cycloalkyl, C3-C9 cycloalkyl, C3-C10 cycloalkyl, C3-C11. Cycloalkyl, C3-C20 cycloalkyl, C3-C4 substituted cycloalkyl, C3-C5 substituted cycloalkyl, C3-C6 substituted cycloalkyl, C3-C7 substituted cycloalkyl, C3-C8 substituted cycloalkyl, C3-C9 substituted cycloalkyl , C3-C10 substituted cycloalkyl, C3-C11 substituted cycloalkyl or C3-C20 substituted cycloalkyl. For example, cycloalkyl is exemplified by cyclopropyl, cyclohexyl and the like. “Substituted cycloalkyl group” refers to a group in which cycloalkyl hydrogen is substituted.

In the present specification, the “alkoxy group” refers to a monovalent group generated by loss of a hydrogen atom of a hydroxy group of an alcohol, and is generally represented by C _n H _{2n + 1} O— (where n is 1 or more). Is an integer). Specific examples include C1-C2 alkoxy, C1-C3 alkoxy, C1-C4 alkoxy, C1-C5 alkoxy, C1-C6 alkoxy, C1-C7 alkoxy, C1-C8 alkoxy, C1-C9 alkoxy, C1-C10 alkoxy, C1-C11 alkoxy, C1-C20 alkoxy, C1-C2 substituted alkoxy, C1-C3 substituted alkoxy, C1-C4 substituted alkoxy, C1-C5 substituted alkoxy, C1-C6 substituted alkoxy, C1-C7 substituted alkoxy, C1-C8 substituted It can be alkoxy, C1-C9 substituted alkoxy, C1-C10 substituted alkoxy, C1-C11 substituted alkoxy or C1-C20 substituted alkoxy. Here, for example, C1-C10 alkoxy means linear or branched alkoxy containing 1 to 10 carbon atoms, and includes methoxy (CH ₃ O—), ethoxy (C ₂ H ₅ O—), An example is n-propoxy (CH ₃ CH ₂ CH ₂ O—). “Substituted alkoxy group” refers to a group in which hydrogen of an alkoxy group is substituted.

  As used herein, “heterocyclic group” refers to a group having a cyclic structure including carbon and heteroatoms. Here, the hetero atom is selected from the group consisting of O, S and N, and may be the same or different, and may be contained in one or more than one. Heterocyclic groups can be aromatic or non-aromatic and can be monocyclic or polycyclic. The heterocyclic group may be substituted. “Substituted heterocyclic group” refers to a group in which hydrogen of the heterocyclic group is substituted.

In the present specification, the “aryl group” refers to a group formed by elimination of one hydrogen atom bonded to an aromatic hydrocarbon ring. From benzene, a phenyl group (C ₆ H ₅ —), from toluene, a tolyl group (CH ₃ C ₆ H ₄ —), from xylene, a xylyl group ((CH ₃ ) ₂ C ₆ H ₃ —), from naphthalene, naphthyl group _(C 10 _H 8 -), phenanthryl group from phenanthrene _(C 14 _H 9 -), anthracenyl groups _(C 14 _H 9 -) from anthracene, tetracenyl group from tetracene _(C 18 _{H 11} -), from chrysene chrysenyl group _(C 18 _{H 11} -), the pyrenyl group from pyrene _(C 18 _{H 11} -), from benzopyrene, benzopyrenyl group _(C 20 _{H 11} -) pentacenyl group of pentacene _(C 22 _{H 13} -) is Be guided.

  In the present specification, the “heteroaryl group” refers to a group in which one or more carbon atoms constituting the aromatic hydrocarbon ring are substituted with a heteroatom. Examples include, but are not limited to, pyridine, pyrrole, thiophene, furan, imidazole, oxazole, thiazole, indole, quinoline, isoquinoline, quinoxaline, pyrazine, and benzimidazole.

In the present specification, the “aryloxy group” refers to a monovalent group formed by losing a hydrogen atom of a hydroxy group of an aryl group substituted by a hydroxy group. For example, but not limited thereto, C _{6 H 5 O-, CH 3 C} 6 H 4 O -, (CH 3) 2 C 6 H 3 O-, C 10 H 8 O- and the like.

  In this specification, the “thioalkoxy group” is a group in which the oxygen atom of the “alkoxy group” is substituted with a sulfur atom, and is generally represented by —SR (where R is an alkyl group).

  In the present specification, the “alkoxycarbonyl group” refers to a group represented by —C (O) OR (where R is an alkyl group). “Substituted alkoxycarbonyl group” refers to an alkoxycarbonyl group in which hydrogen is substituted.

In the present specification, the “alkylcarbonyl group” refers to a monovalent group formed by removing OH from a carboxylic acid. Representative examples of the alkylcarbonyl group include acetyl (CH ₃ CO—), benzoyl (C ₆ H ₅ CO—), and the like. “Substituted alkylcarbonyl group” refers to a group in which hydrogen of an alkyl group is substituted.

  In the present specification, the “aminocarbonyl group” is a group obtained by substituting hydrogen of ammonia or amine with an acid group (acyl group). “Substituted aminocarbonyl group” refers to a group in which hydrogen on nitrogen is substituted. An aminocarbonyl group is also referred to as an amide.

  As used herein, “base” refers to a substance that receives a proton, according to the Bronsted-Lorry definition. Although not limited to this, For example, an alkali metal, an alkoxy alkali metal, an alkali metal hydroxide, etc. are mentioned.

  As used herein, “alkoxyalkali metal” is a compound represented by the chemical formula ROM (wherein R is a substituted or unsubstituted alkyl group, and M is an alkali metal), such as sodium methoxide, Examples include potassium methoxide, sodium ethoxide, potassium ethoxide, tertiary butoxide sodium, and tertiary butoxide potassium.

  As used herein, “alkali metal hydroxide” refers to lithium hydroxide, sodium hydroxide, potassium hydroxide, rubidium hydroxide, cesium hydroxide and francium hydroxide.

  In the present specification, the “ether solvent” is one having an ether bond in a solvent molecule, for example, tetrahydrofuran (THF), diethyl ether, dioxane, 1,2-dimethoxyethane (DME), methyl -Tert-butyl ether (MTBE), cyclopentyl methyl ether (CPME), tetrahydropyran, diisopropyl ether, ethylene glycol monoethyl ether, ethylene glycol monomethyl ether, ethylene glycol diethyl ether, ethylene glycol dimethyl ether, ethylene glycol butyl ether, diethylene glycol monomethyl ether, propylene Glycol monoethyl ether, propylene glycol dimethyl ether, butyl methyl ether, diisopropyl ether Le, anisole, ethyl phenyl ether, diphenyl ether, and the like.

In this specification, the “phenethyl group” refers to a group represented by —CH ₂ CH ₂ Ph, and the “substituted phenethyl group” is a group in which hydrogen of the phenethyl group is substituted.

  In the present specification, “group other than phenethyl group” means hydrogen, halogen group, unsubstituted alkyl group, substituted or unsubstituted cycloalkyl group, substituted or unsubstituted alkoxy group, substituted or unsubstituted heterocyclic group Substituted or unsubstituted aryl group, substituted or unsubstituted heteroaryl group, substituted or unsubstituted aryloxy group, substituted or unsubstituted thioalkoxy group, substituted or unsubstituted alkoxycarbonyl group, substituted or unsubstituted It is a group selected from the group consisting of an alkylcarbonyl group and a substituted or unsubstituted aminocarbonyl group.

  In the present specification, the “catalytic amount” refers to a catalytic amount when the required amount of a reagent (for example, a base) with respect to a mole of the substrate is theoretically half or less of a mole.

  In the present specification, the term “phase transfer catalyst” refers to a case where chemical species to be reacted exist in two phases and carry one chemical species and carry it to the layer where the other chemical species exists. This refers to a catalyst that causes a reaction. For example, quaternary amines, crown ethers, cryptants and the like can be mentioned.

  As used herein, “homogeneous solvent” refers to a solvent having no interface in the solution. The homogeneous solvent may be one type of solvent or a combination of a plurality of solvents. For example, when a combination solvent that is arbitrarily mixed is used, such as THF / diethyl ether, a boundary solvent is not present in the solution, and thus a uniform solvent is used, while a combination solvent that is divided into two layers such as water / benzene is used. In this case, since a boundary surface exists between water and benzene, it is not a uniform solvent. An engineer in the field can appropriately determine whether or not two types of solvents become a homogeneous solvent. Whether or not the two types of solvents become a uniform solvent is not affected by the mixing ratio of the solvents. In the present specification, when all the raw materials are dissolved in this homogeneous solvent at the start of the reaction, even if the product gradually precipitates as a solid during the reaction, it is within the range of the reaction using the homogeneous solvent. Is included.

  “Condition without phase transfer catalyst” naturally includes that the reaction takes place in one phase, ie, “homogeneous solvent”. In addition, when the reaction is carried out in a plurality of phases, it means that no reagent that dissolves in all phases is present in the reaction system.

(Description of Preferred Embodiment)
Hereinafter, preferred embodiments of the present invention will be described. The embodiments provided below are provided for a better understanding of the present invention, and it is understood that the scope of the present invention should not be limited to the following description. Therefore, it is obvious that those skilled in the art can make appropriate modifications within the scope of the present invention with reference to the description in the present specification. It will also be appreciated that the following embodiments of the invention may be used alone or in combination.

In one aspect, the present invention provides the following general formula:

(Where
R ¹ and R ² are each independently hydrogen, halogen group, substituted or unsubstituted alkyl group, substituted or unsubstituted cycloalkyl group, substituted or unsubstituted alkoxy group, substituted or unsubstituted heterocyclic group, substituted Or an unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted aryloxy group, a substituted or unsubstituted thioalkoxy group, a substituted or unsubstituted alkoxycarbonyl group, a substituted or unsubstituted alkylcarbonyl Selected from the group consisting of a group and a substituted or unsubstituted aminocarbonyl group,
R ³ is selected from the group consisting of a substituted or unsubstituted alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted aryl group, and a substituted or unsubstituted heteroaryl group. Which is a selected group) or a salt thereof, which comprises:

And R ³ ₂ P (O) H
In the presence of a catalytic amount of a base in an ethereal solvent to form the compound or a salt thereof. Although not wishing to be bound by theory, in order to selectively obtain an α, β-adduct by the double addition reaction of phosphine oxide to an alkyne in an ether solvent, the end of the alkyne is substituted with a cyano group. It was thought that it was necessary. This is because when one phosphonyl group is introduced into the alkyne due to the presence of the cyano group at the alkyne end,

This is because the alkene introduced with one phosphine oxide as described above is considered to prevent the formation of an α, α-adduct by taking a five-membered ring transition state. It was unexpectedly found that the reaction proceeds in an ether solvent even if the alkyne end is not substituted with a cyano group.

In one aspect, the present invention provides the following general formula:

(Where
R ¹ and R ² are each independently hydrogen, halogen group, substituted or unsubstituted alkyl group, substituted or unsubstituted cycloalkyl group, substituted or unsubstituted alkoxy group, substituted or unsubstituted heterocyclic group, substituted Or an unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted aryloxy group, a substituted or unsubstituted thioalkoxy group, a substituted or unsubstituted alkoxycarbonyl group, a substituted or unsubstituted alkylcarbonyl Selected from the group consisting of a group and a substituted or unsubstituted aminocarbonyl group,
R ³ is a group other than a substituted or unsubstituted phenethyl group)
A method for producing a compound represented by the formula:

And R ³ ₂ P (O) H
Are reacted in the presence of a catalytic amount of a base to form the compound or a salt thereof. While not wishing to be bound by theory, in conventional phosphine oxide double addition reactions to alkynes with bases, the substituents on the phosphorus of the phosphine oxide are limited to substituted or unsubstituted phenethyl groups, and the reaction No investigation was made on the mechanism. This time, even if the substituent on the phosphorus is a group other than a substituted or unsubstituted phenethyl group, it became clear that the reaction proceeds using a catalytic amount of base and the desired product is obtained in high yield. .

One of the reaction mechanisms conceivable in the reaction of the present invention is the reaction mechanism shown below, but is not limited thereto.

That is, the base first takes the proton of the phosphorus compound, and the phosphine oxide anion A is generated. Next, the phosphine oxide anion A reacts with the alkyne and the purified vinyl anion B reacts with the proton to obtain the compound C. This is a reaction mechanism in which a compound containing two phosphine oxides is obtained by reacting this compound C with a phosphine oxide anion A and a purified anion and proton. This reaction mechanism is

In ^t BuOLi presence of a catalytic amount, by reaction with an alkene α and diphenylphosphine oxide, although compounds phosphine oxide was introduced two β is supported by the fact that is generated, but is not limited thereto.

  In one preferred embodiment, the ether solvent is tetrahydrofuran (THF), diethyl ether, dioxane, 1,2-dimethoxyethane (DME), methyl-tert-butyl ether (MTBE), cyclopentyl methyl ether (CPME), phenyl. Selected from the group consisting of methyl ether, tetrahydropyran and diisopropyl ether, preferably tetrahydrofuran (THF). Although not wishing to be bound by theory, ether solvents are easier to handle than DMSO.

  In one preferred embodiment, the group other than the substituted or unsubstituted phenethyl group is a substituted or unsubstituted alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted group. Selected from the group consisting of aryl groups and substituted or unsubstituted heteroaryl groups.

  In one preferred embodiment, the reaction is carried out in the absence of a phase transfer catalyst. The double addition reaction of diphenylphosphine oxide to phenylacetylene using a phase transfer catalyst is known. Although not wishing to be bound by theory, by adding a phase transfer catalyst to a two-phase solvent system of an aqueous phase and an organic phase in which inorganic salts and an organic compound that is sparingly soluble in water are dissolved, a water-soluble inorganic salt is obtained. It is known that the organic phase shifts to a homogeneous phase reaction in the organic phase and the reaction rate is remarkably increased. It has now been found that the reaction proceeds efficiently even in a single phase. Further, since it is not necessary to add inorganic salts and water-insoluble organic compounds or a phase transfer catalyst to the reaction system, there is an advantage that the experimental operation and the purification of the product become easier.

  In a further preferred embodiment, the reaction is performed in a single solvent. Although not wishing to be bound by theory, there is an advantage that the experimental operation becomes simpler because it is not necessary to add a plurality of solvents to the reaction system.

  In a further preferred embodiment, the base is an alkoxy alkali metal or alkali metal hydroxide or a mixture thereof. Although not wishing to be bound by theory, it is because alkoxyalkali metal and alkali metal hydroxide are strong bases, and thus the reaction can proceed efficiently. Preferably, the alkoxy alkali metal is sodium tert-butoxide, potassium tert-butoxide or lithium tert-butoxide, and the alkali metal hydroxide is lithium hydroxide, sodium hydroxide or potassium hydroxide.

In one aspect, the present invention provides the following general formula:

(In the formula, when R ¹ is a substituted or unsubstituted alkyl group, R ² is a halogen group, a substituted or unsubstituted alkyl group, a substituted or unsubstituted cycloalkyl group, or a substituted or unsubstituted alkoxy group. Substituted or unsubstituted heterocyclic group, substituted or unsubstituted aryl group, substituted or unsubstituted heteroaryl group, substituted or unsubstituted aryloxy group, substituted or unsubstituted thioalkoxy group, substituted or unsubstituted Selected from the group consisting of alkoxycarbonyl groups, substituted or unsubstituted alkylcarbonyl groups and substituted or unsubstituted aminocarbonyl groups;
When R ¹ is a group that is not a substituted or unsubstituted alkyl group, R ² is hydrogen, a halogen group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted hetero group. Ring group, substituted or unsubstituted aryl group, substituted or unsubstituted heteroaryl group, substituted or unsubstituted aryloxy group, substituted or unsubstituted thioalkoxy group, substituted or unsubstituted alkoxycarbonyl group, substituted or unsubstituted Selected from the group consisting of substituted alkylcarbonyl groups and substituted or unsubstituted aminocarbonyl groups;
R ³ is selected from the group consisting of a substituted or unsubstituted alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted aryl group, and a substituted or unsubstituted heteroaryl group. (Wherein R ³ is not a phenethyl group) or a salt thereof, provided that the compound is

Provided is a compound or salt thereof.

In one preferred embodiment, the compound has the general formula:

(In the formula, when R ¹ is a substituted or unsubstituted alkyl group or hydrogen, R ² is a halogen group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted hetero group, A group consisting of a cyclic group, a substituted or unsubstituted aryloxy group, a substituted or unsubstituted thioalkoxy group, a substituted or unsubstituted alkoxycarbonyl group, a substituted or unsubstituted alkylcarbonyl group, and a substituted or unsubstituted aminocarbonyl group Selected from
When R ¹ is a group that is not hydrogen and is not a substituted or unsubstituted alkyl group, R ² is a halogen group, a substituted or unsubstituted alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted group Alkoxy group, substituted or unsubstituted heterocyclic group, substituted or unsubstituted aryl group, substituted or unsubstituted heteroaryl group, substituted or unsubstituted aryloxy group, substituted or unsubstituted thioalkoxy group, substituted or unsubstituted Selected from the group consisting of a substituted alkoxycarbonyl group, a substituted or unsubstituted alkylcarbonyl group and a substituted or unsubstituted aminocarbonyl group;
R ³ is selected from the group consisting of a substituted or unsubstituted alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted aryl group, and a substituted or unsubstituted heteroaryl group. But R ³ is not a phenethyl group).

In a further preferred embodiment, the compound is

Selected from the group consisting of Although not wishing to be bound by theory, these compounds are compounds synthesized for the first time by this reaction.

  In one aspect, the present invention provides a flame retardant comprising the above compound or a salt thereof.

(General production example of phosphorus compound of the present invention)
In an inert gas (for example, nitrogen) atmosphere,
R ³ ₂ P (O) H
(Wherein R ³ represents a substituted or unsubstituted alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted aryl group, and a substituted or unsubstituted heteroaryl group. A suitable base (eg lithium tert-butoxide 0.05 mmol) in a reaction vessel (eg glass Schlenk) and a suitable solvent, for example diphenylphosphine oxide 0.2 mmol) (Eg, tetrahydrofuran (THF) (0.15 mL)) is added to dissolve the phosphorus compound and base.

(Wherein R ¹ and R ² are each independently hydrogen, a substituted or unsubstituted alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted aryl group, and A group selected from the group consisting of substituted or unsubstituted heteroaryl groups, for example

0.1 mmol) and stir at an appropriate reaction temperature (eg 70 ° C.) for an appropriate time (eg 4 hours) (if necessary, perform NMR analysis at this stage). The reaction is quenched (eg by adding methanol) and the solvent is distilled off. After that (for example, using GPC or recrystallization)

For example

Get.

By the method of the invention, for example

Can be obtained.

  References such as scientific literature, patents and patent applications cited herein are hereby incorporated by reference in their entirety to the same extent as if each was specifically described.

  The present invention has been described with reference to the preferred embodiments for easy understanding. Hereinafter, the present invention will be described based on examples. However, the above description and the following examples are provided for illustrative purposes only and are not provided for the purpose of limiting the present invention. Accordingly, the scope of the invention is not limited to the embodiments or examples specifically described herein, but is limited only by the claims.

  The present invention will be described more specifically with reference to the following examples and comparative examples. However, the present invention is not construed as being limited thereto, and examples obtained by appropriately combining technical means disclosed in each example. Are also included in the scope of the present invention.

Moreover, the abbreviation used in this specification represents the following meaning.
Bu: butyl Cy: cyclohexyl GC: gas chromatography IR: infrared spectroscopy Me: methyl mp: melting point NMR: nuclear magnetic resonance Ph: phenyl rt: room temperature (for example, 15 ° C. to 25 ° C.)
^t Bu: tert-butyl THF: tetrahydrofuran

Proton nuclear magnetic resonance ( ¹ H NMR) spectra were recorded on a JNM-JNM-ECX400 (400 MHz) FT NMR system using deuterated chloroform as the measurement solvent. A nuclear magnetic resonance ( ³¹ P NMR) spectrum of phosphorus was recorded with a JMN-JX-JX400 (162 MHz) FT NMR system using deuterated chloroform as a measurement solvent. Chemical shifts were expressed in parts per million (ppm) and the residual solvent signal was used as a reference. NMR abbreviations are used as follows: s = singlet, d = doublet, dd = double doublet, ddd = double doublet, dt = double triplet, t = triplet, td = triple doublet, tt = triple triplet, q = Quartet, m = multiplet, br = broad, bs = broad singlet, bt = broad triplet.

  The GC spectrum was measured with Shimadzu GC-2010 or GC-2010plus, and high resolution mass spectrometry was measured with JEOL JMS700.

As the THF, there was used no tetrahydrofuran (dehydration) stabilizer manufactured by Kanto Chemical Co., Inc.
General organic solvents such as methanol used the first grade made by Sigma-Aldrich Japan.
The first grade grade made by Sigma Aldrich Japan was used for chloroform.

As the acetylene gas, a DMF dissolution grade product manufactured by Iwatani Corporation was used.
The phenyl acetylene used was Tokyo Chemical Industry.
Katayama Chemical Co., Ltd. product was used for the phosphorus compound.

Lithium hydroxide used was Kishida Chemical's first grade.
Sodium hydroxide and potassium hydroxide used the first grade grade made by Sigma-Aldrich Japan.
Aldrich products sold as lithium t-butoxide THF solvent (concentration 1M) were used.
Other base catalysts used were Tokyo Kasei products.

Example 1 Base-catalyzed addition of diphenylphosphine oxide to ethynylbenzene

As a model reaction, the ^t BuOLi (5mol%) ethynyl benzene (0.1 mmol) presence, an experiment was performed was added to diphenyl phosphine oxide in THF (0.15mL) (0.2mmol). When the mixture was stirred at 70 ° C. for 4 hours, ethynylbenzene as a starting material was completely consumed, and Compound 1 was quantitatively obtained (confirmed by GC).

(Example 2) Examination of base

The reaction was performed in the same procedure as in Example 1 using various bases. ^{t BuONa, t BuOK,} it was confirmed that proceeds by LiOH and NaOH.

(Example 3) Examination of phosphorus compounds Reaction was carried out by the following procedure using various phosphorus compounds.
Under a nitrogen atmosphere, 0.1 mmol of a phosphorus compound was charged into a glass Schlenk and dissolved in 0.15 mL of THF. Next, 0.2 mmol of phenylacetylene and 5 mol% of the t-BuOLi solution were added, and the mixture was heated and stirred at 70 ° C. The reaction solution was allowed to cool to room temperature, quenched with methanol, and the solvent was distilled off. Then, it isolated and refined using GPC and obtained the target object. The results are shown in Table 2. The reaction proceeded even when the substituent on phosphorus was changed to a cycloalkyl group or an alkyl group.

(Example 4) Examination of alkyne A reaction was carried out by the same procedure as in Example 1 except that entry 16 was used with various alkynes. Entry 16 reacted in the following procedure.
Diphenylphosphine oxide and lithium hydroxide were weighed in an autoclave reactor under a nitrogen atmosphere. After adding THF and stirring, the inside of the reactor was placed in an atmospheric acetylene atmosphere. The autoclave reactor was cooled in an ice bath, and the internal pressure was increased to 0.08 MPa with acetylene gas. Next, the ice bath was removed, and the mixture was heated and stirred using a hot water bath at 70 ° C. for 3 hours. Thereafter, the mixture was allowed to cool to room temperature, returned to normal pressure, and quenched with methanol. After the solvent was distilled off, the product was obtained by dissolving and recrystallizing in ethanol at 70 ° C.

The reaction proceeds even in sterically bulky aromatic alkynes such as 1-ethynyl-2,4,5-trimethylbenzene, 1-chloro-2-ethynylbenzene and 1-ethynylnaphthalene, and is produced in a high yield. I was able to get things. Even when a heteroaromatic alkyne such as 2-ethynylpyridine was used as a substrate, the target product could be obtained in contrast to addition with palladium or rhodium catalyst. Furthermore, it was confirmed that the reaction proceeded even when acetylene gas (entry 16) and internal alkyne (entry 17) were used as alkynes.

(Example 5) Examination of reaction in the presence of water

Under a nitrogen atmosphere, 40 mg of diphenylphosphine oxide, 0.15 mL of THF, and 15 μL of 1-octyne were dissolved in a 1 mL glass vial with a septum. (Entry 1: 3 μL of purified water was added.) 10 μL of t-BuOLi / THF solution (concentration: 1M) was added thereto, and the mixture was heated and stirred at 70 ° C. for 18 hours (in air). Quenched added MeOH0.1ML, check the ¹ H NMR after concentration, confirmed the formation ratio of the by-products. Although by-products were observed in both entries 1 and 2, the reaction proceeded even in the presence of water and oxygen.

  As mentioned above, although this invention has been illustrated using preferable embodiment of this invention, it is understood that the scope of this invention should be construed only by the claims. Patents, patent applications, and other references cited herein should be incorporated by reference in their entirety, as if the contents themselves were specifically described herein. It is understood.

  The inventors have found a base-catalyzed double addition of phosphine oxides to alkynes. The compound obtained by the reaction of the present invention is effective as an additive-type flame retardant in a field requiring high electrical properties (insulating properties) such as a printed wiring board.

Claims (15)

The following general formula

(Where
R ¹ and R ² are each independently hydrogen, halogen group, substituted or unsubstituted alkyl group, substituted or unsubstituted cycloalkyl group, substituted or unsubstituted alkoxy group, substituted or unsubstituted heterocyclic group, substituted Or an unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted aryloxy group, a substituted or unsubstituted thioalkoxy group, a substituted or unsubstituted alkoxycarbonyl group, a substituted or unsubstituted alkylcarbonyl Selected from the group consisting of a group and a substituted or unsubstituted aminocarbonyl group,
R ³ is selected from the group consisting of a substituted or unsubstituted alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted aryl group, and a substituted or unsubstituted heteroaryl group. Is the group selected)
A method for producing a compound represented by the formula:

And R ³ ₂ P (O) H
And in the presence of a catalytic amount of a base in an ether solvent to form the compound or a salt thereof. The following general formula

(Where
R ¹ and R ² are each independently hydrogen, halogen group, substituted or unsubstituted alkyl group, substituted or unsubstituted cycloalkyl group, substituted or unsubstituted alkoxy group, substituted or unsubstituted heterocyclic group, substituted Or an unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted aryloxy group, a substituted or unsubstituted thioalkoxy group, a substituted or unsubstituted alkoxycarbonyl group, a substituted or unsubstituted alkylcarbonyl Selected from the group consisting of a group and a substituted or unsubstituted aminocarbonyl group,
R ³ is a group other than a substituted or unsubstituted phenethyl group)
A method for producing a compound represented by the formula:

And R ³ ₂ P (O) H
And in the presence of a catalytic amount of a base to produce the compound or a salt thereof. The ether solvents include tetrahydrofuran (THF), diethyl ether, dioxane, 1,2-dimethoxyethane (DME), methyl tert-butyl ether (MTBE), cyclopentyl methyl ether (CPME), phenyl methyl ether, tetrahydropyran and diisopropyl. The method of claim 1, selected from the group consisting of ethers. The method according to claim 1, wherein the ether solvent is tetrahydrofuran (THF). The group other than the substituted or unsubstituted phenethyl group includes an unsubstituted alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted aryl group, and a substituted or unsubstituted group. The method of claim 2, wherein the method is selected from the group consisting of heteroaryl groups. The method according to claim 2, wherein the reaction is carried out in the absence of a phase transfer catalyst. The method according to claim 2 or 6, wherein the reaction is carried out in a homogeneous solvent. The method according to any one of claims 1 to 7, wherein the base is an alkoxy alkali metal or an alkali metal hydroxide or a mixture thereof. 9. The method of claim 8, wherein the alkoxy alkali metal is sodium tert-butoxide, potassium tert-butoxide or lithium tert-butoxide. The method of claim 8, wherein the alkali metal hydroxide is lithium hydroxide, sodium hydroxide, or potassium hydroxide. The method according to any one of claims 1 to 10, wherein the reaction vessel does not contain water. The following general formula

(Where
When R ¹ is a substituted or unsubstituted alkyl group, R ² is a halogen group, a substituted or unsubstituted alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted alkoxy group, substituted or unsubstituted A substituted heterocyclic group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted aryloxy group, a substituted or unsubstituted thioalkoxy group, a substituted or unsubstituted alkoxycarbonyl group, Selected from the group consisting of a substituted or unsubstituted alkylcarbonyl group and a substituted or unsubstituted aminocarbonyl group;
When R ¹ is a group that is not a substituted or unsubstituted alkyl group (confirmed) R ² is hydrogen, a halogen group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted alkoxy group, a substituted or non-substituted group A substituted heterocyclic group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted aryloxy group, a substituted or unsubstituted thioalkoxy group, a substituted or unsubstituted alkoxycarbonyl group, Selected from the group consisting of a substituted or unsubstituted alkylcarbonyl group and a substituted or unsubstituted aminocarbonyl group;
R ³ is selected from the group consisting of a substituted or unsubstituted alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted aryl group, and a substituted or unsubstituted heteroaryl group. Selected, provided that R ³ is not a phenethyl group)
Or a salt thereof, provided that the compound is

Not a compound or salt thereof. The following general formula

(Where
When R ¹ is a substituted or unsubstituted alkyl group or hydrogen, R ² is a halogen group, a substituted or unsubstituted alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted alkoxy group, a substituted Or an unsubstituted heterocyclic group, a substituted or unsubstituted aryl group, a substituted or unsubstituted heteroaryl group, a substituted or unsubstituted aryloxy group, a substituted or unsubstituted thioalkoxy group, a substituted or unsubstituted alkoxycarbonyl Selected from the group consisting of a group, a substituted or unsubstituted alkylcarbonyl group and a substituted or unsubstituted aminocarbonyl group;
When R ¹ is a group that is not hydrogen and is not a substituted or unsubstituted alkyl group, R ² is a halogen group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted group Heterocyclic group, substituted or unsubstituted aryl group, substituted or unsubstituted heteroaryl group, substituted or unsubstituted aryloxy group, substituted or unsubstituted thioalkoxy group, substituted or unsubstituted alkoxycarbonyl group, substituted or Selected from the group consisting of unsubstituted alkylcarbonyl groups and substituted or unsubstituted aminocarbonyl groups;
R ³ is selected from the group consisting of a substituted or unsubstituted alkyl group, a substituted or unsubstituted cycloalkyl group, a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted aryl group, and a substituted or unsubstituted heteroaryl group. Selected, provided that R ³ is not a phenethyl group)
The compound or its salt of Claim 12 shown by these.
The compound or its salt of Claim 12 or 13 selected from the group consisting of. The flame retardant containing the compound or its salt of any one of Claims 12-14.