WO2017111087A1

WO2017111087A1 - Monofluorophosphate ester salt, method for producing same, and fluorine ion-releasing composition

Info

Publication number: WO2017111087A1
Application number: PCT/JP2016/088497
Authority: WO
Inventors: 紀敬坂口; 静郁桂; 雅士山本; 西田　哲郎
Original assignee: ステラケミファ株式会社
Priority date: 2015-12-25
Filing date: 2016-12-22
Publication date: 2017-06-29
Also published as: JP2017119690A; JP6925604B2

Abstract

[Problem] To provide: a monofluorophosphate ester salt capable of the sustained release of fluorine ions at a significant amount of release; a method for producing the monofluorophosphate ester salt; and a fluorine ion-releasing composition. [Solution] The monofluorophosphate ester salt of the present invention is characterized by being represented by chemical formula (1). (Mⁿ⁺ represents any one species selected from the group consisting of a hydrogen ion, alkali metal ion, alkaline-earth metal ion, transition metal ion, rare-earth element ion, zinc ion, aluminum ion, gallium ion, indium ion, germanium ion, tin ion, lead ion, and onium ion. R¹ represents a hydrocarbon group that has 1 to 20 carbons or a hydrocarbon group that has 1 to 20 carbons and that has at least one of any of a halogen atom, a heteroatom, and an unsaturated bond. n represents the valence.)

Description

Monofluorophosphate ester salt, process for producing the same, and fluorine ion releasing composition

The present invention relates to a monofluorophosphate ester salt excellent in sustained release of fluorine ions, a production method thereof, and a fluoride ion releasing composition.

Examples of the fluorine-releasing compound capable of releasing fluorine ions include those contained in oral compositions and dental compositions.

Examples of the fluorine releasing compound used in the oral composition include SnF ₂ , NaF, and Na ₂ PO ₃ F (MFP: sodium monofluorophosphate) (see Patent Document 1 below). These fluorine-releasing compounds are known to be formulated for the purpose of preventing dental caries, which is one of oral diseases.

Examples of the fluorine-releasing compound used in the dental composition include, for example, a dental composition having fluorine ion-releasing properties and X-ray contrast properties disclosed in Patent Document 2 below, and Patent Document 3 below. The fluorine ion releasing substance currently disclosed is mentioned. These fluorine-releasing compounds are used in composite resins and glass ionomer cements as so-called fillings for the purpose of repairing defects such as teeth.

However, it is difficult for conventional fluorine-releasing compounds to release a certain amount of fluorine ions continuously, and it is hoped that the property of releasing the fluorine ions in a certain amount over a long period of time, that is, so-called sustained release is improved. It is rare.

JP 2003-128530 A JP 2004-67597 A JP 2003-81731 A

The present invention has been made in view of the above problems, and its object is to provide a monofluorophosphate ester salt capable of continuously releasing fluorine ions in a significant release amount, a method for producing the same, and fluorine ion releasing properties. It is to provide a composition.

The inventors of the present application have studied to solve the conventional problems, and as a result, the monofluorophosphate ester salt exhibits a function of continuously releasing a certain amount of fluorine ions by a reaction via a specific enzyme. As a result, the present invention has been completed.

That is, the monofluorophosphate ester salt according to the present invention is characterized by being represented by the following chemical formula (1) in order to solve the above problems.

(However, M ^{n +} is hydrogen ion, alkali metal ion, alkaline earth metal ion, transition metal ion, rare earth element ion, zinc ion, aluminum ion, gallium ion, indium ion, germanium ion, tin ion, lead ion and onium. R ¹ represents any one selected from the group consisting of ions, wherein R ¹ is a hydrocarbon group having 1 to 20 carbon atoms, or a range having 1 to 20 carbon atoms, and is a halogen atom, heteroatom or Represents a hydrocarbon group having at least one of saturated bonds, wherein n represents a valence.)

In the above configuration, the alkali metal ion is preferably any one selected from the group consisting of lithium ion, sodium ion, potassium ion, rubidium ion, and cesium ion.

In the above-described configuration, the alkaline earth metal ion is preferably any one selected from the group consisting of magnesium ion, calcium ion, strontium ion, and barium ion.

Further, in the above configuration, the transition metal ion is any one selected from the group consisting of manganese ions, cobalt ions, nickel ions, chromium ions, copper ions, silver ions, molybdenum ions, tungsten ions, and vanadium ions. One type is preferable.

In the above structure, the rare earth element ion is scandium ion, yttrium ion, lanthanum ion, cerium ion, praseodymium ion, neodymium ion, promethium ion, samarium ion, europium ion, gadolinium ion, terbium ion, dysprosium. It is preferably any one selected from the group consisting of ions, holmium ions, erbium ions, thulium ions, ytterbium ions, and lutetium ions.

In the above structure, the onium ions are ammonium ions, primary ammonium ions, secondary ammonium ions, tertiary ammonium ions, quaternary ammonium ions, quaternary phosphonium ions and sulfonium ions. It is preferably any one selected from the group consisting of

In order to solve the above-mentioned problem, the method for producing a monofluorophosphate ester salt according to the present invention is obtained by fluorinating a monohalophosphate diester represented by the following chemical formula (2) and represented by the following chemical formula (3). generating a monofluorophosphate diester, and the monofluorophosphate diester, M n ^{+ X 2} n ^(wherein M ^{n +} is an alkali metal ion, alkaline earth metal ions, transition metal ions, rare earth ions, X 1 represents any one selected from the group consisting of zinc ion, aluminum ion, gallium ion, indium ion, germanium ion, tin ion, lead ion and onium ion, wherein X ² is any one of F, Cl, Br or I. (Wherein n represents a valence) is reacted to form a molecule represented by the following chemical formula (1). Characterized by comprising a step of generating a fluoro phosphate salt.

(However, R ¹ and R ² are independently of each other a hydrocarbon group having 1 to 20 carbon atoms, or a carbon group having 1 to 20 carbon atoms, and having a halogen atom, a hetero atom or an unsaturated bond. Represents a hydrocarbon group having at least one of them, X ¹ represents a halogen atom other than F.)

(Wherein R ¹ and R ² are independently of each other a hydrocarbon group having 1 to 20 carbon atoms, or a group having 1 to 20 carbon atoms, and at least one of a halogen atom, a hetero atom and an unsaturated bond) Represents a hydrocarbon group having one.)

(However, said M ^{n +} is from hydrogen, alkali metal ions, alkaline earth metal ions, transition metal ions, rare earth element ions, zinc ions, aluminum ions, gallium ions, indium ions, germanium ions, tin ions, lead ions and onium ions. And R ¹ represents a hydrocarbon group having 1 to 20 carbon atoms, or a range of 1 to 20 carbon atoms, which is a halogen atom, a hetero atom, or an unsaturated bond. A hydrocarbon group having at least one of the above, wherein n represents a valence.)

The fluorine ion-releasing composition according to the present invention is characterized by containing a monofluorophosphate ester salt in order to solve the above-mentioned problems.

The oral composition according to the present invention is characterized by containing a monofluorophosphate ester salt in order to solve the above-mentioned problems.

The dental composition according to the present invention is characterized by containing a monofluorophosphate ester salt in order to solve the above-mentioned problems.

According to the present invention, the monofluorophosphate ester salt represented by the chemical formula (1) can release fluorine ions by a reaction via a specific enzyme, for example, phosphatase. Moreover, according to the monofluorophosphate ester salt having the above-described configuration, it is possible to continuously release fluorine ions in a constant amount, and to have sustained release properties such as excellent sustained release properties.

Furthermore, the fluoride ion-releasing composition of the present invention contains the monofluorophosphate ester salt, so that the fluoride ion can be continuously released by a reaction via a specific enzyme such as the phosphatase. And has a sustained release property such as efficient release of fluorine ions in a constant amount and excellent sustained release.

(Monofluorophosphate ester salt)
First, the monofluorophosphate ester salt according to the present embodiment will be described below.
The monofluorophosphate ester salt of the present embodiment is represented by the following chemical formula (1) and has a sustained release property of fluorine ions. The monofluorophosphate ester salt exhibits a function of releasing fluoride ions by a reaction via a specific enzyme, specifically, phosphatase. In addition, it has a sustained release property such as excellent release over time because it releases fluorine ions continuously over a long period of time and releases it in a constant amount.

Here, the sustained release of fluorine ions is the release of fluorine ions from a monofluorophosphate ester salt, and is a conventional fluorine ion releasing compound (for example, SnF ₂ , NaF, Na ₂ PO ₃ F, etc.). Compared with, it means a release that occurs over a long period of time when a significant amount of release can be obtained. The sustained release of fluoride ions is preferably a release that occurs over a period of at least 4 hours, at least 8 hours, or at least 24 hours.

Also, the sustained release of fluorine ions has a relatively constant or variable release rate. Furthermore, the sustained release of fluoride ions can be a continuous release. The continuity of fluorine ion release and the release amount can be controlled by the type and amount of the phosphatase and the mode of use.

The sustained release of fluorine ions means that the amount of fluorine ions released from the monofluorophosphate ester salt is constant (a constant amount). For example, it means that a more uniform fluorine ion release amount can be obtained as compared with conventional fluorine ion releasing compounds (for example, SnF ₂ , NaF, Na ₂ PO ₃ F, etc.).

Uniform release (sustained release property) of fluorine ions at a constant concentration can be evaluated by S (%) defined by the following formula. For example, when S (%) is a value close to 50%, it indicates that the release of fluorine ions is a constant amount even after a lapse of a certain time, which means that the sustained release property is excellent. Yes.
S (%) = (A ₁ −A ₀ ) / (A ₂ −A ₀ ) × 100 (where A ₀ represents the fluorine ion concentration at 0 hour, and A ₁ represents fluorine after elapse of t ₁ hour. (I ₂ represents the ion concentration, and A ₂ represents the fluorine ion concentration after elapse of t ₂ hours, where 2t ₁ = t ₂ )

Examples of the phosphatase include alkaline phosphatase, acid phosphatase, glucose-1-phosphatase, and protein phosphatase. Of these, acid phosphatase is preferred in the present embodiment.

In the chemical formula (1), M ^{n +} is hydrogen ion, alkali metal ion, alkaline earth metal ion, transition metal ion, rare earth element ion, zinc ion, aluminum ion, gallium ion, indium ion, germanium ion, tin ion, lead. It represents any one selected from the group consisting of ions and onium ions.

The alkali metal ion is not particularly limited and includes lithium ion, sodium ion, potassium ion, rubidium ion, cesium ion and the like. Of these alkali metal ions, potassium ions can impart a pain relieving effect on dentin hypersensitivity to monofluorophosphate esters.

Examples of the alkaline earth metal ions include magnesium ions, calcium ions, strontium ions, barium ions and the like.

The transition metal ion is not particularly limited, and examples thereof include manganese ions, cobalt ions, nickel ions, chromium ions, copper ions, silver ions, molybdenum ions, tungsten ions, vanadium ions, and the like. Of these transition metal ions, copper ions and silver ions can further impart antibacterial activity to the monofluorophosphate ester salt. This antibacterial activity is effective against periodontal bacteria such as P. gingivalis (Porphyromonas gingivalis) and F. nucleatum (Fusobacterium nucleatum), and caries such as S. mutans (Streptococcus mutans) and S. sobrinus (Streptococcus sobrinus). It is effective.

The rare earth element ion is not particularly limited, and for example, scandium ion, yttrium ion, lanthanum ion, cerium ion, praseodymium ion, neodymium ion, promethium ion, samarium ion, europium ion, gadolinium ion, terbium ion, dysprosium ion, holmium Ions, erbium ions, thulium ions, ytterbium ions, lutetium ions, and the like.

Other metal ion species include zinc ions, aluminum ions, gallium ions, indium ions, germanium ions, tin ions, lead ions, and the like. Of these metal ions, tin ions can further impart antibacterial activity to the monofluorophosphate ester salt. The target for which this antibacterial activity is effective is the aforementioned periodontal disease bacteria and caries.

The onium ion is not particularly limited, and ammonium ion (NH ⁴⁺ ), primary ammonium ion, secondary ammonium ion, tertiary ammonium ion, quaternary ammonium ion, quaternary phosphonium ion, sulfonium ion, etc. Is mentioned. The onium ion can further impart antibacterial activity to the monofluorophosphate ester salt. The target for which this antibacterial activity is effective is the aforementioned periodontal disease bacteria and caries.

The primary ammonium ion is not particularly limited, and examples thereof include methylammonium ion, ethylammonium ion, propylammonium ion, and isopropylammonium ion.

The secondary ammonium ion is not particularly limited, and for example, dimethylammonium ion, diethylammonium ion, dipropylammonium ion, dibutylammonium ion, ethylmethylammonium ion, methylpropylammonium ion, methylbutylammonium ion, propylbutylammonium Ion, diisopropylammonium ion and the like.

The tertiary ammonium ion is not particularly limited, and examples thereof include trimethylammonium ion, triethylammonium ion, tripropylammonium ammonium ion, tributylammonium ion, ethyldimethylammonium ion, diethylmethylammonium ion, triisopropylammonium ion, dimethylisopropyl. Ammonium ion, diethylisopropylammonium ion, dimethylpropylammonium ion, butyldimethylammonium ion, 1-methylpyrrolidinium ion, 1-ethylpyrrolidinium ion, 1-propylpyrrolidinium ion, 1-butylpropylpyrrolidinium ion, 1-methyl Imidazolium ion, 1-ethylimidazolium ion, 1-propyli Dazo potassium ion, 1-butyl imidazolium ion, pyrazolium ion, 1-methyl pyrazolium ion, 1-ethyl pyrazolium ion, 1-propyl pyrazolium ion, 1-butyl pyrazolium ion, pyridinium ion, and the like.

The quaternary ammonium forming the quaternary ammonium ion is not particularly limited, and examples thereof include aliphatic quaternary ammoniums, imidazoliums, pyridiniums, pyrazoliums, and pyridaziniums.

Further, the aliphatic quaternary ammoniums are not particularly limited, and examples thereof include tetraethylammonium, tetrapropylammonium, tetraisopropylammonium, trimethylethylammonium, dimethyldiethylammonium, methyltriethylammonium, trimethylpropylammonium, trimethylisopropylammonium, tetra Butylammonium, trimethylbutylammonium, trimethylpentylammonium, trimethylhexylammonium, 1-ethyl-1-methyl-pyrrolidinium, 1-butyl-1-methylpyrrolidinium, 1-ethyl-1-methyl-piperidinium, 1-butyl- 1-methylpiperidinium, octyltrimethylammonium, hexadecyltrimethylammonium, hexade Le (2-hydroxyethyl) dimethyl ammonium, allyl hexadecyl dimethyl ammonium and the like.

The imidazoliums are not particularly limited. For example, 1,3 dimethyl-imidazolium, 1-ethyl-3-methylimidazolium, 1-n-propyl-3-methylimidazolium, 1-n-butyl-3 -Methylimidazolium, 1-n-hexyl-3-methylimidazolium and the like.

The pyridiniums are not particularly limited, and examples thereof include 1-methylpyridinium, 1-ethylpyridinium, 1-n-propylpyridinium, 1-hexylpyridinium, cetylpyridinium and the like.

The pyrazoliums are not particularly limited. For example, 1,2-dimethylpyrazolium, 1-methyl-2-ethylpyrazolium, 1-propyl-2-methylpyrazolium, 1-methyl-2-butyl Pyrazolium, 1-methylpyrazolium, 3-methylpyrazolium, 4-methylpyrazolium, 4-iodopyrazolium, 4-bromopyrazolium, 4-iodo3-methylpyrazolium, 4 -Bromo-3-methylpyrazolium, 3-trifluoromethylpyrazolium.

The pyridaziniums are not particularly limited, and for example, 1-methylpyridazinium, 1-ethylpyridazinium, 1-propylpyridazinium, 1-butylpyridazinium, 3-methylpyridazinium Ni, 4-methylpyridazinium, 3-methoxypyridazinium, 3,6-dichloropyridazinium, 3,6-dichloro-4-methylpyridazinium, 3-chloro-6-methylpyri Examples include dazinium and 3-chloro-6-methoxypyridazinium.

The quaternary phosphonium forming the quaternary phosphonium ion is not particularly limited, and examples thereof include benzyltriphenylphosphonium, tetraethylphosphonium, and tetraphenylphosphonium.

The sulfonium forming the sulfonium ion is not particularly limited, and examples thereof include trimethylsulfonium, triphenylsulfonium, triethylsulfonium, and the like.

Among those listed above as examples of M ^{n +} , from the viewpoint of availability, lithium, sodium ion, potassium, magnesium, calcium, tin, tetraalkylammonium ion, alkylimidazolium ion, alkylpyrrolidinium ion, alkylpyridinium ion Is preferred.

In the chemical formula (1), R ¹ represents a hydrocarbon group or a hydrocarbon group having at least one of a halogen atom, a hetero atom, or an unsaturated bond (hereinafter referred to as “hydrocarbon group having a halogen atom”). .) The hydrocarbon group has 1 to 20 carbon atoms, preferably 1 to 10 carbon atoms. The hydrocarbon group having a halogen atom or the like has 1 to 20 carbon atoms, preferably 1 to 10 carbon atoms, more preferably 1 to 4 carbon atoms. The number of unsaturated bonds is preferably in the range of 1 to 10, more preferably in the range of 1 to 5, and particularly preferably in the range of 1 to 3.

The hydrocarbon group or a hydrocarbon group having a halogen atom or the like is not particularly limited, and examples thereof include a methyl group, an ethyl group, a propyl group, a butyl group, an isopropyl group, a pentyl group, a hexyl group, a heptyl group, and an octyl group. Cyclic alkyl groups, cyclic alkyl groups such as cyclopentyl group, cyclohexyl group, 2-iodoethyl group, 2-bromoethyl group, 2-chloroethyl group, 2-fluoroethyl group, 1,2-diiodoethyl group, 1,2-dibromoethyl Group, 1,2-dichloroethyl group, 1,2-difluoroethyl group, 2,2-diiodoethyl group, 2,2-dibromoethyl group, 2,2-dichloroethyl group, 2,2-difluoroethyl group, 2 , 2,2-tribromoethyl group, 2,2,2-trichloroethyl group, 2,2,2-trifluoroethyl group, hexafluoro -2-chain halogen-containing alkyl groups such as 2-propyl group, cyclic halogen-containing alkyl groups such as 2-iodocyclohexyl group, 2-bromocyclohexyl group, 2-chlorocyclohexyl group, 2-fluorocyclohexyl group, 2-propenyl group, Chain alkenyl groups such as isopropenyl group, 2-butenyl group and 3-butenyl group, cyclic alkenyl groups such as 2-cyclopentenyl group, 2-cyclohexenyl group and 3-cyclohexenyl group, 2-propynyl group, 1- Chain alkynyl groups such as butynyl group, 2-butynyl group, 3-butynyl group, 1-pentynyl group, 2-pentynyl group, 3-pentynyl group, 4-pentynyl group, phenyl group, 3-methoxyphenyl group, 4- Phenyl group such as methoxyphenyl group, 3,5-dimethoxyphenyl group, 4-phenoxyphenyl group, 2-iodine Phenyl group, 2-bromophenyl group, 2-chlorophenyl group, 2-fluorophenyl group, 3-iodophenyl group, 3-bromophenyl group, 3-chlorophenyl group, 3-fluorophenyl group, 4-iodophenyl group, 4 -Including bromophenyl group, 4-chlorophenyl group, 4-fluorophenyl group, 3,5-diiodophenyl group, 3,5-dibromophenyl group, 3,5-dichlorophenyl group, 3,5-difluorophenyl group, etc. And naphthyl groups such as a halogenphenyl group, a 1-naphthyl group, a 2-naphthyl group, and a 3-amino-2-naphthyl group.

The halogen atom means a fluorine, chlorine, bromine or iodine atom. The hydrocarbon group having a halogen atom means that part or all of the hydrogen in the hydrocarbon group may be substituted with any of these halogen atoms. Moreover, a hetero atom means atoms, such as oxygen, nitrogen, or sulfur. The hydrocarbon group having a hetero atom means that part or all of hydrogen and carbon in the hydrocarbon group may be substituted with any of these hetero atoms.

Specific examples of the hydrocarbon group having a hetero atom include a 2-methoxyethyl group, a 2- (2-methoxyethoxy) ethyl group, and a 2- (2- (2-methoxyethoxy) ethoxy) ethyl group. 2- (2- (2- (2-methoxyethoxy) ethoxy) ethoxy) ethyl group, 2-ethoxyethyl and the like.

In the chemical formula (1), n represents a valence. For example, when M is a monovalent cation, n = 1, when it is a divalent cation, n = 2, and when it is a trivalent cation, n = 3.

Specific examples of the monofluorophosphate ester salt represented by the chemical formula (1) include, for example, methyl sodium monofluorophosphate, ethyl sodium monofluorophosphate, propyl sodium monofluorophosphate, monofluorophosphate (2 , 2,2-trichloroethyl) sodium phosphate, sodium monofluorophosphate (2,2,2-trichloroethyl), sodium monofluorophosphate (1,1,1,3,3,3-hexachloroisopropyl), Sodium monofluorophosphate (2,2,2-trifluoroethyl), sodium monofluorophosphate (1,1,1,3,3,3-hexafluoroisopropyl), monofluorophosphate (2-methoxyethyl) Sodium, monofluorophosphate (2- (2-methoxyethoxy) ethyl) sodium , Sodium monofluorophosphate (2- (2- (2-methoxyethoxy) ethoxy) ethyl), sodium monofluorophosphate (2- (2- (2- (2-methoxyethoxy) ethoxy) ethoxy) ethyl) 1-ethyl-3-methylimidazolium monofluorophosphate, 1-ethyl-3-methylimidazolium monofluorophosphate, 1-ethyl-3-methylimidazolium monofluorophosphate (2,2,2 -Trichloroethyl), 1-ethyl-3-methylimidazolium monofluorophosphoric acid (2,2,2-trichloroethyl), 1-ethyl-3-methylimidazolium monofluorophosphoric acid (1,1,1,3 , 3,3-hexachloroisopropyl), 1-ethyl-3-methylimidazolium monofluorophosphate (2,2,2- Trifluoroethyl), 1-ethyl-3-methylimidazolium monofluorophosphate (2,2,2-trifluoroethyl), 1-ethyl-3-methylimidazolium monofluorophosphate (2,2,2- Trifluoroethyl), 1-ethyl-3-methylimidazolium monofluorophosphoric acid (1,1,1,3,3,3-hexafluoroisopropyl), 1-ethyl-3-methylimidazolium monofluorophosphoric acid ( 2-methoxyethyl), 1-ethyl-3-methylimidazolium monofluorophosphate (2- (2-methoxyethoxy) ethyl), 1-ethyl-3-methylimidazolium monofluorophosphate (2- (2- (2-methoxyethoxy) ethoxy) ethyl), 1-ethyl-3-methylimidazolium monofluorophosphate (2- (2- (2- ( 2-methoxyethoxy) ethoxy) ethoxy) ethyl), methyl triethylmethylammonium monofluorophosphate, ethyl triethylmethylammonium monofluorophosphate, propyl triethylmethylammonium monofluorophosphate, triethylmethylammonium monofluorophosphate (2,2 , 2-trichloroethyl), triethylmethylammonium monofluorophosphate (2,2,2-trichloroethyl), triethylmethylammonium monofluorophosphate (1,1,1,3,3,3-hexachloroisopropyl), triethyl Methylammonium monofluorophosphate (2,2,2-trifluoroethyl), triethylmethylammonium monofluorophosphate (2,2,2-trifluoroethyl), triethylmethylammonium Monofluorophosphoric acid (2,2,2-trifluoroethyl), triethylmethylammonium monofluorophosphoric acid (1,1,1,3,3,3-hexafluoroisopropyl), triethylmethylammonium monofluorophosphoric acid (2 -Methoxyethyl), triethylmethylammonium monofluorophosphate (2- (2-methoxyethoxy) ethyl), triethylmethylammonium monofluorophosphate (2- (2- (2-methoxyethoxy) ethoxy) ethyl), triethylmethyl Ammonium monofluorophosphate (2- (2- (2- (2-methoxyethoxy) ethoxy) ethoxy) ethyl), methyl lithium monofluorophosphate, ethyl lithium monofluorophosphate, butyl lithium monofluorophosphate, monofluoro Phosphoric acid (2-ethoxy Ethyl) lithium, ethyl potassium monofluorophosphate, ethyl magnesium monofluorophosphate, ethyl calcium monofluorophosphate, ethyl silver monofluorophosphate, ethyl copper monofluorophosphate, isopropyl lithium monofluorophosphate, monofluorophosphoric acid (2,2,2-trichloroethyl) lithium phosphate, monofluorophosphate (2,2,2-trichloroethyl) lithium, monofluorophosphate (1,1,1,3,3,3-hexachloroisopropyl) Lithium, lithium monofluorophosphate (2,2,2-trifluoroethyl), lithium monofluorophosphate (1,1,1,3,3,3-hexafluoroisopropyl), monofluorophosphate (2-methoxy) Ethyl) lithium, monofluorophosphoric acid (2- (2-methoxyethoxy) B) ethyl) lithium, monofluorophosphate (2- (2- (2-methoxyethoxy) ethoxy) ethyl) lithium, monofluorophosphate (2- (2- (2- (2-methoxyethoxy) ethoxy) ethoxy) ) Ethyl) lithium, ethyl 1-ethylpyridinium monofluorophosphate, ethyl 1-hexylpyridinium monofluorophosphate, ethyl cetylpyridinium monofluorophosphate, ethyl octyltrimethylammonium monofluorophosphate, hexadecyltrimethylammonium monofluorophosphate Examples include ethyl, ethyl hexadecyl (2-hydroxyethyl) dimethylammonium monofluorophosphate, and ethyl allylhexadecyldimethylammonium monofluorophosphate.

(Method for producing monofluorophosphate ester salt)
Next, the manufacturing method of the monofluorophosphate ester salt which concerns on this Embodiment is demonstrated below.

The method for producing a monofluorophosphate ester salt according to the present embodiment includes a step A in which a monohalophosphate diester is fluorinated to produce a monofluorophosphate diester, and the monofluorophosphate diester is reacted with a halide. And at least a step B of producing a monofluorophosphate ester salt.

The monohalophosphate diester used as a raw material in the step A is represented by the following chemical formula (2).

In the above formula (2), wherein R ¹ is the same as R ¹ in Formula (1), it is as previously described. Furthermore, the R ² in the chemical formula (2) is the same as R ¹ in the chemical formula (1). Therefore, R ² is selected from the functional group group listed in the description of R ¹ . However, R ¹ and R ² may be the same type or different from each other. X ¹ represents a halogen atom other than the fluorine atom F.

Fluorination of the monohalophosphoric acid diester by fluorination treatment can be performed, for example, by contacting potassium fluoride or the like as a fluorinating agent in an organic solvent. Thereby, a reaction as shown in the following chemical reaction formula (4) occurs, and a monofluorophosphoric acid diester can be generated.

The reaction start temperature when the monohalophosphate diester and the fluorinating agent start the reaction in a non-aqueous solvent (in an organic solvent) is not particularly limited as long as the reaction proceeds, and is appropriately set according to the reaction species. do it. Usually, it is in the range of 0 ° C. to 200 ° C., and is preferably 20 to 150 ° C., more preferably 40 ° C. to 120 ° C. from the viewpoint of reactivity. By setting the reaction start temperature to 0 ° C. or higher, it is possible to prevent the reaction rate from being significantly attenuated. Moreover, the energy loss by using excess energy can be suppressed by making reaction start temperature into 200 degrees C or less. The method for adjusting the reaction start temperature is not particularly limited, and when cooling and controlling so as to be within the temperature range, the reaction vessel charged with the monohalophosphate diester and the fluorinating agent may be ice-cooled or the like. Can be performed. Moreover, when heating and controlling so that reaction start temperature may be in the said temperature range, it can carry out by using the oil bath etc. which were set to arbitrary temperature.

As the solvent used when the monohalophosphoric acid diester and the fluorinating agent are reacted in a non-aqueous solvent, an aprotic solvent is preferable. By using an aprotic solvent, inhibition of the fluorination reaction can be prevented. When a protic solvent is used, the monohalophosphate diester and the protic solvent may cause a halogen exchange reaction. Further, when such a nucleophilic fluorination reaction is performed, the hydrogen element in the protic solvent and the fluorine anion of the fluorinating agent significantly reduce the fluorination ability due to the influence of hydrogen bonding. Moreover, monohalo phosphoric acid diester can also be used as a solvent.

The aprotic solvent is not particularly limited, and examples thereof include nitriles, esters, ketones, ethers, and halogenated hydrocarbons.

The nitriles are not particularly limited, and examples thereof include acetonitrile and propionitrile. The esters are not particularly limited, and examples thereof include dimethyl carbonate, diethyl carbonate, ethyl methyl carbonate, ethylene carbonate, propylene carbonate, ethyl acetate, methyl acetate, and butyl acetate. The ketones are not particularly limited, and examples thereof include acetone, methyl ethyl ketone, methyl isobutyl ketone, and cyclohexanone. The ethers are not particularly limited, and examples thereof include diethyl ether, tetrahydrofuran, and ethylene glycol. The halogenated hydrocarbon is not particularly limited, and examples thereof include dichloromethane and chloroform. Still other aprotic solvents include, for example, nitromethane, nitroethane, dimethylformamide and the like. These aprotic solvents can be used alone or in combination of two or more.

The fluorinating agent used in the reaction between the monohalophosphate diester and the fluorinating agent is not particularly limited, and examples thereof include alkali metal fluorides, alkaline earth metal fluorides, onium fluorides and the like.

The alkali metal fluoride is not particularly limited, and examples thereof include lithium fluoride, sodium fluoride, potassium fluoride, rubidium fluoride, and cesium fluoride. The alkaline earth metal fluoride is not particularly limited, and examples thereof include beryllium fluoride, magnesium fluoride, calcium fluoride, strontium fluoride, and barium fluoride. The onium fluoride is not particularly limited, and examples thereof include triethylamine trihydrofluoride, triethylamine pentahydrofluoride, viridine hydrofluoride, and tetrabutylammonium fluoride. These fluorinating agents can be used alone or in combination of two or more.

The step B is a step of producing a monofluorophosphate ester salt represented by the chemical formula (1) by reacting a monofluorophosphate diester with the halide.

The halide has a chemical formula M ^{n +} X ² n (where M ^{n +} is an alkali metal ion, alkaline earth metal ion, transition metal ion, rare earth element ion, zinc ion, aluminum ion, gallium ion, indium ion, germanium ion, It represents any one selected from the group consisting of tin ion, lead ion and onium ion, X ² represents a halogen atom of F, Cl, Br or I. The n represents a valence.) It is represented by

Here, since M ^{n +} in the halide is as described above, detailed description thereof is omitted. Moreover, said n in a halide represents a valence similarly to the case of the said General formula (1).

The reaction between the monofluorophosphoric diester and the halide in Step B is as represented by the following chemical reaction formulas (5) and (6).

That is, the halogen of the halide nucleophilically attacks R ² of the monofluorophosphate ester, whereby the monofluorophosphate ester anion containing R ¹ is eliminated, and the alkyl halide represented by R ² X ² is released. Generate. Further, it is presumed that the monofluorophosphate ester salt is formed by the elimination of the monofluorophosphate ester anion to form a salt with a halide counter cation.

Here, when the halide and monofluorophosphoric diester are reacted, two leaving groups represented by the following chemical formulas can be generated.

(The R ¹ represents a hydrocarbon group having 1 to 20 carbon atoms, or a hydrocarbon group having 1 to 20 carbon atoms and having at least one of a halogen atom, a hetero atom and an unsaturated bond. To express.)

(R ² represents a hydrocarbon group having 1 to 20 carbon atoms or a hydrocarbon group having 1 to 20 carbon atoms and having at least one of a halogen atom, a hetero atom and an unsaturated bond. To express.)

When the halide and monofluorophosphoric acid diester are reacted to produce a monofluorophosphoric acid ester salt, when R ¹ and R ² are different from each other, the monofluorophosphoric acid ester anion represented by the chemical formula (7) Is required to be higher than that of the monofluorophosphate ester anion represented by the chemical formula (8). Thus, including R ^1, monofluorophosphate ester salts of the present embodiment can be obtained.

The leaving ability of the monofluorophosphate ester anion represented by the chemical formula (7) or (8), which is a leaving group, is roughly estimated from the pKa value of each proton body, for example. Specifically, the monofluorophosphate anion represented by the chemical formula (7) is represented by the proton form of the monofluorophosphate ester anion, that is, the pKa value of the monofluorophosphate ester is represented by the chemical formula (8). It is preferably smaller than the proton body. The pKa value can be estimated from, for example, Bordwell pKa Table. Alternatively, it can be presumed that those having an electron withdrawing group in the leaving group have high leaving ability.

When producing the monofluorophosphate ester salt by reacting the halide with the monofluorophosphate diester in another non-aqueous solvent, the amount of the halide and monofluorophosphate diester used as long as the desired compound is obtained. Is not particularly limited. Usually, the monofluorophosphoric diester is 0.5 to 5 equivalents, preferably 0.9 to 4 equivalents, more preferably 0.95 to 3.3 equivalents per 1 equivalent of halide. is there. By making the amount of monofluorophosphoric acid diester used 0.5 equivalents or more, it is possible to prevent the reactivity between the halide and the monofluorophosphoric acid diester from deteriorating, and to keep unreacted hydroxide remaining. Can be suppressed. As a result, a decrease in the purity of the monofluorophosphate ester salt can be suppressed. In addition, when the usage-amount of the said monofluoro phosphoric acid diester is larger than 5 equivalents, when distilling this off, the manufacturing time and energy more than needed are needed, and it may become industrially disadvantageous.

The reaction start temperature when the halide and monofluorophosphoric acid diester start the reaction in another non-aqueous solvent is not particularly limited as long as the reaction proceeds, and may be appropriately set according to the reaction species. Good. Usually, it is in the range of 0 ° C. to 200 ° C., and is preferably 20 to 150 ° C., more preferably 40 ° C. to 120 ° C. from the viewpoint of reactivity. By setting the reaction start temperature to 0 ° C. or higher, it is possible to prevent the reaction rate from being significantly attenuated. Moreover, the energy loss by using excess energy can be suppressed by making reaction start temperature into 200 degrees C or less. The method for adjusting the reaction start temperature is not particularly limited, and when cooling and controlling so as to be within the temperature range, the reaction vessel charged with the halide and monofluorophosphoric acid diester is cooled with ice or the like. Can be done. Moreover, when heating and controlling so that reaction start temperature may be in the said temperature range, it can carry out by using the oil bath etc. which were set to arbitrary temperature.

The reaction time when the halide and monofluorophosphoric diester are reacted in another non-aqueous solvent is not particularly limited, and may be set as appropriate according to the reaction species. Usually, it is within the range of 30 minutes to 20 hours, and from the viewpoint of industrial production, 30 minutes to 15 hours is preferable, and 30 minutes to 10 hours is more preferable.

In the reaction between the halide and the monofluorophosphoric diester, the monofluorophosphoric diester can be used as a reaction solvent in addition to the other non-aqueous solvent. In this case, the reaction start temperature at which the halide and monofluorophosphoric acid diester start the reaction is not particularly limited as long as the reaction proceeds, and may be appropriately set according to the reaction species. Usually, it is in the range of 0 ° C. to 200 ° C., and from the viewpoint of reactivity, 20 ° C. to 150 ° C. is preferable, and 40 ° C. to 120 ° C. is more preferable. Further, the reaction time is not particularly limited, and may be appropriately set according to the reaction species. Usually, it is within the range of 30 minutes to 20 hours, and from the viewpoint of industrial production, 30 minutes to 15 hours is preferable, and 30 minutes to 10 hours is more preferable.

The other non-aqueous solvent (organic solvent) is not particularly limited as long as it does not hinder the reaction with other reactants and products. Specific examples include alcohols, nitriles, esters, ketones, ethers, halogenated hydrocarbons and the like. These can be used alone or in combination of two or more.

The alcohols are not particularly limited, and examples thereof include methanol, ethanol, propanol, butanol, isopropyl alcohol, pentanol, hexanol, heptanol, octanol, 2-iodoethanol, 2-bromoethanol, 2-chloroethanol, 2- Fluoroethanol, 1,2-diiodoethanol, 1,2-dibromoethanol, 1,2-dichloroethanol, 1,2-difluoroethanol, 2,2-diiodoethanol, 2,2-dibromoethanol, 2,2 -Dichloroethanol, 2,2-difluoroethanol, 2,2,2-tribromoethanol, 2,2,2-trichloroethanol, 2,2,2-trifluoroethanol, 1,1,1,3,3 3-hexafluoro-2-propanol etc. It is below. These can be used alone or in combination of two or more.

The nitriles are not particularly limited, and examples thereof include acetonitrile and propionitryl. These can be used alone or in combination of two or more.

The esters are not particularly limited, and examples thereof include dimethyl carbonate, diethyl carbonate, ethyl methyl carbonate, ethylene carbonate, propylene carbonate, ethyl acetate, methyl acetate, and butyl acetate. These can be used alone or in combination of two or more.

The ketones are not particularly limited, and examples thereof include acetone, methyl ethyl ketone, methyl isobutyl ketone, and cyclohexanone. These can be used alone or in combination of two or more.

The ethers are not particularly limited, and examples include diethyl ether, tetrahydrofuran, dimethoxyethane, and the like. These can be used alone or in combination of two or more.

The halogenated hydrocarbon is not particularly limited, and examples thereof include dichloromethane and chloroform. These can be used alone or in combination of two or more.

Also, other examples of the other non-aqueous solvent (organic solvent) include nitromethane, nitroethane, dimethylformamide and the like.

The amount of the other non-aqueous solvent (organic solvent) to be used is preferably 1 or more times, more preferably 1 to 200 times, and more preferably 1 to 100 times based on the weight of the monofluorophosphoric acid diester. A double amount is more preferable, and a 1-fold to 50-fold amount is particularly preferable. By making the amount of the organic solvent used more than 1 time, the reactivity of the phosphate triester and hydroxide is prevented from deteriorating, and the decrease in the yield and purity of the phosphate diester salt is suppressed. be able to. The upper limit of the amount of the organic solvent used is not particularly limited, but excessive use of the organic solvent relative to the monofluorophosphoric acid diester requires more energy when distilling it off, which is industrially disadvantageous. It may become. Accordingly, the upper limit of the amount of the organic solvent used is preferably set as appropriate according to the reaction species.

When an organic solvent is used as the reaction solvent, the order of addition of the halide and monofluorophosphoric acid diester is not particularly limited. Moreover, when using monofluorophosphoric diester as a reaction solvent, the addition order of a halide and monofluorophosphoric diester is not specifically limited.

The monofluorophosphoric acid ester salt obtained by the method of the present embodiment is obtained by performing cation exchange using solubility or cation exchange using an ion exchange resin or the like to obtain a monofluorophosphorus having a desired different cation. Acid ester salts can also be produced.

In addition, the monofluorophosphate ester can also be produced by reacting the monofluorophosphate ester salt obtained by the method of the present embodiment with Arrhenius acid such as sulfuric acid or hydrochloric acid. A monofluorophosphate ester can also be obtained by performing proton exchange using an ion exchange resin. Furthermore, a monofluorophosphate ester salt can also be produced by reacting the monofluorophosphate obtained by these methods with a halide or hydroxide.

In the present embodiment, a step of purifying the monofluorophosphate ester salt may be performed immediately after the step of generating the monofluorophosphate ester salt. Further, immediately after the step of producing a monofluorophosphate ester salt having another kind of cation, purification can be performed by cation exchange with respect to the monofluorophosphate ester salt. Furthermore, the purification can be performed immediately after the monofluorophosphate ester is reacted with the halide to produce a monofluorophosphate ester salt. It does not specifically limit as a purification method, For example, the method by operation, such as distillation and drying, The method using adsorption agents, such as activated carbon or an ion exchange resin, etc. are employable. By performing these purifications, the purity of the monofluorophosphate ester salt can be increased.

(Fluorine ion releasing composition)
The monofluorophosphate ester salt of the present embodiment is used as an additive for imparting sustained release of fluoride ions, for example, in fluoride ion releasing compositions such as oral compositions and dental compositions. Can do. In this case, the monofluorophosphate ester salt as the fluorine releasing compound includes at least one kind, and two or more kinds can be used in combination.

The monofluorophosphoric acid ester salt of the present embodiment is, for example, coated with a specific substance such as phosphatase without coating the particle surface with a specific substance such as polysiloxane and controlling the release rate of fluoride ions. Through the reaction via a significant release amount of fluorine ions can be continuously released over a long period of time. As a result, an oral composition or a dental composition that imparts high anti-cariogenic properties to the tooth over a long period of time is made possible.

Examples of the oral composition include a dentifrice composition for preventing caries. Examples of the dental composition include dental coating agents, dental fillers such as dental composite resins and glass ionomer cements, dental adhesives, and dental cements.

In the dentifrice composition, other fluoride ions such as sodium fluoride, tin fluoride, potassium fluoride, sodium monofluorophosphate, sodium fluorosilicate, ammonium fluorosilicate, amine fluoride, ammonium fluoride, etc. A component serving as a supply source may be added and used together with the monofluorophosphate ester salt of the present embodiment. In this case, the addition amount of these components can be appropriately set as necessary.

The addition amount of the monofluorophosphate ester salt is preferably 50 ppm to 10000 ppm, more preferably 50 ppm to 5000 ppm, more preferably, based on the fluorine in the molecule and based on the total amount of the fluorine ion-releasing composition. 100 ppm to 2000 ppm. By making the addition amount 50 ppm or more, it is possible to maintain the amount of fluorine ions to be released. On the other hand, when the additive amount is 10000 ppm or less, when applied to the oral composition additive, fluorosis due to excessive intake of fluorine can be suppressed, and the dental composition additive can be used as an additive. When applied, it is possible to prevent a decrease in handleability as a dental material.

Hereinafter, preferred embodiments of the present invention will be described in detail by way of example. However, the materials, blending amounts, and the like described in the examples do not limit the scope of the present invention only to those unless otherwise limited.

(Precursor synthesis of monofluorophosphate ester salt)
<Synthesis of diethyl monofluorophosphate>
To a 300 mL eggplant flask containing a stir bar, 33.7 g of potassium fluoride and 150 g of acetonitrile were added, and further 50.3 g of diethyl chlorophosphate (manufactured by Tokyo Chemical Industry Co., Ltd.) was added. Subsequently, the mixture was heated and refluxed at 100 ° C. for 7 hours under a nitrogen stream. Thereafter, the solution in the eggplant flask was allowed to cool to room temperature, and excess potassium fluoride and precipitated potassium chloride were removed by suction filtration. The solvent in the filtrate obtained by the evaporator was distilled off to obtain 42 g of diethyl monofluorophosphate as a light yellow transparent liquid as a target monofluorophosphate ester salt.

The raw material diethyl chlorophosphate was subjected to anion analysis by ion chromatography (manufactured by Metrohm, model number: IC-850), and two peaks of chloride ion and diethyl phosphate anion were detected. In addition, when the obtained pale yellow transparent liquid was subjected to anion analysis, two peaks of fluoride ion and diethyl phosphate anion were detected, and the peak of chloride ion disappeared cleanly. Thereby, it was confirmed that diethyl monofluorophosphate was produced. Further, when the obtained pale yellow transparent liquid was subjected to positive ion analysis with LC / MS (manufactured by Waters), a mass peak was observed at m / z = 157.1. This almost coincided with the molecular weight of diethyl monofluorophosphate, and it was confirmed that the obtained pale yellow transparent liquid was diethyl monofluorophosphate.

<Synthesis of ethyl monofluorophosphate>
Into a 50 mL eggplant flask containing a stir bar, 13.7 g of the lithium ethylfluorophosphate and 50 g of diethyl ether were charged. Subsequently, while stirring the solution in the eggplant flask, 4.0 g of sulfuric acid was added little by little. Then, it stirred at normal temperature for 1 hour. Further, filtration under reduced pressure was performed to separate the white precipitate and the filtrate. Then, 9.6 g of ethyl monofluorophosphate which is a colorless and transparent liquid was obtained by distilling off the solvent in the filtrate under reduced pressure.

The obtained colorless and transparent liquid was subjected to anion analysis by ion chromatography (manufactured by Metrohm, model number: IC-850), and one peak was detected at the same detection time as that of the lithium ethylfluorophosphate. In addition, sulfate ions were not detected. This confirmed that the obtained colorless and transparent liquid was ethyl monofluorophosphate.

Example 1
<Synthesis of sodium monofluorophosphate ethyl>
1.9 g of sodium iodide and 10 g of acetonitrile were placed in a 50 mL eggplant flask containing a stirring bar, and 2.0 g of the above-mentioned diethyl monofluorophosphate was further added. Thereafter, the solution in the eggplant flask was heated and refluxed at 120 ° C. for 3 hours under a nitrogen stream. Furthermore, the solution in the eggplant flask was allowed to cool to room temperature, and the precipitate in the solution was filtered off by vacuum filtration. Thereafter, the precipitate was dried at 130 ° C. under a nitrogen stream to obtain 1.5 g of a white solid.

<Analysis>
The obtained white solid was subjected to anion analysis by ion chromatography (manufactured by Metrohm, model number: IC-850), and one new peak was detected. This confirmed that a new anion was generated. Further, when cation analysis was performed by ion chromatography (model number: ICS-1500, manufactured by Dionex), a sodium ion peak was detected. Furthermore, when the obtained white solid was subjected to negative ion analysis by LC / MS (manufactured by Waters), a mass peak was observed at m / z = 16.9. This almost coincided with the molecular weight of the ethyl monofluorophosphate anion, and it was confirmed that the obtained white solid was sodium sodium monofluorophosphate.

(Example 2)
<Synthesis of ethyl lithium monofluorophosphate>
To a 100 mL eggplant flask containing a stirrer, 1.1 g of lithium chloride and 20.0 g of diethyl monofluorophosphate were added. Thereafter, the solution in the eggplant flask was heated and refluxed at 120 ° C. for 1.5 hours under a nitrogen stream. Furthermore, the solution in the eggplant flask was allowed to cool to room temperature, and the precipitate in the solution was filtered off by vacuum filtration. Thereafter, the precipitate was dried at 130 ° C. under a nitrogen stream to obtain 3.0 g of a white solid.

<Analysis>
The obtained white solid was subjected to anion analysis by ion chromatography (manufactured by Metrohm, model number: IC-850), and one new peak was detected. This confirmed that a new anion was generated. Further, when cation analysis was performed by ion chromatography (model number: ICS-1500, manufactured by Dionex), a lithium ion peak was detected. Furthermore, when the obtained white solid was subjected to negative ion analysis by LC / MS (manufactured by Waters), a mass peak was observed at m / z = 16.9. This almost coincided with the molecular weight of the ethyl monofluorophosphate anion, and it was confirmed that the obtained white solid was sodium sodium monofluorophosphate.

(Example 3)
<Synthesis of ethyl potassium monofluorophosphate>
To a 50 mL eggplant flask containing a stirrer, 2.1 g of potassium iodide and 20 g of acetonitrile were added, and then 3.0 g of the above-mentioned diethyl monofluorophosphate was added. Thereafter, the solution in the eggplant flask was heated and refluxed at 140 ° C. to 150 ° C. for 13 hours under a nitrogen stream. Further, the solution in the eggplant flask was allowed to cool to room temperature, and the precipitate in the solution was filtered off by vacuum filtration. Thereafter, the precipitate was dried at 130 ° C. under a nitrogen stream to obtain 2.0 g of a white solid.

<Analysis>
The resulting white solid was subjected to anion analysis by ion chromatography (manufactured by Metrohm, model number: IC-850). As a result, a single new peak was detected with the same detection time as that of the lithium lithium monofluorophosphate. It was done. Thereby, the produced | generated novel anion was an ethyl fluorophosphate anion, and it confirmed that the obtained white solid was ethyl potassium monofluorophosphate.

Example 4
<Synthesis of ethyl magnesium monofluorophosphate>
Into a 50 mL eggplant flask containing a stir bar, 0.6 g of anhydrous magnesium chloride and 5 g of acetonitrile were added, and then 2.0 g of diethyl monofluorophosphate was added. Thereafter, the solution in the eggplant flask was heated and refluxed at 140 to 150 ° C. for 7 hours under a nitrogen stream. Further, the solution in the eggplant flask was allowed to cool to room temperature and then filtered under reduced pressure to separate unreacted magnesium chloride and the filtrate. Subsequently, 1.7 g of a white solid was obtained by distilling off the solvent in the filtrate under reduced pressure.

<Analysis>
The resulting white solid was subjected to anion analysis by ion chromatography (manufactured by Metrohm, model number: IC-850). As a result, a single new peak was detected with the same detection time as that of the lithium lithium monofluorophosphate. It was done. This confirmed that the produced new anion was an ethyl monofluorophosphate anion and the resulting white solid was ethyl magnesium monofluorophosphate.

(Example 5)
<Synthesis of ethyl calcium monofluorophosphate>
To a 50 mL eggplant flask containing a stir bar, 0.7 g of anhydrous calcium chloride and 10 g of acetonitrile were added, and then 2.0 g of diethyl monofluorophosphate was added. Thereafter, the solution in the eggplant flask was heated and refluxed at 140 ° C. to 150 ° C. for 14 hours under a nitrogen stream. Further, the solution in the eggplant flask was allowed to cool to room temperature and then filtered under reduced pressure to separate unreacted calcium chloride and the filtrate. Subsequently, 0.6 g of a white solid was obtained by distilling off the solvent in the filtrate under reduced pressure.

<Analysis>
The obtained white solid was subjected to anion analysis by ion chromatography (manufactured by Metrohm, model number: IC-850). As a result, one new peak was detected with the same detection time as that of the lithium ethylfluorophosphate. It was. Thus, it was confirmed that the generated new anion was an ethyl monofluorophosphate anion, and the obtained white solid was ethyl calcium monofluorophosphate.

(Example 6)
<Synthesis of ethyl silver monofluorophosphate>
1.1 g of silver carbonate (I) and 10 g of water were put into a 50 mL eggplant flask containing a stirring bar. Subsequently, 1.0 g of the ethyl monofluorophosphate was added little by little while stirring the solution in the eggplant flask. Then, it stirred at normal temperature for 2 hours. Furthermore, the precipitate and the filtrate were separated by filtering the solution in the eggplant flask under reduced pressure. Subsequently, 1.6 g of a white solid was obtained by distilling off the solvent in the filtrate under reduced pressure.

<Analysis>
The obtained white solid was subjected to anion analysis by ion chromatography (manufactured by Metrohm, model number: IC-850), and one peak was detected at the same detection time as that of the above-described ethyl lithium monofluorophosphate. . In addition, silver ions were quantified using the Forhardt method, which is one of precipitation titrations (standard solution for volumetric analysis: 0.1 M ammonium thiocyanate solution, indicator: ammonium iron (III) sulfate, titration temperature: room temperature) 43% by mass. This measured value was close to the theoretical value (46% by mass) of silver ion content in ethyl silver monofluorophosphate, and it was confirmed that the obtained white solid was silver silver monofluorophosphate.

(Example 7)
<Synthesis of ethyl copper monofluorophosphate>
To a 50 mL eggplant flask containing a stirrer, 0.4 g of copper (II) hydroxide and 5 g of acetonitrile were charged. Subsequently, 1.0 g of the ethyl monofluorophosphate was added little by little while stirring the solution in the eggplant flask. Thereafter, the solution in the eggplant flask was stirred at room temperature for 1 hour. Furthermore, the precipitate and the filtrate were separated by filtering the solution in the eggplant flask under reduced pressure. Subsequently, the solvent in the filtrate was distilled off under reduced pressure to obtain 1.2 g of a blue-green solid.

<Analysis>
The obtained blue-green solid was subjected to anion analysis by ion chromatography (manufactured by Metrohm, model number: IC-850). It was done. Further, when copper ion was quantified by using iodine titration method which is one of precipitation titration (standard solution for volumetric analysis: 0.1 M sodium thiosulfate solution, titration temperature: room temperature), it was 20% by mass. . This measured value almost coincided with the theoretical value (20% by mass) of copper ion content in copper ethyl fluorophosphate, and it was confirmed that the obtained blue-green solid was copper ethyl fluorophosphate.

(Example 8)
<Synthesis of ethyl 1-ethyl-3-methylimidazolium monofluorophosphate>
To a 50 mL eggplant flask containing a stir bar, 1.1 g of 1-ethyl-3-methylimidazolium chloride was charged, and then 1.0 g of diethyl monofluorophosphate was charged. Thereafter, the solution in the eggplant flask was heated at 110 ° C. to 120 ° C. for 3 hours with stirring to obtain 1.4 g of a yellow transparent oily liquid.

<Analysis>
The obtained yellow transparent oily liquid was subjected to anion analysis by ion chromatography (manufactured by Metrohm, model number: IC-850), and one new peak was detected. This confirmed that a new anion was generated. Furthermore, when the obtained yellow transparent oily liquid was subjected to negative ion analysis by LC / MS (manufactured by Waters), a mass peak was observed at m / z = 16.9. Similarly, when positive ion analysis was performed, a mass peak was observed at m / z = 111.1. This is almost the same as the molecular weights of the anion and cation of ethyl 1-ethyl-3-methylimidazolium monofluorophosphate, and the obtained yellow transparent oily liquid is 1-ethyl-3-methylimidazolium mono It was confirmed to be ethyl fluorophosphate.

Example 9
<Synthesis of ethyl 1-ethylpyridinium monofluorophosphate>
A 50 mL eggplant flask containing a stir bar was charged with 1.8 g of 1-ethylpyridinium bromide and 10 g of acetonitrile, and then 1.5 g of diethyl monofluorophosphate was added. Thereafter, the solution in the eggplant flask was heated and refluxed at 140 ° C. to 150 ° C. for 15 hours under a nitrogen stream. The solution in the eggplant flask was allowed to cool to room temperature, the solvent in the solution was distilled off under reduced pressure, washed with hexane, and vacuum dried at room temperature to obtain 1.2 g of a colorless and transparent oily liquid. .

<Analysis>
The obtained colorless and transparent oily liquid was subjected to anion analysis by ion chromatography (manufactured by Metrohm, Model No .: IC-850). As a result, a new peak was detected with the same detection time as that of the lithium ethylfluorophosphate. One was detected. As a result, it was confirmed that the produced new anion was an ethyl monofluorophosphate anion, and the obtained colorless and transparent oily liquid was ethyl 1-ethylpyridinium monofluorophosphate.

(Example 10)
<Synthesis of ethyl 1-hexylpyridinium monofluorophosphate>
To a 50 mL eggplant flask containing a stir bar, 4.2 g of 1-hexylpyridinium bromide and 20 g of acetonitrile were added, followed by 5.4 g of diethyl monofluorophosphate. Thereafter, the solution in the eggplant flask was heated and refluxed at 110 to 120 ° C. for 15 hours under a nitrogen stream. The solution in the eggplant flask was allowed to cool to room temperature, the solvent in the solution was distilled off under reduced pressure, washed with hexane, and then vacuum dried at room temperature to obtain 4.9 g of a colorless and transparent oily liquid. .

<Analysis>
The obtained colorless and transparent oily liquid was subjected to anion analysis by ion chromatography (manufactured by Metrohm, model number: IC-850), and one new peak was detected. This confirmed that a new anion was generated. Further, when the obtained colorless and transparent oily liquid was subjected to negative ion analysis by LC / MS (manufactured by Waters), a mass peak was observed at m / z = 127.0. Further, when positive ion analysis was performed in the same manner, a mass peak was observed at m / z = 164.1. This was almost the same as the molecular weight of each anion and cation of ethyl 1-hexylpyridinium monofluorophosphate, and it was confirmed that the obtained colorless and transparent oily liquid was ethyl 1-hexylpyridinium monofluorophosphate. .

(Example 11)
<Synthesis of ethyl cetylpyridinium monofluorophosphate>
4.4 g of anhydrous cetylpyridinium chloride and 20 g of acetonitrile were charged into a 50 mL eggplant flask containing a stir bar, and then 2.7 g of diethyl monofluorophosphate was charged. Thereafter, the solution in the eggplant flask was heated and refluxed at 140 to 150 ° C. for 7 hours under a nitrogen stream. Further, the solution in the eggplant flask was cooled to −10 ° C., and the precipitate in the solution was separated by filtration under reduced pressure to obtain 3.2 g of a white solid.

<Analysis>
The resulting white solid was subjected to anion analysis by ion chromatography (manufactured by Metrohm, model number: IC-850). As a result, a single new peak was detected with the same detection time as that of the lithium lithium monofluorophosphate. It was done. This confirmed that the produced new anion was an ethyl monofluorophosphate anion, and the resulting white solid was ethyl cetylpyridinium monofluorophosphate.

Example 12
<Synthesis of ethyl octyltrimethylammonium monofluorophosphate>
4.4 g of octyltrimethylammonium bromide and 20 g of acetonitrile were added to a 50 mL eggplant flask containing a stir bar, and then 5.4 g of the above diethyl monofluorophosphate was added. Thereafter, the solution in the eggplant flask was heated and refluxed at 110 to 120 ° C. for 15 hours under a nitrogen stream. The solution in the eggplant flask was allowed to cool to room temperature, the solvent in the solution was distilled off under reduced pressure, washed with hexane, and vacuum dried at room temperature to obtain 4.2 g of a colorless and transparent oily liquid. .

<Analysis>
The obtained colorless and transparent oily liquid was subjected to anion analysis by ion chromatography (manufactured by Metrohm, model number: IC-850), and one new peak was detected. This confirmed that a new anion was generated. Further, when the obtained colorless and transparent oily liquid was subjected to negative ion analysis by LC / MS (manufactured by Waters), a mass peak was observed at m / z = 127.0. Similarly, when positive ion analysis was performed, a mass peak was observed at m / z = 172.3. This almost coincided with the molecular weights of the anions and cations of ethyl octyltrimethylammonium monofluorophosphate, and the obtained colorless and transparent oily liquid was confirmed to be ethyl octyltrimethylammonium monofluorophosphate.

(Example 13)
<Synthesis of ethyl hexadecyltrimethylammonium monofluorophosphate>
Into a 50 mL eggplant flask containing a stir bar, 4.5 g of hexadecyltrimethylammonium bromide and 20 g of acetonitrile were added, and then 3.9 g of diethyl monofluorophosphate was added. Thereafter, the solution in the eggplant flask was heated and refluxed at 110 to 120 ° C. for 15 hours under a nitrogen stream. The solution in the eggplant flask was allowed to cool to room temperature, and then the solvent in the solution was distilled off under reduced pressure to obtain a white solid. After recrystallizing with acetone and collecting the precipitated solid by suction filtration, 2.9 g of white solid was obtained by vacuum drying at room temperature.

<Analysis>
The obtained white solid was subjected to anion analysis by ion chromatography (manufactured by Metrohm, model number: IC-850), and one new peak was detected. This confirmed that a new anion was generated. Furthermore, when the obtained white solid was subjected to negative ion analysis by LC / MS (manufactured by Waters), a mass peak was observed at m / z = 127.0. Further, when positive ion analysis was performed in the same manner, a mass peak was observed at m / z = 284.6. This was almost the same as the molecular weight of each of the anion and cation of ethyl hexadecyltrimethylammonium monofluorophosphate, and it was confirmed that the resulting colorless and transparent oily liquid was ethyl hexadecyltrimethylammonium ethylfluorophosphate. .

(Example 14)
<Synthesis of hexadecyl (2-hydroxyethyl) dimethylammonium bromide>
A 50 mL eggplant flask containing a stir bar was charged with 3.5 g of hexadecyldimethylamine and 20 g of acetonitrile, followed by 1.6 g of 2-bromoethanol. Thereafter, the solution in the eggplant flask was heated to reflux at 100 ° C. for 3 hours under a nitrogen stream. The solution in the eggplant flask was allowed to cool to room temperature, and then the solvent in the solution was distilled off under reduced pressure to obtain a white solid. Recrystallization from acetone, decantation of the solvent, and vacuum drying at room temperature gave 4.8 g of hexadecyl (2-hydroxyethyl) dimethylammonium bromide as a white solid.

<Synthesis of hexadecyl (2-hydroxyethyl) dimethylammonium monofluorophosphate>
3.8 g of hexadecyl (2-hydroxyethyl) dimethylammonium bromide and 20 g of acetonitrile were charged into a 50 mL eggplant flask containing a stir bar, followed by 3.0 g of diethyl monofluorophosphate. Thereafter, the solution in the eggplant flask was heated and refluxed at 110 ° C. to 120 ° C. for 3 hours under a nitrogen stream. The solution in the eggplant flask was allowed to cool to room temperature, and then the solvent in the solution was distilled off under reduced pressure to obtain a white solid. After recrystallizing with acetone and decanting the solvent, 2.8 g of white solid was obtained by vacuum drying at room temperature.

The obtained white solid was subjected to anion analysis by ion chromatography (manufactured by Metrohm, model number: IC-850), and one new peak was detected. This confirmed that a new anion was generated. Furthermore, when the obtained white solid was subjected to negative ion analysis by LC / MS (manufactured by Waters), a mass peak was observed at m / z = 127.0. Similarly, when positive ion analysis was performed, a mass peak was observed at m / z = 314.6. This is almost the same as the molecular weight of each of the anions and cations of hexadecyl (2-hydroxyethyl) dimethylammonium ethylfluorophosphate, and the resulting colorless and transparent oily liquid is hexadecyl (2-hydroxyethyl) dimethylammonium mono It was confirmed to be ethyl fluorophosphate.

(Example 15)
<Synthesis of allyl hexadecyldimethylammonium bromide>
Into a 50 mL eggplant flask containing a stir bar, 3.5 g of hexadecyldimethylamine and 20 g of acetonitrile were added, followed by 1.6 g of allyl bromide. Thereafter, the solution in the eggplant flask was heated and refluxed at 60 ° C. for 3 hours under a nitrogen stream. The solution in the eggplant flask was allowed to cool to room temperature, and then the solvent in the solution was distilled off under reduced pressure to obtain a white solid. After recrystallizing with acetone and decanting the solvent, 4.4 g of allylhexadecyldimethylammonium bromide as a white solid was obtained by vacuum drying at room temperature.

<Synthesis of ethyl allylhexadecyldimethylammonium monofluorophosphate>
Into a 50 mL eggplant flask containing a stir bar, 3.8 g of allyl hexadecyldimethylammonium bromide and 20 g of acetonitrile were added, followed by 3.0 g of diethyl monofluorophosphate. Thereafter, the solution in the eggplant flask was heated and refluxed at 110 ° C. to 120 ° C. for 3 hours under a nitrogen stream. Further, the solution in the eggplant flask was allowed to cool to room temperature, and then the solvent in the solution was distilled off under reduced pressure to obtain a colorless and transparent oily liquid. The mixture was recrystallized with acetone under cooling at −20 ° C., decanted from the solvent, and then vacuum dried at room temperature to obtain 1.7 g of a white solid.

The obtained white solid was subjected to anion analysis by ion chromatography (manufactured by Metrohm, model number: IC-850), and one new peak was detected. This confirmed that a new anion was generated. Furthermore, when the obtained white solid was subjected to negative ion analysis by LC / MS (manufactured by Waters), a mass peak was observed at m / z = 127.0. Similarly, when positive ion analysis was performed, a mass peak was observed at m / z = 310.6. As a result, the molecular weights of the anions and cations of ethyl allylhexadecyldimethylammonium monofluorophosphate are almost the same, and the colorless and transparent oily liquid obtained is ethyl allylhexadecyldimethylammonium monofluorophosphate. confirmed.

(Example 16)

<Synthesis of dimethyl fluorophosphate>
To a 100 mL eggplant flask containing a stirrer, 3.9 g of potassium fluoride and 20 g of acetonitrile were added, followed by 6.5 g of dimethyl chlorophosphate. Thereafter, the solution in the eggplant flask was heated and refluxed at 80 ° C. to 100 ° C. for 2 hours under a nitrogen stream. Further, the solution in the eggplant flask was allowed to cool to room temperature and then filtered under reduced pressure to separate the white solid and the filtrate. As a result, an acetonitrile solution of dimethyl fluorophosphate, which is a slightly yellow transparent liquid, was obtained.

<Synthesis of methyl lithium monofluorophosphate>
To a 50 mL eggplant flask containing a stirrer, 1.0 g of anhydrous lithium chloride was added, and then the acetonitrile solution of dimethyl fluorophosphate was added. Thereafter, the solution in the eggplant flask was heated and refluxed at 110 ° C. to 120 ° C. for 4 hours under a nitrogen stream. Further, the solution in the eggplant flask was allowed to cool to room temperature, and then the solvent in the solution was distilled off at 40 ° C. under reduced pressure to obtain 2.1 g of a white solid.

The obtained white solid was subjected to anion analysis by ion chromatography (manufactured by Metrohm, model number: IC-850), and one new peak was detected. This confirmed that a new anion was generated. Furthermore, when the obtained white solid was subjected to negative ion analysis by LC / MS (manufactured by Waters), a mass peak was observed at m / z = 12.9. This almost coincided with the molecular weight of the methyl monofluorophosphate anion, and it was confirmed that the obtained white solid was methyl lithium monofluorophosphate.

(Example 17)
<Synthesis of diisopropyl fluorophosphate>
To a 100 mL eggplant flask containing a stir bar, 5.2 g of potassium fluoride and 20 g of acetonitrile were added, and then 12.0 g of diisopropyl chlorophosphate was added. Thereafter, the solution in the eggplant flask was heated and refluxed at 80 ° C. to 100 ° C. for 2 hours under a nitrogen stream. Further, the solution in the eggplant flask was allowed to cool to room temperature and then filtered under reduced pressure to separate the white solid and the filtrate. Subsequently, by distilling off the solvent in the filtrate at 40 ° C. under reduced pressure, 10.0 g of diisopropyl fluorophosphate, which is a slightly yellow transparent liquid, was obtained.

<Synthesis of isopropyl lithium monofluorophosphate>
Anhydrous lithium bromide (1.2 g) and acetonitrile (20 g) were added to a 100 mL eggplant flask containing a stirrer, followed by the above-described diisopropyl fluorophosphate (5.0 g). Thereafter, the solution in the eggplant flask was heated and refluxed at 110 ° C. to 120 ° C. for 5 hours under a nitrogen stream. Further, the solution in the eggplant flask was allowed to cool to room temperature, and the precipitate in the solution was filtered off by vacuum filtration. Thereafter, the precipitate was dried at 130 ° C. under a nitrogen stream to obtain 1.6 g of a white solid.

The obtained white solid was subjected to anion analysis by ion chromatography (manufactured by Metrohm, model number: IC-850), and one new peak was detected. This confirmed that a new anion was generated. Furthermore, when the obtained white solid was subjected to negative ion analysis by LC / MS (manufactured by Waters), a mass peak was observed at m / z = 140.9. This almost coincided with the molecular weight of the isopropyl monofluorophosphate anion, and it was confirmed that the obtained white solid was isopropyl lithium monofluorophosphate.

(Example 18)
<Synthesis of dibutyl fluorophosphate>
To a 100 mL eggplant flask containing a stir bar, 4.4 g of potassium fluoride and 20 g of acetonitrile were added, and then 11.5 g of dibutyl chlorophosphate was added. Thereafter, the solution in the eggplant flask was heated and refluxed at 80 ° C. to 100 ° C. for 2 hours under a nitrogen stream. Further, the solution in the eggplant flask was allowed to cool to room temperature and then filtered under reduced pressure to separate the white solid and the filtrate. Subsequently, the solvent in the filtrate was distilled off at 40 ° C. under reduced pressure to obtain 6.8 g of dibutyl fluorophosphate which was a slightly yellow transparent liquid.

<Synthesis of butyl lithium monofluorophosphate>
To a 100 mL eggplant flask containing a stir bar, 1.0 g of anhydrous lithium bromide and 20 g of acetonitrile were added, and then 5.0 g of the dibutyl fluorophosphate was added. Thereafter, the solution in the eggplant flask was heated and refluxed at 110 ° C. to 120 ° C. for 3 hours under a nitrogen stream. Further, the solution in the eggplant flask was allowed to cool to room temperature, and the precipitate in the solution was filtered off by vacuum filtration. Thereafter, the precipitate was dried at 130 ° C. under a nitrogen stream to obtain 1.6 g of a white solid.

The obtained white solid was subjected to anion analysis by ion chromatography (manufactured by Metrohm, model number: IC-850), and one new peak was detected. This confirmed that a new anion was generated. Furthermore, when the obtained white solid was subjected to negative ion analysis by LC / MS (manufactured by Waters), a mass peak was observed at m / z = 155.0. This almost coincided with the molecular weight of the butyl monofluorophosphate anion, and it was confirmed that the obtained white solid was butyl lithium monofluorophosphate.

(Example 19)
<Synthesis of bis (2-ethoxyethyl) fluorophosphate>
To a 50 mL eggplant flask containing a stir bar, 1.5 g of potassium fluoride and 16 g of acetonitrile were added, and subsequently, 4.6 g of the bis (2-ethoxyethyl) chlorophosphate was added. Thereafter, the solution in the eggplant flask was heated at 50 ° C. to 60 ° C. for 2 hours under a nitrogen stream while stirring. Furthermore, silica gel was added to the solution and stirred, and the solvent in the solution was distilled off at 40 ° C. under reduced pressure to obtain a white solid mixture containing the target product. A small amount of silica gel was loaded on a column tube equipped with a glass filter, and the resulting white solid mixture was added and extracted with ethyl acetate (flash column). The solvent was distilled off at 40 ° C. under reduced pressure to obtain 1.5 g of bis (2-ethoxyethyl) fluorophosphate, which is a colorless and transparent liquid.

<Synthesis of lithium monofluorophosphate (2-ethoxyethyl)>
Into a 50 mL eggplant flask containing a stir bar, 0.2 g of anhydrous lithium bromide and 10 g of acetonitrile were added, and then 1.0 g of the bis (2-ethoxyethyl) fluorophosphate was added. Thereafter, the solution in the eggplant flask was heated at 50 ° C. to 60 ° C. for 4.5 hours under a nitrogen stream while stirring. Further, the solution in the eggplant flask was allowed to cool to room temperature, and the precipitate in the solution was filtered off by vacuum filtration. Thereafter, the precipitate was dried at 130 ° C. under a nitrogen stream to obtain 0.4 g of a white solid.

The obtained white solid was subjected to anion analysis by ion chromatography (manufactured by Metrohm, model number: IC-850), and one new peak was detected. This confirmed that a new anion was generated. Furthermore, when the obtained white solid was subjected to negative ion analysis by LC / MS (manufactured by Waters), a mass peak was observed at m / z = 170.9. This almost coincided with the molecular weight of the monofluorophosphate (2-ethoxyethyl) anion, and it was confirmed that the obtained white solid was lithium monofluorophosphate (ethoxyethyl).

(Comparative Example 1)
In this comparative example, sodium fluoride (manufactured by Stella Chemifa Co., Ltd.) was used as a compound that imparts fluorine release properties.

(Comparative Example 2)
In this comparative example, sodium monofluorophosphate (manufactured by Strem Chemicals Co., Ltd.) was used as the compound that imparts fluorine release properties.

(Evaluation of sustained release of fluoride ions)
Sample aqueous solutions were prepared using the monofluorophosphate ester salts obtained in Examples 1 to 19, sodium fluoride of Comparative Example 1, and sodium monofluorophosphate of Comparative Example 2, respectively. The abundance of all fluorine atoms in each sample aqueous solution was 1000 ppm. A 0.1% acid phosphatase phosphate buffer solution was prepared using acid phosphatase (3.3 U / mg) and 0.1 M phosphate buffer solution (pH 7) (manufactured by Wako Pure Chemical Industries, Ltd.).

Subsequently, 4.7 g of the sample aqueous solution and 0.3 g of 0.1% acid phosphatase phosphate buffer were placed in a 20 mL vial to prepare an evaluation sample. A vial containing the evaluation sample was placed in a 37 ° C. thermostat and heated for 8 hours. *

Thereafter, the fluoride ion in the evaluation sample was quantitatively analyzed by ion chromatography (manufactured by Metrohm, Model No .: IC-850) at regular intervals, and the fluoride ion concentration after 8 hours was changed to A _8, 4 hours later. the fluoride ion concentration of fluorine ion concentration in the case of a _{4, 0} hours and a _0, according to the following equation to calculate the S (%). The results are shown in Table 1 below.
S (%) = (A ₄ −A ₀ ) / (A ₈ −A ₀ ) × 100

Regarding the release and sustained release of fluorine ions, the closer the value of S is to 50%, the more uniformly the fluorine ions are released over 8 hours and the higher the release. And as shown in following Table 1, about each Example, S (%) showed the value around 50%, respectively, and it was confirmed that it is excellent in the sustained release property of a fluorine ion. On the other hand, it was confirmed that Comparative Examples 1 and 2 were 99% and 68%, respectively, and after 8 hours, both released small amounts of fluorine ions and were inferior in sustained release. .

Claims

A monofluorophosphate ester salt represented by the following chemical formula (1).

(However, M n + is hydrogen ion, alkali metal ion, alkaline earth metal ion, transition metal ion, rare earth element ion, zinc ion, aluminum ion, gallium ion, indium ion, germanium ion, tin ion, lead ion and onium. R 1 represents any one selected from the group consisting of ions, wherein R 1 is a hydrocarbon group having 1 to 20 carbon atoms, or a range having 1 to 20 carbon atoms, and is a halogen atom, heteroatom or Represents a hydrocarbon group having at least one of saturated bonds, wherein n represents a valence.)
The monofluorophosphate ester salt according to claim 1, wherein the alkali metal ion is any one selected from the group consisting of lithium ion, sodium ion, potassium ion, rubidium ion and cesium ion.
The monofluorophosphate ester salt according to claim 1 or 2, wherein the alkaline earth metal ion is any one selected from the group consisting of magnesium ion, calcium ion, strontium ion and barium ion.
The transition metal ion is any one selected from the group consisting of manganese ions, cobalt ions, nickel ions, chromium ions, copper ions, silver ions, molybdenum ions, tungsten ions, and vanadium ions. The monofluorophosphoric acid ester salt of any one.
The rare earth element ion is scandium ion, yttrium ion, lanthanum ion, cerium ion, praseodymium ion, neodymium ion, promethium ion, samarium ion, europium ion, gadolinium ion, terbium ion, dysprosium ion, holmium ion, erbium ion, thulium ion The monofluorophosphate ester salt according to any one of claims 1 to 4, which is any one selected from the group consisting of ytterbium ions and lutetium ions.
The onium ion is any one selected from the group consisting of ammonium ion, primary ammonium ion, secondary ammonium ion, tertiary ammonium ion, quaternary ammonium ion, quaternary phosphonium ion and sulfonium ion. The monofluorophosphate ester salt according to any one of claims 1 to 5, wherein
Fluorinating a monohalophosphate diester represented by the following chemical formula (2) to produce a monofluorophosphate diester represented by the following chemical formula (3);
The monofluorophosphate diester and M n + X 2 n (where M n + is an alkali metal ion, alkaline earth metal ion, transition metal ion, rare earth element ion, zinc ion, aluminum ion, gallium ion, indium ion, germanium) It represents any one selected from the group consisting of ions, tin ions, lead ions, and onium ions, X 2 represents a halogen atom of F, Cl, Br, or I. The n represents a valence. ) To produce a monofluorophosphate ester salt represented by the following chemical formula (1).

(However, R 1 and R 2 are independently of each other a hydrocarbon group having 1 to 20 carbon atoms, or a carbon group having 1 to 20 carbon atoms, and having a halogen atom, a hetero atom or an unsaturated bond. Represents a hydrocarbon group having at least one of them, X 1 represents a halogen atom other than F.)

(Wherein R 1 and R 2 are independently of each other a hydrocarbon group having 1 to 20 carbon atoms, or a group having 1 to 20 carbon atoms, and at least one of a halogen atom, a hetero atom and an unsaturated bond) Represents a hydrocarbon group having one.)

(However, said M n + is from hydrogen, alkali metal ions, alkaline earth metal ions, transition metal ions, rare earth element ions, zinc ions, aluminum ions, gallium ions, indium ions, germanium ions, tin ions, lead ions and onium ions. And R 1 represents a hydrocarbon group having 1 to 20 carbon atoms, or a range of 1 to 20 carbon atoms, which is a halogen atom, a hetero atom, or an unsaturated bond. A hydrocarbon group having at least one of the above, wherein n represents a valence.)
The production of a monofluorophosphate ester salt according to claim 7, wherein the fluorination treatment in the step of producing the monofluorophosphate diester is performed by bringing the monohalophosphate diester and a fluorinating agent into contact with each other in a non-aqueous solvent. Method.
The method for producing a monofluorophosphate ester salt according to claim 8, wherein an alkali metal fluoride, an alkaline earth metal fluoride or an onium fluoride is used as the fluorinating agent.
The method for producing a monofluorophosphate ester salt according to claim 8 or 9, wherein a reaction start temperature of the fluorination treatment is in a range of 0 ° C to 200 ° C.
The any one of aprotic solvents selected from the group consisting of nitriles, esters, ketones, ethers and halogenated hydrocarbons is used as the non-aqueous solvent. A method for producing the monofluorophosphoric acid ester salt described in 1.
In the step of producing the monofluorophosphate ester salt, the monofluorophosphate diester within a range of 0.5 to 5 equivalents in another non-aqueous solvent with respect to 1 equivalent of the M n + X 2 n. The method for producing a monofluorophosphate ester salt according to any one of claims 8 to 11, which is carried out by reaction.
The reaction of the monofluorophosphate diester with the M n + X 2 n in the step of producing the monofluorophosphate ester salt is carried out using the monofluorophosphate diester as a reaction solvent. A method for producing the monofluorophosphate ester salt according to the item.
The reaction of the monofluorophosphate diester and the M n + X 2 n in the step of producing the monofluorophosphate ester salt is performed in another non-aqueous solvent,
The method according to any one of claims 8 to 12, wherein any one selected from the group consisting of alcohols, nitriles, esters, ketones, ethers and halogenated hydrocarbons is used as the other non-aqueous solvent. A method for producing the monofluorophosphate ester salt described above.
The reaction start temperature of the monofluorophosphoric diester and the M n + X 2 n is in the range of 0 ° C to 200 ° C, and the reaction time is in the range of 30 minutes to 20 hours. Of producing a monofluorophosphoric acid ester salt.
A fluoride ion releasing composition comprising the monofluorophosphate ester salt according to any one of claims 1 to 6.
An oral composition comprising the monofluorophosphate ester salt according to any one of claims 1 to 6.
A dental composition comprising the monofluorophosphate ester salt according to any one of claims 1 to 6.