Synthesis method of a disubstituted phosphinic acid and its salts

Abstract

The present invention discloses a method for synthesizing a disubstituted phosphinic acid and its salt. Route 1: A compound of formula (III) is hydrolyzed under acidic conditions to obtain a compound of formula (II), i.e., a disubstituted phosphinic acid; the resulting compound of formula (II) reacts with a metal M1 source to obtain a compound of formula (I), i.e., a disubstituted phosphinic salt. Route 2: A compound of formula (III) is hydrolyzed under alkaline conditions in the presence of a metal M2 source to obtain a compound of formula (Ia), i.e., a disubstituted phosphinic salt; the resulting compound of formula (Ia) reacts with a metal M1 source to obtain a compound of formula (I), i.e., another disubstituted phosphinic salt. #imgabs0##imgabs1#

Description

Technical Field

[0001] The present invention relates to the technical field of chemical synthesis, and in particular to a method for synthesizing a disubstituted phosphinic acid and a salt thereof. Background Art

[0002] Among disubstituted phosphinic acids and their salts, dialkylphosphinic acids and their salts are the most representative and widely used. Their structures contain two C-P bonds. Long-chain dialkylphosphinic acids with 6-10 carbon atoms are primarily used in the extraction and purification of rare metals and rare earth metals. They selectively complex metal ions at specific pH values, separating the target metal ions from the aqueous phase through extraction and phase separation, while also achieving a certain degree of purification. Currently commercialized products include: PC88A, which can be used for the extraction and purification of cobalt and molybdenum; and CYANEX272, a mineral processing extractant with high selectivity and separation coefficient for the extraction and separation of nickel, cobalt, and rare earth elements.

[0003] Furthermore, dialkyl phosphinates can also be used as environmentally friendly flame retardants, with several products already commercially available, such as Exolit OP1230 and Exolit OP1240. Compared to other halogen-free flame retardants, dialkyl phosphinate flame retardants are particularly suitable for electronic devices and components, enabling flame-retardant composite materials to maintain excellent mechanical and thermoelectric properties. Currently, they are widely used in connectors and switch components made from epoxy resin (EP), polylactic acid (PLA), ABS, and nylon (PA), rigid and flexible printed circuit boards, solder mask coatings, and components for the automotive and electronics industries.

[0004] The synthesis methods of dialkylphosphinic acid and its salts are classified according to the PC bond construction and can be mainly divided into the following types:

[0005] Free radical addition reaction is the mainstream method for the synthesis of dialkylphosphinic acid and its salts at this stage.

[0006] Chinese patent publication number CN101475588B discloses the reaction of sodium hypophosphite, acid, and α-olefin in the presence of a free radical initiator to produce a series of dialkylphosphinic acids, which can be used in mineral flotation, metal ion extraction, and other fields. This method is suitable for synthesizing target compounds with the same carbon number as the dialkyl group but with a smaller alkyl group. However, when using olefins with smaller carbon numbers as raw materials, the reaction typically requires an autoclave due to their lower boiling point.

[0007] Aluminum diethylphosphinate, the main ingredient in Exolit OP1230, is also produced using this method, using ethylene, sodium hypophosphite and a catalyst as raw materials.

[0008] In the dialkylphosphinic acid method applicable to this mechanism, phosphorus-containing compounds such as phosphine, hypophosphorous acid, sodium hypophosphite, and hypophosphite esters can also be selected as reaction substrates.

[0009] The Arbuzov reaction is a classic reaction for forming PC bonds. Chinese patent application publication number CN104163831A discloses that ethyl methyl phosphite and halogenated ethane are used as raw materials to produce ethyl methyl phosphite through an Arbuzov reaction. This methyl ethyl phosphinate is then hydrolyzed and salted with a metal M to produce methyl ethyl phosphinate. While the halogenated hydrocarbon raw material is inexpensive and readily available, the substrate has poor reactivity and requires a temperature of 130-140°C to react. Furthermore, because the halogenated hydrocarbon is a gas at these temperatures, the reaction requires pressurized conditions to proceed properly.

[0010] In recent years, with the in-depth development and research of disubstituted phosphinic acids and their salts, their demand has also been increasing. Therefore, it is extremely important to develop a synthesis process for disubstituted phosphinic acids and their salts with mild reaction conditions, higher yield and lower cost. Summary of the Invention

[0011] For the sake of simplicity, the "compound of formula (N) (such as the compound of formula (II))" mentioned below may also include any optical isomers, geometric isomers, tautomers, isomer mixtures or salts of the compound of formula (N).

[0012] Unless otherwise indicated, references herein to "a compound of formula (N) (e.g., a compound of formula (II)") also encompass isotopically labeled compounds in which any atom in the compound is replaced by an isotope thereof. That is, the present invention includes all agriculturally acceptable isotopically labeled compounds of the compound of formula (N), wherein one or more atoms are replaced by atoms having the same atomic number as the atom commonly found in nature but a different atomic mass or mass number.

[0013] Examples of suitable isotopes for inclusion in the compounds of the present invention include isotopes of hydrogen such as 2 H(D) and 3 H(T), isotopes of carbon, such as 11 C. 13 C and 14 C, isotopes of chlorine, such as 37 Cl, isotopes of fluorine, such as 18 F, isotopes of iodine, such as 123 I and 125 I, isotopes of nitrogen, such as 13 N and 15 N, isotopes of oxygen, such as 15 O. 17 O and 18 O, and isotopes of sulfur such as35 S.

[0014] Isotopically labeled compounds of formula (N) can generally be prepared by conventional techniques known to those skilled in the art or by using an appropriate isotopically labeled reagent in place of the non-labeled reagent previously used in an analogous manner to the procedures described in the Examples and Preparations appended herein.

[0015] Certain compounds of the present invention may exist in unsolvated forms as well as solvated forms (including hydrated forms). In general, compounds of formula (N) are encompassed within the scope of the present invention regardless of whether they exist in solvated or unsolvated forms.

[0016] Certain compounds of the present invention may exist in different crystalline or amorphous forms. Regardless of the form in which they exist, the compounds of formula (N) are included within the scope of the present invention.

[0017] To avoid ambiguity, the following definitions are given for the terms used in this document. Unless otherwise specified, the meanings of the terms used in this document are as follows.

[0018] As used herein, the term "substituted" means that one or more (preferably 1 to 5, more preferably 1 to 3) hydrogen atoms in the group are independently replaced by a corresponding number of substituents.

[0019] As used herein, the term "independently" or "independently" means that when there are more than one substituent, the substituents may be the same or different.

[0020] As used herein, the term "optional" or "optionally" means that the event it describes may or may not occur. For example, a group "optionally substituted" means that the group may be unsubstituted or substituted.

[0021] As used herein, the term "heteroatom" refers to oxygen (O), nitrogen (N), or S (O) m (wherein m can be 0, 1 or 2, i.e. a sulfur atom S, or a sulfoxide group SO, or a sulfonyl group S(O)2).

[0022] As used herein, the term "alkyl" refers to a saturated aliphatic hydrocarbon, including straight and branched chains. In some embodiments, the alkyl group has, for example, 1-6 or 1-3 carbon atoms. For example, the term "C1-C6 alkyl" refers to a straight or branched chain radical having 1-6 carbon atoms. The term "C1-C6 alkyl" includes in its definition the term "C 1-6"C1-C3 alkyl", "C1-C3 alkyl" and "C1-C4 alkyl". Examples of alkyl include, but are not limited to, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, 2-pentyl, 3-pentyl, isopentyl, neopentyl, (R)-2-methylbutyl, (S)-2-methylbutyl, 3-methylbutyl, 2,3-dimethylpropyl, 2,3-dimethylbutyl, hexyl, and the like.

[0023] As used herein, the term "C3-C6 cycloalkyl" refers to a cycloalkyl group having 3 to 6 carbon atoms forming a ring. For example, C3-C6 cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl.

[0024] As used herein, the term "n-membered heterocycloalkyl" refers to a cycloalkyl group having m carbon atoms forming a ring and (nm) heteroatoms forming a ring, wherein the heteroatoms are selected from at least one of N, O and S. For example, three-membered to six-membered heterocycloalkyl groups include, but are not limited to, oxetane, thietane, azetidine, tetrahydrofuran, tetrahydrothiophene, pyrrolidine, tetrahydropyran, tetrahydrothiopyran, piperidine, morpholine, and piperazine.

[0025] As used herein, the term "C6-C 10 The term "aryl" refers to an aromatic group having an aromatic ring containing 6 to 10 carbon atoms, preferably a phenyl group.

[0026] As used herein, the term "n-membered heteroaryl" refers to a heteroaryl group having m carbon atoms forming an aromatic ring and (nm) heteroatoms forming an aromatic ring, wherein the heteroatoms are selected from at least one of N, O, and S. For example, five-membered to ten-membered heteroaryl groups include, but are not limited to, pyrazine, pyrazole, pyrrole, furan, thiophene, thiazole, and pyridine.

[0027] As used herein, the term "haloalkyl" refers to an alkyl group having one or more halogen substituents (up to a perhaloalkyl group, i.e., each hydrogen atom of the alkyl group is replaced by a halogen atom). For example, the term "C1-C6 haloalkyl" refers to a C1-C6 alkyl group having one or more halogen substituents (up to a perhaloalkyl group, i.e., each hydrogen atom of the alkyl group is replaced by a halogen atom). As another example, the term "C1 haloalkyl" refers to a methyl group having 1, 2, or 3 halogen substituents. Examples of haloalkyl groups include: CF3, C2F5, CHF2, CH2F, CH2CF3, CH2Cl, etc.

[0028] As used herein, numerical ranges related to the number of substituents, carbon atoms, or ring atoms represent a complete enumeration of all integers within the range, and ranges are intended merely as a simplified notation. For example, "1-4 substituents" means 1, 2, 3, or 4 substituents; "3-8 carbon atoms" means 3, 4, 5, 6, 7, or 8 carbon atoms. Therefore, numerical ranges related to the number of substituents, carbon atoms, or ring atoms also encompass any subranges thereof, and each subrange is considered disclosed herein.

[0029] In a first aspect, the present invention provides a method for synthesizing a disubstituted phosphinic acid, wherein a compound of formula (III) is hydrolyzed under acidic conditions to obtain a compound of formula (II), namely the disubstituted phosphinic acid;

[0030]

[0031] in:

[0032] X 1- is a halide ion or R 2 OSO2O - (sulfate monoester);

[0033] R 1 、R 2 are independently selected from C1-C 18 Alkyl, C2-C 18 Alkenyl, C3-C 18 Cycloalkyl, C6-C 10 Aryl, five-membered to ten-membered heteroaryl, wherein C1-C 18 Alkyl, C2-C 18 Alkenyl, C3-C 18 Cycloalkyl, C6-C 10 Aryl, five-membered to ten-membered heteroaryl, optionally substituted with one or more halogen, carboxyl, hydroxyl, cyano, amino, nitro, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C6 cycloalkyl, C6-C 10 aryl substitution;

[0034] R 3 、R 4 are independently selected from hydrogen, C1-C 18 Alkyl, C2-C 18 Alkenyl, C3-C 18 Cycloalkyl, C6-C 10 Aryl, five-membered to ten-membered heteroaryl, or R 3 and R 4 Together with the nitrogen atom to which it is attached, it forms a three- to six-membered heterocycloalkyl group, wherein C1-C 18 Alkyl, C2-C 18 Alkenyl, C3-C18 Cycloalkyl, C6-C 10 Aryl, five-membered to ten-membered heteroaryl, optionally substituted with one or more halogen, carboxyl, hydroxyl, cyano, amino, nitro, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C6 cycloalkyl, C6-C 10 Aryl substitution.

[0035] According to the first aspect of the present invention, as a preferred embodiment of the compound of formula (III), R 1 、R 2 、R 3 and R 4 Can be independently selected from:

[0036] C1-C 18 Alkyl or C3-C 18 Cycloalkyl, preferably selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, tert-butyl, n-pentyl, isopentyl, sec-pentyl, tert-pentyl, n-hexyl, isohexyl, sec-hexyl, tert-hexyl, n-heptyl, isoheptyl, sec-heptyl, tert-heptyl, n-octyl, isooctyl, sec-octyl, tert-octyl, n-nonyl, isononyl, sec-nonyl, tert-nonyl, n-decyl, isodecyl, sec-decyl, tert-decyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, adamantyl; or

[0037] C2-C 18 Alkenyl, preferably selected from vinyl, propenyl, 1-butenyl, 2-butenyl, isobutenyl, norbornenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl; or

[0038] C6-C 10 Aryl, preferably selected from phenyl, naphthyl; or

[0039] a five- to ten-membered heteroaryl group, preferably selected from pyrazinyl, pyrazolyl, pyrrolyl, furyl, thienyl, thiazolyl, and pyridinyl;

[0040] In addition, R 3 and R 4 It can also form a three- to six-membered heterocycloalkyl group together with the nitrogen atom to which it is attached. The three- to six-membered heterocycloalkyl group can be selected from cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl groups containing zero, one or two heteroatoms selected from O and S and N heteroatoms.

[0041] According to the first aspect of the present invention, the acidic conditions can be provided by an acid. The acid providing the acidic conditions can be selected from at least one of hydrochloric acid, hydrogen chloride, sulfuric acid, hydrobromic acid, hydroiodic acid, phosphoric acid, nitric acid, formic acid, and acetic acid, preferably hydrochloric acid and / or sulfuric acid.

[0042] According to the first aspect of the present invention, the hydrolysis temperature may be 30-120°C (e.g., 40°C, 50°C, 60°C, 70°C, 80°C, 90°C, 100°C, 110°C, 120°C, etc.), preferably 70-110°C.

[0043] According to the first aspect of the present invention, the hydrolyzed 3 R 4 The by-product of the radical can be separated from the compound of formula (II), and then subjected to post-treatment and selectively recycled.

[0044] According to the first aspect of the present invention, the compound of formula (II) can be obtained by adjusting the reaction solution after hydrolysis to a suitable pH value, cooling for crystallization, solid-liquid separation or adding a solvent for extraction, refining and drying.

[0045] In a second aspect, the present invention provides a method for synthesizing a disubstituted phosphinate, comprising the steps of:

[0046] S1, synthesizing a disubstituted phosphinic acid using the synthesis method described in the first aspect of the present invention;

[0047] S2, reacting the disubstituted phosphinic acid synthesized in step S1 with a metal M1 source to obtain a compound of formula (I), i.e., the disubstituted phosphinic acid salt; the metal M1 source is selected from at least one of an oxide, a hydroxide, and a salt of metal M1;

[0048]

[0049] Wherein, M1 is at least one of Al, Zn, Ca, Mg, Fe, Sn, Bi, Zr, Cd, and Ti, preferably at least one of Al and Zn;

[0050] R 1 、R 2 The same as defined in the first aspect of the present invention;

[0051] n represents the valence state of the metal M1 ion.

[0052] According to the second aspect of the present invention, in step S2, the reaction can be carried out at pH = 5-12.

[0053] According to the second aspect of the present invention, in step S2, the pH can be controlled at 5-12 by adding an inorganic base.

[0054] According to the second aspect of the present invention, in step S2, the inorganic base can be selected from at least one of oxides, hydroxides, carbonates, bicarbonates, and basic carbonates of alkali metals and / or alkaline earth metals, and is preferably sodium hydroxide.

[0055] According to the second aspect of the present invention, in step S2, the salt of the metal M1 can be selected from at least one of chlorides, sulfates, bisulfates, nitrates, carbonates, bicarbonates, and basic carbonates of the metal M1.

[0056] According to the second aspect of the present invention, in step S2, the metal M1 source is preferably at least one of chloride, hydroxide, and sulfate of metal M1.

[0057] According to the second aspect of the present invention, in step S2, the reaction temperature may be 10-100°C, preferably 70-100°C.

[0058] According to the second aspect of the present invention, in step S2, the molar ratio of the disubstituted phosphinic acid synthesized in step S1 to the metal M1 source can be 1:0.3-5, preferably 1:0.3-1.5.

[0059] According to the second aspect of the present invention, the NR-containing 3 R 4 The by-product of the radical can be separated from the compound of formula (II) immediately after hydrolysis, and then subjected to post-treatment and selectively recycled, or separated from the compound of formula (I), and then subjected to post-treatment and selectively recycled.

[0060] In a third aspect, the present invention provides a method for synthesizing a disubstituted phosphinate, comprising step S11 and an optionally performed step S12;

[0061] Step S11, hydrolyzing the compound of formula (III) under alkaline conditions in the presence of a metal M2 source to obtain the compound of formula (Ia), i.e., the disubstituted phosphinate; the metal M2 source is selected from at least one of an oxide, a hydroxide, and a salt of metal M2;

[0062] Step S12, reacting the compound of formula (Ia) obtained in step S11 with a metal M1 source to obtain a compound of formula (I), i.e., the disubstituted phosphinate; the metal M1 source is selected from at least one of an oxide, a hydroxide, and a salt of metal M1;

[0063]

[0064] in:

[0065] X 1- 、R 1 、R 2 、R 3 、R 4 The same as defined in the first aspect of the present invention;

[0066] M1 and n are as defined in the second aspect of the present invention;

[0067] M2 is at least one of Li, Na, K, Al, Zn, Ca, and Mg;

[0068] k represents the valence state of the metal M2 ion.

[0069] According to the third aspect of the present invention, in some embodiments, M1 may be different from M2.

[0070] According to the third aspect of the present invention, in step S11, the salt of the metal M2 is selected from at least one of carbonate, bicarbonate, and basic carbonate of the metal M2.

[0071] According to the third aspect of the present invention, in step S11, the metal M2 source is preferably sodium hydroxide.

[0072] According to the third aspect of the present invention, in step S11, the hydrolysis temperature is 30-120°C (for example, 40°C, 50°C, 60°C, 70°C, 80°C, 90°C, 100°C, 110°C, 120°C, etc.), preferably 70-110°C.

[0073] According to the third aspect of the present invention, in step S11, the hydrolyzed 3 R 4 The by-product of the group is separated from the compound of formula (Ia) after hydrolysis, and then subjected to post-treatment and selectively recycled, or separated from the compound of formula (I), and then subjected to post-treatment and selectively recycled.

[0074] According to the third aspect of the present invention, in step S12, the salt of the metal M1 is selected from at least one of chloride, sulfate, bisulfate, nitrate, carbonate, bicarbonate, and basic carbonate of the metal M1.

[0075] According to the third aspect of the present invention, in step S12, the reaction temperature is 10-100°C, preferably 70-100°C.

[0076] According to the third aspect of the present invention, the molar ratio of the compound of formula (Ia) obtained in step S11 to the metal M1 source is 1:0.3-5, preferably 1:0.3-1.5.

[0077] The synthesis method described in the first to third aspects of the present invention, containing -NR 3 R 4 The by-product of the radical is specifically HNR3R4 or its hydrochloride under the corresponding reaction conditions (basic or acidic).

[0078] In the synthesis methods described in the first to third aspects of the present invention, the compound of formula (III) can be obtained by reacting a commercially available compound of formula (IV) with a compound A; the compound A can be selected from R 2 X 2, sulfate compounds R 2 OSO2OR 2 At least one of which X 2 is a halogen;

[0079]

[0080] The compound of formula (IV) can be prepared by commercially available or prior art methods, such as Organic Letters (2004), 6(22), 4105-4107; Journal of the Chemical Society, Dalton Transactions (2002), (6), 1093-1103, etc.

[0081] The preparation of the compound of formula (III) can be carried out in the absence of a solvent or in the presence of an organic solvent. The organic solvent can be selected from aromatic hydrocarbon solvents (e.g., at least one of benzene, toluene, xylene, trimethylbenzene, ethylbenzene, diethylbenzene, isopropylbenzene, diisopropylbenzene, halogenated benzenes (e.g., chlorobenzene), dihalogenated benzenes, etc.), alkane solvents (e.g., at least one of n-hexane, cyclohexane, n-heptane, methylcyclohexane, ethylcyclohexane, etc.), ether solvents (e.g., tetrahydrofuran, methyltetrahydrofuran, methyl tert-butyl ether, diisopropyl ether, methylcyclopentyl ether, ethylene glycol dimethyl ether, dioxane, etc.), At least one of cyclopentane, diethylene glycol dimethyl ether, etc.), ester solvents (for example, at least one of ethyl acetate, isopropyl acetate, butyl acetate, etc.), amide solvents (for example, at least one of N,N-dimethylformamide, N,N-dimethylacetamide, hexamethylphosphoric triamide, N-methylpyrrolidone, 1,3-dimethyl-2-imidazolidinone, etc.), sulfur-containing solvents (for example, at least one of dimethyl sulfoxide, cyclopentane, etc.), preferably at least one selected from toluene and chlorobenzene.

[0082] The reaction temperature for preparing the compound of formula (III) may be 10-130°C (eg, 10°C, 20°C, 40°C, 60°C, 80°C, 100°C, 120°C, etc.).

[0083] The reaction temperature for preparing the compound of formula (III) can be 1-25 hours (eg, 2 hours, 4 hours, 6 hours, 12 hours, 18 hours, 24 hours, etc.).

[0084] The preparation of the compound of formula (III) can be carried out under normal pressure or pressurized conditions, and the gauge pressure of the reaction system can be 0 to 20.0 atm, preferably 0 to 0.5 atm. The pressurized condition can be achieved by holding the pressure in a closed system or adding additional reactants to increase the system pressure. For example, when compound A has a low boiling point (for example, compound A is ethyl chloride, and the boiling point of ethyl chloride is 12.3° C.), it is more suitable to hold the pressure in a closed system or add additional reactants to increase the system pressure.

[0085] The molar ratio of the compound of formula (IV) to compound A may be 1:0.9-10, preferably 1:1.0-1.5.

[0086] Those skilled in the art will appreciate that the definitions and preferences described in one aspect of the present invention are equally applicable to other aspects. Those skilled in the art will appreciate that the embodiments of the various aspects of the present invention can be combined in various ways without departing from the subject matter and ideas of the present application, and these combinations are also included within the scope of the present invention.

[0087] Compared with the prior art, the present invention has the following beneficial effects:

[0088] 1. The substrate has higher reactivity, making the conditions for the construction of the second PC bond milder, avoiding the more stringent reaction conditions of the Grignard reagent method and the olefin condensation reaction with a free radical mechanism;

[0089] 2. Particularly suitable for the synthesis of compounds of formula (I) and formula (II) with different dialkyl groups, and especially suitable for the synthesis of products containing long-chain alkanes in the dialkyl group; and

[0090] 3. The raw materials can be prepared and used in situ. The parameter selection space is large when the preparation process is prepared by reacting alkyl dichlorophosphine with amine, and the reaction is milder. DETAILED DESCRIPTION

[0091] The present invention will be further described below with reference to specific examples. It should be understood that these examples are intended to illustrate the present invention only and are not intended to limit the scope of the present invention. Unless otherwise stated, all reactants used in the examples are commercially available or available through prior art methods; the instruments and equipment used in the synthesis experiments and product analysis and testing are all conventional instruments and equipment commonly used in chemical synthesis.

[0092] Example 1: Synthesis of ethylmethylphosphinate aluminum (I-1)

[0093] 1) Synthesis of compound (III-1)

[0094]

[0095] The compound of formula (IV-1) (50.1 g, 0.263 mol, 1.0 eq.) and 150 g of toluene were added to an autoclave, and ethyl chloride (20.38 g, 0.316 mol, 1.2 eq.) was introduced. The temperature of the system was raised to 70-75°C and kept warm for 4 hours to obtain compound (III-1), which was directly used in the next reaction.

[0096] m / z(ESI)219.10([M-Cl] + ,100%); 31 P NMR (33 MHz) δ: 66.40 ppm.

[0097] 2) Synthesis of ethylmethylphosphinate aluminum (I-1)

[0098]

[0099] To the solution (III-1) was added a 30 wt% sodium hydroxide solution (70.57 g, 0.529 mol, 2.01 eq.), and the temperature was slowly raised to 85-95°C for reaction while distilling off low-boiling substances. After the reaction was complete, the pH of the system was adjusted to 8-9, and a 30 wt% aluminum sulfate solution (51.55 g, 0.045 mol, 0.172 eq.) was added. The internal temperature was maintained at 85-90°C, and stirred for 1 hour. The mixture was cooled, filtered, washed, and dried to obtain 83.1 g of the target compound (I-1), with a content of 98.5% and a yield of 94.5%.

[0100] m / z(ESI)107.03([M-1] - ,100%); 31 P NMR (243MHz, D2O) δ: 72.41ppm.

[0101] Example 2: Synthesis of zinc ethylmethylphosphinate (I-2)

[0102] 1) Synthesis of compound (III-1)

[0103]

[0104] The compound of formula (IV-1) (53.8 g, 0.283 mol, 1.0 eq.) and 160 g of toluene were added to an autoclave, and ethyl chloride (21.89 g, 0.339 mol, 1.2 eq.) was introduced. The temperature of the system was raised to 70-75°C and kept warm for 4 hours to obtain compound (III-1), which was directly used in the next reaction.

[0105] m / z(ESI)219.10([M-Cl] + ,100%); 31P NMR (33 MHz) δ: 66.40 ppm.

[0106] 2) Synthesis of zinc ethylmethylphosphinate (I-2)

[0107]

[0108] To the solution (III-1) was added a 30 wt% sodium hydroxide solution (76.16 g, 0.571 mol, 2.02 eq.), and the temperature was slowly raised to 85-95°C for reaction while distilling off low-boiling substances. After the reaction was complete, the pH of the system was adjusted to 8-9, and a 30 wt% zinc sulfate solution (77.60 g, 0.144 mol, 0.51 eq.) was added. The mixture was stirred at 85-90°C for 1 hour, cooled, filtered, washed, and dried to obtain 73.0 g of the target compound (I-2), with a content of 98.7% and a yield of 95.5%.

[0109] m / z(ESI)107.03([M-1] - ,100%); 31 P NMR (243MHz, D2O) δ: 72.41ppm.

[0110] Example 3: Synthesis of Ethylmethylphosphinic Acid (II-1)

[0111] 1) Synthesis of compound (III-2)

[0112]

[0113] Add the compound of formula (IV-1) (50.2 g, 0.264 mol, 1.0 eq.) and bromoethane (30.19 g, 0.277 mol, 1.05 eq.) to 150 g of toluene, raise the system temperature to 35-40°C and keep the reaction for 10 hours to obtain compound (III-2), which is directly used in the next reaction.

[0114] m / z(ESI)219.25([M-Br] + ,100%); 31 P NMR (33 MHz) δ: 66.50 ppm.

[0115] 2) Synthesis of ethylmethylphosphinic acid (II-1)

[0116]

[0117] To the solution (III-2) was added 30 wt% hydrochloric acid (96.62 g, 0.794 mol, 3.01 eq.), and the temperature was slowly raised to 85-95°C for reaction while distilling off low-boiling substances. After completion of the reaction, the mixture was extracted with ethyl acetate, washed, desolventized, and distilled to obtain 23.6 g of the target compound (II-1), with a content of 98.1% and a yield of 90.1%.

[0118] Example 4: Synthesis of ethylbutylphosphinate aluminum (I-3)

[0119] 1) Synthesis of compound (III-3)

[0120]

[0121] Add the compound of formula (IV-1) (50.6 g, 0.266 mol, 1.0 eq.) and chlorobutane (27.08 g, 0.293 mol, 1.1 eq.) to 150 g of toluene, raise the system temperature to 70-75°C and keep the reaction for 6 hours to obtain compound (III-3), which is directly used in the next reaction.

[0122] m / z(ESI)247.33([M-Cl] + ,100%); 31 P NMR (33 MHz) δ: 68.52 ppm.

[0123] 2) Synthesis of ethylbutylphosphinate aluminum (I-3)

[0124]

[0125] To the above solution (III-3) was added a 30 wt% sodium hydroxide solution (71.98 g, 0.540 mol, 2.03 eq.), and the temperature was slowly raised to 85-95°C for reaction while distilling off low-boiling substances. After the reaction was complete, the pH of the system was adjusted to 8-9, and a 30 wt% aluminum sulfate solution (52.06 g, 0.046 mol, 0.172 eq.) was added. The internal temperature was maintained at 85-90°C, and stirred for 1 hour. The mixture was cooled, filtered, washed, and dried to obtain 93.6 g of the target compound (I-3), with a content of 98.2% and a yield of 89.4%.

[0126] m / z(ESI)135.11([M-1] - ,100%); 31 P NMR (243 MHz, D2O) δ: 48.8.

[0127] Example 5: Synthesis of aluminum dimethylphosphinate (I-4)

[0128] 1) Synthesis of compound (III-4)

[0129]

[0130] Add the compound of formula (IV-1) (55.1 g, 0.290 mol, 1.0 eq.) and dimethyl sulfate (40.18 g, 0.319 mol, 1.1 eq.) to 165 g of toluene, raise the system temperature to 70-75°C and keep the reaction for 4 hours to obtain compound (III-4), which is directly used in the next reaction.

[0131] m / z(ESI)205.21([M-(OSO3Me)] + ,100%); 31 P NMR (33 MHz) δ: 61.82 ppm.

[0132] 2) Synthesis of aluminum dimethylphosphinate (I-4)

[0133]

[0134] To the above solution (III-4), 30 wt% sodium hydroxide solution (77.61 g, 0.582 mol, 2.01 eq.) was added, and the temperature was slowly raised to 85-95°C for reaction while distilling off low-boiling substances. After the reaction was completed, the pH of the system was adjusted to 8-9, and 30 wt% aluminum sulfate solution (56.69 g, 0.050 mol, 0.172 eq.) was added. The internal temperature was maintained at 85-90°C and stirred for 1 hour. The mixture was cooled, filtered, washed, and dried to obtain 78.7 g of the target compound (I-4), with a content of 98.5% and a yield of 93.5%.

[0135] m / z(ESI)93.11([M-1] - ,100%); 31 P NMR (243MHz, D2O) δ: 56.64ppm.

[0136] Example 6: Synthesis of aluminum dimethylphosphinate (I-4)

[0137] 1) Synthesis of compound (III-5)

[0138]

[0139] Add the compound of formula (IV-2) (51.1 g, 0.381 mol, 1.0 eq.) and dimethyl sulfate (52.85 g, 0.419 mol, 1.1 eq.) to 150 g of toluene, raise the system temperature to 70-75°C and keep the reaction for 4 hours to obtain compound (III-5), which is directly used in the next reaction.

[0140] m / z(ESI)149.25([M-(OSO3Me)] + ,100%); 31 P NMR (33 MHz) δ: 68.45 ppm.

[0141] 2) Synthesis of aluminum dimethylphosphinate (I-4)

[0142]

[0143] To the above solution (III-5), 30 wt% sodium hydroxide solution (102.59 g, 0.769 mol, 2.02 eq.) was added, and the temperature was slowly raised to 85-95°C for reaction while distilling off low-boiling substances. After the reaction was completed, the pH of the system was adjusted to 8-9, and 30 wt% aluminum sulfate solution (74.57 g, 0.065 mol, 0.172 eq.) was added. The internal temperature was maintained at 85-90°C and stirred for 1 hour. The mixture was cooled, filtered, washed, and dried to obtain 100.7 g of the target compound (I-4), with a content of 98.2% and a yield of 92.1%.

[0144] m / z(ESI)93.11([M-1] - ,100%); 31 P NMR (243MHz, D2O) δ: 56.64ppm.

[0145] Example 7: Synthesis of ethylphenylphosphinate aluminum (I-5)

[0146] 1) Synthesis of compound (III-6)

[0147]

[0148] Add the compound of formula (IV-3) (50.7 g, 0.201 mol, 1.0 eq.) and bromoethane (24.09 g, 0.221 mol, 1.1 eq.) to 150 g of toluene, raise the system temperature to 35-40°C and keep the reaction for 10 hours to obtain compound (III-6), which is directly used in the next reaction.

[0149] m / z(ESI)281.35([M-Br] + ,100%); 31 P NMR (33 MHz) δ: 58.52 ppm.

[0150] 2) Synthesis of ethylphenylphosphinate aluminum (I-5)

[0151]

[0152] To the above solution (III-6), 30 wt% sodium hydroxide solution (53.85 g, 0.404 mol, 2.01 eq.) was added, and the temperature was slowly raised to 85-95°C for reaction while distilling off low-boiling substances. After the reaction was completed, the pH of the system was adjusted to 8-9, and 30 wt% aluminum sulfate solution (39.33 g, 0.034 mol, 0.172 eq.) was added. The internal temperature was maintained at 85-90°C and stirred for 1 hour. The mixture was cooled, filtered, washed, and dried to obtain 91.3 g of the target compound (I-5), with a content of 98.5% and a yield of 91.5%.

[0153] m / z(ESI)169.17([M-1] - ,100%); 31 P NMR (243MHz, D2O) δ: 44.66ppm.

[0154] Example 8: Synthesis of methyl isooctylphosphinate aluminum (I-6)

[0155] 1) Synthesis of compound (III-7)

[0156]

[0157] Add the compound of formula (IV-1) (51.1 g, 0.269 mol, 1.0 eq.) and chloroisoctane (43.92 g, 0.295 mol, 1.1 eq.) to 150 g of toluene, raise the system temperature to 70-75°C and keep the reaction for 10 hours to obtain compound (III-7), which is directly used in the next reaction.

[0158] m / z(ESI)303.43([M-Cl] + ,100%); 31 P NMR (33 MHz) δ: 68.72 ppm.

[0159] 2) Synthesis of methyl isooctylphosphinate aluminum (I-6)

[0160]

[0161] To the solution (III-7) was added a 30 wt% sodium hydroxide solution (72.69 g, 0.545 mol, 2.03 eq.), and the temperature was slowly raised to 85-95°C for reaction while distilling off low-boiling substances. After the reaction was complete, the pH of the system was adjusted to 8-9, and a 30 wt% aluminum sulfate solution (52.58 g, 0.046 mol, 0.172 eq.) was added. The internal temperature was maintained at 85-90°C, and stirred for 1 hour. The mixture was cooled, filtered, washed, and dried to obtain 118.1 g of the target compound (I-6), with a content of 97.5% and a yield of 84.5%.

[0162] m / z(ESI)191.25([M-1] - ,100%); 31 P NMR (243MHz, D2O) δ: 56.64ppm.

[0163] In addition, it should be understood that after reading the above description of the present invention, those skilled in the art may make various changes or modifications to the present invention, and these equivalent forms also fall within the scope defined by the claims attached to this application.

[0164] It should also be noted that the various specific technical features described in the above specific embodiments can be combined in any appropriate manner without contradiction. In order to avoid unnecessary repetition, the present invention will not further describe various possible combinations.

[0165] In addition, the various embodiments of the present invention may be arbitrarily combined, and as long as they do not violate the concept of the present invention, they should also be regarded as the contents disclosed by the present invention.

Claims

1. A method for synthesizing a disubstituted phosphinate, characterized in that: The method comprises step S11 and an optionally executable step S12; Step S11, hydrolyzing the compound of formula (III) under alkaline conditions in the presence of a metal M2 source to obtain the compound of formula (Ia), i.e., the disubstituted phosphinate; the metal M2 source is selected from at least one of an oxide, a hydroxide, and a salt of metal M2; Step S12, reacting the compound of formula (Ia) obtained in step S11 with a metal M1 source to obtain a compound of formula (I), i.e., the disubstituted phosphinate; the metal M1 source is selected from at least one of an oxide, a hydroxide, and a salt of metal M1; in: X 1- is a halide ion or R 2 OSO2O - ; R 1 、R 2 are independently selected from C1-C 18 Alkyl, C2-C 18 Alkenyl, C3-C 18 Cycloalkyl, C6-C 10 Aryl, five-membered to ten-membered heteroaryl, wherein C1-C 18 Alkyl, C2-C 18 Alkenyl, C3-C 18 Cycloalkyl, C6-C 10 Aryl, five-membered to ten-membered heteroaryl, optionally substituted with one or more halogen, carboxyl, hydroxyl, cyano, amino, nitro, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C6 cycloalkyl, C6-C 10 aryl substitution; R 3 、R 4 are independently selected from hydrogen, C1-C 18 Alkyl, C2-C 18 Alkenyl, C3-C 18 Cycloalkyl, C6-C 10 Aryl, five-membered to ten-membered heteroaryl, or R 3 and R 4 Together with the nitrogen atom to which it is attached, it forms a three- to six-membered heterocycloalkyl group, wherein C1-C 18 Alkyl, C2-C 18 Alkenyl, C3-C 18 Cycloalkyl, C6-C 10 Aryl, five-membered to ten-membered heteroaryl, optionally substituted with one or more halogen, carboxyl, hydroxyl, cyano, amino, nitro, C1-C3 alkyl, C1-C3 haloalkyl, C1-C3 alkoxy, C3-C6 cycloalkyl, C6-C 10 aryl substitution; M2 is at least one of Li, Na, K, Al, Zn, Ca, and Mg; k represents the valence state of the metal M2 ion; M1 is at least one of Al, Zn, Ca, Mg, Fe, Sn, Bi, Zr, Cd, and Ti; n represents the valence state of the metal M1 ion.

2. The synthesis method according to claim 1, wherein The salt of the metal M2 in step S11 is selected from at least one of carbonate, bicarbonate, and basic carbonate of the metal M2.

3. The synthesis method according to claim 1, wherein The hydrolysis temperature in step S11 is 30-120°C.

4. The synthesis method according to claim 3, characterized in that The hydrolysis temperature in step S11 is 70-110°C.

5. The synthesis method according to claim 1, characterized in that The NR-containing 3 R 4 The by-product of the group is separated from the compound of formula (Ia) after hydrolysis, and then subjected to post-treatment and selectively recycled, or separated from the compound of formula (I), and then subjected to post-treatment and selectively recycled. 6 . The synthesis method according to claim 1 , wherein the salt of the metal M1 in step S12 is at least one selected from the group consisting of chloride, sulfate, bisulfate, nitrate, carbonate, bicarbonate, and basic carbonate of the metal M1.

7. The synthesis method according to claim 1, wherein the reaction temperature in step S12 is 10-100°C.

8. The synthesis method according to claim 7, wherein the reaction temperature in step S12 is 70-100°C.

9. The synthesis method according to claim 1, wherein in step S12, the molar ratio of the compound of formula (Ia) obtained in step S11 to the metal M1 source is 1:0.3-5. 10 . The synthesis method according to claim 9 , wherein in step S12, the molar ratio of the compound of formula (Ia) obtained in step S11 to the metal M1 source is 1:0.3-1.

5.

11. The synthesis method according to any one of claims 1 to 10, characterized in that The compound of formula (III) is prepared by reacting the compound of formula (IV) with compound A; wherein the compound A is selected from R 2 X 2 , sulfate compounds R 2 OSO2OR 2 At least one of which X 2 is a halogen; 12. The synthesis method according to claim 11, characterized in that The preparation of the compound of formula (III) is carried out in the absence of a solvent or in the presence of an organic solvent.

13. The synthesis method according to claim 12, characterized in that The organic solvent is selected from at least one of aromatic hydrocarbon solvents, alkane solvents, ether solvents, ester solvents, amide solvents, and sulfur-containing solvents.

14. The synthesis method according to claim 13, characterized in that The aromatic hydrocarbon solvent is at least one of benzene, toluene, xylene, trimethylbenzene, ethylbenzene, diethylbenzene, isopropylbenzene, diisopropylbenzene, halogenated benzene and dihalogenated benzene.

15. The synthesis method according to claim 13, characterized in that The alkane solvent is at least one of n-hexane, cyclohexane, n-heptane, methylcyclohexane, and ethylcyclohexane.

16. The synthesis method according to claim 13, characterized in that The ether solvent is at least one of tetrahydrofuran, methyltetrahydrofuran, methyl tert-butyl ether, diisopropyl ether, methyl cyclopentyl ether, ethylene glycol dimethyl ether, dioxane, and diethylene glycol dimethyl ether.

17. The synthesis method according to claim 13, characterized in that The ester solvent is at least one of ethyl acetate, isopropyl acetate and butyl acetate.

18. The synthesis method according to claim 13, characterized in that The amide solvent is at least one of N,N-dimethylformamide, N,N-dimethylacetamide, hexamethylphosphoric triamide, N-methylpyrrolidone, and 1,3-dimethyl-2-imidazolidinone.

19. The synthesis method according to claim 13, characterized in that The sulfur-containing solvent is at least one of dimethyl sulfoxide and sulfolane.

20. The synthesis method according to claim 11, characterized in that The reaction temperature for preparing the compound of formula (III) is 10-130° C., and the reaction time is 1-25 hours.

21. The synthesis method according to claim 11, characterized in that The preparation of the compound of formula (III) is carried out under normal pressure or pressurized conditions, and the surface pressure of the reaction system is 0-20.0 atm; the pressurized condition is achieved by holding the pressure in a closed system or adding additional reactants to increase the system pressure.

22. The synthesis method according to claim 21, characterized in that The surface pressure of the reaction system is 0 to 0.5 atm.

23. The synthesis method according to claim 11, characterized in that The molar ratio of the compound of formula (IV) to compound A is 1:0.9-10.

24. The synthesis method according to claim 23, characterized in that The molar ratio of the compound of formula (IV) to compound A is 1:1.0-1.5.

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