WO2024051121A1 - 一种4-(羟基甲基膦酰基)-2-羰基丁酸的制备方法 - Google Patents
一种4-(羟基甲基膦酰基)-2-羰基丁酸的制备方法 Download PDFInfo
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- WO2024051121A1 WO2024051121A1 PCT/CN2023/079816 CN2023079816W WO2024051121A1 WO 2024051121 A1 WO2024051121 A1 WO 2024051121A1 CN 2023079816 W CN2023079816 W CN 2023079816W WO 2024051121 A1 WO2024051121 A1 WO 2024051121A1
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- chloride
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- 238000002360 preparation method Methods 0.000 title claims abstract description 31
- YJTNHDYMQPHXFO-UHFFFAOYSA-N 4-(hydroxymethylphosphinyl)-2-oxobutyric acid Chemical compound CP(O)(=O)CCC(=O)C(O)=O YJTNHDYMQPHXFO-UHFFFAOYSA-N 0.000 title abstract 3
- MJDVPXPHTLECMC-UHFFFAOYSA-N prop-2-enoyl cyanide Chemical compound C=CC(=O)C#N MJDVPXPHTLECMC-UHFFFAOYSA-N 0.000 claims abstract description 40
- TUJPSRWSOZCXPK-UHFFFAOYSA-N 2-(oxomethylidene)but-3-enoic acid Chemical compound OC(=O)C(C=C)=C=O TUJPSRWSOZCXPK-UHFFFAOYSA-N 0.000 claims abstract description 37
- 239000002904 solvent Substances 0.000 claims abstract description 37
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 34
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 32
- 239000003112 inhibitor Substances 0.000 claims abstract description 32
- 238000006116 polymerization reaction Methods 0.000 claims abstract description 32
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims abstract description 27
- HFBMWMNUJJDEQZ-UHFFFAOYSA-N acryloyl chloride Chemical compound ClC(=O)C=C HFBMWMNUJJDEQZ-UHFFFAOYSA-N 0.000 claims abstract description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 22
- 239000003054 catalyst Substances 0.000 claims abstract description 19
- 239000000276 potassium ferrocyanide Substances 0.000 claims abstract description 18
- XOGGUFAVLNCTRS-UHFFFAOYSA-N tetrapotassium;iron(2+);hexacyanide Chemical compound [K+].[K+].[K+].[K+].[Fe+2].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-] XOGGUFAVLNCTRS-UHFFFAOYSA-N 0.000 claims abstract description 18
- 238000006467 substitution reaction Methods 0.000 claims abstract description 17
- 238000000746 purification Methods 0.000 claims abstract description 15
- 238000007259 addition reaction Methods 0.000 claims abstract description 12
- 238000004821 distillation Methods 0.000 claims abstract description 11
- FBWXUNCARHZYFO-UHFFFAOYSA-N C(=O)=C(C(=O)O)CCP(=O)(OCO)O Chemical compound C(=O)=C(C(=O)O)CCP(=O)(OCO)O FBWXUNCARHZYFO-UHFFFAOYSA-N 0.000 claims description 34
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 30
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 27
- NWVVVBRKAWDGAB-UHFFFAOYSA-N p-methoxyphenol Chemical compound COC1=CC=C(O)C=C1 NWVVVBRKAWDGAB-UHFFFAOYSA-N 0.000 claims description 20
- ONRKUGHFZWYUJP-UHFFFAOYSA-N methylphosphane dihydrochloride Chemical compound Cl.Cl.PC ONRKUGHFZWYUJP-UHFFFAOYSA-N 0.000 claims description 16
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 15
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 9
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 claims description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 6
- BGNXCDMCOKJUMV-UHFFFAOYSA-N Tert-Butylhydroquinone Chemical compound CC(C)(C)C1=CC(O)=CC=C1O BGNXCDMCOKJUMV-UHFFFAOYSA-N 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- SUSQOBVLVYHIEX-UHFFFAOYSA-N phenylacetonitrile Chemical compound N#CCC1=CC=CC=C1 SUSQOBVLVYHIEX-UHFFFAOYSA-N 0.000 claims description 6
- CNHDIAIOKMXOLK-UHFFFAOYSA-N toluquinol Chemical compound CC1=CC(O)=CC=C1O CNHDIAIOKMXOLK-UHFFFAOYSA-N 0.000 claims description 6
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 claims description 5
- 238000005292 vacuum distillation Methods 0.000 claims description 5
- 239000004250 tert-Butylhydroquinone Substances 0.000 claims description 4
- 235000019281 tert-butylhydroquinone Nutrition 0.000 claims description 4
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 3
- 235000010354 butylated hydroxytoluene Nutrition 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- 239000008096 xylene Substances 0.000 claims description 3
- 238000000034 method Methods 0.000 abstract description 12
- 239000012043 crude product Substances 0.000 abstract description 7
- 238000002156 mixing Methods 0.000 abstract description 7
- 230000008569 process Effects 0.000 abstract description 7
- CDPKWOKGVUHZFR-UHFFFAOYSA-N dichloro(methyl)phosphane Chemical compound CP(Cl)Cl CDPKWOKGVUHZFR-UHFFFAOYSA-N 0.000 abstract 1
- 239000000543 intermediate Substances 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 23
- 239000000203 mixture Substances 0.000 description 22
- 239000000047 product Substances 0.000 description 21
- 239000000243 solution Substances 0.000 description 21
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 10
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- 239000002994 raw material Substances 0.000 description 7
- 239000002253 acid Substances 0.000 description 6
- 235000019270 ammonium chloride Nutrition 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- 150000003839 salts Chemical class 0.000 description 5
- 238000001228 spectrum Methods 0.000 description 5
- 238000001816 cooling Methods 0.000 description 4
- 150000004715 keto acids Chemical class 0.000 description 4
- IAJOBQBIJHVGMQ-UHFFFAOYSA-N 2-amino-4-[hydroxy(methyl)phosphoryl]butanoic acid Chemical compound CP(O)(=O)CCC(N)C(O)=O IAJOBQBIJHVGMQ-UHFFFAOYSA-N 0.000 description 3
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 238000007792 addition Methods 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 230000007062 hydrolysis Effects 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 150000005208 1,4-dihydroxybenzenes Chemical class 0.000 description 2
- -1 3-(ethoxymethylphosphono)propionate Chemical compound 0.000 description 2
- VKEQBMCRQDSRET-UHFFFAOYSA-N Methylone Chemical compound CNC(C)C(=O)C1=CC=C2OCOC2=C1 VKEQBMCRQDSRET-UHFFFAOYSA-N 0.000 description 2
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- PVEOYINWKBTPIZ-UHFFFAOYSA-N but-3-enoic acid Chemical compound OC(=O)CC=C PVEOYINWKBTPIZ-UHFFFAOYSA-N 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 238000003512 Claisen condensation reaction Methods 0.000 description 1
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 1
- 238000006845 Michael addition reaction Methods 0.000 description 1
- AFCIMSXHQSIHQW-UHFFFAOYSA-N [O].[P] Chemical compound [O].[P] AFCIMSXHQSIHQW-UHFFFAOYSA-N 0.000 description 1
- 239000003929 acidic solution Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000007333 cyanation reaction Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 238000006114 decarboxylation reaction Methods 0.000 description 1
- WYACBZDAHNBPPB-UHFFFAOYSA-N diethyl oxalate Chemical compound CCOC(=O)C(=O)OCC WYACBZDAHNBPPB-UHFFFAOYSA-N 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- GZBQGSURWYXEQF-UHFFFAOYSA-N ethoxy(methyl)phosphinous acid Chemical compound CCOP(C)O GZBQGSURWYXEQF-UHFFFAOYSA-N 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- IAJOBQBIJHVGMQ-BYPYZUCNSA-N glufosinate-P Chemical compound CP(O)(=O)CC[C@H](N)C(O)=O IAJOBQBIJHVGMQ-BYPYZUCNSA-N 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- ZFJMTDFOGDGPTF-UHFFFAOYSA-N phosphanium;chloride;hydrochloride Chemical compound P.Cl.Cl ZFJMTDFOGDGPTF-UHFFFAOYSA-N 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000002351 wastewater Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
- C07F9/301—Acyclic saturated acids which can have further substituents on alkyl
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
Definitions
- the present invention relates to the technical field of fine chemicals, and more specifically, to a preparation method of a pesticide intermediate 4-(hydroxymethylphosphono)-2-carbonylbutyric acid.
- PPO 4-(Hydroxymethylphosphono)-2-carbonylbutyric acid
- PPO 4-(Hydroxymethylphosphono)-2-carbonylbutyric acid
- the Chinese patent with publication number CN103665032A discloses a method for preparing glufosinate-ammonium.
- the patent uses oxygen- and phosphorus-containing five-membered heterocyclic phosphonic acid anhydride and cyanide as raw materials, and a cyanation reaction occurs in an organic solvent to generate ketonitriles. compound; and then undergo hydrolysis in an acidic solution to obtain the ketoacid substance 4-(hydroxy Methylphosphono)-2-carbonylbutyric acid.
- the cyclic phosphonic acid anhydride used in this method is difficult to prepare, has high cost, and is difficult to purify.
- the object of the present invention is to provide a preparation method of 4-(hydroxymethylphosphono)-2-carbonylbutyric acid, which has a simple process, mild conditions, easy control, low cost, and high yield. .
- the invention provides a preparation method of 4-(hydroxymethylphosphono)-2-carbonylbutyric acid, which includes the following steps:
- step b) Mix the acryloyl cyanide intermediate obtained in step a) with hydrochloric acid and a polymerization inhibitor, perform a hydrolysis reaction, and then undergo purification to obtain crude 2-carbonyl-3-butenoic acid;
- step b) Mix the crude 2-carbonyl-3-butenoic acid obtained in step b) with the second solvent, methylphosphine dichloride, and perform an addition reaction to obtain a solution containing bisacyl chloride;
- step d) Mix the bisyl chloride-containing solution obtained in step c) with water, perform a hydrolysis reaction, and obtain 4-(hydroxymethylphosphono)-2-carbonylbutyric acid after purification.
- the first solvent in step a) is selected from one or more of acetonitrile, ethyl acetate, tetrahydrofuran and phenylacetonitrile.
- the polymerization inhibitor in step a) is selected from one or more of p-hydroxyanisole, 2,6-di-tert-butyl-p-cresol, tert-butylhydroquinone and methylhydroquinone. kind; the mass ratio of the polymerization inhibitor and acryloyl chloride is (0.001 ⁇ 0.05):1.
- the catalyst in step a) is cuprous cyanide; the molar ratio of the catalyst, potassium ferrocyanide and acryloyl chloride is (0.01 ⁇ 0.1): (0.3 ⁇ 3):1.
- the temperature of the substitution reaction in step a) is 0°C to 100°C, and the time is 0.5h to 48h.
- the temperature of the vacuum distillation in step a) is 10°C to 60°C.
- the temperature of the hydrolysis reaction in step b) is 50°C to 130°C, and the time is 1h to 24h.
- the second solvent in step c) is selected from one or more of dichloromethane, dichloroethane, chloroform, hexane, heptane, benzene, toluene and xylene.
- the temperature of the addition reaction in step c) is 0°C to 100°C, and the time is 1h to 24h.
- the temperature of the hydrolysis reaction in step d) is 0°C to 100°C, and the time is 0.1h to 24h.
- the invention provides a preparation method of 4-(hydroxymethylphosphono)-2-carbonylbutyric acid, which includes the following steps: a) combining acryloyl chloride, a first solvent, a polymerization inhibitor, a catalyst and potassium ferrocyanide Mix, perform a substitution reaction, and obtain an acryl cyanide intermediate after distillation under reduced pressure; b) Mix the acryl cyanide intermediate obtained in step a) with hydrochloric acid and a polymerization inhibitor, perform a hydrolysis reaction, and then purify to obtain 2- Crude carbonyl-3-butenoic acid; c) Mix the crude 2-carbonyl-3-butenoic acid obtained in step b) with the second solvent, methylphosphine dichloride, and perform an addition reaction to obtain bisacyl chloride-containing Solution; d) Mix the bisyl chloride-containing solution obtained in step c) with water, perform a hydrolysis reaction, and obtain 4-(hydroxymethylphosphono)-2-carbonylbutyric acid after purification.
- the preparation method provided by the present invention uses acryloyl chloride as raw material, adds a polymerization inhibitor at the same time, carries out a substitution reaction with potassium ferrocyanide in the presence of a catalyst to obtain acryloyl cyanide, and then hydrolyzes it under acidic conditions.
- 2-Carbonyl-3-butenoic acid, 2-carbonyl-3-butenoic acid and methylphosphine dichloride are added to each other to obtain bisacyl chloride, which is further hydrolyzed and purified to obtain the target product 4-(hydroxymethylphosphono)- 2-Carbonylbutyric acid; the preparation method has simple process, mild conditions, easy control, low cost, and high yield.
- Figure 1 is the GC spectrum of acryloyl cyanide in Example 1 of the present invention.
- Figure 2 is the HPLC spectrum of 4-(hydroxymethylphosphono)-2-carbonylbutyric acid obtained in Example 1 of the present invention
- Figure 3 is the HPLC spectrum of 4-(hydroxymethylphosphono)-2-carbonylbutyric acid standard.
- the invention provides a preparation method of 4-(hydroxymethylphosphono)-2-carbonylbutyric acid, which includes the following step:
- step b) Mix the acryloyl cyanide intermediate obtained in step a) with hydrochloric acid and a polymerization inhibitor, perform a hydrolysis reaction, and then undergo purification to obtain crude 2-carbonyl-3-butenoic acid;
- step b) Mix the crude 2-carbonyl-3-butenoic acid obtained in step b) with the second solvent, methylphosphine dichloride, and perform an addition reaction to obtain a solution containing bisacyl chloride;
- step d) Mix the bisyl chloride-containing solution obtained in step c) with water, perform a hydrolysis reaction, and obtain 4-(hydroxymethylphosphono)-2-carbonylbutyric acid after purification.
- the invention provides a preparation method of 4-(hydroxymethylphosphono)-2-carbonylbutyric acid.
- Acryloyl chloride (formula I below) is used as raw material, while a small amount of polymerization inhibitor is added, and ferrous iron is mixed with ferrous iron in the presence of a catalyst.
- Potassium cyanide undergoes a substitution reaction to obtain acryloyl cyanide (formula II below), which is then hydrolyzed under acidic conditions to obtain 2-carbonyl-3-butenoic acid (formula III below), 2-carbonyl-3-butenoic acid and methyl
- the addition reaction of phosphine dichloride yields bisacyl chloride (formula IV below), which is further hydrolyzed and purified to obtain the target product 4-(hydroxymethylphosphono)-2-carbonylbutyric acid (formula V below);
- acryloyl chloride, a first solvent, a polymerization inhibitor, a catalyst and potassium ferrocyanide are first mixed, a substitution reaction is performed, and an acryl cyanide intermediate is obtained after distillation under reduced pressure.
- the present invention has no special restrictions on the sources of acryloyl chloride and potassium ferrocyanide, and commercially available products well known to those skilled in the art can be used.
- the first solvent is preferably selected from one or more of acetonitrile, ethyl acetate, tetrahydrofuran and phenylacetonitrile, and is more preferably acetonitrile or ethyl acetate.
- the present invention has no special restrictions on the source of the first solvent, and commercially available products well known to those skilled in the art can be used.
- the polymerization inhibitor is preferably selected from p-hydroxyanisole (MEHQ), 2,6-di-tert-butyl-p-cresol (BHT), tert-butylhydroquinone (MTBHQ) and methyl One or more hydroquinones (THQ), more preferably p-hydroxyanisole (MEHQ).
- MEHQ p-hydroxyanisole
- BHT 2,6-di-tert-butyl-p-cresol
- MTBHQ tert-butylhydroquinone
- THQ methyl One or more hydroquinones
- MEHQ methyl One or more hydroquinones
- the mass ratio of the polymerization inhibitor and acryloyl chloride is preferably (0.001-0.05):1, and more preferably (0.002-0.02):1.
- the catalyst is preferably cuprous cyanide.
- the present invention has no special restrictions on the source of the catalyst, and commercially available products well known to those skilled in the art can be used.
- the molar ratio of the catalyst, potassium ferrocyanide and acryloyl chloride is preferably (0.01 ⁇ 0.1): (0.3 ⁇ 3):1, more preferably (0.02 ⁇ 0.05): (0.5 ⁇ 1.5): 1.
- the process of mixing acryloyl chloride, first solvent, polymerization inhibitor, catalyst and potassium ferrocyanide is preferably as follows:
- the temperature is raised to react for a period of time, and after the temperature is lowered, a feed liquid containing acryl cyanide is obtained, and then the acryl cyanide intermediate is separated by distillation under reduced pressure at a certain temperature.
- the temperature of the substitution reaction is preferably 0°C to 100°C, more preferably 50°C to 80°C; the time of the substitution reaction is preferably 0.5h to 48h, more preferably 6h to 12h.
- the temperature of the vacuum distillation is preferably 10°C to 60°C, and more preferably 30°C to 50°C.
- the present invention mixes the obtained acryl cyanide intermediate with hydrochloric acid and a polymerization inhibitor, performs a hydrolysis reaction, and then undergoes purification treatment to obtain crude 2-carbonyl-3-butenoic acid.
- the mass concentration of the hydrochloric acid is preferably 20% to 36%; the present invention has no special restrictions on the source of the hydrochloric acid, and commercially available products well known to those skilled in the art can be used.
- the molar ratio of hydrochloric acid to acryloyl cyanide is preferably (1-15):1, more preferably (2-5):1.
- the polymerization inhibitor is preferably selected from p-hydroxyanisole (MEHQ), 2,6-di-tert-butyl-p-cresol (BHT), tert-butylhydroquinone (MTBHQ) and methyl One or more hydroquinones (THQ), more preferably p-hydroxyanisole (MEHQ).
- MEHQ p-hydroxyanisole
- BHT 2,6-di-tert-butyl-p-cresol
- MTBHQ tert-butylhydroquinone
- THQ methyl One or more hydroquinones
- MEHQ methyl One or more hydroquinones
- the mass ratio of the polymerization inhibitor and acrylic cyanide is preferably (0.001 ⁇ 0.05):1, More preferably, it is (0.005-0.02): 1.
- the process of mixing the obtained acryloyl cyanide intermediate with hydrochloric acid and polymerization inhibitor is preferably as follows:
- the temperature of the hydrolysis reaction is preferably 50°C to 130°C, more preferably 80°C to 110°C; the time of the hydrolysis reaction is preferably 1h to 24h, more preferably 3h to 6h.
- the purification process is preferably as follows:
- the present invention mixes the obtained crude 2-carbonyl-3-butenoic acid with a second solvent and methylphosphine dichloride, and performs an addition reaction to obtain a mixture containing Solution of bisacyl chloride.
- the second solvent is preferably selected from one or more of dichloromethane, dichloroethane, chloroform, hexane, heptane, benzene, toluene and xylene, more preferably dichloromethane , hexane or toluene.
- the present invention has no special restrictions on the source of the second solvent, and commercially available products well known to those skilled in the art can be used.
- the second solvent is preferably subjected to anhydrous treatment to obtain a solvent after anhydrous treatment.
- the present invention has no special restrictions on the source of the methylphosphine dichloride, and commercially available products well known to those skilled in the art can be used.
- the molar ratio of methylphosphine dichloride to acryloyl cyanide is preferably (0.95-1.2):1, more preferably (1-1.05):1.
- the process of mixing the obtained crude 2-carbonyl-3-butenoic acid with the second solvent and methylphosphine dichloride is preferably as follows:
- the temperature of the addition reaction is preferably 0°C to 100°C, more preferably 30°C to 70°C; the time of the addition reaction is preferably 1h to 24h, more preferably 3h to 8h.
- the present invention mixes the obtained solution containing bisacyl chloride with water, performs a hydrolysis reaction, and obtains 4-(hydroxymethylphosphono)-2-carbonylbutyric acid after purification.
- the mass ratio of the water to the second solvent is preferably (0.1-5):1, more preferably (0.5-2):1; water is added slowly for reaction.
- the temperature of the hydrolysis reaction is preferably 0°C to 100°C, more preferably 10°C to 40°C; the time of the hydrolysis reaction is preferably 0.1h to 24h, more preferably 0.5h to 3h.
- the purification process is preferably as follows:
- the second solvent is removed by layering, and the aqueous layer is separated by vacuum distillation to obtain the product 4-(hydroxymethylphosphono)-2-carbonylbutyric acid.
- the invention provides a preparation method of 4-(hydroxymethylphosphono)-2-carbonylbutyric acid, which includes the following steps: a) combining acryloyl chloride, a first solvent, a polymerization inhibitor, a catalyst and potassium ferrocyanide Mix, perform a substitution reaction, and obtain an acryl cyanide intermediate after distillation under reduced pressure; b) Mix the acryl cyanide intermediate obtained in step a) with hydrochloric acid and a polymerization inhibitor, perform a hydrolysis reaction, and then purify to obtain 2- Crude carbonyl-3-butenoic acid; c) Mix the crude 2-carbonyl-3-butenoic acid obtained in step b) with the second solvent, methylphosphine dichloride, and perform an addition reaction to obtain bisacyl chloride-containing Solution; d) Mix the bisyl chloride-containing solution obtained in step c) with water, perform a hydrolysis reaction, and obtain 4-(hydroxymethylphosphono)-2-carbonylbutyric acid after purification.
- the preparation method provided by the present invention uses acryloyl chloride as raw material, adds a polymerization inhibitor at the same time, carries out a substitution reaction with potassium ferrocyanide in the presence of a catalyst to obtain acryloyl cyanide, and then hydrolyzes it under acidic conditions.
- 2-Carbonyl-3-butenoic acid, 2-carbonyl-3-butenoic acid and methylphosphine dichloride are added to each other to obtain bisacyl chloride, which is further hydrolyzed and purified to obtain the target product 4-(hydroxymethylphosphono)- 2-Carbonylbutyric acid; the preparation method has simple process, mild conditions, easy control, low cost, and high yield.
- Example 1 The preparation method provided in Example 1 is adopted, with the difference that: the polymerization inhibitor p-hydroxyanisole is not added in the substitution reaction stage, the solvent in the addition step is hexane (replacing dichloromethane), and other steps are the same as in Example 1. 49.5g of 95% acryloyl cyanide intermediate was obtained with a yield of 58%; 103.3g of the product 4-(hydroxymethylphosphono)-2-carbonylbutyric acid was obtained with a purity of 88% and a yield of 87%.
- Example 1 The preparation method provided in Example 1 is adopted, with the difference that: the solvent in the substitution reaction stage is ethyl acetate (replacing acetonitrile), the solvent in the addition step is toluene (replacing dichloromethane), and other steps are the same as in Example 1. 68.3g of 95% acryloyl cyanide intermediate was obtained with a yield of 80%; 142.5g of product 4-(hydroxymethylphosphono)-2-carbonylbutyric acid was obtained with a purity of 89% and a yield of 88%.
- the solvent in the substitution reaction stage is ethyl acetate (replacing acetonitrile)
- the solvent in the addition step is toluene (replacing dichloromethane)
- other steps are the same as in Example 1. 68.3g of 95% acryloyl cyanide intermediate was obtained with a yield of 80%; 142.5g of product 4-(hydroxymethylphosphono)-2-carbony
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Abstract
Description
Claims (10)
- 一种4-(羟基甲基膦酰基)-2-羰基丁酸的制备方法,包括以下步骤:a)将丙烯酰氯、第一溶剂、阻聚剂、催化剂和亚铁氰化钾混合,进行取代反应,减压蒸馏后得到丙烯酰氰中间体;b)将步骤a)得到的丙烯酰氰中间体与盐酸、阻聚剂混合,进行水解反应,再经纯化处理,得到2-羰基-3-丁烯酸粗品;c)将步骤b)得到的2-羰基-3-丁烯酸粗品与第二溶剂、甲基二氯化膦混合,进行加成反应,得到含有双酰氯的溶液;d)将步骤c)得到的含有双酰氯的溶液与水混合,进行水解反应,纯化后得到4-(羟基甲基膦酰基)-2-羰基丁酸。
- 根据权利要求1所述的制备方法,其特征在于,步骤a)中所述第一溶剂选自乙腈、乙酸乙酯、四氢呋喃和苯乙腈中的一种或多种。
- 根据权利要求1所述的制备方法,其特征在于,步骤a)中所述阻聚剂选自对羟基苯甲醚、2,6-二叔丁基对甲酚、特丁基对苯二酚和甲基氢醌中的一种或多种;所述阻聚剂和丙烯酰氯的质量比为(0.001~0.05):1。
- 根据权利要求1所述的制备方法,其特征在于,步骤a)中所述催化剂为氰化亚铜;所述催化剂、亚铁氰化钾和丙烯酰氯摩尔比为(0.01~0.1):(0.3~3):1。
- 根据权利要求1所述的制备方法,其特征在于,步骤a)中所述取代反应的温度为0℃~100℃,时间为0.5h~48h。
- 根据权利要求1所述的制备方法,其特征在于,步骤a)中所述减压蒸馏的温度为10℃~60℃。
- 根据权利要求1所述的制备方法,其特征在于,步骤b)中所述水解反应的温度为50℃~130℃,时间为1h~24h。
- 根据权利要求1所述的制备方法,其特征在于,步骤c)中所述第二溶剂选自二氯甲烷、二氯乙烷、氯仿、己烷、庚烷、苯、甲苯和二甲苯中的一种或多种。
- 根据权利要求1所述的制备方法,其特征在于,步骤c)中所述加成反应的温度为0℃~100℃,时间为1h~24h。
- 根据权利要求1所述的制备方法,其特征在于,步骤d)中所述水解反应的温度为0℃~100℃,时间为0.1h~24h。
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Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4399287A (en) * | 1979-12-08 | 1983-08-16 | Fbc Limited | Phosphinic acid derivatives |
CN101641363A (zh) * | 2007-03-23 | 2010-02-03 | 明治制果株式会社 | 含磷的α-酮酸的制造方法 |
CN103665032A (zh) * | 2013-12-09 | 2014-03-26 | 江苏七洲绿色化工股份有限公司 | 一种草铵膦的制备方法 |
CN106459110A (zh) * | 2014-05-13 | 2017-02-22 | 拜耳作物科学股份公司 | 制备含磷羟腈的方法 |
CN111004277A (zh) * | 2019-10-29 | 2020-04-14 | 南京红太阳生物化学有限责任公司 | 一种新的草铵膦的制备方法 |
CN114085244A (zh) * | 2021-11-26 | 2022-02-25 | 浙江新安化工集团股份有限公司 | 一种4-(羟基甲基膦酰基)-2-羰基丁酸的制备方法 |
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- 2022-09-08 CN CN202211096537.3A patent/CN117700451A/zh active Pending
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- 2023-03-06 WO PCT/CN2023/079816 patent/WO2024051121A1/zh unknown
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4399287A (en) * | 1979-12-08 | 1983-08-16 | Fbc Limited | Phosphinic acid derivatives |
CN101641363A (zh) * | 2007-03-23 | 2010-02-03 | 明治制果株式会社 | 含磷的α-酮酸的制造方法 |
CN103665032A (zh) * | 2013-12-09 | 2014-03-26 | 江苏七洲绿色化工股份有限公司 | 一种草铵膦的制备方法 |
CN106459110A (zh) * | 2014-05-13 | 2017-02-22 | 拜耳作物科学股份公司 | 制备含磷羟腈的方法 |
CN111004277A (zh) * | 2019-10-29 | 2020-04-14 | 南京红太阳生物化学有限责任公司 | 一种新的草铵膦的制备方法 |
CN114085244A (zh) * | 2021-11-26 | 2022-02-25 | 浙江新安化工集团股份有限公司 | 一种4-(羟基甲基膦酰基)-2-羰基丁酸的制备方法 |
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