CN116375612A - 3,4,5,6-tetrahalophenol sulfophthalein alkali metal salt and preparation method and application thereof - Google Patents
3,4,5,6-tetrahalophenol sulfophthalein alkali metal salt and preparation method and application thereof Download PDFInfo
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- CN116375612A CN116375612A CN202310362539.0A CN202310362539A CN116375612A CN 116375612 A CN116375612 A CN 116375612A CN 202310362539 A CN202310362539 A CN 202310362539A CN 116375612 A CN116375612 A CN 116375612A
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- sulfophthalein
- tetrahalophenol
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- 229910052783 alkali metal Inorganic materials 0.000 title claims abstract description 76
- -1 alkali metal salt Chemical class 0.000 title claims abstract description 76
- 238000002360 preparation method Methods 0.000 title claims abstract description 31
- 238000001953 recrystallisation Methods 0.000 claims abstract description 61
- 239000012043 crude product Substances 0.000 claims abstract description 50
- 150000003839 salts Chemical class 0.000 claims abstract description 26
- 238000005755 formation reaction Methods 0.000 claims abstract description 22
- 102000009027 Albumins Human genes 0.000 claims abstract description 14
- 108010088751 Albumins Proteins 0.000 claims abstract description 14
- 239000000010 aprotic solvent Substances 0.000 claims abstract description 12
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 11
- 239000002696 acid base indicator Substances 0.000 claims abstract description 9
- 239000002904 solvent Substances 0.000 claims description 56
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 44
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 42
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 39
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 35
- 238000006243 chemical reaction Methods 0.000 claims description 32
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 28
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 22
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 20
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 16
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims description 14
- 230000015572 biosynthetic process Effects 0.000 claims description 14
- 238000000034 method Methods 0.000 claims description 11
- SZNYYWIUQFZLLT-UHFFFAOYSA-N 2-methyl-1-(2-methylpropoxy)propane Chemical compound CC(C)COCC(C)C SZNYYWIUQFZLLT-UHFFFAOYSA-N 0.000 claims description 10
- QQQCWVDPMPFUGF-ZDUSSCGKSA-N alpinetin Chemical compound C1([C@H]2OC=3C=C(O)C=C(C=3C(=O)C2)OC)=CC=CC=C1 QQQCWVDPMPFUGF-ZDUSSCGKSA-N 0.000 claims description 9
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 8
- 238000001514 detection method Methods 0.000 claims description 7
- 239000003208 petroleum Substances 0.000 claims description 7
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 6
- 238000002156 mixing Methods 0.000 claims description 6
- 229910052744 lithium Inorganic materials 0.000 claims description 5
- 229910052700 potassium Inorganic materials 0.000 claims description 5
- 229910000288 alkali metal carbonate Inorganic materials 0.000 claims description 4
- 150000008041 alkali metal carbonates Chemical class 0.000 claims description 4
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 claims description 3
- 239000000047 product Substances 0.000 abstract description 53
- 159000000000 sodium salts Chemical class 0.000 abstract description 22
- 229910003002 lithium salt Inorganic materials 0.000 abstract description 16
- 159000000002 lithium salts Chemical class 0.000 abstract description 16
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 abstract description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 13
- 230000009286 beneficial effect Effects 0.000 abstract description 4
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 238000002425 crystallisation Methods 0.000 abstract 1
- 230000008025 crystallization Effects 0.000 abstract 1
- 238000003756 stirring Methods 0.000 description 80
- 238000005303 weighing Methods 0.000 description 42
- 238000001035 drying Methods 0.000 description 40
- 238000001914 filtration Methods 0.000 description 40
- 238000001816 cooling Methods 0.000 description 39
- KXZRECGEDVBJPM-UHFFFAOYSA-N 2,3,4,5-tetrabromophenol Chemical compound OC1=CC(Br)=C(Br)C(Br)=C1Br KXZRECGEDVBJPM-UHFFFAOYSA-N 0.000 description 27
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
- RULKYXXCCZZKDZ-UHFFFAOYSA-N 2,3,4,5-tetrachlorophenol Chemical compound OC1=CC(Cl)=C(Cl)C(Cl)=C1Cl RULKYXXCCZZKDZ-UHFFFAOYSA-N 0.000 description 15
- BIICOIRKMWNHHA-UHFFFAOYSA-N 2,3,4,5-tetraiodophenol Chemical compound OC1=CC(I)=C(I)C(I)=C1I BIICOIRKMWNHHA-UHFFFAOYSA-N 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- 239000012065 filter cake Substances 0.000 description 13
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
- 239000007853 buffer solution Substances 0.000 description 9
- 239000012086 standard solution Substances 0.000 description 9
- 239000002994 raw material Substances 0.000 description 8
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
- 235000017557 sodium bicarbonate Nutrition 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 230000000694 effects Effects 0.000 description 7
- 102000008100 Human Serum Albumin Human genes 0.000 description 6
- 108091006905 Human Serum Albumin Proteins 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000012153 distilled water Substances 0.000 description 6
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 6
- 230000035484 reaction time Effects 0.000 description 6
- XPFJYKARVSSRHE-UHFFFAOYSA-K trisodium;2-hydroxypropane-1,2,3-tricarboxylate;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound [Na+].[Na+].[Na+].OC(=O)CC(O)(C(O)=O)CC(O)=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O XPFJYKARVSSRHE-UHFFFAOYSA-K 0.000 description 6
- 239000007810 chemical reaction solvent Substances 0.000 description 5
- 239000012535 impurity Substances 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- ZPLCXHWYPWVJDL-UHFFFAOYSA-N 4-[(4-hydroxyphenyl)methyl]-1,3-oxazolidin-2-one Chemical compound C1=CC(O)=CC=C1CC1NC(=O)OC1 ZPLCXHWYPWVJDL-UHFFFAOYSA-N 0.000 description 3
- 239000003513 alkali Substances 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 238000011161 development Methods 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- HQRPHMAXFVUBJX-UHFFFAOYSA-M lithium;hydrogen carbonate Chemical compound [Li+].OC([O-])=O HQRPHMAXFVUBJX-UHFFFAOYSA-M 0.000 description 3
- CEQFOVLGLXCDCX-WUKNDPDISA-N methyl red Chemical compound C1=CC(N(C)C)=CC=C1\N=N\C1=CC=CC=C1C(O)=O CEQFOVLGLXCDCX-WUKNDPDISA-N 0.000 description 3
- 229940093429 polyethylene glycol 6000 Drugs 0.000 description 3
- 235000011056 potassium acetate Nutrition 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000007086 side reaction Methods 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 235000017550 sodium carbonate Nutrition 0.000 description 2
- DAJSVUQLFFJUSX-UHFFFAOYSA-M sodium;dodecane-1-sulfonate Chemical compound [Na+].CCCCCCCCCCCCS([O-])(=O)=O DAJSVUQLFFJUSX-UHFFFAOYSA-M 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000000118 hair dye Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000011121 sodium hydroxide Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/01—Sulfonic acids
- C07C309/28—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C309/44—Sulfonic acids having sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing doubly-bound oxygen atoms bound to the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/32—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of salts of sulfonic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/42—Separation; Purification; Stabilisation; Use of additives
- C07C303/44—Separation; Purification
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
- G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
- G01N21/78—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator producing a change of colour
- G01N21/80—Indicating pH value
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
- G01N2333/76—Assays involving albumins other than in routine use for blocking surfaces or for anchoring haptens during immunisation
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Immunology (AREA)
- Physics & Mathematics (AREA)
- Molecular Biology (AREA)
- General Physics & Mathematics (AREA)
- Hematology (AREA)
- Pathology (AREA)
- General Health & Medical Sciences (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Biochemistry (AREA)
- Analytical Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicinal Chemistry (AREA)
- Food Science & Technology (AREA)
- Microbiology (AREA)
- Cell Biology (AREA)
- Biotechnology (AREA)
- Chemical Kinetics & Catalysis (AREA)
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Abstract
The invention provides a 3,4,5,6-tetrahalophenol sulfophthalein alkali metal salt and a preparation method and application thereof, belonging to the technical field of salification of 3,4,5,6-tetrahalophenol sulfophthalein. The alkali metal salt of the tetrahalophenol sulfophthalein is lithium salt of the tetrahalophenol sulfophthalein, sodium salt of the tetrahalophenol sulfophthalein and potassium salt of the tetrahalophenol sulfophthalein; the preparation method of the tetrahalophenol sulfophthalein alkali metal salt comprises the following steps: the tetrahalophenol sulfophthalein and alkali metal salt are subjected to salt formation reaction in an aprotic solvent, crystallization is carried out to prepare a crude product, and then recrystallization is carried out in the aprotic solvent to prepare the tetrahalophenol sulfophthalein alkali metal salt pure product. The preparation method of the tetrahalophenol sulfophthalein alkali metal salt provided by the invention overcomes the problem of poor water solubility of the existing tetrahalophenol sulfophthalein, has the advantages of simple preparation process, mild conditions, high product purity, high yield and low cost, can be used for mass production, and is beneficial to further application in acid-base indicators and albumin diagnostic reagents.
Description
Technical Field
The invention relates to the technical field of salification of 3,4,5,6-tetrahalophenol sulfophthalein, in particular to an alkali metal salt of 3,4,5,6-tetrahalophenol sulfophthalein, a preparation method and application thereof.
Background
3,4,5,6-tetrahalophenol sulfophthalein is an important acid-base indicator used as a protein error indicator in clinical diagnostic reagents, and has the following structural formula:
because 3,4,5,6-tetrahalophenol sulfophthalein is insoluble in water, a large amount of organic solvent is often used for dissolution in the use process, reagent is wasted, and cost is increased, and the problem affects the further research and application of the 3,4,5,6-tetrahalophenol sulfophthalein.
Therefore, how to overcome the defects of the prior art and increase the water solubility of the 3,4,5,6-tetrahalophenol sulfophthalein so as to achieve the purpose of convenient use is a technical problem which needs to be solved at present. .
Disclosure of Invention
The invention aims to provide a 3,4,5,6-tetrahalophenol sulfophthalein alkali metal salt, a preparation method and application thereof, which are used for solving the technical problem that the 3,4,5,6-tetrahalophenol sulfophthalein is difficult to dissolve in water and the use of the sulfophthalein is limited.
In order to achieve the above object, the present invention provides the following technical solutions:
the invention provides a 3,4,5,6-tetrahalophenol sulfophthalein alkali metal salt, wherein the structural formula of the 3,4,5,6-tetrahalophenol sulfophthalein alkali metal salt is as follows:
wherein X is independently Cl, br or I; m is Li, na or K.
The invention provides a preparation method of 3,4,5,6-tetrahalophenol sulfophthalein alkali metal salt, which comprises the following steps:
1) Salt formation: mixing 3,4,5,6-tetrahalophenol sulfophthalein and alkali metal salt in a solvent to perform a salt formation reaction to obtain a crude product of the 3,4,5,6-tetrahalophenol sulfophthalein alkali metal salt;
2) And (5) recrystallizing: and mixing the crude product of the 3,4,5,6-tetrahalophenol sulfophthalein alkali metal salt with a solvent for recrystallization to obtain the 3,4,5,6-tetrahalophenol sulfophthalein alkali metal salt.
Further, in the step 1), the temperature of the salifying reaction is 30-80 ℃, and the time of the salifying reaction is 0.5-24 h.
Further, in the step 1), the solvent is an aprotic solvent, and the aprotic solvent contains one or more of tetrahydrofuran, acetone, acetonitrile, dioxane, ethyl acetate, dichloromethane, chloroform, carbon tetrachloride, diethyl ether, petroleum ether, n-propyl ether, isopropyl ether, n-butyl ether, isobutyl ether and ethylene glycol dimethyl ether.
Further, in the step 1), the alkali metal salt is one or more of alkali metal carbonate, alkali metal acetate and alkali metal bicarbonate; the molar ratio of the 3,4,5,6-tetrahalophenol sulfophthalein to the alkali metal salt is 1:0.9 to 1.8.
Further, in the step 1), the mass-volume ratio of the crude product of the 3,4,5,6-tetrahalophenol sulfophthalein alkali metal salt to the solvent used for the first recrystallization is 1g: 1-20 mL, the mass volume ratio of the crude product of the alkali metal salt of the 3,4,5,6-tetrahalophenol sulfophthalein to the solvent used for the second recrystallization is 1g: 1-20 mL.
Further, in the step 2), the recrystallization is completed in two steps, wherein the solvent used in the first recrystallization is ethyl acetate, methylene dichloride, chloroform or carbon tetrachloride, and the solvent used in the second recrystallization is diethyl ether, petroleum ether, n-propyl ether or isopropyl ether;
the temperature of the recrystallization is 30-80 ℃, and the time of the recrystallization is 0.5-24 h.
Further, in the step 2), the mass volume ratio of the crude product of the 3,4,5,6-tetrahalophenol sulfophthalein alkali metal salt to the solvent is 1g: 1-20 mL.
The invention provides an application of an alkali metal salt of 3,4,5,6-tetrahalophenol sulfophthalein as an acid-base indicator.
The invention provides an application of 3,4,5,6-tetrahalophenol sulfophthalein alkali metal salt in an albumin detection reagent.
The invention has the beneficial effects that:
the invention prepares the 3,4,5,6-tetrahalophenol sulfophthalein alkali metal salt by salifying and recrystallizing the 3,4,5,6-tetrahalophenol sulfophthalein, overcomes the problem of poor water solubility of the existing 3,4,5,6-tetrahalophenol sulfophthalein, has simple preparation method, mild condition, high product purity, high yield and low cost, can be produced in mass, and is beneficial to further application in acid-base indicators and protein indicators.
Detailed Description
The invention provides a 3,4,5,6-tetrahalophenol sulfophthalein alkali metal salt, wherein the structural formula of the 3,4,5,6-tetrahalophenol sulfophthalein alkali metal salt is as follows:
wherein X is independently Cl, br or I; m is Li, na or K.
In the present invention, the alkali metal salt of 3,4,5,6-tetrahalophenol sulfophthalein is preferably 3,4,5, 6-tetrachlorophenol sulfophthalein sodium salt, 3,4,5, 6-tetrabromophenol sulfophthalein sodium salt, 3,4,5, 6-tetraiodophenol sulfophthalein sodium salt, 3,4,5, 6-tetrachlorophenol sulfophthalein lithium salt, 3,4,5, 6-tetraiodophenol sulfophthalein lithium salt, 3,4,5, 6-tetrachlorophenol sulfophthalein potassium salt, 3,4,5, 6-tetrabromophenol sulfophthalein potassium salt or 3,4,5, 6-tetraiodophenol sulfophthalein potassium salt.
The invention provides a preparation method of 3,4,5,6-tetrahalophenol sulfophthalein alkali metal salt, which comprises the following steps:
1) Salt formation: mixing 3,4,5,6-tetrahalophenol sulfophthalein and alkali metal salt in a solvent to perform a salt formation reaction to obtain a crude product of the 3,4,5,6-tetrahalophenol sulfophthalein alkali metal salt;
2) And (5) recrystallizing: and mixing the crude product of the 3,4,5,6-tetrahalophenol sulfophthalein alkali metal salt with a solvent for recrystallization to obtain the 3,4,5,6-tetrahalophenol sulfophthalein alkali metal salt.
In the present invention, the alkali metal salt of 3,4,5,6-tetrahalophenol sulfophthalein is synthesized according to the following reaction scheme:
wherein X is Cl, br or I; m is Li, na or K.
In the present invention, in the step 1), the temperature of the salification reaction is 30 to 80 ℃, preferably 35 to 75 ℃, and more preferably 40 to 70 ℃; the salt-forming reaction time is 0.5 to 24 hours, preferably 1 to 12 hours, and more preferably 2 to 10 hours.
In the present invention, in the step 1), the solvent is an aprotic solvent, and the aprotic solvent contains one or more of tetrahydrofuran, acetone, acetonitrile, dioxane, ethyl acetate, dichloromethane, chloroform, carbon tetrachloride, diethyl ether, petroleum ether, n-propyl ether, isopropyl ether, n-butyl ether, isobutyl ether and ethylene glycol dimethyl ether, preferably one or more of tetrahydrofuran, acetone, acetonitrile and dioxane.
In the invention, if the salt-forming reaction solvent is a proton solvent, the generation of the 3,4,5,6-tetrahalophenol sulfophthalein alkali metal salt is affected, the yield is low, and the method is not suitable for use; the solvent is aprotic solvent, and the yield of the 3,4,5,6-tetrahalophenol sulfophthalein alkali metal salt is high and can be adopted.
In the present invention, in the step 1), the alkali metal salt is one or more of alkali metal carbonate, alkali metal acetate and alkali metal bicarbonate, preferably alkali metal carbonate; the molar ratio of the 3,4,5,6-tetrahalophenol sulfophthalein to the alkali metal salt is 1:0.9 to 1.8, preferably 1:1 to 1.6, and more preferably 1:1.2 to 1.4.
In the invention, in the step 1), the mass volume ratio of the 3,4,5,6-tetrahalophenol sulfophthalein to the solvent is 1g:1 to 20mL, preferably 1g:2 to 16mL, more preferably 1g: 5-10 mL.
In the invention, after salt formation reaction, the yield of the prepared crude product of the 3,4,5,6-tetrahalophenol sulfophthalein alkali metal salt reaches 93.0%, and the purity reaches 94.0%.
In the invention, if the recrystallization solvent is a proton solvent, the purification effect of the 3,4,5,6-tetrahalophenol sulfophthalein alkali metal salt is affected, the purity is lower, the yield is lower, and the method is not suitable for use; the solvent is aprotic solvent, so that the yield is high and the method can be adopted.
In the present invention, in the step 2), the recrystallization is performed in two steps, wherein the solvent used for the first recrystallization is ethyl acetate, dichloromethane, chloroform or carbon tetrachloride, preferably dichloromethane; the solvent used for the second recrystallization is diethyl ether, petroleum ether, n-propyl ether or isopropyl ether, preferably petroleum ether.
In the present invention, in step 2), the alkali metal salt of 3,4,5,6-tetrahalophenol sulfophthalein is insoluble in the solvent and the 3,4,5,6-tetrahalophenol sulfophthalein is soluble, so that the remaining 3,4,5,6-tetrahalophenol sulfophthalein in the reaction can be removed; a second solvent recrystallization, wherein the small polar impurities contained in the 3,4,5,6-tetrahalophenol sulfophthalein alkali metal salt are easily dissolved in the solvent, and the 3,4,5,6-tetrahalophenol sulfophthalein alkali metal salt is insoluble, so that the impurities are removed; therefore, the recrystallization uses two different aprotic solvents to recrystallize once each, and the effect is better.
In the invention, in the step 2), after the two times of recrystallization of aprotic solvents with different properties, the purity of the 3,4,5,6-tetrahalophenol sulfophthalein alkali metal salt product is up to more than 98.0%, and the total yield of the two times of recrystallization is up to 88.0%.
In the present invention, the temperature of the recrystallization is 30 to 80 ℃, preferably 35 to 75 ℃; the recrystallization time is 0.5 to 24 hours, preferably 1 to 12 hours.
In the present invention, when the recrystallization temperature is lower than 35 ℃, the dissolution and dispersion are insufficient; when the temperature of recrystallization is higher than 75 ℃, impurities are generated in the product; when the temperature of the recrystallization is 35-75 ℃, the recrystallization is more sufficient and the effect is better. The recrystallization time is less than 1 hour, and the dissolution and dispersion are insufficient; the recrystallization time is longer than 12 hours, and impurities are generated in the product.
In the invention, the mass volume ratio of the crude product of the 3,4,5,6-tetrahalophenol sulfophthalein alkali metal salt to the solvent used for the first recrystallization is 1g:1 to 20mL, preferably 1g: 2-16 mL; the mass volume ratio of the crude product of the 3,4,5,6-tetrahalophenol sulfophthalein alkali metal salt to the solvent used for the second recrystallization is 1g:1 to 20mL, preferably 1g: 2-16 mL.
In the invention, when the mass-volume ratio of the crude product of the 3,4,5,6-tetrahalophenol sulfophthalein alkali metal salt to the solvent is too large, recrystallization is insufficient, and the purification effect is poor; when the mass-to-volume ratio is too small, reagents are wasted, and the yield is reduced.
The invention provides an application of an alkali metal salt of 3,4,5,6-tetrahalophenol sulfophthalein as an acid-base indicator.
The invention provides an application of 3,4,5,6-tetrahalophenol sulfophthalein alkali metal salt in an albumin detection reagent.
The technical solutions provided by the present invention are described in detail below with reference to examples, but they should not be construed as limiting the scope of the present invention.
The 3,4,5,6-tetrahalophenol sulfophthalein used in the following experimental examples and examples was a commercially available starting material, wherein the purity of 3,4,5, 6-tetrachlorophenol sulfophthalein was 93.23%, the purity of 3,4,5, 6-tetrabromophenol sulfophthalein was 92.05%, and the purity of 3,4,5, 6-tetraiodophenol sulfophthalein was 90.15%.
Experimental example 1
Comparison of the effects of salt formation reactions
(1) 3,4,5, 6-tetrabromophenol sulfophthalein sodium salt
Taking 3,4,5, 6-tetrabromophenol sulfophthalein raw material, weighing 4 parts, adding 67.0 g (0.1 moL) of each part into a reactor respectively, then respectively weighing 1.1eq of sodium hydroxide, sodium carbonate, sodium bicarbonate and sodium acetate, respectively adding 280mL of acetonitrile into the reactor, stirring and reacting for 6 hours at 55 ℃, stopping the reaction, cooling to room temperature, filtering, drying a filter cake, and weighing to obtain a crude product. The relevant experimental data are shown in table 1.
TABLE 1 selection of alkali metal salts
The data in table 1 indicate that: sodium hydroxide is used as reaction alkali, the alkalinity is too strong, the product yield is low, and the purity is low; sodium carbonate, sodium acetate and sodium bicarbonate are used as reaction alkali, the alkalinity is moderate, the yield is higher, the purity is higher, and therefore, the technical effect of the application can be realized only by the specific alkali metal salt.
(2) Alkali metal salt charging equivalent
Taking 3,4,5, 6-tetrabromophenol sulfophthalein raw material, weighing 5 parts, adding 67.0 g (0.1 mol) of each part into a reactor respectively, then respectively weighing 0.9eq, 1.0eq, 1.4eq, 1.6eq and 1.8eq of sodium bicarbonate, respectively adding 350mL of acetone into the reactor, stirring and reacting for 8 hours at 40 ℃, stopping the reaction, cooling to room temperature, filtering, drying a filter cake, and weighing to obtain a crude product. The relevant experimental data are shown in table 2.
TABLE 2 selection of alkali metal salt dosing equivalents
The data in table 2 shows that: the feeding ratio of sodium bicarbonate to 3,4,5,6-tetrahalophenol sulfophthalein is 0.9eq, the reaction is incomplete, and the yield is low; the feed ratio is 1.8eq, the alkali amount is excessive, and the purity of the product is low; the feed ratio is 0.9 to 1.6eq, the yield is higher, and the purity is higher.
(3) Salifying solvent
Taking 3,4,5, 6-tetrabromophenol sulfophthalein raw material, weighing 6 parts, adding 67.0 g (0.1 moL) of each part into a reactor respectively, then weighing 1.15eq of sodium bicarbonate respectively, adding 300mL of tetrahydrofuran, acetone, acetonitrile, dioxane and methanol respectively into the reactors in sequence, reacting for 8 hours at 45 ℃, filtering after the reaction is finished, drying a filter cake, and weighing to obtain a crude product. The relevant experimental data are shown in table 3.
TABLE 3 selection of salt-forming solvents
The data in table 3 indicate that: the reaction solvent is tetrahydrofuran, acetone, acetonitrile or dioxane, the yield can reach more than 93 percent, and the purity is more than 94 percent; the reaction solvent is methanol (proton solvent), and compared with the reaction solvent, the reaction solvent has lower yield and lower purity.
(4) The salt-forming solvent is used in an amount
Taking 3,4,5, 6-tetrabromophenol sulfophthalein raw material, weighing 5 parts, adding 67.0 g (0.1 moL) of each part into a reactor respectively, then weighing 1.2eq of sodium bicarbonate respectively, adding acetonitrile respectively into the reactors according to the mass-volume ratio of 1:1, 1:2, 1:6, 1:16 and 1:18, stirring and reacting for 5 hours at 50 ℃, stopping the reaction, cooling to room temperature, filtering, drying a filter cake, and weighing to obtain a crude product. The relevant experimental data are shown in table 4.
TABLE 4 selection of the amount of salifying solvent used
The data in table 4 indicate that: the mass-volume ratio of the raw materials to the acetonitrile is 1g to 1mL, the reaction is incomplete, and the purity is low; the mass-volume ratio is 1g to 18mL, and the yield is too low; when the mass volume ratio is 1 g:2-18 mL, the crude product has higher yield and higher purity.
(5) Salt formation temperature
Taking 3,4,5, 6-tetrabromophenol sulfophthalein raw material, weighing 5 parts, adding 67.0 g (0.1 moL) of each part into a reactor respectively, weighing 1.3eq of sodium bicarbonate respectively, adding the sodium bicarbonate into the reactor respectively in sequence, adding 500mL of acetonitrile respectively, stirring and reacting at 30 ℃, 35 ℃,50 ℃,75 ℃ and 80 ℃ for 6 hours respectively, stopping the reaction, cooling to room temperature, filtering, drying a filter cake, and weighing to obtain a crude product. The relevant experimental data are shown in table 5.
TABLE 5 selection of salt formation temperatures
The data in table 5 shows that: the reaction temperature is 30 ℃, the reaction is incomplete, the yield is low, and the purity is low; the reaction temperature is 80 ℃, the side reaction is increased, the yield is low, and the purity is low; the reaction temperature is 35-75 ℃, and the obtained crude product has high yield and purity.
(6) Salt formation reaction time
Taking 3,4,5, 6-tetrabromophenol sulfophthalein raw material, weighing 5 parts, adding 67.0 g (0.1 moL) of each part into a reactor respectively, weighing 1.3eq of sodium bicarbonate respectively, adding 500mL of dioxane respectively, stirring at 50 ℃ respectively for 0.5 hour, 1 hour, 6 hours, 12 hours and 13 hours, stopping the reaction, cooling to room temperature, filtering, drying a filter cake, and weighing to obtain a crude product. The relevant experimental data are shown in table 6.
TABLE 6 selection of salt formation reaction times
The data in table 6 shows that: the reaction time is 0.5 hour, the reaction is not complete, the yield is low, and the purity is low; the reaction time is 13 hours, the side reaction is increased, the yield is low, and the purity is low; the reaction time is 1-12 hours, and the obtained crude product has high yield and high purity.
Experimental example 2
Comparison of the recrystallization Effect
Salt forming reaction: taking 3,4,5, 6-tetrabromophenol sulfophthalein raw material, weighing 3349.8 g (5.0 moL), adding into a reactor, adding 504.1 g of sodium bicarbonate, adding 12L of acetonitrile, stirring at 60 ℃ for reaction for 4 hours, stopping stirring, cooling to room temperature, filtering, drying a filter cake, and collecting to obtain 3293.6 g of crude product with the yield of 95.2% and the purity of 95.36%, wherein the crude product is used in the next experiment;
(1) First recrystallization solvent
Taking the 3,4,5, 6-tetrabromophenol sulfophthalein sodium salt crude product prepared in the last step, weighing 5 parts, adding 100 g of each part into a reactor, respectively adding 400mL of ethyl acetate, dichloromethane, chloroform, carbon tetrachloride and methanol, respectively stirring at 50 ℃ for 3 hours, stopping stirring, cooling to room temperature, filtering, drying a filter cake, and weighing to obtain a pure product. The relevant experimental data are shown in table 7.
TABLE 7 selection of first recrystallization solvent
The data in table 7 indicate that: the first recrystallization solvent is ethyl acetate, dichloromethane and chloroform, the product yield is higher, the purity is higher, and the solvent is carbon tetrachloride product yield and purity are slightly lower; when the solvent is methanol, the yield and purity of the product are low.
(2) Second recrystallization solvent
First recrystallization: taking the 3,4,5, 6-tetrabromophenol sulfophthalein sodium salt crude product prepared in the previous step, weighing 600.0 g, adding into a reactor, adding 1.8L of ethyl acetate, stirring for 3 hours at 50 ℃, stopping stirring, cooling to room temperature, filtering, drying a filter cake, weighing to prepare 571.2 g of a product, wherein the yield is 95.2%, and the purity is 97.22%, and using in the next step of experiment;
and (3) secondary recrystallization: taking the first recrystallized product of the previous step, weighing 5 parts, adding 100 g of each part into a reactor, adding 500mL of diethyl ether, isopropyl ether, isobutyl ether, n-propyl ether and ethanol respectively, stirring at 35 ℃ for 10 hours, stopping stirring, cooling to room temperature, filtering, drying a filter cake, weighing, and obtaining a pure product, wherein relevant experimental data are shown in Table 8.
TABLE 8 selection of the second recrystallization solvent
The data in table 8 indicate that: the second recrystallization solvent is diethyl ether, isobutyl ether, isopropyl ether and n-propyl ether, the purity of the obtained pure product is more than 99%, and the yield of the second recrystallization is more than 94%; when the second recrystallization solvent is methanol, the purity and yield of the obtained product are low.
(3) The amount of recrystallization solvent used
Taking the 3,4,5, 6-tetrabromophenol sulfophthalein sodium salt crude product prepared in the last step, weighing 5 parts, adding 100 g of each part into a reactor, adding ethyl acetate according to the mass-volume ratio of 1:1, 1:2, 1:6, 1:16 and 1:18 respectively, stirring at 60 ℃ for 2 hours, stopping stirring, cooling to room temperature, filtering, drying a filter cake, weighing, and obtaining a product, wherein related experimental data are shown in table 9.
TABLE 9 selection of the amount of recrystallization solvent used
The data in table 9 indicate that: the mass volume ratio of the 3,4,5, 6-tetrabromophenol sulfophthalein crude product to ethyl acetate is 1g to 1mL, the stirring and the dispersion are insufficient, and the purity of the product is low; when the mass-volume ratio is 1g to 18mL, the yield of the product is too low; when the mass volume ratio is 1 g:2-18 mL, the yield is higher, and the purity is higher.
(4) Recrystallization temperature
Taking the 3,4,5, 6-tetrabromophenol sulfophthalein sodium salt crude product prepared in the last step, weighing 5 parts, adding 100 g of each part into a reactor, adding 500mL of chloroform respectively, stirring for 4 hours at 30 ℃, 35 ℃,55 ℃,75 ℃ and 80 ℃, stopping stirring, cooling to room temperature, filtering, drying a filter cake, weighing to obtain a product, and relevant experimental data are shown in Table 10.
Table 10 selection of recrystallization temperature
The data in table 10 shows that: the recrystallization temperature is 30 ℃, the recrystallization is insufficient, and the purity is low; the temperature is 80 ℃, and the purity is reduced to some extent; the reaction temperature is 35-75 ℃, and the product has high yield and purity.
(5) Recrystallization time
Taking the 3,4,5, 6-tetrabromophenol sulfophthalein sodium salt crude product prepared in the last step, weighing 5 parts, adding 100 g of each part into a reactor in sequence, then adding ethyl acetate according to the mass-volume ratio of 1g to 2mL, respectively stirring for 0.5 hour, 1 hour, 6 hours, 12 hours and 13 hours, stopping stirring, cooling to room temperature, filtering, drying a filter cake, weighing, and obtaining the product, wherein related experimental data are shown in table 11.
TABLE 11 selection of recrystallization times
The data in table 11 shows that: the recrystallization time is 0.5 hour, the recrystallization is insufficient, the purity is not improved, and the purity is lower; the recrystallization time is 13 hours, the product newly generates impurities, and the purity is reduced; the recrystallization time is 1-12 hours, the product yield is high, and the purity is high.
Example 1
Preparation of 3,4,5,6-tetrahalophenol sulfophthalein lithium salt
1) Preparation of 3,4,5, 6-tetrachlorophenol sulfophthalein lithium salt
Salt formation: 49.2 g (0.1 mol) of 3,4,5, 6-tetrachlorophenol sulfophthalein is weighed and added into a reactor, 1.1eq of lithium bicarbonate is added, 300mL of tetrahydrofuran is added, stirring reaction is carried out for 3 hours at 65 ℃, stirring is stopped, cooling to room temperature, filtering, drying and collection are carried out, and 47.3 g of crude product is obtained;
and (5) recrystallizing: adding all crude products obtained in the previous step into a reactor, adding 300mL of dichloromethane, stirring for 2 hours at 40 ℃, stopping stirring, cooling to room temperature, filtering, drying and collecting the obtained product to obtain a product; and (3) adding all the products obtained in the last step into a reactor, adding 300mL of isopropyl ether, stirring at 60 ℃ for 1 hour, stopping stirring, cooling to room temperature, filtering, drying, and collecting 42.2 g of 3,4,5, 6-tetrachlorophenol sulfophthalein lithium salt, wherein the total yield is 84.8%, and the purity is 99.32%.
2) Preparation of 3,4,5, 6-tetrabromophenol sulfophthalein lithium salt
Salt formation: weighing 67.0 g (0.1 mol) of 3,4,5, 6-tetrabromophenol sulfophthalein, adding 1.2eq of lithium bicarbonate into a reactor, adding 250mL of acetone, stirring at 40 ℃ for reaction for 5 hours, stopping stirring, cooling to room temperature, filtering, drying and collecting to obtain 64.2 g of crude product;
and (5) recrystallizing: adding all crude products obtained in the previous step into a reactor, adding 300mL of dichloromethane, stirring for 2 hours at 40 ℃, stopping stirring, cooling to room temperature, filtering, drying and collecting the obtained product to obtain a product; adding all the products obtained in the last step into a reactor, adding 300mL of isopropyl ether, stirring at 60 ℃ for 1 hour, stopping stirring, cooling to room temperature, filtering, drying, and collecting 55.6 g of 3,4,5, 6-tetrabromophenol sulfophthalein lithium salt, wherein the total yield is 82.3%, and the purity is 99.37%.
3) Preparation of 3,4,5, 6-tetraiodophenol sulfophthalein lithium salt
Salt formation: weighing 85.8 g (0.1 mol) of 3,4,5, 6-tetraiodophenol sulfophthalein, adding 1.2eq of lithium bicarbonate into a reactor, adding 250mL of acetone, stirring at 40 ℃ for reaction for 5 hours, stopping stirring, cooling to room temperature, filtering, drying and collecting to obtain 81.5 g of crude product;
and (5) recrystallizing: adding all crude products obtained in the previous step into a reactor, adding 300mL of dichloromethane, stirring for 2 hours at 40 ℃, stopping stirring, cooling to room temperature, filtering, drying and collecting the obtained product to obtain a product; all the products obtained in the last step are added into a reactor, 300mL of isopropyl ether is added, stirring is stopped for 1 hour at 60 ℃, stirring is stopped, cooling is carried out to room temperature, filtering and drying are carried out, 69.8 g of 3,4,5, 6-tetraiodophenol sulfophthalein lithium salt is obtained, the total yield is 81.4%, and the purity is 99.51%.
Example 2
Preparation of 3,4,5,6-tetrahalophenol sulfophthalein sodium salt
1) Preparation of 3,4,5, 6-tetrachlorophenol sulfophthalein sodium salt
Salt formation: 49.2 g (0.1 mol) of 3,4,5, 6-tetrachlorophenol sulfophthalein is weighed and added into a reactor, 1.0eq of sodium carbonate is added, 300mL of dioxane is added, stirring reaction is carried out at 75 ℃ for 2 hours, stirring is stopped, cooling to room temperature, filtering, drying and collecting to obtain 48.3 g of crude product;
and (5) recrystallizing: adding all crude products obtained in the previous step into a reactor, adding 200mL of chloroform, stirring for 2 hours at 50 ℃, stopping stirring, cooling to room temperature, filtering, drying and collecting the obtained product to obtain a product; and (3) adding all the products obtained in the last step into a reactor, adding 300mL of isopropyl ether, stirring at 60 ℃ for 1 hour, stopping stirring, cooling to room temperature, filtering, drying, and collecting to obtain 42.9 g of 3,4,5, 6-tetrachlorophenol sulfophthalein sodium salt, wherein the total yield is 83.4%, and the purity is 99.32%.
2) Preparation of 3,4,5, 6-tetrabromophenol sulfophthalein sodium salt
Salt formation: 67.0 g (0.1 mol) of 3,4,5, 6-tetrabromophenol sulfophthalein is weighed and added into a reactor, 1.2eq of sodium carbonate is added, 350mL of acetonitrile is added, stirring reaction is carried out for 5 hours at 40 ℃, stirring is stopped, cooling to room temperature, filtering, drying and collection are carried out, and 63.6 g of crude product is obtained;
and (5) recrystallizing: adding all crude products obtained in the previous step into a reactor, adding 200mL of carbon tetrachloride, stirring for 2 hours at 40 ℃, stopping stirring, cooling to room temperature, filtering, drying and collecting the obtained product to obtain a product; all the products obtained in the last step are added into a reactor, 200mL of diethyl ether is added, stirring is carried out for 11 hours at 35 ℃, stirring is stopped, cooling to room temperature is carried out, filtering and drying are carried out, 56.7 g of 3,4,5, 6-tetrabromophenolsulfonephthalein sodium salt is obtained after collection, the total yield is 81.9%, and the purity is 99.47%.
3) Preparation of 3,4,5, 6-tetraiodophenol sulfophthalein sodium salt
Salt formation: weighing 85.8 g (0.1 mol) of 3,4,5, 6-tetraiodophenol sulfophthalein, adding 1.4eq of sodium carbonate into a reactor, adding 400mL of acetone, stirring at 40 ℃ for reaction for 5 hours, stopping stirring, cooling to room temperature, filtering, drying and collecting to obtain 80.9 g of crude product;
and (5) recrystallizing: adding all crude products obtained in the previous step into a reactor, adding 250mL of ethyl acetate, stirring for 2 hours at 40 ℃, stopping stirring, cooling to room temperature, filtering, drying and collecting the obtained product to obtain a product; adding all the products obtained in the last step into a reactor, adding 200mL of n-propyl ether, stirring at 60 ℃ for 3 hours, stopping stirring, cooling to room temperature, filtering, drying, and collecting 73.1 g of 3,4,5, 6-tetraiodophenol sulfophthalein sodium salt, wherein the total yield is 83.1%, and the purity is 99.53%.
Example 3
Preparation of 3,4,5,6-tetrahalophenol sulfophthalein potassium salt
1) Preparation of 3,4,5, 6-tetrachlorophenol sulfophthalein potassium salt
Salt formation: 49.2 g (0.1 mol) of 3,4,5, 6-tetrachlorophenol sulfophthalein is weighed and added into a reactor, 1.2eq of potassium acetate is added, 300mL of acetone is added, stirring reaction is carried out for 12 hours at 40 ℃, stirring is stopped, cooling to room temperature, filtering, drying and collection are carried out, and 49.3 g of crude product is obtained;
and (5) recrystallizing: adding all crude products obtained in the previous step into a reactor, adding 200mL of chloroform, stirring for 2 hours at 55 ℃, stopping stirring, cooling to room temperature, filtering, drying and collecting the obtained product to obtain a product; adding all the products obtained in the last step into a reactor, adding 200mL of isopropyl ether, stirring for 1 hour at 55 ℃, stopping stirring, cooling to room temperature, filtering, drying and collecting 43.1 g of 3,4,5, 6-tetrachloro-phenol sulfophthalein potassium salt, wherein the total yield is 81.2%, and the purity is 99.41%.
2) Preparation of 3,4,5, 6-tetrabromo-phenol sulfophthalein potassium salt
Salt formation: weighing 67.0 g (0.1 mol) of 3,4,5, 6-tetrabromophenol sulfophthalein, adding 1.4eq of potassium acetate into a reactor, adding 250mL of acetonitrile, stirring at 60 ℃ for 2 hours, stopping stirring, cooling to room temperature, filtering, drying and collecting to obtain 65.8 g of crude product;
and (5) recrystallizing: adding all crude products obtained in the previous step into a reactor, adding 150mL of carbon tetrachloride, stirring at 75 ℃ for 2 hours, stopping stirring, cooling to room temperature, filtering, drying and collecting the obtained product; adding all the products obtained in the last step into a reactor, adding 200mL of diethyl ether, stirring at 35 ℃ for 12 hours, stopping stirring, cooling to room temperature, filtering, drying and collecting 58.5 g of 3,4,5, 6-tetrabromophenol sulfophthalein potassium salt, wherein the total yield is 82.6%, and the purity is 99.35%.
3) Preparation of 3,4,5, 6-tetraiodophenol sulfophthalein potassium salt
Salt formation: weighing 85.8 g (0.1 mol) of 3,4,5, 6-tetraiodophenol sulfophthalein, adding 1.6eq of potassium acetate into a reactor, adding 200mL of tetrahydrofuran, stirring at 60 ℃ for reaction for 5 hours, stopping stirring, cooling to room temperature, filtering, drying and collecting 84.2 g of crude product;
and (5) recrystallizing: adding all crude products obtained in the previous step into a reactor, adding 200mL of ethyl acetate, stirring for 3 hours at 50 ℃, stopping stirring, cooling to room temperature, filtering, drying and collecting the obtained product to obtain a product; adding all the products obtained in the last step into a reactor, adding 200mL of isopropyl ether, stirring at 60 ℃ for 3 hours, stopping stirring, cooling to room temperature, filtering, drying, and collecting to obtain 72.7 g of 3,4,5, 6-tetraiodophenol sulfophthalein potassium salt, wherein the total yield is 81.1%, and the purity is 99.19%.
Test case
The solubility of the lithium salt of 3,4,5,6-tetrahalophenol sulfophthalein, the sodium salt of 3,4,5,6-tetrahalophenol sulfophthalein, the potassium salt of 3,4,5,6-tetrahalophenol sulfophthalein obtained in examples 1 to 3 and 3,4,5,6-tetrahalophenol sulfophthalein was measured, and the results of the comparison of the data are shown in Table 12.
TABLE 12 solubility of alkali metal salts of 3,4,5,6-tetrahalophenol sulfophthalein obtained in examples 1-3
Definition of name terms for solubility representation:
is very soluble: means that 1g (mL) of solute can be dissolved in less than 1mL of solvent;
easily soluble: means that 1g (mL) of solute can be dissolved in 1-less than 10mL of solvent;
dissolving: means that 1g (mL) of solute can be dissolved in 10-less than 30mL of solvent;
slightly soluble: means that 1g (mL) of solute can be dissolved in 30-less than 100mL of solvent;
slightly dissolving: means that 1g (mL) of solute can be dissolved in 100-less than 1000mL of solvent;
very slightly dissolving: dissolving means that 1g (mL) of solute can be dissolved in 1000-less than 10000mL of solvent;
hardly soluble or insoluble: dissolution means that 1g (mL) of solute is not completely dissolved in 10000mL of solvent;
it can be seen in table 12 that the solubility of the lithium, sodium and potassium 3,4,5,6-tetrahalophenol sulfophthalein salts, and 3,4,5,6-tetrahalophenol sulfophthalein salts in water is significantly increased.
Example 4
Application of 3,4,5,6-tetrahalophenol sulfophthalein lithium salt in detection reagent
1) Preparing a solution: preparing a color development liquid: weighing 0.35 g of 3,4,5, 6-tetrachlorophenol sulfophthalein lithium salt and 0.45 g of sodium dodecyl sulfate, adding into 100mL of distilled water, and uniformly stirring for later use; albumin standard solution preparation: weighing human serum albumin, dissolving with distilled water, and preparing into concentration gradients of 0.1 g/L, 0.2 g/L, 0.4 g/L, 0.8 g/L, 1.6 g/L and 3.2 g/L respectively for later use; buffer solution preparation: preparing 100mL of citric acid-sodium citrate buffer solution with pH of 3.0, and uniformly stirring for later use;
2) Determination of albumin content: and respectively adding 4.0mL of citric acid-sodium citrate buffer solution into 7 colorimetric tubes, adding 100 mu L of chromogenic solution, respectively adding 100 mu L of 6 concentrations of human serum albumin standard solution, adding 100 mu L of protein standard solution to be detected, and directly measuring the albumin content in a sample to be detected by using an established standard curve.
Example 5
Application of 3,4,5,6-tetrahalophenol sulfophthalein sodium salt in detection reagent
1) Preparing a solution: preparing a color development liquid: respectively weighing 0.38 g of 3,4,5, 6-tetrabromophenol sulfophthalein sodium salt and 0.40 g of sodium dodecyl sulfonate, adding into 100mL of distilled water, and uniformly stirring for later use; albumin standard solution preparation: weighing human serum albumin, dissolving with distilled water, and preparing into concentration gradients of 0.1 g/L, 0.2 g/L, 0.4 g/L, 0.8 g/L, 1.6 g/L and 3.2 g/L respectively for later use; preparing a buffer solution: preparing 100mL of citric acid-sodium citrate buffer solution with pH of 3.0, and uniformly stirring for later use;
determination of albumin content: and respectively adding 4.5mL of citric acid-sodium citrate buffer solution into 7 colorimetric tubes, adding 100 mu L of chromogenic solution, respectively adding 100 mu L of 6 concentrations of human serum albumin standard solution, adding 100 mu L of protein standard solution to be detected, and directly measuring the albumin content in a sample to be detected by using an established standard curve.
Example 6
Application of 3,4,5,6-tetrahalophenol sulfophthalein potassium salt in detection reagent
1) Preparing a solution: preparing a color development liquid: respectively weighing 0.42 g of 3,4,5, 6-tetraiodophenol sulfophthalein potassium salt and 0.42 g of sodium dodecyl sulfonate, adding into 100mL of distilled water, and uniformly stirring for later use; albumin standard solution preparation: weighing human serum albumin, dissolving with distilled water, and preparing into concentration gradients of 0.1 g/L, 0.2 g/L, 0.4 g/L, 0.8 g/L, 1.6 g/L and 3.2 g/L respectively for later use; buffer solution preparation: preparing 100mL of citric acid-sodium citrate buffer solution with pH of 3.0, and uniformly stirring for later use;
2) Determination of albumin content: and respectively adding 3.7mL of citric acid-sodium citrate buffer solution into 7 colorimetric tubes, adding 100 mu L of chromogenic solution, respectively adding 100 mu L of 6 concentrations of human serum albumin standard solution, adding 100 mu L of protein standard solution to be detected, and directly measuring the albumin content in a sample to be detected by using an established standard curve.
Example 7
Application of 3,4,5,6-tetrahalophenol sulfophthalein lithium salt in acid-base indicator
0.5 g of 3,4,5, 6-tetrachlorophenol sulfophthalein lithium salt, 15 g of polyethylene glycol 6000, 12mL of sodium dodecyl sulfate, 0.1 g of bromothymol blue and 15mL of methyl red are weighed, sequentially added into 1000mL of aqueous solution, stirred for 0.5 hour, then immersed in filter paper, dried, cut, stuck on a film and prepared into pH test paper for standby.
Example 8
Application of 3,4,5,6-tetrahalophenol sulfophthalein sodium salt in acid-base indicator
0.5 g of 3,4,5, 6-tetrabromophenol sulfophthalein sodium salt, 15 g of polyethylene glycol 6000, 12mL of sodium dodecyl sulfate, 0.1 g of bromothymol blue and 15mL of methyl red are weighed, sequentially added into 1000mL of aqueous solution, stirred for 0.5 hour, then immersed in filter paper, dried, cut, stuck on a film and prepared into pH test paper for standby.
Example 9
Application of 3,4,5,6-tetrahalophenol sulfophthalein potassium salt in acid-base indicator
0.5 g of 3,4,5, 6-tetraiodophenol sulfophthalein lithium salt, 15 g of polyethylene glycol 6000, 12mL of sodium dodecyl sulfate, 0.1 g of bromothymol blue and 15mL of methyl red are weighed, sequentially added into 1000mL of aqueous solution, stirred for 0.5 hour, then immersed in filter paper, dried, cut, stuck on a film and prepared into pH test paper for standby.
From the above examples, the present invention provides an alkali metal salt of 3,4,5,6-tetrahalophenol sulfophthalein, and its preparation method and application. According to the invention, the 3,4,5,6-tetrahalophenol sulfophthalein is subjected to salification and recrystallization to obtain the 3,4,5,6-tetrahalophenol sulfophthalein alkali metal salt, so that the problem of poor water solubility of the existing 3,4,5,6-tetrahalophenol sulfophthalein is solved, and the purity of the finally prepared 3,4,5,6-tetrahalophenol sulfophthalein alkali metal salt product reaches 99.0%, and the total yield reaches 80%; the preparation method is simple, mild in condition, high in product purity, high in yield and low in cost, can be used for mass production, and is beneficial to further application in albumin detection reagents and hair dyes.
The foregoing is merely a preferred embodiment of the present invention and it should be noted that modifications and adaptations to those skilled in the art may be made without departing from the principles of the present invention, which are intended to be comprehended within the scope of the present invention.
Claims (10)
1. An alkali metal salt of 3,4,5,6-tetrahalophenol sulfophthalein, wherein the alkali metal salt of 3,4,5,6-tetrahalophenol sulfophthalein has the following structural formula:
wherein X is independently Cl, br or I; m is Li, na or K.
2. The process for the preparation of an alkali metal salt of 3,4,5,6-tetrahalophenol sulfophthalein according to claim 1, comprising the steps of:
1) Salt formation: mixing 3,4,5,6-tetrahalophenol sulfophthalein and alkali metal salt in a solvent to perform a salt formation reaction to obtain a crude product of the 3,4,5,6-tetrahalophenol sulfophthalein alkali metal salt;
2) And (5) recrystallizing: and mixing the crude product of the 3,4,5,6-tetrahalophenol sulfophthalein alkali metal salt with a solvent for recrystallization to obtain the 3,4,5,6-tetrahalophenol sulfophthalein alkali metal salt.
3. The method according to claim 2, wherein in the step 1), the salt forming reaction is carried out at a temperature of 30 to 80 ℃ for a time of 0.5 to 24 hours.
4. The method according to claim 2 or 3, wherein in the step 1), the solvent is an aprotic solvent, and the aprotic solvent contains one or more of tetrahydrofuran, acetone, acetonitrile, dioxane, ethyl acetate, methylene chloride, chloroform, carbon tetrachloride, diethyl ether, petroleum ether, n-propyl ether, isopropyl ether, n-butyl ether, isobutyl ether, and ethylene glycol dimethyl ether.
5. The method according to claim 4, wherein in the step 1), the alkali metal salt is one or more of alkali metal carbonate, alkali metal acetate and alkali metal hydrogencarbonate; the molar ratio of the 3,4,5,6-tetrahalophenol sulfophthalein to the alkali metal salt is 1:0.9 to 1.8.
6. The method according to claim 2, 3 or 5, wherein in the step 1), the mass-to-volume ratio of the 3,4,5,6-tetrahalophenol sulfophthalein to the solvent is 1g: 1-20 mL.
7. The method according to claim 6, wherein in the step 2), the recrystallization is performed in two steps, the solvent used in the first recrystallization is ethyl acetate, methylene chloride, chloroform or carbon tetrachloride, and the solvent used in the second recrystallization is diethyl ether, petroleum ether, n-propyl ether or isopropyl ether;
the temperature of the recrystallization is 30-80 ℃, and the time of the recrystallization is 0.5-24 h.
8. The process according to claim 7, wherein in step 2), the mass to volume ratio of the crude 3,4,5,6-tetrahalophenol sulfophthalein alkali metal salt to the solvent used for the first recrystallization is 1g: 1-20 mL, the mass volume ratio of the crude product of the alkali metal salt of the 3,4,5,6-tetrahalophenol sulfophthalein to the solvent used for the second recrystallization is 1g: 1-20 mL.
9. Use of the alkali metal salt of 3,4,5,6-tetrahalophenol sulfophthalein as an acid-base indicator of claim 1.
10. Use of the alkali metal salt of 3,4,5,6-tetrahalophenol sulfophthalein as claimed in claim 1 in an albumin detection reagent.
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| CN202310362539.0A CN116375612A (en) | 2023-04-06 | 2023-04-06 | 3,4,5,6-tetrahalophenol sulfophthalein alkali metal salt and preparation method and application thereof |
| ZA2023/06925A ZA202306925B (en) | 2023-04-06 | 2023-07-07 | 3,4,5,6-tetrahalophenolsulfonphthalein alkali metal salt, preparation method therefor and use thereof |
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| CN202310362539.0A CN116375612A (en) | 2023-04-06 | 2023-04-06 | 3,4,5,6-tetrahalophenol sulfophthalein alkali metal salt and preparation method and application thereof |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000030632A1 (en) * | 1998-11-23 | 2000-06-02 | Eisai Co., Ltd. | Aryl and heteroaryl compounds useful as fibroblast growth factor antagonists |
| CN102617410A (en) * | 2012-03-15 | 2012-08-01 | 长春万成生物电子工程有限公司 | Method for purifying 3,4,5,6-tetrahalogenated phenolsulfonphthalein |
| WO2019121631A1 (en) * | 2017-12-21 | 2019-06-27 | L'oreal | Process for treating keratin fibers using a halochromic fluorescein direct dye, an alkaline revealer and then an acidic eraser |
| US20210096080A1 (en) * | 2019-09-30 | 2021-04-01 | Chungdo Pharm. Co., Ltd | Test strip for detecting microalbumin in urine with high sensitivity |
-
2023
- 2023-04-06 CN CN202310362539.0A patent/CN116375612A/en active Pending
- 2023-07-07 ZA ZA2023/06925A patent/ZA202306925B/en unknown
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2000030632A1 (en) * | 1998-11-23 | 2000-06-02 | Eisai Co., Ltd. | Aryl and heteroaryl compounds useful as fibroblast growth factor antagonists |
| CN102617410A (en) * | 2012-03-15 | 2012-08-01 | 长春万成生物电子工程有限公司 | Method for purifying 3,4,5,6-tetrahalogenated phenolsulfonphthalein |
| WO2019121631A1 (en) * | 2017-12-21 | 2019-06-27 | L'oreal | Process for treating keratin fibers using a halochromic fluorescein direct dye, an alkaline revealer and then an acidic eraser |
| US20210096080A1 (en) * | 2019-09-30 | 2021-04-01 | Chungdo Pharm. Co., Ltd | Test strip for detecting microalbumin in urine with high sensitivity |
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| Title |
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| KIM JIN-BAEK等, 《JOURNAL OF PHOTOPOLYMER SCIENCE AND TECHNOLOGY》/POST-EXPOSURE DELAY EFFECT IN CHEMICALLY AMPLIFIED RESISTS, vol. 14, no. 3, 25 May 2001 (2001-05-25) * |
| ORNDORFF W. R.等, 《JOURNAL OF THE AMERICAN CHEMICAL SOCIETY》/PHENOLSULFONEPHTHALEIN AND SOME OF ITS DERIVATIVES, vol. 45, 1 February 1923 (1923-02-01), pages 497 * |
| pages 1, Retrieved from the Internet <URL:https://m.chem960.com/offer/4870461/> * |
| SHAH MILLA等, 《JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY, A: CHEMISTRY 》/PHOTOCHEMISTRY AND PHOTOINITIATOR PROPERTIES OF NOVEL 1-CHLORO-SUBSTITUTED THIOXANTHONES. III: PRELIMINARY STUDY OF THE PHOTOACID GENERATION, vol. 111, no. 1, 12 August 1997 (1997-08-12) * |
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