CN105646324A - Preparation method of high-purity indole - Google Patents
Preparation method of high-purity indole Download PDFInfo
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- CN105646324A CN105646324A CN201610116882.7A CN201610116882A CN105646324A CN 105646324 A CN105646324 A CN 105646324A CN 201610116882 A CN201610116882 A CN 201610116882A CN 105646324 A CN105646324 A CN 105646324A
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- indole
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- indoline
- sodium
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- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 title claims abstract description 140
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 title claims abstract description 61
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 title claims abstract description 61
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- ZFRKQXVRDFCRJG-UHFFFAOYSA-N skatole Chemical compound C1=CC=C2C(C)=CNC2=C1 ZFRKQXVRDFCRJG-UHFFFAOYSA-N 0.000 claims abstract description 25
- 229910052708 sodium Inorganic materials 0.000 claims abstract description 16
- 239000011734 sodium Substances 0.000 claims abstract description 16
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims abstract description 16
- 238000006243 chemical reaction Methods 0.000 claims abstract description 13
- 239000012535 impurity Substances 0.000 claims abstract description 10
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 10
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 claims abstract description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 28
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 claims description 22
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- 238000001914 filtration Methods 0.000 claims description 11
- 235000010265 sodium sulphite Nutrition 0.000 claims description 11
- 239000007864 aqueous solution Substances 0.000 claims description 8
- 230000015572 biosynthetic process Effects 0.000 claims description 8
- 239000000376 reactant Substances 0.000 claims description 7
- 239000012043 crude product Substances 0.000 claims description 6
- 230000007062 hydrolysis Effects 0.000 claims description 6
- 238000006460 hydrolysis reaction Methods 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 6
- 238000001816 cooling Methods 0.000 claims description 5
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 4
- 229910052700 potassium Inorganic materials 0.000 claims description 4
- 239000011591 potassium Substances 0.000 claims description 4
- 239000000047 product Substances 0.000 claims description 4
- 238000002425 crystallisation Methods 0.000 claims description 3
- 230000008025 crystallization Effects 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 9
- 239000000654 additive Substances 0.000 abstract description 4
- 230000000996 additive effect Effects 0.000 abstract description 4
- 239000002904 solvent Substances 0.000 abstract description 4
- 238000005406 washing Methods 0.000 abstract description 4
- 239000003513 alkali Substances 0.000 abstract description 2
- 239000000463 material Substances 0.000 abstract description 2
- 239000002994 raw material Substances 0.000 abstract description 2
- 239000012429 reaction media Substances 0.000 abstract description 2
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 abstract 2
- 230000003301 hydrolyzing effect Effects 0.000 abstract 2
- 229940079827 sodium hydrogen sulfite Drugs 0.000 abstract 2
- 235000019441 ethanol Nutrition 0.000 description 11
- 238000003756 stirring Methods 0.000 description 10
- 239000012065 filter cake Substances 0.000 description 9
- 239000003814 drug Substances 0.000 description 5
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 238000009413 insulation Methods 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- QPUYECUOLPXSFR-UHFFFAOYSA-N 1-methylnaphthalene Chemical compound C1=CC=C2C(C)=CC=CC2=C1 QPUYECUOLPXSFR-UHFFFAOYSA-N 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical group NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 2
- 239000011280 coal tar Substances 0.000 description 2
- 238000006356 dehydrogenation reaction Methods 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000000975 dye Substances 0.000 description 2
- 239000012847 fine chemical Substances 0.000 description 2
- 239000003205 fragrance Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000000575 pesticide Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000007670 refining Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- BNGXYYYYKUGPPF-UHFFFAOYSA-M (3-methylphenyl)methyl-triphenylphosphanium;chloride Chemical compound [Cl-].CC1=CC=CC(C[P+](C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 BNGXYYYYKUGPPF-UHFFFAOYSA-M 0.000 description 1
- CFHJPEDNWULMPW-UHFFFAOYSA-N 1h-indole;potassium Chemical compound [K].C1=CC=C2NC=CC2=C1 CFHJPEDNWULMPW-UHFFFAOYSA-N 0.000 description 1
- RRTQTOBOLIGMED-UHFFFAOYSA-N 2-(carboxyamino)-2-phenylacetic acid Chemical compound OC(=O)NC(C(O)=O)C1=CC=CC=C1 RRTQTOBOLIGMED-UHFFFAOYSA-N 0.000 description 1
- AMXMODDEDUGKDR-UHFFFAOYSA-N 3-hydroxy-1h-indole-2-carboxylic acid Chemical compound C1=CC=C2C(O)=C(C(=O)O)NC2=C1 AMXMODDEDUGKDR-UHFFFAOYSA-N 0.000 description 1
- CGWWRMKUJFUTPT-UHFFFAOYSA-N 3-methyl-1h-indole Chemical compound C1=CC=C2C(C)=CNC2=C1.C1=CC=C2C(C)=CNC2=C1 CGWWRMKUJFUTPT-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N Alumina Chemical compound [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- ODINCKMPIJJUCX-UHFFFAOYSA-N Calcium oxide Chemical compound [Ca]=O ODINCKMPIJJUCX-UHFFFAOYSA-N 0.000 description 1
- 208000035473 Communicable disease Diseases 0.000 description 1
- 241001062009 Indigofera Species 0.000 description 1
- HCUARRIEZVDMPT-UHFFFAOYSA-N Indole-2-carboxylic acid Chemical compound C1=CC=C2NC(C(=O)O)=CC2=C1 HCUARRIEZVDMPT-UHFFFAOYSA-N 0.000 description 1
- 241001397173 Kali <angiosperm> Species 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 229940054051 antipsychotic indole derivative Drugs 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000002475 indoles Chemical class 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000005554 pickling Methods 0.000 description 1
- DJEHXEMURTVAOE-UHFFFAOYSA-M potassium bisulfite Chemical compound [K+].OS([O-])=O DJEHXEMURTVAOE-UHFFFAOYSA-M 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229940074386 skatole Drugs 0.000 description 1
- 238000001256 steam distillation Methods 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Indole Compounds (AREA)
Abstract
The invention relates to a preparation method of high-purity indole and belongs to the technical field of organic synthesis. The preparation method comprises: subjecting indole as a raw material to additive reaction with sodium hydrogen sulfite to obtain 2-sodium sulfonate indoline, solvent washing to remove impurities, and adding alkali for hydrolyzing to obtain the high-purity indole. The preparation method is characterized mainly in that main impurity 3-methylindole contained in indole during a reaction process never reacts with sodium hydrogen sulfite for the purpose of separating indole and 3-methylindole. Both the additive reaction and hydrolytic reaction use as water a reaction medium, a solvent is recyclable, the materials are low in cost, and yield is high.
Description
Technical field
The invention belongs to technical field of organic synthesis, the preparation method relating to a kind of high-purity indole.
Background technology
Indole is a kind of important medicine, pesticide intermediate, is widely used in the production of the fine chemicals such as medicine, pesticide, dyestuff. At very low concentrations, indole has and is similar to colored fragrance indole, is the ingredient of many fragrance of a flower, is widely used in the various essence of preparation.
Benzazole compounds has a series of biological activity. Also being the important fine chemical product of a class, be widely used as organic, dyestuff, medicine and medicine intermediate, its many derivants have significant pharmacologically active. On clinical medicine, some of them indole derivatives has been used for treating multiple disease, such as cancer, tumor, acquired immune deficiency syndrome (AIDS), anti-inflammatory analgesic and viral disease and infectious disease.
Indole has a lot of production method.
1. extract from wash oil fraction
In high temperature coal-tar, containing about indole 0.10-0.16%. Generally can extract from coal tar and wash oil fraction. By wash oil fraction through alkali cleaning, pickling, obtain methylnaphthalene, then rectification in the high efficiency tower of 60 pieces of theoretical plates, cut out 225-256 DEG C of fraction section, hydro-oxidation kali fusion. React and carry out 2-4h at 170-240 DEG C, stir to stopping bubbling. Stand, lower floor's indole potassium is released cooling, after smashing, washs oil removing with benzene at low temperatures. Then it is hydrolyzed at 50-70 DEG C and obtains thick indole oil, it is distilled in the distillation column of 20 pieces of theoretical plates, fetches flow ratio 8-10:1, cut tower top temperature 170-256 DEG C of fraction, cooling, crystallization, centrifugal filtration, obtain refining indole. Then through squeezing, make oil content below 3%, with ethyl alcohol recrystallization, obtain the refining indole that purity is 99%.
2. prepared by adjacent aminoethylbenzene catalytic dehydrogenation
Adjacent aminoethylbenzene is in nitrogen stream, in the presence of aluminum nitrate (or aluminium sesquioxide), at 550 DEG C of dehydrocyclizations, obtains indoline through decompression distillation. Again 640 DEG C of dehydrogenations, obtain indole. Other method for making also has is reacted by ortho-methylnitrobenzene and oxalate, generates O-Nitrophenylfluorone acetone acid and then makes ��-indole-carboxylic acid again, finally together with Calx dry distilling and product; Aniline is heated synthesis of indole with acetylene at 600-650 DEG C; By neighbour's carboxyphenylglycine through 3-hydroxy-2-indole carboxylic acid and indolic acid synthesis of indole; Aoxidizing quiet indigo plant with concentrated nitric acid or chromic acid and obtain istain, the latter and zinc powder carry out distillation and can obtain indole. Nitrocinnamic and 10 parts of potassium hydroxide powder will be mixed, add iron filings post-heating and mixture melt also can be obtained indole.
Indole synthetic method currently mainly: ortho-aminotoluene adds formic acid and generates N-formoxyl ortho-aminotoluene and water, N-formoxyl ortho-aminotoluene generates indole after adding potassium hydroxide at high temperature cyclization, finally adopts steam distillation, and cooling is filtered, obtained indole.
But, no matter it is extract indole, or synthesis of indole, all more or less containing major impurity 3-methylindole, 3-methylindole (3-methylindole) has excrement smelly, has another name called scatol (skatole), breath during concentration height is nauseating, has a strong impact on indole quality.
Need high-purity indole in actual use, content >=99.5%, even 99.9%, 3-methylindole��0.5%, even less than 0.1%.
Owing to 3-methylindole and indole physicochemical properties are closely similar, general physical separation method such as rectification recrystallization method is difficult to them thoroughly to separate, principles of the invention is ingenious to utilize the major impurity 3-methylindole contained in indole in course of reaction not react with sodium sulfite, and reach indole and 3-methylindole separate purpose. Content >=99.5% can be obtained, even the high-purity indole of more than 99.9%.
Summary of the invention
The preparation method of a kind of high-purity indole, comprises the following steps:
(1) synthesis 2-sodium sulfonate indoline: by indole dissolving crude product in alcohol organic solvent, reacting 15-30h in 20��30 DEG C after addition sodium sulfite or bisulfite aqueous solutions of potassium, reaction terminates rear reactant liquor and to obtain intermediate 2-sodium sulfonate indoline through filtering, wash, drying;
(2) hydrolysis: intermediate 2-sodium sulfonate indoline adds sodium hydroxide or potassium hydroxide aqueous solution backflow 12-20h, reactant liquor cooling crystallization, to obtain high-purity indole product through filtering, wash, drying.
Wherein, sodium sulfite or bisulfite aqueous solutions of potassium described in step (1), mass concentration is 20��30%, and addition is 6��10 times of indole quality.
In step (1), alcohol organic solvent is at least one in methanol, ethanol and isopropanol; 1��5 times of alcohol organic solvent addition indole weight.
In step (2), the mass concentration of sodium hydroxide or potassium hydroxide aqueous solution is 5��15%, and addition is 3��5 times of intermediate 2-sodium sulfonate indoline quality.
The impurity contained in indole crude product in step (1) is not limited to 3-methylindole, is also applied for other impurity not reacted with sodium sulfite.
The present invention is with indole for raw material, passes through and sodium sulfite additive reaction, obtains 2-sodium sulfonate indoline, and solvent wash removes impurity, and then alkaline hydrolysis prepares high-purity indole. The major impurity 3-methylindole contained in indole in course of reaction does not react with sodium sulfite, and reach indole and 3-methylindole separate purpose. The present invention uses water to be reaction medium in additive reaction and hydrolysis, recycled solvent, and cost of material is low, and yield is high.
Detailed description of the invention
Embodiment 1
The preparation method of a kind of high-purity indole, comprises the following steps:
(1) synthesis 2-sodium sulfonate indoline: suction 250kg ethanol in 2000L reactor, opens stirring, puts into 140kg indole crude product, stirring and dissolving. Starting to drip the sodium sulfite solution 1400kg of 20%, control time for adding is 2h. Dropwise rear 30 DEG C of insulation 20h. Reactant liquor is through sucking filtration, washing with alcohol after completion of the reaction, obtains about 300kg intermediate 2-sodium sulfonate indoline.
(2) hydrolysis: filter cake proceeds to alkaline hydrolysis still (the about 300kg of filter cake), the 1000L that adds water stirs, and is then dividedly in some parts sodium hydroxide 100kg, heats up and steams ethanol, interior temperature more than 95 DEG C, and keep refluxing on a small quantity 20h.Being cooled to 20 DEG C, sucking filtration is centrifuged, and washes filter cake with water. Obtain the about 125kg of high-purity indole.
Embodiment 2
The preparation method of a kind of high-purity indole, comprises the following steps:
(1) synthesis 2-sodium sulfonate indoline: suction 700kg methanol in 2000L reactor, opens stirring, puts into 140kg indole, stirring and dissolving. Starting to drip the bisulfite potassium solution 840kg of 23%, control time for adding is 3h. Dropwise rear 35 DEG C of insulation 20h. Reactant liquor is through sucking filtration, methanol washing after completion of the reaction, obtains about 300kg intermediate 2-sodium sulfonate indoline.
(2) hydrolysis: filter cake proceeds to alkaline hydrolysis still (the about 300kg of filter cake), the 1000L that adds water stirs, and is then dividedly in some parts potassium hydroxide 100kg, heats up and steams methanol, interior temperature more than 95 DEG C, and keep refluxing on a small quantity 20h. Being cooled to 20 DEG C, sucking filtration is centrifuged, and washes filter cake with water. Obtain the about 120kg of high-purity indole.
Embodiment 3
The preparation method of a kind of high-purity indole, comprises the following steps:
(1) synthesis 2-sodium sulfonate indoline: suction 250kg ethanol in 2000L reactor, opens stirring, puts into 140kg indole crude product, stirring and dissolving. Starting to drip the sodium sulfite solution 900kg of 30%, control time for adding is 2h. Dropwise rear 30 DEG C of insulation 20h. Reactant liquor is through sucking filtration, washing with alcohol after completion of the reaction, obtains about 290kg intermediate 2-sodium sulfonate indoline.
(2) hydrolysis: filter cake proceeds to alkaline hydrolysis still (the about 290kg of filter cake), the 1000L that adds water stirs, and is then dividedly in some parts sodium hydroxide 100kg, heats up and steams ethanol, interior temperature more than 95 DEG C, keeps a small amount of backflow 20 hours. Being cooled to 20 DEG C, sucking filtration is centrifuged, and washes filter cake with water. Obtain the about 118kg of high-purity indole.
Claims (5)
1. the preparation method of a high-purity indole, it is characterised in that comprise the following steps:
(1) synthesis 2-sodium sulfonate indoline: by indole dissolving crude product in alcohol organic solvent, reacting 15-30h in 20��30 DEG C after addition sodium sulfite or bisulfite aqueous solutions of potassium, reaction terminates rear reactant liquor and to obtain intermediate 2-sodium sulfonate indoline through filtering, wash, drying;
(2) hydrolysis: intermediate 2-sodium sulfonate indoline adds sodium hydroxide or potassium hydroxide aqueous solution backflow 12-20h, reactant liquor cooling crystallization, to obtain high-purity indole product through filtering, wash, drying.
2. the preparation method of a kind of high-purity indole according to claim 1, it is characterised in that sodium sulfite or bisulfite aqueous solutions of potassium described in step (1), mass concentration is 20��30%, and addition is 6��10 times of indole quality.
3. the preparation method of a kind of high-purity indole according to claim 1, it is characterised in that in step (1), alcohol organic solvent is at least one in methanol, ethanol and isopropanol; 1��5 times of alcohol organic solvent addition indole weight.
4. the preparation method of a kind of high-purity indole according to claim 1, it is characterized in that, in step (2), the mass concentration of sodium hydroxide or potassium hydroxide aqueous solution is 5��15%, and addition is 3��5 times of intermediate 2-sodium sulfonate indoline quality.
5. the preparation method of a kind of high-purity indole according to claim 1, it is characterized in that, the impurity contained in indole crude product in step (1) is not limited to 3-methylindole, is also applied for other impurity not reacted with sodium sulfite.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN110878040A (en) * | 2018-09-06 | 2020-03-13 | 中国石油化工股份有限公司 | Method for preparing indole from o-toluidine |
| CN111187196A (en) * | 2018-11-15 | 2020-05-22 | 有限会社佐藤企画 | Purification method of tar indole |
| CN112279799A (en) * | 2019-07-26 | 2021-01-29 | 中石化南京化工研究院有限公司 | Method for preparing spice-grade indole by extraction crystallization |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110878040A (en) * | 2018-09-06 | 2020-03-13 | 中国石油化工股份有限公司 | Method for preparing indole from o-toluidine |
| CN110878040B (en) * | 2018-09-06 | 2022-08-09 | 中国石油化工股份有限公司 | Method for preparing indole from o-toluidine |
| CN111187196A (en) * | 2018-11-15 | 2020-05-22 | 有限会社佐藤企画 | Purification method of tar indole |
| CN111187196B (en) * | 2018-11-15 | 2023-05-30 | 有限会社佐藤企画 | Method for purifying tar indole |
| CN112279799A (en) * | 2019-07-26 | 2021-01-29 | 中石化南京化工研究院有限公司 | Method for preparing spice-grade indole by extraction crystallization |
| CN112279799B (en) * | 2019-07-26 | 2022-02-22 | 中石化南京化工研究院有限公司 | Method for preparing spice-grade indole by extraction crystallization |
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| CN105646324B (en) | 2019-04-16 |
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Denomination of invention: A method for preparing high-purity indole Granted publication date: 20190416 Pledgee: Rudong sub branch of Bank of China Ltd. Pledgor: NANTONG WANNIANCHANG PHARMACEUTICAL Co.,Ltd. Registration number: Y2024980026380 |
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