CN102993167B - Preparation method of selenium caprylate - Google Patents
Preparation method of selenium caprylate Download PDFInfo
- Publication number
- CN102993167B CN102993167B CN201210439729.XA CN201210439729A CN102993167B CN 102993167 B CN102993167 B CN 102993167B CN 201210439729 A CN201210439729 A CN 201210439729A CN 102993167 B CN102993167 B CN 102993167B
- Authority
- CN
- China
- Prior art keywords
- selenium
- sodium
- reaction
- dichloro
- sad
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- IPDBFHHCXGUAKV-UHFFFAOYSA-N OC(CCCCC1SSCC1)O Chemical compound OC(CCCCC1SSCC1)O IPDBFHHCXGUAKV-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to a preparation method of selenium caprylate, and belongs to the technical field of medicine synthesis, solving the problems of conventional synthesis methods that environmental pollution is serious since a large amount of chloroform is adopted and product yield is low. The preparation method comprises the following steps: A, carrying out hydrolysis reaction on 6, 8-dichloro ethyl caprylate and alkali metal hydroxide aqueous solution, so as to obtain reaction liquid containing sodium 6, 8-dichloro caprylate; B, adding sodium diselenide aqueous solution to the reaction liquid in step A so as to realize the reaction between the sodium 6, 8-dichloro caprylate and the sodium diselenide, adding inorganic acid to acidify after the reaction, and then filtering and drying to obtain the compound which is selenium caprylate as shown in formula I. The preparation method of selenium caprylate has the advantages that the synthetic process is short, the intermediate product is directly adopted to play a role in the following reaction without being preprocessed, and the operation is easy to carry out; the extraction under chloroform and the like can be eliminated, so that the advantage of being environment-friendly is realized; and the yield of the selenium caprylate is up to 65%, and the purity is up to 90%.
Description
Technical field
The present invention relates to a kind of preparation method of Thioctic Acid analogue, in particular, relate to the preparation method that a kind of selenium is sad, belong to technical field of medicine synthesis.
Background technology
Seleno Thioctic Acid, is called for short selenium sad,, on the basis of Thioctic Acid, the sulphur atom of 6,8 is replaced to the product obtaining with selenium atom.Selenium is sad No. CAS: 6708-13-0, and the chemical structural formula that selenium is sad is as follows:
Because selenium is sad, there is multiple physiologically active, as anti-oxidant, reducing blood-fat, antibacterial isoreactivity, at pharmaceutical field, be with a wide range of applications.Also more about the bibliographical information of the sad synthetic method of selenium in prior art, still, exists molar product yield low mostly, and reaction process adopts chloroform as reaction solvent, the defect large to environmental influence.As Swedish patent (notification number: SE170093C, the day for announcing: January 19 nineteen sixty) disclosed and a kind ofly take 6,8-dichloro-octanoic acid ethyl ester as raw material, reacted and obtain 6 with benzyl selenol, 8-dibenzyl seleno ethyl octylate, then react cyclization to obtain selenium sad with the liquid ammonia solution of sodium amide.The shortcoming of this route is that raw materials used benzyl selenol is rareer, and uses sodium metal and liquefied ammonia in reaction, and reaction conditions is harsher, and molar yield is lower, and molar yield is below 55%.Bergson and for example, G(Bergson, G; Acta chemica Scandinavica, 1958,12,582-583.) report with 6,8-dichloro-octanoic acid ethyl ester and Na
2se
2reaction first obtains 6,8-, bis-selenium ethyl octylates, and then hydrolysis to obtain selenium sad; The shortcoming of this route, first by 6,8-dichloro-octanoic acid ethyl ester and Na
2se
2reaction, inorganic salt sodium selenide reacts in two-phase and reacts with organism, is equivalent to not homogeneous reaction, is unfavorable for carrying out corresponsively, affect molar yield and the quality of product, molar product yield is too low, can only reach 25% left and right, and, the method need to adopt a large amount of organic solvents, chloroforms to extract, treating processes is numerous and diverse, and solvent chloroform has the pollution of environment larger, is unfavorable for suitability for industrialized production.In sum, in the sad building-up process of existing selenium, there is following defect: in building-up process, use a large amount of organic solvent (as chloroform, toluene etc.), big for environment pollution, and the molar yield of product generally lower (25%～55%).
Summary of the invention
The present invention is directed to above problems of the prior art, the preparation method that a kind of selenium is sad is provided, the technical problem of solution is that to realize molar product yield high, and does not adopt chloroform to realize the effect that reduces environmental pollution.
The object of the invention is to be achieved by the following technical programs, the preparation method that a kind of selenium is sad, the method comprises the following steps:
A, 6,8-dichloro-octanoic acid ethyl ester is hydrolyzed and is reacted with alkali-metal hydroxide aqueous solution, obtain the reaction solution of 6,8-dichloro-octanoic acid sodium;
B, in the reaction solution of steps A, add the sodium diselenide aqueous solution, 6,8-dichloro-octanoic acid sodium is reacted with sodium diselenide, after reaction finishes, add mineral acid to carry out acidification, filter, dry, obtain formula I compound selenium sad;
The present invention, by the processing that first 6,8-dichloro-octanoic acid ethyl ester is hydrolyzed, obtains corresponding 6,8-dichloro-octanoic acid sodium, and the 6,8-dichloro-octanoic acid sodium obtaining reacts with sodium diselenide again, then adds mineral acid to carry out obtaining selenium after acidification sad.The intermediate 6 generating, 8-dicloro caprylate sodium and sodium diselenide are all water miscible salt, can be dissolved in water and react accordingly, the effect that realization is reacted in single_phase system, improve molar yield and the reaction efficiency of product, thereby solve existing raw material 6,8-dichloro-octanoic acid ethyl ester and the sodium diselenide (Na that first adopts 6,8-dichloro-octanoic acid ethyl ester to react existing reaction with sodium diselenide
2se
2) respectively in two-phase system, both do not dissolve each other, and are unfavorable for the carrying out of reaction, reaction molar yield is low, and molar yield can only reach 25% defect.And the present invention reacts with sodium diselenide by first 6,8-dichloro-octanoic acid ethyl ester being hydrolyzed into 6,8-dichloro-octanoic acid sodium again, directly reaction in water, does not need to adopt the steps such as a large amount of chloroforms extracts, and has simplified operational path, has reduced the pollution to environment.In addition, the intermediate that hydrolysis reaction of the present invention obtains does not need to process, and the reaction solution of the 6,8-dichloro-octanoic acid sodium obtaining after the hydrolysis of 6,8-dichloro-octanoic acid ethyl ester is directly used in to next step reaction, further simplifies production technique yet.
In the sad preparation method of above-mentioned selenium, the hydrolysis reaction described in steps A carries out under alcoholic solvent exists, and described alcoholic solvent is selected from C
1～C
4alcoholic solvent.Because raw material 6,8-dichloro-octanoic acid ethyl ester is ester soluble compound, water insoluble, thus affect the efficiency of hydrolysis reaction, easily make reaction solution darken, affect the color and luster of product.And C
1～C
4alcoholic solvent can either dissolve each other with water, can make raw material 6 again, 8-dicloro caprylate ethyl ester dissolves, by add a certain amount of alcoholic solvent in hydrolysis reaction system, thereby be equivalent to hydrolysis reaction carries out in single_phase system, improve the efficiency of hydrolysis reaction, be conducive to the carrying out of reaction, quality and the color and luster requirement that can improve again product.As preferably, described alcoholic solvent is alcohol solvent.Adopt alcohol solvent to recycle, and also less to the pollution of environment.Described alcoholic solvent add-on is (mass ratio) 3～6 times of 6,8-dichloro-octanoic acid ethyl ester.
In the sad preparation method of above-mentioned selenium, the temperature of the hydrolysis reaction described in steps A is 40 ℃～70 ℃, and the described reaction times is 1～5 hour.If hydrolysising reacting temperature is too high, can make the color burn of reaction solution, affect the quality of the finished product; If the temperature mistake of hydrolysis reaction, is unfavorable for the carrying out of hydrolysis reaction affecting reaction efficiency.
In the sad preparation method of above-mentioned selenium, alkali-metal oxyhydroxide described in steps A is as sodium hydroxide, potassium hydroxide etc., excellent is that preferably the alkali-metal hydroxide aqueous solution described in steps A is that mass concentration is 5%～20% aqueous sodium hydroxide solution.
In the sad preparation method of above-mentioned selenium, a kind of synthetic sodium diselenide that the sodium diselenide aqueous solution described in step B can disclose according to people such as Yang Xiangliang and the novel method of organic diselenide prepare (" novel method of a kind of synthetic sodium diselenide and organic diselenide ", the people such as Yang Xiangliang, Chinese Journal of Inorganic Chemistry, the 6th phase the 17th volume, November calendar year 2001,905-907).In particular, the sodium diselenide aqueous solution described in step B adopts following methods to prepare:
A, sodium hydroxide is soluble in water, then add selenium powder and cetyl trimethylammonium bromide, be mixed with selenium solution;
B, by NaBH
4be added to the water and be mixed with corresponding solution with sodium hydroxide;
C, under protection of inert gas, the solution obtaining in step b is joined in the selenium solution in above-mentioned steps a, under room temperature, react 0.5～1.5 hour, be then warming up to 90 ℃ and continue reaction 0.5～1 hour, obtain Na
2se
2the aqueous solution.
In the sad preparation method of above-mentioned selenium, the temperature of the reaction described in step B is 50 ℃～80 ℃, and the described reaction times is 1～3 hour.
In the sad preparation method of above-mentioned selenium, the mineral acid described in step B is that mass concentration is 5%～20% aqueous hydrochloric acid.By adding aqueous hydrochloric acid to carry out acidification, it is sad that the intermediate product selenium Sodium octoate that makes to generate changes into final product selenium.
In the sad preparation method of above-mentioned selenium, described in step B, add mineral acid to carry out also comprising before acidification to add the gac processing of decolouring.By decolouring, process quality and the purity that can further improve product.As preferably, the add-on of described gac is 1～3 times of weight of 6,8-dichloro-octanoic acid ethyl ester.As further preferably, the add-on of described gac is 1.5～2.0 times of weight of 6,8-dichloro-octanoic acid ethyl ester.
In the sad preparation method of above-mentioned selenium, the mol ratio of the 6,8-dichloro-octanoic acid ethyl ester described in steps A and alkali-metal oxyhydroxide is 1:1～3, as preferably, described 6,8-dichloro-octanoic acid ethyl ester and the mol ratio of alkali-metal oxyhydroxide are 1:1.5～2.2.
In the sad preparation method of above-mentioned selenium, described 6,8-dichloro-octanoic acid ethyl ester and the mol ratio of sodium selenide are 1:1～3.As preferably, described 6,8-dichloro-octanoic acid ethyl ester and the mol ratio of sodium diselenide are 1:1.05～1.5.
The sad preparation method of above-mentioned selenium of the present invention, can represent by following reaction equation:
In sum, the present invention compared with prior art, has the following advantages:
1. the sad preparation method of selenium of the present invention, has synthetic route short, be easier to operation, and intermediate product 6,8-dichloro-octanoic acid sodium does not need first to separate, and directly the reaction solution obtaining is reacted for next step, is more conducive to production operation; Raw material used is easy to get, and has and reduces production costs, and practicality is high, is conducive to the advantage of industrial applications.
2. the sad preparation method of selenium of the present invention, by synthetic method is improved, do not need to adopt chloroform to extract, reduced the pollution to environment, and owing to not needing the aftertreatments such as extraction, be more conducive to process, simplified generating process, and the present invention mainly be take water as reaction solvent, has environment amenable advantage.
3. the sad preparation method of selenium of the present invention, has advantages of that molar product yield and purity are high, and the finished product molar yield can reach more than 65%, and product purity can reach more than 90%.
Accompanying drawing explanation
Fig. 1 is that selenium of the present invention is sad
1h-NMR spectrogram;
Fig. 2 is the MS spectrogram that selenium of the present invention is sad;
Fig. 3 is the IR spectrogram that selenium of the present invention is sad.
Embodiment
Below by specific embodiment, technical scheme of the present invention is described in further detail, but the present invention is not limited to these embodiment.
Sodium diselenide (Na described in following examples
2se
2) aqueous solution prepares in accordance with the following methods:
A, by 10g(0.25mol) sodium hydroxide is dissolved in 125mL water, then adds 19.75g(250mmol) selenium powder and 500mg cetyl trimethylammonium bromide, be mixed with selenium solution;
B, by 0.75g(33mmol) NaBH
4add in another four-hole bottle with 1g sodium hydrate solid, add 25mL water dissolution under cooling with ice-water bath, be mixed with corresponding solution;
C, under nitrogen protection, under agitation condition, the solution obtaining in above-mentioned steps b is joined in the selenium solution in above-mentioned steps a, under room temperature, react 1 hour, be then warming up to 90 ℃ and continue reaction 0.5 hour, obtain Na
2se
2the aqueous solution.The Na obtaining
2se
2it is sad that the aqueous solution does not need processing can be directly used in synthetic selenium.
Embodiment 1
By 6.01g(25mmol) 6, in the four-hole bottle that 8-dicloro caprylate ethyl ester adds, and then the mass content that the adds 44mL alcohol solvent that is 95%, the aqueous sodium hydroxide solution 40g that mass concentration is 5%, be heated to 40 ℃, controlling temperature of reaction is 40 ℃ of reactions 5 hours that are hydrolyzed, after reaction finishes, obtain the reaction solution of faint yellow 6,8-dichloro-octanoic acid sodium;
To above-mentioned 6, in the reaction solution of 8-dicloro caprylate sodium, drip the sodium diselenide aqueous solution, wherein, add the amount of the sodium diselenide aqueous solution to make sodium diselenide and 6, the mol ratio of 8-dicloro caprylate ethyl ester is 1:1, in dropping process, control temperature at 45 ℃～50 ℃, time for adding is about 2 hours, dropwise, continue to control temperature at 50 ℃, make 6, 8-dicloro caprylate sodium continues to react 3 hours with sodium diselenide, after reaction finishes, be cooled to 40 ℃, add 8g gac, stir after 30 minutes, filtered while hot is removed gac, collect filtrate, the filtrate of collection is added in another four-hole bottle, carry out underpressure distillation and remove the ethanol in system, in decompression process, control temperature and be no more than 50 ℃, remove after most of ethanol, in residual solution, add water to 400mL, then under agitation condition, be cooled to 0 ℃, the dilute hydrochloric acid solution that dropping mass concentration is 5% carries out acidification, regulate pH value to 2, separate out a large amount of chocolate solid matters, suction filtration, it is sad that oven dry obtains final product selenium, HPLC purity 93.4%, molar yield is 70%.
Embodiment 2
By 6.01g(25mmol) 6, in the four-hole bottle that 8-dicloro caprylate ethyl ester adds, and then the mass content that the adds 44mL alcohol solvent that is 95%, the potassium hydroxide aqueous solution 42g that mass concentration is 10%, be heated to 45 ℃, controlling temperature of reaction is 45 ℃ of reactions 3 hours that are hydrolyzed, after reaction finishes, obtain the reaction solution of faint yellow 6,8-dichloro-octanoic acid sodium;
To obtained above 6, in the reaction solution of 8-dicloro caprylate sodium, drip the sodium diselenide aqueous solution, wherein, add the amount of the sodium diselenide aqueous solution to make sodium diselenide and 6, the mol ratio of 8-dicloro caprylate ethyl ester is 1.5:1, in dropping process, control temperature at 50 ℃～55 ℃, time for adding is about 2 hours, after dropwising, continue to control temperature at 55 ℃, make 6, 8-dicloro caprylate sodium continues to react 2.5 hours with sodium diselenide, after reaction finishes, be cooled to 40 ℃, add 12g gac, being warming up to 50 ℃ continues to stir after 30 minutes, filtered while hot is removed gac, collect filtrate, the filtrate of collection is added in another four-hole bottle, carry out underpressure distillation and reclaim alcohol solvent, in decompression process, control temperature and be no more than 50 ℃, reclaim after most of ethanol, in residual solution, add water to 500mL, then under agitation condition, be cooled to 0 ℃, the dilute hydrochloric acid solution that dropping mass concentration is 20% carries out acidification, regulation system pH value to 2, separate out a large amount of chocolate solid matters, suction filtration, the solid matter obtaining is dried to such an extent that final product selenium is sad, HPLC purity 92.5%, molar yield is 66%.
Embodiment 3
By 6.01g(25mmol) 6, in the four-hole bottle that 8-dicloro caprylate ethyl ester adds, and then the mass content that the adds 44mL alcohol solvent that is 95%, the aqueous sodium hydroxide solution 5g that mass concentration is 20%, be heated to 50 ℃, controlling temperature of reaction is 50 ℃ of reactions 2.0 hours that are hydrolyzed, after reaction finishes, obtain the reaction solution of faint yellow 6,8-dichloro-octanoic acid sodium;
To obtained above 6, in the reaction solution of 8-dicloro caprylate sodium, drip the sodium diselenide aqueous solution, wherein, add the amount of the sodium diselenide aqueous solution to make sodium diselenide and 6, the mol ratio of 8-dicloro caprylate ethyl ester is 1.2:1, in dropping process, control temperature temperature at 55 ℃～60 ℃, time for adding is about 1.5 hours, dropwise, continue to control temperature at 60 ℃, make 6, 8-dicloro caprylate sodium continues to react 2.0 hours with sodium diselenide, after reaction finishes, be cooled to 40 ℃, add 12g gac, being warming up to 50 ℃ continues to stir after 30 minutes, filtered while hot is removed gac, collect filtrate, the filtrate of collection is added in another four-hole bottle, carry out underpressure distillation and reclaim alcohol solvent, in decompression process, control temperature and be no more than 50 ℃, reclaim after most of ethanol, in residual solution, add water to 400mL, then under agitation condition, be cooled to 0 ℃, the dilution heat of sulfuric acid that dropping mass concentration is 5% carries out acidification, regulate pH value to 2, separate out a large amount of chocolate solid matters, suction filtration, the solid matter obtaining is dried to such an extent that final product selenium is sad, HPLC purity 91.6%, molar yield is 66.2%.
Embodiment 4
By 6.01g(25mmol) 6, in the four-hole bottle that 8-dicloro caprylate ethyl ester adds, adding mass concentration is 5% aqueous sodium hydroxide solution 40g, be heated to 70 ℃, controlling temperature of reaction is 70 ℃ of reactions 8 hours that are hydrolyzed, after reaction finishes, obtain the reaction solution of faint yellow 6,8-dichloro-octanoic acid sodium;
To above-mentioned 6, in the reaction solution of 8-dicloro caprylate sodium, drip mass concentration and be 10% the sodium diselenide aqueous solution, wherein, the add-on of the sodium diselenide aqueous solution makes sodium diselenide and 6, the mol ratio of 8-dicloro caprylate ethyl ester is 2:1, in dropping process, control temperature temperature at 60 ℃～65 ℃, time for adding is about 1.5 hours, dropwise, continue to control temperature at 65 ℃, make 6, 8-dicloro caprylate sodium continues to react 2.0 hours with sodium diselenide, after reaction finishes, be cooled to 40 ℃, add 8g gac, be warming up to 50 ℃, stir after 30 minutes, filtered while hot is removed gac, collect filtrate, the filtrate of collection is added in another four-hole bottle, add again water to 400mL, then under agitation condition, be cooled to 0 ℃, the dilute hydrochloric acid solution that dropping mass concentration is 5% carries out acidification, regulate pH value to 2, separate out a large amount of chocolate solid matters, suction filtration, it is sad that oven dry obtains final product selenium, the HPLC purity of product is 93.5%, molar yield is 72%.
Embodiment 5
By 6.01g(25mmol) 6, in the four-hole bottle that 8-dicloro caprylate ethyl ester adds, adding mass concentration is 5% aqueous sodium hydroxide solution 60g, be heated to 55 ℃, controlling temperature of reaction is 55 ℃ of reactions 5 hours that are hydrolyzed, after reaction finishes, obtain the reaction solution of faint yellow 6,8-dichloro-octanoic acid sodium;
To above-mentioned 6, in the reaction solution of 8-dicloro caprylate sodium, drip mass concentration and be 15% the sodium diselenide aqueous solution, wherein, the add-on of the sodium diselenide aqueous solution makes sodium diselenide and 6, the mol ratio of 8-dicloro caprylate ethyl ester is 1.05:1, in dropping process, control temperature temperature at 70 ℃～75 ℃, time for adding is about 2.5 hours, dropwise, continue to control temperature at 75 ℃, make 6, 8-dicloro caprylate sodium continues to react 1.5 hours with sodium diselenide, after reaction finishes, be cooled to 40 ℃, add 15g gac, be warming up to 50 ℃, stir after 30 minutes, filtered while hot is removed gac, collect filtrate, the filtrate of collection is added in another four-hole bottle, slowly add again water to 400mL, then under agitation condition, be cooled to 0 ℃, the dilute hydrochloric acid solution that dropping mass concentration is 5% carries out acidification, regulate pH value to 2, separate out a large amount of chocolate solid matters, suction filtration, the solid matter obtaining is dried, obtain final product selenium sad, the HPLC purity of product is 94%, molar yield is 69.8%.
Embodiment 6
By 6.01g(25mmol) 6, in the four-hole bottle that 8-dicloro caprylate ethyl ester adds, adding mass concentration is 5% aqueous sodium hydroxide solution 60g, be heated to 55 ℃, controlling temperature of reaction is 50 ℃ of reactions 3.0 hours that are hydrolyzed, after reaction finishes, obtain the reaction solution of faint yellow 6,8-dichloro-octanoic acid sodium;
To above-mentioned 6, in the reaction solution of 8-dicloro caprylate sodium, drip mass concentration and be 15% the sodium diselenide aqueous solution, wherein, the add-on of the sodium diselenide aqueous solution makes sodium diselenide and 6, the mol ratio of 8-dicloro caprylate ethyl ester is 2.5:1, in dropping process, control temperature temperature at 70 ℃～75 ℃, time for adding is about 2.5 hours, dropwise, be warming up to 80 ℃, and control temperature at 80 ℃, make 6, 8-dicloro caprylate sodium continues to react 1.0 hours with sodium selenide, after reaction finishes, be cooled to 40 ℃, add 10g gac, be warming up to 50 ℃, stir after 30 minutes, filtered while hot is removed gac, collect filtrate, the filtrate of collection is added in another four-hole bottle, slowly add again water to 300mL, then under agitation condition, be cooled to 0 ℃, the dilute hydrochloric acid solution that dropping mass concentration is 5% carries out acidification, regulate pH value to 2, separate out a large amount of chocolate solid matters, stir after 15 minutes, suction filtration, the solid matter obtaining is dried, obtain final product selenium sad, the HPLC purity of product is 94.5%, molar yield is 68.2%.
Embodiment 7
By 6.01g(25mmol) 6, in the four-hole bottle that 8-dicloro caprylate ethyl ester adds, and then add the aqueous sodium hydroxide solution 40g that 44mL propyl alcohol solvent, mass concentration are 5%, be heated to 40 ℃, controlling temperature of reaction is 40 ℃ of reactions 4.5 hours that are hydrolyzed, after reaction finishes, obtain the reaction solution of faint yellow 6,8-dichloro-octanoic acid sodium;
To above-mentioned 6, in the reaction solution of 8-dicloro caprylate sodium, drip the sodium diselenide aqueous solution, wherein, the add-on of the sodium diselenide aqueous solution makes sodium diselenide and 6, the mol ratio of 8-dicloro caprylate ethyl ester is 1.2:1, in dropping process, control temperature at 55 ℃～58 ℃, time for adding is about 2 hours, dropwise, continue to control temperature at 56 ℃, make 6, 8-dicloro caprylate sodium continues to react 2.0 hours with sodium diselenide, after reaction finishes, be cooled to 40 ℃, add 10g gac, be warming up to 50 ℃, stir after 30 minutes, filtered while hot is removed gac, collect filtrate, the filtrate of collection is added in another four-hole bottle, carry out underpressure distillation and reclaim propyl alcohol solvent, in decompression process, control temperature and be no more than 50 ℃, reclaim after most of propyl alcohol solvent, in residual solution, add water to 350mL, then under agitation condition, be cooled to 0 ℃, the dilute hydrochloric acid solution that dropping mass concentration is 5% carries out acidification, regulate pH value to 2, separate out a large amount of chocolate solid matters, suction filtration, the solid matter obtaining is dried, obtain final product selenium sad, HPLC purity is 92.3%, molar yield is 67.6%.
Embodiment 8
By 6.01g(25mmol) 6, in the four-hole bottle that 8-dicloro caprylate ethyl ester adds, and then add the aqueous sodium hydroxide solution 60g that 40mL methanol solvate, mass concentration are 5%, be heated to 45 ℃, controlling temperature of reaction is 45 ℃ of reactions 3.5 hours that are hydrolyzed, after reaction finishes, obtain the reaction solution of faint yellow 6,8-dichloro-octanoic acid sodium;
To above-mentioned 6, in the reaction solution of 8-dicloro caprylate sodium, drip the sodium diselenide aqueous solution, wherein, the add-on of the sodium diselenide aqueous solution makes sodium diselenide and 6, the mol ratio of 8-dicloro caprylate ethyl ester is 3.0:1, in dropping process, control temperature at 58 ℃～60 ℃, time for adding is about 2 hours, dropwise, continue to control temperature at 60 ℃, make 6, 8-dicloro caprylate sodium continues to react 1 hour with sodium diselenide, after reaction finishes, be cooled to 20 ℃, add 10g gac, then be warming up to 40 ℃, stir after 30 minutes, filtered while hot is removed gac, collect filtrate, the filtrate of collection is added in another four-hole bottle, carry out underpressure distillation and reclaim methanol solvate, in decompression process, control temperature and be no more than 40 ℃, reclaim after most of methanol solvate, in residual solution, add water to 350mL, then under agitation condition, be cooled to 0 ℃, the dilute hydrochloric acid solution that dropping mass concentration is 5% carries out acidification, regulate pH value to 2, separate out a large amount of chocolate solid matters, suction filtration, the solid matter obtaining is dried, obtain final product selenium sad, HPLC purity is 91.5%, molar yield is 66.5%.
Specific embodiment described in the present invention is only to the explanation for example of the present invention's spirit.Those skilled in the art can make various modifications or supplement or adopt similar mode to substitute described specific embodiment, but can't depart from spirit of the present invention or surmount the defined scope of appended claims.
Although the present invention has been made a detailed description and has quoted as proof some specific embodiments, to those skilled in the art, only otherwise it is obvious leaving that the spirit and scope of the present invention can make various changes or revise.
Claims (9)
1. the sad preparation method of selenium, is characterized in that, the method comprises the following steps:
A, 6,8-dichloro-octanoic acid ethyl ester is hydrolyzed and is reacted with alkali-metal hydroxide aqueous solution, obtain the reaction solution of 6,8-dichloro-octanoic acid sodium;
In B, the reaction solution that obtains to steps A, add the sodium diselenide aqueous solution, making 6,8-dichloro-octanoic acid sodium is to react under the condition of 50 ℃～80 ℃ in temperature with sodium diselenide, after reaction finishes, add mineral acid to carry out acidification, filter, dry, obtain formula I compound selenium sad; The mol ratio of described 6,8-dichloro-octanoic acid ethyl ester and sodium diselenide is 1:1～3;
2. the sad preparation method of selenium according to claim 1, is characterized in that, the hydrolysis reaction described in steps A carries out under alcoholic solvent exists, and described alcoholic solvent is selected from the alcoholic solvent of C1～C4.
3. the sad preparation method of selenium according to claim 2, is characterized in that, the temperature of the hydrolysis reaction described in steps A is 40 ℃～70 ℃, and the described reaction times is 1～5 hour.
4. the sad preparation method of selenium according to claim 1, is characterized in that, the alkali-metal hydroxide aqueous solution described in steps A is that mass concentration is 5%～20% aqueous sodium hydroxide solution.
5. according to the sad preparation method of selenium described in claim 1-4 any one, it is characterized in that, the reaction times described in step B is 1～3 hour.
6. according to the sad preparation method of selenium described in claim 1-4 any one, it is characterized in that, the mineral acid described in step B is that mass concentration is 5%～20% aqueous hydrochloric acid.
7. according to the sad preparation method of selenium described in claim 1-4 any one, it is characterized in that, described in step B, add mineral acid to carry out also comprising before acidification to add the gac processing of decolouring.
8. the sad preparation method of selenium according to claim 7, is characterized in that, the add-on of described gac is 1～3 times of weight of 6,8-dichloro-octanoic acid ethyl ester.
9. the sad preparation method of selenium according to claim 1, is characterized in that, the mol ratio of the 6,8-dichloro-octanoic acid ethyl ester described in steps A and alkali-metal oxyhydroxide is 1:1～3.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210439729.XA CN102993167B (en) | 2012-11-07 | 2012-11-07 | Preparation method of selenium caprylate |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210439729.XA CN102993167B (en) | 2012-11-07 | 2012-11-07 | Preparation method of selenium caprylate |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN102993167A CN102993167A (en) | 2013-03-27 |
| CN102993167B true CN102993167B (en) | 2014-10-29 |
Family
ID=47922338
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210439729.XA Expired - Fee Related CN102993167B (en) | 2012-11-07 | 2012-11-07 | Preparation method of selenium caprylate |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN102993167B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115043816B (en) * | 2022-06-29 | 2023-10-24 | 浙江中医药大学 | Chiral resolution method of selenium octanoic acid |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101607955B (en) * | 2008-06-18 | 2012-11-28 | 上海津力化工有限公司 | Preparation method for low-residue lipoic acid |
-
2012
- 2012-11-07 CN CN201210439729.XA patent/CN102993167B/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN102993167A (en) | 2013-03-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106349245A (en) | Sitagliptin phosphate impurities, method for preparing same and application of sitagliptin phosphate impurities | |
| CN103524447A (en) | Method for synthesizing rivaroxaban intermediate 4-(4-aminophenyl)-3-molindone | |
| CN110627761A (en) | Method for synthesizing myricetin | |
| CN105254575A (en) | Synthetic method for sulfadiazine | |
| CN101781264B (en) | Production method of 1-methyl-5-mercapto-1,2,3,4-tetrazole | |
| CN105646580A (en) | Method for producing pentahydrate s-ornidazole disodium phosphate | |
| CN102442972B (en) | Industrial preparation method for pramipexole and its dihydrochloride monohydrate | |
| CN102993167B (en) | Preparation method of selenium caprylate | |
| CN106957255B (en) | Methylisoindoline of 5 bromines of one kind (R) N Boc 1 and its preparation method and application | |
| CN101979399A (en) | Method for producing important steroid hormone dexamethasone methyl tetraenes intermediate | |
| CN109438307A (en) | A kind of preparation method of L- selenomethionine | |
| CN104402849B (en) | The new preparation process of Ta Simeiqiong intermediate | |
| CN110734398B (en) | New preparation method of 2-chloronicotinic acid | |
| CN102993092A (en) | Synthetic method for 2-Chloronicotinicacid | |
| CN101239947B (en) | Method for preparing cryptotanshinone | |
| CN112939893B (en) | Synthesis method of 4- (4-aminophenyl) -3-morpholinone | |
| CN106905145A (en) | A kind of preparation method of high-purity crocetin | |
| CN103130717B (en) | Preparation method of 2-benzo diazepine anthrone | |
| CN101665417B (en) | One-pot process for synthesizing 1,2,3-trimethoxy-benzene by using o-vanillin | |
| CN106966912A (en) | (R) preparation method of 3 amino butanols | |
| CN105418507A (en) | Preparation method for 1-(3-methyl-1-phenyl-1H-pyrazole-5-yl)piperazine | |
| CN103435530A (en) | Preparation method of D-tryptophan lower alcohol ester hydrochloride with high optical purity | |
| CN110155975B (en) | Method for improving solubility of stannous pyrophosphate | |
| CN102875460A (en) | Method for preparing sorafenib | |
| CN102786511B (en) | Improved method for preparing fupentixol dihydrochloride intermediate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| TR01 | Transfer of patent right | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20200603 Address after: 318000 room 243-b, Huazhong building, Taizhou Development Zone, Zhejiang Province Patentee after: Taizhou Furui Biotechnology Co.,Ltd. Address before: 318000 No. 788, Taizhou Economic Development Zone, Zhejiang, Xueyuan Road Patentee before: TAIZHOU VOCATIONAL & TECHNICAL College |
|
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20141029 Termination date: 20201107 |