CN101274886A - Preparation for 6,8-dicloro caprylate - Google Patents
Preparation for 6,8-dicloro caprylate Download PDFInfo
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- CN101274886A CN101274886A CNA2008101090300A CN200810109030A CN101274886A CN 101274886 A CN101274886 A CN 101274886A CN A2008101090300 A CNA2008101090300 A CN A2008101090300A CN 200810109030 A CN200810109030 A CN 200810109030A CN 101274886 A CN101274886 A CN 101274886A
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Abstract
The invention relates to a preparation method of 6, 8-dichloro octanoic acid which pertains to the technical field of the preparation of raw materials used for lipoic acid. Firstly, 6, 8-dichloro octanoic acid ethyl ester is dissolved in a diluent to obtain diluted 6, 8-dichloro octanoic acid ethyl ester liquid; alkali is added into the diluted 6, 8-dichloro octanoic acid ethyl ester liquid to be hydrolyzed; then the diluent is steamed out and after acidification, extraction by using an organic solvent is carried out; at last, the 6, 8-dichloro octanoic acid is obtained after water washing and concentration. The preparation method has the advantages of: high yield and high product content due to complete hydrolysis; compared with the prior art, as no acid hydrolysis and re-distillation are needed, no pollution to the environment can be generated, hydrolysis time is shortened and energy is saved, thus meeting the requirements of industrial production.
Description
Technical field
The invention belongs to the preparing technical field of the raw material used of preparation Thioctic Acid, be specifically related to a kind of 6, the preparation method of 8-two chloroctanoic acids.
Background technology
6,8-two chloroctanoic acids (6,8-dichloro-octanoic acid), chemical structural formula is as follows:
6,8-two chloroctanoic acids are preparation alpha-lipoic acid and the raw material that (R or S type) alpha-lipoic acid of optically-active is arranged.
Nineteen fifty-one U.S. scientist Reed etc. isolates the natural product of biologically active first from pork liver, its physiologically active only is confined to R-(+), S-(-) non-activity.
Clinically, R-(+) alpha-lipoic acid is used for the treatment of diseases such as neurotic diabetes, ischemia-reperfusion more and more; R-(+) alpha-lipoic acid also has curative effect to multiple diseases such as hepatopathy, senile dementia, cataract, heart troubles in addition, and can effectively suppress the diffusion of HIV-1 in cell.
The synthetic method of R-(+) alpha-lipoic acid is a lot, mainly contains asymmetric synthesis method, enzyme catalysis synthesis method and chemical resolution method, and wherein chemical resolution method has been realized suitability for industrialized production.
The method of utilizing Split Method to prepare alpha-lipoic acid of comparative maturity mainly contains two kinds at present: a kind of is direct resolving racemic alpha-lipoic acid; Another kind is to split 6 earlier, 8-two chloroctanoic acids, and with R-(+)-6, the sad esterification of 8-dichloro, after sodium disulfide replaced, hydrolysis generated R-(+) Thioctic Acid.
The method of direct resolving racemic alpha-lipoic acid, it is too high to split second half S-(-) Thioctic Acid recycling cost of back, thus adopt elder generation to split 6, the method for 8-two chloroctanoic acids, cost can reduce greatly.
Originally produce 6, the method of 8-two chloroctanoic acids is: with acid hydrolysis 6,8-dichloro ethyl octylate, since this method make 6,8-two chloroctanoic acid content are low, need distillation again, distillation then causes yield low again, hydrolysis time is long, energy consumption is high, therefore and be not suitable for suitability for industrialized production produce a large amount of acid and environment is produced pollute, and distillation can produce large amount of sewage again.
The object of the present invention is to provide a kind of 6; the preparation method of 8-two chloroctanoic acids; this method gained 6; 8-two chloroctanoic acid content height; owing to do not need a large amount of acid and do not need to distill again, the short a large amount of generations that help suppressing sewage of hydrolysis time, thereby help protecting environment and use and satisfy the suitability for industrialized production requirement.
Summary of the invention
The objective of the invention is to finish like this, a kind of 6, the preparation method of 8-two chloroctanoic acids, it is earlier with 6,8-dichloro ethyl octylate is dissolved in the thinner, obtain diluting 6,8-dichloro ethyl octylate liquid material; Again alkali is joined 6 of described dilution, be hydrolyzed in the 8-dichloro ethyl octylate liquid material; Boil off thinner then, after acidifying, use organic solvent extraction again; After washing, concentrate and obtain 6,8-two chloroctanoic acids.
In a specific embodiment of the present invention, described 6, the weight ratio of 8-dichloro ethyl octylate and thinner is 1: 2.6～16.
In another specific embodiment of the present invention, described 6, the mol ratio of 8-dichloro ethyl octylate and alkali is 1: 1～2, and the concentration of described alkali is 10～30%.
Go back in the specific embodiment of the present invention, described thinner is an alcoholic solvent, and described alcoholic solvent is formic acid, ethanol.
In another specific embodiment of the present invention, described 6,8-dichloro ethyl octylate is 6 of a commercially available technical grade, 8-dichloro ethyl octylate.
In another specific embodiment of the present invention, describedly be hydrolyzed to the reflux hydrolysis, the time of reflux hydrolysis is 4～8 hours, and the pH value of hydrolysis is 9～10, and the Heating temperature of described heating is 20～80 ℃.
More of the present invention and in specific embodiment, described alkali is oxyhydroxide, carbonate or the supercarbonate of basic metal or alkaline-earth metal.
In of the present invention and then specific embodiment, the used acid of described acidifying is organic acid or mineral acid.
Of the present invention again more and in specific embodiment, described organic acid is formic acid, acetate or propionic acid; Described mineral acid is sulfuric acid, hydrochloric acid, nitric acid or phosphoric acid.
In again of the present invention and then specific embodiment, described organic solvent is aliphatics, fragrant same clan organic solvent.
The advantage of the inventive method: because hydrolysis is complete, so yield height, product content height; Owing to compared with the prior art do not need and do not need to distill again, thereby can not produce pollution, shorten hydrolysis time, save energy consumption, thereby can satisfy the suitability for industrialized production requirement to environment with acid hydrolysis.
Embodiment:
The following examples can make those skilled in the art more fully understand the present invention, but do not limit the present invention in any way.
Embodiment 1
In the 10000ml reaction flask, add 6 of commercially available technical grade, 8-dichloro ethyl octylate 500 gram (content is 98%) adds methyl alcohol 1700ml, obtain diluting 6,8-dichloro ethyl octylate liquid material, to 6 of dilution, 8-dichloro ethyl octylate liquid material is hydrolyzed, specifically: be dissolved in the 414 gram water in the described 5000ml reaction flask of dissolving back adding with 100 gram sodium hydroxide (content is 99%), the pH value is 10, reflux 4.5 hours, reflux temperature is 65 ℃, after reaction is good, boils off methyl alcohol, add 200ml water and 300ml toluene, add concentrated hydrochloric acid, the pH value is at 1 o'clock, static layering, water layer is used the 300ml methylbenzene extraction again, the combining methylbenzene layer, wash with water to organic phase no acidic, with after the Sodium sulfate anhydrous.min(99) dehydration, pressure reducing and steaming toluene, get 6,8-two chloroctanoic acid concentrated solutions 442 grams, HPLC content is 96.2%, molar yield is: 98.2%.
Embodiment 2
In the 10000ml reaction flask, add 6 of commercially available technical grade, 8-dichloro ethyl octylate 500 gram (content is 98%) adds methyl alcohol 5000ml, obtain diluting 6,8-dichloro ethyl octylate liquid material, to 6 of dilution, 8-dichloro ethyl octylate liquid material is hydrolyzed, specifically: be dissolved in the 414 gram water in the described 5000ml reaction flask of dissolving back adding with 100 gram sodium hydroxide (content is 99%), the pH value is 10, reflux 4.5 hours, reflux temperature is 65 ℃, after reaction is good, boils off methyl alcohol, add 200ml water and 300ml toluene, add concentrated hydrochloric acid, the pH value is at 1 o'clock, static layering, water layer is used the 300ml methylbenzene extraction again, the combining methylbenzene layer, wash with water to organic phase no acidic, with after the Sodium sulfate anhydrous.min(99) dehydration, pressure reducing and steaming toluene, get 6,8-two chloroctanoic acid concentrated solutions 442.5 grams, HPLC content is 96.3%, molar yield is: 98.4%.
Embodiment 3
In the 10000ml reaction flask, add 6 of commercially available technical grade, 8-dichloro ethyl octylate 500 gram (content is 98%) adds methyl alcohol 8000ml, obtain diluting 6,8-dichloro ethyl octylate liquid material, to 6 of dilution, 8-dichloro ethyl octylate liquid material is hydrolyzed, specifically: be dissolved in the 414 gram water in the described 5000ml reaction flask of dissolving back adding with 100 gram sodium hydroxide (content is 99%), the pH value is 10, reflux 4.5 hours, reflux temperature is 65 ℃, after reaction is good, boils off methyl alcohol, add 200ml water and 300ml toluene, add spirit acid, the pH value is at 1 o'clock, static layering, water layer is used the 300ml methylbenzene extraction again, the combining methylbenzene layer, wash with water to organic phase no acidic, with after the Sodium sulfate anhydrous.min(99) dehydration, pressure reducing and steaming toluene, get 6,8-two chloroctanoic acid concentrated solutions 442.2 grams, HPLC content is 96.18%, molar yield is: 98.2%.
Embodiment 4
In the 10000ml reaction flask, add 6 of commercially available technical grade, 8-dichloro ethyl octylate 500 grams (content is 98%), add ethanol 500ml, obtain diluting 6,8-dichloro ethyl octylate liquid material, to 6 of dilution, 8-dichloro ethyl octylate liquid material is hydrolyzed, specifically: be dissolved in the 414 gram water in the described 5000ml reaction flask of dissolving back adding with 100 gram sodium hydroxide (content is 99%), the pH value is 10, reflux 4.5 hours, reflux temperature is 65 ℃, after reaction is good, boils off ethanol, add 200ml water and 300ml ethyl acetate, add spirit acid, the pH value is at 1 o'clock, static layering, water layer is used the 300ml ethyl acetate extraction again, the combining methylbenzene layer, wash with water to organic phase no acidic, with after the Sodium sulfate anhydrous.min(99) dehydration, pressure reducing and steaming toluene, get 6,8-two chloroctanoic acid concentrated solutions 411.4 grams, HPLC content is 94.5%, molar yield is: 89.8%.
Embodiment 5
In the 10000ml reaction flask, add 6 of commercially available technical grade, 8-dichloro ethyl octylate 500 grams (content is 98%), add ethanol 1700ml, obtain diluting 6,8-dichloro ethyl octylate liquid material, to 6 of dilution, 8-dichloro ethyl octylate liquid material is hydrolyzed, specifically: be dissolved in the 340 gram water in the described 5000ml reaction flask of dissolving back adding with 82.09 gram sodium hydroxide (content is 99%), the pH value is 9, reflux 4.5 hours, reflux temperature is 65 ℃, after reaction is good, boils off ethanol, add 200ml water and 300ml ethyl acetate, add 15% sulfuric acid, the pH value is at 1 o'clock, static layering, water layer is used the 300ml ethyl acetate extraction again, the combining methylbenzene layer, wash with water to organic phase no acidic, with after the Sodium sulfate anhydrous.min(99) dehydration, pressure reducing and steaming toluene, get 6,8-two chloroctanoic acid concentrated solutions 427.9 grams, HPLC content is 95.9%, molar yield is: 94.8%.
Embodiment 6
In the 10000ml reaction flask, add 6 of commercially available technical grade, 8-dichloro ethyl octylate 500 grams (content is 98%), add methyl alcohol 1700ml, obtain diluting 6,8-dichloro ethyl octylate liquid material, to 6 of dilution, 8-dichloro ethyl octylate liquid material is hydrolyzed, specifically: be dissolved in the 550 gram water in the described 5000ml reaction flask of dissolving back adding with 131.36 gram sodium hydroxide (content is 99%), the pH value is 12, reflux 4.5 hours, reflux temperature is 65 ℃, and good back 4.5 hours of reaction boils off methyl alcohol, add 200ml water and 300ml ethyl acetate, add 15% sulfuric acid, the pH value is at 1 o'clock, static layering, water layer is used the 300ml ethyl acetate extraction again, the combining methylbenzene layer, wash with water to organic phase no acidic, with after the Sodium sulfate anhydrous.min(99) dehydration, pressure reducing and steaming toluene, get 6,8-two chloroctanoic acid concentrated solutions 419.8 grams, HPLC content is 94.8%, molar yield is: 91.9%.
Embodiment 7
In the 10000ml reaction flask, add 6 of commercially available technical grade, 8-dichloro ethyl octylate 500 grams (content is 98%), add methyl alcohol 1700ml, obtain diluting 6,8-dichloro ethyl octylate liquid material, to 6 of dilution, 8-dichloro ethyl octylate liquid material is hydrolyzed, and specifically: be dissolved in 164.2 gram sodium hydroxide (content is 99%) that dissolving back adds in the described 5000ml reaction flask in the 680 gram water, the pH value is 12, reflux, boil off methyl alcohol, add 200ml water and 300ml toluene, add concentrated hydrochloric acid, the pH value was at 1 o'clock, static layering, water layer are used the 300ml methylbenzene extraction again, the combining methylbenzene layer, wash with water to organic phase no acidic, after the Sodium sulfate anhydrous.min(99) dehydration, pressure reducing and steaming toluene gets 6,8-two chloroctanoic acid concentrated solutions 411.7 grams, HPLC content is 93.8%, molar yield is: 89.2%.
Embodiment 8
In the 10000ml reaction flask, add 6 of commercially available technical grade, 8-dichloro ethyl octylate 500 gram (content is 98%) adds methyl alcohol 1700ml, obtain diluting 6,8-dichloro ethyl octylate liquid material, to 6 of dilution, 8-dichloro ethyl octylate liquid material is hydrolyzed, specifically: be dissolved in the 900 gram water in the described 5000ml reaction flask of dissolving back adding with 100 gram sodium hydroxide (content is 99%), the pH value is 10, reflux 4.5 hours, reflux temperature is 65 ℃, after reaction is good, boils off methyl alcohol, add 200ml water and 300ml toluene, add concentrated hydrochloric acid, the pH value is at 1 o'clock, static layering, water layer is used the 300ml methylbenzene extraction again, the combining methylbenzene layer, wash with water to organic phase no acidic, with after the Sodium sulfate anhydrous.min(99) dehydration, pressure reducing and steaming toluene, get 6,8-two chloroctanoic acid concentrated solutions 442.2 grams, HPLC content is 96.18%, molar yield is: 98.2%.
Embodiment 9
In the 10000ml reaction flask, add 6 of commercially available technical grade, 8-dichloro ethyl octylate 500 gram (content is 98%) adds methyl alcohol 1700ml, obtain diluting 6,8-dichloro ethyl octylate liquid material, to 6 of dilution, 8-dichloro ethyl octylate liquid material is hydrolyzed, specifically: be dissolved in the 186 gram water in the described 5000ml reaction flask of dissolving back adding with 100 gram sodium hydroxide (content is 99%), the pH value is 10, reflux 4.5 hours, reflux temperature is 65 ℃, after reaction is good, boils off methyl alcohol, add 200ml water and 300ml toluene, add concentrated hydrochloric acid, the pH value is at 1 o'clock, static layering, water layer is used the 300ml methylbenzene extraction again, the combining methylbenzene layer, wash with water to organic phase no acidic, with after the Sodium sulfate anhydrous.min(99) dehydration, pressure reducing and steaming toluene, get 6,8-two chloroctanoic acid concentrated solutions 437.4 grams, HPLC content is 95.80%, molar yield is: 96.77%.
Embodiment 10
In the 10000ml reaction flask, add 6 of commercially available technical grade, 8-dichloro ethyl octylate 500 gram (content is 98%) adds methyl alcohol 1700ml, obtain diluting 6,8-dichloro ethyl octylate liquid material, to 6 of dilution, 8-dichloro ethyl octylate liquid material is hydrolyzed, specifically: be dissolved in the 186 gram water in the described 5000ml reaction flask of dissolving back adding with 100 gram sodium hydroxide (content is 99%), the pH value is 10, reflux 4.5 hours, reflux temperature is 65 ℃, after reaction is good, boils off methyl alcohol, add 200ml water and 300ml toluene, add concentrated hydrochloric acid, the pH value is at 1 o'clock, static layering, water layer is used the 234ml methylbenzene extraction again, the combining methylbenzene layer, wash with water to organic phase no acidic, with after the Sodium sulfate anhydrous.min(99) dehydration, pressure reducing and steaming toluene, get 6,8-two chloroctanoic acid concentrated solutions 430.4 grams, HPLC content is 95.40%, molar yield is: 94.83%.
Embodiment 11
In the 10000ml reaction flask, add 6 of commercially available technical grade, 8-dichloro ethyl octylate 500 gram (content is 98%) adds ethanol 1700ml, obtain diluting 6,8-dichloro ethyl octylate liquid material, to 6 of dilution, 8-dichloro ethyl octylate liquid material is hydrolyzed, specifically: be dissolved in the 186 gram water in the described 5000ml reaction flask of dissolving back adding with 100 gram sodium hydroxide (content is 99%), the pH value is 10, reflux 4.5 hours, reflux temperature is 65 ℃, after reaction is good, boils off ethanol, add 200ml water and 300ml toluene, add concentrated hydrochloric acid, the pH value is at 1 o'clock, static layering, water layer is used the 234ml methylbenzene extraction again, the combining methylbenzene layer, wash with water to organic phase no acidic, with after the Sodium sulfate anhydrous.min(99) dehydration, pressure reducing and steaming toluene, get 6,8-two chloroctanoic acid concentrated solutions 441.8 grams, HPLC content is 96.18%, molar yield is: 98.10%.
Embodiment 12
In the 10000ml reaction flask, add 6 of commercially available technical grade, 8-dichloro ethyl octylate 500 grams (content is 98%), add methyl alcohol 1700ml, obtain diluting 6,8-dichloro ethyl octylate liquid material, to 6 of dilution, 8-dichloro ethyl octylate liquid material is hydrolyzed, specifically: be dissolved in the 414 gram water in the described 5000ml reaction flask of dissolving back adding with 100 gram sodium hydroxide (content is 99%), the pH value is 10, reflux 4.5 hours, reflux temperature is 65 ℃, and good back 2 hours of reaction boils off methyl alcohol, add 200ml water and 300ml toluene, add concentrated hydrochloric acid, the pH value is at 1 o'clock, static layering, water layer is used the 300ml methylbenzene extraction again, the combining methylbenzene layer, wash with water to organic phase no acidic, with after the Sodium sulfate anhydrous.min(99) dehydration, pressure reducing and steaming toluene, get 6,8-two chloroctanoic acid concentrated solutions 417.3 grams, HPLC content is 91.59%, molar yield is: 88.27%.
Embodiment 13
In the 10000ml reaction flask, add 6 of commercially available technical grade, 8-dichloro ethyl octylate 500 grams (content is 98%), add methyl alcohol 1700ml, obtain diluting 6,8-dichloro ethyl octylate liquid material, to 6 of dilution, 8-dichloro ethyl octylate liquid material is hydrolyzed, and specifically: be dissolved in 100 gram sodium hydroxide (content is 99%) that dissolving back adds in the described 5000ml reaction flask in the 414 gram water, the pH value is 10, reflux 6 hours, boil off methyl alcohol, add 200ml water and 300ml toluene, add concentrated hydrochloric acid, the pH value was at 1 o'clock, static layering, water layer are used the 300ml methylbenzene extraction again, the combining methylbenzene layer, wash with water to organic phase no acidic, after the Sodium sulfate anhydrous.min(99) dehydration, pressure reducing and steaming toluene gets 6,8-two chloroctanoic acid concentrated solutions 442.56 grams, HPLC content is 96.19%, molar yield is: 98.31%.
Embodiment 14
In the 10000ml reaction flask, add 6 of commercially available technical grade, 8-dichloro ethyl octylate 500 grams (content is 98%), add methyl alcohol 1700ml, obtain diluting 6,8-dichloro ethyl octylate liquid material, to 6 of dilution, 8-dichloro ethyl octylate liquid material is hydrolyzed, specifically: be dissolved in the 414 gram water in the described 5000ml reaction flask of dissolving back adding with 100 gram sodium hydroxide (content is 99%), the pH value is 10, reflux 4.5 hours, reflux temperature is 65 ℃, and good back 8 hours of reaction boils off methyl alcohol, add 200ml water and 300ml toluene, add concentrated hydrochloric acid, the pH value is at 1 o'clock, static layering, water layer is used the 300ml methylbenzene extraction again, the combining methylbenzene layer, wash with water to organic phase no acidic, with after the Sodium sulfate anhydrous.min(99) dehydration, pressure reducing and steaming toluene, get 6,8-two chloroctanoic acid concentrated solutions 442.14 grams, HPLC content is 96.21%, molar yield is: 98.24%.
Embodiment 15
In the 10000ml reaction flask, add 6 of commercially available technical grade, 8-dichloro ethyl octylate 500 grams (content is 98%), add methyl alcohol 1700ml, obtain diluting 6,8-dichloro ethyl octylate liquid material, to 6 of dilution, 8-dichloro ethyl octylate liquid material is hydrolyzed, and specifically: be dissolved in 346.1 gram salt of wormwood (content is 99%) that dissolving back adds in the described 5000ml reaction flask in the 1450 gram water, the pH value is 9.5, reflux 4.5 hours, boil off methyl alcohol, add 200ml water and 300ml toluene, add concentrated hydrochloric acid, the pH value was at 1 o'clock, static layering, water layer are used the 300ml methylbenzene extraction again, the combining methylbenzene layer, wash with water to organic phase no acidic, after the Sodium sulfate anhydrous.min(99) dehydration, pressure reducing and steaming toluene gets 6,8-two chloroctanoic acid concentrated solutions 442.14 grams, HPLC content is 96.21%, molar yield is: 98.24%.
Embodiment 16
In the 10000ml reaction flask, add 6 of commercially available technical grade, 8-dichloro ethyl octylate 500 gram (content is 98%) adds methyl alcohol 1700ml, obtain diluting 6,8-dichloro ethyl octylate liquid material, to 6 of dilution, 8-dichloro ethyl octylate liquid material is hydrolyzed, specifically: be dissolved in the 880 gram water in the described 5000ml reaction flask of dissolving back adding with 210.4 gram sodium bicarbonates (content is 99%), the pH value is 9, reflux 4.5 hours, reflux temperature is 65 ℃, after reaction is good, boils off methyl alcohol, add 200ml water and 300ml toluene, add concentrated hydrochloric acid, the pH value is at 1 o'clock, static layering, water layer is used the 300ml methylbenzene extraction again, the combining methylbenzene layer, wash with water to organic phase no acidic, with after the Sodium sulfate anhydrous.min(99) dehydration, pressure reducing and steaming toluene, get 6,8-two chloroctanoic acid concentrated solutions 442.5 grams, HPLC content is 96.4%, molar yield is: 98.51%.
Embodiment 17
In the 10000ml reaction flask, add 6 of commercially available technical grade, 8-dichloro ethyl octylate 500 gram (content is 98%) adds methyl alcohol 1700ml, obtain diluting 6,8-dichloro ethyl octylate liquid material, to 6 of dilution, 8-dichloro ethyl octylate liquid material is hydrolyzed, specifically: be dissolved in the 414 gram water in the described 5000ml reaction flask of dissolving back adding with 100 gram sodium hydroxide (content is 99%), the pH value is 10, reflux 4.5 hours, reflux temperature is 65 ℃, after reaction is good, boils off methyl alcohol, add 200ml water and 300ml toluene, add 30% acetate, the pH value is at 1 o'clock, static layering, water layer is used the 300ml methylbenzene extraction again, the combining methylbenzene layer, wash with water to organic phase no acidic, with after the Sodium sulfate anhydrous.min(99) dehydration, pressure reducing and steaming toluene, get 6,8-two chloroctanoic acid concentrated solutions 441.8 grams, HPLC content is 96.22%, molar yield is: 98.17%.
Embodiment 18
In the 10000ml reaction flask, add 6 of commercially available technical grade, 8-dichloro ethyl octylate 500 gram (content is 98%) adds methyl alcohol 1700ml, obtain diluting 6,8-dichloro ethyl octylate liquid material, to 6 of dilution, 8-dichloro ethyl octylate liquid material is hydrolyzed, specifically: be dissolved in the 414 gram water in the described 5000ml reaction flask of dissolving back adding with 100 gram sodium hydroxide (content is 99%), the pH value is 10, reflux 4.5 hours, reflux temperature is 65 ℃, after reaction is good, boils off methyl alcohol, add 200ml water and 300ml toluene, add 30% sulfuric acid, the pH value is at 1 o'clock, static layering, water layer is used the 300ml methylbenzene extraction again, the combining methylbenzene layer, wash with water to organic phase no acidic, with after the Sodium sulfate anhydrous.min(99) dehydration, pressure reducing and steaming toluene, get 6,8-two chloroctanoic acid concentrated solutions 442.2 grams, HPLC content is 96.18%, molar yield is: 98.22%.
Embodiment 19
In the 10000ml reaction flask, add 6 of commercially available technical grade, 8-dichloro ethyl octylate 500 grams (content is 98%), add methyl alcohol 1700ml, obtain diluting 6,8-dichloro ethyl octylate liquid material, to 6 of dilution, 8-dichloro ethyl octylate liquid material is hydrolyzed, and specifically: be dissolved in 100 gram sodium hydroxide (content is 99%) that dissolving back adds in the described 5000ml reaction flask in the 414 gram water, the pH value is 10, heating and temperature control is at 20 ℃, boil off methyl alcohol, add 200ml water and 300ml toluene, add phosphoric acid, the pH value was at 1 o'clock, static layering, water layer are used the 300ml methylbenzene extraction again, the combining methylbenzene layer, wash with water to organic phase no acidic, after the Sodium sulfate anhydrous.min(99) dehydration, pressure reducing and steaming toluene gets 6,8-two chloroctanoic acid concentrated solutions 405 grams, HPLC content is 93.71%, molar yield is: 87.65%.
Embodiment 20
In the 10000ml reaction flask, add 6 of commercially available technical grade, 8-dichloro ethyl octylate 500 grams (content is 98%), add methyl alcohol 1700ml, obtain diluting 6,8-dichloro ethyl octylate liquid material, to 6 of dilution, 8-dichloro ethyl octylate liquid material is hydrolyzed, and specifically: be dissolved in 100 gram sodium hydroxide (content is 99%) that dissolving back adds in the described 5000ml reaction flask in the 414 gram water, the pH value is 10, heating and temperature control is at 35 ℃, boil off methyl alcohol, add 200ml water and 300ml toluene, add phosphoric acid, the pH value was at 1 o'clock, static layering, water layer are used the 300ml methylbenzene extraction again, the combining methylbenzene layer, wash with water to organic phase no acidic, after the Sodium sulfate anhydrous.min(99) dehydration, pressure reducing and steaming toluene gets 6,8-two chloroctanoic acid concentrated solutions 417 grams, HPLC content is 94.14%, molar yield is: 90.66%.
Embodiment 21
In the 10000ml reaction flask, add 6 of commercially available technical grade, 8-dichloro ethyl octylate 500 grams (content is 98%), add methyl alcohol 1700ml, obtain diluting 6,8-dichloro ethyl octylate liquid material, to 6 of dilution, 8-dichloro ethyl octylate liquid material is hydrolyzed, and specifically: be dissolved in 100 gram sodium hydroxide (content is 99%) that dissolving back adds in the described 5000ml reaction flask in the 414 gram water, the pH value is 10, heating and temperature control is at 50 ℃, boil off methyl alcohol, add 200ml water and 300ml toluene, add concentrated hydrochloric acid, the pH value was at 1 o'clock, static layering, water layer are used the 300ml methylbenzene extraction again, the combining methylbenzene layer, wash with water to organic phase no acidic, after the Sodium sulfate anhydrous.min(99) dehydration, pressure reducing and steaming toluene gets 6,8-two chloroctanoic acid concentrated solutions 421 grams, HPLC content is 93.95%, molar yield is: 91.35%.
Embodiment 22
In the 10000ml reaction flask, add 6 of commercially available technical grade, 8-dichloro ethyl octylate 500 gram (content is 98%) adds methyl alcohol 1700ml, obtain diluting 6,8-dichloro ethyl octylate liquid material, to 6 of dilution, 8-dichloro ethyl octylate liquid material is hydrolyzed, specifically: be dissolved in the 900 gram water in the described 5000ml reaction flask of dissolving back adding with 100 gram sodium hydroxide (content is 99%), the pH value is 10, heated 4.5 hours, temperature is 80 ℃, after reaction is good, boils off methyl alcohol, add 200ml water and 300ml toluene, add concentrated hydrochloric acid, the pH value is at 1 o'clock, static layering, water layer is used the 300ml methylbenzene extraction again, the combining methylbenzene layer, wash with water to organic phase no acidic, with after the Sodium sulfate anhydrous.min(99) dehydration, pressure reducing and steaming toluene, get 6,8-two chloroctanoic acid concentrated solutions 440.5 grams, HPLC content is 96.08%, molar yield is: 97.74%.
Claims (10)
1, a kind of 6, the preparation method of 8-two chloroctanoic acids is characterized in that it is earlier with 6, and 8-dichloro ethyl octylate is dissolved in the thinner, obtain diluting 6,8-dichloro ethyl octylate liquid material; Again alkali is joined 6 of described dilution, be hydrolyzed in the 8-dichloro ethyl octylate liquid material; Boil off thinner then, after acidifying, use organic solvent extraction again; After washing, concentrate and obtain 6,8-two chloroctanoic acids.
2, according to claim 16, the preparation method of 8-two chloroctanoic acids is characterized in that describedly 6, and the weight ratio of 8-dichloro ethyl octylate and thinner is 1: 2.6～16.
3, according to claim 16, the preparation method of 8-two chloroctanoic acids is characterized in that describedly 6, and the mol ratio of 8-dichloro ethyl octylate and alkali is 1: 1～2, and the concentration of described alkali is 10～30%.
4, according to claim 1 and 26, the preparation method of 8-two chloroctanoic acids is characterized in that described thinner is an alcoholic solvent, and described alcoholic solvent is methyl alcohol, ethanol.
5, described 6 according to the arbitrary claim of claim 1-3, the preparation method of 8-two chloroctanoic acids is characterized in that describedly 6, and 8-dichloro ethyl octylate is 6 of a commercially available technical grade, 8-dichloro ethyl octylate.
6, according to claim 16, the preparation method of 8-two chloroctanoic acids is characterized in that the described reflux hydrolysis that is hydrolyzed to, and the time of reflux hydrolysis is 4～8 hours, and the pH value of hydrolysis is 9～12, and the Heating temperature of described heating is 20～80 ℃.
7, according to claim 1 or 3 described 6, the preparation method of 8-two chloroctanoic acids is characterized in that described alkali is oxyhydroxide, carbonate or the supercarbonate of basic metal or alkaline-earth metal.
8, according to claim 16, the preparation method of 8-two chloroctanoic acids is characterized in that the used acid of described acidifying is organic acid or mineral acid.
9, according to claim 86, the preparation method of 8-two chloroctanoic acids is characterized in that described organic acid is formic acid, acetate or propionic acid; Described mineral acid is sulfuric acid, hydrochloric acid, nitric acid or phosphoric acid.
10, according to claim 16, the preparation method of 8-two chloroctanoic acids is characterized in that described organic solvent is aliphatics, fragrant same clan organic solvent.
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| CNA2008101090300A CN101274886A (en) | 2008-05-09 | 2008-05-09 | Preparation for 6,8-dicloro caprylate |
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| CNA2008101090300A CN101274886A (en) | 2008-05-09 | 2008-05-09 | Preparation for 6,8-dicloro caprylate |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106966900A (en) * | 2016-01-13 | 2017-07-21 | 江苏同禾药业有限公司 | A kind of preparation method of 6,8- dicloro caprylates ethyl ester |
| CN112479878A (en) * | 2020-11-27 | 2021-03-12 | 青岛化赫医药科技有限公司 | Method for preparing 6, 8-dichloro ethyl caprylate |
-
2008
- 2008-05-09 CN CNA2008101090300A patent/CN101274886A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106966900A (en) * | 2016-01-13 | 2017-07-21 | 江苏同禾药业有限公司 | A kind of preparation method of 6,8- dicloro caprylates ethyl ester |
| CN112479878A (en) * | 2020-11-27 | 2021-03-12 | 青岛化赫医药科技有限公司 | Method for preparing 6, 8-dichloro ethyl caprylate |
| CN112479878B (en) * | 2020-11-27 | 2023-03-28 | 上海巽田科技股份有限公司 | Method for preparing 6, 8-dichloro ethyl caprylate |
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Open date: 20081001 |