CN100408555C - Preparation method of 4-chlorine-3-hydroxybutyronitrile - Google Patents
Preparation method of 4-chlorine-3-hydroxybutyronitrile Download PDFInfo
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- CN100408555C CN100408555C CNB2006100218581A CN200610021858A CN100408555C CN 100408555 C CN100408555 C CN 100408555C CN B2006100218581 A CNB2006100218581 A CN B2006100218581A CN 200610021858 A CN200610021858 A CN 200610021858A CN 100408555 C CN100408555 C CN 100408555C
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- hydroxybutyronitrile
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- epoxy chloropropane
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Abstract
The invention discloses a preparing method of 4-chloride-3-hydroxyl butyronitrile, which comprises the following steps: 1) blending epichlorohydrin and alkaline catalyst with molar rate at 1:1.0-1.5; adding 50-100% formonitrile to synthesize the product; 2) adjusting the reacting liquid to weak acid; distilling in the vacuum to obtain the product; recycling non-reacting epichlorohydrin.
Description
Technical field:
The present invention is relevant with the preparation method of 4-chloro-3-hydroxybutyronitrile.
Background technology:
The method of the existing 4-of preparation chloro-3-hydroxybutyronitrile mainly contains following two kinds, and all there is weak point in these methods.
1, sodium cyanide method:
This method is mixed epoxy chloropropane with water, slowly add sodium cyanide solution then, and constantly regulate pH value with sulfuric acid, and make its scope accurately remain on pH value in the scope of 8-10, reaction solution gets target product through last handling processes such as insulation, extraction, rectifying.
2, prussic acid-sodium sulphate method:
This method is mixed epoxy chloropropane with saturated aqueous sodium sulfate, keep pH value in the scope of 8-10, obtains 4-chloro-3-hydroxybutyronitrile with the prussic acid reaction, and reaction solution obtains target product through last handling processes such as insulation, extraction, rectifying.
These methods all do not exist yield high and produce a large amount of cyanide wastewater, need to handle a large amount of sodium sulfate simultaneously, and the three wastes are handled comparatively shortcoming such as difficulty.In document clear and 63-316578, WO2004/092114, gram B975722 etc., associated description is arranged.
Summary of the invention:
The objective of the invention is provides a kind of high yield in order to overcome above deficiency, low cost, the preparation method of the 4-chloro-3-hydroxybutyronitrile that the three wastes are few.
The object of the present invention is achieved like this:
The preparation method of 4-chloro-3-hydroxybutyronitrile of the present invention comprises the steps:
1) epoxy chloropropane is mixed with basic catalyst, in molar ratio epoxy chloropropane: prussic acid=1: 1.0-1.5, adding mass percentage content is the synthetic 4-chloro-3-hydroxybutyronitrile of prussic acid reaction of 50%-100%;
2) above-mentioned reaction solution is adjusted to pH=5.5～6.5 slightly acidics with acid after rectification under vacuum obtains 4-chloro-3-hydroxybutyronitrile product.The intact epoxy chloropropane of unreacted recycles.
Adding the prussic acid reaction after above-mentioned epoxy chloropropane and basic catalyst and the solvent again synthesizes-4-chloro-3-hydroxybutyronitrile, solvent and the intact epoxy chloropropane of unreacted were told in underpressure distillation after reaction solution was adjusted to pH=5.5～6.5 slightly acidics with acid, obtain 4-chloro-3-hydroxybutyronitrile crude product, 4-chloro-3-hydroxybutyronitrile crude product obtains 4-chloro-3-hydroxybutyronitrile product, epoxy chloropropane in molar ratio through rectification under vacuum: solvent=1: 1-18.
Above-mentioned solvent is a carbonatoms less than 4 alcohols or water.
Above-mentioned solvent adopts methyl alcohol or ethanol.
Above-mentioned epoxy chloropropane and pure mol ratio are 1: 2～3.
Above-mentioned basic catalyst consumption is the 0.01%-10% of epoxy chloropropane quality.
Above-mentioned basic catalyst is at least a kind of in strong base weak acid salt or the organic amine, the strong base weak acid salt is at least a kind of in alkali metal formate, alkali metal acetate, basic metal oxalate, alkaline carbonate, the alkali metal hydrocarbonate, as sodium formiate, sodium-acetate, sodium oxalate, yellow soda ash, sodium bicarbonate etc., organic amine is at least a kind of in primary amine class, secondary amine class, tertiary amines, the polyamines class, as methylamine, dimethylamine, Trimethylamine 99, ethamine, quadrol, propylamine, diethylamine, Isopropylamine, Diisopropylamine, n-Butyl Amine 99 etc.
When regulating acidity, preferentially selects above-mentioned reaction solution organic acid for use, preferably a kind of in formic acid, acetate, oxalic acid, the tosic acid.
Above-mentioned 4-chloro-3-hydroxybutyronitrile crude product is that 660 handkerchiefs, temperature make 4-chloro-3-hydroxybutyronitrile product 150～160 ℃ of following underpressure distillation at pressure.
Chemical equation involved in the present invention is as follows:
Present method has been avoided the generation of cyanide wastewater and sodium sulfate byproduct, has simplified purification step, has higher transformation efficiency, the yield height, and cost is low, and the three wastes are few, the enabling environment protection.
Embodiment:
Embodiment 1:
Having thermometer, prolong, in 500ml three flasks of agitator, add epoxy chloropropane (mass percentage content is 99%) 153.5 grams, methyl alcohol 120 grams, Trimethylamine 99 4.0 grams, under 60 ℃ of temperature, slowly dripping mass percent is 98% prussic acid, 47.2 grams, the dropping time is 80 minutes, insulation reaction 400 minutes finishes, and is slightly acidic (pH value between 5.5～6.5, same down) with the pH value of formic acid conditioned reaction liquid, then the reaction solution underpressure distillation is gone out light constituent and (comprise solvent, the epoxy chloropropane that unreacted is intact etc., down together) 110 grams, wherein, the epoxy chloropropane mass percentage content is 3%, get 4-chloro-3-hydroxybutyronitrile crude product 194 grams, analyzing mass percentage content is 94.7% (HPLC), changes it over to rectifying column rectifying, get target fraction 4-chloro-3-hydroxybutyronitrile 179.4 grams, mass percentage content is 98.6% (HPLC), in epoxy chloropropane, and product yield 92.09%.Raffinate burns.
Embodiment 2:
By embodiment 1 operation that feeds intake, different is that Trimethylamine 99 4.0 grams are changed to Diisopropylamine 3.0 grams, after reaction finishes, pH value with formic acid conditioned reaction liquid is a slightly acidic, the reaction solution underpressure distillation is gone out light constituent 108 grams, and wherein, the epoxy chloropropane mass percentage content is 2%.Get 4-chloro-3-hydroxybutyronitrile crude product 195.3 grams, analyzing mass percentage content is 95.2% (HPLC), changes the rectifying column rectification and purification over to, get target fraction 4-chloro-3-hydroxybutyronitrile 183.4 grams, mass percentage content is 98.2% (HPLC), in epoxy chloropropane, and product yield 93.06%.Raffinate burns.
Embodiment 3:
By embodiment 1 operation that feeds intake, different is that Trimethylamine 99 4.0 grams are changed to sodium-acetate 4.0 grams, after reaction finishes, pH value with formic acid conditioned reaction liquid is a slightly acidic, the reaction solution underpressure distillation is gone out light constituent 98 grams, and wherein, the epoxy chloropropane mass percentage content is 3.3%.Get 4-chloro-3-hydroxybutyronitrile crude product 192.8 grams, analyzing mass percentage content is 94.2% (HPLC), changes the rectifying column rectification and purification over to, get target fraction 4-chloro-3-hydroxybutyronitrile 177.7 grams, mass percentage content 98.7% (HPLC), in epoxy chloropropane, product yield 91.28%.Raffinate burns.
Embodiment 4:
By embodiment 1 operation that feeds intake, different is to change 120 gram methyl alcohol into 120 gram water, after reaction finishes, pH value with formic acid conditioned reaction liquid is a slightly acidic, the reaction solution underpressure distillation is gone out light component 102 grams, and wherein, the epoxy chloropropane mass percentage content is 2.4%.Get 4-chloro-3-hydroxybutyronitrile crude product 187.6 grams, analyzing mass percentage content is 94.4% (HPLC), changes the rectifying column rectification and purification over to, gets target fraction 4-chloro-3-hydroxybutyronitrile 173.2 gram mass degrees 98.9% (HPLC), in epoxy chloropropane, product yield 88.68%.Raffinate burns to not having.
Embodiment 5:
By embodiment 1 operation that feeds intake, different is solubilizing agent not, after reaction finishes, pH value with formic acid conditioned reaction liquid is a slightly acidic, change reaction solution over to the rectifying column rectification and purification, get target fraction 4-chloro-3-hydroxybutyronitrile 173.3 grams, mass percentage content 99.1% (HPLC), in epoxy chloropropane, product yield 87.48%.Raffinate burns.
The various embodiments described above are that content of the present invention is further described, but this should be interpreted as that the scope of the above-mentioned theme of the present invention only limits to the foregoing description.All technology that realizes based on foregoing all belong to protection scope of the present invention.
Claims (7)
1. the preparation method of 4-chloro-3-hydroxybutyronitrile comprises the steps:
1) epoxy chloropropane is mixed with basic catalyst, in molar ratio epoxy chloropropane: prussic acid=1: 1.0-1.5, adding mass percentage content is the synthetic 4-chloro-3-hydroxybutyronitrile of prussic acid reaction of 50%-100%;
2) above-mentioned reaction solution is adjusted to pH=5.5～6.5 slightly acidics with acid after rectification under vacuum obtains 4-chloro-3-hydroxybutyronitrile product;
Above-mentioned basic catalyst is at least a kind of in strong base weak acid salt or the organic amine, the strong base weak acid salt is at least a kind of in sodium formiate, sodium-acetate, sodium oxalate, yellow soda ash, the sodium bicarbonate, organic amine is at least a kind of in methylamine, dimethylamine, Trimethylamine 99, ethamine, quadrol, propylamine, diethylamine, Isopropylamine, Diisopropylamine, the n-Butyl Amine 99, when regulating acidity, selects above-mentioned reaction solution organic acid for use, i.e. a kind of in formic acid, acetate, oxalic acid, the tosic acid.
2. the preparation method of 4-chloro-3-hydroxybutyronitrile as claimed in claim 1, it is characterized in that and to add the synthetic 4-chloro-3-hydroxybutyronitrile of prussic acid reaction after epoxy chloropropane and basic catalyst and the solvent again, solvent and the intact epoxy chloropropane of unreacted were told in underpressure distillation after reaction solution was adjusted to pH=5.5～6.5 slightly acidics with acid, obtain 4-chloro-3-hydroxybutyronitrile crude product, 4-chloro-3-hydroxybutyronitrile crude product obtains 4-chloro-3-hydroxybutyronitrile product, epoxy chloropropane in molar ratio through rectification under vacuum: solvent=1: 1-18.
3. the preparation method of 4-chloro-3-hydroxybutyronitrile as claimed in claim 2 is characterized in that solvent is a carbonatoms less than 4 alcohols or water.
4. the preparation method of 4-chloro-3-hydroxybutyronitrile as claimed in claim 3 is characterized in that solvent adopts methyl alcohol or ethanol.
5. the preparation method of 4-chloro-3-hydroxybutyronitrile as claimed in claim 3 is characterized in that epoxy chloropropane and pure mol ratio are 1: 2～3.
6. as the preparation method of the described 4-chloro-of one of claim 1～5 3-hydroxybutyronitrile, it is characterized in that the basic catalyst consumption is the 0.01%-10% of epoxy chloropropane quality.
7. as the preparation method of described 4-chloro-3 hydroxybutyronitriles of one of claim 2～5, it is characterized in that 4-chloro-3-hydroxybutyronitrile crude product is that 660 handkerchiefs, temperature make 4-chloro-3-hydroxybutyronitrile product 150～160 ℃ of following underpressure distillation at pressure.
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Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103467291A (en) * | 2013-09-26 | 2013-12-25 | 南京年吉冷冻食品有限公司 | New chemical synthetic method for ethyl 3-hydroxybutyrate |
| CN108484441A (en) * | 2018-05-15 | 2018-09-04 | 常州兰陵制药有限公司 | Levocarnitine intermediate L-（-）The synthetic method of chlorination 3- cyano -2- hydroxypropyl trimethylammonium amine |
| CN111875520A (en) * | 2020-08-03 | 2020-11-03 | 连云港宏业化工有限公司 | Novel synthesis method of (S) -4-chloro-3-hydroxybutyronitrile |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63316758A (en) * | 1987-06-18 | 1988-12-26 | Osaka Soda Co Ltd | Production of 4-chloro-3-hydroxybutyronitrile |
| JPH01139559A (en) * | 1987-11-25 | 1989-06-01 | Earth Chem Corp Ltd | Production of 4-chloro-3-hydroxybutyronitrile |
| US5210031A (en) * | 1989-07-20 | 1993-05-11 | Nitto Chemical Industry Co., Ltd. | Process for the production of R(-)-4-halo-3-hydroxybutyronitrile |
| JPH05310671A (en) * | 1992-05-14 | 1993-11-22 | Daiso Co Ltd | Production of 4-chloro-3-hydroxybutyronitrile |
| JP2002241357A (en) * | 2001-02-19 | 2002-08-28 | Mitsubishi Rayon Co Ltd | Method for producing 4-chloro-3-hydroxybutyronitrile |
| JP2004182607A (en) * | 2002-11-29 | 2004-07-02 | Mitsubishi Rayon Co Ltd | Method for producing 4-chloro-3-hydroxybutyronitrile |
| CN1764636A (en) * | 2003-04-16 | 2006-04-26 | 株式会社Lg生命科学 | Process for preparing 4-chloro-3-hydroxybutanoic acid ester |
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2006
- 2006-09-15 CN CNB2006100218581A patent/CN100408555C/en not_active Expired - Fee Related
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63316758A (en) * | 1987-06-18 | 1988-12-26 | Osaka Soda Co Ltd | Production of 4-chloro-3-hydroxybutyronitrile |
| JPH01139559A (en) * | 1987-11-25 | 1989-06-01 | Earth Chem Corp Ltd | Production of 4-chloro-3-hydroxybutyronitrile |
| US5210031A (en) * | 1989-07-20 | 1993-05-11 | Nitto Chemical Industry Co., Ltd. | Process for the production of R(-)-4-halo-3-hydroxybutyronitrile |
| JPH05310671A (en) * | 1992-05-14 | 1993-11-22 | Daiso Co Ltd | Production of 4-chloro-3-hydroxybutyronitrile |
| JP2002241357A (en) * | 2001-02-19 | 2002-08-28 | Mitsubishi Rayon Co Ltd | Method for producing 4-chloro-3-hydroxybutyronitrile |
| JP2004182607A (en) * | 2002-11-29 | 2004-07-02 | Mitsubishi Rayon Co Ltd | Method for producing 4-chloro-3-hydroxybutyronitrile |
| CN1764636A (en) * | 2003-04-16 | 2006-04-26 | 株式会社Lg生命科学 | Process for preparing 4-chloro-3-hydroxybutanoic acid ester |
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