CN104447329A - Preparation method of 2-chloroacetoacetic acid ethyl ester - Google Patents
Preparation method of 2-chloroacetoacetic acid ethyl ester Download PDFInfo
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- CN104447329A CN104447329A CN201410593416.9A CN201410593416A CN104447329A CN 104447329 A CN104447329 A CN 104447329A CN 201410593416 A CN201410593416 A CN 201410593416A CN 104447329 A CN104447329 A CN 104447329A
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- Prior art keywords
- preparation
- chloroacetyl acetacetic
- acetacetic ester
- oxidation
- aceto acetate
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/307—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by introduction of halogen; by substitution of halogen atoms by other halogen atoms
-
- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
- C01B17/00—Sulfur; Compounds thereof
- C01B17/69—Sulfur trioxide; Sulfuric acid
- C01B17/74—Preparation
- C01B17/76—Preparation by contact processes
- C01B17/775—Liquid phase contacting processes or wet catalysis processes
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- C—CHEMISTRY; METALLURGY
- C01—INORGANIC CHEMISTRY
- C01B—NON-METALLIC ELEMENTS; COMPOUNDS THEREOF; METALLOIDS OR COMPOUNDS THEREOF NOT COVERED BY SUBCLASS C01C
- C01B7/00—Halogens; Halogen acids
- C01B7/01—Chlorine; Hydrogen chloride
- C01B7/07—Purification ; Separation
- C01B7/0706—Purification ; Separation of hydrogen chloride
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- Organic Chemistry (AREA)
- Inorganic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of 2-chloroacetoacetic acid ethyl ester. The preparation method comprises the following step: with acetoacetic acid ethyl ester as a starting raw material, performing separation on sulfur dioxide and hydrogen chloride by virtue of four steps namely chlorination, a step of producing dilute sulfuric acid by oxidizing sulfur dioxide by virtue of oxidative deacidification, hydrochloric acid distillation and rectification to obtain 2-chloroacetoacetic acid ethyl ester. Compared with the prior art, the preparation method disclosed by the invention has the advantages that 1, complete separation between hydrogen chloride and sulfur dioxide can be achieved by virtue of an oxidative deacidification technology; 2, high-quality sulfuric acid and hydrochloric acid can be produced as byproducts, and certain economic benefits can be generated; and 3, a process for removing sulfur dioxide and hydrogen chloride by virtue of water washing in a conventional 2-chloroacetoacetic acid ethyl ester synthesis process can be replaced, and energy conservation and environmental protection can be achieved.
Description
Technical field
The present invention relates to a kind of preparation method of medicine intermediate, be specifically related to a kind of preparation method of 2-chloroacetyl acetacetic ester.
Background technology
2-chloroacetyl acetacetic ester is a kind of colourless to light yellow transparent liquid, is mainly used in field of medicaments, especially synthesizes the key intermediate of cefodizime, have wide market outlook.
Through searching related data and comparative analysis, the operational path of synthesis 2-chloroacetyl acetacetic ester mainly contains two both at home and abroad at present, as follows respectively:
1, chlorine method: be that chlorizating agent carries out chlorination with chlorine, this route due to chlorine molecule too active, all chlorination can be carried out in the 2-position of methyl aceto acetate and 4-position, and transformation efficiency is impartial, therefore what obtain is the mixture of 2-chloroacetyl acetacetic ester and 4-chloroacetyl acetacetic ester, seldom (being about 2-3 DEG C at reduced pressure conditions), separation difficulty, in the industrial production without actual utility value for the boiling point difference of 2-chloroacetyl acetacetic ester and 4-chloroacetyl acetacetic ester.
2, SULPHURYL CHLORIDE method: be that chlorizating agent carries out chlorination with SULPHURYL CHLORIDE, because the activity of SULPHURYL CHLORIDE is lower, and a chlorine atom can only be utilized, therefore the program does not have the by product of 4-position to produce substantially, but it also has shortcoming inherently fairly obvious, that is exactly that the Atom economy of SULPHURYL CHLORIDE is poor, while generation product, the hydrogenchloride of meeting by-product equivalent and sulfurous gas, traditional technique is as sodium carbonate with a large amount of water or mineral alkali, the hydrogenchloride dissolved in the neutralization such as sodium bicarbonate washing 2-chloroacetyl acetacetic ester and sulfurous gas, causing a part of product is dissolved in water, yield lower (<90%), high expensive, produce the acid waste water of a large amount of high COD simultaneously, environmental pollution is larger.
Summary of the invention
Technical problem to be solved by this invention is to provide a kind of preparation method of 2-chloroacetyl acetacetic ester, more precisely the synthesis of green economy and a method for the hydrogenchloride and sulfurous gas that are separated 2-chloroacetyl acetacetic ester and by-product, overcome the problems such as prior art ubiquitous 2-chloroacetyl acetacetic ester yield is low, wastewater flow rate is large, high COD spent acid cannot process.
The technical solution adopted for the present invention to solve the technical problems is: take methyl aceto acetate as starting raw material, 2-chloroacetyl acetacetic ester is obtained through SULPHURYL CHLORIDE chlorination, hydrogen peroxide oxidation depickling, salt acid distillation, rectifying four step, by hydrogen peroxide oxidation by product sulfurous gas in oxidation depickling step, oxidizing sulfur dioxide is generated dilute sulphuric acid, by distilling out hydrochloric acid, realize being separated of sulfurous gas and hydrogenchloride, then obtain 2-chloroacetyl acetacetic ester by rectifying.Concrete steps are as follows:
1) chlorination: add methyl aceto acetate in reactor, in methyl aceto acetate, SULPHURYL CHLORIDE 2 hours are dripped under normal temperature, keep temperature in the kettle to be 80-100 DEG C, vacuum tightness-0.3-0.35MPa in dropping process, after dropwising, reactor is incubated 2 hours at 80-100 DEG C;
2) be oxidized depickling: the hydrogenchloride produced in chlorination process and sulfur dioxide gas are introduced in oxidation extracting tower by vacuum, open oxidation extracting tower spray, the sulfurous gas generated with hydrogen peroxide oxidation.
3) salt acid distillation: step 1) insulation after, distill out hydrochloric acid at 100-110 DEG C;
4) rectifying: 2-chloroacetyl acetacetic ester is obtained to thick product rectifying.
Described step 1) in the add-on of SULPHURYL CHLORIDE be the 1.03-1.45 of methyl aceto acetate quality doubly.
Described step 2) in the concentration of hydrogen peroxide be 20wt%, add-on be the 0.5-5 of methyl aceto acetate quality doubly, preferably, add-on be the 2.5-3.5 of methyl aceto acetate quality doubly.
Described step 2) oxidation depickling carry out under condition of negative pressure, temperature controls at 45-85 DEG C, pressure-controlling at-0.02--0.05MPa, preferably, oxidation depickling temperature be 65-75 DEG C.
Described step 4) in the yield of 2-chloroacetyl acetacetic ester be greater than 93%.
The present invention has following beneficial effect:
1, by hydrogen peroxide oxidation depickling and hydrochloric acid still-process, being separated completely of hydrogenchloride and sulfurous gas is achieved;
2, the yield of 2-chloroacetyl acetacetic ester reaches more than 93%, and does not have discharge of wastewater, and yield is high, energy-conserving and environment-protective;
3, the content reclaiming hydrochloric acid is greater than 10%, and sulfuric acid content is greater than 60%, and the hydrochloric acid of recovery and sulfuric acid organic content, below 0.1%, meet the demand of common product, as production marketing, can create certain economic benefit.
Embodiment
Be below specific embodiments of the invention, technical scheme of the present invention is described further, but protection scope of the present invention is not limited to these embodiments.Every do not deviate from the present invention's design change or equivalent substituting include within protection scope of the present invention.
Embodiment 1
Methyl aceto acetate 130kg is added in reactor, normal temperature drips SULPHURYL CHLORIDE 135kg (1.03 times) in lower 2 hours, dropping process keeps chlorination temperature in the kettle at 80-100 DEG C, vacuum tightness remains on-0.3-0.35MPa, the hydrogenchloride produced in reaction and sulfur dioxide gas are introduced in oxidation extracting tower by vacuum, open oxidation extracting tower spray, controlled oxidization temperature is at 55-65 DEG C, pressure-0.02--0.05MPa, use the sulfurous gas that 400kg (3.1 times, 20%) hydrogen peroxide oxidation generates.After dripping SULPHURYL CHLORIDE, by chlorination tank 80-100 DEG C of insulation 2 hours, after insulation, distill out hydrochloric acid 360kg (10.1%) at 100-110 DEG C, sulfuric acid 140kg (69.8%).Crude product obtains 2-chloroacetyl acetacetic ester 153.8kg after rectifying, yield 93.5%.
Embodiment 2
Methyl aceto acetate 130kg is added in reactor, normal temperature drips SULPHURYL CHLORIDE 149kg (1.15 times) in lower 2 hours, dropping process keeps chlorination temperature in the kettle at 80-100 DEG C, vacuum tightness remains on-0.3-0.5MPa, the hydrogenchloride produced in reaction and sulfur dioxide gas are introduced in oxidation extracting tower by vacuum, open oxidation extracting tower spray, controlled oxidization temperature is at 45-60 DEG C, pressure-0.02--0.05MPa, use the sulfurous gas that 300kg (2.3 times, 20%) hydrogen peroxide oxidation generates.After dripping SULPHURYL CHLORIDE, by chlorination tank 80-100 DEG C of insulation 1 hour, after insulation, distill out hydrochloric acid 240kg (15.2%) at 100-110 DEG C, sulfuric acid 158kg (62%).Crude product obtains 2-chloroacetyl acetacetic ester 153kg after rectifying, yield 93.1%.
Embodiment 3
Methyl aceto acetate 130kg is added in reactor, normal temperature drips SULPHURYL CHLORIDE 140kg (1.07 times) in lower 2 hours, dropping process keeps chlorination temperature in the kettle at 80-100 DEG C, vacuum tightness remains on-0.4-0.5MPa, the hydrogenchloride produced in reaction and sulfur dioxide gas are introduced in oxidation extracting tower by vacuum, open oxidation extracting tower spray, controlled oxidization temperature is at 65-75 DEG C, pressure-0.02--0.05MPa, use the sulfurous gas that 65kg (0.5 times, 20%) hydrogen peroxide oxidation generates.After dripping SULPHURYL CHLORIDE, by chlorination tank 80-100 DEG C of insulation 2 hours, after insulation, distill out hydrochloric acid 180kg (20.3%) at 100-110 DEG C, sulfuric acid 116kg (84.5%).Crude product obtains 2-chloroacetyl acetacetic ester 155.1kg after rectifying, yield 94.0%.
Embodiment 4
Methyl aceto acetate 130kg is added in reactor, normal temperature drips SULPHURYL CHLORIDE 188.5kg (1.45 times) in lower 2 hours, dropping process keeps chlorination temperature in the kettle at 80-100 DEG C, vacuum tightness remains on-0.4-0.5MPa, the hydrogenchloride produced in reaction and sulfur dioxide gas are introduced in oxidation extracting tower by vacuum, open oxidation extracting tower spray, controlled oxidization temperature is at 75-85 DEG C, pressure-0.02--0.05MPa, use the sulfurous gas that 650kg (5 times, 20%) hydrogen peroxide oxidation generates.After dripping SULPHURYL CHLORIDE, by chlorination tank 80-100 DEG C of insulation 2 hours, after insulation, distill out hydrochloric acid 310kg (21.4%) at 100-110 DEG C, sulfuric acid 163kg (73.4%).Crude product obtains 2-chloroacetyl acetacetic ester 154.1kg after rectifying, yield 93.4%.
Embodiment 3 is the embodiments under the optimum condition of this programme; below be only the part exemplary embodiments of this programme; those skilled in the art can adopt other embodiment to realize completely within the protection domain of the technical program; and all can make the appropriate adjustments parameters such as proportioning raw materials, temperature of reaction, times, just do not repeat one by one at this.
Claims (7)
1. a preparation method for 2-chloroacetyl acetacetic ester, is characterized in that, comprises the following steps:
1) chlorination: add methyl aceto acetate in reactor, in methyl aceto acetate, SULPHURYL CHLORIDE 2 hours are dripped under normal temperature, keep temperature in the kettle to be 80-100 DEG C, vacuum tightness-0.3-0.35MPa in dropping process, after dropwising, reactor is incubated 2 hours at 80-100 DEG C;
2) be oxidized depickling: the hydrogenchloride produced in chlorination process and sulfur dioxide gas are introduced in oxidation extracting tower by vacuum, open oxidation extracting tower spray, the sulfurous gas generated with hydrogen peroxide oxidation.
3) salt acid distillation: step 1) insulation after, distill out hydrochloric acid at 100-110 DEG C;
4) rectifying: 2-chloroacetyl acetacetic ester is obtained to thick product rectifying.
2. the preparation method of 2-chloroacetyl acetacetic ester according to claim 1, is characterized in that, described step 1) in the add-on of SULPHURYL CHLORIDE be the 1.03-1.45 of methyl aceto acetate quality doubly.
3. the preparation method of 2-chloroacetyl acetacetic ester according to claim 1, is characterized in that, described step 2) in the concentration of hydrogen peroxide be 20wt%, add-on be the 0.5-5 of methyl aceto acetate quality doubly.
4. the preparation method of 2-chloroacetyl acetacetic ester according to claim 3, is characterized in that, the add-on of described hydrogen peroxide is 2.5-3.5 times of methyl aceto acetate quality.
5. the preparation method of 2-chloroacetyl acetacetic ester according to claim 1, is characterized in that, described step 2) oxidation depickling carry out under condition of negative pressure, temperature controls at 45-85 DEG C, and pressure-controlling is at-0.02--0.05MPa.
6. the preparation method of 2-chloroacetyl acetacetic ester according to claim 5, is characterized in that, the temperature of described oxidation depickling is 65-75 DEG C.
7., according to the preparation method of the arbitrary described 2-chloroacetyl acetacetic ester of claim 1-6, it is characterized in that, described step 4) in the yield of 2-chloroacetyl acetacetic ester be greater than 93%.
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| CN201410593416.9A CN104447329A (en) | 2014-10-29 | 2014-10-29 | Preparation method of 2-chloroacetoacetic acid ethyl ester |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105061210A (en) * | 2015-07-22 | 2015-11-18 | 蚌埠中实化学技术有限公司 | Preparation method for ethyl 2-chloroacetoacetate |
| CN112154121A (en) * | 2018-05-23 | 2020-12-29 | 阿科玛法国公司 | Method for preparing lithium salt of bis (fluorosulfonyl) imide |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103570533A (en) * | 2013-11-14 | 2014-02-12 | 大连九信生物化工科技有限公司 | Preparation method of 2-chloro-4, 4, 4 trifluoroacetyl ethyl acetate |
| CN103833550A (en) * | 2014-03-25 | 2014-06-04 | 杜承贤 | Preparation method for organic intermediate 2-chloroacetoacetic acid ethyl ester |
-
2014
- 2014-10-29 CN CN201410593416.9A patent/CN104447329A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103570533A (en) * | 2013-11-14 | 2014-02-12 | 大连九信生物化工科技有限公司 | Preparation method of 2-chloro-4, 4, 4 trifluoroacetyl ethyl acetate |
| CN103833550A (en) * | 2014-03-25 | 2014-06-04 | 杜承贤 | Preparation method for organic intermediate 2-chloroacetoacetic acid ethyl ester |
Non-Patent Citations (1)
| Title |
|---|
| 雒丽丽等: "离子色谱法测定食品中的二氧化硫", 《食品科技》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105061210A (en) * | 2015-07-22 | 2015-11-18 | 蚌埠中实化学技术有限公司 | Preparation method for ethyl 2-chloroacetoacetate |
| CN112154121A (en) * | 2018-05-23 | 2020-12-29 | 阿科玛法国公司 | Method for preparing lithium salt of bis (fluorosulfonyl) imide |
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Application publication date: 20150325 |