CN112479853B - Preparation method of D-2-chloropropionyl chloride and D-2-chloropropionyl chloride - Google Patents
Preparation method of D-2-chloropropionyl chloride and D-2-chloropropionyl chloride Download PDFInfo
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- 238000002360 preparation method Methods 0.000 title abstract description 24
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims abstract description 146
- 238000006243 chemical reaction Methods 0.000 claims abstract description 111
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims abstract description 70
- GAWAYYRQGQZKCR-UWTATZPHSA-N (2r)-2-chloropropanoic acid Chemical compound C[C@@H](Cl)C(O)=O GAWAYYRQGQZKCR-UWTATZPHSA-N 0.000 claims abstract description 39
- LZCLXQDLBQLTDK-BYPYZUCNSA-N ethyl (2S)-lactate Chemical compound CCOC(=O)[C@H](C)O LZCLXQDLBQLTDK-BYPYZUCNSA-N 0.000 claims abstract description 36
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims abstract description 35
- 235000019253 formic acid Nutrition 0.000 claims abstract description 35
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 32
- 238000004321 preservation Methods 0.000 claims abstract description 31
- 239000011347 resin Substances 0.000 claims abstract description 28
- 229920005989 resin Polymers 0.000 claims abstract description 28
- 239000003054 catalyst Substances 0.000 claims abstract description 20
- 238000001914 filtration Methods 0.000 claims abstract description 19
- 238000004821 distillation Methods 0.000 claims abstract description 16
- 230000006837 decompression Effects 0.000 claims abstract description 13
- 238000010438 heat treatment Methods 0.000 claims abstract description 13
- 238000001816 cooling Methods 0.000 claims abstract description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 28
- 239000000047 product Substances 0.000 claims description 28
- 238000000034 method Methods 0.000 claims description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 14
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 14
- 239000002253 acid Substances 0.000 claims description 13
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- 239000006227 byproduct Substances 0.000 claims description 8
- 238000001035 drying Methods 0.000 claims description 7
- 239000000706 filtrate Substances 0.000 claims description 7
- 238000005406 washing Methods 0.000 claims description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 4
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 claims description 2
- 239000003729 cation exchange resin Substances 0.000 claims description 2
- 125000000542 sulfonic acid group Chemical group 0.000 claims description 2
- 238000009413 insulation Methods 0.000 claims 1
- 239000000543 intermediate Substances 0.000 abstract description 14
- 238000011031 large-scale manufacturing process Methods 0.000 abstract description 5
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 230000007062 hydrolysis Effects 0.000 description 18
- 238000006460 hydrolysis reaction Methods 0.000 description 18
- 238000001228 spectrum Methods 0.000 description 15
- JVTAAEKCZFNVCJ-REOHCLBHSA-N L-lactic acid Chemical compound C[C@H](O)C(O)=O JVTAAEKCZFNVCJ-REOHCLBHSA-N 0.000 description 13
- 239000007789 gas Substances 0.000 description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
- 230000001276 controlling effect Effects 0.000 description 7
- 230000008569 process Effects 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- RSWGJHLUYNHPMX-UHFFFAOYSA-N 1,4a-dimethyl-7-propan-2-yl-2,3,4,4b,5,6,10,10a-octahydrophenanthrene-1-carboxylic acid Chemical compound C12CCC(C(C)C)=CC2=CCC2C1(C)CCCC2(C)C(O)=O RSWGJHLUYNHPMX-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
- 238000005660 chlorination reaction Methods 0.000 description 6
- 238000001514 detection method Methods 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 239000012535 impurity Substances 0.000 description 6
- 230000014759 maintenance of location Effects 0.000 description 6
- 238000005457 optimization Methods 0.000 description 6
- 239000002994 raw material Substances 0.000 description 6
- 239000008213 purified water Substances 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000003197 catalytic effect Effects 0.000 description 3
- 238000006555 catalytic reaction Methods 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 238000005086 pumping Methods 0.000 description 3
- 230000009257 reactivity Effects 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 235000016236 parenteral nutrition Nutrition 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- XVMSFILGAMDHEY-UHFFFAOYSA-N 6-(4-aminophenyl)sulfonylpyridin-3-amine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=N1 XVMSFILGAMDHEY-UHFFFAOYSA-N 0.000 description 1
- HJCMDXDYPOUFDY-WHFBIAKZSA-N Ala-Gln Chemical compound C[C@H](N)C(=O)N[C@H](C(O)=O)CCC(N)=O HJCMDXDYPOUFDY-WHFBIAKZSA-N 0.000 description 1
- 229960002648 alanylglutamine Drugs 0.000 description 1
- 108010044940 alanylglutamine Proteins 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000001925 catabolic effect Effects 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 230000003166 hypermetabolic effect Effects 0.000 description 1
- 229940101629 l- methyl lactate Drugs 0.000 description 1
- 229940116871 l-lactate Drugs 0.000 description 1
- 229960002373 loxoprofen Drugs 0.000 description 1
- YMBXTVYHTMGZDW-UHFFFAOYSA-N loxoprofen Chemical compound C1=CC(C(C(O)=O)C)=CC=C1CC1C(=O)CCC1 YMBXTVYHTMGZDW-UHFFFAOYSA-N 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- LPEKGGXMPWTOCB-VKHMYHEASA-N methyl (S)-lactate Chemical compound COC(=O)[C@H](C)O LPEKGGXMPWTOCB-VKHMYHEASA-N 0.000 description 1
- 238000012803 optimization experiment Methods 0.000 description 1
- 125000001477 organic nitrogen group Chemical group 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 239000005871 repellent Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- -1 tertiary amine organic bases Chemical class 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/09—Preparation of carboxylic acids or their salts, halides or anhydrides from carboxylic acid esters or lactones
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/06—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides containing polymers
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/58—Preparation of carboxylic acid halides
- C07C51/60—Preparation of carboxylic acid halides by conversion of carboxylic acids or their anhydrides or esters, lactones, salts into halides with the same carboxylic acid part
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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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention is applicable to the technical field of synthesis of medical intermediates, and provides a preparation method of D-2-chloropropionyl chloride and D-2-chloropropionyl chloride, which comprises the following steps: adding L-ethyl lactate and a catalyst into a reaction container, dropwise adding thionyl chloride at the temperature of-10 to 10 ℃, and heating to 65 to 70 ℃ for heat preservation reaction; after the reaction is finished, the temperature is reduced to 10 to 30 ℃, and the D-2-ethyl chloropropionate is obtained after the treatment such as decompression concentration; then adding resin, anhydrous formic acid and water, heating to 70-100 ℃, and reacting for 2-5 h; after the reaction is finished, cooling to 10-30 ℃, and filtering and distilling to obtain D-2-chloropropionic acid; then, the thionyl chloride is dripped at the temperature of 0 to 5 ℃, the temperature is raised to 45 to 65 ℃ for heat preservation reaction, and the product is obtained after decompression concentration and distillation treatment. The invention realizes the large-scale production of the D-2-chloropropionyl chloride with the level of 10 kg, has high yield and purity, can recycle the catalyst, and does not need rectification equipment.
Description
Technical Field
The invention belongs to the technical field of synthesis of medical intermediates, and particularly relates to a preparation method of D-2-chloropropionyl chloride and D-2-chloropropionyl chloride.
Background
D-2-chloropropionyl chloride is an important intermediate of the parenteral nutrition alanyl glutamine, a component of parenteral nutrition, and is suitable for patients in need of glutamine supplementation, including patients in catabolic and hypermetabolic conditions. Meanwhile, the D-2-chloropropionyl chloride is also the initial raw material of the anti-inflammatory analgesic drug loxoprofen sodium.
The existing synthetic method of D-2-chloropropionyl chloride mainly uses anhydrous L-lactic acid or L-lactate as raw materials; wherein, anhydrous L-lactic acid is used as a raw material, and the anhydrous L-lactic acid and a chlorination reagent thionyl chloride are catalyzed by organic nitrogen base such as pyridine and the like to synthesize D-2-chloropropionyl chloride in one step. Because the anhydrous L-lactic acid can be partially self-polymerized, the content of raw materials is reduced by the polylactic acid, and a large amount of L-lactic acid sold on the market is water-containing and cannot be used in a water-repellent reaction system such as thionyl chloride, the method limits the mass production. Meanwhile, the method adopts a one-step method for synthesis, the amount of byproducts is large, and the subsequent rectification separation difficulty is high.
In addition, the prior art also adopts L-methyl lactate to replace anhydrous L-lactic acid as a raw material, and D-2-chloropropionyl chloride is synthesized through three steps of chlorination, hydrolysis and chloroacylation. However, in the method, in the step of synthesizing the D-2-chloropropionic acid by hydrolyzing the ethyl D-2-chloropropionate, a sodium hydroxide aqueous solution is used as a reaction system, the hydrolysis risk exists in the chloro group of the ethyl D-2-chloropropionate, the pH value is required to be regulated by hydrochloric acid in the post-treatment, the chloroform is used for extraction for many times, the operation is complex, and the yield is lower. Meanwhile, the D-2-chloropropionyl chloride product of the method needs to be rectified and separated, so that the equipment and energy consumption cost of large-scale production are increased.
Therefore, the existing synthesis method of the D-2-chloropropionyl chloride has the problems of low yield, incapability of recycling reagents and high cost caused by the need of introducing rectification equipment.
Disclosure of Invention
The embodiment of the invention aims to provide a preparation method of D-2-chloropropionyl chloride, and aims to solve the problems that the existing synthesis method of D-2-chloropropionyl chloride is low in yield, reagents cannot be recycled, and rectification equipment is required to be introduced to cause high cost.
The embodiment of the invention is realized in such a way that the preparation method of the D-2-chloropropionyl chloride comprises the following steps:
adding L-ethyl lactate and a catalyst into a reaction container, dropwise adding thionyl chloride at the temperature of-10 ℃, and after the completion of the dropwise adding of the thionyl chloride, raising the temperature to 65-70 ℃ for carrying out heat preservation reaction, wherein the weight ratio of the L-ethyl lactate to the catalyst is 1:0.003-0.009, and the weight ratio of the L-ethyl lactate to the thionyl chloride is 1:1.0-1.3;
after the heat preservation reaction is finished, the temperature is reduced to 10-30 ℃, and the D-2-ethyl chloropropionate is obtained after the decompression concentration, the washing, the drying and the filtering treatment;
adding resin, anhydrous formic acid and water into the D-2-ethyl chloropropionate, heating to 70-100 ℃, and reacting for 2-5 hours, wherein the weight ratio of the D-2-ethyl chloropropionate to the anhydrous formic acid is 1:0.8-1.3, and the water content of the system is 7-15%;
after the reaction is finished, cooling to 10-30 ℃, and filtering and distilling to obtain D-2-chloropropionic acid;
dropwise adding thionyl chloride into the D-2-chloropropionic acid at the temperature of 0-5 ℃, and after the completion of the dropwise adding of the thionyl chloride, raising the temperature to 45-65 ℃ for carrying out heat preservation reaction, wherein the weight ratio of the D-2-chloropropionic acid to the thionyl chloride is 1:1.1-1.4;
and (3) concentrating under reduced pressure and distilling after the heat preservation reaction is finished to obtain D-2-chloropropionyl chloride.
Another object of an embodiment of the present invention is D-2-chloropropionyl chloride, which is prepared by the method for preparing D-2-chloropropionyl chloride according to any one of claims 1 to 9.
According to the preparation method of the D-2-chloropropionyl chloride, L-ethyl lactate is used as a starting material, high-purity D-2-chloropropionyl chloride is prepared through three steps of parameter optimization such as chlorination, hydrolysis and chloroacylation and introduction of catalyst resin in the hydrolysis step, the single-step average yield verified at the level of 10 kg reaches 93.4%, and the purity is 99.4%, and compared with the prior art, on one hand, the method adopts a resin/formic acid catalytic system in the hydrolysis step, the system moisture content is optimized, hydrolysis impurities of ortho-chloro groups are effectively inhibited, the high-efficiency and specific reactivity is improved, the yield and purity of an intermediate D-2-chloropropionic acid are improved, the resin/formic acid can be recycled, and the material cost is effectively reduced; on the other hand, the high-purity product D-2-chloropropionyl chloride can be separated by adopting conventional distillation through the parameter optimization of a high-efficiency catalytic reaction system and other steps in the hydrolysis step, so that the use of a rectifying tower in large-scale production is omitted, and the production cost is obviously reduced.
Drawings
FIG. 1 is a GC spectrum of the D-2-chloropropionyl chloride product provided in example 1 of the present invention;
FIG. 2 is a HNMR spectrum of the D-2-chloropropionyl chloride product provided in example 1 of the present invention;
FIG. 3 is a GC spectrum of the D-2-chloropropionyl chloride product provided in example 2 of the present invention;
FIG. 4 is a HNMR spectrum of the D-2-chloropropionyl chloride product provided in example 2 of the present invention;
FIG. 5 is a GC spectrum of the D-2-chloropropionyl chloride product provided in example 3 of the present invention;
FIG. 6 is a HNMR spectrum of the D-2-chloropropionyl chloride product provided in example 3 of the present invention.
Detailed Description
The present invention will be described in further detail with reference to the drawings and examples, in order to make the objects, technical solutions and advantages of the present invention more apparent. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention.
The embodiment of the invention provides a preparation method of D-2-chloropropionyl chloride, which adopts L-ethyl lactate as a starting material to prepare high-purity D-2-chloropropionyl chloride by three-step parameter optimization such as chlorination, hydrolysis and chloroacylation and the introduction of hydrolysis step catalyst resin, wherein the single-step average yield verified at 10 kg level is 93.4% and the purity is 99.4%, and compared with the prior art, on one hand, the invention adopts a resin/formic acid catalytic system in the hydrolysis step, the system moisture content is optimized, the hydrolysis impurity of ortho-chloro groups is effectively inhibited, the high-efficiency and specific reactivity improves the yield and purity of intermediate D-2-chloropropionic acid, and the resin/formic acid can be recycled, thereby effectively reducing the material cost; on the other hand, the high-purity product D-2-chloropropionyl chloride can be separated by adopting conventional distillation through the parameter optimization of a high-efficiency catalytic reaction system and other steps in the hydrolysis step, so that the use of a rectifying tower in large-scale production is omitted, and the production cost is obviously reduced.
In the embodiment of the invention, L-ethyl lactate is used as a starting material, and D-2-chloropropionyl chloride is prepared through three steps of chlorination, hydrolysis and chloroacyl, and the reaction formula is as follows:
in the embodiment of the invention, the preparation method of the D-2-chloropropionyl chloride comprises the following steps:
in the step S101, adding L-ethyl lactate and a catalyst into a reaction container, dropwise adding thionyl chloride at the temperature of-10 ℃, and after the completion of the dropwise adding of the thionyl chloride, raising the temperature to 65-70 ℃ for heat preservation reaction; the weight ratio of the L-ethyl lactate to the catalyst is 1:0.003-0.009, and the weight ratio of the L-ethyl lactate to the thionyl chloride is 1:1.0-1.3.
In the embodiment of the invention, the catalyst is pyridine, N-dimethylformamide or other tertiary amine organic bases, and preferably pyridine.
In a preferred embodiment of the present invention, the steps of adding L-ethyl lactate and a catalyst into a reaction vessel, dropwise adding thionyl chloride at a temperature of-10 to 10 ℃, and raising the temperature to 65 to 70 ℃ to perform a heat preservation reaction after the completion of the dropwise adding of the thionyl chloride, include:
adding L-ethyl lactate and a catalyst into a reaction container, dropwise adding thionyl chloride at the temperature of-5 ℃, and after the completion of the dropwise adding of the thionyl chloride, heating to 65-70 ℃ for heat preservation reaction, wherein the heat preservation reaction is carried out for 3 hours.
In a preferred embodiment of the invention, the weight ratio of the L-ethyl lactate to the catalyst is preferably 1:0.006; the weight ratio of the L-ethyl lactate to the thionyl chloride is preferably 1:1.1.
In the step S102, after the heat preservation reaction is finished, the temperature is reduced to 10-30 ℃, and the D-2-ethyl chloropropionate is obtained after the decompression concentration, the washing, the drying and the filtering treatment.
In the embodiment of the invention, the temperature in the reaction bottle is reduced to 10-30 ℃, the thionyl chloride and the acid gas are removed by decompression concentration, the reaction bottle is washed by water, dried by anhydrous sodium sulfate and filtered to obtain the D-2-ethyl chloropropionate.
In the step S103, resin, anhydrous formic acid and water are added into the D-2-ethyl chloropropionate, the temperature is raised to 70-100 ℃, the reaction is carried out for 2-5 hours, the weight ratio of the D-2-ethyl chloropropionate to the anhydrous formic acid is 1:0.8-1.3, and the water content of the system is 7.9-10.2%.
In the embodiment of the invention, the resin is 732 type cation exchange resin with sulfonic acid groups, and the resin can be recycled after being activated.
In a preferred embodiment of the invention, the weight ratio of the ethyl D-2-chloropropionate to the anhydrous formic acid is preferably 1:1.
In a preferred embodiment of the invention, the water content of the system is preferably 8% to 10%.
In the step S104, after the reaction is finished, the temperature is reduced to 10-30 ℃, and the D-2-chloropropionic acid is obtained through filtration and distillation treatment.
In a preferred embodiment of the present invention, after the reaction is completed, the temperature is reduced to 10-30 ℃, and the step of filtering and distilling to obtain D-2-chloropropionic acid comprises:
after the reaction is finished, cooling to 10-30 ℃, filtering the reaction solution, distilling the filtrate at normal pressure to remove formic acid and byproduct ethanol, and performing reduced pressure distillation, wherein the internal temperature is controlled to be less than or equal to 90 ℃, and the vacuum degree is controlled to be more than or equal to 0.095Mpa, so as to obtain the D-2-chloropropionic acid.
In the step S105, thionyl chloride is dropwise added into the D-2-chloropropionic acid at the temperature of 0-5 ℃, after the completion of the dropwise addition of the thionyl chloride, the temperature is raised to 45-65 ℃ for heat preservation reaction, and the weight ratio of the D-2-chloropropionic acid to the thionyl chloride is 1:1.1-1.4.
In a preferred embodiment of the invention, the weight ratio of D-2-chloropropionic acid to thionyl chloride is 1:1.3.
In a preferred embodiment of the present invention, the step of dropping thionyl chloride into the D-2-chloropropionic acid at a temperature of 0 to 5 ℃ and raising the temperature to 45 to 65 ℃ for heat preservation reaction after the completion of the dropping of the thionyl chloride comprises:
and dropwise adding thionyl chloride into the D-2-chloropropionic acid at the temperature of 0-5 ℃, and after the completion of the dropwise adding of the thionyl chloride, raising the temperature to 50-55 ℃ for heat preservation reaction.
In the step S106, after the heat preservation reaction is finished, the reduced pressure concentration and distillation treatment are carried out to obtain the D-2-chloropropionyl chloride.
In a preferred embodiment of the present invention, the step of concentrating under reduced pressure and distilling to obtain D-2-chloropropionyl chloride after the heat preservation reaction is completed comprises:
after the heat preservation reaction is finished, concentrating under reduced pressure to remove thionyl chloride and acid gas, carrying out normal pressure distillation to obtain a product, controlling the temperature to be less than or equal to 115 ℃, and collecting fractions at 102-113 ℃ to obtain D-2-chloropropionyl chloride.
In a preferred embodiment of the present invention, the step of adding resin, anhydrous formic acid and water into the ethyl D-2-chloropropionate, heating to 70-100 ℃ and reacting for 2-5 hours comprises the following steps:
resin, anhydrous formic acid and water are added into the ethyl D-2-chloropropionate, the temperature is raised to 85 to 90 ℃, and the reaction is carried out for 3 hours.
The embodiment of the invention also provides the D-2-chloropropionyl chloride, which is prepared by the preparation method of the D-2-chloropropionyl chloride.
Examples of certain embodiments of the invention are given below and are not intended to limit the scope of the invention.
In addition, it should be noted that the numerical values set forth in the following examples are as precise as possible, but those skilled in the art will understand that each numerical value should be construed as a divisor rather than an absolute precise numerical value due to measurement errors and experimental operation problems that cannot be avoided. For example, it should be understood that the weight values of the respective raw materials for preparing D-2-chloropropionyl chloride with respect to the respective examples may have an error of ±2 or ±1 due to an error of a weighing instrument.
Example 1
Step a, preparation of ethyl D-2-chloropropionate
To the reaction flask was added 110. 110g L-ethyl lactate, 0.66g pyridine. The temperature was lowered to-5℃and the addition of 132g of thionyl chloride was started. Controlling the reaction temperature below 0 ℃ for 1.5h, after the dropwise addition, raising the temperature in a reaction bottle to 69 ℃, preserving heat for 3h, after the heat preservation is finished, lowering the temperature in the reaction bottle to 25 ℃, depressurizing, pumping out thionyl chloride and acid gas, washing 20g with water, drying with anhydrous sodium sulfate, and filtering to obtain 126g D-2-ethyl chloropropionate, wherein the yield is 98.9%, and the purity is 99.5%.
Step b, preparation of D-2-chloropropionic acid
50g of resin, 151g of anhydrous formic acid and 126g D-2-ethyl chloropropionate are sequentially added into a reaction bottle, a proper amount of purified water is added, and the water content of a detection system is 7.6%. The temperature was raised to 84℃and the reaction was carried out for 3.5h. After the reaction is finished, the temperature is reduced to 21 ℃, the reaction solution is filtered, the filtrate is distilled under normal pressure to remove formic acid and byproduct ethanol, then the distillation is performed under reduced pressure, the internal temperature is controlled to be less than or equal to 90 ℃, the vacuum degree is controlled to be more than or equal to 0.095Mpa, and the fraction at 80-90 ℃ is collected to obtain 88g D-2-chloropropionic acid, the yield is 87.6%, and the purity is 99.4%.
Step c, preparation of D-2-chloropropionyl chloride
88g D-2-chloropropionic acid is added into a reaction bottle, the temperature is reduced to 3 ℃, 123g of thionyl chloride is slowly added dropwise, the reaction temperature is controlled below 5 ℃ for 1.5 hours, the temperature is increased to 60 ℃, and the reaction is carried out for 3 hours under heat preservation. After the reaction is finished, the thionyl chloride and the acid gas are removed by decompression concentration, normal pressure distillation is carried out on the product, the temperature is controlled to be less than or equal to 115 ℃, and the fraction at 102-113 ℃ is collected to obtain 94g D-2-chloropropionyl chloride, the yield is 91.3%, and the purity is 98.8%.
FIG. 1 is a GC spectrum of the D-2-chloropropionyl chloride product prepared in example 1 of the present invention: the retention time of the D-2-chloropropionyl chloride product was 8.69min and the peak area content was 98.8%. The retention time of the largest single impurity was 9.43min and the peak area content was 0.46%.
FIG. 2 is a HNMR spectrum of the D-2-chloropropionyl chloride product prepared in example 1 of the present invention: the D-2-chloropropionyl chloride product has 4 hydrogen atoms in total, and is detected in nuclear magnetic hydrogen spectrum detection. Wherein, 1 hydrogen atom of the methine shows a peak at chemical shift delta=4.63-4.68, and is influenced by ortho-methyl to show a quadruple peak. The 3 hydrogen atoms of the methyl group show peaks at chemical shifts delta=1.81 to 1.82, and are influenced by the ortho-methine group to show double peaks. At chemical shift δ=7.26 is the deuterated chloroform solvent peak.
Example 2
Step a, preparation of ethyl D-2-chloropropionate
To the reaction flask was added 125. 125g L-ethyl lactate, 0.75g pyridine. The temperature was lowered to 0℃and the addition of 138g of thionyl chloride was started. Controlling the reaction temperature below 5 ℃ for 2 hours, raising the temperature in a reaction bottle to 66 ℃, preserving heat for 3 hours, reducing the temperature in the reaction bottle to 27 ℃, pumping out thionyl chloride and acid gas under reduced pressure, washing with 25g of water, drying with anhydrous sodium sulfate, and filtering to obtain 143g D-2-ethyl chloropropionate, wherein the yield is 99.1%, and the purity is 99.4%.
Step b, preparation of D-2-chloropropionic acid
57g of resin, 145g of anhydrous formic acid and 143g D-2-ethyl chloropropionate are sequentially added into a reaction bottle, a proper amount of purified water is added, and the water content of a detection system is 9.1%. Heating to 88 ℃, and reacting for 3 hours. After the reaction is finished, the temperature is reduced to 24 ℃, the reaction solution is filtered, the filtrate is distilled under normal pressure to remove formic acid and byproduct ethanol, then the distillation is performed under reduced pressure, the internal temperature is controlled to be less than or equal to 90 ℃, the vacuum degree is controlled to be more than or equal to 0.095Mpa, and the fraction at 80-90 ℃ is collected to obtain 100g D-2-chloropropionic acid, the yield is 88.3%, and the purity is 99.5%.
Step c, preparation of D-2-chloropropionyl chloride
Adding 100g D-2-chloropropionic acid into a reaction bottle, reducing the temperature to 0 ℃, starting to slowly dropwise add 130g of thionyl chloride, controlling the reaction temperature below 5 ℃, after 2h dropwise adding, raising the temperature to 54 ℃, and preserving the heat for 3h. After the reaction is finished, the thionyl chloride and the acid gas are removed by decompression concentration, normal pressure distillation is carried out on the product, the temperature is controlled to be less than or equal to 115 ℃, and the fraction at 102-113 ℃ is collected to obtain 106g D-2-chloropropionyl chloride, the yield is 90.4%, and the purity is 99.2%.
FIG. 3 is a GC spectrum of the D-2-chloropropionyl chloride product prepared in example 2 of the present invention: the retention time of the D-2-chloropropionyl chloride product was 8.69min and the peak area content was 99.2%. The retention time of the largest single impurity was 9.77min and the peak area content was 0.28%.
FIG. 4 is a HNMR spectrum of the D-2-chloropropionyl chloride product prepared in example 2 of the present invention: the D-2-chloropropionyl chloride product has 4 hydrogen atoms in total, and is detected in nuclear magnetic hydrogen spectrum detection. Wherein, 1 hydrogen atom of the methine shows a peak at chemical shift delta=4.63-4.68, and is influenced by ortho-methyl to show a quadruple peak. The 3 hydrogen atoms of the methyl group show peaks at chemical shifts delta=1.81 to 1.82, and are influenced by the ortho-methine group to show double peaks. At chemical shift δ=7.26 is the deuterated chloroform solvent peak.
Example 3
Step a, preparation of ethyl D-2-chloropropionate
To the reaction flask was added 18.5Kg of L-ethyl lactate and 0.11Kg of pyridine. The temperature was lowered to 0℃and 20.4Kg of thionyl chloride was started to be added dropwise. Controlling the reaction temperature below 5 ℃ for 3.5 hours, after the dropwise addition, raising the temperature in a reaction bottle to 65 ℃, preserving heat for 3 hours, after the heat preservation is finished, reducing the temperature in the reaction bottle to 28 ℃, decompressing, pumping out thionyl chloride and acid gas, washing with 3.8Kg of water, drying with anhydrous sodium sulfate, and filtering to obtain 21.2Kg of D-2-ethyl chloropropionate, wherein the yield is 99.2 percent and the purity is 99.6 percent.
Step b, preparation of D-2-chloropropionic acid
8.5Kg of resin, 21.3Kg of anhydrous formic acid and 21.2Kg of D-2-ethyl chloropropionate are sequentially added into a reaction bottle, a proper amount of purified water is added, and the water content of a detection system is 8.8%. Heating to 87 ℃ and reacting for 3 hours. After the reaction is finished, the temperature is reduced to 26 ℃, the reaction solution is filtered, the filtrate is distilled under normal pressure to remove formic acid and byproduct ethanol, then the distillation is performed under reduced pressure, the internal temperature is controlled to be less than or equal to 90 ℃, the vacuum degree is controlled to be more than or equal to 0.095Mpa, and the fraction at 80-90 ℃ is collected to obtain 15.1Kg of D-2-chloropropionic acid, the yield is 89.5%, and the purity is 99.5%.
Step c, preparation of D-2-chloropropionyl chloride
15.1Kg of D-2-chloropropionic acid is added into a reaction bottle, the temperature is reduced to 2 ℃, 19.6Kg of thionyl chloride is slowly added dropwise, the reaction temperature is controlled to be lower than 5 ℃, the dropwise addition is completed for 4 hours, the temperature is increased to 52 ℃, and the reaction is carried out for 3 hours under the condition of heat preservation. After the reaction is finished, the sulfoxide chloride and the acid gas are removed by decompression concentration, the product is distilled under normal pressure, the temperature is controlled to be less than or equal to 115 ℃, and the fraction at 102-113 ℃ is collected to obtain 16.2Kg of D-2-chloropropionyl chloride, the yield is 91.9 percent, and the purity is 99.4 percent.
FIG. 5 is a GC spectrum of the D-2-chloropropionyl chloride product prepared in example 3 of the present invention: the retention time of the D-2-chloropropionyl chloride product was 8.79min and the peak area content was 99.4%. The retention time of the largest single impurity was 11.14min and the peak area content was 0.17%.
FIG. 6 is a HNMR spectrum of the D-2-chloropropionyl chloride product prepared in example 3 of the present invention: the D-2-chloropropionyl chloride product has 4 hydrogen atoms in total, and is detected in nuclear magnetic hydrogen spectrum detection. Wherein, 1 hydrogen atom of the methine shows a peak at chemical shift delta=4.63-4.68, and is influenced by ortho-methyl to show a quadruple peak. The 3 hydrogen atoms of the methyl group show peaks at chemical shifts delta=1.81 to 1.83, and the peaks are influenced by the ortho-methine group and show double peaks. At chemical shift δ=7.26 is the deuterated chloroform solvent peak.
In the embodiment of the invention, relevant optimization experiment design is carried out on each technological parameter of the preparation method of the D-2-chloropropionyl chloride in the early development process, wherein the use amount of a catalyst, the use amount of thionyl chloride and the dripping temperature of the thionyl chloride in the preparation process of the ethyl D-2-chloropropionate are optimized, and the specific experiment groups 1-14 are shown below.
Experimental groups 1-5: the usage amount of pyridine is as follows: the purity and yield of the corresponding intermediate D-2-ethyl chloropropionate when the weight ratio of the L-ethyl lactate to the pyridine is 1:0.001, 1:0.003, 1:0.006, 1:0.009 and 1:0.012 are shown in Table 1.
The specific experimental process is as follows: l-ethyl lactate and pyridine are added into a reaction bottle, and the weight ratio of the L-ethyl lactate to the pyridine in five groups of experiments is 1:0.001, 1:0.003, 1:0.006, 1:0.009 and 1:0.012 respectively. The temperature is reduced to 5 ℃, the thionyl chloride is added dropwise, the temperature is controlled to be 5-10 ℃, and the weight ratio of the L-ethyl lactate to the thionyl chloride is 1:1.3. And after the dripping is finished, the temperature in the reaction bottle is increased to 65 ℃, the reaction is carried out for 3 hours under the condition of heat preservation, the temperature in the reaction bottle is reduced to 23 ℃, the thionyl chloride and the acid gas are removed through decompression concentration, the reaction bottle is washed with water, dried over anhydrous sodium sulfate, and the D-2-ethyl chloropropionate is obtained through filtration.
TABLE 1
Experimental groups 6-11: the usage amount of thionyl chloride is as follows: the weight ratio of L-ethyl lactate to thionyl chloride is 1:0.9, 1:1.0, 1:1.1, 1:1.2, 1:1.3, 1:1.4, and the purity and yield of the intermediate D-2-ethyl chloropropionate are shown in Table 2.
The specific experimental process is as follows: l-ethyl lactate and pyridine are added into a reaction bottle, and the weight ratio of the L-ethyl lactate to the pyridine is 1:0.006. The temperature is reduced to 7 ℃, the thionyl chloride is added dropwise, the temperature is controlled to be 5-10 ℃, and the weight ratio of the L-ethyl lactate to the thionyl chloride in the six groups of experiments is 1:0.9, 1:1.0, 1:1.1, 1:1.2, 1:1.3 and 1:1.4 respectively. And after the dripping is finished, the temperature in the reaction bottle is increased to 70 ℃, the reaction is carried out for 3.5 hours under the condition of heat preservation, the temperature in the reaction bottle is reduced to 21 ℃, the thionyl chloride and the acid gas are removed through decompression concentration, the water washing, the drying with anhydrous sodium sulfate and the filtration are carried out, and the D-2-ethyl chloropropionate is obtained.
TABLE 2
Experimental groups 12-14: thionyl chloride dropwise addition temperature: the purity and yield of the intermediate D-2-chloropropionic acid ethyl ester corresponding to-10 to-5 ℃ and-5 to 5 ℃ and 5 to 10 ℃ are shown in Table 3.
The specific experimental process is as follows: l-ethyl lactate and pyridine are added into a reaction bottle, and the weight ratio of the L-ethyl lactate to the pyridine is 1:0.006. The temperature is reduced to-10 ℃, the thionyl chloride is added dropwise, the dripping temperatures of three groups of experiments are respectively controlled at-10 to-5 ℃, 5 to 5 ℃ and 5 to 10 ℃, and the weight ratio of the L-ethyl lactate to the thionyl chloride is 1:1.3. And after the dripping is finished, the temperature in the reaction bottle is increased to 70 ℃, the reaction is carried out for 3 hours under the condition of heat preservation, the temperature in the reaction bottle is reduced to 25 ℃, the thionyl chloride and the acid gas are removed through decompression concentration, the reaction bottle is washed with water, dried over anhydrous sodium sulfate, and the D-2-ethyl chloropropionate is obtained through filtration.
TABLE 3 Table 3
| Experimental group | Sulfoxide chloride drop temperature | Intermediate D-2-ethyl chloropropionate purity | Yield is good |
| 12 | -10～-5℃ | 98.96％ | 97.9％ |
| 13 | -5～5℃ | 99.04％ | 98.2％ |
| 14 | 5～10℃ | 98.83％ | 97.4％ |
Wherein, the use amount of anhydrous formic acid in the preparation process of D-2-chloropropionic acid and the water content of a reaction system are optimized, and the specific examples are shown in the following experimental groups 15-25.
Experimental groups 15-19: the consumption of anhydrous formic acid is as follows: the purity and yield of the intermediate D-2-ethyl chloropropionate corresponding to the weight ratio of the D-2-ethyl chloropropionate to the anhydrous formic acid are respectively 1:0.6, 1:0.8, 1:1, 1:1.3 and 1:1.5 as shown in table 4.
The specific experimental process is as follows: resin, anhydrous formic acid, a proper amount of purified water and D-2-ethyl chloropropionate are sequentially added into a reaction bottle, the weight ratio of the D-2-ethyl chloropropionate to the resin is 1:0.4, the weight ratio of the D-2-ethyl chloropropionate to the anhydrous formic acid in five groups of experiments is 1:0.6, 1:0.8, 1:1, 1:1.3 and 1:1.5, and the water content of the system is 7.1%. Heating to 83 ℃ and reacting for 4.5h. After the reaction is finished, cooling to 24 ℃, filtering the reaction solution, distilling the filtrate at normal pressure to remove formic acid and byproduct ethanol, then distilling under reduced pressure, controlling the internal temperature to be less than or equal to 90 ℃ and the vacuum degree to be more than or equal to 0.095Mpa, thus obtaining the D-2-chloropropionic acid.
TABLE 4 Table 4
Experimental groups 20-25: the purity and yield of the intermediate D-2-ethyl chloropropionate corresponding to the water content of the reaction system of 6.1%, 6.8%, 7.9%, 10.2%, 15.1% and 15.9% are shown in Table 5.
The specific experimental process is as follows: resin, anhydrous formic acid, a proper amount of purified water and D-2-ethyl chloropropionate are sequentially added into a reaction bottle, the weight ratio of the D-2-ethyl chloropropionate to the resin is 1:0.4, the weight ratio of the D-2-ethyl chloropropionate to the anhydrous formic acid is 1:1, and the water content of six groups of experimental systems is 6.7%, 6.8%, 7.9%, 10.2%, 15.1% and 15.2% respectively. Heating to 90 ℃, and reacting for 5 hours. After the reaction is finished, cooling to 25 ℃, filtering the reaction solution, distilling the filtrate at normal pressure to remove formic acid and byproduct ethanol, then distilling under reduced pressure, controlling the internal temperature to be less than or equal to 90 ℃ and the vacuum degree to be more than or equal to 0.095Mpa, thus obtaining the D-2-chloropropionic acid.
TABLE 5
| Experimental group | Moisture content of the System | Purity of intermediate D-2-chloropropionic acid | Yield is good |
| 20 | 6.7％ | 96.99％ | 83.9％ |
| 21 | 6.8％ | 97.79％ | 87.8％ |
| 22 | 7.9％ | 99.30％ | 89.6％ |
| 23 | 10.2％ | 99.35％ | 90.2％ |
| 24 | 15.1％ | 98.33％ | 87.5％ |
| 25 | 15.2％ | 95.02％ | 82.6％ |
Wherein, the dosage of thionyl chloride in the preparation process of D-2-chloropropionyl chloride is optimized, and the specific reference is shown in the following experimental groups 26-31.
Experimental groups 26-31: the usage amount of thionyl chloride is as follows: the purity and yield of the intermediate D-2-ethyl chloropropionate corresponding to 1:1.0, 1:1.1, 1:1.2, 1:1.3, 1:1.4 and 1:1.5 are shown in Table 6.
The specific experimental process is as follows: d-2-chloropropionic acid is added into a reaction bottle, the temperature is reduced to 2 ℃, thionyl chloride is slowly added dropwise, and the weight ratio of the D-2-chloropropionic acid to the thionyl chloride in six groups of experiments is 1:1.0, 1:1.1, 1:1.2, 1:1.3, 1:1.4 and 1:1.5 respectively. After the completion of the dropwise addition, the temperature was raised to 59℃and the reaction was continued for 3 hours at a constant temperature. After the reaction is finished, the thionyl chloride and the acid gas are removed by decompression concentration, normal pressure distillation is carried out on the product, the temperature is controlled to be less than or equal to 115 ℃, and the fraction at 102-113 ℃ is collected to obtain the D-2-chloropropionyl chloride.
TABLE 6
| Experimental group | Weight ratio of D-2-chloropropionic acid to thionyl chloride | Purity of D-2-chloropropionyl chloride | Yield is good |
| 26 | 1:1.0 | 92.16％ | 80.3％ |
| 27 | 1:1.1 | 98.57％ | 87.2％ |
| 28 | 1:1.2 | 99.02％ | 90.5％ |
| 29 | 1:1.3 | 99.11％ | 90.7％ |
| 30 | 1:1.4 | 98.81％ | 89.6％ |
| 31 | 1:1.5 | 93.88％ | 81.9％ |
In summary, the preparation method of D-2-chloropropionyl chloride provided by the embodiment of the invention adopts L-ethyl lactate as a starting material, prepares high-purity D-2-chloropropionyl chloride through three-step parameter optimization such as chlorination, hydrolysis, chloroacylation and the like and the introduction of catalyst resin in the hydrolysis step, and has the single-step average yield of 93.4 percent and the purity of 99.4 percent verified at the level of 10 kg, and compared with the prior art, on one hand, the invention adopts a resin/formic acid catalytic system in the hydrolysis step, optimizes the system moisture content, effectively inhibits hydrolysis impurities of ortho-chloro groups, improves the yield and purity of intermediate D-2-chloropropionic acid with high-efficiency and specific reactivity, and can be recycled and used for resin/formic acid, thereby effectively reducing the material cost; on the other hand, the high-purity product D-2-chloropropionyl chloride can be separated by adopting conventional distillation through the parameter optimization of a high-efficiency catalytic reaction system and other steps in the hydrolysis step, so that the use of a rectifying tower in large-scale production is omitted, and the production cost is obviously reduced.
The foregoing examples illustrate only a few embodiments of the invention and are described in detail herein without thereby limiting the scope of the invention. It should be noted that it will be apparent to those skilled in the art that several variations and modifications can be made without departing from the spirit of the invention, which are all within the scope of the invention. Accordingly, the scope of protection of the present invention is to be determined by the appended claims.
The foregoing description of the preferred embodiments of the invention is not intended to be limiting, but rather is intended to cover all modifications, equivalents, and alternatives falling within the spirit and principles of the invention.
Claims (8)
1. A method for preparing D-2-chloropropionyl chloride, which is characterized by comprising the following steps:
adding L-ethyl lactate and a catalyst into a reaction container, dropwise adding thionyl chloride at the temperature of-5 ℃, and after the completion of the dropwise adding of the thionyl chloride, raising the temperature to 65-70 ℃ for carrying out heat preservation reaction, wherein the weight ratio of the L-ethyl lactate to the catalyst is 1:0.003-0.009, and the weight ratio of the L-ethyl lactate to the thionyl chloride is 1:1.0-1.3;
after the heat preservation reaction is finished, the temperature is reduced to 10-30 ℃, and the D-2-ethyl chloropropionate is obtained after the decompression concentration, the washing, the drying and the filtering treatment;
adding resin, anhydrous formic acid and water into the D-2-ethyl chloropropionate, heating to 70-100 ℃, and reacting for 2-5 hours, wherein the weight ratio of the D-2-ethyl chloropropionate to the anhydrous formic acid is 1:0.8-1.3, and the water content of the system is 7.9-10.2%;
after the reaction is finished, cooling to 10-30 ℃, and filtering and distilling to obtain D-2-chloropropionic acid;
dropwise adding thionyl chloride into the D-2-chloropropionic acid at the temperature of 0-5 ℃, and after the completion of the dropwise adding of the thionyl chloride, raising the temperature to 45-65 ℃ for carrying out heat preservation reaction, wherein the weight ratio of the D-2-chloropropionic acid to the thionyl chloride is 1:1.1-1.4;
and (3) concentrating under reduced pressure and distilling after the heat preservation reaction is finished to obtain D-2-chloropropionyl chloride.
2. The method for preparing D-2-chloropropionyl chloride according to claim 1, wherein the catalyst is pyridine or N, N-dimethylformamide.
3. The method for preparing D-2-chloropropionyl chloride according to claim 1, wherein the step of adding L-ethyl lactate and a catalyst into a reaction vessel, dropwise adding thionyl chloride at a temperature of-5 to 5 ℃, and heating to 65 to 70 ℃ to perform a thermal insulation reaction after the completion of the dropwise addition of the thionyl chloride comprises the steps of:
adding L-ethyl lactate and a catalyst into a reaction container, dropwise adding thionyl chloride at the temperature of-5 ℃, and after the completion of the dropwise adding of the thionyl chloride, heating to 65-70 ℃ for heat preservation reaction, wherein the heat preservation reaction is carried out for 3 hours.
4. The method for preparing D-2-chloropropionyl chloride according to claim 1, wherein the weight ratio of the L-ethyl lactate to the catalyst is 1:0.006; the weight ratio of the L-ethyl lactate to the thionyl chloride is 1:1.1; the weight ratio of the D-2-chloropropionic acid to the thionyl chloride is 1:1.3.
5. The method for preparing D-2-chloropropionyl chloride according to claim 1, wherein the weight ratio of the D-2-chloropropionate to the resin is 1:0.4; the resin is 732 type cation exchange resin with sulfonic acid groups.
6. The method for preparing D-2-chloropropionyl chloride according to claim 1, wherein the step of cooling to 10-30 ℃ after the reaction is finished, filtering and distilling to obtain D-2-chloropropionic acid comprises the following steps:
after the reaction is finished, cooling to 10-30 ℃, filtering the reaction solution, distilling the filtrate at normal pressure to remove formic acid and byproduct ethanol, and performing reduced pressure distillation, wherein the internal temperature is controlled to be less than or equal to 90 ℃, and the vacuum degree is controlled to be more than or equal to 0.095Mpa, so as to obtain the D-2-chloropropionic acid.
7. The method for preparing D-2-chloropropionyl chloride according to claim 1, wherein the step of concentrating under reduced pressure and distilling after the end of the heat-preserving reaction to obtain D-2-chloropropionyl chloride comprises the following steps:
after the heat preservation reaction is finished, concentrating under reduced pressure to remove thionyl chloride and acid gas, carrying out normal pressure distillation to obtain a product, controlling the temperature to be less than or equal to 115 ℃, and collecting fractions at 102-113 ℃ to obtain D-2-chloropropionyl chloride.
8. The method for preparing D-2-chloropropionyl chloride according to claim 1, wherein the step of adding resin, anhydrous formic acid and water into the ethyl D-2-chloropropionate, heating to 70-100 ℃ and reacting for 2-5 hours comprises the steps of:
resin, anhydrous formic acid and water are added into the ethyl D-2-chloropropionate, the temperature is raised to 85 to 90 ℃, and the reaction is carried out for 3 hours.
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