CN114907198B - Preparation method of 1-chloro-1-chloroacetyl propane - Google Patents
Preparation method of 1-chloro-1-chloroacetyl propane Download PDFInfo
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- CN114907198B CN114907198B CN202210769920.4A CN202210769920A CN114907198B CN 114907198 B CN114907198 B CN 114907198B CN 202210769920 A CN202210769920 A CN 202210769920A CN 114907198 B CN114907198 B CN 114907198B
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- ATUOYWHBWRKTHZ-UHFFFAOYSA-N dimethylmethane Natural products CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 title claims abstract description 51
- 239000001294 propane Substances 0.000 title claims abstract description 51
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 99
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 60
- 239000000243 solution Substances 0.000 claims abstract description 56
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims abstract description 49
- 238000000034 method Methods 0.000 claims abstract description 40
- 238000005660 chlorination reaction Methods 0.000 claims abstract description 36
- OMQHDIHZSDEIFH-UHFFFAOYSA-N 3-Acetyldihydro-2(3H)-furanone Chemical compound CC(=O)C1CCOC1=O OMQHDIHZSDEIFH-UHFFFAOYSA-N 0.000 claims abstract description 32
- 239000012074 organic phase Substances 0.000 claims abstract description 27
- 239000003999 initiator Substances 0.000 claims abstract description 26
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 20
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 20
- 239000007864 aqueous solution Substances 0.000 claims abstract description 20
- 239000000460 chlorine Substances 0.000 claims abstract description 20
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 20
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims abstract description 17
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims abstract description 17
- 238000002156 mixing Methods 0.000 claims abstract description 13
- 238000007363 ring formation reaction Methods 0.000 claims abstract description 13
- 238000006243 chemical reaction Methods 0.000 claims description 36
- 238000010438 heat treatment Methods 0.000 claims description 24
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 claims description 14
- 238000010992 reflux Methods 0.000 claims description 14
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- UICXTANXZJJIBC-UHFFFAOYSA-N 1-(1-hydroperoxycyclohexyl)peroxycyclohexan-1-ol Chemical group C1CCCCC1(O)OOC1(OO)CCCCC1 UICXTANXZJJIBC-UHFFFAOYSA-N 0.000 claims description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 8
- 230000018044 dehydration Effects 0.000 claims description 8
- 238000006297 dehydration reaction Methods 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 8
- 238000001035 drying Methods 0.000 claims description 6
- 239000004342 Benzoyl peroxide Substances 0.000 claims description 5
- 235000019400 benzoyl peroxide Nutrition 0.000 claims description 5
- 238000004821 distillation Methods 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 11
- 230000015572 biosynthetic process Effects 0.000 abstract description 9
- 230000000977 initiatory effect Effects 0.000 abstract description 9
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 abstract description 6
- 239000012320 chlorinating reagent Substances 0.000 abstract description 6
- 230000003213 activating effect Effects 0.000 abstract 1
- 239000000543 intermediate Substances 0.000 description 39
- 239000000047 product Substances 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000005406 washing Methods 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 3
- 239000002699 waste material Substances 0.000 description 3
- 239000006227 byproduct Substances 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- YEJRWHAVMIAJKC-UHFFFAOYSA-N gamma-butyrolactone Natural products O=C1CCCO1 YEJRWHAVMIAJKC-UHFFFAOYSA-N 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000007142 ring opening reaction Methods 0.000 description 2
- 230000000630 rising effect Effects 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- KADOHHPNWMXGNG-UHFFFAOYSA-N 1-(1-chlorocyclopropyl)ethanone Chemical compound CC(=O)C1(Cl)CC1 KADOHHPNWMXGNG-UHFFFAOYSA-N 0.000 description 1
- MNHVNIJQQRJYDH-UHFFFAOYSA-N 2-[2-(1-chlorocyclopropyl)-3-(2-chlorophenyl)-2-hydroxypropyl]-1,2-dihydro-1,2,4-triazole-3-thione Chemical compound N1=CNC(=S)N1CC(C1(Cl)CC1)(O)CC1=CC=CC=C1Cl MNHVNIJQQRJYDH-UHFFFAOYSA-N 0.000 description 1
- NOSBOKVYSXXKFL-UHFFFAOYSA-N 3,5-dichloropentan-2-one Chemical compound CC(=O)C(Cl)CCCl NOSBOKVYSXXKFL-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 239000005825 Prothioconazole Substances 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 238000007664 blowing Methods 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000010812 external standard method Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- 238000011020 pilot scale process Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 238000004904 shortening Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/63—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by introduction of halogen; by substitution of halogen atoms by other halogen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/56—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds
- C07C45/57—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds with oxygen as the only heteroatom
- C07C45/59—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds with oxygen as the only heteroatom in five-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/67—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by isomerisation; by change of size of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
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- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to the technical field of chemical synthesis, and particularly discloses a preparation method of 1-chloro-1-chloroacetyl propane. The preparation method of the 1-chloro-1-chloroacetyl propane comprises the following steps: a. activating an initiator; b. adding an activated initiator and methanol into the alpha-acetyl-gamma-butyrolactone, and introducing chlorine to carry out chlorination reaction; then adding hydrogen chloride to obtain an intermediate M1 solution; c. mixing sodium hydroxide aqueous solution and dichloromethane, dropwise adding an intermediate M1 solution for cyclization reaction, and collecting an organic phase; d. adding the activated initiator and methanol into the organic phase, introducing chlorine gas, and performing chlorination reaction to obtain 1-chloro-1-chloroacetyl propane. The preparation method provided by the invention realizes that chlorine is used as a chlorinating reagent for two times in the synthesis process of 1-chloro-1-chloroacetyl propane, reduces the initiation time of the chlorination reaction, and obviously improves the yield and purity of 1-chloro-1-chloroacetyl propane.
Description
Technical Field
The invention relates to the technical field of chemical synthesis, in particular to a preparation method of 1-chloro-1-chloroacetyl propane.
Background
1-Chloro-1-chloroacetyl propane is a key intermediate for the synthesis of prothioconazole. The existing synthesis process of 1-chloro-1-chloroacetyl propane mainly uses alpha-acetyl-gamma-butyrolactone as raw material, and is prepared through chlorination, hydrolysis ring opening, cyclization and re-chlorination, and the process flow is as follows:
The two-time chlorination reaction conditions in the synthetic route of the 1-chloro-1-chloroacetyl propane are very harsh, a large amount of three wastes can be generated, and the two-time chlorination reaction is a key factor for limiting the production cost. In the chlorination reaction process, sulfonyl chloride is mostly adopted as a chlorination reagent, and a large amount of sulfur dioxide can be generated in a reaction system by adopting the sulfonyl chloride as the chlorination reagent, and mixed acid can be formed by sulfur dioxide and chlorine byproduct hydrogen chloride, so that the products are difficult to separate. In the latter case, chlorine is used as a chlorinating agent for reaction during secondary chlorination, but the direct chlorine connection leads to difficult control of the reaction, easy instant initiation and high safety risk. In addition, the intermediate of each step in the synthesis route of directly introducing chlorine to carry out the chlorination reaction needs to be obtained independently, the operation is complex, the process period is long, the problems of lower yield exist in hydrolysis ring opening and cyclization, and the manufacturing cost of the product is greatly increased.
In addition, in order to shorten the synthetic route of 1-chloro-1-chloroacetyl propane, 3, 5-dichloro-2-pentanone or 1- (1-chlorocyclopropyl) ethanone is directly used as a starting material to prepare 1-chloro-1-chloroacetyl propane, and the method shortens the route, but the purchasing cost of the starting material is extremely high and is not suitable for industrial production; there is also a process for shortening the synthetic route of 1-chloro-1-chloroacetyl propane by primary chlorination. The synthesis methods of the plurality of 1-chloro-1-chloroacetyl propane have the defects of long chlorination initiation time, high impurity content of products, harsh reaction conditions and difficult control.
Disclosure of Invention
Aiming at the problems existing in the existing preparation method of 1-chloro-1-chloroacetyl propane, the invention provides a preparation method of 1-chloro-1-chloroacetyl propane, which realizes that chlorine is used as a chlorinating agent for two times of chlorination in the synthesis process of 1-chloro-1-chloroacetyl propane, reduces the initiation time of chlorination reaction, avoids potential risks caused by instant initiation, reduces the generation of byproducts and three wastes, effectively ensures forward progress of the reaction, and remarkably improves the yield and purity of 1-chloro-1-chloroacetyl propane.
In order to achieve the above purpose, the embodiment of the invention adopts the following technical scheme:
a method for preparing 1-chloro-1-chloroacetyl propane, comprising the following steps:
a. Adding an initiator into a solvent, and carrying out reflux dehydration to obtain an activated initiator solution;
b. Adding the activated initiator solution and methanol into alpha-acetyl-gamma-butyrolactone, and introducing chlorine at the temperature of minus 10 ℃ to 0 ℃ for a first chlorination reaction; then heating to 40-50 ℃, and adding hydrogen chloride aqueous solution for reaction to obtain an intermediate M1 solution;
c. mixing sodium hydroxide aqueous solution and dichloromethane, heating to 30-50 ℃, dropwise adding the intermediate M1 solution for cyclization reaction, standing for layering after the reaction is finished, and collecting an organic phase;
d. Drying and dehydrating the organic phase, adding the activated initiator solution and methanol, introducing chlorine at the temperature of-10 ℃ to 0 ℃ for secondary chlorination reaction, adding saturated saline water into the obtained reaction liquid, fully and uniformly mixing, standing for layering, collecting an organic phase, and carrying out reduced pressure distillation to obtain light yellow oily matter, namely the 1-chloro-1-chloroacetyl propane.
Compared with the prior art, the preparation method of the 1-chloro-1-chloroacetyl propane realizes that chlorine is used as a chlorinating reagent in two times of chlorination reactions, avoids the use of high-pollution and high-cost chlorinating reagents such as sulfonyl chloride and the like, and solves the problem that the chlorinating reagents and products are difficult to separate; the invention can obviously improve the activity and selectivity of the chlorination reaction by adding the specific activated initiator solution, greatly shorten the initiation time of the chlorination reaction, improve the yield and purity of the chlorination product and effectively reduce the risk brought by the instant initiation of the chlorination reaction.
The invention uses dichloromethane and sodium hydroxide aqueous solution system to carry out two-phase cyclization reaction, so that the cyclization product continuously enters into organic phase in the reaction process, the continuous forward progress of the reaction is ensured, the impurities generated by the existence of an alkaline system are reduced, the use of phase transfer catalyst is avoided, in addition, the cooperation of a specific initiator and the cyclization system ensures that the cyclization temperature is lower (30-50 ℃), the reaction condition is mild, and the operation is simple.
In addition, the other two intermediates in the synthesis process of the 1-chloro-1-chloroacetyl propane can exist only in an intermediate form, and the process does not need to be independently obtained and purified, so that the preparation period is shortened, the reaction yield is improved, the manufacturing cost is reduced, the tar problem caused by the process of the intermediates is effectively avoided, and the process is suitable for large-scale synthesis in factories.
Preferably, in step a, the initiator is cyclohexanone peroxide, azobisisobutyronitrile, azobisisoheptonitrile or benzoyl peroxide.
The use of the above-described initiator can further shorten the initiation time of the chlorination reaction.
Preferably, in step a, the solvent is dichloromethane or methanol.
Preferably, in the step a, the mass ratio of the initiator to the dichloromethane is 1:8-12.
Preferably, in the step a, the end point of the reflux dehydration is that the water content of the reflux liquid is less than or equal to 0.5 percent.
Preferably, in step b, the mass of initiator in the activated initiator solution corresponds to 0.3% -0.5% of the mass of α -acetyl- γ -butyrolactone.
Preferably, in step b, the mass of the methanol corresponds to 5% -10% of the mass of the α -acetyl- γ -butyrolactone.
Preferably, in the step b, the chlorine gas is introduced in an amount of 1 to 1.3 times the molar amount of the alpha-acetyl-gamma-butyrolactone.
Preferably, in step b, the time for the first chlorination reaction is 1 to 1.5 hours.
Preferably, in step b, the concentration of the aqueous hydrogen chloride solution is 25wt.% to 35wt.%.
Preferably, in the step b, the content of hydrogen chloride in the hydrogen chloride aqueous solution is 1 to 1.3 times of the molar amount of the alpha-acetyl-gamma-butyrolactone.
Preferably, in step b, the reaction is carried out for a period of 2 to 5 hours after the addition of the aqueous hydrogen chloride solution.
Preferably, in step c, the concentration of the aqueous sodium hydroxide solution is 15wt.% to 30wt.%.
Preferably, in step c, the volume ratio of the aqueous sodium hydroxide solution to the dichloromethane is 1-1.5:1.
Preferably, in step c, the sodium hydroxide aqueous solution has a sodium hydroxide content of 1 to 1.5 times the molar amount of the intermediate M1.
Preferably, in step d, the mass of initiator in the activated initiator solution corresponds to 0.3% to 0.5% of the mass of intermediate M1.
Preferably, in step d, the mass of methanol corresponds to 5% -10% of the mass of intermediate M1.
Preferably, in the step d, the chlorine gas is introduced in an amount of 1 to 1.3 times the molar amount of the intermediate M1.
Preferably, in step d, the second chlorination reaction takes 1 to 1.5 hours.
Preferably, in the step d, the addition volume of the saturated saline is 0.3-0.5 times of the volume of the reaction solution.
Preferably, in step d, the reduced pressure distillation process includes: heating the organic phase to 30-40 ℃ under the vacuum degree of minus 0.08-minus 0.09MPa, distilling to remove the solvent, then continuously heating to 120-150 ℃, and distilling until no fraction is produced.
Detailed Description
The present invention will be described in further detail with reference to the following 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.
Example 1
A method for preparing 1-chloro-1-chloroacetyl propane, comprising the following steps:
a. Adding benzoyl peroxide into dichloromethane which is 10 times of the mass of the benzoyl peroxide, carrying out reflux dehydration until the water content of a reflux system is less than 0.5%, obtaining an activated benzoyl peroxide solution, and cooling to room temperature for standby;
b. adding activated benzoyl peroxide solution and methanol into the alpha-acetyl-gamma-butyrolactone, wherein the added mass of the activated benzoyl peroxide is equivalent to 0.4% of the mass of the alpha-acetyl-gamma-butyrolactone, and the added mass of the methanol is equivalent to 8% of the mass of the alpha-acetyl-gamma-butyrolactone; then, introducing chlorine which is 1.2 times of the molar quantity of the alpha-acetyl-gamma-butyrolactone at the temperature of minus 5 ℃ for reaction for 70min, and changing the system color from pale yellow to bright yellow; then heating to 45 ℃, adding 30wt.% hydrogen chloride aqueous solution to react for 2-5h, wherein the content of hydrogen chloride is 1.2 times of the molar quantity of alpha-acetyl-gamma-butyrolactone, and obtaining an intermediate M1 solution;
c. mixing a sodium hydroxide aqueous solution with the concentration of 20wt.% and methylene dichloride according to the volume ratio of 1:1, heating to 40 ℃, dropwise adding an intermediate M1 solution for cyclization reaction, wherein the content of sodium hydroxide is 1.2 times of the molar amount of the dropwise added intermediate M1, standing for layering after the reaction is finished, and collecting an organic phase;
d. Adding anhydrous sodium sulfate into an organic phase, drying, dehydrating, separating, filtering, adding activated benzoyl peroxide solution and methanol into the filtrate, wherein the mass of benzoyl peroxide is equal to 0.4% of the mass of the intermediate M1, the mass of methanol is equal to 8% of the mass of the intermediate M1, then introducing chlorine gas which is equal to 1.2 times of the molar quantity of the intermediate M1 at-5 ℃ for a second chlorination reaction, reacting for 70min, adding saturated saline which is equal to 0.4 times of the volume of the reaction solution into the obtained reaction solution, fully mixing (washing), standing for layering, and collecting an organic phase; under the vacuum degree of-0.08 MPa, firstly heating the organic phase to 35 ℃, distilling to remove methanol, then continuously heating to 130 ℃, and distilling until no fraction is produced, thus obtaining the light yellow oily substance, namely the 1-chloro-1-chloroacetyl propane.
The structural formula of the synthesis process of the 1-chloro-1-chloroacetyl propane is as follows:
Therefore, the other two intermediates in the synthesis process of the 1-chloro-1-chloroacetyl propane can exist only in an intermediate form, and the process does not need to obtain and purify independently, so that the preparation period is shortened, the reaction yield is improved, the manufacturing cost is reduced, and the tar problem caused by the process of the intermediates is effectively avoided.
Example 2
A method for preparing 1-chloro-1-chloroacetyl propane, comprising the following steps:
a. Adding cyclohexanone peroxide into methylene dichloride which is 8 times of the mass of the cyclohexanone peroxide, carrying out reflux dehydration until the water content of a reflux system is less than 0.5%, obtaining an activated cyclohexanone peroxide solution, and cooling to room temperature for standby;
b. Adding activated cyclohexanone peroxide solution and methanol into the alpha-acetyl-gamma-butyrolactone, wherein the added mass of the activated cyclohexanone peroxide is equivalent to 0.3% of the mass of the alpha-acetyl-gamma-butyrolactone, and the added mass of the methanol is equivalent to 5% of the mass of the alpha-acetyl-gamma-butyrolactone; then introducing chlorine with the same molar weight as the alpha-acetyl-gamma-butyrolactone at the temperature of minus 10 ℃ for reacting for 1h, and changing the system color from pale yellow to bright yellow; then heating to 40 ℃, adding 25wt.% hydrogen chloride aqueous solution to react for 2 hours, wherein the content of hydrogen chloride is the same as the molar quantity of the alpha-acetyl-gamma-butyrolactone, and obtaining an intermediate M1 solution;
c. Mixing 15wt.% sodium hydroxide aqueous solution and methylene dichloride according to a volume ratio of 1.2:1, heating to 30 ℃, dropwise adding an intermediate M1 solution for cyclization reaction, wherein the content of sodium hydroxide is the same as the mol amount of the dropwise added intermediate M1, standing for layering after the reaction is finished, and collecting an organic phase;
d. Adding anhydrous sodium sulfate into an organic phase, drying, dehydrating, separating, filtering, adding activated cyclohexanone peroxide solution and methanol into the filtrate, wherein the mass of cyclohexanone peroxide is equal to 0.3% of the mass of an intermediate M1, the mass of methanol is equal to 5% of the mass of the intermediate M1, then introducing chlorine with the same molar quantity as the intermediate M1 at-10 ℃ for a second chlorination reaction, reacting for 1h, adding saturated saline water which is equal to 0.3 times of the volume of the reaction solution into the obtained reaction solution, fully mixing (washing), standing for layering, and collecting an organic phase; under the vacuum degree of-0.09 MPa, firstly heating the organic phase to 30 ℃, distilling to remove methanol, then continuously heating to 120 ℃, and distilling until no fraction is produced, thus obtaining the light yellow oily substance, namely the 1-chloro-1-chloroacetyl propane.
Example 3
A method for preparing 1-chloro-1-chloroacetyl propane, comprising the following steps:
a. Adding azobisisobutyronitrile into methanol which is 12 times of the azobisisobutyronitrile in mass, carrying out reflux dehydration until the water content of a reflux system is less than 0.5%, obtaining an activated azobisisobutyronitrile solution, and cooling to room temperature for standby;
b. Adding activated azobisisobutyronitrile solution and methanol into the alpha-acetyl-gamma-butyrolactone, wherein the added mass of the activated azobisisobutyronitrile is equivalent to 0.5% of the mass of the alpha-acetyl-gamma-butyrolactone, and the added mass of the methanol is equivalent to 10% of the mass of the alpha-acetyl-gamma-butyrolactone; then, chlorine which is 1.3 times of the molar quantity of the alpha-acetyl-gamma-butyrolactone is introduced at the temperature of 0 ℃ to react for 1.5 hours, and the system color is changed from pale yellow to bright yellow; then heating to 50 ℃, adding a 35wt.% hydrogen chloride aqueous solution to react for 5 hours, wherein the content of hydrogen chloride is 1.3 times of the molar quantity of the alpha-acetyl-gamma-butyrolactone, and obtaining an intermediate M1 solution;
c. Mixing 30wt.% sodium hydroxide aqueous solution and methylene dichloride according to a volume ratio of 1.5:1, heating to 50 ℃, dropwise adding an intermediate M1 solution for cyclization reaction, wherein the content of sodium hydroxide is 1.5 times of the molar amount of the dropwise added intermediate M1, standing for layering after the reaction is finished, and collecting an organic phase;
d. Adding anhydrous sodium sulfate into an organic phase, drying, dehydrating, separating, filtering, adding an activated azobisisobutyronitrile solution and methanol into the filtrate, wherein the mass of azobisisobutyronitrile is equal to 0.5% of the mass of the intermediate M1, the mass of methanol is equal to 10% of the mass of the intermediate M1, then introducing chlorine gas which is equal to 1.3 times of the molar quantity of the intermediate M1 at 0 ℃, performing a second chlorination reaction for 1.5h, adding saturated saline water which is equal to 0.5 times of the volume of the reaction solution into the obtained reaction solution, fully mixing (washing), standing for layering, and collecting an organic phase; under the vacuum degree of-0.08 MPa, firstly heating the organic phase to 40 ℃, distilling to remove methanol, then continuously heating to 150 ℃, and distilling until no fraction is produced, thus obtaining the light yellow oily substance, namely the 1-chloro-1-chloroacetyl propane.
Example 4
A method for preparing 1-chloro-1-chloroacetyl propane, comprising the following steps:
a. Adding azodiisoheptonitrile into dichloromethane which is 10 times of the azodiisoheptonitrile in mass, carrying out reflux dehydration until the water content of a reflux system is less than 0.5%, obtaining an activated azodiisoheptonitrile solution, and cooling to room temperature for standby;
b. Adding activated benzoyl peroxide solution and methanol into the alpha-acetyl-gamma-butyrolactone, wherein the added mass of the activated azodiisoheptonitrile is equivalent to 0.4% of the mass of the alpha-acetyl-gamma-butyrolactone, and the added mass of the methanol is equivalent to 8% of the mass of the alpha-acetyl-gamma-butyrolactone; then, introducing chlorine which is 1.2 times of the molar quantity of the alpha-acetyl-gamma-butyrolactone at the temperature of minus 5 ℃ for reaction for 70min, and changing the system color from pale yellow to bright yellow; then heating to 45 ℃, adding 30wt.% hydrogen chloride aqueous solution to react for 2-5h, wherein the content of hydrogen chloride is 1.2 times of the molar quantity of alpha-acetyl-gamma-butyrolactone, and obtaining an intermediate M1 solution;
c. mixing a sodium hydroxide aqueous solution with the concentration of 20wt.% and methylene dichloride according to the volume ratio of 1:1, heating to 40 ℃, dropwise adding an intermediate M1 solution for cyclization reaction, wherein the content of sodium hydroxide is 1.2 times of the molar amount of the dropwise added intermediate M1, standing for layering after the reaction is finished, and collecting an organic phase;
d. Adding anhydrous sodium sulfate into an organic phase, drying, dehydrating, separating, filtering, adding an activated azodiisoheptanenitrile solution and methanol into the filtrate, wherein the mass of the azodiisoheptanenitrile is equal to 0.4% of the mass of the intermediate M1, the mass of the methanol is equal to 8% of the mass of the intermediate M1, then introducing chlorine gas which is equal to 1.2 times of the molar quantity of the intermediate M1 at-5 ℃, performing secondary chlorination reaction for 70min, adding saturated saline which is equal to 0.4 times of the volume of the reaction solution into the obtained reaction solution, fully mixing (washing), standing for layering, and collecting an organic phase; under the vacuum degree of-0.08 MPa, firstly heating the organic phase to 35 ℃, distilling to remove methanol, then continuously heating to 130 ℃, and distilling until no fraction is produced, thus obtaining the light yellow oily substance, namely the 1-chloro-1-chloroacetyl propane.
Test examples
The yield, purity and content of 1-chloro-1-chloroacetyl propane prepared in examples 1 to 4 were examined and analyzed.
1. Instrument and reagents:
Gas chromatograph, model Agilent8890GC, sample injector: an autosampler; chromatographic column: HP-530 m.times.320.times.0.25. Mu.m; a FID detector; solvent: dichloromethane (dichloromethane)
2. Purity measurement:
Chromatographic conditions:
sample configuration: accurately weighing a sample, and diluting the sample to 20mg/Ml by using acetone;
Sample injector: the sample injection amount is 1 mu L;
sample inlet temperature: 250 ℃, split ratio: 20:1;
Chromatographic column: constant flow, flow 2mL/min;
column box: initial value 90 ℃, keeping 1min,30 ℃/min rising to 190 ℃, keeping 3min,30 ℃/min rising to 260 ℃ and keeping 2.4min, and then running at 40 ℃ for 1min;
A detector: the temperature of the detection chamber is 280 ℃, the air flow rate is 300mL/min, the hydrogen flow rate is mL/min, and the tail blowing (N 2) flow rate is 25mL/min.
3. Content determination
The analysis method comprises the following steps: the determination method is consistent with the purity determination method;
Sample detection: after precisely weighing the sample, diluting the sample with acetone to a solution containing 0.1mg per 1mL, detecting the sample according to a given analysis method, and taking a proper amount of a reference substance for detection by the same method. And calculating according to an external standard method and peak area to obtain the product.
4. Yield calculation
(1) M1 yield= (M 2×M1)/(m1×M2) ×100%;
M 1 =a-acetyl- γ -butyrolactone charge, M 2 =m1 charge;
M 1 = a-acetyl- γ -butyrolactone molecular weight, M 2 = M1 molecular weight.
(2) 1-Chloro-1-chloroacetyl propane yield= (m 2×M1)/(m1×M2) ×100%;
M 1 = M1 charge, M 2 = 1-chloro-1-chloroacetyl propane charge;
M 1 = M1 molecular weight, M 2 = 1-chloro-1-chloroacetyl propane molecular weight.
5. Detecting the analysis result
The analytical results of the intermediate M1 prepared in examples 1 to 4 are shown in Table 1.
Table 1M1 analytical test results
The analytical results of the 1-chloro-1-chloroacetyl propane prepared in examples 1 to 4 are shown in Table 2.
Table 21 analysis and detection results of chloro-1-chloroacetyl propane
As can be seen from tables 1 and 2: in the two-time chlorination process, the initiation time and the chlorine introducing time of the reaction are short, the chlorination reaction is quicker, the reaction efficiency is high, and the reaction period is short. The total yield of the 1-chloro-1-chloroacetyl propane prepared by the method can reach 82% -88%, the method has obvious cost advantages, and the purity and the content of the 1-chloro-1-chloroacetyl propane are higher, so that the method has obvious quality advantages.
The method provided by the invention has the advantages that the 800 kg-level pilot scale amplification is realized in the workshop in all the embodiments 1-4, the process is stable and reliable, the actual operation and the three wastes discharge meet the workshop requirements, and the method is suitable for commercial mass production.
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, or alternatives falling within the spirit and principles of the invention.
Claims (9)
1. A preparation method of 1-chloro-1-chloroacetyl propane is characterized by comprising the following steps: the method comprises the following steps:
a. Adding an initiator into a solvent, and carrying out reflux dehydration to obtain an activated initiator solution;
The initiator is cyclohexanone peroxide, azobisisobutyronitrile, azobisisoheptonitrile or benzoyl peroxide; the solvent is dichloromethane or methanol; the mass ratio of the initiator to the solvent is 1:8-12; the end point of the reflux dehydration is that the water content of the reflux liquid is less than or equal to 0.5 percent;
b. Adding the activated initiator solution and methanol into alpha-acetyl-gamma-butyrolactone, and introducing chlorine at the temperature of-10-0 ℃ to perform a first chlorination reaction; then heating to 40-50 ℃, and adding hydrogen chloride aqueous solution for reaction to obtain an intermediate M1 solution;
The concentration of the aqueous hydrogen chloride solution is 25wt.% to 35wt.%; the content of hydrogen chloride in the hydrogen chloride aqueous solution is 1 to 1.3 times of the molar quantity of the alpha-acetyl-gamma-butyrolactone;
c. mixing sodium hydroxide aqueous solution and dichloromethane, heating to 30-50 ℃, dropwise adding the intermediate M1 solution for cyclization reaction, standing for layering after the reaction is finished, and collecting an organic phase;
the volume ratio of the sodium hydroxide aqueous solution to the dichloromethane is 1-1.5:1, a step of;
d. and (3) drying and dehydrating the organic phase, adding the activated initiator solution and methanol, introducing chlorine at the temperature of-10-0 ℃ for a second chlorination reaction, adding saturated saline water into the obtained reaction solution, fully and uniformly mixing, standing for layering, collecting an organic phase, and carrying out reduced pressure distillation to obtain light yellow oily matter, namely the 1-chloro-1-chloroacetyl propane.
2. The process for the preparation of 1-chloro-1-chloroacetyl propane according to claim 1, wherein: in the step b, the mass of the initiator in the activated initiator solution is equivalent to 0.3-0.5% of the mass of the alpha-acetyl-gamma-butyrolactone;
And/or in step b, the mass of the methanol corresponds to 5% -10% of the mass of the α -acetyl- γ -butyrolactone.
3. The process for the preparation of 1-chloro-1-chloroacetyl propane according to claim 1, wherein: in the step b, the introducing amount of the chlorine is 1 to 1.3 times of the molar amount of the alpha-acetyl-gamma-butyrolactone;
And/or in the step b, the time of the first chlorination reaction is 1 to 1.5 hours.
4. The process for the preparation of 1-chloro-1-chloroacetyl propane according to claim 1, wherein: in the step b, the reaction is carried out for 2-5h after the hydrogen chloride aqueous solution is added.
5. The process for the preparation of 1-chloro-1-chloroacetyl propane according to claim 1, wherein: in step c, the concentration of the aqueous sodium hydroxide solution is 15wt.% to 30wt.%;
and/or in step c, the sodium hydroxide content of the sodium hydroxide aqueous solution is 1 to 1.5 times of the molar amount of the intermediate M1.
6. The process for the preparation of 1-chloro-1-chloroacetyl propane according to claim 1, wherein: in the step d, the mass of the initiator in the activated initiator solution is equivalent to 0.3-0.5% of the mass of the intermediate M1;
And/or in step d, the mass of methanol corresponds to 5% -10% of the mass of intermediate M1.
7. The process for the preparation of 1-chloro-1-chloroacetyl propane according to claim 1, wherein: in the step d, the introducing amount of the chlorine is 1 to 1.3 times of the molar amount of the intermediate M1;
And/or in the step d, the time of the second chlorination reaction is 1-1.5h.
8. The process for the preparation of 1-chloro-1-chloroacetyl propane according to claim 1, wherein: in the step d, the adding volume of the saturated saline is 0.3-0.5 times of the volume of the reaction solution.
9. The process for the preparation of 1-chloro-1-chloroacetyl propane according to claim 1, wherein: in step d, the reduced pressure distillation process comprises: heating the organic phase to 30-40 ℃ under the vacuum degree of minus 0.08-minus 0.09MPa, distilling to remove the solvent, then continuously heating to 120-150 ℃, and distilling until no fraction is produced.
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