Preparation method of dichlorochrysanthemic acid intermediate 3, 3-dimethyl-4, 6, 6, 6-tetrachloro hexanoic acid methyl (ethyl) ester

Abstract

The invention relates to the technical field of compound production, and discloses a preparation method of a dichlorochrysanthemic acid intermediate 3, 3-dimethyl-4, 6, 6, 6-tetrachloro-hexanoic acid methyl (ethyl) ester, which comprises the following steps: S1, uniformly mixing and heating raw materials carbon tetrachloride and 3, 3-dimethyl-4, 6, 6, 6-tetrachloro-hexanoic acid methyl (ethyl) ester in a reactor to obtain a mixed reaction solution; s2, dissolving a catalyst in an ester organic solvent to obtain a catalyst mixed solution; the catalyst is preferably dibenzoyl peroxide; s3, dropwise adding the catalyst mixed solution into the mixed reaction solution for reaction under the protection of nitrogen; s4, when the conversion rate of the 3, 3-dimethyl-4-pentenoic acid methyl (ethyl) ester is larger than or equal to 98.5%, a free radical trapping agent is dropwise added, after stirring reaction, post-treatment is carried out, and the tetrachloro chrysanthemic acid methyl (ethyl) ester is obtained. According to the scheme, the catalyst is dissolved in the solvent and dropwise added, and the free radical trapping agent is added in the later stage, so that the risk of blocking the free radical chain reaction due to unsafe factors such as overheating or non-uniform distribution of peroxide in the reaction is effectively inhibited, the safety and the reliability are improved, and the industrial large-scale production is more facilitated.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of compound production, and in particular to a preparation method of 3,3-dimethyl-4,6,6,6-tetrachlorohexanoic acid methyl (or ethyl) ester, which is an intermediate of dichlorophene acid. BACKGROUND

[0002] Pyrethroid pesticides, as an important part of modern pesticides, have been widely used in the fields of agricultural pest control and health prevention due to their advantages of high efficiency, low toxicity and good environmental compatibility. Dichlorophene acid methyl (or ethyl) ester, as a key intermediate of pyrethroid pesticides, has outstanding insecticidal effect, and the activity of cis-isomer is significantly higher than that of trans-isomer. Compared with traditional organophosphorus and organochlorine pesticides, dichlorophene acid pesticides have high activity, short residual time, lower toxicity to humans and animals, and smaller environmental risk. At present, nearly one hundred kinds of commercial pyrethroid insecticides and herbicides have been derived, accounting for about 20% of the global insecticide sales, and are important chemicals for ensuring agricultural production and public health safety.

[0003] In the process of industrial scale synthesis of dichlorophene acid methyl (or ethyl) ester, 3,3-dimethyl-4,6,6,6-tetrachlorohexanoic acid methyl (or ethyl) ester (also known as tetrachlorophene acid methyl (or ethyl) ester) is a key intermediate, and its preparation efficiency directly affects the production cost and industrialization process of downstream products. At present, the synthesis methods of dichlorophene acid methyl (or ethyl) ester can be summarized into six categories according to the domestic and foreign literature reports: (1) Farkas method, proposed by S.F. Farkas et al. in 1957, which is to react 1,1-dichloro-4-methyl-1,3-pentadiene with diazovinyl acetate in the presence of copper catalyst; (2) Sagami method, developed by Sagami Central Research Institute of Japan, which is to generate methyl (or ethyl) chalconate by condensation of 3-methyl-2-butene alcohol and trimethyl orthoacetate in the presence of phosphoric acid, and then to generate tetrachlorophene acid methyl (or ethyl) ester by reacting with carbon tetrachloride in the presence of benzoyl peroxide; (3) Sagami-Kuraray method, which is to condense a mixture of trichloroalkenol with trimethyl orthoacetate to obtain methyl trichlorohexenoate using isobutyric acid as a catalyst, and then to generate dichlorophene acid by dehydrochlorination cyclization; (4) cyclobutanone method, developed by Ciba-Geigy Company in Switzerland, which is to generate a cyclobutanone intermediate by multi-step reaction of carbon tetrachloride, acrylonitrile and isobutene, and then to obtain the product by Favorski rearrangement and alkali treatment; (5) NRDC method, developed by the National Research Development Corporation in the United Kingdom, which is to prepare by ozonization, hydrolysis and Wittig reaction of chrysanthemic acid methyl (or ethyl) ester; (6) vinylidene chloride method, developed by Shanghai Institute of Chemical Physics of Chinese Academy of Sciences, which is to generate an intermediate by a series of reactions of isoprene, hydrogen chloride and vinylidene chloride, and then to generate the target product by a similar reaction of Sagami method. However, the prior art still has obvious defects and deficiencies in industrial application: on the one hand, in the mainstream route represented by the phase mode method, the free radical addition reaction of carbon tetrachloride and methyl (or ethyl) chrysophanate requires the use of solid peroxide (such as benzoyl peroxide BPO) as an initiator, and such an initiator needs to be added in batches several times, which is complicated to operate. Specifically, repeated temperature rising and falling and repeated removal of the charging hole not only increases the labor intensity of workers, but also consumes time and energy. In mass production, even if the stirring speed and temperature are reduced, part of the organic gas still overflows from the charging hole when the solid catalyst is repeatedly added, causing negative environmental factors such as safety and hygiene in the production site. In addition, the solid material added at a higher temperature is difficult to disperse quickly, and the risk of free radical chain reaction caused by the aggregation of peroxide in the later stage of the reaction is easy to cause great safety hazards in industrial production. On the other hand, some studies (such as the existing technology CN102060703A disclosed a method for synthesizing 3,3,-dimethyl-4,6,6,6-tetrachlorohexanoic acid methyl ester) use a transition metal and amine composite catalyst system, and the mixed catalyst and raw material are mixed in several steps, which can improve the yield of the addition product, but there is still a problem of low catalytic efficiency caused by uneven dispersion of the catalyst. When the transition metal catalyst is mixed with the raw material methyl chrysophanate and carbon tetrachloride, and then the solution of the other catalyst is added dropwise under heating, there is also a risk of explosive polymerization due to the excessive local concentration of the catalyst. At the same time, the post-treatment process of the composite catalyst system is more complex, such as the complicated procedures of solid catalyst filtration and organic amine separation, which not only increases the production energy consumption, but also produces a large amount of organic waste liquid and solid waste, significantly increasing the environmental protection treatment cost. In addition, carbon tetrachloride, as a large-tonnage by-product (annual output exceeds 200,000 tons) of chlorocarbon production, although it needs to be disposed of locally due to environmental protection policy requirements, the existing technology has not fully utilized its potential in raw material cost and environmental protection benefits, and the preparation process needs to be optimized to meet the demand of industrial scale production.

[0004] In summary, the development of a preparation method for 3,3-dimethyl-4,6,6,6-tetrachlorohexanoic acid methyl (or ethyl) ester, a dichlorophene intermediate, with a simple catalyst system, high catalytic efficiency and high safety, not only effectively makes up for the deficiencies of the prior art, but also effectively solves the problems of production safety hazards caused by complex catalysts and uneven mixing in the process of producing 3,3-dimethyl-4,6,6,6-tetrachlorohexanoic acid methyl (or ethyl) ester, a dichlorophene intermediate, which is very important for the safe and efficient production of 3,3-dimethyl-4,6,6,6-tetrachlorohexanoic acid methyl (or ethyl) ester, a dichlorophene intermediate. SUMMARY

[0005] The application aims to provide a preparation method of dichlorophenoxyacetic acid intermediate 3,3-dimethyl-4,6,6,6-tetrachlorohexanoic acid methyl (or ethyl) ester, so as to solve the technical problem of low catalytic efficiency caused by uneven dispersion of catalysts in the production of dichlorophenoxyacetic acid intermediate 3,3-dimethyl-4,6,6,6-tetrachlorohexanoic acid methyl ester in the prior art.

[0006] To achieve the above-mentioned purpose, the application adopts the following technical scheme: a preparation method of dichlorophenoxyacetic acid intermediate 3,3-dimethyl-4,6,6,6-tetrachlorohexanoic acid methyl (or ethyl) ester, comprising the following steps: S1, uniformly mixing raw material carbon tetrachloride and methyl (or ethyl) benzoate in a reactor, stirring and heating to obtain a mixed reaction liquid; S2, dissolving a catalyst in an ester organic solvent to obtain a catalyst mixed liquid; the catalyst is any one of diphenyl peroxide (BPO), di-tert-butyl peroxide (DTBP), tert-butyl benzene peroxide (TBPB), methyl ethyl ketone peroxide (MEKP), cyclohexanone peroxide (CHP) and inorganic peroxide; S3, dropping the catalyst mixed liquid into the mixed reaction liquid under nitrogen protection for reaction; S4, when the conversion rate of the methyl (or ethyl) benzoate raw material is greater than or equal to 98.5%, a free radical trapping agent is added, and after stirring for 0.8-1.2 hours, the dichlorophenoxyacetic acid intermediate 3,3-dimethyl-4,6,6,6-tetrachlorohexanoic acid methyl (or ethyl) ester is obtained through post-treatment.

[0007] The principle and advantages of the scheme are: In the scheme, the catalyst is dissolved in an organic solvent and then dropped into the heated reaction mixture, which effectively avoids the problems of low catalytic efficiency or local reaction too intense to cause explosive polymerization caused by uneven mixing of solid catalysts with raw materials, and after the reaction is completed, a free radical trapping agent is added to the reaction liquid to actively and efficiently terminate any residual free radical active centers, thereby effectively preventing unwanted side reactions, improving the purity of the reaction product and improving production efficiency.

[0008] 1. Compared with the existing technology, in which the production of dichlorophenoxyacetic acid methyl (or ethyl) ester intermediate is affected by the uneven dispersion of catalysts caused by uneven mixing of solid catalysts with raw materials, the scheme dissolves the catalyst in an organic solvent and then drops it into the heated reaction mixture, in which the liquid catalyst and the reaction liquid are quickly mixed and evenly distributed to form active reaction centers, so that the free radical addition reaction is uniformly and efficiently carried out, neither the low reaction efficiency caused by uneven contact nor the explosive polymerization caused by too high local catalyst concentration, thus balancing the production efficiency and safety.

[0009] 2. Compared with the existing technology that uses solid peroxide and requires multiple batches of addition, which has the disadvantages of cumbersome operation, time-consuming and energy-intensive, low efficiency and low safety, this solution uses a solvent to first dissolve BPO before adding it dropwise into the reaction system. This not only effectively improves the dissolution and dispersion effect and efficiency of BPO in the reaction system and improves the reaction efficiency, but also effectively avoids explosive polymerization and improves production safety.

[0010] Specifically, this scheme adds benzoyl peroxide (BPO) as a free radical initiator, which can effectively initiate the rapid reaction. The specific process is as follows: First stage: Initiating free radical generation and starting the reaction chain: BPO is a typical organic peroxide with an unstable peroxy bond (-OO-) in its molecular structure. Under heating or light conditions, it easily undergoes homolytic cleavage, generating two benzoyloxy free radicals (•OCOC6H5). These free radicals have high reactivity and can rapidly abstract a chlorine atom from a carbon tetrachloride (CCl4) molecule, causing CCl4 to homolytically cleave into a trichloromethyl free radical (•CCl3) and hydrogen chloride (HCl). The generated •CCl3, as a key reactive intermediate, further attacks the carbon-carbon double bond (C=C) in the methyl (ethyl) benzoate molecule, initiating the opening of the double bond and its combination with the bond to form a new carbon free radical intermediate, thereby initiating the chain process of the free radical addition reaction. In the second stage, the chain reaction continues: During the reaction, the initial free radicals generated by the decomposition of BPO continuously generate new free radical intermediates (such as carbon free radicals formed by combining with methyl (ethyl) benzoate) through steps such as abstracting chlorine atoms and attacking double bonds. These intermediates can continue to react with carbon tetrachloride, repeating the cycle of "abstracting chlorine atoms - generating new free radicals," driving the reaction chain to continue growing until the starting materials (methyl (ethyl) benzoate and carbon tetrachloride) are fully converted or the free radicals undergo a termination reaction (such as the combination of two free radicals to form a stable molecule). Therefore, the initiation role of BPO is the core driving force ensuring that the reaction enters a sustained state from the initial stage.

[0011] 3. Compared with the existing technology that uses a catalytic system of transition metal and amine composite, which leads to a complex catalyst recovery process, this solution uses only one catalyst, which is not only lower in cost, but also simpler and more efficient in the product purification stage, further simplifying the production process and reducing costs.

[0012] 4. This scheme actively and efficiently terminates any residual free radical active centers by adding a free radical scavenger to the system after the reaction is completed, thereby effectively preventing unwanted side reactions, improving the purity of the reaction product, and increasing production efficiency. In addition, it effectively suppresses the risk of free radical chain reactions being blocked by peroxides due to unsafe factors such as overheating or uneven distribution during the reaction, improving safety and reliability, and making it more conducive to large-scale industrial production.

[0013] Preferably, as an improvement, the molar ratio of methyl (ethyl) benzil: carbon tetrachloride: catalyst: free radical trapping agent is 1: 2-3.5: 0.04-0.08: 0.001-0.005, preferably 1: 3: 0.05: 0.002.

[0014] Technical effects: The above settings facilitate high yield, high purity, high efficiency, and high selectivity of the free radical addition reaction, thereby improving production efficiency and product yield. Through long-term experiments, the applicant has found that if carbon tetrachloride is insufficient, the conversion rate will be low, polymerization will be severe, and both yield and purity will decrease; if carbon tetrachloride is excessive, the post-processing burden will be heavy, and economic benefits will be poor. If the catalyst is insufficient, the reaction will be slow, resulting in low conversion rate and poor efficiency; if the catalyst is excessive, the side reaction will increase dramatically, the product will be complex, the purity will be poor, the yield will decrease, and the safety risk will be high. If the free radical trapping agent is insufficient, the polymerization will be out of control, tar will be rampant, yield and purity will collapse, and equipment will be contaminated; if the trapping agent is excessive, the main reaction will be inhibited, the conversion rate will be low, the yield will decrease, and new impurities will be introduced.

[0015] Preferably, as an improvement, in S2, the catalyst is preferably benzoyl peroxide (BPO).

[0016] Technical effects: The above settings facilitate improved reaction stability and conversion efficiency. Specifically, the 10-hour half-life temperature of BPO is about 82°C, which is highly matched with the typical operating temperature (80-90°C) of the addition reaction of methyl (ethyl) benzil and carbon tetrachloride. The PhC(O)O• free radicals generated by the decomposition of BPO have moderate reactivity and good hydrogen extraction ability, effectively ensuring that the reaction proceeds orderly and uniformly, thereby effectively balancing reaction efficiency and safety. Through long-term experiments, the applicant has found that the amount and decomposition efficiency of BPO directly affect the initial concentration of free radicals in the reaction system. An appropriate amount of BPO can provide sufficient free radical initiation source, accelerate the reaction startup speed, and increase the reaction rate; however, if the amount is too high, the free radical concentration may be too high, causing the coupling termination reaction between free radicals to intensify, thereby reducing the yield of the target product. In addition, the decomposition rate of BPO is significantly affected by temperature, and in processes such as the phase transfer method, the reaction temperature needs to be controlled to match the decomposition rhythm of BPO, ensuring the dynamic balance between free radical generation and consumption, thereby optimizing reaction efficiency.

[0017] Preferably, as an improvement, in S2, the ester organic solvent is one or more of ethyl acetate, isopropyl acetate, butyl acetate, methyl propionate, ethyl propionate, butyl propionate, isopropyl propionate, methyl butyrate, ethyl butyrate, isopropyl butyrate, dibutyl phthalate (DBP), and methyl phthalate (DMP) mixed in any ratio; preferably methyl phthalate (DMP).

[0018] Technical effects, the scheme adopts the above settings, which facilitates good dissolution of reactants, catalysts and products, and ensures homogeneous / quasi-homogeneous reaction; in addition, the ester oil solvent used in the scheme is inert in the reaction and does not participate in the reaction to affect the reaction process.

[0019] Preferably, as an improvement, in S2, the mass ratio of the catalyst and the ester organic solvent is 1:2-5, preferably 1:2.5.

[0020] Technical effects, the scheme adopts the above settings, which facilitates "efficient mass transfer-concentration balance-thermal stability-economic separation" four-dimensional coordination, and promotes uniform and efficient reaction. Through long-term experiments, the applicant found that if the amount of solvent is insufficient, the catalyst will be severely agglomerated and settled due to high slurry viscosity and poor dispersion, thereby greatly reducing the three-phase contact area and mass transfer efficiency, and the reaction rate will drop sharply; the reaction heat cannot be discharged in time due to the deterioration of heat transfer, thereby causing local overheating (>120℃), causing catalyst sintering deactivation, product decomposition and coking, and a sharp increase in side reactions (isomerization, dechlorination, etc.), resulting in a collapse of product yield and purity. If the amount of solvent is excessive, the concentration of reactants will be diluted too much, thereby reducing the effective collision frequency of ·CCl3 free radicals and methyl (ethyl) benzoate, and the reaction rate will slow down significantly, resulting in a decrease in production capacity; the volume of ineffective solvent will occupy the reactor space, thereby reducing the equipment utilization and increasing the energy consumption per batch; it will also increase the amount of carbon tetrachloride recovery (boiling point 76.7℃), thereby greatly increasing the distillation energy consumption and condensation cost, and the residual solvent may contaminate the product.

[0021] Preferably, as an improvement, in S1 and S3, the temperature of heating, dropping and reaction is 75-95℃, and the pressure is normal pressure.

[0022] Technical effects, the scheme adopts the above setting, 75~95℃ matches the half-life temperature (82℃) of BPO, ensures the stable generation of free radicals, avoids the lack of low temperature initiation or the decomposition of high temperature explosion. And the upper limit of the temperature effectively blocks the high temperature polymerization path (high temperature polymerization increases the generation of tar), protects the selectivity of the product; The normal pressure operation can avoid the excessive side reaction driven by pressure (such as the deep decomposition of carbon tetrachloride into phosgene). Avoid high pressure equipment investment, reduce safety risk and investment cost. The applicant found through experiments that if the temperature is too low, the free radical initiation will be slow due to the insufficient decomposition rate of BPO, so that the reaction time is greatly prolonged (even not started), and the raw material conversion rate is reduced. The temperature is too low, the efficiency of ·CCl3 free radical attack on double bond will be reduced due to the insufficient kinetic energy of reactant molecules, and the yield of product will be reduced. If the temperature is too high, the free radical concentration will increase rapidly due to the out-of-control decomposition of BPO, so as to trigger the chain side reaction, and the tar generated will reduce the purity of the product. In addition, high temperature will make the product thermally decompose, so as to reduce the yield of main product; In addition, the temperature is too high, which will cause the solvent to vaporize violently (the boiling point of carbon tetrachloride is 76.7℃), so as to cause the pressure of the reaction kettle to rise sharply, break the normal pressure system, and the risk of leakage and explosion will increase sharply.

[0023] Preferably, as an improvement, in S3, the dropping speed is 0.5~1.0g / min, the dropping time is 4~5h, and the reaction time after dropping is 3~4h.

[0024] Technical effects, the scheme adopts the above setting, which is convenient for maintaining low instantaneous concentration of reactants, avoiding local over-basis to induce hydrolysis / elimination side reaction; Slow dropping can also limit the reaction activity, control the ordered contact of closed loop precursor molecules with alkali sites, force the reaction to proceed according to intramolecular nucleophilic substitution path, and block dimerization or polymerization byproducts, so as to effectively improve the yield and purity of the product. The applicant found through long-term experiments that if the dropping speed is too fast, the instantaneous heat release will be intense due to the rapid increase of local reactant concentration, so as to exceed the cooling capacity, cause the system to fly temperature, trigger the decomposition of carbon tetrachloride or the degradation of product dechlorination, and reduce the yield. If the dropping speed is too slow, the reaction time will be prolonged due to the long time hunger of reactants, so as to prolong the invalid working hours and reduce the equipment productivity.

[0025] Preferably, as an improvement, in S4, the radical scavenger is a phenolic antioxidant, including any one of dibutylhydroxytoluene (BHT), butylated hydroxyanisole (BHA), tertiary butylhydroquinone (TBHQ), propyl gallate (PG), 2,2'-methylenebis(4-methyl-6-tert-butylphenol) (antioxidant 2246), pentaerythrityl tetra-(beta-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate) (antioxidant 1010), n-octadecyl beta-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate (antioxidant 1076), 1,3,5-trimethyl-2,4,6-tris(3,5-di-tert-butyl-4-hydroxybenzyl)benzene (antioxidant 330), 1,3,5-tris(3,5-di-tert-butyl-4-hydroxybenzyl)isocyanurate (antioxidant 3114), preferably BHT (dibutylhydroxytoluene).

[0026] Technical effects, the above-mentioned settings can accurately quench the out-of-control free radicals, specifically, the phenolic hydroxyl group (-OH) provides active hydrogen atoms, which can efficiently capture free ·CCl3, carbon-centered radicals, etc. through hydrogen atom transfer (HAT), and the generated phenolic oxygen radicals cannot initiate new chain reactions due to the conjugation / steric effect of the benzene ring, but are dimerized into stable quinones, completely terminating the radical chain growth. The oxidation product (quinone) of the phenolic antioxidant is a neutral, low-polar compound that does not interfere with the main reaction, is easy to separate by alkali washing / distillation in post-processing; and does not have side reactions with catalysts or substrates, ensuring a reaction selectivity of >98% and improving product yield.

[0027] Preferably, as an improvement, the present application also provides a production method of dichlorophenyl acid methyl (ethyl) ester, comprising the following steps: adding 30% sodium methoxide solution dropwise to the above-mentioned methyl (ethyl) tetrachlorophenyl acid ester, and removing two molecules of hydrogen chloride by reaction, to obtain the target product dichlorophenyl acid methyl (ethyl) ester after post-processing; the molar mass ratio of the methyl (ethyl) tetrachlorophenyl acid ester to the 30% sodium methoxide solution is 1:2.2~2.5.

[0028] Technical effects, the present scheme adopts the above setting, the amount of sodium methoxide covers the theoretical amount (2 times) and reserves 10-25% buffer redundancy, which can not only ensure the complete neutralization and removal of 2 molecules of HCl to prevent acid catalytic side reactions, but also compensate for the activity loss of sodium methoxide when it is wet or exposed to air. By selecting 30% sodium methoxide solution, it can provide moderate alkalinity to drive the directional generation of dichlorophenyl acid methyl (ethyl) ester, block the formation of methyl ester by-product by ester exchange, and block the excessive dehalogenation that leads to carbon skeleton fracture. Dropwise addition can disperse the heat of strong base, and the upper limit of molar ratio can effectively avoid local over-alkaline high temperature. And the reaction generates sodium chloride and methanol, which can be removed by water washing, without the burden of complex waste liquid treatment, improving the economic efficiency of post-treatment. The applicant found through long-term experiments that if the amount of sodium methoxide is insufficient, the residual acidic environment caused by incomplete neutralization of HCl will result in insufficient alkaline driving force, causing dehalogenation reaction to stop, resulting in problems such as accumulation of unreacted tetrachloro intermediate, reduced conversion rate, HCl catalytic intramolecular cyclization by-products, and excessive chlorine in the product. If the amount of sodium methoxide is excessive, the high concentration of strong base will intensify the heat release of the system, triggering ester saponification to generate carboxylic acid sodium salt, initiating carbon skeleton fracture to generate small molecule chlorinated olefin fragments, and causing excessive dehalogenation to produce dechlorinated acid methyl (ethyl) ester, reducing product yield. If the concentration of sodium methoxide solution is too low, the volume will be too large, diluting the reactants and reducing the reaction rate; if the concentration of sodium methoxide solution is too high, the viscosity will increase, causing local saponification and resulting in a collapse in yield.

[0029] Preferably, as an improvement, before adding 30% sodium methoxide solution to tetrachlorophenyl acid methyl (ethyl) ester, it also includes adding methanol to tetrachlorophenyl acid methyl (ethyl) ester, and the amount of methanol is 70-90% of the mass of tetrachlorophenyl acid methyl (ethyl) ester.

[0030] Technical effects, the present scheme adopts the above setting, the amount of sodium methoxide covers the theoretical amount (2 times) and reserves 10-25% buffer redundancy, which can not only ensure the complete neutralization and removal of 2 molecules of HCl to prevent acid catalytic side reactions, but also compensate for the activity loss of sodium methoxide when it is wet or exposed to air. By selecting 30% sodium methoxide solution, it can provide moderate alkalinity to drive the directional generation of dichlorophenyl acid methyl (ethyl) ester, block the formation of methyl ester by-product by ester exchange, and block the excessive dehalogenation that leads to carbon skeleton fracture. Dropwise addition can disperse the heat of strong base, and the upper limit of molar ratio can effectively avoid local over-alkaline high temperature. And the reaction generates sodium chloride and methanol, which can be removed by water washing, without the burden of complex waste liquid treatment, improving the economic efficiency of post-treatment. The applicant found through long-term experiments that if the amount of sodium methoxide is insufficient, the residual acidic environment caused by incomplete neutralization of HCl will result in insufficient alkaline driving force, causing dehalogenation reaction to stop, resulting in problems such as accumulation of unreacted tetrachloro intermediate, reduced conversion rate, HCl catalytic intramolecular cyclization by-products, and excessive chlorine in the product. If the amount of sodium methoxide is excessive, the high concentration of strong base will intensify the heat release of the system, triggering ester saponification to generate carboxylic acid sodium salt, initiating carbon skeleton fracture to generate small molecule chlorinated olefin fragments, and causing excessive dehalogenation to produce dechlorinated acid methyl (ethyl) ester, reducing product yield. If the concentration of sodium methoxide solution is too low, the volume will be too large, diluting the reactants and reducing the reaction rate; if the concentration of sodium methoxide solution is too high, the viscosity will increase, causing local saponification and resulting in a collapse in yield.

[0031] Preferably, as an improvement, when methanol is added, the temperature is 5-10℃ when adding 30% sodium methoxide solution; when no methanol is added, the temperature is 20-25℃ when adding 30% sodium methoxide solution.

[0032] Technical effects: The above-mentioned settings are adopted in the scheme, which facilitates accurate matching of the thermodynamic characteristics of the reaction system, and through heat regulation, the reaction efficiency and reaction selectivity are considered, thereby improving the product yield. Specifically, in the methanol system, about 24 kJ / mol of dissolution heat is released when methanol is mixed with sodium methoxide, and low-temperature dropwise addition avoids heat superposition to trigger ester hydrolysis. And low temperature can make the β-elimination energy barrier >80 kJ / mol, forcing the reaction to proceed according to the single-step E2 mechanism, and eliminating the carbon skeleton breaking side reaction. In the solvent-free system, methyl (ethyl) chlorochromate has a melting point of 18-20℃, and 20-25℃ ensures that it is completely melted, avoiding the wrapping of unreacted solids to cause local excess of alkali; and above 20℃ meets the minimum activation energy requirement (>65 kJ / mol) of E2 elimination, ensuring the reaction rate. DETAILED DESCRIPTION

[0033] The application will be further described in detail below in conjunction with examples, but the embodiments of the application are not limited thereto. If not specifically indicated, the technical means used in the following examples and experimental examples are conventional means known to those skilled in the art, and the materials, reagents, etc. used can be obtained from commercial channels.

[0034] General description of the scheme The scheme provides a preparation method of dichlorophenoxyacetic acid intermediate 3,3-dimethyl-4,6,6,6-tetrachlorohexyl (methyl) (ethyl) ester, which comprises the following steps: S1, uniformly mix raw material carbon tetrachloride and methyl (ethyl) benzoate in a reactor, and stir to heat to 75-95℃ under normal pressure to obtain a mixed reaction liquid; S2, dissolve the catalyst in an ester organic solvent to obtain a catalyst mixture liquid; The catalyst is any one of diphenyl peroxide (BPO), di-tert-butyl peroxide (DTBP), tert-butyl peroxyl benzoate (TBPB), methyl ethyl ketone peroxide (MEKP), cyclohexanone peroxide (CHP), and inorganic peroxide.

[0035] The ester organic solvent is one or more of ethyl acetate, isopropyl acetate, butyl acetate, methyl propionate, ethyl propionate, butyl propionate, isopropyl propionate, methyl butyrate, ethyl butyrate, isopropyl butyrate, dibutyl phthalate (DBP), and methyl phthalate (DMP) mixed in any ratio; preferably methyl phthalate (DMP).

[0036] The mass ratio of the catalyst and the ester organic solvent is 1:2-5, preferably 1:2.5.

[0037] S3, under the conditions of nitrogen protection, normal pressure, 75-95℃, the catalyst mixture obtained in S2 is added dropwise into the mixed reaction liquid obtained in S1 to perform reaction; wherein the dropping speed is 0.5-1.0 g / min, the dropping time is 4-5 h, and the reaction time after dropping is completed is 3-4 h.

[0038] S4, when the conversion rate of methyl (or ethyl) chrysophanate raw material is ≥98.5%, a free radical trapping agent is added dropwise, and after stirring for 0.8-1.2 h, the methyl (or ethyl) 3,3-dimethyl-4,6,6,6-tetrachlorohexanoate intermediate of dichlorophenoxyacetic acid is obtained by post-treatment.

[0039] The free radical trapping agent is any one of phenolic antioxidants, including dibutyl hydroxytoluene (BHT), butylated hydroxyanisole (BHA), tertiary butyl hydroquinone (TBHQ), propyl gallate (PG), 2,2'-methylenebis(4-methyl-6-tert-butylphenol) (antioxidant 2246), pentaerythritol tetrakis[β-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate] (antioxidant 1010), n-octadecanol β-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate (antioxidant 1076), 1,3,5-trimethyl-2,4,6-tris(3,5-di-tert-butyl-4-hydroxybenzyl)benzene (antioxidant 330), 1,3,5-tris(3,5-di-tert-butyl-4-hydroxybenzyl)isocyanurate (antioxidant 3114), and preferably BHT (dibutyl hydroxytoluene).

[0040] During the entire reaction process, the molar mass ratio of the materials methyl (or ethyl) chrysophanate: carbon tetrachloride: catalyst: free radical trapping agent is 1:2-3.5:0.04-0.08:0.001-0.005, preferably 1:3:0.05:0.002.

[0041] The scheme also provides a preparation method of methyl (or ethyl) dichlorophenoxyacetate, which comprises the following contents: cooling the above-mentioned methyl (or ethyl) tetrachlorophthalate to 20-25℃, adding 30% sodium methoxide solution dropwise into the methyl (or ethyl) tetrachlorophthalate according to the molar mass ratio of 1:2.2-2.5, and reacting to remove two molecules of hydrogen chloride, so as to obtain the target product methyl (or ethyl) dichlorophenoxyacetate after post-treatment.

[0042] In other embodiments, before adding the 30% sodium methoxide solution dropwise to the methyl (ethyl) tetrachlorophthalate, methanol can also be added to the methyl (ethyl) tetrachlorophthalate, and the amount of methanol is 70-90% of the mass of the methyl (ethyl) tetrachlorophthalate, and then the temperature is lowered to 5-10°C. Then, according to the molar mass ratio of methyl (ethyl) tetrachlorophthalate to 30% sodium methoxide solution being 1:2.2-2.5, the 30% sodium methoxide solution is added dropwise to the methyl (ethyl) tetrachlorophthalate, two molecules of hydrogen chloride are removed by reaction, and the target product methyl (ethyl) dichlorophthalate is obtained after post-treatment.

[0043] Both of the above two processing methods can obtain high product yield and purity.

[0044] Specifically, in the following examples, Examples 1-8 show a preparation method of a dichlorophthalic acid intermediate 3,3-dimethyl-4,6,6,6-tetrachlorohexanoic acid methyl (ethyl) ester, and Examples 9-12 show a preparation method of methyl (ethyl) dichlorophthalate.

[0045] Stage 1: Synthesis of dichlorophthalic acid intermediate 3,3-dimethyl-4,6,6,6-tetrachlorohexanoic acid methyl (ethyl) ester The chemical reaction equation occurring in this stage is as follows (exhibited taking methyl benzoate as an example):

[0046] Example 1 In a reaction kettle equipped with variable speed stirring, a thermometer, a reflux distillation, a high tank, a vacuum and a tail gas absorption system, metered amounts of methyl benzoate 710g (5.0mol), carbon tetrachloride 2310g (15.0mol) were added, and stirring was carried out to heat to 80°C; under nitrogen protection, a mixed solution containing 70% of diphenyl peroxide (BPO) 60.5g (0.25mol) and methyl phthalate (DMP) 151.3g was added dropwise from the high tank to the reaction kettle, the dropwise time was controlled for 4 hours, and the dropwise reaction was carried out for 4 hours; when the conversion rate of methyl benzoate raw material was ≥98.5% in the sample GC control, it was the end point of the reaction, then dibutylhydroxytoluene (BHT) 2.2g (0.01mol) was added, and stirring was carried out for 1 hour; then dilute alkali treatment and water washing treatment were carried out, and the product methyl tetrachlorophthalate 1457g was obtained, with a yield of 98.45% and a content of 98.6%.

[0047] Example 2 In the reactor equipped with variable speed stirring, thermometer, reflux distillation, high tank, vacuum and tail gas absorption system, the ethyl chrysanthemate 781.1g (5.0mol), carbon tetrachloride 2310g (15.0mol) were metered and added, and heated to 85℃ under stirring; under the protection of nitrogen, 60.5g (0.25mol) of 70% content of dibenzoyl peroxide (BPO) and 151.3g of dimethyl phthalate (DMP) were mixed and added dropwise into the reactor from the high tank, the dropwise time was controlled for 5 hours, and the reaction was kept for 3 hours after the dropwise addition; when the conversion rate of ethyl chrysanthemate raw material was ≥98.5% in the GC control sample, it was the end point of the reaction, then 2.2g (0.01mol) of butylated hydroxytoluene (BHT) was added and stirred for 1 hour; the product ethyl tetrachloro chrysanthemate 1535.4g was obtained by dilute alkali treatment and water washing treatment, the yield was 99.01%, and the content was 98.73%.

[0048] Example 3 In the reactor equipped with variable speed stirring, thermometer, reflux distillation, high tank, vacuum and tail gas absorption system, the ethyl chrysanthemate 781.1g (5.0mol), carbon tetrachloride 2310g (15.0mol) were metered and added, and heated to 85℃ under stirring; under the protection of nitrogen, 60.5g (0.25mol) of 70% content of dibenzoyl peroxide (BPO) and 151.3g of dimethyl phthalate (DMP) were mixed and added dropwise into the reactor from the high tank, the dropwise time was controlled for 5 hours, and the reaction was kept for 3 hours after the dropwise addition; when the conversion rate of ethyl chrysanthemate raw material was ≥98.5% in the GC control sample, it was the end point of the reaction, then 2.2g (0.01mol) of butylated hydroxytoluene (BHT) was added and stirred for 1 hour; the product ethyl tetrachloro chrysanthemate 1535.4g was obtained by dilute alkali treatment and water washing treatment, the yield was 99.01%, and the content was 98.73%.

[0049] Example 4 In the reactor equipped with variable speed stirring, thermometer, reflux distillation, high tank, vacuum and tail gas absorption system, the ethyl chrysanthemate 781.1g (5.0mol), carbon tetrachloride 2310g (15.0mol) were metered and added, and heated to 85℃ under stirring; under the protection of nitrogen, 60.5g (0.25mol) of 70% content of dibenzoyl peroxide (BPO) and 151.3g of dimethyl phthalate (DMP) were mixed and added dropwise into the reactor from the high tank, the dropwise time was controlled for 5 hours, and the reaction was kept for 3 hours after the dropwise addition; when the conversion rate of ethyl chrysanthemate raw material was ≥98.5% in the GC control sample, it was the end point of the reaction, then 2.2g (0.01mol) of butylated hydroxytoluene (BHT) was added and stirred for 1 hour; the product ethyl tetrachloro chrysanthemate 1535.4g was obtained by dilute alkali treatment and water washing treatment, the yield was 99.01%, and the content was 98.73%.

[0050] Example 5 In a reaction kettle equipped with variable speed stirring, thermometer, reflux distillation, head tank, vacuum and tail gas absorption system, metered addition of methyl chrysanthemate 710 g (5.0 mol), carbon tetrachloride 2695 g (17.5 mol), stirring and heating to 85°C; under nitrogen protection, a mixture of 70% content of dibenzoyl peroxide (BPO) 60.5 g (0.25 mol) and dibutyl phthalate (DBP) 151.3 g was added dropwise from the head tank into the reaction kettle, the dropwise time was controlled at 4 hours, and after dropping, it was kept at 95°C for 4 hours. When the conversion rate of methyl chrysanthemate raw material was ≥98.5% in the GC control sample, it was the end point of the reaction, then 2.2 g (0.01 mol) of butylated hydroxytoluene (BHT) was added, and stirred for 1 hour. After dilute alkali treatment and water washing treatment, the product methyl tetrachloro chrysanthemate 1471 g was obtained, with a yield of 99.41% and a content of 98.43%.

[0051] Example 6 In a reaction kettle equipped with variable speed stirring, thermometer, reflux distillation, head tank, vacuum and tail gas absorption system, metered addition of methyl chrysanthemate 710 g (5.0 mol), carbon tetrachloride 2310 g (15.0 mol), stirring and heating to 83°C; under nitrogen protection, a mixture of 70% content of dibenzoyl peroxide (BPO) 60.5 g (0.25 mol) and ethyl acetate 151.3 g was added dropwise from the head tank into the reaction kettle, the dropwise time was controlled at 5 hours, and after dropping, it was kept at 95°C for 3 hours. When the conversion rate of methyl chrysanthemate raw material was ≥98.5% in the GC control sample, it was the end point of the reaction, then 2.2 g (0.01 mol) of butylated hydroxytoluene (BHT) was added, and stirred for 1 hour. After dilute alkali treatment and water washing treatment, the product methyl tetrachloro chrysanthemate 1462 g was obtained, with a yield of 98.8% and a content of 98.87%.

[0052] Example 7 In the reactor equipped with variable speed stirring, thermometer, reflux distillation, high tank, vacuum and tail gas absorption system, the measured amount of ethyl chrysanthemate 781.1g (5.0mol), carbon tetrachloride 2310g (15.0mol) was added, and stirred to heat to 83℃; under the protection of nitrogen, a mixture of tert-butyl peroxy benzoate (TBPB) 48.5g (0.25mol) and ethyl acetate 100g was added dropwise into the reactor from the high tank, the dropwise time was controlled for 5 hours, and after the dropwise was completed, it was kept at 95℃ for 3 hours; when the conversion rate of ethyl chrysanthemate raw material was ≥98.5% in the GC control, it was the end point of the reaction, then 2.2g (0.01mol) of dibutyl hydroxyl toluene (BHT) was added and stirred for 1 hour; then the product ethyl tetrachloro chrysanthemate 1,528.8g was obtained by dilute alkali treatment and water washing treatment, the yield was 98.58%, and the content was 99.18%.

[0053] Example 8 In the reactor equipped with variable speed stirring, thermometer, reflux distillation, high tank, vacuum and tail gas absorption system, the measured amount of ethyl chrysanthemate 781.1g (5.0mol), carbon tetrachloride 2310g (15.0mol) was added, and stirred to heat to 83℃; under the protection of nitrogen, a mixture of tert-butyl peroxy benzoate (TBPB) 48.5g (0.25mol) and ethyl acetate 100g was added dropwise into the reactor from the high tank, the dropwise time was controlled for 5 hours, and after the dropwise was completed, it was kept at 95℃ for 3 hours; when the conversion rate of ethyl chrysanthemate raw material was ≥98.5% in the GC control, it was the end point of the reaction, then 2.2g (0.01mol) of dibutyl hydroxyl toluene (BHT) was added and stirred for 1 hour; then the product ethyl tetrachloro chrysanthemate 1,528.8g was obtained by dilute alkali treatment and water washing treatment, the yield was 98.58%, and the content was 99.18%.

[0054] Stage 2: Synthesis of methyl (ethyl) dichloro chrysanthemate The chemical reaction equation of this stage is as follows (taking methyl tetrachloro chrysanthemate as an example):

[0055] Example 9 In the reactor equipped with variable speed stirring, thermometer, reflux distillation, high tank, vacuum and tail gas absorption system, the measured amount of methyl tetrachlorophthalic acid 1460g (4.93mol), methanol 1168g (36.45mol) was added, and the temperature was reduced to 5-10℃ by stirring; then 1952g (10.85mol) of 30% sodium methoxide solution was added dropwise into the reactor from the high tank, the dropwise time was controlled at 4-6 hours, after the dropwise was completed, the reaction was carried out at 20-25℃ for 8-10 hours, when the content of methyl tetrachlorophthalic acid was ≤0.5% in the sample GC control, it was the end point of the reaction; the inorganic salt was removed by centrifugal washing, and the salt was filtered out by vacuum concentration to obtain residual oil methyl dichlorophthalate 1057.6g, the yield was 96.2%, and the content was 97.88%.

[0056] Example 10 In the reactor equipped with variable speed stirring, thermometer, reflux distillation, high tank, vacuum and tail gas absorption system, the measured amount of methyl tetrachlorophthalic acid 1460g (4.93mol), methanol 1168g (36.45mol) was added, and the temperature was reduced to 5-10℃ by stirring; then 1952g (10.85mol) of 30% sodium methoxide solution was added dropwise into the reactor from the high tank, the dropwise time was controlled at 4-6 hours, after the dropwise was completed, the reaction was carried out at 20-25℃ for 8-10 hours, when the content of methyl tetrachlorophthalic acid was ≤0.5% in the sample GC control, it was the end point of the reaction; the inorganic salt was removed by centrifugal washing, and the salt was filtered out by vacuum concentration to obtain residual oil methyl dichlorophthalate 1057.6g, the yield was 96.2%, and the content was 97.88%.

[0057] Example 11 In the reactor equipped with variable speed stirring, thermometer, reflux distillation, high tank, vacuum and tail gas absorption system, the measured amount of methyl tetrachlorophthalic acid 1460g (4.93mol), methanol 1168g (36.45mol) was added, and the temperature was reduced to 5-10℃ by stirring; then 1952g (10.85mol) of 30% sodium methoxide solution was added dropwise into the reactor from the high tank, the dropwise time was controlled at 4-6 hours, after the dropwise was completed, the reaction was carried out at 20-25℃ for 8-10 hours, when the content of methyl tetrachlorophthalic acid was ≤0.5% in the sample GC control, it was the end point of the reaction; the inorganic salt was removed by centrifugal washing, and the salt was filtered out by vacuum concentration to obtain residual oil methyl dichlorophthalate 1057.6g, the yield was 96.2%, and the content was 97.88%.

[0058] Example 12 In the reaction kettle equipped with variable speed stirring, thermometer, reflux distillation, high tank, vacuum and tail gas absorption system, the measured amount of methyl tetrachlorophthalate 1460g (4.93mol) was added, and the temperature was reduced to 20~25℃; then 2218g (12.32mol) of 30% sodium methoxide solution was added from the high tank to the reaction kettle, the dropwise time was controlled at 4~6 hours, the reaction was kept for 8~10 hours after dropping, and the sample was controlled by GC when the content of methyl tetrachlorophthalate was ≤0.5%, which was the end point of the reaction; centrifugal washing was used to remove inorganic salts, and the salt was filtered out after vacuum concentration to obtain residual oil methyl dichlorophthalate 1079g, the yield was 98.2%, and the content was 98.72%.

[0059] In summary, the present application adopts the method of dissolving the catalyst in the solvent and adding dropwise, and the free radical trapping agent is added later, which effectively inhibits the risk of free radical chain reaction caused by overheating or uneven distribution of peroxide in the reaction, improves the safety and reliability, and is more conducive to large-scale industrial production; The present application uses less carbon tetrachloride than the same type of reaction, which improves the utilization rate of equipment and reduces the production cost; The present application uses chlorinated hydrocarbon byproduct carbon tetrachloride to synthesize methyl (or ethyl) dichlorophthalate, which is beneficial to environmental protection and reduces raw material cost; The present application improves the conversion rate of raw materials while maintaining high product yield; The process operation of the present application is simple, the reaction is stable, and it is convenient for large-scale industrial production, and the average yield is more than 98%.

[0060] The above is only an embodiment of the present application, and the specific technical solutions and / or common knowledge of the scheme are not described in detail. It should be noted that for those skilled in the art, without departing from the technical solutions of the present application, some modifications and improvements can be made, which should also be considered as the protection scope of the present application, and these will not affect the effect and practicality of the patent. The protection scope of the present application should be subject to the content of its claims, and the specific implementation mode and the like in the specification can be used to explain the content of the claims.

Claims

1. A process for the preparation of dichlorophenoxyacetic acid intermediate 3,3-dimethyl-4,6,6,6-tetrachlorohexanoic acid methyl (ethyl) ester, characterized by: The method comprises the following steps: S1, mixing raw material carbon tetrachloride and methyl (ethyl) chrysophanate uniformly in a reactor, stirring and heating to obtain a mixed reaction solution; S2, dissolving a catalyst in an ester organic solvent to obtain a catalyst mixed solution; the catalyst is any one of dibenzoyl peroxide, di-tert-butyl peroxide, tert-butyl peroxybenzoate, methyl ethyl ketone peroxide, cyclohexanone peroxide and inorganic peroxide; S3, adding the catalyst mixed solution dropwise into the mixed reaction solution under nitrogen protection for reaction; S4, when the conversion rate of methyl (ethyl) chrysophanate raw material is greater than or equal to 98.5%, a free radical trapping agent is added, and after stirring for 0.8-1.2 hours, a dichlorophenoxyacetic acid intermediate, methyl (ethyl) 3,3-dimethyl-4,6,6,6-tetrachlorohexanoate, is obtained after post-treatment.

2. A process for the preparation of 3,3-dimethyl-4,6,6,6-tetrachlorohexanoic acid methyl (ethyl) ester, an intermediate for dichlorophene according to claim 1, characterized by: The molar mass ratio of methyl (ethyl) chrysophanate: carbon tetrachloride: catalyst: free radical trapping agent is 1: 2-3.5: 0.04-0.08: 0.001-0.

005.

3. A process for the preparation of 3,3-dimethyl-4,6,6,6-tetrachlorohexanoic acid methyl (ethyl) ester, an intermediate of dichlorophenoxyacetic acid according to claim 1, characterized by the fact that: In S2, the catalyst is preferably dibenzoyl peroxide.

4. A process for the preparation of 3,3-dimethyl-4,6,6,6-tetrachlorohexanoic acid methyl (ethyl) ester, an intermediate of dichlorophenoxyacetic acid according to claim 1, characterized by: In S2, the ester organic solvent is one or more of ethyl acetate, isopropyl acetate, butyl acetate, methyl propionate, ethyl propionate, butyl propionate, isopropyl propionate, methyl butyrate, ethyl butyrate, isopropyl butyrate, dibutyl phthalate and methyl phthalate, which are mixed in any ratio; in S2, the mass ratio of the catalyst and the ester organic solvent is 1: 2-5.

5. A process for the preparation of 3,3-dimethyl-4,6,6,6-tetrachlorohexanoic acid methyl (ethyl) ester, an intermediate of dichlorophenoxyacetic acid according to claim 1, characterized by: In S1 and S3, the temperature of heating, dropping and reaction is 75-95°C, and the pressure is normal pressure.

6. A process for the preparation of 3,3-dimethyl-4,6,6,6-tetrachlorohexanoic acid methyl (ethyl) ester, an intermediate of dichlorophenoxyacetic acid according to claim 1, characterized by: In S3, the dropping speed is 0.5-1.0 g / min, the dropping time is 4-5 hours, and the reaction time after dropping is 3-4 hours.

7. A process for the preparation of 3,3-dimethyl-4,6,6,6-tetrachlorohexanoic acid methyl (ethyl) ester, an intermediate of dichlorophenoxyacetic acid according to claim 1, characterized by the fact that: In S4, the free radical trapping agent is a phenolic antioxidant, including any one of dibutylhydroxytoluene, butylhydroxyanisole, tert-butyl hydroquinone, propyl gallate, antioxidant 2246, antioxidant 1010, antioxidant 1076, antioxidant 330 and antioxidant 3114.

8. A process for the production of dichlorvos methyl (ethyl) ester, characterized by: The method comprises the following steps: adding a 30% sodium methoxide solution to methyl (ethyl) tetrachlorophthalate prepared by the method of any one of claims 1-7 to react to remove two molecules of hydrogen chloride, and after post-treatment, obtaining the target product methyl (ethyl) dichlorophenoxyacetate; the molar mass ratio of methyl (ethyl) tetrachlorophthalate to the 30% sodium methoxide solution is 1: 2.2-2.

5.

9. The method for producing methyl (ethyl) dichloroquine according to claim 8, characterized in that: Before adding the 30% sodium methoxide solution to the methyl (ethyl) tetrachlorophthalate, methanol is also added to the methyl (ethyl) tetrachlorophthalate, and the amount of methanol is 70-90% of the mass of the methyl (ethyl) tetrachlorophthalate.

10. The method of producing dichlorophene according to claim 8 or 9, wherein: When adding methanol, the temperature when adding the 30% sodium methoxide solution is 5-10°C; when not adding methanol, the temperature when adding the 30% sodium methoxide solution is 20-25°C.

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