CN112745286B - Preparation method of spirodiclofen diester derivative - Google Patents
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- 239000005664 Spirodiclofen Substances 0.000 title claims abstract description 29
- -1 spirodiclofen diester Chemical class 0.000 title claims abstract description 18
- 238000002360 preparation method Methods 0.000 title claims abstract description 16
- 238000006243 chemical reaction Methods 0.000 claims abstract description 84
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 46
- 239000002253 acid Substances 0.000 claims abstract description 28
- 239000011230 binding agent Substances 0.000 claims abstract description 26
- 150000007529 inorganic bases Chemical class 0.000 claims abstract description 21
- 239000003960 organic solvent Substances 0.000 claims abstract description 21
- 238000000034 method Methods 0.000 claims abstract description 19
- 230000008569 process Effects 0.000 claims abstract description 14
- 238000001914 filtration Methods 0.000 claims abstract description 13
- 239000002994 raw material Substances 0.000 claims abstract description 12
- 150000001263 acyl chlorides Chemical class 0.000 claims abstract description 9
- 239000007790 solid phase Substances 0.000 claims abstract description 4
- 239000002904 solvent Substances 0.000 claims description 28
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 18
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 16
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 16
- KIKARNYYJSEROI-UHFFFAOYSA-N 3-(2,4-dichlorophenyl)-4-hydroxy-1-oxaspiro[4.5]dec-3-en-2-one Chemical compound OC1=C(C=2C(=CC(Cl)=CC=2)Cl)C(=O)OC11CCCCC1 KIKARNYYJSEROI-UHFFFAOYSA-N 0.000 claims description 15
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 15
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 8
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 8
- 239000000126 substance Substances 0.000 claims description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 8
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 5
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 5
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 claims description 2
- POAOYUHQDCAZBD-UHFFFAOYSA-N 2-butoxyethanol Chemical compound CCCCOCCO POAOYUHQDCAZBD-UHFFFAOYSA-N 0.000 claims description 2
- UPGSWASWQBLSKZ-UHFFFAOYSA-N 2-hexoxyethanol Chemical compound CCCCCCOCCO UPGSWASWQBLSKZ-UHFFFAOYSA-N 0.000 claims description 2
- JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims description 2
- 238000002425 crystallisation Methods 0.000 abstract description 7
- 230000008025 crystallization Effects 0.000 abstract description 7
- 125000004201 2,4-dichlorophenyl group Chemical group [H]C1=C([H])C(*)=C(Cl)C([H])=C1Cl 0.000 abstract description 3
- 238000005516 engineering process Methods 0.000 abstract description 2
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 48
- 239000000047 product Substances 0.000 description 26
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- 239000002351 wastewater Substances 0.000 description 18
- DTDSAWVUFPGDMX-UHFFFAOYSA-N spirodiclofen Chemical compound CCC(C)(C)C(=O)OC1=C(C=2C(=CC(Cl)=CC=2)Cl)C(=O)OC11CCCCC1 DTDSAWVUFPGDMX-UHFFFAOYSA-N 0.000 description 17
- 239000012452 mother liquor Substances 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 238000003786 synthesis reaction Methods 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- LDJUYMIFFNTKOI-UHFFFAOYSA-N 2,2-dimethylbutanoyl chloride Chemical compound CCC(C)(C)C(Cl)=O LDJUYMIFFNTKOI-UHFFFAOYSA-N 0.000 description 7
- NRDQFWXVTPZZAZ-UHFFFAOYSA-N butyl carbonochloridate Chemical compound CCCCOC(Cl)=O NRDQFWXVTPZZAZ-UHFFFAOYSA-N 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- 238000004065 wastewater treatment Methods 0.000 description 7
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 6
- 210000003298 dental enamel Anatomy 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 238000005070 sampling Methods 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- 239000003513 alkali Substances 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 238000004821 distillation Methods 0.000 description 5
- 238000007363 ring formation reaction Methods 0.000 description 5
- 238000010025 steaming Methods 0.000 description 5
- 239000002699 waste material Substances 0.000 description 5
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-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
- 238000001514 detection method Methods 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 238000004064 recycling Methods 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- HGUFODBRKLSHSI-UHFFFAOYSA-N 2,3,7,8-tetrachloro-dibenzo-p-dioxin Chemical compound O1C2=CC(Cl)=C(Cl)C=C2OC2=C1C=C(Cl)C(Cl)=C2 HGUFODBRKLSHSI-UHFFFAOYSA-N 0.000 description 3
- 241000238876 Acari Species 0.000 description 3
- 239000003183 carcinogenic agent Substances 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000004321 preservation Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- XKMRRTOUMJRJIA-UHFFFAOYSA-N ammonia nh3 Chemical compound N.N XKMRRTOUMJRJIA-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 230000000711 cancerogenic effect Effects 0.000 description 2
- KBPLFHHGFOOTCA-UHFFFAOYSA-N caprylic alcohol Natural products CCCCCCCCO KBPLFHHGFOOTCA-UHFFFAOYSA-N 0.000 description 2
- 231100000357 carcinogen Toxicity 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 2
- 150000002170 ethers Chemical class 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- 230000000607 poisoning effect Effects 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 239000012265 solid product Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- 239000002912 waste gas Substances 0.000 description 2
- VNTCVNLNEOVBEE-UHFFFAOYSA-N 2,2-dimethyl-3-(2-methylprop-1-enyl)cyclopropane-1-carbonyl chloride Chemical compound CC(C)=CC1C(C(Cl)=O)C1(C)C VNTCVNLNEOVBEE-UHFFFAOYSA-N 0.000 description 1
- 241000207199 Citrus Species 0.000 description 1
- 241000764238 Isis Species 0.000 description 1
- 241000607479 Yersinia pestis Species 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 235000020971 citrus fruits Nutrition 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 235000013601 eggs Nutrition 0.000 description 1
- 230000037149 energy metabolism Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000000749 insecticidal effect Effects 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N n-Octanol Natural products CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 230000003151 ovacidal effect Effects 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000002910 solid waste Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/94—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom spiro-condensed with carbocyclic rings or ring systems, e.g. griseofulvins
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Abstract
The invention provides a preparation method of spirodiclofen diester derivative, which takes 3- (2, 4-dichlorophenyl) -2-oxo-1-oxaspiro [4,5] -dec-3-ene-4-alcohol and acyl chloride as raw materials, takes inorganic base as an acid-binding agent to react in a hydrophilic aprotic organic solvent, the water content of a reaction system is 5-35 percent of the total mass of the system, water is added for crystallization after the reaction is finished, and the solid phase product obtained by filtering is the spirodiclofen diester derivative. The invention ensures the reaction to be smoothly carried out by selecting the reaction temperature and limiting the water content in the reaction system. The invention simplifies the process, is environment-friendly, has the verified yield of more than 97 percent, and is obviously superior to the prior process technology.
Description
Technical Field
The invention belongs to the technical field of chemical synthesis, and particularly relates to a preparation method of a novel spirodiclofen diester derivative.
Background
The chemical name of spirodiclofen is 3- (2, 4-dichlorophenyl) -2-oxo-1-oxaspiro [4,5]]-decyl-3-en-4-ylcarbonate butyl ester of the formula C 20 H 22 C1 2 O 5 The chemical structural formula is shown as follows:
the spirodiclofen diester mainly prevents and treats eggs, nymphs and female adult mites through contact poisoning and stomach poisoning effects, and the action mechanism of the spirodiclofen diester is to inhibit fat synthesis in pest mites and block energy metabolism. The insecticidal composition has outstanding ovicidal effect, has better control effect on harmful mites in different development stages, and can be used in each growth period of citrus. The pure product is white powdery solid; no pungent odor; melting point: 90.2 to 92.6 ℃; boiling point: 251 ℃; distribution coefficient: n-octanol/water Log Pow =4.9 (pH 7, 20 ℃).
Chinese patent application CN102060818A reports a synthesis method of spirodiclofen diester, 3- (2, 4-dichlorophenyl) -2-oxo-1-oxaspiro [4,5] -dec-3-en-4-ol and n-butyl chloroformate are synthesized into spirodiclofen diester by taking triethylamine as an acid-binding agent in dichloroethane solvent, after reaction, alkali washing and water washing are carried out for layering, the temperature is controlled, pressure is reduced for desolventization, solvent is added for recrystallization, the spirodiclofen diester product is obtained, the yield is 80%, and the chemical reaction formula is as follows:
another Chinese patent application CN101255147A also discloses the synthesis of spirodiclofen derivatives, 3- (2, 4-dichlorophenyl) -2-oxo-1-oxaspiro [4,5] -dec-3-ene-4-ol, in an aprotic organic solvent, a tertiary amine compound is used as an acid-binding agent to synthesize the spirodiclofen derivatives with chrysanthemoyl chloride, and after the reaction, the spirodiclofen derivatives are obtained by acid washing, alkali washing, water washing, layering, desolventizing and solvent adding recrystallization, and the yield is 90.1-95.5%.
In another chinese patent application CN104292197A, spirodiclofen is prepared by reacting 3- (2, 4-dichlorophenyl) -2-oxo-1-oxaspiro [4,5] -dec-3-en-4-ol and 2, 2-dimethylbutyryl chloride as raw materials and triethylamine as an acid-binding agent in an aprotic organic solvent, after the reaction is finished, the PH of the reaction solution is adjusted to 10-11, a water phase and an organic phase are obtained by layering, and the water phase is used as an alkali liquor in the next synthesis; washing the organic phase with water, drying with anhydrous sodium sulfate, heating and distilling at normal pressure, and desolventizing to recover triethylamine and the aprotic organic solvent to obtain a solid product. The removed solvent is used for the next batch of synthesis, and the solid product is recrystallized to obtain the spirodiclofen. The invention recycles triethylamine and dichloromethane and directly applies to the next batch of synthesis.
In the existing synthesis processes of spirodiclofen or spirodiclofen and derivatives thereof, the patent applications CN102060818A and CN101255147A both use triethylamine as acid-binding agents, and do not recycle and reuse the triethylamine. The process increases the difficulty of three-waste treatment, has higher production cost and is not beneficial to environmental protection. In the Chinese patent application CN104292197A, triethylamine is used as an acid-binding agent, dichloromethane is used as a solvent, an alkali liquor is added after the reaction to regulate the pH value to layering, anhydrous sodium sulfate is added into the separated organic layer for drying, the triethylamine and the dichloromethane are recovered by heating and distilling for recycling and are applied to the next batch, and the solid is added with 95% ethanol for direct crystallization to obtain the spirodiclofen. However, this process generates a large amount of anhydrous sodium sulfate solid waste, also increasing the cost of disposal; in addition, triethylamine remained in the desolventizing step is mixed with 95% ethanol for crystallization, and fresh ethanol is needed for each crystallization because excessive triethylamine remains, which can not affect the qualified product content but can cause the unqualified product pH value. But the crystallization mother liquor containing a large amount of ethanol, partial triethylamine and partial spirodiclofen products can not be used indiscriminately, thereby greatly increasing the production cost; in addition, the boiling point of dichloromethane is 39.8 ℃, the dichloromethane has the defect of easy volatilization, and the inevitable tail gas enters a three-waste treatment system and is burnt by an incinerator to generate carcinogen dioxin, thereby generating adverse effects on workshop workers and the surrounding environment.
Disclosure of Invention
The invention aims to provide a simpler synthesis method of spirodiclofen diester derivatives, which is expected to avoid the need of recycling triethylamine by not using triethylamine as an acid-binding agent, and avoid using anhydrous sodium sulfate, ethanol and the like in the crystallization process of products so as to reduce the three-waste treatment of the synthesis process.
Although the choice of acid-binding agent may vary, acid chlorides are readily hydrolyzed by reaction with water, and in order to avoid hydrolysis, the prior art describes methods of preparation in which the reaction is carried out in anhydrous organic solvents. In order to match these anhydrous organic solvents, the choice of acid-binding agents is limited, and more environmentally friendly acid-binding agents such as inorganic bases cannot be used.
However, it is desirable in the present invention to use 3- (2, 4-dichlorophenyl) -2-oxo-1-oxaspiro [4,5] -dec-3-en-4-ol and acid chloride as raw materials, and an inorganic base as an acid-binding agent in a hydrophilic aprotic organic solvent containing water, by selecting appropriate conditions so that the reaction can be normally carried out even when a certain amount of water is present in the reaction system. After the reaction is finished, water can be directly added to filter out products, the solvent evaporated from the residual mother liquor can be directly recycled, and the wastewater after the solvent is evaporated can enter a wastewater treatment system and can also be recycled to the process after treatment. The method is expected to avoid the use and recovery of tertiary amine on the premise of synthesizing the spirodiclofen derivative with high efficiency and high yield, so that no ammonia nitrogen and nitrogen oxide are discharged from waste water and waste gas.
Because the preparation method does not use solvents such as dichloromethane, the emission of halogenated substances is avoided, cancerogen dioxin is not generated by burning, and the preparation method is environment-friendly. These environmentally friendly solvents help overcome the problem of difficult separation of the reaction solvent or acid-binding agent from the crystallization solvent.
Based on the thought, the invention provides a preparation method of spirodiclofen diester derivative, and the preparation method is to use 3- (2, 4-dichlorophenyl) -2-oxo-1-oxaspiro [4,5]]-deca-3-en-4-ol and acyl chloride are used as raw materials, inorganic base is used as an acid-binding agent to react in a hydrophilic aprotic organic solvent, water is added to crystallize after the reaction is finished, and a solid-phase product obtained by filtering is the spirodiclofen diester derivative with the chemical formula
Wherein R is
The acyl chloride is chloroformic acid n-butyl ester or 2, 2-dimethyl butyryl chloride.
The chemical reaction formula of the invention is as follows:
in the invention, the inorganic base is one or a mixture of several inorganic bases selected from sodium carbonate, potassium carbonate, sodium hydroxide or potassium hydroxide.
According to a preferred embodiment, the hydrophilic aprotic organic solvent is an etheric aprotic organic solvent, in particular selected from the group consisting of ethylene glycol dimethyl ether, ethylene glycol monomethyl ether, ethylene glycol monobutyl ether, ethylene glycol hexyl ether, acetone, 1, 4-dioxane, tetrahydrofuran or 2-methyltetrahydrofuran.
In the present invention, the hydrophilicity of the aprotic organic solvent is very critical, and they are miscible with water, ensuring that inorganic bases can be used as acid-binding agents in the reaction. Although some prior arts also mention that some ethers such as methyl tert-butyl ether can be used as the aprotic organic solvent, methyl tert-butyl ether is a non-hydrophilic solvent, so that inorganic base cannot be used and only conventional triethylamine or the like can be selected as the acid-binding agent.
In a particularly preferred embodiment, ethylene glycol dimethyl ether is used as solvent.
In the present invention, it is preferred that the molar ratio of 3- (2, 4-dichlorophenyl) -2-oxo-1-oxaspiro [4,5] -dec-3-en-4-ol, acid chloride and inorganic base is 1 to 1.2. Wherein, when the inorganic base is a mixture of two or more inorganic bases, the ratio of the total molar amount of 3- (2, 4-dichlorophenyl) -2-oxo-1-oxaspiro [4,5] -dec-3-en-4-ol and the inorganic base is 1 to 1.5.
Because the reaction system selects the hydrophilic aprotic organic solvent, a certain amount of water in the reaction system is favorable for dissolving the inorganic base. However, control of the reaction conditions is particularly important in order to avoid hydrolysis of the acid chloride. The inventors of the present invention repeatedly verified that the reaction was normally carried out under the condition of controlling the reaction temperature at 0 to 30 ℃ when the total water content of the reaction system was 5 to 35% by mass.
Particularly, the preparation method comprises the steps of putting a hydrophilic aprotic organic solvent and an inorganic base into a reaction kettle to serve as an acid-binding agent, controlling the total water content in the reaction system to be 5-35% of the total mass of the reaction system, mixing, putting 3- (2, 4-dichlorophenyl) -2-oxo-1-oxaspiro [4,5] -dec-3-ene-4-ol, dropwise adding acyl chloride to react, controlling the reaction temperature to be in a proper range by controlling the dropwise adding speed of the acyl chloride, adding water into the reaction kettle after the reaction is finished, stirring, separating out solids, and centrifugally filtering to obtain the product.
Wherein the water in the reaction system is derived from water brought into the reaction system after materials (such as a solvent in a mother liquor) generated in a subsequent stage are recycled, or water additionally added into the system for ensuring that the inorganic base can be dissolved. The control of the total water content is very important for ensuring that the reaction is effectively carried out, and the water content is lower than 5 percent, so that the inorganic base is not dissolved or can not be completely dissolved, and the reaction is not complete; above 35% this will lead to hydrolysis of the acid chloride.
In the present invention, the moisture content in the reaction system was measured by a Karl Fischer moisture meter.
Furthermore, when R is
When the reaction temperature is too high, the dropping speed is adjusted to be 0-30 ℃ by controlling the dropping speed of the n-butyl chloroformate. Stopping dripping if the reaction temperature is lower than 0 ℃, slightly heating to above 0 ℃ and continuing dripping; if the reaction temperature is higher than 30 ℃, the temperature is reduced to 0-30 ℃ for continuous dripping, otherwise, acyl chloride can be hydrolyzed. Therefore, the choice of reaction temperature is critical to the smooth performance of the preparation of the present invention.
Further preferably, when R is
When the reaction is carried out, the reaction temperature is controlled to be 20-30 ℃ by controlling the dropping speed of the chloroformic acid n-butyl ester.
When R is
The reaction temperature was set to 0 to 30 ℃ by controlling the dropping speed of 2, 2-dimethylbutyrylchloride, and similarly, the dropping speed should be adjusted downward when the reaction temperature is too high. Stopping dripping if the reaction temperature is lower than 0 ℃, slightly heating to above 0 ℃ and continuing dripping; if the reaction temperature is higher than 30 ℃, the temperature is reduced to 0-30 ℃ for continuous dripping, otherwise, acyl chloride can be hydrolyzed.
Further preferably, when R is
In this case, the reaction temperature was controlled to 10 to 20 ℃ by controlling the dropping rate of 2, 2-dimethylbutyrylchloride.
Compared with the prior art, the preparation method adopts the hydrophilic ether organic solvent and the inorganic base as the acid-binding agent, and in order to ensure that the reaction can be effectively carried out and the hydrolysis of the raw materials is avoided, the preparation method selects the reaction temperature and limits the water content in the reaction system to ensure that the reaction can be smoothly carried out. The preparation method avoids using triethylamine through the improvement, so that the triethylamine does not need to be recycled, the production process is simplified, and the production cost is greatly reduced. And the wastewater and waste gas generated in the synthesis process do not contain ammonia nitrogen and nitrogen oxide emission, and the method is environment-friendly.
On the other hand, the aprotic organic solvent, particularly hydrophilic ethers, is used as the solvent, so that the aprotic organic solvent can be matched with an environment-friendly inorganic alkali acid-binding agent on the one hand, and on the other hand, the use of volatile dichloromethane or dichloroethane is avoided, the solvent loss is low, no halide exists in tail gas, no carcinogen dioxin is generated by burning, and the environment-friendly effect is realized.
In addition, by selecting proper reaction conditions and matching with a hydrophilic ether solvent and an inorganic base acid-binding agent, the reaction of the invention can be carried out in a system with certain water content, so that after the reaction is finished, water contained in the recovered solvent can not influence the reaction, and the water-containing organic solvents can be reused in the process as long as the total water content in the reaction system is controlled within a specific range. Compared with the prior art, the traditional synthesis process is limited by the characteristic that acyl chloride is easy to hydrolyze, and an anhydrous system is adopted for reaction, so that the solvent can be recycled by removing water in the recycled solvent. Therefore, the preparation method avoids the separation of the organic solvent and the water, and effectively simplifies the process. The solvent is recycled, so that the waste liquid in the system can be directly recycled for reaction (for example, the waste liquid is used for adjusting the total water content in the system) after being treated by a waste water system, and the requirement of reducing the emission of the waste water in the chemical industrial park is met.
The invention has the advantages of less equipment investment, low production cost, short production period and obvious improvement on the prior process technology, and the verified yield reaches 97 percent.
Detailed Description
The following examples serve to illustrate the technical solution of the present invention without limiting it.
Example 1
When R is
Sodium carbonate is used as an acid-binding agent, glycol dimethyl ether is used as a solvent, and the reaction formula is as follows:
adding 1600kg of ethylene glycol dimethyl ether and 180kg of water into a 5000L enamel kettle, starting stirring, adding 168kg of sodium carbonate into the kettle, cooling to 25-30 ℃, adding 450kg of 3- (2, 4-dichlorophenyl) -2-oxo-1-oxaspiro [4,5] -dec-3-ene-4-ol into the kettle, dropwise adding 206kg of n-butyl chloroformate at about 25 ℃, controlling the temperature in the kettle to be 25-30 ℃ during dropwise adding, controlling the dropwise adding time to be 2 hours, carrying out heat preservation reaction for 1 hour after the dropwise adding is finished, sampling and detecting, and displaying that the content of the raw material cyclized substance is less than 0.3% by liquid chromatography analysis, thus finishing the reaction.
After the reaction was completed, 1200kg of water was added to the reactor, and the mixture was stirred for 1 hour. Centrifuging and filtering to obtain 579kg of product.
The obtained product is confirmed by nuclear magnetic hydrogen spectrum, and the result is 1 H NMR(400MHz,CDCl 3 ):δ＝7.39-7.42(s,1H),7.33-7.38(s,1H),7.27-7.32(s,1H),4.09-4.11(s,2H), 1.77-1.89(m,9H),1.56-1.60(m,2H),1.30-1.35(m,3H),0.90-0.93(s, 3H)。ESI-MS:435(M+Na)。
The results confirm that the obtained product is spirodiclofen diester with the content of 98.1 percent and the yield of 97.5 percent.
The mother liquor obtained by filtering enters a mother liquor filtering treatment kettle, and glycol dimethyl ether is collected by normal pressure distillation and can be recycled.
After the atmospheric distillation is finished, the residual wastewater in the kettle enters a wastewater treatment system for treatment (the wastewater contains glycol dimethyl ether, water, sodium chloride, impurities and the like), and the treated wastewater is recycled and reused.
Example 2
When R isIs composed of
Potassium carbonate is used as an acid-binding agent, tetrahydrofuran is used as a solvent, and the reaction formula is shown as
adding 1600kg of tetrahydrofuran and 165kg of water into a 5000L enamel kettle, starting stirring, adding 220kg of potassium carbonate into the kettle, cooling to 20-25 ℃, adding 450kg of 3- (2, 4-dichlorophenyl) -2-oxo-1-oxaspiro [4,5] -dec-3-ene-4-ol into the kettle, dropwise adding 210kg of chloroformic acid n-butyl ester at about 25 ℃, controlling the temperature in the kettle to be 25-30 ℃ during dropwise adding, controlling the dropwise adding time to be 2 hours after dropwise adding, carrying out heat preservation reaction for 1 hour, carrying out sampling detection and analysis, and finishing the reaction when the content of a raw material cyclization product is less than 0.3%.
After the reaction was completed, 1300kg of water was added to the reactor, and the mixture was stirred for 1 hour. Centrifugal filtration is carried out to obtain 582kg of product.
Similar results were obtained in the same manner as in example 1, and it was confirmed that the obtained product was spirodiclofen, whose content was 98.6% and yield was 98.0%.
And (4) allowing the obtained mother liquor to enter a mother liquor filtering treatment kettle, distilling at normal pressure, collecting tetrahydrofuran, and recycling. After the normal pressure steaming is finished, the residual wastewater in the kettle enters a wastewater treatment system for treatment, and the treated wastewater is recycled and reused.
Example 3
When R is
Sodium bicarbonate is used as an acid-binding agent, 1, 4-dioxane is used as a solvent, and the chemical formula is as follows:
1600kg of 1, 4-dioxane and 280kg of water are added into a 5000L enamel kettle, stirring is started, 138kg of sodium bicarbonate is added into the kettle, the temperature is reduced to 20-25 ℃, 450kg of 3- (2, 4-dichlorophenyl) -2-oxo-1-oxaspiro [4,5] -dec-3-ene-4-ol is added into the kettle, 208kg of chloroformic acid n-butyl ester is dropwise added at the temperature of about 25 ℃, the temperature in the kettle is controlled to be 25-30 ℃ during dropwise adding, the dropwise adding time is controlled to be 2 hours, the temperature is kept for reaction for 1 hour after the dropwise adding is finished, sampling detection and analysis are carried out, and when a cyclization product of a raw material is less than 0.3%, the reaction is finished.
After the reaction was completed, 1600kg of water was added to the kettle and stirred for 1 hour after the addition. Centrifuging and filtering to obtain 580kg of product.
Similar results were obtained in the same manner as in example 1, and it was confirmed that the obtained product was spirodiclofen, the content was 98.5%, and the yield was 97.7%. The filtered mother liquor enters a filtered mother liquor treatment kettle, and the 1, 4-dioxane is collected by normal pressure distillation and recovered for reuse. After the normal pressure steaming is finished, the residual wastewater in the kettle enters a wastewater treatment system for treatment, and the treated wastewater is recycled and reused.
Example 4
When R is
The molar ratio is 0.9:0.18 of sodium hydroxide and sodium carbonate are used as acid-binding agents, tetrahydrofuran is used as a solvent, and the reaction formula for synthesizing the spirodiclofen is as follows:
adding 1600kg of tetrahydrofuran and 200kg of water into a 5000L enamel kettle, starting stirring, adding 52kg of sodium hydroxide and 28kg of sodium carbonate into the kettle, cooling to 10-15 ℃, adding 450kg of 3- (2, 4-dichlorophenyl) -2-oxo-1-oxaspiro [4,5] -dec-3-ene-4-ol into the kettle, dropwise adding 207kg of 2, 2-dimethylbutyrylchloride at about 10 ℃, controlling the temperature in the kettle to be 10-20 ℃ during dropwise adding, controlling the dropwise adding time to be 2 hours, carrying out heat preservation reaction for 1 hour after the dropwise adding is finished, carrying out sampling detection and analysis, and finishing the reaction when the content of a raw material cyclization product is less than 0.3%.
After the reaction was completed, 1500kg of water was added to the kettle, and the mixture was stirred for 1 hour. Centrifugal filtration is carried out to obtain 578kg of product.
The nuclear magnetic hydrogen spectrum verification of the obtained product shows that the result is as follows: 1 H NMR(400MHz,CDCl 3 ):δ＝7.31-7.43(m,3H),1.84-1.78(m,10H),1.51-1.56(q,2H),1.18(s,6H), 0.74-0.78(t,3H)。ESI-MS:411.4(M+1)。
the obtained product is confirmed to be spirodiclofen, the content is 98.5 percent, and the yield is 97.8 percent. And (4) allowing the filtered mother liquor to enter a filtered mother liquor treatment kettle, distilling at normal pressure, collecting tetrahydrofuran, and recycling. After the normal pressure steaming is finished, the residual wastewater in the kettle enters a wastewater treatment system for treatment, and the treated wastewater is recycled and reused.
Example 5
When R is
The molar ratio is 0.8:0.24 of sodium hydroxide and potassium carbonate are used as acid-binding agents, glycol dimethyl ether is used as a solvent, and the reaction formula is as follows:
1600kg of ethylene glycol dimethyl ether and 185kg of water are added into a 5000L enamel kettle, stirring is started, 46kg of sodium hydroxide and 48kg of potassium carbonate are added into the kettle, the temperature is reduced to 10-15 ℃, 450kg of 3- (2, 4-dichlorophenyl) -2-oxo-1-oxaspiro [4,5] -dec-3-en-4-ol is added into the kettle, 207kg of 2, 2-dimethylbutyrylchloride is dropwise added at about 10 ℃, the temperature in the kettle is controlled to be 10-20 ℃ during dropwise adding, the dropwise adding time is controlled to be 2 hours, the temperature is kept for reaction for 1 hour after the dropwise adding is finished, sampling detection and analysis are carried out, and when the content of a raw material cyclization product is less than 0.3%, the reaction is finished.
After the reaction was completed, 1350kg of water was added to the kettle, and the mixture was stirred for 1 hour. Centrifugal filtration is carried out to obtain 576kg of products,
similar results were obtained in the same manner as in example 4, and it was confirmed that the obtained product was spirodiclofen, the content was 98.2%, and the yield was 97.5%. The filtered mother liquor enters a filtered mother liquor treatment kettle, and glycol dimethyl ether is collected by normal pressure distillation and recycled. After the normal pressure steaming is finished, the residual wastewater in the kettle enters a wastewater treatment system for treatment, and the treated wastewater is recycled and reused.
Example 6
When R is
Potassium carbonate is used as an acid-binding agent, acetone is used as a solvent, and the reaction formula is as follows:
1200kg of acetone and 160kg of water are added into a 5000L enamel kettle, stirring is started, 225kg of potassium carbonate is added into the kettle, the temperature is reduced to 10-15 ℃, 450kg of 3- (2, 4-dichlorophenyl) -2-oxo-1-oxaspiro [4,5] -dec-3-ene-4-ol is added into the kettle, 210kg of 2, 2-dimethylbutyrylchloride is dropwise added at the temperature of about 10 ℃, the temperature in the kettle is controlled to be 10-20 ℃ during dropwise adding, the dropwise adding time is controlled to be 2 hours after dropwise adding, the temperature is kept for reaction for 1 hour after dropwise adding, sampling, detecting and analyzing, and when the content of a raw material cyclization is less than 0.3%, the reaction is finished.
After the reaction was completed, 1500kg of water was added to the kettle, and the mixture was stirred for 1 hour. After centrifugal filtration, 573kg of spirodiclofen product with the content of 98.3 percent and the yield of 97.0 percent are confirmed. The filtered mother liquor enters a filtered mother liquor treatment kettle, and acetone is collected by normal pressure distillation and recovered for reuse. After the normal pressure steaming is finished, the residual wastewater in the kettle enters a wastewater treatment system for treatment, and the treated wastewater is recycled and reused.
Claims (4)
1. A method for preparing spirodiclofen diester derivative comprises the steps of taking 3- (2, 4-dichlorophenyl) -2-oxo-1-oxaspiro [4,5] -dec-3-ene-4-ol and acyl chloride as raw materials, taking inorganic base as an acid-binding agent to react in a hydrophilic aprotic organic solvent, adding water to crystallize after the reaction is finished, and filtering to obtain a solid-phase product, namely spirodiclofen diester derivative, wherein the chemical formula of the solid-phase product is 5-35% of the total mass of the system
Wherein R is
When R is
When the reaction temperature is controlled to be 20-30 ℃; when R is
When the reaction temperature is controlled to be 10-20 ℃; the hydrophilic aprotic organic solvent is a hydrophilic ether solvent.
2. The preparation method according to claim 1, wherein the inorganic base is selected from one or more of sodium carbonate, potassium carbonate, sodium hydroxide and potassium hydroxide.
3. The method according to claim 1, wherein the hydrophilic ether solvent is selected from the group consisting of ethylene glycol dimethyl ether, ethylene glycol monomethyl ether, ethylene glycol monobutyl ether, ethylene glycol hexyl ether, 1, 4-dioxane, tetrahydrofuran, and 2-methyltetrahydrofuran.
4. The process according to claim 1, wherein the molar ratio of 3- (2, 4-dichlorophenyl) -2-oxo-1-oxaspiro [4,5] -dec-3-en-4-ol, acid chloride and inorganic base is 1.
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