CN117680061A - Full-continuous flow chemical synthesis device and method for clethodim - Google Patents
Full-continuous flow chemical synthesis device and method for clethodim Download PDFInfo
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- 239000005497 Clethodim Substances 0.000 title claims abstract description 37
- SILSDTWXNBZOGF-JWGBMQLESA-N clethodim Chemical compound CCSC(C)CC1CC(O)=C(C(CC)=NOC\C=C\Cl)C(=O)C1 SILSDTWXNBZOGF-JWGBMQLESA-N 0.000 title claims abstract description 37
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 28
- 238000000034 method Methods 0.000 title claims abstract description 26
- 238000006243 chemical reaction Methods 0.000 claims abstract description 61
- 239000007788 liquid Substances 0.000 claims abstract description 61
- 239000000463 material Substances 0.000 claims description 63
- 239000010410 layer Substances 0.000 claims description 26
- 239000012530 fluid Substances 0.000 claims description 25
- 239000000243 solution Substances 0.000 claims description 20
- 239000012071 phase Substances 0.000 claims description 16
- 239000000047 product Substances 0.000 claims description 15
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 11
- -1 polytetrafluoroethylene Polymers 0.000 claims description 11
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 claims description 10
- 238000003860 storage Methods 0.000 claims description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 230000015572 biosynthetic process Effects 0.000 claims description 9
- 229910000856 hastalloy Inorganic materials 0.000 claims description 9
- 229910001220 stainless steel Inorganic materials 0.000 claims description 9
- 239000010935 stainless steel Substances 0.000 claims description 9
- 239000012295 chemical reaction liquid Substances 0.000 claims description 8
- 239000011229 interlayer Substances 0.000 claims description 7
- 238000002156 mixing Methods 0.000 claims description 7
- 239000003208 petroleum Substances 0.000 claims description 7
- 239000000376 reactant Substances 0.000 claims description 6
- 230000001105 regulatory effect Effects 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- QCWXUUIWCKQGHC-UHFFFAOYSA-N Zirconium Chemical compound [Zr] QCWXUUIWCKQGHC-UHFFFAOYSA-N 0.000 claims description 5
- 230000001276 controlling effect Effects 0.000 claims description 5
- 239000011521 glass Substances 0.000 claims description 5
- 239000011259 mixed solution Substances 0.000 claims description 5
- 229920001343 polytetrafluoroethylene Polymers 0.000 claims description 5
- 239000004810 polytetrafluoroethylene Substances 0.000 claims description 5
- 229910052715 tantalum Inorganic materials 0.000 claims description 5
- GUVRBAGPIYLISA-UHFFFAOYSA-N tantalum atom Chemical compound [Ta] GUVRBAGPIYLISA-UHFFFAOYSA-N 0.000 claims description 5
- 239000002699 waste material Substances 0.000 claims description 5
- 229910052726 zirconium Inorganic materials 0.000 claims description 5
- VOYADQIFGGIKAT-UHFFFAOYSA-N 1,3-dibutyl-4-hydroxy-2,6-dioxopyrimidine-5-carboximidamide Chemical compound CCCCn1c(O)c(C(N)=N)c(=O)n(CCCC)c1=O VOYADQIFGGIKAT-UHFFFAOYSA-N 0.000 claims description 4
- 239000012074 organic phase Substances 0.000 claims description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 3
- KXKVLQRXCPHEJC-UHFFFAOYSA-N acetic acid trimethyl ester Natural products COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 claims description 3
- 239000003513 alkali Substances 0.000 claims description 3
- 238000006482 condensation reaction Methods 0.000 claims description 3
- 230000004907 flux Effects 0.000 claims description 2
- 230000005484 gravity Effects 0.000 claims description 2
- 238000006386 neutralization reaction Methods 0.000 claims description 2
- 238000004062 sedimentation Methods 0.000 claims description 2
- 239000012043 crude product Substances 0.000 claims 1
- 230000002401 inhibitory effect Effects 0.000 claims 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 claims 1
- 238000005809 transesterification reaction Methods 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 6
- 238000004519 manufacturing process Methods 0.000 abstract description 5
- 239000000126 substance Substances 0.000 abstract description 5
- 239000000575 pesticide Substances 0.000 abstract description 3
- 238000001308 synthesis method Methods 0.000 abstract description 2
- 230000003321 amplification Effects 0.000 abstract 1
- 230000010354 integration Effects 0.000 abstract 1
- 238000003199 nucleic acid amplification method Methods 0.000 abstract 1
- QDHHCQZDFGDHMP-UHFFFAOYSA-N Chloramine Chemical compound ClN QDHHCQZDFGDHMP-UHFFFAOYSA-N 0.000 description 9
- 241000196324 Embryophyta Species 0.000 description 7
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 6
- UOORRWUZONOOLO-OWOJBTEDSA-N (E)-1,3-dichloropropene Chemical compound ClC\C=C\Cl UOORRWUZONOOLO-OWOJBTEDSA-N 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 238000000926 separation method Methods 0.000 description 4
- UOORRWUZONOOLO-UHFFFAOYSA-N telone II Natural products ClCC=CCl UOORRWUZONOOLO-UHFFFAOYSA-N 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical group [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 239000003444 phase transfer catalyst Substances 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- RRUDCFGSUDOHDG-UHFFFAOYSA-N acetohydroxamic acid Chemical compound CC(O)=NO RRUDCFGSUDOHDG-UHFFFAOYSA-N 0.000 description 2
- 229960001171 acetohydroxamic acid Drugs 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 238000005265 energy consumption Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 230000002363 herbicidal effect Effects 0.000 description 2
- 239000004009 herbicide Substances 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 230000002147 killing effect Effects 0.000 description 2
- 238000000622 liquid--liquid extraction Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000002808 molecular sieve Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 2
- 238000010791 quenching Methods 0.000 description 2
- 230000000171 quenching effect Effects 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000000638 solvent extraction Methods 0.000 description 2
- 230000002194 synthesizing effect Effects 0.000 description 2
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 2
- QQKAZZAULUMMKR-UHFFFAOYSA-N 2-n-hydroxybenzene-1,2-dicarboxamide Chemical compound NC(=O)C1=CC=CC=C1C(=O)NO QQKAZZAULUMMKR-UHFFFAOYSA-N 0.000 description 1
- 229940126062 Compound A Drugs 0.000 description 1
- 241000234653 Cyperus Species 0.000 description 1
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
- 241001070944 Mimosa Species 0.000 description 1
- 235000016462 Mimosa pudica Nutrition 0.000 description 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
- PXAJQJMDEXJWFB-UHFFFAOYSA-N acetone oxime Chemical compound CC(C)=NO PXAJQJMDEXJWFB-UHFFFAOYSA-N 0.000 description 1
- 125000005262 alkoxyamine group Chemical group 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 238000005112 continuous flow technique Methods 0.000 description 1
- 238000010924 continuous production Methods 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- FWFSEYBSWVRWGL-UHFFFAOYSA-N cyclohex-2-enone Chemical compound O=C1CCCC=C1 FWFSEYBSWVRWGL-UHFFFAOYSA-N 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 229930003935 flavonoid Natural products 0.000 description 1
- 150000002215 flavonoids Chemical class 0.000 description 1
- 235000017173 flavonoids Nutrition 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 150000002443 hydroxylamines Chemical class 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
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- Physical Or Chemical Processes And Apparatus (AREA)
Abstract
The invention belongs to the technical field of pesticide chemical industry, and particularly relates to a full-continuous flow chemical synthesis device and method of clethodim. The invention adopts a multi-step continuous reaction system, and provides a clethodim full-continuous chemical synthesis device according to a linear synthesis method through sequential connection of a feed pump, a micro-mixer, a micro-channel reactor, a back pressure valve, a liquid-liquid separator and an online filter, so as to realize continuous manufacture of clethodim. The clethodim full-continuous chemical synthesis device can stably produce products with consistent quality, has high integration degree, small production occupation area and high unit productivity, can adjust the yield according to requirements, and avoids the amplification effect of a kettle type process.
Description
Technical Field
The invention belongs to the technical field of preparation of pesticides for preventing and killing grassy weeds, and particularly relates to a full-continuous flow chemical synthesis device and method for clethodim.
Background
Clethodim (also known as Sai-Di, lei-Tong), chemical name is 2-1- [ (3-chloro-2-allyl) oxy ] iminopropyl-5- [2- (ethyl) propyl ] -3-yl-2-cyclohexene-1-one, is a systemic conduction type stem and leaf treatment herbicide, and has strong killing effect mainly against gramineous weeds. It is applied to the stem and leaf of weed, and is absorbed and transferred to meristem to inhibit the biosynthesis of branched fatty acid and flavonoid in sensitive plant, so as to destroy the cell division of plant, inhibit the activity of meristem and delay growth. Weeds fade and die within 1-3 weeks after application, and leaves dry and die. However, they degrade rapidly in resistant plants to form polar products and lose activity rapidly. Little or no activity on cyperus and dicotyledonous plants.
The chemical structural formula is as follows:
the chemical name of the chloroamine is O-3-chloro-2-propenyl hydroxylamine alkoxy amine compound, and the alkoxy amine group is introduced into ketone compounds in the organic synthesis and the production of new drugs, so that the chloroamine is an important pesticide and medical intermediate, is particularly widely used for synthesizing cyclohexenone herbicide, and is a key intermediate in the clethodim synthesis process. The chemical structural formula is as follows:
in the synthetic route of clethodim, the chlor-amine and intermediate essence trione undergo condensation reaction to generate the clethodim as a final product, and the reaction equation is as follows:
at present, three methods for synthesizing the chloramine compound X are reported in domestic and foreign literature, and the synthetic route is as follows:
in the route I, a large amount of hydrogen chloride gas is introduced into toluene solution of acetonitrile and absolute ethyl alcohol, after long-time stirring, hydroxylamine hydrochloride aqueous solution is dropwise added, stirring is carried out until an organic layer is separated, a compound A is formed, tetrabutylammonium bromide is used as a phase transfer catalyst, and the tetrabutylammonium bromide reacts with trans-1, 3-dichloropropene to obtain a product of a chloramine compound X. The method uses a large amount of hydrogen chloride gas, has serious pollution and corrosion, uses a relatively expensive phase transfer catalyst, and is not beneficial to industrialization in terms of cost and environmental protection.
In the scheme II, N-hydroxyphthalamide and trans-1, 3-dichloropropene are subjected to alkylation reaction by taking dimethyl sulfoxide as a solvent to obtain a compound B, and the reaction operation is simple, so that the compound B can be obtained at normal temperature. However, in the next reaction, the reaction of the compound B and the hydrazine in the ethanol solution needs to be carried out under absolute anhydrous conditions, the anhydrous hydrazine is a highly toxic product, the operation is extremely responsible, the environment is also greatly polluted, and in addition, the anhydrous hydrazine is expensive.
In the route III, ethyl acetate and hydroxylamine hydrochloride are used as raw materials, acetohydroxamic acid is obtained through an acetamido reaction, then alkylation reaction is carried out on the acetohydroxamic acid and trans-1, 3-dichloropropene to obtain a compound C, and finally hydrochloric acid is used for hydrolyzing the compound C to obtain the chloramine.
At present, the route III is a method for industrially preparing the chloramine and is produced in batch by a batch kettle. The method has the advantages of small production scale, low speed, long reaction period, difficult control of the process, low yield, serious resource waste, serious environmental pollution, and easy safety accidents if the partial reaction is operated improperly at a higher temperature. Patent CN114105810a discloses a continuous process for the preparation of chloramine, which, although considerably shorter than the tank reactor time, is independent of each step of reaction, requires recovery of the switching solvent, consumes very much energy and time, and is discontinuous in process.
Liu Jianqing et al prepared acetoxime from hydroxylamine salt and acetone, and then added trans-1, 3-dichloropropene and a phase transfer catalyst to react to obtain chloramine. The method has higher conversion rate and yield, but long reaction period, high temperature and increased risk coefficient.
Disclosure of Invention
In order to overcome the defects of long reaction time, large potential safety hazard, high energy consumption and low efficiency of the traditional intermittent kettle type synthesis mode, the invention provides the full-continuous flow chemical synthesis device and method for clethodim.
The invention provides a full continuous flow chemical synthesis device and method of clethodim, which are sequentially connected by 9 feed pumps, 6 micromixers, 5 microchannel reactors, 3 back pressure valves, 2 liquid-liquid separators and 2 liquid storage tanks according to a clethodim synthesis route to form a full continuous chemical synthesis device matched with the clethodim synthesis route; the method comprises the following steps:
the outlets of the first pump and the second pump are connected to two inlets of the first micro-mixer, the outlet of the first micro-mixer is connected to the inlet of the first micro-channel reactor, the outlet of the first micro-channel reactor and the outlet of the third pump are connected to two inlets of the second micro-mixer, the outlet of the second micro-mixer is connected with the inlet of the second micro-channel reactor, the outlet of the second micro-channel reactor and the outlet of the fourth pump are connected to two inlets of the third micro-mixer, the outlet of the third micro-mixer is connected with the inlet of the third micro-channel reactor, and the outlet of the third micro-channel reactor is connected to the first back pressure valve; the outlet of the first back pressure valve and the outlet of the fifth pump are connected with two inlets of the fourth micro-mixer, the outlet of the fourth micro-mixer is connected with the inlet of the first liquid-liquid separator, the light phase outlet of the first liquid-liquid separator is connected with the first liquid storage tank, the heavy phase outlet of the first liquid-liquid separator is connected with the inlet of the sixth pump, the outlet of the sixth pump and the outlet of the seventh pump are connected with two inlets of the fifth micro-mixer, the outlet of the fifth micro-mixer is connected with the inlet of the fourth micro-channel reactor, and the outlet of the fourth micro-channel reactor is connected with the second back pressure valve; the outlet of the second back pressure valve is connected with the inlet of the second liquid-liquid separator, the heavy phase outlet of the second liquid-liquid separator is connected with the second liquid storage tank, the light phase outlet of the second liquid-liquid separator is connected with the inlet of the eighth pump, the outlet of the eighth pump and the outlet of the ninth pump are connected to the two inlets of the sixth micro-mixer, the outlet of the sixth micro-mixer is connected to the inlet of the fifth micro-channel reactor, the outlet of the fifth micro-channel reactor is connected to the third back pressure valve, and the effluent of the third back pressure valve is a coarse clethodim product.
In the invention, the first, third, sixth, seventh, eighth and ninth pumps are stainless steel 316L plunger pumps for conveying solutions, and the second, fourth and fifth pumps are hastelloy plunger pumps for conveying solutions.
In the present invention, the first to fifth micromixers are a plurality of micromixers connected in series in a zigzag shape, as shown in fig. 2; the device comprises a plurality of back-shaped channels which are connected in series, wherein the first back-shaped channel is provided with a material inlet, and the last back-shaped channel is provided with a material outlet. (wherein, in one character-returning channel, one vertex of the character-returning is an inlet at one end, and is divided into two paths, and the two paths of the character-returning channel are passed through the two paths of the character-returning channel to the two vertices of the character-returning, and then the character-returning channel is turned back to the diagonal vertex to flow out and enter the inlet of the next character-returning channel); the fluid channel is round or square with the size of 100 mu m-20mm, the length of 1-100cm, the applicable flux of 1-3000mL/min, and the material is one or a combination of more of glass, polytetrafluoroethylene, stainless steel, hastelloy, tantalum material and zirconium material.
Preferably, the first to fifth microchannel reactors are tubular microreactors with built-in X-shaped mixing elements, as shown in FIG. 3. The tubular microreactor body is a tubular cavity and is used as a fluid channel; a series of X-shaped members 3 are arranged in the cavity, and a reactant inlet 1 and a reactant outlet 5 are respectively arranged at two ends of the cavity; the outside of the cavity is a heat exchange fluid interlayer, and two ends of the heat exchange fluid interlayer are respectively provided with a heat exchange fluid outlet 2 and a heat exchange fluid inlet 4; the diameter of the fluid channel is 100 mu m-20mm, the length is 1-1000m, and the material is one or the combination of a plurality of glass, polytetrafluoroethylene, stainless steel, hastelloy, tantalum material and zirconium material.
Preferably, the first liquid-liquid separator and the second liquid-liquid separator are designed according to the gravity sedimentation principle, as shown in fig. 4, the main body of the liquid-liquid separator is a cylindrical cavity, the upper end of the cavity is provided with a material inlet 6 to be separated, the upper end of the cavity is also provided with an upper light phase outlet 7, and the lower end of the cavity is provided with a lower heavy phase outlet 10; the outside of the cylindrical cavity is provided with a heat exchange fluid interlayer, the lower part of the heat exchange fluid interlayer is provided with a heat exchange fluid inlet 9, and the upper part of the heat exchange fluid interlayer is provided with a heat exchange fluid outlet 8. The separator has an inner diameter of 1-20cm and a height of 1-200cm, and is made of one or more of glass, polytetrafluoroethylene, stainless steel, hastelloy, tantalum and zirconium.
In the invention, the first back pressure valve, the second back pressure valve and the third back pressure valve are made of one of stainless steel or hastelloy, the size of the connecting pipeline is 1.6mm-10mm, and the pressure condition range is 0.1-10.0Mpa.
In the invention, the first material is methyl acetate, the second material is a mixed solution of hydroxylamine hydrochloride and alkali, the third material is trans-chloropropene chloride, the fourth material is a hydrochloric acid solution with the concentration of 6mol/L, the fifth material is ethyl acetate, the seventh material is a mixed solution of sodium hydroxide and petroleum ether, and the ninth material is a petroleum ether solution of essence trione;
in the invention, the temperature in the first micro-channel reactor is controlled within the range of-10 to 25 ℃; the residence time of the mixed reaction materials in the first micro-channel reactor is 0.1-30 minutes; the back pressure is 0.1-3.0 MPa in the reaction process; the temperature in the second microchannel reactor is controlled within the range of 60-80 ℃; the residence time of the mixed reaction materials in the second micro-channel reactor is 0.1-30 minutes; the back pressure is 0.1-5.0 MPa in the reaction process; the temperature in the third microchannel reactor is controlled within the range of 60-80 ℃; the residence time of the mixed reaction materials in the third micro-channel reactor is 0.1-30 minutes; the back pressure is 0.1-5.0 MPa in the reaction process; the temperature in the fourth microchannel reactor is controlled within the range of 25-40 ℃; the residence time of the mixed reaction materials in the fourth microchannel reactor is 0.1 to 10 minutes; the back pressure is 0.1-5.0 MPa in the reaction process; the temperature in the fifth microchannel reactor is controlled within the range of 30-50 ℃; the residence time of the mixed reaction materials in the fifth micro-channel reactor is 0.1-30 minutes; the back pressure is 0.1-5.0 MPa in the reaction process.
The invention has the beneficial effects that:
the method for preparing clethodim by adopting the full-continuous flow micro-reaction system comprising the micro-mixer, the micro-channel reactor and the continuous extraction separator which are sequentially communicated has the following advantages compared with the synthesis method adopting the traditional intermittent reaction kettle:
1. the full-continuous flow micro-channel reaction system has excellent mass transfer, heat transfer and material molecule mixing performance, so that the reaction time is greatly shortened, the reaction efficiency is greatly improved, and the full synthesis of clethodim can be completed from a few days of the traditional intermittent kettle reaction to about forty minutes;
2. the continuous liquid-liquid quenching, continuous liquid-liquid extraction and continuous liquid-liquid separation of the reaction liquid are simple and convenient to operate in a continuous flow process, the quenching speed is high, the process is safe, the separation effect is good, the extraction efficiency is high, the separation yield is close to the reaction yield, the reaction process and the liquid-liquid extraction separation process are continuously carried out, so that the efficiency of the total process is greatly improved, and the purity of the obtained product is high;
3. the continuous synthesis from raw materials to products is realized, the technological process is continuously carried out, the degree of automation is high, external intervention is not needed in the middle, the space-time efficiency is high, the number of operators and the labor intensity are greatly reduced, and the production cost is remarkably reduced;
4. the full continuous flow micro-channel chemical process can realize multiphase mixing, mass transfer and reaction in the reaction process, the conditions are mild, the operation is simple and convenient, a stirring device is not needed, the energy consumption of the process is greatly reduced, and the industrial production can be rapidly realized.
Drawings
FIG. 1 is a flow chart of a full continuous flow chemical synthesis apparatus for clethodim of the present invention.
FIG. 2 is a schematic representation of the structure of the micromixer of the present invention in series in a zigzag shape.
FIG. 3 is a schematic representation of the tubular microreactor of the present invention incorporating an X-shaped mixing element.
FIG. 4 is a schematic diagram of a liquid-liquid separator according to the present invention.
Reference numerals in the drawings: wherein, the device comprises a 1-reaction material inlet, a 2-heat exchange fluid outlet, a 3-X-shaped component, a 4-heat exchange fluid inlet, a 5-reaction material outlet, a 6-material inlet to be separated, a 7-upper light phase outlet, an 8-heat exchange fluid outlet and a 9-heat exchange fluid inlet; 10-lower heavy phase outlet.
Detailed Description
For the purpose of illustrating in detail the technical content, constructional features, achieved objects and effects of the technical solution, the following description is further made with reference to the accompanying drawings in conjunction with the specific embodiments. The present embodiment is implemented on the premise of the technical scheme of the present invention, and a detailed implementation manner and a specific operation process are provided, but the protection scope of the present invention is not limited to the following embodiments.
For a better description of the objects, technical solutions and advantages of the present invention, the present invention will be further described with reference to the following specific examples.
Example 1
Methyl acetate (1.05 eq.) and hydroxylamine hydrochloride (1.0 eq.), alkali (2.0 eq., 6.355M) were fed by pump 1 and pump 2, respectively, to a first micromixer for mixing, then into a first microchannel reactor 1 (volume: 1.5mL, inner diameter: 0.8 mm), the temperature in the first microchannel reactor 1 was controlled to 5 ℃, after 4 minutes of reaction (i.e., the residence time of the mixed reaction material in the microchannel reactor: 4 minutes), the solution of the reaction compound was discharged from the outlet of the first microchannel reactor 1, and was fed by pump 3 to a second micromixer for mixing, then into a second microchannel reactor (volume: 34mL, inner diameter: 0.8 mm), the temperature in the second microchannel reactor was controlled to 70 ℃, after 10 minutes of reaction (i.e. the residence time of the mixed reactants in the second microchannel reactor is 10 minutes), the reaction solution flows out of the outlet of the second microchannel reactor, is mixed with hydrochloric acid (3 equivalent, 6M) conveyed by a pump 4 in a third micromixer, then enters the third microchannel reactor (the volume is 34mL, the inner diameter is 0.8 mm), the temperature in the third microchannel reactor is controlled to be 70 ℃, after 12 minutes of reaction (i.e. the residence time of the mixed reactants in the third microchannel reactor is 15 minutes), the mixed solution flows out of the outlet of the third microchannel reactor, flows through a first back pressure valve, the reaction pressure in the first microchannel reactor, the second microchannel reactor and the third microchannel reactor is regulated and controlled, the reaction residence time is influenced by the inhibition gas, ensuring the stable flow of the reaction fluid in the microchannel reactor. The effluent of the first back pressure valve and the material 5 conveyed by the pump 5 are mixed in a fourth mixer and then conveyed into a first liquid-liquid separator, an organic phase and a water phase are layered in the first liquid-liquid separator, an upper layer outlet and a lower layer outlet are arranged in the first liquid-liquid separator, the upper layer outlet is connected with the tank 1, and separated upper layer waste liquid is stored. The lower layer outlet is connected with a pump 6, and the lower layer liquid is conveyed to a fifth micromixer through the pump 6, wherein the conveyed lower layer liquid is a material 6 (hydrochloride of the chloramine). The material 7 (1.08 equivalent, 2.23M petroleum ether solution of sodium hydroxide) is conveyed to a fifth micro-mixer through a pump 7, fully mixed in the fifth micro-mixer, then enters a fourth micro-channel reactor, a neutralization reaction occurs at 70 ℃, and the reaction liquid flowing out of the fourth micro-channel reactor flows through a second back pressure valve, wherein the second back pressure valve is used for regulating and controlling the reaction pressure in the fourth micro-channel reactor. The effluent liquid of the second back pressure valve enters a second liquid-liquid separator, an organic phase and a water phase are layered in the second liquid-liquid separator, an upper layer outlet and a lower layer outlet are arranged in the second liquid-liquid separator, and the lower layer outlet is connected with a tank 2 to store separated lower layer waste liquid. The upper layer outlet is connected with a pump 8, and the upper layer liquid is conveyed to a sixth micro-mixer through the pump 8, wherein the conveyed upper layer liquid is a material 8 (petroleum ether solution of chloramine). The material 9 (petroleum ether solution of the refined trione) is conveyed to a sixth micro-mixer through a pump 9, fully mixed in the sixth micro-mixer and then enters a fifth micro-channel reactor, the back pressure in the reaction process is 2.0MPa, the temperature in the fifth micro-channel reactor is controlled to be 50 ℃, after the reaction is carried out for 12 minutes, the reaction liquid flows out from an outlet of the fifth micro-channel reactor and flows through a third back pressure valve, and the third back pressure valve is used for regulating and controlling the reaction pressure in the fifth micro-channel reactor. The liquid flowing out of the third back pressure valve is a coarse product of clethodim, and the clethodim with high purity is obtained through recrystallization. The total yield of the multi-step continuous micro-reaction is 82% and the purity of the product is 97%.
Example 2
This example is identical to example 1, with the only difference that the base of this example is potassium hydroxide, and the resulting clethodim yield is 75% and the product purity is 97%.
Example 3
This example is identical to example 1, with the only difference that the micromixer described in the hydrolysis reaction of this example is a static micromixer, and the yield of clethodim obtained is 80% and the purity of the product is 97%.
Example 4
This example is identical to example 1, with the only difference that the third extractant in this example is cyclohexane. The total yield of the clethodim product is 86%, and the purity of the product is 97%.
Example 5
This example is identical to example 1, except that the water scavenger described in the condensation reaction of this example is a 4A molecular sieve (here not in the form of a split liquid, but rather the molecular sieve is used to directly absorb water). The total yield of the clethodim product is 65%, and the purity of the product is 97%.
In this text or in the figures, pump 1 refers to the first pump, and so on, pump 9 refers to pump 9; mix 1, the first micromixer, and so on, mix 6, the 6 th micromixer; reverse 1, the first microchannel reactor, and so on, reverse 5, the 5 th microchannel reactor; material 1, the first material, and so on, material 9, the ninth material; tank 1, the first liquid storage tank, and so on, tank 2, the 2 nd liquid storage tank. The first liquid-liquid separator and the second liquid-liquid separator are respectively referred to as the 1 part and the 2 part. Back 1-back 3 refer to the first through 3 rd back pressure valves, respectively.
Finally, it should be noted that the above embodiments are only for illustrating the technical solution of the present invention and not for limiting the scope of the present invention, and although the present invention has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that the technical solution of the present invention may be modified or substituted equally without departing from the spirit and scope of the technical solution of the present invention.
Claims (8)
1. A full-continuous flow chemical synthesis device of clethodim is characterized in that 9 feed pumps, 6 micromixers, 5 microchannel reactors, 3 back pressure valves, 2 liquid-liquid separators and 2 liquid storage tanks are sequentially connected according to a clethodim synthesis route to form a full-continuous flow chemical synthesis device matched with the clethodim synthesis route; the method comprises the following steps:
the outlets of the first pump and the second pump are connected to two inlets of the first micro-mixer, the outlet of the first micro-mixer is connected to the inlet of the first micro-channel reactor, the outlet of the first micro-channel reactor and the outlet of the third pump are connected to two inlets of the second micro-mixer, the outlet of the second micro-mixer is connected with the inlet of the second micro-channel reactor, the outlet of the second micro-channel reactor and the outlet of the fourth pump are connected to two inlets of the third micro-mixer, the outlet of the third micro-mixer is connected with the inlet of the third micro-channel reactor, and the outlet of the third micro-channel reactor is connected to the first back pressure valve; the outlet of the first back pressure valve and the outlet of the fifth pump are connected with two inlets of the fourth micro-mixer, the outlet of the fourth micro-mixer is connected with the inlet of the first liquid-liquid separator, the light phase outlet of the first liquid-liquid separator is connected with the first liquid storage tank, the heavy phase outlet of the first liquid-liquid separator is connected with the inlet of the sixth pump, the outlet of the sixth pump and the outlet of the seventh pump are connected with two inlets of the fifth micro-mixer, the outlet of the fifth micro-mixer is connected with the inlet of the fourth micro-channel reactor, and the outlet of the fourth micro-channel reactor is connected with the second back pressure valve; the outlet of the second back pressure valve is connected with the inlet of the second liquid-liquid separator, the heavy phase outlet of the second liquid-liquid separator is connected with the second liquid storage tank, the light phase outlet of the second liquid-liquid separator is connected with the inlet of the eighth pump, the outlet of the eighth pump and the outlet of the ninth pump are connected to the two inlets of the sixth micro-mixer, the outlet of the sixth micro-mixer is connected to the inlet of the fifth micro-channel reactor, the outlet of the fifth micro-channel reactor is connected to the third back pressure valve, and the effluent of the third back pressure valve is a coarse clethodim product.
2. The full continuous flow chemical synthesis device of clethodim according to claim 1, wherein the first, third, sixth, seventh, eighth and ninth pumps are stainless steel 316L plunger pumps for delivering solutions, and the second, fourth and fifth pumps are hastelloy plunger pumps for delivering solutions.
3. The full continuous flow chemical synthesis device of clethodim according to claim 1, wherein the first to sixth micromixers are a plurality of micromixers connected in series in a shape of a Chinese character 'hui', the first channel is provided with a material inlet, the last channel is provided with a material outlet, one vertex of the Chinese character 'hui' is an inlet at one end in one channel, the two channels are divided into two channels, the two channels are connected to the two vertices of the Chinese character 'hui', and the two channels are folded back to the diagonal vertex to flow out and enter the inlet of the next channel; the fluid channel is round or square with the size of 100 mu m-20mm, the length of 1-100cm, the applicable flux of 1-3000mL/min, and the material is one or a combination of more of glass, polytetrafluoroethylene, stainless steel, hastelloy, tantalum material and zirconium material.
4. The full continuous flow chemical synthesis device of clethodim according to claim 1, wherein the first, second, third, fourth and fifth micro-channel reactors are tubular micro-reactors with built-in X-shaped mixing members; the tubular microreactor body is a tubular cavity and is used as a fluid channel; a series of X-shaped components (3) are arranged in the cavity, and two ends of the cavity are respectively provided with a reactant inlet (1) and a reactant outlet (5); the outside of the cavity is a heat exchange fluid interlayer, and two ends of the heat exchange fluid interlayer are respectively provided with a heat exchange fluid outlet (2) and a heat exchange fluid inlet (4); the diameter of the fluid channel is 100 mu m-20mm, the length is 1-1000m, and the material is one or the combination of a plurality of glass, polytetrafluoroethylene, stainless steel, hastelloy, tantalum material and zirconium material.
5. The full continuous flow chemical synthesis device of clethodim according to claim 1, wherein the first and second liquid-liquid separators are designed according to gravity sedimentation principle, the inner diameter of the separator is 1-20cm, and the height is 1-200cm.
6. The full continuous flow chemical synthesis device of clethodim according to claim 1, wherein the first back pressure valve, the second back pressure valve and the third back pressure valve are made of one of stainless steel or hastelloy, the size of the connecting pipeline is 1.6mm-10mm, and the pressure condition range is 0.1-10.0MPa.
7. A method for the full continuous flow chemical synthesis of clethodim based on the device according to one of claims 1 to 6, characterized by the specific process steps:
the prepared first material and the second material are respectively conveyed into a first micro-mixer through a first pump and a second pump to be fully mixed, the mixed materials directly enter a first micro-channel reactor through a connected pipeline to carry out transesterification, the reaction liquid flowing out of the first micro-channel reactor and the third material conveyed by a third pump are fully mixed in a second micro-mixer and then directly enter the second micro-channel reactor, and SN is carried out in the second micro-channel reactor 2 Nucleophilic substitution reaction; the reaction liquid flowing out of the second micro-channel reactor and a fourth material conveyed by a fourth pump are fully mixed in a third micro-mixer and then directly enter the third micro-channel reactor, the reaction liquid flows through a first back pressure valve, and the first back pressure valve has the functions of regulating and controlling the reaction pressures in the first micro-channel reactor, the second micro-channel reactor and the third micro-channel reactor, inhibiting the gas from influencing the reaction residence time and ensuring the stable flow of the reaction fluid in the micro-channel reactors; the effluent of the first back pressure valve and a fifth material conveyed by a fifth pump are fully mixed in a fourth micromixer and then directly enter a first liquid-liquid separator, an organic phase and a water phase are layered in the first liquid-liquid separator, an upper layer outlet and a lower layer outlet are arranged in the first liquid-liquid separator, and the upper layer outlet is connected with a first liquid storage tank to store separated upper layer waste liquid; the lower layer outlet is connected with a sixth pump, the lower layer liquid and a seventh material conveyed by the seventh pump are fully mixed in a fifth micro-mixer and then directly enter a fourth micro-channel reactor, and neutralization reaction is carried out in the fourth micro-channel reactor; the reaction liquid flowing out of the fourth microchannel reactor flows through a second back pressure valve, and the second back pressure valve is used for regulating and controlling the reaction pressure in the fourth microchannel reactor; the effluent liquid of the second back pressure valve enters a second liquid-liquid separator, an organic phase and a water phase are layered in the second liquid-liquid separator, an upper layer outlet and a lower layer outlet are arranged in the second liquid-liquid separator, the lower layer outlet is connected with a second liquid storage tank, and separated lower layer waste liquid is stored; the outlet of the upper layer is connected with an eighth pump, the upper layer liquid and a ninth material conveyed by the ninth pump are fully mixed in a sixth micro-mixer and then directly enter a fifth micro-channel reactor, and condensation reaction is carried out in the fifth micro-channel reactor; the reaction liquid flowing out of the fifth micro-channel reactor flows through a third back pressure valve, and the third back pressure valve is used for regulating and controlling the reaction pressure in the fifth micro-channel reactor; the effluent liquid of the third back pressure valve is the crude product of clethodim;
the first material is methyl acetate, the second material is a mixed solution of hydroxylamine hydrochloride and alkali, the third material is trans-chloropropene chloride, the fourth material is a hydrochloric acid solution with the concentration of 6mol/L, the fifth material is ethyl acetate, the seventh material is a mixed solution of sodium hydroxide and petroleum ether, and the ninth material is a petroleum ether solution of refined trione.
8. The method for the full continuous flow chemical synthesis of clethodim according to claim 7, wherein the temperature in the first micro-channel reactor is controlled within the range of-10 to 25 ℃; the residence time of the mixed reaction materials in the first micro-channel reactor is 0.1-30 minutes; the back pressure is 0.1-3.0 MPa in the reaction process; the temperature in the second microchannel reactor is controlled within the range of 60-80 ℃; the residence time of the mixed reaction materials in the second micro-channel reactor is 0.1-30 minutes; the back pressure is 0.1-5.0 MPa in the reaction process; the temperature in the third microchannel reactor is controlled within the range of 60-80 ℃; the residence time of the mixed reaction materials in the third micro-channel reactor is 0.1-30 minutes; the back pressure is 0.1-5.0 MPa in the reaction process; the temperature in the fourth microchannel reactor is controlled within the range of 25-40 ℃; the residence time of the mixed reaction materials in the fourth microchannel reactor is 0.1 to 10 minutes; the back pressure is 0.1-5.0 MPa in the reaction process; the temperature in the fifth microchannel reactor is controlled within the range of 30-50 ℃; the residence time of the mixed reaction materials in the fifth micro-channel reactor is 0.1-30 minutes; the back pressure is 0.1-5.0 MPa in the reaction process.
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