CN115028576A - Production process of 3, 5-dichloro-2, 6-dimethyl-4-hydroxypyridine - Google Patents
Production process of 3, 5-dichloro-2, 6-dimethyl-4-hydroxypyridine Download PDFInfo
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- CN115028576A CN115028576A CN202210705398.3A CN202210705398A CN115028576A CN 115028576 A CN115028576 A CN 115028576A CN 202210705398 A CN202210705398 A CN 202210705398A CN 115028576 A CN115028576 A CN 115028576A
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- ZDPIZLCVJAAHHR-UHFFFAOYSA-N Clopidol Chemical compound CC1=NC(C)=C(Cl)C(O)=C1Cl ZDPIZLCVJAAHHR-UHFFFAOYSA-N 0.000 title claims abstract description 36
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 36
- 238000000034 method Methods 0.000 claims abstract description 51
- 239000004287 Dehydroacetic acid Substances 0.000 claims abstract description 49
- 235000019258 dehydroacetic acid Nutrition 0.000 claims abstract description 49
- JEQRBTDTEKWZBW-UHFFFAOYSA-N dehydroacetic acid Chemical compound CC(=O)C1=C(O)OC(C)=CC1=O JEQRBTDTEKWZBW-UHFFFAOYSA-N 0.000 claims abstract description 49
- 229940061632 dehydroacetic acid Drugs 0.000 claims abstract description 49
- PGRHXDWITVMQBC-UHFFFAOYSA-N dehydroacetic acid Natural products CC(=O)C1C(=O)OC(C)=CC1=O PGRHXDWITVMQBC-UHFFFAOYSA-N 0.000 claims abstract description 49
- 238000002425 crystallisation Methods 0.000 claims abstract description 43
- 230000008025 crystallization Effects 0.000 claims abstract description 43
- 239000002994 raw material Substances 0.000 claims abstract description 25
- 238000005660 chlorination reaction Methods 0.000 claims abstract description 23
- 238000000746 purification Methods 0.000 claims abstract description 19
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims abstract description 17
- 235000011114 ammonium hydroxide Nutrition 0.000 claims abstract description 17
- 238000007670 refining Methods 0.000 claims abstract description 8
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims abstract description 3
- 239000007788 liquid Substances 0.000 claims description 55
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 46
- 238000006243 chemical reaction Methods 0.000 claims description 45
- 239000000463 material Substances 0.000 claims description 35
- 239000000047 product Substances 0.000 claims description 31
- 238000000967 suction filtration Methods 0.000 claims description 30
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 24
- 239000000460 chlorine Substances 0.000 claims description 24
- 229910052801 chlorine Inorganic materials 0.000 claims description 24
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 23
- 239000003651 drinking water Substances 0.000 claims description 22
- 235000020188 drinking water Nutrition 0.000 claims description 22
- 239000000706 filtrate Substances 0.000 claims description 22
- 238000005406 washing Methods 0.000 claims description 21
- 238000001816 cooling Methods 0.000 claims description 20
- 239000012452 mother liquor Substances 0.000 claims description 19
- 238000004321 preservation Methods 0.000 claims description 19
- 238000001035 drying Methods 0.000 claims description 18
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 17
- 238000001704 evaporation Methods 0.000 claims description 17
- 230000008020 evaporation Effects 0.000 claims description 17
- 238000000605 extraction Methods 0.000 claims description 15
- 238000002156 mixing Methods 0.000 claims description 15
- 239000006227 byproduct Substances 0.000 claims description 12
- 235000010288 sodium nitrite Nutrition 0.000 claims description 12
- 239000000243 solution Substances 0.000 claims description 12
- YHUUZKCUQVILTK-UHFFFAOYSA-N 2,3-dimethylpyridin-4-amine Chemical compound CC1=NC=CC(N)=C1C YHUUZKCUQVILTK-UHFFFAOYSA-N 0.000 claims description 11
- 238000004176 ammonification Methods 0.000 claims description 10
- PTURTHBRTGJYRN-UHFFFAOYSA-N 2,3-dimethyl-1h-pyridin-4-one Chemical compound CC=1NC=CC(=O)C=1C PTURTHBRTGJYRN-UHFFFAOYSA-N 0.000 claims description 9
- 239000012043 crude product Substances 0.000 claims description 9
- 238000000926 separation method Methods 0.000 claims description 8
- 239000011343 solid material Substances 0.000 claims description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 7
- 238000007599 discharging Methods 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 3
- 238000007605 air drying Methods 0.000 claims description 2
- 238000005576 amination reaction Methods 0.000 claims description 2
- 239000011259 mixed solution Substances 0.000 claims description 2
- 238000009423 ventilation Methods 0.000 claims description 2
- 239000007795 chemical reaction product Substances 0.000 claims 1
- 239000000843 powder Substances 0.000 abstract description 8
- 238000002844 melting Methods 0.000 abstract description 7
- 230000008018 melting Effects 0.000 abstract description 7
- 230000001165 anti-coccidial effect Effects 0.000 abstract description 4
- 239000005500 Clopyralid Substances 0.000 abstract description 3
- 239000003054 catalyst Substances 0.000 abstract description 3
- HUBANNPOLNYSAD-UHFFFAOYSA-N clopyralid Chemical compound OC(=O)C1=NC(Cl)=CC=C1Cl HUBANNPOLNYSAD-UHFFFAOYSA-N 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 3
- 238000005265 energy consumption Methods 0.000 abstract description 3
- 230000036632 reaction speed Effects 0.000 abstract description 3
- 239000002904 solvent Substances 0.000 abstract description 3
- 239000002351 wastewater Substances 0.000 abstract description 3
- 230000002950 deficient Effects 0.000 abstract description 2
- 238000012824 chemical production Methods 0.000 abstract 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 239000007787 solid Substances 0.000 description 8
- 239000000779 smoke Substances 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
- 239000013058 crude material Substances 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 239000010413 mother solution Substances 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 2
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 2
- 239000001099 ammonium carbonate Substances 0.000 description 2
- 150000004982 aromatic amines Chemical class 0.000 description 2
- WASQWSOJHCZDFK-UHFFFAOYSA-N diketene Chemical compound C=C1CC(=O)O1 WASQWSOJHCZDFK-UHFFFAOYSA-N 0.000 description 2
- ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- -1 3, 5-dichloro-2, 6-dimethylpyridine phenol Chemical compound 0.000 description 1
- XTYNIPUFKBBALX-UHFFFAOYSA-N 3-chloro-1h-pyridin-2-one Chemical compound OC1=NC=CC=C1Cl XTYNIPUFKBBALX-UHFFFAOYSA-N 0.000 description 1
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 1
- 208000003495 Coccidiosis Diseases 0.000 description 1
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 1
- 206010023076 Isosporiasis Diseases 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 241000283903 Ovis aries Species 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 235000012538 ammonium bicarbonate Nutrition 0.000 description 1
- 235000012501 ammonium carbonate Nutrition 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 229960000731 clopidol Drugs 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 229910001867 inorganic solvent Inorganic materials 0.000 description 1
- 239000003049 inorganic solvent Substances 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 230000009965 odorless effect Effects 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 230000009967 tasteless effect Effects 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/68—One oxygen atom attached in position 4
Abstract
The invention discloses a production process of 3, 5-dichloro-2, 6-dimethyl-4-hydroxypyridine, and relates to the technical field of chemical production of anticoccidial medicament namely clopyralid. The 3, 5-dichloro-2, 6-dimethyl-4-hydroxypyridine finished product is obtained by taking 93% crude dehydroacetic acid, 20% ammonia water and liquid chlorine as main raw materials and performing the steps of an ammoniation process, a purification process, a chlorination process, a crystallization process, a refining process and the like, and is white powder, the melting point is more than 320 ℃, and the mass content is more than 99.90%. The method realizes the reutilization of the defective dehydroacetic acid, reduces the unit consumption by 7.13-15.13% and improves the utilization rate of the raw materials by 1.08-1.46 times compared with the prior art, and has the advantages of high relative safety degree, less process steps, no need of participation of a solvent, no use of a catalyst, low production cost, recyclable raw materials, high reaction speed, low energy consumption of wastewater, good product quality and the like.
Description
Technical Field
The invention relates to the technical field of production processes of anticoccidial clopyralid, in particular to a production process of 3, 5-dichloro-2, 6-dimethyl-4-hydroxypyridine.
Background
3, 5-dichloro-2, 6-dimethyl-4-hydroxypyridine, also known as clopyralid, 3, 5-dichloro-2, 6-dimethyl-4-pyridinol, white crystalline powder, odorless and tasteless, insoluble in water, slightly soluble in methanol, easily soluble in concentrated acid and alkali liquor, is a medicament which is widely used for preventing coccidiosis of chicks, young rabbits, lambs and calves and is developed by Dow company in 1968.
At present, the production process of 3, 5-dichloro-2, 6-dimethyl-4-hydroxypyridine which is common in industry is to prepare dehydroacetic acid by starting from diketene, and synthesize the chlorohydroxypyridine by a two-step (ammonification and chlorination) or three-step (hydrolysis, ammonification and chlorination) reaction by taking the dehydroacetic acid as a raw material. Publication No. CN1044462A discloses a method for preparing 3, 5-dichloro-2, 6-dimethylpyridine phenol by a normal pressure method, which adopts a two-step synthesis method, and avoids the limitation of a conventional production method on high requirements of equipment, but the yield of the process is unstable, the minimum yield is only 70%, the ammoniation process uses a large amount of organic solvents (such as ethylene glycol, hexanol, DMF, and the like, and the consumption is 2.5 times of the raw materials), ammonia gas is used to replace ammonia water in the embodiment with higher yield, the problems of ammonia gas leakage, pipeline corrosion and the like are easily caused in the actual production, and the method is not suitable for industrial production; because the ammonia gas is seriously excessive (the mol ratio of the ammonia to the dehydroacetic acid is 3:1), the ammonification reaction temperature is raised to 140-150 ℃, the pressure in the kettle can reach 1.3-1.5 MPa at the moment through laboratory verification, the method belongs to high-pressure reaction, the ammonification process only needs at least 24 hours to be realized, the process period is too long, and the method is not suitable for industrial popularization.
In the research on the synthesis of 2, 6-dimethyl-3, 5-dichloro-4-pyridinol and the anticoccidial effect thereof, such as Rongfeiyun, and the like, diketene is used as a raw material, and the yield of a finished product is 77.2 percent; zhangzhao et al 2, 6-dimethyl-3, 5-dichloro-4-hydroxypyridine synthesis research uses pure dehydroacetic acid as raw material, and the yield of the finished product is 57%; pure dehydroacetic acid is used as a raw material in 'technological improvement of anticoccidial drug clopidol' such as Zhushui ploughing, and the yield of a finished product is 61-74%; gong Rui et al research on synthesis of Peroprol uses pure dehydroacetic acid as raw material, and the yield of finished product is 66.7%; in conclusion, when pure dehydroacetic acid is used as a raw material, the product yield is about 57-77.2%, the utilization rate of the raw material is not high, the material and cost are seriously wasted, and the development of the product is restricted.
Therefore, the research and development of the production process of 3, 5-dichloro-2, 6-dimethyl-4-hydroxypyridine, which has the advantages of high relative safety degree, few process steps, no need of organic solvent, no catalyst, low production cost, recyclable raw materials, high reaction speed, less energy consumption of wastewater, good product quality and the like, and is suitable for industrial large-scale production, is urgent.
Disclosure of Invention
In order to solve the technical problems, the invention provides a production process of 3, 5-dichloro-2, 6-dimethyl-4-hydroxypyridine, which has the advantages of high relative safety degree, few process steps, no need of solvent participation, no use of catalyst, low production cost, recyclable raw materials, high reaction speed, low energy consumption of wastewater, good product quality and the like.
In order to realize the technical purpose, the invention adopts the following scheme:
a production process of 3, 5-dichloro-2, 6-dimethyl-4-hydroxypyridine is characterized in that raw materials comprise crude dehydroacetic acid, ammonia water and chlorine gas, and the production process comprises the following steps:
s1, an ammoniation process: putting the crude dehydroacetic acid, ammonia water and drinking water into an ammoniation reaction kettle according to the weight ratio of 1: 0.6-0.8: 1.05-1.40 to carry out ammoniation reaction to obtain ammoniation liquid containing a main product dimethyl-4-hydroxypyridine and a byproduct dimethyl-4-aminopyridine;
s2, a purification process: the phenol hydroxyl conversion is carried out on the amino of the byproduct dimethyl-4-aminopyridine by utilizing the diazotization-hydrolysis principle of aromatic amine under strong acid condition; mixing the ammoniated solution obtained in the step S1 with the crystallization mother solution according to the volume ratio of 1: 1.1-1.2, adding sodium nitrite into the mixed solution according to the weight ratio of 1: 0.015-0.035 of the ammoniated solution, fully mixing, dropwise adding concentrated hydrochloric acid with the mass concentration of 31% at the temperature of 35-45 ℃ of the kettle until the pH value in the kettle is 1.0-2.0, and carrying out heat preservation reaction; after the heat preservation reaction is finished, adding 2-4% of activated carbon (based on the weight of the crude dehydroacetic acid) when the pH value in the kettle is adjusted to 3.0-4.0 by using 30 wt% of sodium hydroxide solution, slowly raising the temperature of the kettle, carrying out heat preservation and decoloration, and then carrying out suction filtration to obtain a filtrate, namely a purified solution;
s3, a chlorination process: and (3) putting the purified liquid obtained in the step (S2) into a chlorination kettle, cooling to room temperature, slowly introducing chlorine (based on the weight of the crude dehydroacetic acid) according to the weight ratio of 1: 0.7-0.9, introducing chlorine for 6-8 hours, controlling the reaction temperature and the pressure in the kettle, keeping the temperature for 30min, and then releasing pressure to obtain the chlorinated liquid.
S4, a crystallization process: and (3) dropwise adding the chloride obtained in the step (S3) into an evaporation crystallization kettle, controlling the evaporation temperature to evaporate and concentrate the chloride solution, adding a small amount of 31% concentrated hydrochloric acid (about 10L) after concentration to extract, and cooling to room temperature after extraction for 40min to obtain a crude product feed liquid.
S5, refining: discharging the crude product liquid obtained in the step S4 into a suction filtration barrel, carrying out suction filtration for solid-liquid separation, respectively collecting solid and filtrate, carrying out suction filtration and washing on the solid for multiple times by using drinking water until the pH value of washing water is 6-7, transferring the material into a throwing filter cylinder, carrying out centrifugal throwing on the material, and transferring wet material into a dryer for ventilation drying to obtain a finished product; the filtrate can be used as crystallization mother liquor of S2 for application (the crystallization mother liquor is a preparation liquid during the first feeding, and the filtrate is used as the crystallization mother liquor during the subsequent feeding).
Further, the mass concentration of the crude dehydroacetic acid is 93%, the mass concentration of ammonia water is 20%, and the mass concentration of the crude dehydroacetic acid: ammonia water: the weight ratio of the drinking water is 1: 0.6-0.8: 1.05-1.40.
Further, the pressure in the amination reaction kettle is controlled to be 1.75 +/-0.05 MPa, the temperature is controlled to be 200.0 +/-5.0 ℃, and the heat preservation time is 2-3 hours in S1; when the percentage contents of a main product dimethyl-4-hydroxypyridine and a byproduct dimethyl-4-aminopyridine in the kettle are respectively 75-78% and 3-6%, and the pressure in the ammonification reaction kettle is kept constant, the temperature is reduced and the pressure is reduced to the normal temperature and normal pressure state, and the ammonification reaction is finished.
Further, the pressure in the purification reaction kettle in S2 is normal pressure, and the crystallization mother liquor is prepared by concentrated hydrochloric acid with the mass concentration of 31% and drinking water according to the volume ratio of 1: 4-5; the weight ratio of the sodium nitrite to the ammoniated liquid is 1: 0.015-0.035.
Further, during the heat preservation reaction in S2, the material in the kettle is kept for 3 hours until the generation of bubbles is stopped; the using amount of the active carbon is 2-4% of the weight of the crude dehydroacetic acid, the temperature in the kettle is 95-100 ℃ during heat preservation and decoloration, and the heat preservation and decoloration time is 30 min.
Further, the total amount of chlorine in the S3 is 0.7-0.9 times of the weight of the crude dehydroacetic acid, the pressure in the chlorination kettle is controlled at 0.05 +/-0.01 MPa, and the temperature is controlled at 40.0 +/-0.05 ℃.
Further, in S3, when smoke is generated in the chlorination kettle and the pressure in the chlorination kettle starts to rise, the chlorine introduction is stopped.
Further, the evaporation temperature in S4 is controlled at 95-110 ℃, when the feed liquid in the evaporation crystallization kettle is concentrated to the remaining one third, the temperature of the evaporation crystallization kettle is reduced to 60-70 ℃ for extraction, and the amount of hydrochloric acid used in the extraction is 9-11L.
Further, S5 washes the solid material with hot water of 80 ℃ or above, the washing times are 6-8, and each washing time is 10-15 min.
Further, throwing materials in S5 for 55-65 min until the moisture of the materials is less than or equal to 15%, and carrying out blast drying; and controlling the air inlet temperature of the forced air drying at 155-165 ℃, controlling the air outlet temperature at 55-65 ℃, and drying until the moisture of the material is less than or equal to 0.5% to obtain a finished product.
The pure 3, 5-dichloro-2, 6-dimethyl-4-hydroxypyridine product is white powder, has a melting point of more than 320 ℃ and a mass content of more than 99.90%.
The reaction process of the invention is as follows:
compared with the prior art, the invention has the beneficial effects that:
1) the ammonification process disclosed by the invention is carried out in a high-temperature high-pressure reaction mode, so that the reaction time can be obviously shortened, the reaction is promoted to be carried out in the positive direction, the conversion rate of main and auxiliary products is improved, the unit consumption of dehydroacetic acid is reduced, and the total conversion rate of the main and auxiliary products reaches 77-83%;
2) according to the ammoniation process, the inorganic solvent drinking water is adopted to replace an organic solvent to participate in the reaction, so that the production cost is reduced, the risk that the pipeline is blocked by-products such as ammonium carbonate and ammonium bicarbonate generated when the solvent is recovered by evaporation reflux in the traditional process is avoided, and the potential safety hazard is solved from the source;
3) according to the ammonification process, the molar ratio of the dehydroacetic acid and the ammonia water as raw materials is only 1: 1.2-1.5, which is far lower than 1: 2-4 mentioned in the prior art, so that the production cost is obviously reduced on the premise of improving the product yield;
4) according to the purification process, the aromatic amine diazotization-hydrolysis principle under the strong acid condition is utilized to carry out phenolic hydroxyl conversion on the amino of the byproduct dimethyl-4-aminopyridine, so that the utilization rate of the raw material dehydroacetic acid is remarkably improved, and the aim of low investment and high yield is fulfilled;
5) the crude dehydroacetic acid used in the invention is used as a raw material, wherein the mass content of the dehydroacetic acid is only 93%, so that the comprehensive utilization of defective dehydroacetic acid is realized while the production cost is reduced;
6) in the production process, the unit consumption of the crude dehydroacetic acid raw material (the mass of the crude dehydroacetic acid required by 3, 5-dichloro-2, 6-dimethyl-4-hydroxypyridine in each unit mass of production) is only 1.051-1.161, compared with the prior art, the unit consumption is reduced by 7.13-15.13%, the utilization rate of the raw material is improved to 77-83%, and the production cost is obviously reduced.
Detailed Description
The present invention will be described in detail with reference to the following embodiments in order to fully understand the objects, features and effects of the invention, but the present invention is not limited thereto.
Example 1
A production process of 3, 5-dichloro-2, 6-dimethyl-4-hydroxypyridine comprises the following steps:
s1, an ammoniation process: the crude dehydroacetic acid, ammonia water and drinking water are put into an ammoniation reaction kettle according to the weight ratio of 1:0.619:1.08, the pressure in the kettle is controlled to be 1.75 +/-0.05 MPa, the temperature is controlled to be 200.0 +/-5.0 ℃, the temperature is reduced and the pressure is reduced after the temperature is kept for 2.3 hours, and the ammoniation liquid containing 75 percent of main product dimethyl-4-hydroxypyridine and 4 percent of byproduct dimethyl-4-aminopyridine is obtained.
S2, a purification process: adding a crystallization mother liquor (prepared according to the volume ratio of 31 wt% concentrated hydrochloric acid to drinking water of 1: 4) into a purification reaction kettle under the normal pressure state, mixing the ammoniated liquor obtained in S1 with the crystallization mother liquor according to the volume ratio of 1:1.132, then adding sodium nitrite, wherein the weight ratio of the ammoniated liquor to sodium nitrite is 1:0.0152, fully mixing, uniformly dropwise adding 31 wt% concentrated hydrochloric acid at the kettle temperature of 35-45 ℃ until the pH value in the kettle is 1.0-2.0, and then preserving heat for 3 hours. After the heat preservation reaction is finished, adjusting the pH value in the kettle to 3.0-4.0 by using 30 wt% of sodium hydroxide solution, adding 2.67% of activated carbon (based on the weight of the crude dehydroacetic acid), heating to 95-100 ℃, carrying out heat preservation and decoloration for 30min, carrying out suction filtration, and collecting filtrate to obtain the purified liquid.
S3, a chlorination process: and (3) putting the purified liquid obtained in the step (S2) into a chlorination kettle, cooling to room temperature, slowly introducing chlorine, wherein the weight ratio of the crude dehydroacetic acid to the chlorine is 1:0.73, the chlorine introduction time is 6-8 hours, the pressure in the kettle is controlled to be 0.05 +/-0.01 MPa, and the temperature in the kettle is controlled to be 40.0 +/-0.5 ℃. Stopping introducing chlorine when smoke is generated in the kettle and the pressure in the kettle rises, preserving the temperature for 30min, and then releasing the pressure to obtain the chlorinated liquid.
S4, a crystallization process: and (2) dropwise adding the chloridized liquid obtained in the step (S3) into an evaporation crystallization kettle, controlling the temperature in the kettle to be 95-110 ℃ for material concentration, finishing concentration when the volume of the material liquid is concentrated to the remaining one third, cooling the temperature in the kettle to 60-70 ℃, adding a small amount of 31 wt% concentrated hydrochloric acid (about 10L) for extraction, and continuously cooling to room temperature after 40min of extraction to obtain a crude material liquid.
S5, a refining process: discharging the crude material liquid obtained in the step S4 into a suction filtration barrel, carrying out suction filtration for solid-liquid separation, respectively collecting solid materials and filtrate, carrying out suction filtration washing on the solid materials for 6-8 times by using water with the temperature of more than 80 ℃, washing for 10-15 min each time, transferring the washed materials into a spin-drying filter cylinder for centrifugal spin-drying for about 60min when the pH value of washing water is 6-7, carrying out blast drying when the water content of the materials is not higher than 15%, controlling the air inlet temperature at 155-165 ℃, controlling the air outlet temperature at 55-65 ℃, and drying until the water content of the materials is not higher than 0.5%, thus obtaining a finished product; the filtrate obtained by suction filtration was used as a mother solution for crystallization of S2.
The pure 3, 5-dichloro-2, 6-dimethyl-4-hydroxypyridine obtained in example 1 is white powder, the melting point is higher than 320 ℃, the content is 100.2%, the yield is 76.92%, and the unit consumption is 1: 1.137.
Example 2
A production process of 3, 5-dichloro-2, 6-dimethyl-4-hydroxypyridine comprises the following steps:
s1, an ammoniation process: putting the crude dehydroacetic acid, ammonia water and drinking water into an ammoniation reaction kettle according to the weight ratio of 1:0.650:1.15, controlling the pressure in the kettle to be 1.75 +/-0.05 MPa and the temperature to be 200.0 +/-5.0 ℃, keeping the temperature for 2.5 hours, and then reducing the temperature and the pressure to obtain ammoniation liquid containing 76 percent of main product dimethyl-4-hydroxypyridine and 5 percent of byproduct dimethyl-4-aminopyridine.
S2, a purification process: adding a crystallization mother liquor (prepared according to the volume ratio of 31 wt% concentrated hydrochloric acid to drinking water of 1: 5) into a purification reaction kettle under the normal pressure state, mixing the ammoniated liquor obtained in S1 and the crystallization mother liquor according to the volume ratio of 1:1.144, then adding sodium nitrite, wherein the weight ratio of the ammoniated liquor to sodium nitrite is 1:0.0304, fully mixing, uniformly dropwise adding 31 wt% concentrated hydrochloric acid at the temperature of 35-45 ℃ until the pH value in the kettle is 1.0-2.0, preserving heat for 3 hours, after the heat preservation reaction is finished, adjusting the pH value in the kettle to 3.0-4.0 by using 30 wt% sodium hydroxide solution, adding 2.79% activated carbon (based on the weight of crude dehydroacetic acid), heating to 95-100 ℃, preserving heat for 30 minutes, carrying out suction filtration, and collecting filtrate to obtain the purification liquor.
S3, a chlorination process: and (3) putting the purified liquid obtained in the step (S2) into a chlorination kettle, cooling to room temperature, slowly introducing chlorine, controlling the weight ratio of the crude dehydroacetic acid to the chlorine to be 1:0.84, introducing chlorine for 6-8 hours, controlling the pressure in the kettle to be 0.05 +/-0.01 MPa and 40.0 +/-0.5 ℃, stopping introducing chlorine when smoke is generated in the kettle and the pressure in the kettle is increased, preserving heat for 30min, and releasing pressure to obtain the chlorinated liquid.
S4, a crystallization process: and (3) dropwise adding the chloride obtained in the step (S3) into an evaporation crystallization kettle, controlling the temperature in the kettle to be 95-110 ℃ for material concentration, ending concentration when the volume of the feed liquid is concentrated to the remaining one third, cooling to 60-70 ℃, adding a small amount of 31% concentrated hydrochloric acid (about 10L) for extraction, and continuously cooling to room temperature after 40min of extraction to obtain a crude product feed liquid.
S5, a refining process: discharging the crude product liquid obtained in the step S4 into a suction filtration device, carrying out suction filtration to carry out solid-liquid separation, respectively collecting solid materials and filtrate, carrying out suction filtration washing on the solid materials for 6-8 times by using water with the temperature of more than 80 ℃, carrying out suction filtration washing for 10-15 min each time, transferring the materials into a throwing filter cylinder, carrying out centrifugal throwing for about 60min when the pH value of washing water is 6-7, carrying out blast drying when the water content of the materials is not higher than 15%, controlling the air inlet temperature at 155-165 ℃, the air outlet temperature at 55-65 ℃, and drying until the water content of the materials is not higher than 0.5%, thus obtaining a finished product; the filtrate obtained by suction filtration is reused as a crystallization mother liquor of S2.
The pure 3, 5-dichloro-2, 6-dimethyl-4-hydroxypyridine obtained in example 2 was white powder, melting point was > 320 ℃, content was 99.9%, yield was 79.30%, unit consumption was 1: 1.103.
Example 3
A production process of 3, 5-dichloro-2, 6-dimethyl-4-hydroxypyridine comprises the following steps:
s1, an ammoniation process: the crude dehydroacetic acid, ammonia water and drinking water are put into an ammoniation reaction kettle according to the weight ratio of 1:0.674:1.18, the pressure in the kettle is controlled to be 1.75 +/-0.05 MPa, the temperature is controlled to be 200.0 +/-5.0 ℃, the temperature is reduced and the pressure is reduced after the temperature is kept for 2.8 hours, and the ammoniation liquid containing 77 percent of main product dimethyl-4-hydroxypyridine and 6 percent of by-product dimethyl-4-aminopyridine is obtained.
S2, a purification process: adding crystallization mother liquor (prepared according to the volume ratio of 31 wt% concentrated hydrochloric acid to drinking water of 1: 4.5) into a purification reaction kettle under the normal pressure state, mixing the ammoniated liquor obtained from S1 with the crystallization mother liquor according to the volume ratio of 1:1.126, then adding sodium nitrite with the weight ratio of 1:0.0228 of the ammoniated liquor, fully mixing, uniformly dripping 31% concentrated hydrochloric acid at the temperature of 35-45 ℃ until the pH value in the kettle is 1.0-2.0, preserving heat for 3 hours, after the heat preservation reaction is finished, adjusting the pH value in the kettle to 3.0-4.0 by using 30 wt% sodium hydroxide solution, adding 2.83% active carbon (based on the weight of crude dehydroacetic acid), heating to 95-100 ℃, preserving heat, decolorizing for 30 minutes, then carrying out suction filtration, and collecting filtrate to obtain the purified liquor.
S3, a chlorination process: and (3) putting the purified liquid obtained in the step (S2) into a chlorination kettle, cooling to room temperature, slowly introducing chlorine (based on the weight of the crude dehydroacetic acid) according to the weight ratio of 1:0.85, introducing chlorine for 6-8 hours, controlling the pressure in the kettle to be 0.05 +/-0.01 MPa and 40.0 +/-0.5 ℃, stopping introducing chlorine when smoke is generated in the kettle and the pressure in the kettle is increased, preserving heat for 30min, and releasing pressure to obtain the chlorinated liquid.
S4, a crystallization process: and (3) dropwise adding the chloride obtained in the step (S3) into an evaporation crystallization kettle, controlling the temperature in the kettle to be 95-110 ℃ for material concentration, ending concentration when the volume of the feed liquid is concentrated to the remaining one third, cooling to 60-70 ℃, adding a small amount of 31% concentrated hydrochloric acid (about 10L) for extraction, and continuously cooling to room temperature after 40min of extraction to obtain a crude product feed liquid.
S5, a refining process: discharging the crude material liquid obtained in the step S4 into a suction filter, carrying out suction filtration to carry out solid-liquid separation, respectively collecting solid and filtrate, carrying out suction filtration washing on the solid for 6-8 times by using drinking water with the temperature of more than 80 ℃, carrying out 10-15 min each time, transferring the material into a throwing filter cylinder to carry out centrifugal throwing for about 60min when the pH value of washing water is 6-7, carrying out blast drying when the water content of the material is not higher than 15%, controlling the air inlet temperature at 155-165 ℃, the air outlet temperature at 55-65 ℃, and drying until the water content of the material is not higher than 0.5%, thus obtaining a finished product; the filtrate obtained by suction filtration was used as a mother solution for crystallization of S2.
The pure 3, 5-dichloro-2, 6-dimethyl-4-hydroxypyridine obtained in example 3 was white powder, melting point > 320 ℃, content 100.4%, yield 80.84%, unit consumption 1: 1.082.
Example 4
A production process of 3, 5-dichloro-2, 6-dimethyl-4-hydroxypyridine comprises the following steps:
s1, an ammoniation process: the crude dehydroacetic acid, ammonia water and drinking water are put into an ammoniation reaction kettle according to the weight ratio of 1:0.703:1.225, the pressure in the kettle is controlled to be 1.75 plus or minus 0.05MPa, the temperature is controlled to be 200.0 plus or minus 5.0 ℃, the temperature is reduced and the pressure is reduced after the temperature is maintained for 3 hours, and the ammoniation liquid of 78 percent of main product dimethyl-4-hydroxypyridine and 6 percent of by-product dimethyl-4-aminopyridine is obtained.
S2, a purification process: adding crystallization mother liquor (prepared according to the proportion of 31% concentrated hydrochloric acid in volume ratio to drinking water being 1: 4.5) into a purification reaction kettle under the normal pressure state, mixing the ammoniated liquor obtained in S1 with the crystallization mother liquor according to the volume ratio of 1:1.136, then adding sodium nitrite in the weight ratio of 1:0.0277 of the ammoniated liquor, fully mixing, uniformly dropwise adding 31% concentrated hydrochloric acid at the temperature of 35-45 ℃ until the pH value in the kettle is 1.0-2.0, preserving heat for 3 hours, after the heat preservation reaction is finished, adjusting the pH value in the kettle to 3.0-4.0 by using 30 wt% sodium hydroxide solution, adding 2.89% activated carbon (based on the weight of crude dehydroacetic acid), heating to 95-100 ℃, preserving heat and decoloring for 30 minutes, then carrying out suction filtration, and collecting filtrate to obtain the purified liquor.
S3, a chlorination process: and (3) putting the purified liquid obtained in the step (S2) into a chlorination kettle, cooling to room temperature, slowly introducing chlorine (based on the weight of the crude dehydroacetic acid) according to the weight ratio of 1:0.87, introducing chlorine for 6-8 hours, controlling the pressure in the kettle to be 0.05 +/-0.01 MPa and 40.0 +/-0.5 ℃, stopping introducing chlorine when smoke is generated in the kettle and the pressure in the kettle is increased, preserving heat for 30min, and releasing pressure to obtain the chlorinated liquid.
S4, a crystallization process: and (3) dropwise adding the chloride obtained in the step (S3) into an evaporation crystallization kettle, controlling the temperature in the kettle to be 95-110 ℃ for material concentration, ending concentration when the volume of the feed liquid is concentrated to the remaining one third, cooling to 60-70 ℃, adding a small amount of 31% concentrated hydrochloric acid (about 10L) for extraction, and continuously cooling to room temperature after extraction for 40min to obtain a crude product feed liquid.
S5, a refining process: discharging the crude material liquid obtained in the step S4 into a suction filter, carrying out suction filtration to carry out solid-liquid separation, respectively collecting solid and filtrate, carrying out suction filtration washing on the solid for 6-8 times by using drinking water with the temperature of more than 80 ℃, carrying out 10-15 min each time, transferring the material into a throwing filter cylinder to carry out centrifugal throwing for about 60min when the pH value of washing water is 6-7, carrying out blast drying when the water content of the material is not higher than 15%, controlling the air inlet temperature at 155-165 ℃, the air outlet temperature at 55-65 ℃, and drying until the water content of the material is not higher than 0.5%, thus obtaining a finished product; the filtrate obtained by suction filtration was used as a mother solution for crystallization of S2.
The pure 3, 5-dichloro-2, 6-dimethyl-4-hydroxypyridine obtained in example 4 was white powder, melting point was > 320 ℃, content was 100.5%, yield was 83.23%, unit consumption was 1: 1.05.
Example 5
A production process of 3, 5-dichloro-2, 6-dimethyl-4-hydroxypyridine comprises the following steps:
s1, an ammoniation process: putting the crude dehydroacetic acid, ammonia water and drinking water into an ammoniation reaction kettle according to the weight ratio of 1:0.756:1.382, controlling the pressure in the kettle to be 1.75 +/-0.05 MPa and the temperature to be 200.0 +/-5.0 ℃, cooling and reducing the pressure after keeping the temperature for 2.5 hours to obtain ammoniation liquid of 77 percent of main product dimethyl-4-hydroxypyridine and 4 percent of byproduct dimethyl-4-aminopyridine;
s2, a purification process: adding crystallization mother liquor (prepared according to the proportion of 31% concentrated hydrochloric acid to drinking water in volume ratio of 1: 5) into a purification reaction kettle under the normal pressure state, mixing the ammoniated liquor obtained in S1 with the crystallization mother liquor in volume ratio of 1:1.151, then adding sodium nitrite in weight ratio of 1:0.0248 of the ammoniated liquor, fully mixing, uniformly dropwise adding 31% concentrated hydrochloric acid at the kettle temperature of 35-45 ℃ until the pH value in the kettle is 1.0-2.0, preserving heat for 3 hours, after the heat preservation reaction is finished, adjusting the pH value in the kettle to 3.0-4.0 by using 30 wt% sodium hydroxide solution, adding 3.05% of activated carbon (based on the weight of crude dehydroacetic acid), heating to 95-100 ℃, preserving heat for 30min, carrying out suction filtration, and collecting filtrate to obtain the purification liquor;
s3, a chlorination process: and (3) putting the purified liquid obtained in the step (S2) into a chlorination kettle, cooling to room temperature, slowly introducing chlorine (based on the weight of the crude dehydroacetic acid) according to the weight ratio of 1:0.90, introducing chlorine for 6-8 hours, controlling the pressure in the kettle to be 0.05 +/-0.01 MPa and 40.0 +/-0.5 ℃, stopping introducing chlorine when smoke is generated in the kettle and the pressure in the kettle is increased, preserving heat for 30min, and releasing pressure to obtain the chlorinated liquid.
S4, a crystallization process: and (3) dropwise adding the chloride obtained in the step (S3) into an evaporation crystallization kettle, controlling the temperature in the kettle to be 95-110 ℃ for material concentration, ending concentration when the volume of the feed liquid is concentrated to the remaining one third, cooling to 60-70 ℃, adding a small amount of 31% concentrated hydrochloric acid (about 10L) for extraction, and continuously cooling to room temperature after extraction for 40min to obtain a crude product feed liquid.
S5, a refining process: discharging the crude material liquid obtained in the step S4 into a suction filter, carrying out suction filtration to carry out solid-liquid separation, respectively collecting solid and filtrate, carrying out suction filtration washing on the solid for 6-8 times by using drinking water with the temperature of more than 80 ℃, carrying out 10-15 min each time, transferring the material into a throwing filter cylinder to carry out centrifugal throwing for about 60min when the pH value of washing water is 6-7, carrying out blast drying when the water content of the material is not higher than 15%, controlling the air inlet temperature at 155-165 ℃, the air outlet temperature at 55-65 ℃, and drying until the water content of the material is not higher than 0.5%, thus obtaining a finished product; the filtrate obtained by suction filtration is reused as a crystallization mother liquor of S2.
The pure 3, 5-dichloro-2, 6-dimethyl-4-hydroxypyridine obtained in example 5 was white powder, melting point was > 320 ℃, content was 100.0%, yield was 77.12%, unit consumption was 1: 1.134.
The main raw materials of the crude dehydroacetic acid, ammonia water, drinking water, crystallization mother liquor, sodium nitrite, activated carbon, chlorine and the like of the above examples 1 to 5, the weight, content, yield, unit consumption (mass of the crude dehydroacetic acid consumed per unit mass of produced 3, 5-dichloro-2, 6-dimethyl-4-hydroxypyridine), and the like are shown in the following table.
The above table shows that the utilization rate of the crude dehydroacetic acid as the main raw material of the production method provided by the invention reaches 77-83%, compared with the existing patent and thesis technologies, the utilization rate is improved by 1.08-1.46 times, the unit consumption is reduced by 7.13-15.13%, and the production method is very suitable for industrial popularization.
The comparison of the present application with the prior art is as follows:
compared with the prior art, the scheme adopts the raw material proportion to select a numerical value which is obviously different from the prior art, the product yield is obviously higher than that of the production process of the same raw material, and the production period of the chlorination process is obviously shortened.
Finally, it is noted that: the above lists only illustrate preferred embodiments of the invention, and it is of course possible for those skilled in the art to make changes and modifications to the invention, and such changes and modifications are considered to be within the scope of the invention as defined by the claims and their equivalents.
Claims (9)
1. A production process of 3, 5-dichloro-2, 6-dimethyl-4-hydroxypyridine is characterized in that raw materials comprise crude dehydroacetic acid, ammonia water and chlorine gas, and the production process comprises the following steps:
s1, ammoniation reaction: putting the crude dehydroacetic acid, ammonia water and drinking water into an ammoniation reaction kettle according to a proportion to carry out ammoniation reaction to obtain ammoniation liquid containing a main product dimethyl-4-hydroxypyridine and a byproduct dimethyl-4-aminopyridine;
s2, purification process: and (3) mixing the ammoniated solution obtained in the step (S1) with the crystallization mother liquor according to the volume ratio of 1: mixing the raw materials in a purification reaction kettle according to the proportion of 1.1-1.2, adding sodium nitrite into the mixed solution, fully mixing, dropwise adding concentrated hydrochloric acid with the mass concentration of 31% at the temperature of 35-45 ℃ to adjust the pH value in the kettle to be 1.0-2.0, and then carrying out heat preservation reaction; after the heat preservation reaction is finished, adjusting the pH value in the kettle to be 3.0-4.0, then adding activated carbon, slowly raising the temperature in the kettle, carrying out heat preservation and decoloration, and then carrying out suction filtration to obtain a filtrate, namely a purified solution;
s3, chlorination process: putting the purified liquid obtained in the step S2 into a chlorination kettle, cooling to room temperature, slowly introducing chlorine for 6-8 h, controlling the reaction temperature and the pressure in the chlorination kettle, keeping the temperature for 30min, and then releasing pressure to obtain chlorinated liquid;
s4, crystallization process: dropwise adding the chloride obtained in the step S3 into an evaporation crystallization kettle, controlling the evaporation temperature to perform evaporation concentration, adding concentrated hydrochloric acid with the mass concentration of 31% after the concentration is finished, extracting for 40min, and cooling to room temperature to obtain a crude product feed liquid;
s5, refining: discharging the crude product feed liquid obtained in the step S4 into a suction filtration barrel for solid-liquid separation, respectively collecting solid materials and filtrate, and using the filtrate as crystallization mother liquid of the step S2; and (3) carrying out suction filtration washing on the solid material by using water, and when the pH value of washing water is 6-7, carrying out centrifugal separation on the washed material to obtain a wet material, and carrying out ventilation drying to obtain a finished product.
2. The process for producing 3, 5-dichloro-2, 6-dimethyl-4-hydroxypyridine according to claim 1, wherein the mass concentration of the crude dehydroacetic acid is 93%, the mass concentration of ammonia water is 20%, and the mass ratio of the crude dehydroacetic acid: ammonia water: the weight ratio of the drinking water is 1: 0.6-0.8: 1.05-1.40.
3. The production process of 3, 5-dichloro-2, 6-dimethyl-4-hydroxypyridine according to claim 1, wherein the pressure in an amination reaction kettle in S1 is controlled to be 1.75 +/-0.05 MPa, the temperature is controlled to be 200.0 +/-5.0 ℃, and the heat preservation time is 2-3 hours; and when the percentages of the main product dimethyl-4-hydroxypyridine and the byproduct dimethyl-4-aminopyridine in the kettle are respectively 75-78% and 3-6%, and the pressure in the ammonification reaction kettle is kept constant, reducing the temperature and reducing the pressure to finish the ammonification reaction.
4. The production process of 3, 5-dichloro-2, 6-dimethyl-4-hydroxypyridine according to claim 1, wherein the pressure in the purification reaction kettle in S2 is normal pressure, and the crystallization mother liquor is prepared by concentrated hydrochloric acid with a mass concentration of 31% and drinking water according to a volume ratio of 1: 4-5; the weight ratio of the sodium nitrite to the ammoniated liquid is 1: 0.015-0.035.
5. The process for producing 3, 5-dichloro-2, 6-dimethyl-4-hydroxypyridine according to claim 1, wherein in the step of maintaining the temperature of the reaction product in S2, the material in the reactor is maintained for 3 hours until the generation of bubbles is stopped; the using amount of the active carbon is 2-4% of the weight of the crude dehydroacetic acid, the temperature in the kettle is 95-100 ℃ during heat preservation and decoloration, and the heat preservation and decoloration time is 30 min.
6. The process for producing 3, 5-dichloro-2, 6-dimethyl-4-hydroxypyridine according to claim 1, wherein the total amount of chlorine in S3 is 0.7-0.9 times of the weight of the crude dehydroacetic acid, the pressure in the chlorination reactor is controlled to 0.05 +/-0.01 MPa, and the temperature is controlled to 40.0 +/-0.05 ℃.
7. The process for producing 3, 5-dichloro-2, 6-dimethyl-4-hydroxypyridine according to claim 1, wherein the evaporation temperature in S4 is controlled to 95-110 ℃, and when the feed liquid in the evaporation crystallization kettle is concentrated to the remaining one third of the volume, the evaporation crystallization kettle is cooled to 60-70 ℃ for extraction, and the amount of hydrochloric acid used in the extraction is 9-11L.
8. The production process of 3, 5-dichloro-2, 6-dimethyl-4-hydroxypyridine according to claim 1, wherein S5 is used for washing the solid material with hot water of 80 ℃ or higher, the washing times are 6-8, and each washing time is 10-15 min.
9. The production process of 3, 5-dichloro-2, 6-dimethyl-4-hydroxypyridine according to claim 1, wherein the material throwing time in S5 is 55-65 min, and blast drying is carried out until the moisture of the material is less than or equal to 15%; and controlling the air inlet temperature of the forced air drying at 155-165 ℃, controlling the air outlet temperature at 55-65 ℃, and drying until the moisture of the material is less than or equal to 0.5% to obtain a finished product.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1044462A (en) * | 1989-01-26 | 1990-08-08 | 程丽波 | Non-pressure process preparation 3,5-two chloro-2,6-lutidine phenol |
| CN105753776A (en) * | 2015-12-14 | 2016-07-13 | 浙江工业大学 | Preparation method of 2, 6-dimethyl-3, 5-dichloro-4-hydroxypyridine |
-
2022
- 2022-06-21 CN CN202210705398.3A patent/CN115028576B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1044462A (en) * | 1989-01-26 | 1990-08-08 | 程丽波 | Non-pressure process preparation 3,5-two chloro-2,6-lutidine phenol |
| CN105753776A (en) * | 2015-12-14 | 2016-07-13 | 浙江工业大学 | Preparation method of 2, 6-dimethyl-3, 5-dichloro-4-hydroxypyridine |
Non-Patent Citations (6)
| Title |
|---|
| REICH, MARVIN F.等: "Pyrido[ 3,4-e]-1,2,4-triazines and Related Heterocycles as Potential Antifungal Agents", 《JOURNAL OF MEDICINAL CHEMISTRY》 * |
| 张昭等: "2，6-二甲基-35-二氯-4-羟基吡啶合成工艺研究", 《精细化工》 * |
| 朱永耕等: "抗球虫药氯吡多的工艺改进", 《医药工业》 * |
| 杨 绿等: "4-羟基吡啶合成研究", 《化学世界》 * |
| 王斐云等: "2,6-二甲基-3,5-二氯-4-吡啶醇的合成及其抗球虫作用的研究", 《2,6-二甲基-3,5-二氯-4-吡啶醇的合成及其抗球虫作用的研究》 * |
| 龚锐等: "氯吡醇合成方法的研究", 《化学世界》 * |
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