CN116924996A - Synthesis process of dichloropyrimidine - Google Patents
Synthesis process of dichloropyrimidine Download PDFInfo
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- CN116924996A CN116924996A CN202310863232.9A CN202310863232A CN116924996A CN 116924996 A CN116924996 A CN 116924996A CN 202310863232 A CN202310863232 A CN 202310863232A CN 116924996 A CN116924996 A CN 116924996A
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- Prior art keywords
- dichloropyrimidine
- dihydroxypyrimidine
- reaction
- catalyst
- phosphorus oxychloride
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- XJPZKYIHCLDXST-UHFFFAOYSA-N 4,6-dichloropyrimidine Chemical compound ClC1=CC(Cl)=NC=N1 XJPZKYIHCLDXST-UHFFFAOYSA-N 0.000 title claims abstract description 34
- 238000000034 method Methods 0.000 title claims abstract description 22
- 230000015572 biosynthetic process Effects 0.000 title claims abstract description 10
- 238000003786 synthesis reaction Methods 0.000 title claims abstract description 10
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims abstract description 52
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims abstract description 45
- 238000006243 chemical reaction Methods 0.000 claims abstract description 38
- DUFGYCAXVIUXIP-UHFFFAOYSA-N 4,6-dihydroxypyrimidine Chemical compound OC1=CC(O)=NC=N1 DUFGYCAXVIUXIP-UHFFFAOYSA-N 0.000 claims abstract description 27
- 239000003054 catalyst Substances 0.000 claims abstract description 26
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 10
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims description 16
- 238000001816 cooling Methods 0.000 claims description 12
- 238000003756 stirring Methods 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- 239000007788 liquid Substances 0.000 claims description 7
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 claims description 6
- 238000002425 crystallisation Methods 0.000 claims description 6
- 230000008025 crystallization Effects 0.000 claims description 6
- 238000001035 drying Methods 0.000 claims description 6
- 238000001914 filtration Methods 0.000 claims description 6
- JGTDKDDEWSWWIU-UHFFFAOYSA-N CC1=CC=CC=C1.ClC1=NC=NC(=C1)Cl Chemical compound CC1=CC=CC=C1.ClC1=NC=NC(=C1)Cl JGTDKDDEWSWWIU-UHFFFAOYSA-N 0.000 claims description 4
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 4
- 150000001875 compounds Chemical class 0.000 claims description 2
- 238000010438 heat treatment Methods 0.000 claims description 2
- 239000012265 solid product Substances 0.000 claims description 2
- 230000008901 benefit Effects 0.000 abstract description 4
- 239000002994 raw material Substances 0.000 abstract description 4
- 239000005730 Azoxystrobin Substances 0.000 abstract description 2
- WFDXOXNFNRHQEC-GHRIWEEISA-N azoxystrobin Chemical compound CO\C=C(\C(=O)OC)C1=CC=CC=C1OC1=CC(OC=2C(=CC=CC=2)C#N)=NC=N1 WFDXOXNFNRHQEC-GHRIWEEISA-N 0.000 abstract description 2
- 239000012320 chlorinating reagent Substances 0.000 abstract description 2
- 239000007810 chemical reaction solvent Substances 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- 229940079593 drug Drugs 0.000 abstract 1
- 239000007787 solid Substances 0.000 description 7
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 6
- 229910052698 phosphorus Inorganic materials 0.000 description 6
- 239000011574 phosphorus Substances 0.000 description 6
- 229910019142 PO4 Inorganic materials 0.000 description 4
- 239000006227 byproduct Substances 0.000 description 4
- 238000001514 detection method Methods 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 4
- 239000010452 phosphate Substances 0.000 description 4
- 238000011084 recovery Methods 0.000 description 4
- 238000005070 sampling Methods 0.000 description 4
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000002351 wastewater Substances 0.000 description 3
- 239000003513 alkali Substances 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 238000005660 chlorination reaction Methods 0.000 description 2
- 238000003912 environmental pollution Methods 0.000 description 2
- 238000009776 industrial production Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 238000011112 process operation Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 238000004064 recycling Methods 0.000 description 2
- 239000005758 Cyprodinil Substances 0.000 description 1
- 241000917122 Greenidea Species 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000003889 chemical engineering Methods 0.000 description 1
- MPMSMUBQXQALQI-UHFFFAOYSA-N cobalt phthalocyanine Chemical compound [Co+2].C12=CC=CC=C2C(N=C2[N-]C(C3=CC=CC=C32)=N2)=NC1=NC([C]1C=CC=CC1=1)=NC=1N=C1[C]3C=CC=CC3=C2[N-]1 MPMSMUBQXQALQI-UHFFFAOYSA-N 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- HAORKNGNJCEJBX-UHFFFAOYSA-N cyprodinil Chemical compound N=1C(C)=CC(C2CC2)=NC=1NC1=CC=CC=C1 HAORKNGNJCEJBX-UHFFFAOYSA-N 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000000967 suction filtration Methods 0.000 description 1
- 229960002135 sulfadimidine Drugs 0.000 description 1
- ASWVTGNCAZCNNR-UHFFFAOYSA-N sulfamethazine Chemical compound CC1=CC(C)=NC(NS(=O)(=O)C=2C=CC(N)=CC=2)=N1 ASWVTGNCAZCNNR-UHFFFAOYSA-N 0.000 description 1
- 229960005404 sulfamethoxazole Drugs 0.000 description 1
- JLKIGFTWXXRPMT-UHFFFAOYSA-N sulphamethoxazole Chemical compound O1C(C)=CC(NS(=O)(=O)C=2C=CC(N)=CC=2)=N1 JLKIGFTWXXRPMT-UHFFFAOYSA-N 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/30—Halogen atoms or nitro radicals
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J31/00—Catalysts comprising hydrides, coordination complexes or organic compounds
- B01J31/02—Catalysts comprising hydrides, coordination complexes or organic compounds containing organic compounds or metal hydrides
- B01J31/0234—Nitrogen-, phosphorus-, arsenic- or antimony-containing compounds
- B01J31/0235—Nitrogen containing compounds
- B01J31/0237—Amines
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Materials Engineering (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention provides a synthesis process of 4, 6-dichloropyrimidine, which takes phosphorus oxychloride as a chlorinating agent of a reaction, takes 4, 6-dihydroxypyrimidine as a raw material, takes toluene as a reaction solvent, and adopts a specific catalyst to react to obtain dichloropyrimidine. The invention has the advantages of low reaction temperature, simple operation, high reaction yield in the process of synthesizing the 4, 6-dichloropyrimidine, and the catalyst for reaction can be recycled and reused, and the prepared dichloropyrimidine can be used as an intermediate for synthesizing azoxystrobin medicines.
Description
Technical Field
The invention belongs to the technical field of fine chemical engineering, and particularly relates to a preparation method of 4, 6-dichloropyrimidine.
Background
The dichloropyrimidine serving as an important medical intermediate can be used for producing, for example, sulfadimidine, sulfamethoxazole, sulfa Mo Tuoxin, sulfa-6-methoxypyrimidine and the like, and can also be used as an intermediate for synthesizing the bactericide azoxystrobin, so that the cyprodinil can be widely studied and put into production.
According to the report of related literature, two methods for synthesizing 4, 6-dichloropyrimidine by using 4, 6-dihydroxypyrimidine as a raw material are mainly adopted:
(1) Phosphorus oxychloride chlorination process: 4, 6-dihydroxypyrimidine is taken as a raw material, and phosphorus oxychloride is taken as a chlorinating agent to synthesize 4, 6-dichloropyrimidine in the presence of anhydrous triethylamine as a catalyst; the method has the main disadvantage of generating a large amount of phosphorus-containing wastewater and needing to recycle the catalyst.
(2) Solid phosgene chlorination process: 4, 6-dihydroxypyrimidine is used as raw material, and solid phosgene is used to replace phosphorus oxychloride to synthesize 4, 6-dichloropyrimidine. Any organic alkali is not used in the reaction, so that the complicated process of recycling and reusing the organic alkali is avoided, and high-cost catalysts such as cobalt phthalocyanine, triphenylphosphine oxide or trialkylphosphine oxide are used in the reaction. The reaction yield is low, the phosgene is extremely toxic and dangerous, and the safety control difficulty is high in the actual use process.
。
Disclosure of Invention
The invention aims to: the invention aims to overcome the defects of the prior art and provide a dichloropyrimidine synthesis method which is efficient, simple in operation and treatment and high in yield.
The technical scheme is as follows: the synthesis process of dichloropyrimidine of the invention is characterized in that: the reaction equation is shown as a formula (I), and specifically comprises the following steps:
(1) Adding quantitative 4, 6-dihydroxypyrimidine, toluene and a catalyst into a clean reaction kettle, uniformly stirring, and adding quantitative phosphorus oxychloride into an overhead tank;
(2) Heating the reaction kettle system of the 4, 6-dihydroxypyrimidine, toluene and the catalyst in the step (1) to 60-70 ℃, dropwise adding phosphorus oxychloride in a high-level tank into the reaction kettle, and then preserving heat for 6-7 hours until the 4, 6-dihydroxypyrimidine completely reacts;
(3) Cooling the system after the reaction in the step (2) to room temperature, adding water under stirring to hydrolyze the rest phosphorus oxychloride, standing for layering, and separating out upper dichloropyrimidine toluene solution;
(4) And transferring the dichloropyrimidine toluene liquid into a crystallization device, cooling, crystallizing, filtering, rinsing and drying to obtain a 4, 6-dichloropyrimidine solid product.
Further, as a preferred embodiment, the catalyst in the step (1) is selected from one of compounds represented by the following formula (II);
R 1 = H、Me、Et、Bu、Bn、i-one of Pr or Ph;
R 2 = H、Me、Et、Bu、Bn、i-one of Pr, ph or Ph;
R 3 = H、Me、Et、Bu、Bn、i-pr, ph or Ph.
Further, as a preferred embodiment, the catalyst in the step (1) is selected from one or more of N, N-dimethylaniline, dimethylamine or diisopropylethylamine.
Further, as a preferred embodiment, the total amount of 4, 6-dihydroxypyrimidine and phosphorus oxychloride added in the reaction process of the step (2) is 1:1.5 to 2.5, wherein the molar ratio of the total addition amount of the 4, 6-dihydroxypyrimidine and phosphorus oxychloride is 1:2;
further, as a preferred embodiment, the total amount of the 4, 6-dihydroxypyrimidine and the catalyst added is 1:0.5 to 1.0.
Further, as a preferred embodiment, in the step (1), the mass ratio of the 4, 6-dihydroxypyrimidine to toluene is 1: 4-6.
Further, as a preferred embodiment, the mass ratio of the 4, 6-dihydroxypyrimidine added in the step (1) to the water added in the step (3) is 1: 6-8.
The beneficial effects are that: (1) The scheme of the invention has simple process operation and high dichloropyrimidine yield, and can be used for industrial production; the synthesis of dichloropyrimidine can be realized by using various organic amine catalysts; (2) The catalyst and the phosphate can be recycled in the subsequent process, wherein the recovery rate of the catalyst is extremely high and reaches more than 97.5%, the catalyst has economic benefit, and the phosphorus-containing byproduct can be further used for other synthesis, so that the environmental pollution is avoided; (3) The required temperature of the reaction is low, the reaction is only carried out at 60-70 ℃, and other methods for synthesizing dichloropyrimidine by adopting phosphorus oxychloride generally need about 100 ℃, thus embodying the concept of green. (4) The reaction also provides the catalyst for the reaction for the first time, such as diisopropylethylamine, and the like, has breakthrough innovation and higher reaction yield.
Drawings
FIG. 1 is a nuclear magnetic resonance spectrum of the product of the present invention.
Description of the embodiments
The following description of the embodiments of the present invention will be made clearly and completely with reference to the accompanying drawings, in which it is apparent that the embodiments described are only some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Examples
To a clean 500ml four-necked flask, 23g of 4, 6-dihydroxypyrimidine, 100g of toluene and 26.1g of diisopropylethylamine were charged, and 61.9g of phosphorus oxychloride was added to the dropping funnel to be added dropwise. Stirring is started, when the temperature is raised to 60-70 ℃, phosphorus oxychloride is started to be added dropwise, the temperature is kept for 6-7 h after the dropwise addition is finished, sampling detection is carried out, the content of 4, 6-dihydroxypyrimidine is less than 1% after HPLC analysis, and the reaction is stopped. Cooling to room temperature, adding 160g of water into a reaction bottle to hydrolyze residual phosphorus oxychloride, standing and layering; transferring the upper toluene liquid into a crystallization device, cooling, crystallizing, filtering, rinsing and drying to obtain 4, 6-dichloropyrimidine solid, wherein the content is 98.4%, and the yield is 94.1%.
The implementation method for recycling the catalyst and the phosphorus-containing byproducts in the wastewater of the reaction system in the embodiment specifically comprises the following steps:
250g of dichloropyrimidine production wastewater is put into a clean 500ml four-mouth bottle, 30% NaOH solution is dripped into the bottle, the PH is regulated to 14, the temperature is raised to 25 ℃, the bottle is kept still for half an hour, the upper diisopropylethylamine is obtained after liquid separation, the crude product is distilled, the fraction at 115-130 ℃ is collected to obtain 38.2g of catalyst, the recovery rate is 97.5%, the temperature is reduced to 15 ℃ to precipitate phosphate solid, 127g of phosphate is phosphorus-containing byproduct, and the recovery rate of phosphorus is 95.2% by suction filtration.
As shown in FIG. 1, the nuclear magnetic resonance spectrum of the product in this example is analyzed by the spectrum 1 H NMR (400 MHz, CDCl 3 ) Delta 8.75 (s, 1H), 7.40 (s, 1H), and the peak position of the characteristic peak in the spectrogram corresponds to the functional group of 4, 6-dichloropyrimidine, thus proving that the scheme of the embodiment successfully synthesizes 4, 6-dichloropyrimidine.
Examples
23g of 4, 6-dihydroxypyrimidine, 100g of toluene and 24.3g of N, N-dimethylaniline are introduced into a clean 500ml four-necked flask, and 61.9g of phosphorus oxychloride is added to the dropping funnel for dropping. Stirring is started, when the temperature is raised to 60-70 ℃, phosphorus oxychloride is started to be added dropwise, the temperature is kept for 6-7 h after the dropwise addition is finished, sampling detection is carried out, the content of 4, 6-dihydroxypyrimidine is less than 1% after HPLC analysis, and the reaction is stopped. Cooling to room temperature, adding 160g of water into a reaction bottle to hydrolyze residual phosphorus oxychloride, standing and layering; and transferring the upper toluene liquid into a crystallization device, cooling, crystallizing, filtering, rinsing and drying to obtain the 4, 6-dichloropyrimidine solid, wherein the content is 98.2%, and the yield is 93.0%.
Examples
To a clean 500ml four-necked flask, 23g of 4, 6-dihydroxypyrimidine, 100g of toluene and 19.4g of diisopropylethylamine were charged, and 61.9g of phosphorus oxychloride was added to the dropping funnel to be added dropwise. Stirring is started, when the temperature is raised to 60-70 ℃, phosphorus oxychloride is started to be added dropwise, the temperature is kept for 6-7 h after the dropwise addition is finished, sampling detection is carried out, the content of 4, 6-dihydroxypyrimidine is less than 1% after HPLC analysis, and the reaction is stopped. Cooling to room temperature, adding 160g of water into a reaction bottle to hydrolyze residual phosphorus oxychloride, standing and layering; and transferring the upper toluene liquid into a crystallization device, cooling, crystallizing, filtering, rinsing and drying to obtain 4, 6-dichloropyrimidine solid, wherein the content is 97.2%, and the yield is 91.6%.
Examples
To a clean 500ml four-necked flask, 23g of 4, 6-dihydroxypyrimidine, 100g of toluene and 13.1g of diisopropylethylamine were charged, and 61.9g of phosphorus oxychloride was added to the dropping funnel to be added dropwise. Stirring is started, when the temperature is raised to 60-70 ℃, phosphorus oxychloride is started to be added dropwise, the temperature is kept for 6-7 h after the dropwise addition is finished, sampling detection is carried out, the content of 4, 6-dihydroxypyrimidine is less than 1% after HPLC analysis, and the reaction is stopped. Cooling to room temperature, adding 160g of water into a reaction bottle to hydrolyze residual phosphorus oxychloride, standing and layering; and transferring the upper toluene liquid into a crystallization device, cooling, crystallizing, filtering, rinsing and drying to obtain the 4, 6-dichloropyrimidine solid, wherein the content is 98.1%, and the yield is 87.5%.
The above examples prove that the technical scheme of the invention has simple process operation and high dichloropyrimidine yield, and can be used for industrial production; the synthesis of dichloropyrimidine can be realized by using various organic amine catalysts; the catalyst and the phosphate can be recycled in the follow-up process, wherein the recovery rate of the catalyst is extremely high, the economic benefit is achieved, and the phosphorus-containing byproducts can be further used for other synthesis, so that the environmental pollution is avoided; the required temperature of the reaction is low, and the reaction is only carried out at 60-70 ℃, so that the green idea is reflected. The reaction also provides the catalyst for the reaction for the first time, such as diisopropylethylamine and the like, and has the advantages of high reaction yield and strong innovation.
As described above, although the present invention has been shown and described with reference to certain preferred embodiments, it is not to be construed as limiting the invention itself. Various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims.
Claims (9)
1. A synthesis process of dichloropyrimidine is characterized in that: the reaction equation is shown as a formula (I), and specifically comprises the following steps:
2. adding quantitative 4, 6-dihydroxypyrimidine, toluene and a catalyst into a clean reaction kettle, uniformly stirring, and adding quantitative phosphorus oxychloride into an overhead tank;
heating the reaction kettle system of the 4, 6-dihydroxypyrimidine, toluene and the catalyst in the step (1) to 60-70 ℃, dropwise adding phosphorus oxychloride in a high-level tank into the reaction kettle, and then preserving heat for 6-7 hours until the 4, 6-dihydroxypyrimidine completely reacts;
cooling the system after the reaction in the step (2) to room temperature, adding water under stirring to hydrolyze the rest phosphorus oxychloride, standing for layering, and separating out upper dichloropyrimidine toluene solution;
and transferring the dichloropyrimidine toluene liquid into a crystallization device, cooling, crystallizing, filtering, rinsing and drying to obtain a 4, 6-dichloropyrimidine solid product.
3. The process for synthesizing dichloropyrimidine as claimed in claim 1, wherein: the catalyst in the step (1) is selected from one of compounds shown in the following formula (II);
4. wherein:
R 1 = H、Me、Et、Bu、Bn、i-one of Pr or Ph;
R 2 = H、Me、Et、Bu、Bn、i-one of Pr, ph or Ph;
R 3 = H、Me、Et、Bu、Bn、i-pr, ph or Ph.
5. The process for synthesizing dichloropyrimidine as claimed in claim 2, wherein: the catalyst in the step (1) is selected from one or more of N, N-dimethylaniline, dimethylamine or diisopropylethylamine.
6. The process for synthesizing dichloropyrimidine as claimed in claim 1, wherein: the total addition molar ratio of 4, 6-dihydroxypyrimidine and phosphorus oxychloride in the reaction process of the step (2) is 1: 1.5-2.5.
7. A process for the synthesis of dichloropyrimidine as claimed in claim 3 wherein: the molar ratio of the total addition amount of the 4, 6-dihydroxypyrimidine and the catalyst is 1:0.5 to 1.0.
8. The process for synthesizing dichloropyrimidine as claimed in claim 1, wherein: in the step (1), the mass ratio of the 4, 6-dihydroxypyrimidine to the toluene is 1: 4-6.
9. The process for synthesizing dichloropyrimidine as claimed in claim 1, wherein: the mass ratio of the 4, 6-dihydroxypyrimidine added in the step (1) to the water added in the step (3) is 1: 6-8.
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| CN202310863232.9A CN116924996A (en) | 2023-07-14 | 2023-07-14 | Synthesis process of dichloropyrimidine |
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| CN202310863232.9A CN116924996A (en) | 2023-07-14 | 2023-07-14 | Synthesis process of dichloropyrimidine |
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