CN117820280A - Preparation method of propiconazole intermediate - Google Patents
Preparation method of propiconazole intermediate Download PDFInfo
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- CN117820280A CN117820280A CN202311748796.4A CN202311748796A CN117820280A CN 117820280 A CN117820280 A CN 117820280A CN 202311748796 A CN202311748796 A CN 202311748796A CN 117820280 A CN117820280 A CN 117820280A
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- propiconazole
- reaction
- dichlorophenyl
- propyl
- methyl
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- 239000005822 Propiconazole Substances 0.000 title claims abstract description 24
- STJLVHWMYQXCPB-UHFFFAOYSA-N propiconazole Chemical compound O1C(CCC)COC1(C=1C(=CC(Cl)=CC=1)Cl)CN1N=CN=C1 STJLVHWMYQXCPB-UHFFFAOYSA-N 0.000 title claims abstract description 24
- 238000002360 preparation method Methods 0.000 title claims abstract description 15
- 238000006243 chemical reaction Methods 0.000 claims abstract description 37
- ZOVODRUFYPBAKW-UHFFFAOYSA-N 2-(2,4-dichlorophenyl)-2-methyl-4-propyl-1,3-dioxolane Chemical compound O1C(CCC)COC1(C)C1=CC=C(Cl)C=C1Cl ZOVODRUFYPBAKW-UHFFFAOYSA-N 0.000 claims abstract description 17
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 claims abstract description 14
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 claims abstract description 11
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 claims abstract description 11
- XUXNAKZDHHEHPC-UHFFFAOYSA-M sodium bromate Chemical compound [Na+].[O-]Br(=O)=O XUXNAKZDHHEHPC-UHFFFAOYSA-M 0.000 claims abstract description 10
- PJVTZAKVRVBCMJ-UHFFFAOYSA-N 2-(bromomethyl)-2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolane Chemical compound O1C(CCC)COC1(CBr)C1=CC=C(Cl)C=C1Cl PJVTZAKVRVBCMJ-UHFFFAOYSA-N 0.000 claims abstract description 9
- 238000004519 manufacturing process Methods 0.000 claims abstract description 8
- 239000003960 organic solvent Substances 0.000 claims abstract description 8
- 238000000034 method Methods 0.000 claims abstract description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000004289 sodium hydrogen sulphite Substances 0.000 claims abstract description 5
- 238000010438 heat treatment Methods 0.000 claims abstract description 3
- 238000003756 stirring Methods 0.000 claims abstract description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 12
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical group CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 238000004821 distillation Methods 0.000 claims description 3
- 239000012044 organic layer Substances 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
- 239000003054 catalyst Substances 0.000 claims description 2
- 230000007935 neutral effect Effects 0.000 claims description 2
- 238000004321 preservation Methods 0.000 claims description 2
- 230000001105 regulatory effect Effects 0.000 claims description 2
- 238000005893 bromination reaction Methods 0.000 abstract description 14
- 230000031709 bromination Effects 0.000 abstract description 6
- 230000003197 catalytic effect Effects 0.000 abstract description 4
- 230000036632 reaction speed Effects 0.000 abstract description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- 239000003899 bactericide agent Substances 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 230000000694 effects Effects 0.000 description 2
- 238000003912 environmental pollution Methods 0.000 description 2
- 150000003852 triazoles Chemical group 0.000 description 2
- XMCRWEBERCXJCH-UHFFFAOYSA-N 1-(2,4-dichlorophenyl)ethanone Chemical compound CC(=O)C1=CC=C(Cl)C=C1Cl XMCRWEBERCXJCH-UHFFFAOYSA-N 0.000 description 1
- 241000235349 Ascomycota Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 241000221198 Basidiomycota Species 0.000 description 1
- -1 Dichloroethane (dichloroethane) Acetonitrile Tetrahydrofuran Chemical compound 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000221785 Erysiphales Species 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 229930182558 Sterol Natural products 0.000 description 1
- 241000209140 Triticum Species 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 230000032798 delamination Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000011987 methylation Effects 0.000 description 1
- 238000007069 methylation reaction Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- WCVRQHFDJLLWFE-UHFFFAOYSA-N pentane-1,2-diol Chemical compound CCCC(O)CO WCVRQHFDJLLWFE-UHFFFAOYSA-N 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 150000003432 sterols Chemical class 0.000 description 1
- 235000003702 sterols Nutrition 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of propiconazole intermediate, which comprises the steps of sequentially adding water, sodium bromate, an organic solvent, 2- (2, 4-dichlorophenyl) -2-methyl-4-propyl-1, 3-dioxolane and azodiisobutyronitrile into a reaction bottle, stirring and heating to 30-100 ℃, dropwise adding sodium bisulfite solution, keeping the temperature at the reaction temperature for reacting for 1-4 h, and after the reaction is finished, performing post-treatment to obtain propiconazole intermediate 2- (2, 4-dichlorophenyl) -2-bromomethyl-4-propyl-1, 3-dioxolane. The method adopts a catalytic bromination system of sodium bromate, sodium bisulphite and azodiisobutyronitrile, and the catalytic bromination system not only greatly accelerates the bromination reaction speed, but also greatly improves the conversion rate of the bromination reaction, thereby obtaining higher reaction yield, and simultaneously, the product purity is higher, thereby being suitable for industrial mass production.
Description
Technical Field
The invention belongs to the technical field of bactericide intermediate preparation, and particularly relates to a preparation method of propiconazole intermediate.
Background
Propiconazole is triazole bactericide developed by the company Zhengda, belongs to sterol methylation inhibitor, is systemic bactericide with protection and treatment effects, can be absorbed by roots, stems and leaves, can be quickly conducted upwards in plant plants, can prevent and treat diseases caused by ascomycetes, basidiomycetes and half-known bacteria, and has better prevention and treatment effects on wheat take-all, powdery mildew, rust disease, root rot, rice bakanae disease and sigatoka.
The general synthetic route for propiconazole is: taking 2, 4-dichloro acetophenone and 1, 2-pentanediol as starting materials, carrying out cyclization reaction to obtain a first intermediate 2- (2, 4-dichlorophenyl) -2-methyl-4-propyl-1, 3-dioxolane, carrying out bromination reaction to obtain a second intermediate 2- (2, 4-dichlorophenyl) -2-bromomethyl-4-propyl-1, 3-dioxolane, and condensing with triazole to obtain propiconazole [ see document 1-document 4 ], wherein the specific synthetic route is as follows:
。
for the second bromination reaction in the above synthetic route, the prior art has problems of: (1) The intermediate 2- (2, 4-dichlorophenyl) -2-methyl-4-propyl-1, 3-dioxolane is an unstable substance, and the bromination by adopting liquid bromine is easy to generate reversible reaction, so that the conversion rate of the bromination reaction is lower, and the method is not suitable for industrial mass production. (2) In the prior art, liquid bromine is basically used as a brominating agent, on one hand, the liquid bromine has strong volatility, is unsafe to use and difficult to meter, and on the other hand, the liquid bromine has slower bromination reaction, and the generated bromination tail gas is difficult to treat and has serious environmental pollution.
Document 1: chinese patent document CN101323612a, publication date is 12 months and 17 days of 2008.
Document 2: chinese patent document CN101781290a, publication date is 2010, 07, 21.
Document 3: chinese patent document CN102225935a, publication date is 2011, 10, 26.
Document 4: chinese patent document CN113444077a, publication date is 2021, 09, 28.
Disclosure of Invention
The invention aims to solve the problems and provide a preparation method of propiconazole intermediate with high safety, less environmental pollution, high reaction speed and high reaction yield.
The technical scheme for realizing the aim of the invention is as follows: a preparation method of propiconazole intermediate 2- (2, 4-dichlorophenyl) -2-bromomethyl-4-propyl-1, 3-dioxolane, which is characterized by comprising the following steps:
(1) sequentially adding water, a brominating agent sodium bromate, an organic solvent, 2- (2, 4-dichlorophenyl) -2-methyl-4-propyl-1, 3-dioxolan and a catalyst azodiisobutyronitrile into a reaction bottle, stirring and heating to 30-100 ℃, dropwise adding a sodium bisulfite solution, and carrying out heat preservation reaction for 1-4 h at the reaction temperature.
(2) After the reaction is finished, the reaction system is cooled to room temperature (15-25 ℃ and the same applies below), the pH value of the reaction system is regulated to be neutral, the reaction system is kept stand for layering, the organic layer is washed by water, and the solvent is removed by reduced pressure distillation, so as to obtain the propiconazole intermediate 2- (2, 4-dichlorophenyl) -2-bromomethyl-4-propyl-1, 3-dioxolane.
The steps are as aboveIn (b), the organic solvent is dichloroethane, acetonitrile, tetrahydrofuran or toluene, preferably dichloroethane or acetonitrile, more preferably dichloroethane.
In the step (1), the reaction temperature is 50 to 80 ℃.
In the step (1), the molar ratio of the 2- (2, 4-dichlorophenyl) -2-methyl-4-propyl-1, 3-dioxolan to the sodium bromate is 1:2-1:3, preferably 1:2-1:2.2.
In the step (1), the molar ratio of the 2- (2, 4-dichlorophenyl) -2-methyl-4-propyl-1, 3-dioxolan to the azobisisobutyronitrile is 1:0.01-1:0.1, preferably 1:0.03-1:0.08.
In the step (1), the molar ratio of the 2- (2, 4-dichlorophenyl) -2-methyl-4-propyl-1, 3-dioxolan to the sodium bisulphite is 1:5-1:7, preferably 1:5-1:5.5.
The invention has the positive effects that: the method adopts a catalytic bromination system of sodium bromate, sodium bisulphite and azodiisobutyronitrile, and the catalytic bromination system not only greatly accelerates the bromination reaction speed of 2- (2, 4-dichlorophenyl) -2-methyl-4-propyl-1, 3-dioxolane, but also greatly improves the conversion rate of the bromination reaction of 2- (2, 4-dichlorophenyl) -2-methyl-4-propyl-1, 3-dioxolane, thereby obtaining higher reaction yield and higher product purity, and being suitable for industrialized mass production.
Detailed Description
Example 1
The preparation method of the propiconazole intermediate 2- (2, 4-dichlorophenyl) -2-bromomethyl-4-propyl-1, 3-dioxolane in the embodiment is specifically as follows:
300g of water, 92.87g of sodium bromate (0.615 mol), 300g of dichloroethane, 82.5g of 2- (2, 4-dichlorophenyl) -2-methyl-4-propyl-1, 3-dioxolan (0.3 mol) and 1.97g of azobisisobutyronitrile (0.012 mol) are sequentially added into a reaction flask, stirred and heated to 70+/-2 ℃, 497.25g of 32wt% sodium bisulfite solution (1.53 mol) is added dropwise, and after the completion of the dropwise addition, the reaction is carried out at 70+/-2 ℃ for 2 hours.
After the reaction was completed, the reaction system was cooled to room temperature, a 30wt% aqueous sodium hydroxide solution was added dropwise to adjust the ph=7.0 of the reaction system, the mixture was allowed to stand for delamination, the organic layer was washed with water, and the solvent was removed by distillation under reduced pressure to give 101.2g of a pale yellow liquid 2- (2, 4-dichlorophenyl) -2-bromomethyl-4-propyl-1, 3-dioxolane in a yield of 95.3% and a GC purity of 98.6%.
Example 2 to example 3
The propiconazole intermediate preparation method of each example is basically the same as that of example 1, except for the organic solvent and the reaction temperature, and is specifically shown in table 1.
TABLE 1
| Example 1 | Example 2 | Example 3 | |
| Organic solvents | Dichloroethane (dichloroethane) | Acetonitrile | Tetrahydrofuran (THF) |
| Reaction temperature | 70±2℃ | 70±2℃ | 60±2℃ |
| Product(s) | 101.2g | 99.9g | 90.9g |
| Yield is good | 95.3% | 94.1% | 85.6% |
| Purity of | 98.6% | 97.5% | 95.2% |
Example 4 to example 8
The preparation method of each example was basically the same as that of example 1, except that table 2 was shown.
TABLE 2
| Example 1 | Example 4 | Example 5 | Example 6 | Example 7 | Example 8 | |
| Sodium bromate | 92.87g，0.615mol | 92.87g，0.615mol | 92.87g，0.615mol | 99.67g，0.66mol | 99.67g，0.66mol | 99.67g，0.66mol |
| Azobisisobutyronitrile | 1.97g，0.012mol | 0.985g，0.006mol | 3.94g，0.024mol | 1.97g，0.012mol | 0.985g，0.006mol | 3.94g，0.024mol |
| 32wt% sodium bisulfite solution | 497.25g，1.53mol | 497.25g，1.53mol | 497.25g，1.53mol | 536.25g，1.65mol | 536.25g，1.65mol | 536.25g，1.65mol |
| Product(s) | 101.2g | 95.8g | 102.2g | 101.9g | 98.3g | 103.1g |
| Yield is good | 95.3% | 90.2% | 96.2% | 96.0% | 92.6% | 97.1% |
| Purity of | 98.6% | 97.2% | 98.7% | 98.8% | 97.9% | 99.0% |
Comparative example 1
The difference between this comparative example and example 1 is that: in the step (1), azodiisobutyronitrile is not added, and after the results of the reactions for 2h, 5h and 8h, the target product 2- (2, 4-dichlorophenyl) -2-bromomethyl-4-propyl-1, 3-dioxolane is not detected in the reaction system.
Comparative example 2
The difference between this comparative example and example 1 is that: and (3) after the sodium bisulfite solution is not added in the step (1) and the reaction is carried out for 2 hours, 5 hours and 8 hours, the target product 2- (2, 4-dichlorophenyl) -2-bromomethyl-4-propyl-1, 3-dioxolane is not detected in the reaction system.
Claims (10)
1. The preparation method of the propiconazole intermediate is characterized by comprising the following steps:
(1) sequentially adding water, a brominating agent sodium bromate, an organic solvent, 2- (2, 4-dichlorophenyl) -2-methyl-4-propyl-1, 3-dioxolan and a catalyst azodiisobutyronitrile into a reaction bottle, stirring and heating to 30-100 ℃, dropwise adding a sodium bisulfite solution, and carrying out heat preservation reaction for 1-4 h at the reaction temperature after the dropwise addition;
(2) after the reaction is finished, the reaction system is cooled to room temperature, the pH value of the reaction system is regulated to be neutral, the reaction system is kept stand for layering, the organic layer is washed by water, and the solvent is removed by reduced pressure distillation to obtain the propiconazole intermediate 2- (2, 4-dichlorophenyl) -2-bromomethyl-4-propyl-1, 3-dioxolane.
2. The process for preparing propiconazole intermediate according to claim 1, wherein: in the step (1), the organic solvent is dichloroethane, acetonitrile, tetrahydrofuran or toluene.
3. The process for preparing propiconazole intermediate according to claim 2, wherein: in the step (1), the organic solvent is dichloroethane or acetonitrile.
4. A process for the preparation of propiconazole intermediate according to any one of claims 1 to 3, wherein: in the step (1), the reaction temperature is 50 to 80 ℃.
5. A process for the preparation of propiconazole intermediate according to any one of claims 1 to 3, wherein: in the step (1), the molar ratio of the 2- (2, 4-dichlorophenyl) -2-methyl-4-propyl-1, 3-dioxolan to the sodium bromate is 1:2-1:3.
6. The process for preparing propiconazole intermediate according to claim 5, wherein: in the step (1), the molar ratio of the 2- (2, 4-dichlorophenyl) -2-methyl-4-propyl-1, 3-dioxolan to the sodium bromate is 1:2-1:2.2.
7. A process for the preparation of propiconazole intermediate according to any one of claims 1 to 3, wherein: in the step (1), the molar ratio of the 2- (2, 4-dichlorophenyl) -2-methyl-4-propyl-1, 3-dioxolan to the azodiisobutyronitrile is 1:0.01-1:0.1.
8. The process for preparing propiconazole intermediate according to claim 7, wherein: in the step (1), the molar ratio of the 2- (2, 4-dichlorophenyl) -2-methyl-4-propyl-1, 3-dioxolan to the azodiisobutyronitrile is 1:0.03-1:0.08.
9. A process for the preparation of propiconazole intermediate according to any one of claims 1 to 3, wherein: in the step (1), the molar ratio of the 2- (2, 4-dichlorophenyl) -2-methyl-4-propyl-1, 3-dioxolan to the sodium bisulphite is 1:5-1:7.
10. The process for preparing propiconazole intermediate according to claim 9, wherein: in the step (1), the molar ratio of the 2- (2, 4-dichlorophenyl) -2-methyl-4-propyl-1, 3-dioxolan to the sodium bisulphite is 1:5-1:5.5.
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