CN117586141A - Preparation method of fenhexamid - Google Patents
Preparation method of fenhexamid Download PDFInfo
- Publication number
- CN117586141A CN117586141A CN202311592560.6A CN202311592560A CN117586141A CN 117586141 A CN117586141 A CN 117586141A CN 202311592560 A CN202311592560 A CN 202311592560A CN 117586141 A CN117586141 A CN 117586141A
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- CN
- China
- Prior art keywords
- hydroxyaniline
- dichloro
- preparation
- cyproconazole
- methylcyclohexane
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- VDLGAVXLJYLFDH-UHFFFAOYSA-N fenhexamid Chemical compound C=1C=C(O)C(Cl)=C(Cl)C=1NC(=O)C1(C)CCCCC1 VDLGAVXLJYLFDH-UHFFFAOYSA-N 0.000 title abstract description 6
- 239000005776 Fenhexamid Substances 0.000 title abstract description 5
- 238000006243 chemical reaction Methods 0.000 claims abstract description 21
- OQHWFUQNSLMSBG-UHFFFAOYSA-N 4-amino-2,3-dichlorophenol Chemical compound NC1=CC=C(O)C(Cl)=C1Cl OQHWFUQNSLMSBG-UHFFFAOYSA-N 0.000 claims abstract description 19
- -1 1-methylcyclohexane acyl chloride Chemical class 0.000 claims abstract description 13
- UFNOUKDBUJZYDE-UHFFFAOYSA-N 2-(4-chlorophenyl)-3-cyclopropyl-1-(1H-1,2,4-triazol-1-yl)butan-2-ol Chemical compound C1=NC=NN1CC(O)(C=1C=CC(Cl)=CC=1)C(C)C1CC1 UFNOUKDBUJZYDE-UHFFFAOYSA-N 0.000 claims abstract description 12
- 239000005757 Cyproconazole Substances 0.000 claims abstract description 12
- 239000002904 solvent Substances 0.000 claims abstract description 10
- 239000002253 acid Substances 0.000 claims abstract description 9
- 239000011230 binding agent Substances 0.000 claims abstract description 9
- 239000003223 protective agent Substances 0.000 claims abstract description 8
- 238000006482 condensation reaction Methods 0.000 claims abstract description 7
- 239000002994 raw material Substances 0.000 claims abstract description 6
- 150000003950 cyclic amides Chemical class 0.000 claims abstract description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 28
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 21
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 10
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 claims description 9
- DCFKHNIGBAHNSS-UHFFFAOYSA-N chloro(triethyl)silane Chemical compound CC[Si](Cl)(CC)CC DCFKHNIGBAHNSS-UHFFFAOYSA-N 0.000 claims description 6
- 239000005051 trimethylchlorosilane Substances 0.000 claims description 6
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 3
- 229940043279 diisopropylamine Drugs 0.000 claims description 3
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 claims description 3
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 claims description 3
- 239000008096 xylene Substances 0.000 claims description 3
- 125000003944 tolyl group Chemical group 0.000 claims description 2
- 239000006227 byproduct Substances 0.000 abstract description 4
- 238000009776 industrial production Methods 0.000 abstract description 3
- 230000002349 favourable effect Effects 0.000 abstract description 2
- 239000000047 product Substances 0.000 abstract description 2
- 238000003786 synthesis reaction Methods 0.000 abstract description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 239000008399 tap water Substances 0.000 description 5
- 235000020679 tap water Nutrition 0.000 description 5
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 239000003899 bactericide agent Substances 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010034133 Pathogen resistance Diseases 0.000 description 1
- 241000221662 Sclerotinia Species 0.000 description 1
- 241000219094 Vitaceae Species 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 235000021021 grapes Nutrition 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
- C07F7/1872—Preparation; Treatments not provided for in C07F7/20
- C07F7/188—Preparation; Treatments not provided for in C07F7/20 by reactions involving the formation of Si-O linkages
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
-
- 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
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
Abstract
The invention relates to the field of chemical synthesis, in particular to a preparation method of fenhexamid, which comprises the following steps: 2, 3-dichloro-4-hydroxyaniline and 1-methylcyclohexane acyl chloride are used as main raw materials, a protective agent, a solvent and an acid binding agent are added, and the cyclic amide is obtained through condensation reaction. The preparation method of the cyproconazole provided by the invention has the advantages of short route, mild reaction conditions, higher product yield and content and small byproducts, is favorable for industrial production of the cyproconazole, and has good application prospect.
Description
Technical Field
The invention relates to the field of chemical synthesis, in particular to a preparation method of fenhexamid.
Background
The fenhexamid (trade name Elevate, password, teldor, etc.) is a novel amide systemic bactericide developed by Bayer in Germany, is very effective for preventing and treating gray mold, sclerotinia, and the like, is also effective for strains with resistance to other medicaments, and has no cross resistance with the existing bactericide. The method is mainly used for preventing and controlling diseases of vegetables, grapes, fruit trees and the like.
Huang Wei et al reported that 2, 3-dichloro-4-hydroxyaniline and 1-methylcyclohexane acyl chloride are used as main raw materials, toluene is used as a solvent, and the reflux reaction is performed to obtain the cyproconazole with a yield of 90%.
Ling Gang et al, report that 2, 3-dichloro-4-hydroxyaniline and 1-methylcyclohexane acyl chloride are used as main raw materials, toluene is used as a solvent, triethylamine is used as an acid-binding agent, and the reflux reaction is carried out to obtain the cyproconazole with the yield of 92.4%.
Both of these methods suffer from similar disadvantages: the yield is lower, the reaction temperature is higher, and esterification byproducts are easy to generate.
Therefore, the preparation method of the cyproconazole with mild reaction conditions, higher yield and small byproducts is developed, and has important significance for industrial production of the cyproconazole.
Disclosure of Invention
The invention aims to provide a novel preparation method of cyproconazole aiming at the problems existing in the prior art.
In order to achieve the above purpose, the technical scheme of the invention is as follows: a preparation method of the cyproconazole comprises the following steps:
2, 3-dichloro-4-hydroxyaniline and 1-methylcyclohexane acyl chloride are used as main raw materials, a protective agent, a solvent and an acid binding agent are added, and the cyclic amide is obtained through condensation reaction.
Further, the protective agent is trimethylchlorosilane, triethylchlorosilane or tert-butyldimethylchlorosilane;
further, the solvent is toluene or xylene, preferably toluene;
further, the acid binding agent is triethylamine, isopropylamine or diisopropylamine;
further, the molar ratio of the protective agent to the 2, 3-dichloro-4-hydroxyaniline is 1:1 to 1.5:1, more preferably 1.1:1;
further, the weight ratio of the solvent to the 2, 3-dichloro-4-hydroxyaniline is 1:1 to 10:1, more preferably 5:1 to 6:1;
further, the molar ratio of the acid-binding agent to the 2, 3-dichloro-4-hydroxyaniline is 1:1-5:1, more preferably 2:1-3:1;
further, the molar ratio of the 1-methylcyclohexane acyl chloride to the 2, 3-dichloro-4-hydroxyaniline is 1:1-1.5:1, and more preferably 1.1:1;
further, the reaction temperature of the condensation reaction is 20 to 50 ℃, preferably 20 to 30 ℃.
Further, a novel preparation method of the cyproconazole comprises the following steps: 2, 3-dichloro-4-hydroxyaniline and 1-methylcyclohexane acyl chloride are used as main raw materials, trimethylchlorosilane is used as a protective agent, toluene is used as a solvent, triethylamine is used as an acid binding agent, and the cyclic amide is obtained through condensation reaction;
the reaction route is as follows:
the beneficial effects of the invention are as follows: the preparation method of the cyproconazole provided by the invention has the advantages of short route, mild reaction conditions, higher product yield and content and small byproducts, is favorable for industrial production of the cyproconazole, and has good application prospect.
Drawings
Fig. 1: hydrogen profile in example 1.
Detailed Description
Example 1
2, 3-dichloro-4-hydroxyaniline (35.6 g,0.2 mol) was added to a 500ml reaction flask, 178g of toluene, triethylamine (42.5 g,0.42 mol) was added thereto, the temperature was lowered to 20 to 30℃and trimethylchlorosilane (23.9 g,0.22 mol) was slowly added dropwise thereto, stirred for 1 hour, 1-methylcyclohexane acyl chloride (35.3 g,0.22 mol) was added dropwise thereto, the reaction was carried out at 20 to 30℃for 5 hours with maintaining the temperature, the pH was adjusted to 4 to 5 with dilute hydrochloric acid, then the temperature was lowered to 10℃and filtered, washed with tap water, and dried to obtain 57.7g of cycloxapride, the yield was 95.5% and the content was 99.8%.
Example 2
2, 3-dichloro-4-hydroxyaniline (35.6 g,0.2 mol) was added to a 500ml reaction flask, 213.6g of toluene, isopropylamine (24.8 g,0.42 mol) was added, the temperature was lowered to 20 to 30℃and trimethylchlorosilane (23.9 g,0.22 mol) was slowly added dropwise, stirred for 1 hour, 1-methylcyclohexane acyl chloride (35.3 g,0.22 mol) was added dropwise, the reaction was carried out at 20 to 30℃for 5 hours under heat preservation, the pH was adjusted to 4 to 5 with dilute hydrochloric acid, then the temperature was lowered to 10℃and filtered, washed with tap water and dried to obtain 57.6g of cycloxapride, the yield was 95.4% and the content was 99.7%.
Example 3
2, 3-dichloro-4-hydroxyaniline (35.6 g,0.2 mol) was added to a 500ml reaction flask, 178g of xylene, triethylamine (42.5 g,0.42 mol) was added, the temperature was lowered to 20 to 30℃and triethylchlorosilane (33.1 g,0.22 mol) was slowly added dropwise, stirred for 1 hour, 1-methylcyclohexane acyl chloride (35.3 g,0.22 mol) was added dropwise, the reaction was carried out at 20 to 30℃for 5 hours with a constant temperature, the pH was adjusted to 4 to 5 with dilute hydrochloric acid, then the temperature was lowered to 10℃and filtered, washed with tap water, and dried to obtain 57.7g of cycloxapride, the yield was 95.5% and the content was 99.5%.
Example 4
2, 3-dichloro-4-hydroxyaniline (35.6 g,0.2 mol) was added to a 500ml reaction flask, 178g of toluene, diisopropylamine (46.5 g,0.46 mol) was added, the temperature was lowered to 20 to 30℃and trimethylchlorosilane (23.9 g,0.22 mol) was slowly added dropwise, stirred for 1 hour, 1-methylcyclohexane acyl chloride (35.3 g,0.22 mol) was added dropwise, the reaction was carried out at 20 to 30℃for 5 hours with a temperature-keeping reaction, the pH was adjusted to 4 to 5 with dilute hydrochloric acid, then the temperature was lowered to 10℃and filtered, washed with tap water, and dried to obtain 57.5g of cycloxapride, the yield was 95.1% and the content was 99.8%.
Example 5
2, 3-dichloro-4-hydroxyaniline (35.6 g,0.2 mol) was added to a 500ml reaction flask, 178g of toluene, triethylamine (42.5 g,0.42 mol) was added thereto, the temperature was lowered to 20 to 30℃and tert-butyldimethylsilyl chloride (33.1 g,0.22 mol) was slowly added dropwise thereto, stirred for 1 hour, 1-methylcyclohexane acyl chloride (41.7 g,0.26 mol) was added dropwise thereto, the reaction was carried out at 20 to 30℃for 5 hours under heat preservation, the pH was adjusted to 4 to 5 with dilute hydrochloric acid, then the temperature was lowered to 10℃and filtered, and the mixture was washed with tap water and dried to obtain 57.6g of cycloxapride, the yield was 95.3% and the content was 99.8%.
The foregoing is merely illustrative of the present invention, and the present invention is not limited thereto, and any changes or substitutions easily contemplated by those skilled in the art within the scope of the present invention should be included in the present invention. Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims.
Claims (9)
1. The preparation method of the cyproconazole is characterized by comprising the following steps:
2, 3-dichloro-4-hydroxyaniline and 1-methylcyclohexane acyl chloride are taken as main raw materials, a protective agent, a solvent and an acid binding agent are added, and the cyclic amide is obtained through condensation reaction, wherein the reaction temperature of the condensation reaction is 20-50 ℃.
2. The method according to claim 1, wherein the protective agent is one or more of trimethylchlorosilane, triethylchlorosilane or t-butyldimethylchlorosilane.
3. The method of claim 1, wherein the solvent is toluene or xylene.
4. The method according to claim 1, wherein the acid binding agent is one or more of triethylamine, isopropylamine or diisopropylamine.
5. The method according to claim 1, wherein the molar ratio of the protecting agent to 2, 3-dichloro-4-hydroxyaniline is between 1:1 and 1.5:1.
6. The method according to claim 1, wherein the weight ratio of the solvent to 2, 3-dichloro-4-hydroxyaniline is 1:1 to 10:1.
7. The method according to claim 1, wherein the molar ratio of the acid-binding agent to 2, 3-dichloro-4-hydroxyaniline is between 1:1 and 5:1.
8. The method according to claim 1, wherein the molar ratio of 1-methylcyclohexane acyl chloride to 2, 3-dichloro-4-hydroxyaniline is 1:1 to 1.5:1.
9. The method according to claim 1, wherein the reaction temperature of the condensation reaction is 20 to 30 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311592560.6A CN117586141A (en) | 2023-11-27 | 2023-11-27 | Preparation method of fenhexamid |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311592560.6A CN117586141A (en) | 2023-11-27 | 2023-11-27 | Preparation method of fenhexamid |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN117586141A true CN117586141A (en) | 2024-02-23 |
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ID=89909520
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202311592560.6A Pending CN117586141A (en) | 2023-11-27 | 2023-11-27 | Preparation method of fenhexamid |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN117586141A (en) |
-
2023
- 2023-11-27 CN CN202311592560.6A patent/CN117586141A/en active Pending
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