Preparation method of pyraflufen-ethyl key intermediate

Abstract

The invention relates to the field of synthesis of pesticide intermediates, in particular to a preparation method of a pyraflufen-ethyl key intermediate, which is characterized in that a compound 1 shown in the following figure and CO are subjected to carbonyl insertion reaction in ethanol under the catalysis of a cobalt catalyst to generate a compound 2, and the latter is the key intermediate of the pesticide pyraflufen-ethyl. According to the method, the conversion of alpha-chloroketone to beta-keto ester is realized in one step, the route is simplified, the use of expensive reagents is avoided, the cost is reduced, three wastes, reaction and post-treatment are simple, the defects in the prior art are overcome, and the method has industrial value. # imgabs0 #

Description

Technical Field

[0001] The present invention relates to the field of synthesis of pesticide intermediates, and particularly to a preparation method of a key intermediate of pyraflufen-ethyl. Background Art

[0002] Pyraflufen-ethyl, with the chemical name of ethyl 2-chloro-5-[4-chloro-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl]-4-fluorophenoxyacetate and the English name of ethyl 2-chloro-5-[4-chloro-5-(difluoromethoxy)-1-methyl-1H-pyrazol-3-yl]-4-fluorophenoxyace, its mechanism of action is to inhibit the protoporphyrinogen-4 oxidase in plants, and utilize the different active metabolites generated by the differences in the absorption and deposition of the drug by wheat and weeds to achieve the purpose of selectively controlling weeds in wheat fields.

[0003] The synthesis of pyraflufen-ethyl and this key intermediate mainly has the following several routes:

[0004] Route 1: Yang Guozhang, Herbicides for Wheat Fields - Pyraflufen-ethyl, World Pesticides, 2011, 33(6), 55 - 56. reported the following synthesis route:

[0005]

[0006] Route 2: Japanese Patent JP3646224B2 reported the second route, specifically as follows:

[0007]

[0008] Similar to the above first route, the difference is that the cyano group is first hydrolyzed into an amide, then reacted with sodium cyanide, and then the ring is closed. The subsequent steps are similar to those of Route 1.

[0009] Although the methods reported in the above-mentioned literatures can all obtain the product, the routes for constructing the pyrazole ring precursor (referring to the substance reacting with methylhydrazine or its salt) are relatively complex, with many steps and the use of highly toxic sodium cyanide. Since the product is easily soluble in water under alkaline conditions, acid needs to be added during post-treatment, and this process will generate highly toxic volatile hydrogen cyanide, and the lethal concentration of the latter in the air is as low as three ten-thousandths. Whether it is laboratory operation or industrial production, it is very troublesome.

[0010] Route 3: CN1059200C discloses a method for preparing this key intermediate by carbonylation insertion reaction under the catalysis of palladium using 2-fluoro-4-chloro-5-cyanoethoxy-α-chloroacetophenone as the raw material, as shown in the following reaction formula:

[0011]

[0012] Although the target product can be obtained by this process and the yield is at a moderately high level, the palladium catalyst used is too expensive, resulting in high costs. The phosphine ligand used also has a high price and generates phosphorus-containing wastewater, making it difficult to achieve industrial production. SUMMARY OF THE INVENTION

[0013] The object of the present invention is to provide a method for preparing the intermediate of pyraclonil β-ketoester in view of the problems existing in the prior art, simplifying the route and avoiding the use of highly toxic sodium cyanide and expensive palladium catalyst.

[0014] To achieve the above object, the technical solution of the present invention is: a method for preparing a key intermediate of pyraclonil, the method comprising: a carbonylation reaction of compound 1 with CO in ethanol under the catalysis of zinc powder, NaHSO3 or Na2SO3, and a cobalt salt catalyst to generate compound 2, namely the key intermediate of pyraclonil. The reaction formula is as follows:

[0015]

[0016] Preferably, the cobalt salt catalyst is a salt formed by Co 2 + and a chemically acceptable anion, such as cobalt(II) acetate, cobalt(II) sulfate, cobalt(II) chloride, cobalt(II) bromide; the molar ratio of the cobalt salt catalyst to compound 1 is 0.02-0.2:1; preferably, the molar ratio of the cobalt salt catalyst to compound 1 is 0.03-0.2:1; preferably, the molar ratio of the cobalt salt catalyst to compound 1 is 0.03-0.15:1. Preferably, the molar ratio of the cobalt salt catalyst to compound 1 is 0.06-0.15:1.

[0017] Preferably, the CO pressure is 10-30 atm. Preferably, the CO pressure is 15-30 atm.

[0018] Preferably, the reaction temperature is 30-110 °C. Preferably, the reaction temperature is 50-110 °C; preferably, the reaction temperature is 60-110 °C; preferably, the reaction temperature is 70-110 °C;

[0019] Preferably, the mass ratio of zinc powder to compound 1 is 0.05-0.15:1. Preferably, the mass ratio of zinc powder to compound 1 is 0.09-0.15:1. Preferably, the mass ratio of zinc powder to compound 1 is 0.09-0.12:1.

[0020] Preferably, the mass ratio of Na2SO3 or NaHSO3 to compound 1 is 0.1-0.5:1. Preferably, the mass ratio of Na2SO3 or NaHSO3 to compound 1 is 0.2-0.5:1.

[0021] Preferably, the mass ratio of ethanol to Compound 1 is 3 - 8:1. More preferably, the mass ratio of ethanol to Compound 1 is 5 - 8:1.

[0022] The beneficial effects of the present invention are as follows: Using Compound 1 as the raw material, through the carbonylation reaction of a cheap cobalt salt catalyst, the conversion of α-chloroketone to β-ketoester is achieved in one step, simplifying the route, avoiding the use of expensive reagents, reducing costs and waste, with simple reaction and post-treatment, overcoming the deficiencies of the prior art, and having industrial value. Description of the Drawings

[0023] Figure 1 is Example 1 1 1H NMR spectrum. Detailed Embodiments

[0024] Example 1 Preparation of Intermediate 2

[0025] Add 500 mL of ethanol, 10 g of zinc powder, 5 g of cobalt chloride, and 30 g of sodium bisulfite to a 1000 mL autoclave. After purging with carbon monoxide twice, ventilate to 20 atm, heat to 30 - 40 °C, hold the reaction for 3 h, then cool down and release the pressure. Add 100 g of the raw material chloride (1), heat to 90 °C, hold for 6 h, and sample to detect the progress of the reaction. Filter the reaction solution by suction. After distilling off ethanol under reduced pressure from the filtrate, slowly add 50 g of 36% hydrochloric acid, then dropwise add 800 g of pure water. A large amount of solid precipitates. Filter by suction to obtain 106.4 g of the crude product. Then recrystallize with petroleum ether:ethyl acetate = 5:1. After vacuum drying the product, 86.1 g of a pale yellow solid is obtained, with a yield of 75.3% and an HPLC purity of 99.1%.

[0026] Product Structure Characterization: 1 1H NMR (DMSO-d 6 , δ) 7.74 (d, 1H, J = 10.0 Hz), 7.48 (d, 1H, J = 6.0 Hz), 5.063 - 5.056 (m, 2H), 5.025 (s, 2H), 4.19 (q, 2H, J = 6.4 Hz), 1.23 (t, 3H, J = 6.4 Hz), ESI-MS: 300, 302 [M+H + .

[0027] As a comparison, using the method reported in Synthetic Communications, 1990, 20(17), 2631 - 2640, the carbonylation reaction was carried out with the substrate Compound 1 used in the present invention, and the yield fluctuated around 20%, which was consistent with the literature report.

[0028] Example 2 Screening of the Type and Dosage of Cobalt Salt Catalyst

[0029] Using the method of Example 1, with other conditions unchanged, the following results are obtained:

[0030] Types of cobalt salts Dosage of cobalt salts Yield HPLC purity <![CDATA[CoCl2]]> 2g 65.6％ 98.2％ <![CDATA[CoCl2]]> 4g 74.5％ 98.5％ <![CDATA[CoCl2]]> 6g 75.5％ 99.0％ <![CDATA[CoCl2]]> 8g 75.9％ 99.1％ <![CDATA[CoCl2]]> 10g 76.0％ 99.1％ <![CDATA[Co(OAc)2]]> 2g 67.4％ 98.5％ <![CDATA[Co(OAc)2]]> 4g 75.3％ 98.6％ <![CDATA[Co(OAc)2]]> 6g 77.2％ 99.2％ <![CDATA[Co(OAc)2]]> 8g 76.7％ 99.3％ <![CDATA[Co(OAc)2]]> 10g 76.9％ 99.3％ <![CDATA[CoBr2]]> 2g 60.3％ 98.7％ <![CDATA[CoBr2]]> 4g 74.7％ 99.0％ <![CDATA[CoBr2]]> 6g 76.9％ 99.3％ <![CDATA[CoBr2]]> 8g 77.4％ 99.4％ <![CDATA[CoBr2]]> 10g 77.6％ 99.4％

[0031] Example 3 CO Pressure Screening

[0032] Using the method of Example 1, with other conditions unchanged, only changing the pressure of CO, the following results are obtained:

[0033]

[0034]

[0035] Example 4 Temperature Screening

[0036] Using the method of Example 1, with other conditions unchanged, only changing the temperature, the following results are obtained:

[0037] Temperature Yield HPLC purity 50℃ 32.7％ Not detected 60℃ 48.6％ Not detected 70℃ 60.5％ 98.7％ 80℃ 67.4％ 98.8％ 90℃ 75.3％ 99.1％ 100℃ 76.4％ 99.0％ 110℃ 72.1％ 98.9％

[0038] Example 5 Zinc Powder Dosage Screening

[0039] Using the method of Example 1, with other conditions unchanged, only changing the dosage of zinc powder, the following results are obtained:

[0040] Dosage of zinc powder Yield HPLC purity 8g 66.3％ 98.2％ 9g 72.4％ 98.9％ 10g 75.3％ 99.1％ 11g 77.0％ 99.0％ 12g 76.8％ 99.1％

[0041] Example 6 Sodium Sulfite (Bisulfite) Dosage Screening

[0042] Using the method of Example 1, with other conditions unchanged, only changing the dosage of sodium sulfite or sodium bisulfite, the following results are obtained:

[0043]

[0044]

[0045] As described above, it is only the specific implementation manners of the present invention, but the protection scope of the present invention is not limited thereto. Any variations or substitutions that can be easily thought of by those skilled in the art within the technical scope disclosed by the present invention should be covered within the protection scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims described.

Claims

1. A preparation method of a key intermediate of pyraflufen-ethyl, characterized in that, The method includes: Compound 1 reacts with CO in ethanol under the catalysis of zinc powder, NaHSO3 or Na2SO3, and a cobalt salt catalyst to carry out a carbonylation reaction to generate Compound 2, that is, the key intermediate of pyraclonil, and the reaction formula is as follows:

2. The preparation method according to claim 1, wherein The cobalt salt catalyst is a salt formed by Co 2+ and a chemically acceptable anion, and the molar ratio of the cobalt salt catalyst to Compound 1 is 0.02 - 0.2:

1.

3. The preparation method according to claim 1, characterized in that, The CO pressure is 10 - 30 atm.

4. The preparation method according to claim 1, wherein The reaction temperature is 30 - 110 °C.

5. The preparation method according to claim 1, characterized in that, The mass ratio of zinc powder to Compound 1 is 0.05 - 0.15:

1.

6. The preparation method according to claim 1, characterized in that, The mass ratio of Na2SO3 or NaHSO3 to Compound 1 is 0.1 - 0.5:

1.

7. The preparation method according to claim 1, characterized in that The mass ratio of ethanol to Compound 1 is 3 - 8:1.

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