CN119462633A - Sulfopyrrole (L.) Harf Synthesis method of azole - Google Patents

Abstract

The invention discloses a method for synthesizing sulfonepyraclostrobin, wherein raw material A and air are used as raw materials, and an oxidation reaction is carried out under the catalysis of an Fe (III) catalyst to obtain sulfonepyraclostrobin. The method has mild reaction conditions, high yield, less three wastes, avoids the use and storage of hydrogen peroxide, has low cost, and is suitable for industrial production.

Description

Sulfopyrrole (L.) Harf Synthesis method of azole

Technical Field

The invention relates to a synthesis method of haloxyfop-R-methyl, in particular to a synthesis method of haloxyfop-R-methyl with simple synthesis process and simple operation, belonging to the technical field of organic synthesis.

Background

The fenpyr-ethyl is developed by Japanese combinatorial chemical Co., ltd, and has the chemical name of 3- [5- (difluoromethoxy) -1-methyl-3- (trifluoromethyl) pyrazol-4-ylmethyl sulfonyl ] -4, 5-dihydro-5, 5-dimethyl-1, 2-isoxazole, and has the following structure:

the fenpyrazamine can be used as a pre-emergence soil treatment agent for most crop fields, is absorbed by weed young roots and young buds after application, inhibits early growth of seedlings, damages meristematic tissues and coleoptile, and is a serious potential inhibitor in biosynthesis of VLCFA (very long side chain fatty acid) (C20-C30) in plants.

The synthesis of haloxyfop-methyl is reported in the following prior art:

Patent CN102666503a discloses that it can use hydrogen peroxide to perform oxidation reaction, specifically as follows:

The oxidation process using the oxidant hydrogen peroxide is reported in patent CN116761802a, and is specifically as follows:

most of the processes of the preparation method of the fenpyr reported in the current literature adopt hydrogen peroxide for oxidation reaction, but because of the characteristic that the hydrogen peroxide is easy to decompose, safety risks exist in storage and use, and accidents of the hydrogen peroxide occur frequently in recent years, so that a safer oxidation mode is selected to be solved urgently.

Disclosure of Invention

Aiming at the defects existing in the prior art, the invention provides a synthesis method of the haloxyfop-R-methyl, which takes air as an oxidant and carries out oxidation reaction under the catalysis of a catalyst to synthesize the haloxyfop-R-methyl, and the method has the advantages of mild reaction condition, high safety, low cost, less three wastes and suitability for industrial production.

The specific technical scheme of the invention is as follows:

a synthesis method of the haloxyfop-R-methyl takes raw material A and air as raw materials, and carries out oxidation reaction under the catalysis of Fe (III) catalyst to obtain the haloxyfop-R-methyl, wherein the reaction formula is as follows:

In the synthesis method, raw material A is used as an intermediate, air is used as an oxidant, and oxidation reaction is carried out under the catalysis of Fe (III) catalyst, so as to obtain the fenpyrad. Wherein, the raw material A can be purchased from the market or can be synthesized by itself according to the method reported in the prior art.

Further, in the above synthesis method, the Fe (III) catalyst is a trivalent iron salt, and may be Fe(NO₃)₃·9H₂O、Fe(NO₃)₃、Fe(OAc)₃、FeCl₃、Fe₂(SO₄)₃、FeBr₃ or the like, and the catalyst may be one kind or two or more kinds.

Further, in the above synthesis method, the molar ratio of the raw material a to the Fe (III) catalyst is 1:1% -15%, for example, 1:1%, 1:2%, 1:3%, 1:4%, 1:5%, 1:6%, 1:7%, 1:8%, 1:9%, 1:10%, 1:11%, 1:12%, 1:13%, 1:14%, 1:15%.

Further, in the above synthesis method, air is introduced into the system during the reaction to a pressure of 0.11-0.3 MPa, for example, the pressure during the reaction may be 0.11 Mpa、0.12 Mpa、0.13 Mpa、0.14 Mpa、0.15 Mpa、0.16 Mpa、0.17 Mpa、0.18 Mpa、0.19 Mpa、0.20Mpa、0.21 Mpa、0.22 Mpa、0.23 Mpa、0.24 Mpa、0.25 Mpa、0.26 Mpa、0.27 Mpa、0.28 Mpa、0.29 Mpa、0.30Mpa.

Further, in the above synthesis method, the reaction is performed in a solvent which acts as a reaction medium, and the solvent is at least one of acetic acid, chloroacetic acid, trifluoroacetic acid, difluoroacetic acid, and propionic acid, and the amount of the solvent is adjusted as needed.

Further, in the above synthesis method, the reaction temperature is 60 ℃ to 100 ℃, for example 60 ℃, 65 ℃, 70 ℃, 75 ℃, 80 ℃, 85 ℃,90 ℃, 95 ℃ and 100 ℃, preferably 75 to 85 ℃. At this reaction temperature, the raw material A reacts rapidly with air in the presence of a catalyst for a reaction time of <4 hours, for example, 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 3.9h, and generally for about 3 hours.

In the synthesis method, the specific reaction steps are that the raw material A, the catalyst and the solvent are mixed during the reaction, then air is introduced, and the reaction is carried out after the reaction temperature is raised. After the reaction is finished, filtering and separating while the reaction is hot, collecting mother liquor, adding water for cooling and crystallizing, and centrifugally separating to obtain a product. The invention has simple post-treatment and easy operation, and the obtained product has high purity and high yield.

The invention provides a novel method for synthesizing metazopyr, the raw material A, the catalyst and the air are directly reacted in one step to obtain the fenpyrad. Compared with the existing synthesis method using chemical oxidants such as hydrogen peroxide, the invention has the following advantages:

(1) The method has the advantages of few reaction steps, high reaction speed, simple synthesis process, mild reaction conditions and few side reactions, improves the reaction selectivity and the reaction yield through the selection of the process conditions, improves the product purity, and is verified that under the preferable process conditions, the product yield is more than 93 percent and the purity can be more than 98 percent;

(2) The product obtained by the invention is easy to separate, the post-treatment is simple and extensive, and the method is suitable for large-scale production;

(3) The three wastes generated in the synthesis process are less, the method is easy to treat and has good environmental protection;

(4) The invention creatively uses an air catalysis mode to oxidize in the preparation process of the fenpyrad, avoids using hydrogen peroxide which is easy to decompose, improves the safety of the process, reduces the cost and achieves intrinsic safety.

Detailed Description

The technical scheme of the present invention will be further described with reference to specific examples, but the present invention is not limited to the following examples. The raw materials used in the present invention are commercially available unless otherwise specified. Or may be synthesized by itself according to methods reported in the prior art.

The following concentrations are mass percent concentrations unless otherwise specified.

In the following examples, the yield is calculated as yield= (product mass. Product purity/product molecular weight)/product theoretical molar mass. Times.100%.

Example 1

Under the condition of room temperature, 20ml of acetic acid, 5.0g (content 87%) of raw material A and 0.737g of catalyst Fe (NO ₃)₃·9H₂ O are added into a reactor and stirred, air is introduced into the reactor to maintain the pressure of 0.15MPa, the temperature is raised to 80 ℃ for reaction, the reaction is kept at the temperature for 3.0hr, after the HPLC detection reaction is completed, the reaction liquid is filtered by heating, filtrate is collected, then 20g of water is added into the filtrate dropwise, the temperature is slowly reduced for crystallization, after the temperature is reduced to 5 ℃, the temperature is kept for 1hr, 4.62g of white solid is obtained after filtration, the purity is 98.4% by HPLC detection, and the yield is 96% based on the raw material A.

Example 2

Adding 20ml of trifluoroacetic acid, 5.0g (content 87%) of raw material A and 0.439g of catalyst Fe (NO 3) ₃ into a reactor at room temperature, stirring, introducing air into the reactor, maintaining the pressure at 0.25MPa, heating to 75 ℃ for reaction, preserving heat for 3.0hr, thermally filtering the reaction liquid after the HPLC detection reaction is complete, collecting filtrate, then dropwise adding 20g of water into the filtrate, slowly cooling for crystallization, cooling to 5 ℃, preserving heat for 1hr, filtering to obtain 4.61g of white solid, detecting by HPLC, wherein the purity is 98.3%, and the yield is 95.7% calculated by raw material A.

Example 3

Under the condition of room temperature, 20ml of acetic acid, 5.0g (content 87%) of raw material A and 0.439g of catalyst Fe (NO ₃)₃ are added into a reactor and stirred, air is introduced into the reactor to maintain the pressure of 0.2MPa, the temperature is raised to 95 ℃ for reaction, the reaction is kept for 3.0hr, after the HPLC detection reaction is completed, the reaction liquid is filtered by heating, the filtrate is collected, then 20g of water is added into the filtrate in a dropwise manner, the temperature is slowly reduced for crystallization, after the temperature is reduced to 5 ℃, the temperature is kept for 1hr, the white solid 4.57g is obtained after filtration, the purity is 98.1% by HPLC detection, and the yield is 94.7% based on the raw material A.

Example 4

Under the condition of room temperature, adding 20ml of acetic acid, 5.0g (content 87%) of raw material A and 0.244g of catalyst Fe (NO ₃)₃·9H₂ O, stirring, introducing air into the reactor, maintaining the pressure at 0.15MPa, heating to 85 ℃ for reaction, preserving heat for 3.0hr, thermally filtering the reaction liquid after the HPLC detection reaction is complete, collecting filtrate, then dropwise adding 20g of water into the filtrate, slowly cooling for crystallization, cooling to 5 ℃, preserving heat for 1hr, filtering to obtain 4.62g of white solid, detecting by HPLC, wherein the purity is 98.3%, and the yield is 95.9% calculated by raw material A.

Example 5

The preparation of paraquat sulfone was carried out as in example 1, except that the solvent of the reaction was 20ml chloroacetic acid, the reaction pressure was 0.14MPa, and the remaining steps were unchanged. The purity was 98.1% by detection, and the yield was 94.5% based on the starting material A.

Example 6

The preparation of metazachlor was carried out in the same manner as in example 1 except that the catalyst used for the reaction was 0.001mol of iron acetate, the reaction pressure was 0.18MPa, and the remaining steps were unchanged. The purity was found to be 98% and the yield was found to be 93.5% based on starting material A.

Example 7

The preparation of metazachlor was carried out in the same manner as in example 1, except that the reaction temperature was 70℃and the reaction pressure was 0.25MPa, with the remaining steps unchanged. The purity was found to be 98.1% and the yield was found to be 95.5% based on the starting material A.

Example 8

The preparation of topiramate was carried out according to the method of example 1, except that the reaction temperature was 80℃and the reaction catalyst was 0.001mol of ferric bromide, the remaining steps were unchanged. The purity was found to be 98.1% and the yield was found to be 93.5% based on the starting material A.

Comparative example 1

The preparation of topiramate was carried out according to the method of example 1, except that no catalyst was added, the reaction temperature was 80℃and the remaining steps were unchanged. The reaction is carried out for 3 hours, the raw materials are not reacted, the reaction is prolonged for 12 hours, the reaction is still carried out, and the experiment is stopped.

The invention has been described in detail with reference to preferred embodiments thereof. However, variations and additions to the various embodiments will also be apparent to those of ordinary skill in the art upon a review of the foregoing description. It is the intention of the applicant that all such variations and additions fall within the scope of the claims of the invention. The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. Unless defined otherwise, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Any modification and improvement of the product, and the substitution and use of similar or similar substances in the scope of the patent claims are all included in the protection scope of the invention.

Claims (10)

1. A method for synthesizing sulfonepyraclostrobin, characterized in that: raw material A and air are used as raw materials, and an oxidation reaction is carried out under the catalysis of an Fe (III) catalyst to obtain sulfonepyraclostrobin; the reaction formula is as follows: . 2. The synthesis method according to claim 1, characterized in that the Fe(III) catalyst is a trivalent iron salt. 3. The synthesis method according to claim 2, characterized in that the Fe(III) catalyst is at least one of Fe( _NO3 ) ₃ · _9H2O , Fe( _NO3 ) ₃ , Fe(OAc) ₃ , _FeCl3 , Fe2( _SO4 ) ₃ , _{and FeBr3} . 4. The synthesis method according to claim 1, 2 or 3, characterized in that the molar ratio of raw material A to Fe(III) catalyst is 1:1% to 15%. 5. The synthesis method according to claim 1, 2 or 3, characterized in that during the reaction, the air pressure in the system is 0.11-0.3 MPa. 6. The synthesis method according to claim 1, 2 or 3, characterized in that the reaction temperature is 60-100°C. 7. The synthesis method according to claim 6 is characterized in that the reaction time is less than 4 hours. 8. The synthesis method according to claim 1, 2 or 3, characterized in that the reaction is carried out in a solvent. 9. The synthesis method according to claim 8, characterized in that the solvent is at least one of acetic acid, chloroacetic acid, trifluoroacetic acid, difluoroacetic acid, and propionic acid. 10. The synthesis method according to claim 8, characterized in that: during the reaction, the raw material A, the catalyst and the solvent are mixed, and then air is introduced and the temperature is raised to the reaction temperature to react.