CN114539045B - Racemization method of trans-L-chrysanthemic acid - Google Patents
Racemization method of trans-L-chrysanthemic acid Download PDFInfo
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- CN114539045B CN114539045B CN202011292956.5A CN202011292956A CN114539045B CN 114539045 B CN114539045 B CN 114539045B CN 202011292956 A CN202011292956 A CN 202011292956A CN 114539045 B CN114539045 B CN 114539045B
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- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/09—Preparation of carboxylic acids or their salts, halides or anhydrides from carboxylic acid esters or lactones
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- C07C67/00—Preparation of carboxylic acid esters
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- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
Abstract
A general racemization method of trans-L-chrysanthemic acid, which belongs to the field of organic synthesis. Esterifying trans-L-chrysanthemic acid, racemizing with Lewis acid in solvent at 70-120deg.C for 4-6 hr, adding water, reacting for 2 hr, washing oil layer with water, desolventizing, acidifying, and filtering to obtain trans-chrysanthemic acid with structure shown in the following formula I:
Description
Technical Field
The invention relates to the technical field of chemical synthesis, in particular to a general racemization method of trans-L-chrysanthemic acid.
Background
Pyrethroids are widely used worldwide as an important class of hygiene and agricultural pesticides. Most pyrethroid compounds contain a cyclopropane structure and have multiple optical isomers. The biological activity of different optical isomers has a great difference, one of the optical isomers has a remarkable effect, while the other isomers are generally ineffective or inefficient and even generate high toxic and side effects, such as allethrin and prallethrin have eight chiral isomers, wherein trans- (R, S) -has the best insecticidal activity, and cis- (R, S) -has the highest activity in eight isomers of cypermethrin, so that the efficient preparation of high-optical-purity pyrethroid compounds has been a long-sought goal in the scientific and enterprise industries.
The key to preparing the high optical purity chiral pyrethroid insecticide is the high-efficiency synthesis of chiral chrysanthemic acid intermediate. The general chiral chrysanthemic acid intermediates comprise trans-dextrorotation first chrysanthemic acid, cis-dextrorotation DV chrysanthemic acid, trans-dextrorotation DV chrysanthemic acid and the like. At present, the chiral chrysanthemic acid intermediates are all obtained by chiral resolution methods. Because half of chiral invalid bodies can be generated in the splitting process, how to use the chiral invalid bodies has important significance for saving raw materials, reducing resource waste, reducing three wastes, saving the production cost of chiral chrysanthemic acid and the like. An important way to use chiral invalid is to racemize the chiral invalid and then re-split the chiral invalid. The most studied at present is racemization of trans-L-first chrysanthemic acid, of which the more typical method is: 1. chrysanthemic acid halide-lewis acid method: the method comprises the steps of halogenating trans-L-first chrysanthemic acid, generally acyl chloridizing, racemizing by using Lewis acid as a catalyst, and then performing alkaline hydrolysis and acidification treatment to obtain trans-racemized first chrysanthemic acid [ G.Suzukamo, chem.Inform.1985,16,154].2. Chrysanthemum anhydride-lewis acid method: the method converts trans-L-first chrysanthemic acid into chrysanthemic anhydride, racemizes the chrysanthemic acid under the action of Lewis acid, and prepares trans-first chrysanthemic acid through hydrolysis (EP 0061880). 3. Photoinitiation method: the process uses phenyl ethyl ketone, phenyl isobutyl ketone, etc. as initiator and racemizes trans-l-first chrysanthemic acid under irradiation of low pressure mercury lamp (DE 2013924). 4. Chemical initiation method: the chemical initiators used are generally peroxides or azo compounds and the catalysts may be Lewis acids, mercaptans (phenols), bromine-containing compounds and the like (EP 0165070). However, these racemization methods of the first chrysanthemic acid are not applicable to racemization of trans-levorotatory DV-chrysanthemic acid and trans-levorotatory 3-acetyl-2, 2-dimethylcyclopropane carboxylic acid. At present, racemization of trans-L-DV-chrysanthemic acid is not reported in industrial application, but racemization research of trans-L-3-acetyl-2, 2-dimethylcyclopropane carboxylic acid is not reported in literature, and racemization of trans-L-chrysanthemic acid is still an important challenge facing current chrysanthemic acid production enterprises. Therefore, the development of a general racemization method for trans-L-chrysanthemic acid has positive significance for high-efficiency utilization of resources, production cost saving and the like.
Disclosure of Invention
The invention aims to obtain trans-racemization chrysanthemic acid through two steps of esterification and racemization by trans-L-chrysanthemic acid with low drug effect or invalid, so as to realize the recycling of trans-racemization chrysanthemic acid, improve the utilization rate of raw materials and reduce the production cost. In order to solve the technical problems, the invention adopts the following technical scheme:
esterifying trans-L-chrysanthemic acid, racemizing the obtained trans-L-chrysanthemic acid ethyl ester with Lewis acid in a solvent at 70-120 ℃ for 4-6 hours, adding water with the same mass as the solvent, continuously reacting for 2 hours, washing an oil layer with water, desolventizing, acidifying, and filtering to obtain the solid trans-chrysanthemic acid.
In the technical scheme of the invention, the trans-L-chrysanthemic acid (I) comprises trans-L-3-acetyl-2, 2-dimethylcyclopropane carboxylic acid (I-1), trans-L-first chrysanthemic acid (I-2) and trans-L-DV chrysanthemic acid (I-3), and the structure is as follows:
in the technical scheme of the invention, the racemization process of the trans-L-chrysanthemic acid is carried out according to the following reaction route:
in the above technical scheme, the lewis acid is one or more of aluminum trichloride, zinc chloride, ferric bromide and boron trifluoride.
In the technical scheme, the solvent is one or more of toluene, acetonitrile, dichloroethane, methanol, ethanol, isopropanol, dioxane, dimethyl sulfoxide and N, N-dimethylformamide.
In the technical scheme, the molar ratio of the trans-L-ethyl chrysanthemate to the Lewis acid is 1:0.1-0.5.
In the technical scheme, the weight ratio of the trans-L-ethyl chrysanthemate to the solvent is 1:2-10.
In the above technical scheme, the acid used in the acidification is one of hydrochloric acid and sulfuric acid.
The invention has the beneficial effects that:
the method for racemizing trans-L-chrysanthemic acid has the characteristics of strong universality, mild reaction process conditions, simple operation, high raceme yield and the like, and is favorable for industrial production.
Drawings
The invention will be described in further detail with reference to the accompanying drawings and embodiments:
FIG. 1 is a nuclear magnetic resonance spectrum of trans 3-acetyl-2, 2-dimethylcyclopropane carboxylic acid;
FIG. 2 is a diagram of a trans first hydrogen chrysanthemate spectrum;
FIG. 3 is a graph of trans DV chrysanthemic acid hydrogen spectrum;
Detailed Description
The following examples further illustrate the invention, but are not intended to limit it.
Nuclear magnetic resonance was determined by Bruker NMR, GC analysis conditions were as follows: agilent Technologies, inc.19091G-B233, HP-CHIRAL-20B,30 m.times. 0.250mm,0.25Micron,30to 240 ℃and 2.5mL/min (10.631 psi) at 130℃for a holding time of 60min.
Esterification reaction
15.6g (0.1 mol,95.5% ee) of trans-form 3-acetyl-2, 2-dimethylcyclopropane carboxylic acid, 50g of ethanol and 1.56g of concentrated sulfuric acid are added into a 100mL single-port bottle, reflux reaction is carried out for 3 hours, the temperature is reduced to room temperature after the reaction is finished, the ethanol is removed by decompression concentration, 30g of water is added for washing twice, saturated saline water is added, and anhydrous sodium sulfate is dried for standby.
Example 1
17.0g (0.1 mol) of trans-L-3-acetyl-2, 2-dimethylcyclopropane carboxylic acid ethyl ester prepared by esterification reaction, 50g of toluene and 2.67g (0.02 mol) of aluminum trichloride are heated and reflux-reacted for 5 hours, 50g of water is added, reflux is continued for 2 hours, the temperature is reduced to room temperature, standing and liquid separation are carried out, the organic layer is decompressed, concentrated and desolventized, 2mol/L of hydrochloric acid 50g is added, stirring is carried out at room temperature for 1 hour, 12.5g of trans-racemic 3-acetyl-2, 2-dimethylcyclopropane carboxylic acid is separated out, and the yield is 80%. Toluene is added into the aqueous solution for extraction, and the organic layer is concentrated to recover trans-L-3-acetyl-2, 2-dimethylcyclopropane carboxylic acid, so that the aqueous solution can be recycled. 1 H NMR(400MHz,Chloroform-d)δ2.56(d,J＝5.8Hz,1H),2.37(dd,J＝5.5,1.7hz,1 h), 2.28 (d, j=1.4 hz,3 h), 1.38 (d, j=1.6 hz,3 h), 1.20 (d, j=1.7 hz,3 h). The detected product is trans-L-3-acetyl-2, 2-dimethylcyclopropane carboxylic acid, and a nuclear magnetic resonance hydrogen spectrum is shown as 1.
Example 2
17.0g (0.1 mol) of trans-L-3-acetyl-2, 2-dimethylcyclopropane carboxylic acid ethyl ester prepared by esterification reaction, 50g of dichloroethane and 2.73g (0.02 mol) of zinc chloride are reacted under heating reflux for 4 hours, 50g of water is added, the reflux is continued for 2 hours, the temperature is reduced to room temperature, the solution is separated by standing, the organic layer is concentrated under reduced pressure to remove the solvent, 50g of 2mol/L hydrochloric acid is added, the stirring is carried out at room temperature for 1 hour, 13.2g of trans-racemic 3-acetyl-2, 2-dimethylcyclopropane carboxylic acid is separated out, and the yield is 84.6%. Toluene is added into the aqueous solution for extraction, and the organic layer is concentrated to recover trans-L-3-acetyl-2, 2-dimethylcyclopropane carboxylic acid, so that the aqueous solution can be recycled.
Example 3
17.0g (0.1 mol) of trans-L-3-acetyl-2, 2-dimethylcyclopropane carboxylic acid ethyl ester prepared by esterification reaction, 50g of dioxane, 5.9g (0.02 mol) of ferric bromide are heated and refluxed for 4 hours, 50g of water is added, reflux is continued for 2 hours, the temperature is reduced to room temperature, standing and liquid separation are carried out, the organic layer is decompressed, concentrated and the solvent is removed, 2mol/L hydrochloric acid is added, the mixture is stirred for 1 hour at room temperature, 12.2g of trans-racemization 3-acetyl-2, 2-dimethylcyclopropane carboxylic acid is separated out, and the yield is 78.2%. Toluene is added into the aqueous solution for extraction, and trans-L-3-acetyl-2, 2-dimethylcyclopropane carboxylic acid is recovered by concentration, so that the aqueous solution can be recycled.
Example 4
17.0g (0.1 mol) of trans-L-3-acetyl-2, 2-dimethylcyclopropane carboxylic acid ethyl ester prepared by esterification reaction, 50g of methanol, 1.36g (0.02 mol) of boron trifluoride are heated and reflux-reacted for 6 hours, 50g of water is added, reflux is continued for 2 hours, after the solvent is removed by decompression concentration, 50g of 2mol/L hydrochloric acid is added, stirring is carried out for 1 hour at room temperature, 14.3g of trans-racemic 3-acetyl-2, 2-dimethylcyclopropane carboxylic acid is separated out, and the yield is 91.6%. Toluene is added into the aqueous solution for extraction, and trans-L-3-acetyl-2, 2-dimethylcyclopropane carboxylic acid is recovered by concentration, so that the aqueous solution can be recycled.
Example 5
Esterification reaction to obtain19.6g (0.1 mol) of prepared trans-L-first chrysanthemic acid ethyl ester, 50g of dichloroethane and 2.67g (0.02 mol) of aluminum trichloride are reacted for 6 hours under heating reflux, 50g of water is added, reflux is continued for 2 hours, the mixture is kept still at room temperature, after the solvent is removed by decompression concentration, 50g of 2mol/L hydrochloric acid is added, the mixture is stirred for 1 hour at room temperature, 15.3g of trans-racemic first chrysanthemic acid is separated out, and the yield is 91.1%. Toluene is added into the aqueous solution for extraction, and trans-L-first chrysanthemic acid is recovered by concentration, so that the aqueous solution can be recycled. 1 H NMR (400 mhz, chloroform-d) delta 8.03 (s, 1H), 4.90 (dt, j=7.8, 1.5hz, 1H), 2.18 (s, 1H), 2.09 (dd, j=7.8, 5.3hz, 1H), 1.73-1.69 (m, 6H), 1.30 (s, 3H), 1.15 (s, 3H). The detected product is trans-L-first chrysanthemic acid, and the hydrogen spectrogram is shown as 2.
Example 6
The reaction of 23.7g (0.1 mol) of trans-L-DV chrysanthemic acid ethyl ester, 50g of dichloroethane and 1.36g (0.02 mol) of boron trifluoride under heating reflux is carried out for 6 hours, 50g of water is added, the reflux is continued for 2 hours, the mixture is kept stand at room temperature, after the solvent is removed by decompression concentration, 50g of 2mol/L hydrochloric acid is added, the mixture is stirred at room temperature for 1 hour, 18.6g of trans-D-DV chrysanthemic acid is separated out, and the yield is 86.1%. Toluene is added into the aqueous solution for extraction, and trans-L-DV chrysanthemic acid is recovered by concentration, so that the aqueous solution can be recycled. 1 H NMR (400 mhz, chloroform-d) delta 5.59 (d, j=8.3 hz, 1H), 2.16 (d, j=5.6 hz, 1H), 1.55 (d, j=5.2 hz, 1H), 1.33-1.21 (m, 3H), 1.17 (s, 3H). The detected product is trans DV chrysanthemic acid, and the hydrogen spectrum is shown in figure 3.
The above examples are only for illustrating the technical concept and technical features of the present invention, and should not be construed as limiting the scope of the present invention. All equivalent changes or modifications made in accordance with the essence of the present invention should be included in the scope of the present invention.
Claims (5)
1. A racemization method of trans-L-chrysanthemic acid, which is characterized by comprising the following steps: the method comprises the following steps:
esterifying trans-L-chrysanthemic acid ethyl ester, racemizing the obtained trans-L-chrysanthemic acid ethyl ester with Lewis acid in a solvent at 70-120 ℃ for 4-6 hours, adding water with the same mass as the solvent, continuously reacting for 2 hours, washing an oil layer with water, desolventizing, acidifying, and filtering to obtain a solid trans-chrysanthemic acid;
the trans-L-chrysanthemic acid is selected from trans-3-acetyl-2, 2-dimethylcyclopropanecarboxylic acid (I-1), trans-first chrysanthemic acid (I-2) and trans-DV chrysanthemic acid (I-3), and has the following structure:
the Lewis acid is one or more of aluminum trichloride, zinc chloride, ferric bromide and boron trifluoride.
2. A process for racemizing trans-l-chrysanthemic acid according to claim 1, characterized in that: the solvent is one or more of toluene, acetonitrile, dichloroethane, methanol, ethanol, isopropanol, dioxane, dimethyl sulfoxide and N, N-dimethylformamide.
3. A process for racemizing trans-l-chrysanthemic acid according to claim 1, characterized in that: the mol ratio of the trans-L-ethyl chrysanthemate to the Lewis acid is 1:0.1-0.5.
4. A process for racemizing trans-l-chrysanthemic acid according to claim 1, characterized in that: the weight ratio of the trans-L-ethyl chrysanthemate to the solvent is 1:2-10.
5. A process for racemizing trans-l-chrysanthemic acid according to claim 1, characterized in that: the acid used in the acidification is one of hydrochloric acid and sulfuric acid.
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| US4485257A (en) * | 1981-03-30 | 1984-11-27 | Sumitomo Chemical Company, Limited | Process for preparing racemized cyclopropanecarboxylic acids or their derivatives |
| JPS60174744A (en) * | 1984-02-22 | 1985-09-09 | Sumitomo Chem Co Ltd | Method for racemizing chrysanthemum-monocarboxylic acid derivative |
| JPS63196542A (en) * | 1987-02-10 | 1988-08-15 | Sumitomo Chem Co Ltd | Racemization of optically active chrysanthemum monocarboxylic acids |
| JP2000302723A (en) * | 1999-04-22 | 2000-10-31 | Sumitomo Chem Co Ltd | Racemization of dihalovinyl-cyclopropanecarboxylic acids |
| CN1397542A (en) * | 2001-07-18 | 2003-02-19 | 住友化学工业株式会社 | Process to enable recemation of optical rotatary vinyl substituted cyclopropane carboxylic compound |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5337858B2 (en) * | 1973-11-12 | 1978-10-12 | ||
| JP2600354B2 (en) * | 1988-12-21 | 1997-04-16 | 住友化学工業株式会社 | Method for producing racemic chrysanthemic acids |
| CN108276288A (en) * | 2018-03-12 | 2018-07-13 | 江苏扬农化工股份有限公司 | A kind of racemization method of left-handed trans-chrysanthemate Arrcostab |
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Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4485257A (en) * | 1981-03-30 | 1984-11-27 | Sumitomo Chemical Company, Limited | Process for preparing racemized cyclopropanecarboxylic acids or their derivatives |
| JPS60174744A (en) * | 1984-02-22 | 1985-09-09 | Sumitomo Chem Co Ltd | Method for racemizing chrysanthemum-monocarboxylic acid derivative |
| JPS63196542A (en) * | 1987-02-10 | 1988-08-15 | Sumitomo Chem Co Ltd | Racemization of optically active chrysanthemum monocarboxylic acids |
| JP2000302723A (en) * | 1999-04-22 | 2000-10-31 | Sumitomo Chem Co Ltd | Racemization of dihalovinyl-cyclopropanecarboxylic acids |
| CN1397542A (en) * | 2001-07-18 | 2003-02-19 | 住友化学工业株式会社 | Process to enable recemation of optical rotatary vinyl substituted cyclopropane carboxylic compound |
| CN105272848A (en) * | 2014-07-08 | 2016-01-27 | 沈阳古德科技有限公司 | Preparation method for 3-(2,2-dichloroethyenyl)-2,2-dimethylcyclopropanecarboxylic acid |
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