CN111187144A - Synthetic method of 3-chloro-2-methyl biphenyl and derivatives thereof - Google Patents
Synthetic method of 3-chloro-2-methyl biphenyl and derivatives thereof Download PDFInfo
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- CN111187144A CN111187144A CN201811357577.2A CN201811357577A CN111187144A CN 111187144 A CN111187144 A CN 111187144A CN 201811357577 A CN201811357577 A CN 201811357577A CN 111187144 A CN111187144 A CN 111187144A
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- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/26—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton
- C07C17/263—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by condensation reactions
- C07C17/2632—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by condensation reactions involving an organo-magnesium compound, e.g. Grignard synthesis
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- C07C209/74—Preparation of compounds containing amino groups bound to a carbon skeleton from amines, by reactions not involving amino groups, e.g. reduction of unsaturated amines, aromatisation, or substitution of the carbon skeleton by halogenation, hydrohalogenation, dehalogenation, or dehydrohalogenation
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Abstract
The invention discloses a method for synthesizing 3-chloro-2-methyl biphenyl and derivatives thereof, in particular to a method for synthesizing a bifenthrin intermediate 3-chloro-2-methyl biphenyl and derivatives thereof, wherein 3-chloro-2-methyl biphenyl is synthesized by taking monochlorobenzene and 2, 5-dichlorotoluene as raw materials in an organic solvent under the catalysis of Lewis acid, the yield of the 3-chloro-2-methyl biphenyl synthesized by the method can reach 85.6%, and the content can reach 96.2%. The solvent used in the method can be used in the reaction system after being recovered and treated, and the catalyst can be used in more than 5 batches through the internal filtration system.
Description
Technical Field
The invention relates to a synthetic method of 3-chloro-2-methyl biphenyl and derivatives thereof, in particular to a synthetic method of a bifenthrin intermediate 3-chloro-2-methyl biphenyl and derivatives thereof.
Background
Among the coupling reagents of aromatic ring, iodo aromatic hydrocarbon is easiest, bromo aromatic hydrocarbon is inferior, and chloro aromatic hydrocarbon is hardest, which is related to the activity of halogenated aromatic hydrocarbon. The activity of chlorinated aromatic hydrocarbon is far lower than that of iodo aromatic hydrocarbon. Therefore, few reports are made in the literature on the modification of the coupling reaction of chlorinated aromatic hydrocarbons. In the existing literature, most of coupling reagents used in metal-catalyzed aromatic ring coupling reaction are arylboronic acid compounds, the arylboronic acid, the iodoarene and the bromoarene are expensive, and meanwhile, the byproduct recycling process in industrial production is complex and the process cost is high, so that the method has important significance in industrial production by using the chlorinated arene as the coupling reagent.
Disclosure of Invention
The invention aims to solve the technical problem of the prior art and provides a synthetic method of a bifenthrin intermediate 3-chloro-2-methylbiphenyl and derivatives thereof, a method for selectively coupling chlorinated aromatic hydrocarbon with dichloroaromatic hydrocarbon by taking chlorinated aromatic hydrocarbon as a raw material and a compound prepared by the method.
In order to achieve the purpose, the invention adopts the following technical scheme:
a synthetic method of bifenthrin intermediate 3-chloro-2-methyl biphenyl and derivatives thereof comprises the following steps:
(1) preparing Grignard liquid: adding a compound I shown in a formula I and a magnesium strip into an organic solvent, adding an initiator into the system, and initiating at 60-120 ℃; after the initiation is successful, dropwise adding the mixed solution of the compound I and the organic solvent into the system, and performing a Grignard reaction at 20-120 ℃ to synthesize a Grignard solution in one step; filtering unreacted magnesium strips, directly carrying out the next reaction on the Grignard solution without further post-treatment, and keeping the Grignard solution for later use;
(2) synthesis of Compound III: taking the Grignard solution obtained in the step (1) and a compound II shown in a formula II as raw materials, carrying out a coupling reaction in an organic solvent under the catalysis of a selective coupling catalyst at 40-120 ℃, and carrying out one-step coupling synthesis on a compound III shown in a formula III;
(3) and (3) post-treatment: dropwise adding hydrochloric acid into the system obtained in the step (2) to adjust the pH value to be less than 1, and then sequentially carrying out standing layering, oil layer washing desolventizing and reduced pressure distillation to obtain a compound III, namely 3-chloro-2-methylbiphenyl and derivatives thereof;
the reaction equation is:
wherein, R1 is alkyl, amino, acyl, acylamino, alkoxy, R2 is alkyl, amino, acyl, acylamino, alkoxy.
In the above technical scheme, in the step (1), the initiator is iodine simple substance or 1, 2-dibromoethane.
In the technical scheme, in the step (1), the molar ratio of the initiating compound I to the dropwise adding compound I is 2.5-5: 1.
In the above technical scheme, in the step (1), the molar ratio of the initiator to the initiating compound I is 0.01-0.1:1 during initiation.
In the technical scheme, in the step (1), the molar ratio of the magnesium strip to the initiating compound I is 10-20:1 during initiation.
In the above technical scheme, in the step (1), the organic solvent is a mixture of any one, two or more of tetrahydrofuran, methyltetrahydrofuran, 2-dimethyltetrahydrofuran, diethyl ether, toluene, benzene, heptane, cyclohexane, octane and isooctane mixed in any ratio.
In the above technical scheme, in the step (1), the weight ratio of the organic solvent to the initiating compound I is 2-7: 1; after the successful initiation, the weight ratio of the organic solvent to the compound I is 2-7: 1.
in the above technical scheme, in the step (2), the organic solvent is a mixture of any one, two or more of tetrahydrofuran, methyltetrahydrofuran, 2-dimethyltetrahydrofuran, diethyl ether, toluene, benzene, heptane, cyclohexane, octane and isooctane mixed in any ratio.
In the above technical scheme, in the step (2), the weight ratio of the organic solvent to the grignard solution is 0.1-10: 1.
In the above technical scheme, in the step (2), the selective coupling catalyst is a mixture of any one, two or more of palladium chloride, palladium acetate (bis-triphenylphosphine), bis (triphenylphosphine) palladium dichloride, ruthenium chloride, rhodium chloride, cobalt chloride, nickel bromide, copper iodide, cuprous iodide and cuprous bromide mixed in any proportion.
In the above technical scheme, in the step (2), the molar ratio of the selective coupling catalyst to the compound II is 0.01-0.5: 1.
In the above technical scheme, in the step (2), the molar ratio of the initiation to the total consumption of the compound I and the compound II after the initiation is successful is 0.8-1.8: 1.
The technical scheme of the invention has the advantages that:
1. the Grignard group in the method is a group which is relatively chemically inert in the traditional chemistry, and the reaction activity is low.
2. The aromatic ring chlorine atom in the coupling group in the method is a difficult-to-leave group, and the chemical activity is low.
3. The reaction activities of two atoms on an aromatic ring in a coupling group in the method are the same, a double-coupling phenomenon is easy to occur during coupling, and the chlorobiphenyl product can be selectively coupled with one end of chlorine atom only by utilizing the method.
4. The halogenated aromatic hydrocarbon compound provided by the invention can be used for preparing a series of compounds with biphenyl structures and containing chlorine atoms, so that the halogenated aromatic hydrocarbon compound has important application value for preparing chlorinated biphenyl key intermediates in industrial production.
5. The catalyst in the method provided by the invention can directly catalyze the coupling reaction with high efficiency without adding a ligand.
6. The method provided by the invention has good compatibility on different functional groups of the substrate.
Detailed Description
The following detailed description of the embodiments of the present invention is provided, but the present invention is not limited to the following descriptions:
example 1: synthesis of 3-chloro-2-methylbiphenyl
The method comprises the following steps:
(1) preparation of a benzene monochloride Grignard solution: adding 50g of anhydrous benzene monochloride, 161g of magnesium strips, 200g of anhydrous methyltetrahydrofuran and 50g of anhydrous isooctane into a 2L reaction bottle under the protection of nitrogen, heating to 110 ℃, and adding 3g of iodine particles for initiation; after the initiation is successful, dropwise adding a mixed solution of 200g of anhydrous benzene monochloride and 800g of anhydrous methyl tetrahydrofuran, finishing dropping for 4h, keeping the temperature for 2h at 110 ℃ after the dropping is finished, filtering unreacted magnesium strips, and using Grignard solution for later use.
(2) Synthesis of 3-chloro-2-methylbiphenyl: under the protection of nitrogen, 357.6g of anhydrous 2, 5-dichlorotoluene, 1430g of anhydrous methyltetrahydrofuran and 8.5g of palladium chloride are added into a 5L reaction bottle, the temperature is raised to 60 ℃, the Grignard solution in the step (1) is dripped into the reaction bottle, dripping is finished for 2h, and the reaction is carried out for 4h under the heat preservation at 60 ℃ after dripping is finished.
(3) And (3) post-treatment: and (3) dropwise adding 36% hydrochloric acid into the system in the step (2) at 0-5 ℃ to adjust the pH value to be less than 1, heating to 30-40 ℃ after adjustment, stirring for 0.5h, standing for layering after stirring, removing solvent under normal pressure after washing an oil layer, and distilling under reduced pressure after removing solvent to obtain 385g of 3-chlorobenzene-2-methylbiphenyl, wherein the yield is 85.6%, and the GC content is 96.2%.
Example 2: synthesizing to obtain 4- (2-chloro-3-methylphenyl) aniline
(1) Preparation of p-amino-chlorobenzene grignard solution: adding 56.7g of anhydrous p-amino chlorobenzene, 161g of magnesium strips, 227g of anhydrous methyl tetrahydrofuran and 57g of anhydrous isooctane into a 2L reaction bottle under the protection of nitrogen, heating to 110 ℃, adding 3g of iodine particles for initiation, dropwise adding 226.7g of anhydrous p-amino chlorobenzene and 907g of anhydrous methyl tetrahydrofuran mixed solution after successful initiation, finishing dripping for 4 hours, preserving the temperature for 2 hours at 110 ℃ after dripping, filtering unreacted magnesium strips, and using Grignard liquid.
(2) Synthesis of 4- (2-chloro-3-methylphenyl) aniline: under the protection of nitrogen, 357.6g of anhydrous 2, 5-dichlorotoluene, 1430g of anhydrous methyltetrahydrofuran and 8.5g of palladium chloride are added into a 5L reaction bottle, the temperature is raised to 60 ℃, the Grignard solution is dripped in the reaction bottle after 2h, and the reaction is carried out for 4h at 60 ℃ after dripping.
(3) And (3) post-treatment: and (2) dropwise adding 36% hydrochloric acid into the Grignard solution at 0-5 ℃ to regulate the pH to be less than 1, heating to 30-40 ℃ after regulation, stirring for 0.5h, standing for layering after stirring, washing an oil layer, and then carrying out desolventizing at normal pressure, carrying out reduced pressure distillation after desolventizing to obtain 371g of 4- (2-chloro-3-methylphenyl) aniline, wherein the yield is 76.8%, and the GC content is 98.9%.
Example 3: synthesis of 2-chloro-6- (4-fluorophenyl) toluene
(1) Preparation of p-fluorobenzene Grignard solution: adding 58g of anhydrous p-chlorobenzene, 161g of magnesium strips, 232g of anhydrous methyl tetrahydrofuran and 58g of anhydrous isooctane into a 2L reaction bottle under the protection of nitrogen, heating to 110 ℃, adding 3g of iodine particles for initiation, dropwise adding a mixed solution of 232g of anhydrous p-chlorobenzene and 928g of anhydrous methyl tetrahydrofuran after successful initiation, finishing dropwise adding for 4 hours, keeping the temperature for 2 hours at 110 ℃ after dropwise adding, filtering unreacted magnesium strips, and keeping Grignard liquid for later use.
(2) Synthesis of 2-chloro-6- (4-fluorophenyl) toluene: under the protection of nitrogen, 357.6g of anhydrous 2, 5-dichlorotoluene, 1430g of anhydrous methyltetrahydrofuran and 8.5g of palladium chloride are added into a 5L reaction bottle, the temperature is raised to 60 ℃, the Grignard solution is dripped in the reaction bottle after 2h, and the reaction is carried out for 4h at 60 ℃ after dripping.
(3) And (3) post-treatment: and (2) dropwise adding 36% hydrochloric acid into the Grignard solution at 0-5 ℃ to regulate the pH value to be less than 1, heating to 30-40 ℃ after regulation, stirring for 0.5h, standing for layering after stirring, washing an oil layer, performing desolventization at normal pressure, performing reduced pressure distillation after desolventization to obtain 412.4g of 2-chloro-6- (4-fluorophenyl) toluene, wherein the yield is 84.2%, and the GC content is 95.7%.
Example 4: synthesis of 3-chloro-5- (4-fluorophenyl) 4-methylaniline
(1) Preparation of p-fluorobenzene Grignard solution: adding 58g of anhydrous p-chlorobenzene, 161g of magnesium strips, 232g of anhydrous methyl tetrahydrofuran and 58g of anhydrous isooctane into a 2L reaction bottle under the protection of nitrogen, heating to 110 ℃, adding 3g of iodine particles for initiation, dropwise adding a mixed solution of 232g of anhydrous p-chlorobenzene and 928g of anhydrous methyl tetrahydrofuran after successful initiation, finishing dropwise adding for 4 hours, keeping the temperature for 2 hours at 110 ℃ after dropwise adding, filtering unreacted magnesium strips, and keeping Grignard liquid for later use.
(2) Synthesis of 3-chloro-5- (4-fluorophenyl) 4-methylaniline: under the protection of nitrogen, 391g of anhydrous 3, 5-dichloro-4-methylaniline, 1563g of anhydrous methyltetrahydrofuran and 8.5g of palladium chloride are added into a 5L reaction bottle, the temperature is raised to 60 ℃, the Grignard solution is dripped in the reaction bottle for 2h, and the reaction is carried out for 4h under the condition of 60 ℃ after dripping.
(3) And (3) post-treatment: and (2) dropwise adding 36% hydrochloric acid into the Grignard solution at 0-5 ℃ to regulate the pH value to be less than 1, heating to 30-40 ℃ after regulation, stirring for 0.5h, standing for layering after stirring, washing an oil layer, performing desolventization at normal pressure, performing reduced pressure distillation after desolventization to obtain 462.4g of 3-chloro-5- (4-fluorophenyl) 4-methylaniline, wherein the yield is 88.4%, and the GC content is 96.2%.
Example 5: synthesis of 2-chloro-4-nitro-6- (4-fluorophenyl) toluene
(1) Preparation of p-fluorobenzene Grignard solution: adding 58g of anhydrous p-chlorobenzene, 161g of magnesium strips, 232g of anhydrous methyl tetrahydrofuran and 58g of anhydrous isooctane into a 2L reaction bottle under the protection of nitrogen, heating to 110 ℃, adding 3g of iodine particles for initiation, dropwise adding a mixed solution of 232g of anhydrous p-chlorobenzene and 928g of anhydrous methyl tetrahydrofuran after successful initiation, finishing dropwise adding for 4 hours, keeping the temperature for 2 hours at 110 ℃ after dropwise adding, filtering unreacted magnesium strips, and keeping Grignard liquid for later use.
(2) Synthesis of 2-chloro-4-nitro-6- (4-fluorophenyl) toluene: under the protection of nitrogen, 457.5g of anhydrous 2, 5-dichloro-4-nitrotoluene, 1830g of anhydrous methyltetrahydrofuran and 8.5g of palladium chloride are added into a 5L reaction bottle, the temperature is raised to 60 ℃, the Grignard solution is dripped into the reaction bottle for 2 hours, and the reaction is carried out for 4 hours at 60 ℃ after dripping.
(3) And (3) post-treatment: and (2) dropwise adding 36% hydrochloric acid into the Grignard solution at 0-5 ℃ to regulate the pH value to be less than 1, heating to 30-40 ℃ after regulation, stirring for 0.5h, standing for layering after stirring, washing an oil layer, performing desolventization at normal pressure, performing vacuum distillation after desolventization to obtain 494.1g of 2-chloro-4-nitro-6- (4-fluorophenyl) toluene, wherein the yield is 83.8%, and the GC content is 97.3%.
Example 6: synthesis of 2-chloro-4-nitro-6- (3-methylphenyl) toluene
(1) Preparation of m-chlorotoluene Grignard solution: adding 56.2g of anhydrous m-chlorotoluene, 161g of magnesium strips, 225g of anhydrous methyltetrahydrofuran and 56.2g of anhydrous isooctane into a 2L reaction bottle under the protection of nitrogen, heating to 110 ℃, adding 1.5g of iodine particles for initiation, dropwise adding a mixed solution of 225g of anhydrous m-chlorotoluene and 900g of anhydrous methyltetrahydrofuran after successful initiation, finishing dropping for 4 hours, preserving heat at 110 ℃ for 2 hours after dropping, filtering unreacted magnesium strips, and using Grignard liquid for later use.
(2) Synthesis of 2-chloro-4-nitro-6- (3-methylphenyl) toluene: under the protection of nitrogen, 457.5g of anhydrous 2, 5-dichloro-4-nitrotoluene, 1830g of anhydrous methyltetrahydrofuran and 8.5g of palladium chloride are added into a 5L reaction bottle, the temperature is raised to 60 ℃, the Grignard solution is dripped into the reaction bottle for 2 hours, and the reaction is carried out for 4 hours at 60 ℃ after dripping.
(3) And (3) post-treatment: and (2) dropwise adding 36% hydrochloric acid into the Grignard solution at 0-5 ℃ to regulate the pH value to be less than 1, heating to 20-30 ℃ after regulation, stirring for 0.5h, standing for layering after stirring, washing an oil layer, performing desolventization at normal pressure, performing reduced pressure distillation after desolventization to obtain 467.5g of 2-chloro-4-nitro-6- (3-methylphenyl) toluene, wherein the yield is 80.5%, and the GC content is 94.8%.
Example 7: synthesis of 2-chloro-4-amino-6- (3-methylphenyl) toluene
(1) Preparation of m-chlorotoluene Grignard solution: adding 56.2g of anhydrous m-chlorotoluene, 161g of magnesium strips, 225g of anhydrous methyltetrahydrofuran and 56.2g of anhydrous isooctane into a 2L reaction bottle under the protection of nitrogen, heating to 110 ℃, adding 1.5g of iodine particles for initiation, dropwise adding a mixed solution of 225g of anhydrous m-chlorotoluene and 900g of anhydrous methyltetrahydrofuran after successful initiation, finishing dropping for 4 hours, preserving heat at 110 ℃ for 2 hours after dropping, filtering unreacted magnesium strips, and using Grignard liquid for later use.
(2) Synthesis of 2-chloro-4-amino-6- (3-methylphenyl) toluene: under the protection of nitrogen, 391g of anhydrous 3, 5-dichloro-4-methylaniline, 1563g of anhydrous methyltetrahydrofuran and 8.5g of palladium chloride are added into a 5L reaction bottle, the temperature is raised to 60 ℃, the Grignard solution is dripped in the reaction bottle for 2h, and the reaction is carried out for 4h under the condition of 60 ℃ after dripping.
(3) And (3) post-treatment: and (2) dropwise adding 36% hydrochloric acid into the Grignard solution at 0-5 ℃ to regulate the pH to be less than 1, heating to 30-40 ℃ after regulation, stirring for 0.5h, standing for layering after stirring, washing an oil layer, performing desolventization at normal pressure, performing reduced pressure distillation after desolventization to obtain 342.3g of 2-chloro-4-amino-6- (3-methylphenyl) toluene, wherein the yield is 76.8%, and the GC content is 98.9%.
Example 8: synthesis of 3-fluoro-2-chloro-4- (m-methylphenyl) toluene
(1) Preparation of m-chlorotoluene Grignard solution: adding 56.2g of anhydrous m-chlorotoluene, 161g of magnesium strips, 225g of anhydrous methyltetrahydrofuran and 56.2g of anhydrous isooctane into a 2L reaction bottle under the protection of nitrogen, heating to 110 ℃, adding 1.5g of iodine particles for initiation, dropwise adding a mixed solution of 225g of anhydrous m-chlorotoluene and 900g of anhydrous methyltetrahydrofuran after successful initiation, finishing dropping for 4 hours, preserving heat at 110 ℃ for 2 hours after dropping, filtering unreacted magnesium strips, and using Grignard liquid for later use.
(2) Synthesis of 3-fluoro-2-chloro-4- (m-methylphenyl) toluene: under the protection of nitrogen, 397g of anhydrous 3-fluoro-2, 5-dichlorotoluene, 1590g of anhydrous methyltetrahydrofuran and 8.5g of palladium chloride are added into a 5L reaction bottle, the temperature is raised to 60 ℃, the Grignard solution is dropwise added, the dropwise addition is completed within 2h, and the heat preservation reaction is carried out for 4h at 60 ℃ after the dropwise addition is completed.
(3) And (3) post-treatment: and (2) dropwise adding 36% hydrochloric acid into the Grignard solution at 0-5 ℃ to regulate the pH to be less than 1, heating to 30-40 ℃ after regulation, stirring for 0.5h, standing for layering after stirring, washing an oil layer, performing desolventization at normal pressure, performing reduced pressure distillation after desolventization to obtain 428.6g of 3-fluoro-2-chloro-4- (m-methylphenyl) toluene, wherein the yield is 82.3%, and the GC content is 96.6%.
Example 9: synthesis of 3-tert-butyl-2-chloro-6- (m-methylphenyl) toluene
(1) Preparation of m-chlorotoluene Grignard solution: adding 56.2g of anhydrous m-chlorotoluene, 161g of magnesium strips, 225g of anhydrous methyltetrahydrofuran and 56.2g of anhydrous isooctane into a 2L reaction bottle under the protection of nitrogen, heating to 110 ℃, adding 1.5g of iodine particles for initiation, dropwise adding a mixed solution of 225g of anhydrous m-chlorotoluene and 900g of anhydrous methyltetrahydrofuran after successful initiation, finishing dropping for 4 hours, preserving heat at 110 ℃ for 2 hours after dropping, filtering unreacted magnesium strips, and using Grignard liquid for later use.
(2) Synthesis of 3-tert-butyl-2-chloro-6- (m-methylphenyl) toluene: 482g of anhydrous 3-tert-butyl-2, 5-dichlorotoluene, 1928g of anhydrous methyltetrahydrofuran and 8.5g of palladium chloride are added into a 5L reaction bottle under the protection of nitrogen, the temperature is raised to 60 ℃, the Grignard solution is added dropwise after 2h, and the heat preservation reaction is carried out for 4h at 60 ℃ after the dropwise addition.
(3) And (3) post-treatment: and (2) dropwise adding 36% hydrochloric acid into the Grignard solution at 0-5 ℃ to regulate the pH to be less than 1, heating to 30-40 ℃ after regulation, stirring for 0.5h, standing for layering after stirring, washing an oil layer, performing desolventization at normal pressure, performing reduced pressure distillation after desolventization to obtain 529.0g of 3-tert-butyl-2-chloro-6- (m-methylphenyl) toluene, wherein the yield is 87.4%, and the GC content is 97.2%.
The above examples are only for illustrating the technical concept and features of the present invention, and are not intended to limit the scope of the present invention. All equivalent changes or modifications made according to the spirit of the present invention should be covered within the protection scope of the present invention.
Claims (10)
1. A synthetic method of 3-chloro-2-methylbiphenyl and derivatives thereof is characterized by comprising the following steps:
(1) preparing Grignard liquid: adding a compound I shown in a formula I and a magnesium strip into an organic solvent, adding an initiator into the system, and initiating at 60-120 ℃; after the initiation is successful, dropwise adding a mixed solution of the compound I and an organic solvent into the system, carrying out a Grignard reaction at 20-120 ℃ to synthesize a Grignard solution in one step, and filtering unreacted magnesium strips for later use;
(2) synthesis of Compound III: taking the Grignard solution obtained in the step (1) and a compound II shown in a formula II as raw materials, carrying out a coupling reaction in an organic solvent under the catalysis of a selective coupling catalyst at 40-120 ℃, and carrying out one-step coupling synthesis on a compound III shown in a formula III;
(3) and (3) post-treatment: dropwise adding hydrochloric acid into the system obtained in the step (2) to adjust the pH value to be less than 1, and then sequentially carrying out standing layering, oil layer washing desolventizing and reduced pressure distillation to obtain a compound III, namely 3-chloro-2-methylbiphenyl and derivatives thereof;
the reaction equation is:
wherein, R1 is alkyl, amino, acyl, acylamino, alkoxy, R2 is alkyl, amino, acyl, acylamino, alkoxy.
2. The synthesis method according to claim 1, wherein in the step (1), the initiator is elementary iodine or 1, 2-dibromoethane; when initiating, the molar ratio of the initiator to the initiating compound I is 0.01-0.1: 1.
3. The synthesis method according to claim 1, wherein in the step (1), the molar ratio of the initiating compound I to the dropwise adding compound I is 2.5-5: 1.
4. The synthesis method according to claim 1, wherein in the step (1), the molar ratio of the magnesium strips to the initiating compound I is 10-20:1 during initiation.
5. The synthesis method according to claim 1, wherein in step (1), the organic solvent is one or a mixture of two or more of tetrahydrofuran, methyltetrahydrofuran, 2-dimethyltetrahydrofuran, diethyl ether, toluene, benzene, heptane, cyclohexane, octane, and isooctane in any ratio.
6. The synthesis method according to claim 1, wherein in the step (1), the weight ratio of the organic solvent to the initiating compound I is 2-7: 1; after the successful initiation, the weight ratio of the organic solvent to the compound I is 2-7: 1.
7. the synthesis method according to claim 1, wherein in the step (2), the organic solvent is one or a mixture of two or more of tetrahydrofuran, methyltetrahydrofuran, 2-dimethyltetrahydrofuran, diethyl ether, toluene, benzene, heptane, cyclohexane, octane and isooctane in any ratio.
8. The method according to claim 1, wherein in the step (2), the weight ratio of the organic solvent to the Grignard solution is 0.1-10: 1.
9. The synthesis method according to claim 1, wherein in the step (2), the selective coupling catalyst is any one of palladium chloride, palladium acetate, palladium (bis-triphenylphosphine) acetate, bis (triphenylphosphine) palladium dichloride, ruthenium chloride, rhodium chloride, cobalt chloride, nickel bromide, copper iodide, cuprous iodide, and cuprous bromide, or a mixture of two or more thereof mixed in any ratio.
10. The synthesis method according to claim 1, wherein in the step (2), the molar ratio of the selective coupling catalyst to the compound II is 0.01-0.5: 1; the molar ratio of the compound I to the compound II is 0.8-1.8: 1.
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| CN201811357577.2A Pending CN111187144A (en) | 2018-11-15 | 2018-11-15 | Synthetic method of 3-chloro-2-methyl biphenyl and derivatives thereof |
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| CN (1) | CN111187144A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1985001045A1 (en) * | 1983-08-19 | 1985-03-14 | Fmc Corporation | Catalyzed grignard coupling process |
| CN1935761A (en) * | 2006-09-27 | 2007-03-28 | 荆和祥 | Method for preparing 2-methyl-3-phenyl benzil alcohol |
| CN101130485A (en) * | 2007-08-24 | 2008-02-27 | 盐城科菲特生化技术有限公司 | Process for producing 2- methyl group -3- phenylbenzene methanol cleanly |
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2018
- 2018-11-15 CN CN201811357577.2A patent/CN111187144A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1985001045A1 (en) * | 1983-08-19 | 1985-03-14 | Fmc Corporation | Catalyzed grignard coupling process |
| CN1935761A (en) * | 2006-09-27 | 2007-03-28 | 荆和祥 | Method for preparing 2-methyl-3-phenyl benzil alcohol |
| CN101130485A (en) * | 2007-08-24 | 2008-02-27 | 盐城科菲特生化技术有限公司 | Process for producing 2- methyl group -3- phenylbenzene methanol cleanly |
Non-Patent Citations (1)
| Title |
|---|
| YOSHIHARU IKOMA ET AL.: "Non-Ligated Nickel Chloride-Catalyzed Cross-Coupling of Aromatic Grignard Reagents with Aryl Halides", 《SYNTHESIS》 * |
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Application publication date: 20200522 |