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Grignard reagent and aryl halide coupled alkyl introduction method by metal catalysis

A metal catalyzed Grignard and metal catalyst technology, applied in the field of aromatic hydrocarbon alkylation, can solve the problems of high alkylation reaction temperature, containing many by-products, complicated catalyst preparation, etc., and achieves high conversion rate, stable yield, The effect of suppressing isomerization

Inactive Publication Date: 2012-06-27
ASYMCHEM LAB TIANJIN +4
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, the most common synthesis method for preparing alkylpyridines is the aldehyde ammonia method (CN200910063599.2), that is, under the action of a catalyst, the use of aldehyde ammonia gas phase synthesis of alkylpyridines, this method also has complex catalyst preparation, requires high-temperature roasting, alkylation Disadvantages such as high reaction temperature
[0005] The above alkylation methods have disadvantages such as complex catalyst preparation, harsh reaction conditions, and many by-products in the product. In order to solve the drawbacks in the prior art, it is urgent to find a method that is easy to operate, mild in conditions, high in product purity and suitable for scale. Synthetic route for chemical production

Method used

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  • Grignard reagent and aryl halide coupled alkyl introduction method by metal catalysis
  • Grignard reagent and aryl halide coupled alkyl introduction method by metal catalysis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] A method for preparing 2-cyclopropylpyridine, characterized in that the specific preparation steps are as follows:

[0027] (1) Add cuprous oxide 1.9g (0.03eq), 2-chloropyridine 50g (0.44mol, 1eq), 1,4-dioxane 50mL (1mL / g) successively into a 2L reaction flask, and cool down to - 10±2°C.

[0028] (2) Add 462 g (1.0 eq, 10%) of cyclopropylmagnesium chloride Grignard reagent dropwise into the reaction flask, after the drop is complete, keep warm at -10±2° C. until the HPLC detection reaction ends.

[0029] (3) Add 100 mL (2 mL / g) of saturated ammonium chloride solution to the reaction system to terminate the reaction.

[0030] (4) Extract the system obtained in step (3) once with 100 mL (2 mL / g) of 1,4-dioxane, separate the liquids to obtain an organic phase, concentrate the organic phase until there is no fraction, and obtain 35.68 g of the product with a yield of 68 %, HPLC purity 99.0%.

[0031] The NMR data of the resulting product is as follows: H-NMR: (300MHZ, CD...

Embodiment 2

[0033] A method for preparing 3-methylindole, characterized in that the specific preparation steps are as follows:

[0034] (1) Add 108g (0.1eq) of lithium chloride, 5kg (25.5mol, 1eq) of 3-bromoindole, and 50kg (10mL / g) of anisole to a 200L reactor in sequence, and cool down to 10±2°C.

[0035] (2) Add 56 kg (2.0 eq, 15%) of methylmagnesium bromide Grignard reagent dropwise into the reaction kettle, after dropping, keep warm at 10±2° C. until the HPLC detection reaction ends.

[0036] (3) Add 32 kg (6 mL / g) of saturated ammonium chloride solution to the reaction system to terminate the reaction.

[0037] (4) Extract the system obtained in step (3) once with 30 kg (6 mL / g) of anisole, separate the liquids to obtain an organic phase, and concentrate the organic phase until there is no fraction to obtain 2.2 kg of the product, with a purity of 98.9% and a yield of 66%. .

[0038] The NMR data of the resulting product is as follows: H-NMR: (300MHZ, CDCl3), δ0.57&0.32 (H on cycl...

Embodiment 3

[0040] A method for preparing 2-isopropylpyridine, characterized in that the specific preparation steps are as follows:

[0041] (1) Add 1.9kg (0.06eq) of anhydrous manganese chloride, 40kg (253mol, 1.0eq) of 2-bromopyridine, and 178kg (5mL / g) of tetrahydrofuran to a 1000L reactor, and cool down to 0±2°C.

[0042] (2) Add 176 kg (1.3 eq, 12%) of isopropylmagnesium chloride Grignard reagent dropwise to the reaction kettle, after dropping, keep warm at 0±2° C. until the HPLC detection reaction ends.

[0043] (3) Add 170 kg (4 mL / g) of saturated ammonium chloride solution to the reaction system to terminate the reaction.

[0044] (4) The system obtained in step (3) was extracted once with 143kg (4mL / g) tetrahydrofuran, separated to obtain an organic phase, and the organic phase was concentrated to no fraction to obtain 23.5kg of product with a purity of 98.9% and a yield of 77%.

[0045] The NMR data of the resulting product is as follows: H-NMR: (300MHZ, DMSO), δ1.29 (H of two ...

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Abstract

Disclosed is a Grignard reagent and aryl halide coupled alkyl introduction method by metal catalysis. According to the invention, commercialized or easily prepared aryl halide Ar-X is selected as a main raw material, wherein Ar is phenyl ring or C4-C8 heterocyclic benzenoid and X is I or Br or Cl. A final product Ar-R is obtained by coupling of the Grignard reagent RMgX with the aryl halide, wherein Ar is phenyl ring or C4-C8 heterocyclic benzenoid, X is I or Br or Cl, and R is C1-C5 alkyl or C3-C6 cycloalkyl. The raw materials used in the synthetic method are all cheap and easily available. The chemical conditions are mild. During the whole production process, the method is simple to operate, is a feasible synthetic technology with low pollution, and provides a novel thinking and method for the preparation of alkyl aromatics.

Description

(1) Technical field: [0001] The invention relates to a method for alkylating aromatic hydrocarbons, in particular to a method for introducing an alkyl group through the coupling of a metal-catalyzed Grignard reagent and a halogenated aromatic hydrocarbon. (two) background technology: [0002] As an important synthetic method, alkylation reaction is widely used in many chemical production and synthesis of pharmaceutical intermediates. [0003] The method for synthesizing alkylbenzenes in the industry mainly takes benzene and olefins as raw materials, uses self-made aluminum catalyst (CN90103279.4), molecular sieve (zeolite) (CN99102571.7), smectite clay (CN01804283.X) etc. as catalyst, and Alkylation is mostly accomplished under conditions of high temperature and high pressure. Because the preparation of the catalyst used in this method is complicated, and the obtained product has many by-products, its application is generally only in the oil refining industry, which has gre...

Claims

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Application Information

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IPC IPC(8): C07B49/00C07D213/16C07D213/127C07D209/08
Inventor 洪浩陈朝勇周炎
Owner ASYMCHEM LAB TIANJIN
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