CN111978314A - A kind of preparation method of secondary amine compound containing thiazole ring - Google Patents

Abstract

The invention relates to a preparation method of a secondary amine compound containing a thiazole ring. It is prepared by dissolving primary amine, 2-chloro-5-thiazole aldehyde and anhydrous sodium acetate in an organic solvent, and microwave synthesis in a weak acid environment to prepare (E)-N-(2-chlorothiazole-5-yl)methylene Amine derivatives, (E)-N-(2-chlorothiazole-5-yl) methyleneamine derivatives and sodium borohydride in organic solvent hydrogenation reduction to obtain N-(2-chlorothiazole-5-yl ) methylamine derivatives. The preparation method is simple, the operation is convenient, the reaction is fast, the green environmental protection requirements are met, and the economic benefit is improved.

Description

A kind of preparation method of secondary amine compound containing thiazole ring

technical field

The invention relates to a preparation method of a secondary amine compound containing a thiazole ring.

Background technique

Thiazole ring is a kind of five-membered aromatic heterocyclic ring containing nitrogen and sulfur heteroatoms, which is rich in electrons, easy to form hydrogen bonds, coordinate with metal ions, and interact with various non-covalent bonds such as stacking, electrostatic and hydrophobic interactions. Thiazole compounds are widely used in medicine, pesticides, materials, biological dyes and other fields. Thiazoles can bind to a variety of enzymes and receptors in vivo and exhibit a variety of biological activities. Many thiazoles have been used in clinical practice, such as the antibiotic drug Cefixime, the anticancer drug Dasa Dasatinib and other drugs are the first-line drugs of choice in clinical practice. The research and development of thiazole pesticides is very active, with excellent herbicidal, plant growth regulation, bactericidal, and insecticidal effects. There are a large number of thiazole pesticides such as Thiabendazole, Thiamethoxam, and Fenthiaprop. etc. for agricultural production. Amine compounds are important organic synthesis intermediates, which can be used in the preparation of medical drugs, as well as in the synthesis of various insecticides, fungicides, herbicides, such as Mefenacet, Thiamethoxam, etc. . By synthesizing a series of secondary amine compounds containing thiazole ring, the advantages of the two are combined to obtain high-efficiency and low-toxicity biological activity for pesticide research and development. For example, the mesoionic insecticides of DuPont Company in the United States have pyrimidine ring-containing triflumezopyrim and thiazole ring-containing dicloromezotiaz, which have excellent activity, unique structure, and unusual physiological effects, providing new pest control measures.

SUMMARY OF THE INVENTION

In view of the above problems existing in the prior art, the purpose of the present invention is to provide a preparation method of a secondary amine compound containing a thiazole ring; the present invention is based on the structure of primary amine RNH ₂ and 2-chloro-5-thiazole aldehyde, by reducing the amine A series of secondary amine compounds were first synthesized from aldehydes and amines by microwave, and then reduced to a series of secondary amine compounds with sodium borohydride, and finally a series of N-(2-chlorothiazole-5-yl) was designed and synthesized. methylamine compound.

Described a kind of preparation method of secondary amine compound containing thiazole ring, the structural formula of described secondary amine compound containing thiazole ring is shown in formula (I), it is characterized in that described preparation method comprises the following steps:

1) Dissolve primary amine, 2-chloro-5-thiazolaldehyde and anhydrous sodium acetate in organic solvent A, add acid as a catalyst, and place in a microwave reactor to react to obtain (E) shown in formula (II) -N-(2-chlorothiazole-5-yl)methyleneamine derivatives;

2) The (E)-N-(2-chlorothiazole-5-yl)methyleneamine derivative represented by the formula (II) obtained in step 1) is mixed with sodium borohydride in organic solvent B at room temperature Carry out hydrogenation reduction reaction, post-treatment to obtain N-(2-chlorothiazole-5-yl)methylamine derivative represented by formula (I),

In primary amine RNH ₂ , formula (I) and formula (II): R is an alkyl group, an alkoxy group, an aryl group, a heterocyclic group, and the substituents in the primary amine are the same as R.

The method for preparing a thiazole ring-containing secondary amine compound is characterized in that the material ratio of 2-chloro-5-thiazole aldehyde to primary amine in step 1) is 1:0.7-1.4; 2- The mass ratio of chloro-5-thiazolaldehyde to anhydrous sodium acetate was 1:2-3.

The method for preparing a thiazole ring-containing secondary amine compound is characterized in that the acid in step 1) is glacial acetic acid or hydrochloric acid.

The method for preparing a thiazole ring-containing secondary amine compound is characterized in that the organic solvent A in step 1) is ethanol, toluene or dimethylformamide.

The method for preparing a thiazole ring-containing secondary amine compound is characterized in that the reaction time of the microwave heating reaction in step 1) is 10-30 minutes, the microwave power is 200-300W, and the reaction temperature is 90-150°C.

The method for preparing a thiazole ring-containing secondary amine compound is characterized in that (E)-N-(2-chlorothiazole-5-yl)methyleneamine derivative and hydroboration in step 2) The ratio of the amount of sodium to the substance is 1:0.75-2.

The method for preparing a thiazole ring-containing secondary amine compound is characterized in that the organic solvent B in step 2) is methanol, ethanol, tetrahydrofuran or dichloromethane.

The method for preparing a thiazole ring-containing secondary amine compound is characterized in that the post-processing process in step 2) is as follows: after the reaction is completed, the solvent is removed by rotary evaporation, and ethyl acetate and water with a volume ratio of 1:1 are used. 1:1 mixed solvent extraction, the separated organic phase was dried with anhydrous sodium sulfate, and purified by column to obtain the product.

The reaction process of the N-(2-chlorothiazole-5-yl) methylamine derivative of the present invention is as follows:

By adopting the above-mentioned technology, compared with the prior art, the present invention achieves the following beneficial effects:

Based on the structure of primary amine and 2-chloro-5-thiazole aldehyde, the invention firstly microwaves aldehyde and amine to synthesize a series of secondary amine compounds by means of reductive amination, and then reduces them into a series of secondary amines with sodium borohydride The compound, finally designed and synthesized a series of N-(2-chlorothiazole-5-yl) methylamine compounds, the reaction time is short, the operation is convenient, the conversion rate is high, and the economic benefit is high, and the compounds obtained by the present invention can be used for preparation Ionic insecticides.

Detailed ways

The present invention is further described below in conjunction with specific embodiment, but the protection scope of the present invention is not limited to this:

Example 1 Preparation of N-(2-chlorothiazole-5-methyl)-3-methyl-2-pyridinamine

2-Chloro-5-thiazolaldehyde (1.00g, 6.76mmol), 3-methyl-2-pyridinamine (0.73g, 6.76mmol), anhydrous sodium acetate (1.11g, 13.54mmol) were dissolved in ethanol (15ml) ) in, drip glacial acetic acid (0.5ml), place microwave reactor and react 15 minutes under the condition of 90 ℃, 300W, the reaction finishes filtering, gas chromatograph detects conversion rate 77.232%, and precipitation obtains (E) -N-(2-chlorothiazole-5-methylene)-3-methyl-2-pyridinamine crude, (E)-N-(2-chlorothiazole-5-methylene)-3-methyl Base-2-pyridylamine (1.50g, 6.30mmol) and sodium borohydride (0.24g, 6.32mmol) were dissolved in ethanol (15ml), stirred at room temperature for about 3 hours, followed by TLC, after the reaction was completed, the solvent was spin-dried, and acetic acid was used. Ethyl ester (15ml) and water (15ml) were mixed and extracted, the organic phase was separated and dried with anhydrous sodium sulfate, filtered, and purified by column purification with pure petroleum ether to obtain N-(2-chlorothiazole- 5-Methyl)-3-methyl-2-pyridinamine.

N-(2-Chlorothiazol-5-methyl)-3-methyl-2-pyridinamine: white solid, two-step yield: 65.3%; ¹ H NMR (CDCl ₃ , 500 MHz), δ: 8.08 (s , 1H, thiazole), 7.44(s, 1H, pyridin), 7.28-7.27(m, 1H, pyridin), 6.65-6.63(m, 1H, pyridin), 4.78(d, J=6.5Hz, 2H, CH ₂ ), 4.56 (s, 1H, NH), 2.10 (s, 2H, _CH3 ).

Example 2 Preparation of N-(2-chlorothiazole-5-yl) methylaniline

2-Chloro-5-thiazolaldehyde (1.00g, 6.76mmol), aniline (0.63g, 6.77mmol), anhydrous sodium acetate (1.11g, 13.54mmol) were dissolved in ethanol (15ml), and glacial acetic acid ( 0.5ml), placed in the microwave reactor and reacted for 15 minutes under the condition of 90 ° C, 300W, the reaction was completed and filtered, the gas chromatograph detected the conversion rate of 95.232%, and the precipitation obtained (E)-N-(2-chlorothiazole) -5-yl) methylene aniline crude product, (E)-N-(2-chlorothiazole-5-yl) methylene aniline (1.50 g, 6.73 mmol), sodium borohydride (0.25 g, 6.59 mmol) Dissolve in ethanol (15ml), stir at room temperature for about 3 hours, follow the reaction by TLC, spin dry the solvent after the reaction, mix and extract with ethyl acetate (15ml) and water (15ml), separate the organic phase and dry with anhydrous sodium sulfate, filter , purified by column with pure petroleum ether to obtain N-(2-chlorothiazole-5-yl)methylaniline represented by formula (A2).

N-(2-chlorothiazole-5-yl)methylaniline: pale yellow oil, two-step yield: 85.3%; ¹ H NMR (CDCl ₃ , 500MHz), δ: 7.47(s,1H,thiazole), 7.25 -7.19(m, 2H, ph), 6.83-6.79(m, 1H, ph), 6.69-6.66(m, 2H, ph), 4.50(d, J=5.5Hz, 2H, CH ₂ ), 4.08(s ,1H,NH).

Example 3 Preparation of N-((2-chlorothiazole-5-yl)methyl)-3,4-dimethylaniline

2-Chloro-5-thiazolaldehyde (1.00 g, 6.76 mmol), 3,4-dimethylaniline (0.82 g, 6.78 mmol), and anhydrous sodium acetate (1.11 g, 13.54 mmol) were dissolved in ethanol (15 ml) In, add glacial acetic acid (0.5ml) dropwise, place microwave reactor and react 15 minutes under the condition of 90 ℃, 300W, after the reaction is completed, filter, gas chromatograph detects conversion rate 77.835%, and precipitation obtains (E)- Crude N-((2-chlorothiazole-5-yl)methylene)-3,4-dimethylaniline, (E)-N-((2-chlorothiazole-5-yl)methylene) -3,4-Dimethylaniline (1.50g, 5.98mmol) and sodium borohydride (0.23g, 6.05mmol) were dissolved in ethanol (15ml), stirred at room temperature for about 3 hours, followed by TLC, and the solvent was spin-dried after the reaction was completed , mixed with ethyl acetate (15ml) and water (15ml) for extraction, the organic phase was separated and dried with anhydrous sodium sulfate, filtered, and purified by column with pure petroleum ether to obtain N-((2) represented by formula (A3). -Chlorothiazol-5-yl)methyl)-3,4-dimethylaniline.

N-(2-Chlorothiazol-5-yl)-3,4-methylaniline: brown oil, two-step yield: 73.1%.

Example 4 Preparation of N-((2-chlorothiazole-5-yl)methyl)-4-ethylaniline

2-Chloro-5-thiazolaldehyde (1.00g, 6.76mmol), 4-ethylaniline (0.82g, 6.78mmol), anhydrous sodium acetate (1.11g, 13.54mmol) were dissolved in ethanol (15ml), dropwise Add glacial acetic acid (0.5ml), place microwave reactor and react 15 minutes under the condition of 90 ℃, 300W, filter after completion of reaction, gas chromatograph detects transformation efficiency 72.281%, and precipitation obtains (E)-N-( (2-chlorothiazole-5-yl)methylene)-4-ethylaniline crude product, (E)-N-((2-chlorothiazole-5-yl)methylene)-4-ethylaniline (1.50g, 5.98mmol), sodium borohydride (0.23g, 6.05mmol) were dissolved in ethanol (15ml), stirred at room temperature for about 3 hours, TLC tracked the reaction, after the reaction was completed, the solvent was spin-dried and mixed with ethyl acetate (15ml). Water (15ml) was mixed and extracted, the organic phase was separated and dried with anhydrous sodium sulfate, filtered, and purified by column with pure petroleum ether to obtain N-((2-chlorothiazole-5-yl)methan represented by formula (A4). base)-4-ethylaniline.

N-(2-chlorothiazole-5-yl)-4-ethylaniline: brown oil, two-step yield: 67.9%; ¹ H NMR (CDCl ₃ , 500 MHz), δ: 7.46 (s,1H,thiazole) , 7.06 (d, J=8.5 Hz, 2H, ph), 6.63-6.61 (m, 2H, ph), 4.47 (s, 2H, _CH2 ), 3.94 (s, 1H, NH).

Example 5 Preparation of N-((2-chlorothiazole-5-yl)methyl)-2,6-diethylaniline

2-Chloro-5-thiazolaldehyde (1.00g, 6.76mmol), 2,6-diethylaniline (1.01g, 6.78mmol), anhydrous sodium acetate (1.11g, 13.54mmol) were dissolved in ethanol (15ml) In, add glacial acetic acid (0.5ml) dropwise, place microwave reactor and react 20 minutes under the condition of 90 ℃, 300W, after the reaction is completed, filter, gas chromatograph detects conversion rate 89.265%, and precipitation obtains (E)- Crude N-((2-chlorothiazole-5-yl)methylene)-2,6-diethylaniline, (E)-N-((2-chlorothiazole-5-yl)methylene) -2,6-Diethylaniline (1.50g, 5.38mmol) and sodium borohydride (0.20g, 5.26mmol) were dissolved in ethanol (15ml), stirred at room temperature for about 3 hours, followed by TLC, and the solvent was spin-dried after the reaction was completed , extracted by mixing ethyl acetate (15ml) and water (15ml), separating the organic phase and drying with anhydrous sodium sulfate, filtering, and purifying with pure petroleum ether through column to obtain N-((2) shown in formula (A5). -Chlorothiazol-5-yl)methyl)-2,6-diethylaniline.

N-(2-Chlorothiazol-5-yl)-2,6-diethylaniline: dark red oil, two-step yield: 85.5%. The yield of the conventional method was 80.9%.

Example 6 Preparation of N-((2-chlorothiazole-5-yl)methyl)-3-isopropylaniline

2-Chloro-5-thiazolaldehyde (1.00g, 6.76mmol), 3-isopropylaniline (0.91g, 6.74mmol), anhydrous sodium acetate (1.11g, 13.54mmol) were dissolved in ethanol (15ml), Glacial acetic acid (0.5ml) was added dropwise, placed in a microwave reactor and reacted for 25 minutes under the conditions of 90° C. and 300W, the reaction was completed and filtered, the gas chromatograph detected the conversion rate as 93.060%, and the precipitation obtained (E)-N- ((2-chlorothiazole-5-yl)methylene)-3-isopropylaniline crude product, (E)-N-((2-chlorothiazole-5-yl)methylene)-3-isopropylaniline Propylaniline (1.50g, 5.66mmol) and sodium borohydride (0.21g, 5.53mmol) were dissolved in ethanol (15ml), stirred at room temperature for about 3 hours, followed by TLC, the reaction was completed and the solvent was spin-dried, and ethyl acetate ( 15ml) mixed with water (15ml) and extracted, the organic phase was separated and dried with anhydrous sodium sulfate, filtered, and purified by column with pure petroleum ether to obtain N-((2-chlorothiazole-5-) represented by formula (A6). yl) methyl)-3-isopropylaniline.

N-(2-Chlorothiazol-5-yl)-3-isopropylaniline: dark red oil, two-step yield: 88.7%; ¹ H NMR (CDCl ₃ , 500 MHz), δ: 7.47 (s, 1H, thiazole), 7.16-7.13(m, 1H, ph), 6.70(d, J=7.5Hz, 1H, ph), 6.59(s, 1H, ph), 6.51-6.49(m, 1H, ph), 4.49( d, J=5.5Hz, 2H, _CH2 ), 4.04 (s, 1H, NH), 2.87-2.81 (m, 1H, CH), 1.30-1.24 (m, 6H, _CH3 ).

Example 7 Preparation of N-((2-chlorothiazole-5-yl)methyl)-2-methoxyaniline

2-Chloro-5-thiazolaldehyde (1.00 g, 6.76 mmol), 2-methoxyaniline (0.83 g, 6.75 mmol), and anhydrous sodium acetate (1.11 g, 13.54 mmol) were dissolved in ethanol (15 ml), Glacial acetic acid (0.5ml) was added dropwise, placed in a microwave reactor and reacted for 25 minutes under the conditions of 90° C. and 300W, the reaction was completed and filtered, the gas chromatograph detected the conversion rate as 94.811%, and the precipitation obtained (E)-N- ((2-chlorothiazole-5-yl)methylene)-2-methoxyaniline crude product, (E)-N-((2-chlorothiazole-5-yl)methylene)-2-methyl Oxyaniline (1.50g, 5.93mmol) and sodium borohydride (0.23g, 6.05mmol) were dissolved in ethanol (15ml), stirred at room temperature for about 3 hours, followed by TLC, the reaction was completed and the solvent was spin-dried, and ethyl acetate ( 15ml) was mixed with water (15ml) and extracted, the organic phase was separated and dried with anhydrous sodium sulfate, filtered, and purified by column with pure petroleum ether to obtain N-((2-chlorothiazole-5-) represented by formula (A7). yl) methyl)-2-methoxyaniline.

N-(2-Chlorothiazol-5-yl)-2-methoxyaniline: brown oil, two-step yield: 90.1%.

Example 8 Preparation of N-((2-chlorothiazole-5-yl)methyl)-2,5-dimethoxyaniline

2-Chloro-5-thiazolaldehyde (1.00g, 6.76mmol), 2,5-dimethoxyaniline (1.03g, 6.73mmol), anhydrous sodium acetate (1.11g, 13.54mmol) were dissolved in ethanol (15ml) ) in, drip glacial acetic acid (0.5ml), place microwave reactor and react 25 minutes under the condition of 90 ℃, 300W, the reaction finishes filtering, gas chromatograph detects conversion rate 81.096%, and precipitation obtains (E) -N-((2-chlorothiazole-5-yl)methylene)-2,5-dimethoxyaniline crude product, (E)-N-((2-chlorothiazole-5-yl)methylene Base)-2,5-dimethoxyaniline (1.50g, 5.30mmol), sodium borohydride (0.20g, 5.26mmol) were dissolved in ethanol (15ml), stirred at room temperature for about 3 hours, TLC tracked the reaction, the reaction was completed Spin dry the solvent, mix and extract with ethyl acetate (15ml) and water (15ml), separate the organic phase and dry with anhydrous sodium sulfate, filter, and purify with pure petroleum ether to obtain the N- ((2-Chlorothiazol-5-yl)methyl)-2,5-dimethoxyaniline.

N-(2-Chlorothiazol-5-yl)-2,5-dimethoxyaniline: black oil, two-step yield: 77.4%.

Example 9 Preparation of N-((2-chlorothiazole-5-yl)methyl)-3-fluoroaniline

2-Chloro-5-thiazolaldehyde (1.00 g, 6.76 mmol), 3-fluoroaniline (0.75 g, 6.76 mmol), and anhydrous sodium acetate (1.11 g, 13.54 mmol) were dissolved in ethanol (15 ml), and added dropwise Glacial acetic acid (0.5ml) was placed in the microwave reactor and reacted for 30 minutes under the condition of 90 ° C, 300W, the reaction was completed and filtered, the gas chromatograph detected the conversion rate of 89.625%, and the precipitation obtained (E)-N-(( 2-chlorothiazole-5-yl)methylene)-3-fluoroaniline crude product, (E)-N-((2-chlorothiazole-5-yl)methylene)-3-fluoroaniline (1.50g) , 6.22mmol), sodium borohydride (0.24g, 6.32mmol) were dissolved in ethanol (15ml), stirred at room temperature for about 3 hours, TLC tracked the reaction, the reaction was completed by spin-drying the solvent, with ethyl acetate (15ml) and water (15ml) ) mixed extraction, the organic phase was separated and dried with anhydrous sodium sulfate, filtered, and purified by column with pure petroleum ether to obtain N-((2-chlorothiazole-5-yl)methyl)- 3-Fluoroaniline.

N-(2-chlorothiazole-5-yl)-3-fluoroaniline: dark red oil, two-step yield: 85.4%; ¹ H NMR (CDCl ₃ , 500MHz), δ: 7.48(s,1H,thiazole) , 7.16-7.09 (m, 1H, ph), 6.51-6.34 (m, 3H, ph), 4.47 (d, J=5.5Hz, 2H, _CH2 ), 4.22 (s, 1H, NH).

Example 10 Preparation of N-((2-chlorothiazole-5-yl)methyl)-3,4-difluoroaniline

2-Chloro-5-thiazolaldehyde (1.00 g, 6.76 mmol), 3,4-difluoroaniline (0.87 g, 6.74 mmol), anhydrous sodium acetate (1.11 g, 13.54 mmol) were dissolved in ethanol (15 ml) , glacial acetic acid (0.5ml) was added dropwise, placed in a microwave reactor and reacted for 30 minutes under the condition of 90 ° C, 300W, the reaction was completed and filtered, the gas chromatograph detected the conversion rate of 78.945%, and the precipitation obtained (E)-N -((2-chlorothiazole-5-yl)methylene)-3,4-difluoroaniline crude product, (E)-N-((2-chlorothiazole-5-yl)methylene)-3 , 4-Difluoroaniline (1.50g, 5.79mmol), sodium borohydride (0.22g, 5.79mmol) were dissolved in ethanol (15ml), stirred at room temperature for about 3 hours, TLC followed the reaction, after the reaction was completed, the solvent was spin-dried, and acetic acid was used. Ethyl ester (15ml) and water (15ml) were mixed and extracted, the organic phase was separated and dried with anhydrous sodium sulfate, filtered, and purified by column with pure petroleum ether to obtain N-((2-chlorothiazole) represented by formula (A11). -5-yl)methyl)-3,4-difluoroaniline.

N-(2-Chlorothiazol-5-yl)-3,4-difluoroaniline: dark red oil, two-step yield: 74.2%.

Example 11 Preparation of N-((2-chlorothiazole-5-yl)methyl)-2-trifluoromethylaniline

2-Chloro-5-thiazolaldehyde (1.00 g, 6.76 mmol), 2-trifluoromethylaniline (1.09 g, 6.77 mmol), anhydrous sodium acetate (1.11 g, 13.54 mmol) were dissolved in ethanol (15 ml) , glacial acetic acid (0.5ml) was added dropwise, placed in a microwave reactor and reacted for 20 minutes under the condition of 90° C., 300W, the reaction was completed and filtered, the gas chromatograph detected the conversion rate of 73.864%, and the precipitation obtained (E)-N -((2-chlorothiazole-5-yl)methylene)-2-trifluoromethylaniline crude product, (E)-N-((2-chlorothiazole-5-yl)methylene)-2 -Trifluoromethylaniline (1.50g, 5.15mmol), sodium borohydride (0.20g, 5.26mmol) were dissolved in ethanol (15ml), stirred at room temperature for about 3 hours, TLC followed the reaction, after the reaction was completed, the solvent was spin-dried, and acetic acid was used. Ethyl ester (15ml) and water (15ml) were mixed and extracted, the organic phase was separated and dried with anhydrous sodium sulfate, filtered, and purified by column with pure petroleum ether to obtain N-((2-chlorothiazole) represented by formula (A11). -5-yl)methyl)-2-trifluoromethylaniline.

N-(2-Chlorothiazol-5-yl)-2-trifluoromethylaniline: dark red oil, two-step yield: 70.1%.

Example 12 Preparation of N-((2-chlorothiazole-5-yl)methyl)-4-trifluoromethylaniline

2-Chloro-5-thiazolaldehyde (1.00 g, 6.76 mmol), 4-trifluoromethylaniline (1.09 g, 6.77 mmol), anhydrous sodium acetate (1.11 g, 13.54 mmol) were dissolved in ethanol (15 ml) , glacial acetic acid (0.5ml) was added dropwise, placed in a microwave reactor and reacted for 25 minutes under the conditions of 90° C., 300W, the reaction was completed and filtered, the gas chromatograph detected the conversion rate of 99.494%, and the precipitation obtained (E)-N -((2-chlorothiazole-5-yl)methylene)-4-trifluoromethylaniline crude product, (E)-N-((2-chlorothiazole-5-yl)methylene)-4 -Trifluoromethylaniline (1.50g, 5.15mmol), sodium borohydride (0.20g, 5.26mmol) were dissolved in ethanol (15ml), stirred at room temperature for about 3 hours, TLC followed the reaction, after the reaction was completed, the solvent was spin-dried, and acetic acid was used. Ethyl ester (15ml) and water (15ml) were mixed and extracted, the organic phase was separated and dried with anhydrous sodium sulfate, filtered, and purified by column with pure petroleum ether to obtain N-((2-chlorothiazole) represented by formula (A12) -5-yl)methyl)-4-trifluoromethylaniline.

N-(2-Chlorothiazol-5-yl)-4-trifluoromethylaniline: brown oil, two-step yield: 90.2%.

Example 13 Preparation of N-((2-chlorothiazole-5-yl)methyl)-2-trifluoromethoxyaniline

2-Chloro-5-thiazolaldehyde (1.00 g, 6.76 mmol), 2-trifluoromethoxyaniline (1.19 g, 6.72 mmol), anhydrous sodium acetate (1.11 g, 13.54 mmol) were dissolved in ethanol (15 ml) In, add glacial acetic acid (0.5ml) dropwise, place microwave reactor and react 20 minutes under the condition of 90 ℃, 300W, the reaction finishes filtering, gas chromatograph detects conversion rate 84.715%, precipitation obtains (E)- Crude N-((2-chlorothiazole-5-yl)methylene)-2-trifluoromethoxyaniline, (E)-N-((2-chlorothiazole-5-yl)methylene) -2-Trifluoromethoxyaniline (1.50g, 4.89mmol) and sodium borohydride (0.19g, 5.00mmol) were dissolved in ethanol (15ml), stirred at room temperature for about 3 hours, followed by TLC, and the solvent was spin-dried after the reaction was completed , mixed with ethyl acetate (15ml) and water (15ml) for extraction, the organic phase was separated and dried with anhydrous sodium sulfate, filtered, and purified by column with pure petroleum ether to obtain N-((2) represented by formula (A13). -Chlorothiazol-5-yl)methyl)-2-trifluoromethoxyaniline.

N-(2-Chlorothiazol-5-yl)-2-trifluoromethoxyaniline: yellow oil, two-step yield: 80.3%.

Example 14 Preparation of 3-chloro-N-((2-chlorothiazole-5-yl)methyl)aniline

2-Chloro-5-thiazolaldehyde (1.00 g, 6.76 mmol), 3-chloroaniline (0.86 g, 6.72 mmol), and anhydrous sodium acetate (1.11 g, 13.54 mmol) were dissolved in ethanol (15 ml), and added dropwise Glacial acetic acid (0.5ml) was placed in a microwave reactor and reacted for 15 minutes under the condition of 90°C and 300W, the reaction was completed and filtered, and the gas chromatograph detected the conversion rate as 71.290%, and the precipitation obtained (E)-3-chloro- Crude N-((2-chlorothiazole-5-yl)methylene)aniline, (E)-3-chloro-N-((2-chlorothiazole-5-yl)methylene)aniline (1.50 g) , 5.81mmol), sodium borohydride (0.22g, 5.79mmol) were dissolved in ethanol (15ml), stirred at room temperature for about 3 hours, TLC tracked the reaction, the reaction was completed and the solvent was spin-dried, and ethyl acetate (15ml) and water (15ml) were used. ) mixed extraction, the organic phase was separated and dried with anhydrous sodium sulfate, filtered, and purified by column with pure petroleum ether to obtain 3-chloro-N-((2-chlorothiazole-5-yl) represented by formula (A14) methyl)aniline.

3-Chloro-N-(2-chlorothiazole-5-yl)-3,4-methylaniline: yellow oil, two-step yield: 68.1%; ¹ H NMR (CDCl ₃ , 500 MHz), δ: 7.47 ( s,1H,thiazole),7.13-7.09(m,1H,ph),6.77-6.76(m,1H,ph),6.66(s,1H,ph),6.54-6.52(m,1H,ph),4.45 (d, J=5.5Hz, 2H, _CH2 ), 4.14 (s, 1H, NH).

Example 15 Preparation of 4-chloro-N-((2-chlorothiazole-5-yl)methyl)aniline

2-Chloro-5-thiazolaldehyde (1.00 g, 6.76 mmol), 4-chloroaniline (0.86 g, 6.72 mmol), and anhydrous sodium acetate (1.11 g, 13.54 mmol) were dissolved in ethanol (15 ml), and added dropwise Glacial acetic acid (0.5ml) was placed in a microwave reactor and reacted for 15 minutes under the condition of 90° C. and 300W, the reaction was completed and filtered, and the gas chromatograph detected that the conversion rate was 72.354%, and the precipitation obtained (E)-4-chloro- Crude N-((2-chlorothiazole-5-yl)methylene)aniline, (E)-4-chloro-N-((2-chlorothiazole-5-yl)methylene)aniline (1.50 g) , 5.81mmol), sodium borohydride (0.22g, 5.79mmol) were dissolved in ethanol (15ml), stirred at room temperature for about 3 hours, TLC tracked the reaction, the reaction was completed and the solvent was spin-dried, and ethyl acetate (15ml) and water (15ml) were used. ) mixed extraction, separated the organic phase and dried with anhydrous sodium sulfate, filtered, and purified by column with pure petroleum ether to obtain 4-chloro-N-((2-chlorothiazole-5-yl) represented by formula (A15) methyl)aniline.

4-Chloro-N-(2-chlorothiazole-5-yl)-3,4-methylaniline: yellow oil, two-step yield: 67.7%; ¹ H NMR (CDCl ₃ , 500 MHz), δ: 7.45 ( s, 1H, thiazole), 7.17-7.14 (m, 2H, ph), 6.60-6.57 (m, 2H, ph), 4.47 (d, J=5Hz, 2H, CH ₂ ), 4.12 (s, 1H, NH ).

The compounds obtained in the present invention can be used to prepare mesoionic insecticides.

Claims (8)

1. a preparation method of a secondary amine compound containing a thiazole ring, the structural formula of the secondary amine compound containing a thiazole ring is shown in the formula (I), and it is characterized in that the preparation method comprises the steps: 1) Dissolve primary amine RNH ₂ , 2-chloro-5-thiazolaldehyde and anhydrous sodium acetate in organic solvent A, add acid as a catalyst, and place in a microwave reactor to react to obtain (II) shown in formula (II). E)-N-(2-chlorothiazole-5-yl)methyleneamine derivatives;

2) The (E)-N-(2-chlorothiazole-5-yl)methyleneamine derivative represented by the formula (II) obtained in step 1) is mixed with sodium borohydride in organic solvent B at room temperature Carry out hydrogenation reduction reaction, post-treatment to obtain N-(2-chlorothiazole-5-yl)methylamine derivative represented by formula (I),

In primary amine RNH ₂ , formula (I) and formula (II): R is an alkyl group, an alkoxy group, an aryl group, a heterocyclic group, and the substituents in the primary amine are the same as R. 2. the preparation method of a kind of secondary amine compound containing thiazole ring according to claim 1, it is characterized in that the material amount ratio of the 2-chloro-5-thiazole aldehyde in step 1) and primary amine is 1: 0.7-1.4; the substance amount ratio of 2-chloro-5-thiazolaldehyde to anhydrous sodium acetate is 1:2-3. 3. the preparation method of a kind of secondary amine compound containing thiazole ring according to claim 1 is characterized in that the acid in step 1) is glacial acetic acid or hydrochloric acid. 4. the preparation method of a kind of secondary amine compound containing thiazole ring according to claim 1 is characterized in that the organic solvent A in step 1) is ethanol, toluene or dimethylformamide. 5. the preparation method of a kind of secondary amine compound containing thiazole ring according to claim 1, it is characterized in that the reaction time of the microwave heating reaction in step 1) is 10-30 minutes, microwave power 200-300W, reaction Temperature 90-150℃. 6. the preparation method of a kind of secondary amine compound containing thiazole ring according to claim 1 is characterized in that (E)-N-(2-chlorothiazole-5-yl) methylene in step 2) The substance amount ratio of amine derivative to sodium borohydride was 1:0.75-2. 7. The preparation method of a thiazole ring-containing secondary amine compound according to claim 1, wherein the organic solvent B in step 2) is methanol, ethanol, tetrahydrofuran or dichloromethane. 8. the preparation method of a kind of secondary amine compound containing thiazole ring according to claim 1 is characterized in that the post-processing process in step 2) is as follows: the reaction is completed and the solvent is removed by rotary evaporation, and the volume ratio is 1:1 The ethyl acetate and water 1:1 mixed solvent was extracted, the organic phase was separated, dried with anhydrous sodium sulfate, and purified by column to obtain the product.