CN105198801A - N-(4-chloro-3-picolyl)-2-(3-methylbenzamide) benzamide as well as preparation method and application thereof - Google Patents

Abstract

The present invention relates to N-(4-chloro-3-pyridylmethyl)-2-(3-methylbenzamido)benzamide and its preparation method and application, which starts with 2-nitrobenzoic acid Raw materials, react with thionyl chloride or phosphorus oxychloride to generate 2-nitrobenzoyl chloride, and then react with 2-chloro-5-aminomethylpyridine to generate 2-nitro-N-(4-chloro-3 -pyridylmethyl)benzamide, the intermediate is reduced by iron powder to obtain 2-amino-N-(4-chloro-3-pyridylmethyl)benzamide, and finally reacted with 3-methylbenzoyl chloride to generate The final product is N-(4-chloro-3-pyridylmethyl)-2-(3-methylbenzamido)benzamide. Beneficial effects of the present invention: the total reaction yield is 42%. Compared with the existing phthalamide compounds, the compound has the advantages of simple structure, mild reaction conditions and low cost, and has great development potential.

Description

N-(4-chloro-3-pyridylmethyl)-2-(3-methylbenzamido)benzamide and its preparation method and use

technical field

The present invention relates to N-(4-chloro-3-pyridylmethyl)-2-(3-methylbenzamido)benzamide and its preparation method and use.

Background technique

Agricultural production is inseparable from pesticides. Pesticides are important means of production in agricultural production. Pesticides have made great contributions to agricultural development and ensuring high grain yields. However, with the continuous development of our country's economy, more and more efforts are being made to protect the environment, and the safety standards of pesticides are getting higher and higher. The pesticides that have a great impact on the environment are gradually restricted or even eliminated. In addition, due to the long-term and high-dose use of certain pesticide varieties, insects gradually develop resistance, resulting in an increase in the frequency and dosage of pesticides. Therefore, new pesticide varieties with new mechanisms of action and novel structures should be continuously developed.

The ryanodine receptor is a new insecticide target discovered in recent years. Phthalamides and o-carboxamidobenzamides have been found to act on insect ryanodine receptors. Great potential for safe insecticides.

Contents of the invention

The technical problem to be solved in the present invention is to design and synthesize N-(4-chloro-3-pyridylmethyl)-2-(3-methylbenzamide) based on the principles of bioelectronic isosterism and active group combination. ) benzamide compound, and the insecticidal activity research was carried out by spraying method, which has high insecticidal activity and great development potential.

The technical solution adopted by the present invention to solve the problems of the technologies described above is: N-(4-chloro-3-pyridylmethyl)-2-(3-methylbenzamido)benzamide, which has the following formula I Represented structural formula:

The preparation method of N-(4-chloro-3-pyridylmethyl)-2-(3-methylbenzamido) benzamide, it is starting raw material with 2-nitrobenzoic acid, through and dichloro The reaction of sulfoxide or phosphorus oxychloride produces 2-nitrobenzoyl chloride, which is then reacted with 2-chloro-5-aminomethylpyridine to produce 2-nitro-N-(4-chloro-3-pyridylmethyl)benzene Formamide, the intermediate is reduced by iron powder to obtain 2-amino-N-(4-chloro-3-pyridylmethyl)benzamide, and finally reacted with 3-methylbenzoyl chloride to generate the final product N-(4 -Chloro-3-pyridylmethyl)-2-(3-methylbenzamido)benzamide; its reaction scheme is as follows:

According to the above scheme, the specific steps for generating 2-nitrobenzoyl chloride by reacting 2-nitrobenzoic acid with thionyl chloride or phosphorus oxychloride are: mixing 2-nitrobenzoic acid and an appropriate amount of thionyl chloride or trichloro Add phosphine into the flask, heat and reflux for a certain period of time, evaporate the solvent under reduced pressure to obtain 2-nitrobenzoyl chloride; the molar ratio of raw materials is 2-nitrobenzoic acid:thionyl chloride or phosphorus oxychloride=1 : 1 ~ 15; the reaction temperature is 40 ~ 100 ℃; the reaction time is 3 ~ 10h.

According to the above scheme, the specific steps for generating 2-nitro-N-(4-chloro-3-pyridylmethyl)benzamide in the reaction of 2-chloro-5-aminomethylpyridine are: add anhydrous solvent in the reaction vessel , triethylamine and 2-chloro-5-aminopicoline hydrochloride, slowly drop 2-nitrobenzoyl chloride into it under stirring at 0°C, stir at a certain temperature for reaction, follow the reaction by TLC, and wait for the reaction to complete. Dilute with ethyl acetate and water, extract the aqueous layer with ethyl acetate, combine the organic layers, wash the organic layer with NaHCO ₃ aqueous solution until neutral, then wash with saturated brine, dry over anhydrous Na ₂ SO ₄ , filter, and remove under reduced pressure dissolved, and recrystallized to obtain the target product; the molar ratio of raw materials is 2-chloro-5-aminopicoline: 2-nitrobenzoyl chloride: triethylamine=1:1～5:1～10; the reaction temperature is 20 ~50°C; the reaction time is 0.5~3h.

According to the above scheme, the synthetic steps of 2-amino-N-(4-chloro-3-pyridylmethyl)benzamide are: add glacial acetic acid in the reaction vessel, a certain amount of 2-nitro-N-(4- Chloro-3-pyridylmethyl) benzamide and reduced iron powder, heated and stirred at a certain temperature, TLC followed the reaction, after the reaction was completed, filtered while hot, the filtrate was concentrated and extracted with ethyl acetate, the organic layers were combined, and the organic layer was used NaHCO ₃ solution was washed to neutrality, then washed with saturated brine, and dried over anhydrous Na ₂ SO ₄ to obtain 2-amino-N-(4-chloro-3-pyridylmethyl)benzamide; the molar ratio of raw materials was 2- Nitro-N-(4-chloro-3-pyridylmethyl)benzamide: glacial acetic acid: iron powder = 1:1~10:1~10, the reaction temperature is 30~80°C; the reaction time is 2~10h .

According to the above scheme, the synthetic steps of N-(4-chloro-3-pyridylmethyl)-2-(3-methylbenzamido)benzamide are: add a certain amount of solvent, triethyl Amine and 2-amino-N-(4-chloro-3-pyridylmethyl)benzamide, under ice bath and strong stirring, add quantitative 3-methylbenzoyl chloride to the above reaction bottle, stir and react, and follow the reaction by TLC , after the reaction is over, pour it into ice water, concentrate under reduced pressure, extract with ethyl acetate, combine the organic layers, wash the organic layer with NaHCO ₃ aqueous solution to neutrality, then wash with saturated brine, anhydrous Na ₂ SO ₄ Dry, filter, and desolvate under reduced pressure to obtain a light yellow solid, and obtain the target product N-(4-chloro-3-pyridylmethyl)-2-(3-methylbenzamido)benzamide through column chromatography ; The molar ratio of raw materials is 2-amino-N-(4-chloro-3-pyridylmethyl)benzamide: triethylamine: 3-methylbenzoyl chloride=1:1～10:1～5); The reaction temperature is 0-50°C; the reaction time is 0.5-3h.

The application of the N-(4-chloro-3-pyridylmethyl)-2-(3-methylbenzamido)benzamide as an insecticide.

Beneficial effects of the present invention: the present invention takes 2-nitrobenzoic acid as a raw material and synthesizes a new compound N-(4-chloro-3-pyridylmethyl)- 2-(3-methylbenzamido)benzamide, compared with the existing phthalamide compounds, has the advantages of simple structure, mild reaction conditions, low cost, etc., and has great development potential.

Detailed ways

In order to further understand the present invention, the present invention will be described in detail below in conjunction with specific examples. Compound synthetic route of the present invention is as follows:

Example 1

Synthesis of 2-Nitrobenzoyl Chloride 2

Add 4.18g (0.025mol) of o-nitrobenzoic acid and 20mL (0.275mol) of thionyl chloride into a 50mL flask, heat to reflux at 80°C for 6h, evaporate the solvent under reduced pressure to obtain 3.7g of o-nitrobenzoyl chloride (0.02mol), yield 80%.

Example 2

Synthesis of 2-nitro-N-(4-chloro-3-pyridylmethyl)benzamide 3

Add 15mL of anhydrous THF, 5g (0.05mol) triethylamine and 4.28g (0.02mol) 2-chloro-5-aminomethylpyridine hydrochloride in a 50mL three-necked flask, and mix o-nitrobenzyl 3.7g (0.02mol) of anhydrous THF solution of acid chloride was slowly added dropwise into a three-necked flask, stirred and reacted at 25°C for 1h, and followed by TLC. After the reaction was completed, it was diluted with 30mL ethyl acetate and 25mL water, and the aqueous layer was washed with ethyl acetate ( 20mL×2) extraction, combined organic layers, washed the organic layer with 1.2mol/L NaHCO ₃ aqueous solution until neutral, then washed with saturated brine, dried over anhydrous Na ₂ SO ₄ , filtered, and precipitated under reduced pressure to obtain, ethanol: water =10:1 Recrystallization gave 4.77g of light yellow solid, yield: 82%.

Example 3

Synthesis of 2-amino-N-(4-chloro-3-pyridylmethyl)benzamide 4

Synthesis of 15mL THF, 40mL H ₂ O, 5mL (0.1mol) glacial acetic acid, 3.6g (0.014mol) 2-nitro-N-(4-chloro-3-pyridylmethyl)benzamide 4 in a 100mL three-necked flask and 3.92g (0.07mol) reduced iron powder, heated and stirred at 40°C for 4h, TLC followed the reaction, after the reaction was completed, filtered while hot, the filtrate was concentrated and extracted with ethyl acetate (30mL×3), the organic layers were combined, and the organic layer Wash with 1.2mol/L NaHCO ₃ solution to neutrality, then wash with saturated brine, dry with anhydrous Na ₂ SO ₄ , filter, concentrate to about 20ml and pass through dry HCl gas to obtain 3.23g yellow solid, yield: 88 %.

Example 4

Synthesis of N-(4-chloro-3-pyridylmethyl)-2-(3-methylbenzamido)benzamide 5

Add 15mL of anhydrous THF, 252mg (2.5mmol) of triethylamine and 261mg (1mmol) of 2-amino-N-(4-chloro-3-pyridylmethyl)benzamide into a 25mL one-necked flask, ice bath and vigorously stir Slowly add 220mg (1.42mmol) of newly prepared 3-methylbenzoyl chloride into the flask in batches, stir and react at 25°C for 1h, follow the reaction by TLC, pour into 20mL of ice water after the reaction is completed, and concentrate under reduced pressure to about 10mL , extracted with ethyl acetate (10mL×3), combined the organic layers, washed the organic layer with 1.2mol/L NaHCO ₃ aqueous solution until neutral, then washed with saturated brine, dried over anhydrous Na ₂ SO ₄ , filtered, and desolvated under reduced pressure , to obtain a light yellow solid, column chromatography obtained 380mg (1.0mol) white solid target product N-(4-chloro-3-pyridylmethyl)-2-(3-methylbenzamido)benzamide 5 , yield 70%, mp134～135℃MS, m/Z(%): 380(M+1) ⁺¹ H-NMR: (CDCl ₃ ,400MHz)δ: 2.45(s,3H), 4.63(m, 2H),7.02(m,1H),7.40～7.52(6H),7.71～7.83(3H),8.66(m,1H),8.74(m,1H),11.86(d,J＝2.0MHz,1H), .

Elemental analysis results: Ana1.calcdforC ₂₁ H ₁₈ N ₃ O ₂ Cl, C66.40, H4.78, N11.06; foundC66.43, H4.56, N10.89

Example 5

The compound to be tested, N-(4-chloro-3-pyridylmethyl)-2-(3-methylbenzamido)benzamide was made into 1000ppm with acetone, then diluted with water to 200ppm and cultivated in the greenhouse for 6 days Wheat (10 strains/seedling tube) was sprayed. After the liquid medicine is air-dried, the seedling-raising tube is put into the seedling-raising rack, and the seedling-raising rack is immersed in water. A wire mesh support is placed on the wheat seedlings, wheat leaves for cultivating wheat aphids are placed on the gauze, and the inoculation treatment is carried out so that the wheat aphids evenly migrate to the wheat. Remove the roving after 24 hours, the wheat plants have been transferred to the wheat seedlings, there is enough space between the wheat seedling tubes, and the seedling racks have water so that the aphids cannot be transferred between the seedling tubes. The wheat seedlings were cultivated in the greenhouse for 5 days, the number of aphids on the wheat seedlings of each treatment was checked, and the control effect was calculated. The 24-hour insecticidal effect is 61%.

The compound of the present invention, N-(4-chloro-3-pyridylmethyl)-2-(3-methylbenzamido)benzamide 5 has better insecticidal activity and has further development as insecticide potential.

Claims (7)

1. N-(4-chloro-3-pyridylmethyl)-2-(3-methylbenzamido) benzamide, which has the structural formula represented by the following formula I: . 2. The preparation method of N-(4-chloro-3-pyridylmethyl)-2-(3-methylbenzamido) benzamide, it is starting raw material with 2-nitrobenzoic acid, through and The reaction of thionyl chloride or phosphorus oxychloride produces 2-nitrobenzoyl chloride, which is then reacted with 2-chloro-5-aminomethylpyridine to form 2-nitro-N-(4-chloro-3-pyridylmethyl ) benzamide, the intermediate is reduced by iron powder to obtain 2-amino-N-(4-chloro-3-pyridylmethyl)benzamide, and finally reacts with 3-methylbenzoyl chloride to generate the final product N- (4-chloro-3-pyridylmethyl)-2-(3-methylbenzamido)benzamide; its reaction scheme is as follows: 3. the preparation method of N-(4-chloro-3-pyridylmethyl)-2-(3-methylbenzamido) benzamide according to claim 2 is characterized in that 2-nitrobenzene The specific steps for the reaction of formic acid with thionyl chloride or phosphorus oxychloride to generate 2-nitrobenzoyl chloride are: 2-nitrobenzoic acid and an appropriate amount of thionyl chloride or phosphorus oxychloride are added to the flask, heated to reflux After a certain period of time, the solvent is evaporated under reduced pressure to obtain 2-nitrobenzoyl chloride; the molar ratio of raw materials is 2-nitrobenzoic acid:thionyl chloride or phosphorus oxychloride=1:1~15; the reaction temperature is 40 ~100°C; reaction time is 3~10h. 4. the preparation method of N-(4-chloro-3-pyridylmethyl)-2-(3-methylbenzamido) benzamide according to claim 2 is characterized in that 2-chloro-5 The specific steps for generating 2-nitro-N-(4-chloro-3-pyridylmethyl)benzamide by reaction of amine methylpyridine are: adding anhydrous solvent, triethylamine and 2-chloro- 5-Aminomethylpyridine hydrochloride, slowly add 2-nitrobenzoyl chloride dropwise under stirring at 0°C, stir at a certain temperature for reaction, follow the reaction by TLC, and dilute with ethyl acetate and water after the reaction is completed, then dilute with water The layers were extracted with ethyl acetate, the organic layers were combined, and the organic layer was washed with NaHCO ₃ aqueous solution to neutrality, then washed with saturated brine, dried with anhydrous Na ₂ SO ₄ , filtered, desolvated under reduced pressure, and recrystallized to obtain the target product; raw material The molar ratio is 2-chloro-5-aminopicoline: 2-nitrobenzoyl chloride: triethylamine=1:1～5:1～10; the reaction temperature is 20～50°C; the reaction time is 0.5～ 3h. 5. the preparation method of N-(4-chloro-3-pyridylmethyl)-2-(3-methylbenzamido) benzamide according to claim 2 is characterized in that 2-amino-N -(4-chloro-3-pyridylmethyl)benzamide is synthesized in specific steps: add glacial acetic acid in a reaction vessel, a certain amount of 2-nitro-N-(4-chloro-3-pyridylmethyl)benzene Formamide and reduced iron powder, heating and stirring at a certain temperature, TLC tracking reaction, after the reaction is completed, filter while hot, and extract the filtrate with ethyl acetate after concentration, combine the organic layer, wash the organic layer with NaHCO ₃ solution until neutral, and then Wash with saturated brine and dry over anhydrous Na ₂ SO ₄ to obtain 2-amino-N-(4-chloro-3-pyridylmethyl)benzamide; the molar ratio of raw materials is 2-nitro-N-(4-chloro -3-pyridylmethyl)benzamide: glacial acetic acid: iron powder = 1:1~10:1~10, the reaction temperature is 30~80°C; the reaction time is 2~10h. 6. the preparation method of N-(4-chloro-3-pyridylmethyl)-2-(3-methylbenzamido) benzamide according to claim 2 is characterized in that N-(4- The synthetic concrete steps of chloro-3-pyridylmethyl)-2-(3-methylbenzamido) benzamide are: add a certain amount of solvent, triethylamine and 2-amino-N-( 4-Chloro-3-pyridylmethyl)benzamide, add quantitative 3-methylbenzoyl chloride to the above-mentioned reaction bottle under ice bath and strong stirring, stir the reaction, follow the reaction by TLC, after the reaction is completed, pour it into into ice water, concentrated under reduced pressure, extracted with ethyl acetate, combined the organic layers, washed the organic layer with NaHCO ₃ aqueous solution until neutral, then washed with saturated brine, dried over anhydrous Na ₂ SO ₄ , filtered, and precipitated under reduced pressure, Obtain pale yellow solid, obtain target product N-(4-chloro-3-pyridylmethyl)-2-(3-methylbenzamido)benzamide through column chromatography; The mol ratio of raw material is 2-amino -N-(4-chloro-3-pyridylmethyl)benzamide: triethylamine: 3-methylbenzoyl chloride=1:1～10:1～5); the reaction temperature is 0～50°C; the reaction The time is 0.5 ~ 3h. 7. the application of N-(4-chloro-3-pyridylmethyl)-2-(3-methylbenzamido) benzamide as claimed in claim 1 as insecticide.