Fluorine-containing nicotinyl urea compounds and preparation method and application thereof

Abstract

The invention discloses a fluorine-containing nicotinyl urea compound. The structural formula of the fluorine-containing nicotinyl urea compound is as shown in the specification. In a formula (I), H on a benzene ring is monosubstituted or polysubstituted by substituent groups R, wherein n is an integer from 1 to 5 and represents the number of the substituent groups R on the benzene ring; when n is1, H on the benzene ring is monosubstituted by the substituent group R; when n is from 2 to 5, H on the benzene ring is polysubstituted by the substituent groups R; and the substituent groups R on different substituent positions are same or different. The invention also provides a preparation method and application of the fluorine-containing nicotinyl urea compound. As a bactericide, the fluorine-containing nicotinyl urea compound is used for inhibiting botrytis cinerea, gibberella zeae, sclerotinia sclerotiorum or physalospora piricola.

Description

technical field

[0001] The invention relates to a preparation method and application of a fluorine-containing nicotinyl urea compound. Background technique

[0002] Amide fungicides are a kind of common fungicides, which are widely used in crop disease control. There have been a lot of research on the synthesis and biological activity of amide fungicides at home and abroad; heterocyclic compounds have good selectivity, high activity, Low toxicity and other characteristics have become the focus of research and development of agricultural fungicides at home and abroad in recent years. Many compounds containing heterocyclic structures have been used as commercial fungicides and are widely used in the control of crop diseases.

[0003] And amides are one of the most common compounds in natural bioactive molecules and synthetic organic compounds. The synthesis of amides has important applications in medicinal chemistry, biochemistry and polymer synthesis. Research shows that mo...

Examples

Embodiment 1

[0046] Example 1, The preparation of 2-chloro-N-(4-fluorophenylcarbamoyl)nicotinamide compounds, the following steps are carried out in sequence:

[0047] 1) Add 2-chloronicotinic acid (3.4g, 22mmol) and thionyl chloride (10mL) into a 100mL flask, heat and stir under reflux for 3h, at this time the reaction solution changes from turbid to clear, and continue to reflux for 30min;

[0048] Afterwards, the reaction solution was subjected to rotary evaporation (the rotary evaporation temperature was 50° C.) to remove excess thionyl chloride to obtain a yellow transparent liquid, and the yellow crystal precipitated after the yellow transparent liquid was cooled to room temperature was 2-chloronicotinoyl chloride;

[0049]2) Dilute all the 2-chloronicotinoyl chloride obtained in step 1) with 8mL of dichloromethane to prepare a 2-chloronicotinyl chloride solution for later use; slowly drop the above-prepared 2-chloronicotinyl chloride solution under ice bath conditions Add in 25% (ma...

Embodiment 2

[0056] Change the substituted aniline in step 4) of Example 1 from 4-fluoroaniline to 3,4-difluoroaniline, and the dosage remains unchanged at 1.1 mmol; the rest is the same as in Example 1;

[0057] The final reaction to obtain the target product A2;

[0058] (A2) White solid, yield: 57.6%, melting point: 218-221°C. 1 H NMR (CDCl 3 ,500MHz),δ:7.09-7.18(m,2H,Ph),7.45-7.48(m,1H,Py),7.55-7.59(m,1H,Ph),8.10-8.22(m,1H,Py), 8.62-8.64(m,1H,Py),9.47(s,1H,NH),10.52(s,1H,NH);HRMS(ESI)for C 13 h 8 CIF 2 N 3 o 2 m / z: Calculated, 312.0346, Found, 312.0364[M+H] + .

[0059] The structural formula of A2 is:

[0060]

Embodiment 3

[0062] Change the substituted aniline in step 4) of Example 1 from 4-fluoroaniline to 4-trifluoromethylaniline, and the amount remains unchanged at 1.1 mmol; the rest is the same as in Example 1;

[0063] Final reaction obtains target product A3;

[0064] (A3) White solid, yield: 57.9%, melting point: 213-215°C. 1 H NMR (CDCl 3 ,500MHz), δ:7.56-7.59(m,1H,Py),7.71(d,J=6.8Hz,2H,Ph),7.81(d,J=6.8Hz,2H,Ph),8.11-8.13(m ,1H,Py),8.55-8.57(m,1H,Py),10.54(s,1H,NH),11.44(s,1H,NH); HRMS(ESI)forC 14 h 9 CIF 3 N 3 o 2 m / z: Calculated, 344.0408, Found, 344.0444[M+H] + .

[0065] The structural formula of A3 is:

[0066]

technical field

[0001] The invention relates to a preparation method and application of a fluorine-containing nicotinyl urea compound. Background technique

[0002] Amide fungicides are a kind of common fungicides, which are widely used in crop disease control. There have been a lot of research on the synthesis and biological activity of amide fungicides at home and abroad; heterocyclic compounds have good selectivity, high activity, Low toxicity and other characteristics have become the focus of research and development of agricultural fungicides at home and abroad in recent years. Many compounds containing heterocyclic structures have been used as commercial fungicides and are widely used in the control of crop diseases.

[0003] And amides are one of the most common compounds in natural bioactive molecules and synthetic organic compounds. The synthesis of amides has important applications in medicinal chemistry, biochemistry and polymer synthesis. Research shows that mo...

Examples

Embodiment 1

[0046] Example 1, The preparation of 2-chloro-N-(4-fluorophenylcarbamoyl)nicotinamide compounds, the following steps are carried out in sequence:

[0047] 1) Add 2-chloronicotinic acid (3.4g, 22mmol) and thionyl chloride (10mL) into a 100mL flask, heat and stir under reflux for 3h, at this time the reaction solution changes from turbid to clear, and continue to reflux for 30min;

[0048] Afterwards, the reaction solution was subjected to rotary evaporation (the rotary evaporation temperature was 50° C.) to remove excess thionyl chloride to obtain a yellow transparent liquid, and the yellow crystal precipitated after the yellow transparent liquid was cooled to room temperature was 2-chloronicotinoyl chloride;

[0049]2) Dilute all the 2-chloronicotinoyl chloride obtained in step 1) with 8mL of dichloromethane to prepare a 2-chloronicotinyl chloride solution for later use; slowly drop the above-prepared 2-chloronicotinyl chloride solution under ice bath conditions Add in 25% (ma...

Embodiment 2

[0056] Change the substituted aniline in step 4) of Example 1 from 4-fluoroaniline to 3,4-difluoroaniline, and the dosage remains unchanged at 1.1 mmol; the rest is the same as in Example 1;

[0057] The final reaction to obtain the target product A2;

[0058] (A2) White solid, yield: 57.6%, melting point: 218-221°C. 1 H NMR (CDCl 3 ,500MHz),δ:7.09-7.18(m,2H,Ph),7.45-7.48(m,1H,Py),7.55-7.59(m,1H,Ph),8.10-8.22(m,1H,Py), 8.62-8.64(m,1H,Py),9.47(s,1H,NH),10.52(s,1H,NH);HRMS(ESI)for C 13 h 8 CIF 2 N 3 o 2 m / z: Calculated, 312.0346, Found, 312.0364[M+H] + .

[0059] The structural formula of A2 is:

[0060]

Embodiment 3

[0062] Change the substituted aniline in step 4) of Example 1 from 4-fluoroaniline to 4-trifluoromethylaniline, and the amount remains unchanged at 1.1 mmol; the rest is the same as in Example 1;

[0063] Final reaction obtains target product A3;

[0064] (A3) White solid, yield: 57.9%, melting point: 213-215°C. 1 H NMR (CDCl 3 ,500MHz), δ:7.56-7.59(m,1H,Py),7.71(d,J=6.8Hz,2H,Ph),7.81(d,J=6.8Hz,2H,Ph),8.11-8.13(m ,1H,Py),8.55-8.57(m,1H,Py),10.54(s,1H,NH),11.44(s,1H,NH); HRMS(ESI)forC 14 h 9 CIF 3 N 3 o 2 m / z: Calculated, 344.0408, Found, 344.0444[M+H] + .

[0065] The structural formula of A3 is:

[0066]

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