RU2421992C1 - 2,4-dichlorophenoxyacetic acid herbicide antidote - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention relates to biologically active chemical substances. Proposed is use of N-aryl-3-amino-4,6-dimethyltheno [2,3-b]pyridyl-2-carboxamides as substances which lower the negative effect of the 2,4-dichlorophenoxyacetic acid herbicide on sunflower plants. The effect is achieved by using N-aryl-3-amino-4,6-dimethyltheno [2,3-b]pyridyl-2-carboxamides to treat damaged sunflower plants a day after applying the herbicide.

EFFECT: wider range of synthetic biologically active substances for use in agriculture as 2,4-D antidotes.

1 tbl, 5 ex

Description

The invention relates to the protection of seedlings and vegetative plants of sunflower from the phytotoxic effect of 2,4-D herbicides, which are proposed compounds of the formula 1-3:

where 1 R = H, X = 4-chloro 2,5-dimethoxyphenyl;

2 R = H, X = 3-fluorophenyl;

3 R = CI, X = 2-bromophenyl;

Compounds 1-3 are known (catalogs Aurora Screening Library and Labo Test Stock), however, their antidote properties were identified for the first time.

As you know, sunflower is an extremely sensitive crop to 2,4-D group herbicides, and, in case of unintentional hit of a herbicide on its crops, losses can be up to 100%, depending on the dose [D.I. Chkanikov, M.S. . Sokolov. The herbicidal effect of 2,4-D and other halo phenoxy acids. M .: Nauka, 1973].

Until now, the protection of vegetative sunflower plants from the damaging effects of 2,4-D remains relevant and unresolved.

The closest analogue in structure and properties of the claimed compounds is N- (4-fluorophenyl) -3-amino-4,6-dimethylthieno [2,3-b] pyridyl-2-carboxamide of the formula 4 ["Method for the protection of vegetative sunflower plants from damaging action 2,4-D ", US Pat. RF №2277333 dated 06/10/2006, application No. 2005103585 dated 02/14/2005]:

Compound 4 (prototype) in the field at a dose of 200 g / ha on vegetative sunflower plants exhibits an antidote effect in relation to 2,4-D of about 23% and can be used as a sunflower protection product. However, the activity of antidote 4 is not high enough.

The objective of the present invention is to expand the arsenal of biologically active substances obtained synthetically, for use in agriculture as antidotes.

This is achieved by using N-aryl-3-amino-4,6-dimethylthieno [2,3-b] pyridyl-2-carboxamides 1-3 on damaged vegetative sunflower plants.

Moreover, the claimed compounds receive in accordance with the following

scheme:

By the interaction of 4,6-dimethyl-5-R-3-cyano-2 (1H) -pyridinethione (A, B) with N-aryl-2-chloroacetamide in the presence of an equivalent of KOH in a DMF solution, an intermediate product (CE) is synthesized, which, without isolation from the reaction mass, when an equimolar amount of alkali is added, is cyclized to the target compounds 1-3 [A.V. Kadushkin, I.F. Faermark, G.Ya. Mark, V.G. Granik. Synthesis and biological properties of 4-phenylamino, 4-dimethylamino-3-cyano-pyridinothione-2 and the preparation of thieno [2,3-b] pyridines based on them. - Chem. farm. g. - 1992. - T.26. - No. 11-12. - S. 62-66].

The invention is illustrated by the following examples.

Example 1. N- (2,5-dimethoxy-4-chlorophenyl) -3-amino-4,6-dimethylthieno [2,3-b] pyridyl-2-carboxamide (compound 1).

To a suspension of 1.2 g (7.3 mmol) of 4,6-dimethyl-3-cyano-2 (1H) -pyridinethione in 25 ml of DMF is added a solution of 0.41 g (7.3 mmol) of KOH in a minimum amount of water and stirred until the precipitate is completely dissolved. Then, a solution of 2.2 g (7.3 mmol) of N- (2,5-dimethoxy-4-chlorophenyl) -2-chloroacetamide in 10 ml of DMF was added to the reaction mixture and stirred at room temperature for 40-50 minutes. After repeated addition of an aqueous solution of 0.41 g (7.3 mmol) KOH, stirring was continued for another 1 h, at the end, the reaction mixture was diluted with water twice and the precipitate formed was filtered off and dried. After recrystallization from a mixture of ethanol: DMF = 1: 1, 1.75 g (61%) of target product 1 are obtained in the form of crystals with a melting point of 237-239 ° C.

Found,%: C 54.88; H 4.54; N, 10.62. C ₁₈ H ₁₈ CIN ₃ O ₃ S.

Calculated,%: C 55.17; H 4.63; N, 10.72.

¹ H NMR spectrum, δ, ppm (group): 2.49 (s, 3H, 4-CH ₃ Ru); 2.71 (s, 3H, 6-CH ₃ Ru); 3.69 (s, 3H, 2-OCH ₃ ); 3.87 (s, 3H, 5-OCH ₃ ); 6.72 (s, 1H, 3-H Ar); 6.87 (s, 1H, 5-N Ru); 7.68 (s, 1H, 6-H Ar); 12.85 (br s, 1H, NH).

Example 2. N- (3-fluorophenyl) -3-amino-4,6-dimethylthieno [2,3-b] pyridyl-2-carboxamide (compound 2).

To a suspension of 1.2 g (7.3 mmol) of 4,6-dimethyl-3-cyano-2 (1H) -pyridinethione in 25 ml of DMF is added a solution of 0.41 g (7.3 mmol) of KOH in a minimum amount of water and stirred until the precipitate is completely dissolved. Then a solution of 1.37 g (7.3 mmol) of N- (3-fluorophenyl) -2-chloroacetamide in 10 ml of DMF is added to the reaction mixture and stirred at room temperature for 30-40 minutes. After repeated addition of an aqueous solution of 0.41 g (7.3 mmol) KOH, stirring was continued for another 40 minutes, at the end, the reaction mixture was diluted with water twice and the precipitate formed was filtered off and dried. After recrystallization from ethanol: DMF = 1: 1, 1.57 g (68%) of target product 2 are obtained in the form of crystals with a melting point of 217-219 ° C.

Found,%: C 60.62; H 4.33; N, 13.49. C ₁₆ H ₁₄ FN ₃ OS.

Calculated,%: C 60.94; H 4.47; N, 13.32.

Nuclear Magnetic Resonance Spectrum ¹ H δ, ppm (group): 2.55 (s, 3H, CH ₃ -4); 2.74 (s, 3H, CH ₃ -6);

6.90 ... 7.68 (m, 4H, Ar); 7.03 (br s, 2H, NH ₂ ); 7.08 (s, 1H, 5-N Ru); 9.10 (br s, 1H, NH).

Example 3. N- (2-bromophenyl) -3-amino-4,6-dimethyl-5-chlorothieno [2,3-b] pyridyl-2-carboxamide (compound 3).

To a suspension of 1.45 g (7.3 mmol) of 4,6-dimethyl-5-chloro-3-cyano-2 (1H) -pyridinethione in 30 ml of DMF was added a solution of 0.41 g (7.3 mmol) of KOH in a minimum amount of water and mix until the precipitate is completely dissolved. Then, a solution of 1.8 g (7.3 mmol) of N- (2-bromophenyl) -2-chloroacetamide in 10 ml of DMF was added to the reaction mixture and stirred at room temperature for 30-40 minutes. After repeated addition of an aqueous solution of 0.41 g (7.3 mmol) KOH, stirring was continued for another 40 minutes, at the end, the reaction mixture was diluted with water twice and the precipitate formed was filtered off and dried. After recrystallization from a mixture of ethanol: DMF = 1: 1, 2.40 g (80%) of target product 3 are obtained in the form of crystals with a melting point of 242-244 ° C.

Found,%: C 46.61; H 3.31; N, 10.42. C ₁₆ H ₁₃ BrCIN ₃ OS.

Calculated,%: C 46.79; H 3.19; N, 10.23.

¹ H NMR spectrum, δ, ppm (group): 2.56 (s, 3H, CH ₃ -4); 2.87 (s, 3H, CH ₃ -6); 6.97 (s 2H, NH ₂ ); 7.20 ... 7.72 (m, 4H, Ar); 9.48 (br s, 1H, NH).

Example 4. N- (4-fluorophenyl) -3-amino-4,6-dimethylthieno [2,3-b] pyridyl-2-carboxamide (compound 4).

To a suspension of 1.2 g (7.3 mmol) of 4,6-dimethyl-3-cyano-2 (1H) -pyridinethione in 25 ml of DMF is added a solution of 0.41 g (7.3 mmol) of KOH in a minimum amount of water and stirred until the precipitate is completely dissolved. Then, a solution of 1.37 g (7.3 mmol) of N- (4-fluorophenyl) -2-chloroacetamide in 10 ml of DMF is added to the reaction mixture and stirred at room temperature for 30-40 minutes. After repeated addition of an aqueous solution of 0.41 g (7.3 mmol) KOH, stirring was continued for another 40 minutes, at the end, the reaction mixture was diluted with water twice and the precipitate formed was filtered off and dried. After recrystallization from acetone, 1.8 g (78%) of the desired product 4 are obtained in the form of crystals with mp. 192-193 ° C.

Found,%: C 61.15; H 4.52; N, 13.54. C ₁₆ H ₁₄ FN ₃ OS.

Calculated,%: C 60.94; H 4.47; N, 13.32.

¹ H NMR spectrum, δ, ppm (group): 2.55 (s, 3H, CH ₃ -4); 2.74 (s, 3H, CH ₃ -6);

7.16 ... 7.38 (m, 4H, Ar); 7.03 (br s, 2H, NH ₂ ); 7.08 (s, 1H, 5-N Ru); 9.10 (br s, 1H, NH).

Example 5. Evaluation of compounds 1-4 for antidote activity on sunflower plants in a field experiment.

Evaluation of the antidote activity of the claimed compounds 1-3 and prototype (compound 4) was carried out on the experimental field of VNIIBZR. The tests were carried out according to the following procedure.

In the field, sunflower plants of the VNIIMK 8883 cultivar were treated with 2,4-dichlorophenoxyacetic acid butyl ether at a dose of 18 g / ha in a 10-16 leaf phase and the antidote solution at a dose of 200 g / ha with a working fluid flow rate of 500 l / ha was applied a day later .

In the experiment, the following options are provided:

- control - untreated plants;

- "herbicide" (standard) - plants treated with a herbicide;

- “herbicide + antidote” - plants treated with herbicide and antidote.

The experiments were carried out on plots with an area of 2.8 m ² , five repetition.

Harvesting of sunflower seeds was carried out at the time of complete ripening of seeds. The antidote effect was determined by the absolute value of the yield increase to the herbicidal standard and in percentage by the formula:

A _x - antidote effect,%;

A - crop in the variant antidote + herbicide;

E - crop in the standard version (herbicide).

The data obtained are statistically processed using t - student criterion.

The test results are presented in the table.

Table Antidote activity of N-aryl-3-amino-4,6-dimethylthieno [2,3-b] pyridyl-2-carboxamides (compounds 1-3) and prototype (compound 4) in relation to 2,4-D in sunflower Antidote Dose of antidote, g / ha Experience Options 2,4-D (herbicide) 2,4-D + antidote Productivity c / ha Productivity c / ha Antidote activity c / ha % Compound 1 200 13.8 20,4 6.6 48 * Compound 2 200 13.8 18.0 4.2 thirty* Compound 3 200 13.8 22.3 8.5 61 * Compound 4 (prototype) 200 13.8 17.0 3.2 23 * The control - 26.04 - - -

* The differences between the options are significant at P = 0.90

Thus, the use of the inventive N-aryl-3-amino-4,6-dimethylthieno [2,3-b] pyridyl-2-carboxamides 1-3 as an antidote allows for an antidote effect of 30-61% against 23% the prototype (compound 4), and also expand the range of known antidotes.

Claims (1)

The antidotes of the sunflower 2,4-dichlorophenoxyacetic acid herbicide, which are N-aryl-3-amino-4,6-dimethylthieno [2,3-b] pyridyl-2-carboxamides of the formula 1-3:

where 1 R = H, X = 4-chloro 2,5-dimethoxyphenyl;
2 R = H, X = 3-fluorophenyl;
3 R = Cl, X = 2-bromophenyl.