RU2287273C1 - Using n-substituted 3-cyano-4,6-dimethyl-5-chloropyridyl-2-sulfonylamides as antidotes of herbicide 2,4-dichlorophenoxyacetic acid in sunflower - Google Patents

Abstract

FIELD: organic chemistry, antidotes, agriculture.

SUBSTANCE: invention describes using N-substituted 3-cyano-4,6-dimethyl-5-chloropyridyl-2-sulfonylamides of the formula (1-2):

wherein in (1) R means benzimidozolyl-1; in (2) R means furfurylamino-group as antidotes of herbicide 2,4-dichlorophenoxyacetic acid in sunflower. Invention provides expanding assortment of biologically active substances prepared by synthetic method for their using in agriculture as antidotes against 2,4-D. Method involves treatment of sunflower seedlings damaged with herbicide by proposed N-substituted 3-cyano-4,6-dimethyl-5-chloropyridyl-2-sulfonylamides.

EFFECT: valuable biological properties of antidotes.

1 tbl, 3 ex

Description

The invention relates to chemical biologically active substances of the pyridine series of the formula 1-2:

1 R = benzimidazolyl-1;

2 R = furfurylamino;

able to reduce the phytotoxic effect of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) on sunflower plants (antidotes). Compound 1 was synthesized for the first time, compound 2 was previously known (Chemical Blok Stok Library Catalog, Cas Registry No. 698994-57-9, 08/10/2004).

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 action 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 chemical structure of the claimed compounds and, at the same time, analogue in properties is the well-known antibacterial drug Sulfalen ["Antidote of hormonal-type herbicides of action of 2,4-dichlorophenoxyacetic acid and 4-amino-3,5,6-trichloropicolinic acids." RF Patent No. 2043021 of 09/10/95, application No. 5042089 of 05/14/92] of formula 3:

This compound is widely used as an antibacterial agent in medical practice, its synthesis is described in the literature [V. G. Belikov. Pharmaceutical Chemistry. - M.: Higher School, 1985, p. 383, 768]. However, Sulfalen does not have a sufficiently high antidote activity.

The objective of the present invention is to expand the arsenal of biologically active substances obtained synthetically for use in agriculture as a means of protecting vegetative sunflower plants from the damaging effects of 2,4-D (antidote).

This is achieved by treating damaged sunflower plants with N-substituted 3-cyano-4,6-dimethyl-5-chloropyridyl-2-sulfonylamides 1-2.

The synthesis of the claimed compounds 1-2 was carried out in a known manner - the interaction of 3-cyano-4,6-dimethyl-5-chloropyridyl-2-sulfonyl chloride with amines in the presence of triethylamine at room temperature in anhydrous benzene [see New sulfonamides: Application 1211567, Japan, MKI ⁴ C 07 D 213/74, 241/04 from 08.24.89].

The invention is illustrated by the following examples.

Example 1. 2 - [(benzimidazol-1-yl) -sulfonyl] -3-cyano-4,6-dimethyl-5-chloropyridine (compound 1).

To a suspension of 0.43 g (0.0036 mol) of benzimidazole and 0.31 g (0.0031 mol) of triethylamine in 15 ml of absolute benzene is added a solution of 0.8 g (0.0031 mol) of 3-cyano-4.6 -dimethyl-5-chloropyridyl-2-sulfonyl chloride and stirred at room temperature for 8 hours. The reaction mass was separated from the precipitate Et ₃ N × HCl by filtration, evaporated to dryness, the residue was recrystallized from hexane: ethyl acetate = 2: 1, 0.9 g (84%) of target compound 1 were obtained in the form of white crystals with mp. = 132-133 ° C.

Found,%: C 51.68; H 3.12; N, 16.41; S 9.44; C ₁₅ H ₁₁ ClN ₄ O ₄ S;

Calculated,%: C 51.95; H 3.20; N, 16.16; S 9.23.

Mass spectrum, m / z (relates, intensity): M ⁺ 346 (78); 281 (80); 182 (22); 165 (79); 138 (43); 102 (74); 90 (100).

Example 2. N-furfurylamino-3-cyano-4,6-dimethyl-5-chloropyridyl-2-sulfonylamide (compound 2).

To a solution of 0.49 g (0.0050 mol) of furfurylamine and 0.45 g (0.0045 mol) of triethylamine in 20 ml of absolute benzene, a solution of 1.2 g (0.0045 mol) of 3-cyano-4 is added dropwise. 6-dimethyl-5-chloropyridyl-2-sulfonyl chloride in 15 ml of absolute benzene, maintaining the temperature of the reaction mixture in the range of 12-15 ° C. Upon completion of the addition, the temperature was slowly raised to room temperature and stirring was continued for another 4 hours. The precipitate formed is filtered off, washed extensively with water, and dried. The residue after evaporation of the benzene solution is combined with the precipitate, recrystallized from hexane: ethyl acetate = 2: 1, 1.05 g (70%) of target compound 2 are obtained in the form of a white crystalline powder, mp = 138-139 ° C.

Found,%: C 47.61; H 3.54; N, 12.70; S 9.62; C ₁₃ H ₁₂ ClN ₃ O ₃ S.

Calculated,%: C 47.97; H 3.72; N, 3.72; S 9.83.

PMR, δ, ppm (group): 2.60 (3H, s, 4-CH ₃ Ru); 2.65 (3H, s. 6-CH ₃ Ru); 4.27 (2H, s, CH ₂ ); 6.20 ... 7.45 (3H, m, CH of furan ring); 8.85 (1H, s, NH).

Mass spectrum, m / z (relates, intensity): M ⁺ 325 (3); 261 (10); 232 (17); 213 (15); 166 (100); 138 (18); 131 (22); 102 (34); 96 (58); 81 (45).

Example 3. Evaluation of compounds 1-6 for antidote activity on sunflower seedlings.

Sprouted sunflower seeds with a long germinal root of 2-4 mm were placed for 1 h in a solution of 2,4-dichlorophenoxyacetic acid (2,4-D) at a concentration of 10 ^-3 % in the calculation of obtaining 40-60% inhibition of growth of hypocotyl. After the herbicidal action, the seedlings were washed with water and placed in solutions of substances tested for antidote activity at concentrations of 10 ^-2 , 10 ^-3 , 10 ^-4 , 10 ^-5 % (variant herbicide + antidote). After 1 h, the seeds were washed with water and laid out on strips of filter paper (size 10 × 75 cm) of 20 pieces, which were rolled up and placed in glasses with 50 ml of water. Further seed germination was carried out in a thermostat for 3 days at a temperature of 28 ° C. The temperature of solutions and wash water is 28 ° C.

The seeds of the herbicide variant (reference standard) were kept for 1 hour in a solution of 2,4-D at a concentration of 10 ^-3 % and 1 hour in water.

The seeds of the control variant were kept in water for 2 hours.

The experiment was repeated three times. In each repetition, 20 seeds were used.

The protective (antidote) effect was determined by increasing the length of the hypocotyl and root in the herbicide + antidote variant relative to the mentioned values in the "herbicide" (standard) variant.

Statistical processing of experimental data was carried out using Student's t-test at P = 0.95.

The research results are shown in the table.

As can be seen from the table, the use of N-substituted 3-cyano-4,6-dimethyl-5-chloropyridyl-2-sulfonylamides 1-2, which are proposed as antidotes, against the background of the action of the herbicide, sharply reduces the toxic effect of the herbicide.

Compounds 1-2 leveled the negative effect of 2,4-D on the hypocotyl of sunflower seedlings by 24-51% when used in three or more concentrations, while the antidote effect of Sulfalen (prototype) was 12-22%.

Compounds 1-2 reduced the inhibitory effect of 2,4-D on the roots of seedlings by 28-45% also when used in three or more concentrations, and Sulfalen (prototype) showed an antidote effect at the level of 16-31%.

Thus, the use of the inventive N-substituted 3-cyano-4,6-dimethyl-5-chloropyridyl-2-sulfonylamides as antidotes can effectively protect sunflower from the negative effects of 2,4-D, as well as expand the range of known antidotes.

Table
Antidote activity of N-substituted 3-cyano-4,6-dimethyl-5-chloropyridyl-2-sulfonylamides and their prototype 2,4-D on sunflower seedlings of the VNIIMK-8883 variety. A drug Concentration, Hypocotyl Length Root length % mm K 2,4-D,% mm K 2,4-D,% The control 0 74 eleven 2,4-D 10 ^-3 41 44 2,4-D + compound 1 10 ^-2
10 ^-3
10 ^-4
10 ^-5 51
48
52
55 124 *
116
128 *
133 * 59
57
fifty
61 133 *
129 *
141 *
138 * 2,4-D + compound 2 10 ^-2
10 ^-3
10 ^-4
10 ^-5 fifty
56
51
62 121
137 *
124 *
151 * 56
59
64
62 128 *
134 *
145 *
142 * 2,4-D + compound 3 (prototype) 10 ^-2
10 ^-3
10 ^-4
10 ^-5 46
48
fifty
47 112
118 *
122 *
115 * 58
479
52
51 131 *
107
118 *
116 * * Differences between options are significant at P = 0.95

Claims (2)

The use of N-substituted 3-cyano-4,6-dimethyl-5-chloropyridyl-2-sulfonylamides of the formula 1-2

where 1. R = benzimidosolyl-1; 2. R = furfurylamino, as antidotes for the herbicide of 2,4-dichlorophenoxyacetic acid in sunflower.