RU2850699C1 - Use of n-(chloroacetyl)phenothiazine as antidote to 2,4-d on sunflowers - Google Patents

Abstract

FIELD: agrochemistry.

SUBSTANCE: invention relates to plant protection products. The compound N-(chloroacetyl)phenothiazine of formula:

is proposed for use as an antidote to the herbicide 2,4-dichlorophenoxyacetic acid on sunflowers.

EFFECT: expanded arsenal of heterocyclic compounds used to protect sunflower plants from the phytotoxic effects of the herbicide 2,4-dichlorophenoxyacetic acid.

1 cl, 1 tbl, 1 ex

Description

The invention relates to synthetic, biologically active substances from a series of heterocyclic compounds used to protect sunflower plants from the phytotoxic action of the herbicide 2,4-dichlorophenoxyacetic acid (antidotes).

As is known, sunflower is an extremely sensitive crop to hormonal herbicides of the 2,4-D group, and in cases of unintentional contact of the herbicide with its crops, losses can amount to up to 100%, depending on the dose [Chkanikov D. I., Sokolov M. S. Herbicidal action of 2,4-D and other halophenoxy acids, Moscow: Nauka, 1973, 95 p.]. Despite intensive research to find new antidotes, the protection of vegetative sunflower plants from the damaging effects of 2,4-D remains relevant and unresolved [Strelkov V. D., Dyaduchenko L. V., Dmitriev I. G. Synthesis of new herbicide antidotes for sunflower. Krasnodar: Prosveshchenie-Yug, 2014. P. 79].

The closest analogue in structure and properties to the claimed compounds is 3-amino-2-[N-(4-fluorophenyl)carbamido]-4,6-dimethylthieno[2,3-b]pyridine of the formula1[pat. No. 2277333 RF, IPC A01N 25/32 (2006.01) A01P 15/00 (2006.01)]:

Compound 1 (the prototype) exhibits a 22-24% antidote effect against 2,4-D in field conditions at a dose of 200 g/ha on vegetative sunflower plants and can be used as a sunflower pesticide. However, its antidote activity is not high enough, and a dose of 200 g/ha is quite high and may cause negative environmental problems.

The technical result of the claimed invention is the expansion of the arsenal of biologically active substances obtained synthetically for their use in agriculture as antidotes.

The technical result is achieved by using N-(chloroacetyl)phenothiazine 2 :

exhibiting antidote activity against 2,4-dichlorophenoxyacetic acid on sunflower seedlings under laboratory conditions.

N-(Chloroacetyl)phenothiazine 2received using a modified procedure based on the method from [A. Marcu, U. Schurigt, K. Müller, H. Moll, R. L. Krauth-Siegel, H. Prinz. Inhibitory effect of phenothiazine- and phenoxazine-derived chloroacetamides on Leishmania major growth and Trypanosoma brucei trypanothione reductase // Eur. J. Med. Chem., 2016, vol. 108, p. 436; DOI: 10.1016/j.ejmech.2015.11.023] - the chloroacetyl chloride reaction4with unsubstituted phenothiazine3[Pozharsky, A.F. Practical Work on the Chemistry of Heterocycles: A Textbook for Chemical Specialties at Universities / A.F. Pozharsky, V.A. Anisimova, E.B. Tsupak; ed. B.A. Tertov; Rostov State University. - Rostov-on-Don: Rostov University Publishing House, 1988. - p. 20] in boiling anhydrous toluene. The product was obtained in 67% yield.

Preparation of N-(chloroacetyl)phenothiazine 2. Unsubstituted phenothiazine (5.66 g, 0.0284 mol) was dissolved with stirring in absolute toluene (25 ml, pre-dried over sodium) and 2.50 ml (0.0314 mol) of chloroacetyl chloride were added dropwise to the solution. The resulting solution was refluxed with stirring for 3.5 h, the reaction progress was monitored by TLC. The mixture was cooled and purified by filtration through silica gel to remove dark blue phenothiazine oxidation products. The filtrate was evaporated in vacuo, the crystalline mass was further purified by recrystallization from n -butanol. Yield 67%, mp 188–189°C. 110-112°C (lit. [A. Marcu, U. Schurigt, K. Müller, H. Moll, RL Krauth-Siegel, H. Prinz. Inhibitory effect of phenothiazine- and phenoxazine-derived chloroacetamides on Leishmania major growth and Trypanosoma brucei trypanothione reductase // Eur. J. Med. Chem., 2016, vol. 108, p. 436; DOI: 10.1016/j.ejmech.2015.11.023]: mp 111-112°C); light-brown crystals. IR spectrum, ν/cm ^-1 : 3068, 2952 (C-H), 1670 (C=O). ^1H NMR spectrum (DMSO _-d6 , δ, ppm, J /Hz): 4.50 (s, 2H, _ClCH2 ); 7.31-7.35 (m, 2 N, H-Ar); 7.39-7.43 (m, 2 H, H-Ar); 7.58 (dd, 2 H, H-Ar, ³ J = 7.7, ⁴ J = 1.3); 7.69 (d, 2 H, H-Ar, ³ J = 7.8). ^13C NMR spectrum DEPTQ (DMSO _- d6 , δ, ppm, J /Hz): 42.8 ( _ClCH2 ); 126.9* (2 CH Ar); 127.5* (4 CH Ar); 128.1* (2 CH Ar); 132.3 (C ^4a , C ^5a Ar); 137.6 (C ^9a , C ^10a Ar); 165.0 (C=O). *Signal in antiphase.

Example 1. Evaluation of compound 2 for antidote activity on sunflower seedlings.

Sprouted seeds of the Master sunflower variety with an embryonic radicle length of 2-4 mm are placed for 1 hour in a solution of 2,4-dichlorophenoxyacetic acid (2,4-D) at a concentration of ^10-3 %, calculated to achieve 40-60% inhibition of hypocotyl growth. After herbicide exposure, the seedlings are washed with water and placed in a solution of the substances being tested for antidote activity at concentrations of ^10-2 , ^10-3 , ^10-4 , and ^10-5 % (herbicide+antidote variant).

After 1 hour, the seeds are rinsed with water and laid out on filter paper strips (10 x 75 cm), 20 seeds per strip, rolled into rolls and placed in beakers with 50 ml of water. Further seed germination is carried out in a thermostat for 3 days at 28°C. The temperature of the solutions and rinse water is 28°C. Seeds of the "herbicide" treatment (comparison standard) are soaked in a 2,4-D solution at a concentration of ^10-3 % for 1 hour and in water for 1 hour. Seeds of the control treatment are soaked in water for 2 hours. The experiment is repeated three times, with 20 seeds used in each replicate.

The protective (antidote) effect is determined by the increase in hypocotyl and root length in the herbicide+antidote treatment relative to the herbicide (standard) treatment (as a percentage). Statistical analysis of the experimental data was performed using Student's t -test at P = 0.95.

The results of the research are presented in Table 1.

Table 1 - Antidote activity of compounds 1 (prototype) and N-(chloroacetyl)phenothiazine 2 to the herbicide 2,4-D on sunflower seedlings of the Master variety.

Preparation Concentration,
% Hypocotyl length Root length mm to 2,4-D,% mm to 2,4-D,% Control 0 110 - 111 - 2,4-D 10 ^-3 62 - 73 - 2,4-D+
N-(chloroacetyl)-phenothiazine 2 10 ^-2
10 ^-3
10 ^-4
10 ^-5 85.5
76
84
80.5 138*
123*
136*
130* 97
104
101
101 133*
143*
138*
138* 2,4-D+
connection 1 (prototype) 10 ^-2
10 ^-3
10 ^-4
10 ^-5 71
79
72.5
69.5 115*
127*
117*
112* 89
89
90.5
89 122*
122*
124*
122*

*Differences between variants are significant at P=0.95.

As can be seen from the data in Table 1, the use of N-(chloroacetyl)phenothiazine 2 , proposed as an antidote, significantly weakens the toxic effect of the herbicide. Compound 2 reduced the negative effect of 2,4-D on the hypocotyls of sunflower seedlings by 23-38% when used mainly at three or more concentrations, while compound 1 (the prototype) showed an antidote effect of 12-27%.

N-(Chloroacetyl)phenothiazine 2 reduced the inhibitory effect of 2,4-D on seedling roots by 33-43% also when used in three or more concentrations, while compound 1 (prototype) exhibited an antidote effect at the level of 22-24%.

Claims (3)

Use of N-(chloroacetyl)phenothiazine as an antidote to 2,4-dichlorophenoxyacetic acid on sunflower.