RU2492647C1 - 2-(1n-benzimidazol-2-yl)-5'-nitrobenzoic acid-antidote of hormonic action herbicide of 2,4-dichlorphenoxyacetic acid and method of its obtaining - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention relates to agriculture. 2-(1N-benzimidazol-2-yl)-5'-nitrobenzoic acid of formula 1 is antidote for protection of sunflower seedlings from negative action of herbicide of 2,4-dichlorophenoxyacetic acid:

Interaction of o-phenylenediamine with 2-formyl-5-nitrobenzoic acid in ratio 1:1 in acetic acid at room temperature for 1.5 hour is carried out.

EFFECT: invention makes it possible to reduce temperature mode and reduce reaction time.

2 cl, 4 tbl, 2 ex

Description

The invention relates to a new biologically active compound - 2- (1H-benzimidazol-2-yl) -5'-nitrobenzoic acid of the formula 1, which protects seedlings and vegetative sunflower plants from the negative effect of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D ), and the method for its preparation.

Compound 1, its chemical and biological properties are not described in the literature.

Known substances are antidotes with the ability to weaken the toxic effect of herbicides on crops. Antidotes enhance the metabolic detoxification of the herbicide in the plant, in particular by increasing the activity of the glutathione-S-transferase system. They are introduced into the soil separately and together with herbicides, or are used for presowing treatment of seeds [Strelkov V.D. Search for new plant growth regulators and herbicidal antidotes. // Actual issues of plant biologization. Pushchino, 2000. - S.152-155; Gilyazetdinov Sh.Ya., Uzyanbaev A.Kh., Lukyanov S.A., Mukhutdinov F.G. Study of growth-regulating and protective activity of immunostimulants in a mixture with herbicides. // Creation of highly productive agroecosystems based on a new paradigm of nature management: Sat. doc. scientific-practical conf. Ufa, 2001, S.372-378].

The preparation 2-n- (aminobenzenesulfamido) -5-ethyl-1,3,4-thiadiazole (ethazole), which is an analogue in properties, possesses antidote activity against 2,4-D [Patent No. 2040898 of the Russian Federation. The antidote of the herbicide of the hormonal action of 2,4-dichlorophenoxyacetic acid on vegetative sunflower plants / V.D. Strelkov, L.I. Isakova, M.I. Kalita, L.N. Litvinova, T.I. Chubenko // B. I., No. 22, 46 (1995)] and having structural formula 2.

An analogue in the structure of the claimed compound is 2- (1H-benzimidazol-2-yl) benzoic acid [2- (2-carboxyphenyl) benzimidazole] of formula 3 [B.V. Lyaskovsky, Z.V. Voitenko, A.V. Kovtunenko. 11H-Isoindolo [2,1-a] benzimidazoles. // HGS, No. 3, 323-351 (2007)]; [Christopher J. Perry. A new kinetic model for the asid-catalysed reactions of N- (2-aminophenyl) phthalamic acid in aqueous media. // J. Chem. Soc. Perkin Trans. 2: Physical Organic Chem .; 5; 1997; 977]; [A. Bistrzycki Ueber die Einwirkung von o-Diaminen auf o-Aldehydobenzoesauren. // Chem. Ber., 1891; Bd. 24; S.627-630].

Information on the antidote activity of the analogue in structure is not available in the literature.

The method for producing 2- (1H-benzimidazol-2-yl) benzoic acid [2- (2-carboxyphenyl) benzimidazole] (3) consists in boiling in methanol equimolar amounts of o-phenylenediamine (o-FDA) and 2-formylbenzoic acid (in the presence of catalytic amounts of acetic acid) for 3 hours. The product is concentrated, filtered and recrystallized from ethanol, yield 89%. [Sh.N. Khattab., Y.H. Seham, A. EL-Faham, A.M. EL-Massry, A. Amer. Reaction of Phthalaldehydic Acid with Diffirent Substituted Aniline as well as Hidrazine Derivatives. // J. Heterocyclic Chem., Vol. 44, pp. 617-626.]. The final structure of compound 3 was established in [L.Yu. Ukhin, L.G. Kuzmina, L.V. Belousova, E.N. Shepelenko. o-Formylbenzoic acid in the synthesis of benzimidazole derivatives. // Thesis. doc. to the second international Scientific conference "New directions in the chemistry of heterocyclic compounds", Zheleznovodsk, 2011, p.241];

The presented method for producing an analogue in structure (compound 3) is an analogous method.

The technical result of the invention is the synthesis of a new compound in a series of 2-substituted benzimidazoles - the antidotes of the herbicide of the hormonal action of 2,4-dichlorophenoxyacetic acid - in order to expand the range of substances for this purpose and simplify the method for their preparation.

The technical result is achieved by the fact that 2- (1H-benzimidazol-2-yl) -5'-nitrobenzoic acid of formula 1 has the antidote properties of the hormonal action of 2,4-dichlorophenoxyacetic acid to protect seedlings and vegetative plants of sunflower, which leads to an increase in yield sunflower seeds.

In the method for producing 2- (1H-benzimidazol-2-yl) -5'-nitrobenzoic acid of formula 1, o-PDA is reacted with 2-formyl-5-nitrobenzoic acid 4 in a 1: 1 ratio in acetic acid at room temperature.

Although this interaction proceeds as a sequence of reactions of the formation of monoimine A followed by heterocyclization to benzimidazoline B and the dehydrogenation reactions characteristic of interactions of o-PDA with oxo compounds [K.N. Zelenin, I.V. Ukraintsev, V.V. Alekseev. Intermediates for the reaction of o-phenylenediamine with carbonyl compounds and their subsequent transformations. // CGS, 363, 1998], it is not possible to isolate intermediate products A and B under these conditions. The progress of the reaction was monitored by TLC (Silufol UV-254 plates, benzene-alcohol system (4: 1), the developer was iodine vapor).

Compound 1 was identified by a combination of elemental analysis, IR and PMR spectroscopy, and mass spectrometry. IR spectra were recorded in liquid paraffin, PMR spectra were recorded in DMSO-d ₆ solution.

The invention is illustrated by the following examples.

Example 1. The study of the antidote activity of 2- (1H-benzimidazol-2-yl) -5'-nitrobenzoic acid 1.

Tests of compound 1 for antidote activity to 2,4-D were carried out on sunflower cultivar "Master" in laboratory and field conditions. In laboratory studies, germinated sunflower seeds with a germinal root length of 2-4 mm are placed for 1 h in a solution of 2,4-dichloroacetic acid at a concentration of 10 ^-3 % in the calculation of obtaining 40-60% inhibition of growth of hypocotyl (reference standard). After the herbicidal action, the seedlings are washed with water and placed in a solution of test compound 1 at concentrations of 10 ^-2 , 10 ^-3 , 10 ^-4 , 10 ^-5 % (variant herbicide + antidote). After 1 hour, the seeds are washed with water and laid out on strips of filter paper (10 × 75 cm) of 20 pieces, which are rolled up and placed in glasses with water (~ 50 ml). Further germination is carried out in a thermostat for 3 days at t = 28 ° C. Then measure the length of the hypocotyl and the root of the sunflower seedlings. At the same time, an analogue is tested on the properties of 2-n- (aminobenzenesulfamido) -5-ethyl-1,3,4-thiodiazole (2). The controls are unprocessed seeds.

Antidote activity is estimated by increasing the length of the root and hypocotyl of the seedlings in the herbicide + antidote variant compared to the herbicidal variant (reference).

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

The test results are presented in tables 1, 2. Compound 1 at a concentration of 10 ^-3 increases the length of the hypocotyl by 14%, and at a concentration of 10 ^-5 - by 19%. At antidote concentrations of 10 ^-2 and 10 ^{-5, the} test substance increases the root length by 20% and 36%, respectively, compared with the standard.

An analogue in properties increases the length of the hypocotyl by 5-8%, and the root from 9 to 14%.

Field tests of compound 1 for antidote activity to 2,4-D were carried out on the experimental field of VNIIBZR.

Sunflower plants of the Master variety in the 10-16 leaf phase are treated with 2,4-D herbicide at a dose of 12 g / ha and an antidote (compound 1) at a dose of 200 g / ha at a flow rate of 500 l / ha is applied in a day. Similarly experience an analogue in properties - thiodiazole 2.

In the experiment, the following options were provided:

- herbicide + antidote - plants treated with a herbicide and after 1 day an antidote;

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

- control - untreated plants.

The experiments were carried out on plots with an area of 3 m ² , the repetition of five. Harvesting of sunflower was carried out at the time of complete ripening of seeds. The antidote (protective) effect was determined by increasing the yield of sunflower seeds in the herbicide + antidote variant relative to the herbicidal variant, which was taken as the standard.

The test results are presented in table 3, from which it follows that the increase in the yield of sunflower when using an antidote (compound 1) is 14%, relative to the standard, and the use of the analogue in properties is 10%.

Since the proposed compound 1 reduces the toxicity of the herbicide 2,4-D for sunflower, this allows without harm to the yield of cultivated plants to use the maximum dose of land herbicide in the presence of the corresponding antidote [Isakova L.I. Improving the safety of herbicides for cultivated plants (foreign experience). // Agro-industrial production: experience, problems and development trends. 1988. No. 1. p. 35-44].

Example 2. Obtaining 2- (1H-benzimidazol-2-yl) -5'-nitrobenzoic acid. (1, table 4).

Option 1a. A mixture of 0.78 g (0.004 mol) of 5-nitro-2-formylbenzoic acid (4) and 0.432 g (0.004 mol) of o-PDA in 5-7 ml of glacial acetic acid was stirred at room temperature (18-20 ° C) in within 1.5 hours. At the end of the reaction (TLC control), the precipitate formed is filtered off, recrystallized from dimethylformamide, washed with water, and dried. The yield is 0.92 g (81%).

Melting point 290-293 ° C.

Found,%: C 59.22; H 3.30; N, 14.95; C ₁₄ H ₉ N ₃ O ₄ ;

Calculated,%: C 59.36; H 3.18; N, 14.84.

Compound 1, both in the solid state and in solution, is in the zwitter-terionic form, which is confirmed by spectral data.

IR spectrum (liquid paraffin, ν, cm ^-1 ): 2000 .... 1800 (NH ⁺ ); 1610 (COO ^- ); 1526, 1358 (NO ₂ ).

¹ H NMR Spectrum (DMSO-d ₆ ; * δ, ppm, J, Hz): 7.27 (1H, dd, H-7); 7.29 (1H, dd, H-4); 7.64 (1H, dd, H-6); 7.66 (1H, dd, H-5, ³ J _6.7 = ³ J _5.6 = ³ J _4.5 = 6.0; ⁴ J _5.7 = ⁴ J _4.6 = 3 , 0); 8.12 (1H, dd, H-4 ', ³ J _{3', 4 '} = 7.0; ⁴ J _{4', 6 '} = 2.4); 8.52 (2H, m, H-3 '+ H-6').

Mass spectrum, m / z: M ⁺ (265).

From the experimental material for the preparation of product 1 shows that the optimal option for its synthesis is option 1A (table 4). Changing the temperature, reaction time or ratio of reagents is impractical, since it leads to a decrease in the yield of the target product.

The proposed method for producing compound 1 is simple in execution. The advantage of this method is not the complexity of the process and its adaptability: the use of acetic acid as a solvent and catalyst, the reaction at room temperature and the reduction of its time, which distinguishes it from the analogue method.

Table 3. The antidote activity of 2- (1H-benzimidazol-2-yl) -5'-nitrobenzoic acid (1) and the analogue of 2,4-D (2) properties on Master sunflower in field trials. Antidote Experience option the control 2,4-D (reference) 2,4-D + antidote productivity, kg / ha productivity, kg / ha productivity, kg / ha Antidote activity, increase to the standard c / ha % one 43,4 15.3 17.5 2.2 fourteen Analog (2) 37.1 17.0 18.7 1.7 10

Table 4 The conditions for the synthesis of compound 1. Example The ratio of the starting reagents; o-PDA: 5-nitro-2-formylbenzoic acid Temperature ° C Min time R _{f the} reaction mass (benzene-alcohol, 4: 1) Product yield,% 1a 1: 1 18-20 90 0,07 81.0 1b 1: 1 10-12 90 60.3 1c 1: 1 40-45 90 55,2 1g 1: 1,1 18-20 150 73.0

Claims (2)

1. 2- (1H-benzimidazol-2-yl) -5'-nitrobenzoic acid of formula 1 is the antidote of the hormone-acting herbicide 2,4-dichlorophenoxyacetic acid (2,4-D), which protects the seedlings and vegetative sunflower plants from the above herbicide

2. A method of obtaining 2- (1H-benzimidazol-2-yl) -5'-nitrobenzoic acid of the formula 1, characterized in that o-phenylenediamine is reacted with 2-formyl-5-nitrobenzoic acid in a ratio of 1: 1 in acetic acid at room temperature for 1.5 hours: