RU1547262C - 3- [(4,5,6,7 - tetrahydro -4- oxo -5,7- dimetryl -1- phenyl -1h- indazol -3- yl)- methyl]- glutarimide showing fungicidal activity against neck onion rot pathogen - Google Patents

Abstract

The invention relates to nitroheterocyclic substances, in particular 3- (4, 5, 6, 7-tetrahydro-4-oxo-5,7-dimethyl-1-phenyl-1H-indazol-3-yl) -methyl-glutarimide - a fungicide against the pathogen neck rot of onions, and can be used in agriculture. The goal is to create a more active and less toxic compound of the indicated class. The synthesis is carried out by the reaction of hydrazine hydrate with 3- 2-oxo-2- {5, 7-dimethyl-2, 6-dioxocyclohexylNethyl} - glutarimide in absolute ethanol under boiling . Yield 83%; tll. 196.5-199 ° C; gross f-la C N N O; 1 R F (lethal concentration against onion neck rot pathogens CK 0.000037 versus 0.000042% for fentyuram and 0.000047% for the TMTD standard, the toxicity of which for rats LD 400 rabbits is 210 mg / kg, in the presence of damage to the nervous system, liver, gastrointestinal tract, hematopoietic organs and thyroid gland. The new compound has low toxicity, i.e., a dose of 3000 mg / kg does not cause death of animals and has practically no side effects or any pathological changes in internal organs 1 tab.

Description

The invention relates to a new biologically active chemical compound, namely 3 - {(4,5,6,7-tetrahydro-4-oxo-5,7-dimethyl-1-phenyl-1H-indazol-3-yl) methyl - -glutarimide, which has fungicidal activity against the causative agent of onion rot rot (Botrytis allil), and therefore it can be used in agriculture to create preparations for controlling this fungal disease of this agricultural crop.

The purpose of the invention is to find a new derivative of glutarimide exhibiting high fungicidal activity against onion neck rot pathogens and lower toxicity.

PRI me R 1. 3- (4,5, b, 7-tetrahydro-4-oxo-5,7-dimethyl-1-phenyl-1H-indazol-3-yl) - methyl-glutarimide,

0.3 g (0.001 mol) of a solution of 3- 2-oxo-2- (5,7-dimethyl-2,6-dioxocyclohexyl} ethyl glutarimide and 0.12 ml (0.0012 mol) of phenylhydrazine are boiled t in 100 ml of absolute ethyl alcohol under reflux for 4-5 hours, after which it is acidified with dilute hydrochloric acid to pH 3. The solution is evaporated, the oily residue is dissolved in chloroform, washed with successively diluted solutions of hydrochloric acid, sodium hydroxide and water and dried over anhydrous magnesium sulfate.The residue after distillation of the solvent was recrystallized from acetone. oluchayut 0.31 g (83%) of yellowish crystals of the title product; mp, 136,5- 199,0 ° C.

Found,%: M 68.96: H 6.42; N 11.59

C2iH23N303.

Calculated,%: C 69.04; H, 6.30; N, 11.51.

IR spectrum, v. 3230, 1727, 1692, 1663 (KBg).

PMR spectrum, V.M.A., 92 (ZN, d, J 7.2 Hz); 1.22 (S, d, 6.6 Hz); 2.43 (2H, M); 2.59 (H, M); 3.03 (2H, M); 0.32 (N, M); 7.48 (5H, M); 8.06 (H, broad s),

Determination of the fungicidal activity of the new compound was carried out by means of i-laboratory contact method of application. The method is based on the introduction of acetone solutions of new substances into an agarized nutrient medium with subsequent sowing of a test object on its surface.

The test object was a culture of the onion cervical rot pathogen (Botrytis alMI); standards - TMTD fungicides and fentiurams included in the List of chemical and biological agents for controlling pests, 5 useful plants and weeds and

plant growth regulators approved for use in agriculture for 1986-1990 g. Experience swings 8 times. The test substances were used in the final trials of 0.1-0.00001% of active substances in aqueous acetone solutions. After a series of tests, the calculation of average lethal concentrations (SKbo) ensuring the death of 50% of the spores of plant pathogens was performed. Comparative toxic (CKso,% d) compound 3- (4,5,6,7-hetrahydro-4-oxo-5,7-dimethyl-1-phenyl-1H-indazol-3-yl) methyl glutarimide and TMTD standards and fentyuram for the phytopathogenic pathogen of onion neck rot (Botrytis allii) is given below.

.Acting substanceCKso,% D.V.

3 - {(4,5,6,7-Tetrahydro-4-oxo-5, 7-dimethyl-1-phenyl-1 H-indazol-3-yl) methyl T-glutarimide 0, 000037

TMTD0.000047

Fentyuram0.000042

As can be seen from the above data, 3-G (4,5,6,7-tetrahydro-4-oxo-5,7-dimethyl-1 phenl-1 H-indazol-3-yl) methyl glutarimide has a contact effect and its Fu1-cicidal activity is not inferior to the TMTD standards and fungicides and fentyuram.

Acute toxicity of the compound has been studied in relation to warm-blooded animals. Introducing into the stomach white we- ujaiv 3- (4,5, b, 7-tetrahydro-4-oxo-5,7-dimethyl-1-phenyl-1H-indazol-3-yl) -methyl-glutarimide as a suspension in peach oil in

a dose of 300-3000 mg / kg does not cause death of animals. There are no signs of poisoning, except that during the first hours after the administration of the substance in high doses, some suppression of the animals, a decrease in their motor activity, is observed. In a pathoanatomical study performed 7-10 days after injection of the compound, no pathological changes in the internal organs were detected.

The results obtained allowed the assignment of 3 - {(4,5, b, 7-tetrahydro-4-oxo-5,7-dimethyl-1-phenyl-1 H-indazop-3-yl) -methyl-glu- tarimid to the group of low toxic substances.

At the same time, reference compounds are more toxic compounds. Tec, TMTD (tetrzmethylthiuram disulfide) - medium toxic, LDBO for rats 400, rabbits 210 mg / kg, has a pronounced cumulative property Cumulation coefficient for rats at 1/2 LD50 2.85.

TMTD increases sensitivity to alcohol and is a lipotropic home. It affects the nervous system, liver, gastrointestinal tract, blood-forming organs, and causes hyperplasia of the thyroid gland. Irritating to the respiratory tract and gastrointestinal tract. Fentyuram - combined drug, Mixture

tetramethylthiuram disulfide (TMTD 40%), the γ-isomer of hexachlorocyclohexane (γ-isomer of HCH 20%), trichlorophenol - copper (TCFM 10%) and kaolin (30%). Compound of medium toxicity, LDzo, when administered to the stomach for white mice 331 mg / kg. Cumulative properties are moderate. The cumulation coefficient with the introduction of 1/2 Ldbo 4,5. In acute and chronic poisoning, a number of dystrophic and reactive inflammatory changes develop in the organs. By gravity and

the frequency of damage to internal organs is dominated by the liver (antitoxic function is inhibited). Intoxication is accompanied by a decrease in the content of hemoglobin, red blood cells, white blood cells, and inhibition of the activity of metal-containing enzymes. Fentyuram dust causes swelling of the conjunctiva of the eyes - burning of the skin of the face and hands, of the nasal mucosa and eyes is observed.

Thus, the new compound is less toxic than the known TMTD and fentiuram preparations and is not inferior to them in active ™.

and

(56) Copyright certificate of the USSR No. 738330, cl. C 07 F 231/54, 1978.

Pesticide Handbook Ed. Bear L, I., Kiev: Harvest, 1974, p. 222-229.

Formula and zobretbn and showing fungicidal activity in

3- (4, 5, 6, 7-Tetrahydro-4-oxo-5,7-di-9P in relation to the causative agent of neck rot

methyl-1 -fe n yl -1H-n n dazol-3-yl-methyl-glu-tarimide of the formula

Luke.

fsn.

 the relation

Luke.