Product with insecticidal activity

Abstract

FIELD: agrochemistry.SUBSTANCE: new biologically active compounds with insecticidal activity. Compound 6',7'-diethoxy-4H'-spiro[cyclopentane-1,3'-isoquinoline] hydrochloride of formula Ihas pronounced insecticidal activity.EFFECT: proposed compound 6',7'-diethoxy-4H'-spiro[cyclopentane-1,3'-isoquinoline] hydrochloride exhibits high insecticidal activity, causing death of insects within 3-4 minutes, and is non-toxic to humans and farm animals.1 cl, 1 tbl, 2 ex

Description

[0001] The invention relates to biologically active compounds, namely 6',7'-diethoxy-4H'-spiro[cyclopentane-1,3'-isoquinoline] hydrochloride of formula I,

[0002]

[0003] possesses insecticidal (larvicidal) activity, which suggests the possibility of its use in medicine, veterinary medicine and agriculture.

[0004] Structural analogs of the claimed compound are known, obtained by the reaction of dialkylbenzylcarbinols with hydrogen cyanide (Mikhailovsky, A.G. Synthesis of azomethines of the isoquinoline series / A.G. Mikhailovsky, B.B. Alexandrov, M.I. Vakhrin / / Chemistry of heterocyclic compounds. - 1992. - No. 8. - P. 1144). The analog, closest in structure, possessing insecticidal activity, is (N-benzylamide)-2-(3-methyl-6-methoxy-7-ethoxy-3,4-dihydroisoquinolyl-1)-ethanoic acid hydrochloride, exhibiting insecticidal action (patent RF 2529504 C2, published 09.27.2014, BI No. 27).

[0005] The effective insecticidal drug diazinon, which is currently widely used in veterinary medicine and agriculture, was taken as a comparison standard (www.vidal.ru / veterinar / bukva / rus-d).

[0006] The aim of this invention is to find a compound among 3,3-dialkyl-3,4-dihydroisoquinolines that has a pronounced insecticidal effect with low or moderate toxicity. This aim is achieved by obtaining 6',7'-diethoxy-4H'-spiro[cyclopentane-1,3'-isoquinoline] hydrochloride of formula I by the reaction of 1-(3,4-diethoxybenzyl)-cyclopentanol with hydrogen cyanide in a toluene / acetic acid / sulfuric acid heterophase system according to the scheme:

[0007]

[0008] Example 1. Obtaining the claimed compound I.

[0009] To a mixture of 3.10 g (0.01 mol) of 1-(3,4-diethoxybenzyl)-cyclopentanol and 0.98 g (0.015 mol) of 1-(3,4-diethoxybenzyl)-cyclopentanol and 0.98 g (0.015 mol) of potassium cyanide in 50 ml of dry toluene were added sequentially 2 ml of glacial acetic acid and 4 ml of concentrated sulfuric acid with vigorous stirring. The mixture was vigorously stirred for 30 minutes at a temperature of 60-70 °C, cooled to 20 °C, poured into 150 ml of ice water, and the organic layer was separated. The aqueous phase was neutralized with ammonia solution. The precipitated oil was extracted with ether. The ethereal extract was dried with NaOH, and approximately ¼ of the ether was distilled off. When dry HCl was passed through ether, a precipitate of hydrochloride I formed, which was filtered off, dried, and recrystallized from isopropyl alcohol. Yield 1.98 g (64%). Mp 167 - 168 °C. Found, %: C 69.83; H 7.68; N 4.61; Cl 11.37. C 17 H 23 NO2HCl. Calculated, %: C 65.95; H 7.81; N 4.52; Cl 11.45. IR spectrum of the base in vaseline oil, ν cm -1:1630 (C=N).

[0010] NMR spectrum (CDCl3), δ. ppm: 1.31 t (3H, C N 3СН2О); 1.34 t (3Н, С N 3CH2O); 1.72 - 1.77 m (4H, CH2C N 2C N 2CH2); 2.05 - 2.24 m (4H, C N 2СН2СН2С N 2); 2.99 s (2H, 4-CH2); 4.06 k (2H, CH3C N 2O); 4.17 k (2H, CH3C N 2O); 6.70 s (5-H); 7.36 s (8-H); 8.91 s (НС=N); 14.51 s (NH + ).

[0011] The claimed compound I is a yellow crystalline substance, soluble in water, chloroform, dimethyl sulfoxide, difficultly soluble in alcohol, insoluble in benzene and toluene.

[0012] Example 2. Study of biological activity.

[0013] To determine acute toxicity, the method of determining the average lethal dose by V.B. Prozorovsky was used [Prozorovsky V.B., Express method for determining the average effective dose and its error / / V.B. Prozorovsky, M.N. Prozorovskaya, V.M. Demchenko / / Pharmacology and toxicology. - 1978. - No. 4. - P. 497-502].

[0014] Acute toxicity was determined in experiments on white nonlinear mice of both sexes weighing 24-28 g, maintained on a standard vivarium diet. The test compound was administered orally in four doses. Each pair of animals received one dose in ascending order. To calculate the LD 50 The results obtained on 8 mice were used.

[0015] Acute toxicity (LD 50 The oral toxicity of the claimed compound was 289.0±9.2 mg / kg. According to GOST 32419-2022 "Interstate Standard. Hazard Classification of Chemical Products. General Requirements," the compound studied belongs to Class 3 compounds, i.e., it is moderately toxic.

[0016] The insecticidal activity was studied using a previously developed method [Mikhailovsky, A.G. Antiarrhythmic, hemostatic, anthelmintic and larvicidal activity of 3,3-dialkyl-substituted analogs of drotaverine / A.G. Mikhailovsky, E.S. Pogorelova, I.P. Rudakova, A.V. Starkova, N.N. Pershina / / Chemical and Pharmaceutical Journal. - 2021. - Vol. 55, No. 5. - Pp. 9-12]. 5 ml of a 0.1% aqueous solution of the studied compounds were placed in a Petri dish and 5 Chironomidae mosquito larvae (bloodworms) were immersed in it. The time of death of each individual was recorded by the cessation of motor activity in response to mechanical irritation. Diazinon, a very effective insecticide currently used in veterinary practice and agriculture, was used as a comparison drug [www.vidal.ru / veterinar / bukva / rus-d].

[0017] The test results are presented in Table 1. As can be seen from the table, diazinon causes death of larvae within 17 minutes, while the claimed compound I kills them in just 3.4 minutes, i.e., 5 times faster. Furthermore, compared to the comparison drug, compound I is 17 times less toxic (289 / 17). Diazinon is an organophosphorus compound, which is extremely hazardous to human health and the environment, and therefore is currently being banned (see link in Table 1).

[0018] Table 1

[0019] Insecticidal activity of the claimed compound and the comparison standard

[0020] Compound Lifespan of larvae, min LD50, mg / kg, orally, mice Diazinon 17,0 ± 1,87 17,0* Compound (I) 3,4 ± 0,51 289,0±9,2

[0021] *https: / / translated.turbopages.org / proxy_u / en-ru.ru.1a01c522-6838331a-682690f9-74722d776562 / https / en.wikipedia.org / wiki / Diazinon

[0022] The mentioned analogue in the structure of isoquinoline (patent RF 2529504 C2) has lower toxicity (1720 mg / kg). At the same time, compound I in terms of LD 50According to the classification, it is moderately toxic, making it acceptable for practical use. The named analogue causes death of larvae within 32.8 minutes, i.e., compared to the claimed substance, it is 9.64 times slower (32.8 / 3.4).

[0023] Thus, the claimed compound is significantly superior to the comparison drug both in terms of activity and toxicity, and in terms of activity it is significantly superior to its closest analogue in structure.

[0024] Therefore, the claimed compound can find application as an insecticidal (larvicidal) agent in medicine, veterinary science and agriculture.

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