RU2844680C1 - N-[(azol-1-yl)alkoxyphenyl]-4-chloro-1,2,3-dithiazole-5-imines, method for production thereof and fungicidal compositions based thereon - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: group of inventions relates to organic chemistry and includes N-[(azol-1-yl)alkoxyphenyl]-4-chloro-1,2,3-dithiazole-5-imines of formula I, agrochemically or pharmaceutically acceptable salts thereof, a process for their preparation and fungicidal compositions based thereon. In formula I Az(CH₂)_nO is an azol-1-ylalkoxy group bonded to the phenyl fragment at position 2 or 3 or 4 of the benzene ring, Az denotes an azole heterocyclic fragment, specifically 1,2,4-triazol-1-yl, imidazol-1-yl or benzimidazol-1-yl, n denotes integer from 1 to 4.

EFFECT: compounds of general formula I, which are effective against phytopathogenic fungi, a method for production thereof is disclosed.

3 cl, 7 tbl, 6 ex

Description

The invention relates to the chemistry of five-membered heterocyclic compounds, namely, to new N -[(azol-1-yl)alkoxyphenyl]-4-chloro-1,2,3-dithiazole-5-imines and fungicidal compositions based on them of general formula I :

where Az( _CH2 ) _nO is an azol-1-yl alkoxy group bound to the phenyl moiety at position 2, or 3, or 4 of the benzene ring, Az is an azole heterocyclic moiety, namely 1,2,4-triazol-1-yl, imidazol-1-yl or benzimidazol-1-yl, n is an integer from 1 to 4, as well as their agrochemically or pharmaceutically acceptable salts.

Compounds of general formula I can find application as agricultural, industrial, medical or veterinary fungicides.

The invention also relates to methods for producing compounds of general formula I and the use of these compounds in compositions with other active and auxiliary compounds for combating fungal diseases of agricultural crops, animals and humans.

The closest in structure and method of preparation to the claimed N -[(azol-1-yl)alkoxyphenyl]-4-chloro-1,2,3-dithiazol-5-imines of general formula I is a series of 4-chloro- N -aryl-1,2,3-dithiazol-5-imines of general formula II , where X denotes a hydrogen or halogen atom or a nitro group.

Compounds II are obtained by the reaction of 4,5-dichloro-1,2,3-dithiazol-1-ium chloride III with anilines in methylene chloride in the presence of pyridine at room temperature in an inert argon atmosphere for 8 h [Appel R. et al. Synthese und Reaktionen des 4,5-Dichlor-1,2,3-dithiazolium-chlorides // Chemische Berichte. – 1985. – Vol. 118, No. 4. – P. 1632-1643].

The closest in structure to the claimed compounds of general formula I and possessing biological activity is a series of 4-chloro -N -aryl-1,2,3-dithiazole-5-imines of general formula II , where X is a hydrogen or halogen atom or a nitro group. Compounds II exhibit fungicidal activity against phytopathogenic fungi and suppress the development of microorganisms in vitro at a concentration of 500 mg/l [Patent. US 4059590, IPC C07D 285/00. Certain 4-halo-5-aryl-1,2,3-dithiazole compounds and their preparation/ Moore JE, applicant and patent holder Chevron Research Company, San Francisco, Calif. – No. 698,383. – Claimed 21.06.1976, published 22.11.1977. – 7 p.].

The purpose of this invention is to increase the effectiveness of the fight against phytopathogenic fungi and expand the range of chemical plant protection products.

The stated problem is solved by obtaining [new N -[(azol-1-yl)alkoxyphenyl]-4-chloro-1,2,3-dithiazol-5-imines of general formula I , where Az(CH ₂ ) _n O is an azol-1-yl alkoxy group bound to a phenyl fragment at position 2, 3 or 4 of the benzene ring, Az is an azole heterocyclic fragment, namely, 1,2,4-triazol-1-yl, imidazol-1-yl or benzimidazol-1-yl, n is an integer from 1 to 4, possessing fungicidal activity, as well as by increasing the effectiveness of fungicidal preparations due to the use of compounds of general formula I and expanding the range of fungicides.

The problem set is solved by developing a method for obtaining new chlorides of N -[(azol-1-yl)alkoxyphenyl]-4-chloro-1,2,3-dithiazol-5-imines of general formula I , where Az(CH ₂ ) _n O is an azol-1-yl alkoxy group bound to the phenyl fragment at position 2, 3 or 4 of the benzene ring, Az is an azole heterocyclic fragment, namely 1,2,4-triazol-1-yl, imidazol-1-yl or benzimidazol-1-yl, n is an integer from 1 to 4, which are obtained by reacting 4,5-dichloro-1,2,3-dithiazol-1-ium chloride III with (azol-1-yl)alkoxyanilines of general formula IV , where Az is an azole heterocyclic fragment, namely 1,2,4-triazol-1-yl, imidazol-1-yl or benzimidazol-1-yl, n is an integer from 1 to 4, in non-polar solvents at room temperature under argon atmosphere.

4,5-Dichloro-1,2,3-dithiazol-1-ium chloride III is obtained according to a well-known literature method [Appel R. et al. Synthese und Reaktionen des 4,5-Dichlor-1,2,3-dithiazolium-chlorides // Chemische Berichte. – 1985. – Vol. 118, No. 4. – P. 1632-1643]. Azol-1-yl alkoxyanilines IV are prepared by alkylation of azoles with 2-(nitrophenoxy)alkyl bromides V in the presence of a base in polar aprotic solvents upon heating to give nitrophenoxyalkyl-1-azoles of the general formula VI , where Az is an azole heterocyclic moiety, namely, 1,2,4-triazol-1-yl, imidazol-1-yl or benzimidazol-1-yl, n is an integer from 1 to 4 [Abdelhameed A. et al. Synthesis and Antileishmanial Evaluation of Arylimidamide-Azole Hybrids Containing a Phenoxyalkyl Linker // ACS infectious diseases. - 2021. - Vol. 7, No. 7. - P. 1901-1922; Pat. 2329646 RF, IPC A01N 43/653, C07D 249/08. Use of substituted 1-(2-phenoxyethyl)-1,2,4-triazoles as fungicidal agents and a fungicidal composition based on them / Popkov S.V., Kovalenko L.V., applicant and patent holder Russian University of Chemical Technology. – No. 2005126222/04. – Claimed 18.08.2005, published 27.07.2008. – 8 p.].

Nitrophenoxyalkyl-1-azoles of general formula VI are further reduced in the presence of tin chloride in polar aprotic solvents upon heating to the corresponding (azol-1-yl alkoxy)anilines of general formula IV [Abdelhameed A. et al. Synthesis and Antileishmanial Evaluation of Arylimidamide–Azole Hybrids Containing a Phenoxyalkyl Linker // ACS infectious diseases. – 2021. – Vol. 7, No. 7. – P. 1901-1922].

The effectiveness of pesticide use is largely determined by the form of the preparation and the conditions of contact of the chemical compound with harmful organisms. The choice of the most economical and effective form of the preparation is determined primarily by the physicochemical properties of the active compound and the method of its application; in many cases, the selectivity of the preparation also depends on its form. The most universal forms of pesticide application are wettable powders, granulated preparations, microencapsulated preparations, emulsion concentrates, pastes, and aqueous suspensions. In addition to the active substance, the composition of the preparation form of the preparation may also include surfactants, fillers, solvents, etc. A well-known preparation is triadimefon , which is used in the form of a 5.25% wettable powder, 10% emulsifying concentrate to combat diseases of wheat, rye, barley, sugar beet, apple trees, cucumbers during the growing season, and also as a seed dressing. [Pesticides and Plant Growth Regulators: Reference ed. / N.N. Melnikov, K.V. Novozhilov, S.R. Belan. – M.: Chemistry, 1995, p. 24, p. 287].

The stated problem is solved by developing fungicidal compositions containing N -[(azol-1-yl)alkoxyphenyl]-4-chloro-1,2,3-dithiazol-5-imines of general formula I , where Az( _CH2 ) _nO is an azol-1-ylalkoxy group bound to a phenyl fragment at position 2, 3 or 4 of the benzene ring, Az is an azole heterocyclic fragment, namely, 1,2,4-triazol-1-yl, imidazol-1-yl or benzimidazol-1-yl, n is an integer from 1 to 4, as well as their agrochemically and pharmaceutically acceptable salts, in a concentration of 0.3-25% by weight and auxiliary substances that can be effectively used to combat harmful fungal diseases of agricultural crops, animals or humans.

The invention can be illustrated by the following examples.

Example 1. Preparation of 4,5-dichloro-1,2,3-dithiazol-1-ium chloride ( 1 )

To a mixture of 9.67 g (0.07 mol) of sulfur monochloride in 0.3 ml of dry methylene chloride are added 1.082 g (0.014 mol) of chloroacetonitrile in 0.3 ml of methylene chloride and the mixture is stirred at room temperature under argon for 18 h. The precipitate is filtered off under argon. 2.394 g (80%) of 4,5-dichloro-1,2,3-dithiazol-1-ium chloride with a m.p. of 169-170 °C are obtained.

IR spectrum ( k , cm ^-1 ; KBr): 1384, 1278, 1252, 1082, 915, 827, 627, 603, 519.

Example 2. Preparation of 1-(2-(3-nitrophenoxy)ethyl)-1 H -1,2,4-triazole ( 2 )

To a solution of 0.5 g (2.03 mmol) of 1-(2-bromoethoxy)-3-nitrobenzene in 50 ml of dry acetonitrile are added 0.28 g (4.06 mmol) of 1,2,4-triazole and 0.56 g (4.06 mmol) of potassium carbonate and the mixture is boiled for 7 h. The solvent is evaporated on a RPI in a water-jet pump vacuum, water is added to the reaction mass, and the mixture is extracted with methylene chloride. The organic phase is dried over magnesium sulfate and evaporated on a RPI in a water-jet pump vacuum. The residue is recrystallized from diethyl ether. 0.25 g (53%) of 1-(2-(3-nitrophenoxy)ethyl)-1 H -1,2,4-triazole with a m.p. 95-96 °C.

^1H NMR spectrum (δ, ppm; J , Hz, CDCl ₃ ) 4.44 t (2H, CH ₂ , J ³ =5.0 Hz), 4.63 t (2H, CH ₂ , J ³ =5.0 Hz), 7.18 d (1H, 1CH _Ar , J ³ =8.3), 7.43 t (1H, 1CH _Ar , J ³ =8.2 Hz), 7.69 s (1H, 1CH _Ar ), 7.85 d (1H, 1CH _Ar , J ³ =8.2 Hz), 7.97 s (1H, ³ CH _Trz ), 8.24 s (1H, ⁵ CH _Trz ).

¹³ C NMR spectrum (δ, ppm; J , Hz, CDCl ₃ ) 48.98 (CH ₂ ), 67.42 (CH ₂ ), 108.94 (C _Ar ), 116.71 (C _Ar ), 121.54 (C _Ar ), 130.27 (C _Ar ), 144.07 (C ⁵ _Trz ), 149.21 (C _Ar ), 152.39 (C ³ _Trz ), 158.41 (C _Ar ).

Mass spectrum, m/z: [M+H ⁺ ] ⁺ 235.04 (Calculated for C ₁₀ H ₁₁ N ₄ O ₃ ⁺ : 235.08 [M+H ⁺ ] ⁺ ).

Table 1. Yields and physicochemical properties of nitrophenoxyalkyl-1-azoles VI

Compound Position of the azol-1-yl alkoxy group A n Reaction time, h T. of melting point of the product, °C Exit, % 2 3 Trz 2 7 95-96 53 5 I 16 - 56 6 Bzim 22 115-116 56 7 4 Trz 5 115-116 94 8 I 25 56-57 67 9 Bzim 9 153-154 73 10 2 Trz 5 81-85 57 11 I 10 82-83 54 12 Bzim 19 128-129 57

* – the substance is a liquid.

Table 2. Spectral properties of nitrophenoxyalkyl-1-azoles VI

Compound ^1H NMR spectrum, δ, ppm, (J/Hz), in CDCl ₃ 2 4.44 t (2H, CH ₂ , J ³ =5.0 Hz), 4.63 t (2H, CH ₂ , J ³ =5.0 Hz), 7.18 d (1H, 1CH _Ar , J ³ =8.3), 7.43 t (1H, 1CH _Ar , J ³ =8.2 Hz), 7.69 s (1H, 1CH _Ar ), 7.85 d (1H, 1CH _Ar , J ³ =8.2 Hz), 7.97 s (1H, ³ CH _Trz ), 8.24 s (1H, ⁵ CH _Trz ) 5 4.32 t (2H, CH ₂ , J ³ =5.1 Hz), 4.42 t (2H, CH ₂ , J ³ =5.1 Hz), 7.07 s (1H, ⁴ CH _Im ), 7.10 s (1H, ⁵ CH _Im ), 7.22 d (1H, 1CH _Ar , J ³ =8.3 Hz), 7.46 t (1H, 1CH _Ar , J ³ =8.2 Hz), 7.62 s (1H, ² CH _Im ), 7.71 s (1H, 1CH _Ar ), 7.88 d (1H, 1CH _Ar , J ³ =8.0 Hz)

End of table 2

Compound ^1H NMR spectrum, δ, ppm, (J/Hz), in CDCl ₃ 6 4.40 t (2H, CH ₂ , J ³ =5.0 Hz), 4.64 t (2H, CH ₂ , J ³ =5.1 Hz), 7.16 d (1H, 1CH _Ar , J ³ =8.3 Hz), 7.30-7.45 m (3H, ^5,6,7 CH _Bzim ), 7.50 d (1H, ⁴ CH _Bzim , J ³ =7.7 Hz), 7.67 s (1H, 1CH _Ar ), 7.83 d (2H, 2CH _Ar , J ³ =7.8 Hz), 8.05 s (1H, ² CH _Bzim ) 7 4.47 t (2H, CH ₂ , J ³ =4.9 Hz), 4.64 t (2H, CH ₂ , J ³ =5.0 Hz), 6.93 d (2H, 2CH _Ar , J ³ =9.5 Hz), 7.99 s (1H, ³ CH _Trz ), 8.15–8.29 m (2H, 2CH _Ar , 1H, ⁵ CH _Trz ) 8 ¹ H NMR (δ, ppm; J , Hz, CDCl ₃ ) 4.34 t (2H, CH ₂ , J ³ = 5.4 Hz), 4.42 t (2H, CH ₂ , J ³ = 5.4 Hz), 6.95 d (2H, 2CH _Ar , J ³ = 9.4 Hz), 7.06 s (1H, ² CH _Im ), 7.11 s (1H, ⁴ CH _Im ), 7.62 s (1H, ⁵ CH _Im ), 8.22 d (2H, 2CH _Ar , J ³ = 9.2 Hz) 9 4.41 t (2H, CH ₂ , J ³ =5.1 Hz), 4.65 t (2H, CH ₂ , J ³ =5.1 Hz), 6.90 d (2H, 2CH _Ar , J ³ =9.1 Hz), 7.32–7.41 m (2H, ^5.6 CH _Bzim ), 7.46–7.54 m (1H, ⁷ CH _Bzim ) 7.85 d (1H, ⁴ CH _Bzim , J ³ =7.0 Hz), 8.04 s (1H, ² CH _Bzim ), 8.17 d (2H, 2CH _Ar , J ³ =9.1 Hz) 10 4.46 t (2H, CH _2, J ³ =4.8 Hz), 4.67 t (2H, CH ₂ , J ³ =4.8 Hz), 6.95-7.19 m (2H, 2CH _Ar ), 7.54 t (1H, 1CH _Ar , J ³ =5.2 Hz) 7.89 d (1H, 1CH _Ar , J ³ =8.1 Hz), 7.97 s (1H, ³ CH _Trz ), 8.37 s (1H, ⁵ CH _Trz ) 11 4.33 t (2H, CH ₂ , J ³ =5.1 Hz), 4.43 t (2H, CH ₂ , J ³ =5.1 Hz), 6.97 d (1H, 1CH _Ar , J ³ =8.3 Hz), 7.06-7.13 m (2H, ^4.5 CH _Im ), 7.16 s (1H, 1CH _Ar ), 7.53 t (1H, 1CH _Ar , J ³ =7.8 Hz), 7.63 s (1H, ² CH _Im ), 7.89 d (1H, 1CH _Ar , J ³ =8.1 Hz) 12 4.40 t (2H, CH ₂ , J ³ =5.0 Hz), 4.66 t (2H, CH ₂ , J ³ =5.0 Hz), 6.91 d (1H, 1CH _Ar , J ³ =8.4 Hz), 7.05 t (1H, 1CH _Ar , J ³ =7.8 Hz), 7.28-7.39 m (2H, ^5.6 CH _Bzim ), 7.41-7.53 m (2H, 1CH _Ar , ⁷ CH _Bzim ), 7.79-7.90 m (2H, 1CH _Ar , ⁴ CH _Bzim ), 8.14 s (1H, ² CH _Bzim )

Example 3. Preparation of 3-(2-(1 H -1,2,4-triazol-1-yl)ethoxy)aniline ( 3 )

To a solution of 0.10 g (0.427 mmol) of 1-(2-(3-nitrophenoxy)ethyl)-1 H -1,2,4-triazole in 10 ml of ethyl acetate was added 0.48 g (2.135 mmol) of tin (II) chloride dihydrate and the mixture was boiled for 14 h. The reaction mixture was cooled, 1 M NaOH solution was added to pH = 11, and the mixture was extracted with ethyl acetate. The organic phase was dried over magnesium sulfate and evaporated on a RPI in a water-jet pump vacuum. 0.75 g (86%) of 3-(2-(1 H -1,2,4-triazol-1-yl)ethoxy)aniline was obtained as an oil.

¹ H NMR spectrum (δ, ppm; J , Hz, CDCl ₃ ) 3.75 s (2H, NH ₂ ), 4.29 t (2H, CH ₂ , J ³ =5.0 Hz), 4.54 t (2H, CH ₂ , J ³ =5.0 Hz), 6.20 s (1H, 1CH _Ar ), 6.22-6.37 m (2H, 2CH _Ar ), 7.05 t (1H, 1CH _Ar , J ³ =8.1 Hz), 7.96 s (1H, ³ CH _Trz ), 8.22 s (1H, ⁵ CH _Trz ).

¹³ C NMR spectrum (δ, ppm; J , Hz, CDCl ₃ ) 49.27 (CH ₂ ), 65.43 (CH ₂ ), 101.70 (C _Ar ), 104.21 (C _Ar ), 108.77 (C _Ar ), 130.29 (C _Ar ), 144.01 (C ³ _Trz ), 147.98 (C _Ar ), 151.96 (C ⁵ _Trz ), 158.98 (C _Ar ).

Mass spectrum, m/z: [M+H ⁺ ] ⁺ 204.30 (Calculated for C ₁₀ H ₁₂ N ₄ O ⁺ : 204.10 [M ⁺ ]).

Table 3. Yields and physicochemical properties of azole-1-yl alkoxyanilines IV

Compound Position of the azol-1-yl alkoxy group A n Reaction time, h Exit, % 3 3 Trz 2 14 86 13 I 16 97 14 Bzim 22 99 15 4 Trz 12 79 16 I 12 82 17 Bzim 12 89 18 2 Trz 12 95 19 I 12 82 20 Bzim 22 72

Table 4. Spectral properties of azole-1-yl alkoxyanilines IV

Compound ^1H NMR spectrum, δ, ppm, (J/Hz), in CDCl ₃ 3 3.75 s (2H, NH ₂ ), 4.29 t (2H, CH ₂ , J ³ =5.0 Hz), 4.54 t (2H, CH ₂ , J ³ =5.0 Hz), 6.20 s (1H, 1CH _Ar ), 6.22-6.37 m (2H, 2CH _Ar ), 7.05 t (1H, 1CH _Ar , J ³ =8.1 Hz), 7.96 s (1H, ³ CH _Trz ), 8.22 s (1H, ⁵ CH _Trz ) 13 3.46 s (2H, NH ₂ ), 4.17 t (2H, CH ₂ , J ³ =5.1 Hz), 4.30 t (2H, CH ₂ , J ³ =5.1 Hz), 6.21 s (1H, 1CH _Ar ), 6.25-6.41 m (2H, 2CH _Ar ), 7.00-7.13 m (3H, 1CH _Ar , ^4.5 CH _Im ), 7.59 s (1H. ² CH _Im ) 14 3.67 s (2H, NH ₂ ), 4.28 t (2H, CH ₂ , J ³ =5.2 Hz), 4.55 t (2H, CH ₂ , J ³ =5.2 Hz), 6.19 s (1H, 1CH _Ar ), 6.22-6.40 m (2H, 2CH _Ar ), 7.04 t (1H, J ³ =8.1 Hz, 1CH _Ar ), 7.26-7.42 m (2H, ^5.6 CH _Bzim ), 7.42-7.53 m (1H, ⁷ CH _Bzim ), 7.78-7.89 m (1H, ⁴ CH _Bzim ), 8.05 s (1H, ² CH _Bzim ) 15 3.50 s (2H, NH ₂ ), 4.27 t (2H, CH ₂ , J ³ =5.0 Hz), 4.53 t (2H, CH ₂ , J ³ =5.0 Hz), 6.62 d (2H, 2CH _Ar , J ³ =8.9 Hz), 6.69 d (2H, 2CH _Ar , J ³ =9.0 Hz), 7.97 s (1H, ³ CH _Trz ), 8.23 s (1H, ⁵ CH _Trz ) 16 3.38 s (2H, NH ₂ ), 4.16 t (2H, CH ₂ , J ³ =5.1 Hz), 4.29 t (2H, CH ₂ , J ³ =5.4 Hz), 6.64 d (2H, 2CH _Ar , J ³ =8.9 Hz), 6.72 d (2H, 2CH _Ar , J ³ =9.0 Hz), 7.05 s (1H, ² CH _Im ), 7.09 s (1H, ⁴ CH _Im ), 7.59 s (1H, ⁵ CH _Im ) 17 3.38 s (2H, NH ₂ ), 4.25 t (2H, CH ₂ , J ³ =5.2 Hz), 4.53 t (2H, CH ₂ , J ³ =5.2 Hz), 6.61 d (2H, 2CH _Ar , J ³ =8.9 Hz), 6.68 d (2H, 2CH _Ar , J ³ =8.8 Hz), 7.29–7.38 m (2H, ^5.6 CH _Bzim ), 7.45–7.51 m (1H, ⁷ CH _Bzim ), 7.79–7.88 m (1H, ⁴ CH _Bzim ), 8.04 s (1H, ² CH _Bzim )

End of table 4

Compound ^1H NMR spectrum, δ, ppm, (J/Hz), in CDCl ₃ 18 3.74 s (2H, NH ₂ ), 4.41 t (2H, CH ₂ , J ³ =5.0 Hz), 4.60 t (2H, CH ₂ , J ³ =5.0 Hz), 6.66-6.81 m (4H, 4CH _Ar ), 8.01 s (1H, ³ CH _Trz ), 8.23 s (1H, ⁵ CH _trz ) 19 4.14 s (2H, NH ₂ ), 4.26 t (2H, CH ₂ , J ³ =4.9 Hz), 4.36 t (2H, CH ₂ , J ³ =4.9 Hz), 6.69-6.89 m (4H, 4CH _Ar ), 7.06 s (1H, ² CH _Im ), 7.12 s (1H, ⁴ CH _Im ), 7.63 s (1H, ⁵ CH _Im ) 20 3.58 s (2H, NH ₂ ), 4.34 t (2H, CH ₂ , J ³ =5.3 Hz), 4.61 t (2H, CH ₂ , J ³ =5.2 Hz), 6.63-6.87 m (4H, 4CH _Ar ), 7.31-7.42 m (2H, ^5.6 CH _Bzim ), 7.50 d (1H, J ³ =7.8 Hz, ⁷ CH _Bzim ), 7.83 d (1H, J =7.8 Hz, ⁴ CH _Bzim ), 8.01 s (1H, ² CH _Bzim )

Example 4. Preparation of N -(3-[(2-(1 H -1,2,4-triazol-1-yl)ethoxy)]phenyl)-4-chloro-5 H -1,2,3-dithiazol-5-imine hydrochloride ( 4 )

To a solution of 0.051 g (0.245 mmol) of 4,5-dichloro-1,2,3-dithiazol-1-ium chloride in 2 ml of dry methylene chloride was added 0.05 g (0.245 mmol) of 3-(2-(1 H -1,2,4-triazol-1-yl)ethoxy)aniline in 2 ml of dry methylene chloride and the mixture was stirred at room temperature for 24 h under an argon atmosphere. The precipitate was filtered off on a Schott filter and washed with methylene chloride. 0.074 g (80%) of N -(3-(2-(1 H -1,2,4-triazol-1-yl)ethoxy)phenyl)-4-chloro-5 H -1,2,3-dithiazol-5-imine hydrochloride was obtained with a m.p. 95-97 °C.

¹ H NMR (δ, ppm; J , Hz, DMSO- d6 ): 4.37-4.47 m (2H, CH ₂ ), 4.65-4.76 m (2H, CH ₂ ), 6.70-6.90 m (1H, 1CH _Ar ), 6.93-7.06 m (2H, 2CH _Ar ), 7.33-7.46 m (1H, 1CH _Ar ), 8.48 s (1H, ³ CH _Trz ), 9.30 (1H, ⁵ CH _Trz ).

¹³ C NMR spectrum (δ, ppm; J , Hz, DMSO- d6 ) 49.21 ( _CH2 ), 65.60 ( _CH2 ), 110.27 ( _CAr ), 113.80 (CAr), 116.09 ( _CAr ), 130.76 _{(CAr )} , _{132.96 (C3Trz} ⁾ , 143.74 (C ⁵ _Trz ), 148.44 (C _Ar ), 152.79 (C ⁴ _dithiazole ), 158.37 (C _Ar ), 159.07 (C ⁵ _dithiazole ).

Mass spectrum, m/z: 340.05 [M+H] ⁺ (Calculated for C ₁₂ H ₁₁ ClN ₅ OS ₂ ⁺ : 340.01 [M+H] ⁺ ).

Table 5. Yields and physicochemical properties of N -(azol-1-yl)alkoxyphenyl-4-chloro-1,2,3-dithiazol-5-imines I

Compound Position of the azol-1-yl alkoxy group A n Reaction time, h T. of melting product, ^O WITH Exit, % 4 3 Trz 2 24 95-97 80 21 I 60-65 80

End of table 5

Compound Position of the azol-1-yl alkoxy group A n Reaction time, h T. of melting product, ^O WITH Exit, % 22 3 Bzim 2 24 85-87 70 23 4 Trz 175-177 43 24 I 140-145 71 25 Bzim 115-116 81 26 2 Trz 120-122 62 27 I 70-75 79 28 Bzim 120-125 57

Table 6. Spectral properties of N -[(azol-1-yl)alkoxyphenyl]-4-chloro-1,2,3-dithiazol-5-imines I

Compound ¹ H NMR spectrum, δ, ppm, (J/Hz), in d ₆ -DMSO 4 4.37-4.47 m (2H, CH ₂ ), 4.65-4.76 m (2H, CH ₂ ), 6.70-6.90 m (1H, 1CH _Ar ), 6.93-7.06 m (2H, 2CH _Ar ), 7.33-7.46 m (1H, 1CH _Ar ), 8.48 s (1H, ³ CH _Trz ), 9.30 (1H, ⁵ CH _Trz ) 21 4.41 t (2H, CH ₂ , J ³ =5.0 Hz), 4.60-4.68 m (2H, CH ₂ ), 7.03-7.06 m (2H, 2CH _Ar ), 7.19-7.26 m (2H, 2CH _Ar ), 7.69-7.74 m (1H, ⁴ CH _Im ), 7.87 m (1H, ⁵ CH _Im ), 9.30 s (1H, ² CH _Im ) 22 4.46-4.54 m (2H, CH ₂ ), 4.95-5.01 m (2H, CH ₂ ), 6.71 s (1H, 1CH _Ar ), 6.73-6.81 m (1H, 1CH _Ar ), 6.94-7.01 m (1H, 1CH _Ar ), 7.36 t (1H, J ³ = 8.0 Hz, 1CH _Ar ), 7.59-7.71 m (2H, ^5.6 CH _Bzim ), 7.89 d (1H, ⁷ CH _Bzim , J ³ =8.1 Hz), 8.12-8.19 m (1H, ⁴ CH _Bzim ), 9.85 s (1H, ² CH _Bzim ) 23 4.41 t (2H, CH ₂ , J ³ =5.1 Hz), 4.61 t (2H, CH ₂ , J ³ =5.1 Hz), 7.06 d (2H, 2CH _Ar , J ³ =8.8 Hz), 7.23 d (2H, 2CH _Ar , J ³ =8.8 Hz), 8.01 s (1H, ³ CH _Trz ), 8.61 s (1H, ⁵ CH _Trz ) 24 4.44 t (2H, CH ₂ , J ³ =5.0 Hz), 4.60-4.68 m (2H, CH ₂ ), 7.06-7.10 m (2H, 2CH _Ar ), 7.19-7.26 m (2H, 2CH _Ar ), 7.69-7.74 m (1H, ⁴ CH _Im ), 7.88 m (1H, ⁵ CH _Im ), 9.30 s (1H, ² CH _Im ) 25 4.46-4.57 m (2H, CH ₂ ), 4.94-5.03 m (2H, CH ₂ ), 7.03 d (2H, 2CH _Ar , J ³ =8.7 Hz), 7.21 d (1H, ⁵ CH _Bzim , J ³ =9.2 Hz), 7.35 d (1H, ⁶ CH _Bzim , J ³ =9.1 Hz), 7.59-7.73 m (2H, 2CH _Ar ), 7.87-7.96 m (1H, ⁷ CH _Bzim ), 8.11-8.21 m (1H, ⁴ CH _Bzim ), 9.84 s (1H, ² CH _Bzim ) 26 4.40 t (2H, CH ₂ , J ³ = 5.0 Hz), 4.66 t (2H, CH ₂ , J ³ = 5.0 Hz), 7.02-7.06 m (2H, 2CH _Ar ), 7.13-7.21 m (2H, 2CH _Ar ), 8.52 s (1H, ³ CH _Trz ), 9.27 s (1H, ⁵ CH _Trz ) 27 4.41 t (2H, CH ₂ , J ³ =4.9 Hz), 4.61 t (2H, CH ₂ , J ³ =4.9 Hz), 7.01-7.11 m (3H, 3CH _Ar ), 7.35-7.40 m (1H, 1CH _Ar ), 7.63-7.68 m (1H, ⁴ CH _Im ), 7.74-7.81 m (1H, ⁵ CH _Im ), 9.17 s (1H, ² CH _Im )

End of table 6

28 4.51 t (2H, CH ₂ , J ³ = 4.9 Hz), 4.94 t (2H, CH ₂ , J ³ = 4.8 Hz), 6.95-7.04 m (2H, 2CH _Ar ), 7.12-7.21 m (2H, 2CH _Ar ), 7.49-7.62 m (2H, ^5,6 CH _Bzim ), 7.86 d (1H, ⁷ CH _Bzim , J ³ = 8.2 Hz), 8.03 d (1H, ⁴ CH _Bzim , J ³ = 8.1 Hz), 9.76 s (1H, ² CH _Bzim )

Example 5

Fungicidal activity tests of N- (azol-1-yl)alkoxyphenyl-4-chloro-1,2,3-dithiazol-5-imine hydrochlorides of general formula I were performed in vitro experiments on five phytopathogenic fungi: Fuzarium oxysporum (Fo), Fuzarium moniliforme (Fm) – causative agents of fusarium, Rhizoctonia solani (Rs) – causative agent of rhizoctonia, Bipolaris sorociniana (Bs) – causative agent of root rot and Venturia inaequalis (Vi) – causative agent of apple scab [Methodological recommendations for determining the fungicidal activity of new compounds. Cherkassy: NIITEKhIM. 1984. 34 p.]. The effect of the preparations on the radial growth of mycelium was determined by dissolving the compound composition in acetone (0.3%) and adding an aliquot to potato sucrose agar at 50°C to a concentration of 30 mg/l of the active substance. The final concentration of acetone in the control solutions with the active substances was 1%. Fungal cultures were applied to the agar surface with a needle in Petri dishes containing 15 ml of agar medium. The samples were kept in an incubator at 25°C and radial growth was measured after 3 days. The fungicidal effect of the preparations was compared with the widely used fungicide triadimefon at the same concentration. The percentage of inhibition was calculated according to Abbott in relation to the untreated control. The test results are presented in Table 7.

Table 7. Results of tests of N -[(azol-1-yl)alkoxyphenyl]-4-chloro-1,2,3-dithiazol-5-imines I hydrochlorides for fungicidal activity at a concentration of 30 mg/l

No. Position of the azol-1-yl alkoxy group R ₁ Suppression of microorganism growth, % V. i. R. s. F. o. F. m. B.s. 4 3 Trz 42 100 20 28 28 21 I 51 100 28 31 39

End of table 7

No. Position of the azol-1-yl alkoxy group R ₁ Suppression of microorganism growth, % V. i. R. s. F. o. F. m. B.s. 22 3 Bzim 42 100 33 28 37 24 4 I 77 100 23 27 41 25 Bzim 63 100 28 28 33 26 2 Trz 44 100 23 40 33 27 I 50 100 15 16 34 28 Bzim 38 100 25 24 54 Reference* 41 43 77 87 44

Designations: Vi – Venturia inaequalis, Rs – Rhizoctonia solani, Fo – Fusarium oxysporum, Fm – Fusarium moniliforme, Bs – Bipolaris sorokiniana.

* – Triadimefon – 3,3-dimethyl-1-(1,2,4-triazol-1-yl)-1-(4-chlorophenoxy)-butanone-2.

Example 6. Composition of the emulsion concentrate of compound 4 (3% by weight)

Active ingredient: N -[(2-(2-(1 H -1,2,4-triazol-1-yl)ethoxy)phenyl)]-4-chloro-5 H -1,2,3-dithiazol-5-imine hydrochloride – 3 g

Alkylbenzenesulfonic acid calcium salt (ABS) – 2 g

Oxyethylated octylphenol (OP-7) – 8 g

Cyclohexanone - 26 g

o-Xylene – 22 g

Petroleum solvent – 39 g

According to the results of in vitro fungicidal tests of N -[(azol-1-yl)alkoxyphenyl]-4-chloro-1,2,3-dithiazol-5-imines I hydrochlorides, it was revealed that compounds 4, 21, 22, 24, 25, 26, 27, 28 are superior in fungitoxicity to the standard, the known fungicide triadimefon (3,3-dimethyl-1-(1,2,4-triazol-1-yl)-1-(4-chlorophenoxy)-2-butanone), in relation to two types of phytopathogenic fungi: Venturia inaequalis, Rhizoctonia solani and can be used as a means of combating potato rhizoctonia and apple scab. These phytopathogenic fungi affect agricultural crops that are important for the Russian Federation. The presented compounds are close in terms of fungicidal activity to the compounds of general formula II presented in the prototype, and can be obtained from raw materials commercially available in the territory of the Russian Federation.

Claims (8)

1. N -[(azol-1-yl)alkoxyphenyl]-4-chloro-1,2,3-dithiazol-5-imines of general formula I : where Az( _CH2 ) _nO is an azol-1-yl alkoxy group bound to the phenyl moiety at position 2, or 3, or 4 of the benzene ring, Az is an azole heterocyclic moiety, namely 1,2,4-triazol-1-yl, imidazol-1-yl or benzimidazol-1-yl, n is an integer from 1 to 4, as well as their agrochemically or pharmaceutically acceptable salts. 2. A method for preparing N -[(azol-1-yl)alkoxyphenyl]-4-chloro-1,2,3-dithiazol-5-imines of general formula I , where Az( _CH2 ) _nO is an azol-1-ylalkoxy group bound to the phenyl moiety at position 2, 3 or 4 of the benzene ring, Az is an azole heterocyclic moiety, namely 1,2,4-triazol-1-yl, imidazol-1-yl or benzimidazol-1-yl, n is an integer from 1 to 4, which consists in that 4,5-dichloro-1,2,3-dithiazol-1-ium chloride III is reacted with azol-1-yl alkoxyanilines of general formula IV , where Az is an azole heterocyclic fragment, namely 1,2,4-triazol-1-yl, imidazol-1-yl or benzimidazol-1-yl, n is an integer from 1 to 4, in non-polar solvents at room temperature in an argon atmosphere. 3. A fungicidal composition containing a fungicide in a concentration of 0.3-25% by weight and auxiliary substances, characterized in that N -[(azol-1-yl)alkoxyphenyl]-4-chloro-1,2,3-dithiazol-5-imines I according to claim 1 is used as the fungicide.