Substituted 1-(pyridinyl-3)-2-azollaceae, their method of preparation and fungicidal composition based on them

 

(57) Abstract:

Describes substituted 1-(pyridinyl-3)-2-azollaceae General formula I

where R = alkyl or cycloalkyl, X = N or CH, which is produced by interaction of oxiranes formula II with a triazole or imidazole in the presence of a base at 100 to 150°C, and fungicidal composition based on them

The technical result consists in obtaining the compounds active against malicious fungi. 3 N. p. F.-ly, 1 table.

The invention relates to the chemistry of heterocyclic compounds, namely to substituted 1-(pyridinyl-3)-2-azolylmethyl General formula I

where R means a hydrogen atom, an unbranched or branched alkyl with a number of carbon atoms of from one to eight, cycloalkyl with the number of carbon atoms from three to eight, cycloalkenyl with the total number of atoms from four to ten, alkylsilanes with the total number of atoms from four to ten, X denotes a nitrogen atom or CH group, which possess fungicidal activity and can be used as agricultural, industrial, medical or veterinary fungicides.

Known 1-pyridinyl-2-imidazolidinone General form is an unsubstituted thienyl or substituted or unsubstituted phenyl, R3means a hydrogen atom or methyl group [Application Germany No. 3345813 A1, class C 07 D 401/06, 1983], which have antidepressant activity and can be used in medicine.

Known 2-thiazoleethanol General formula III, and their salts with acids and complexes with metals, where R1means alkyl, cycloalkyl or phenyl, R2means phenyl or benzyl, which possess fungicidal activity [U.S. Pat. U.S. No. 4623654, class A 01 N 43/653, 1984]

Known reaction join oxirane imidazole and triazole with the formation of substituted 2-azollaceae-1, which is held in the environment of high-boiling aprotic solvent, for example, N-methylpyrrolidone, dimethylformamide or dimethyl sulfoxide, at 100 to 150°C in the presence of water or without it [J. M. Bentley, R. V. Jones, P. J. Wareham. A general anionic mechanism for thermodinamic control of regioselectivity in the N-alkylation of heterocycles //Tetrahedron Letters. 1989. Vol. 30. No. 30. P. 4013-4016].

Depending on the physicochemical properties of the drug, its purpose and method of use of the pesticides used in the form of different preparative forms (compositions), for example in the form of powders, granular preparations, microencapsulated drugs, solutions in water and organic solvents, moisten the ESCWA contain various fillers and additives, the nature of which is determined by the specific conditions of use of this form. Thus, solutions of pesticides in water or organic solvents, which are used for spraying plants, soil by various methods, impregnation materials contain active substance and the solvent, but may also contain acidity regulators, surfactants, dyes, softeners, synergistic additives. Known drug DNOC, which is used in aqueous solution for spraying orchards and vineyards in a concentration of 0.1-0.2% [Pesticides and plant growth regulators /N. N. Melnikov, K. C. Novozhilov, S. R. Belan. - M.: Chemistry, 1995, S. 9-26, 242].

The technical problem solved by the present invention is to expand the range of fungicides for effective action against harmful fungi.

To solve this problem, synthesize substituted 1-(pyridinyl-3)-2-azollaceae General formula I, having fungicidal activity.

According to the invention substituted 1-(pyridinyl-3)-2-azollaceae formula I is produced by interaction of substituted 2-(pyridinyl-3)oxirane formula IV with a triazole or imidazole in the presence of solid alkali metal hydroxide in the environment is of insulted, at 100 to 150°C in the presence of water or without it

where R and X have the same meanings as in formula I.

Substituted 2-(pyridinyl-3)oxirane formula IV is produced by interaction of pyridinylamino General formula V with salts trimethylsilane in dimethyl sulfoxide or dimethyl sulfide in the presence of a strong base, for example, of potassium tert-butylate, tert-Aminata sodium or sodium hydride, or in the interfacial conditions at a temperature of from -10 to +5°C

where R means the same as in formula I, AND-means the anion of the acid, IN-means basis.

For other substrates such reaction is known [E. J. Corey, M. Chaykovsky. Dimethyloxosulfonium methylide ((CH3)2SO2and dimethylsulfonium methylide ((CH3)2SCH2). Formation and application to organic syntheses //Journal of the American Chemical Society. 1965. Vol. 87. No. 6. P. 1353-1364].

Pyridinylmethyl formula V can be obtained by the interaction of 3-cyanopyridine with ORGANOMETALLIC compounds [P. S. Teague, A. R. Ballentine. Some pyridylhydantoins //J. Am. Chem. Soc. 1953. Vol. 75. P. 3429] or metallizovannogo pyridine derivatives of carboxylic acids:

where R means the same as in formula I, Y represents the group CN, CON(CH3)2, COOAlk, COHal, Z denotes Li, MgHal, CdHal.

Example 2. 1-(Pyridinyl-3)-3,3-Dimethylbutane-1. The output is 33%, so Kip.118-123°C / 1 mm RT. Art. an NMR Spectrum1H (DMSO-d6, , M. D., J, Hz): 1,05 (s, N, CH3), 2,95 (s, 2H, CH2), at 7.55 (DD, 1H, CH of perid., J1=0,4, J2=0,2), 8,30 (d, 1H, CH of perid., J=0,4), is 8.75 (d, 1H, CH of perid., J=0,20), 9,12 (s, 1H, CH of pyrid.).

Example 3. 2-(Pyridinyl-3)-2-cyclohexyloxy. To a mixture of 9.45 g (0.05 mol) peridiniales is giving 30 min a solution of 4.63 g (0.063 mol) of tert-butoxide potassium in 31 ml of DMSO. The mixture is stirred for 15 min, cooled in a mixture of ice and salt, and within 30 minutes, poured dropwise 150 ml of water. The product is extracted l3(G ml). The extract was washed with water (3×30 ml) and 20 ml of brine. The solution is dried over MgSO4and the solvent is distilled off in vacuum. Get 8.05 g (to 85.2%) of oxirane. An NMR spectrum1H (DMSO-d6, , M. D., J, Hz): 0.75 to about 1.75 (m, 11 H, CH cyclohexyl.), 2,70-3,10 (AB system, 2 H, CH2, J=8,0), 7,38 (DD, 1 H, 5-CH of Pirin, J1=0,42, J2=0,21), 7,66 (dt, 1 H, 4-CH of perid., J1=0,42, J2=0,1), to 8.45 (DD, 1 H, 6-CH of perid., J1=0,21, J2=0,1), of 8.47 (d, 1 H, 2-CH of perid., J=0,1).

Example 4. 2-(Pyridinyl-3)-2-(2,2-dimethylpropyl)oxiran. Yield 61%. An NMR spectrum1H (DMSO-d6, , M. D., J, Hz): 0.75 in (C, N, CH3), 98 (s, 2H, CH2), 2,90 (AB-system, 2H, CH2, J=4,8), 7,37 (DD, 1H, CH of perid., J1=0,4, J2=0,2), 7,83 (d, 1H, CH of perid., J=0,4), and 8.5 (d, 1H, CH of perid., J=0,2), 8,67 (s, 1H, CH of pyrid.).

Example 5. 1-(3-Pyridinyl)-2-(1,2,4-triazole-1-yl)-1-cyclohexylmethanol (1). To a solution of 1.68 g (8.3 mmol) of 2-(3-pyridinyl)-2-cyclohexyloxy and 0.57 g (8.3 mmol) of triazole in 5.63 ml of DMF was added 0.033 ml of water, 0.11 g of sodium hydroxide and stirred for 4 h at a temperature of 120°C. the Reaction mass is then cooled and poured into 40 ml of water. The precipitated crystals are filtered, MSO-d6, , M. D., J, Hz): 0,80-of 1.95 (m, 11 H, CH cyclohex.), 4,70-5,40 (AB system, 2 H, CH2, J=14,2), 4,7 (s, 1 H, HE), 7,26 (DD, 1 H, CH-pired., J1=0,38, J2=0,30), of 7.69 (dt, 1 H, CH of perid., J1=0,38, J2=0,07), 7,76 (s, 1 H, CH is triaz.), 8,21 (s, 1 H, CH is triaz.), of 8.37 (DD, 1 H, CH of perid., J1=0,2, J2=0,07), 8,54 (d, 1 H, CH of perid., J=0,07).

Example 6. 1-(3-Pyridinyl)-2-(imidazol-1-yl)-1-cyclohexylmethanol (2). So pl. 134-135°C. an NMR Spectrum1H (DMSO-d6, , M. D., J, Hz): 0,80-of 1.95 (m, 11 H, CH cyclohexyl.), of 4.45 (AB system, 2 H, CH2, J=1,89), 5,31 (s, 1H, HE), 6,63, 6,82 (both s, 1 H, CH imide.), of 7.25 (DD, 1 H, 5-CH of perid., J1=0,42, J2=0,28), 7,32 (s, 1 H, CH imide.), 7,72 (d, 1 H, 4-CH of perid., J=0,42), at 8.36 (d, 1 H, 6-CH of perid., J=0,28), 8,56 (s, 1 H, 2-CH of pyrid.).

Example 7. 1-(2,2-Dimethylpropyl)-1-(3-pyridinyl)-2-(1,2,4-triazole-1-yl)ethanol (3). Yield 79%, so pl. 92-94°C. an NMR Spectrum1H (DMSO-d6, (M. D., J, Hz): 0,6 (with, IN, CH3), and 1.9 (AB-system, 2H, CH2Alif., J=6;43), of 4.45 (AB-system, 2H, CH2Oh, J=2,14), 5,38 (s, 1H, HE), from 7.24 (DD, CH of Pirin, J1=0,48, J2=0,2), 7,73 (s, 1H, CH is triaz.), of 7.75 (d, 1H, CH of Pirin, J=0,48), 8,18 (s, 1H, CH is triaz.), 8,35 (d, 1H, CH of perid., J=0,2), at 8.60 (s, 1H, CH of pyrid.).

Example 8. 1-(2,2-Dimethylpropyl)-1-(3-pyridinyl)-2-(imidazol-1-yl)ethanol (4). Yield 86%, so pl. 195-196°C. an NMR Spectrum1H (DMSO-d6, , M. D., J, Hz): 0,68 (s, N, CH31=0,47, J2=0,26), to 7.77 (d, 1H, CH of pyridine, J=0,47), 8,32 (d, 1H, CH of pyridine, J=0,26), to 8.62 (s, 1H, CH of pyridine)

Example 9. Testing the biological activity of the compounds was performed in vitro experiments. In the molten sacharose-potato agar was added to the test substance in the form of a composition containing 0,377% active ingredient, the rest - acetone, 1 ml per 100 ml of agar. To receive agar medium containing 30 mg/l of the test compound. To the medium control was added with pure acetone in the same amount. So prepared medium was poured into Petri dishes, cooled and the surface of the hardened agar were sown pieces of fungal mycelium, after which the cups were incubated for 3 days at 250,5°C. Inhibition of mycelium growth was calculated in percentage of the untreated control. As a reference used commercial fungicide triadimefon in the same concentration. The test results presented in the table.

1. Substituted 1-(pyridinyl-3)-2-azollaceae General formula I

where R is an unbranched or branched alkyl with a number of carbon atoms from one to the East is CLASS="ptx2">2. The method of obtaining substituted 1-(pyridinyl-3)-2-azollaceae General formula I

where R is an unbranched or branched alkyl with a number of carbon atoms of from one to eight, cycloalkyl with the number of carbon atoms from three to eight;

X means nitrogen atom or CH group,

namely, that substituted 2-(pyridinyl-3)oxiran formula II

where R is an unbranched or branched alkyl with a number of carbon atoms of from one to eight, cycloalkyl with the number of carbon atoms from three to eight,

enter into reaction with a triazole or imidazole in the presence of solid alkali metal hydroxide in the environment of high-boiling polar aprotic solvent at 100 to 150°C in the presence of water or without it.

3. Fungicidal composition comprising a fungicide at a concentration of 0.1 to 99% and excipients, characterized in that as a fungicide use of substituted 1-(pyridinyl-3)-2-azollaceae under item 1.



 

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