DE2918590A1 - 5,6,7,8-Tetra:hydro-quinoline derivs. - broad spectrum fungicides and bactericides esp. useful for treating leaf diseases - Google Patents

Abstract

derivs. of formula (I) are new. R1 is H, 1-12C alkyl, benzyl, phenyl (opt. substd. by 1 or 2 Cl or by CF3 or 1-4C alkyl), -16C alkoxy-carbonyl, aryl-aminocarbonyl (in which aryl is opt. substd. by halogen, CF3, NO2 or 1-5C alkyl) N-alkyl-aryl aminocarbonyl (where alkyl has 1-3C and aryl is opt. substd. by halogen, CF3, or 1-4C alkyl), aminocarbonyl, 1-10C alkylaminocarbonyl, or di-(1-10C) alkylaminocarbonyl; R2 is H, opt. branched 1-12C alkyl, benzyl, phenyl (opt. substd. by 2 Cl or CF3, NO2 or 1-4C alkyl), 1-6C alkoxycarbonyl, phenylthio morpholino, piperidino, arylamino (in which aryl is substd. by halogen or 1-4C alkyl), di (1-6C) alkylaminomethyl morpholinomethyl or piperidinomethy; or R1 and R2 are together -CH2CH2CH2CH2-;R3 is H or 1-4C alkyl;R4 is H or opt. branched 1-12C alkyl;R5 is H or 1-4C alkyl;R6 is H or 1-6C alkyl;A is SH, Cl or -OR7;R7 is -SO2NR8R9 or -COOR10;R8 is opt. branched 1-10C alkyl, Ph or H and R9 is H or opt. branched 1-10C alkyl, or R8 and R9 together are -(CH2)-n, -CH2CH2OCH2CH2- or -CH2CH2N-(Me)CH2CH2- where n = 4 or 5; and R10 is 1-10C alkyl or Ph opt. substd. by halogen or NO2. (I) are biocides with a relatively broad spectrum of activity against fungi and bacteria, and are esp. useful for treating diseases of leaves. (I) are effective e.g. against phytopathogenic fungi and bacteria such as Botrytic cinerea and Xanthomonas oryltae, as well as against non-phytopathogenic fungi and bacteria such as Penicillium funiculosum and E. coli.

Description

New 5,6,7,8-tetrahydroquinolines, their production and use

The invention relates to new 5,6,7,8 tetrahydrocninolines, their synthesis as well as their use as fungicidal and bactericidal agents.

The new compounds are derived from 5,6,7, ß-tetrahydroquinoln and have the general formula (I) in which R1 stands for hydrogen, a straight-chain or branched alkyl radical with 1 to 12 carbon atoms, a benzyl radical, a phenyl radical which can be substituted by one or two chlorine atoms or by trifluoromethyl or by an alkyl radical with 1 to 4 carbon atoms, for an alkoxycarbonyl radical with 1 to 6 carbon atoms, for arylaminocarbonyl, where the aryl radical can be substituted by halogen, trifluoromethyl, nitro or alkyl with 1 to 5 carbon atoms, for N-alkylarylaminocarbonyl, the alkyl group being one with 1 to 3 carbon atoms, and the aryl group by halogen , -CF3 or alkyl with 1 to 4 carbon atoms can be substituted for aminocarbonyl, for alkylaminocarbonyl with 1 to 10 carbon atoms or for dialkylaminocarbonyl with 1 to 10 carbon atoms each, R2 is hydrogen, a straight-chain or branched alkyl radical with 1 to 12 carbon atoms, a Benzyl radical, a phenyl radical connected by one or two chlorine atoms e or by trifluoromethyl or by nitro or by alkyl having 1 to 4 carbon atoms, an alkoxycarbonyl radical having 1 to 6 carbon atoms, a phenylthio, rQorpholino or piperidino radical, an arylamino radical, where aryl by halogen or alkyl having 1 to 4 carbon atoms may be substituted, a dialkylaminomethyl radical with 1 to 6 carbon atoms in each of the alkyl chains, a morpholinomethyl radical or a piperidinoinethyl radical, or R1 and R2 together stand for -CH2CH2CH2CH2-, which has the meaning of hydrogen or an alkyl radical with 1 to 4 carbon atoms, R4 Is hydrogen, a straight or branched alkyl radical having 1 to 12 carbon atoms, R5 is hydrogen or an alkyl radical having 1 to 4 carbon atoms, and R6 is hydrogen or an alkyl radical having 1 to 6 carbon atoms, while A is either -SH or chlorine or radical the formula -DR7 etaht R7 the meaning of 10 or -COOR and then R8 = a straight-chain or branched alkyl radical with 1 to 10 carbon atoms, or phenyl or hydrogen, R9 = hydrogen, a straight-chain or branched alkyl radical with up to 10 carbon atoms, or R8 and R9 together for radicals of the structure -CH2CH2CH2CH2-, -CH2CH2CH2CH2CH2- t -CH2CH2 0CH2CH2- or and R10 = alkyl having 1 to 10 carbon atoms or phenyl, which can be substituted by halogen or nitro.

Since the ring nitrogen atom in position 1 has basic properties, the compounds can also be in the form of salts with inorganic or organic Acids are present.

Examples of such salts are salts with inorganic acids, e.g. B. phosphates, phosphite chlorides, bromides, iodides, sulfates and salts with organic Mono- or polycarboxylic acids such as. 8th.

Acetates, laurates, citrates, tartrates, oxalates, benzoates, sulfonates or phosphonates.

Those of the new compounds described by the formula (1) in which A = -DR7 can be prepared in such a way that 1 mol of a 4-oxy-5,6,7,8-tetrahydroquinoline of the formula (II a ) or the tautomeric form (II b) (R1 to R6 see above) with 1 to 1.1 mol of chlorides of the general formulas (III) or (IV) ClOOR10 (IV) in which R8 to R10 have the meaning given above, in the presence of an inorganic or a tertiary organic base and in the presence or absence of an inert solvent at 50 to 140 Cc.

One proceeds here in detail and preferably in such a way that one first the compound (II a) or (II b) in an inert solvent, such as. B. toluene, Xylene, dioxane or tetrahydrofuran or in acetonitrile or dimethylformamide at 50 to 140, preferably 80 to 120 ° C, then the acid chloride (III) or (IV) is added and then neutralized with a suitable base.

Suitable bases are inorganic bases, e.g. 8. Na2C03, K2 CO3 or also tertiary organic bases, e.g. B. triethylamine or pyridine.

If one wishes to obtain compounds of the formula (I) in which A = -SH, 1 mol of a 4-oxy-5,6,7,8-tetrahydroquinoline of the formula (II a) or of the tautomeric form is left (II b) react with 1 to 1.2 molar equivalent of P2S5 in the presence or absence of an inert solvent at 100 to 200 ° C.

In this case, one works preferably without a solvent by the Compound (II a) or (II b) is melted together with the phosphorus sulfide and the melt is taken up in dilute alkali after it has reacted. The desired Compound is then obtained from the alkaline solution by acidification, taking under Acids, diluted mineral acids and C02 are to be understood. Generally works one in the temperature range from 100 to 200 Cc, preferably at 140 to 180 Cc to achieve homogeneous melting.

The compounds of the general formula (I) with A = -SH can, however also produced in the presence of solvents that do not themselves react with P2S5 will. Such solvents are e.g. 8th.

Dioxane, toluoyl, xylene or glycol dimethyl ether. In this case it will in the temperature range from 80 to 180, preferably 100 to 160 ° C implemented. the The desired compounds are then obtained after filtering the solutions by evaporation won the same.

The 4-chloro-5,6,7,8-tetrahydroquinolines can analogously to the process by E. Echiai, M. Takahashi and R. Tanabe, Chem. Pharm.

Bull. Soc. Yep 15 (9), 1385 (1967), the 2-methyl-4-oxy-5,6,7,8-tetrahydroquinoline implement with POCl3, are represented. The 4-oxy-5,6,7, B-tetrahydroquinolines serve as starting material of the formulas (II a) and (II b) are readily accessible by hydrogenation from 4-oxyquinolines (e.g. according to C.A. 84, (1976), 105422b; DE-OS 2 426 851). Examples are 2-methyl-4-oxy-5,6,7,8-tetrahydroquinoline, 2-methyl-6-isopropyl-4-oxy-5,6,7,8-tetrahydroquinoline, 2-propyl-B-isopropyl-4-oxy-tetrahydroquinoline, 2,6-dimethyl-4-oxy-tetrahydroquinoline, 2,8-dimethyl-4-oxy-tetrahydroquinoline, 2,3-dimethyl-4-oxy-tetrahydroquinoline, 2-methyl-3-morpholino-4-oxy-tetrahydroquinoline, 9-oxy-1, 2,3,4,5,6,7,8-octahydroacridine, 2-methyl-3-chloro-4-oxy-tetrahydroquinoline, 2-carboxymethyl-3,6-dimethyl-4-oxy-tetrahydroquinoline, 2-phenyl-4-oxy-tetrahydroquinoline and 3-phenyl-4-oxytetrahydroquinoline. The chlorocarbonic acid alkyl or aryl esters rrormel (IV)] and chlorosulfamides [formula (III)] are prepared by known methods, e.g. B. N. C. Hansen, Acta Chem. Scand. 17 (1963) No. 7, page 2141, DE-OS 2 514 646; L. F. Audrieth and M. v.

Brauchitseh, J. Org. Chem. 21: 426-8 (1956); R. Wegler and K. Bodenbrenner, Liebigs Ann. Chem. 624 (1959), 25 - 9 and the references in textbooks, z. 5. Organikum, VEB-Verlag der Wissenschaften, Berlin 1967, page 397 (7th edition) representable.

Representative representatives of these starting materials are z. B. chlorocarbonic acid-methyl-, -ethyl -, - ri-butyl -, - n-hexyl -, - phenyl or -nitrophenyl ester, dimethylaminosulfamoyl chloride, Morpholinosulfamoyl chloride and dibutylsulfamoyl chloride, piperidylsulfamoyl chloride, Cyclohexyl methyl sulfamoyl chloride and diisopropyl sulfamoyl chloride.

The new compounds are colorless to pale yellow, crystalline Solids containing 4-chloro compounds, generally colorless liquids, contained in most organic solvents, but are hardly soluble in water and preferably used as biocides. They have a relatively broad impact kung against fungi and bacteria and are also suitable for combating leaf diseases.

The new compounds are particularly effective against phytopathogens Mushrooms, such as B. Powdery mildew species, Botrytis cinerea, rust fungi, Cercospora betae, Cladosporium fuluum, Fusicladium dendriticum and Rhizoctonia solani. An excellent one The compounds show activity against those belonging to the Phycomycetes class Oomycetes such as B. Peronospora, Phytophthora, Pseudoperonospora, Plasmopara and Phythium. They also show a good effect against phytopathogenic bacteria such as z. B. Xanthomonas oryzae, Xanthomonas citri, Xanthomonas malvacearum, Erwinia carotovora and Corynebacterium michiganense and Xanthomonas phaseoli.

Also used to combat non-phytopathogenic fungi and bacteria that growing on tachnian substrates and degrading or destroying them are the compounds excellently suited. So they record, inter alia. Aureobasidium pullulans, Ulocladium consortiale, Aspergillus niger, Penicillium funiculosum, Poria monticola and Coniophora puteana. Also the bacteria Escherichia coli, Bacillus subtilis and Aerobacter aerogenes are inhibited in their growth.

The substances can be used in the usual way as dusts, wettable powders, Formulate dispersions or emulsion concentrates.

The content of the total active ingredient is preferably 10 to 90% by weight. In addition, the formulations contain the usual adhesive, wetting, dispersing, filling and carriers.

The invention is to be explained in more detail by the following examples.

Example 1 4- (N, N-Dimethylsulfamoyloxy) -2-methyl-5,6,7,8-tetrahydroquinoline To 74 g of 2-ethyl-4-oxy-5,6,7,8-tstrahydroquinoline (0.455 mol) in 400 72 g (0.5 mol) of dimethylaminosulfamoyl chloride are added dropwise at 100 ° C. then 50 g (0.5 mol) of triethylamine are added and the mixture is kept at 100 ° C. for a further 10 minutes. It is allowed to cool, the salt is filtered off with suction and the toluene of the mother liquor is rotated in vacuo away. The oily residue crystallizes out after some time.

Melting point: 122; Yield: 102 g (76) C12H18N2 03S MW: 270 calcd .: C 53.3 H 6.7 N 10.4 found: 53.5 6.8 10.3 Example 2 4- (n-Butoxycarbonyloxy) -2 -methyl-5,6,7,8-tetrahydroquinoline 74 g (0.455 mol) of 2-methyl-4-oxy-5,6,7,8-tetrahydroquinoline are first in 100 ml of toluene for 90 s with 68.3 g ( 0.5 mol) of n-butyl chlorocarbonate, then mixed with 50.5 g (0.5 mol) of triethylamine. The mixture is stirred at 90 ° C. for a further 30 minutes, 150 ml of toluene are added, the mixture is cooled and the salt is filtered off with suction. The mother liquor is spun off and the oily residue is distilled in a high vacuum at 0.8 mbar. Yield: 90 g (72%) C15H21 NO3 MW: 263 calc .: C 68.4 H 8.0 N 5.3 found: 68.3 8.3 5.2 Analogously to Examples 1 and 2, the following were prepared: Example name Ausbsute boiling point or No. (%) Melting point (° C) 3 4- (N-Cyclohexyl-N-methylsulfamloxy) -2-methyl-5,6,7,8- 78 66 tetrahydroquinoline 4 4- (N, N-diisopropylsulfamoyloxy) -2-methyl-5,6,7,8- 40 84 tetrahydroquinoline 5 4- (piperidylsulfamoyloxy) -2-methyl-5,6,7,8-tetra-35 60 hydroquinoline 6 4- (morpholinesulfamoyloxy) -2-methyl-5,6,7,8-tetra-69 103 hydroquinoline 7 4- (N, N-dibutylsulfamoxyloxy) -2-methyl-5,6,7,8-tetra-62 48 hydroquinoline 8 4- (phenoxycarbonyloxy) -2-methyl-5,6,7,8-tetra-56 82 hydroquinoline 9 4- (methoxycarbonyloxy) -2-methyl-5,6,7,8-tetra- 44 109-113 / hydroquinoline 1.07 mbar 10 4- (4'-nitrophenoxycarbonyloxy) -2-methyl-5,6,7,8 72 156 tetrahydroquinoline Example 11 4-Chloro-2-methyl-6-isopropyl-5,6,7,8-tetrahydroquinoline 220 g (1.07 moles) of 2-methyl-6-isopropyl-4-oxy-5,6,7,8 Tetrahydroquinoline are slowly poured over 250 ml of phosphorus oxychloride and then refluxed for about 3 hours. The excess phosphorus oxychloride is then distilled off and the residue is poured onto ice. It is neutralized with NaOH or Na2CO3 to pH 8, then extracted with methylene chloride and dried over NaSO4. It is filtered, the methylene chloride is evaporated and the residue is distilled in a high vacuum at 0.4 mbar / 112 ° C. The yield of chloride is 179.1 g.

The following 4-chloro compounds were prepared in analogy: E.g. R1 R2 R3 R4 R5 R6 boiling point or No. Schmalzpunkt (° C) 12 n-C3H. HHHH i-C3H7 116 / 0.4 mbar 13 CH3 HH CH3 HH 93 / 0.27 mbar 14 CH3 HHHH CH3 88 / 0.4 mbar 15 CH3 CH3 HHHH 113-7 16 CH3 morph. HHHH 132 / 0.2 mbar 17 - (EH2> 4- HHHH 52-3 18 CH3 Cl HHHH 80-90 / 0.113 ibar 19 CDOCH CH3 H CH3 HH 54-60 20 C6H5 HHHHH 128 / 0.055 21 H C6H5 HHHH mbar 143-150 / 0.3 mbar 22 CH3 HHHHH 80 / 0.2 mbar Example 23 4-Mercapto-2-methyl-5,6,?, 8-tetrahydroquinoline 150 g of 4-oxy-2-methyl-5,6,7,8-tetrahydroquinoline and 240 g of phosphorus penta sulfide were homogenized and heated in the flask until a uniform melt is created. After cooling, it is taken up in ethanol, diluted with H20, filtered and spun off in vacuo. It is now adjusted to about pH 8 with dilute NaOH and etherified. The aqueous phase is saturated with CO 2, the mercapto compound precipitating out. It is suctioned off and recrystallized from water / ethanol. 120 g yield of product with a melting point of 215 to 217 ° C.

Examples 24 to 30 In the following examples, in which the biological Effectiveness of the substances according to the invention is shown, are the letters A to J for the comparison agents mentioned below: A = N- (trichloromethylthio) phthalimide 8 = Maneb-Zineb mixed complex (Mancozeb) C = # Mergal S 40 O = #Mergel AT liquid = #Mergel CAB 40 F = #Mergel AF G = 2- (Methoxy-carbonylamino) -benzimidazole H = #Mergel S 88 (zinc dithiocarbamate + substance G) J = pentachlorophenol Example 24 vine plants, which were raised from cuttings of the Plasmopara-susceptible variety Müller-Thurgau, were in the 4-leaf stage with aqueous suspensions of the claimed compounds tropfnaa treated. The application concentrations were 500, 250, 125 and 60 ml of active ingredient per liter of spray mixture After the spray coating has dried on the plants were inoculated with a zoosporangia suspension of Plasmopara viticcla and dripping wet in a climatic chamber at a temperature of 20 cC and a relative 100% humidity.

After 24 hours, the infected plants were removed from the climatic chamber and in a greenhouse with a temperature of 23 ° C and humidity brought about 80 to 90%.

After an incubation period of 7 days, the plants were moistened9 and placed in the climatic chamber overnight and the disease was caused to break out. The infection evaluation was then carried out. The degree of infection was expressed in% of the infected leaf area in comparison to the untreated, infected control plants and is shown in Table 1 Verb.gew. % Plasmopara viticola infestation at mg active ingredient / Example liters of spray liquid 500 250 125 60 14 0 0 0 0 Comparison middle A 0 3 5 10 B 5 10 25 25 untreated, in- fiz. plants 100 EXAMPLE 25 In each case 0.02 ml of a bacterial suspension of Bacillus subtilis were applied drop-shaped in Petri dishes to nutrient media (standard I nutrient agar for bacteria); The claimed compounds in the concentrations given in Table 2 had previously been added to the agar in the liquid state.

The plates inoculated with bacteria were evaluated after four days; the inhibition of growth compared to the control (= inoculated Agar without added active ingredient = 0% inhibition) rated.

Commercially available mercury-free products were used as comparison means (C, D, E, F), which were used with the same active ingredients as the claimed compounds.

Table 2 Connection according to inhibition in% of Bacillus subtilis at mg of active ingredient Example per liter of agar 1000 500 100 50 10 23 100 100 100 80 - Comparative middle C 50 25 D 50 25 E 100 50 - - - F 50 25 - - - Example 26 The method was carried out according to Example 25. Instead of Bacillus subtilis, the compounds were tested against Aerobacter aerogenes.

Table 3 Connection according to inhibition in% of Aerobacter aerogenes at mg Example active ingredient per liter of agar 1000 500 100 10 100 100 0 Comparative middle G 50 50 0 F 50 50 0 H 50 50 0 Example 27 In each case 0.02 ml of a spore suspension from Ulocladium consortiale was placed in drops in petri dishes on nutrient medium (biomalt agar for fungi); The claimed compounds in the concentrations given in Table 4 had previously been added to the agar in the liquid state. 6 days after inoculation of the plates, the diameter of the fungal colonies on the agar was measured and the growth inhibition caused by the preparations expressed in%, based on the control (= inoculated agar without added active ingredient = 0% inhibition).

Commercially available mercury-free products were used as comparison means (C, O, E, F), which were used with the same active ingredients as the claimed compounds.

Table 4 Verb according to % Inhibition of uloccladium consortials at mg Example active ingredient per liter of agar 1000 500 100 50 10 5 1 0.5 15 100 100 100 50 10 5 1 0.5 13 100 100 100 100 100 80 0 0 Compare- middle C 0 0 100 80 30 0 0 0 D 100 20 0 0 0 0 0 0 E 100 100 60 0 0 0 0 0 F 100 100 80 0 0 0 0 0 Example 28 The tests were carried out methodically in accordance with Example 27. The claimed compounds were tested here against Aursou basidium pullulans Table 5 Verb. According to inhibition in% of Aureobasidium pullulans at mg example active ingredient per liter of agar 1000 500 100 50 10 23 100 100 100 80 50 15 100 100 100 100 50 13 100 100 100 100 80 equal middle ital 100 | 50 EXAMPLE 29 In each case 0.02 ml of a spore suspension of Xanthomonas citri were applied drop-shaped in Petri dishes to nutrient medium (Biomalz agar for fungi); The compounds claimed had previously been added to the agar in the liquid state in the concentrations given in Table 6. The plates inoculated with bacteria were evaluated after 4 days; the inhibition of growth was rated in comparison to the control (= inoculated agar without addition of active ingredient = 0% inhibition).

Table 6 According to inhibition in% of Xanthomonas citri in m Example active ingredient per liter of agar 250 125 60 30 15 23 100 100 100 100 35

Claims (5)

Claims Compounds of the general formula (I) in which R1 stands for hydrogen, a straight-chain or branched alkyl radical with 1 to 12 carbon atoms, a benzyl radical, a phenyl radical which can be substituted by one or two chlorine atoms or by trifluoromethyl or by an alkyl radical with 1 to 4 carbon atoms, for an alkoxycarbonyl radical with 1 up to 6 carbon atoms, for arylaminocarbonyl, where the aryl radical can be substituted by halogen, trifluoromethyl, nitro or alkyl with 1 to 5 carbon atoms, for N-alkylarylaminocarbonyl, the alkyl group being one with 1 to 3 carbon atoms, and the aryl group by halogen, -CF3 or alkyl with 1 to 4 carbon atoms can be substituted for aminocarbonyl, for alkylaminocarbonyl with 1 to 10 carbon atoms or for dialkylaminocarbonyl with 1 to 10 carbon atoms each, R2 represents hydrogen, a straight-chain or branched alkyl radical with 1 to 12 carbon atoms, a benzyl radical , a phenyl radical, which is replaced by one or two chlorine atoms or can be substituted by trifluoromethyl or by nitro or by alkyl having 1 to 4 carbon atoms, an alkoxycarbonyl radical having 1 to 6 carbon atoms, a phenylthio, morpholine p or piperidino radical, an arylamino radical, where aryl is substituted by halogen or alkyl having 1 to 4 carbon atoms can be, a dialkylaminomethyl radical with 1 to 6 carbon atoms in the alkyl chains, a morpholinomethyl radical or a piperidinomethyl radical, or R1 and R2 together stand for -CH2CH2CH2CH2 -, R3 has the meaning of hydrogen or an alkyl radical with 1 to 4 carbon atoms, R4 Is hydrogen, a straight or branched alkyl radical having 1 to 12 carbon atoms, R5 is hydrogen or an alkyl radical having 1 to 4 carbon atoms, and R6 is hydrogen or an alkyl radical having 1 to 6 carbon atoms, while A is either -SH or chlorine or one Remainder of the formula -OR. where R7 is the meaning of or -COOR10 and then R 8 = a straight-chain or branched alkyl radical with 1 to 10 carbon atoms, or phenyl or hydrogen 9 = hydrogen, a straight-chain or branched alkyl radical with 1 to 10 carbon atoms, or R and R9 together for radicals of the structure - CH2CH2CH2CH2-, -CH2CH2CH2CH2-, -CH2CH2CH2CH2- or stand, and R10 = alkyl with 1 to 10 carbon atoms or phenyl, which can be substituted by halogen or nitro. 2. Process for the preparation of the compounds according to Claim 1, in which A = -0R7, characterized in that 1 ol of a 4-oxy-5,6,7,8-tetrahydroquinoline of the formula (II a) or the tautomeric form (II b) with 1 to 1.1 mol of chlorides of the general formulas (III) or (IV) ClOOR10 (IV) in which R8 to R10 have the meaning given in claim 1, is reacted in the presence of a tertiary organic base and in the presence or absence of an inert solvent for 50 to 140 s. 3. Process for the preparation of such compounds according to Claim 1, in which A = -SH, characterized in that 1 mol of a 4-oxy-5s6,7s8-tetrahydroquinoline of the formula (II a) or of the tautomeric form (II b) with 1 to 1.2 molar equivalent of P2S5 in the presence or absence of an inert solvent at 100 to 200 ° C, the reaction product is then treated with dilute aqueous alkali and then the desired process product is isolated by acidification. 4. Biocidal agents, characterized by a content of compounds according to claim 1 in addition to customary formulation auxiliaries. 5. Use of the compounds according to claim 1 as fungicides, bactericides and to combat leaf diseases.