IL106765A - N-methylamides, processes and intermediates for their preparation and their use as pesticides - Google Patents

Abstract

N-methylamides of the formula I <IMAGE> in which R denotes alkyl or cyclopropyl, the radicals A denote hydrogen, halogen, cyano, nitro, alkyl, cycloalkyl, OR<1>, cycloalkyloxy, haloalkyl, haloalkyloxy, alkenyl, alkenyloxy, alkynyl, alkoxyalkyl, cyanoalkyl, nitroalkyl, phenyl, phenoxy, C(O)R<1>, CO2R<1>, C(O)NR<1>R<2>, C(S)NR<1>R<2>, NR<1>R <2>, NR<1>C(O)R<2>, NR<1>CO2R<2>, OC(O)R<1>, SR<1>, S(O)R<1>, S(O)2R<1>, the groups -C(R<1>)=NR<2>, -N=CR <1>R<2>, <IMAGE> where the radicals R<1>, R<2> and R<3> denote hydrogen or C1-C6-alkyl or X denotes S, O and NR<3> and n denotes the numbers 0 or 1, or two of the groups Am in adjacent positions together denote the group -CH=CH-CH=CH and m represents the numbers 1, 2 or 3, and fungicides containing these compounds.

Description

106765/2 N-Methylamides, processes and intermediates for their preparation and their use as pesticides BASF Aktiengesellschaft C. 91064 The present invention relates to novel N-methyl-amides, processes and intermediates for their preparation and processes for controlling pests, in particular fungi, insects, nematodes and spider mites, using these compounds .

It is known to use substituted N-methylamides as pesticides (cf . EP-A 463 488, EP-A 398 692) . However, their action is unsatisfactory.

It has surprisingly been found that N-methyl-amides of the general formula I have an excellent fungicidal, insecticidal, nematicidal and acaricidal action which is better than that of the known N-methylamides .

The fungicidal action is preferred.

The radicals mentioned under the general formula I can have, for example, the following meanings: R is methyl; R' is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl or tert-butyl.

On account of the C=N double bonds, the novel compounds of the general formula I can be obtained as E/Z isomer mixtures. These can be separated into the individual components in a conventional manner, for example by crystallization or chromatography. Both the individual isomeric compounds and their mixtures are covered by the invention and can be used as pesticides. As a rule, however, the compounds according to the invention are mainly obtained in the (E, E) configuration. These isomers are also preferred with respect to their action.

Formula I, (E, E) configuration The novel compounds of the formula I can be prepared, for example, as follows: Starting from the compounds of the formula 2 , where X = OH, CI or 0 (0χ-(4 -alkyl) [disclosed in EP-A 463 488, EP-A 472 300 and EP-A 426 460] , the monomethy1amides I according to the invention can be obtained analogously to methods known from the literature by reaction with methylamine (cf . Organikum; 16th edition (1985) p. 408 et seq.).

A particularly advantageous method of preparing the compounds I is to react O-benzylhydroxylamine 3_ with the phenylketones 4 (cf. D. Otzanak, J. Chem. Soc . , Chem. Commun. 1986, 903) . The intermediate 3_ required for this can surprisingly be prepared particularly smoothly and advantageously in a simple reaction by triple aminolysis of 3a (with methylamine) .

This one- step reaction procedure 3a -* 3_ avoids the conventional more involved and more elaborate two-step procedure, eg. setting free the O-benzylhydroxylamine group from the phthalimide protective group with the aid of hydrazinolysis and beforehand or subsequently converting the methyl ester - - group to the methylamide . The high yields of this reaction are surprising, although normally the optimum conditions are very different on the one hand for the aminolysis of a methyl ester to the methylamide and on the other hand for setting free an O-benzyl-hydroxylamine from the corresponding O-benzylhydroxyphthalimide .

The phenyIketones 4 are known or can be prepared analogously to known processes (Houben-Weyl, Vol. 7/2a and 7/3a) .

The novel compounds of the formula I are also obtained by reacting a monomethylamide benzyl compound 5., in which L is a leaving group (eg. bromine, chlorine, iodine, mesylate, tosylate or triflate) (cf., eg. EP-A 398 692 and EP-A 463 488) with an oxime of the formula 6 (cf., eg., Houbon-Weyl [sic], Vol. 10/1, p. 1186 et seq. ) .

The oximes 6. are known or can be prepared by known processes (cf. Houben-Weyl, Vol. 10/4; J. Med. Chem. 26, (1983) 1360) .

The novel compounds of the formula I can furthermore be prepared by reacting the benzyl alcohol 7 with the oximes 6. in a conventional manner (cf . J. Jurczak, Synthesis Alternatively, for this purpose the ketoamides 8. can be reacted in a conventional manner with methoxyamine [sic] (hydrochloride) to give the novel compounds I [cf., eg. DE-A 36 23 921) .

The ketoamides 8. themselves can be obtained, for example, from the ketoesters 9. by aminolysis, the keto-esters 9 themselves being accessible either by Pinner reaction from the benzoyl cyanides 10. or by reaction of the oximes 6. with the benzyl compounds 11.

- - Suitable further starting materials for the preparation of the ketoamides 8 or of the ketoesters 9. are the aryl halides 19 (Hal = chlorine, bromine or iodine) . These can be converted into the corresponding organometal by metallization (eg. with magnesium, methyl-magnesium bromide, sodium or n-butyllithium) , which can then be reacted with oxalic acid derivatives (eg. oxalic acid diester, oxalic acid ester N-methylamide) to give the products 8. or 9 (cf., eg., (L.M. Weinstock, Synth. Commun. 11, (1981) 943) .

The cyanooxime ethers 12 can also be converted with methylamine in a conventional manner into the novel compounds of the formula I (cf. EP-A 468 775).

The cyanooxime ethers 12 are obtained, for ex-ample, according to known processes by reaction of the oximes 6 with the benzyl bromide 13.

The ketoamides of the formula 8. can additionally be obtained in a simple manner from the nitrilium salts 17 by hydrolysis either in acidic or in alkaline solution (cf. Houben-Weyl, Vol. E5/part 2, p. 1580 et seq.).

The nitrilium salts of the formula 17. are easily accessible, for example, from the compounds of the formula 10. by reaction with trimethyloxonium salts such as, for example, trimethyloxonium tetrafluoborate or by reaction of 10 with, for example, methyl trifluoro-methanesulfonate (cf. Houben-Weyl, Vol. E5/part 2, pp. 1573-6) .

In a corresponding manner, the compounds of the general formula I can also be obtained easily from nitrilium salts of the formula 18 by hydrolysis in acidic or alkaline solution (cf . Houben-Weyl, Vol. E5/part 2, p. 1580 et seq. ) .

The nitrilium salts of the formula 18 in turn are easily accessible, for example, from the compounds of the formula 12. by reaction with trimethyloxonxum salts such as, for example, trimethyloxonxum tetrafluoborate or by reaction of 12. with, for example, methyl trifluoro-methanesulfonate (cf. Houben-Weyl, Vol. E5/part 2, pp. 1573-6) .

The novel compounds of the formula I can also be prepared by methylation of suitable intermediates such as, for example, 14 - 16..

- - Alkylation expediently takes place in the presence of a base such as, for example, KOH, K2C03 or triethylamine. Suitable alkylating agents are methyl halides or dimethylsulfate (cf., for example, Houben-Weyl, Vol. X/l pp. 1186 et seq; or G.L. Isele, Synthesis, (1971) 266) .

The substituents R and shown in the formulae 2. - 19. have the meanings given in claim 1. The substitu- ent L is a leaving group such as, for example, halogen (chlorine, bromine or iodine) , tosylate, mesylate or triflate.

The following examples are intended to illustrate the preparation of the novel active compounds and of the novel intermediates : - - EXAMPLE 1 Preparation of methyl E-2 -methoxyimino-2 -[ (2' -phthal-imidooxymethy1) phenyl] acetate 59 g (0.58 mol) of triethylamine are added dropwise to a solution of 150 g (0.52 mol) of methyl 2 -methoxyimino-2 - 12' -bromomethyl) phenyl] acetate and 85 g (0.52 mol) of N-hydroxyphthalimide in 350 ml of N-methyl-pyrrolidone. The reaction mixture is stirred at 70 °C for 2 h and poured into 2 1 of ice-water, and the precipit-ated crystals are filtered off with suction and taken up in methylene chloride. After washing the organic phase with water, drying it over sodium sulfate and removing the solvent on a rotary evaporator, 168 g (88% yield) of methyl E-2 -methoxyimino-2- [ (2' -phthalimidooxymethyl) -phenyl] acetate are obtained as a pale gray powder of melting point 152 - 153 °C.

½-NMR (CDC13) δ = 3.81 (s, 3H) ; 3.95 (s, 3H) ; 5.05 (s, 2H) ; 7.12 - 7.81 (m, 8H) ppm.

EXAMPLE 2 Preparation of N-methyl-E-2 -methoxyimino-2 -[ (2' -amino-oxymethyl) phenyl] acetamide 168 g (0.46 mol) of methyl E-2 -methoxyimino-2- [ (2' -phthalimidooxymethyl) phenyl] acetate are treated with 1 1 of 40% strength aqueous monomethylamine solution and the mixture is stirred at 40°C for 4 h. After cooling, it is extracted with methylene chloride, and the organic phase is washed with water, dried over sodium sulfate and concentrated. After crystallization of the residue from methyl tert-butyl ether/n-hexane, 92 g (84% yield) of N-methyl-E-2 -methoxyimino-2 - [ (2' -aminooxy-methyl) henyl] acetamide are obtained as pale yellow crystals of melting point 78 - 81°C. The mother liquor contains further final product. 1H-NMR (CDCI3) : 6 = 2.91 (d, 3H) ; 3.94 (s, ' 3H) ; 4.58 (s, 2H) ; 5.28 (s, br, 2H) ; 6.88 (s, br, 1H) ; 7.14 - 7.43 (m, 4H) ppm.

- - EXAMPLE 3 Preparation of E-2 -methoxyimino-2 - (2' -methylphenyl) aceto-nitrile. 188 g (1.68 mol) of dry potassium tert-butoxide are introduced into 2 1 of dry toluene and treated rapidly with 200 g (1.53 mol) of ortho-methylbenzyl cyanide and 173 g (1.68 mol) of tert-butyl nitrite in 200 ml of toluene. The mixture warms up to about 70 °C, and is stirred for 2h and treated with 1 1 of methyl tert-butyl ether. The yellow potassium salt is filtered off with suction, washed with methyl tert-butyl ether and dried under reduced pressure at 50 °C. 290 g (1.46 mol) of this salt are then introduced into 2.5 1 of dry acetone with 20 g (0.15 mol) of potas-sium carbonate. While 234 g (1.65 mol) of iodomethane are added dropwise, the temperature rises to about 35 °C. The mixture is stirred overnight and then partitioned between water and methyl tert-butyl ether. The organic phase is washed with water, dried over Na2S04, concentrated and distilled under reduced pressure (b.p. = 95 - 100 °C/ 0.3 - 0.1 mm). 229 g (78% total yield) of the title compound are thus obtained as a poorly mobile liquid. ^-NMR (CDC13) : δ = 2.53 (s, 3H) ; 4.22 (s, 3H) ; 7.2 - 7.4 (m, 3H) ; 7.54 (dd, 1H) ppm.

EXAMPLE 4 Preparation of E-2 -methoxyimino-2 - (2 ' -bromomethylphenyl) -acetonitrile . 48 g (0.28 mol) of E-2 -methoxyimino-2 - (2 ' -methyl-phenyl) acetonitrile and 54 g (0.30 mol) of N-bromosuccin-imide are introduced into 250 ml of carbon tetrachloride.

The mixture is illuminated from outside with an Hg vapor lamp (300 W) for 40 min. The succinimide is filtered off with suction and the solution is evaporated under reduced pressure. 62 g (88% yield) of the title compound remain, which is about 80% strength according to the result of the 1H-NMR spectrum.

½-NMR (CDCI3) : δ = 4.27 (s, 3H) ; 4.80 (s, 2H); 7.4 - 7.5 (m, 3H) ; 7.69 - - (dd, 1H) ppm.

EXAMPLE 5 Preparation of N-methyl-2 -methoximino-2- [2' -bromomethyl) -phenyl] acetamide 10 g of N-methyl-2-methoximino-2- [ (2 -methyl-phenyloxymethyl) phenyl] acetamide are introduced into 50 ml of dichloromethane. At 10°C# 9 g of HBr gas is passed into this solution. It is then allowed to thaw and is stirred at room temperature for 3 days. 50 ml of dichloromethane are added, and the mixture is washed with 5% strength NaOH and with water, dried and concentrated. 7 g of the title compound are obtained as a pale brown solid.

M.p.: 128 - 129°C ^-H-NMR (CDC13 / TMS) : S. 2.95 (d, 3H) ; 3.95 (s, 3H) ; 4.35 (s, 2H) ; 6.85 (NH) ; 7.1-7.5 ppm (m, 4H) .

EXAMPLE 6 Preparation of N-methyl-2 -methoximino-2 -[ (2' -chloro-methyl) henyl] acetamide At 10°C, 18.8 g of a boron trichloride solution (1 molar in n-hexane) is added dropwise to a solution of 2 g (6.4 mmol) of N-methyl-2 -methoximino-2- [ (2-methyl-phenyloxymethyl) henyl] acetamide in 30 ml of dichloro-methane, and the mixture is then refluxed for 1.5 hours. Subsequently, 8.2 g of methanol are added and the mixture is stirred overnight at room temperature. After washing with 5% strength NaOH and with water, drying and concentrating, 1.2 g (78%) of the title compound are obtained as a solid.

½-NMR (CDC13 / TMS): δ = 2.96 (s, 3H) ; 3.96 (s, 3H) ; 4.46 (s, 2H) ; 6.86 (NH) 7.13-7.49 ppm (m, 4H) .

EXAMPLE A (process for preparing the compounds I) Preparation of N-methyl-2-methoximino-2- [2' -1' ' - (4' ' ' -methylphenyl) -1' ' -methyl) iminoxymethyl] phenylacetamide A spatula tip full of tetra-n-butylammonium iodide is added to a solution of 2 g (7 mmol) of oxime ether amide bromide (from Example (5) in 20 ml of dichloromethane, followed by a solution of 1.2 g (7 mmol) of p-methylacetophenone oxime in 10 ml of dichlormethane. 20 ml of 10% strength NaOH are then added dropwise and the mixture is refluxed for 6 hours. After phase separation, extraction with dichloromethane, drying and concentration, the residue is chromatographed on silica gel using hexane/methyl tert-butyl ether. 1.1 g (45%) of the title compound remain.

^- R (CDCI3/TMS) : δ = 2.18; 2.34 (s, 3H) ; 2.85 (d, 3H) ; 3.95 (s, 3H) ; 5.09 (s, 2H) ; 6.67 (NH) ; 7.12- 7.50 ppm (m, 8H) .

EXAMPLE B (process for preparing the compounds I) Preparation of 4-methoxyacetophenone oxime O- [2-bromo] benzyl ether A solution of 14 g (85 mmol) of p-methoxyaceto-phenone oxime is added dropwise under nitrogen to a suspension of 2.8 g (94 mml [sic]) of NaH (80% strength) in 250 ml of DMF, and the mixture is stirred at room temperature for 2 hours. A solution of 21.3 g (85 mmol) of o-bromobenzyl chloride in 10 ml of DMP is then added dropwise and the mixture is stirred for 1.5 hours. After hydrolysis with 10% strength HCl, extraction with methyl tert-butyl ether, drying and concentration, 27.7 g (98%) of the title compound remain as a yellowish-brown oil. ^i-N R (CDCI3 / IKS) : δ = 2.21; 3.85 (s, 3H) ; 5.34 (s, 2H) ; 6.91-7.66 ppm (m, 8H) .

EXAMPLE C (process for preparing the compounds I) Preparation of N-methyl-2-methoximino-2- [2' - (1' ' - (4' ' ' -methoxyphenyl) 1' ' -methyl) iminooxymethyl] phenylacetamide 6.6 g (15 mmol) of n-butyllithium ( [lacuna] % strength solution in hexane) are added at -78°C and under nitrogen to a solution of 5 g (15 mmol) of bromide (from Example 11 [sic]) in 40 ml of THF, and 4.4 g (30 mmol) of diethyl oxalate are run in immediately afterwards. After thawing, water is added, followed by extraction with methyl tert-butyl ether, drying and concentration. The residue is chromatographed on silica gel using hexane/methyl tert-butyl ether. 2.7 g (51%) of the corresponding a-keto ester are obtained as an oil. 50 ml of a 40% strength N-methylamine solution are added to a solution of 400 mg of this keto ester in 10 ml of THF, and the mixture is heated at 50 °C for 1 hour. 2 g of methoxyamine [sic] hydrochloride are then added and the mixture is again heated at 50 °C for 1 hour. After cooling, extraction with dichloromethane, drying and concentration, 300 mg of the title compound remain. ^-NMR (CDC13 / TMS) : δ = 2.15; 3.13; 3.77 (s, 3H) ; 2.86 (d, 3H) ; 5.06 (s, 2H) ; 6.84-7.56 ppm (m, 8H) .

Further compounds of the formula I according to the invention are shown in Table 1. The compounds can be obtained by the processes described above .

TABLE 1 - - The novel compounds are suitable as fungicides and insecticides.

The fungicidal compounds according to the invention, or the compositions containing them, may be applied, for instance, in the form of directly sprayable solutions, powders, suspensions (including high-percentage aqueous oily or other suspensions) , dispersions, emulsions, oil dispersions, pastes, dusting compositions, broadcasting compositions or granules, by spraying, atomizing, dusting, broadcasting or watering. The application forms depend on the intended uses; they should at all events ensure as fine a distribution of the active compounds according to the invention as possible.

Normally, the plants are sprayed or dusted with the active compounds or the seeds of the plants are - -treated with the active compounds.

The formulations are prepared in a known manner, for example by extending the active compound with solvents and/or carriers, with or without the use of emulsifiers and dispersants; if water is used as a diluent, it is also possible to employ other organic solvents as auxiliary solvents. Suitable auxiliaries for this purpose are essentially solvents such as aromatics (eg. xylene) , chlorinated aromatics (eg. chlorobenzenes) , paraffins (eg. crude oil fractions) , alcohols (eg. methanol, butanol) , ketones (eg. cyclohexanone) , amines (eg. ethanolamine) , amides (eg. dimethylformamide) , and water; carriers such as ground natural minerals (eg. kaolins, aluminas, talc and chalk) and ground synthetic minerals (eg. highly dispersed silica and silicates) ; emulsifiers such as nonionic and anionic emulsifiers (eg. polyoxyethylene fatty alcohol ethers, alkylsulfonates and arylsulfonates) ; and dispersants such as lignin-sulfite waste liquors and methylcellulose .

Suitable surfactants are the alkali metal, alkaline earth metal and ammonium salts of aromatic sulfonic acids, eg. lignosulfonic acid, phenolsulfonic acid, naphthalenesulfonic acid and dibutylnaphthalene-sulfonic acid, and of fatty acids, alkyl- and alkylaryl-sulfonates, alkyl, lauryl ether and fatty alcohol sulfates, and salts of sulfated hexadecanols, heptadeconals and octadecanols, and of fatty alcohol glycol ethers, condensation products of sulfonated naphthalene and its derivatives with formaldehyde, condensation products of naphthalene or naphthalene-sulfonic acids with phenol and formaldehyde, polyoxyethylene octylphenol [sic] ethers, ethoxylated isooctylphenol, octylphenol or nonylphenol, alkylphenol [sic] polyglycol ethers, tributylphenyl polyglycol ethers, alkylaryl polyether alcohols, isotridecyl alcohol, fatty alcohol ethylene oxide condensates, ethoxylated castor oil, polyoxyethylene alkyl ethers or polyoxypropylene [sic] , lauryl alcohol polyglycol ether acetate, sorbitol esters, lignin-sulfite waste liquors - -and methylcellulose .

Powder, broadcasting and dusting compositions may be prepared by mixing or grinding the active substances together with a solid carrier.

Granules, eg. coated, impregnated or homogenous granules, may be prepared by binding the active compounds to solid carriers. Solid carriers are mineral earths such as silica gel, silicas, silica gels [sic] , silicates, talc, kaolin, limestone, lime, chalk, bole, loess, clay, dolomite, diatomaceous earth, calcium sulfate, magnesium sulfate, magnesium oxide, ground plastics, fertilizers such as ammonium sulfate, ammonium phosphate, ammonium nitrate, ureas and vegetable products such as grain meal, bark meal, wood meal and nutshell meal, cellulose powders or other solid carriers.

The compounds are extremely effective against a broad spectrum of phytopathogenic fungi, in particular those from the class consisting of the Ascomycetes and Basidiomycetes . Some of them have a systemic action and can be used as foliar and soil fungicides.

They are of particular importance for controlling a large number of fungi in various crops such as wheat, rye, barley, oats, rice, Indian corn, grass, cotton, soybeans, coffee, sugar cane, grapes, fruit plants and ornamentals and vegetable plants such as cucumbers, beans and cucurbits .

The compounds are applied by treating the fungi or the seeds, plants, materials or the soil to be protected from fungal attack with a fungicidally active amount of the active compounds.

Application takes place before or after infection of the materials, plants or seeds by the fungi.

Specifically, the compounds I are suitable for controlling the following plant diseases: Erysiphe graminis (powdery mildew) in cereals, Erysiphe cichoracearum and Sphaerotheca fuliginea in cucurbits, Podosphaera leucotricha in apples, Uncinula necator in grapevines, - - Puccinia species in cereals, Rhizoctonia species in cotton and lawns, Ustilago species in cereals and sugar cane, Venturia inaequalis (scab) in apples, Helminthosporium species in cereals, Septoria nodorum in wheat, Botrytis cinerea (gray mold) in strawberries and grapevines, Cercospora arachidicola in groundnuts, Pseudocercosporella herpotrichoides in wheat and barley, Pyricularia oryzae in rice, Phytophthora infestans in potatoes and tomatoes, Fusarium and Verticillium species in various plants, Plasmopara viticola in grapevines, Alternaria species in fruit and vegetables.

The novel compounds may also be used for protecting materials (timber) , for example against Paecilomyces variotii.

The fungicidal compositions generally contain from 0.1 to 95, preferably from 0.5 to 90, % by weight of active compound.

The application rates are, depending on the type of effect desired, from 0.02 to 3 kg of active compound per ha.

In the case of seed treatment, active compound rates of from 0.001 to 50, preferably from 0.01 to 10, g per kilogram of seed are generally required.

When the agents according to the invention are used as fungicides, they may be present together with other active compounds, for example with herbicides, insecticides, growth regulators, other fungicides or else with fertilizers.

When mixed with other fungicides, the spectrum of fungicidal action is frequently increased.

Claims (8)

- Claims

1. An N-methylamide of the formula I where R is methyl and R1 is C1-C4-alkyl

2. A process for preparing N-methylamides of the formula I as claimed in claim 1, which comprises reacting a benzyl derivative of the formula II where L is a leaving group, with an oxime of the formula III R CH3

3. 10.67 $ 5 - 20 - 3. A process for preparing N-methylamides of the formula I as claimed in claim 1, wherein the compound IV is converted using methylamine into the O-benzylhydroxyl-amine V and this is reacted with a ketone of the formula VI R

4. A process for preparing N-methylamides of the formula I as claimed in claim 1, wherein a cyanooxime of the formula VII - is reacted with methylamine and the product is then treated, if desired, with a methylating agent.

5. A compound of the formula V as set forth in claim 3 V - 22 - 1067 ? 5 / 2

6. A compound of the formula IX

7. A fungicide containing an inert carrier and a fungicidally active amount of an N-methylamide of the formula I as claimed in claim 1.

8. A process for controlling fungi, which comprises treating the fungi or the materials, plants, seeds or the soil threatened by fungal attack with a fungicidally active amount of a compound of the formula I as claimed in claim 1.