NL8003737A - HALOGEN ACETAMIDES AND METHODS FOR PREPARING THESE COMPOUNDS AND PREPARATIONS CONTAINING THEM. - Google Patents

Description

t. 1

Haloacetamides and methods of preparing these compounds and of preparations containing them.

One aspect of the invention relates to haloacetamides having fungicidal and bactericidal properties and methods of preparing these haloacetamides and of compositions containing them.

Thus, the invention further relates to a method for combating or controlling phytopathogenic fungi and bacteria by contacting said fungi or bacteria or the area on which they are located with a fungicidal or bactericidal effective amount of one or more number of compounds of formula 1, wherein X represents a halogen atom with a sequence number of 17 to 35 and R represents a hydrogen atom or an alkyl group with at most 4 carbon atoms, wherein if R is an alkyl group with 1 to 4 carbon atoms, X is a bromine atom.

The invention is particularly indicated for the prevention or control of fungi and bacteria in or on plants, seeds or soil.

The designation "soil" used in this description includes any conventional growing medium, both natural and artificial.

The amount of compound (s) of formula 1 to be used to obtain the desired effect will, as will be appreciated, depend on various factors, such as the area to be treated, for example, whether a plant, the soil or a seed treatment it is contemplated, the type of fungi or bacteria, the method of administration, for example, or the compound as a foliage spray, to treat 8003737 2 r. , soil or as a seed preparation, the conditions of the treatment, such as the time of administration, whether prophylactic or therapeutic treatment is used, the compound to be treated, etc.

In general, however, satisfactory results are obtained when the compound (s) is applied to I.

an area, for example on crops or the soil, in an amount between about 0.1 to 10, preferably about 0.2 to 5, kg (active ingredient) per hectare. This treatment can be repeated if desired, for example, at intervals of 8 to 30 days. If the compound (s) is used as a seed preparation, satisfactory results are obtained if the compound (s) is in an amount of between about 0.05 to 0.5, preferably between about 0.1 to 0.3, g per kg seed is used.

When R represents an alkyl group with up to 4 carbon atoms, this alkyl group may be branched, for example, a sec-butyl group, or a straight-chain butyl group. Suitable examples of straight chain alkyl groups are the methyl, n-propyl and n-butyl group, in particular the n-propyl group. X is a chlorine or bromine atom. X represents a bromine atom, then R is preferably a hydrogen atom.

Especially recommended compounds of the invention are 2-bromo-N-cyclopropyl-acetamide and 2-bromo-N-25-cyclopropyl-N-n-propyl-acetamide.

The compounds of formula la, wherein R 1 represents a hydrogen atom, a straight chain alkyl group having 2 to 4 carbon atoms or a branched alkyl group having 4 carbon atoms are new and are also part of the invention.

The invention also provides a method of preparing compounds of formula la by reacting a compound of formula 2, wherein Rj has the meaning indicated above, with 2-bromoacetyl bromide. The process according to the invention can be carried out according to a method known per se for the preparation of haloacetamides, for example in an inert organic environment, preferably in the presence of an acid acceptor, for example in a trialkylamine, such as triethylamine.

The preparation of the compound of formula la wherein R 1 represents a hydrogen atom, hereinafter referred to as compound 1b, is preferably at a reduced temperature, especially at a temperature between about -10 to about + 5 ° C, preferably at about 0 ° C.

The preparation of the compounds of formula la in which R 1 does not represent a hydrogen atom (the compounds 1c) is preferably carried out at moderate temperatures, for example between about 15 ° C and 35 ° C, preferably between about 20 and 25 ° C.

The reaction is preferably allowed to proceed under substantially anhydrous conditions. Examples of suitable inert organic media are halogenated hydrocarbons, such as and, if any of the reactants or the acid acceptor are liquid at the reaction temperature, an excess thereof.

The compounds of the formula (I) according to the invention can be recovered and purified in a usual manner.

Compounds of the invention of formula 1 not described by formula la are known intermediates for the manufacture of pharmaceuticals (see U.S. Patent 3,532,749).

The compounds of formula II are known as well as 2-bromoacetyl bromide or can be obtained by suitable methods reported in the literature to prepare their known analogs.

Fungi against which the compounds of the invention of formula 1 are particularly effective are, for example, those of the genus Fusarium spp., For example F. oxysporum f.sp.lycopersici in tomatoes F. oxysporum f.sp. cotton vasinfectum 35 F. oxysporum f.sp. cubense in bananas F. solani in vegetables 8003736

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4 F. culmorum in cereal products F. graminearum in cereal products

Verticillium spp., For example V. albo-atrum in a wide variety of economically important crops, such as cotton, hops, alfalfa and solanaceous crops, V.theobromae in bananas, Colletotrichum spp., For example C.lindemuthianum in beans, Phytophthora spp., for example Ph.cactorum,

Ph.parasitica, and Ph. cinnamomi in susceptible plants;

Pythium spp., For example P. aphanidermatum in sugar beet, 10 Thielaviopsis basicola on a wide variety of crops,

Stereum spp., For example Stereum purpureum in pome and stone fruit trees of the order istilaginales, for example U. maydis in grain,

Venturis spp., For example V. inaegualis in apples, 15 Phoma spp., For example Ph. betae on sugar beets and Pyricularia spp., for example P.oryzae on rice.

Bacteria against which the compounds of the formula I according to the invention are particularly effective are those of the genus Xanthomonas spp., For example X. malvacearum in cotton, X. pelargonii in Pelargonium and Pseudomonas spp., For example P. tomato in tomatoes, P ♦ syringae in susceptible plants.

Fungi and bacteria of the aforementioned genus species cause considerable damage in the agricultural field, for example in tomatoes, cotton and cereals, as well as in arboriculture and ornamental plants and are difficult to prevent or control.

The compounds of the formula I according to the invention are particularly useful against Fusarium, Phytophthora, Isilaginales, Pythium, Colletotrichum, Stereum,

Thielaviopsis, Verticillium, Phoma, Venturia, Pyricularia, Pseudomonas and Xanthomonas.

The compounds of the invention can be used in preparations having a fungicidal and bactericidal effect. The preparation of such compositions containing one or more of the compounds of the invention of formula I and des 8003737, optionally an inert carrier for preparations containing a fungicide or bactericidal composition is also part of the invention.

In general, such preparations will contain about 0.01 to 90% by weight, preferably between about 0.1 and 60% by weight, of active ingredient. It may be concentrated preparations which must be diluted before use, when dilute preparations are ready for use. Examples of special preparation forms are wettable powders, concentrated emulsions, sprayable preparations, sprayable preparations, granules and preparations from which the active ingredient is slowly released, optionally containing conventional carriers and optionally other agrochemical additives and / or additives. 15 may be included. Emulsified concentrated preparations generally contain between about 10 and 70% by weight, preferably between about 20 and 60% by weight, of the active ingredient.

Solid, in particular particulate, preparations are recommended.

The formulations which are particularly suitable for spraying preferably contain a surfactant such as a liquid polyglycol ether, a higher alkyl sulfate or a lignin sulfonate.

In addition, fungicides, bactericides and other beneficial materials, such as insecticides, may be present in the compositions and these composition forms are included in further embodiments of the invention.

Concentrated fungicidal formulation compositions generally contain between about 2 and 80% by weight, preferably between about 5 and 70% by weight, of one or more compounds of the invention of Formula 1 as active ingredient. Uses of these preparations will generally contain between about 0.01 and 10% by weight of one or more compounds of the invention of the formula 1 as active ingredient.

The fungicidal bactericidal activity of the compounds of the invention according to the formula (I) was determined according to conventional tests, as described, for example, below:

Test Method A: A vivo test using the tomato wilt (Fusarium oxysporun f.sp. lycopersici).

Lycopersicon esculentum cv. "Rheinland's Rubm" (tomatoes) was grown for 10 days in a mixture of 10 peat dust and sand in plant boxes. Steam sterilized peat dust was infected with Fusarium inoculum and then the mixture was treated by a soil mixing method to obtain concentrations of 160, 40 and 10 ppm active ingredient per volume of soil. After transferring the treated, infected peat dust into plastic pots with a diameter of 6 cm, these pots were planted with tomato seedlings from the plant boxes. The plants were then incubated for 21 days at a temperature of 27 ° C and a relative humidity between 60 and 70%. The efficacy of the active ingredient treatment was determined by comparing the degree of wilt (symptoms) with that of untreated, correspondingly grafted, control plants.

A fungicidal activity was observed with each of the compounds described in Examples I-IV, in particular the compounds of Examples I and III.

A similar test performed on Pythium aphanidermatum on cucumbers and Phorna beta on sugar beets gave similar results.

Research Method B: The in vitro test using Ustilago maydis (corn fire).

Different concentrations of the active ingredient were taken up in malt agar plates to give concentrations of 0.8-200 ppm ai. The plates were then inoculated by spraying a spore suspension of U. maydis on it or by 8003737. Apply 7 piece of agar containing the fungus to the center of the plate. The plates were then incubated at room temperature for 2-5 days. The effectiveness of the active ingredient treatment was determined by comparing the growth of the shade 5 to that in untreated plates seeded in a similar manner.

A fungicidal activity was observed with each of the compounds of Examples I-IV, in particular the compounds of Examples I-III.

Analogous studies leading to similar results were performed on the following fungi bacteria:

Venturia inaequalis, Pyricularia oryzae,

Phytophthora cactorum, Stereum purpureum, 15 Thielaviopsis basicola, Verticillium albo-atrum, Colletotrichum lindemuthianum,

Pseudomonas tomatoes and XanthOmonas pelargonii.

In addition to the usual carriers and surfactants, the compositions of the invention containing one or more of the compounds of the invention of the formula 1 may also deactivate other special purpose additives such as, for example, stabilizers (for solid compositions on carriers with an active surface), agents for improving the adhesion to plants, corrosion inhibitors, anti-foaming agents and dyes.

Examples are given below for preparing preparations having a fungicidal and bactericidal action: a) Granules

5 g of a compound of the formula 1, for example 2-bromo-N-cyclopropyl-acetamide or 2-bromo-N-cyclopropyl-Nn-propylacetamide, were dissolved in 10 g of an aromatic solvent, for example with a boiling point between 185 and 213 ° C.

This solution was then sprayed onto 90 g of crushed, well-sieved, pumice (grain size 0.3-1 mm) using 8003737 8

ft. J

a common technique.

b) Concentrated emulsion.

25 parts of a compound according to the invention of the formula I, for example 2-bromo-N-cyclopropyl-acetamide or 2-bromo-N-cyclopropyl-Nn-propyl-acetamide, were mixed with 30 wt. parts of isoctylphenyloctaglycol ether and 45 wt. parts of a petroleum fraction with a boiling range between 210 and 280 ° C (D2q: 0.92). This concentrated preparation was diluted with water to obtain the desired concentration.

c) wettable powder.

50 parts by weight of a compound according to the invention of the formula 1, for example 2-bromo-N-cyclo-15-propyl-acetamide or 2-bromo-N-cyclopropyl-N-propyl-acetamide, were mixed with 2 wt. parts of sodium lauryl sulfate, 3 parts of sodium lignin sulfonate and 45 parts of kaolinite. This concentrated preparation can be diluted with water to the desired concentration.

20 d) Seed preparation.

45 parts of a compound according to the invention of the formula I, for example 2-bromo-N-cyclo-propyl-acetamide or 2-bromo-N-cyclopropyl-Nn-propyl-acet-amide, were mixed with 1.5 parts. parts of diamylphenol decaglycol etherethylene oxide adduct, 2 parts of a thin liquid lubricating oil, 51 parts of fine talc and 0.5 parts of rhodamine B as a dye. This mixture was then milled in a contraplex mill at 10,000 revolutions per minute until an average particle size of less than 20 microns was obtained. The dry powder obtained has good adhesion and can be applied to seeds, for example by mixing in a slow-rotating vessel for 2 to 5 minutes.

Other conventional forms, such as paints useful for treating plant wounds, are also included in the invention.

8003737 * 9

In the following examples, room temperature is between 20 and 30 ° C unless otherwise indicated.

Example I; 2-bromo - N-cyclopropylacetamide.

6.92 ml (0.1 mol) cyclopropylamine was mixed with 13.9 ml (0.1 mol) triethylamine in 250 ml methylene chloride and this mixture was cooled to 0 ° C. Then, with stirring and for 0.75 hours, 8.75 ml (0.1 mol) of 2-bromoacetyl bromide dissolved in 50 ml of methylene chloride was added dropwise, the temperature of the reaction mixture being cooled to 0 ° by external cooling. C loved. The temperature of the mixture was then allowed to rise to room temperature and stirred for an additional 18 hours. The reaction mixture was then worked up by washing it twice with 50 ml portions of a saturated aqueous sodium bicarbonate solution, then 50 ml of a sodium chloride solution, drying over anhydrous sodium sulfate, filtering and evaporating the filtrate under reduced pressure to give a tan solid product which, after recrystallization from a mixture of hexane and methylene chloride (9: 1), gave the title compound as a tan compound having a melting point of 114-116 ° C.

Example II: 2-chloro-N-cyclopropyl-acetamide.

Repeating the procedure described in Example I, however, using an approximately equivalent amount of 2-chloroacetyl chloride instead of 2-bromo-acetyl bromide, there is obtained 2-chloro-N-cyclopropyl-acetamide, m.p. 84- 85 ° C.

Example III: 2-Bromo-N-cyclopropyl-N-n-propyl-acetamide.

6 g (0.06 mole) of N-cyclopropyl-n-propylamine and 6.12 g (8.6 ml; 0.06 mole) of triethylamine were placed in about 150 ml of methylene chloride in a vessel equipped with a stirrer. der, gas inlet pipe and an addition funnel. To this was added 12.3 g (5.3 ml; 0.06 mol) of α-bromoacetyl bromide in 20 ml of methylene at a temperature of between 20 and 25 ° C, for 40 minutes, with introduction of dry nitrogen and with stirring. -35 chloride and then stir the reaction mixture for an additional hour.

The mixture was then washed three times with 30 ml portions of 8003737 ". * 10 10% hydrochloric acid, three times with 30 ml portions of a 10% aqueous sodium bicarbonate solution and finally twice with 30 ml portions of an aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and distilled off the solvent to give 5 the crude title compound is obtained, which is purified by distillation at 100 ° C and 0.2 mm Hg using a ball-tube apparatus.

NMR (δ in CDCl3): 0.80 (multiplet; 7H); 1.52 (multiplet; 2H); 3.26 (triplet; 2H); 4.04 (singlet; 2H).

The N-cyclo-propyl-n-propylamine used as starting material was obtained by reaction of cyclopropylamine with propionyl chloride and reduction of the thus obtained N-cyclopropyl-propylamide (melting point: 39-41 ° C) with borane in tetrahydrofuran.

Example IV

According to the procedure of Example III, but instead of the N-cyclopropyl-n-propylamine, an approximately equivalent amount of a) N-cyclopropyl-methylamine, - b) N-cyclopropyl-ethylamine; c) N-cyclopropyl-n-butylamine or d) N-cyclopropyl-sec-butylamine, were used in a corresponding manner, respectively a) 2-bromo-N-cyclopropyl-N-methyl-acetamide; b) 2-bromo-N-cyclopropyl-N-ethyl-acetamide; c) 2-Bromo-N-cyclopropyl-N-n-butyl-acetamide and d) 2-Bromo-N-cyclopropyl-N-sec-butyl-acetamide.

Product d) gave the following data: 30 NMR (in CDCl 3) s 4.13 (singlet; 2H); 3.20 (duplicate, coupling constant 1.16; 2H); 2.80 (multiplet; 1H); 0.7-1.0 (duplicate plus multiplet; 10H).

35 8003737

Claims (24)

A method for preventing or controlling phytopathogenic fungi and bacteria, characterized in that a fungicidally or bactericidally effective amount of one or a number of compounds of the formula 1, in which these fungi or bacteria or the area in which they are located, is X represents a halogen atom with a sequence number from 17 to 35 and R represents a hydrogen atom or an alkyl group with at most 4 carbon atoms, wherein if R is an alkyl group with at most 4 carbon atoms X represents a bromine atom. Method according to claim 1, characterized in that plants, seeds and / or soil are treated. 3. Process according to any one of the preceding claims, characterized in that a compound of formula 1 is used in which R is an alkyl group with at most 4 carbon atoms. Process according to any one of the preceding claims, characterized in that a compound of formula 1 is used in which R represents a straight-chain alkyl group with at most 4 carbon atoms. 5 Rj is an n-propyl group, Process according to claim 4, characterized in that a compound of formula 1 is used, in which R is an n-propyl group. 6. Process according to claims 1-3, characterized in that a compound of formula 1 is used in which R is a Branched alkyl group with at most 4 carbon atoms. Process according to claim 1 or 2, characterized in that a compound of formula 1 is used, in which R is a hydrogen atom. 8. Process according to claim 1, 2 or 7, characterized in that a compound of formula 1 is used in which X is a bromine atom. Process according to any one of the preceding claims, characterized in that the development of fungi is prevented or combated. 10. A method according to claim 9, characterized in that the fungus in question is a Phytophthora, istilaginales, 8003737 »Fusarium, Pythium, Stereum, Thielaviopsis, Fhoma, Venturia, Pyricularia or Verticillium fungus. 11. A process for preparing a preparation having a fungicidal or bactericidal effect, characterized in that one or a number of compounds according to the invention of the formula 1, as defined in claim 1, is introduced into a dosage form suitable for such use. 12. Process according to claim 11, characterized in that an inert carrier suitable for fungicide or bactericide is also included in the preparation. Process according to claim 11 or 12, characterized in that a preparation is prepared which contains 0.01-90% by weight of one or more compounds of the invention according to the formula 1. Process according to claim 13, characterized in that a concentrated preparation is prepared containing 2-80% by weight of one or more compounds of the invention according to the formula 1. 15. A method according to claim 13, characterized in that an applicable preparation is prepared containing 0.01-10% by weight of one or more compounds according to the invention of the formula 1. 16. Process according to claims 11-15, characterized in that one or more compounds of the formula I are used in which R represents a straight-chain alkyl group with at most 4 carbon atoms. Process according to Claim 16, characterized in that a compound of formula 1 is used in which R is an n-propyl group. 18. Process according to claims 11-15, characterized in that one or more compounds according to the invention of formula 1 are used in which X a bromine atom and R represent a hydrogen atom. 19. Compounds of formula la, wherein R 1 represents a hydrogen atom, a straight chain alkyl group having 2 to 4 carbon atoms or a branched chain alkyl group having 4 carbon 8003737 * atoms. Compounds according to claim 19, wherein Rj is a hydrogen atom, Compounds according to claim 19, wherein Compounds according to claim 18, wherein R 1 represents a sec.-butyl group. 23. A process for riding a cyclic compound, characterized in that a compound of formula la as defined in claim 19 is prepared by compounding a compound of formula 2, wherein R 1 has a meaning defined in claim 19. react with 2-bromoacetyl bromide. 24. Methods as described in description 15 and / or examples Jf ^ 7 '8003737 * -, * CHe I "CH— N —CO - CHjX -I CHj CH2 ^" CH — N - CO — CHjBr, / la CHS CHj ^ CH - NH - R, 2 0¾ 8003737 SANDOZ AG in Basel, Switzerland