MXPA99004980A - New benzoylphenylurea insecticides and methods of using certain benzoylphenylureas to control cockroaches, ants, fleas, and termites - Google Patents

Abstract

Compounds of formula (I) wherein R1 and R2 are H, methyl, or ethyl, have unexpected activity against cockroaches, ants, fleas, and termites. Compounds wherein at least one of R1 and R2 is methyl or ethyl are novel.

Description

NEW INSECTICIDES OF BENZOILFENI UREA AND METHODS TO USE CERTAIN BENZOYLPHENILUREAS TO CONTROL COCKROACHES, ANTS. FLEAS, AND TERMITES BACKGROUND OF THE INVENTION This invention provides novel benzoyl phenylurea insecticides and novel methods for inhibiting cockroaches, ants, fleas, and termites. A broad class of benzoyl phenylurea insecticides is described in U.S. Patent No. 3,748,356. European Patent Application 263438 discloses that certain N-substituted phenyl-N'-substituted benzoyl-N-methylureas are highly safe for beneficial aquatic crustaceans while exhibiting insecticidal activities equal to or greater than non-alkylated analogues. Hexaflumuron, a commercially significant benzoylphenylurea, is described in U.S. Patent No. 4,468,405. The use of hexaflumuron in methods for controlling termites is described in WO 93/2401 1. The use of hexaflumuron to control cockroaches is described in WO 94/03066. The compound N- [3,5-dichloro-2-fluoro-4- (1, 1, 2,3,3,3-hexafluoropropoxy) fenii] -N '- (2,6-difluorobenzoyl) urea is described DE 3827133 and European Patent Application A 243,790, but there was no description of the unexpected activity of the compound against cockroaches, ants, fleas, and termites. We have discovered that certain benzoyl phenylurea compounds, some of which are novel, have substantially greater activity against cockroaches, ants, fleas, and termites than would have been expected based on comparison with the closest prior art, ie, hexaflumuron. . Another significant property of the novel compounds of the invention is their surprisingly low toxicity to Daphnia.

BRIEF DESCRIPTION OF THE INVENTION The invention provides a method for controlling cockroaches, ants, fleas, or termites which comprises delivering an effective amount of a compound of the formula (I): wherein R1 and R2 are H, methyl, or ethyl, in a location where control of cockroaches, ants, fleas, or termites is desired. More specifically, the invention provides: A method for controlling cockroaches which comprises a compound of formula (I), in an amount effective to control cockroaches, to a location where control of cockroaches is desired; A method for controlling ants which comprises delivering a compound of the formula (I), in an effective amount to control ants, to a location where ant control is desired.

A method for controlling fleas which comprises delivering a compound of formula (1), in an effective amount to control fleas, to a location where flea control is desired; and A method for controlling termites which comprises delivering a compound of formula (1), in an amount effective to control termites, to a location where termite control is desired. The invention also provides novel compounds of the formula (II): wherein R1 and R2 are H, methyl, or ethyl, provided that at least one of R1 and R2 is methyl or ethyl.

DETAILED DESCRIPTION OF THE INVENTION Intermediate 1: 2,6-difluorobenzoyl isocyanate A mixture of 0.52 g of 2,6-difluorobenzamide and 0.33 ml of oxalyl chloride was stirred under reflux in 15 ml of 1,2-dichloroethane overnight. The solvent was removed under vacuum and 10 ml of 1,2-dichloroethane was added. The solvent was removed under vacuum to leave the title intermediate, which could be used directly or dissolved in 1,2-dichloroethane and stored for future use.

Intermediate 2: 3l5-dichloro-4- (1, 1, 2,3,3,3-hexafluoropropoxy) aniline X522838 To a solution of 2.0 g of 4-amino-2,6-dichlorophenol in 40 mL of tetrahydrofuran at room temperature was added 0.7 g of 87% potassium hydroxide. The mixture was heated to 40 ° C and stirred for 10 minutes, then cooled to 0 ° C. Hexafluoropropene was bubbled in for 5 minutes, and the mixture was stirred at room temperature overnight. It was then concentrated under vacuum until dry. The residue was dissolved in 50 mL of dichloroethane and washed with 20 mL of brine solution. The organic layer was separated and filtered through phase separation filter paper and then concentrated under vacuum to an oil. This was diluted with 50 mL of dichloromethane and 50 mL of heptane and reconcentrated to give 3.05 g of 3, 5-dichloro-4- (1, 1, 2,3,3,3-hexafluoropropoxy) aniline as a brown oil. The nmr spectrum of proton and F19 were consistent with the proposed structure.

Intermediate 3: 3,5-dichloro-2-fluoro-4- (1, 1 .2.3.3,3-hexafluoropropoxy) aniline X522838 X549988 To a solution of 2.50 g of 3,5-dichloro-4- (1,1-2,3,3,3-hexafluoropropoxy) aniline in 60 mL of acetonitrile under a nitrogen atmosphere at room temperature was added 2.57 g. of 1-chloromethyl-4-fluoro-1,4-diazoniabicyclo [2.2.2] octane bis (tetrafluoroborate) SELECTFLUORlm (Air Products) as a portion over a period of 10 minutes. The mixture was heated at 70 ° C for a period of one hour, then cooled to room temperature and poured into 100 mL of a saturated sodium bicarbonate solution. The product was extracted with 150 mL of ethyl acetate. The organic layer was separated, washed with 50 mL of brine solution, separated and dried over magnesium sulfate. The magnesium sulfate was removed by filtration, and the filtrate was concentrated under vacuum to give 2.52 g of a dark oil. The product was chromatographed using a Michel-Miller low pressure silica gel column, eluted with heptane / ethyl acetate, 6: 1. Similar fractions were combined and concentrated in vacuo to a brown oil, 1.19 g. The proton and nmr F19 spectra were consistent with the proposed structure. Anal, caled C9H4CÍ2F7N1O1; C, 31.24; H, 1 17; N, 4.05. Found: C, 31.52; H, 1 fifteen; N, 4.02.

Intermediate 4: 3,5-dichloro-2-fluoro-4- (1,1, 2,3,3,3-hexafluoropropoxy) -N-ethyl aniline H X539988 X572213 To a solution of 0.28 g of 3,5-dichloro-2-fluoro-4- (1, 1, 2,3,3,3-hexafluoropropoxy) aniline in 8 mL of glacial acetic acid at room temperature under a nitrogen atmosphere slowly added 0.31 g of sodium borohydride. The addition was carried out for a period of 1.5 hours through a funnel of addition of solids between 25-34 ° C with cooling of ice water. The mixture was stirred at room temperature overnight. Then 80 mL of water was added to the reaction mixture and the pH was carefully adjusted to 7 by the addition of solid sodium carbonate. The product was extracted with 80 mL of ethyl acetate. The organic layer was separated, washed with brine solution, separated, and dried over magnesium sulfate. The magnesium sulfate was removed by filtration, and the filtrate was concentrated under vacuum to give a brown oil 0.29 g. The product was chromatographed using a Michel-Miller low pressure silica gel column eluted with heptane / ethyl acetate 9: 1. The similar fractions were combined and concentrated under vacuum to give 0.19 g of a brown oil. H1-NMR d 1.28 (t, 3H), 3.17 (q, 4H), 3.95 (bs, 1 H), 4.94-5.21 (md, 1 H), 6.59 (d, 1 H). Anal, caled CnH8Cl2F7N: C, 35.31; H, 2.16; N, 3.74. Found: C, 35.32; H, 2.14; N, Preparation of Products Compound 1: N-r3.5-dichloro-2-fluoro-4- (1.1, 2,3,3, 3-hexafluoropropoxy) -phenyl] -N '- (2,6-difluorobenzoyl) urea X549988 X550007 To one of 1.31 g of 3,5-dichloro-2-fluoro-4- (1, 1, 2,3,3,3-hexafluoropropoxy) aniline in 5 mL of 1,2-dichloroethane under a nitrogen atmosphere at room temperature At room temperature, 0.87 g of 2,6-difluorobenzoyl isocyanate dissolved in 10 mL of dichloroethane was added dropwise in a period of 10 minutes. The mixture was stirred, heated at 40 ° C for a period of one hour, then concentrated under vacuum to a 2.0 g brown solid. The mixture was chromatographed using a Michel-Miller low pressure silica gel column eluted with dichloromethane / heptane 4: 1. The similar fractions were combined and concentrated under vacuum to give 1.67 g of a light brown solid, mp 156-7 °. C. The nmr spectra of proton and F19 were consistent with the proposed structure. Anal, caled C 17 H 7 Cl 2 F 9 N 2 O 3: C, 38.58; H, 1.33; N, 5.29. Found: C, 38.64; H, 1.40; N, 5.44.

Compound 2: N-r3,5-dichloro-2-fluoro-4- (1, 1, 2,3,3,3-hexafluoropropoxy) fenip-N '^ (2,6 ^ difluorobenzoyl) ^ N ^ ethylurea X572213 X570143 To a solution of 1.00 g of 3,5-dichloro-2-fluoro-4- (1, 1, 2,3,3,3-hexafluoropropoxy) -N-ethyl aniline in 2 mL of 1, 2-dichloroethane under a nitrogen atmosphere at room temperature was added 0.54 g of 2,6-difluorobenzoyl isocyanate dissolved in 6 mL of dichloroethane per drop over a period of 10 minutes. The mixture was stirred and heated at 40 ° C for a period of 1.5 hours. Analysis by thin layer silica gel chromatography, heptane / ethyl acetate 4: 1 indicated incomplete reaction. To the mixture was added 0.13 g of 2,6-difiuorobenzoyl isocyanate in 1.5 mL of 1,2-dichloroethane, and the mixture was heated at 40 ° C for 2.5 hours. Analysis by TLC indicated complete reaction. The reaction mixture was concentrated under vacuum to give an oil, 1.64 g, which was chromatographed using a Michel-Miller low pressure silica gel column eluted with heptane / ethyl acetate 4: 1. The similar fractions were combined and concentrated under vacuum to give a white solid, 0.87 g, mp 106-14 ° C. The nmr proton and mass spectra were consistent with the proposed structure. Anal, caled C, 40.95; H, 1 .99; N, 5.03. Found: C, 40.89; H, 1.92; N, 5.03.

Compound 3: N-f3,5-dichloro-2-fluoro-4- (1, 1, 2,3,3,3-hexafluoropropoxy) fenip-N- (2,6-difluorobenzoyl) -N'-ethyl urea X550007 X574158 Dissolve 1.65 g of N- [3,5-dichloro-2-fluoro-4- (1, 1, 2, 3,3,3-hexafluoropropoxy) phenyl] -N '- = (2,6-difluorobenzoyl) urea in 10 mL of N, N = dimethylformamide and add 0.22 g of 87% potassium hydroxide. Cool to 0 ° C and add 0.97 g of iodoethane. Stir at 0 ° C for a period of 7 hours. Store in a refrigerator at 0 ° C for one night. Analysis by thin layer chromatography of dichloromethane on silica gel shows product that is formed with remaining starting urea. The reaction was treated as before at 0 ° C for the next two days. Additional amounts of iodoethane, 1.94 g, and 0.10 g of 87% potassium hydroxide were added. Pour the reaction mixture into 50 mL of brine solution and extract with 80 mL of ethyl acetate. Separate the organic layer and dry in magnesium sulfate. Filter the drying agent and concentrate the filtrate under vacuum to a red oil, 2.63 g. Chromatograph using a column of low-pressure silica gel Michel-Miller and elute with heptane / dichloromethane, 2: 1. Collect the similar fractions and concentrate under vacuum to 0.18 g of a pink solid, mp 105-06 ° C. The nmr proton and mass spectra were consistent with the proposed structure. Anal, caled C 9HuCI2F9N2O3: C, 40.95; H, 1 .99; N, 5.03. Found: C, 40.99; H, 1.85; N, 4.98.

Biological Activity German cockroach of 2nd molt (Blattella germanica) I fl Exposure by ingestion of low dose, continuous (corn flour treated) Proportions: 0.19, 0.78, 3.12, 12.5, 50, 200 ppm what hexaflumuron.

German 2nd Dwarf Cockroach (Blattella germanica) Exposure to limited ingestion (48 hr) to treated maize meal. Proportions: 1, 10, 100, 1000, 10000 ppm LCso (ppm) Compound 21 days 42 days Compound 1 < 22.2 < 9.1 Compound 2 21 .1 12.8 Hexaflumuron > 10,000 > 10,000 Under limited exposure, Compounds 1 and 2 were more potent than hexaflumuron in both 21 and 42 days after exposure.

Cat flea (Ctenocephalides felis) Continuous exposure of larva to treated medium, impact on the exit of the subsequent adult.

Proportions: 0.1, 1.0, 10, 100, 1000 ppm LCso Compound (ppm) LC90 (ppm) Compound 1 2.8 22 Compound 2 12.7 18.6 hexaflumuron 65.7 333.5 Compounds 1 and 2 were both much more effective than hexaflumuron against cat fleas.

Underground Termite (Reticulitermes flavipes) Continuous exposure (56 days) to treated paper. Proportions: 0.78, 3.12, 12.5, 50, 200 ppm LC50 (ppm) LT5Q (days) for treatment Compound 35 days 56 days with 200 ppm Compound 1 31 .2 < 0.78 27.6 Compound 2 < 0.78 < Q.7S not calculated Hexaflumuron > 200 1 .3 33.8 Low exposure < continued, Compounds 1 and 2 were more potent and faster acting than hexaflumuron.

Underground Termite (Reticulitermes flavipes) Limited exposure (7 days) with mortality determined at 14, 28, 42 and 56 days 33399 T) Under limited exposure, a high proportion of Compound 1 induced more mortality more prematurely than hexaflumuron.

Ant studies Ant bait studies were carried out in the laboratory with imported Red Fire Ant (RIFA). { Solenopsis invicta) and Ant Pharaoh (Monomorum pharaonis). Chitin synthesis inhibitors, such as the compounds of the invention, control ants by killing the larva and / or pupa that molts and potentially preventing the incubation of eggs. Because adults are not affected, control is measured by effects on the offspring. The studies involved bait exposure of 3-4 days. These limited exposure studies more accurately represent actual world bait availability than continuous exposure. specified reduction of pups. Percentage of reduction of pups reached at the end of the study listed in parentheses. n Compound 1 is significantly more potent than hexaflumuron based on a short exposure study with RIFA.

Activity against Daphnia 48-hour exposure to treated water.

Compounds 2 and 3, the alkylated derivatives of Compound 1, were much less active against Daphnia than Compound 1 and hexaflumuron; this is surprising since the activities of Compounds 1, 2, and 3 in cockroaches are very similar.

Formulations In order to facilitate the application of the compounds of the formula (!) To the desired location, or to facilitate storage, transport or handling, the compound is normally formulated with a carrier and / or surface tension agent. A carrier in the present context is any material with which the compound of the formula (I) (active ingredient) is formulated to facilitate application to the site, or storage, transport or handling. A carrier can be a solid or a liquid, including a material that is normally gaseous but which has been compressed to form a 1 -1 liquid. Any of the carriers normally used or known in the formulation of insecticidal compositions can be used. The compositions according to the invention contain from 0.0001 to 99.9% by weight of active ingredient. Preferably, the compositions according to the invention contain from 0.001 to 10.0% by weight of active ingredient although proportions as low as 0.0001% may be useful in some circumstances. Suitable solid carriers include natural and synthetic clays and silicates, for example, natural silicas such as diatomaceous earths; magnesium silicates, for example talcs; magnesium aluminum silicates, for example attapulgites and vermiculites; aluminum silicates, for example kaolinites, montmorillonites and micas; calcium carbonate; calcium sulfate; ammonium sulphate; synthetic oxides of hydrated silicon and synthetic calcium or aluminum silicates; elements, for example carbon and sulfur; natural and synthetic resins, for example coumarone resins, polyvinyl chloride, and styrene polymers and copolymers; solid polychlorophenols; betumen; waxes; agar; and solid fertilizers, for example superphosphates. Cellulose-based materials, for example wood, sawdust, agar, paper products, cotton linters, or Methocel®, as well as the other solid carriers are attractive by themselves or at least non-repellent to termites are particularly suitable and preferred. Mixtures of different solids are frequently suitable. For example, a mixture of wood powder and agar formulated as a solid containing moisture would be preferable. ? 1 Suitable liquid carriers include water; alcohols, for example isopropanol and glycols; ketones, for example acetone, methyl ethyl ketone, methyl isobutyl ketone, isophorone and cyclohexanone; aromatic or aliphatic hydrocarbons, for example benzene, toluene and xylene; fractions of petroleum, for example kerosene and light mineral oils; chlorinated hydrocarbons, for example carbon tetrachloride, perchlorethylene and trichlorethylene; polar organic liquids, such as dimethyl formamide, dimethyl acetamide, dimethyl sulfoxide and N-methylpyrrolidone; oils derived from plants, such as corn oil and peanut oil. Mixtures of different liquids are frequently suitable, for example a mixture of isophorone with a polar organic solvent such as N-methylpyrrolidone, as are mixtures of solid and liquid carriers. The pesticidal compositions are often formulated and transported in a concentrated form which is subsequently diluted by the user before application. The presence of small amounts of a carrier which is a surface tension agent facilitates this dissolution process. Thus, it is suitable to use at least one carrier in such a composition which is a surface tension agent. For example, the composition may contain at least two carriers, at least one of which is a surface tension agent. A surface tension agent may be an emulsifying agent, a dispersing agent or a wetting agent; it can be non-ionic or ionic. Examples of suitable surface tension agents include the sodium or calcium salts of polyacrylic acids and lignin sulphonic acids; the condensation of fatty acids or aliphatic amines or amides containing l? at least 12 carbon atoms in the molecule with ethylene oxide and / or propylene oxide; fatty acid esters of glycerol, sorbitol, sucrose or pentaerythritol; condensates of these with ethylene oxide and / or propylene oxide; condensates of these with ethylene oxide and / or propylene oxide; condensation products of fatty alcohol or alkyl phenols, for example p-octylphenol or p-octylcresol, with ethylene oxide and / or propylene oxide; sulfates or sulfonates of these condensation products; alkali metal or alkaline earth metal salts, preferably sodium salts, or sulfuric or sulfonic acid esters containing at least 10 carbon atoms in the molecule, for example sodium lauryl sulfate, secondary sodium alkyl sulphates, sodium salts of sulfinated castor oil, and sodium alkylaryl sulphonates such as dodecylbenzene sulfonate; and polymers of ethylene oxide and copolymers of ethylene oxide and propylene oxide. Pesticidal compositions can be formulated for example as wettable powders, powders, granules, ropes, solutions, emulsifiable concentrates, emulsions, concentrates and aerosols in suspension. Wettable powders usually contain 25, 50 or 75% by weight of active ingredient and usually contain in addition to the inert solid carrier, 3-10% by weight of a dispersing agent and, when necessary, 0-10% by weight of stabilizer ( es) and / or other additives such as penetrants or adherents. The powders are usually formulated as a powder concentrate having a composition similar to that of a T7 wettable powder. but without a dispersant, and are diluted in the field with additional solid carrier to give a composition that usually contains 0.5-10% by weight active ingredient. The granules are usually prepared to have a size between 10 and 100 mesh BS (1,676-0,152 mm), and can be manufactured, for example, by agglomeration or impregnation techniques. Generally, the granules will contain 0.01 -75% by weight of active ingredient and 0-10% by weight of additives such as stabilizers, surfactants, slow release modifiers and agglutination agents. The so-called "dry powders with fluidity" consist of relatively small granules having a relatively high concentration of active ingredient. Of particular interest in current practice are granular formulations dispersible in water. These are in the dry form, hard granules that are essentially free of dust, and are resistant to wear by handling, thus minimizing dust formation. Upon contact with water, the granules disintegrate rapidly to form stable suspensions of the particles of active material. Such formulation contains 90% or more by weight of finely divided active material, 3-7% by weight of a mixture of surfactants, which act as wetting, dispersing, suspending and agglutinating agents, and 1-3% by weight of a carrier finely divided, which acts as a re-suspension agent. Sebs are prepared by, for example, combining a mixture of a suitable food source, such as sawdust for termites or grain or food for cockroaches, with an amount of active ingredient I R enough to provide the desired result; for example, from about 0.001 to about 20% by weight of active ingredient and forming the mixture into a paste by the addition of about 1% to 5% of a water-based binder such as agar. The mixture as a paste can be applied as it is or it can be packed in a housing such as a wooden pin with an outside hole or a plastic tube or place of seals. In other embodiments, sheets of paper or cardboard can be sprayed with or bathed in a diluted formulation containing the active ingredient. Sebs are a preferred embodiment of the present invention. Emulsifiable concentrates usually contain, in addition to a solvent and, when necessary, a co-solvent, 10-50% by weight by volume of emulsifiers and 0-20% by weight by volume of other additives such as stabilizers, penetrants and corrosion inhibitors. Suspension concentrates are usually compounded to obtain a product with stable, non-sediment fluidity that usually contains 10-75% by weight of active ingredient, 0.5-15% by weight dispersion agents, 0.1-10% by weight of dispersants, suspending such as protective colloids and thixotropic agents, 0-10% by weight of other additives such as defoamers, corrosion inhibitors, stabilizers, penetrants and adherents, and water or an organic liquid in which the active ingredient is substantially insoluble; certain organic solids or inorganic salts may be present dissolved in the formulation to help prevent settling or as anti-freeze agents for water. 1 Q Aqueous dispersions and emulsions are compositions obtainable by dissolving a wettable powder or a concentrate with water. The emulsions mentioned may be of the water-in-oil or oil-in-water type, and may have a thick consistency such as "mayonnaise". The method for applying a compound of Formula (I) to combat termites comprises applying the compound, conveniently in a composition comprising the compound of Formula (1) and a carrier as described above, to a site or area to be treated for Termites, such as soil or wood, already subject to infestation or attack by termites or that are intended to protect from termite infestation. The active ingredient is, of course, applied in an amount sufficient to effect the desired action of combating termite infestation. This dosage depends on many factors, including the carrier employed, the method and conditions of application, whether the formulation is present in place in the form of a film, or as discrete particles or as a tallow, the film thickness or particle size, the degree of infestation by termites, and the like. The proper consideration and resolution of these factors to provide the necessary dose of the active ingredient in the place to be protected are within the skill of those skilled in the art. In general, however, the effective dose of the compound of the invention at the site to be protected-that is, the dose to which the thermite has access-is in the order of 0.001 to 1.0% based on the total weight of the composition, although under some circumstances effective concentration Ift It can be as small as 0.0001% or as large as 2%, on the same basis. When used to control cockroaches, it is preferred to use the active ingredient in a treated tallow or as a surface treatment. When used to control ants, it is preferred to use the active ingredient in a liquid tallow or granular tallow. When used to control termites, it is preferred to use the active ingredient in a cellulose based tallow. When used to control fleas, it is preferred to use the active ingredient on a treated substrate. Suitable formulations include granules for cockroach granules, in paste, or powder, sprays for cockroaches and / or fleas SP or WP, tallow for termites with cellulose base, tallow for liquid or granular ants, treatments for topical animals or through food against fleas.

Claims (9)

1. ??
2. CLAIMS 1. A method for controlling cockroaches comprising a compound of the formula (I) wherein R1 and R2 are H, methyl, or ethyl, in an amount effective to control cockroaches, to a location where cockroach control is desired. 2. A method for controlling ants that comprises delivering a compound of the formula (I) wherein R1 and R2 are H, methyl, or ethyl, in an effective amount to control ants, to a location where ant control is desired.
3. 3. A method for controlling fleas comprising delivering a compound of the formula (I) wherein R1 and R2 are H, methyl, or ethyl, in an amount effective to control fleas, 9? to a location where flea control is desired.
4. 4. A method for controlling termites comprising delivering a compound of the formula (I) wherein R1 and R2 are H, methyl, or ethyl, in an amount effective to control termites, to a location where termite control is desired.
5. 5. A compound of the formula (II) wherein R1 and R2 are H, methyl, or ethyl, provided that at least one of R1 and R2 is methyl or ethyl.
6. 6. A pesticidal composition comprising an effective amount of a compound of claim 5 in combination with a carrier.
7. 7. A tallow for cockroaches comprising a compound of claim 5 in a conventional tallow.
8. 8. A tallow for ants comprising a compound of claim 5 in combination with a conventional tallow.
9. 9. A tallow for termites comprising a compound of claim 5 in combination with a conventional tallow.