Thiophenylureas, their production and use

The present invention relates to benzoylurea derivatives of the formula: ##STR2## wherein X.sup.1 is hydrogen or halogen; X.sup.2 is halogen; Y.sup.1, Y.sup.2 and Y.sup.3 are hydrogen, halogen or alkyl, whereby at least one of Y.sup.1, Y.sup.2 and Y.sup.3 is other than hydrogen; and R is hydrogen or a group represented by the formula --CF.sub.a Z.sub.b H.sub.(3-a-b) wherein a and b are 0, 1, 2 or 3, with a+b.ltoreq.3 and Z is halogen, which are novel compounds possessing excellent insecticidal activities. The invention also related to a process for producing the same, and to insecticides containing the same.
Some of N-(2,6-dihalogenobenzoyl)-N'-(substituted-phenyl)urea derivatives which are benzoylurea derivatives have heretofore been known to possess insecticidal activity (e.g., British Pat. Nos. 1324293 and 1501607, U.S. Pat. No. 4,277,499, European Patent Publication Nos. 71279 and 88343, etc.). However, the insecticidal effect produced by the benzoylurea derivatives which have been concretely synthesized is far from being satisfactory.
The present inventors, after extensive research and investigation into a compound exhibiting excellent insecticidal effect, succeeded in the synthesis of novel benzoylurea derivatives of the formula [I], which have not concretely been synthesized so far, through the reaction of a compound of the formula: ##STR3## with a compound of the formula: ##STR4## wherein X.sup.1, X.sup.2, Y.sup.1, Y.sup.2, Y.sup.3 and R are as defined hereinbefore; and one of W.sup.1 and W.sup.2 is --N.dbd.C.dbd.O (isocyanato) and the other is amino. The inventors found that these compounds [I] unexpectedly exhibit insecticidal (particularly, molt inhibitory) and ovicidal activities superior to those of known compounds having analogous structure thereto and also are of lessened toxicities toward mammals and fishes, thus finding application as a safe insecticide exerting less adverse effects on the environment.
Thus, the present invention relates to:
(1) Benzoylurea derivatives [I],
(2) A process for producing the benzoylurea derivatives [I], which comprises reacting a compound of the formula: ##STR5## wherein X.sup.1 and X.sup.2 are as defined hereinbefore, with a compound of the formula: ##STR6## wherein Y.sup.1, Y.sup.2, Y.sup.3 and R are as defined hereinbefore, (3) A process for producing the benzoylurea derivatives [I], which comprises reacting a compound of the formula: ##STR7## wherein X.sup.1 and X.sup.2 are as defined hereinbefore, with a compound of the formula: ##STR8## wherein Y.sup.1, Y.sup.2, Y.sup.3 and R are as defined hereinbefore, and (4) Insecticidal compositions characteristically featured by containing the benzoylurea derivative [I].
In the above formulae, X.sup.1 is hydrogen or halogen. As the halogen represented by X.sup.1, there are used, for example, Cl, Br, F and I. Preferable examples of X.sup.1 include, for example, hydrogen, Cl or F. X.sup.2 is halogen. As the halogen represented by X.sup.2, there are used those as mentioned for X.sup.1. Preferable examples of X.sup.2 include, for example, Cl and F. Y.sup.1, Y.sup.2 and Y.sup.3 are hydrogen, halogen or alkyl, whereby at least one of Y.sup.1, Y.sup.2 and Y.sup.3 is other than hydrogen. As the halogen represented by Y.sup.1, Y.sup.2 and Y.sup.3, there are used, for example, those as mentioned for the above X.sup.1. As the alkyl represented by Y.sup.1, Y.sup.2 and Y.sup.3, there are used, for example, straight-chain or branched chain lower alkyl of 1 to 4 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl and t-butyl. Preferable examples of Y.sup.1, Y.sup.2 and Y.sup.3 include, for example, hydrogen, Cl, F and methyl. R is hydrogen or a group represented by the formula --CF.sub.a Z.sub.b H.sub.(3-a-b) wherein a and b are 0, 1, 2 or 3, with a+b.ltoreq.3 and Z is halogen. As the halogen represented by Z, there are used, for example, those as mentioned for X.sup.1. In the case of b being not less than 2, the halogen represented by Z may be the same or different. As concrete examples of the group represented by the formula --CF.sub.a Z.sub.b H.sub.(3-a-b), there are used, for example, CF.sub.3, CCl.sub.3, CBr.sub.3, CI.sub.3, CF.sub.2 Cl, CF.sub.2 Br, CFCl.sub.2, CFI.sub.2, CFBr.sub.2, CFClBr, CCl.sub.2 Br, CClBr.sub.2, CHF.sub.2, CHFCl, CHFBr, CHClBr, CHCl.sub.2, CH.sub.2 F, CH.sub.2 Cl, CH.sub.2 Br and CH.sub.3. Preferable examples of R include, for example, CF.sub.3, CHF.sub.2, CHFCl, CHFBr and CHCl.sub.2.
Preferable examples of the benzoylurea derivatives [I] or the object products of the present invention include, for example, compounds represented by the formula: ##STR9## wherein X.sup.1a is F or Cl; X.sup.2a is F or Cl in the case of X.sup.1a being F, or hydrogen or Cl in the case of X.sup.1a being Cl; Y.sup.1a is Br, Cl, F or methyl; Y.sup.2a is hydrogen, Cl or methyl; and Z' is F or Cl, compounds represented by the formula: ##STR10## wherein X.sup.1a, X.sup.2a and Z' are as defined hereinbefore; Y.sup.1b is hydrogen or F; Y.sup.2b is Br, Cl, F or methyl; and Y.sup.3a is hydrogen, Cl, F or methyl, and compounds represented by the formula: ##STR11## wherein X.sup.1a, X.sup.2a and Z' are as defined hereinbefore; Y.sup.2c is Br, Cl or F; and Y.sup.3b is F or Cl. Particularly preferable examples of the derivatives [I] are, for example, compounds represented by the formula: ##STR12## wherein X.sup.2b is F or Cl; Y.sup.1c is F or Cl; and Y.sup.2d is hydrogen or Cl, compounds represented by the formula: ##STR13## wherein the symbols are as defined hereinbefore, compounds represented by the formula: ##STR14## wherein X.sup.2b and Y.sup.3b are as defined hereinbefore, and compounds represented by the formula: ##STR15## wherein the symbols are as defined hereinbefore.
The objective product [I] of the present invention can exist as isomers, when an asymmetric carbon is present in R, and may consist of individual isomers or a mixture thereof.
The benzoylurea derivatives [I] of the present invention possess enhanced insecticidal and ovicidal effects, and can produce adequate insecticidal and ovicidal effects in less used amount as compared with known analogous compounds. Besides offering the economical advantage that the applied amount can be reduced, the benzoylurea derivatives [I] of the present invention are exceedingly low in toxicity toward mammals and also low in fish toxicity, with less adverse effects on the environment, and are therefore effective for exterminating and preventing hatching of household insect pests, harmful insects parasitic on animals and plants, forest insect pests, etc. They demonstrate powerful insecticidal activities, particularly molt inhibitory activities against larvae, by allowing insect pests to directly contact, or to ingest, the compounds [I], for example, spraying them directly on animals and plants parasitized with insect pests. In addition, the compounds [I] of the present invention exhibit ovicidal and sterilizing activities and the like. The compounds [I] of the present invention, with their reduced phytotoxicity and lowered fish toxicity, provide combined characteristics of safety and advantage in utilizing for example as an agent for exterminating and preventing hatching of forest insect pests.
The compounds [I] of the present invention and insecticidal compositions containing them are effective for exterminating and preventing hatching of, for example, insect pests of the order Lepidoptera, such as Spodopteralitura, Plutella xylostella, Pieris rapae crucivora, Chilo suppressalis, Plusia nigrisigna, Halicoverpa assulta, Pseudaletia separata, Mamestra brassicae, Adoxophyes orana, Pleuroptya derogata, Cnaphalocrocis medinalis, Phthorimaea operculella, Hyphautria cunea and Lymantria dispar; insect pests of the order Coleoptera, such as Henosepilachna vigintioctopunctata, Aulacophora femoralis, Phyllotreata striolata, Oulema oryzae, Echinocnemus squameus, Leptinotorsa decemlineata, Lissorhoptrus oryzophilus and Anthonomus grandis; insect pests of the order Diptera, such as Musca domestica, Culex pipiens pallens, Tabanus trigonus, Hylemya antiqua and Hylemya platura; insect pests of the order Orthoptera, such as Locusta migratoria and Gryllotalpa africana; insect pests of Dictyoptera, such as Blattella germanica and Periplaneta fuliginosa; insect pests of the order Isoptera, such as Reticulitermes speratus; and nematodes, such as Aphelenchoides besseyi.
In utilizing the benzoylurea derivatives [I] of the present invention as an insecticide or/and ovicide, such derivatives may be formulated into the application forms which general agricultural chemicals can take; namely, one or more of the compounds [I], depending upon the purpose of application, are dissolved or suspended in a suitable liquid carrier, or mixed or adsorbed with an appropriate solid carrier to process them into the desired forms of preparations, such as emulsifiable concentrate (emulsion), oil or solvent preparation, wettable powder, powder, granule, tablet, spray and ointment. As the preferable forms of preparations, there are used, for example, emulsifiable concentrate, wettable powder, powder and granule. These preparations can be prepared, if desired, in accordance with per se known methods by adding, for example, emulsifying agents, suspending agents, spreaders, penetrants, wetting agents, tackifiers and stabilizers.
The proportion of the benzoylurea derivatives [I] contained in the insecticidal or/and ovicidal composition of the present invention, for example, is suitably in the range of 5 to 90 weight % in the case of emulsifiable concentrate and wettable powder, being appropriately in the region of 0.1 to 10 weight % in the case of oil or solvent preparation and powder, and is suitably in the range of 1 to 20 weight % in the case of granule, varying with the purpose of application, and these concentrations may be suitably altered according to the purpose of application. In applying the emulsifiable concentrate and wettable powder, for example, it is recommendable to dilute and extend (e.g., to 100 to 100000 times the original volume) them properly with water and the like.
Suitable examples of the liquid carrier which is used in the preparation of the insecticidal or/and ovicidal composition of the present invention include solvents, such as water, alcohols (e.g., methyl alcohol, ethyl alcohol, ethylene glycol, etc.), ketones (e.g., acetone, methyl ethyl ketone, etc.), ethers (e.g., dioxane, tetrahydrofurane, cellosolve, etc.), aliphatic hydrocarbons (e.g., gasoline, kerosene, light oil, fuel oil, machine oil, etc.), aromatic hydrocarbons (e.g., benzene, toluene, xylene, solvent naphtha, methylnaphthalene, etc.), halogenated hydrocarbons (e.g., chloroform, carbon tetrachloride, etc.), acid amides (e.g., dimethylformamide, dimethylacetamide, etc.), esters (e.g., ethyl acetate, butyl acetate, mono-, di- or triglycerol esters of lower fatty acids of 2 to 6 carbon atoms, etc.), and nitriles (e.g., acetonitrile, etc.), and these are used in one kind or as a mixture of not less than two kinds thereof. The proportion of the liquid carrier contained in the insecticidal or/and ovicidal composition of the present invention varies depending upon the form of preparations and may, for example, range from 5 to 90 weight %, preferably from 15 to 50 weight %, in the case of emulsifiable concentrate. As the solid carrier, there are used, for example, vegetable powders (e.g., soybean meal, tobacco meal, wheat flour, wood flour, etc.), mineral powders (e.g., clays, such as kaolin, bentonite and acid clay, talcs, such as stealite powder and pencil stone or pagodite powder, silicas, such as diatomaceous earth and mica powder, etc.), and furthermore alumina, powdered sulfur, activated carbon, and the like, and these are used in one kind or as a mixture of not less than two kinds thereof. The proportion of the solid carrier contained in the insecticidal or/and ovicidal composition of the present invention varies depending upon the form of preparations, and may, for example, range from 10 to 98 weight %, preferably from 15 to 50 weight %, in the case of wettable powder, powder and granule.
As the ointment base to be used in formulating the insecticidal or/and ovicidal composition of the present invention into an ointment, there can be suitably selected, for example, polyethylene glycol [H(OCH.sub.2 CH.sub.2).sub.n OH wherein n is about 4 to 14], pectin, polyhydric alcohol esters of higher fatty acids (having 10 to 20 carbon atoms), such as mono-, di- or triglycerol esters of stearic acid, cellulose derivatives, such as methylcellulose, sodium arginate, bentonite, higher alcohols, polyhydric alcohols, such as glycerol, petrolatum, white petrolatum, liquid paraffin, lard, all kinds of vegetable oils, lanolin, dehydrated lanolin, hardened oil and resins, in one kind, as a mixture of not less than two kinds thereof or as an admixture thereof with a variety of surface active agents. The proportion of the ointment bases contained in the insecticidal or/and ovicidal composition of the present invention may range from 50 to 95 weight %, preferably from 70 to 90 weight %.
As the surface active agent which is used, for example, as an emulsifier, spreader, penetrant or dispersing agent, in the preparation of the insecticidal or/and ovicidal composition of the present invention, there are employed, if desired, soaps, polyoxyalkylaryl esters (e.g., Nonal.RTM., produced by Takemoto Oils & Fats Co. of Japan, etc.), alkyl sulfates (e.g., Emaru 10.RTM. and Emaru 40.RTM., produced by Kao-Atlas Co. of Japan, etc.), alkyl sulfonates (e.g., Neogen.RTM. and Neogen T.RTM., produced by Daiichi Kogyo Seiyaku Co. of Japan: and Neopelex.RTM., produced by Kao-Atlas Co. of Japan, etc.), polyethylene glycol ethers (e.g., Nonipol 85.RTM., Nonipol 100.RTM. and Nonipol 160.RTM., produced by Sanyo Chemical Industries of Japan, etc.), polyhydric alcohol esters (e.g., Tween 20.RTM. and Tween 80.RTM., produced by Kao-Atlas Co. of Japan, etc.) and the like. The proportion of these surface active agents contained in the insecticidal or/and ovicidal composition of the present invention varies depending upon the form of preparations, and may, for example, range from 1 to 20 weight %, preferably from 3 to 10 weight %, in the case of emulsifiable concentrate; from 3 to 30 weight %, preferably from 5 to 20 weight %, in the case of wettable powder; and from 0.01 to 10 weight %, preferably from 0.1 to 5 weight %, in the case of powder and granule.
Also, it is possible to apply mixtures formed by formulating the compound [I] of the present invention suitably with, for example, other kinds of insecticides (e.g., pyrethrin insecticides, organic phosphate insecticides, carbamate insecticides, natural insecticides, etc.), acaricides, nematicides, herbicides, plant hormones, plant growth regulators, fungicides and bactericides (e.g., fungicides and bactericides based on copper, chlorinated hydrocarbons, organic sulfur compounds and phenol compounds, etc.), synergists, attractants, repellents, colorants and fertilizers to such an extent as may not adversely affect the insecticidal or/and ovicidal effect produced by the benzoylurea derivatives [I] of the present invention.
The insecticidal or/and ovicidal composition of the present invention can be used in the same manner as ordinary insecticidal or/and ovicidal compositions, for example, by treatment of seedling culture boxes, spraying the stems and leaves of crops, spraying living insect bodies, underwater application in paddy fields and soil treatment. In such cases, the application amount can be varied over a wide range according to the time of application, location of application, method of application, etc., but it is generally desirable to conduct application in such a way that the active ingredient may range from 10 g to 2000 g, preferably from 50 g to 1000 g, per hectare.
Concretely, application is carried out by diluting an emulsifiable concentrate of the present invention formed by the mixing of 15 to 25 weight % of N-(2,6-difluorobenzoyl)-N'-[2-fluoro-4-(1,1,2,2-tetrafluoroethylthio)phenyl]urea or the object product [I] of the present application, 70 to 80 weight % of dimethylformamide as a liquid carrier and 3 to 10 weight % of polyoxyethylene glycol ether as a surface active agent with water containing 0.01 to 0.05% of Dain.RTM. (produced by Takeda Chemical Industries, Ltd. of Japan) or a spreader to a concentration of 2 to 20 ppm and spraying the resulting aqueous solution on a place infested with Spodoptera litura at a rate of 0.5 to 5 g as an active ingredient per are.
The compound [I] of the present invention can be produced by reacting the compound [IV] with the compound [V]. In this reaction, the compound [IV] may be used in the proportion in the range of 1 to 1.2 moles per mole of the compound [V]. Generally, the reaction is desirably carried out in a suitable solvent, and may be conducted in inert solvent, for example, aliphatic and aromatic hydrocarbons, such as pentane, hexane, heptane, cyclohexane, petroleum ether, petroleum benzine, benzene, toluene and xylene; halogenated hydrocarbons, such as dichloromethane, chloroform, carbon tetrachloride and dichlorobenzene; ethers, such as ethyl ether, dioxane and tetrahydrofurane; nitriles, such as acetonitrile; and esters, such as ethyl acetate. The reaction temperature may generally range from about 0.degree. to about 120.degree. C., preferably from about 10.degree. to 50.degree. C. As to the reaction time, the reaction proceeds over a period of time in the range of 5 minutes to 24 hours, but may normally be terminated within a length of time in the range of 20 minutes to 2 hours. The termination of the reaction can be confirmed by thin-layer chromatography and the like.
Furthermore, the compound [I] of the present invention can be produced by reacting the compound [VI] with the compound [VII]. The compound [VII] may be used in the proportion in the range of 1 to 1.2 moles per mole of the compound [VI]. Generally, the reaction is desirably carried out in a suitable solvent, and may be conducted in inert solvent, for example, aliphatic and aromatic hydrocarbons, such as pentane, hexane, heptane, cyclohexane, petroleum ether, petroleum benzine, benzene, toluene and xylene; halogenated hydrocarbons, such as dichloromethane, chloroform, carbon tetrachloride and dichlorobenzene; ethers, such as ethyl ether, dioxane and tetrahydrofurane; nitriles, such as acetonitrile; and esters, such as ethyl acetate. The reaction temperature may from about 30.degree. to 150.degree. C., preferably from about 50.degree. to 150.degree. C. As to the reaction time, the reaction proceeds over a period of time in the range of about 30 minutes to 48 hours, but may normally be terminated within a length of time in the range of 1 to 24 hours. The termination of the reaction can be confirmed by thin-layer chromatography and the like.
Moreover, the compound [I] of the present invention can be produced, for example, by the method as shown in the following formulae. ##STR16## wherein the symbols are as defined hereinbefore.
The reaction of [IV] and [III'] can be carried out in a manner similar to the reaction of [IV] and [V]. The compound [IV] may be preferably used in the proportion in the range of 1 to 1.2 moles per mole of the compound [III']. The reaction normally is desirably carried out in a suitable solvent. As the solvent, there may be used those as mentioned for the reaction of [IV] and [V]. Normally, the reaction temperature may range from about 0.degree. to about 120.degree. C., preferably from about 10.degree. to 50.degree. C. As to the reaction time, the reaction proceeds over a period of time in the range of 5 minutes to 24 hours, but may normally be terminated within a length of time in the range of 20 minutes to 2 hours. The resulting compound [I'] can be isolated and purified by known means as mentioned hereinafter, but can also be subjected, as a reaction mixture without being separated, to the subsequent reaction as a starting material. The compound [I] can also be produced, in accordance with the known methods as described for example in J. Org. Chem., 29, 895-898 (1964); and J, Gen, Chem. USSR, 39, 2011-2016 (1969), by perfluoroalkylation of the compound [I'].
The compound [I] of the present invention thus obtained can be isolated and purified from the reaction mixture by per se known means, such as crystallization, recrystallization, precipitation, extraction, concentration and chromatography.
The starting compound [IV], which is used in the production of the benzoylurea derivatives [I] of the present invention, can be produced, for example, by the methods, or methods analogous thereto, as described in J. Org. Chem., 27, 3742 (1962); ibid., 30, 4306 (1965). The starting compound [V] can be produced, for example, by a method analogous to the known methods as described in J. Am. Chem. Soc., 82, 5116 (1960); J. Org. Chem., 29,895 (1964), and besides, can also be produced, for example, by the method as shown in the following reaction formulae or methods analogous thereto. ##STR17## wherein Y.sup.1, Y.sup.2 and Y.sup.3 are as defined hereinbefore. Also, the starting compound [VI] can be produced, for example, by the methods, or methods analogous thereto, as described in J. Med. Chem., 11, 814 (1963); Beilstein `Handbuch der Organischen Chemie`, 9, 336. The starting compound [VII] can be produced, for example, by the method as described in U.S. Pat. No. 4277499, the procedure of reacting the compound [V] with phosgene in accordance with the known methods, or methods analogous thereto.

The reference examples, examples and test examples are given in the following to describe the present invention more specifically, but it is to be understood that this invention shall not be limited by them. The symbols used in Reference Examples, Examples and Test Examples have the following meanings.
______________________________________ ml: milliliter l: liter g: gram kg: kilogram Me: methyl %: (weight) percent b.p.: boiling point m.p.: melting point Comp'd: Compound cm: centimeter mm: millimeter______________________________________
REFERENCE EXAMPLE 1
To 550 ml of methanol were added 111 g of 2-fluoroaniline and 240 g of sodium thiocyanate, and the mixture was cooled to 0.degree. C. A cooled (0.degree. C.) solution of 176 g of bromine in 500 ml of methanol saturated with sodium bromide was added dropwise to the mixture over the period of 1 hour 15 minutes under stirring. In the course of this, cooling was effected so that the internal temperature might be maintained at not more than 3.degree. C. After the addition of bromine was completed, the reaction mixture was poured in 2 l of cold water, and 100 g of sodium hydrogencarbonate was added to make the mixture weakly alkaline. The crystals, which separated out, were recovered by filtration and washed with cold water to give 144.5 g of crude 2-fluoro-4-thiocyanatoaniline.
REFERENCE EXAMPLE 2
To a mixed solution consisting of 200 ml of conc. hydrochloric acid and 50 ml of ethanol was added 50 g of crude 2-fluoro-4-thiocyanatoaniline, and the mixture was heated under reflux for 8 hours. The crystals, which separated out upon standing overnight, were recovered by filtration and dried in a desiccator to give 44 g of crude 2-fluoro-4-mercaptoaniline hydrochloride. 44 g of crude 2-fluoro-4-mercaptoaniline hydrochloride was suspended in 100 ml of dioxane, and 30 g of triethylamine was added to the suspension. Tetrafluoroethylene was passed into the mixture over the period of 1.5 hours under heating at 50.degree. to 60.degree. C. with stirring (tetrafluoroethylene was generated in accordance with the conventional method by reacting 40 ml of 1,2-dibromotetrafluoroethane with 100 g of powdered zinc in methanol). After the conclusion of the reaction, the reaction mixture was diluted with water and extracted twice with 100 ml of dichloromethane. The dichloromethane extract was dehydrated with anhydrous magnesium sulfate and concentrated to dryness under reduced pressure to give 42.1 g of a yellow oily material. The oily material was distilled under reduced pressure to give 29.5 g of 2-fluoro-4-(1,1,2,2-tetrafluoroethylthio)-aniline as a colorless liquid having a boiling point of 70.degree. to 72.degree. C./0.6 mmHg.
By the procedures similar to the above Reference Examples, the 4-(1,1,2,2-tetrafluoroethylthio)-aniline derivatives as shown in the below table were synthesized. The results are tabulated in Table 1.
TABLE 1______________________________________ ##STR18## Boiling pointY.sup.1 Y.sup.2 Y.sup.3 (melting point), .degree.C.______________________________________Cl H H 84.about.86/0.2 mmHgMe H H 90-91/0.3 mmHgH F H 81-82/0.1.about.0.2 mmHgH Cl H 113-115/0.3 mmHgH Me H 97-100/0.2 mmHgH Cl Cl (56-56.5)Cl Cl H 122-125/0.3 mmHgH Cl F 92-93/0.15 mmHgF H F 63-64/0.3 mmHgBr H H 105-106/0.5 mmHgMe Me H 122/1.5 mmHgH Me Me 125/1.5 mmHgH Cl Me 115-121/1.about.2 mmHg______________________________________
REFERENCE EXAMPLE 3
In 20 ml of dimethylformamide was dissolved 12.0 g of 2-fluoro-4-mercaptoaniline, and 8.5 g of triethylamine was added to the solution. Trifluorochloroethylene was passed into the mixture over the period of 25 minutes under heating at 50.degree. to 60.degree. C. with stirring (trifluorochloroethylene was generated in accordance with the conventional method by reacting 31 g of 1,1,2-trifluoro-trichloroethane with 90 g of powdered zinc in ethanol). After the conclusion of the reaction, the reaction mixture was diluted with water and extracted with toluene. The toluene layer was washed with water, 10% NaOH aqueous solution and water successively in the mentioned order, dehydrated with anhydrous magnesium sulfate and concentrated to dryness under reduced pressure to give 17.5 g of a brownish oily material. The oily material was distilled under reduced pressure to 13.7 g of 2-fluoro-4-(1,1,2-trifluoro-2-chloroethylthio)aniline as a colorless liquid having a boiling point of 95.degree. to 98.degree. C./0.2 mmHg.
By the similar procedure, the 4-(1,1,2-trifluoro-2-chloroethylthio)aniline derivatives as shown in the below table were synthesized. The results are tabulated in Table 2.
TABLE 2______________________________________ ##STR19##Y.sup.1 Y.sup.2 Y.sup.3 Boiling point, .degree.C.______________________________________Cl H H 108-109/0.3 mmHgH Cl Cl 124-126/0.15 mmHgCl Cl H 128-130/0.2-0.3 mmHgMe H H 117-118/0.6 mmHgF H F 75-77/0.2 mmHgBr H H 133-135/1.0 mmHgMe Me H 140/1.5 mmHgH Me Me 125/0.6 mmHgH Cl Me Oily material (Acetyl deriva- tive melting at 133-134.degree. C.)______________________________________
REFERENCE EXAMPLE 4
In 20 ml of methanol was dissolved 18.4 g of 2-fluoro-4-mercaptoaniline hydrochloride, and after cooling at 0.degree. C., 39.4 g of 28% sodium methylate was added dropwise to the solution. 30 minutes later, the insoluble matter was filtered out, and the filtrate was concentrated to dryness under reduced pressure. 200 ml of dioxane was added to the residue, and 23 g of chlorodifluoromethane was blown into the mixture under heating at 50.degree. C. with stirring. After cooling, the reaction mixture was extracted with toluene. The toluene extract was washed with water, dehydrated with anhydrous magnesium sulfate and concentrated to dryness under reduced pressure, followed by distillation to give 11.5 g of 2-fluoro-4-difluoromethylthioaniline, b.p. of 65.degree.-67.degree. C./0.2 mmHg.
By the similar procedure, the 4-difluoromethylthioaniline derivatives as shown in the below table were synthesized. The results are tabulated in Table 3.
TABLE 3______________________________________ ##STR20## Boiling pointY.sup.1 Y.sup.2 Y.sup.3 (melting point), .degree.C.______________________________________Cl H H 96-97/0.2 mmHgMe H H 92-93/0.2 mmHgH F H 103-104/1 mmHgH Cl H 114-115/0.2 mmHgCl Cl H (57-58)F H F 80-82/0.3 mmHgBr H H 118-119/0.2-0.3 mmHg______________________________________
EXAMPLE 1
In 15 ml of toluene was dissolved 2.6 g of 2-fluoro-4-(1,1,2-trifluoro-2-chloroethylthio)aniline, and 1.8 g of 2,6-difluorobenzoylisocyanate was added dropwise to the solution at room temperature (20.degree. to 25.degree. C.). After the reaction was allowed to proceed at the same temperature for 1 hour, the crystals, which separated out, were recovered by filtration and washed wiht toluene to give 3.6 g of N-(2,6-difluorobenzoyl)-N'-[2-fluoro-4-(1,1,2-trifluoro-2-chloroethylthio)phenyl]urea (Compound No. 39), m.p. of 172.degree.-173.degree. C.
Elemental analysis, for C.sub.16 H.sub.9 N.sub.2 F.sub.6 ClO.sub.2 S. Calcd.: C, 43.40%; H, 2.05%; N, 6.33%. Found: C, 43.50%; H, 2.05%; N, 6.29%.
EXAMPLE 2
In 20 ml of toluene was dissolved 1.0 g of 2-fluoro-4-(1,1,2,2-tetrafluoroethylthio)aniline, and 0.8 g of 2,6-difluorobenzoyl isocyanate was added dropwise to the solution at room temperature (20.degree. to 25.degree. C.). After the reaction was allowed to proceed at the same temperature for 30 minutes, the crystals, which separated out, were recovered by filtration and washed with toluene to give 1.5 g of N-(2,6-difluorobenzoyl)-N'-[2-fluoro-4-(1,1,2,2-tetrafluoro-ethylthio)phenyl]urea (Compound No. 1), m.p. of 177.degree.-179.degree. C.
Elemental analysis, for C.sub.16 H.sub.9 N.sub.2 F.sub.7 O.sub.2 S. Calcd.: C, 45.08%; H, 2.13%; N, 6.57%. Found: C, 45.06%; H, 2.07%; N, 6.59%.
EXAMPLE 3
In 15 ml of toluene was dissolved 1.0 g of 2-fluoro-4-difluoromethylthioaniline, and 1.0 g of 2,6-difluorobenzoyl isocyanate was added dropwise to the solution at room temperature (20.degree. to 25.degree. C.). After the reaction was allowed to proceed at the same temperature for 30 minutes, the crystals, which separated out, were recovered by filtration and washed with toluene to give 1.5 g of N-(2,6-difluorobenzoyl)-N'-(2-fluoro-4-difluoromethylthiophenyl)urea (Compound No. 55). Recrystallization from acetone gave crystals having a melting point of 172.degree.-173.degree. C.
Elemental analysis, for C.sub.15 H.sub.9 N.sub.2 F.sub.5 O.sub.2 S. Calcd.: C, 47.88%; H, 2.41%; N, 7.44%. Found: C, 47.94%; H, 2.34%; N, 7.37%.
EXAMPLE 4
To 140 ml of 4% phosgen-toluene solution was added 3.6 g of 2-fluoro-4-(1,1,2,2-tetrafluoroethylthio)aniline, and the mixture was heated under reflux for 3 hours. After the conclusion of the reaction, the reaction mixture was concentrated to dryness under reduced pressure to give 2-fluoro-4-(1,1,2,2-tetrafluoroethylthio)phenyl isocyanate as an oily material. The oily material was dissolved in 50 ml of xylene, and 1.5 g of 2,6-difluorobenzamide was added to the solution, followed by heating under reflux for 20 hours. After the conclusion of the reaction, the reaction mixture was cooled (0.degree. C.), and the crystals which separated out were recovered by filtration, and further recrystallized from acetone to give N-(2,6-difluorobenzoyl)-N'-[2-fluoro-4-(1,1,2,2-tetrafluoroethylthio)phenyl]urea (Compound No. 1) as crystals having a m.p. of 177.degree.-179.degree. C. The resulting compound was found to show no decrease in melting point even when admixed with the authentic sample as obtained in Example 2.
By the procedures similar to the above examples, the benzoylurea derivatives [I] as shown in the below table were synthesized. The results are tabulated in Table 4, in which the compounds as synthesized in Examples 1 through 3 are included.
TABLE 4______________________________________ ##STR21## [I]Comp'd MeltingNo. X.sup.1 X.sup.2 Y.sup.1 Y.sup.2 Y.sup.3 R point, .degree.C.______________________________________1 F F F H H CHF.sub.2 177-1792 F Cl F H H CHF.sub.2 195-196.53 Cl Cl F H H CHF.sub.2 228-2304 Cl H F H H CHF.sub.2 152-153.55 F F Cl H H CHF.sub.2 1456 F Cl Cl H H CHF.sub.2 169-1717 Cl Cl Cl H H CHF.sub.2 200-2018 Cl H Cl H H CHF.sub.2 130-1319 F F Me H H CHF.sub.2 141-14210 F Cl Me H H CHF.sub.2 147-14911 Cl Cl Me H H CHF.sub. 2 175-17712 Cl H Me H H CHF.sub.2 125-12613 F F H F H CHF.sub.2 190-19214 F Cl H F H CHF.sub.2 191-19215 Cl Cl H F H CHF.sub.2 209-21116 Cl H H F H CHF.sub.2 189-19017 F F H Cl H CHF.sub.2 186-18718 F Cl H Cl H CHF.sub.2 191-19319 Cl Cl H Cl H CHF.sub.2 187-18820 Cl H H Cl H CHF.sub.2 202-20321 F F H Me H CHF.sub.2 191-19222 F Cl H Me H CHF.sub.2 171-17223 Cl Cl H Me H CHF.sub.2 194-19624 Cl H H Me H CHF.sub.2 176-17725 F F H Cl Cl CHF.sub.2 189-19026 F Cl H Cl Cl CHF.sub.2 206.5-207.527 Cl Cl H Cl Cl CHF.sub.2 190-19128 Cl H H Cl Cl CHF.sub.2 18229 F F Cl Cl H CHF.sub.2 153-153.5(2/5 CHCl.sub.3)*30 F Cl Cl Cl H CHF.sub.2 187-189(1/10 CHCl.sub.3)*31 Cl Cl Cl Cl H CHF.sub.2 202-20432 Cl H Cl Cl H CHF.sub.2 187-18933 F F H Cl F CHF.sub.2 179-18034 Cl H H Cl F CHF.sub.2 194-19535 F F F H F CHF.sub.2 197-19836 F Cl F H F CHF.sub.2 191-19237 Cl Cl F H F CHF.sub.2 190-19238 Cl H F H F CHF.sub.2 16239 F F F H H CHFCl 172-17340 F Cl F H H CHFCl 190-191(1/14 toluene)*41 Cl Cl F H H CHFCl 207-20842 Cl H F H H CHFCl 150-15143 F F H F H CHFCl 189-19044 F F H Cl Cl CHFCl 181-183(1/10 CHCl.sub.3)*45 F Cl H Cl Cl CHFCl 200-203(1/10 CHCl.sub.3)*46 Cl Cl H Cl Cl CHFCl 191-19347 Cl H H Cl Cl CHFCl 162-163(1/5 CHCl.sub.3)*48 F F Cl Cl H CHFCl 158-15949 F Cl Cl Cl H CHFCl 177-17850 Cl Cl Cl Cl H CHFCl 176-178(0.04 toluene)*51 Cl H Cl Cl H CHFCl 179-18052 F F F H F CHFCl 19653 Cl Cl F H F CHFCl 19754 Cl H F H F CHFCl 15955 F F F H H H 172-17356 F Cl F H H H 196-19757 Cl Cl F H H H 212-21358 Cl H F H H H 150-15259 F F Cl H H H 187-18860 F Cl Cl H H H 188-18961 Cl Cl Cl H H H 221-22262 Cl H Cl H H H 145-14663 F F Me H H H 200-20164 F Cl Me H H H 156-15765 Cl Cl Me H H H 180-18266 Cl H Me H H H 155-15667 F F H F H H 183.5-184.568 F Cl H F H H 191-192.569 Cl Cl H F H H 202-20470 Cl H H F H H 196-19771 F F H Cl H H 171-17272 F Cl H Cl H H 217-21873 Cl Cl H Cl H H 219-22074 Cl H H Cl H H 200-20175 F F H Br H H 179-180.576 F Cl H Br H H 201-20277 Cl Cl H Br H H 208-20978 Cl H H Br H H 200-20179 F F H Me H H 185-18680 F Cl H Me H H 213-21481 Cl Cl H Me H H 222-22382 Cl H H Me H H 181-18283 F F H Cl Cl H 183-18484 F Cl H Cl Cl H 215-21785 Cl Cl H Cl Cl H 215-21786 Cl H H Cl Cl H 168-16987 F F Cl Cl H H 223-22488 F Cl Cl Cl H H 228-23089 Cl Cl Cl Cl H H 233-23590 Cl H Cl Cl H H 206-20791 F F H Cl F H 176-17792 F Cl H Cl F H 214-21693 Cl Cl H Cl F H 217-21994 Cl H H Cl F H 169-17095 F F F H F H 18596 Cl Cl F H F H 21297 Cl H F H F H 17498 F F Me H Me H 205-20699 Cl H Me H Me H 176-178100 F F Br H H CHF.sub.2 138-139101 Cl H Br H H CHF.sub.2 130-131102 F F H Me Me CHF.sub.2 151-152103 Cl H H Me Me CHF.sub.2 157-158104 F F Me Me H CHF.sub.2 145-146105 Cl H Me Me H CHF.sub.2 145-146106 F F H Cl Me CHF.sub.2 158-159107 Cl H H Cl Me CHF.sub.2 160-161108 F F Br H H CHFCl 148-149109 Cl H Br H H CHFCl 131-132110 F F H Me Me CHFCl 146-147111 Cl H H Me Me CHFCl 148-149112 F F Me Me H CHFCl 150- 151113 Cl H Me Me H CHFCl 145-146114 F F H Cl Me CHFCl 157-159115 Cl H H Cl Me CHFCl 173-174116 F F Cl H H CHFCl 133-134117 F Cl Cl H H CHFCl 176-177118 Cl Cl Cl H H CHFCl 180-181119 Cl H Cl H H CHFCl 136-137______________________________________ *The parenthesized figures following the melting points indicate the content of impurities contained. Me denotes a methyl group.
EXAMPLE 5
(Emulsifiable concentrate)
______________________________________Compound No. 1 20 weight %Dimethylformamide 75 weight %Polyoxyethylene glycol ether (Nonipol 5 weight %85 .RTM., produced by Sanyo Chemical Ind.of Japan)______________________________________
An emulsifiable concentrate formed by mixing the above ingredients (to be sprayed after diluting with water to a desired concentration on the occasion of use).
EXAMPLE 6
(Wettable powder)
______________________________________Compound No. 39 25 weight %Polyoxyethylene glycol ether (Nonipol 6 weight %85 .RTM., produced by Sanyo Chemical Ind.of Japan)Diatomaceous earth 69 weight %______________________________________
A wettable powder formed by mixing the above ingredients (to be sprayed after diluting with water to a desired concentration on the occasion of use).
EXAMPLE 7
(Wettable powder)
______________________________________Compound No. 55 25 weight %Sodium lignin sulfonate 5 weight %Polyoxyethylene glycol ether (Nonipol 5 weight %85 .RTM., produced by Sanyo Chemical Ind.of Japan)Clay 65 weight %______________________________________
A wettable powder formed by uniformly mixing and pulverizing the above ingredients (to be sprayed after diluting with water to a desired concentration on the occasion of use).
EXAMPLE 8
(Powder)
______________________________________Compound No. 1 10 weight %Clay 89.3 weight %Silicone 0.5 weight %Polyethylene glycol ether 0.2 weight %______________________________________
A powder formed by uniformly mixing and pulverizing the above ingredients.
EXAMPLE 9
(Granule)
______________________________________Compound NO. 1 5 weight %Clay 72 weight %Bentonite 20 weight %Polyoxyethylene glycol ether (Nonipol 0.5 weight %85 .RTM., produced by Sanyo Chemical Ind. ofJapan)Sodium carboxymethyl cellulose 2.5 weight %______________________________________
The above ingredients were uniformly mixed and pulverized, and water of 8 weight % against the total weight was added to the mixture, followed by kneading thoroughly. Subsequently, the mixture was processed into granules, which were dried to a granular preparation, in accordance with the conventional method.
EXAMPLE 10
(Granule)
______________________________________Compound No. 39 2 weight %Sodium lignin sulfonate 5 weight %Bentonite 93 weight %______________________________________
The above ingredients were uniformly mixed and pulverized, and water of 10 weight % against the total weight was added to the mixture, followed by kneading thoroughly. Subsequently, the mixture was processed into granules, which were dried to a granular preparation, in accordance with the conventional method.
TEST EXAMPLE 1
Insecticidal effect against Spodoptera litura
A test compound was processed into an emulsifiable concentrate in accordance with the same formulation as described in Example 5, followed by dilution with water to prepare 2 and 10 ppm treatment solutions (admixed with 0.03% of Spreader Dain.RTM.). 20 ml each of the treatment solutions were sprayed to soybean seedlings (14 days after germination) grown in a pot in a spray chamber with use of a spray gun (with a spraying pressure of 1 kg/cm.sup.2). One day after spraying, two treated leaves were cut off and placed in an ice-cream cup (with a diameter of 6 cm and a depth of 4 cm), in which 10 third-instar larvae of Spodoptera litura were released. After releasing, the above cup was placed in a room (25.degree. C.), and examined for a number of dead larvae 4 days later. The test was repeated twice, whereby the test results were expressed in terms of rate of death (%) as shown in Table 5.
TEST EXAMPLE 2
Insecticidal effect against Plutella xylostella
In accordance with the same formulation and preparation method as described in Test Example 1, there were prepared 3.3 and 10 ppm treatment solutions of a test compound, and 20 ml each of the treatment solutions were sprayed to seedlings (25 days after germination) of Hatsuka-daikon (a kind of radish) grown in a pot by the same spraying procedure as in Test Example 1. 2 hours after spraying, two treated leaves were cut off and placed in an ice-cream cup, in which 10 second-instar larvae of Plutella xylostella were released. After releasing, the above cup was placed in a room (25.degree. C.) and examined for a number of dead larvae 4 days later. The test was repeated twice, whereby the test results were expressed in terms of rate of death (%) as shown in Table 6.
TEST EXAMPLE 3
Insecticidal effect against Adoxophyes orana
In accordance with the same formulation as described in Example 6, a test compound was processed into a wettable powder, followed by dilution with water to prepare 5 and 20 ppm treatment solutions (admixed with 0.03% of Spreader Dain.RTM.). The whole leaves of soybean seedlings (14 days after germination) grown in a pot were immersed in each of the treatment solutions for 10 seconds and air-dried, and two leaves thus treated were cut off and placed in an ice-cream cup, in which 10 second-instar larvae of Adoxophyes orana were released. After releasing, the above cup was placed in a room (25.degree. C.) and examined for a number of dead larvae 7 days later. The test was repeated twice, whereby the test results were expressed in terms of rate of death (%) as shown in Table 7.
TEST EXAMPLE 4
Insecticidal effect against Henosepilachna vigintioctopunctata
In accordance with the same formulation and preparation method as described in Test Example 1, there were prepared 4 and 20 ppm treatment solutions of a test compound, and a cut piece (5 mm thick) of potato was immersed in each of the treatment solutions for 10 seconds, air-dried and transferred into a Petri dish (with a diameter of 9 cm), in which 10 second-instar larvae of Henosepilachna vigintioctopunctata were released. After releasing, the Petri dish was placed in a room (25.degree. C.), and examined for a number of dead larvae 7 days later. The test was repeated twice, whereby the test results were expressed in terms of rate of death (%) as shown in Table 8.
In the respective tests mentioned above, the following compounds were used as a control compound.
Control compound A=Dimilin:
N-(4-chlorophenyl)-N'-(2,6-difluorobenzoyl)urea (Diflubenzuron) ##STR22## Control compound B=Acephate: N-acetylphosphoramidothiol acid O,S-dimethyl ##STR23## Control compound C=the compound in European Patent Publication No. 71279. ##STR24##
TABLE 5:______________________________________ Spodoptera Spodoptera litura litura rate of rate ofComp'd death (%) Comp'd death (%)No. 2 ppm 10 ppm No. 2 ppm 10 ppm______________________________________ 1 100 100 58 100 100 2 100 100 59 100 100 3 100 100 60 100 100 4 100 100 62 95 100 5 100 100 63 100 100 6 100 100 64 100 100 7 -- 100 65 -- 100 8 100 100 66 100 100 9 100 100 69 -- 10010 100 100 71 -- 10011 90 100 72 -- 10012 100 100 75 90 10013 85 100 76 95 10014 100 100 78 100 10015 100 100 79 -- 10016 -- 100 80 90 10017 100 100 82 -- 10018 100 100 83 100 10019 85 100 86 95 10020 95 100 87 100 10021 100 100 88 100 10022 100 100 91 100 10023 100 100 92 -- 10024 100 100 94 100 10025 100 100 95 100 10026 85 100 96 -- 10028 100 100 97 100 10029 100 100 98 100 10030 100 100 100 100 10031 -- 100 101 95 10032 100 100 102 100 10033 100 100 103 -- 10034 100 100 104 100 10035 100 100 105 100 10036 100 100 106 100 10037 85 100 107 95 10038 100 100 108 100 10039 100 100 109 100 10040 100 100 110 100 10041 100 100 111 100 10042 100 100 112 100 10043 100 100 113 100 10044 100 100 114 100 10045 100 100 115 100 10047 100 100 116 100 10048 100 100 117 100 10049 100 100 118 100 10050 100 100 119 95 10051 100 100 Control 10 9552 100 100 comp'd A53 95 100 Control 10 054 100 100 comp'd B55 100 100 Control 30 --56 100 100 comp'd C57 -- 100 none 0 0______________________________________
TABLE 6______________________________________ Plutella Plutella xylostella xylostella rate of rate ofComp'd death (%) Comp'd death (%)No. 3.3 ppm 10 ppm No. 3.3 ppm 10 ppm______________________________________ 1 100 100 68 100 100 2 100 100 69 -- 100 4 100 100 71 100 100 5 100 100 75 90 100 6 100 100 76 95 100 8 100 100 78 100 100 9 100 100 79 -- 10010 95 100 80 90 10012 95 100 82 -- 10013 100 100 83 100 10014 100 100 86 95 10015 -- 100 87 100 10016 95 100 88 100 10017 100 100 91 100 10018 100 100 92 -- 10021 100 100 94 100 10022 100 100 95 100 10024 100 100 96 -- 10025 100 100 97 100 10026 100 100 98 100 10028 100 100 100 100 10029 100 100 101 95 10030 100 100 102 100 10032 100 100 103 -- 10033 100 100 104 100 10034 100 100 105 100 10035 100 100 106 100 10038 100 100 107 95 10039 100 100 108 100 10040 100 100 109 100 10041 100 100 110 100 10042 100 100 111 100 10043 100 100 112 100 10044 100 100 113 100 10045 100 100 114 100 10047 100 100 115 100 10049 100 100 116 100 10051 100 100 117 100 10052 -- 100 118 100 10053 100 100 119 95 10054 100 100 Control 10 9555 100 100 comp'd A56 100 100 Control 0 058 100 100 comp'B62 -- 100 Control 30 --63 100 100 comp'd C64 -- 100 none 0 067 100 100______________________________________
TABLE 7______________________________________ Adoxophyes Adoxophyes orana orana rate of rate ofComp'd death (%) Comp'd death (%)No. 5 ppm 20 ppm No. 5 ppm 20 ppm______________________________________ 1 80 100 50 80 100 2 100 100 51 100 100 3 -- 100 52 95 100 4 95 100 56 95 100 5 100 100 87 -- 100 6 90 100 100 100 100 8 85 100 102 95 100 9 100 100 103 95 10010 100 100 104 100 10011 80 100 105 100 10012 90 100 106 100 10014 95 100 107 -- 9522 95 100 108 100 10025 100 100 109 95 10026 -- 100 110 95 10028 -- 100 111 95 10029 100 100 112 100 10030 100 100 113 100 10032 90 100 114 95 10033 100 100 115 90 10034 100 100 116 100 10039 100 100 117 100 10040 100 100 118 95 10041 100 100 119 100 10042 95 100 Control 0 044 100 100 comp'd A45 90 100 Control 0 047 95 100 comp'd B48 100 100 none 0 049 100 100______________________________________
TABLE 8______________________________________ Henosepilachna Henosepilachna vigintiocto- vigintiocto- punctata punctata rate of rate ofComp'd death (%) death (%)No. 4 ppm 20 ppm No. 4 ppm 20 ppm______________________________________ 2 100 100 50 85 100 3 100 100 52 100 100 4 100 100 53 95 95 5 100 100 54 100 100 7 95 95 58 -- 95 8 -- 95 59 -- 10010 100 100 63 90 10011 100 100 64 95 10013 90 100 67 90 10014 100 100 68 100 10015 100 100 69 90 10016 -- 100 70 -- 10017 100 100 75 90 10018 100 100 76 95 10020 90 100 77 -- 9021 95 95 78 100 10023 90 100 79 95 10024 100 100 81 95 9525 85 100 83 95 9526 100 100 84 95 9527 100 100 87 100 10028 100 100 88 -- 9529 100 100 91 100 10030 100 100 102 95 10031 95 100 103 90 9532 100 100 104 90 9535 -- 95 105 100 10036 80 95 107 90 10037 100 100 110 95 10038 75 90 111 95 10039 100 100 112 100 10040 95 95 113 90 10041 100 100 114 -- 10042 75 100 Control 60 8043 100 100 comp'd A44 100 100 Control 0 045 100 100 comp'd B46 100 100 Control -- 5047 95 100 comp'C48 90 100 none 0 049 95 100______________________________________

Number	Name	Date
4013717	Wellinga et al.	Mar 1977
4089975	Wade et al.	May 1978
4276310	Sirrenberg et al.	Jun 1981
4277499	Sirrenberg et al.	Jul 1981
4348412	Ehrenfreund	Sep 1982

Number	Date	Country
71279	Feb 1983	EPX
2106499	Apr 1983	GBX
2106500	Apr 1983	GBX
2106501	Apr 1983	GBX

Thiophenylureas, their production and use

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