Benzoxazine compound or salt thereof, insect growth inhibitor comprising the compound, and selective lepidopteran pest control agent comprising the compound as active ingredient

Abstract

To provide a new agent for pest control which can be put to practical use.SOLUTION: There is provided a benzoxazine compound represented by general formula (1) or a salt thereof.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a benzoxazine compound or a salt thereof, an insect growth inhibitor comprising said compound, and a selective lepidopteran pest control agent containing said compound as an active ingredient. [Background technology]

[0002] Juvenile hormone (JH) is a sesquiterpenoid hormone unique to arthropods, including insects. It is a multifunctional hormone involved in various physiological phenomena at all stages of life, from egg to adult, including embryonic development, molting, metamorphosis, sexual maturation, and diapause. For example, during the larval stage, JH is known to regulate molting and metamorphosis by working cooperatively with ecdysteroids (Non-Patent Document 1). It has been shown that molting from larva to larva occurs when ecdysteroids are secreted in the presence of JH in the body fluids, whereas metamorphosis from larva to pupa or adult occurs when ecdysteroids are secreted in the absence of JH. Furthermore, during adulthood, JH often acts independently to promote gonadal maturation, such as the synthesis and secretion of vitellogenic proteins in the fat body. JH is also known to play a crucial role in various stages of insect development, including diapause and caste differentiation in social insects. In recent years, methoprenetolerant (hereinafter sometimes referred to as "Met") has been identified as a JH receptor and has attracted attention as a new target molecule for growth regulators of insects and other arthropods. Therefore, if the activity of Met could be artificially controlled, it would not only disrupt the physiological functions of arthropods, but also be highly selective for arthropods, resulting in an ideal pest control agent that would have no or very little effect on humans and mammals and be highly safe. Therefore, JH and JH analogs (JH-like compounds) that mimic the molecular structure of this JH have been researched.

[0003] To date, various JH analogs, such as methoprene and pyriproxyfen, have been developed that exhibit biological activities similar to JH, such as metamorphosis inhibition activity (e.g., Patent Document 1). However, these JH analogs have the effect of extending the larval stage, which may actually increase damage to insects whose damaging stage is the larval stage, such as lepidopteran insects. Therefore, there is a need for the development of JH antagonists that, unlike JH analogs, suppress the action of JH. As a natural JH antagonist, LE3B, a component contained in the fruit of the Japanese quince (L. saxifraga), whose chemical structure is shown below, has been reported to not only exhibit JH antagonist activity but also inhibit ovarian maturation in Aedes aegypti mosquitoes in a reporter gene assay using the JH receptor of Aedes aegypti (Non-Patent Document 2). On the other hand, synthetic JH antagonists such as ethyl 4-[2-(tert-butylcarbonyloxy)butoxy]benzoate (ETB), ethyl 4-[(6-substituted 2,2-dimethyl-2H-chromen-7-yl)methoxy]benzoate (KF38), and ethyl 4-[(7-substituted 1,4-benzodioxan-6-yl)methyl]benzoate (NY03) have been reported to induce precocious metamorphosis in the larvae of silkworms and tobacco hornworms (Non-Patent Documents 3-6). However, these JH antagonists all have low physiological activity and have not yet been put to practical use. The present inventors have discovered ethyl 3-(4-{[7-(4-methoxycarbonylbenzyloxy)-1,4-benzodioxan-6-yl]methyl}phenyl)-2-propenoate (hereinafter referred to as "EMBP"), which exhibits high precocious metamorphosis-inducing activity in silkworm larvae, and have demonstrated that it suppresses the expression of JH early response genes in the silkworm epidermis (Patent Document 2). Furthermore, they have reported that EMBP acts as a JH antagonist, as it inhibits the action of JH in a reporter assay using silkworm cultured cells (Non-Patent Document 7). [ka] [Prior art documents]

Patent Documents

[0004]

Patent Document 1

Patent Document 2

Non-Patent Documents

[0005]

Non-Patent Document 1

Non-Patent Document 2

Non-Patent Document 3

Non-Patent Document 4

Non-Patent Document 5

Non-Patent Document 6

Non-Patent Document 7

Summary of the Invention

Problems to be Solved by the Invention

[0006] Compounds with JH agonistic activity are thought to be able to suppress population densities in the next generation by inhibiting pupation and adulthood. However, treating herbivorous pests with these JH agonistic compounds with a long life cycle can extend the larval stage, potentially increasing herbivorous damage. In contrast, compounds with JH antagonistic activity can inhibit molting to the pre- and final-stage larvae, which are the most damaging stages. This can minimize herbivorous damage by inducing precocious metamorphosis or stunted development, and also suppress the population densities of pest insects in the next generation. An object of the present invention is to provide a new pest control agent that can be put into practical use. [Means for solving the problem]

[0007] The present inventors have continued to study the mechanism of action of EMBP at the molecular level, and have conducted exploratory research into new compounds with the aim of creating novel compounds with JH antagonist activity. As a result, they have discovered a new group of compounds that exhibit growth inhibitory activity against insects different from that of EMBP, thereby solving the above-mentioned problem.

[0008] Specifically, the present invention provides the following: 1. A benzoxazine compound represented by general formula (1) or a salt thereof: [ka] (In the formula, R1 is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, and R2 and R3 are each independently a hydrogen atom, a halogen atom, a nitro group, a cyano group, an alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, a halogenated alkyl group having 1 to 6 carbon atoms, an alkoxycarbonyl group having 1 to 6 carbon atoms, or an alkoxycarbonylethenyl group having 1 to 6 carbon atoms.) 2. The benzoxazine compound or salt thereof according to 1., wherein R1 is an alkyl group having 1 to 6 carbon atoms, R2 is an alkoxycarbonyl group having 1 to 6 carbon atoms, and R3 is a hydrogen atom. 3. Ethyl (E)-3-{4-[7-(4-methoxycarbonylbenzyloxy)-1,4-benzodioxan-6-yloxy]phenyl}-2-propenoate. 4. An insect growth inhibitor comprising the benzoxazine compound or a salt thereof according to any one of 1. to 3. 5. A selective lepidopteran pest control agent containing the benzoxazine compound or salt thereof according to any one of 1. to 3. above as an active ingredient. [Effects of the Invention]

[0009] Unlike EMBP, the benzoxazine compound represented by general formula (1) of the present invention or a salt thereof does not exhibit any precocious metamorphosis-inducing activity in silkworm larvae, while it exhibits growth inhibitory activity against the beet armyworm, an agricultural pest. In view of its selective biological activity against pests, it has great potential as a selective pest control agent. Such a compound group having pest selectivity has not yet been reported, and it will be extremely useful in finding new directions for pest control in the agricultural field in the future. [Brief explanation of the drawings]

[0010] [Figure 1] FIG. 1 is a graph showing the relative fluorescence intensity (%) at each concentration of the compound of the present invention (compound 8b: indicated as EMBOP in FIG. 1) and the compound described in Patent Document 2 (EMBP) in the test for confirming JH antagonist activity by reporter assay using cultured silkworm cells in "Test Example 3" of the Examples. DETAILED DESCRIPTION OF THE INVENTION

[0011] The present invention will be described in detail below. (Benzoxazine Compound of the Present Invention or Salt thereof) The compound of the present invention is a benzoxazine compound represented by general formula (1) or a salt thereof. [ka] (In the formula, R1 is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, and R2 and R3 are each independently a hydrogen atom, a halogen atom, a nitro group, a cyano group, an alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, a halogenated alkyl group having 1 to 6 carbon atoms, an alkoxycarbonyl group having 1 to 6 carbon atoms, or an alkoxycarbonylethenyl group having 1 to 6 carbon atoms.)

[0012] In the definition of general formula (1) of the present invention, the term "alkyl group having 1 to 6 carbon atoms" means a linear alkyl group having 1 to 6 carbon atoms or a branched alkyl group having 3 to 6 carbon atoms, such as a methyl group, an ethyl group, a normal propyl group, an isopropyl group, a normal butyl group, an isobutyl group, a secondary butyl group, a tertiary butyl group, a normal pentyl group, an isopentyl group, a tertiary pentyl group, a neopentyl group, a 2,3-dimethylpropyl group, a 1-ethylpropyl group, a 1-methylbutyl group, a 2-methylbutyl group, a normal hexyl group, an isohexyl group, a 2-hexyl group, a 3-hexyl group, a 2-methylpentyl group, a 3-methylpentyl group, a 1,1,2-trimethylpropyl group, or a 3,3-dimethylbutyl group. The term "alkoxy group having 1 to 6 carbon atoms" refers to a linear alkoxy group having 1 to 6 carbon atoms or a branched alkoxy group having 3 to 6 carbon atoms, such as a methoxy group, ethoxy group, normal propoxy group, isopropoxy group, normal butoxy group, secondary butoxy group, tertiary butoxy group, normal pentyloxy group, isopentyloxy group, tertiary pentyloxy group, neopentyloxy group, 2,3-dimethylpropyloxy group, 1-ethylpropyloxy group, 1-methylbutyloxy group, normal hexyloxy group, isohexyloxy group, or 1,1,2-trimethylpropyloxy group. The term "halogenated alkyl group having 1 to 6 carbon atoms" refers to a group in which a linear alkyl group having 1 to 6 carbon atoms or a branched alkyl group having 3 to 6 carbon atoms is substituted with a chlorine atom, bromine atom, iodine atom, or fluorine atom, such as a fluoromethyl group, difluoromethyl group, trifluoromethyl group, 2,2,2-trifluoroethyl group, perfluoroethyl group, perfluoropropyl group, perfluorobutyl group, perfluoropentyl group, perfluorohexyl group, perfluoroisopropyl group, perfluoroisobutyl group, chloromethyl group, chloroethyl group, chloropropyl group, bromomethyl group, bromoethyl group, bromopropyl group, methyl iodide group, ethyl iodide group, or propyl iodide group. The term "alkoxycarbonyl group having 1 to 6 carbon atoms" refers to a group in which an alkoxy group having 1 to 6 carbon atoms is bonded to a carbonyl group, such as methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, tert-butoxycarbonyl, pentyloxycarbonyl, or hexyloxycarbonyl. The "alkoxycarbonylethenyl group having 1 to 6 carbon atoms" means a group in which an alkoxy having 1 to 6 carbon atoms is bonded to a carbonylethenyl, such as methoxycarbonylethenyl, ethoxycarbonylethenyl, propoxycarbonylethenyl, butoxycarbonylethenyl, tert-butoxycarbonylethenyl, pentyloxycarbonylethenyl, or hexyloxycarbonylethenyl. "Halogen atom" means a chlorine atom, bromine atom, iodine atom or fluorine atom.

[0013] Examples of salts of the benzoxazine compound represented by general formula (1) of the present invention include inorganic acid salts such as hydrochloride, sulfate, nitrate, phosphate, hydrobromide, and hydroiodide; organic acid salts such as acetate, fumarate, maleate, oxalate, methanesulfonate, benzenesulfonate, and paratoluenesulfonate; and salts with inorganic or organic bases such as sodium ion, potassium ion, calcium ion, and trimethylammonium.

[0014] The benzoxazine compound represented by general formula (1) of the present invention or a salt thereof may have one or more asymmetric centers in its structural formula, and may exist as two or more optical isomers and diastereomers, but the present invention encompasses all of the optical isomers and mixtures containing them in any ratio. Furthermore, the benzoxazine compound represented by general formula (1) of the present invention or a salt thereof may have two geometric isomers derived from a carbon-carbon double bond in its structural formula, and the present invention encompasses all of the geometric isomers and mixtures containing them in any ratio.

[0015] R1 in the general formula (1) of the present invention is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, preferably an alkyl group having 1 to 6 carbon atoms, and more preferably an alkyl group having 1 to 3 carbon atoms. In the general formula (1) of the present invention, R2 and R3 are each independently a hydrogen atom, a halogen atom, a nitro group, a cyano group, an alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, a halogenated alkyl group having 1 to 6 carbon atoms, an alkoxycarbonyl group having 1 to 6 carbon atoms, or an alkoxycarbonylethenyl group having 1 to 6 carbon atoms. Among these, it is preferred that R2 is a hydrogen atom, a halogen atom, a nitro group, an alkyl group having 1 to 6 carbon atoms, a halogenated alkyl group having 1 to 6 carbon atoms, an alkoxycarbonyl group having 1 to 6 carbon atoms, or an alkoxycarbonylethenyl group having 1 to 6 carbon atoms, and R3 is a hydrogen atom. It is further preferred that R2 is an alkyl group having 1 to 6 carbon atoms or an alkoxycarbonyl group having 1 to 6 carbon atoms, and R3 is a hydrogen atom. It is particularly preferred that R2 is an alkoxycarbonyl group having 1 to 6 carbon atoms, and R3 is a hydrogen atom. Furthermore, when R2 is a substituent other than a hydrogen atom, it is preferably at the 4-position on the benzene ring, and further, when R3 is a substituent other than a hydrogen atom, it is preferably at the 2- or 3-position on the benzene ring. The benzoxazine compound represented by general formula (1) of the present invention or a salt thereof is preferably a compound or a salt thereof in which R1 is an alkyl group having 1 to 6 carbon atoms, R2 is an alkoxycarbonyl group having 1 to 6 carbon atoms, and R3 is a hydrogen atom, and among these, ethyl (E)-3-{4-[7-(4-methoxycarbonylbenzyloxy)-1,4-benzodioxan-6-yloxy]phenyl}-2-propenoate (a compound in which R1 is an ethyl group, R2 is a 4-methoxycarbonyl group, and R3 is a hydrogen atom) is more preferred.

[0016] The benzoxazine compound or a salt thereof of the present invention can be produced, for example, by the production method shown below, but the production method of the benzoxazine compound or a salt thereof of the present invention is not limited to these examples. [ka]

[0017] Starting from 6-hydroxybenzodioxane, 7-hydroxybenzodioxane-6-carbaldehyde (1) was synthesized using ethylmagnesium chloride and paraformaldehyde. The hydroxyl group was then protected with chloromethyl methyl ether (2). Further Baeyer-Villiger oxidation with m-chloroperbenzoic acid followed by basic hydrolysis afforded 6-methoxymethoxy-7-hydroxy-1,4-benzodioxane (3). This was then reacted with 4-fluorobenzonitrile (4) and reduced to the aldehyde (5) with diisobutylaluminum hydride. Subsequently, a Wittig-Horner reaction afforded the α,β-unsaturated ester (6). The methoxymethyl group was then deprotected under acidic conditions (7), and the resulting compound (8) was obtained by reaction with benzyl halides bearing various substituents on the benzene ring.

[0018] In producing the benzoxazine compound or a salt thereof of the present invention, after the reaction in each step is completed, post-treatment can be carried out as needed by conventional methods, and the product can be isolated. That is, post-treatment procedures such as filtration, washing, extraction, pH adjustment, dehydration, and concentration can be carried out individually or in combination of two or more procedures, and the product can be isolated by concentration, crystallization, reprecipitation, column chromatography, etc. Furthermore, the isolated product can be further purified by carrying out one or more operations, such as crystallization, reprecipitation, column chromatography, extraction, and stirring and washing of the crystals with a solvent, either individually or in combination of two or more procedures, as needed. The chemical structure of the product in each step can be confirmed by known techniques, such as nuclear magnetic resonance (NMR), infrared spectroscopy (IR), and mass spectrometry (MS).

[0019] (Insect growth inhibitor of the present invention) As will be explained in detail in the Examples below, the benzoxazine compound or its salt of the present invention does not exhibit precocious metamorphosis-inducing activity in silkworms, unlike EMBP, and furthermore, its activity in reporter assays is approximately 1 / 40 of that of EMBP, confirming that it does not have JH antagonist activity in silkworms. On the other hand, it was confirmed that the benzoxazine compound or its salt of the present invention exhibits lethal activity against final-stage larvae of S. exigua by inducing metamorphosis failure. Moreover, it was also confirmed that EMBP induced excessive molting or molting failure in final-stage larvae of S. exigua at high doses, but did not induce metamorphosis failure. Thus, although the benzoxazine compounds or salts thereof of the present invention have a similar basic chemical structure to conventional compounds having JH antagonist activity such as EMBP, their biological activities against silkworms and beet armyworms are significantly different, and they exhibit a completely unpredictable growth inhibitory activity that induces metamorphosis failure.

[0020] (Selective Lepidoptera Pest Control Agent of the Present Invention) As described above, the benzoxazine compound or its salt of the present invention does not exhibit any biological activity against silkworms, but induces metamorphosis failure and exhibits growth inhibitory activity against final-stage larvae of the beet armyworm. This characteristic biological activity exhibits a selective control effect against agricultural pests. A selective lepidopteran pest control agent containing the benzoxazine compound or its salt of the present invention as an active ingredient functions as a selective metamorphosis failure inducer against lepidopteran pests and exhibits the effect of selectively controlling agricultural pests. For example, when raising mulberries, which are necessary for raising silkworms, a selective lepidopteran pest control agent containing the benzoxazine compound of the present invention or a salt thereof as an active ingredient can be used to control pests on mulberry, thereby making it possible to exterminate pests that damage mulberry. This makes it possible to feed mulberry plants to which the selective lepidopteran pest control agent has been attached without harming the silkworms, which is useful in agricultural applications.

[0021] The selective lepidopteran pest control agent of the present invention is used by mixing with an inert carrier such as a solid carrier, a liquid carrier, etc. in the same manner as conventional agricultural chemicals. The selective lepidopteran pest control agent of the present invention can be formulated into wettable powders, water-soluble powders, flowable powders, microcapsules, emulsifiable concentrates, dusts, granules, etc. The content of the active ingredient consisting of the benzoxazine compound of the present invention or a salt thereof in the selective lepidopteran pest control agent of the present invention is generally in the range of 0.1 to 100% by weight, preferably 0.2 to 90% by weight, more preferably 0.5 to 80% by weight.

[0022] Examples of solid carriers used in formulations include fine powders and granules of clays (kaolin clay, diatomaceous earth, bentonite, fubasami clay, acid clay, etc.), synthetic hydrous silicon oxide, talc, ceramics, other inorganic minerals (sericite, quartz, sulfur, activated carbon, calcium carbonate, hydrated silica, etc.), chemical fertilizers (ammonium sulfate, ammonium phosphate, ammonium nitrate, urea, ammonium chloride, etc.), and synthetic resins (polyester resins such as polypropylene, polyacrylonitrile, polymethyl methacrylate, polyethylene terephthalate, nylon resins such as nylon-6, nylon-11, nylon-66, polyamide resins, polyvinyl chloride, polyvinylidene chloride, vinyl chloride-propylene copolymer, etc.). Examples of liquid carriers include water, alcohols (methanol, ethanol, isopropyl alcohol, butanol, hexanol, benzyl alcohol, ethylene glycol, propylene glycol, phenoxyethanol, etc.), ketones (acetone, methyl ethyl ketone, cyclohexanone, etc.), aromatic hydrocarbons (toluene, xylene, ethylbenzene, dodecylbenzene, phenylxylylethane, methylnaphthalene, etc.), aliphatic hydrocarbons (hexane, cyclohexane, kerosene, diesel, etc.), esters (ethyl acetate, butyl acetate, isopropyl myristate, ethyl oleate, diisopropyl adipate, diisobutyl adipate, propylene glycol monomethyl ester), and the like. ether acetate, etc.), nitriles (acetonitrile, isobutyronitrile, etc.), ethers (diisopropyl ether, 1,4-dioxane, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, diethylene glycol monomethyl ether, propylene glycol monomethyl ether, dipropylene glycol monomethyl ether, 3-methoxy-3-methyl-1-butanol, etc.), amides (N,N-dimethylformamide (hereinafter referred to as "DMF"), N,N-dimethylacetamide, etc.), sulfoxides (dimethyl sulfoxide (hereinafter referred to as "DMSO"), etc.), propylene carbonate, and vegetable oils (soybean oil, cottonseed oil, etc.).

[0023] When the selective lepidopteran pest control agent of the present invention is formulated, surfactants and other formulation adjuvants may be further added as needed. Examples of surfactants include nonionic surfactants such as polyoxyethylene alkyl ethers, polyoxyethylene alkylaryl ethers, and polyethylene glycol fatty acid esters, and anionic surfactants such as alkyl sulfonates, alkyl benzene sulfonates, and alkyl sulfates. Other formulation adjuvants include adhesives, dispersants, colorants, and stabilizers, such as casein, gelatin, sugars (starch, gum arabic, cellulose derivatives, alginic acid, etc.), lignin derivatives, bentonite, synthetic water-soluble polymers (polyvinyl alcohol, polyvinylpyrrolidone, polyacrylic acids, etc.), PAP (isopropyl acid phosphate), BHT (2,6-di-tert-butyl-4-methylphenol), and BHA (a mixture of 2-tert-butyl-4-methoxyphenol and 3-tert-butyl-4-methoxyphenol).

[0024] When the selective lepidopteran pest control agent of the present invention is formulated as a wettable powder, water-soluble powder, flowable powder, microcapsule preparation, or emulsion, it is usually applied after being diluted with water so that the concentration of the active ingredient consisting of the benzoxazine compound of the present invention or a salt thereof is 0.1 to 10,000 ppm, and when it is formulated as a dust or granule preparation, it is applied as is.

[0025] Examples of lepidopteran pests against which the selective lepidopteran pest control agent of the present invention is effective include the following. Lepidoptera pests: moths such as the rice suppressor moth (Chilosuppressalis), rice leafroller (Cnaphalocrocis medinalis), European corn borer (Ostrinia nubilalis), Hellullaundalis, grass moth (Parapediasia teterrella), cotton bollard (Notarcha derogata), and Indian meal moth (Plodia interpunctella); common cutworm (Spodoptera litura), armyworm (Pseudaletia separata), armyworm moth (Mamestrabrassicae); noctuid moths such as the Trichoplusia, Heliotis, and Helicoverpa genera; cabbage white butterflies (Pieris Examples of such insects include pierid butterflies such as Acanthoptera rapae, tortrix moths such as the genus Adoxophyes, the pear fruit moth (Grapholitamolesta), and the codling moth (Cydia pomonella), fruit moths such as the peach fruit moth (Carposina niponensis), leafminers such as the genus Lionetia, tussock moths such as the genera Lymantria and Euploctys, diamondback moths such as Plutella xylostella, tooth moths such as the pink bollworm (Pectinophoragossypiella), tiger moths such as the fall webworm (Hyphantria cunea), and broad-leaved moths such as the burr moth (Tinea translucens) and the brown burr moth (Tineola bisselliella).

[0026] When the selective lepidopteran pest control agent of the present invention is used to control animal ectoparasites, application can be by spot-on application, pour-on application, or other methods. Spot-on application typically involves dripping or applying a liquid formulation to the skin of a host animal, such as the back of the scapulae. Pour-on application typically involves pouring a liquid formulation along the dorsal line of the host animal's body. The amount of treatment for an animal varies depending on the type of target animal or ectoparasite to be controlled, but is typically 0.05 to 1000 mg / kg, preferably 0.1 to 200 mg / kg, of the active ingredient having JH antagonist activity per kg of live weight of the target animal.

[0027] Ectoparasites that can be controlled by the selective lepidopteran pest control agent of the present invention include various harmful arthropods known as ectoparasites of host animals, and specific examples thereof include Diptera pests such as the house fly (Musca domestica), the European house fly (Musca hervei), the black house fly (Musca bezzii), the horn fly (Haematobia irritans), the black spotted black fly (Simulium iwatens), the cow midge (Culicoides oxystoma), the red horse fly (Tabanus chrysurus), the mosquito (Culex pipiens), and the Asian tiger mosquito (Aedes albopictus); Phthiraptera pests such as the cat louse (Haematopinuseurysternus) and the sheep louse (Damalinia ovis); and the cat flea (Ctenocephalides felis, dog flea (Ctenocephalidescanis), and rat flea (Xenopsylla cheopis). [Example]

[0028] The present invention will be explained below by way of examples, including synthesis examples of compounds, physical property data, and test examples, but the technical scope of the present invention is not limited to these examples. 1H-NMR (Bruker Biospin AV400M, 400 MHz, internal standard: TMS) data was used.

[0029] <Synthesis examples and physical property data> 7-Hydroxy-1,4-benzodioxane-6-carbaldehyde(1) 6-Hydroxy-1,4-benzodioxane (5.0 g, 32.8 mmol) was dissolved in 30 mL of THF and cooled with ice water. 3 M ethylmagnesium bromide in THF (65.7 mL, 131 mmol) was added dropwise to this solution and stirred at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in 30 mL of benzene. hexamethylphosphoric triamide (14.7 g, 82.1 mmol) and 7.0 g of paraformaldehyde were added, and the mixture was heated at 80 °C overnight. The reaction mixture was acidified with 1 M hydrochloric acid and then extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dehydrated over anhydrous sodium sulfate. After concentration under reduced pressure, the resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate = 3:1) to obtain compound (1) (4.50 g, 76%). 1 H-NMR (CDCl3) δ: 4.30(4H, m, OCH2CH2O), 6.45 (1H, s, phenyl), 7.01 (1H, s, phenyl), 9.66 (1H, s, OH), 10.92 (1H, s, CHO).

[0030] 7-Methoxymethoxy-1,4-benzodioxane-6-carbaldehyde(2) Compound (1) (4.50 g, 24.9 mmol) was dissolved in 100 mL of dichloromethane and cooled with ice water. Diisopropylethylamine (4.84 g, 37.4 mmol) and chloromethyl methyl ether (3.02 g, 37.4 mmol) were added to this solution and stirred for 7 hours under ice cooling. The reaction mixture was extracted with ethyl acetate, and the organic layer was washed with 1 M aqueous sodium hydroxide solution, water, and saturated brine, dehydrated over anhydrous sodium sulfate, and concentrated under reduced pressure. Diethyl ether was added to the residue and the mixture was recrystallized to give compound (2) (4.30 g, 77%). 1H-NMR (CDCl3) δ: 3.51 (3H, s, OCH3), 4.27 (4H,m, OCH2CH2O), 5.20 (2H, s, OCH2O), 6.72 (1H, s,phenyl), 7.36 (1H, s, phenyl), 10.30 (1H, s, CHO).

[0031] 7-Methoxymethoxy-6-hydroxy-1,4-benzodioxane(3) Compound (2) (4.30 g, 19.2 mmol) was dissolved in 100 mL of dichloromethane and cooled with ice water. m-Chloroperbenzoic acid (containing water) (5.67 g, 23.0 mmol) was added to this solution and stirred at 50 °C overnight. The reaction mixture was extracted with ethyl acetate, and the organic layer was washed with saturated aqueous sodium bicarbonate, water, and saturated brine, dehydrated over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was dissolved in 50 mL of ethanol, and 10 mL of 1 M aqueous sodium hydroxide was added. The mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure, and then 50 mL of saturated aqueous ammonium chloride was added. The mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dehydrated over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate = 2:1) to give compound (3) (3.63 g, 89%). 1 H-NMR (CDCl3) δ: 3.51 (3H, s, OCH3), 4.19 (4H,m, OCH2CH2O), 5.09 (2H, s, OCH2O), 5.68 (1H,s, OH), 6.49 (1H, s, phenyl), 6.66 (1H, s, phenyl).

[0032] 4-(7-Methoxymethoxy-1,4-benzodioxan-6-yloxy)benzonitrile (4) Compound (3) (2.0 g, 9.4 mmol) was dissolved in 20 mL of dimethyl sulfoxide, and then anhydrous sodium carbonate (1.95 g, 14.1 mmol) and 4-fluorobenzonitrile (1.71 g, 14.1 mmol) were added. The mixture was stirred at 80 °C overnight. The reaction mixture was extracted with ethyl acetate, and the organic layer was washed with 1 M aqueous sodium hydroxide solution, water, and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate = 2:1) to give compound (4) (1.67 g, 57%). 1 H-NMR (CDCl3) δ: 3.34 (3H, s, OCH3), 4.25 (4H,m, OCH2CH2O), 4.99 (2H, s, OCH2O), 6.64 (1H, s,phenyl), 6.80 (1H, s, phenyl), 6.94 (2H, d, J=8.9 Hz, phenyl), 7.56 (1H, d,J=8.9 Hz, phenyl).

[0033] 4-(7-Methoxymethoxy-1,4-benzodioxan-6-yloxy)benzaldehyde (5) Compound (4) (1.0 g, 3.2 mmol) was dissolved in 20 mL of dichloromethane and cooled to ice. 1 M diisobutylaluminum hydride in hexane (4.79 mL, 4.8 mmol) was added to this solution and stirred for 7 hours under ice cooling. 30 mL of saturated aqueous ammonium chloride was added, and the reaction mixture was extracted with ethyl acetate. The organic layer was washed with water and saturated brine and dehydrated over anhydrous sodium sulfate. After concentration under reduced pressure, the resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate = 3:1) to give compound (5) (0.96 g, 95%). 1H-NMR (CDCl3) δ: 3.34 (3H, s, OCH3), 4.25 (4H,m, OCH2CH2O), 4.99 (2H, s, OCH2O), 6.66 (1H, s,phenyl), 6.81 (1H, s, phenyl), 6.99 (2H, d, J=8.8 Hz, phenyl), 7.81 (2H, d,J=8.8 Hz, phenyl), 9.90 (1H, s, CHO).

[0034] Ethyl (E)-3-[4-(7-methoxymethoxy-1,4-benzodioxan-6-yloxy)phenyl]-2-propenate (6a) Compound (5) (0.90 g, 2.8 mmol) was dissolved in 20 mL of ethanol, and then triethyl phosphonoacetate (0.77 g, 3.4 mmol) and sodium ethoxide (0.23 g, 3.4 mmol) were added and stirred at 50 °C overnight. The reaction mixture was extracted with ethyl acetate, and the organic layer was washed with water and saturated brine, dehydrated over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (n-hexane:ethyl acetate = 3:1) to give compound (6a) (1.00 g, 91%). 1 H-NMR (CDCl3) δ : 1.33 (3H, t, J=7.1 Hz, CH3),3.37 (3H, s, OCH3), 4.25 (6H, m, OCH2CH2O, OCH2),5.01 (2H, s, OCH2O), 6.31 (1H, d, J=16.0 Hz, CH), 6.62 (1H, s, phenyl), 6.79 (1H, s, phenyl), 6.90 (2H, d, J=8.8 Hz, phenyl), 7.44 (2H, t, J=8.8Hz, phenyl), 7.63 (1H, d, J=16.0 Hz, CH).

[0035] Compound (6b) was synthesized using trimethyl phosphonoacetate and sodium methoxide in the same manner as compound (6a). Only the yield and NMR data are shown below. Methyl (E)-3-[4-(7-methoxymethoxy-1,4-benzodioxan-6-yloxy)phenyl]-2-propenate (6b) 100% yield 1 H-NMR (CDCl3) δ : 3.37 (3H, s, OCH3), 3.79 (3H, s, OCH3),4.24 (4H, m, OCH2CH2O), 5.01 (2H, s, OCH2O), 6.31 (1H, d, J=16.0 Hz, CH), 6.62 (1H, s, phenyl),6.79 (1H, s, phenyl), 6.90 (1H, d, J=8.7 Hz, phenyl), 7.44 (1H, d, J=8.7 Hz,phenyl), 7.64 (1H, d, J=16.0 Hz, CH).

[0036] Ethyl (E)-3-[4-(7-hydroxy-1,4-benzodioxan-6-yloxy)phenyl]-2-propenate (7a) Compound (6a) (1.00 g, 2.6 mmol) was dissolved in 20 mL of ethanol, and then 2 mL of concentrated hydrochloric acid was added and stirred at room temperature overnight. The reaction mixture was extracted with ethyl acetate, and the organic layer was washed with water and saturated brine, dehydrated over anhydrous sodium sulfate, and then concentrated under reduced pressure. The resulting residue was recrystallized with diethyl ether to give compound (7a) (0.76 g, 89%). 1 H-NMR (CDCl3) δ :1.33 (3H, t,J=7.1 Hz, CH3), 4.24 (6H, m, OCH2CH2O, OCH2),5.04 (1H, s, OH), 6.33 (1H, d, J=16.0 Hz, CH), 6.53 (1H, s, phenyl), 6.60 (1H, s, phenyl), 6.98 (2H, d, J=8.7 Hz, phenyl), 7.48 (3H, d, J=8.7 Hz, phenyl),7.63 (1H, d, J=16.0 Hz, CH).

[0037] Compound (7b) was synthesized in the same manner as compound (7a). Only the yield and NMR data are shown below. Methyl (E)-3-[4-(7-hydroxy-1,4-benzodioxan-6-yloxy)phenyl]-2-propenate (7b) Yield 85% 1 H-NMR (CDCl3) δ:3.80 (3H, s, OCH3),4.22 (6H, m,OCH2CH2O), 5.03 (1H, br, OH), 6.34 (1H, d, J=16.0Hz, CH), 6.53 (1H, s, phenyl), 6.60 (1H, s, phenyl), 6.98 (2H, d, J=8.7 Hz, phenyl),7.48 (2H, d, J=8.7 H, phenyl z), 7.65 (1H, d, J=16.0 Hz, CH).

[0038] Ethyl (E)-3-[4-(7-benzyloxy-1,4-benzodioxan-6-yloxy)phenyl]-2-propenate (8a): Compound 8a Compound (7a) (0.060 g, 0.18 mmol) was dissolved in 5 mL of N,N-dimethylformamide, and benzyl bromide (0.036 g, 0.21 mmol) and anhydrous potassium carbonate (0.029 g, 0.21 mmol) were added, followed by stirring overnight at 50° C. The reaction mixture was extracted with ethyl acetate, and the organic layer was washed with 1 M aqueous sodium hydroxide solution, water, and saturated brine, dehydrated over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=4:1) to obtain compound (8a) (0.073 g, 96%). 1H-NMR (CDCl3) δ:1.33 (3H, t, J=7.1 Hz, CH3), 4.25 (7H, m,OCH2CH2O, OCH2), 4.94 (2H, s, OCH2),6.32 (1H, d, J=16.0 Hz, CH), 6.59 (1H, s, phenyl), 6.67 (1H, s, phenyl), 6.90(2H, d, J=8.7 Hz, phenyl), 7.10 (2H, m, phenyl), 7.23 (2H, m, phenyl), 7.37(1H, m, phenyl), 7.44 (2H, t, J=8.7 Hz, phenyl), 7.65 (1H, d, J=16.0 Hz, CH).

[0039] Compounds 8b to 8i were synthesized in the same manner as compound 8a, except that compound (7b) and the corresponding benzyl halide were used instead of compound (7a). Compound 8j was synthesized in the same manner as compound 8a, except that compound (7b) and the corresponding benzyl halide were used instead of compound (7a). Only the yield and NMR data are given below. Ethyl (E)-3-{4-[7-(4-methoxycarbonylbenzyloxy)-1,4-benzodioxan-6-yloxy]phenyl}-2-propenate (8b): Compound 8b Yield 76% 1 H-NMR (CDCl3) δ:1.34 (3H, t, J=7.1 Hz, CH3),3.90 (3H, s, OCH3), 4.26 (6H, m, OCH2CH2O, OCH2),4.99 (2H, s, OCH2), 6.32 (1H, d, J=16.0 Hz, CH), 6.56 (1H, s, phenyl),6.68 (1H, s, phenyl), 6.90 (2H, d, J=8.6 Hz, phenyl), 7.18 (2H, t, J=8.6 Hz, phenyl), 7.45 (2H, d, J=8.6 Hz, phenyl), 7.65 (1H, d, J=16.0 Hz, CH), 7.91 (2H, d, J=8.6 Hz, phenyl).

[0040] Ethyl (E)-3-{4-[7-(3-methoxycarbonylbenzyloxy)-1,4-benzodioxan-6-yloxy]phenyl}-2-propenate (8c): Compound 8c 100% yield 1 H-NMR (CDCl3) δ : 1.33 (3H, t, J=7.1 Hz, CH3),3.89 (3H, s, OCH3), 4.25 (6H, m, OCH2CH2O, OCH2),4.98 (2H, s, OCH2), 6.31 (1H, d, J=16.0 Hz, CH), 6.58 (1H, s, phenyl),6.68 (1H, s, phenyl), 6.90 (2H, d, J=8.6 Hz, phenyl), 7.29 (2H, m, phenyl),7.44 (2H, d, J=8.6 Hz), 7.64 (1H, d, J=16.0 Hz), 7.90 (2H, m, phenyl).

[0041] Ethyl (E)-3-(4-{7-[4-(2-methoxycarbonyl)ethenylbenzyloxy]-1,4-benzodioxan-6-yloxy}phenyl)-2-propenate (8d): Compound 8d Yield 85% 1H-NMR (CDCl3) δ:1.34 (3H, t, J=7.1 Hz, CH3), 3.80 (3H, s, OCH3), 4.26 (6H, m, OCH2CH2O, OCH2), 4.95 (2H, s, OCH2), 6.32 (1H, d, J=16.0 Hz, CH), 6.39 (1H, d, J=16.0Hz, CH), 6.57 (1H, s, phenyl), 6.68 (1H, s, phenyl), 6.90 (2H, d, J=8.7 Hz,phenyl), 7.13 (2H, d, J=8.1 Hz, phenyl), 7.39 (2H, d, J=8.1 Hz, phenyl), 7.45(2H, d, J=8.7 Hz, phenyl), 7.63 (1H, d, J=16.0 Hz, CH), 7.65 (1H, d, J=16.0 Hz, CH).

[0042] エチル(E)―3-{4-[7-(4-t-ブチルベンジルオキシ)-1,4-ベンCompound 8e (8e) Yield 74% 1 H-NMR (CDCl3)δ:1.28 (9H, s, CH3), 1.33 (3H, t,J=7.1 Hz, CH3), 4.25 (6H, m, OCH2CH2O, OCH2), 4.91 (2H, s, OCH2), 6.32 (1H, d, J=16.0 Hz, CH), 6.61 (1H, s, phenyl), 6.66 (1H, s, phenyl), 6.90 (2H, d, J=8.7 Hz, phenyl), 7.05 (2H, d, J=8.6 Hz, phenyl), 7.26 (2H, d, J=8.6 Hz, phenyl), 7.44 (2H, d, J=8.7 Hz), 7.65 (1H, d,J=16.0 Hz, CH).

[0043] Ethyl (E)-3-{4-[7-(4-methoxybenzyloxy)-1,4-benzodioxan-6-yloxy]phenyl}-2-propenate (8f): Compound 8f 100% yield 1 H-NMR (CDCl3) δ:1.33 (3H, t, J=7.1 Hz, CH3), 3.76 (3H, s,OCH3), 4.25 (6H, m, OCH2CH2O, OCH2),4.87 (2H, s, OCH2), 6.32 (1H, d, J=16.0 Hz, CH), 6.59 (1H, s, phenyl),6.66 (1H, s, phenyl), 6.76 (2H, d, J=8.8 Hz, phenyl), 6.88 (2H, d, J=8.8 Hz, phenyl), 7.02 (2H, d, J=8.8 Hz, phenyl), 7.44 (2H, d, J=8.8 Hz, phenyl), 7.65(1H, d, J = 16.0 Hz, CH).

[0044] Ethyl (E)-3-{4-[7-(4-chlorobenzyloxy)-1,4-benzodioxan-6-yloxy]phenyl}-2-propenate (8g): Compound 8g Yield 78% 1 H-NMR (CDCl3) δ : 1.34 (3H, t, J=7.1 Hz, CH3),4.25 (6H, m, OCH2CH2O, OCH2), 4.90 (2H, s, OCH2),6.32 (1H, d, J=16.0 Hz, CH), 6.56 (1H, s, phenyl), 6.67 (1H, s, phenyl), 6.88(2H, d, J=8.6 Hz, phenyl), 7.03 (2H, d, J=8.6 Hz, phenyl), 7.20 (2H, d, J=8.6Hz, phenyl), 7.44 (2H, t, J=8.6 Hz, phenyl), 7.65 (1H, d, J=16.0 Hz, CH).

[0045] Ethyl (E)-3-{4-[7-(4-trifluoromethylbenzyloxy)-1,4-benzodioxan-6-yloxy]phenyl}-2-propenate (8h): Compound 8h Yield 96% 1 H-NMR (CDCl3) δ : 1.33 (3H, t, J=7.1 Hz, CH3),4.26 (6H, m, OCH2CH2O, OCH2), 4.99 (2H, s, OCH2),6.32 (1H, d, J=16.0 Hz, CH), 6.57 (1H, s, phenyl), 6.69 (1H, s, phenyl), 6.90(2H, d, J=8.7 Hz, phenyl), 7.23 (2H, d, J=8.1 Hz, phenyl), 7.45 (2H, d, J=8.7Hz, phenyl), 7.49 (2H, d, J=8.1 Hz, phenyl), 7.64 (1H, d, J=16.0 Hz, CH).

[0046] Ethyl (E)-3-{4-[7-(4-nitrobenzyloxy)-1,4-benzodioxan-6-yloxy]phenyl}-2-propenate (8i): Compound 8i Yield 97% 1 H-NMR (CDCl3) δ : 1.34 (3H, t, J=7.1 Hz, CH3),4.25 (6H, m, OCH2CH2O, OCH2), 5.03 (2H, s, OCH2),6.33 (1H, d, J=16.0 Hz, CH), 6.56 (1H, s, phenyl), 6.70 (1H, s, phenyl), 6.91(2H, d, J=8.7 Hz, phenyl), 7.28 (2H, t, J=8.7 Hz, phenyl), 7.46 (2H, d, J=8.7Hz, phenyl), 7.64 (1H, d, J=16.0 Hz, CH), 8.10 (2H, d, J=8.7 Hz, phenyl).

[0047] Methyl (E)-3-{4-[7-(4-methoxycarbonylbenzyloxy)-1,4-benzodioxan-6-yloxy]phenyl}-2-propenate (8j): Compound 8j Yield 92% 1 H-NMR (CDCl3) δ : 3.80 (3H, s, OCH3), 3.89 (3H, s, OCH3),4.24 (4H, m, OCH2CH2O), 4.99 (2H, s, OCH2),6.32 (1H, d, J=16.0 Hz, CH), 6.56 (1H, s, phenyl), 6.68 (1H, s, phenyl), 6.90(2H, d, J=8.6 Hz, phenyl), 7.18 (2H, d, J=8.6 H, phenyl z), 7.45 (2H, d, J=8.6Hz, phenyl), 7.66 (1H, d, J=16.0 Hz, CH), 7.90 (2H, d, J=8.6 Hz, phenyl).

[0048] <Test Example 1> Confirmation test of growth inhibitory activity using final-stage larvae of the beet armyworm The test insects were beet armyworm larvae, which were reared in an incubator with a 16-hour light and 8-hour dark period at 25±2°C and fed Insector LFS (manufactured by Nippon Nosan Kogyo Co., Ltd.). Fifth-instar beet armyworm larvae within 24 hours of molting were used. Furthermore, compounds 8a to 8j, which are specific examples of the compounds of the present invention, and EMBP obtained by the production method described in Patent Document 2 were used as test compounds. The test compounds were diluted with acetone to concentrations of 0.5μg / μL, 0.05μg / μL, 0.005μg / μL, and 0.0005μg / μL, and 2μL of acetone solution was applied to the dorsal thorax of 10 test insects for each test compound. Control test insects were treated with acetone only, and after treatment, they were reared under normal conditions. The number of individuals that underwent excessive molting, abnormal molting, or abnormal metamorphosis, as well as the number of individuals that metamorphosed into normal pupae, were counted. The results are shown in Table 1. In Table 1, compound 8b is listed alongside "EMBOP."

[0049] [Table 1]

[0050] The results in Table 1 demonstrate that the benzoxazine compounds of the present invention represented by general formula (1) are a group of compounds that exhibit metamorphosis inhibitory activity against S. exigua. Among all the test compounds, compound 8b (EMBOP) in particular exhibited strong metamorphosis inhibition against S. exigua when treated with 1 μg per test insect. On the other hand, it has been revealed that EMBP, which is reported in Patent Document 2 to exhibit JH antagonist activity in silkworm larvae, exhibits excessive molting and molting inhibitory activity when treated at high doses, and exhibits biological activity different from that of the compounds of the present invention such as compound 8b.

[0051] <Test Example 2> Confirmation test of precocious metamorphosis inducing activity (anti-JH activity) using 3rd instar silkworm larvae Silkworm larvae (Shunrei x Kanetsuki) were reared in a thermostatic chamber with 12 hours of light and 12 hours of darkness at 25±2°C, and were fed Silkmate 2S (manufactured by Nippon Nosan Kogyo Co., Ltd.). Silkworm larvae that had been in the third instar for 24 hours after molting were used. Furthermore, compounds 8a to 8j, which are specific examples of the compounds of the present invention, and EMBP obtained by the production method described in Patent Document 2 were used as test compounds. The test compounds were diluted with acetone to 0.5 μg / μL, 0.05 μg / μL, and 0.005 μg / μL, and 20 test insects were treated with 2 μL of acetone solution on the dorsal thorax of each test compound. Control insects were treated with acetone only and then reared under normal conditions. Each test was performed twice. The anti-JH activity of the test compounds was evaluated as the average percentage (%) obtained by dividing the number of test insects that underwent precocious metamorphosis by the number of test insects (20) used in the test. The test compounds and their anti-JH activities are shown in Table 2. In Table 2, compound 8b is listed as "EMBOP."

[0052] [Table 2]

[0053] The results in Table 2 show that EMBP, which has been reported to exhibit JH antagonist activity in silkworms, exhibited high precocious metamorphosis-inducing activity. On the other hand, it was revealed that the benzoxazine compound of the present invention represented by general formula (1), which induces metamorphosis failure in the beet armyworm, does not exhibit any JH antagonist activity in the silkworm.

[0054] <Test Example 3> Confirmation test of JH antagonist activity by reporter assay using cultured silkworm cells As test compounds, compound 8b (EMBOP), which is a specific example of the compound of the present invention, and EMBP obtained by the production method described in Patent Document 2 were used. We used BmN_JF&AR cells, a silkworm cultured cell line genetically modified to express firefly luciferase in response to JH. When these cells were simultaneously treated with JH and a JH antagonist, the expression of firefly luciferase, which is normally induced by JH, was inhibited by the JH antagonist, resulting in a decrease in luciferase activity (Fluc). This phenomenon was utilized to confirm the JH antagonist activity of test compounds. JH1, the major JH in silkworms, was used in 96-well plates for each of the following experimental groups, and the following experimental groups and controls were prepared. Experimental group: 100 μL of medium containing JH1 (final concentration 1 nM) + 1 μL of DMSO solution containing each test compound Control: 100 μL of medium without JH1 + 1 μL of DMSO BmN_JF&AR cells (5 × 10 5 The plates were sealed and cultured at 26°C for 20 hours. Thereafter, the medium was discarded, 20 μL of Passive Lysis Buffer (Promega) was added, the mixture was shaken on a shaker for 10 minutes, and the mixture was dispensed into a new 96-well plate. 50 μL of Luciferase Assay Buffer II (Promega) was dispensed into each well, and firefly luciferase activity (hereinafter sometimes referred to as "Fluc") was measured using a luminometer ARVO (PerkinElmer). The Fluc measurement results at each test concentration of the test compound were normalized using the following formula, with the experimental group with the highest Fluc value (the experimental group with no effect of the JH antagonist) set as 100%. (calculation formula) Normalized response (%) = {(Fluc mean value at test concentration - Mean n ) ÷ (Average Fluc value at 0.1 nM - Mean n )}×100 Mean n : Mean Fluc of control Figure 1 shows a graph obtained by performing nonlinear regression using GraphPad Prism (ver. 9) on the normalized response (%) at each test concentration. In Figure 1, compound 8b is represented as "EMBOP."

[0055] The JH antagonist activity of each test compound was calculated using GraphPad Prism (ver. 9) from Figure 1 as the 50% inhibitory concentration (IC 50 ) was calculated and evaluated. 50 is 4.5 nM, and the IC of compound 8b 50 was calculated to be 176 nM. These results demonstrate that EMBP, which has a high precocious metamorphosis-inducing activity in silkworm larvae, also exhibits high JH antagonist activity in vitro. On the other hand, compound 8b, a specific example of a compound of the present invention, which exhibits growth inhibitory activity against beet armyworm but does not exhibit precocious metamorphosis-inducing activity in silkworms, was found to have JH antagonist activity that is approximately 1 / 40 of that of EMBP.

[0056] The results of the above "Test Examples 1" to "Test Examples 3" revealed that compound 8b, a specific example of the compound of the present invention, exhibits metamorphosis inhibitory activity against beet armyworm, but does not act as a JH antagonist against silkworm both in vivo and in vitro. [Industrial Applicability]

[0057] The benzoxazine compound represented by the general formula (1) of the present invention or a salt thereof, unlike EMBP described in Patent Document 2, does not exhibit any activity of inducing precocious metamorphosis in silkworm larvae, but exhibits growth inhibitory activity against the beet armyworm, an agricultural pest, and has selective biological activity against pests, making it highly promising as a selective pest control agent. Such a compound group having pest selectivity has not yet been reported, and it will be extremely useful in finding new directions for pest control in the agricultural field in the future.

Claims

1. A benzoxazine compound represented by general formula (1) or a salt thereof: 【Chemistry 1】 (In the formula, R １ is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms, R ２ , R ３ are each independently a hydrogen atom, a halogen atom, a nitro group, a cyano group, an alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 6 carbon atoms, a halogenated alkyl group having 1 to 6 carbon atoms, an alkoxycarbonyl group having 1 to 6 carbon atoms, or an alkoxycarbonylethenyl group having 1 to 6 carbon atoms.

2. R １ is an alkyl group having 1 to 6 carbon atoms, R ２ is an alkoxycarbonyl group having 1 to 6 carbon atoms, R ３ The benzoxazine compound or a salt thereof according to claim 1 , wherein represents a hydrogen atom.

3. Ethyl (E)-3-{4-[7-(4-methoxycarbonylbenzyloxy)-1,4-benzodioxan-6-yloxy]phenyl}-2-propenoate.

4. An insect growth inhibitor comprising the benzoxazine compound or a salt thereof according to any one of claims 1 to 3.

5. A selective lepidopteran pest control agent comprising the benzoxazine compound or salt thereof according to any one of claims 1 to 3 as an active ingredient.

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