Potato white cyst nematode control agent

Abstract

To provide an industrially readily-available hatching promoter for Globodera pallida eggs, and an agent and a method for control using the hatching promoter.SOLUTION: A Globodera pallida control agent contains a compound represented by a following formula (I) as an active ingredient [where Ar is a substituted or unsubstituted phenyl group or the like; R1's independently represent a substituted or unsubstituted C1-6 alkyl group, a substituted or unsubstituted C2-6 alkenyl group or the like; R2 is a hydrogen atom, or a substituted or unsubstituted C1-6 alkyl group; a moiety -Y-X- is a group represented by *-N(Rb)-C(=X1)-** or the like; X1's independently represent an oxygen atom or a sulfur atom; Rb is a hydrogen atom or the like; where, * denotes a position of bonding to a carbon atom having two R1's; ** denotes a position of bonding to Z; Z is a substituted or unsubstituted methylene group or a substituted or unsubstituted dimethylene group].SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a potato cyst nematode control agent, specifically, to a potato cyst nematode control agent that uses lactones and lactams having an effect of inducing hatching of potato cyst nematode eggs to induce suicidal hatching, thereby enabling a reduction in the density of potato cyst nematodes. [Background technology]

[0002] Potato cyst nematodes, especially the potato white cyst nematode (Globodera pallida) (hereinafter referred to as "Gp"), are major pests of potatoes worldwide. Gp parasitizes potato roots and reduces the yield, causing huge losses every year. Gp eggs are densely packed together and protected in a shell called a cyst (100-400 eggs), and are highly resistant to low temperatures and dryness. Therefore, if the eggs in the cyst do not hatch, they can survive in the soil for a long period of time, for over a decade. When potatoes are planted in a field, the eggs react sensitively to a specific chemical substance (a hatching promoter) secreted from the potato roots, causing them to hatch all at once. The hatched Gp larvae emerge from the cyst and parasitize the potato roots, causing damage. Female Gp absorb nutrients from the roots, swell and grow, lay eggs inside their own bodies, and then turn into cysts while still attached to the potato roots. When the potatoes are harvested, the cysts leave the roots and remain in the soil. If the next potato crop is planted with the cysts left in the soil, the next potato crop will also be affected.

[0003] Methods for controlling Gp include (1) application of pesticides, (2) cultivation of Solanaceae capture crops (such as tomatoes and eggplants), and (3) cultivation of resistant potatoes. (1) The pesticide that has been confirmed to be effective in reducing the density of Gp is ​​DD agent, whose main ingredient is 1,3-dichloropropene, but DD agent is designated as a hazardous substance and is irritating and toxic, so there are concerns about its adverse effects on the soil, surrounding environment, and the health of workers. This agent not only kills harmful cyst nematodes, but also various nematodes and microorganisms in the soil randomly, so its impact on the biological environment in particular is enormous. (2) Solanaceae trap crops secrete a hatching-promoting substance from their roots, which causes the eggs contained in Gp cysts in the field soil to hatch and the larvae to invade and parasitize the roots. However, the Gp cannot obtain enough nutrients from the Solanaceae trap crop to grow, and most of them die before reaching adulthood. This reduces the Gp density in the field soil. However, during the cultivation period of the Solanaceae trap crop, it becomes impossible to grow any commercially valuable crops in that field. (3) Gp-resistant potatoes secrete a hatching-promoting substance from their roots, just like regular potatoes, but this resistance inhibits the growth of parasitized larvae, causing many of them to die. Therefore, if Gp-resistant potatoes are cultivated in a field contaminated with Gp cysts, the Gp density will decrease as in (2), and potatoes can be harvested. However, since it is necessary to accumulate multiple resistance genes to give potatoes a high level of resistance, it takes a lot of time and effort. For this reason, there are only a few Gp-resistant potato varieties that can be used, and potato varieties with suitable quality cannot be cultivated. In addition, since it has been confirmed that the Gp resistance of potatoes will eventually be broken and the Gp of the broken strain will become apparent, caution is required in using them. Therefore, all of the methods (1) to (3) have problems.

[0004] (4) A method of controlling Gp has been proposed in which a naturally derived hatching promoter is sprayed on a Gp-infected field during the season when potatoes are not cultivated, thereby hatching Gp eggs and causing them to starve to death. Solanoeclepin A is known as a naturally derived hatching promoter (Patent Document 1). Solanoeclepin A is a compound having a tricyclodecane structure isolated from a hydroponic culture solution of potatoes. Although the structure is unknown, a hatching promoter isolated from an exudate of potato or tomato roots is also known (Patent Document 2). Such naturally derived hatching promoters can also be obtained from the roots of solanaceae plants, or from calluses or hairy roots produced therefrom. However, the amount of hatching promoter obtained by either method is small, and it is difficult to secure the amount required for practical use. For this reason, a practical method of controlling Gp using a naturally derived hatching promoter has not been developed. (5) Non-natural and inorganic hatching promoters for Gp eggs have been reported (Non-Patent Document 1). Specifically, it is disclosed that picrolonic acid, sodium metavanadate, sodium orthovanadate, and sodium thiocyanate exhibit hatching activity of approximately 30, 70, 60, and 30%, respectively, compared to natural hatching promoters. However, these hatching promoters are difficult to put into practical use because they have insufficient hatching activity or are harmful substances. (6) A method of using a mixture of hatching promoters derived from natural and non-natural sources has also been proposed (Patent Document 3). Specifically, it is disclosed that the hatching rate of Gp eggs using a mixture of 4-hydroxybenzyl alcohol and potato root exudate (PRD) is 60% (control is 10%). However, the hatching activity is insufficient, and there are problems with practical application.

[0005] Incidentally, 4-aryl-2-pyrrolidinones such as (compound 1) 5,5-dimethyl-4-phenyl-2-pyrrolidinone (CAS: 20894-20-6), (compound 2) 5,5-dimethyl-4-(4-methylphenyl)-2-pyrrolidinone (CAS: 1477653-30-7), (compound 3) 5,5-dimethyl-4-(4-chlorophenyl)-2-pyrrolidinone (CAS: 36263-12-4), (compound 4) 5,5-dimethyl-4-(4-bromophenyl)-2-pyrrolidinone (CAS: 2423033-43-4), and (compound 5) 1-hydroxy-5,5-dimethyl-4-phenyl-2-pyrrolidinone (CAS: 22307-02-4) are known in the literature (Non-Patent Documents 2 and 3). In addition, (compound 6) 5,5-dimethyl-4-(4-methoxyphenyl)-2-pyrrolidinone (CAS: 1493722-32-9), (compound 7) 5,5-dimethyl-4-(4-trifluoromethylphenyl)-2-pyrrolidinone (CAS: 1467865-26-4), (compound 8) 5,5-dimethyl-4-(4-fluorophenyl)-2-pyrrolidinone (CAS: 1495515-81-5), (compound 9) 5,5-dimethyl-4-(3-methylphenyl)-2-pyrrolidinone (CAS: 1480195-09-2), (compound 10) 5,5-dimethyl-4-(2-methylphenyl)-2-pyrrolidinone (C AS: 1466249-92-2), (compound 11) 5,5-dimethyl-4-(2,5-dimethyl-phenyl)-2-pyrrolidinone (CAS: 1469103-51-2), (compound 12) 5,5-dimethyl-4-(3,4-difluoro-phenyl)-2-pyrrolidinone (CAS: 1472745-56-4), (compound 13) 5,5-dimethyl-4-(3,4,5-trifluoro-phenyl)-2-pyrrolidinone (CAS: 1484547-30-9), (compound 14) 5,5-dimethyl-4-(2,4-dimethyl-phenyl)-2-pyrrolidinone (CAS: 1488690-56-7), etc. are commercially available. (Compound 15) 3,5,5-trimethyl-4-phenyl-2-pyrrolidinone (CAS: 2003396-63-0) is a compound registered in the CAS registry. The physiological actions of these 4-aryl-2-pyrrolidinones are unknown.

[0006] (Compound 16) 5,5-dimethyl-4-phenylpyrrolidine-2-thione (CAS: 35418-39-4) is also a known compound in the literature. Its physiological action is unknown (Non-Patent Document 4).

[0007] 4-aryl-dihydrofuran-2(3H)-ones such as (Compound 17) 5,5-dimethyl-4-phenyldihydrofuran-2(3H)-one (CAS: 13133-96-5), (Compound 18) 5,5-dimethyl-4-(p-tolyl)dihydrofuran-2(3H)-one (CAS: 63507-01-7), (Compound 19) 4-(4-fluorophenyl)-5,5-dimethyldihydrofuran-2(3H)-one (CAS: 245487-39-2), and (Compound 20) 5,5-dimethyl-4-(o-tolyl)dihydrofuran-2(3H)-one (CAS: 73689-82-4) are known in the literature (Non-Patent Documents 5 to 7). It has been described that compound 17 has papaverine-like activity, which is a vasodilator and an antispasmodic (Non-Patent Document 6), and that it is an inflammation inhibitor (Non-Patent Document 7). (Compound 21) 3,3-Dimethyl-4-phenyl-cyclopentanone (CAS: 22273-76-3) is a compound known in the literature (Non-Patent Document 8). [Prior art documents] [Patent documents]

[0008] [Patent Document 1] WO93 / 02083A1 [Patent Document 2] WO99 / 59414 [Patent Document 3] WO2019 / 032549A1 [Non-patent literature]

[0009] [Non-Patent Document 1] Journal of Nematology, Volume: 33, Issue: 4, Pages: 195-202, 2001 [Non-Patent Document 2] Journal of the American Chemical Society, Volume: 142, Issue: 19, Pages: 8672-8681, 2020 [Non-Patent Document 3] Australian Journal of Chemistry, Volume: 41, Issue: 1, Pages: 37-47, 1988 [Non-Patent Document 4] Australian Journal of Chemistry, Volume: 26, Issue: 10, Pages: 2177-82, 1973 [Non-Patent Document 5] Journal of the American Chemical Society, Volume: 121, Issue: 33, Pages: 7708-7709, 1999 [Non-Patent Document 6] Praktikates Akademias Athenon, Volume Date: 1982, Volume: 57, Pages: 515-28, 1983 [Non-Patent Document 7] European Journal of Medicinal Chemistry, Volume: 12, Issue: 1, Pages: 9-11, 1977 [Non-Patent Document 8] Tetrahedron Letters, Issue: 9, Pages: 749-52, 1969 Summary of the Invention [Problem to be solved by the invention]

[0010] In the prior art for controlling Gp, the method using pesticides (1) is subject to great concern over environmental destruction and adverse effects on cultivated land and marine resources, and its use is limited or restricted in major potato exporting countries. The method of cultivating Solanaceae capture crops (2) has commercial disadvantages, and the cultivation of Gp-resistant potato varieties (3) must be avoided from continuous planting due to concerns over the emergence of breakthrough strains. The methods of applying hatching promoters (4) to (6) to the soil to promote suicidal hatching of Gp eggs and kill them are highly effective if hatching promoters derived from natural products are used, as they have high hatching activity, but the amount of hatching promoter cannot be secured, and hatching promoters derived from non-natural products or inorganic substances have poor hatching activity and cannot be expected to be effective, and none of these methods are yet to be put into practical use.

[0011] However, the method of controlling Gp using hatching promoters does not have direct biocidal activity, and acts only on Gp, and is not expected to have any adverse effects on other organisms, so it is extremely advantageous in terms of environmental conservation and ensuring the safety of applicators, etc. In addition, as long as it is during the crop rotation period when potatoes are not being cultivated, the treatment time can be freely selected, and there is an advantage in that it does not interfere with production activities. Therefore, an object of the present invention is to provide a hatching promoter for Gp eggs that is easily available industrially, and a control agent and a control method using the same. [Means for solving the problem]

[0012] It has been found that the compound of formula (I) exhibits a significantly higher hatching-promoting effect on Gp eggs than known non-naturally derived or inorganic hatching-promoting substances. That is, the present invention encompasses the following embodiments. [1] A potato cyst nematode control agent comprising, as an active ingredient, at least one selected from the group consisting of a compound represented by the following formula (I), a stereoisomer thereof, and a salt thereof:

[0013] [ka]

[0014] [In the formula, Ar represents a substituted or unsubstituted phenyl group or a substituted or unsubstituted naphthyl group; R 1 each independently represents a substituted or unsubstituted C1-6 alkyl group, a substituted or unsubstituted C2-6 alkenyl group, a substituted or unsubstituted C2-6 alkynyl group, a substituted or unsubstituted C3-6 cycloalkyl group, a substituted or unsubstituted phenyl group, or a substituted or unsubstituted naphthyl group; R 2 represents a hydrogen atom or a substituted or unsubstituted C1-6 alkyl group; The partial structure -YX- is *-CH 2 -C(=X 1 )-**, *-OC(=X 1 )-**, *-SC(=X 1 )-**, *-N(R b )-C(=X 1 )-** or *-NH-SO 2 - represents a group represented by **; where * is two R 1 indicates the bonding position to the carbon atom having the symbol **, and indicates the bonding position to Z; X 1 each independently represents an oxygen atom or a sulfur atom; R b are each independently a hydrogen atom, a hydroxyl group, or R b1 A group represented by -C(=O)-, R b1 A group represented by OC(=O)-, R b1 A group represented by NH-C(=O)- or R b1 2 represents a group represented by NC(=O)-; R b1 each independently represents a substituted or unsubstituted C1-6 alkyl group, a substituted or unsubstituted C2-6 alkenyl group, a substituted or unsubstituted C2-6 alkynyl group, a substituted or unsubstituted C3-6 cycloalkyl group, a substituted or unsubstituted phenyl group, or a substituted or unsubstituted naphthyl group; Z represents a substituted or unsubstituted methylene group, or a substituted or unsubstituted dimethylene group; When Z is a substituted methylene group, R 2 and the substituent on the methylene group may together form a single bond or a methylene group.

[0015] [2] The potato cyst nematode control agent according to [1], wherein Z in formula (I) is a substituted or unsubstituted methylene group. [3] The potato cyst nematode control agent according to [1], wherein Z in formula (I) is a substituted or unsubstituted dimethylene group. [4] The partial structure -YX- in formula (I) is *-OC(=X 1 )-**, *-SC(=X 1 )-** or *-N(R b )-C(=X 1 )-**. The potato cyst nematode control agent according to [1], [5] The partial structure -YX- in the formula (I) is *-CH 2 -C(=X 1 )-**. The potato cyst nematode control agent according to [1], [6] The partial structure -YX- in formula (I) is *-NH-SO 2 The potato cyst nematode control agent according to [1], wherein the group is represented by -**. [7] The potato cyst nematode control agent according to [2], wherein the partial structure -YX- in formula (I) is a group represented by -OC(=O)-**, a group represented by -OC(=S)-**, a group represented by -SC(=O)-**, a group represented by -NH-C(=O)-**, a group represented by -N(OH)-C(=O)-**, or a group represented by -NH-C(=S)-**. [8] The potato cyst nematode control agent according to [2], wherein the partial structure -YX- in formula (I) is a group represented by -OC(=O)-**, a group represented by -SC(=O)-**, or a group represented by -NH-C(=O)-**.

[0016] [9] A hatching promoter for eggs of potato cyst nematode, comprising as an active ingredient at least one selected from the group consisting of a compound represented by the following formula (I), a stereoisomer thereof, and a salt thereof:

[0017] [ka]

[0018] [In the formula, Ar represents a substituted or unsubstituted phenyl group or a substituted or unsubstituted naphthyl group; R 1 each independently represents a substituted or unsubstituted C1-6 alkyl group, a substituted or unsubstituted C2-6 alkenyl group, a substituted or unsubstituted C2-6 alkynyl group, a substituted or unsubstituted C3-6 cycloalkyl group, a substituted or unsubstituted phenyl group, or a substituted or unsubstituted naphthyl group; R 2 represents a hydrogen atom or a substituted or unsubstituted C1-6 alkyl group; The partial structure -YX- is *-CH 2 -C(=X 1 )-**, *-OC(=X 1 )-**, *-SC(=X 1 )-**, *-N(R b )-C(=X 1 )-** or *-NH-SO 2 - represents a group represented by **; where * is two R 1 indicates the bonding position to the carbon atom having the symbol **, and indicates the bonding position to Z; X 1 each independently represents an oxygen atom or a sulfur atom; R b are each independently a hydrogen atom, a hydroxyl group, or R b1 A group represented by -C(=O)-, R b1 A group represented by OC(=O)-, R b1 A group represented by NH-C(=O)- or R b1 2represents a group represented by NC(=O)-; R b1 each independently represents a substituted or unsubstituted C1-6 alkyl group, a substituted or unsubstituted C2-6 alkenyl group, a substituted or unsubstituted C2-6 alkynyl group, a substituted or unsubstituted C3-6 cycloalkyl group, a substituted or unsubstituted phenyl group, or a substituted or unsubstituted naphthyl group; Z represents a substituted or unsubstituted methylene group, or a substituted or unsubstituted dimethylene group; When Z is a substituted methylene group, R 2 and the substituent on the methylene group may together form a single bond or a methylene group.

[10] A method for controlling potato cyst nematodes, comprising a step of applying the control agent or hatching promoter according to any one of [1] to [9] to field soil inhabited by potato cyst nematodes.

[0019]

[11] A compound represented by the following formula (Ia), a stereoisomer thereof, or a salt thereof:

[0020] [ka]

[0021] [In the formula, Ar represents a substituted or unsubstituted phenyl group, or a substituted or unsubstituted naphthyl group; R 1 each independently represents a substituted or unsubstituted C1-6 alkyl group, a substituted or unsubstituted C2-6 alkenyl group, a substituted or unsubstituted C2-6 alkynyl group, a substituted or unsubstituted C3-6 cycloalkyl group, a substituted or unsubstituted phenyl group, or a substituted or unsubstituted naphthyl group; R 2 represents a hydrogen atom or a substituted or unsubstituted C1-6 alkyl group; Substructure -Y a -X a - is *-OC(=X1a )-**, *-SC(=X 1a )-** or *-NH-C(=X 1a )-** represents a group; where * is two R 1 indicates the bond position to the carbon atom having a Indicates the bond position with; X 1a each independently represents an oxygen atom or a sulfur atom; Z a represents a substituted or unsubstituted dimethylene group.

[0022]

[12] A compound represented by the following formula (Ib), a stereoisomer thereof, or a salt thereof:

[0023] [ka]

[0024] [In the formula, Ar represents a substituted or unsubstituted phenyl group, or a substituted or unsubstituted naphthyl group; R 1 each independently represents a substituted or unsubstituted C1-6 alkyl group, a substituted or unsubstituted C2-6 alkenyl group, a substituted or unsubstituted C2-6 alkynyl group, a substituted or unsubstituted C3-6 cycloalkyl group, a substituted or unsubstituted phenyl group, or a substituted or unsubstituted naphthyl group; R 2 represents a hydrogen atom or a substituted or unsubstituted C1-6 alkyl group; Substructure -Y b -X b - is a group represented by *-OC(=S)-**, *-SC(=O)-**, or *-NH-SO 2 - represents a group represented by **; where * is two R 1 indicates the bond position to the carbon atom having b Indicates the bond position with; Z brepresents a substituted or unsubstituted methylene group.

[0025]

[13] A compound represented by the following formula (Ic), a stereoisomer thereof, or a salt thereof:

[0026] [ka]

[0027] [In the formula, Ar represents a substituted or unsubstituted phenyl group, or a substituted or unsubstituted naphthyl group; R 1 each independently represents a substituted or unsubstituted C1-6 alkyl group, a substituted or unsubstituted C2-6 alkenyl group, a substituted or unsubstituted C2-6 alkynyl group, a substituted or unsubstituted C3-6 cycloalkyl group, a substituted or unsubstituted phenyl group, or a substituted or unsubstituted naphthyl group; X 1 represents an oxygen atom or a sulfur atom.

[0028]

[14] A hatching promoter for potato cyst nematodes containing as an active ingredient one or more of the following: 5,5-dimethyl-4-phenyl-2-pyrrolidinone having a specific rotation of (-), 5,5-dimethyl-4-(4-methylphenyl)-2-pyrrolidinone having a specific rotation of (-), 5,5-dimethyl-4-(4-chlorophenyl)-2-pyrrolidinone having a specific rotation of (-), or 4-(4-chlorophenyl)-3,3-dimethylisothiazolidine-1,1-dioxide having a specific rotation of (-). Effect of the Invention

[0029] The control agent or hatching accelerator of the present invention realizes environmentally friendly control of Gp, the most important potato pest, and not only contributes to a significant improvement in potato productivity but also greatly contributes to the relaxation of restrictions on potato varieties to be produced, thus ultimately contributing to the improvement of quality and yield in the agricultural field. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0030] [Compounds represented by formula (I), stereoisomers thereof, or salts thereof] One aspect of the present invention is an agent for controlling potato cyst nematodes, which contains as an active ingredient at least one selected from a compound represented by the following formula (I), a stereoisomer thereof, and a salt thereof: The compound represented by formula (I) (sometimes referred to as compound (I)), its stereoisomer, or a salt thereof is a substance that promotes the hatching of Gp eggs. That is, one aspect of the present invention is a hatching promoter for potato cyst nematode eggs, which contains as an active ingredient at least one selected from a compound represented by the following formula (I), its stereoisomer, and a salt thereof: Compound (I) can hatch Gp eggs by contacting them with the eggs in the Gp cysts. If compound (I) can be brought into contact with Gp cysts to artificially hatch Gp eggs in a situation where there is no potato around the Gp cysts to serve as a nutrient source, the hatched Gp can be driven into a state of starvation and killed.

[0031] [ka]

[0032] In the formula, Ar represents a substituted or unsubstituted phenyl group, or a substituted or unsubstituted naphthyl group; R 1 each independently represents a substituted or unsubstituted C1-6 alkyl group, a substituted or unsubstituted C2-6 alkenyl group, a substituted or unsubstituted C2-6 alkynyl group, a substituted or unsubstituted C3-6 cycloalkyl group, a substituted or unsubstituted phenyl group, or a substituted or unsubstituted naphthyl group; R 2 represents a hydrogen atom or a substituted or unsubstituted C1-6 alkyl group; The partial structure -YX- is *-CH 2 -C(=X 1 )-**, *-OC(=X1 )-**, *-SC(=X 1 )-**, *-N(R b )-C(=X 1 )-** or *-NH-SO 2 - represents a group represented by **; where * is two R 1 indicates the bonding position to the carbon atom having the symbol **, and indicates the bonding position to Z; X 1 each independently represents an oxygen atom or a sulfur atom; R b are each independently a hydrogen atom, a hydroxyl group, or R b1 a group represented by -C(=O)-, R b1 A group represented by OC(=O)-, R b1 A group represented by NH-C(=O)- or R b1 2 represents a group represented by NC(=O)-; R b1 each independently represents a substituted or unsubstituted C1-6 alkyl group, a substituted or unsubstituted C2-6 alkenyl group, a substituted or unsubstituted C2-6 alkynyl group, a substituted or unsubstituted C3-6 cycloalkyl group, a substituted or unsubstituted phenyl group, or a substituted or unsubstituted naphthyl group; Z represents a substituted or unsubstituted methylene group, or a substituted or unsubstituted dimethylene group; When Z is a substituted methylene group, R 2 and the substituent on the methylene group may together form a single bond, or a methylene group.

[0033] Compound (I) also includes hydrates, various solvates, and crystalline polymorphs. Compound (I) may also exist as stereoisomers based on asymmetric carbons and diastereomers. All optically active isomers and mixtures of optically active isomers of such isomers are within the scope of the present invention. The present invention also includes salts thereof. Details of the salts will be described later.

[0034] The term "unsubstituted" as used herein means that only the group that serves as the mother nucleus is present. When there is no description of "substituted" and only the name of the group that serves as the mother nucleus is described, it means "unsubstituted" unless otherwise specified. On the other hand, the term "substituted" means that any hydrogen atom of the core group is replaced with a group (substituent) having the same or different structure as the core group. Thus, a "substituent" is another group bonded to the core group. The number of substituents may be one or more. The two or more substituents may be the same or different. Terms such as "C1-6" indicate that the number of carbon atoms in the parent group is 1 to 6. This number of carbon atoms does not include the number of carbon atoms in the substituents. For example, a butyl group having an ethoxy group as a substituent is classified as a C2 alkoxy C4 alkyl group.

[0035] The "substituent" is not particularly limited as long as it is chemically permissible and has the effect of the present invention. Examples of groups that can be the "substituent" are shown below. C1-6 alkyl groups such as methyl, ethyl, n-propyl, I-propyl, n-butyl, s-butyl, I-butyl, t-butyl, n-pentyl, and n-hexyl groups; C2-6 alkenyl groups such as vinyl group, 1-propenyl group, 2-propenyl group (allyl group), 1-butenyl group, 2-butenyl group, 3-butenyl group, 1-methyl-2-propenyl group, and 2-methyl-2-propenyl group; C2-6 alkynyl groups, such as an ethynyl group, a 1-propynyl group, a 2-propynyl group, a 1-butynyl group, a 2-butynyl group, a 3-butynyl group, or a 1-methyl-2-propynyl group;

[0036] C3-6 cycloalkyl groups such as a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, and a cyclohexyl group; Phenyl group, naphthyl group; Phenyl C1-6 alkyl groups such as benzyl and phenethyl groups; 3- to 6-membered heterocyclyl groups; 3-6 membered heterocyclyl C1-6 alkyl group;

[0037] Hydroxyl; C1-6 alkoxy groups, such as a methoxy group, an ethoxy group, an n-propoxy group, an I-propoxy group, an n-butoxy group, an s-butoxy group, an I-butoxy group, or a t-butoxy group; C2-6 alkenyloxy groups such as a vinyloxy group, an allyloxy group, a propenyloxy group, or a butenyloxy group; C2-6 alkynyloxy groups such as ethynyloxy groups and propargyloxy groups; Phenoxy group, naphthoxy group; benzyloxy group, phenethyloxy group; 5- to 6-membered heteroaryloxy groups such as thiazolyloxy groups and pyridyloxy groups; 5-6-membered heteroaryl C1-6 alkyloxy groups such as thiazolylmethyloxy groups and pyridylmethyloxy groups;

[0038] Formyl group; C1-6 alkylcarbonyl groups such as acetyl and propionyl groups; Formyloxy group; C1-6 alkylcarbonyloxy groups such as acetyloxy and propionyloxy; Benzoyl group; C1-6 alkoxycarbonyl groups, such as a methoxycarbonyl group, an ethoxycarbonyl group, an n-propoxycarbonyl group, an I-propoxycarbonyl group, an n-butoxycarbonyl group, or a t-butoxycarbonyl group; C1-6 alkoxycarbonyloxy groups, such as a methoxycarbonyloxy group, an ethoxycarbonyloxy group, an n-propoxycarbonyloxy group, an I-propoxycarbonyloxy group, an n-butoxycarbonyloxy group, or a t-butoxycarbonyloxy group; Carboxyl group;

[0039] halogeno groups such as fluoro, chloro, bromo, and iodo groups; C1-6 haloalkyl groups such as a chloromethyl group, a chloroethyl group, a difluoromethyl group, a trifluoromethyl group, a 2,2,2-trifluoroethyl group, a 1,2-dichloro-n-propyl group, and a 1-fluoro-n-butyl group; C2-6 haloalkenyl groups, such as a 2-chloro-1-propenyl group and a 2-fluoro-1-butenyl group; C2-6 haloalkynyl groups such as a 4,4-dichloro-1-butynyl group, a 4-fluoro-1-pentynyl group, or a 5-bromo-2-pentynyl group; C1-6 haloalkoxy groups, such as a difluoromethoxy group, a trifluoromethoxy group, a 2,2,2-trifluoroethoxy group, or a 2,3-dichlorobutoxy group; C2-6 haloalkenyloxy groups, such as a 2-chloropropenyloxy group or a 3-bromobutenyloxy group; C1-6 haloalkylcarbonyl groups such as a chloroacetyl group, a trifluoroacetyl group, or a trichloroacetyl group;

[0040] Amino group; C1-6 alkyl-substituted amino groups such as methylamino, dimethylamino, and diethylamino groups; Anilino group, naphthylamino group; phenyl C1-6 alkylamino groups such as benzylamino and phenethylamino groups; Formylamino group; C1-6 alkylcarbonylamino groups, such as an acetylamino group, a propanoylamino group, a butyrylamino group, or an I-propylcarbonylamino group; C1-6 alkoxycarbonylamino groups, such as a methoxycarbonylamino group, an ethoxycarbonylamino group, an n-propoxycarbonylamino group, or an I-propoxycarbonylamino group; Unsubstituted or substituted aminocarbonyl groups, such as an aminocarbonyl group, a dimethylaminocarbonyl group, a phenylaminocarbonyl group, or an N-phenyl-N-methylaminocarbonyl group; Aminocarbonyloxy group; C1-6 alkyl-substituted aminocarbonyloxy groups such as an ethylaminocarbonyloxy group and a dimethylaminocarbonyloxy group;

[0041] Mercapto group; C1-6 alkylthio groups, such as a methylthio group, an ethylthio group, an n-propylthio group, an I-propylthio group, an n-butylthio group, an I-butylthio group, an s-butylthio group, or a t-butylthio group; C1-6 haloalkylthio groups, such as a trifluoromethylthio group and a 2,2,2-trifluoroethylthio group;

[0042] C1-6 alkylsulfinyl groups such as a methylsulfinyl group, an ethylsulfinyl group, or a t-butylsulfinyl group; C1-6 haloalkylsulfinyl groups such as a trifluoromethylsulfinyl group and a 2,2,2-trifluoroethylsulfinyl group; C1-6 alkylsulfonyl groups such as a methylsulfonyl group, an ethylsulfonyl group, or a t-butylsulfonyl group; C1-6 haloalkylsulfonyl groups such as a trifluoromethylsulfonyl group or a 2,2,2-trifluoroethylsulfonyl group; Phenylsulfonyl group; 5- to 6-membered heteroarylsulfonyl groups, such as thiazolylsulfonyl groups and pyridylsulfonyl groups;

[0043] Pentafluorosulfanyl group; Cyano group;Nitro group;

[0044] In addition, any hydrogen atom in these "substituents" may be substituted with a group of a different structure. In this case, examples of the "substituent" include a C1-6 alkyl group, a C1-6 haloalkyl group, a C1-6 alkoxy group, a C1-6 haloalkoxy group, a halogeno group, a cyano group, and a nitro group.

[0045] The above-mentioned "3- to 6-membered heterocyclyl group" refers to a 3-, 4-, 5-, or 6-membered ring group containing 1 to 4 heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur atoms as ring constituent atoms. The heterocyclyl group may be either a monocyclic or polycyclic ring. In the polycyclic heterocyclyl group, as long as at least one ring is a heterocyclic ring, the remaining rings may be either a saturated alicyclic ring, an unsaturated alicyclic ring, or an aromatic ring. Examples of the "3- to 6-membered heterocyclyl group" include a 3- to 6-membered saturated heterocyclyl group, a 5- to 6-membered unsaturated heterocyclyl group, and a 5- to 6-membered heteroaryl group.

[0046] Examples of the 3- to 6-membered saturated heterocyclyl group include an aziridinyl group, an epoxy group, an azetidinyl group, a pyrrolidinyl group, a tetrahydrofuranyl group, a dioxolanyl group, a tetrahydropyranyl group, a piperidyl group, a piperazinyl group, a morpholinyl group, and a dioxanyl group. Examples of the 5- to 6-membered unsaturated heterocyclyl group include a pyrrolinyl group, a dihydrofuranyl group, an imidazolinyl group, a pyrazolinyl group, an oxazolinyl group, an isoxazolinyl group, a thiazolinyl group, an isothiazolinyl group, a dihydropyranyl group, and a dihydrooxazinyl group.

[0047] Examples of the 5-membered heteroaryl group include a pyrrolyl group, a furyl group, a thienyl group, an imidazolyl group, a pyrazolyl group, an oxazolyl group, an isoxazolyl group, a thiazolyl group, an isothiazolyl group, a triazolyl group, an oxadiazolyl group, a thiadiazolyl group, and a tetrazolyl group. Examples of the 6-membered heteroaryl group include a pyridyl group, a pyrazinyl group, a pyrimidinyl group, a pyridazinyl group, and a triazinyl group.

[0048] [Ar] Ar represents a substituted or unsubstituted phenyl group, or a substituted or unsubstituted naphthyl group. Substituents on the "phenyl group" or "naphthyl group" in Ar include halogeno groups such as fluoro, chloro, bromo, and iodo groups; C1-6 alkyl groups such as methyl, ethyl, n-propyl, I-propyl, n-butyl, s-butyl, I-butyl, t-butyl, n-pentyl, and n-hexyl groups; C1-6 halogen groups such as chloromethyl, chloroethyl, trifluoromethyl, 1,2-dichloro-n-propyl, and 1-fluoro-n-butyl groups; Alkyl groups; hydroxyl groups; C1-6 alkoxy groups such as methoxy, ethoxy, n-propoxy, I-propoxy, n-butoxy, s-butoxy, I-butoxy, and t-butoxy groups; C1-6 haloalkoxy groups such as 2-chloro-n-propoxy, 2,3-dichlorobutoxy, and trifluoromethoxy groups; C6-10 aryl groups such as phenyl and naphthyl groups; 4-methylphenyl, 4-methoxyphenyl, 4-chlorophenyl, 4-trifluoromethylphenyl, and the like. a C6-10 aryl group substituted with a C1-6 alkyl group, a C1-6 alkoxy group, a halogeno group, a C1-6 haloalkyl group, or a C1-6 haloalkoxy group, such as a phenyl group or a 4-trifluoromethoxyphenyl group; a 5-membered heteroaryl group such as a pyrrolyl group, a furyl group, a thienyl group, an imidazolyl group, a pyrazolyl group, an oxazolyl group, an isoxazolyl group, a thiazolyl group, an isothiazolyl group, a triazolyl group, an oxadiazolyl group, a thiadiazolyl group, or a tetrazolyl group; Preferred are: a 5-membered heteroaryl group substituted with a C1-6 alkyl group, a C1-6 alkoxy group, a halogeno group, a C1-6 haloalkyl group, or a C1-6 haloalkoxy group; a 6-membered heteroaryl group such as a pyridyl group, a pyrazinyl group, a pyrimidinyl group, a pyridazinyl group, or a triazinyl group; a 6-membered heteroaryl group substituted with a C1-6 alkyl group, a C1-6 alkoxy group, a halogeno group, a C1-6 haloalkyl group, or a C1-6 haloalkoxy group; or a cyano group.

[0049] [R 1 〕 R 1each independently represents a substituted or unsubstituted C1-6 alkyl group, a substituted or unsubstituted C2-6 alkenyl group, a substituted or unsubstituted C2-6 alkynyl group, a substituted or unsubstituted C3-6 cycloalkyl group, a substituted or unsubstituted phenyl group, or a substituted or unsubstituted naphthyl group.

[0050] R 1 Examples of the "C1-6 alkyl group" in the above formula include a methyl group, an ethyl group, an n-propyl group, an n-butyl group, an n-pentyl group, an n-hexyl group, an I-propyl group, an I-butyl group, an s-butyl group, an t-butyl group, an I-pentyl group, a neopentyl group, a 2-methylbutyl group, and an I-hexyl group. R 1 Examples of the "C2-6 alkenyl group" in the above formula include a vinyl group and a 1-propenyl group. R 1 Examples of the "C2-6 alkynyl group" in the above formula include an ethynyl group and a 1-propynyl group.

[0051] R 1In the above, examples of the substituents on the "C1-6 alkyl group", "C2-6 alkenyl group", or "C2-6 alkynyl group" include halogeno groups such as fluoro group, chloro group, bromo group, and iodo group; hydroxyl group; C1-6 alkoxy groups such as methoxy group, ethoxy group, n-propoxy group, I-propoxy group, n-butoxy group, s-butoxy group, I-butoxy group, and t-butoxy group; C1-6 haloalkoxy groups such as 2-chloro-n-propoxy group, 2,3-dichlorobutoxy group, and trifluoromethoxy group; C3-6 cycloalkyl groups such as cyclopropyl group, cyclobutyl group, cyclopentyl group, and cyclohexyl group; phenyl group, naphthyl group; and C1-6 alkyl groups and C1-6 alkoxy groups such as 4-methylphenyl group, 4-methoxyphenyl group, 4-chlorophenyl group, 4-trifluoromethylphenyl group, and 4-trifluoromethoxyphenyl group. , a phenyl group substituted by a halogeno group, a C1-6 haloalkyl group, or a C1-6 haloalkoxy group; a 5-membered ring heteroaryl group such as a pyrrolyl group, a furyl group, a thienyl group, an imidazolyl group, a pyrazolyl group, an oxazolyl group, an isoxazolyl group, a thiazolyl group, an isothiazolyl group, a triazolyl group, an oxadiazolyl group, a thiadiazolyl group, or a tetrazolyl group; a 5-membered ring heteroaryl group substituted by a C1-6 alkyl group, a C1-6 alkoxy group, a halogeno group, a C1-6 haloalkyl group, or a C1-6 haloalkoxy group; a 6-membered ring heteroaryl group such as a pyridyl group, a pyrazinyl group, a pyrimidinyl group, a pyridazinyl group, or a triazinyl group; a 6-membered ring heteroaryl group substituted by a C1-6 alkyl group, a C1-6 alkoxy group, a halogeno group, a C1-6 haloalkyl group, or a C1-6 haloalkoxy group; or a cyano group is preferred.

[0052] R 1 Examples of the "C3-6 cycloalkyl group" in the above formula include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, and a cyclohexyl group.

[0053] R 1In the above, examples of the substituents on the "C3-6 cycloalkyl group", "phenyl group", or "naphthyl group" include halogeno groups such as fluoro group, chloro group, bromo group, and iodo group; C1-6 alkyl groups such as methyl group, ethyl group, n-propyl group, I-propyl group, n-butyl group, s-butyl group, I-butyl group, t-butyl group, n-pentyl group, and n-hexyl group; chloromethyl group, chloroethyl group, trifluoromethyl group, 1,2-dichloro-n-propyl group, 1-fluoro-n-butyl group, C1-6 haloalkyl groups such as hydroxyl groups; C1-6 alkoxy groups such as methoxy, ethoxy, n-propoxy, I-propoxy, n-butoxy, s-butoxy, I-butoxy, and t-butoxy groups; C1-6 haloalkoxy groups such as 2-chloro-n-propoxy, 2,3-dichlorobutoxy, and trifluoromethoxy groups; C6-10 aryl groups such as phenyl and naphthyl groups; 4-methylphenyl, 4-methoxyphenyl, 4-chlorophenyl, 4-trifluorophenyl, and the like. C6-10 aryl groups substituted with a C1-6 alkyl group, a C1-6 alkoxy group, a halogeno group, a C1-6 haloalkyl group, or a C1-6 haloalkoxy group, such as a fluoromethylphenyl group or a 4-trifluoromethoxyphenyl group; 5-membered heteroaryl groups such as a pyrrolyl group, a furyl group, a thienyl group, an imidazolyl group, a pyrazolyl group, an oxazolyl group, an isoxazolyl group, a thiazolyl group, an isothiazolyl group, a triazolyl group, an oxadiazolyl group, a thiadiazolyl group, and a tetrazolyl group; Preferred are an alkyl group; a 5-membered heteroaryl group substituted with a C1-6 alkyl group, a C1-6 alkoxy group, a halogeno group, a C1-6 haloalkyl group, or a C1-6 haloalkoxy group; a 6-membered heteroaryl group such as a pyridyl group, a pyrazinyl group, a pyrimidinyl group, a pyridazinyl group, or a triazinyl group; a 6-membered heteroaryl group substituted with a C1-6 alkyl group, a C1-6 alkoxy group, a halogeno group, a C1-6 haloalkyl group, or a C1-6 haloalkoxy group; or a cyano group.

[0054] In the present invention, R 1 is preferably a "substituted or unsubstituted C1 to C6 alkyl group", and particularly preferably a methyl group.

[0055] [R 2 〕 R 2 represents a hydrogen atom, or a substituted or unsubstituted C1-6 alkyl group. R 2 Specific examples of the "substituted or unsubstituted C1-6 alkyl group" in 1 The same examples as those given above can be mentioned. In the present invention, R 2 is preferably a hydrogen atom.

[0056] [-YX-] The partial structure -YX- is *-CH 2 -C(=X 1 )-**, *-OC(=X 1 )-**, *-SC(=X 1 )-**, *-N(R b )-C(=X 1 )-** or *-NH-SO 2 - represents a group represented by **. where * is two R 1 indicates the bonding position to the carbon atom having the formula (I), and ** indicates the bonding position to Z; X 1 each independently represents an oxygen atom or a sulfur atom; R b is a hydrogen atom, a hydroxyl group, R b1 A group represented by -C(=O)-, R b1 A group represented by OC(=O)-, R b1 A group represented by NH-C(=O)- or R b1 2 This represents a group represented by NC(=O)-. R b1 each independently represents a substituted or unsubstituted C1-6 alkyl group, a substituted or unsubstituted C2-6 alkenyl group, a substituted or unsubstituted C2-6 alkynyl group, a substituted or unsubstituted C3-6 cycloalkyl group, a substituted or unsubstituted phenyl group, or a substituted or unsubstituted naphthyl group.

[0057] R b1Specific examples of "substituted or unsubstituted C1-6 alkyl group", "substituted or unsubstituted C2-6 alkenyl group", "substituted or unsubstituted C2-6 alkynyl group", "substituted or unsubstituted C3-6 cycloalkyl group", "substituted or unsubstituted phenyl group", or "substituted or unsubstituted naphthyl group" in 1 The same examples as those given above can be mentioned.

[0058] R b "R b1 Examples of the group represented by -C(=O)- include an acetyl group, a benzoyl group, and the like. R b "R b1 Examples of the group represented by OC(=O)-- include a methoxycarbonyl group, a t-butoxycarbonyl group, and the like. R b "R b1 Examples of the group represented by NH-C(=O)- include a methylaminocarbonyl group, an I-propylaminocarbonyl group, and the like. R b "R b1 2 Examples of the group represented by NC(=O)-- include a dimethylaminocarbonyl group, a diethylaminocarbonyl group, and the like. In the present invention, R b is preferably a hydrogen atom or a hydroxyl group.

[0059] [Z] Z represents a substituted or unsubstituted methylene group, or a substituted or unsubstituted dimethylene group. When Z is a substituted methylene group, R 2 and the substituent on the methylene group may together form a single bond, or a methylene group.

[0060] The substituent on the "methylene group" or "dimethylene group" in Z is preferably a C1-6 alkyl group such as a methyl group, an ethyl group, an n-propyl group, an I-propyl group, an n-butyl group, an s-butyl group, an I-butyl group, a t-butyl group, an n-pentyl group, or an n-hexyl group; a C1-6 haloalkyl group such as a chloromethyl group, a chloroethyl group, a trifluoromethyl group, a 1,2-dichloro-n-propyl group, or a 1-fluoro-n-butyl group; a C1-6 alkoxy group such as a methoxy group, an ethoxy group, an n-propoxy group, an I-propoxy group, an n-butoxy group, an s-butoxy group, an I-butoxy group, or a t-butoxy group; a C1-6 haloalkoxy group such as a 2-chloro-n-propoxy group, a 2,3-dichlorobutoxy group, or a trifluoromethoxy group; or a cyano group.

[0061] When Z is a substituted methylene group, R 2 An example of a compound in which a substituent on a methylene group combines with another substituent on the methylene group to form a methylene group is a compound represented by the following formula (I-c').

[0062] [ka]

[0063] In the formula, Ar, R 1 and -YX- have the same definitions as those in formula (I).

[0064] When Z is a substituted methylene group, R 2 An example of a compound in which a substituent on a methylene group combines with another substituent on a methylene group to form a single bond is a compound represented by the following formula (I-d').

[0065] [ka]

[0066] In the formula, Ar, R 1 and -YX- have the same definitions as those in formula (I). R Zrepresents a hydrogen atom, a C1-6 alkyl group, a C1-6 haloalkyl group, a C1-6 alkoxy group, a C1-6 haloalkoxy group, or a cyano group.

[0067] [Compound represented by formula (Ia), its stereoisomer or salt thereof] One aspect of the present invention is a compound represented by the following formula (Ia), a stereoisomer thereof, or a salt thereof:

[0068] [ka]

[0069] In the formula, Ar represents a substituted or unsubstituted phenyl group, or a substituted or unsubstituted naphthyl group; R 1 each independently represents a substituted or unsubstituted C1-6 alkyl group, a substituted or unsubstituted C2-6 alkenyl group, a substituted or unsubstituted C2-6 alkynyl group, a substituted or unsubstituted C3-6 cycloalkyl group, a substituted or unsubstituted phenyl group, or a substituted or unsubstituted naphthyl group; R 2 represents a hydrogen atom or a substituted or unsubstituted C1-6 alkyl group; Substructure -Y a -X a - is *-OC(=X 1a )-**, *-SC(=X 1a )-** or *-NH-C(=X 1a )-** represents a group; where * is two R 1 indicates the bond position to the carbon atom having a Indicates the bond position with; X 1a each independently represents an oxygen atom or a sulfur atom; Z a represents a substituted or unsubstituted dimethylene group.

[0070] In the formula, Ar, R 1 , and R2 have the same definitions as those in formula (I). Z a In the above formula, the substituent on the "dimethylene group" is preferably a C1-6 alkyl group such as a methyl group, an ethyl group, an n-propyl group, an I-propyl group, an n-butyl group, an s-butyl group, an I-butyl group, a t-butyl group, an n-pentyl group, or an n-hexyl group; a C1-6 haloalkyl group such as a chloromethyl group, a chloroethyl group, a trifluoromethyl group, a 1,2-dichloro-n-propyl group, or a 1-fluoro-n-butyl group; a C1-6 alkoxy group such as a methoxy group, an ethoxy group, an n-propoxy group, an I-propoxy group, an n-butoxy group, an s-butoxy group, an I-butoxy group, or a t-butoxy group; a C1-6 haloalkoxy group such as a 2-chloro-n-propoxy group, a 2,3-dichlorobutoxy group, or a trifluoromethoxy group; or a cyano group.

[0071] [Compound represented by formula (Ib), its stereoisomer or salt thereof] One aspect of the present invention is a compound represented by the following formula (Ib), a stereoisomer thereof, or a salt thereof:

[0072] [ka]

[0073] In the formula, Ar represents a substituted or unsubstituted phenyl group, or a substituted or unsubstituted naphthyl group; R 1 each independently represents a substituted or unsubstituted C1-6 alkyl group, a substituted or unsubstituted C2-6 alkenyl group, a substituted or unsubstituted C2-6 alkynyl group, a substituted or unsubstituted C3-6 cycloalkyl group, a substituted or unsubstituted phenyl group, or a substituted or unsubstituted naphthyl group; R 2 represents a hydrogen atom or a substituted or unsubstituted C1-6 alkyl group; Substructure -Y b -X b- is a group represented by *-OC(=S)-**, *-SC(=O)-**, or *-NH-SO 2 - represents a group represented by **; where * is two R 1 indicates the bond position to the carbon atom having b Indicates the bond position with; Z b represents a substituted or unsubstituted methylene group.

[0074] In the formula, Ar, R 1 , and R 2 have the same definitions as those in formula (I). Z b In the above formula, the substituent on the "methylene group" is preferably a C1-6 alkyl group such as a methyl group, an ethyl group, an n-propyl group, an I-propyl group, an n-butyl group, an s-butyl group, an I-butyl group, a t-butyl group, an n-pentyl group, or an n-hexyl group; a C1-6 haloalkyl group such as a chloromethyl group, a chloroethyl group, a trifluoromethyl group, a 1,2-dichloro-n-propyl group, or a 1-fluoro-n-butyl group; a C1-6 alkoxy group such as a methoxy group, an ethoxy group, an n-propoxy group, an I-propoxy group, an n-butoxy group, an s-butoxy group, an I-butoxy group, or a t-butoxy group; a C1-6 haloalkoxy group such as a 2-chloro-n-propoxy group, a 2,3-dichlorobutoxy group, or a trifluoromethoxy group; or a cyano group.

[0075] [Compound represented by formula (Ic), its stereoisomer or salt thereof] One aspect of the present invention is a compound represented by the following formula (Ic), a stereoisomer thereof, or a salt thereof.

[0076] [ka]

[0077] In the formula, Ar represents a substituted or unsubstituted phenyl group, or a substituted or unsubstituted naphthyl group; R 1each independently represents a substituted or unsubstituted C1-6 alkyl group, a substituted or unsubstituted C2-6 alkenyl group, a substituted or unsubstituted C2-6 alkynyl group, a substituted or unsubstituted C3-6 cycloalkyl group, a substituted or unsubstituted phenyl group, or a substituted or unsubstituted naphthyl group; X 1 represents an oxygen atom or a sulfur atom.

[0078] In the formula, Ar and R 1 have the same definitions as those in formula (I).

[0079] [Method for producing compound (I)] The method for producing compound (I) is not limited. For example, compound (I) of the present invention can be obtained by utilizing known reactions such as those described in the following reaction schemes and examples.

[0080] (Reaction Scheme 1-1) Among the compounds represented by formula (Ib), a method for preparing the compound of formula (Ib-1) shown below is outlined in the following Reaction Scheme 1-1.

[0081] [ka]

[0082] The symbols in formula (Ib-1) have the same meanings as those in formula (I). The symbols in formula (IM-1) have the same meanings as those in formula (I). R represents a lower alkyl group. The nitro group in the compound of formula (IM-1) can be reduced with zinc under acidic conditions and cyclized, for example by heating, to prepare the compound of formula (Ib-1).

[0083] (Reaction Scheme 1-2) A method for preparing the compound of formula (IM-1) is outlined below in Reaction Scheme 1-2.

[0084] [ka]

[0085] The symbols in formula (IM-2) have the same meanings as those in formula (I). R represents a lower alkyl group. The symbols in formula (IM-3) have the same meanings as those in formula (I). Compounds of formula (IM-1) can be prepared by Michael addition reaction of nitroalkanes of formula (IM-3) with cinnamic acid esters of formula (IM-2) in the presence of a suitable organic base.

[0086] (Reaction Scheme 2-1) Among the compounds represented by formula (Ia), a method for preparing the compound represented by formula (Ia-1) shown below is outlined in the following Reaction Scheme 2-1.

[0087] [ka]

[0088] The symbols in formula (Ia-1) have the same meanings as those in formula (I). The symbols in formula (IM-4) have the same meanings as those in formula (I). R represents a lower alkyl group. The nitro group in the compound of formula (IM-4) can be reduced with zinc under acidic conditions and cyclized, for example by heating, to prepare the compound of formula (Ia-1).

[0089] (Reaction Scheme 2-2) A method for preparing the compound of formula (IM-4) is outlined in the following Reaction Scheme 2-2.

[0090] [ka]

[0091] The symbols in formula (IM-5) have the same meanings as those in formula (I). The symbols in formula (IM-6) have the same meanings as those in formula (I). R' represents a lower alkyl group. The symbols in formula (IM-7) have the same meanings as those in formula (I). Compounds of formula (IM-6) can be prepared by Wittig reaction of aldehydes of formula (IM-7). The phosphonium salt used is preferably (methoxymethyl)triphenylphosphonium chloride. The enol ether in the compound of formula (IM-6) is hydrolyzed to prepare the aldehyde of formula (IM-5). The aldehyde is oxidized to a carboxylic acid, which is then esterified to prepare the compound of formula (IM-4). The oxidation is preferably carried out using the Claus-Spinnick oxidation, which has high functional group selectivity.

[0092] (Reaction Scheme 2-3) A method for preparing the compound of formula [IM-7] is outlined in the following Reaction Scheme 2-3.

[0093] [ka]

[0094] The symbols in formula (IM-8) have the same meanings as those in formula (I). The compound of formula (IM-7) can be prepared by Michael addition reaction of nitroalkane of formula (IM-3) with cinnamylaldehyde of formula (IM-8) in the presence of a suitable organic base.

[0095] (Reaction Scheme 3-1) Among the compounds represented by formula (Ia), a method for preparing the compound of formula (Ia-2) shown below is outlined in the following Reaction Scheme 3-1.

[0096] [ka]

[0097] The symbols in formula (Ia-2) have the same meanings as those in formula (I). The symbols in formula (IM-9) have the same meanings as those in formula (I). R represents a lower alkyl group. The compound of formula (Ia-2) can be prepared by reacting the compound of formula (IM-9) with trimethylaluminum in the presence of a palladium complex. Here, the palladium complex undergoes oxidative hatching between the sulfur and the cyano group in formula (IM-9). Trimethylaluminum transfers the methyl group to palladium, and the compound of formula (IM-9) becomes an alkylthioaluminum. Palladium is regenerated as a catalyst by reductive elimination to release acetonitrile. The resulting alkylthioaluminum reacts with an ester in the molecule to give the compound of formula (Ia-2).

[0098] (Reaction Scheme 3-2) A method for preparing the compound of formula (IM-9) is outlined below in Reaction Scheme 3-2.

[0099] [ka]

[0100] The symbols in formula (IM-10) have the same meanings as those in formula (I). R represents a lower alkyl group. The compound of formula (IM-9) is reacted with the olefin of formula (IM-10) by the reaction of Fe(III) / NaBH 4 The compound can be prepared by thiocyanation via the following reaction: In this case, the method described in Organic Letters, Volume 14, Issue 6, Pages 1428-1431, 2012 can be referred to.

[0101] (Reaction Scheme 3-3) A method for preparing the compound of formula (IM-10) is outlined below in Reaction Scheme 3-3.

[0102] [ka]

[0103] The symbols in formula (IM-11) have the same meanings as those in formula (I). The symbols in formula (IM-12) have the same meanings as those in formula (I). The symbols in formula (IM-13) have the same meanings as those in formula (I). Ts represents a tosyl group. The compound of formula (IM-12) can be prepared by cyanating the compound of formula (IM-13). The leaving group is preferably a tosyloxy group. The cyano group is reduced to an imine by DIBAL reduction, and the resulting imine is hydrolyzed to prepare an aldehyde of formula (IM-11). This aldehyde is oxidized to a carboxylic acid, and finally esterified to prepare a compound of formula (IM-10). The oxidation condition is preferably the Claus-Spinnick oxidation, which has high functional group selectivity.

[0104] (Reaction Scheme 3-4) A method for preparing compounds of formula (IM-13) is outlined below in Reaction Schemes 3-4.

[0105] [ka]

[0106] The symbols in formula (IM-14) have the same meanings as those in formula (I). R represents a lower alkyl group. The ester moiety in the compound of formula (IM-14) can be converted to a hydroxyl group by DIBAL reduction or the like, and then reacted with TsCl or the like to prepare the compound of formula (IM-13).

[0107] (Reaction Scheme 3-5) Methods for preparing compounds of formula (IM-14) are outlined below in Reaction Schemes 3-5.

[0108] [ka]

[0109] The symbols in formula (IM-15) have the same meanings as those in formula (I). The symbols in formula (IM-16) have the same meanings as those in formula (I). R represents a lower alkyl group. The compound of formula [IM-14] is MeC(OR) 3 (R is a lower alkyl group) to the allylic alcohol of formula (IM-15), by Johnson-Claisen rearrangement. Compounds of formula (IM-15) can be prepared by DIBAL reduction of cinnamic esters of formula (IM-16).

[0110] (Reaction Scheme 4) Among the compounds represented by formula (Ib), a method for preparing the compound of formula (Ib-3) shown below is outlined in the following Reaction Scheme 4.

[0111] [ka]

[0112] The symbols in formula (Ib-2) have the same meanings as those in formula (I). The symbols in formula (Ib-3) have the same meanings as those in formula (I). The compound of formula (Ib-3) can be prepared by reacting the compound of formula (Ib-2) with Lawesson's reagent.

[0113] (Reaction Scheme 5) Among the compounds represented by formula (Ib), a method for preparing the compound of formula (Ib-4) shown below is outlined in the following Reaction Scheme 5.

[0114] [ka]

[0115] The symbols in formula (Ib-4) have the same meanings as those in formula (I). The thiolactone of formula (Ib-4) can be prepared by isomerizing the thionolactone of formula (Ib-3) using a Lewis acid as a catalyst. In this case, the method described in Tetrahedron Letters, Volume 47, Issue 34, Pages 6067-6070, 2006 can be used as a reference.

[0116] (Reaction Scheme 6-1) Among the compounds represented by formula (Ib), a method for preparing the compound of formula (Ib-5) shown below is outlined in the following Reaction Scheme 6-1.

[0117] [ka]

[0118] The symbols in formula (Ib-5) have the same meanings as those in formula (I). The symbols in formula (IM-17) have the same meanings as those in formula (I). The symbols in formula (IM-18) have the same meanings as those in formula (I). The nitro group in the compound of formula (IM-18) can be reduced with zinc under acidic conditions to give the compound of formula (IM-17), which can then be cyclized by heating or the like to prepare the compound of formula (Ib-5).

[0119] (Reaction Scheme 6-2) A method for preparing a compound of formula (IM-18) is outlined below in Reaction Scheme 6-2.

[0120] [ka]

[0121] The symbols in formula (IM-19) have the same meanings as those in formula (I). Compounds of formula (IM-18) can be prepared by addition reaction of nitroalkanes of formula (IM-3) with compounds of formula (IM-19) in the presence of a suitable organic base.

[0122] (Reaction Scheme 6-3) A method for preparing compounds of formula (IM-19) is outlined below in Reaction Scheme 6-3.

[0123] [ka]

[0124] The symbols in formula (IM-20) have the same meanings as those in formula (I). The symbols in formula (IM-21) have the same meanings as those in formula (I). The aromatic vinyl of formula (IM-21) can be reacted with sulfonyl chloride in DMF solvent to produce the compound of formula (IM-20), which can then be reacted with phenol in the presence of an organic base or the like to prepare the compound.

[0125] (Reaction Scheme 7-1) Among the compounds represented by formula (Ic), a method for preparing the compound of formula (Ic-1) shown below is outlined in the following Reaction Scheme 7-1.

[0126] [ka]

[0127] The symbols in formula (IM-22) have the same meanings as those in formula (I). The symbols in formula (IM-23) have the same meanings as those in formula (I). The methylol moiety of the compound of formula (IM-23) can be converted to a carboxylic acid by oxidation with chromic acid or the like, and then cyclized in the presence of a suitable dehydrating agent (IM-23), to prepare the compound of formula (IM-22). Further, by carrying out deprotection, the compound of formula (Ic-1) can be prepared.

[0128] (Reaction Scheme 7-2) A method for preparing a compound of formula (IM-23) is outlined below in Reaction Scheme 7-2.

[0129] [ka]

[0130] The symbols in formula (IM-24) have the same meanings as those in formula (I). Ar in formula (IM-25) has the same meaning as that in formula (I). The compound of formula (IM-24) can be prepared by reacting the compound of formula (IM-25) with a Grignard reagent in the presence of an organotitanium compound such as titanium tetraisopropoxide. 1 It is expressed as MgX. 1 has the same meaning as in formula (I), and X represents a halogeno group. The compound of formula (IM-23) can be prepared by reacting the compound of formula (IM-24) with di-t-butyl dicarbonate (Boc 2 O) or the like, followed by Boc protection.

[0131] (Reaction Scheme 7-3) A method for preparing compounds of formula (IM-25) is outlined below in Reaction Scheme 7-3.

[0132] [ka]

[0133] Ar in formula (IM-26) has the same meaning as that in formula (I). The compound of formula (IM-25) can be prepared by coupling reaction of the arylacetonitrile of formula (IM-26) with epichlorohydrin in the presence of a metal amide such as sodium bis(trimethylsilyl)amide.

[0134] 〔salt〕 The salt of compound (I) and its stereoisomers is not particularly limited as long as it is an agriculturally and horticulturally acceptable salt. For example, it can be salts of inorganic acids such as hydrochloric acid and sulfuric acid; salts of organic acids such as acetic acid and lactic acid; salts of alkali metals such as lithium, sodium, and potassium; salts of alkaline earth metals such as calcium and magnesium; salts of transition metals such as iron and copper; salts of organic bases such as triethylamine, tributylamine, pyridine, and hydrazine; and ammonia. The salts of compound (I) and its stereoisomers can be obtained from compound (I) and its stereoisomers by known methods.

[0135] The compounds shown in Table 1 below are known compounds and can be produced by known methods. They can also be purchased and used. The CAS numbers of each compound are also listed in the table.

[0136] [Table 1] TIFF0007628231000031.tif214121TIFF0007628231000032.tif134121

[0137] [Potato white cyst nematode control agent] One aspect of the present invention is an agent for controlling potato cyst nematodes, which contains as an active ingredient at least one selected from the compound represented by the above formula (I), a stereoisomer thereof, and a salt thereof.

[0138] The control agent of the present invention may consist of at least one selected from compound (I), its stereoisomers, and salts thereof, or may be formulated into a form generally available for agricultural chemicals, such as a wettable powder, granules, dust, emulsifiable concentrate, water-soluble concentrate, suspension, flowable, etc.

[0139] When preparing the formulation, known additives or carriers can be used. That is, one embodiment of the present invention is a control agent comprising an agrochemically acceptable solid carrier and / or liquid carrier. When a solid dosage form is intended, solid carriers such as vegetable powders such as soybean flour and wheat flour, mineral fine powders such as diatomaceous earth, apatite, gypsum, talc, bentonite, pyrophyllite, and clay, and organic and inorganic compounds such as sodium benzoate, urea, and mirabilite can be used. When a liquid dosage form is desired, liquid carriers such as petroleum fractions such as kerosene, xylene and solvent naphtha, cyclohexane, cyclohexanone, dimethylformamide, dimethylsulfoxide, alcohol, acetone, trichloroethylene, methyl isobutyl ketone, mineral oil, vegetable oil, water, and the like can be used.

[0140] In the formulation, surfactants can be added as necessary. Examples of surfactants include nonionic surfactants such as polyoxyethylene-added alkyl phenyl ethers, polyoxyethylene-added alkyl ethers, polyoxyethylene-added higher fatty acid esters, polyoxyethylene-added sorbitan higher fatty acid esters, polyoxyethylene-added tristyryl phenyl ethers, etc., sulfate salts of polyoxyethylene-added alkyl phenyl ethers, alkyl naphthalene sulfonates, polycarboxylates, lignin sulfonates, formaldehyde condensates of alkyl naphthalene sulfonates, and isobutylene-maleic anhydride copolymers.

[0141] The control agent of the present invention can be appropriately set in terms of the active ingredient concentration depending on the formulation. For example, the active ingredient concentration in wettable powder is preferably 5 to 90% by weight, more preferably 10 to 85% by weight. The active ingredient concentration in emulsifiable concentrate is preferably 3 to 70% by weight, more preferably 5 to 60% by weight. The active ingredient concentration in granules is preferably 0.01 to 50% by weight, more preferably 0.05 to 40% by weight.

[0142] The wettable powder or emulsifiable concentrate thus obtained can be diluted with water to a desired concentration to form a suspension or emulsion, while the granules can be directly sprayed or mixed into the soil. When the control agent of the present invention is applied to a field, an appropriate amount of 0.1 g or more of the active ingredient can be applied per hectare.

[0143] [Method of application of potato white cyst nematode control agent] The control agent of the present invention is applied to field soil inhabited by potato cyst nematodes during the season when potatoes are not being cultivated. The control agent of the present invention is characterized in that its active ingredient is a substance that promotes the hatching of Gp eggs. Therefore, by applying the control agent of the present invention, Gp eggs can be hatched. When potatoes are not cultivated, that is, in a situation where potatoes that serve as a nutrient source are not present, the control agent of the present invention is applied to artificially hatch Gp eggs, making it possible to drive the hatched Gp into a state of starvation and kill them. The control agent of the present invention can hatch Gp eggs, but is preferably applied between spring and autumn, which is suitable for hatching of Gp eggs. During this period, it is preferable to apply the control agent of the present invention before and after the cultivation of rotation crops.

[0144] In this way, by eradicating Gp from the soil before cultivating potatoes, a stable potato harvest can be achieved. That is, one embodiment of the present invention is a method for controlling potato cyst nematodes, which comprises a step of applying the control agent of the present invention or the hatching promoter of the present invention to soil in which potatoes are grown prior to cultivation of the potatoes.

[0145] Gp cysts tend to be distributed at a depth of 0 to 20 cm in soil. In order to bring the control agent of the present invention into contact with the Gp cysts distributed there, a general soil treatment method may be used, such as soil mixing, soil injection, soil drenching, etc. For example, if the formulation is in liquid form, it can be diluted to a prescribed concentration to prepare a spray solution, which can then be sprayed over the entire field with a sprayer and mixed with a rotary mixer. If the formulation is in granular form, it can be sprayed with a fertilizer spreader and mixed with a rotary mixer. EXAMPLES

[0146] [Production Example of Compound (I)] [Production Example 1] Synthesis of 6,6-dimethyl-5-(p-tolyl)piperidin-2-one (compound A-3) [Process 1]

[0147] [ka]

[0148] A mixture of 4-methylcinnamaldehyde (98.89 g), dichloromethane (2.5 L), 2-nitropropane (122.32 g) and diethylamine (100.27 g) was stirred at room temperature overnight. The mixture was added with 1N hydrochloric acid and extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. 150.54 g of intermediate 1 represented by the above formula was obtained with a yield of 95.9%. The obtained intermediate 1 1 The H-NMR data is shown below. 1 H-NMR (CDCl 3 , 399.78MHz): δ=952(s, 1H, CHO), 7.26-7.05 (m, 4H, ArH), 3.97-3.94 (m, 1H, -C(Ar)H-), 3.07-2.65(m, 2H, -CH2-), 2.32 (s, 3H, ArCH3), 1.57 (s, 3H, -CH3), 1.47s (s, 3H, -CH3). [Process 2]

[0149] [ka]

[0150] To a mixture of (methoxymethyl)triphenylphosphonium chloride (10.28 g) and THF (100 ml), potassium tert-butoxide (3.14 g) was added under ice cooling, and the mixture was stirred for 30 minutes. Intermediate 1 (4.71 g) was added, and the mixture was further stirred for 30 minutes. The mixture was warmed to room temperature and stirred for 4.5 hours. Water was added to the resulting mixture, and the mixture was extracted with ethyl acetate. The resulting organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was subjected to silica gel chromatography (hexane:ethyl acetate=9:1) to obtain 4.26 g of intermediate 2 represented by the above formula with a yield of 80.9%. [Step 3]

[0151] [ka]

[0152] To a mixture of intermediate 2 (4.26 g) and THF (30 ml) was added 4N hydrochloric acid under ice cooling. The mixture was warmed to room temperature and stirred for 1.5 hours. The mixture was added with water and extracted with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. Sodium chlorite (5.86 g), sodium hydrogen phosphate (5.05 g), amylene (11.36 g), tert-butyl alcohol (50 ml) and water (16 ml) were added to the concentrated residue, and the mixture was stirred at room temperature overnight. Water was added to the mixture obtained, and the mixture was extracted with dichloromethane. The organic layer obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. Methanol (80 ml) was added to the concentrated residue, and a 10% hexane solution of trimethylsilyldiazomethane (55.5 g) was added dropwise at room temperature. The resulting mixture was stirred at room temperature for 1.5 hours and concentrated under reduced pressure. The resulting residue was subjected to silica gel chromatography (hexane:ethyl acetate=9:1) to obtain 2.58 g of intermediate 3 represented by the above formula with a yield of 57.0%. The obtained intermediate 3 1 The H-NMR data is shown below. 1 H-NMR (CDCl 3 , 399.78MHz): δ=7.20(d, 2H, J = 8.4 Hz, ArH), 7.06 (d,2H, J = 8.4 Hz, ArH),3.60 (s, 3H, -COOCH3), 3.33-3.29 (m, 1H, -C(Ar)H-), 2.33 (s, 3H, ArCH3),2.14-1.84 (m, 4H, -CH2CH2-), 1.60 (s, 3H, -CH3), 1.43s (s, 3H, -CH3). [Step 4]

[0153] [ka]

[0154] A mixture of intermediate 3 (2.58 g), acetic acid (50 ml) and zinc (12.02 g) was stirred at 60° C. overnight. The resulting mixture was allowed to cool to room temperature and filtered through Celite. Water was added to the resulting filtrate, and the mixture was extracted with ethyl acetate. The resulting organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was subjected to silica gel chromatography (ethyl acetate:methanol=9:1) to obtain 0.81 g of compound A-3 with a yield of 40.5%.

[0155] [Production Example 2] Synthesis of 5-(4-chlorophenyl)-6,6-dimethyltetrahydro-2H-thiopyran-2-one (Compound A-6) [Process 1]

[0156] [ka]

[0157] To a mixture of ethyl (E)-3-(4-chlorophenyl)-2-methylacrylate (4.63 mg) and THF (9.7 ml), a 1.03 M hexane solution (4.7 ml) of DIBAL-H was added at −78° C. After heating to 0° C., the mixture was stirred for 1 hour. The mixture was stirred at room temperature for 1 hour, and then extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. Toluene (9.7 ml), triethyl orthoacetate (3.5 ml) and propionic acid (14.5 μl) were added to the concentrated residue, and the mixture was stirred under reflux overnight. After cooling to room temperature, water was added and the mixture was extracted with diethyl ether. The organic layer obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue obtained was subjected to silica gel chromatography (hexane:ethyl acetate=98:2) to obtain 400.2 mg of intermediate 4 represented by the above formula with a yield of 82.0%. The obtained intermediate 4 1 The H-NMR data is shown below. 1 H-NMR (CDCl 3 , 500.16MHz): δ=7.26(d, 2H, J = 6.3 Hz, ArH), 7.16 (d, 2H, J = 8.1 Hz, ArH), 4.89 (s, 2H, =CH2),4.09-4.02 (m, 2H, -COOCH2-), 3.76 (t, 1H, J = 8.0 Hz, -(Ar)CH-), 2.84 (dd, 1H,J = 7.5 Hz, 15.5 Hz, -CH2COO-), 2.69 (dd, 1H, J = 8.1 Hz, 14.9 Hz, -CH2COO-),1.60 (s, 3H, -CH3), 1.17 (t, 3H, J = 7.4 Hz, -COOCH2CH3). [Process 2]

[0158] [ka]

[0159] To a mixture of intermediate 4 (199.3 mg) and dichloromethane (3.9 ml), a 1.03 M hexane solution (1.91 ml) of DIBAL-H was added at −78° C. After heating to 0° C., the mixture was stirred for 30 minutes. A saturated aqueous solution of potassium sodium tartrate was added to the resulting mixture, which was stirred at room temperature for 1 hour and then extracted with dichloromethane. The resulting organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was subjected to silica gel chromatography (hexane:ethyl acetate=8:2) to quantitatively obtain 165.8 mg of intermediate 5 represented by the above formula. The obtained intermediate 5 1 The H-NMR data is shown below. 1 H-NMR (CDCl 3 , 500.16MHz): δ=7.27(d, 2H, J = 8.6 Hz, ArH), 7.16 (d, 2H, J = 8.6 Hz, ArH), 4.94 (s, 1H, =CH2),4.87 (s, 1H, =CH2), 3.63 (td, 1H, J = 6.3 Hz, 10.4 Hz, -CH2-), 3.56 (t, 1H, J =6.3 Hz, 10.4 Hz, - CH2-), 3.41 (t, 1H, J = 8.0 Hz, -CH2O-), 2.13 (qd, 1H, J =6.9 Hz, 13.8 Hz, -(Ar)CH-), 1.96-1.88 (m, 1H, -CH2-), 1.57 (s, 3H, -CH3). [Step 3]

[0160] [ka]

[0161] A mixture of intermediate 5 (165.8 mg), dichloromethane (3.9 ml), triethylamine (285 μl), tosyl chloride (195.5 mg) and 4-dimethylaminopyridine (4.8 mg) was stirred at room temperature overnight. Saturated sodium bicarbonate water was added to the obtained mixture, and the mixture was extracted with dichloroethane. The obtained organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel chromatography (hexane: ethyl acetate = 95: 5) to obtain 269.1 mg of intermediate 6 represented by the above formula with a yield of 93.0%. The obtained intermediate 61 The H-NMR data is shown below. 1 H-NMR (CDCl 3 , 500.16MHz): δ=7.74(d, 2H, J = 8.1 Hz, -SO2ArH), 7.33 (d, 2H, J = 8.0 Hz, -ArH), 7.19 (d, 2H, J =8.1 Hz, ArH), 7.01 (d, 2H, J = 8.6 Hz, -SO2ArH), 4.84 (s, 1H=CH2), 4.81 (s, 1H,=CH2), 4.01 (td, 1H, J = 5.7 Hz, 9.8 Hz, -CH2-), 3.86-3.82 (m, 1H, -CH2-), 3.29(t, 1H, J = 8.1 Hz, -(Ar)CH-), 2.46 (s, 3H, -ArCH3), 2.23 (qd, 1H, J = 6.9 Hz,14.3 Hz, -CH2-), 1.99-1.92 (m, 1H, -CH2-), 1.50 (s, 3H, -CH3). [Step 4]

[0162] [ka]

[0163] A mixture of Intermediate 6 (168.2 mg), dimethyl sulfoxide (0.92 ml) and sodium cyanide (113 mg) was stirred at 75° C. for 1 hour. The mixture was cooled to room temperature, saturated sodium bicarbonate water was added, and the mixture was extracted with diethyl ether. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography (hexane:ethyl acetate=95:5) to quantitatively obtain 105.3 mg of intermediate 7 represented by the above formula. The obtained intermediate 7 1 The H-NMR data is shown below. 1 H-NMR (CDCl 3, 500.16MHz): δ=7.30(d, 2H, J = 8.6 Hz, ArH), 7.15 (d, 2H, J = 8.0 Hz, ArH), 4.94 (s, 2H, =CH2),3.32 (t, 1H, J = 8.0 Hz, -(Ar)CH-), 2.33-2.27 (m, 1H, -CH2-), 2.24-2.16 (m, 2H, -CH2-), 2.04-1.97 (m, 1H, -CH2-), 1.57 (s, 3H, -CH3). [Step 5]

[0164] [ka]

[0165] To a mixture of intermediate 7 (105.3 mg) and dichloromethane (2.3 ml), a 1.03 M hexane solution (895 μl) of DIBAL-H was added at −78° C. The mixture was heated to 0° C. and stirred for 30 minutes. The mixture was stirred at room temperature for 1 hour, and then extracted with dichloromethane. The organic layer was washed with saturated aqueous sodium bicarbonate, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. To the resulting residue were added sodium chlorite (208.5 mg), sodium hydrogen phosphate (179.8 mg), amylene (497 μl), tert-butyl alcohol (1.73 ml) and water (576 μl), and the mixture was stirred at room temperature for 30 minutes. The mixture was added with water and extracted with ethyl acetate, and the organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. Methanol (2.3 ml) was added to the concentrated residue, and a 10% hexane solution (1.15 ml) of trimethylsilyldiazomethane was added dropwise at room temperature. The resulting mixture was stirred at room temperature for 30 minutes and concentrated under reduced pressure. The resulting residue was subjected to silica gel chromatography (hexane:ethyl acetate=98:2) to obtain 106.1 mg of intermediate 8 represented by the above formula with a yield of 91%. The obtained intermediate 8 1 The H-NMR data is shown below. 1 H-NMR (CDCl 3 , 500.16MHz): δ=7.27(d, 2H, J = 8.6 Hz, ArH), 7.14 (d, 2H, J = 8.6 Hz, ArH), 4.92 (s, 1H, =CH2),4.88 (s, 1H, =CH2), 3.65 (s, 3H-COOCH3), 3.18 (t, 1H, J = 7.5 Hz, -(Ar)CH-),2.30-2.21 (m, 2H, -CH2-), 2.18-2.11 (m, 1H, -CH2-), 2.05-1.97 (m, 1H, -CH2-),1.55 (s, 3H, -CH3). [Step 6]

[0166] [ka]

[0167] To a mixture of iron(III) oxalate hexahydrate (491.1 mg) and water (8.5 ml), potassium thiocyanate (197.3 mg), ethanol (8.1 ml), intermediate 8 (51.3 mg) and sodium borohydride (49.1 mg) were added under ice cooling, and the mixture was stirred for 1.5 hours under an argon atmosphere. Aqueous ammonia was added to the mixture obtained, and the mixture was extracted with dichloromethane. The organic layer obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue obtained was subjected to silica gel chromatography (hexane:ethyl acetate=8:2) to obtain 40.0 mg of intermediate 9 represented by the above formula with a yield of 64.0%. The obtained intermediate 9 1 The H-NMR data is shown below. 1 H-NMR (CDCl 3, 500.16MHz): δ=7.33(d, 2H, J = 8.0 Hz, ArH), 7.16 (d, 2H, J = 8.6 Hz, ArH), 3.63 (s, 3H, -COOCH3),2.91-2.88 (m, 1H, -(Ar)CH-), 2.40-2.33 (m, 1H, -CH2-), 2.13-2.03 (m, 3H,-CH2CH2-), 1.51 (s, 3H, -CH3), 1.48 (s, 3H, -CH3). [Step 7]

[0168] [ka]

[0169] A mixture of intermediate 9 (7.6 mg), benzene (240 μl), a 2 M solution of trimethylaluminum in toluene (24.4 μl), and bis(tri-tert-butylphosphine)palladium(0) (2.5 mg) was stirred at room temperature for 30 minutes under an argon atmosphere. The mixture was added with saturated aqueous sodium bicarbonate and extracted with diethyl ether. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel chromatography (hexane:ethyl acetate=9:10) to obtain 3.3 mg of compound A-6 with a yield of 53.0%.

[0170] [Production Example 3] Synthesis of 5,5-dimethyl-4-(p-tolyl)dihydrofuran-2(3H)-thione (Compound B-2)

[0171] [ka]

[0172] A mixture of compound 18 (0.23 g), toluene (10 ml) and Lawesson's reagent (0.89 g) was stirred under reflux overnight. The mixture was cooled to room temperature and concentrated under reduced pressure, and the residue was subjected to silica gel chromatography (hexane:ethyl acetate=9:1) to obtain 0.19 g of compound B-2 with a yield of 81.9%.

[0173] [Production Example 4] Synthesis of 5,5-dimethyl-4-(p-tolyl)dihydrothiophen-2(3H)-one (Compound B-6)

[0174] [ka]

[0175] A mixture of compound B-2 (0.19 g), 1,2-dichloroethane (9 mL) and a 1 M hexane solution of ethylaluminum dichloride (1.4 mL) was stirred at 70° C. overnight. The mixture obtained was allowed to cool to room temperature and extracted with dichloromethane. The organic layer obtained was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue obtained was subjected to silica gel chromatography (hexane:ethyl acetate=95:5) to obtain 0.10 g of compound B-6 with a yield of 50.5%.

[0176] [Production Example 5] Synthesis of 4-(4-chlorophenyl)-3,3-dimethylisothiazolidine-1,1-dioxide (compound B-12) [Process 1]

[0177] [ka]

[0178] Sulfuryl chloride (13.4 ml) was added to DMF (12.8 ml) under ice cooling. After stirring at room temperature for 30 minutes, 4-chloro-styrene (11.50 g) was added. The resulting mixture was stirred at 90° C. for 3 hours. The mixture was cooled to room temperature, water was added, and the mixture was extracted with dichloromethane, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. To the concentrated residue obtained, dichloromethane (300 ml) and triethylamine (12.6 g) were added, and phenol (8.21 g) was added under ice cooling, and the mixture obtained was stirred at room temperature overnight. Saturated saline was added, and the mixture was extracted with dichloromethane. The obtained organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel chromatography (hexane:ethyl acetate=9:1) to obtain 10.94 g of intermediate 10 represented by the above formula with a yield of 44.7%. The obtained intermediate 10 1 The H-NMR data is shown below. 1 H-NMR (CDCl 3 , 399.78MHz): δ=7.50-7.24(m, 10H, ArH, -CH=CH-), 6.84 (d, 2H, J = 15.6 Hz, -CH=CH-). [Process 2]

[0179] [ka]

[0180] A mixture of Intermediate 10 (10.94 g), acetonitrile (100 ml), 2-nitropropane (4.96 g) and DBU (8.48 g) was stirred at room temperature overnight. 1N hydrochloric acid was added, and the mixture was extracted with diethyl ether. The obtained organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel chromatography (hexane:ethyl acetate=9:1) to obtain 9.43 g of intermediate 11 represented by the above formula with a yield of 66.2%. The obtained intermediate 11 1 The H-NMR data is shown below. 1 H-NMR (CDCl 3, 399.78MHz): δ=7.36-7.26(m, 5H, ArH), 7.18-7.15 (m, 2H, ArH), 6.99-6.97 (m, 2H, ArH), 3.96-3.74 (m, 3H,-C(Ar)HCH2-), 1.58 (s, 6H, -CH3). [Step 3]

[0181] [ka]

[0182] A mixture of intermediate 11 (1.15 g), acetic acid (15 ml) and zinc (3.92 g) was stirred at 50° C. overnight. The mixture was allowed to cool to room temperature and filtered through Celite. Water was added to the filtrate, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure, and the residue was subjected to silica gel chromatography (ethyl acetate:methanol=8:2) to obtain 0.42 g of intermediate 12 represented by the above formula with a yield of 39.5%. The obtained intermediate 12 1 The H-NMR data is shown below. 1 H-NMR (CDCl 3 , 399.78MHz): δ=7.33-7.22(m, 7H, ArH), 7.00-6.97 (m, 2H, ArH), 4.12-4.08 (m, 1H, -CH2-), 3.77-3.75 (m,1H, -CH2-), 3.24-3.20 (m, 1H, -C(Ar)H-), 1.15 (s, 3H, -CH3), 1.03 (s, 3H, -CH3). [Step 3]

[0183] [ka]

[0184] A mixture of intermediate 12 (0.42 g) and toluene (6.0 ml) was stirred under reflux overnight. The mixture was cooled to room temperature and concentrated under reduced pressure. The residue was subjected to silica gel chromatography (hexane:ethyl acetate=5:5) to obtain 0.21 g of compound B-12 with a yield of 79.4%.

[0185] [Production Example 6] Synthesis of 4,4-dimethyl-5-phenyl-3-azabicyclo[3.1.0]hexan-2-one (compound C-1) [Process 1]

[0186] [ka]

[0187] THF (10 ml) was added to a 1.9M NaHMDS / THF solution (39.5 ml) and cooled to -10° C. A mixed solution of benzyl cyanide (3.51 g) and THF (45 ml) was added dropwise to this solution and stirred at -10° C. for 10 minutes. Epichlorohydrin (2.54 ml) was added to the resulting mixture and stirred at room temperature overnight. The mixture was stirred at room temperature for 1.5 hours after adding 4M dioxane hydrochloric acid (30 ml), and extracted with diethyl ether The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. To the concentrated residue, THF (50 ml) and 3MMeMgCl / THF solution (32 ml) were added in that order, and the mixture was stirred under heating and reflux for 30 minutes. After the mixture was cooled to room temperature, tetraisopropyl orthotitanate (8.18 ml) was added dropwise, and the mixture was stirred at room temperature for 3 days. To the resulting mixture, saturated aqueous ammonium chloride solution and 2N hydrochloric acid were added under ice cooling, and the mixture was filtered through Celite. The filtrate was washed with ethyl acetate, and then saturated aqueous sodium bicarbonate solution was added to the resulting aqueous layer to make it basic. The aqueous layer was extracted with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. To the resulting concentrated residue were added dichloromethane (25 ml) and di-tert-butyl dicarbonate (2.60 g), and the mixture was stirred at room temperature overnight. The resulting mixture was concentrated under reduced pressure, and the residue was subjected to silica gel chromatography (hexane:ethyl acetate=2:1) ​​to obtain 1.13 g of intermediate 13 represented by the above formula with a yield of 12.3%. The obtained intermediate 13 1 The H-NMR data is shown below. 1 H-NMR (CDCl 3 , 399.78MHz): δ=7.35-7.19(m, 5H, ArH), 5.41-5.35 (m, 1H, -NH-), 4.31 (s, 1H, -OH), 4.11-3.77 (m, 2H,-CH2-), 1.48 (s, 3H, -CH3), 1.46 (s, 9H, -(CH3)3), 1.29 (s, 3H, -CH3),1.28-1.24 (m, 1H, -CH2-), 1.15-1.11 (m, 1H, -CH2-), 0.77-0.65 (m, 1H, -C(C)H-). [Process 2]

[0188] [ka]

[0189] A mixture of intermediate 13 (1.13 g), DMF (30 ml), molecular sieves 4A (4 g) and pyridinium dichromate (4.18 g) was stirred at room temperature overnight. The resulting mixture was ice-cooled and filtered through Celite. Water and 2N hydrochloric acid were added to the resulting filtrate, and the mixture was extracted with diethyl ether. The resulting organic layer was washed with saturated saline, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel chromatography (hexane:ethyl acetate=4:1) to obtain 0.91 g of intermediate 14 represented by the above formula with a yield of 81.6%. The obtained intermediate 14 1 The H-NMR data is shown below. 1 H-NMR (CDCl 3, 399.78MHz): δ=7.35-7.31(m, 5H, ArH), 2.25 (dd, 1H, -COC(C)H-), 1.60 (s, 3H, -CH3), 1.53 (s, 9H,-(CH3)3), 1.36-1.30 (m, 2H, -CH2-), 1.25 (s, 3H, -CH3). [Step 3]

[0190] [ka]

[0191] A mixture of Intermediate 14 (0.50 g), dichloromethane (7 ml) and 4M dioxane hydrochloric acid (3.32 ml) was stirred at room temperature for 3 hours. To the resulting mixture was added saturated sodium bicarbonate water under ice cooling, and the mixture was extracted with dichloromethane. The resulting organic layer was concentrated under reduced pressure, and the residue was subjected to silica gel chromatography (hexane:ethyl acetate=1:1) to obtain 0.32 g of compound C-1 with a yield of 95.2%.

[0192] An example of the compound of the above Production Example and the compound (I) produced by a similar method are shown in Tables 2 to 5. The melting points are also shown as physical property values.

[0193] [Table 2]

[0194] [Table 3] TIFF0007628231000055.tif107135

[0195] [Table 4]

[0196] [Table 5] TIFF0007628231000058.tif214129TIFF0007628231000059.tif81129

[0197] Among the compounds listed in Tables 2 to 5, the compounds marked with an * in the melting point column were compounds having the properties of amorphous or viscous oil. 1 The H-NMR data is shown below. Compound No. A-1: 1 H-NMR (CDCl 3 ,500.16MHz): δ=7.32-7.21(m, 5H, ArH), 5.64 (brs, 1H, -NH-), 2.87-2.84 (m, 1H,-C(Ar)H-), 2.60-1.91 (m, 4H, -CH2CH2-), 1.20 (s, 3H, -CH3), 1.08 (s, 3H, -CH3). Compound No. A-3: 1 H-NMR (CDCl 3 ,399.78MHz): δ=7.26-7.08 (m, 4H, ArH), 5.61(brs, 1H, -NH-), 2.84-2.80 (m, 1H,-C(Ar)H-), 2.60-1.87 (m, 4H, -CH2CH2-), 2.31(s ,3H, ArCH3), 1.19 (s, 3H, -CH3),1.07 (s, 3H, -CH3). Compound No. A-4: 1 H-NMR (CDCl 3 ,500.16MHz): δ=7.99 (d, 2H, J = 8.1Hz, ArH), 7.30 (d, 2H, J = 8.1Hz, ArH), 5.79(brs, 1H, -NH-), 3.92 (s, 3H, -COOCH3), 2.94-2.91 (m, 1H, -C(Ar)H-), 2.61-1.92(m, 4H, -CH2CH2-), 1.21 (s, 3H, -CH3), 1.08 (s, 3H, -CH3). Compound No. A-5: 1 H-NMR (CDCl 3,500.16MHz): δ=7.33-7.28 (m, 3H, ArH), 7.22-7.20 (m, 2H, ArH), 3.15-3.13 (m, 1H,-C(Ar)H-), 2.85-2.10 (m, 4H, -CH2CH2-), 1.39 (s, 3H, -CH3), 1.32 (s, 3H, -CH3). Compound number A-6: 1 H-NMR (CDCl 3 ,500.16MHz): δ=7.32-7.31 (d, 2H, J = 8.6 Hz, ArH), 7.16-7.14 (d, 2H, J = 8.0 Hz, ArH), 3.14 (dd, 1H, J = 1.7 Hz, 12.0 Hz, -C(Ar)H-), 2.86-2.81 (m, 1H,-CH2CH2-), 2.74 (ddd, 1H, J = 5.8 Hz, 12.1 Hz, 17.8 Hz, -CH2CH2-), 2.58-2.49(m, 1H, -CH2CH2-), 2.10-2.05 (m, 1H, -CH2CH2-), 2.85-2.06 (m, 4H, -CH2CH2-),1.36 (s, 3H, -CH3), 1.30(s, 3H, -CH3). Compound No. A-7: 1 H-NMR (CDCl 3 ,500.16MHz): δ=7.13 (d, 2H, J = 8.1Hz, ArH), 7.09 (d, 2H, J = 8.0 Hz, ArH), 3.11-3.09 (m, 1H, -C(Ar)H-), 2.85-2.06 (m, 4H, -CH2CH2-), 2.34(s, 3H, ArCH3), 1.37(s, 3H, -CH3), 1.30 (s, 3H, -CH3). Compound number B-1: 1 H-NMR (CDCl 3 ,500.16MHz): δ=7.37-7.18 (m, 5H, ArH), 3.55-3.49 (m, 3H, -C(Ar)HCH2-), 1.64 (s, 3H,-CH3), 1.12 (s, 3H, -CH3). Compound number B-2:1 H-NMR (CDCl 3 ,500.16MHz): δ=7.17-7.07 (m, 4H, ArH), 3.50-3.48 (m, 3H, -C(Ar)HCH2-), 2.35 (s, 3H,ArCH3), 1.62 (s, 3H, -CH3), 1.12 (s, 3H, -CH3). Compound number B-3: 1 H-NMR (CDCl 3 ,500.16MHz): δ=7.26-6.94 (m, 3H, ArH), 3.79-3.39 (m, 3H, -C(Ar)HCH2-), 2.30 (s, 3H, -ArCH3), 2.28 (s, 3H, -ArCH3), 1.64 (s, 3H, -CH3), 1.16 (s, 3H, -CH3). Compound number B-4: 1 H-NMR (CDCl 3 ,500.16MHz): δ=7.36-7.22 (m, 5H, ArH), 3.63-2.87 (m, 3H, -C(Ar)HCH2-), 1.57 (s, 3H,-CH3), 1.31 (s, 3H, -CH3). Compound number B-5: 1 H-NMR (CDCl 3 ,500.16MHz): δ=7.49 (d, 2H, J = 8.6 Hz, ArH), 7.13 (d, 2H, J = 8.6 Hz, ArH), 3.58-2.87 (m, 3H, -C(Ar)HCH2-), 1.55 (s, 3H, -CH3), 1.29 (s, 3H, -CH3). Compound number B-9: 1 H-NMR (CDCl 3 ,500.16MHz): δ=7.39-7.24 (m, 5H, ArH), 4.26 (brs, 1H, -NH-), 3.79-3.53 (m, 3H,-C(Ar)HCH2-), 1.40 (s, 3H, -CH3), 1.11 (s, 3H, -CH3). Compound number B-10: 1 H-NMR (CDCl 3,500.16MHz): δ=7.52-7.12 (m, 4H, ArH), 4.20 (brs, 1H, -NH-), 3.75-3.54 (m, 3H,-C(Ar)HCH2-), 1.40 (s, 3H, -CH3), 1.11 (s, 3H, -CH3). Compound number B-12: 1 H-NMR (CDCl 3 ,500.16MHz): δ=7.37-7.18 (m, 4H, ArH), 4.27 (brs, 1H, -NH-), 3.74-3.55 (m, 3H,-C(Ar)HCH2-), 1.40 (s, 3H, -CH3), 1.10 (s, 3H, -CH3). Compound number C-1: 1 H-NMR (CDCl 3 , 399.78MHz): δ=7.35-7.28 (m, 5H, ArH), 5.06 (s, 1H, -NH-), 2.20-2.16 (m, 1H,-COCH-), 1.38 (s, 3H, -CH3), 1.35-1.33 (dd, 1H, -CH2-), 1.28-1.25 (dd, 1H,-CH2-), 1.08 (s, 3H, -CH3). Compound number D-2: 1 H-NMR (CDCl 3 ,399.78MHz): δ=7.06-7.01 (m, 3H, ArH), 3.77-3.73 (m, 1H, -C(Ar)H-), 3.04-2.81 (m,2H, -CH2-), 2.32 (s ,3H, ArCH3), 2.30 (s ,3H, ArCH3), 1.54 (s, 3H, -CH3), 1.09 (s, 3H, -CH3). Compound number D-4: 1 H-NMR (CDCl 3, 399.78 MHz): δ = 6.94 (s, 1H, ArH), 6.81 (s, 1H, ArH), 3.45 - 3.41 (m, 1H, -C(Ar)H-), 3.02 - 2.82 (m, 2H, -CH2-), 2.32 (s, 6H, ArCH3), 1.54 (s, 3H, -CH3), 1.06 (s, 3H, -CH3). Compound number D - 5: 1 1H - NMR(CDCl 3 , 399.78 MHz): δ = 7.20 - 7.12 (m, 4H, ArH), 3.51 - 3.47 (m, 1H, -C(Ar)H-), 3.03 - 2.83 (m, 2H, -CH2-), 2.65 (q, 2H, J = 7.6 Hz, 15.6 Hz, -ArCH2-), 1.54 (s, 3H, -CH3), 1.23 (t, 3H, J = 7.2 Hz, -CH2CH3), 1.05 (s, 3H, -CH3). Compound number D - 19: 1 1H - NMR(CDCl 3 , 399.78 MHz): δ = 7.09 (s, 1H, ArH), 7.05 - 7.00 (m, 2H, ArH), 6.41 (brs, 1H, -NH-), 5.86 (d, 1H, J = 2Hz, =CH-), 2.50 (s, 3H, ArCH3), 2.24 (s, 3H, ArCH3), 1.41 (s, 6H, -CH3).

[0198] [Method for producing optically active compounds] The following optically active compound No. 2 (referred to as compound No. 2(-)) was also produced. * in the chemical formula indicates that it is an enantiomer - excess compound.

[0199] [Chemical formula]

[0200] The specific rotation of compound 2(-) was (-). In detail, the specific rotation [α] (365 nm, 25°C) was -98.8 (c1.057, dichloromethane). The melting point was 154-155°C. The enantiomeric excess was 99.8% ee. The manufacturing method is shown below.

[0201] [Production Example 7] Synthesis of (-)-5,5-dimethyl-4-(4-methylphenyl)-2-pyrrolidinone (compound 2(-)) [Process 1]

[0202] [ka]

[0203] A mixture of ethyl (E)-3-(p-tolyl)acrylate (118.59 g), acetonitrile (300 ml), 2-nitropropane (140.24 mL) and DBU (232.60 mL) was stirred at room temperature overnight. 1N hydrochloric acid was added, and the mixture was extracted with diethyl ether. The obtained organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel chromatography (hexane:ethyl acetate=95:5) to obtain 150.35 g of intermediate 15 represented by the above formula with a yield of 86.3%. The obtained intermediate 15 1 The H-NMR data is shown below. 1 H-NMR (CDCl 3 , 399.78MHz): δ=7.12-7.07(m, 4H, ArH), 4.02-3.90 (m, 2H, -COOCH2-), 3.88-3.84 (m, 1H, -C(Ar)H-),2.89-2.60 (m, 2H, - CH2COO-), 2.31 (s, 3H, -ArCH3),1.57 (s, 3H, -CH3), 1.48 (s, 3H, -CH3), 1.05 (t, 3H, J = 6.8 Hz, -CH2CH3). [Process 2]

[0204] [ka]

[0205] A mixture of Intermediate 15 (5.58 g), methanol (20 ml), and potassium hydroxide (1.68 g) was stirred at room temperature overnight. Water was added to the resulting mixture, and the mixture was extracted with diethyl ether. Concentrated hydrochloric acid was added to the resulting aqueous layer, and the mixture was extracted with dichloroethane. The resulting organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 3.75 g of intermediate 16 represented by the above formula with a yield of 74.6%. The obtained intermediate 16 1 The H-NMR data is shown below. 1 H-NMR (CDCl 3 , 399.78MHz): δ=7.12-7.05(m, 4H, ArH), 3.83-3.79 (m, 1H, -C(Ar)H-), 2.91-2.61 (m, 2H, - CH2COO-), 2.31(s, 3H, -ArCH3), 1.54 (s, 3H, -CH3), 1.45 (s, 3H, -CH3). [Step 3]

[0206] [ka]

[0207] A mixture of intermediate 16 (2.51 g), dichloromethane (200 ml), (S)-1-(naphthalen-2-yl)ethan-1-amine (2.10 g), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (3.83 g) and 4-dimethylaminopyridine (0.37 g) was stirred at room temperature overnight. Water was added to the obtained mixture, and the mixture was extracted with dichloroethane. The obtained organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The obtained residue was subjected to silica gel chromatography (hexane:ethyl acetate=1:1) to obtain 1.91 g of intermediate 17-1 represented by the above formula with a yield of 94.6%, and 1.84 g of intermediate 17-2 with a yield of 91.1%. The obtained intermediate 17-1 1 The H-NMR data is shown below. 1 H-NMR (CDCl 3 , 399.78MHz): δ=7.80-7.73 (m, 3H, ArH), 7.53 (s, 1H,ArH), 7.49-7.43 (m, 2H, ArH), 7.19-7.17 (m, 1H, ArH), 7.13-7.06 (m, 4H, ArH),5.48 (brd, 1H, J = 7.6 Hz, -NH-), 5.09-5.02 (m, 1H, -C*(Me)H-), 3.78-3.74 (m,1H, -C(Ar)H-), 2.71-2.62 (m, 2H, - CH2CO-), 2.32 (s, 3H, -ArCH3), 1.55 (s, 3H, -CH3), 1.52 (s, 3H, -CH3), 1.28-1.23 (m, 3H,C*-CH3). The obtained intermediate 17-2 1 The H-NMR data is shown below. 1 H-NMR (CDCl 3, 399.78MHz): δ=7.78-7.75 (m, 1H, ArH), 7.69-7.66 (m,1H, ArH), 7.61 (d, 1H, J = 8 Hz, ArH), 7.47-7.41 (m, 2H, ArH), 7.38 (s, 1H,ArH), 7.05-7.01 (m, 4H, ArH), 6.89-6.86 (m, 1H, ArH), 5.48 (brd, 1H, J = 8.4Hz, -NH-), 5.13-5.05 (m, 1H, -C*(Me)H-), 3.79-3.75 (m, 1H, -C(Ar)H-), 2.72-2.61(m, 2H, - CH2CO-), 2.27 (s, 3H, -ArCH3), 1.55 (s, 3H,-CH3), 1.54 (s, 3H, -CH3), 1.44-1.42 (m, 3H, C*-CH3). [Step 4]

[0208] [ka]

[0209] A mixture of intermediate 17-1 (1.90 g), acetic acid (15 ml), acetic anhydride (30 ml) and sodium nitrite (3.24 g) was stirred at room temperature overnight. The mixture was added with aqueous sodium bicarbonate and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. THF (30 mL), water (15 mL) and lithium hydroxide (0.22 g) were added to the residue, and the mixture was stirred at room temperature overnight. Water was added to the resulting mixture, and the mixture was extracted with diethyl ether. Concentrated hydrochloric acid was added to the resulting aqueous layer, and the mixture was extracted with dichloroethane. The resulting organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 0.75 g of intermediate 16-1 represented by the above formula with a yield of 63.6%. [Step 5]

[0210] [ka]

[0211] To a mixture of intermediate 16-1 (0.75 g), diethyl ether (12 ml), and methanol (3 ml), a 10% hexane solution of trimethylsilyldiazomethane (3.0 ml) was added under ice cooling. After warming to room temperature, the mixture was stirred for 1 hour. Acetic acid was added to the resulting mixture, and the mixture was concentrated under reduced pressure. The resulting residue was subjected to silica gel chromatography (hexane:ethyl acetate=9:1) to obtain 0.70 g of intermediate 18-1 represented by the above formula with a yield of 88.4%. The obtained intermediate 18-1 1 The H-NMR data is shown below. 1 H-NMR (CDCl 3 , 399.78MHz): δ=7.12-7.07(m, 4H, ArH), 3.88-3.85 (m, 1H, -C(Ar)H-), 3.51 (s, 3H,-COOCH3), 2.91-2.61 (m, 2H, - CH2COO-), 2.31 (s, 3H, -ArCH3), 1.56 (s, 3H,-CH3), 1.47 (s, 3H, -CH3). [Step 6]

[0212] [ka]

[0213] A mixture of intermediate 18-1 (0.70 g), ethanol (12 mL), a saturated aqueous ammonium chloride solution (3 ml) and zinc (1.46 g) was stirred under reflux overnight. The resulting mixture was allowed to cool to room temperature and filtered through Celite. Water was added to the resulting filtrate, and the mixture was extracted with ethyl acetate. The resulting organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was subjected to silica gel chromatography (ethyl acetate:methanol=9:1) to obtain 0.43 g of compound 2(-) (99.8% ee) with a yield of 76.7%.

[0214] Similarly, the optically active compound No. 1 shown below (referred to as Compound No. 1(-)) was also prepared. The symbol * in the chemical formula indicates that the compound is an enantiomerically excess compound.

[0215] [ka]

[0216] The specific rotation of compound 1(-) was (-). In detail, the specific rotation [α] (365 nm, 25°C) was -110.4 (c1.087, dichloromethane). The melting point was 119-121°C. The enantiomeric excess was 99.7% ee.

[0217] Similarly, the optically active compound No. 3 shown below (referred to as Compound No. 3(-)) was also prepared. The symbol * in the chemical formula indicates that the compound is an enantiomerically excess compound.

[0218] [ka]

[0219] The specific rotation of compound 3(-) was (-). In detail, the specific rotation [α] (365 nm, 25°C) was -86.3 (c1.629, dichloromethane). The melting point was 174-175°C. The enantiomeric excess was 99.2% ee.

[0220] The following optically active compound No. B-12 (referred to as Compound No. B-12(-)) was also prepared. * in the chemical formula indicates that the compound is an enantiomerically excess compound.

[0221] [ka]

[0222] This compound was produced by preparative purification using a chiral separation column. The specific rotation of compound B-12(-) was (-). In detail, the specific rotation [α] (365 nm, 25°C) was -53.88 (c1.629, dichloromethane). The enantiomeric excess was 99.9% ee.

[0223] The conditions for fractionation are as follows: The sample for fractionation was prepared by adding 2-propanol to compound B-12 to prepare a solution with a concentration of 20 mg / mL, and further adding n-heptane to this to prepare a solution with a concentration of 10 mg / mL. (Isolation conditions) Column:CHIRALART Cellulose-C(5μm) 250x30mm ID Eluent:n-heptane / 2-propanol(50 / 50) Flow rate: 21.3 mL / min Temperature:ambient Detection: UV at 230 nm Load: 330 mg (10 mg / mL) System:LC-Forte / R(YMC)

[0224] Using the above manufacturing method as a reference, compounds with specific rotation (+) were also manufactured. The physical property data for each compound are shown below. Compound No. 1(+): (+)-5,5-Dimethyl-4-phenyl-2-pyrrolidinone The specific rotation [α] (365 nm, 25°C) was +110.2 (c1.375, dichloromethane). The melting point was 120-121°C. The enantiomeric excess was 99.7% ee. Compound No. 2(+): (+)-5,5-Dimethyl-4-(4-methylphenyl)-2-pyrrolidinone The specific rotation [α] (365 nm, 25°C) was +94.2 (c1.143, dichloromethane). The melting point was 154-155°C. The enantiomeric excess was 98.8% ee. Compound No. 3(+): (+)-5,5-Dimethyl-4-(4-chlorophenyl)-2-pyrrolidinone The specific rotation [α] (365 nm, 25°C) was +86.3 (c0.792, dichloromethane). The melting point was 174-175°C. The enantiomeric excess was 99.6% ee. Compound No. B-12(+): (+)-4-(4-chlorophenyl)-3,3-dimethylisothiazolidine-1,1-dioxide The specific rotation [α] (365 nm, 25°C) was +56.09 (c0.792, dichloromethane). The melting point was 179-180°C. The enantiomeric excess was 99.9% ee.

[0225] [Formulation example] Some formulation examples of the control agent of the present invention are shown below, but the compound (I) (active ingredient), additives and their addition ratios are not limited to these examples and can be changed in a wide range. Parts in the formulation examples indicate parts by weight. (Formulation Example 1) Wettable powder Compound (I) 20 parts White carbon 20 copies 52 parts diatomaceous earth Sodium alkyl sulfate 8 parts The above ingredients are mixed uniformly and finely crushed to obtain a wettable powder containing 20% ​​active ingredient. (Formulation Example 2) Emulsion Compound (I) 20 parts Xylene 55 parts Dimethylformamide 15 parts Polyoxyethylene phenyl ether 10 parts Mix and dissolve the above ingredients to obtain an emulsion containing 20% ​​active ingredient. (Formulation Example 3) Granules Compound (I) 5 parts Talc 40 parts Clay 38 parts Bentonite 10 parts Sodium alkyl sulfate 7 parts The above ingredients are mixed uniformly and finely pulverized, then granulated into particles with a diameter of 0.5 to 1.0 mm to obtain a granule containing 5% of the active ingredient. (Formulation Example 4) Liquid Compound (I) 10 parts Dimethyl sulfoxide 75 parts Polyoxyethylene alkyl ether 5 parts Polyoxyethylene higher fatty acid ether 10 parts Mix and dissolve the above ingredients to obtain a solution containing 10% active ingredient.

[0226] [Biological test example] (Test Example 1) Evaluation test of the effect of promoting hatching of potato cyst nematode eggs (liquid immersion test) (1) Preparation of test solutions A predetermined amount of compound (I) was dissolved in an aqueous solution containing 0.05% (v / v) polyoxyethylene sorbitan monolaurate (Tween 20) to prepare a 100 ppm solution of compound (I). The 100 ppm solution of Compound (I) was further diluted with a 0.05% (v / v) aqueous Tween 20 solution to prepare a test solution with a Compound (I) concentration of 2 ppm. (2) Test method Cysts of potato white cyst nematodes grown in a greenhouse the previous year or earlier were collected, immersed in distilled water, and incubated at 16°C for about 2 weeks. The cysts were then crushed with a scalpel to remove the eggs, and an egg suspension was obtained. After adjusting the density to about 600 eggs per mL, Tween 20 was added to a concentration of 0.05% (v / v). 1 mL of this egg suspension was placed in a 13.5 mL screw-cap glass vial (inner diameter 2.1 cm, height 4.8 cm), and 1 mL of a test solution containing 2 ppm of compound (I) was added to each vial, which was then covered and incubated at 16°C. After about two weeks, 1 mL of the solution was taken out and the number of hatched larvae and unhatched eggs were counted under a stereomicroscope. Two replicates were set up for each compound, and the average hatching rate was calculated. (3) Test results The test results are shown in Table 6 below.

[0227] [Table 6] TIFF0007628231000071.tif17071

[0228] (4) Test results for optically active compounds The test results for the optically active compounds among the compounds (I) are shown in Table 7. Note that for some compounds, tests were carried out at even lower concentrations.

[0229] [Table 7]

[0230] (Test Example 2) Potato cyst nematode density reduction test (pot test) (1) Preparation of test solutions 20 mg of compound (I) was dissolved in 1 mL of dimethyl sulfoxide, and 199 mL of 0.1% aqueous polyoxyethylene sorbitan monolaurate solution was added to obtain a test solution with a concentration of 100 ppm of compound (I). This was then diluted 10 times with distilled water to prepare a test solution with a concentration of 10 ppm. (2) Test method Soil was collected from fields infested with potato cyst nematodes, and the egg density was investigated as follows: Cysts were separated and crushed from 100 g of dried soil by the sieving cyst flushing method, and the number of eggs was counted under a stereomicroscope. This was taken as the initial density. 32 mL of the test solution, which had been adjusted to 100 ppm or 10 ppm, was added to 800 mL of collected field soil and mixed thoroughly, then packed into 10.5 cm long pots (top diameter 10.5 cm, height 22.5 cm), and placed in a greenhouse without plants for 30 days. Each pot was irrigated with 26 mL of distilled water every 6 to 7 days. After 30 days, the soil was poured into an aluminum tray and air-dried, and the cysts were isolated from 100 g of dried soil in the same manner as above, and the number of remaining eggs was counted (density after treatment). Three pots were set up per concentration for each compound, and the average density reduction rate was calculated from the initial density and each post-treatment density. (3) Test results This test was carried out for the compounds Nos. 2, 3, 4, 5, 12, 18, A-3, and D-15. The pots that were not treated with the compounds were used as untreated plots. The test results are shown in Table 8 below.

[0231] [Table 8]

[0232] (Test Example 3) Potato cyst nematode density reduction test (field small plot test) (1) Preparation of test solutions A 10% solution of compound No. 2 was prepared with reference to Preparation Example 4. This 10% solution was diluted with distilled water to prepare test solutions with concentrations of 300 ppm, 30 ppm, and 3 ppm. (2) Test method Small plots were set up in fields where potato white cyst nematodes occur, and compound formulations were treated to investigate the effect of reducing nematode density. Small plots were set up by rolling 25 cm wide polyvinyl chloride boards into cylinders with a diameter of 30 cm, and burying them to a depth of 20 cm. Many of these were set up in the field, and soil was collected for the initial density survey. Then, test solutions of each concentration were sprayed at a rate of 5 or 1 L per square meter (70.7 mL / frame) and mixed with a transplant trowel (approximately 15 cm deep). This resulted in four treatment zones with different amounts of drug applied, with the respective amounts being 1500, 300, 30, and 3 g per 10 ares. Approximately 80 days later, the soil within the frame was sampled, and the nematode egg density in the soil was investigated as follows: Cysts were isolated from 100 g of dried soil by sieving and cyst flushing method, crushed with a scalpel to remove the eggs, suspended in distilled water, and a certain amount was taken, and the number of eggs was counted under a stereomicroscope. Four plots were set up for each concentration, and the average density reduction rate was calculated from the initial density and the density after treatment. (3) Test results Treatment with the compound (compound number 2) significantly reduced the Gp density in the soil. The rate of reduction in Gp density for each dose of the drug was as follows. When the dose was 30 g or more per 10 a, the Gp density was reduced by more than 80%, demonstrating its outstanding effect in reducing density. Dropping amount 1500g / 10a:98.4% 300g / 10a:94.4% 30g / 10a:88.8% 3g / 10a: 65.6% 0g / 10a (untreated): 9.0% (average of 4 areas)

[0233] Since compounds selected randomly from among the compounds (I) exhibit the above-mentioned effects, it can be understood that the compounds (I), including compounds not listed as examples, are compounds that exhibit a high Gp control effect.

Claims

1. A potato cyst nematode control agent comprising, as an active ingredient, at least one selected from a compound represented by the following formula (I), a stereoisomer thereof, and a salt thereof: 【Chemistry 1】 [In the formula, Ar represents a substituted or unsubstituted phenyl group or a substituted or unsubstituted naphthyl group; R １ each independently represents a substituted or unsubstituted C1-6 alkyl group, a substituted or unsubstituted C2-6 alkenyl group, a substituted or unsubstituted C2-6 alkynyl group, a substituted or unsubstituted C3-6 cycloalkyl group, a substituted or unsubstituted phenyl group, or a substituted or unsubstituted naphthyl group; R ２ represents a hydrogen atom or a substituted or unsubstituted C1-6 alkyl group; The partial structure -Y-X- is *-CH ２ -C(=X １ )-**, *-O-C(=X １ )-**, *-S-C(=X １ )-**, *-N(R ｂ )-C(=X １ )-**, or *-NH-SO ２ - represents a group represented by **; Here, * is two R １ indicates the bonding position to the carbon atom having the symbol **, and indicates the bonding position to Z; X １ each independently represents an oxygen atom or a sulfur atom; R ｂ is a hydrogen atom, a hydroxyl group, R ｂ１ A group represented by -C(=O)-, R ｂ１ A group represented by O-C(=O)-, R ｂ１ A group represented by NH-C(=O)-, or R ｂ１ ２ represents a group represented by N-C(=O)-; R ｂ１ each independently represents a substituted or unsubstituted C1-6 alkyl group, a substituted or unsubstituted C2-6 alkenyl group, a substituted or unsubstituted C2-6 alkynyl group, a substituted or unsubstituted C3-6 cycloalkyl group, a substituted or unsubstituted phenyl group, or a substituted or unsubstituted naphthyl group; Z represents a substituted or unsubstituted methylene group, or a substituted or unsubstituted dimethylene group; When Z is a substituted methylene group, R ２ and the substituent on the methylene group may together form a single bond or a methylene group.

2. The potato cyst nematode control agent according to claim 1, wherein Z in formula (I) is a substituted or unsubstituted methylene group.

3. The potato white cyst nematode control agent according to claim 1, wherein Z in formula (I) is a substituted or unsubstituted dimethylene group.

4. The partial structure -Y-X- in formula (I) is *-O-C(=X １ )-**, *-S-C(=X １ )-**, or *-N(R ｂ )-C(=X １ )-** is a group represented by The potato white cyst nematode control agent according to claim 1 .

5. The partial structure -Y-X- in formula (I) is *-CH ２ -C(=X １ )-** is a group represented by The potato white cyst nematode control agent according to claim 1 .

6. The partial structure -Y-X- in formula (I) is *-NH-SO ２ The potato cyst nematode control agent according to claim 1, wherein the group is represented by -**.

7. The potato white cyst nematode control agent according to claim 2, wherein -Y-X- in the partial structure in formula (I) is a group represented by -O-C(=O)-**, a group represented by -O-C(=S)-**, a group represented by -S-C(=O)-**, a group represented by -NH-C(=O)-**, a group represented by -N(OH)-C(=O)-**, or a group represented by -NH-C(=S)-**.

8. The potato white cyst nematode control agent according to claim 2, wherein the partial structure -Y-X- in formula (I) is a group represented by -O-C(=O)-**, a group represented by -S-C(=O)-**, or a group represented by -NH-C(=O)-**.

9. A hatching promoter for eggs of potato cyst nematode, comprising as an active ingredient at least one selected from the group consisting of a compound represented by the following formula (I), a stereoisomer thereof and a salt thereof: 【Chemistry 2】 [In the formula, Ar represents a substituted or unsubstituted phenyl group or a substituted or unsubstituted naphthyl group; R １ each independently represents a substituted or unsubstituted C1-6 alkyl group, a substituted or unsubstituted C2-6 alkenyl group, a substituted or unsubstituted C2-6 alkynyl group, a substituted or unsubstituted C3-6 cycloalkyl group, a substituted or unsubstituted phenyl group, or a substituted or unsubstituted naphthyl group; R ２ represents a hydrogen atom or a substituted or unsubstituted C1-6 alkyl group; The partial structure -Y-X- is *-CH ２ -C(=X １ )-**, *-O-C(=X １ )-**, *-S-C(=X １ )-**, *-N(R ｂ )-C(=X １ )-**, or *-NH-SO ２ - represents a group represented by **; Here, * is two R １ indicates the bonding position to the carbon atom having the symbol **, and indicates the bonding position to Z; X １ each independently represents an oxygen atom or a sulfur atom; R ｂ is a hydrogen atom, a hydroxyl group, R ｂ１ A group represented by -C(=O)-, R ｂ１ A group represented by O—C(═O)—, R ｂ１ A group represented by NH-C(=O)-, or R ｂ１ ２ represents a group represented by N-C(=O)-; R ｂ１ each independently represents a substituted or unsubstituted C1-6 alkyl group, a substituted or unsubstituted C2-6 alkenyl group, a substituted or unsubstituted C2-6 alkynyl group, a substituted or unsubstituted C3-6 cycloalkyl group, a substituted or unsubstituted phenyl group, or a substituted or unsubstituted naphthyl group; Z represents a substituted or unsubstituted methylene group, or a substituted or unsubstituted dimethylene group; When Z is a substituted methylene group, R ２ and the substituent on the methylene group may together form a single bond or a methylene group.

10. A method for controlling potato cyst nematodes, comprising a step of applying the control agent or hatching promoter according to any one of claims 1 to 9 to field soil inhabited by potato cyst nematodes.

11. A compound represented by the following formula (Ia), a stereoisomer thereof or a salt thereof: 【Chemistry 3】 [In the formula, Ar represents a substituted or unsubstituted phenyl group, or a substituted or unsubstituted naphthyl group; R １ each independently represents a substituted or unsubstituted C1-6 alkyl group, a substituted or unsubstituted C2-6 alkenyl group, a substituted or unsubstituted C2-6 alkynyl group, a substituted or unsubstituted C3-6 cycloalkyl group, a substituted or unsubstituted phenyl group, or a substituted or unsubstituted naphthyl group; R ２ represents a hydrogen atom or a substituted or unsubstituted C1-6 alkyl group; Partial structure -Y ａ -X ａ - is *-S-C(=X １ａ )-** or *-NH-C(=X １ａ )-** represents a group; Here, * is two R １ indicates the bonding position to the carbon atom having Z ａ indicates the position of bond to X １ａ each independently represents an oxygen atom or a sulfur atom; Z ａ represents a substituted or unsubstituted dimethylene group.

12. A compound represented by the following formula (I-b), a stereoisomer thereof or a salt thereof: 【Chemistry 4】 [In the formula, Ar represents a substituted or unsubstituted phenyl group, or a substituted or unsubstituted naphthyl group; R １ each independently represents a substituted or unsubstituted C1-6 alkyl group, a substituted or unsubstituted C2-6 alkenyl group, a substituted or unsubstituted C2-6 alkynyl group, a substituted or unsubstituted C3-6 cycloalkyl group, a substituted or unsubstituted phenyl group, or a substituted or unsubstituted naphthyl group; R ２ represents a hydrogen atom or a substituted or unsubstituted C1-6 alkyl group; Partial structure -Y ｂ -X ｂ - is a group represented by *-O-C(=S)-**, a group represented by *-S-C(=O)-**, or *-NH-SO ２ - represents a group represented by **; Here, * is two R １ indicates the bonding position to the carbon atom having Z ｂ indicates the position of bond to Z ｂ represents a substituted or unsubstituted methylene group.

13. A compound represented by the following formula (I-c), a stereoisomer thereof or a salt thereof: 【Chemistry 5】 [In the formula, Ar represents a substituted or unsubstituted phenyl group, or a substituted or unsubstituted naphthyl group; R １ each independently represents a substituted or unsubstituted C1-6 alkyl group, a substituted or unsubstituted C2-6 alkenyl group, a substituted or unsubstituted C2-6 alkynyl group, a substituted or unsubstituted C3-6 cycloalkyl group, a substituted or unsubstituted phenyl group, or a substituted or unsubstituted naphthyl group; X １ represents an oxygen atom or a sulfur atom.

14. A hatching promoter for potato white cyst nematodes containing as an active ingredient one or more of 5,5-dimethyl-4-phenyl-2-pyrrolidinone having a specific rotation of (-), 5,5-dimethyl-4-(4-methylphenyl)-2-pyrrolidinone having a specific rotation of (-), 5,5-dimethyl-4-(4-chlorophenyl)-2-pyrrolidinone having a specific rotation of (-), or 4-(4-chlorophenyl)-3,3-dimethylisothiazolidine-1,1-dioxide having a specific rotation of (-).

Images