JPH0841018A - Thiosemicarbazide derivative and nematocide - Google Patents

Abstract

PURPOSE:To obtain a new thiosemicarbazide derivative having potent activity on various kinds of nematode, and low in toxicity to humans and livestock. CONSTITUTION:This thiosemicarbazide derivative is expressed by formula 1 (R is a lower alkyl; X is a halogen, lower alkyl, lower haloalkyl, lower alkoxyl, cyano or nitro; (n) is 0, 1 or 2; (m) is l-3; Y is O or NH), e.g. a compound of formula 1 (where, X is cyano; (n) and (m) are each 1; Y is O; R is t-butyl; X is a substituent on the 4-site of the phenyl ring). The compound of formula 1 is obtained, for example, by reaction between a phenyl isothiocyanate compound of formula 2 and a hydrazine compound of formula 3.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a novel thiosemicarbazide derivative and a nematicide containing the derivative as an active ingredient.

[0002]

2. Description of the Related Art Conventionally, DD is used for controlling nematodes.
Fumigants such as (1,3-dichloropropane) and chloropicrin and carbamate agents such as oxamyl have been used, but these drugs have a drawback that they are highly toxic to humans and animals. Therefore, it is desired to develop a new drug that is effective against various nematodes and harmless to humans and animals.

[0003]

[Means for Solving the Problems] The inventors of the present invention have made various studies in order to develop a drug having a strong activity against various nematodes based on such a situation. As a result, a certain thiosemicarbazide derivative was found to be various. They found that they have extremely strong insecticidal activity against nematodes and have low toxicity to humans and livestock, and thus completed the present invention.

That is, the present invention has the general formula

[0005]

Embedded image

[In the formula, R represents a lower alkyl group. X is a halogen atom, a lower alkyl group, a lower haloalkyl group,
A lower alkoxy group, a cyano group or a nitro group is shown. n represents 0, 1 or 2. m shows the integer of 1-3. Y represents an oxygen atom or NH. ] A nematicide characterized by containing the thiosemicarbazide derivative and the derivative as an active ingredient.

In the present specification, each group represented by R and X is as follows.

Examples of the lower alkyl group include methyl,
Ethyl, propyl, isopropyl, butyl, tert-
Examples thereof include linear or branched alkyl groups having 1 to 6 carbon atoms such as butyl, pentyl and hexyl groups. Of these, the tert-butyl group is particularly preferable.

Examples of the halogen atom include chlorine atom, bromine atom, fluorine atom, iodine atom and the like. Of these, chlorine atom is particularly preferable.

The lower haloalkyl group is a carbon having 1 to 3 halogen atoms such as chloromethyl, trifluoromethyl, 2-chloroethyl, 1-chloroethyl, 1,2-dichloroethyl, 2-bromoethyl and 3-chloropropyl. The straight-chain or branched-chain alkyl group of several 1-6 can be mentioned. Of these, a trifluoromethyl group is particularly preferable.

Examples of the lower alkoxy group include linear or branched alkoxy groups having 1 to 6 carbon atoms such as methoxy, ethoxy, propoxy, isopropoxy, butoxy, tert-butoxy, pentyloxy and hexyloxy groups. it can.

X is preferably a halogen atom, a cyano group or a nitro group. Further, the substitution position of X is preferably the 3-position and / or 4-position on the phenyl ring.

Typical compounds among the compounds of the present invention are shown below.

A compound of the general formula (1) in which X is a halogen atom, n is 1 or 2, m is 1, Y is an oxygen atom, and R is a tert-butyl group; X is a lower alkyl group, n is 1, m. 1, Y is an oxygen atom, R is a tert-butyl group; a compound of the general formula (1); X is a lower haloalkyl group, n is 1,
A compound of the general formula (1) in which m is 1, Y is an oxygen atom, and R is a tert-butyl group; X is a lower alkoxy group, n is 1, m is 1, Y is an oxygen atom, and R is a tert-butyl group. A compound of the general formula (1), wherein X is a cyano group, n is 1, m
Is 1; Y is an oxygen atom; R is a tert-butyl group; a compound of the general formula (1); X is a nitro group, n is 1, m is 1,
A compound of the general formula (1) in which Y is an oxygen atom and R is a tert-butyl group; X is a halogen atom, n is 1 or 2, and m.
Is 2, a Y is an oxygen atom, and R is a tert-butyl group; a compound of the general formula (1); X is a cyano group, n is 1, m is 2,
A compound of the general formula (1) in which Y is an oxygen atom and R is a tert-butyl group; X is a nitro group, n is 1, m is 2, Y is an oxygen atom, and R is a tert-butyl group. 1)
A compound of X: X is a halogen atom, n is 1 or 2, m is 1,
A general formula (1) in which Y is NH and R is a tert-butyl group.
A compound wherein X is a halogen atom, n is 1 or 2, and m is 2,
A general formula (1) in which Y is NH and R is a tert-butyl group.
A compound of X: cyano group, n is 1, m is 1, Y is NH,
A compound of the general formula (1), wherein R is a tert-butyl group;
X is a nitro group, n is 1, m is 1, Y is NH, R is ter
A compound of the general formula (1) which is a t-butyl group; a compound of the general formula (1) in which X is a cyano group, n is 1, m is 2, Y is NH, and R is a tert-butyl group; X is nitro. A compound of the general formula (1), wherein n is 1, m is 2, Y is NH, and R is a tert-butyl group.

The compound of the present invention represented by the above-mentioned general formula (1) is a novel compound which has not been described in the literature, and acts effectively on a wide variety of nematodes. Examples of nematodes that act particularly effectively include sweet potato nematodes, walnut nematodes, nematodes nematodes, and potato cyst nematodes.

The compound of the present invention is produced, for example, according to the method shown in the following reaction formula-1.

[0017]

Embedded image

[In the formula, R, X, n, m and Y are the same as defined above. That is, according to the above reaction formula-1, the compound (1) of the present invention is produced by reacting the phenylisothiocyanates (2) and the hydrazines (3). Such a reaction can usually be carried out in a suitable solvent. Examples of the solvent used include halogenated hydrocarbons such as chloroform, dichloromethane and 1,2-dichloroethane, aromatic hydrocarbons such as benzene and toluene, ethers such as diethyl ether and tetrahydrofuran, acetonitrile, propionitrile and the like. And the like. The use ratio of the compound (2) and the compound (3) is not particularly limited, but usually the former is about 0.5 to 2 times mol, preferably 1 to 1.2 times the former.
It is good to double it. The reaction usually proceeds well at 5 to 50 ° C. and is generally completed in about 1 to 10 hours.

The compound (2) used as a starting material in the above reaction scheme-1 is industrially available at a low cost, or can be easily produced from the corresponding aniline by a conventional method. As the other raw material compound (3), a commercially available product can be used as it is. Further, this compound (3) is disclosed in JP-A-6-157443.
It can be easily manufactured according to the method described in the publication.

The compound of the present invention obtained by the above method is
It can be easily isolated and purified from the reaction product by an ordinary separation means such as a solvent extraction method, a recrystallization method and a column chromatography method. According to the above manufacturing method,
The compound of the present invention can be produced in high yield and high purity.

When the compound of the present invention is used as a nematicide, an emulsion, a wettable powder, a water solvent, granules, fine granules, granules, powders, coating agents, spray formulations, aerosol formulations,
It can be used in various formulation forms such as a microcapsule formulation, a fumigation formulation, and a fumigation formulation.

In preparing these preparations, various surfactants can be used for emulsification, dispersion, suspension and foaming. For example, nonionic surfactants include polyoxyethylene alkyl ether. , Polyoxyethylene alkyl ester, polyoxyethylene sorbitan alkyl ester, etc., anionic surfactants such as alkyl benzene sulfonate, alkyl sulfosuccinate, alkyl sulfate, polyoxyethylene alkyl sulfate, allyl sulfonate, lignin sulfite, etc. Each can be used.

As the solubilizer, diluent or carrier,
Various organic solvents, various aerosol propellants, various natural minerals, various synthetic compounds and the like can be used. Examples of the organic solvent include benzene, toluene, xylene, ethylbenzene, chlorobenzene, alkylnaphthalene,
Chlorethylene, cyclohexanone, methyl ethyl ketone, methyl isobutyl ketone, alcohols, cellosolves, dimethylformamide, dimethyl sulfoxide,
Acetonitrile, mineral oil fraction, water and the like are preferably used. Examples of aerosol propellants include propane, butane, halogenated hydrocarbons, nitrogen, carbon dioxide and the like. These preparations may be colored with an organic or inorganic dye or pigment.

In producing the above various preparations, the compound of the present invention is contained in an amount of about 0.1-95% by weight, preferably 0.5-.
It can be formulated to contain 90% by weight. The prepared preparation can be used as it is or diluted with a carrier or water, and depending on the purpose of use, it may be used in an amount of about 0.
It may be freely diluted in the range of 0001 to 100% by weight, and preferably diluted to contain 0.001 to 10% by weight of the active ingredient.

[0025]

EXAMPLES The present invention will be further clarified below with reference to Production Examples and Test Examples of the compounds of the present invention.

Production Example 1 A solution of 0.80 g of hydrazinoacetic acid t-butyl ester in 20 ml of dichloromethane was added dropwise at room temperature with a solution of 0.73 g of isothiocyanic acid 4-cyanophenyl ester in 20 ml of dichloromethane. The reaction product was stirred at room temperature for 4 hours, the solvent was distilled off under reduced pressure, and the obtained crude product was purified by silica gel column chromatography (dichloromethane: ethyl acetate = 9: 1) to give white crystals of the present invention. Compound (Compound 1, X is a cyano group, n = 1, m = 1, Y = oxygen atom, R = tert-methyl group, and the substitution position of X is 4-position on the phenyl ring. Compound) 1.2
6 g was obtained.

Yield 82% Melting point: 140-141 ° C. ¹ H-NMR (CDCl ₃ ) δppm; 1.5 (9H,
_{s, (CH 3) 3 C} ), 4.3 (2H, s, NH 2),
4.9 (2H, s, CH ₂ N), 7.6 (4H, dd,
Ar-H), 10.2-10.5 (1H, br, N
H).

Compounds 2 to 10 produced according to Production Example 1
Is shown in Table 1.

[0029]

[Table 1]

1) ¹ H-NMR (CDCl ₃ ) δpp
m; 1.5 (9H, s, (CH 3) 3 C), 4.2 (2
_{H, s, NH 2),} 4.9 (2H, s, CH 2 N),
7.1-7.7 (5H, m, Ar-H), 9.8-9.
9 (1H, br, NH).

2) ¹ H-NMR (CDCl ₃ ) δpp
m; 1.5 (9H, s, (CH 3) 3 C), 4.2 (2
_{H, s, NH 2),} 4.9 (2H, s, CH 2 N),
7.3 (4H, dd, Ar-H), 9.7-9.9 (1
H, br, NH).

3) ¹ H-NMR (CDCl ₃ ) δpp
m; 1.5 (9H, s, (CH 3) 3 C), 2.3 (3
_{H, s, CH 3),} 4.2 (2H, s, NH 2), 4.
9 (2H, s, CH ₂ N), 7.2 (4H, dd, Ar
-H), 9.6-9.9 (1H, br, NH).

4) ¹ H-NMR (CDCl ₃ ) δpp
m; 1.5 (9H, s, (CH 3) 3 C), 3.8 (3
_{H, s, OCH 3),} 4.2 (2H, s, NH 2),
4.9 (2H, s, CH ₂ N), 7.1 (4H, dd,
Ar-H), 9.6-9.9 (1H, br, NH).

5) ¹ H-NMR (CDCl ₃ ) δpp
m; 1.5 (9H, s, (CH 3) 3 C), 4.3 (2
_{H, s, NH 2),} 4.9 (2H, s, CH 2 N),
7.7 (4H, m, Ar-H), 10.0-10.3
(1H, br, NH).

6) ¹ H-NMR (CDCl ₃ ) δpp
m; 1.5 (9H, s, (CH 3) 3 C), 4.4 (2
_{H, s, NH 2),} 4.9 (2H, s, CH 2 N),
8.1 (4H, m, Ar-H), 10.3-10.6
(1H, br, NH).

7) ¹ H-NMR (CDCl ₃ ) δpp
m; 1.5 (9H, s, (CH 3) 3 C), 4.3 (2
_{H, s, NH 2),} 4.9 (2H, s, CH 2 N),
6.9-8.5 (4H, m, Ar-H), 10.2-1
0.5 (1H, br, NH).

8) ¹ H-NMR (CDCl ₃ ) δpp
m; 1.5 (9H, s, (CH 3) 3 C), 4.3 (2
_{H, s, NH 2),} 4.9 (2H, s, CH 2 N),
7.3-8.6 (4H, m, Ar-H), 10.0-1
0.4 (1H, br, NH).

9) ¹ H-NMR (CDCl ₃ ) δpp
m; 1.5 (9H, s, (CH 3) 3 C), 4.3 (2
_{H, s, NH 2),} 4.9 (2H, s, CH 2 N),
7.2-8.0 (4H, m, Ar-H), 9.9-1
0.1 (1H, br, NH).

Production Example 2 3-hydrazinopropionic acid t-butyl ester 1.0
isothiocyanic acid 4 in 20 ml of dichloromethane solution.
-Nitrophenyl ester 1.1 g of dichloromethane 2
The 0 ml solution was added dropwise at room temperature. The reaction product was stirred at room temperature for 2 hours, and then the solvent was distilled off under reduced pressure to obtain a crude product, which was then subjected to a silica gel column (dichloromethane: ethyl acetate = 9:
The compound of the present invention (Compound 11,
X is a nitro group, n = 1, m = 2, Y = oxygen atom, R = t
Thus, 1.9 g of the compound of the above general formula (1) in which the substitution position of ert-methyl group and X is the 4-position on the phenyl ring was obtained.

Yield 88%, melting point 122-123 ° C. ¹ H-NMR (CDCl ₃ ) δ ppm; 1.4 (9H,
_{s, (CH 3) 3 C} ), 2.9 (2H, t, CH 2),
4.3 (2H, t, CH ₂ ), 4.8 (2H, s, NH
₂ ), 8.0 (4H, dd, Ar-H), 10.1-1
0.4 (1H, br, NH) From the above results, it was confirmed that the product obtained was compound 11.

Compounds 12 to 2 produced according to Production Example 2
5 is shown in Table 2.

[0042]

[Table 2]

10)¹1 H-NMR (DMSO-d₆)
δppm; 1.3 (9H, s, (CH₃)₃C), 4.
8 (2H, s, CH₂), 7.0-7.3 (1H, b
r, NH), 7.7 (4H, dd, Ar-H) 11)¹1 H-NMR (DMSO-d₆) Δppm;
1.3 (9H, s, (CH ₃)₃C), 4.8 (2H,
s, CH₂), 7.2-7.5 (1H, br, NH),
8.0 (4H, dd, Ar-H) 12)¹1 H-NMR (DMSO-d₆) Δppm;
1.3 (9H, s, (CH₃)₃C), 4.8 (2H,
s, CH₂), 7.0-7.2 (1H, br, NH),
7.3-8.3 (4H, m, Ar-H) 13)¹1 H-NMR (DMSO-d₆) Δppm;
1.4 (9H, s, (CH₃)₃C), 4.8 (2H,
s, CH₂), 7.2-7.4 (1H, br, NH),
7.4-8.7 (4H, m, Ar-H) 14)¹H-NMR (CDCl₃) Δppm; 1.5
(9H, s, (CH₃)₃C), 2.9 (2H, t, C
H₂), 4.3 (2H, t, CH₂) 4.6 (2H,
s, NH₂), 7.4 (4H, dd, Ar-H), 9.
6-9.9 (1H, br, NH) 15)¹H-NMR (CDCl₃) Δppm; 1.4
(9H, s, (CH₃)₃C), 2.9 (2H, t, C
H₂), 4.2 (2H, t, CH₂), 4.7 (2H,
s, NH₂), 7.7 (4H, dd, Ar-H), 1
0.0-10.3 (1H, br, NH) 16)¹H-NMR (CDCl₃) Δppm; 1.5
(9H, s, (CH₃)₃C), 2.9 (2H, t, C
H₂), 4.3 (2H, t, CH₂), 4.7 (2H,
s, NH₂), 7.3-8.1 (4H, m, Ar-
H), 9.8-10.1 (1H, br, NH) 17)¹H-NMR (CDCl₃) Δppm; 1.5
(9H, s, (CH₃)₃C), 2.9 (2H, t, C
H₂), 4.3 (2H, t, CH₂), 4.7 (2H,
s, NH₂), 7.4-8.6 (4H, dd, Ar-
H), 9.9-10.1 (1H, br, NH) 18)¹H-NMR (CDCl₃) Δppm; 1.5
(9H, s, (CH₃)₃C), 2.9 (2H, t, C
H₂), 4.2 (2H, t, CH₂), 4.7 (2H,
s, NH₂), 7.3-8.4 (4H, dd, Ar-
H), 9.9-10.1 (1H, br, NH) 19)¹H-NMR (CDCl₃) Δppm; 0.7
-1.9 (7H, m), 3.0 (2H, t, CH₂),
3.9-4.5 (4H, m), 4.7 (2H, s, NH
₂), 7.7 (4H, dd, Ar-H), 9.9-1
0.3 (1H, br, NH) 20)¹H-NMR (CDCl₃) Δppm; 0.7
-1.9 (7H, m), 3.0 (2H, t, CH₂),
3.9-4.5 (4H, m), 4.7 (2H, s, NH
₂), 8.0 (4H, dd, Ar-H), 10.1-1
0.4 (1H, br, NH).

21) ¹ H-NMR (CDCl ₃ ) δp
pm; 0.7-2.0 (7H, m), 3.0 (2H,
_{t, CH 2), 3.9-4.5 (} 4H, m), 4.7
_{(2H, s, NH 2)} , 7.3-8.2 (4H, m, A
r-H), 9.8-10.1 (1H , br, NH) 22) 1 H-NMR (CDCl 3) δppm; 0.7
-1.9 (7H, m), 3.0 (2H, t, CH 2),
3.9-4.5 (4H, m), 4.7 (2H, s, NH
₂ ), 7.3-8.6 (4H, m, Ar-H), 9.9
-10.1 (1H, br, NH) 23) 1 H-NMR (CDCl 3) δppm; 1.2
5 (6H, d, (CH ₃ ) ₂ CH), 2.9 (2H,
t, CH ₂ ), 4.3 (2H, t, CH ₂ ), 4.7
(2H, s, NH ₂ ), 5.0 (1H, m, CH),
7.7 (4H, dd, Ar-H), 10.0-10.2.
(1H, br, NH) 24) ¹ H-NMR (CDCl ₃ ) δppm; 1.2
5 (6H, d, (CH ₃ ) ₂ CH), 2.9 (2H,
t, CH ₂ ), 4.3 (2H, t, CH ₂ ), 4.7
(2H, s, NH ₂ ), 5.0 (1H, m, CH),
7.2-8.1 (4H, m, Ar-H), 9.7-1
0.1 (1H, br, NH) 25) ¹ H-NMR (CDCl ₃ ) δppm; 1.4
_{(9H, s, (CH 3} ) 3 C), 1.8-2.7 (4
H, m), 4.0-4.5 (4H, m), 7.7 (4
H, dd, Ar-H), 10.0-10.3 (1H, b
r, NH) 26) ¹ H-NMR (CDCl ₃ ) δppm; 1.4
_{(9H, s, (CH 3} ) 3 C), 1.8-2.7 (4
H, m), 4.0-4.5 (4H, m), 7.3-8.
1 (4H, dd, Ar-H), 9.8-10.1 (1
H, br, NH) 27) ¹ H-NMR (DMSO-d ₆ ) δppm;
1.3 (9H, s, (CH 3) 3 C), 2.7 (2H,
t, CH ₂ ), 4.3 (2H, t, CH ₂ ), 4.6-
_{5.3 (2H, br, NH 2} ), 6.8-7.0 (1
H, br, NH), 7.4 (4H, dd, Ar-H),
9.7-10.1 (1H, br, NH) 28) ¹ H-NMR (DMSO-d ₆ ) δppm;
1.3 (9H, s, (CH 3) 3 C), 2.7 (2H,
t, CH ₂ ), 4.3 (2H, t, CH ₂ ), 4.7-
_{5.4 (2H, br, NH 2} ), 6.6-6.9 (1
H, br, NH), 7.7 (4H, dd, Ar-H) 29) ¹ H-NMR (DMSO-d ₆ ) δ ppm;
1.3 (9H, s, (CH 3) 3 C), 2.7 (2H,
_{t, CH 2), 4.2 (} 2H, t, CH 2), 6.9-
7.2 (1H, br, NH), 8.0 (4H, dd, A
r-H) 30) ¹ H-NMR (DMSO-d ₆ ) δppm;
1.3 (9H, s, (CH 3) 3 C), 2.8 (2H,
t, CH ₂ ), 4.3 (2H, t, CH ₂ ), 4.8
_{(2H, s, NH 2)} , 7.3-8.2 (4H, m, A
r-H), 9.8-10.1 (1H, br, NH).

31) ¹ H-NMR (DMSO-d ₆ ).
δppm; 1.3 (9H, s, (CH ₃ ) ₃ C), 2.
8 (2H, t, CH ₂ ), 4.3 (2H, t, C
_{H 2), 4.8 (2H,} s, NH 2), 7.3-8.7
(1H, m, Ar-H), 9.9-10.2 (1H, b
r, NH) 32) ¹ H-NMR (DMSO-d ₆ ) δppm;
2.8 (2H, t, CH ₂ ), 4.3 (2H, t, CH 2
_{2), 4.6 (1H, d} , CH 3), 4.8 (2H,
_{s, NH 2), 7.3-8.7 (} 1H, m, Ar-
H), 9.9-10.2 (1H, br, NH) 33) ¹ H-NMR (DMSO-d ₆ ) δppm;
2.8 (2H, t, CH ₂ ), 4.3 (2H, t, CH 2
_{2), 4.6 (1H, d} , CH 3), 4.8 (2H,
_{s, NH 2), 7.3-8.2 (} 4H, m, Ar-
H), 9.8-10.1 (1H, br, NH).

Test Example 1 (Test for Sweet potato Nematode) A 5 ml vial was charged with 2 g of 25-100 mesh clear sand, and 0.25 ml of the drug solution and a nematode (Sweetroot nematode, second stage larvae) suspension of 0. 25 ml (600 nematodes / 0.25 ml) was poured, covered with a sealon film, and placed in the dark at 25 ° C. 48 hours after the treatment, remove the lid, put 2 ml of water in the vial and stir. Immediately after the clear sand has settled, the supernatant is sucked out and transferred to a Syracuse watch glass to determine whether it is alive or dead under a stereoscopic microscope. I asked for the rate. The results are shown in Table 3. Test compound No. in Table 3
Corresponds to Compound No. in Production Example.

[0047]

[Table 3]

Test Example 2 (Test for Curcuma cinerea ) C. elegans ( Curcuma communis , Pratylenc)
hus vulnus ) grown in callus culture of alfalfa is separated into callus and medium with a lock stick,
The callus was set in a Bellman funnel device and allowed to stand at 25 ° C. After the nematodes were collected 48 hours later, adult and old larvae were collected while washing the nematode population in which each stage was mixed with a 400-mesh sieve, and used for the test. An insecticidal test was conducted in the same manner as in Test Example 1 except that adult and old larvae were used as test nematodes. After 24 hours, the life and death of adult and old larvae were discriminated, and the mortality rate was calculated. The results are shown in Table 4. The test compound No. in Table 4 corresponds to the compound No. in the production example.

[0049]

[Table 4]

 ─────────────────────────────────────────────────── ─── Continuation of front page (72) Inventor Keizaburo Murai 615 Hanamyo, Satoura-cho, Satoura-cho, Naruto-shi, Tokushima Otsuka Chemical Co., Ltd. Naruto Laboratory

Claims (2)

[Claims] 1. A compound of the general formula [In the formula, R represents a lower alkyl group. X represents a halogen atom, a lower alkyl group, a lower haloalkyl group, a lower alkoxy group, a cyano group or a nitro group. n represents 0, 1 or 2. m shows the integer of 1-3. Y represents an oxygen atom or NH. ] The thiosemicarbazide derivative represented by these. 2. A nematicide containing the thiosemicarbazide derivative according to claim 1 as an active ingredient.