JPH05271170A - Amide compound and pest repellent and pest control agent using the same - Google Patents

Abstract

(57) [Summary] [Purpose] An amide compound derived from a physiologically active natural product that is safer and has a high activity repellent effect and eradication effect against various sanitary pests and unpleasant pests, and containing it as an active ingredient. The present invention provides a pest repellent, an insecticide and an acaricide having both the sustainability of the repellent effect and the exterminating effect and the activity retention at a low concentration. [Structure] The following chemical formula 1 (wherein R ₁ is citronellal, 1
-P -Menten- 9-are, α-camphorene al
Dehydr, from the group consisting of β-camphorene aldehyde
Remove the aldehyde group of the selected monoterpenyl aldehyde
There residues in which Monoterupeniru group, R ₂ and R ₃ are also H and iso 1 to 6 carbon atoms saturated or unsaturated hydrocarbon group of normal (except in the case of R ₂ and R ₃ are both H )
Is. Amide represented by), the by incorporating a suitable carrier as an active ingredient, mosquitoes, flies,
It can be used as a pest repellent such as cockroaches and mites , and a pest control agent such as insecticides and acaricides. [Chemical 1]

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a novel amide compound excellent in repellent effect and exterminating effect against pests, particularly an amide compound having a terpenyl group derived from a natural product, and pest repellents and insecticides containing them. The present invention relates to a pest control agent such as a mite agent.

[0002]

2. Description of the Related Art Attempts to use repellent substances for controlling agricultural pests and sanitary pests have been made for a long time, and many natural products have been used. Recently, the relationship between the life of living organisms and essential oils of plants has become known, and it has been clarified that various terpenoids contained in plant components are repellent to certain insects. It is being defeated. For example, it has been reported that the monoterpenoids menthol and citronellal are repellent to mosquitoes, and linalool, geraniol, menthol and the like are repellent to cockroaches (Japanese Patent Laid-Open No. 53-86021 and Shin Inazuka). 1: Journal of Japan Society of Pesticides, 7 (2), 145 (19)
82)). On the other hand, in recent years, as a repellent against sanitary pests such as mosquitoes and cockroaches, DEET (N, N-diethyl-
m-toluamide) is commercially available and widely used.

[0003]

DISCLOSURE OF THE INVENTION Problems to be Solved by the Invention
T is not always satisfactory in that the target pest species are limited in efficacy and the residual effect is short, and there is a suspicion in terms of safety. Therefore, attention has been paid to the above-mentioned bioactive natural products which are widely distributed in nature. As the conditions for which establishment of these bioactive natural products as repellents is expected, it is desirable that (1)
There are no restrictions on the application site, (2) extremely low toxicity to humans and animals, (3) long shelf life, and (4) small amount of effect.

Therefore, an object of the present invention is to find a safer physiologically active compound having a high activity repellent effect or a eradication effect equal to or higher than DEET against various sanitary pests and unpleasant pests. is there. Further, an object of the present invention is to provide a pest repellent, an insecticide and an acaricide having both the maintenance of the repellent effect and the exterminating effect and the retention of the activity at a low concentration.

[0005]

Means and Actions for Solving the Problems The present inventors have
As a result of earnest research on physiologically active compounds, the following 5

[Chemical 5] (In the formula, R ₁ is a monoterpenyl group, R ₂ and R ₃ are H and an iso- or normal saturated or unsaturated hydrocarbon group having 1 to 6 carbon atoms (provided that both R ₂ and R ₃ are H. The amide compound represented by the general formula (1) of (1) has high activity of DEET or higher, repellent effect and control effect against a wide variety of pests, and high residual effect, and It was found that when it is applied to the human body, it has low penetrability into the skin and has a long-lasting effect, and thus completed the present invention.

Among the amide compounds of the above general formula (1), citronellal, 1-p-menthene-9-al,
An amide derivative of a monoterpene selected from the group of related compounds consisting of α-camphorene aldehyde, β-camphorene aldehyde, myrtenal, perilaldehyde, and citral, especially when R ₂ and R ₃ are both methyl group, ethyl group or propyl group. It is advantageous that a certain amide compound is excellent in pest repellent effect and extermination effect even at a low concentration, and has a high activity sustaining effect.

Regarding the relationship between the basic skeleton of the compound and the persistence of repellent activity and repellent activity, among the terpenoids, those which are repellent to mosquitoes and cockroaches include terpene alcohols such as menthol, citronellal, linalool, and perillaldehyde, or There are aldehydes, and by converting these compounds into compounds having an amide group this time, the activity and durability could be further increased.
However, among the terpenylamide compounds, the repellent activity, the exterminating activity, and their persistence were found to be different depending on the terpene skeleton. That is, it was the compound based on the limonene skeleton that showed excellent activity and durability in the secondary screening test that was actually applied to human skin. In addition, DEET and the compound of the present invention have a structurally common site having an amide group and an ethyl group.
Since N-diethyldiamide and N, N-diethyl [2- (propoxycarbonyl) ethyl] carboxamide also show high repellent activity, this common structural site is closely related to repellent and exterminating properties. It is thought that there is.

The pests on which the amide compound of the present invention effectively acts include, for example, mosquitoes, flies, cockroaches, mites, etc. By incorporating the amide compound of the present invention as an active ingredient in a suitable carrier, Pest repellent,
It can be used as a pest control agent such as insecticides and acaricides. Further, the amide compound of the present invention is a film forming agent, a moisturizer, a pH adjusting agent, a rust preventive agent, an emulsifier, a dispersant, a spreading agent, a stabilizer, a solvent, an antioxidant, a propellant, and a volatilization adjusting, if desired. Oils, emulsions, wettable powders, sprays,
It can be used in the form of aerosols, smoke agents, coating agents, electrotranspiration agents, powders, granules and the like.

Hereinafter, the present invention will be described more specifically by showing a method for synthesizing the amide compound of the present invention and various potency tests. Synthetic Method: First, a general synthetic method of the amide compound according to the present invention will be outlined. Monoterpenyl nitriles prepared from a starting material, monoterpenyl aldehyde or camphor oxime, are hydrolyzed to form a carboxylic acid. It is synthesized and acid chloride is induced by chloridation. Then, the desired monoterpenylamide compound is synthesized by a condensation reaction of this acid chloride with an alkylamine or a dialkylamine. The amide compound according to the present invention is not limited to those synthesized according to the above reaction route, and those synthesized according to other possible reaction routes are also within the scope of the present invention, and the reaction conditions and the like are also known to those skilled in the art. If there is a test, appropriate conditions can be set appropriately.

As a representative example, FIG. 1 shows an overall reaction route diagram for the synthesis of the following amide compounds. (1) Citronellyl amide represented by the following chemical formula 6

[Chemical 6] Compound A: R ₂ , R ₃ = CH ₃ Compound B: R ₂ , R ₃ = C ₂ H ₅ Compound C: R ₂ , R ₃ = C ₃ H ₇

(2) 1-p-menthene-9-amide represented by the following chemical formula 7

[Chemical 7] Compound D: R ₂ , R ₃ = CH ₃ Compound E: R ₂ , R ₃ = C ₂ H ₅ Compound F: R ₂ , R ₃ = C ₃ H ₇

(3) α-camphorenamide represented by the following chemical formula 8

[Chemical 8] Compound G: R ₂ , R ₃ = CH ₃ Compound H: R ₂ , R ₃ = C ₂ H ₅ Compound I: R ₂ , R ₃ = C ₃ H ₇

(4) β-camphorenamide represented by the following chemical formula 9

[Chemical 9] Compound J: R ₂ , R ₃ = CH ₃ Compound K: R ₂ , R ₃ = C ₂ H ₅ Compound L: R ₂ , R ₃ = C ₃ H ₇

(5) Miltenylamide represented by the following chemical formula 10

[Chemical 10] Compound M: R ₂ , R ₃ = CH ₃ Compound N: R ₂ , R ₃ = C ₂ H ₅ Compound O: R ₂ , R ₃ = C ₃ H ₇

(6) Perilamide represented by the following chemical formula 11

[Chemical 11] Compound P: R ₂ , R ₃ = CH ₃ Compound Q: R ₂ , R ₃ = C ₂ H ₅ Compound R: R ₂ , R ₃ = C ₃ H ₇

(7) Citraamide represented by the following chemical formula 12

[Chemical 12] Compound S: R ₂ , R ₃ = CH ₃ Compound T: R ₂ , R ₃ = C ₂ H ₅ Compound U: R ₂ , R ₃ = C ₃ H ₇

Referring to FIG. 1, monoterpenyl nitriles [1b] (-)-3,7-dimethyl-2-octene nitrile (abbreviated as citronellyl nitrile), [2]
b] (+)-1-p-menthene-9-nitrile, [5
b] (−)-6,6-dimethylbicyclo [3.1.1]
Hept-2-ene-2-carbonitrile (abbreviation: miltenyl nitrile), [6b] (-)-4-isopropenyl-
1-cyclohexene-1-carbonitrile (abbreviation perillanitrile), and [7b] 3,7-dimethyl-2,6-
Octadiene nitrile (abbreviated as citranitrile) is a corresponding aldehyde derivative [1a] citronellal,
[2a] 1-p-menthen-9-al, [5a] myltenal, [6a] perilaldehyde, and [7a] citral were converted into β-of dimethylhydrazine and methyl iodide.
It can be easily synthesized by nitriding by elimination reaction and hydrolysis. On the other hand, [3b] α-camphorene nitrile and [4b] β-camphorene nitrile are d
-The camphor oxime obtained by reacting camphor with hydroxylamine in pyridine can be easily synthesized by treating with 25% sulfuric acid (or formic acid) and concentrated hydrochloric acid, respectively.

The seven kinds of terpenyl nitriles [1b] to [7b] thus obtained were hydrolyzed using a KOH-methanol solution, and the corresponding carboxylic acid [1c] (+)-was obtained. 3,7-Dimethyl-2-octenoic acid, [2c] (+)-1-p-menthen-9-yl-acetic acid, [3c] (+)-α-camphorenic acid, [4c] β
-Camphorenic acid, [5c] (-)-6,6-dimethylbicyclo [3.1.1] hept-2-ene-2-carboxylic acid, [6c] (-)-4-isopropenyl-1-cyclohexene It is derived to -1-carboxylic acid and [7c] 3,7-dimethyl-2,6-octadienoic acid. Each of the synthesized carboxylic acids was chlorided with thionyl chloride to give a highly reactive acid chloride, and then each of the alkylamines or dialkylamines (R = -CH
_3, -C ₂ H _5, performs a condensation reaction with -C ₃ H _7), respectively led to the corresponding condensation product A～U. Regarding the chemical structures of these products, IR and ¹ H-NMR spectra were measured, and they were confirmed from the respective characteristic spectral data obtained. The R ₁ group [1] to
[7] corresponds to the above-mentioned amide compounds (1) to (7) and is referred to in the present specification as a terpenyl group (meaning a residue obtained by removing an aldehyde group from terpenyl aldehyde which is a starting material). Is shown.

[0019]

EXAMPLES Specific synthesis examples of the amide compound will be shown below. Synthesis of monoterpenyl nitriles [1b] to [7b]: Synthesis of [1b] (-)-3,7-dimethyl-2-octenenitrile: 0.2 mol of citronellal and 0.2 of N, N-dimethylhydrazine. 30 mole of a mixture of dry benzene
After dissolving in 0 mL, the mixture was heated under reflux until the theoretical amount of water was obtained. After cooling the reaction solution, 0.2 mol of methyl iodide was added and the mixture was heated under reflux for 4 hours. Then 0.1 M NaOH
-200 mL of a methanol solution was added for hydrolysis. After completion of the reaction, the reaction mixture was operated according to a conventional method and distilled under reduced pressure to obtain (-)-3,7-dimethyl-2-octenenitrile in a yield of 80%. The structure of the product was confirmed by an infrared absorption spectrum (manufactured by JASCO Corporation, IR-810 type) and a nuclear magnetic resonance spectrum (manufactured by JEOL Ltd., JNM-MH-100 used), and the purity of the compound was confirmed. Is a gas chromatography (manufactured by Yanaco, G-
3800, OV-17, glass column φ3 mm x 2.5
m) (also for the following products). As a result, the boiling point is 60 to 63 ° C./5 mmHg, the refractive index n _D ²⁰ = 1.4490, and the density d ₄ ²⁰ = 0.856.
0, the specific rotation [α] _W ²⁰ = −7.7 ° (stock solution). The refractive index and the specific rotation were measured using an Abbe refractometer 2T type manufactured by Atago Co., Ltd. and an AA-5 type optical rotation meter manufactured by Atago Co., Ltd., respectively.

[2b] (+)-1-p-Menten-9-
Synthesis of nitrile: (+)-1-p-menthene-9-nitrile was obtained in a yield of 7 by the same operation as the nitration reaction of [1b] except that 1-p-menthene-9-ar was used.
Obtained at 1%. The boiling point of the obtained compound is 116 to 118 ° C.
/ 10 mmHg, refractive index n _D ²⁰ = 1.5021, density d
₄ ²⁰ = 1.0124, specific optical rotation [α] _W ²⁰ = + 108.
It was 6 ° (stock solution).

Synthesis of [3b] (+)-α-camphorenenitrile: 1M NaO per 100 g of (+)-camphor.
200 g of hydroxylamine hydrochloride in 1000 mL of H-ethanol solution was reacted at 100 ° C. for 24 hours (+).
-Camphor oxime was obtained with a yield of 92%, which was then treated with 300 mL of 25% sulfuric acid at 100 ° C for 30 minutes to obtain α-camphorene nitrile with a yield of 95%.
The obtained compound has a boiling point of 51 to 52 ° C./1 mmHg, a refractive index n _D ²⁰ = 1.4674, a density d ₄ ²⁰ = 0.855.
2. Specific rotation [α] _W ²⁰ = + 4.8 ° (stock solution).

[4b] Synthesis of β-camphorene nitrile: β-camphorene was prepared by the same procedure as the oximation reaction and nitration reaction of [3b] except that 200 mL of concentrated hydrochloric acid was used instead of 25% sulfuric acid. Yield 85
Earned in%. The boiling point of the obtained compound is 80 to 82 ° C / 5m.
mHg, refractive index n _D ²⁰ = 1.4672, density d ₄ ²⁰ =
It was 0.8211.

Synthesis of [5b] (-)-6,6-dimethylbicyclo [3.1.1] hept-2-ene-2-carbonitrile: With the nitration reaction of the above [1b] except that miltenal is used. By the same operation, (-)-6,6-dimethylbicyclo [3.1.1] hept-2-ene-2-
Carbonitrile was obtained with a yield of 70%. The boiling point of the obtained compound was 72 to 76 ° C./5 mmHg, and the refractive index n _D ²⁰ = 1.
4391, density d ₄ ²⁰ = 0.9889, specific optical rotation [α]
_W ²⁰ = −47 ° (stock solution).

[6b] (-)-4-isopropenyl-1
-Synthesis of cyclohexene-1-carbonitrile: (-)-4-isopropenyl-1 was prepared by the same procedure as the nitration reaction of [1b] except that perilaldehyde was used.
-Cyclohexene-1-carbonitrile was obtained with a yield of 62%. The boiling point of the obtained compound is 85 to 93 ° C./7 mmH.
g, refractive index n _D ²⁰ = 1.4940, density d ₄ ²⁰ = 0.9
724, specific rotation [α] _W ²⁰ = −89 ° (stock solution).

[7b] Synthesis of 3,7-dimethyl-2,6-octadiene nitrile: 3,7,3-dimethyl-2,6-octadienenitrile was prepared by the same operation as the nitration reaction of [1b] except that citral was used.
-Dimethyl-2,6-octadiene nitrile yield 80
Earned in%. The boiling point of the obtained compound is 69 to 71 ° C / 5m.
mHg, refractive index n _D ²⁰ = 1.4753, density d ₄ ²⁰ =
It was 0.8530.

Monoterpenylcarboxylic acid [1c] to [7]
Synthesis of c]: Synthesis of [1c] (+)-3,7-dimethyl-2-octenoic acid: 300 m equipped with stirrer, reflux condenser, dropping funnel
(4) (-)-3,7- of the above [1b] in a four-necked L flask.
Take a mixed solution of 10 g (0.066 mol) of dimethyl-2-octenenitrile and 70 mL of methanol, and add 0.4 M
After adding 100 mL of KOH-methanol solution, 20
Heated to reflux for hours. After completion of the reaction, operation was carried out in the usual way, and then distillation was performed under reduced pressure to obtain (+)-3,7-dimethyl-2-octenoic acid in a yield of 89%. The boiling point of the obtained compound is 91 to 92 ° C./2 mmHg, and the refractive index n _D ²⁰ = 1.465.
1, density d ₄ ²⁰ = 0.9308, specific rotation [α] _W ²⁰ =
It was + 5.5 ° (stock solution).

[2c] (+)-1-p-menthene-9-
Synthesis of yl = acetic acid: (+)-1-p-menthen-9-yl = acetic acid was collected from (+)-1-p-menthene-9-nitrile by the same operation as the hydrolysis reaction of the above [1c]. It was obtained at a rate of 78%. The boiling point of the obtained compound is 81 to 83 ° C /
4 mmHg, refractive index n _D ²⁰ = 1.4814, density d ₄ ²⁰
= 0.9164, and specific rotation [α] _W ²⁰ = + 86 ° (stock solution).

Synthesis of [3c] (+)-α-camphorene acid: From (+)-α-camphorene nitrile, the above [1]
By the same operation as in the hydrolysis reaction of c], (+)-α-camphorenic acid was obtained with a yield of 80%. The boiling point of the obtained compound was 96 ° C./3 mmHg, and the refractive index n _D ²⁰ = 1.470.
1, density d ₄ ²⁰ = 0.8980, specific rotation [α] _W ²⁰ =
It was + 10.0 ° (stock solution).

Synthesis of [4c] β-camphorenic acid: β-
By the same operation as the above-mentioned hydrolysis reaction of [1c] from camphorene nitrile, β-camphorenic acid was obtained with a yield of 82%. The boiling point of the obtained compound is 160 ° C / 11 mmH.
g, refractive index n _D ²⁰ = 1.4712, density d ₄ ²⁰ = 1.0
It was 156.

Synthesis of [5c] (-)-6,6-dimethylbicyclo [3.1.1] hept-2-ene-2-carboxylic acid: (-)-6,6-dimethylbicyclo [3.1] ．
1] From the hept-2-ene-2-carbonitrile, by the same operation as the hydrolysis reaction of the above [1c], (-)-
6,6-Dimethylbicyclo [3.1.1] hept-2-
The ene-2-carboxylic acid was obtained with a yield of 74%. The melting point of the obtained compound was 45 to 46 ° C., and the specific optical rotation [α] _W ²⁰ = −3
It was 1.2 ° (solution concentration c = 1 g / 1 mL ethanol).

[6c] (-)-4-isopropenyl-1
-Synthesis of cyclohexene-1-carboxylic acid: (-)-4
-(-)-4-isopropenyl-1-cyclohexene-1-carboxylic acid was obtained from -isopropenyl-1-cyclohexene-1-carbonitrile by the same operation as the hydrolysis reaction of the above [1c] with a yield of 76%. It was The melting point of the obtained compound is 118 to 119 ° C., and the specific optical rotation [α] _W ²⁰ = −8.
It was 0.6 ° (solution concentration c = 1 g / 1 mL ethanol).

[7c] Synthesis of 3,7-dimethyl-2,6-octadienoic acid: 3,7-Dimethyl-2,6-octadienenitrile was prepared from 3,7-dimethyl-2,6-octadienenitrile by the same procedure as in the above-mentioned hydrolysis reaction [1c]. 7-Dimethyl-2,6-octadienoic acid was obtained with a yield of 56%. The boiling point of the obtained compound is 60 to
The temperature was 61 ° C./3 mmHg, the refractive index was n _D ²⁰ = 1.4753, and the density was d ₄ ²⁰ = 0.9703.

Synthesis of Monoterpenylamide Compounds A to U: Synthesis of Citronellylamide: (1) Compound A: (+)-3 in a 50 mL four-necked flask equipped with stirrer, calcium chloride tube and dropping funnel. , 7
1.0 g (0.006 mol) of dimethyl-2-octenoic acid and 0.3 mL of HPMA (hexamethylphosphor (tolu) amide (amide solvent)) were taken, and thionyl chloride was adjusted to 0. After dropping 86 g (0.007 mol), the mixture was stirred for 0.5 hours, thionyl chloride was distilled off under reduced pressure, 1.0 mL of 33% dimethylamine aqueous solution was added dropwise, and the mixture was stirred at room temperature for 1.5 hours. After the reaction,
The crude reaction oil obtained by the conventional method was distilled under reduced pressure to obtain (-)-N, N-dimethyl-3,7-dimethyl-6-.
Octaenamide was obtained in a yield of 63%.

(2) Compound B: (-)-N, N- by the same procedure as the condensation reaction of (1) above except that 1 mL of 44% diethylamine aqueous solution was used instead of dimethylamine.
Diethyl-3,7-dimethyl-6-octaenamide was obtained in a yield of 72%. (3) Compound C: (-)-N, N- by the same operation as the condensation reaction of (1) above except that 1 mL of dipropylamine and triethylamine were used instead of dimethylamine.
Dipropyl-3,7-dimethyl-6-octaenamide was obtained in a yield of 85%.

Synthesis of 1-p-menthen-9-amide: Compounds D, E and F: (+)-3,7-dimethyl-2-
Instead of octenoic acid, the starting material was (+)-1-p-
The above (1), except that Menten-9-yl = acetic acid is used,
By the same operation as the condensation reaction of (2) and (3), the corresponding N, N-dimethylamide compound D, N, N-
Diethylamide compound E and N, N-dipropylamide compound F were obtained.

Synthesis of α-camphorenamide: Compounds G, H and I: (+)-3,7-dimethyl-2-
By the same operation as the condensation reaction of the above (1), (2) and (3), except that (+)-α-camphorenic acid was used as a starting material instead of octenoic acid, the corresponding N, N-dimethylamide was obtained. Compound G, N, N-diethylamide compound H and N, N-dipropylamide compound I were obtained.

Synthesis of β-camphorenamide: Compounds J, K and L: (+)-3,7-dimethyl-2-
By the same operation as the condensation reaction of the above (1), (2) and (3) except that β-camphorenic acid was used as a starting material instead of octenoic acid, the corresponding N, N-dimethylamide compounds J and N were respectively obtained. , N-diethylamide compound K
And N, N-dipropylamide compound L were obtained.

Synthesis of mirtenylamide: Compounds M, N and O: (+)-3,7-dimethyl-2-
Instead of octenoic acid, (-)-6,6-
Dimethylbicyclo [3.1.1] hept-2-ene-2
-By the same operation as the condensation reaction of the above (1), (2) and (3) except using a carboxylic acid, the corresponding N, N-dimethylamide compound M, N, N-diethylamide compound N and N, N -Dipropylamide compound O was obtained.

Synthesis of perilamide: Compounds P, Q and R: (+)-3,7-dimethyl-2-
By the same operation as the condensation reaction of the above (1), (2) and (3), except that (-)-4-isopropenyl-1-cyclohexene-1-carboxylic acid is used as a starting material instead of octenoic acid, Corresponding N, N-dimethylamide compound P, N, N-diethylamide compound Q and N, N-dipropylamide compound R, respectively, were obtained.

Synthesis of citraamide: Compounds S, T and U: (+)-3,7-dimethyl-2-
The above (1), except that 3,7-dimethyl-2,6-octadienoic acid is used as a starting material instead of octenoic acid.
By the same operation as the condensation reaction of (2) and (3), the corresponding N, N-dimethylamide compound S, N, N-
Diethylamide compound T and N, N-dipropylamide compound U were obtained.

Table 1 shows the physical constants and yields of the 21 kinds of monoterpenylamide compounds obtained by the above operation, and Table 2 shows the spectrum data.

[Table 1]

[0042]

[Table 2] Compounds A to U have an IR spectrum of 16
Absorption of carbonyl around 25 to 1650 cm ^-1 , ¹ H
-In the NMR spectrum, the structure was confirmed by characteristic absorptions of trisubstituted olefin proton, methylene derived from tertiary amide, methyl proton, allylmethyl, and gem-CH ₃ .

The following are some examples of the preparation of various dosage forms using the compound Q.

[0044]

[0045]

Next, various efficacy tests were carried out on the above-mentioned monoterpenylamide compound for the repellent effect and the exterminating effect. The results are shown below.

Test Example 1 The above-mentioned compounds P, Q and R (N, N-dimethylamide compound P, N, N- of perylamide) against Aedes albopictus
The repellent effect of diethylamide compound Q and N, N-dipropylamide compound R) was tested. In addition, perilaldehyde and DEET were also tested for comparison. The test method is as follows. Test method: 30 cm × 40 cm × height 30 c shown in FIG.
Approximately 300 adult Aedes albopictus females were released in a wire net cage 1 of m, and a predetermined amount of the test agent 3 was applied to the arm 2 of the subject.
Was inserted through the sleeve 4 and the number of bites (animals) per 3 minutes was counted over time. The amount of drug processed is 2g / m
² and the drug application was performed by diluting a drug solution (2.5% W /
0.2 mL of V) was applied to each place. One test was performed by 4 subjects. 2 arms per subject 4
Among the drug treatment areas applied to the places, the treatment continuation was discontinued at that time for the treatment areas where the bite by the test insect was severely observed.

The test results (number of bites for 3 minutes / average of 4 subjects) are shown in Table 3 below.

[Table 3] As is clear from the test results shown in Table 3, the monoterpenyl amide compound (perylamide) of the present invention has extremely high repellent activity as compared with its starting material, perillaldehyde, and is comparable to DEET. However, it can be seen that the activity and durability as a repellent are excellent. Also,
It can be seen that among the monoterpenylamide compounds of the present invention, the amide group-modifying group is more excellent in repellent activity than the dimethyl group and the diethyl group are compared with the dipropyl group.

Test Example 2 The above compounds B (citronellyl amide), E (1-p-menthene-9-amide), H (α) against Aedes albopictus
-Camphorenamide), K (β-camphorenamide), N (miltenylamide), Q (perilamide) and T (citramide) (all N, N-diethylamide compounds) were tested for repellent effect. DEET was also tested for comparison. The test method was the same as in Test Example 1 above.

The test results are shown in Table 4 below.

[Table 4] As is clear from the test results shown in Table 4, the monoterpenylamide compound of the present invention is extremely excellent in activity and durability as a repellent as compared with DEET.

Test Example 3 The above compounds B (citronellyl amide), E (1-p-menthene-9-amide) and H (α-
Camphorenamide), K (β-camphorenamide), N (miltenylamide), Q (perilamide) and T (citramide) (all N, N-diethylamide compounds) were tested for repellent effect. DEET was also tested for comparison. Test method: Each test agent was treated with a chemical treatment amount of 0.1, 0.5,
Acetone solution (0.039, 0.192, 0.77% W / V) diluted to a predetermined concentration to give 2.0 g / m ^2.
Apply 1 mL of filter paper (Toyo filter paper 5A, 7 cmφ) to 1
Air dried for hours. Then, as shown in FIG. 3, about 600 test insects were placed in an adult rearing cage 5 (30 × 30 × 40 cm stainless steel 16 mesh knitting basket), and each test agent-treated filter paper 6 and untreated The filter paper 7 was hung. Ten minutes after the filter paper was hung, the number of test insects remaining on each filter paper was counted, and the repellent rate was calculated by the following formula. (If the repellency rate is negative, the repellency rate is 0.)

The test results are shown in Table 5 below.

[Table 5] As is clear from the test results shown in Table 5, the monoterpenylamide compound of the present invention is superior in activity as a repellent against housefly as compared with DEET, and is excellent in repellent effect even at a low concentration. I understand that

Test Example 4 The above compounds B (citronellyl amide), E (1-p-menthene-9-amide), and H against German cockroach
(Α-camphorenamide), K (β-camphorenamide), N (miltenylamide), Q (perylamide)
And the repellent effect of T (citraamide) (both N, N-diethylamide compounds) were tested. DEET was also tested for comparison. Test method: As shown in FIG. 4, a shelter 9 (1 × 2c) in which a plywood board was assembled in a cross with 10 male and female German cockroaches in an acrylic box 8 of 20 × 20 cm.
m), a container 10 containing food (solid feed) and a container 11 containing water are arranged and prepared for one day, and a predetermined amount of the test agent is placed in one corner of the acrylic box as shown in the figure. A 7 × 7 cm filter paper 12 (treated area) coated with was placed in another corner of an untreated filter paper 13 (untreated area).

The treatment section was treated with an acetone solution (1.23% W) diluted to a predetermined concentration so that the amount of drug treated was 2 g / m ^2.
/ V) 2 mL of Toyo Filter Paper No. 12.5 cm in diameter. 5A
It was applied to the above, dried in air for 1 hour, and cut into 7 × 7 cm. Then, the number of test insects remaining on the wooden shelters placed on both the treated and untreated filter papers was counted over time. Individuals still in the shelter were shaken off every day and the positions of the treated and untreated plots were exchanged. The repetition was repeated 3 times, the average number of individuals in each section was calculated, and the repellent rate was calculated by the following formula. The numbers of individuals in the feeding and water areas were excluded from the calculation. (If the repellency rate is negative, the repellency rate is 0.)

The test results are shown in Table 6 below.

[Table 6] As is clear from the test results shown in Table 6, the monoterpenyl amide compound of the present invention is superior in activity and durability as a repellent against German cockroaches as compared with DEET.

Test Example 5 The above compounds B (citronellyl amide), E (1-p-menthene-9-amide), H against German cockroach
(Α-camphorenamide), K (β-camphorenamide), N (miltenylamide), Q (perylamide)
And T (citraamide) (both N, N-diethylamide compounds) were tested for insecticidal effect. DEET was also tested for comparison. Test method: glass plate forced contact method 1 mL of an acetone solution (2% W / V) diluted with the test agent to a prescribed concentration so that the drug treatment amount was 2 g / m ² was applied.
An air-dried 10 × 10 cm glass plate was used. Separately, vaseline was applied to the inner wall, and a waist-high petri dish having a diameter of 9 cm and containing 10 female German cockroach adults was prepared. The hip-high Petri dish was turned upside down, the test insects were forcibly contacted with the glass plate for 24 hours, and the number of dead insects was observed. The repetition was performed 3 times.

The test results are shown in Table 7 below.

[Table 7] As is clear from the test results shown in Table 7, DEET
Has no insecticidal activity against German cockroaches, whereas the monoterpenylamide compound of the present invention has excellent activity as an insecticide against German cockroaches.

Test Example 6 The above-mentioned compounds B (citronellyl amide), E (1-p-menthene-) were treated against the mite, Plutella xylostella and Dermatophagoides farinae.
9-amide), H (α-camphorenamide), K (β
-Camphorenamide), N (miltenylamide), Q
The acaricidal effect of (perylamide) and T (citraamide) (both N, N-diethylamide compounds) was tested. DEET was also tested for comparison. Test method: Clip method 2 mL of an acetone solution (0.67% W / V) obtained by diluting each test agent to a predetermined concentration so that the amount of drug to be treated was 1 g / m ² was applied to Toyo Filter Paper No. 1 having a diameter of 12.5 cm. It was applied to 5A, air-dried for 1 hour, folded in two, and a test mite was put inside the piece and sealed with a clip. The clip was opened 24 hours later, the mortality rate was investigated, and the corrected mortality rate was calculated by the following formula (3 repetitions). (If the corrected mortality rate takes a negative value, the corrected mortality rate shall be 0.)

The test results are shown in Table 8 below.

[Table 8] As is clear from the test results shown in Table 8, DEET
It can be seen that the monoterpenylamide compound of the present invention is extremely excellent in activity as an acaricide against the mites of the genus Aedes albicans and Dermatophagoides farinae as compared with the above.

Test Example 7 The above compounds B (citronellylamide), E (1-p-menthene-) were treated against the mite, Plutella xylostella, and Dermatophagoides farinae.
9-amide), H (α-camphorenamide), K (β
-Camphorenamide), N (miltenylamide), Q
The growth inhibitory effects of (perylamide) and T (citramide) (both N, N-diethylamide compounds) were tested. DEET was also tested for comparison. Test method: medium mixing method Acetone solution of each test agent (0.
10% of 1% W / V) was added, and acetone was evaporated and mixed to make the drug concentration 100 ppm. This is serially diluted with powdered feed to 2 times, 50, 25,
It was adjusted to be 12.5 and 6.25 ppm. The mites were added to these treated powders at 300 / g, and under the optimum conditions (humidity was 85% for the diamondback mites, humidity was 75% for the Dermatophagoides farinae, and the temperature was 27 ° C).
After storage for a predetermined number of days (4 weeks for the mite mite, 6 weeks for the mite dust mite), the number of live mites in the medium was examined, and the growth inhibition rate was calculated by the following formula. The 90% growth inhibitory concentration (IC90) was calculated from the results of the growth inhibitory rate at each concentration step.

The test results are shown in Table 9 below.

[Table 9] From the test results shown in Table 9, it can be seen that the monoterpenylamide compound of the present invention is extremely excellent in activity and durability as an acaricide against helminth mites and Dermatophagoides farinae compared to DEET.

Test Example 8 The above-mentioned compounds B (citronellyl amide), E (1-p-menthene-) were treated against the mites of the diamondback moth, Dermatophagoides farinae.
9-amide), H (α-camphorenamide), K (β
-Camphorenamide), N (miltenylamide), Q
(Perilamide) and T (citramide) (both N, N-diethylamide compounds) were tested for mite repellent effect. DEET was also tested for comparison. Test method: 1 g of a medium having a mite density of 10,000 / g was placed in a petri dish having a diameter of 7 cm, and allowed to stand for 3 hours until the mite became stable. On the other hand, an acetone solution (0.67%) was prepared by diluting each test agent to a prescribed concentration so that the amount of drug treated was 1 g / m ^2.
2 mL of Toyo filter paper with a diameter of 12.5 cm. 5
It was applied to A, air-dried for 1 hour, cut into 4 × 4 cm pieces, placed on the above-mentioned medium, and a black paper cut into 2.5 × 2.5 cm pieces was placed on the medium. I counted the number. In addition, an untreated section using filter paper not coated with each test agent was also provided, and the repellency rate was calculated by the following formula.

The test results are shown in Table 10 below.

[Table 10] As is clear from the test results shown in Table 10, DEE
It can be seen that the monoterpenylamide compound of the present invention is superior to T in activity as a tick repellent against the mites, Plutella mites and Dermatophagoides farinae.

[0064]

INDUSTRIAL APPLICABILITY As described above, the terpenylamide compound according to the present invention has high repellent activity, insecticidal activity and acaricidal activity which are higher than those of DEET which is commercially available against a wide variety of harmful insects, and the residual Highly effective. Further, it has a low permeability to the skin, and is therefore considered to be advantageous in safety over DEET. Therefore, by using the terpenylamide compound according to the present invention as an active ingredient of pest repellents, insecticides, acaricides, etc., excellent repellent effect and extermination against a wide variety of pests such as mosquitoes, flies, cockroaches and mites. Exert an effect.

[Brief description of drawings]

1 is an overall reaction scheme for synthesizing the amide compound of the present invention.

FIG. 2 is a schematic configuration diagram showing a partially broken view of a test apparatus used in Test Examples 1 and 2.

FIG. 3 is a schematic configuration diagram showing a partially broken test apparatus used in Test Example 3;

FIG. 4 is a schematic plan view of a German cockroach repellent test device used in Test Example 4.

[Explanation of symbols]

 1 Wire net cage 2 Arms 3 Sample application area 4 Sleeve 5 Adult breeding cage 6 Sample agent treated filter paper 7 Untreated filter paper 8 Acrylic box 9 Plywood shelter 10 Food container 11 Water container 12 Sample agent treated filter paper 13 Untreated filter paper

[Procedure amendment]

[Submission date] October 5, 1992

[Procedure Amendment 1]

[Document name to be amended] Statement

[Name of item to be corrected] Full text

[Correction method] Change

[Correction content]

[Document name] Statement

Title: Amide compound and pest repellent and pest control agent using the same

[Claims]

[Chemical 1] (In the formula, R ₁ is citronellal, 1-p-menthene-9
-Earl, α-camphorene aldehyde and β-can
Monotel selected from the group consisting of foren and aldehyde
Monoterpenyl group which is a residue of penenyl aldehyde except for aldehyde group , R ₂ and R ₃ are H and iso- or normal saturated or unsaturated hydrocarbon group having 1 to 6 carbon atoms (provided that R is ₂ and R ₃ are both H). ) An amide compound represented by the general formula:

[Chemical 2] (In the formula, R ₁ is citronellal, 1-p-menthene-9
-Earl, α-camphorene aldehyde and β-can
Monotel selected from the group consisting of foren and aldehyde
Monoterpenyl group which is a residue of penenyl aldehyde except for aldehyde group , R ₂ and R ₃ are H and iso- or normal saturated or unsaturated hydrocarbon group having 1 to 6 carbon atoms (provided that R is ₂ and R ₃ are both H). ) A pest repellent comprising an amide compound represented by the general formula (1) as an active ingredient.

[Chemical 3] (In the formula, R ₁ is citronellal, 1-p-menthene-9
-Earl, α-camphorene aldehyde and β-can
Monotel selected from the group consisting of foren and aldehyde
Monoterpenyl group which is a residue of penenyl aldehyde except for aldehyde group , R ₂ and R ₃ are H and iso- or normal saturated or unsaturated hydrocarbon group having 1 to 6 carbon atoms (provided that R is ₂ and R ₃ are both H). ) An insecticide containing an amide compound represented by the general formula (1) as an active ingredient.

[Chemical 4] (In the formula, R ₁ is citronellal, 1-p-menthene-9
-Earl, α-camphorene aldehyde and β-can
Monotel selected from the group consisting of foren and aldehyde
Monoterpenyl group which is a residue of penenyl aldehyde except for aldehyde group , R ₂ and R ₃ are H and iso- or normal saturated or unsaturated hydrocarbon group having 1 to 6 carbon atoms (provided that R is ₂ and R ₃ are both H). ) An acaricide containing an amide compound represented by the general formula (1) as an active ingredient.

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a novel amide compound excellent in repellent effect and exterminating effect against pests, particularly an amide compound having a terpenyl group derived from a natural product, and pest repellents and insecticides containing them. The present invention relates to a pest control agent such as a mite agent.

[0002]

2. Description of the Related Art Attempts to use repellent substances for controlling agricultural pests and sanitary pests have been made for a long time, and many natural products have been used. Recently, the relationship between the life of living organisms and essential oils of plants has become known, and it has been clarified that various terpenoids contained in plant components are repellent to certain insects. It is being defeated. For example, it has been reported that the monoterpenoids menthol and citronellal are repellent to mosquitoes, and linalool, geraniol, menthol and the like are repellent to cockroaches (Japanese Patent Laid-Open No. 53-86021 and Shin Inazuka). 1: Journal of Japan Society of Pesticides, 7 (2), 145 (19)
82)). On the other hand, in recent years, as a repellent against sanitary pests such as mosquitoes and cockroaches, DEET (N, N-diethyl-
m-toluamide) is commercially available and widely used.

[0003]

DISCLOSURE OF THE INVENTION Problems to be Solved by the Invention
T is not always satisfactory in that the target pest species are limited in efficacy and the residual effect is short, and there is a suspicion in terms of safety. Therefore, attention has been paid to the above-mentioned bioactive natural products which are widely distributed in nature. As the conditions for which establishment of these bioactive natural products as repellents is expected, it is desirable that (1)
There are no restrictions on the application site, (2) extremely low toxicity to humans and animals, (3) long shelf life, and (4) small amount of effect.

Therefore, an object of the present invention is to find a safer physiologically active compound having a high activity repellent effect or a eradication effect equal to or higher than DEET against various sanitary pests and unpleasant pests. is there. Further, an object of the present invention is to provide a pest repellent, an insecticide and an acaricide having both the maintenance of the repellent effect and the exterminating effect and the retention of the activity at a low concentration.

[0005]

Means and Actions for Solving the Problems The present inventors have
As a result of earnest research on physiologically active compounds, the following 5

[Chemical 5] (In the formula, R ₁ is citronellal, 1-p-menthene-9
-Earl, α-camphorene aldehyde and β-can
Monotel selected from the group consisting of foren and aldehyde
Monoterpenyl group which is a residue of penenyl aldehyde except for aldehyde group , R ₂ and R ₃ are H and iso- or normal saturated or unsaturated hydrocarbon group having 1 to 6 carbon atoms (provided that R is ₂ and R ₃ are both H). ) The amide compound represented by the general formula (1) is DE
High activity over ET, repellent effect and control effect against a wide variety of pests, and high residual effect, and further low permeability to the skin when applied to human body and high sustaining effect. The present invention has been completed and the present invention has been completed. Among the amide compounds of the above general formula (1),
Also, both methyl groups and R ₂ and R ₃ especially, excellent pest repelling effect and extermination effect in the amide compound is low concentrations an ethyl group or a propyl group, is advantageous because high activity lasting effect.

[0006] The relationship between the persistence of the basic skeleton and repellent activity and extermination activity of a compound of the terpenoid, those showing the repellency mosquito and cockroaches menthol, citronellal, Rinaro Le of which terpene alcohol or aldehyde Therefore, by converting these compounds to compounds having an amide group, it was possible to further enhance the activity and the durability. However, among the terpenylamide compounds, the repellent activity, the exterminating activity, and their persistence were found to be different depending on the terpene skeleton. That is, it was the compound based on the limonene skeleton that showed excellent activity and durability in the secondary screening test that was actually applied to human skin. In addition, DEET and the compound of the present invention have an amide group and an ethyl group as structurally common sites. This analog compound, N, N-diethyldiamide or N, N-diethyl [2 Since-(propoxycarbonyl) ethyl] carboxamide and the like also show high repellent activity, it is considered that this common structural site is closely related to repellent property and repellent property.

[0007] As pests which amide compounds act effectively in the present invention, for example mosquitoes, flies, cockroaches, etc. can be mentioned mite, by incorporating a suitable carrier an amide compound of the present invention as an active ingredient, Pest repellent,
It can be used as a pest control agent such as insecticides and acaricides. Further, the amide compound of the present invention is a film forming agent, a moisturizer, a pH adjusting agent, a rust preventive agent, an emulsifier, a dispersant, a spreading agent, a stabilizer, a solvent, an antioxidant, a propellant, and a volatilization adjusting, if desired. Oils, emulsions, wettable powders, sprays,
It can be used in the form of aerosols, smoke agents, coating agents, electrotranspiration agents, powders, granules and the like.

[0008] Hereinafter, further specifically described the present invention shows a method of synthesis and various efficacy testing of the amide compounds of the present invention. Synthetic Method: First, the general synthetic method of the amide compound according to the present invention will be outlined. Monoterpenyl nitriles prepared from the starting material monoterpenyl aldehyde or camphor oxime are hydrolyzed to form carboxylic acid. It is synthesized and acid chloride is induced by chloridation. Then, the desired monoterpenylamide compound is synthesized by a condensation reaction of this acid chloride with an alkylamine or a dialkylamine. The amide compound according to the present invention is not limited to those synthesized according to the above reaction route, and those synthesized according to other possible reaction routes are also within the scope of the present invention, and the reaction conditions and the like are also known to those skilled in the art. If there is a test, appropriate conditions can be set appropriately.

[0009] As a representative example, Figure 1 shows the overall reaction path diagram of the synthesis of the amide compounds shown below. (1) Citronellyl amide represented by the following chemical formula 6

[Chemical 6] Compound A: R ₂ , R ₃ = CH ₃ Compound B: R ₂ , R ₃ = C ₂ H ₅ Compound C: R ₂ , R ₃ = C ₃ H ₇

[0010] (2) 1-p- menthene-9-amide represented by the following formula 7

[Chemical 7] Compound D: R ₂ , R ₃ = CH ₃ Compound E: R ₂ , R ₃ = C ₂ H ₅ Compound F: R ₂ , R ₃ = C ₃ H ₇

[0011] (3) alpha-Kan follower Ren amide represented by the following formula 8

[Chemical 8] Compound G: R ₂ , R ₃ = CH ₃ Compound H: R ₂ , R ₃ = C ₂ H ₅ Compound I: R ₂ , R ₃ = C ₃ H ₇

[0012] (4) beta-Kan follower Ren amide represented by the following Chemical Formula 9

[Chemical 9] Compound J: R ₂ , R ₃ = CH ₃ Compound K: R ₂ , R ₃ = C ₂ H ₅ Compound L: R ₂ , R ₃ = C ₃ H ₇

[0013] Referring to FIG. 1, the mono ether Bae sulfonyl nitriles [1b] (-) - 3,7-dimethyl-2-octene nitrile (abbreviation citronellyl nitrile) and [2
b] (+) - 1- p- menthene-9-nitrile, beta and corresponding aldehyde [1a] citronellal and [2a] 1-p- menthene-9 are dimethylhydrazine and methyl iodide -Easily synthesized by nitriding by elimination reaction and hydrolysis. On the other hand, [3b] α-camphorene nitrile and [4b] β
-Camphorene nitrile can be easily synthesized by treating camphor oxime obtained by reacting d-camphor with hydroxylamine in pyridine with 25% sulfuric acid (or formic acid) and concentrated hydrochloric acid, respectively.

[0014] hydrolysis was carried out using a KOH- methanol solution of such four types obtained in the Tel Bae alkenyl nitriles [1b] ~ [4 b] , corresponding carboxylic acid [1c] (+) -3,7-Dimethyl-2-octenoic acid, [2c] (+)-1-p-menthen-9-yl = acetic acid, [3c] (+)-α-camphorenic acid and [4c].
Induces to β-camphorenic acid. The synthesized respective carboxylic acid performs chloride by thionyl chloride, after an acid chloride thereof rich in reactivity, each alkyl amine or dialkyl amines _{(R = -CH 3, -C 2} H
₅ performs a condensation reaction with the -C ₃ H _7), respectively led to the corresponding condensation product A to L. Regarding the chemical structures of these products, IR and ¹ H-NMR spectra were measured, and they were confirmed from the respective characteristic spectral data obtained. The R ₁ groups [1] to [ 4 ] shown in FIG. 1 correspond to the amide compounds (1) to ( 4 ) described above, and are referred to in the present specification as terpenyl groups (terpenyl which is a starting material). It means a residue obtained by removing an aldehyde group from an aldehyde).

[ 0015 ]

EXAMPLES Specific synthesis examples of the amide compound will be shown below. Synthetic mono- Tel Bae sulfonyl nitrile [1b] ~ [4 b] : [1b] (-) - Synthesis of 3,7-dimethyl-2-octene nitrile: citronellal 0.2 mole of N, N-dimethylhydrazine 0. 2 mol of the mixture is dried with benzene 30
After dissolving in 0 mL, the mixture was heated under reflux until the theoretical amount of water was obtained. After cooling the reaction solution, 0.2 mol of methyl iodide was added and the mixture was heated under reflux for 4 hours. Then 0.1 M NaOH
-200 mL of a methanol solution was added for hydrolysis. After completion of the reaction, the reaction mixture was operated according to a conventional method and distilled under reduced pressure to obtain (-)-3,7-dimethyl-2-octenenitrile in a yield of 80%. The structure of the product was confirmed by an infrared absorption spectrum (manufactured by JASCO Corporation, IR-810 type) and a nuclear magnetic resonance spectrum (manufactured by JEOL Ltd., JNM-MH-100 used), and the purity of the compound was confirmed. Is a gas chromatography (manufactured by Yanaco, G-
3800, OV-17, glass column φ3 mm x 2.5
m) (also for the following products). As a result, the boiling point is 60 to 63 ° C./5 mmHg, the refractive index n _D ²⁰ = 1.4490, and the density d ₄ ²⁰ = 0.856.
0, the specific rotation [α] _W ²⁰ = −7.7 ° (stock solution). The refractive index and the specific rotation were measured using an Abbe refractometer 2T type manufactured by Atago Co., Ltd. and an AA-5 type optical rotation meter manufactured by Atago Co., Ltd., respectively.

[0016] [2b] (+) - 1 -p- Menten-9
Synthesis of nitrile: (+)-1-p-menthene-9-nitrile was obtained in a yield of 7 by the same operation as the nitration reaction of [1b] except that 1-p-menthene-9-ar was used.
Obtained at 1%. The boiling point of the obtained compound is 116 to 118 ° C.
/ 10 mmHg, refractive index n _D ²⁰ = 1.5021, density d
₄ ²⁰ = 1.0124, specific optical rotation [α] _W ²⁰ = + 108.
It was 6 ° (stock solution).

[0017] [3b] (+) - Synthesis of α- cans follower Ren nitrile: (+) - camphor 100g to 1M NaO
200 g of hydroxylamine hydrochloride in 1000 mL of H-ethanol solution was reacted at 100 ° C. for 24 hours (+).
-Camphor oxime was obtained with a yield of 92%, which was then treated with 300 mL of 25% sulfuric acid at 100 ° C for 30 minutes to obtain α-camphorene nitrile with a yield of 95%.
The obtained compound has a boiling point of 51 to 52 ° C./1 mmHg, a refractive index n _D ²⁰ = 1.4674, a density d ₄ ²⁰ = 0.855.
2. Specific rotation [α] _W ²⁰ = + 4.8 ° (stock solution).

[0018] [4b] beta-Kan follower Synthesis of Ren carbonitrile by except using concentrated hydrochloric acid 200mL instead of 25% sulfuric acid oximation reaction and nitrile reaction the same operation as described above [3b], beta-Kanforen Yield 85
Earned in%. The boiling point of the obtained compound is 80 to 82 ° C / 5m.
mHg, refractive index n _D ²⁰ = 1.4672, density d ₄ ²⁰ =
It was 0.8211.

[0019] Mono Tel Bae alkenyl carboxylic acid [1c] ~ [4
Synthesis of c]: Synthesis of [1c] (+)-3,7-dimethyl-2-octenoic acid: 300 m equipped with stirrer, reflux condenser, dropping funnel
(4) (-)-3,7- of the above [1b] was added to an L four-necked flask.
Take a mixed solution of 10 g (0.066 mol) of dimethyl-2-octenenitrile and 70 mL of methanol, and add 0.4 M
After adding 100 mL of KOH-methanol solution, 20
Heated to reflux for hours. After completion of the reaction, operation was carried out in the usual way, and then distillation was carried out under reduced pressure to obtain (+)-3,7-dimethyl-2-octenoic acid with a yield of 89%. The boiling point of the obtained compound is 91 to 92 ° C./2 mmHg, and the refractive index n _D ²⁰ = 1.465.
1, density d ₄ ²⁰ = 0.9308, specific rotation [α] _W ²⁰ =
It was + 5.5 ° (stock solution).

[0020] [2c] (+) - 1 -p- Menten-9
Synthesis of yl = acetic acid: (+)-1-p-menthen-9-yl = acetic acid was collected from (+)-1-p-menthene-9-nitrile by the same operation as the hydrolysis reaction of the above [1c]. It was obtained at a rate of 78%. The boiling point of the obtained compound is 81 to 83 ° C /
4 mmHg, refractive index n _D ²⁰ = 1.4814, density d ₄ ²⁰
= 0.9164, and specific rotation [α] _W ²⁰ = + 86 ° (stock solution).

[0021] [3c] (+) - Synthesis of alpha-Kanforen acid: (+) - α- cans follower Ren nitrile from above [1
By the same operation as in the hydrolysis reaction of c], (+)-α-camphorenic acid was obtained with a yield of 80%. The boiling point of the obtained compound was 96 ° C./3 mmHg, and the refractive index n _D ²⁰ = 1.470.
1, density d ₄ ²⁰ = 0.8980, specific rotation [α] _W ²⁰ =
It was + 10.0 ° (stock solution).

[0022] The synthesis of [4c] β- Kanforen acid: β-
By the same operation as the above-mentioned hydrolysis reaction of [1c] from camphorene nitrile, β-camphorenic acid was obtained with a yield of 82%. The boiling point of the obtained compound is 160 ° C / 11 mmH.
g, refractive index n _D ²⁰ = 1.4712, density d ₄ ²⁰ = 1.0
It was 156.

[0023] Synthesis of mono-ether Bae sulfonylamide compounds A to L: Synthesis of citronellyl amide: (1) Compound A: stirrer, four-necked flask 50mL equipped with a calcium chloride tube and a dropping funnel (+) - 3 , 7
1.0 g (0.006 mol) of dimethyl-2-octenoic acid and 0.3 mL of HPMA (hexamethylphosphor (tolu) amide (amide solvent)) were taken, and thionyl chloride was adjusted to 0. After dropping 86 g (0.007 mol), the mixture was stirred for 0.5 hours, thionyl chloride was distilled off under reduced pressure, 1.0 mL of 33% dimethylamine aqueous solution was added dropwise, and the mixture was stirred at room temperature for 1.5 hours. After the reaction,
The crude reaction oil obtained by the conventional method was distilled under reduced pressure to obtain (-)-N, N-dimethyl-3,7-dimethyl-6-.
Octaenamide was obtained in a yield of 63%.

[0024] (2) Compound B: but using 44% diethylamine aqueous solution 1mL instead of dimethylamine by the same operation as the condensation reaction of the above (1), (-) - N, N-
Diethyl-3,7-dimethyl-6-octaenamide was obtained in a yield of 72%. (3) Compound C: (-)-N, N- by the same operation as the condensation reaction of (1) above except that 1 mL of dipropylamine and triethylamine were used instead of dimethylamine.
Dipropyl-3,7-dimethyl-6-octaenamide was obtained in a yield of 85%.

[0025] 1-p-menthene-9-amide Synthesis of Compound D, E and F: (+) - 3,7- dimethyl-2-
Instead of octenoic acid, the starting material was (+)-1-p-
The above (1), except that Menten-9-yl = acetic acid is used,
By the same operation as the condensation reaction of (2) and (3), the corresponding N, N-dimethylamide compound D, N, N-
Diethylamide compound E and N, N-dipropylamide compound F were obtained.

The α- cans follower Synthesis of Ren amide: Compound G, H and I: (+) - 3,7- dimethyl-2-
By the same operation as the condensation reaction of the above (1), (2) and (3), except that (+)-α-camphorenic acid was used as a starting material instead of octenoic acid, the corresponding N, N-dimethylamide was obtained. Compound G, N, N-diethylamide compound H and N, N-dipropylamide compound I were obtained.

The β- cans follower Synthesis of Ren amide Compound J, K and L: (+) - 3,7- dimethyl-2-
By the same operation as the condensation reaction of the above (1), (2) and (3) except that β-camphorenic acid was used as a starting material instead of octenoic acid, the corresponding N, N-dimethylamide compounds J and N were respectively obtained. , N-diethylamide compound K
And N, N-dipropylamide compound L were obtained.

The physical constants and yields of 12 kinds of mono-ether Bae sulfonyl amide compound obtained by the above operations in Table 1, also shows the spectral data in Table 2.

[Table 1]

[ 0029 ]

[Table 2] Compounds A to L have an IR spectrum of 16
Absorption of carbonyl around 25 to 1650 cm ^-1 , ¹ H
-In the NMR spectrum, the structure was confirmed by characteristic absorptions of trisubstituted olefin proton, methylene derived from tertiary amide, methyl proton, allylmethyl, and gem-CH ₃ .

[ 0030 ] Below, several examples of preparation examples for various dosage forms using the above compounds will be shown.

[ 0031 ]

[ 0032 ]

Next, has performed a variety of efficacy tested for repellency and extermination effect on the mono-ether Bae sulfonyl amide compounds, are shown below.

[0034] The relative Test Example 1 albopictus Compound B (citronellyl amide), E (1-p- menthene-9-amide), H (alpha
-Camphorenamide) and K (β-camphorenamide ) ( both N, N-diethylamide compounds) were tested for repellent effect. DEET was also tested for comparison. The test method is as follows . Test method: 30 cm × 40 cm × height 30 c shown in FIG.
Approximately 300 adult Aedes albopictus females are placed in a wire net cage 1 of m.
The arm 2 of the subject who was released and applied a prescribed amount of the test agent 3 therein.
Insert it through the sleeve 4 and
The number of bites (animals) of each was counted . The amount of drug processed is 2g / m
² and the drug application was applied to one arm of the subject in a 5 × 5 cm area
Chemical solution diluted with ethanol (2.5% W /
0.2 mL of V) was applied to each place. One test
It was performed by four test subjects . 2 arms per subject 4
Of the drug-treated area applied to the place, the
For the treatment area where the bite was recognized severely, at that time
The test was discontinued .

The test results (of thorns咬数/ 4 subjects 3 minutes
The average) is shown in Table 3 below.

[Table 3 ] As is clear from the test results shown in Table 3 , the monoterpenylamide compound of the present invention is extremely excellent in activity and durability as a repellent as compared with DEET.

[0036] The compound against Test Example 2 housefly B (citronellyl amide), E (1-p- menthene-9-amide), H (alpha-
Camphorenamide) and K (β-camphorenamide ) ( both N, N-diethylamide compounds) were tested for repellent effect. DEET was also tested for comparison. Test method: Each test agent was treated with a chemical treatment amount of 0.1, 0.5,
Acetone solution (0.039, 0.192, 0.77% W / V) diluted to a predetermined concentration to give 2.0 g / m ^2.
Apply 1 mL of filter paper (Toyo filter paper 5A, 7 cmφ) to 1
Air dried for hours. Then, as shown in FIG. 3, about 600 test insects were placed in an adult rearing cage 5 (30 × 30 × 40 cm stainless steel 16 mesh knitting basket), and each test agent-treated filter paper 6 and untreated The filter paper 7 was hung. Ten minutes after the filter paper was hung, the number of test insects remaining on each filter paper was counted, and the repellent rate was calculated by the following formula. (If the repellency rate is negative, the repellency rate is 0.)

[0037] The test results are shown in Table 4 below.

[Table 4 ] As is clear from the test results shown in Table 4 , the monoterpenylamide compound of the present invention is superior in activity as a repellent against houseflies as compared with DEET, and is excellent in repellent effect even at low concentrations. I understand that

[0038] The relative Test Example 3 German cockroaches Compound B (citronellyl amide), E (1-p- menthene-9-amide), H
(Α-camphorenamide) and K (β-camphorenamide ) ( both are N, N-diethylamide compounds)
Was tested for its repellent effect. DEET was also tested for comparison. Test method: As shown in FIG. 4, a shelter 9 (1 × 2c) in which a plywood board was assembled in a cross with 10 male and female German cockroaches in an acrylic box 8 of 20 × 20 cm.
m), a container 10 containing food (solid feed) and a container 11 containing water are arranged and prepared for one day, and a predetermined amount of the test agent is placed in one corner of the acrylic box as shown in the figure. A 7 × 7 cm filter paper 12 (treated area) coated with was placed in another corner of an untreated filter paper 13 (untreated area).

[ 0039 ] The treatment section was treated with an acetone solution (1.23% W) diluted to a predetermined concentration so that the amount of drug treated was 2 g / m ^2.
/ V) 2 mL of Toyo Filter Paper No. 12.5 cm in diameter. 5A
It was applied to the above, dried in air for 1 hour, and cut into 7 × 7 cm. Then, the number of test insects remaining on the wooden shelters placed on both the treated and untreated filter papers was counted over time. Individuals still in the shelter were shaken off every day and the positions of the treated and untreated plots were exchanged. The repetition was repeated 3 times, the average number of individuals in each section was calculated, and the repellent rate was calculated by the following formula. The numbers of individuals in the feeding and water areas were excluded from the calculation. (If the repellency rate is negative, the repellency rate is 0.)

[0040] The test results are shown in Table 5 below.

[Table 5 ] As is clear from the test results shown in Table 5 , the monoterpenylamide compound of the present invention is superior in activity and durability as a repellent against German cockroaches as compared with DEET.

[0041] The compound against Test Example 4 German cockroaches B (citronellyl amide), E (1-p- menthene-9-amide), H
(Α-camphorenamide) and K (β-camphorenamide ) ( both are N, N-diethylamide compounds)
Was tested for insecticidal effect. DEET was also tested for comparison. Test method: glass plate forced contact method 1 mL of an acetone solution (2% W / V) diluted with the test agent to a prescribed concentration so that the drug treatment amount was 2 g / m ² was applied.
An air-dried 10 × 10 cm glass plate was used. Separately, vaseline was applied to the inner wall, and a waist-high petri dish having a diameter of 9 cm and containing 10 female German cockroach adults was prepared. The hip-high Petri dish was turned upside down, the test insects were forcibly contacted with the glass plate for 24 hours, and the number of dead insects was observed. The repetition was performed 3 times.

[0042] The test results are shown in Table 6 below.

[Table 6 ] As is clear from the test results shown in Table 6 , DEET
Has no insecticidal activity against German cockroaches, whereas the monoterpenylamide compound of the present invention has excellent activity as an insecticide against German cockroaches.

[0043] The relative Test Example 5 Tyrophagus and D. farinae compound B (citronellyl amide), E (1-p- menthene -
9-amide), H (α-camphorenamide), and K
The acaricidal effect of (β-camphorenamide ) ( all N, N-diethylamide compounds) was tested. DEET was also tested for comparison. Test method: Clip method 2 mL of an acetone solution (0.67% W / V) obtained by diluting each test agent to a predetermined concentration so that the amount of drug to be treated was 1 g / m ² was applied to Toyo Filter Paper No. 1 having a diameter of 12.5 cm. It was applied to 5A, air-dried for 1 hour, folded in two, and a test mite was put inside the piece and sealed with a clip. The clip was opened 24 hours later, the mortality rate was investigated, and the corrected mortality rate was calculated by the following formula (3 repetitions). (If the corrected mortality rate takes a negative value, the corrected mortality rate shall be 0.)

[0044] The test results are shown in Table 7 below.

[Table 7 ] As is clear from the test results shown in Table 7 , DEET
It can be seen that the monoterpenylamide compound of the present invention is extremely excellent in activity as an acaricide against the mites of the genus Aedes albicans and Dermatophagoides farinae as compared with the above.

[0045] The relative Test Example 6 Tyrophagus and D. farinae compound B (citronellyl amide), E (1-p- menthene -
9-amide), H (α-camphorenamide), and K
The growth inhibitory effect of (β-camphorenamide ) ( all N, N-diethylamide compounds) was tested. DEET was also tested for comparison. Test method: medium mixing method Acetone solution of each test agent (0.
10% of 1% W / V) was added, and acetone was evaporated and mixed to make the drug concentration 100 ppm. This is serially diluted with powdered feed to 2 times, 50, 25,
It was adjusted to be 12.5 and 6.25 ppm. The mites were added to these treated powders at 300 / g, and under the optimum conditions (humidity was 85% for the diamondback mites, humidity was 75% for the Dermatophagoides farinae, and the temperature was 27 ° C).
After storage for a predetermined number of days (4 weeks for the mite mite, 6 weeks for the mite dust mite), the number of live mites in the medium was examined, and the growth inhibition rate was calculated by the following formula. The 90% growth inhibitory concentration (IC90) was calculated from the results of the growth inhibitory rate at each concentration step.

[0046] The test results are shown in Table 8 below.

[Table 8 ] From the test results shown in Table 8 , it can be seen that the monoterpenylamide compound of the present invention is extremely excellent in activity and durability as an acaricide against acarid mites and Dermatophagoides farinae compared to DEET.

[0047] The relative Test Example 7 Tyrophagus and D. farinae compound B (citronellyl amide), E (1-p- menthene -
9-amide), H (α-camphorenamide), and K
The mite repellent effect of (β-camphorenamide ) ( all N, N-diethylamide compounds) was tested. DEET was also tested for comparison. Test method: 1 g of a medium having a mite density of 10,000 / g was placed in a petri dish having a diameter of 7 cm, and allowed to stand for 3 hours until the mite became stable. On the other hand, an acetone solution (0.67%) was prepared by diluting each test agent to a prescribed concentration so that the amount of drug treated was 1 g / m ^2.
2 mL of Toyo filter paper with a diameter of 12.5 cm. 5
It was applied to A, air-dried for 1 hour, cut into 4 × 4 cm pieces, placed on the above-mentioned medium, and a black paper cut into 2.5 × 2.5 cm pieces was placed on the medium. I counted the number. In addition, an untreated section using filter paper not coated with each test agent was also provided, and the repellency rate was calculated by the following formula.

[0048] The test results are shown in Table 9 below.

[Table 9 ] As is clear from the test results shown in Table 9 , DEET
It can be seen that the monoterpenylamide compound of the present invention is superior in activity as a mite repellent against the mites, Plutella mites and Dermatophagoides farinae, in comparison with the above.

[ 0049 ]

INDUSTRIAL APPLICABILITY As described above, the terpenylamide compound according to the present invention has high repellent activity, insecticidal activity and acaricidal activity which are higher than those of DEET which is commercially available against a wide variety of harmful insects, and the residual Highly effective. Further, it has a low permeability to the skin, and is therefore considered to be advantageous in safety over DEET. Therefore, by using the terpenylamide compound according to the present invention as an active ingredient of pest repellents, insecticides, acaricides, etc., excellent repellent effect and extermination against a wide variety of pests such as mosquitoes, flies, cockroaches and mites. Exert an effect.

[Brief description of drawings]

1 is an overall reaction scheme for synthesizing the amide compound of the present invention.

FIG. 2 is a schematic configuration diagram showing a partially broken view of the test apparatus used in Test Example 1.

FIG. 3 is a schematic configuration diagram showing a partially broken test apparatus used in Test Example 2 ;

FIG. 4 is a schematic plan view of a German cockroach repellent test device used in Test Example 3 .

[Explanation of symbols] 1 wire mesh cage 2 arms 3 test agent application area 4 sleeve 5 adult cage 6 test agent treated filter paper 7 untreated filter paper 8 acrylic box 9 plywood shelter 10 bait container 11 water container 12 test agent treatment Filter paper 13 Untreated filter paper

[Procedure Amendment 2]

[Document name to be corrected] Drawing

[Name of item to be corrected] Figure 1

[Correction method] Change

[Correction content]

[Figure 1]

Claims (6)

[Claims] 1. The following chemical formula 1 (In the formula, R ₁ is a monoterpenyl group, R ₂ and R ₃ are H and an iso- or normal saturated or unsaturated hydrocarbon group having 1 to 6 carbon atoms (provided that both R ₂ and R ₃ are H. ) Is an amide compound represented by the general formula of). 2. Citronellal, 1-p-Menten-9
An amide compound according to claim 1, which is an amide derivative of a monoterpene selected from the group consisting of -are, α-camphorene aldehyde, β-camphorene aldehyde, myrtenal, perilaldehyde and citral. 3. The amide compound according to claim 1, wherein R ₂ and R ₃ are both a methyl group, an ethyl group or a propyl group. 4. The following chemical formula 2 (In the formula, R ₁ is a monoterpenyl group, R ₂ and R ₃ are H and an iso- or normal saturated or unsaturated hydrocarbon group having 1 to 6 carbon atoms (provided that both R ₂ and R ₃ are H. ) The pest repellent containing an amide compound represented by the general formula (1) as an active ingredient. 5. The following chemical formula 3 (In the formula, R ₁ is a monoterpenyl group, R ₂ and R ₃ are H and an iso- or normal saturated or unsaturated hydrocarbon group having 1 to 6 carbon atoms (provided that both R ₂ and R ₃ are H. ) Is an amide compound represented by the general formula (1) as an active ingredient. 6. The following chemical formula 4 (In the formula, R ₁ is a monoterpenyl group, R ₂ and R ₃ are H and an iso- or normal saturated or unsaturated hydrocarbon group having 1 to 6 carbon atoms (provided that both R ₂ and R ₃ are H. ) Is a mitotic agent containing an amide compound represented by the general formula as an active ingredient.