JPS60199804A - Repellent for injurious organism - Google Patents

Abstract

PURPOSE:A repellent for injurious insects, containing a specific p-menthane derivative as an active constituent, and useful for protecting animals from blood- sucking injurious insects and mites, etc. CONSTITUTION:A repellent for injurious organisms contaning a p-menthane derivative of formula I , (R is OH, 1-9C alkylcarbonyloxy, phenylsulfonyloxy or Cl), e.g. p-menthane-3,8-diol or p-menthane-3-n-butyloxy-8-ol, as an active constituent. The above-mentioned compound of formula I (R is OH) is obtained by extracting or purifying a eucalyptus or cyclizing (+)-citronellal in sulfuric acid. Alternatively, the compound of formula I (R is R1) is obtained by reacting p-menthane-3,8-diol with a compound of formula II [(CH3-substituted) 1-9C alkyl]. The above-mentioned compound is used directly or by adding a carrier or assistant to form the compound into an emulsion, powder or cream, etc.

Description

Detailed Description of the Invention The present invention is based on the general formula % (1) (wherein, 几 is a hydroxyl group, a C, to C9 alkylcarbonyloxy group, a sulfonyloxy group which may have a methyl group, The present invention relates to a pest repellent characterized by containing as an active ingredient a p-menthane derivative represented by a C1-C2 alkylcarbonyloxy group or a chlorine atom.

Currently, there are a large number of diseases transmitted by pests, particularly insects and ticks, that are important worldwide due to their wide spread, large number of infected people, and fatality rates. In particular, diseases caused by biologically transmitted blood-sucking pests and ticks are a big problem.For example, mosquitoes cause malaria, yellow fever, dengue, phyciliosis, etc., blackflies cause onchocerciasis, etc.1. Fleas cause diseases such as onchocerciasis, etc. plague,
Tsutsugamushi causes typhus, etc., tsutsugamushi causes tsutsugamzo disease, etc. Many of these 11 play a specific role in the propagation of pathogens such as viruses, rickettsia, bacteria, protozoa, and nematodes. For example, pests or ticks that suck the blood of a diseased animal and carry the pathogen can infect other people, livestock such as pigs, or pets such as dogs when they suck blood again, and the power of transmission is immeasurable. In addition, when blood is sucked, blood is not lost, itching, rash, etc.
The damage caused by dermatitis etc. is also significant. Chickens reduce their egg production, and dairy cows reduce their milk production.

As described above, damage caused by blood-sucking pests and mites is significant, and insecticides are generally used to control them. However, these pests come from many sources, reproduce actively, and have complex ecology, so it is extremely difficult to completely control them using insecticides. Therefore, repellents are used to protect animals from these blood-sucking pests and mites.

Currently known repellents include N-diethyl-meth-
toluamide, dialkyl phthalate, 2-ethyl-1,
Although there are 3-1\xanediol and the like, none of them have a satisfactory repellent effect, and there is a strong desire for the emergence of a new repellent.

The present inventors noticed that there were few insects around eucalyptus trees, and as a result of intensive research, they confirmed that there was a substance in eucalyptus leaves that repelled harmful organisms, and the chemical structure was determined by the formula In (1), it was revealed that R is p-menthane-3,8-diol, which is a hydroxyl group, and further research on its derivatives led to the completion of the present invention.

The compound of formula (1) of the present invention can be produced as follows.

(2) p-menthane-3,8-thiol It can also be obtained by extraction and purification from p-menthane, but Agric.

13io1. cl+em, 46(1) p-319
(1982) (J-Am, Cbem, Soc, ring closure of citronellal in sulfuric acid,
75.2367 (1953).

(1) A compound of formula (11) in which RIJ''-C1 to C3 are alkylcarbonyloxy groups is produced as shown below.

i.e. p-menthane-3,8-diol in a tertiary amine such as pyridine or in an inert organic solvent such as benzene, toluene, cyclohexane, methyl ethyl ketone in the presence of a tertiary amine such as pyridine with the formula % formula %(2) (wherein R1 may have an alkyl group or methyl group of 01 to C0) and a compound represented by 0 to 80°C, preferably 30 to 6
It can be obtained by reacting at 0°C.

■ A compound in which 1t in formula (1) is a phenylsulfonyloxy group which may have a methyl group is substituted for the compound of formula (2) in the method of ■ by formula % formula % (3) (wherein 1 (2 represents a phenyl group which may have a methyl group) It can be obtained by carrying out the same reaction as in method ① except that 2 represents a phenyl group which may have a methyl group.

■ In formula (1), I(, is a chlorine atom) A compound of formula (1) obtained by the method of It can be obtained by reacting a curing agent such as thionyl chloride or lithium chloride in an inert organic solvent such as acetone or methyl ethyl ketone, preferably under heating and reflux.

A compound in which R in formula (1) is an 01-C2 alkyl carnocoyl group is prepared by adding p-menthane-3,8-diol to R.I. in an organic solvent such as pyridine. Add an alkyl isocyanate represented by NCO (3) (in the formula, R3 represents a Cl-C2 alkyl group) and heat at 50°C to 12°C.
It can be obtained by heating reaction at 0°C.

Below is a synthesis example of the compound of the present invention! show.

Synthesis Example 1 p-menthane-3,8-cis-diol (([s compound x
1) and p-menthane-3,8-trans-diol (compound Nll2): In an Erlenmeyer flask (100 ml volume), add 20.0 bar of ('→-citronellal ([α] crystallite + 10.23). 13
mol) and cooled the reaction vessel to 0°C. 5 for this
% sulfuric acid aqueous solution was slowly added dropwise without stirring, and the reaction solution was stirred at room temperature for 27 hours. After extracting the organic layer 4 times with 100 ml of ether, the ether phase was extracted with 5 ml of ether.
It was washed three times with 100% aqueous sodium carbonate solution, three times with 100 ml of saturated saline, and dried over 1 ml of anhydrous sodium sulfate. After concentrating the ether, the crude extract was subjected to Norica gel column chromatography (71 Tsukagel 500!).
7- ;Solvent system ether-hexane) 6.319・(42%) of ketsis isomer and 252g of trans isomer
(17%) 11 crystallized within the year. It was dissolved in a small amount of ether and recrystallized from hexane.

Cis form Trans form Synthesis example 2 p-menthane-3-n-butyloxy-8-ol (
Synthesis of compound N115): In a three-day flask (10 ml volume), (-1-1p-menthane-3,8-nosudiol 71.3 #1 g (0,414
m+nol), add 1 ml of pyridine and dissolve.
The mixture was stirred while cooling in a water bath. The reaction vessel was tightly stoppered with a stopper and a silicone cap, and 66 m9 (0.62 mmol) of n-butyryl chloride was slowly dripped through the silicone cap using a microsyringe. After stirring for 20 minutes, the water bath was removed and the mixture was stirred at room temperature. Next, the mixture was stirred at 500G for 12 hours and extracted with ether. The ether layer is IN = hydrochloric acid 20 m
It was washed twice, then washed four times with 20 ml of a 5% aqueous sodium carbonate solution, and four times with 20 ml of saturated saline.

After drying over anhydrous magnesium sulfate and removing the ether, approximately 70 m5 (70% yield) of crude crystals of the target product are obtained.

Synthesis Example 3 Synthesis of p-menthane-3-tosyloxo-8-ol (compound N110): In a three-day flask (10me volume), add p-menthane-3°8-
219-(1.27 mmol) of trans-diol was taken and 4 ml of pyridine was added to dissolve it. The reaction vessel was stirred while being cooled in a water bath, and tosyl chloride 5 was added to it.
2 imq (2,73 mmo+) was slowly added.

Stirring was carried out at 20° C. for 22 hr, with the entire reaction vessel wrapped in aluminum foil to block light. 8 ml of reaction water was added and extracted three times with 30 ml of ether, and the ether layer was washed four times with 40 ml of 2N hydrochloric acid and three times with 40 ml of saturated brine.

After drying over anhydrous magnesium sulfate, ether is removed to obtain 395 mg of crude extract. that it is a tosylated product,'
Synthesis example 4 p-menthane-3-chloro-8-ol (compound 11) confirmed by H-NM solution and IR
) Synthesis: Three-day flask (10 ml volume) equipped with a condenser
Take 395 ml of the crude extract from the previous section and add 6 ml of dehydrated acetone.
ml was added and dissolved. Lithium chloride 109 m9
(2.57 mmol) was gradually added, zeolite was added, and the mixture was heated under reflux for 14 hours in an oil bath. After cooling with water, 10 ml of water was added and extracted three times with 25 ml of ether.

The ether layer was washed four times with 40me saturated brine and dried over anhydrous magnesium sulfate. The ether was concentrated under reduced pressure to obtain 365 m9 of crude extract. Gas chromad and TLC
Two components were detected, and the chlorinated product was separated using column chroma) (Si02). White needle-shaped crystal target 121mp (
The yield from p-menthane-3°8-trans-diol was 50%).

Synthesis Example 5 Synthesis of p-menthane-3-methylcarbamoyloxy-8-ol (Compound N12) 2 Examples of compounds obtained by the above method are listed below.

p-menthane-3,8-cyan 3250m-'(OH)Sudiol M, W, 172 p-)ton17-3.8-) 3250GI+-'(OH
) Lance-diol M, W, 172 p-menthane-3,8-cis-diol 1P (0,00
58 mol) of dried pyridine. Add 0.994P (0,0174 mol) of methyl isocyanate and add 10
After reacting at 0 to 102°C for 13 hours, pyridine is distilled off and the mixture is extracted with ethyl acetate. The extract was washed with water, dried over anhydrous sodium sulfate, filtered, and concentrated. The resulting product was purified by column chromatography using 7 silica gel to give 0.6 g of white crystals, melting point 10 f1.
A target product exhibiting a temperature of ~105°C was obtained.

When using the compound of formula (31) of the present invention, depending on the purpose of use, the active ingredient compound may be used as it is, or an adjuvant may be used in combination to promote or stabilize the effect. For example, the above-mentioned effective The component compounds can be blended with alcohol and applied directly to areas where pest repellency is required, but preferably in various forms suitable for the application method, such as lotions, emulsions, oils, creams, and fumes. It can be used in the form of , aerosols, granules, resins, notes, soaps, etc.

In actual use, these various formulations can be used directly as they are, or they can be diluted with water to a desired concentration. For example, in the case of a person, cream or lotion is applied to the exposed area. In the case of plague dogs, it is used by soaking it in resin and inserting it into the collar.

Examples of the auxiliary agent here include a carrier (liquid diluent or solid diluent), various surfactants, or organic raw materials.

Among carriers, liquid diluents include aromatic hydrocarbons such as toluene, quinolene, and methylnaphthalene, alcohols such as inbanol and glycol, esters such as butyl acetate, ketones such as cyclohexanone, and amides such as dimethylformamide. , sulfoxides such as dimethyl sulfoxide, ceasorp such as ethyl cellosolve,
Petroleum fractions such as kerosene, knee f such as dibutyl ether, etc.
/lz 14, chlorinated hydrocarbons such as chlorobenzene, animal and vegetable oils, fatty acids and their esters, and water.

Among the carriers, solid diluents include clay, kaolin, talc, diatomaceous earth, silica, calcium carbonate, montmorillonite, bentonite, feldspar, quartz, alumina, and the like.

Surfactants include, for example, Stair 1J trimethylammonium chloride, higher alcohols, sodium sulfate, sodium liquninsulfonate, sodium naphthalenesulfonate formalin condensation, which are used as spreading agents, emulsifiers, wetting agents, dispersants and disintegrants. ammonium polyoxyethylene alkylbenzene sulfonate,
Cationic surfactants, anionic surfactants, nonionic surfactants such as sodium alkylbenzene sulfonate, polyethylene alkylphenyl ether, polyoxyethylene alkyl ether, lauryl betaine, etc.
Surface 14/I: Ionic interface , polyvinyl alcohol, polyethylene glycol, sodium polyacrylate, gum arabic, inglobilamide fist phosphate, xanthan gum, and the like.

All formulations can be used alone as they are, as well as herbicides, insecticides, plant growth regulators, acaricides, fungicides, sublimation insect repellents, known pest repellents, efficacy enhancers, coloring agents, etc.
It can also be used in combination with fragrances and stabilizers.

The content of the active ingredient compound in the repellent of the present invention varies depending on the formulation form, application method, and other conditions.
It is used in a range of 95% (by weight).

The preferred content of the active ingredient varies depending on the form of the preparation. For example, in the case of powder, the amount of active ingredients is 0.5~
20 pieces of book 111 + translation of Imahoki I soup 80~99.5
%, in the case of emulsions, the amount of active ingredients is 5-80%, and the content of adjuvants is 20-95%, and in the case of floaglu, the amount of active ingredients is 5-70%, and the content of adjuvants is 20-95%. The content is 30-95%, and in the case of water use agents, the amount of active ingredients is 20%.
~90%, the content of adjuvants is 10-80%,
For granules and microgranules, the amount of active ingredient is 0.5-15%, and the content of auxiliary agents is 85-995%. For lawn yong, the amount of active ingredients is 05-20%, and the content of adjuvants is 80-995%, and for cream, the amount of active ingredients is 01-20%, and the content of adjuvants is 80-999%.
%.

Next, formulation examples of the pest repellent of the present invention will be described in more detail, but the types and blending ratios of additives are not limited to these and can be used in a wide range.

Note that "part" means "1 part by weight".

Formulation Example 1 To 10 parts of emulsion active ingredient Compound No. 1, 65 parts of a mixture of xylene and methylnaphthalene (1:1) was added and dissolved, and then to this was added a mixture of nonylphenol oxide ethylene condensate and calcium tododecylbenzenesulfonate (8 parts). :2)25
Mix the two parts to make an emulsion. The basic rule is the same\or,
Dilute it 10 to 100 times with water and use it as a spraying agent or coating agent.

Formulation example 2. After adding 97 parts of a mixture of Merck and calcium carbonate (1:1) to 401 parts of active ingredient compound No. 401 and mixing and grinding to sufficiently evenly disperse and blend, 2 parts of silicic anhydride was further added and mixed and pulverized. Use as a powder. The main rule is to use it by spreading it.

Formulation example 3. An aerosol is obtained by dissolving 505 parts of aerosol active ingredient compound number in 15 parts of a mixture of methylnaphthalene and cyclohexane (1:1), and further mixing with 80 parts of Freon to make a homogeneous solution, and processing it into an aerosol form. It will be done.

The basic rule is to use it by spraying it.

Formulation example 4. Cream active ingredient compound number 301 parts, stearic acid 13 parts,
Add 2 parts of cetyl alcohol, 1 part of lanolin, 2 parts of liquid paraffin, and 67 parts of water and heat to dissolve and mix.Furthermore, 14 parts of heated glycerin is injected and stirred well to form a cream. The basic rule is to use it as is by applying it to the human body and animal body.

Formulation Example 5 Lotion 7 parts stearic acid, 0.5 parts lanolin and Tween 6
0 (polyoxyethylene sorbitan monostearate)
The mixture consisting of 7 parts is heated to 80°C and placed in a mixture of 82 parts of water and 25 parts of salicylic acid (at 60°C), and an additional 301 parts of active ingredient compound number is added with rapid stirring to form a lotion. The basic rule is to use it by applying or spraying it on the human body or animal body.

The applied amount of the active ingredient compound of the pest repellent of the present invention is:
The dosage may be determined as appropriate depending on the dosage form, application method, application area, etc., but in the case of lotions and creams, the amount to be used is, for example, in order to prevent damage from blood-sucking pests and mites. When applied to the skin of animals, the amount of active ingredient compound is 0.0 per 1 d of area to be applied.
1 m9 or more; preferably about 10~~ per 177Z'
It is appropriate to have an IP exist.

Test examples will be shown below to explain the present invention in more detail. In addition, the compounds shown in Table 1 were used in the test. The test compound number in each test example corresponds to the compound number in Table 1.

Test Example 1: Blood-sucking repellency test against adult Aedes albopictus A lotion containing a predetermined amount of the compound of the present invention was uniformly applied to a bag-shaped 12 ctn x 7 m wire mesh to hold a mouse in an amount of 50 ml per t m2.

After air drying for 30 minutes at room temperature, mice were fixed therein. A mouse was placed in an insect rearing cage containing 50 male and 50 male Aedes albopictus adults 5 to 7 days after emergence, and 3
The animal was given a chance to suck blood for 0 minutes. After killing the test insects in a dry heat oven, the presence or absence of blood sucking was observed and recorded. The results are shown in Table 2.

From the above table in Table 2, it was confirmed that all p-menthane derivatives used as active ingredients in the present invention have a blood-sucking repellent effect, and among them, compound number 1.7.2 shows particularly excellent activity. .

Note that the repellency rate was calculated using the following formula.

Test example 2. Test for sustainability of repellent effect of compounds In order to examine the sustainability of repellent effects of compounds, the same wire mesh (treated with 1% compound) used in Table 2 was tested in the same manner as in Table 2 after 5 days had elapsed. Ta. The results are shown in Table 3.

As is clear from Table 3, all of the compounds have a sustained repellent effect, which is superior to known compounds.

Test Example 3.7 Blood-sucking repellency test against Culex pipiens adults The blood-sucking repellency effect on Culex pipiens adults was investigated. The test method was based on Test Example 1, but the chance for blood feeding was set for 16 hours from 5pm to 9am the next day. The results are shown in Table 4.

Compound Nos. 7 and 2 exhibit higher 11a than known compounds and exhibit excellent repellent effects.

Patent applicant: Nippon Kayaku Co., Ltd.

Claims (1)

[Claims] General formula (1) (In the formula, 1t is a hydroxyl group, a 01-C3 alkylcarbonyloxy group, a phenylsulfonyloxy group which may have a methyl group, a C, -C2 noalkylcarbamoyloxy A pest repellent containing p-menthane derivative 4 (representing a group or a chlorine atom) as an active ingredient.