KR800001449B1 - Preparation of Aryl Terpenoid Insect Maturation Inhibitor - Google Patents

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Description

Preparation of Aryl Terpenoid Insect Maturation Inhibitor

The present invention relates to the preparation of novel aryl terpenoid compounds effective in preventing the maturation of insects, in particular flies and mosquitoes, and controlling their development.

One of Schwartz told me that arylterpenoid compounds exhibit juvenyl hormone activity against some insects.

(LiFe Science 10, Part II Bio Chem. Gen. Mol. Biol., 1125-1132, 1971 and J. Econ, Entomol, 67,177-180, 1974), however, as is apparent from the results published in these two publications No correlation could be expected from the correlation. For example, there was no active correlation between the geometric isomers or the compounds whose structural differences were only substitutions on the aromatic share of the molecule.

Therefore, it is unexpected and surprising that the novel arylterpenoid compounds according to the present invention have a close correlation with each other and exert an extremely high effect on various kinds of pairs.

That is, the present invention is one of the objectives, by applying directly to insect larvae such as flies and mosquitoes or to the chrysalis to interfere with their development process to prevent the transformation from pupa to adult Is to provide.

It is still another object of the present invention to provide a novel compound which can prevent maturation transformation from larvae and pupa in advance by applying to natural growth media such as flies and mosquitoes.

It is another object of the present invention to provide a novel compound that feeds livestock or other animals and contains active ingredients in their excrement, which is a natural growth medium of the insect, thereby inhibiting the metamorphosis of flies and mosquitoes.

Another object of the present invention is to remove a novel compound that can suppress transformation of flies, mosquitoes, and the like by spraying a hostile place in and around the liver house.

The novel compounds according to the present invention having the advantage of satisfying the targets as described above have the following general structural formula.

In the above formula,

A is alkyl having 1 to 5 carbon atoms, preferably alkyl isofurophyll or alkyl with Sec-butyl; Alkoxy having 1 to 4 carbon atoms; Alkylthio having 1 to 4 carbon atoms; Nitro or 3,40 methylenedioxy, where A is preferably on para, is preferably on para, preferably an alkyl having 1 to 5 carbon atoms; R and R ¹ are individually methyl or ethyl, preferably methyl; R ² is preferably alkyl having 1 to 4 carbon atoms, or preferably methyl or ethyl, with methyl being most advantageous.

The novel compounds of the above structural formulas according to the present invention are applied directly to insect larvae or pupa, or applied to natural growth media such as feces of animals by placing them in food or feed of animals such as livestock or poultry. It is effective in suppressing the growth metamorphosis of flies and mosquitoes by various application methods such as quenching or spraying around livestock.

In particular, the present invention relates to novel aryl terpenoid compounds that are well known in housefly Musca domestica (L.), gold fly Musca autumnalis debeer, stable fly Stomoxys calcitrans (L.), Creeper Haematobia irritans (L.) and mosquitoes, Anopheles quadrimaculatus and the like. Emphasis is placed on preparation and their active action. Some structures and names of such compounds are listed in Table 1. All of these compounds were tested by applying them directly to insect pupa, some of which were fed to runaways or sprayed onto incubators containing artificial insect growth media. An arylterpenoid compound according to the present invention is generally prepared according to the following scheme.

Scheme 1

Wherein A, R, R ¹ and R ² are as defined above.

Benzyl alcohol, used as starting material, is freed from the ortho isomer, which is contaminated by the radial mass. Chloride and triphenylphosphonium salts are produced according to conventional methods and are almost quantified. The Wittig reaction (glass reaction 14, pp. 270-490, published by John Wiley & Sons, 1965) was carried out in anhydrous ethanol based on sodium epoxide. Thus, a 60:40 mixture of the Z and E isomers is obtained in a yield of 80% The alkoxy mercury-dehydration reaction is carried out by using a suitable alcohol (R ² OH) as a solvent (J. Med. Chem., Vol. 12, pp. 191-192, 1969 edition, see) Yield 80-90% Now, the remaining double-valent table catalyzes PtO ₂ It is atmospheric pressure (大 수소) and hydrogenated (水 素 添加).

As an example for illustrating the typical thing of the manufacturing method by this invention, the preparation example of the number 4 of Table 1, and a compound is demonstrated in detail.

Table 1 Preparation of No. 4 Compound

P-isopropylbenzylchloride

=1,5212P-isopropylbenzyl alcohol (128 g, 0.85 mol.) Was added dropwise to 400 ml of concentrated Hcl with stirring, maintaining the temperature at 25 to 30 ° C. during this addition period. The reaction mixture was stirred for 4 hours and then poured into 500 ml of ice water to complete the reaction and extracted with hexane. Next, this hexane extract was washed until neutralized to give 135 g (yield 93%) of P-isopurofilbenzylchloride. Boiling point 108 degrees Celsius / 18mm

= 1,5212

P-isopropylbenzyl triphenylphosphonium chloride

P-isopurofilbenzylchloride (168.5 g, 1 mol) and triphenylphosphine (275 g, 1.05 mol) were refluxed in acetonitrile (600 mL) overnight. About 300 mL of acetonitrile were removed under vacuum and 500 mL of ether was added. The salt was left to determine, filtered off and washed with ether.

388 g (yield 90%) of the desired salt was obtained in the first collection of the hard body. Some additional salt could be recovered from the mother liquor.

4,8-dimethyl-1- (P-isofurophylphenyl) -nona-1,7-diene

Sodium (21 g, 0.9 at) was added to 1500 mL of anhydrous ethanol and stirred, and 388 g of P-isopropylbenzyltriphenylphosphonium chloride was added to the solution. As a result, the phosphorane solution was cooled to 15 ° C-20 ° C. (The pale orange color disappears as the temperature decreases.) The reaction mixture was refluxed for 40 hours while dropwise addition of vacuum distilled citronellal (150 g, 1 mol). The cooled reaction mixture was filtered to remove sodium chloride, most of the alcohol was distilled off under vacuum, and 500 mL of hexane was added. Triphenylphosphine oxide was left to crystallize and filtered. The solvent was removed from the mother liquor under vacuum and again 500 ml of hexane was added. Then, 500 ml of hexane was added again by cooling. Subsequently, triphenylphosphine oxide was recovered by cooling again. Hexane was evaporated again and the residue was distilled into some isoflavol (contaminant of citronellal), followed by some isoflavol (contaminant of citronellal) followed by 200 g (82% yield) of desired product. Got it.

Boiling point 150-145 ° C / 0.1mm

=1.5172E to Z ratio, about 40: 60,

= 1.5172

4, 8-Dimethyl-1- (P-isofurophylphenyl) -non-1-ene

16 g (0.7 g at) of sodium was added to 600 ml of ammonia solution and stirred. In this solution, 93 g (0.34 mol) of 4, 8-dimethyl-1- (P-isopurophyl) was added to 125 ml of mustetrahydrofuran. A solution containing phenyl) nona-1 and 7-diene was added dropwise, but the total addition time was 1 hour. The excess sodium was destroyed by careful addition of methanol to the sodium, then 200 mL of hexane was added and the ammonia was left to evaporate. NH ₄ Cl saturated solution was carefully added to the residue. The organic layer was separated, the aqueous layer was diluted with water, and hexane was extracted twice. The mixed hexane layer was washed with water, diluted with HCI and brine and dried. Hexane was evaporated and the residue was distilled off to give the title product.

Quantity 88 g (94%)

Boiling point 130-135 ℃ / 0.1mm

=1. 4938

= 1. 4938

9-ethoxy-1- (P-isopurophyl-phenyl) -4, 8-dimethylnonane

Stirring a solution containing 27 g (0.1 mol) of 4,8-dimethyl-1- (P-isofurophylphenyl) -non-1-ene in 125 ml anhydrous ethanol, and 34 g (0.11 mol) Mercury acetate was added dropwise at room temperature. The mixture was stirred for 1 hour, ie all of the second mercury acetate was dissolved. The reaction mixture was then cooled to 5 ° C. and 15 g of NaOH contained in 100 ml of 80% ethanol was added dropwise to maintain the reaction mixture at 25 ° C. or lower. Then, 3.5 g of NaBH ₃ was added in portions, and the mixture was kept at 25 ° C or lower again. Hexane (200 mL) and 200 mL of water were added and the mixture was stirred until the water temperature solidified. The organic layer was separated and the aqueous layer was extracted with two portions of 100 mL of hexane. This mixed hexane layer was extracted with water and diluted with dryness, water and brine. The organic layer was then dried to remove hexane in vacuo. The residue was distilled at 145 ° C./0.1 mm to obtain 28.5 g (yield 90%) of the title compound.

=1.4806

= 1.4806

The effects of these new compounds on houseflies and gold flies were determined according to a procedure by Miller et al. (J. ECon Entomol. 63, pp. 853 to 855, 1970). Harris) et al. (J. Econ. Entomol. 66, pp. 1099-1102, 1973). In essence, these procedures are carried out by implanting eggs or larvae of the insects of interest into the feces of excreted animals or artificial media containing the compounds to be tested. The test results are shown in Table 2. The effect of these compounds on stable flies and house flies was described in J. Econ. As determined in Entomol, pages 65, 1361-1364, 1972, it was determined by application to the skin of the pupal chrysalis.

Compounds No. 2 and No. 4 of Table 1 were tested by spraying fly larvae or eggs on the feces of livestock fed them in addition to the above procedure. The larvae of falcons and gold flies were sprayed on animal feces fed test compounds and tested according to Miller and Uebel procedures (J.Econ.Entomol. Pp. 67,69-70, 1974). Eggs from flies were planted in feces of animal-fed livestock and tested according to the procedure described above by one of Harris. The test results are shown in Table 3. The spray test was conducted according to the procedure described by Wright (J. Econ. Entomol. 65, pp. 1361-1364, 1972). Contains 25 parts by weight of the compound to be tested, 65 parts by weight of xylene, 10 parts by weight of nonionic surfactant, and octylphenoxypolyethoxyethanol (Triton x-100) contained in 100 ml of water Appropriate amounts of one emulsified concentrate were sprayed into the incubator containing the artificial medium and the 4 day old housefly larva or 6 day old stable larvae. A spray-treated incubator is placed in the cage to prepare for adult transformation. Percentage of metamorphosis was determined by counting adult females after 14 days of spraying.

As shown in Table 2, the novel compound according to the present invention exhibited a highly active effect when tested by sprinkling larvae or eggs on the natural growth medium of the gold fly in the manner described above. Compounds No. 1 and No. 2 showed a high effect on the sofa. In general, gold flies were more resistant to maturation inhibiting compounds than couch flies. Since compounds Nos. 3 and 4 exhibited a high inhibitory effect on gold flies, testing of these compounds was omitted. It was.

In the four kinds of flies adopted for the purpose of the present invention, the ranks of the weakest to the most resistant to the action of the maturation inhibitory compound were house flies, gold flies, stable flies, and sophiri. Of course, there may be occasional exceptions to this general sequence.

When 0.1 to 0.01 μg of acetone solution of each of the six compounds of the present invention was applied to the skin of stable flies and housefly larvae, it was found that they were sufficient to prevent metamorphosis.

The test results of feeding the compounds of Table 1 No. 2 and No. 4 to livestock are presented in Table 3. In this test, subjects were fed to livestock for a week, but feces from day 3 were used for the test. Compound 4 showed the best action against four flies.

In the spray test of the compounds of Nos. 2 and 4, both of them showed excellent effect. In particular, the effect was higher at 10 mg / sq. These spray test results are presented in Table 4.

In addition to the four types of flies, the novel compounds mentioned above according to the present invention showed significant effects on Anopheles quadrimaculatus and two other mosquitoes. In other words, the extremely low LC-50 values—water fungus lethality in the water and 50% metamorphosis—are surprising numbers for those working in the field. The test results are presented in Tables 5 and 6. The test procedure used here is a conventional method, an alternative of which is described in Mosguito News, pages 31,540-543, 1971.

It is remarkable that the novel compounds according to the present invention show a great effect on fly species and mosquitoes, and show very low action when tested on conventional test insects T molitor and O fasciatus. It is to say that the compound of the present invention has. In fact, in the test for them, the fourth compound of Table 1 had no activity, and even other compounds had only a slight degree even if they had action. An important point to note here is that in general, if a substance or compound is tested against T molitors and O fasciatus as described above, it is found that there is no activity at all or only a weak action, then other insects It is known that there is no need for testing. The reason is that the two insect species are more sensitive to the influence of the juvenyl hormone-like substance than any other insect species. Therefore, the extremely high activating effect exhibited by the compounds of the present invention against four flies and three mosquitoes is an advantage that has never been predicted or expected before.

[Table 1]

[Table 2]

[Table 3]

[Table 4]

[Table 5]

[Table 6]

Claims (1)

As described above in the text, a method for preparing an arylterpenoid insect-maturation inhibitor represented by the following structural formula (II), which is obtained by adding hydrogen to a compound having a double bond represented by the following structural formula (I).

Wherein A is alkyl having 1 to 5 carbon atoms, alkoxythio, nitro or 3,4-methylenedioxy having 1 to 4 carbon atoms and 1 to 4 carbon atoms, R and R ¹ is methyl or ethyl individually, and R ² is alkyl having 1 to 4 carbon atoms.