JPH07610B2 - Novel isoquinoline derivative - Google Patents

Description

TECHNICAL FIELD The present invention relates to a novel isoquinoline derivative. And this compound is useful as an agricultural / horticultural germicide or its intermediate.

[Prior Art] Various reports on the addition reaction at the 1-position of an isoquinoline quaternary salt, for example, N-benzoylisoquinoline quaternary salt (W.
E.McEwen et al., Chem. Rev., 55 , 511 (1955)), N-benzylisoquinoline quaternary salt (F. Brohnke, et al., Chem. Ber.,
90, 227 (1957)) or N- methyl isoquinoline quaternary salt (NJLeon ard etal., J.Am.Chem.Soc. , 71, 3405 (194
9)) and the like are known, but little is known about N-alkylisoquinoline quaternary salts except for the above N-methyl.

Further, JP-A-59-219,203 discloses a 1,2,3,4-tetrahydroisoquinoline derivative, and JP-A-59-219,204 discloses a 1,2,3,4-tetrahydroisoquinolinium salt derivative. However, none of them discloses 1-substituted isoquinoline.

[Problems to be Solved by the Invention] The present invention relates to the above-mentioned JP-A-59-219,203 and JP-A-59-219,2.
It was created based on the finding that the isoquinoline derivative as described in each of the 03 publications is effective against disease caused by certain bacteria and filamentous fungi. It is an object of the present invention to provide a novel isoquinoline derivative useful as a body, and particularly to provide a novel isoquinoline compound having an indole skeleton added to the 1-position of the isoquinoline skeleton.

[Means for Solving Problems] That is, the present invention provides the following general formula (I) or (II) (wherein X represents an alkyl group, a halogen or a nitro group, and Y represents an alkyl group, a halogen, Nitro group, amino group,
It represents a hydroxy group or a carboxy group, R represents an alkyl group, and m and n are integers from 0 to 2. ) It is an isoquinoline derivative represented by.

In the isoquinoline derivative of the present invention, the substituent X in the above general formulas (I) and (II) is preferably chlorine or bromine when it is a halogen, and is preferably a methyl group when it is an alkyl group. The substitution position is 3 to 8 positions of the isoquinoline skeleton, and when two substituents X are present, they may be the same or different substituents. In addition, the substituent Y
For, a methyl group is preferred when it is an alkyl group, chlorine or bromine is preferred when it is a halogen,
Further, the substitution position is 2-position and / or 4- to 7-position of the indole skeleton, and when two substituents Y are present, they may be the same substituent or different substituents. May be. Further, the substituent R is preferably an alkyl group having 1 to 20 carbon atoms, and the alkyl group may have an oxygen-containing group such as a hydroxy group and an alkoxy group in the substituent, and ethylene. It may contain an unsaturated bond such as a bond.

The compounds of the present invention represented by the above general formulas (I) and (II) can be produced, for example, by the following method.

That is, first, a nuclear nitrogen atom of isoquinoline is alkylated with an alkylating agent such as an alkyl halide to produce an N-alkylisoquinolinium salt, and the N-alkylisoquinolinium salt is reacted with indole in the presence of an alkali. Then, the obtained reaction mixture is extracted with an organic solvent, washed with water to remove unreacted materials, and then dried to remove the solvent to obtain the desired compound of the general formula (II).

Next, the compound of the general formula (II) thus obtained is hydrogenated by, for example, hydrogenation with sodium borohydride or catalytic hydrogenation in the presence of a platinum catalyst to give the compound represented by the general formula (I). To produce the compound.

The isoquinoline derivative of the present invention obtained in this manner is effective against various pathogenic bacteria which cause great damage in crop cultivation in agriculture, horticulture and the like. As the disease controlled by the compound of the present invention, many diseases can be mentioned, but typically, tangerine ulcer disease (Xanthomonas citri), which is a bacterial disease, and rice leaf blight (Xanthomonas)
oryzae), cucumber spot bacterial disease (Pseudomonas lachrym)
-ans), kanlan soft rot (Erwinia aroideae), etc., and rice sesame leaf blight (Cochliobolua miyabean), which is a filamentous fungal disease.
ua), rice blast (Piricularia oryzae), mandarin orange spot (Diaporthe citri), apple spot blight (Alternari)
a mali), Cucumber plague (Phytophthora parasitic)
a) and tomato anthracnose (Glomerella phomoides). Among them, the compound of the present invention is a significant disease of mandarin oranges, and it is difficult to control at the same time, and simultaneously exerts a remarkable effect against bacterial mandarin orange ulcer disease and filamentous fungal mandarin orange spot disease, and against individual diseases. It is not necessary to separately spray the medicine, which is extremely useful in terms of work simplification.
Since the compound of the present invention also has an action as an insecticide such as acaricide, it can be used for this purpose.

When used as an agricultural fungicide, the compounds of the present invention are formulated with surfactants, solvents, diluents, dispersants, emulsifiers, wetting agents, adhesives, thickeners, fertilizers and other liquid or solid carriers. As a result, it can be used in the form of a formulation that is easy to use as an agricultural chemical, and examples of the form of the formulation include wettable powders, emulsions, water solvents, powders, water-diffusing oils, granules, and the like. Any formulation form can be used.

[Examples] The present invention will be described below based on Examples, Formulation Examples and Test Examples.

I. Examples Example 1 [Production of compounds represented by the general formula (II)] Isoquinolines (39 mmole) shown in Table 1 and alkyl halides (43 mmole) shown in Table 1 were dissolved in 5 ml of dimethylformamide. The mixture was reacted at 150 ° C for 5 hours. Dimethylformamide in the reaction mixture was distilled off under reduced pressure using a glass tube oven, and the residue was washed with isopropyl ether to obtain an alkylisoquinolinium salt in a yield shown in Table 1.

3 g of the obtained alkylisoquinolinium salt and purified indole (to a molar ratio of alkylisoquinolinium salt of 0.9) were dissolved in 30 ml of acetonitrile, and the mixture was stirred at room temperature or under water cooling with respect to the alkylisoquinolinium salt. Equimolar
10 wt% -potassium hydroxide aqueous solution was added dropwise, and after reacting for 30 to 60 minutes, the reaction mixture was transferred to a separating funnel, and an oil layer separated between the upper acetonitrile layer and the lower aqueous layer was separated, This was dissolved in dichloromethane or chloroform, washed with water, dried over sodium sulfate, and then the solvent was removed at a temperature of 40 ° C. or lower to obtain the desired product of the general formula (II). Each of the obtained products was a reddish brown viscous grease. Further, the crude yield and purity of the product represented by the general formula (II) and the chemical shift (δ: ppm) of ¹ H-NMR of methylene hydrogen of the alkyl group bonded to the N atom at the 2-position of the isoquinoline skeleton Is shown in Table 1.

Further, Table 2 shows more detailed ¹ H-NMR, ¹³ C-NMR and mass spectrum analysis results of the compounds Nos. 4 and 11 shown in Table 1 above. In Table 2, α in ¹ H-NMR and ¹³ C-NMR is the position of the carbon bonded to the N atom of the isoquinoline skeleton, is the 1-position of the isoquinoline skeleton, and is the 3-position of the isoquinoline skeleton. ,
Indicates the 4-position of the isoquinoline skeleton, and ′ indicates the 2-position of the indole skeleton.

Also, laurylisoquinolinium chloride was used as the alkylisoquinolinium salt, the indole derivative shown in Table 3 was used in place of the purified indole, and the product was extracted with carbon tetrachloride for chromatographic separation. Then, a compound represented by the general formula (II) was produced in the same manner as above, except that the compound was distilled at room temperature and then dried under reduced pressure for purification. The yield of the obtained product and its properties are shown in Table 3.

Example 2 [Production of Compound Represented by General Formula (I)] N-alkylisoquinolinium halide of alkyl group R shown in Table 4 and purified indole were dissolved in methanol or acetonitrile, and dissolved in this solution. A 28 wt% CH ₃ ONa methanol solution or a 10% KOH aqueous solution was added, and the reaction was carried out for about 2 days. The solvent was distilled off from the resulting reaction mixture, the residue was amberlysted and then reduced with NaBH ₄ . Then, the reaction product was purified by a silica gel column (eluent chloroform) to obtain a compound of the general formula (I) having the substituents X, Y and R shown in Table 4. The obtained products were all in the form of yellowish brown oils, and the yields and properties are shown in Table 4. Also, ¹³ C-NM of compound Nos. 22 and 23 were used.
The results of analysis by R and mass spectra are shown in Table 5, respectively. In the ¹³ C-NMR data, α, and are the same as in Table 2, and ′ indicates the 3-position of the indole skeleton.

II. Formulation Example (1) Emulsion No. 1 compound 10.0 parts by weight Xylol 86.5 parts by weight Emulgen 909 (Kao Soap Co., Ltd. trade name) 2.0 parts by weight Neoperex C70 (Kao Soap Co., Ltd. trade name) 1.5 parts by weight Parts The above agents are uniformly mixed with stirring to prepare an emulsion, which is diluted with water or used as it is.

(2) Wettable powder No. 11 compound 20.0 parts by weight Neoperex No6F (Kao Soap Co., Ltd. product name) 3.0 parts by weight Solpol 8070 (Toho Chemical Co., Ltd. product name) 4.0 parts by weight White carbon 5.0 parts by weight Clay 68.0 parts by weight The above chemicals may be uniformly pulverized and mixed to prepare a wettable powder, which may be diluted with water before use, or may be mixed with soil before use.

(3) Powder No. 15 compound 5.0 parts by weight Talc 95.0 parts by weight The above chemicals are uniformly pulverized and mixed to prepare a powder, which is used as it is or after mixing with soil.

III. Test example (No.-1) Rice sesame leaf blight disease seedling test A 1000ppm concentration drug solution is filled and dispersed in rice (cultivar: Tonawase) seedlings, and one day after air-drying, spore suspension of rice sesame leaf blight fungus A liquid (spore concentration (magnification: 150 times): 6 to 8 per field of view) is sprayed and inoculated, left in a humid chamber at 25 ° C for 24 hours, and one week later, the number of lesions per leaf is counted. : Suppression rate 95% or more, B: Suppression rate 50 ~
95% and C: Suppression rate was 50% or less. The results are shown in Table 6.

(No.-2) Cucumber epidemic leaf piece test A zoospore of a cucumber epidemic bacterium, which is prepared by cultivating a 1,000 ppm-concentrated drug solution on the underside of cucumber (cultivar: Sagamihanjiro) and culturing the cucumber fruit in advance one day after air-drying. Inoculate 10,000 leaves / ml at 2 spots per leaf, incubate in a dark room at 28 ° C and inspect 2 days later. A: No invasion of fungus was observed, B: Part of inoculated part Bacterial invasion is observed, but lesions do not spread, C: Bacterial invasion is observed throughout the inoculated area, but no lesions spread to non-inoculated areas, and D: lesions It was expanded to the non-inoculated part and evaluated in four stages, which is equivalent to the case of no treatment. The results are shown in Table 6.

(No.-3) Citrus sunspot mortar test 1,00 in a summer citrus seedling seedling that had been pruned beforehand to produce new leaves
A 1 ppm solution of 0 ppm concentration was applied and dispersed, and one day after air-drying, a spore suspension of citrus black spot spores (spore concentration (magnification: 150 times): 200 per field) was sprayed and inoculated. After putting in the time, manage in the greenhouse, count the number of lesions after 2-3 weeks,
The diseased leaf rate and the number of lesions per leaf were obtained and evaluated in three stages: A: inhibition rate of 95% or more, B: inhibition rate of 50 to 95%, and C: inhibition rate of 50% or less. The results are shown in Table 6.

(No.-4) Rice sesame leaf blight disease seedling test A chemical solution having the concentration shown in Table 7 was applied to rice (cultivar: Tonawase) seedlings and dispersed, and after 1 day of air drying, a spore suspension of rice sesame leaf blight fungus. (Spore concentration (magnification: 150 times): 6 to 8 per field of view) is sprayed and inoculated, left in a humid chamber at 25 ° C for 24 hours, and one week later, the number of lesions per leaf is counted, and A: Suppression rate 95% or more, B: Suppression rate
50 to 95% and C: Inhibition rate was 50% or less. The results are shown in Table 7.

(No.-5) Citrus ulcer disease pot test No. 7 was applied to the summer seedling seedling pots that had been pruned beforehand to produce new leaves.
A solution of the concentration shown in the table was applied and dispersed, and after 1 day of air-drying, a suspension of citrus ulcer disease (concentration: 2 × 10 ⁸ cells / ml) was sprayed and inoculated, and placed in a humid chamber at 27 ° C. for 24 hours. After management in a greenhouse, the number of lesions was counted 2 to 3 weeks later, and the diseased leaf rate and the number of lesions per leaf were determined. The results are shown in Table 7.

[Effects of the Invention] The novel isoquinoline derivative of the present invention can be used as it is or in a predetermined formulation form as a fungicide for agricultural and horticultural use, as an insecticide, or as an intermediate thereof. It is a very useful compound.

Claims (1)

[Claims] 1. The following general formula (I) or (II) (Wherein X represents an alkyl group, a halogen or a nitro group, Y represents an alkyl group, a halogen, a nitro group, an amino group, a hydroxy group or a carboxy group, R represents an alkyl group, and m and n are 0. Is an integer of 2).