JPS6032631B2 - r-pyridone compounds, their production methods, and agricultural drugs comprising these compounds - Google Patents

Description

[Detailed description of the invention]

The present invention is based on the general formula (wherein R and R2 represent a lower alkyl group, and R is a linear or branched saturated hydrocarbon group having 5 or more carbon atoms, or a phenyl group. A novel y-pyridone compound represented by a straight-chain or branched saturated hydrocarbon group or a straight-chain or branched unsaturated hydrocarbon group and the general formula ( In the formula R,
, R2 and R are as described above), and agricultural drugs containing them as active ingredients. In living organisms, electron transport systems are essential for the progression of biochemical reactions such as respiration and photosynthesis. The insecticidal components piericidin A and B produced by Strep mycesmobaraensis are involved in the coenzyme Ubiqujn in the mitochondrial electron transport chain.
It is known to strongly inhibit the action site of o fertilizer. The present inventors have discovered that such pierjcidin
The present invention was completed by conducting research to find the essential structure for the expression of similar activities. (In the formula, R, , R2 and R have the same meanings as above.) (In the formula, R, , R2 and R have the same meanings as above.) That is, synthesis of asymmetric tetrasubstituted Q-pyridone which is the object of the present invention. Although there is almost no precedent for this method, as a result of examining various synthetic methods, the method for synthesizing 6-alkyl-4-hydroxy-2,3-dimethyl-pyridine was completed for the first time using the route shown in 'a} above. Furthermore, as a result of various studies on new synthetic reactions, the present inventors have also developed a simple and efficient method for synthesizing y-pyridone compounds such as 'b' above. That is, 1, obtained by alkylating acetylacetone,
4-Amino-3-methylventer-3-ene-2 which can be synthesized by treating 1-diacetylethane with 28% NH for 40 days
-ion is converted into a dianionic state using 2 equivalents of lithium diisopropylamide as a base, and then acylated with an ester and neutralized after the reaction completes to obtain y-pyridone in a high yield. The y-pyridone compounds synthesized by the above method are generally solid at room temperature and are soluble in alcohol and chloroform, but are soluble in ethyl acetate, ether, benzene,
It is indestructible or soluble in solvents such as hexane. Each of the IR, NMR, Mase, etc. spectra exhibits a characteristic pattern that is thought to be derived from the core portion in common for all compounds. On the other hand, all of the y-pyrone compounds synthesized by the above method 'a' were lipophilic oily substances. The spectra of each instrumental analysis showed a typical pattern of pyrone compounds. The effects of the synthesized y-pyridone compounds on the photosynthetic system were examined by testing their ability to inhibit the Hill reaction using chloroplasts extracted from spinach leaves. The Hill reaction inhibiting activity of the y-pyridone derivatives is listed in the table below. As a result, it was found that y-pyridone compounds, which have the same layer budget pattern as plastoquinone, exhibit Hill reaction inhibitory activity. EXAMPLES Next, Examples will be given to further specifically explain the present invention, but the present invention is not limited to the following Examples. Example 1-1 (In the formula, R has the same meaning as above) Q-ethyl acetopropionate

[1', 144 mol (1 mol) was mixed with ethylene glycol 68 mol (1.1 mol) and anhydrous benzene 400 ml, Dean-Stark
It was placed in the round bottom flask of the first customer who followed the trap. Add 0.0% p-toluenesulfonic acid to this mixture as an acid catalyst.
4 mol (0.024 mol) was added, and the mixture was heated in a Boan-Stark trap until 18 ml of water separated, and the benzene was refluxed. After cooling the reaction solution to room temperature, 1
Wash with 50' of 10% caustic soda solution, then 10'
Washing with 0' water was repeated three times. The organic phase was dried with anhydrous potato salt and purified by vacuum distillation. Objective Q-
Ketalized product of ethyl acetopropionate [2} is 74
Distilled at ℃/3 Hg, yield is 170 yen (yield 85%)
Met. 200 equipped with Ken Azusa machine, dropping funnel and reflux condenser cooled with dry ice-acetone cryogen.
A four-necked flask was cooled to -80° C., taking care to keep the inside dry, and 50 μm of liquid ammonia was poured into it. Sodium amide was prepared from this ammonia and 1.15 moles (0.05 mol) of metallic sodium by a known method. The sodium amide was suspended in 50' of anhydrous ether and inamyl methyl ketone 2 was added under room temperature conditions.
．． A solution of 0.85 mmol (0.025 mol) of 2.0 in anhydrous ether was added dropwise over about 10 minutes with vigorous stirring. After dropping, stirring was continued for 10 minutes, and then a solution of 9.4 mol (0.05 mol) of Q-ethyl acetopropionate ketalized compound '2) in 20 volumes of anhydrous ether was added dropwise over 15 minutes. . After that, heating under reflux was continued for 3 hours, and finally the reaction solution was added to ice water above 100%, and the pH was adjusted to 6~6 with 2N hydrochloric acid.
Neutralized to 7. The target product was extracted with ether, washed successively with saturated sodium carbonate solution and water, dried over anhydrous moss salt, and the ether was distilled off.The target product was present in the residue, but was subjected to the ring closure reaction without purification. . Mixture 4.2 containing 3-methyl-2,4-diketobentiisoamyl-ketone-2ethylene ketal as the main component was gradually added with 10 m of concentrated sulfuric acid while thoroughly pressing under ice-cooling. added. After cooling and stirring for 1 hour, 200ml of ice water was added, and the mixture was further neutralized to 7-8 with sodium bicarbonate and extracted with ethyl acetate. After distilling off the ethyl acetate, the extract was
Purification was performed by silica gel column chromatography using an elution solvent system of hexane-ethyl acetate. Target 6-isoamyl-2,3-dimethyl-y-pyrone'
4} is 6 in the hexane: ethyl acetate = 7:3 elution division.
37 females (0.003 mol) were obtained. [The yield from the ketal compound of Q-ethyl acetopropionate is 1
3%] 6-isoamyl-2,3-dimethyl-y-pyrone 578 (0.003 mol) was heated with 30' of 28% aqueous ammonia in a sealed tube to 150-160°C for 1 hour. After the reaction was completed, aqueous ammonia was distilled off, and the residue was recrystallized from hot ethyl acetate to obtain 432 6-isoamyl-2,3-dimethyl-y-pyridone '5'. The final stage yield is 75%. Example 1-2 3.55 moles of heptyl methyl ketone (0.0 .025
A solution of 20 mol) of anhydrous ether was added dropwise over a period of about 10 minutes with vigorous stirring. After 10 minutes had elapsed after the completion of the dropwise addition, an anhydrous ether solution containing 9.4 mm (0.05 mol) of the ketalized product of ethyl Q-acetopropionate '2'' and 20 mm was added over about 15 minutes. Thereafter, heating under reflux was continued for 3 hours, and finally the reaction solution was added to 100 ml of ice water, and further neutralized to pH 6-7 with 2N diluted hydrochloric acid. The neutralized solution was extracted with ether, washed with rice bran and dried according to a conventional method, and then the ether was distilled off.
．． After 9 days, a crude product, 3-methyl-2,4-diketobenzenebutyl-ketone-2-ethylene ketal '3i, was obtained. To this crude product was gradually added 10 ml of concentrated sulfuric acid while stirring vigorously under ice-cooling. After cooling and cooling for 1 hour, 200ml of ice water was added, followed by neutralization to pH 7-8 with sodium bicarbonate, and extraction with ethyl acetate. After distilling off the solvent, the extract was purified by silica gel column chromatography. The target 6-heptyl-2,3-dimethyl-y-pyrone was obtained in the elution section of hexane:ethyl acetate = 7:3 with 0 pglue. 12%)
. 6-hebutyl-2,3-dimethyl-y-pyrone 450
After heating 9 (0.002 mol) of 20 with 28% ammonia water in a sealed tube at 150 to 160°C for 1 hour, the ammonia water was distilled off to obtain a crude product with 0 spots. ,
Recrystallization from hot ethyl acetate yielded 31 traces of pure 6-heptyl-2,3-dimethyl-y-pyridone'5}
was obtained (yield 70%). Example 2-1 When 1,1-diacetyl ethane (6) (1 mole) was mixed with 28% ammonia water, heated in an open flask for about 18 minutes, and then left at 4°C overnight, a needle-like mixture was formed. Sublimable crystals were obtained. After the crystals were filtered and thoroughly dried, they were purified by sublimation under reduced pressure to obtain 4-amino-3-methyl-2keto-3-pentenylketone '7} of 90 min. yield 80%).
1.13 (0.01 mol) of 4-amino-3-methyl-2keto-3-bentenylketone '7- was dissolved in 20' of anhydrous tetrahydrofuran in a nitrogen-purged flask equipped with a reflux condenser and a rubber septum. 2.2 mmol (0.022 mol) of diisopropylamine and 2 mmol of hexamethylene phosphoric triamide (
HMmT) and 15% n-butyl lithium-
A hexane solution (0.022 mol) was prepared, and a tium diisopropylamide solution was added while cooling on ice and stirred well. Next, remove the ice cube, continue to incubate at room temperature for one hour, and add 2.12 mols (0.01 mol) of ethyl undecenoate to 20 [
A THF solution was added. After 30 minutes, heat under reflux for 2 hours, then add 1N hydrochloric acid to the reaction solution for 10 minutes.
The skin was extracted three times with chloroform. After extraction, the mixture was sequentially washed with saturated sodium carbonate solution and saturated brine, dried, and the solvent was distilled off. The concentrated condensation residue was dissolved in hot ethyl acetate, cooled, and the resulting residue was collected. The insoluble solution was crystallized with carbon tetrachloride-ethyl acetate to obtain 1.25 mmol (0.005 mol) of 2,3-dimethyl-6-undecenyl-y-pyridone '9' as colorless flaky crystals (yield rate 48%). Example 2-2 1.13 mol (0.01 mol) of 4-amino-3-methyl-2-keto-3-bentenyl ketone [7] was dissolved in 20 ml of anhydrous tetrahydrofuran, and under the same conditions as above, 0.0 A solution of .022 mol of lithium diisopropylamide was added, and after incubation for 1 hour at room temperature, a solution of 2.84 mol of ethyl palmitate (0.01 mol) in anhydrous tetrahydrofuran was added. After 30 minutes, the temperature was raised and the mixture was heated under reflux for 2 hours. At the end of the reaction, 50 μl of 1N hydrochloric acid was added, extracted 3 times with 100 μl of chloroform, and the same procedure as described above was performed.
2,3-dimethyl-6-palmityl-y-pyridone was obtained as a powdery crystal with a yield of 46.6%. Example 2 131.13 (0.01 mol) of 4-amino-3-methyl-2-keto-3-bentenyl ketone '7' was made into a solution of 20' of anhydrous tetrahydrofuran, and added to it under the same conditions as above. .022 moles of lithium di-sof. After adding ropyramide solution and incubating for one hour at room temperature,
A solution of 1.72 ml (0.01 mol) of ethyl 3-methylenanthate in 10' anhydrous tetrahydrofuran was added. 3
After 0 minutes, the temperature was raised and heated under reflux for 2 hours. At the end of the reaction, add 50' of 1N hydrochloric acid and dilute with 100' of 1N hydrochloric acid.
Extracted three times with chloroform and followed the same procedure as above]
．． 2,3-dimethyl-6-(3
'-methylhexyl)-pyridone was obtained (yield 48
%). Example 2-4 1.13 g (0.01 mol) of 4-amino-3-methyl-2-keto-3-bentenyl ketone [7} was dissolved in 20 g of anhydrous tetrahydrofuran and treated under the same conditions as above. 0 at
．． After adding 0 mol of lithium diisopropylamide solution and incubating at room temperature for 1 hour, 1 mol of ethyl dihydrocinnamate was added.
．． A solution of 78 mol (0.01 mol) of 10 [anhydrous tetrahydrofuran] was added and the same reaction conditions as for the other compounds in the series were carried out.
Through the same procedure, 2,3-dimethyl-61 (0.8 minutes)
Z-phenylethyl)-y-pyridone was obtained as colorless plate crystals (yield 35%). Next, typical compounds obtained by the method of the present invention will be listed, but the present invention is not limited to the following exemplified compounds. The compound of the present invention has a similar structure to plastoquinone, which plays an important role in plant photosynthesis, and is expected to have interesting physiological effects in plant photosynthesis. Table 1 below shows the extract from spinach leaves. This figure shows the results of an experiment using Loplast to inhibit the Hill reaction. The substance of the present invention is 10-3 to 10 as shown in the table.
- At a concentration of 5 molar, it clearly inhibits the Hill reaction by 50% and has an anti-plastoquinone effect, which means that it has applications as a pesticide with plant growth regulation or herbicidal activity due to its photosynthesis-inhibiting effect. It is expected to be useful as a new physiologically active substance. Table-1 Table-2

Claims (1)

[Claims] 1. General formula ▲ Numerical formula, chemical formula, table, etc. ▼ a saturated hydrocarbon group, a linear or branched saturated hydrocarbon group substituted with a phenyl group, or a linear or branched unsaturated hydrocarbon group) γ-pyridone compound. 2 General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R_1 and R_2 represent lower alkyl groups, and R
_3 represents an alkyl group) is reacted with ethylene glycol to form the general formula ▲mathematical formula,
There are chemical formulas, tables, etc. ▼ (In the formula, R_1, R_2 and R_3 have the same meanings as above) We obtain a ketal compound represented by this product and the general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (Formula R is a linear or branched saturated hydrocarbon group having 5 or more carbon atoms, a linear or branched saturated hydrocarbon group substituted with a phenyl group, or A ketone compound represented by a linear or branched unsaturated hydrocarbon group is reacted with a ketone compound represented by a straight-chain or branched unsaturated hydrocarbon group, and then the ring is closed to form the general formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R_1, R_2 and R has the same meaning as above), and further treats it with aqueous ammonia.There are mathematical formulas, chemical formulas, tables, etc.▼ (In the formula, R_1, R_2 and R has the same meaning as above). 3 General formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (In the formula, R_1 and R_2 represent lower alkyl groups) A diketone compound and ammonia water are reacted to form the general formula ▲ Numerical formulas, chemical formulas, tables, etc. ▼ Obtain an enaminoketone represented by (in the formula, R_1 and R_2 have the same meanings as above), and then combine this with the general formula R
COOR_3 (In the formula, R is a linear or branched saturated hydrocarbon group having 5 or more carbon atoms, or a linear or branched saturated hydrocarbon group substituted with a phenyl group. or a straight-chain or branched unsaturated hydrocarbon group, and R_3 represents an alkyl group), and then ring-closing. There are chemical formulas, tables, etc. ▼ (R_ in the formula
1, R_2 and R have the same meanings as above). 4 General formula ▲ Numerical formula, chemical formula, table, etc. ▼ (In the formula, R_1 and R_2 represent a lower alkyl group, and R is a linear or branched saturated hydrocarbon group having 5 or more carbon atoms. or a straight-chain or branched saturated hydrocarbon group substituted with a phenyl group, or a straight-chain or branched unsaturated hydrocarbon group) as an active ingredient. An agricultural agent having plant growth inhibiting and herbicidal activity, characterized in that it contains as follows.