JPS58170758A - Gamma-pyridone derivative - Google Patents

Abstract

NEW MATERIAL:The gamma-pyridone derivative of formula I (R1 and R2 are lower alkyl; R is saturated or unsaturated hydrocarbon group which may have phenyl group as substituent group). EXAMPLE:2,3-Dimethyl-6-undecenyl-gamma-pyridone. USE:An agricultural chemical active to inhibit Hill reaction with chloroplast extracted from the leaves of spinach. It is solid at normal temperature, soluble in alcohol and chloroform, and insoluble or hardly soluble in ethyl acetate, ether, benzene, hexane, etc. PROCESS:The compound of formula I can be prepared, e.g. by (1) alkylating acetylacetone of formula II, (2) treating the resultant 1,1-diacetylethane of formula III with NH4OH to obtain 4-amino-3-methylpent-3-en-2-one of formula IV, (3) converting the compound to dianionized state with lithium diisopropyl amide base, and (4) acylating with the ester of formula V.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention is based on the general formula (wherein R and island represent a lower alkyl group, and R represents a linear or branched saturated or unsaturated hydrocarbon group). The present invention relates to a novel compound represented by the following formula (the hydrocarbon bulk group may be substituted with a phenyl group), a method for producing the same, and S steel for AM.

In living organisms, the electron transport system is an essential system for rounding, which promotes respiration and biochemical reactions in the photo-synthetic part. 8tr@
pt@wyc*s mbara*nmkm C1 child's respectable component pl@r1gisli, B goes to the O electron transfer system in the mitochondria and coenzyme Utriqui
It is known that it inhibits the action of noa@ in a similar manner. The inventors believe that such piericld
The present invention was completed by conducting research to find the essential structure of rounding that lnatoms contain.

(In the formula, -R, 1, R, and 8 have the same meanings as above.) (In the formula, R1, R1, and 8 have the same meanings as 錺闭.)
In other words, although there is almost no precedent for the synthesis of asymmetric tetrasubstituted r-pyridones, which is the object of the present invention, several synthesis methods have been studied, and the results are shown in Figure (a). Complete the synthesis method of first-alkyl-4- and do-4xy-2,5-dialkyl-pyridine.

Furthermore, various studies have been carried out on threat reactions such as the one described in (b) above, which are simple and efficient.
Also send out the Pyridon trout conductor O-wei machine.

That is, by alkylating acetylacetone, 1191
．． 281 of 1-diacedelethane! 4-A-kenno 3-methylventer-5-ene-2 that is hidden in the building due to Nagi OH treatment
-one is reduced to a dianionic form using 2 amounts of lithium diisopropylamide as a base, and then acylated with an ester and neutralized after the reaction completes to obtain r-pyridone in high yield.

The r-pyridone derivatives threatened by the O method are generally solid in coulometric terms, and are soluble in alcohol and chloroform, but are insoluble or sparingly soluble in ethyl acetate, ether, pen, and hexanofluoride. .IR,NM
The spectra a, Mall, etc. all exhibit a characteristic pattern that appears to be squared in the bone core region, which is common to all O compounds.

The effect of the synthesized niner-pyridone derivatives on the photosynthetic system was examined by extracting them from spinach cords and assaying their ability to inhibit the leech reaction using nineroplasts. r-
The Hill reaction inhibitory activity of pyridone conductors is listed in the table below.

r with the same substitution mode as plastoquinone
-Pyridone derivatives were found to exhibit Hill reaction inhibition**.

Next, a ninth example will be given to explain the present invention in more detail, but the present invention is not limited to the following examples.

Example 1-1 11) (2) (8 in the formula has the same meaning as above) -ethyl monoacetoprobionic acid (1), 144) (14
Mix the ethylene glycol 6.P (1.1 kg) with one Ben (400-ml), connect it to the Dean starter trap, and place it in the round-bottom class of the 91st judge.
As an acid catalyst, Cp-)luenesulfonic acid α4P (
Add α024 mol) and heat until 18-water separates into a Dean-Stark trap to reflux the benzene. After cooling the reactant to room temperature, 150 d of
Wash with 011I curved soil, then 100TIL
Repeat washing with water for 3 times.

The organic phase was dried over anhydrous sodium sulfate and purified by vacuum distillation. Ketalized product of ethyl α-acetopropionate (2)
is distilled at 74℃/Swas direction, and the dilution volume is 170? (
IiL rate 85-→゛ and nine.

Equipped with a stirrer, a dropping tube, and a reflux condenser cooled by a dry ice-acetone storage medium, the four-necked flask was cooled to -80°C while being careful to keep the internal dry state under pressure. Inject liquid ammonia into the circle. Sodium hydroxide was prepared from this ammonia and 1.151 (LO5 ml) of sodium metal.
．． A 20-anhydrous ether solution of 85S1' ((LO25 liters) was added dropwise with vigorous stirring over about 10 minutes. Stirring was continued for 10 minutes, and then a ketalized product of ethyl α-acetonoglobionate (phantom 9. 4) Make (α054L) a solution of 204% in anhydrous ether and add the 9 parts dropwise over 15 minutes.Continue heating under reflux and stirring for an hour.Finally, add the reaction solution to 100% ice water and dilute with 2N hydrochloric acid. 911 4
Neutralizes to ~7 and 9. The product was extracted with ether, washed sequentially with saturated sodium carbonate and water, and dried over anhydrous sodium sulfate.The ether was removed, and the remaining residue was subjected to the W4il1 reaction without being purified.

Sulfuric acid No. 1 was gradually added to hot metal 42) whose main component is S-methyl-2,4-diketobentyl-amyl-ketone-2-ethylene ketal (3) with sufficient stirring under water cooling. added. After cooling and stirring for 1 hour, 200-liter of ice water was added and the mixture was diluted with 200 liters of ice water. Sodium cleavage pH 7~
8 and extracted with ethyl acetate. After distilling off the ethyl acetate, the extract was purified by silica gel column chromatography using an elution solvent system of hequinane-ethyl acetate. 6-Itsa-ken-2,3-dimethyl-r-pyrone (4) is hechunan/acetic acid xf (7t 5 ) O
1l output eK457q ((1005 mol) obtained 9 [α
-The yield from the ketalized product (2) of ethyl acetopropionate is 15-].

] 6-Itsuanru 2,5-dimethyl r-bi-47578
(alpha0054) was heated in a sealed tube with 50-28-ammonium water to 150-140'C for 12 hours. After the reaction was completed, aqueous ammonia was distilled off, and the residue was recrystallized from hot ethyl acetate to obtain 452 ml of 6-yneyl-2,5-dimethyl-r-pyridone (5). The final stage yield is 75-.

Example 1-2 Heptyl methyl ketone & 55F (1025 mol) was added under room temperature conditions to a reaction solution prepared by suspending α05 mol of 9 cumoid used in Example 1-1 in 50-g anhydrous ether.
20Wd acupuncture water ether happy liquid was added dropwise for #10 minutes with vigorous stirring. After 10 minutes after the completion of the dropwise addition, 94? (
α054L) was made into a 20-mL anhydrous ether fII solution and the pellets were added over a period of about 1 s. Thereafter, the mixture was heated under reflux and stirred for 3 hours, and finally the reaction solution was added to 100% ice water and further neutralized to pH 6-7 with 2N diluted hydrochloric acid. The neutralized solution was extracted with ether, washed and dried according to a conventional method, and after 9 hours, the ether was distilled off. ) crude product 5-methyl-2,4-diketobenzenylheptyl-ketone-2-ethylene ketal (3) was obtained. While cooling with water, 10-0-sulfuric acid was gradually added to this crude product with vigorous stirring. After cooling and stirring for 1 hour, 200-mL 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. Intermediate 6-hebutyl-2,5-dimethyl-r-pyrone was obtained at 680 d in the hequinane/ethyl acetate (7 t! $) 0 elution section (ketalized product of ethyl a-acetopropionate (2) 12-).

6-to 1f-2.3-dimethyl-r-pyrone 450
Heat dgC10024L) with 20-28 bags of ammonia water in a sealed tube for 150-140'CK for 15 hours, then add 1* of air water to obtain 380#OIl product, which is recrystallized with hot ethyl acetate. The final product was 515q of pure 6-hegyl-2,3-dimethyl-
r-pyridone (5) was obtained (yield: 7o).

Example 2-1.

(6) (7) Den) (9) 1.1-Diacetylethane (6N14P (14L)
Mix with 28-ammonium water of J and add approximately 1 ml of water in an open flask.
After 5 minutes of fighting Jl heat up and leave it at 4℃ in the evening, it becomes needle-like OJ! I can't get Kenyu Sosaki. Separate the crystals into two [After sufficient operation,
Purification was carried out by sublimation under reduced pressure to obtain 90t04-amino-
5-methyl-2keto-5-pentenylketo/())
I9 (yield 80%).

t13t (α01 mol) of 4-a-3-methyl-2
Keto 5-pentenyl ketone (7) was placed in a 9-volume displacement flask equipped with 20 d of anhydrous tetrahydro-7, a reflux condenser, and a rubber septum, and 2
．． 2? (α022 mol) of diisopropylamine and 2d
Hequinamethylene phosphor reactor (nPT)
) and 15-n-butyllithium of 1417 was developed from a medium solution (α022 mol), and a solution of 9 lithium diisopropylamide was added under ice-cooling, followed by thorough stirring. Next, remove the water bath, stir for 1 hour at room temperature, and then add 2.12P (CL'014 #) of ethyl undelongate.
D 20 IIjTH Film ml was added. S.

After stirring the mixture under heating under reflux for 2 hours, 50-1N hydrochloric acid was added to the reaction solution, and the mixture was extracted three times with 1001111-chloroform. The extract was a saturated sodium bicarbonate solution;
The mixture was washed successively with saturated brine, dried, and the solvent was distilled off. The residue was treated with hot ethyl acetate and sulfur, cooled, and the resulting impurities were collected.

The compound was crystallized with carbon tetrachloride-ethyl acetate to give 1.25 P (0005 mol) as colorless 7-lake crystals.
C) 2,3-dimethyl-6-unzocenyl-r-pyridone (9) was obtained (yield 48-).

Example 2-2 4-Aζ no 3-methyl-2 of tlst (α01 mol)
-Keto-3-pentenyl ketone (7) was dissolved in 20- anhydrous tetrahydro7rane and treated under the same conditions as above with α0
Add a 22 molar lithium diinoprobylamide solution;
After stirring for 1 hour at a rich temperature, Pal (ethyl tinate 2.8
4sL (α01L) of 10mm water in tetrahydrofuran was added. After 50 minutes, the temperature was raised and the mixture was heated under reflux and stirred for 2 hours. At the end of the reaction, 50-1N hydrochloric acid was added, extracted 5 times with 100-chloroform, and the same procedure as described above was followed to obtain 2,3-dimethyl-6-valmityl-r-pyridone (1.557) as powdered crystals. 9) was obtained (yield: 4 shifts, 4 seconds).

Example 2-5 1,13 ft (α01 mol)
Anhydrous tetrahydrofuran (L) was prepared, and lyticum diisoglobilanate of α0224 L was added thereto under the same conditions as in the case of the test, stirred at room temperature for 1 hour, and then 3-methylenanthate was added. Ethyl t72) (α01 mol) 01 Q@
Add J anhydrous tetra and Doro 7 run solution and make a circle. After 30 minutes, the temperature was raised and the mixture was heated under reflux and stirred for 2 hours. At the end of the reaction, add 50-1N hydrochloric acid, extract with 1001170 chloroform, and add 1.0 IP through the same procedure as above.
2,3-dimethyl-6-(5'-methylhexyl)-r-pyridone was obtained as a loaf-like crystal (yield: 48).

Example 2-4 4-a-3-methyl-2 of t13P (α01 mol)
-Keto-5-pentenyl ketone (7) in 20-0 anhydrous tetrahydrofuran! 1. , α under the same conditions as the error
Add 0.224 liters of lithium diisoglobil azide and stir at room temperature for 1 hour.
Adding 78F (α01 mol) 0101ij-water tetrahydrofuran solution and following the same reaction conditions and procedure as for the other O compounds, α8t of 2,3-dimethyl-6-(2′
-7ethyl)-r-pyrido/ was obtained as colorless plate crystals (song rate 35m).

Next, nine representative compounds obtained by superimposed light method tI& are listed, but the present invention is not limited to the 40 defined by the following exemplified compound K111.

Properties IR ( 1598° 1380.

1500.

1376° 1475° 1350° 1495° 1355° 475 1550.

1495°1345°1516 6J2 (IHs) λ34 (3Hs)
2131553 2.02 (3Hs) (
:CL)sOυ]L447 6.30(IHs)2
．． 55 (3Hs) 2271350 2.0
0(5Hs) [CD5OD)1410 &2
7 (IHs) 2.56 (5Hs) 1513
1200 2.00 (5Hs) [:CDm01)
] 1412 6.55 (IHs) 2.28 (5
Hs) 1931200 2.08(3i(
5) CCDsOD) 1410 6.24 (LM
s) 2.55 (3Hm) 2211200
2.00 (3t(5)CCDsOD) 1404 6
．． 27(11(S) 2.23(3Hs) 22
11195 2.03 (3Hs) (CDnOD) Properties 640.1625, 1510 α95 (3Hd) 1
．． 60 (3Hs) 261200
1.66C5Hs) 2.04(5Hs) 2.34(
3Hs)! 1L02 (IHt) 6.04 (IH5) 635.16'20.1510 1.57, 1.64
, 1.68 (each AHs) 259490.120
0 1.04.2.54 (each 5H8) 5.0
0 (IHm) 5.24 (H (t) 6.04 (1t (s) 1.57, 1°64 (3Hs each) 1.68 327
(61(& ), 2.04, 2.34(!r&f s
) 5.00 (2) 1 m) 5.24 (IHt) 6.04
(l) (s) i, p 7 + 1.64 (5Hs each) 1.68
395 (9Hs) 2.04.2.54 (5Hs each) 5
．． 00(3i(m)5.24(IHtJ 61)4(
IH5) 188 (1211b) 1.70 (3Hs) 401
2.04, 2.54 (5Ha each) 5.24 (H(t) &04(IHs)i raw IR(ν)m-' MvlR(δ in
CDCJs) ”+na)Cppm 5201510.1412 5.98 (IHs)
2.40 (5Hs), 261580.1351
．． N97 1.98 (AHs) CCC Taku〕NO
, 1495, 14056, 15 (IHs) 2.58
(3Hs) 277576.1350.1190
1.99(3)('s) CCDCl5"
J612.1498.1410 6.04 (In
s) 2.22(3)(s) 553578.1
350.1190 2.04 (3H5) (CDCJ
s) 612.1500.1410 6.02 (1t
(s) 2.20 (5Hs) 361576.
1350.11ν0 2.04 (AHs)
CCDCgs)615.1510,1410 6.
00 (IHs) 2.38 (3Hs) 415
580.135011200 1.98 (5rl
5) CCC &) 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. Tables 1 and 2 below show the results of an experiment on the inhibition effect on the Hill reaction using chloroplasts extracted from spinach leaves.

The material of the present invention is 10-" to 10'" as shown in the table.
One mol of S clearly inhibits the Hill reaction by 50% and has an antagonistic effect on plastoquinone, which means that it has relevant uses as a photosynthesis inhibitor, plant growth inhibitor, and herbicide. It is also expected to be useful as a new physiologically active storehouse.

Claims (1)

[Claims] General formula (in the formula, R3 and islands represent a lower alkyl group, R represents a linear or branched 0III group, and 9 represents an unsaturated hydrocarbon group; r-pyrido/trout conductor represented by (the group may be substituted with a phenyl group).