KR810000834B1 - Process for preparing 3-phenyl-5-substituted-4(1h)-pyridones (thiones) - Google Patents

Abstract

Title compds. (I; R = Me, Et, acetoxy, OH; R1 = halo, alkyl, halo-substituted C1-4 alkyl, NO2, COOH, OH, C1-2 alkoxycarbonyl; R2 = cyano, C1-3 alkoxycarbonyl, C1-4 alkyl, halo, OH, C1-3 alkoxy-substituted C1-4 alkyl, thienyl; X = O, S; m = 0-2), useful as a herbicide, were prepd. by reacting compounds II[one of Q1 and Q2 is H, the other: CHNHY(Y = H, OH, Me, Et) with formylating or aminoformylating agent or by reacting compds. II[Q1,Q2 = :CHOH or CHN(R3)2 (R3 is C1-3 alkyl or forms pyrrolidino, etc. with adjacent N) with YNH2 or by hydrolyzing to give III(Y = H, OH), which were alkylated or esterified to give corresponding compds. (Y = R).

Description

Method for preparing 3-phenyl-5-substituted-4 (1H) -pyridone (thione)

The present invention relates to a process for preparing 3-phenyl-5-substituted-4 (1H) -pyridone (thione) and acid addition salts thereof of formula

In the above structural formula,

X is oxygen or sulfur,

R is methyl, ethyl, acetoxy or hydroxy,

이고R ¹ is independently halo, alkyl having 1 to 4 carbon atoms, alkyl having 1 to 4 carbon atoms substituted with halo, nitro, carboxy, hydroxy, alkoxycarbonyl having 1 to 2 carbon atoms, -OR ³ , -SR ³ ,- SO-R ³ or -SO ₂ -R ³ , R ² is cyano, alkoxycarbonyl having 1 to 3 carbon atoms, alkyl having 1 to 4 carbon atoms, halo, hydroxy or alkoxy having 1 to 3 carbon atoms Alkyl of 1 to 4, thienyl, -OR ⁴ , -SR ⁴ , -SO-R ⁴ , -SO ₂ -R ⁴ or-

ego

R ⁴ is alkyl having 1 to 2 carbon atoms, alkyl having 1 to 2 carbon atoms substituted with halo, benzyl or phenyl,

R ⁴ is alkyl having 1 to 6 carbon atoms, hydroxy or alkyl substituted with halo, alkyl having 1 to 6 carbon atoms, alkenyl having 2 to 4 carbon atoms, benzyl, phenyl or trifluorotomethyl, halo, alkyl having 1 to 3 carbon atoms, Nitrile, phenyl substituted with alkylthio having 1 to 3 carbon atoms or alkoxy having 1 to 3 carbon atoms,

R ⁵ is independently halo, alkyl having 1 to 4 carbon atoms, alkyl having 1 to 4 carbon atoms substituted with halo, nitro, carboxy, hydroxy, alkoxycarbonyl having 1 to 2 carbon atoms, -OR ⁶ , -SR ⁶ ,- SO-R ⁶ , or -SO ₂ -R ⁶ ,

R ⁶ is alkyl having 1 to 2 carbon atoms, alkyl having 1 to 2 carbon atoms substituted with halo, benzyl or phenyl,

m and n are independently 0, 1 or 2.

M is 1 or 2 when X is oxygen, R is methyl, and R ² is unsubstituted phenyl.

The present invention belongs to the field of agrochemicals and provides a method for producing novel herbicides for use before and after germination and to provide a method for the composition of the compounds used for weed removal. Since weed removal is an important issue in increasing crop yields, farmers have emerged as an indispensable tool for herbicides and therefore new and improved herbicide compounds are constantly in demand.

Although much research has been conducted in the field of agrochemicals, no effective compound has been previously published that is closely related to the compound of formula (1).

Flihalopyridine having two or more chlorine atoms and other alkyl and halosubstituents on the pyridine ring is completely different from known herbicides and compounds of formula (1).

Pyridone has been studied more extensively in organic chemistry. For example, Ishibe et al. Reported the translocation of 3,5-diphenyl-1,2,6-trimethyl-4 (1H) -pyridone [J. Am. Chem. Soc. 95,3396-3397 (1973). Such compounds are not herbicides. Leonard et al teach 3,5-dibenzyl-1-methyl-4 (1H) -pyridone synthesis method [J. Am. Chem. Soc. 77, 1852-1855 (1955)], but this compound also does not have herbicidal action.

Leonard also published 3,5-di (substituted-benzylidene) tetrahydro-4-pyridones [J. Am. Chem. Soc 79,156-160 (1957)], but these compounds also have no herbicidal action. Wright et al teach several kinds of 4-pyridone compounds containing 2,6-diphenyl-1-methyl-4 (1H) -pyridone and related compounds with phenyl ring substituents [J. org. Chem. 25,538-546 (1960)], but none of these compounds show herbicidal effect.

Recently, an interesting paper was published by El-Colli et al. [J. Hetero. Chem. 10,665-667 (published September 7, 1973). El-coli contains 3,5-diphenyl-1-methyl-4 (1H) -pyridone and related compounds as 1,5-dihydroxy-2,4-diphenyl-1,4-pentadiene- A synthetic method of reacting with methylamine of 3-one sodium salt has been described.

The present invention provides a novel process for producing novel 3-phenyl-4 (1H) -pyridones (thiions) effective against a wide range of weeds.

Methods and compositions of application compounds for weed removal have also been described which are particularly effective for cotton or rice cropland.

The novel compounds of formula (I) and acid addition salts thereof of the present invention are those in which R ¹ , R ² and m are as defined above and Q ¹ and Q ² are the other if one is a hydrogen atom, one is = CHNHY where Y is hydrogen, hydroxy, methyl or ethyl) or a compound of formula (II) is reacted with a formylating or amino formylating agent or Q ¹ and Q ² are = CHCO and = CHN (R ⁷ ) ₂ Wherein R ⁷ groups are independently alkyl having 1 to 3 carbon atoms or combine with adjacent nitrogen atoms to form pyrrolidino, piperidino, morpholino or N-methyl piperazino.

Reacting a compound of formula (II) with a compound of formula YNH ₂ (Y is as defined above) or an acid addition salt thereof to obtain a compound of formula (I), wherein if the = CHN (R ⁷ ) ₂ group is When derived from hydrolysis with an aqueous base or acid, the following structural formula (III) is obtained, followed by alkylation or esterification of the structural formula (III) with Y being hydrogen or hydroxy, respectively, to obtain the corresponding compound with Y being R When the compound of formula (I) wherein X is sulfur is intended, the compound is prepared by treating the compound of formula (I) wherein X is oxygen with P ₂ S ₅ and recovering the product in the form of acid addition salt as needed.

A preferred group of such compounds is when m is 1 and one R ¹ group is in the meta position of the phenyl ring attached.

Very preferred compounds are when R ^{1 in} this group is trifluoro methyl.

Particularly preferred compounds are those of the following structural formula (IV).

In the above structural formula,

X is oxygen or sulfur,

R ¹⁰ is methyl or ethyl,

R ⁸ is minor, trifluoromethyl, alkyl having 1 to 3 carbon atoms, halo, methoxy or methylthio,

R ⁶ is alkyl having 1 to 4 carbon atoms, alkoxy having 1 to 3 carbon atoms, alkylthio having 1 to 3 carbon atoms, phenyl, phenoxy, phenylthio or phenyl, trifluoro methyl, alkyl having 1 to 3 carbon atoms, halo, Phenoxy or phenylthio monosubstituted with oxy or methylthio.

The above-mentioned compounds may form acid addition salts, which salts are effective substances of the present invention. Preferred salts are hydrohalides such as hydroidide, hydrobromide, hydrochloride and hydro fluoride. Sulphonic acid salts are particularly preferred and these salts include sulfonates, methylsulfonates and toluenesulfonates.

Preferred synthesis of the compound of formula (I) is an improvement of the method such as El-Colli cited above.

Suitably substituted 1-phenyl-2-propanone is treated with the amine salt of the desired R substituent in an aqueous medium at a low temperature with a product that is formylated with sodium methoxide and ethyl formate in ether. The resulting intermediate is 1- (R-amino) -2-phenyl-1-buten-3-one of formula (II).

Other pyridine is also formed by this process according to the method of El-Coli et al. Butenone is reformylated and optionally cyclicized as described above to form 1-substituted-3-phenyl-4 (1H) -pyridone of formula (I).

Another preferred synthesis is similar to the one described above, but initially uses an amino formylation process instead of formylation. Preferred amino formylating agents are formmihalides such as the reaction product of phosgene and dimethylformamide.

The intermediate from which di-aminoformylated propanone is substituted with the amine or amine salt of the R substituent and hydrolyzed with acid or alkali to form 1-substituted 3-phenyl-4 (1H) -pyridone.

As chemists can expect, amines, YNH ₂ can be used in salt form and preferred hydro halide salts are hydrochloride, hydrobromide and the like. Such salts are sometimes more convenient than free amines.

The formylating agent used in this process is selected from the general reagents used for this reaction. Preferred reagents are formic acid esters of the formula

Similar formylation is described in organic synthesis 300-02 (vol III 1955).

Esters are used in the presence of strong bases, preferably alkali metal alkoxides such as sodium methoxide, potassium ethoxide and lithium propoxide. In addition, bases such as alkali metal hydrides and alkali metal amides and inorganic bases such as alkali metal carbonates and hydroxides may also be used. Strong organic bases such as diazobicyclononane and diazobicycloundecan are also useful.

The reaction of the formylating agent is carried out in aprotic solvents commonly used in chemical synthesis. Ethyl ethers are usually preferred solvents but generally ethers such as ethyl propylether, ethyl butylether, 1,2-dimethoxyethane and tetrahydrofuran, aromatic solvents such as benzene and xylene and alkanes such as hexane and octane Can be used as the formylating agent solvent.

Because strong bases are used in the formylation reaction, they are obtained in maximum yield at low temperatures. It is preferable to react between -25 ° C and 10 ° C. The reaction mixture may be left to warm to room temperature, but may be left to warm up after the reaction proceeds to completion. The reaction time is 1 to 24 hours is suitable for economically obtaining the yield in the formylation reaction.

The aminoformylating agent used in this synthesis can be any compound as long as it can react with an active methylene group to induce a = CHN (R ⁷ ) ₂ group or an acid addition salt thereof.

인 포메이트 에스테르 아미날류, 구조식

인 포름아마이드 아세틸류, 구조식

인 트리스(포르밀아미노) 메탄류 및 구조식

할로인 포름이미늄 할라이드 중에서 선택할 수 있다.These reagents are ortformamides of the structure HC [N (R ⁷ ) ₂ ] ₃ ,

Informate ester amines, structural formula

Phosphorus formamide acetyl, structural formula

Intris (formylamino) methane and structural formula

Haloin can be selected from formimium halides.

Q ³ is oxygen or sulfur and R ¹¹ is alkyl or phenyl having 1 to 6 carbon atoms.

References to aminoformylating agents include carboxylic acid derivatives 420-506 of Debolf (Academic pres 1970) and chemistry 87-96 (plenum press 1968) of imidoyl halides of Ulrich. Bredrek et al. Have published a number of papers on these reagents and reactions.

Ber. 101, 4048-56 (1968); Ber 104, 2709-26 (1971);

Ber. 106, 3732-42 (1973); Ber. 97, 3397-406 (1964);

Ann. 762, 62-72 (1972); Ber. 97, 3407-17 (1964);

Ber. 103, 210-21 (1970); Angew. chem 78, 147 (1966);

Ber. 98, 2887-96 (1965); Ber. 96 1505-14 (1963);

Ber. 104, 3475-85 (1971); Ber. 101, 41-50 (1968);

Ber. 106, 3725-31 (1973); Angew. Chem. Int'l. ed. S. 132 (1966).

As a paper other than the above title, Krautsberger et al. derphcrm. 301, 881-96 (1968) and 302, 362-75 (1969), and Bayernarten et al., J. Org. Chem. 32, 3293-94 (1967).

Aminoformylation is typically carried out at elevated temperatures of about 50 ° C. to 200 ° C. in the absence of solvent. However, solvents such as dimethylformamide are sometimes used, especially when the boiling point of the reaction mixture must be raised.

When aminoformylated with formimide halides, the aprotic solvent as described above for the formylated solvent is used at a temperature of 0 ° C. to 50 ° C., preferably at room temperature. If desired, halogenated solvents such as chloroform and methylene chloride may also be used for such aminoformylation.

Substitution with YNH ₂ can achieve the best performance in protic solvent, of which alkanol is preferred and ethanol is the most suitable solvent. The exchange reaction uses a temperature of -20 ° C to 100 ° C, but room temperature is satisfactorily preferred.

Starting materials of formula (II) may be prepared by reacting a compound of formula (V) with a reagent selected from the group consisting of formylating agents and aminoformylating agents.

In the above structural formula,

R ¹ , R ₂ and m are as defined above.

If a formylating agent is used, a ketone intermediate of formula (VI) is produced.

Reaction with an aminoformylating agent yields an enamino ketone of the formula

The organic chemists will understand that the first formylation or aminoformylation in structures (VI) and (iii) occurs on one side of the ketone but can occur on either side of the ketone depending on the activation properties of R ¹ and R ² . .

The reaction pathway is the same in either case. In various instances it can be seen that the product of the formylation or amino formylation process is actually a mixture containing two possible mono- and di-substituted compounds.

The matched compound is again formylated or aminoformylated to be substituted with an amine of formula YNH ₂ .

This process can be performed in any order.

If the substitution takes place first, the intermediate is the enaminoketone of the formula

Formylation or aminoformylation of the enaminoketone, which may also be represented by formula (II), produces pyridones. As soon as the intermediate is closed, another methylene group is present in the second group.

Formylation or aminoformylation of compound (VI) or (iii) yields an intermediate of the structure

Compounds similar to the inverted formyl and aminoformyl groups are the same as compounds (XI) in all respects.

One of the three intermediates, all of which can be represented by formula (II), is simply reacted with the amine of formula YNH ₂ to form pyridone.

2-propanone, the starting material of formula (V), can be prepared by the synthesis method according to the literature.

See, Coan et al., J. Am. Chem. Soc. 76,501 (1954); Sullivan et al., “Disodium Tetracarbonylferrate”, American Laboratory 49-56 (June 1974); Collman et al., “Synthesis of Hemifluorinted Ketones using Disodium Tetracarbonylferrate”, J. Am. Chem. Soc. 95, 2689-91 (1973); Collman et al., “ACYI and Alkyl Tetracacarbonylferrate Complexes as Intermediates in the Synthesis of Aldehydes and Ketones”, J. Am. Chem. Soc. 94, 2516-18 (1972).

Structural compounds are also prepared as follows.

Reaction (A) can also be carried out in the reverse manner as follows.

If the 3 and 5 substitutions of the pyridone product of formula (I) are the same, phosgene as carbonyl halide may be used to form starting materials of the formula (II) with the same Q ³ and Q ² .

In general, it is simply used in the continuous process of extraction, neutralization or removal of excess solvent or reactant after separation without purification of the intermediates in the synthesis.

Enamine acylation (A-C) is carried out in the above-mentioned aprotic solvent in the presence of a base such as tertiary amine, alkali metal carbonate, magnesium oxide and the like.

Sometimes after the pyridone compound is formed, more synthesis is needed. For example, it is convenient to substitute the oxygen atom after making the corresponding hydroxy-substituted compound so that the alkoxy R ¹ and R ⁵ substituents form the same compound.

The pyridine thiones of formula (I) can be readily prepared by treating the corresponding pyridones with P ₂ S ₅ at the reflux temperature in the pyridine according to known methods.

The 1-acetoxy compound of formula (I) is prepared by mincing with the corresponding 1-hydroxy pyridone using NH ₂ OH as the amine and then esterifying this product with acetic anhydride.

Other 1-substituents are obtained according to the suitable Y substituents on the amine, YNH ₂ used in the preparation of the pyridones.

In the following production practice, any one of the desired structural formula (I) compounds can be used by those skilled in the organic chemistry field.

The following examples show various processes according to the formula (I) compound prepared. However, any compound of formula (I) can be made by suitably changing all of the various processes. Many of the example compounds are made by the general process for preparing the compound of formula (I).

In this case it will be readily apparent that an organic chemist of ordinary skill has made some modifications to the example process required to prepare the compound in another embodiment.

The temperature is in degrees Celsius and the Nuclear Resonance (NMR) spectra were measured using tetramethylsilane as the internal standard with a 60-mega Hertz instrument and expressed in frequencies per second (cps). Melting point (m.p) was measured using the temperature meter.

In the first example, various processes for preparing the pyridone of the formula (I) by preparing the compound of the formula (III), which is the enamino ketone of the formula (VII), followed by aminoformylation and amination with the compound of the formula YNH ₂ .

Production method 1 below describes the formation of enamino ketones.

[Preparation 1]

1-dimethylamino-4- (3-nitrophenoxy) -2- (3-trifluoromethylphenyl) -1-butene-3- is 7.29 g of N-diethyl-3-trifluoromethyl styrylamine And 2.4 g of pyridine is dissolved in 6.45 g of 3-nitro-phenoxyacetyl chloride in 100 ml of diethyl ether and the mixture cooled to 0 ° C. is added dropwise to 60 ml of diethyl ether. After the addition, the mixture is stirred at 0 ° C. for 2 hours and further stirred at room temperature for 16 hours.

The reaction mixture is filtered, and the residue obtained by evaporation of the filtrate under vacuum is treated with dichloromethane, washed with water, dehydrated with magnesium sulfate, and evaporated under vacuum.

Example 1

1-Methyl-3- (3-nitrophenoxy) -5- (3-trifluoro methyl phenyl) -4 (1H) -pyridone

The residue obtained in Preparation 1 was heated to reflux for 10 hours by adding 50 ml of dimethylformamide dimethyl acetal, and then the reaction mixture was concentrated in vacuo and the residue oil was treated with 100 ml of ethanol. 10 g of methylamine hydrochloride is added and the mixture is heated at reflux for 10 hours. The reaction mixture is evaporated in vacuo, the residue is treated with dichloromethane, washed with water and then with saturated sodium chloride solution, dehydrated with magnesium sulfate and evaporated under vacuum to give a black oil. The residue oil is chromatographed on the silica gel with benzene, and then chromatographed with a mixed solvent with benzene which increases the ethyl acetate amount.

The product is eluted with 80% benzene and 20% ethyl acetate. The product containing the fractions is combined and evaporated in vacuo to give an oil.

Treatment of the oil with isopropyl ether followed by recrystallization with isopropyl ether / dichloromethane yields 2.9 g of pyridone of the name. Melting Point: 171 to 172 ° C

The following example compounds are prepared in a similar manner to Example 1. Some modifications are needed to prepare several other compounds.

Example 2

3- (4-methoxy-3-methylphenyl) -1-methyl-5-phenyl-4 (1H) -pyridon, melting point 157-160 ° C., yield 2.5%

Example 3

3- (3-Bromo-4-methylphenyl) -1-methyl-5-phenyl-4 (1H) -pyridon, melting point 168-170 ° C., yield 13%

Example 4

1-methyl-3- (3-nitrophenyl) -5- (3-trifluoromethyl-phenyl) -4 (1H) -pyridone, melting point 209 to 211 ° C., yield 51%

Example 5

1-Methyl-3-phenyl-5- (3-peptiophenyl) -4 (1H) -pyridon, mass spectrometer, MI, 369, yield 8% The following compounds are prepared by oxidation of the compounds with hydrogen peroxide in acetic acid. .

Example 6

1-methyl-3-phenyl-5- (3-phenylsulfonyl phenyl) -4 (1H) -pyridone, melting point 65-72 ° C., yield 48% The following compounds are prepared according to the process of Example 1.

Example 7

3- (2-Chloro-4-fluorophenyl) -1-methyl-5-phenyl-4 (1H) -pyridon, melting point 190-192 ° C., yield 5%

Example 8

3- (3,4-dimethylphenyl) -1-methyl-5-phenyl-4 (1H) -pyridone, melting point 108-111 ° C., yield 5%

Example 9

3- (3,5-dimethylphenyl) -1-methyl-5-phenyl-4 (1H) -pyridone, melting point 148 to 150 ° C., yield 10%

Example 10

3- (3-butylphenyl) -1-methyl-5-phenyl-4 (1H) -pyridon, melting point 87-89 ° C., yield 6%

Example 11

3- (2,5-dimethylphenyl) -1-methyl-5-phenyl-4 (1H) -pyridone, melting point 188 to 190 ° C., yield 4%

Example 12

3- (2,4-dimethylphenyl) -1-methyl-5-phenyl-4 (1H) -pyridone, melting point 153 to 155 ° C., yield 3%

Example 13

1-methyl-3-phenoxy-5- (3-trifluoromethylphenyl) -4 (1H) -pyridone, melting point 144-145 ° C., yield 15%

Example 14

3-ethoxycarbonyl-1-methyl-5- (3-trifluoro methyl-phenyl) -4 (1H) -pyridone, melting point 151 to 152 ° C., yield 62%

Example 15

1-methyl-3- (3-trifluoromethylphenyl) -5-phenyl-thio-4 (1H) -pyridon, melting point 164-165 DEG C, yield 18%

Example 16

3- (2,4-Dichlorophenoxy) -1-methyl-5- (3-trifluoro-methylphenyl) -4 (1H) -pyridone, melting point 129-130 ° C., yield 40%

Example 17

1-methyl-3- (2-thienyl) -5- (3-trifluoro methyl-phenyl) -4 (1H) -pyridone, melting point 185-186 ° C., yield 84%

Example 18

3-ethylthio-1-methyl-5-phenyl-4 (1H) -pyridon, melting point 94-95 ° C., yield 40%

Example 19

3-Ethylthio-1-methyl-5- (3-trifluoromethylphenyl) -4 (1H) -pyridon, melting point 84-85 ° C., yield 40% The following example compound is obtained by converting the compound of Example 19 to methylene di Prepared by oxidation with hydrogen peroxide at about 0 ° C. in chloride.

Example 20

3-ethylsulfonyl-1-methyl-5- (3-trifluoromethyl-phenyl) -4 (1H) -pyridone, melting point 196-198 ° C., yield 70%

The following compound is prepared by oxidizing the compound of Example 19 with sodium peroxoate for 16 hours in aqueous methanol at room temperature.

Example 21

3-ethylsulfinyl-1-methyl-5- (3-trifluoromethyl-phenyl) -4 (1H) -pyridone, melting point 146-148 ° C., yield 82%

The following compounds were prepared according to the process of Example 1.

Example 22

3- (5-Bromo-2-fluorophenyl) -1-methyl-5-phenyl-4 (1H) -pyridon, melting point 148-150 ° C., yield 6%

Example 23

1-methyl-3- (5-nitro-2-methylphenyl) -5-phenyl-4 (1H) -pyridone, melting point 185-187 ° C., yield 5%

Example 24

3-cyano-5- (2,5-nimethoxyphenyl) -1-methyl-4 (1H) -pyridon, melting point 209 to 211 ° C., yield 4%

Example 25

3- (2,6-dichlorophenyl) -1-methyl-5-phenyl-4 (1H) -pyridone, melting point 223 to 226 ° C., yield 20%

Example 26

3-ethoxycarbonyl-1-methyl-5-phenyl-4 (1H) -pyridone, melting point 107-108 ° C., yield 68%

Example 27

1-methyl-3-propylthio-5- (3-trifluoromethyl phenyl) -4 (1H) -pyridone, melting point 101-102 ° C., yield 25%

Example 28

3-butylthio-1-methyl-5- (3-trifluoromethyl phenyl) -4 (1H) -pyridone, melting point 109-110 ° C., yield 35%

Example 29

1-methyl-3-methylthio-5- (3-trifluoromethyl phenyl) -4 (1H) -pyridone, melting point 121-122 ° C., yield 20%

Example 30

1-methyl-3- (3-trifluoromethylphenyl) -5- (4-tri-fluoromethyl phenyl) -4 (1H) -pyridone, melting point 110-113 ° C., yield 10%

Example 31

1-Methyl-3- (3-trifluoromethyl phenyl) -5-trifluoro-methylio-4 (1H) -pyridon, melting point 122-124 ° C., yield 21%

Example 32

3- (3,4-dimethoxy phenyl) -1-methyl-5- (3-trifluoro-methyl phenyl) -4 (1H) -pyridon, melting point 148-150 ° C., yield 10%

Example 33

3- (5-fluoro-2-indo phenyl) -1-methyl-5-phenyl-4 (1H) -pyridone and 3- (2-bromo-5-fluorophenyl) -1-methyl-5 A mixture of -phenyl-4 (1H) -pyridone, mixed melting point 211-214 캜, yield 7%

Example 34

3-benzylthio-1-methyl-5- (3-trifluoro methyl phenyl) -4 (1H) -pyridone, melting point 121-122 ° C., yield 40%

Example 35

3- (4-benzyloxyphenyl) -1-methyl-5- (3-trifluoro-methylphenyl) -4 (1H) -pyridon, amorphous, yield 10%

Example 36

1,3-diethyl-5- (3-trifluoromethylphenyl) -4 (1H) -pyridone, melting point 67-70 ° C., yield 3% The following compounds are present in 5% palladium on carbon, which is a hydrogenation catalyst in acetic acid The compound of Example 35 is prepared under hydrogenation.

Example 37

3- (4-hydroxyphenyl) -1-methyl-5- (3-trifluoro methyl-phenyl) -4 (1H) -pyridone, melting point 162 to 163 ° C., yield 50%

The general procedure of Example 1 is used to prepare the following compounds.

Example 38

3- (4-Chloro-3-trifluoromethylphenyl) -5-ethoxy-1-methyl-4 (1H) -pyridon, melting point 158-159 ° C., yield 15%

Example 39

1-Methyl-3-isopropylthio-5- (3-trifluoro methyl-phenyl) -4 (1H) -pyridone, melting point 93-94 ° C., yield 32%

Example 40

3- (4-Chloro-3-trifluoro methyl phenyl) -5-ethyl thio-1-methyl-4 (1H) -pyridone, melting point 115-116 ° C., yield 11%

Example 41

3- (4-Chloro-3-trifluoromethylphenyl) -1-methyl-5-phenyl-4 (1H) -pyridon, melting point 154-155 캜, yield 17%

Example 42

3- (2,5-dimethylphenyl) -1-methyl-5- (3-trifluoromethylphenyl) -4 (1H) -pyridon, lubricating gum 165-167 ° C., yield 2%

Example 43

3- (3,5-dimethylphenyl) -1-methyl-5- (3-trifluoromethylphenyl) -4 (1H) -pyridone, melting point 160-163 ° C., yield 6%

Example 44

3- (2,4-Dichlorophenyl) -1-methyl-5- (3-trifluoro-methylphenyl) -4 (1H) -pyridone, melting point 139-142 ° C yield 11%

Example 45

1-methyl-3-phenyl-5- (2-trifluoromethylphenyl) -4 (1H) -pyridone, melting point 168-171 ° C., yield 14%

Example 46

1-methyl-3- (2-trifluoromethylphenyl) -5- (3-trifluoromethylphenyl) -4 (1H) -pyridone, melting point 135-138 ° C., yield 24%

Example 47

3- (3,4-dimethyl phenyl) -1-methyl-5- (3-trifluoro-methyl phenyl) -4 (1H) -pyridon, melting point 150-153 ° C., yield 15%

Example 48

3- (3-iodophenyl) -1-methyl-5- (3-trifluoromethylphenyl) -4 (1H) -pyridone, melting point 178-181 ° C., yield 15%

Example 49

3-ethyl-1-methyl-5- (3-methoxyphenyl) -4 (1H) -pyridone, yield 5%, mass spectrometer MI, 243

Example 50

1-Methyl-3- (3-iodophenyl) -5-phenyl-4 (1H) -pyridon, melting point 190-193 ° C., yield 8%

Example 51

1-methyl-3- (4-methoxyphenoxy) -5- (3-trifluoromethylphenyl) -4 (1H) -pyridone, melting point 119-120 ° C., yield 25%

Example 52

1-methyl-3- (4-chloro-3-trifluoromethylphenyl) -5-trifluoromethyl) -4 (1H) -pyridone, melting point 164-165 DEG C, yield 2%

Example 53

1-methyl-3- (4-chloro-3-trifluoromethylphenyl) -5-trifluoromethyl) -4 (1H) -pyridone, melting point 164-165 DEG C, yield 2%

Example 54

1-methyl-3- (4-chloro-3-trifluoromethylphenyl) -5-propyl-4 (1H) -pyridone, melting point 141 to 142 ° C., yield 8%

Example 55

1-Methyl-3-isopropylthio-5- (4-chloro-3-trifluoro-methyl phenyl) -4 (1H) -pyridon, melting point 127-129 ° C., yield 15%

Example 56

1-methyl-3- (4-chloro-3-trifluoro methyl phenyl) -5-propylthio-4 (1H) -pyridone, melting point 128-130 ° C., yield 15%

Example 57

1-methyl-3- (4-chloro-3-trifluoro methyl phenyl) -5- (2-thienyl) -4 (1H) -pyridone, melting point 166-168 ° C., yield 10%

Example 58

3-ethyl-1-methyl-5- (4-chloro-3-trifluoromethyl-phenyl) -4 (1H) -pyridone, melting point 121-123 ° C., yield 1%

Example 59

1-methyl-3- (2,4-dimethylphenyl) -5- (3-trifluoromethylphenyl) -4 (1H) -pyridone, melting point 128-131 ° C., yield 6%

Example 60

3-isopropoxy-1-methyl-5- (3-trifluoromethylphenyl) -4 (1H) -pyridon, mass spectrometer MI, 311, yield 1%

Example 61

1-Methyl-3- (4-chlorophenoxy) -5- (3-trifluoromethyl-phenyl) -4 (1H) -pyridon, melting point 90-91 ° C., yield 15%

Example 62

1-methyl-3- (3-methylthiophenyl) -5- (trifluoromethylphenyl) -4 (1H) -pyridone, melting point 150-153 ° C. yield 25%

The following compound is prepared by oxidizing the compound of Example 62 with hydrogen peroxide in pyridine at room temperature.

Example 63

1-methyl-3- (3-methyl sulfonyl phenyl) -5- (3-triblueomethyl phenyl) -4 (1H) -pyridone, melting point 180-183 ° C. yield 20%

The general process of Example 1 is used to prepare the following compounds.

Example 64

1-Methyl-3- (3-trifluoro methylphenoxy) -5- (3-trifluoro methylphenyl) -4 (1H) -pyridone, melting point 93-95 ° C., yield 40%

Example 65

3- (4-methoxyphenyl) -1-methyl-5- (3-trifluoro methylphenyl) -4 (1H) -pyridone, melting point 160-162 ° C., yield 40%

Example 66

3- (2,3-Dichlorophenoxy) -1-methyl-5- (3-trifluoro-methylphenyl) -4 (1H) -pyridone, melting point 200-202 ° C., yield 30%

Example 67

3- (3,5-Dichlorophenoxy) -1-methyl-5- (3-trifluoro-methylphenyl) -4 (1H) pyridone, melting point 128-130 ° C., yield 30%

Example 68

3- (3,4-Dichlorophenoxy) -1-methyl-5- (3-trifluoro-methylphenyl) -4 (1H) -pyridone, melting point 127-129 ° C. yield 20%

Example 69

3- (4-Chloro-3-trifluoromethylphenyl) -1-methyl-5-isopropyl-4 (1H) -pyrazone, melting point 85-87 ° C. yield 25%

Example 70

3- (2,5-Dichlorophenoxy) -1-methyl-5- (3-trifluoro-methylphenyl) -4 (1H) -pyridone, melting point 162-164 ° C yield 28%

Example 71

1-methyl-3- (4-methylthiophenoxy) -5- (3-trifluoromethylphenyl) -4 (1H) -pyridone, melting point 138-140 ° C. yield 17%

Example 72

3-Isobutylthio-1-methyl-5- (3-trifluoromethyl-phenyl) -4 (1H) -pyridon, mass spectrometer MI, 341, yield 1%

Example 73

3- t -butylthio-1-methyl-5- (3-trifluoromethyl-phenyl) -4 (1H) -pyridone, melting point 124-125 ° C., yield 1%

Example 74

3- S -butylthio-1-methyl-5- (3-trifluoromethylfetyl) -4 (1H) -pyridon, mass spectrometer MI, 341, yield 1%

Example 75

1-methyl-3- (4-nitrophenoxy) -5- (3-trifluoromethyl-phenyl) -4 (1H) -pyridone, melting point 160-161 ° C., yield 21%

Example 75

3-Methyl-1-hydroxy-5- (3-trifluoromethylphenyl) -4 (1H) -pyridon, melting point 134-136 ° C., yield 1%

Example 76

1-methyl-3-trifluoromethylsulfonyl-5- (3-trifluoromethylphenyl) -4 (1H) -pyridone, solvent point 155-157 ° C., yield 1%

Example 77

1-methyl-3- (3-trifluoro methylphenyl) -5- (3-trifluoro methylthiophenyl) -4 (1H) -pyridone, multiline at NMR 8.0-7.1 ppm, singlet at 3.27 ppm , Yield 1%

Due diligence example 78

1-methyl-3- (3-trifluoromethylphenyl) -5- (3-trifluoromethylsulfonylphenyl) -4 (1H) -pyridone, melting point 164-166 DEG C, yield 1%

Due diligence example 79

1-methyl-3- (2,2,2-trifluoro ethoxy) -5- (3-trifluoromethylphenyl) -4 (1H) -pyradone, multiplet appearing at NMR8.0-7.1 ppm, 4. Quadruple at 6ppm, singlet at 3.7ppm, yield 1%

Due diligence 79A

1-methyl-3- (2-nitrophenyl) -5- (3-trifluoromethyl-phenyl) -4 (1H)-, pyridone, melting point 230-232 ° C. yield 10%

Examples of the following group are prepared by aminoformylating ketone of formula (V) to prepare bis (aminoformylated) compound of formula (II), and then reacting with an amine of formula YNH ₂ to obtain the desired compound of formula (Ι). The preparation method of the compound which produces a pyridone is demonstrated.

[Method 2]

1,5-di (dimethylamino) -2- (3-methylphenyl) -4- (3-trifluoromethylphenyl) -1,4-pentadiene-3- is 4.5 g of 1- (3-methylphenyl)- 3- (3-trifluoromethyl) -2-propanone is mixed with 20 ml of dimethylformamide dimethylacetal and heated under reflux for 16 hours. The reaction mixture is concentrated in vacuo to give an oily residue.

Example 80

1-Methyl-3- (3-methylphenyl) -5- (3-trifluoromethyl-phenyl) -4 (1H) -pyridon

The residue of Preparation 2 is treated with 100 ml of methanol and 10 g of methylamine hydrochloride is added. The mixture is heated at reflux for 16 h and then concentrated in vacuo. The residue is treated with chloroform and washed with water and dilute hydrochloric acid. The solution is eluted with a solvent of benzene / ethyl acetate (1: 1) on a silica gel chromatography column. The products containing fractions are combined and evaporated to dryness in vacuo. The residue was treated with hexane and recrystallized to yield 0.4 g of the above named product. Melting Point 155-157 ℃

The following example compounds are prepared in a similar manner to Example 80 above.

Example 81

1-methyl-3- (2-methylphenyl) -5- (3-trifluoromethyl-phenyl) -4 (1H) -pyridone, melting point 144-147 ° C., yield 5%

Example 82

1-methyl-3- (4-methylphenyl) -5- (3-trifluoromethylphenyl) -4 (1H) -pyridone, solvent point 154 to 156 ° C., casting rate 6%

Example 83

5- (3-methoxycarbonylphenyl) -1-methyl-3- (4-methyl-phenyl) -4 (1H) -pyridone, melting point 85-88 ° C., yield 5%

Example 84

5- (3-methoxycarbonylphenyl) -1-methyl-3- (3-methylphenyl) -4 (1H) -pyridone, melting point 180-183 ° C., yield 1%

Example 85

3-methoxy-1-methyl-5- (3-trifluoromethylphenyl) -4 (1H) -pyridone, melting point 173 to 175 ° C., yield 18%

Example 86

3- (4-Bromophenyl) -1-methyl-5- (3-methylphenyl) -4 (1H) -pyridone, melting point 201 to 204 ° C., yield 21%

Example 87

3- (3,4-Dichlorophenyl) -1-methyl-5- (3-trifluoromethyl-phenyl) -4 (1H) -pyridon, melting point 109-112 ° C., yield 4%

Example 88

3,5-bis- (3,5-dichlorophenyl) -1-methyl-4 (1H) -pyridone, melting point 275 to 278 ° C, yield 14%

Example 89

3- (3,4-Dichlorophenyl) -1-methyl-5- (3-methyl-phenyl) -4 (1H) -pyridon, mass spectrometer MI, 342, yield 10%

Example 90

3- (3,4-Dichlorophenyl) -5- (3,4-dimethylphenyl) -1-methyl-4 (1H) -pyridone, melting point 150-152 ° C., yield 6%

Example 91

3- (3-Chlorophenyl) -1-methyl-5- (2-methylphenyl) -4 (1H) -pyridon, melting point 171-173 ° C., yield 12%

Example 92

3- (4-Bromophenyl) -1-methyl-5- (3-trifluoromethyl-phenyl) -4 (1H) -pyridone, melting point 144-146 degreeC, yield 30%

The next compound is prepared by refluxing the compound in 60% sulfuric acid.

Example 93

3- (4-Bromophenyl) -5- (3-carboxyphenyl) -1-methyl-4 (1H) -pyridine, melting point 259-263 ° C., yield 50% The following compound was prepared according to the process of Example 80 do.

Example 94

3- (3-Chlorophenyl) -1-methyl-5- (4-trifluoromethyl-phenyl) -4 (1H) -pyridon, melting point 147-151 ° C., yield 2%

Example 95

3- (2-methylphenyl) -5- (4-methylphenyl) -1-methyl-4 (1H) -pyridon, melting point 151 to 154 ° C., yield 6%

Example 96

3- (3-methylphenyl) -5- (4-methylphenyl) -1-methyl-4 (1H) -pyridon, melting point 155-157 ° C., yield 28%

Example 97

3- (2-Chlorophenyl) -5- (2-methylphenyl) -1-methyl-4 (1H) -pyridon, melting point 87-91 ° C., yield 1%

Example 98

1-methyl-3,5-bis (4-methylphenyl) -4 (1H) -pyridone, melting point 212 to 214 ° C, yield 3%

Example 99

1-methyl-3- (3-chlorophenyl) -5- (3,4-dichlorophenyl) -4 (1H) -pyridone, melting point 107-110 ° C., yield 10%

Example 100

1-methyl-3- (3,4-dichlorophenyl) -5- (2-methyl-phenyl) -4 (1H) -pyridone, melting point 103 to 106 ° C, yield 10%

Example 101

1-methyl-3- (2-chlorophenyl) -5- (3,4-dichlorophenyl) -4 (1H) -pyridone, melting point 169 to 171 ° C., yield 25%

Example 102

1-methyl-3- (3-bromophenyl) -5- (3,4-dichlorophenyl) -4 (1H) -pyridone, melting point 152 to 154 ° C., yield 10%

Example 103

1-methyl-3- (3,5-dichlorophenyl) -5- (3-trifluoromethylphenyl) -4 (1H) -pyridone, melting point 156-160 ° C., yield 30%

Example 104

1-methyl-3- (3-bromophenyl) -5- (3-methylphenyl) -4 (1H) -pyridone, melting point 144-147 ° C., yield 3%

Example 105

1-methyl-3,5-bis (3-methylphenyl) -4 (1H) -pyridone, melting point 148 to 150 ° C., yield 8%

Example 106

1-Methyl-3- (3-fluorophenyl) -5- (2,5-dimethyl-phenyl) -4 (1H) -pyridon, mass spectrometer MI, 307, yield 10%

Example 107

3- (3-Bromophenyl) -1-methyl-5- (2-methylphenyl) -4 (1H) -pyridon, mass spectrometer MI, 353, yield 2%

Example 108

3- (3-Bromophenyl) -5- (2-chlorophenyl) -1-methyl-4 (1H) -pyridon, melting point 177-179 ° C., yield 10%

Example 109

3- (2-Bromophenyl) -1-methyl-5- (3-trifluoromethyl-phenyl) -4 (1H) -pyridon, melting point 197-199 ° C., yield 15%

Example 110

3- (2,3-dimethoxyphenyl) -1-methyl-5- (3-trifluoro methylphenyl) -4 (1H) -pyridone, melting point 153 to 155 ° C., yield 20%

Example 111

3- (2-methoxyphenyl) -1-methyl-5- (3-trifluoromethyl-phenyl) -4 (1H) -pyridone, melting point 193-196 ° C., yield 10%

Example 112

3- (2-ethylphenyl) -1-methyl-5- (3-trifluoromethylphenyl) -4 (1H) -pyridon, melting point 123-125 ° C., yield 15%

Example 113

3- (3-Bromo-4-methylphenyl) -1-methyl-5- (3-trifluoromethylphenyl) -4 (1H) -pyridon, melting point 158-161 ° C., yield 30%

Example 114

3- (4-Ethoxy-4-methoxyphenyl-1-methyl-5- (3-trifluoromethylphenyl) -4 (1H) -pyridone, mass spectrometer MI, 403, yield 10%

Example 115

3- (1-hydroxyethyl) -1-methyl-5- (3-trifluoromethyl-phenyl) -4 (1H) -pyridone, mass spectrometer MI, 297, yield 1%

Example 116

3- (1-methoxyethyl) -1-methyl-5- (3-trifluoromethyl-phenyl) -4 (1H) -pyridon, mass spectrometer MI, 311, yield 1%

The following preparations and examples provide a process for preparing the compound of formula (I) in a number of processes in which propanone in structure (IV) is formylated, substituted with an amine, and then formylated to form pyridone of formula (I). It is explained.

[Process 3]

2,4-bis (3-trifluoromethylphenyl) -1-methylamino-1-buten-3-one

2.2 g of 1,3-bis (3-trifluoromethylphenyl) -2-propanone was mixed with a solution of 1 g of sodium methoxide dissolved in 50 ml of methyl formate, and the mixture was left at room temperature overnight. Evaporate and dry in vacuo. To the residue was added 3 g of ethylamine hydrochloride as an aqueous solution, the solution was extracted with ethyl acetate and the extract was evaporated to dryness.

Example 117

1-ethyl-3,5-bis (3-trifluoromethylphenyl) -4 (1H) -pyridone

The product of Preparation 3 is treated with sodium methoxide and ethylformate as described in Preparation 3, the reaction compound is left for 4 hours, evaporated, dried and treated with ethylamine hydrochloride in water as described in Preparation 3 . The reaction mixture was extracted with ethyl acetate and determined by addition of hexane to give 0.85 g of the above named product. Melting point 185 ℃

The following preparation and examples are described the methods for synthesizing the amino-Q ¹ and Q ² is formyl group, a formyl group in formula (Ⅱ) amine and the reaction sikimeuroseo formula (Ⅰ) compounds of compound.

[Process 4]

1-diethylamino-5-hydroxy-4-ethoxy-2- (3-trifluoromethylphenyl) -1,4-pentadien-3-one

Enamine is formed according to the method of Preparation 1 with 4.86 g of N-diethyl-3-trifluoromethyl styrylamine and 2.44 g of ethoxyacetyl chloride. To enamine added 75 ml of tetrahydrofuran at 0 ° C., 3.2 g of sodium methoxide and 4.4 g of ethylformate were added. After stirring the mixture for 3 hours, an intermediate compound of the above name is prepared.

Example 118

1-Methyl-3-ethoxy-5- (3-trifluoromethylphenyl) -4 (1H) -pyridon

The solution, the product of Preparation 4, is mixed with 50 ml of 40% aqueous methylamine and 5 g of methylamine hydrochloride, then the solution is stirred overnight at room temperature, evaporated and dried in vacuo. The residue is treated with dichloromethane, washed with water and then dehydrated with magnesium sulfate. The filtered black residue is treated with cold isopropyl ether.

Recrystallization of the product from isopropyl ether / dichloromethane yielded 1.6 g of the desired product. Melting point 131 to 133 ° C

The following examples prepare compounds of formula (I) in various processes to produce the desired product by reacting a compound of formula (II) wherein one of Q ¹ and Q ² is an aminopropyl group and the amino substituent is Y with a formylating agent. How to do this.

[Method 5]

1-methylamino-2- (4-chloro-3-trifluoromethylphenyl) -4-phenoxy-1-buren-3-one

Acylated enamines are prepared according to the process of Preparation 1 from 5.6 g of 4-chloro-3-trifluoromethyl-N-diethyl styryl subline and 3.4 g of phenoxy acetyl chloride.

The resulting acylated enamines of formula VI are suspended in 100 ml of ethanol and treated with 50 ml of 40% aqueous methylamine. The reaction mixture is stirred for 30 minutes and then concentrated in vacuo. The concentrated residue was treated with 600 ml of dimethyl ether, washed with water and then dehydrated with magnesium sulfate. The reaction mixture is evaporated to dryness.

Example 119

1-Methyl-3- (4-chloro-3-trifluoromethylphenyl) -5-phenoxy-4 (1H) -pyridon

The product of Preparation 5 is treated with 100 ml of dichloromethane and 50 ml of ethylformate and 10 g of sodium methoxide are added. After stirring the reaction mixture for 40 minutes, 5 g of sodium methoxide is further added and the mixture is stirred for 16 hours. The solution was washed with dilute hydrochloric acid, dilute sodium hydroxide and saturated sodium chloride, then dehydrated with magnesium sulfate and evaporated in vacuo to give 6 g of oil. This oil was purified by chromatography on silica gel using 1: 1 ethyl acetate toluene as eluent to afford 2.06 g of the above named product. Melting Point 130 ~ 131 ℃

The following example is prepared according to the process of Example 119 above.

Example 120

1-Methyl-3-arylthio-5 (3-trifluoromethylphenyl) -4 (lH) -pyridone, melting point 74-75 ° C., yield 5%

Example 121

1-methyl-3-methoxy-5-phenyl-4 (1H) -pyridone, melting point 153 to 155 ° C., yield 10%

The following examples illustrate various processes for preparing the compound of formula (I) by reacting a compound of formula (II), which is an amino formyl group substituted with a Q ^{1 to} Y group, with an aminoformylating agent.

Example 122

1-methyl-3- (1-methylbutylthio) -5- (3-trifluoromethylphenyl) -4 (1H) -pyridone

1-Methylamino-4- (1-methylbutylthio) -2- (3-trifluoromethylphenyl) -1-buten-3-one was prepared according to the process of Preparation 5. To this intermediate was added 150 ml of toluene and 5 ml of dimethylformamide dimethyl acetal, and the mixture was then arranged at reflux for 24 hours. Evaporation of the reaction mixture under vacuum yields an oil. Purification of the oil by chromatography yields 1.5 g of the purified product of the above name. Yield approximately 10% mass spectroscopy confirms 355 molecular ions.

The following example compound is prepared by the synthesis method used in Example 122.

Example 123

3- (2-Hydroxypropyl) -1-methyl-5- (3-triflouro-methylphenyl) -4 (1H) -pyridone, melting point 99-102 ° C., yield 10%

Example 124

1-methyl-3- (2-methyl-2-promenylthio) -5- (3-trifluoromethylphenyl) -4 (1H) -pyridone, melting point 86-88 ° C., yield 10%

Example 125

3-ethylthio-5- (2-chloro-5-trifluoro methylphenyl) -1-methyl-4 (1H) -pyridon, melting point 127-129 ° C., yield 15%

Example 126

3- (2-Chloro-5-trifluoromethylphenyl) -1-methyl-5-phenyl-4 (1H) -pyridon, melting point 150-152 ° C., yield 30%

Example 127

3- (2-Chloro-5-trifluoromethylphenyl) -1-methyl-5- (3-trifluoromethylphenyl) -4 (1H) -pyridon, NMR peak is polyline at 8.0 to 7.2 ppm, 3.57 Single line at ppm, yield 40%

The following example illustrates a method for preparing a compound of formula (I) by reacting an amine of formula YNH ₂ with an intermediate of formula (II), which is an aminoformyl group, if the haga or formyl group is Q ¹ .

[Preparation 6]

1-diethylamino-5-highoxy-2-phenyl-4- (3-trifluoromethylphenyl) -1,4-pentaien-3-one

10 g of 1-hydroxy-4-phenyl-2- (3-trifluoro methylphenyl) -1-buten-3-one were prepared according to the process of Preparation 3, to which excess dimethylformamide diethyl acetal was added. The mixture is then heated to reflux for 12 hours.

The reaction mixture is cooled down and concentrated in vacuo to afford the intermediate of the name.

Example 128

1-hydroxy-3-pepe-5- (3-trifluoro methylphenyl) -4 (1H) -pyridone

The intermediate obtained in Preparation 6 is dissolved with ethanol and mixed with 10 g of hydroxyamine hydroxychloride. The mixture is heated under reflux for 6 hours and cooled to crystallize the product. It is filtered out of the reaction mixture and recrystallized from ethanol / hexane to give 2.0 g of the above named product. Melting point 240 ~ 243 ℃

The following example is prepared according to the process of Example 128.

Example 129

3- (3-carboxyphenyl) -1-methyl-5-phenyl-4 (1H) -pyridone, melting point 265 to 267 ° C., yield 1% The following compound was prepared and esterified according to the procedure of Example 128; .

Example 130

1-acetoxy-3-phenyl-5- (3-trifluoromethylphenyl) -4 (1H) -pyridone, melting point 232-235 ° C., yield 5%

The following example illustrates the preparation of pyridone thiones.

Example 131

5 g of 1-methyl-3- (3-bromophenyl) -5-phenyl-4 (1H) -pyridinethione 1-methyl-3- (3-bromophenyl) -5-phenyl-4 (1H)- Pyridone is mixed with 5 g of phosphorus pentasulfide in pyridine and heated at reflux for 2 hours. The mixture is slowly poured into water and filtered. The solid material is dried in air and then crystallized from ethanol to give 3.1 g of the product of the above name. Melting Point 185 ~ 188 ℃

Example 132

1-methyl-3- (4-chlorophenyl) -5- (3-trifluoromethylphenyl) -4 (1H) -pyridinethione, melting point 239 to 242 ° C, yield 25%

Example 133

1-methyl-3- (3-methylphenyl) -5- (3-trifluoromethylphenyl) -4 (1H) -pyridinethione, melting point 193-196 ° C., yield 50%

Example 134

1-methyl-3- (2-methylphenyl) -5- (3-trifluoromethylphenyl) -4 (1H) -pyridinethione, melting point 193-195 ° C., yield 35%

Example 135

1-methyl-3-propyl-5- (3-trifluoromethylphenyl) -4 (1H) -pyridinethione, melting point 145 to 148 ° C., yield 40%

Example 136

1-Methyl-3-phenoxy-5- (3-trifluoromethylphenyl) -4 (1H) -pyridinethione, melting point 127-131 degreeC, yield 40%

Example 137

3-ethylthio-1-methyl-5- (3-trifluoromethylphenyl) -4 (1H) -pyridinethione, melting point 136-138 ° C., yield 55%

Example 138

3-Ethoxy-1-methyl-5- (3-trifluoromethylphenyl) -4 (1H) -pyridinethione, melting point 153 to 155 ° C., yield 5%

The compounds of Examples 80-138 are also prepared according to the process of Example 1.

The compounds of Examples 1-79 and 117-138 are also prepared according to the process of Example 80.

The compounds of Examples 1-116 and 118-138 are also prepared according to the process of Example 117.

The compounds of Examples 1-117 and 119-138 are also prepared according to the process of Example 118.

The compounds of Examples 1-118 and 122-138 are also prepared according to the process of Example 119.

The compounds of Examples 1-121 and 128-138 are also prepared according to the process of Example 122.

The compounds of Examples 1-127 and 131-138 are also prepared according to the process of Example 128.

The herbicidal effects of the compounds described above were tested to determine the herbicidal effects of these compounds. The excellent results obtained with this compound in the representative tests described below are good examples of the good action of the compounds.

The percentage of compound used is given in this specification and claims as compound Kg per hectare of land (Kg / ha). Blanks in the table below do not test compounds against named species. In some cases, the values obtained by repeating the test for the plant species were averaged.

Untreated controls or floats were included in all tests. The control ratio obtained with this compound is a value obtained in comparison with plants or floats treated with modulators.

In the test, plants were graded 1-5, with 1 representing normal plants and 5 representing dead trees or no germination.

Fill a sterile loam with a flat metal tray and plant the plant seeds in the table below. Give each manure. The test compound was used after germination and before germination. After 12 days of seeding, the germinated plant was sprayed with the present compound for post-germination test, and the seed was sprayed with the soil on the day of seeding by the pre-germination test.

Each test compound is dissolved at a ratio of 6 g per 100 ml of acetone: ethanol (= 1: 1) and 2 g per 100 ml of anionic nonionic surfactant is used in the solution. Deionized water is added to 1 ml of this solution to make 12 ml, and the resulting solution is sprayed on each tray at an application rate of 9.0 kg / ha of the test compound. After treatment with the compounds, each tray is transferred to a greenhouse and watered if necessary for 10 to 13 days after application. Untreated control plants were standard in each test.

TABLE 2

In another test, NATO barn yard grass was planted in a large metal pot and pyridone compounds were applied in three different ways. Compounds used in all tests were formulated with 50% hydration.

A. A test compound with the following designation was incorporated into the soil surface of 8 cm height in the pot according to the application rate of the table below, sowing rice and seeds to a depth of 1.8 to 2.5 cm, and watered daily until the rice grew to 5 to 8 cm. Then add more water to a depth of 5 to 8 cm and maintain this state for the duration of the test.

B. Fill the pot with soil and sow seeds as above. Water the pot so that the water of 5-8 cm depth fills and transfer the rice seedlings to the pot. Three days after rice seedlings are planted, the test compound is sprayed onto the water.

C. Incorporate the test compound into the surface 8 cm high and seed the seed to a depth of 1.8 to 2.5 cm. Water is added to the pot so that the depth of water is 5 to 8 cm, and 5 days after the rice seedling treatment, it is transferred to the pot. Three weeks later, the evaluation of rice injuries and removed blood was divided into grades 0-10. 0 indicates no injury and 10 indicates complete removal. The results are described in the table below.

Tests on a typical herbaceous weed make a pond 1 m in diameter and 1/2 m deep, earth the pond and fill it with water. Myelin sheaths are planted in ponds and the compounds of the invention are treated at the application rates shown in the table below. Application rates are calculated in ppm relative to the total weight of water in each pond. After 3, 7 and 12 weeks of treatment with the test compounds in the pond, various weed removal rates were measured and the results of the three methods for each weed were recorded in the following table.

The broadly superior action of the compounds of formula (I) is clearly illustrated in the above examples. In the examples the effect of the compound on annual weeds is indicated. In other words, it was effective not only on easily removed broadleaf such as tusks, but also on poorly removed broadleaf such as branch, locust and sicklepod. Furthermore, the compounds also remove perennial weeds such as Johnsongrass, Buckwheat, Bermuda and Nutsedge which are very difficult to remove.

The compound can also remove algae and myelin weeds (e.g., kuntail, hydila, etc.) and furthermore, woods such as mesquite, which are economically harmful weeds in dry climates. Remove even plants. Botanists will therefore recognize that the compounds can be used to remove unwanted and undesirable woody plants. Examples of the compounds have shown that the compounds are effective against all types of weeds.

A preferred herbicidal method is a method of selectively removing herbaceous weeds.

In particular, the present compound has a herbicidal effect when treated before and after germination. Therefore, weeds can be removed by using the present compound on the ground where weed seeds germinate, or by directly using the germinated weeds. When used before germination, the compound is removed during or after germination.

When the present compound is used for weedy weeds, it is effective to suspend or dissolve the compound in water in which weeds are grown or to treat the compound in soil with roots.

Since the present compound has an excellent effect, the method of using the present compound for weed removal is important in the present invention. This method is to remove the weeds selectively by treating the above-mentioned compounds with the weeds in an effective amount to be herbicide. In the present invention, weed seeds which come into contact with the compound due to pre-germination treatment of the compound were regarded as weeds.

The germination treatment of the present compound is effective even if it is treated on the surface of the ground or incorporated in the ground, as shown in the examples.

By way of example, the majority of compounds are harmless when treated at the right time and at the right time for many crops such as peanuts, soybeans, sorghum, wheat and fruit trees.

Since the compound is particularly harmless to cotton, the use of the compound to remove weeds of cotton cropland is desirable in the present invention.

In the table it was shown that the compound is also safe for rice. It is therefore a preferred compound for removing weeds in rice cultivation, especially rice bed.

The compound can also be used for complete removal of plants at suitable application rates. That is, it is used to completely remove vegetation on planted land, factory sites and roadsides that have been left for a while. Even in perennial weeds and woody plant removal, the compound is fully herbicidal.

The property of selectively removing weeds is noteworthy. Weeds include, but are not limited to, unwanted and undesirable whole plants. Cotton crops, for example, remove not only weeds such as Johnsongrass and Cauliflower, but also unsuitable native grain plants from cotton cultivation. Treatment at a suitable rate can selectively remove weeds, as is known to botanists.

The proportion of the weeds removed by the treatment of the present compound is determined according to the type of the weeds and the amount of the treated compound. In most cases, the entire weed is removed, but sometimes only a portion of the weed is removed or damaged as described in the above embodiment. Although only some of the weeds are removed or damaged, it can be seen that the use of this compound is effective and beneficial. It is also beneficial to simply damage the weeds because normally growing crops shadow the damaged weeds, which have slowed growth.

The best rate of application of this compound to remove various weeds depends on the application of the compound, climate, soil type, water and organics in the soil, and other factors. However, the optimum application rate is in practically all cases ranging from 0.1 to 20 kg / ha. Typically, the optimum ratio is 0.1 to 5 kg / ha. In a rice bed, 0.025-2 kg / ha becomes a preferable range.

Since the compound is effective both before and after germination, the time when the compound is treated in soil or weed is wide. In either case of growing or germinating weeds, minimal weeds can be removed by treating the present compounds. Treatment of the compound with soil during winter can remove weeds that germinate in the following spring.

The effect of the compounds on myelin sheaths is the same as for the effects on ground weeds. Treatment of the compound at the above-described application ratios is effective. Therefore, the herbicidal method of the present invention is also effective for myelin weeds and can generally remove myelin sheaths according to the method used for weed removal.

When the compound is used for weed removal in annual grains, it is best to pre-germinate the compound in soil for planting crops. When compounding into soil, it is common to mix the compound just before planting, and to treat the surface immediately after planting.

The compounds are treated in soil or germinated weeds in a manner commonly used in agriculture. The compound can be treated in soil as a water dispersant or granular. Typically, the water dispersant of the compound is treated to germinated weeds. The soil or the soil in which the plant is growing is reformed and used in various forms of sprays and granules, which are widely used for spraying pesticides. When incorporating the compound into the soil, instruments commonly used for soil mixing, such as a harrow, rotary hoe, and the like, are effectively used.

The present compounds are commonly used to practice the present invention in the form of important herbicidal compositions of the present invention. Herbicidal compositions of the present invention include the compound of the present invention and an inert carrier. In general, the compositions are formulated in the usual manner used in agrochemicals, and this composition is new because of the presence of new herbicidal compounds.

Sometimes the compound is formulated as a concentrated composition. That is, the soil or leaves are treated in the form of an aqueous dispersion or emulsion containing the compound in the range of 0.1% to 5%. The aqueous dispersion or emulsion composition is a conventional known solid material such as a hydrating agent or a conventional known liquid material such as an emulsion concentrate. Wetting agents are finely milled mixtures of compounds, inert carriers and surfactants. The concentration of this compound is 10 to 90%. Inert carriers are commonly selected from attapulgite, clay, kaolin, montmorillonite, diatomaceous earth or purified silicates. Effective surfactants are contained from 0.5% to 10% in hydrating agents and selected from nonionic surfactants such as sulfonated lignin, polymerized naphthalene sulfonates, naphthalene sulfonates, alkylbenzene sulfonates, alkyl sulfates and ethylene oxide adducts of phenols. do.

Typical emulsion concentrates of the novel compounds are conveniently contained between 100 and 500 g of compound per liter of liquid dissolved in an inert carrier which is a mixture of a water immiscible solvent and an emulsion. Effective organic solvents include aromatics, in particular xylene and petroleum fractions, in particular high boiling naphthalene and olefin fractions of petroleum. Many other organic solvents can also be used, such as terpene solvents, and alcohol complex compounds such as 2-ethoxy-ethanol are also possible. Suitable emulsions for emulsion concentrates are selected according to the type of surfactant used in the hydrating agent.

Special forms of emulsion concentrate compositions are used to form inert emulsions. These emulsions have an aqueous phase dispersed in an oil phase and have been used for many years in the agrochemical industry. This is particularly effective after germination of the compounds and in the treatment of myelin sheaths. Because it adheres well to the leaves and does not disperse easily in water. Therefore, simply adjust the specific gravity so that the inert emulsion is placed exactly on top or bottom of the water. The inert emulsion composition contains a mixture of solvent and surfactant balanced to produce an inert emulsion when mixed with the converted oil, water. [Reference: US Patent No. 3,197,229]

Another form of composition effective for the application of water as paddy fields or weed weed treatment is in the form of hydrophobic films. When the composition is treated with water, it is diffused to the water surface, so that the purpose of herbicide treatment can be achieved even when the composition is misapplied. The composition is based on hydrophobic liquids such as xylene dissolved or suspended in herbicides.

When the present compound is used in soil as a pre-germination treatment, it is easy to formulate it as a granule. Such formulations are typically dispersions of the compound in granular inert carriers such as coarse ground clay. The particle size of the granules is typically 0.1 to 3 mm. A conventional granulation formulation process is to dissolve the present compound in an inexpensive solvent and mix this solution with the carrier in a suitable mixer. A slightly more expensive method is to disperse the compound in wet clay masses or other inert carriers, dry and grind coarsely to produce the desired granular product. Granulation is also particularly effective for weed processing.

The simultaneous application of two or more pesticides at the same time for the removal of several different types of weeds or other pests has become customary in the field of agrochemicals.

The compounds of the present invention are well mixed with other pesticides and are preferably, easily and effectively mixed with insecticides, fungicides, nematicides and other herbicides.

Among the compounds of the present invention, there are compounds which have not only herbicidal action but also other biological actions. For example, among the pyridones of the present invention, some of the pyridones can be used to combat viral bacteria causing diseases in humans and livestock. Insecticidal and acaricides, which control mosquitoes, house flies, spotted mites, Mexican beetles and pests, have also been shown in this compound.

Claims (1)

If one of Q ¹ and Q ² is two hydrogen atoms, the other is = CHNHY (where Y is hydrogen, hydroxy, methyl or ethyl) to form a compound of formula (II) or a formylating or aminoformylating agent. Or a compound of formula (II) wherein Q ¹ and Q ² are each = CHOH or CHN (R ⁷ ) ₂ , with a compound of formula YNH ₂ , wherein Y is as defined above, or an acid addition salt thereof And if = CHN (R ⁷ ) ₂ group is derived from formimide halide, it is hydrolyzed with aqueous base or acid to obtain the following structural formula (III) and then Y is hydrogen or hydroxy Alkylated or esterified to obtain the corresponding compound wherein Y is R, and if X is sulfur, the compound of formula (I) wherein X is oxygen is treated with P ₂ S ₅ . Structural formula (Ⅰ) or acid Process for preparing addition salts.

In the above structural formula X is oxygen or sulfur, R is methyl, ethyl, acetoxy or hydroxy, R ¹ is independently halo, alkyl having 1 to 4 carbon atoms, alkyl having 1 to 4 carbon atoms substituted with halo, nitro, carboxy, hydroxy, alkoxycarbonyl having 1 to 2 carbon atoms, -OR ³ , -SR ³ ,- SC-R ³ or -SO ₂ -R ³ R ² is cyano, alkoxycarbonyl having 1 to 3 carbon atoms, alkyl having 1 to 4 carbon atoms, halohydroxy or alkyl having 1 to 4 carbon atoms substituted with alkoxy having 1 to 3 carbon atoms, thienyl, -CR ⁴ ,- SR ⁴ , -SC-R ⁴ , -SO ₂ -R ⁴ or

ego R ³ is alkyl having 1 to 2 carbons, alkyl having 1 to 2 carbon atoms substituted with halo, benzyl or phenyl R ⁴ is alkyl having 1 to 6 carbon atoms, hydroxy or alkyl substituted with halo, alkyl having 1 to 6 carbon atoms, alkenyl having 2 to 4 carbon atoms, benzyl, phenyl or trifluoromethyl, halo, alkyl having 1 to 3 carbon atoms, Nitro, phenyl substituted by alkylthio having 1 to 3 carbon atoms or alkoxy having 1 to 3 carbon atoms, R ⁵ is independently halo, alkyl having 1 to 4 carbon atoms, alkyl having 1 to 4 carbon atoms substituted with halo, nitro, carboxy, hydroxy, alkoxy carbonyl having 1 to 2 carbon atoms, -OR ⁶ , -SR ⁶ ,- SO-R ⁶ or -SO ₂ -R ⁶ R ⁶ is alkyl having 1 to 2 carbon atoms, alkyl having 1 to 2 carbon atoms substituted with halo, benzyl or phenyl, m and n are independently 0, 1 or 2. X is oxygen, R is metal, and R ² is unsubstituted phenyl m is 1 or 2 R ⁷ groups independently combine with alkyl of 1 to 3 carbon atoms or adjacent nitrogen atoms to form pyrrolidide, piperidino, morpholino or N-methylpiperazino.