KR880001297B1 - Herbicidal aryl triazolinones - Google Patents

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Description

Herbicide Aryl Triazolinone

The present invention relates to weed control in fields where it is necessary to suppress the growth of agriculture, horticulture, and other unwanted plants. More particularly, the present invention relates to specific herbicidal aryl triazolinones, compositions thereof, methods for preparing the same, methods for preventing or killing unwanted plant growth by using herbicide compositions before or after germination in areas where weed control is desired. It is about. The compounds of the present invention can be effectively used to control a variety of flowering and varieties of both plant and broadleaf species. The present invention is particularly advantageous in the agricultural field; The various compounds described herein exhibit desirable selectivity for certain crops at doses that inhibit the growth of various weeds or kill weeds.

One aspect of the invention relates to herbicidal compounds of the general formula (I)

In which R ² is CHF ₂ or CH ₂ F; X is bromine, chlorine, or fluorine or haloalkyl (eg CF ₃ ); R ¹ is halogen (eg chlorine), alkyl (eg alkyl having 1 to 5 carbon atoms), haloalkyl (eg haloalkyl having 1 to 5 carbon atoms such as difluoromethyl), alkoxyalkyl (eg methoxymethyl Alcoholcyalkyl having 2 to 6 carbon atoms, cyanoalkyl (e.g. cyanoalkyl having 2 to 6 carbon atoms such as cyanomethyl), arylalkyl such as benzyl, alkylthio (e.g. carbon atoms such as methylthio) To alkylthio) or the corresponding alkylsulfinyl or alkylsulfonyl, or alkylthioalkyl (e.g. alkylthioalkyl having independently 1 to 3 carbon atoms for each alkyl, such as methylthiomethyl), or the corresponding alkylsulphi Alkylalkyl or alkylsulfonyl alkyl; Y is bromine, chlorine, fluorine, haloalkyl (eg FCH ₂ ), or a radical of the formula R ⁸ OCH _2- , R ⁸ SCH _2- , R ⁸ SOCH ₂ -or R ⁸ SO ₂ CH _2- , wherein In which R ⁸ is C ₁ -C ₃ alkyl, C ₂ -C ₅ alkenyl or C ₃ -C ₅ alkynyl (eg CH ₃ OCH _2- , CH ₃ SCH _2- , CH ₂ = CHCH ₂ OCH _2- , CH ₂ = CHCH ₂ SCH _2- , CH = CCH ₂ OCH ₂ -or CH = C-CH ₂ SCH _2- , or R ⁸ is also phenyl (or phenyl substituted by halogen, alkyl, haloalkyl or the like; see, Compound 50) to be described later; R ³ is an alkylene radical (eg lower alkylene such as —CH ₂ — or —CH (CH ₃ ) —) or a haloalkylene radical (eg —CHF—); R ⁴ is an alkyl radical (eg CH ₃ , C ₂ H ₅ , C ₃ H ₇ , C ₄ H ₉ ).

Preferred are those in which R ¹ is methyl and R ² is CHF ₂ , in particular compounds in which X is chlorine or (more preferably) fluorine and Y is chlorine.

Some of the compounds described above are different from other similar compounds in which R ² described in US Pat. No. 4,318,731 is hydrogen, an alkyl group or an alkenyl group. It has now been found that by substituting an alkyl group with a CHF ₂ or CH ₂ F group, a much better herbicidal compound is obtained. This can be seen, for example, from Table (I), which shows the results of a test in which the following two compounds were each applied at a rate of 0.125 kg per hectare.

A. Compounds wherein R ² is CHF ₂ (Compound 5 to be described later)

B. The same compound in a different manner, wherein R ² is C ₂ H ₅ (Compound 62 of the above-mentioned US patent)

Representative compounds according to this aspect of the invention are shown in Table 2 below.

The herbicidal esters of the invention described above can be hydrolyzed to give the compounds of the general formula described above wherein the substituent in the para position for the corresponding acid, ie, -OR ³ COOH (carboxy alkoxy). We also found that these acids are less potent but effective herbicides than the corresponding esters. The acid is also useful as an intermediate in the production of other herbicidal compounds (by esterification or amide formation methods). The acid can be converted to its salts such as sodium, potassium, ammonium, calcium, magnesium or mono, di or trialkylammonium salts, and these salts can also be used as herbicides.

Representative acids and salts are shown in Table 3 below.

According to another aspect of the present invention it has been found that the compound of formula II is an effective herbicidal compound:

Wherein R ⁴ is a substituted alkyl group, an alkenyl group (e.g. allyl or metaryl) or alkynyl group (e.g. propargyl), or a 5- or 6-membered monovalent ring having a valence present on a ring carbon atom Cyclic groups (eg aromatic or heterocyclic or cycloaliphatic rings); Z is O or S.

Corresponding compounds in which Z is sulfur and R ⁴ is unsubstituted alkyl (eg alkyl having 1 to 4 carbon atoms) have also been found to be effective herbicides. With respect to R ⁴ , examples of suitable substituents on the alkyl group are as follows: nitro; Halo (Cl, F, Br); Furyl or tetrahydroburyl; Acetyl (CH3CO); -CO-N (R ^II ) (R ^III ) wherein -N (R ^II ) (R ^III ) is ammonia or primary or secondary amine (e.g., methylamine, diethylamine or other lower alkylamine) Residues (lack of hydrogen); Cyano; -COOR ^IV, wherein R ^IV is an alcohol moiety (e.g., a moiety of a lower alkanol such as methyl or ethyl radical); Phenyl or substituted phenyl; Alkylamino, dialkylamino or trialkylammonium salts (eg, those shown in compound B20 described below); Alkoxy, alkylthio, alkylsulfinyl or alkylsulfonyl (alkyl in these radicals is preferably methyl or other lower alkyl) or phenoxy, phenylthio, phenylsulfinyl, or phenylsulfonyl (phenyl moiety in these radicals Substituted or unsubstituted). If R ⁴ is alkenyl or alkynyl, it may be substituted with one of the foregoing substituents.

Substituents for the above substituted phenyls include, for example, alkyl, haloalkyl, alkoxy, alkylthio, alkylsulfinyl, alkylsulfonyl, halogen, cyano, nitro, hydroxy, amino or alkyl or dialkylamino or carboxyl. There is this.

Preference is given to compounds wherein X, Y, R ¹ and R ² are as defined in formula (I), wherein X is chlorine or (more preferably) fluorine, Y is chlorine, R ¹ is methyl and R ² is Particular preference is given to compounds which are CHF ₂ . However, within the broader aspect of the invention R ² substituents are alkyl (e.g. alkyl having 1 to 5 carbon atoms), haloalkyl (e.g. haloalkyl having 1 to 5 carbon atoms such as CHF ₂ ), alkenes having 2 to 5 carbon atoms. Kenyl (eg allyl), alkynyl (eg propargyl) having 3 to 5 carbon atoms, cyanoalkyl (eg CH ₂ CN or CH ₂ CH ₂ CN), thiocyanoalkyl (eg CH ₂ SCN) or Group of the general formula-alkylene-Y ¹ -R ⁵ , wherein the alkylene group (eg -CH _2- ) has 1 to 5 carbon atoms, and Y ¹ is oxygen or S (O) r (where r Is 0 to 2) and R ⁵ is alkyl (e.g., alkyl having 1 to 5 carbon atoms, such as methyl), alkenyl (e.g. allyl) having 2 to 5 carbon atoms, or alkynyl (e.g. ).

Representative compounds according to this aspect of the invention are shown in Table 4 below.

In another aspect of the present invention, it has been found that the compound of formula III is an effective herbicidal compound.

은 -NH₂, 또는 1급 또는 2급 아민의 잔기 또는 설폰아미드의 잔기이다.Wherein R ³ is an alkylene radical (eg -CH ₂ -or -CH (CH ₃ )-) or a haloalkylene radical (eg -CHF-),

Is -NH ₂ , or a residue of a primary or secondary amine or a residue of sulfonamide.

For example, R ⁶ and R ⁷ are each independently H, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, alkoxy, alkylsulfonyl, haloalkylsulfonyl, cycloalkylsulfonyl, arylsulfonyl (thienylsul Heteroarylsulfonyl, such as fonyl), aralkylsulfonyl, aminosulfonyl, dialkylaminosulfonyl, alkylaminosulfonyl, alkenylsulfonyl, phenylalkenylsulfonyl.

R ⁵ may be a bicyclic or polycyclic radical such as benzofuranyl, dihydrobenzofuranyl, benzofuransulfonyl, dihydrobenzofuransulfonyl, naphthalenesulfonyl, benzodioxosulfonyl, anthraquinonesulfonyl have. Any of R ⁶ , R ⁷ is halogen, nitro, amino, alkoxy, alkyl, haloalkoxy, alkenyloxy, haloalkenyloxy, alkoxyalkoxy, alkoxyalkylthio, cyano, aminocarbonyloxy, alkylaminocarbonyloxy Or one or more substituents such as dialkylaminocarbonyloxy, acylamino, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl or hydroxycarbonyl, provided that R ⁶ , When any one of R ⁷ is bound to nitrogen of the general formula (III) by oxygen or sulfur atom, the other of R ⁶ , R ⁷ is H or a group bonded to the nitrogen by carbon-nitrogen bond or as described below. Same salt-forming group).

)를 형성하도록 이가 그룹을 이룰 수 있고, 이 또한 활성 제초제(예. 화합물 C62)이며, 가수분해되면 화합물 C58 및 C59와 같은 다른 활성 제초제를 생성할 수 있다.R ⁶ and R ⁷ together may form a divalent group such as an alkylene or haloalkylene or alkyloxyalkylene group or thioether, or a corresponding sulfine or sulfone thereof (so, for example, NR ⁶ R ⁷ Together form a pyrrolidino, piperidino, morpholino or thiazolidino ring), any of which may contain a carboxylic acid ester or an amide substituent. Salt-forming groups (eg when R ⁶ is alkylsulfonyl, cycloalkylsulfonyl or arylsulfonyl) can be metal (eg Na, K or Ca) or ammonium (eg NH ₄ or lower alkyl-substituted ammonium) May be). R ⁶ and R ⁷ are each NR ⁶ R ⁷ , for example, a saccharin ring structure (eg.

Divalent groups to form), which are also active herbicides (e.g., compound C62), and when hydrolyzed can produce other active herbicides such as compounds C58 and C59.

을 적절한 산 클로라이드와 반응시켜 수득할 수 있다.Compound C62 is for example saccharin

Can be obtained by reaction with an appropriate acid chloride.

In this aspect of the invention (formula (III)), X, Y and R ¹ may be the same as defined in formula (I), and R ² may be the same as defined in formula (II). . Preference is given to compounds in which R ¹ is methyl and R ² is CHF ₂ , in particular compounds in which X is chlorine or (more particularly) fluorine and Y is chlorine.

Representative compounds according to this aspect of the invention are shown in Table 5 below.

Another aspect of the invention relates to herbicidal compounds of the general formula (IV)

또는

(여기서 각 일킬 그룹은 바람직하게는 메틸과 같은 저급 알킬이다)의 케톡심과 같은 옥심의 진기이며, X, Y, R¹및 R²은 일반식(I)(X, Y 및 R¹에 대해) 및 일반식(II)(R²에 대해)에서 정의한 것과 동일하다. 바람직하게는, X는 염소 또는 (더욱 바람직하게는) 불소이고, Y는 염소이며 R¹은 메틸이고 R²는 CHF₂이며 ; 이러한 종류의 대표적인 몇몇 화합물에서, 라디칼 OR³COOR₉는

또는

이고 X는 불소이며 Y는 염소이고 R¹은 메틸이며 R²은 메틸이며 R²는 CHF₂이고 ; 대표적인 다른 화합물은 다른 기 정의는 동일하나, 단 Y가 Br 또는 CF₃인 화합물이다. 일반식(IV) 화합물은 상응하는 산 클로라이드(즉, 벤젠환의 5-위치에서의 치환체가 -OR³COCl인 화합물)를 트리에틸아민 또는 탄산나트륨 또는 수산화나트륨과 같은 HCl에 대한 수용체의 존재하에서 상응하는 옥심과 반응시켜 제조할 수 있다.In the above formula, OR ⁹ is a structural formula

or

(Where each ilky group is preferably a lower alkyl such as methyl) is a oxime radical such as ketoxime, where X, Y, R ¹ and R ² are of the general formula (I) (X, Y and R ¹ ) And the same as defined in formula (II) (relative to R ² ). Preferably, X is chlorine or (more preferably) fluorine, Y is chlorine, R ¹ is methyl and R ² is CHF ₂ ; In some representative compounds of this kind, the radical OR ³ COOR ₉ is

or

X is fluorine, Y is chlorine, R ¹ is methyl, R ² is methyl and R ² is CHF ₂ ; Exemplary other compounds are compounds having the same group definitions, except that Y is Br or CF ₃ . Formula (IV) compounds react the corresponding acid chlorides (i.e., compounds in which the substituent at the 5-position of the benzene ring is -OR ³ COCl) in the presence of a receptor for HCl such as triethylamine or sodium carbonate or sodium hydroxide. It can be prepared by reacting with an oxime.

In each aspect of the invention the alkyl, alkenyl, alkynyl or alkylene radicals are preferably preferably less than 6 carbon atoms.

The compounds of the present invention can be prepared by the methods generally described in the literature or by methods analogous or identical to those in the art. One method is to start with an intermediate whose hydroxyl at the para position for "X" is hydroxyl. For example, X and Y described in "Synthetic Process Example 6" of GB 2 090 250, published July 7, 1982, is Cl and R ¹ is CH ₃ and R ² Intermediates with CHF ₂ can be used (other corresponding compounds with R ² CH ₂ F use chlorofluoromethane in place of chlorodifluoromethane used in “Synthesis Method Example 1” of the published patent application). To manufacture). The group of intermediates can then be converted to the desired substituents by reaction of the intermediate with the appropriate bromide by conventional etherification reactions, for example in the presence of known HBr receptors such as NaH, or K ₂ CO ₃ and NaI mixtures.

As described in Examples 2 and 3 below, substituted phenylhydrazines can be used in the synthesis, after which the hydrazine moiety is modified so that the triazoline forms a ring. This modification reaction (in Examples 2 and 3 is carried out by reacting with another phosphoryl azido reacted with pyruvic acid) using other methods such as treating the substituted phenylhydrazine with any of the following four types of reagents: You can also do:

(a) Internal salts of 3- (1-imino-alkylmercapto) -1-propanesulfonic acid, as shown in the scheme below, which is described in Reid and Schmidt, Ann. Chem. Can be prepared from 1, 3-propanesultone and thioamide according to the method described in 676, 114 (1964)] to form amidrazone and then reacted with a phosgene source (which is also described in Example 15). Is).

(Wherein Ar is an aromatic group as described later)

(b) treatment with the imidate esters of the general formula (e.g., as described in Neilson et al "The Chemistry of Amidrazones; Chem. Rev 70, 151 (1970) at page 156). ) And then react with the phosgene source as in (a) above.

(Wherein R ^c and R ^d are alkyl or other suitable radical)

(c) general formula in the presence of a base according to the following scheme

[Wherein R ^a and R ^b are lower alkyl and R ¹ is as defined above (eg methyl)]

(d) haloalkylnitriles [eg. Fluoroalkyl, fluorochloroalkyl or fluorobromoalkylnitrile (e.g. ClCF ₂ CN)] and then reacted with a phosgene source, the reaction is for example as shown in the scheme below (and also described in Example 16). To form an aryl 3-haloalkyl triazoline:

In Examples 2 and 3 below, the “Ar” portion of the aryl hydrazine, whose hydrazine portion is subsequently modified so that the triazoline forms a ring, has an alkoxy group at its position. In each of the methods described above (and in Examples 2 and 3), the Ar group is instead a phenyl radical or fluorophenyl (e.g. 2-fluorophenyl) or nitrophenyl (e.g. 3-nitrophenyl), alkoxyphenyl ( Eg, 3-methoxyphenyl) or, most preferably, halonitrophenyl, in particular fluoronitrophenyl (eg 2-fluoro-5-nitrophenyl) or haloalkoxyphenyl (eg 2-fluoro-5) -Alkoxyphenyl), and then the aryl triazoline is treated with (a) the alkyl at the 4-position of the trazoline ring to be alkylated (in known methods, for example, to add a preferred -CHF ₂ substituent, such as ClCHF _2). Fluoroalkyl halides are treated with alkyl) and (b) halogenated with chlorine or bromine (eg by reaction with Cl ₂ , Br ₂ or SO ₂ Cl ₂ ) so that additional substituents can introduce additional substituents into the aromatic ring. Can be. For example, the 4-position nitrogen may first be alkylated and then the nitro group (if present) may be reduced to an amino group in a conventional manner, and the amino group may be converted to a hydroxyl group (for conventional diazotization). ), Then preferably OH can be etherified to form an alkoxy (eg methoxy) group, followed by halogenation of the compound as described above to introduce halogen substituents or substituents on the benzene ring.

The resulting compound can then form the herbicidal compound of the invention at the 5-position of the benzene ring. For example, in order to prepare a preferred compound of the present invention having a 2-fluoro substituent on the benzene ring, 2-fluoro-5-nitrophenylhydrazine can be used as a starting compound, which is treated as described above and continuously 1- (2-fluoro-5-nitrophenyl) -4, 5-dihydro-3-methyl-1, 2, 4-triazol-5 (1H) -one, 1- (2-fluoro-5 A series of novel compounds can be obtained, such as -nitrophenyl-4, 5-dihydro-4-difluoromethyl-3-methyl-1, 2, 4-triazol-5 (1H) -one. The compounds can subsequently be converted to the corresponding novel compounds having -NH ₂ , -OH and (preferably) -OCH ₃ at the 5-position of the benzene ring, followed by halogenation, for example 4- Chloro or bromo substituents can be introduced at the position, in the initial stage, for example before changing the nitro group, the 4-position of the triazoline ring is alkylated. This alkylation step, instead of the above, is carried out after the above-mentioned halogenation step of the benzene ring or the alkoxy (or other) group of the 5-position of the benzene ring described above in general formulas (I), (II), (III), and (IV). (And Table 2, 3, 4 and 5) may be delayed until after the step of powering up to the groups illustrated at that location.

Similarly, if the reagent (s) used in the reaction with aryl hydrazine is to produce triazolinones having haloalkyl (eg CHF ₂ ) groups instead of alkyl groups on the carbon at the 3-position of the heterocyclic ring, A series of novel compounds that are subsequently added are (continue from 2-fluoro-5-nitrophenylhydrazine) 1- (2-fluoro-5-nitrophenyl) -4, 5-dihydro-3-difluoro methyl- 1, 2, 4-triazol-5 (1H) -one, 1- (2-fluoro-5-nitrophenyl) -4, 5-dihydro-4-methyl (or difluoromethyl) -3- Compounds such as methyl-1, 2, 4-triazol-5 (1H) -one will be included. These compounds can subsequently be converted into the corresponding novel compounds having -NH ₂ , -OH and (preferably) -OCH ₃ at the 5-position of the benzene ring, followed by halogenation, for example 4- of the benzene ring. Chloro or bromo substituents can be introduced at the position.

When arylhydrazine is 3-nitrophenyl hydrazine (instead of 2-fluoro-5-nitrophenyl-hydrazine), the new series of compounds produced are sequentially 1- (3-nitrophenyl) -4, 5-di Compounds such as hydro-4-methyl (or difluoromethyl) -3-methyl-1, 2, 4-triazol-5 (1H) -one will be included. These compounds can be converted successively to the corresponding novel compounds having -NH ₂ , -OH and (preferably) -OCH ₃ in the 3-position of the benzene ring, followed by halogenation, e.g. Bromo substituents can be introduced.

Example 11 below describes a process for the preparation of compounds of the invention having sulfonamide groups at the 5-position of the benzene ring by (a) reacting a compound having an oxypropionic acid substituent at the 5-position with (aryl) arylsulfonyl isocyanate. .

와 반응시키는 방법이다. 이러한 반응은 염기 존재하에(예를들어 탄산나트륨 또는 탄산칼륨 존재하에 아세톤중에서) 수행할 수 있다. 이 방법은 하기 실시예 14에 기술되어 있다.Another method of introducing sulfonamide groups is (a) a compound having a phenolic OH group at the 5-position, and (b) a reactive aryl substituent (e.g., Br, Cl, mesylate or tosylate) at the alkane moiety of the molecule. N-aryl (or alkyl, etc.) sulfonylalkanoic acid amides having, for example

It is reacted with. This reaction can be carried out in the presence of a base (eg in acetone in the presence of sodium carbonate or potassium carbonate). This method is described in Example 14 below.

The following examples illustrate the preparation of the compounds of the invention.

Ethyl [2,4-dichloro-5- (4-difluoromethyl-4,5-dihydro-3-methyl-5-oxo-1H-1, 2,4-triazol-1-yl) phenoxy ]acetate

1- (2,4-dichloro-5-hydroxyphenyl) -4-difluoromethyl-4, 5, -dihydro-3-methyl-1, 2, 4-triazole-5 (1H in 100 ml of acetone To a stirred mixture of 15.0 g (0.048 mol) of potassium ion and 3.4 g (0.024 mol) of potassium carbonate is added 8.1 g (0.048 mol) of ethyl bromoacetate. The resulting mixture is stirred at reflux for 3 hours. After cooling, the mixture is evaporated under reduced pressure to give a residue. This residue is partitioned between diethyl ether and water. The organic phase is washed with 10% aqueous sodium hydroxide solution, then dried over anhydrous magnesium sulfate and filtered. The filtrate is evaporated under reduced pressure to give 17.8 g of a solid. This solid bovine fraction was recrystallized from methanol and water to give ethyl [2, 4-dichloro-5- (4-difluoromethyl-4, 5-dihydro-3-methyl-5-oxo-1H-1, 2 , 4-triazol-1-yl) phenoxy] acetate (melting point 118-119 ° C; compound 17) is obtained.

The nmr spectrum is consistent with the proposed structure.

The following compounds were also prepared according to the method of Example 1 in 1- (2, 4-dichloro-5-hydroxyphenyl) -4-difluoromethyl-4, 5-dihydro-3-methyl-1, 2, 4-triazol-5 (1H) -one; 1- (4-chloro-2-fluoro-5-hydroxyphenyl) -4-difluoromethyl-4, 5-dihydro-3-methyl-1, 2, 4-triazole-5 (1H) -On ; 2- [2,4-dichloro-5- (4-difluoromethyl-4, 5-dihydro-3-methyl--5-oxo-1H-1, 2, 4-triazol-1-yl) Phenoxy] propionic acid, compound A1; Or 2- [4-chloro-2-fluoro-5- (4-difluoromethyl-4, 5-dihydro-3-methyl-5-oxo-1H-1, 2, 4-triazole-1 -Yl) phenoxy] pyrionic acid, compound A2 and one of the following reagents;

Example 2

2- [4-chloro-2-fluoro-5- (4-difluoromethyl-4, 5-dihydro-3-methyl-5-oxo-1H-1, 2, 4-triazole-1- Phenoxy] propionic acid

Step A: Preparation of 4-chloro-2-fluoro-5-methoxyaniline from 2-chloro-4-fluorophenol

Intermediate 4-chloro-2-fluoro-5-methoxyaniline is a 2-chloro-4-fluorophenol which is commercially available as described in detail by E.Nagano et al. In EP 69,855. From 5-step synthesis.

Step B: 4-Chloro-2-fluoro-5-methoxyphenylhydrazine

A stirred solution of 48.0 g (0.27 mole) of 4-chloro-2-fluoro-5-methoxyaniline in 500 ml of concentrated hydrochloric acid is cooled to −5 ° C. and 23.5 g (0.34 mole) of sodium nitrite in 100 ml of water are added dropwise. After the addition is complete, the reaction mixture is stirred at 0 ° C. for 1 hour. A second solution of 154.0 g (0.68 mol) of stannous chloride in 225 ml of concentrated hydrochloric acid is cooled to 0 ° C, and the cold diazonium solution prepared above is slowly added thereto. After the addition is complete the reaction mixture is allowed to warm to ambient temperature. The reaction mixture is filtered to collect solids.

This solid is dissolved in 50% aqueous sodium hydroxide solution and the solution is extracted with toluene. The toluene extract is dried over magnesium sulfate and filtered. The filtrate is concentrated under reduced pressure to give 22.4 g of 4-chloro-2-fluoro-5-methoxyphenylhydrazine in the solid state.

The nmr spectrum is consistent with the proposed structure.

Step C: Pyruvic acid, 4-chloro-2-fluoro-5-methoxyphenylhydrazone

A stirred solution of 21.0 g (0.11 mol) of 4-chloro-2-fluoro-5-methoxyphenylhydrazine and 100 ml of 10% aqueous hydrochloric acid in 100 ml of ethanol was warmed to 40 ° C. and 10.0 (0.114 mol) of pyruvic acid in 20 ml of water Add. After the addition is complete, the reaction mixture is stirred for 1 hour. Further 50 ml of water are added and the reaction mixture is filtered to collect the solid. The solid is air dried to yield 29.0 g of pyruvic acid, 4-chloro-2-fluoro-5-methoxyphenyl-hydrazone (melting point 166-169 ° C.).

The nmr spectrum is consistent with the proposed structure.

Step D: 1- (4-Chloro-2-fluoro-5-methoxyphenyl) -4, 5-dihydro-3methyl-1, 2, 4-triazol-5 (1H) -one

Pyruvic acid in 500 ml of toluene, 27.0 g (0.104 mol) of 4-chloro-2-fluoro-5-methoxyphenylhydrazone, 29.0 g (0.105 mol) of diphenylphosphoryl azide and 11.0 g (0.108 mol) of triethylamine ) Is stirred for 4 hours under reflux. The reaction mixture is cooled to ambient temperature and extracted with 10% aqueous sodium hydroxide solution. The extract is neutralized with gaseous carbon dioxide and filtered to collect solids. The solid was air dried to give 1- (4-chloro-2-fluoro-5-methoxyphenyl) -4, 5-dihydro-3methyl-1, 2, 4-triazol-5 (1H) -one ( Melting point 193 to 195 ° C.) to 11.0 g.

The nmr spectrum is consistent with the proposed structure.

Step E: 1- (4-Chloro-2-fluoro-5-methoxyphenyl) -4, 5-dihydro-4-difluoroethyl-3-methyl-1, 2, 4-triazole-5 (1H) -on

1- (4-chloro-2-fluoro-5-methoxyphenyl) -4, 5-dihydro-3-methyl-1, 2, 4-triazol-5 (1H) -one 10.0 in 250 ml of cyclohexane A stirred mixture of g (0.039 mol), 10.0 g (0.031 mol) of tetrabutylammonium bromide and 10.0 g (0.25 mol) of sodium hydroxide is warmed to 60 ° C. Chlorodifluoromethane (10.0 g, 0.12 mole) is introduced into the reaction mixture. After the addition is complete, the reaction mixture is stirred for 1 hour while warming to reflux. The thermal solution is inclined from the residue of the pot and cooled to ambient temperature. Methylene chloride is added to the cooled mixture to dissolve the solid precipitate. The mixture is washed with 10% hydrochloric acid and then with 10% aqueous sodium hydroxide solution.

The organic layer is dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure to give 1- (4-chloro-2-fluoro-5-methoxyphenyl-4-difluoromethyl-4, 5-dihydro-3-methyl-1, 2, 4-triazole 5.0 g of -5 (1H) -one (melting point: 86 to 88 ° C) is obtained.

The nmr spectrum is consistent with the proposed structure.

Step F: 1- (4-Chloro-2-fluoro-5-hydroxyphenyl) -4-difluoromethyl-4, 5-dihydro-3-methyl-1, 2, 4-triazole-5 (1H) -on

1- (4-Chloro-2-fluoro-5-methoxyphenyl) -4-difluoromethyl-4, 5-dihydro-3-methyl-1, 2, 4-triazole- in 20 ml of methylene chloride 4.6 g (0.015 mol) of 5 (1H) -one are cooled to 10 ° C and a solution of 11.2 g (0.045 mol) of boron tribromide in 45 ml of methylene chloride is added. When the addition is complete, the reaction mixture is stirred for 4 hours while warming to ambient temperature, then 100 ml of water is added and stirring is continued for an additional 18 hours. The organic layer is separated, dried over anhydrous magnesium sulfate and then filtered. The filtrate was concentrated under reduced pressure to afford 1- (4-chloro-2-fluoro-5-hydroxyphenyl) -4-difluoromethyl-4, 5-dihydro-3-methyl-1, 2, 4-tria 4.4 g of sol-5 (1H) -one (melting point: 147-152 ° C.) is obtained.

The nmr spectrum is consistent with the proposed structure.

Step G: Methyl 2- [2-chloro-4-fluoro-5- (4-difluoromethyl-4, 5-dihydro-3-methyl-5-oxo-1H-1, 2, 4-tria Zol-1-yl) phenoxy] propionate

1- (4-chloro-2-fluoro-5-hydroxyphenyl) -4-difluoromethyl-4, 5-dihydro-3-methyl-1, 2, in 50 ml of N, N-dimethylformamide To a stirred mixture of 1.5 g (0.0051 mol) of 4-triazol-5 (1H) -one and 0.12 g (0.0051 mol) of sodium hydride is added 0.85 g (0.0051 mol) of methyl 2-bromopropionate. After the addition was complete, the reaction mixture was heated at reflux for 2 hours. Cool to room temperature and stir for about 18 hours. The solvent is removed by evaporation under reduced pressure to give a residue.

This residue is partitioned between diethyl ether and water. The organic phase is washed with 10% aqueous sodium hydroxide solution. The organic phase is dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated under reduced pressure to afford methyl 2- [2-chloro-4-fluoro-5- (4-difluoromethyl-4, 5-dihydro-3-methyl-5-oxo-1H-1, in oily form). 1.5 g of 2, 4-triazol-1-yl) phenoxy] -propionate (compound 3) are obtained.

The nmr spectrum is consistent with the proposed structure.

The following compounds were also prepared by the method G of Example 2 in 1- (2, 4-dichloro-5-hydroxyphenyl) -4-difluoromethyl-4, 5-dihydro-3-methyl-1, 2, 4-triazol-5 (1H) -one; 1- (4-chloro-2-fluoro-5-hydroxyphenyl) -4-difluoromethyl-4, 5-dihydro-3-methyl-1, 2, 4-triazole-5 (1H) -On ; Or may be prepared from Compound A2 and one of the following reagents;

Step H: 2- [2-Chloro-4-fluoro-5- (4-difluoromethyl-4, 5-dihydro-3-methyl-5-oxo-1H-1, 2, 4-triazole -1-yl) phenoxy] propionic acid

Methyl 2- [2-chloro-4-fluoro-5- (4-difluoromethyl-4, 5-dihydro-3-methyl-5-oxo-1H-1, 2, in 15 ml of ethanol and 15 ml of water A stirred mixture of 1.3 g (0.0034 mol) of 4-triazol-1-yl) phenoxy] propionate and 1.0 g (0.018 mol) of potassium hydroxide is heated under reflux for 3 hours. The mixture is cooled to room temperature and left to stand for 2 days. The solvent is evaporated from the mixture to give a solid.

This solid is dissolved in water and the solution is acidified with concentrated hydrochloric acid. The resulting solution is extracted with methylene chloride. The extract is dried over anhydrous magnesium sulfate and filtered. The solvent was evaporated from the filtrate and the solid 2- [2-chloro-4-fluoro-5- (4-difluoromethyl-4, 5-dihydro-3-methyl-5-oxo-1H-1, 0.85 g of 2,4-triazol-1-yl) phenoxy] propionic acid (Compound A2) is obtained (melting point: 50-55 ° C.).

Compound A1 can also be prepared from Compound 2 according to the method of Step H of Example 2.

Example 3

2- [4-chloro-5-4-difluoromethyl-4, 5-dihydro-3-methyl-5-oxo-1H-1, 2, 4-triazol-1-yl) -2-methyl Phenoxy] propionic acid

Step A: 4-Methyl-3-methoxyphenylhydrazine

A stirred mixture of 100.0 g (0.73 mol) of 4methyl-3-methoxyaniline in 800 ml of concentrated hydrochloric acid is cooled to -5 ° C. A solution of 501.5 g (0.73 mol) of sodium nitrite in 250 ml of water is slowly added to the reaction mixture while maintaining the temperature below 0 ° C. The resulting mixture is stirred at −5 ° C. for 30 minutes. A cold solution of 330.0 g (1.46 mol) of tin (II) chloride dihydrate in 360 ml of concentrated hydrochloric acid is added over 1 hour. After the addition is complete, the resulting mixture is allowed to warm to room temperature. The solid precipitate formed is collected by filtration and stirred in 200 ml of water. The mixture is neutralized with 50% aqueous sodium hydroxide solution and extracted with toluene. The extract is dried over anhydrous magnesium sulfate and filtered. The filtrate is evaporated under reduced pressure to give 58.0 g of 4-methyl-3-methoxyphenylhydrazine as oil.

The nmr spectrum is consistent with the proposed structure.

Step B: Pyruvic acid, 4-methyl-3-methoxyphenylhydrazone

33.3 g (0.0378 mol) of pyruvic acid are added to a stirred mixture of 57.6 g (0.0378 mol) of 4-methyl-3-methoxyphenylhydrazine in 400 ml of ethanol and 400 ml of 1N hydrochloric acid. After the addition is complete, the mixture is extracted with methylene chloride. The extract is dried over anhydrous magnesium sulfate and filtered. The filtrate is evaporated under reduced pressure to give 59.0 g of pyruvic acid, 4-methyl-3-methoxyphenyl-hydrazone.

The nmr spectrum is consistent with the proposed structure.

Step C: 4, 5-Dihydro-1- (4-methyl-3-methoxyphenyl) -3-methyl-1, 2, 4-triazol-5 (1H) -one

56.8 g (0.26 mol) of pyruvic acid, 4-methyl-3-methoxyphenyl-hydrazone in 1500 ml of toluene are added. The mixture is heated to 50 ° C. and 70.3 g (0.26 mol) of diphenyl phosphoryl azide are added.

The resulting mixture is heated at reflux for about 18 hours. The mixture is cooled and extracted four times with 200 ml of an aqueous 10% sodium hydroxide solution. The aqueous extracts are combined, washed with toluene and then acidified. The resulting solid was collected by filtration and air dried to give 4, 5-dihydro-1- (4-methyl-3-methoxyphenyl) -3-methyl-1, 2, 4-triazole-5 (1H)- Warm (melting point 164-168 ° C.) 75.0 is obtained.

The nmr spectrum is consistent with the proposed structure.

Step D: 4-fluoromethyl-4, 5-dihydro-1- (4-methyl-3-methoxyphenyl) -3-methyl-1, 2, 4-triazol-5 (1H) -one

60.0 g (0.28) of 4, 5-dihydro-1- (4-methyl-3-methoxyphenyl) -3-methyl-1, 2, 4-triazol-5 (1H) -one in 2 liters of cyclohexane Mole), 60.0 g (0.19 mole) of tetrabutyl ammonium bromide and 60.0 g (1.5 mole) of powdered sodium hydroxide are heated under reflux. 60.0 g (0.67 mol) of gaseous difluorochloromethane are introduced into the mixture over 2 hours. After the addition is complete, the mixture is stirred under reflux for 1 hour and then cooled to 70 ° C. The supernatant is decanted and washed with 10% aqueous hydrochloric acid followed by 10% aqueous sodium hydroxide solution. The organic layer is dried over magnesium sulfate and filtered.

The filtrate is evaporated under reduced pressure to give a solid. The solid is ground with petroleum ether and filtered. The filter cake was air dried to afford 4-difluoromethyl-4, 5-dihydro-1- (4-methyl-3-methoxyphenyl) -3-methyl-1, 2, 4-triazole-5 (1H 18.5 g of) -one are obtained.

The nmr spectrum is consistent with the proposed structure.

Step E: 1- (2-Chloro-4-methyl-5-methoxyphenyl) -4-difluoromethyl-4, 5-dihydro-3-methyl-1, 2, 4-triazole-5 ( 1H) -on

4-difluoromethyl-4, 5-dihydro-1- (4-matic-3-methoxyphenyl) -3-methyl-1, 2, 4-triazol-5 (1H) one 15.0 in 100 ml of chloroform A solution of g (0.056 mol) and 7.5 g (0.056 mol) of sulfuryl chloride is stirred at room temperature for 2 hours. The reaction mixture is concentrated under reduced pressure to give a residue. The residue is dissolved in methylene chloride and washed with 10% aqueous sodium hydroxide solution. The organic layer is dried over magnesium sulfate and filtered. The filtrate was laid under reduced pressure to give solid 1- (2-chloro-4-methyl-5-methoxyphenyl) -4-difluoromethyl-4, 5-dihydro-3-methyl-1, 2, 4 16.5 g of -triazol-5 (1H) -one are obtained.

The nmr spectrum is consistent with the proposed structure.

Step F: 1- (2-Chloro-4-methyl-5-hydroxyphenyl) -4-difluoromethyl-4, 5-dihydro-3-methyl-1, 2, 4-triazole-5 ( 1H) -on

1- (2-Chloro-4-methyl-5-methoxyphenyl) -4-difluoromethyl-4, 5-dihydro-3-methyl-1, 2, 4-triazole-5 in 100 ml of methylene chloride 39.6 g (0.16 mole) of boron trifluoride was added dropwise to 16.0 g (0,053 mole) stirred solution of (1H) -one. The resulting mixture is stirred for 2 days at room temperature. The mixture is washed with 100 ml of water. The filtrate is concentrated under reduced pressure to give an oil. This oil is stirred in petroleum ether: diethyl ether (90:10) to form a solid. The solid was collected by filtration to give 1- (2-chloro-4-methyl-5-hydroxyphenyl) -4-difluoromethyl-4, 5-dihydro-3-methyl-1, 2, 4-triazole -5 (1H) -one (melting point 154-156 占 폚) is obtained.

The nmr spectrum is consistent with the proposed structure.

Step G: Methyl 2- [4-chloro-5- (4-difluoromethyl-4, 5-dihydro-3-methyl-5-oxo-1H-1, 2, 4-triazol-1-yl ) -2-methylphenoxy] -propionate

In a similar manner to Step G of Example 2, 1- (2-chloro-4-methyl-5-hydroxyphenyl) -4-difluoromethyl-4, 5-di in 100 ml of N, N-dimethylformamide 3.0 g (0.01 mol) of hydro-3-methyl-1, 2, 4-triazol-5 (1H) -one, 0.25 g (0.01 mol) of sodium hydride and 1.75 g (0.01 mol) of methyl 2-bromopropionate ) To the methyl 2- [4-chloro-5- (4-difluoromethyl-4, 5-dihydro-3-methyl-5-oxo-1H-1, 2, 4-triazole in oil state 3.7 g of 1-yl) -2-methylphenoxy] propionate (compound 4) are obtained.

The nmr spectrum is consistent with the proposed structure.

Compound 7 is prepared by the method described for compound 4, using step G of ethyl 2-bromopropionate.

Step H: 2- [4-Chloro-5- (4-difluoromethyl-4, 5-dihydro-3-methyl-5-oxo-1H-1, 2, 4-triazol-1-yl) -2-methylphenoxy] -propionic acid

In a similar manner to Step H of Example 2, methyl 2- [4-chloro-5- (4-difluoromethyl-4, 5-dihydro-3-methyl-5-oxo-1H-1, 2, 3.3 g (0.0088 mol) of 4-triazol-1-yl) -2-methylphenoxy] propionate was reacted with 1.5 g (0.27 mol) of potassium hydroxide in 15 ml of water and 50 ml of ethanol to give 2- [4-chloro- 5- (4-Difluoromethyl-4, 5-dihydro-3-methyl-5-oxo-1H-1, 2, 4-triazol-1-yl) -2-methylphenoxy] propionic acid (compound A3) 2.7 g are obtained as a solid (melting point 56 to 60 ° C).

The nmr spectrum is consistent with the proposed structure.

Example 4

2-nitropropyl 2- [2, 4-dichloro-5- (4-difluoromethyl-4, 5-dihydro-3-methyl-5-oxo-1H-1, 2, 4-triazole-1 -Yl) phenoxy] propionate

2- [2,4-dichloro-5- (4-difluoromethyl-4,5-dihydro-3-methyl-5-oxo-1H-1, 2,4-triazole-1- in 60 ml of toluene I) phenoxy] propionic acid (Compound A1) 0.5g (0.0013mol), refluxing a stirring mixture of 2-nitro-1-propane 1.0g (0.0095mol) and 0.05g (0.0003mol) P-toluenesulfonic acid monohydrate Under heating. The water generated during the reaction is collected in a Dean-stark trap and removed. After refluxing for a total of 2 hours, the solvent was distilled off under reduced pressure to obtain a residue. This residue is dissolved in diethyl ether, washed first with water and washed with 10% sodium hydroxide solution. The organic phase is dried over anhydrous sulfuric magnesium and filtered. The filtrate was evaporated to give an oily 2-nitropropyl 2- [2, 4-dichloro-5- (4-difluoromethyl-4, 5-dihydro-3-methyl-5-oxo-1H-1, 2 0.5 g of 4-triazol-1-yl) phenoxy] propionate (Compound B1) are obtained.

The nmr spectrum is consistent with the proposed structure.

Compound 1 is also prepared from Compound A1 and n-butanol according to the method of Example 4.

Example 5

2-propenyl 2- [2, 4-dichloro-5- (4-difluoromethyl-4, 5-dihydro-3-methyl-5-oxo-1H-1, 2, 4-triazole-1 -Yl) phenoxy] propionate

Under dried nitrogen atmosphere, methyl 2- [2,4-dichloro-5- (4-difluoromethyl-4, 5-dihydro-3-methyl-5-oxo in 30 ml of 2-propen-1-ol 0.5 g (0.0013 mol) of -1H-1,2,4-triazol-1-yl) phenoxy] propionate (Compound 2) and about 0.01 g of sodium methoxide are heated under reflux. When about 5 ml of methanol is collected in the Dean-Stark trap, the reaction mixture is cooled slightly and the remaining solvent is removed by distillation under reduced pressure to give a residue. This residue is dissolved in diethyl ether and washed with water. The organic phase is dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated under reduced pressure to give an oily 2-propenyl 2- [2, 4-dichloro-5- (4-difluoromethyl-4, 5-dihydro-3-methyl-5-oxo-1H-1 0.55 g of 2,4-triazol-1-yl) phenoxy] propionate (compound B2) is obtained.

The nmr spectrum is consistent with the proposed structure.

Elemental Analysis of C ₁₆ H ₁₅ N ₃ Cl ₂ F ₂ O ₄

Calculated Value: C, 45.52; H, 3.58; N, 9.95

Found: C, 45.24; H, 3. 76; N, 9.87

The following compounds were prepared according to the method of Example 5 in 1- (2, 4-dichloro-5-hydroxyphenyl) -4-difluoromethyl-4, 5-dihydro-3-methyl-1, 2, 4- Triazole-5 (1H) -one; Compound A1; Or prepared from Compound A2 and the following reagents:

Example 6

N-methylsulfonyl-2- [2, 4-dichloro-5- (4-difluoromethyl-4, 5-dihydro-3-methyl-5-oxo-1H-1, 2, 4-triazole -1-yl) phenoxy] propionamide

Step A: 2- [2, 4-dichloro-5- (4-difluoromethyl-4, 5-dihydro-3-methyl-5-oxo-1H-1, 2, 4-triazole-1- I) phenoxy] propionyl chloride

2- [2,4-dichloro-5- (4-difluoromethyl-4,5-dihydro-3-methyl-5-oxo-1H-1, 2,4-triazole- in 5 ml of thionyl chloride A stirring mixture of 2.9 g (0.0075 mol) of 1-yl) phenoxy] propionic acid (Compound A-1) is heated under reflux for 1.5 h. The mixture is cooled and excess thionyl chloride is evaporated off under reduced pressure to give 3.1 g of oily product.

Step B: N-methylsulfonyl-2- [2, 4-dichloro-5- (4-difluoromethyl-4, 5-dihydro-3-methyl-5-oxo-1H-1, 2, 4 -Triazol-1-yl) phenoxy] propionamide

A mixture of 0.56 g of oil and 0.56 g (0.0059 mol) of methanesulfonamide obtained from Step A is heated to 80 ° C. for 3.5 hours. The mixture is cooled and diluted with water to give a gummy precipitate. The water is decanted and the residue is partitioned between water and methylene chloride. The organic phase is washed three times with 100 ml of water, dried over anhydrous magnesium sulfate and filtered. The filtrate is evaporated under reduced pressure to give a solid which is dissolved in 30 ml of 1N sodium hydroxide and 50 ml of water. The filtrate is evaporated under reduced pressure to give a solid which is dissolved in 30 ml of 1N sodium hydroxide and 50 ml of water. The basic mixture is filtered and the filtrate is acidified with concentrated hydrochloric acid. The formed precipitate is collected by filtration. The filter cake was washed with water and dried to give N-methylsulfonyl-2- [2, 4-dichloro-5- (4-difluoromethyl-4, 5-dihydro-3-methyl-5-oxo-1H-1 0.34 g of 2,4-triazol-1-yl) phenoxy] propionamide (melting point; 185-188 ° C .; compound (3)) is obtained.

The nmr spectrum is consistent with the proposed structure.

Elemental Analysis of C ₁₄ H ₁₄ Cl ₂₁ F ₂ N ₄ O ₅ S

Calc .: C, 36.61; H, 3.07; N, 12.20

Found: C, 36.79; H, 3.0 1; N, 12.41

Compounds C4, C5 and C6 are prepared according to the method of Example 6 using the trifluoromethanesulfonamide, ammonia and methylamine of step B, respectively. Compounds C2 and C18 are prepared from Compound A2 according to the method of Example 6 using the methylamine and methanesulfonamide of Step B, respectively.

Example 7

Ethyl 2- [2,4-dibromo-5- (4-difluoromethyl-4,5-dihydro-3-methyl-5-oxo-1H-1, 2,4-triazole-1- Phenoxy] propionate

Step A: 1- (2, 4-Dibromo-5-methoxyphenyl) -4-difluoromethyl-4, 5-dihydro-3-methyl-1, 2, 4-triazole-5- (1H) -on

1- (3-methoxyphenyl) -4-difluoromethyl-4, 5-dihydro-3-methyl-1, 2, 4-triazol-5 (1H) one in 75 ml of acetic acid (from Example 2 30.0 g (0.19 mole) of bromine are added to 12.0 g (0.047 mole) of a stirred mixture prepared from 3-methoxyaniline using the methods B to E. The mixture is heated under reflux for 6 hours and then cooled. The solvent is removed by distillation to give a residue. This residue is dissolved in diethyl-ether and the resulting solution is first washed with an aqueous 10% sodium thiosulfate solution and then washed with water. The organic solution is dried over anhydrous magnesium sulfate and filtered. The filtrate is evaporated under reduced pressure to give a solid. The solid was triturated in petroleum ether and filtered to give 1- (2, 4-dibromo-5-methoxyphenyl-4-difluoromethyl-4, 5-dihydro-3-methyl-1, 2, 4 17.4 g of -triazol-5 (1H) -one are obtained.

The nmr spectrum is consistent with the proposed structure.

Step B: 2- (2, 4-Dibromo-5-hydroxyphenyl) -4-difluoromethyl-4, 5-dihydro-3-1, 2, 4-triazole-5 (1H) -On

1 (2,4-Dibromo-5-methoxyphenyl) -4-difluoromethyl-4, 5-dihydro-3-methyl-1, 2, 4-triazole-5 (in 100 ml of methylene chloride) A mixture of 17.2 g (0.042 mol) of 1H) -one and 50.6 g (0.020 mol) of boron trifluoride is stirred at room temperature for 18 hours. The mixture is washed with 50 ml of water and evaporated to dry the organic phase over magnesium sulfate.

The mixture was filtered and the filtrate was evaporated under reduced pressure to give solid 1- (2,4-dibromo-5-hydroxyphenyl) -4-difluoromethyl-4, 5-dihydro-3-methyl- 16.1 g of 1, 2, 4-triazol-5 (1H) -one are obtained.

The nmr spectrum is consistent with the proposed structure.

Step C: Ethyl 2- [2, 4-dibromo-5- (4-difluoromethyl-4, 5-dihydro-3-methyl-5-oxo-1H-1, 2, 4-triazole -1-yl) phenoxy] propionate

1- (2,4-dibromo-5-hydroxyphenyl-4-difluoromethyl-4, 5-dihydro-3-methyl-1, 2, 4- in 60 ml of N, N-dimethylformamide To a stirred solution of 1.25 g (0.0031 mol) of triazole-5 (1H) -one is added 0.57 g (0.0033 mol) of ethyl 2-bromopropionate The resulting mixture is heated at 130 ° C. for 2 hours and then cooled The solvent is evaporated from the mixture under reduced pressure to give a solid which is dissolved in diethylter and the solution is washed with water first and then washed with 10% sodium hydroxide solution The organic solution is dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated under reduced pressure to give an oily ethyl 2- [2, 4-dibromo-5- (4-difluoromethyl-4, 5-dihydro-3-methyl-5-oxo-1H-1 1.0 g of 2, 4-triazol-1-yl) phenoxy] propionate (compound 8) are obtained.

The nmr spectrum is consistent with the proposed structure.

Example 8

1-methylpropyl 2- [2, 4-dichloro-5- (4-difluoromethyl-4, 5-dihydro-3-methyl-5-oxo-1H-1, 2, 4-triazole-1 -Yl) phenoxy] propionate

2- [2,4-dichloro-5- (4-difluoromethyl-4, 5-dihydro-3-methyl-5-oxo-1H-1, 2, 4-triazole- in 15 ml of secondary butanol To 7 g of 1-yl) phenoxy] propionyl chloride (prepared in Step A of Example 6) was added 0.27 g (0.0027 mol) of triethylamine. The reaction mixture is stirred at room temperature for 20 hours and then heated at 70 ° C. for 1-1 / 2 hours. Cool the mixture and stir at room temperature for about 18 hours. Removal of the solvent by evaporation under reduced pressure yielded a residue, which was partitioned between diethyl ether and water. The organic phase is washed sequentially with water, 10% aqueous hydrochloric acid, saturated aqueous sodium bicarbonate solution and water. The organic phase is dried over anhydrous magnesium sulfate and then filtered. The filtrate was evaporated under reduced pressure to yield an oily 1-methylpropyl 2- [2, 4-dichloro-5- (4-difluoromethyl-4, 5-dihydro-3-methyl-5-oxo-1H-1 0.42 of 2,4-triazol-1-yl) phenoxy-]-propionate (compound 12) is obtained.

The nmr spectrum is consistent with the proposed structure.

Compound B4 can also be prepared from the acid chloride and 2-propyn-1-ol of compound A2 using the method of Example 8.

Example 9

Ethyl [2,4-dichloro-5- (4-difluoromethyl-4,5-dihydro-3-methyl-5-oxo-1H-1, 2,4-triazol-1-yl) phenoxy ] Fluoroacetate

1- (2,4-dichloro-5-hydroxyphenyl) -4-difluoromethyl-4, 5-dihydro-3-methyl-1, 2, 4-triazole-5 (1H) in 50 ml of ethanol To a stirred mixture of 2.0 g (0.0065 mol) of -one and 0.91 g (0.0065 mol) of ethyl chlorofluoroacetate is added a solution of 0.15 g (0.0065 mol) of sodium in 5 ml of ethanol. The reaction mixture is heated at reflux for 34 h. The mixture is cooled and the solvent is evaporated off under reduced pressure to give a residue. This residue is dissolved in diethyl ether and the solution is washed with water first and then washed with 10% aqueous sodium hydroxide solution. The organic phase is dried over anhydrous magnesium sulfate and then filtered. The filtrate was evaporated under reduced pressure to yield ethyl [2, 4-dichloro-5- (4-difluoromethyl-4, 5-dihydro-3-methyl-5-oxo-1H-1, 2, 4-triazole- 0.95 g of 1-yl) phenoxy] fluoroacetate (Compound 51) is obtained as an oil.

The nmr spectrum is consistent with the proposed structure.

Example 10

Ethyl 2- [2,4-dichloro-5- (4-difluoromethyl-4, 5-dihydro-3-methyl-5-oxo-1H-1, 2, 4-triazol-1-yl) Phenoxy] propionate

Step A: 1- [2, 4-dichloro-5- (1- (methylethoxy) phenyl] -4-fluoromethyl-4, 5-dihydro-3-methyl-1, 2, 4-triazole -5 (1H) -on

1- [2,4-dichloro-5- (1-methylethoxy) phenyl] -4, 5-dihydro-3-methyl1, 2, 4-triazole-5 in 45 ml of N, N-dimethylformamide 6.0 g (0.020 mol) of (1H) -one is added to 0.55 g (0.022 mol) of sodium hydride in 30 ml of N, N-dimethylformamide. The reaction mixture is stirred at room temperature for 15 minutes. Chloro-fluoromethanol, is added dropwise to the stirred reaction mixture by condensing the gas over anhydrous ice condenser. The mixture is slowly heated to 60 ° C. during the addition and at this temperature the mixture begins to reflux. When the chlorofluoromethane addition is stopped and the reaction mixture is slowly heated to 60 ° C. at this temperature the mixture begins to reflux. The chlorofluoromethane addition is stopped and the reaction mixture is allowed to cool to room temperature and left to stand for about 18 hours. Resume heating at reflux and add an additional amount of chlorofluoromethanol for 10 minutes. After the addition is complete the reaction mixture is heated to reflux for 1 hour and then cooled. The solvent is distilled off under reduced pressure to give a residue. This residue is partitioned between diethyl ether and water. The organic phase is first washed with 1N sodium hydroxide and then washed with water. The organic solution is dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated under reduced pressure to yield 1- [2,4-dichloro-5- (1-methylethoxy) phenyl] -4-fluoromethyl-4, 5-dihydro-3-methyl-1, 2, 4- 3.8 g of triazole- (1H) -one are obtained as an oil.

The nmr spectrum is consistent with the proposed structure.

Step B: 1- (2, 4-Dichloro-5-hydroxyphenyl) -4-fluoromethyl-4, 5-dihydro-3-methyl-1, 2, 4-triazole-5 (1H)- On

To 5 ml of stirred concentrated sulfuric acid, 1- [2,4-dichloro-5- (1-methylethoxy) phenyl] -4-fluoromethyl-4, 5-dihydro-3-methyl-1, 2, 4- 0.53 g (0.0016 mole) of triazole-5 (1H) -one is added dropwise. After the addition is complete the mixture is stirred for 2.5 hours at room temperature. The mixture is poured into 100 ml of water and stirred for 30 minutes. The aqueous mixture is extracted with diethyl ether and the extract is washed with water. The organic phase is dried over anhydrous magnesium sulfate and filtered. The filtrate was evaporated under reduced pressure to give solid 1- (2,4-dichloro-5-hydroxyphenyl) -4-fluoromethyl-4, 5-dihydro-3-methyl-1, 2, 4-triazole 0.34 g of -5 (1H) -one is obtained.

The nmr spectrum is consistent with the proposed structure.

The reaction was carried out with 1- [2, 4-dichloro-5- (1-methylethoxy)]-4-fluoromethyl-4, 5-dihydro-3-methyl-1, 2, 4-triazole-5 Repeat with 2.8 g (1H) -one to obtain further 1.9 g of product.

Step C: Ethyl 2- [2, 4-dichloro-5- (4-difluoromethyl-4, 5-dihydro-3-methyl-5-oxo-1H-1, 2, 4-triazole-1 -Yl) phenoxy] propionate

1- (2,4-Dichloro-5-hydroxyphenyl) -4-fluoromethyl-4, 5-dihydro-3-methyl-1, 2, 4-triazole-5 (1H)-in 15 ml of acetone A mixture of 0.56 g (0.0019 mol) and 1.1 g (0.0076 mol) of anhydrous potassium carbonate is stirred for 15 minutes. Sodium iodide (ca. 0.01 g) and 0.37 g (0.002 mol) ethyl 2-bromopropionate are added and the resulting mixture is heated at reflux for 1.5 h. Cool the mixture and filter. The filtrate is evaporated under reduced pressure to give a residue. This residue is partitioned between diethyl ether and water. The organic phase is washed with water, dried over anhydrous magnesium sulfate and filtered. The filtrate is evaporated under reduced pressure to give an oil. This oil is stirred in n-pentane and the supernatant is decanted to give an oily residue. The oil was dried at 70 DEG C under nitrogen to afford ethyl 2- [2,4-dichloro-5- (4-difluoromethyl-4, 5-dihydro-3-methyl-5-oxo-1H-1, 0.70 g of 2,4-triazol-1-yl) phenoxy] propionate (compound 13) is obtained.

The nmr spectrum is consistent with the proposed structure.

Example 11

N- (4-methylphenylsulfonyl) -2- [2-chloro-4-fluoro-5- (4-difluoromethyl-4, 5-dihydro-3-methyl-5-oxo-1H-1 , 2, 4-triazol-1-yl) phenoxy] propionamide

2- [2-Chloro-4-fluoro-5- (4-difluoromethyl-4, 5-dihydro-methyl-5-oxo-1H-1, 2, 4-triazole- in 50 ml of toluene 0.78 g (0.0021 mol) of 1-yl) phenoxy] propionic acid, 0.42 g (0.0021 mol) of P-toluenesulfonyl isocyanate and 0.05 g (0.004 mol) of 4-dimethylamino-pyridine under reflux for about 18 hours Heat during. The mixture is cooled to room temperature and stirred for 24 hours. The solvent is evaporated off under reduced pressure to give a residue. The residue is purified by column chromatography on silica gel, eluting with toluene: ethyl acetate (1: 1). The appropriate fractions were combined and evaporated under reduced pressure to give N- (4-methylphenylsulfonyl) -2- [2-chloro-4-fluoro-5- (4-difluoromethyl-4, 5-dihydro-) in the solid state. 0.7 g of 3-methyl-5-oxo-1H-1, 2, 4-triazol-1-yl) phenoxy] propionamide (Compound C10) are obtained.

The nmr spectrum is consistent with the proposed structure.

Compound C25 is prepared according to the method of Example 11 using 2-chlorobenzenesulfonyl isocyanate.

Example 12

2- [2-chloro-4-fluoro-5- (4-difluoromethyl-4, 5-dihydro-3-methyl-5-oxo-1H-1, 2, 4-triazole-1- (I) phenoxy] propionic acid, sodium salt.

2- [2-chloro-4-fluoro-5- (4-difluoromethyl-4, 5-dihydro-3-methyl-5-oxo-1H-1, 2, 4- in 30 ml of tetrahydrofuran A mixture of 1.0 g (0.0027 mol) of triazol-1-yl) phenoxy] propionic acid and 0.07 g (0.0027 mol) of sodium hydride is stirred at room temperature for about 18 hours. The solvent was evaporated off to give a solid 2- [2-chloro-4-fluoro-5- (4-difluoromethyl-4, 5-dihydro-3-methyl-5-oxo-1H-1, 2 0.9 g of 4-triazol-1-yl) phenoxy] propionic acid and sodium salt (Compound A4) are obtained.

Compounds C19 and C20 are prepared from compounds C18 and C10, respectively, according to the method of Example 12. Compound A6 is prepared from Compound A2 using isopropylamine instead of sodium hydride in a similar manner as in Example 12.

Example 13

[2,4-dichloro-5- (3-difluoromethyl-4, 5-dihydro-4-methyl-5-oxo-1H-1, 2, 4-triazol-1-yl) phenoxyacet amides

Step A: Ethyl Difluoroacetylcarbamate

65.4 g (0.55 mol) of thionyl chloride are added to 50.0 g (0.52 mol) of difluoroacetic acid with stirring for 30 minutes. The gas released during addition is recovered to the reaction mixture by condensation on an anhydrous ice condenser. After the addition is complete the mixture is stirred at room temperature for about 2 hours. 46.4 g (0.52 mol) of urethane are added and the reaction mixture is heated to 60-70 ° C. for 3 hours after the addition is complete. The mixture is cooled to room temperature and stirred for about 18 hours. The mixture is heated to about 75 ° C. for 2 hours and then cooled. The mixture is evaporated under reduced pressure to give an oily residue. This residue crystallizes when left unattended. The crystallized residue was washed with petroleum ether and filtered to give 68.4 g of ethyl difluoroacetylcarbamate (melting point 55-57 ° C.).

Step B: 1- [2, 4-dichloro-5- (1-methylethoxy) phenyl] -3-difluoromethyl-4, 5-dihydro-1, 2, 4-triazole-5 (1H )-On

2.5 g (0.02 mol) of phosphorus in a stirred solution of 11.8 g (0.05 mol) of 2,4dichloro-5- (1-methylethoxy) -phenylhydrazine and 10.0 g (0.06 mol) of difluoroacetylcarbamate in 130 ml of xylene ) After complete addition the mixture is heated under reflux for 1.5 hours and then cooled to room temperature for about 18 hours. The reaction mixture is decanted from the thick residue in the reaction flask and washed with water. The washed mixture is extracted with 10% aqueous sodium hydroxide solution. The basic extract is acidified with concentrated hydrochloric acid to form an oily precipitate. The water phase is inclined from the oily residue and the residue is washed by adding clean water.

This residue is dissolved in 160 ml of methylene chloride and filtered through a pad of celite. The filtrate is dried over anhydrous magnesium sulfate and filtered. The filtrate is evaporated under reduced pressure to give a semisolid residue. The residue was triturated with about 125 ml of petroleum ether and 1- [2, 4-dichloro-5- (1-methylethoxy) phenyl] -3-difluoromethyl-4, 5-dihydro-1, 2, 4- Triazol-5 (1H) -one 8.2 is obtained.

Step C: 1- [2, 4-dichloro-5- (1-methylethoxy) phenyl] -3-difluoromethyl-4, 5-dihydro-4-methyl-1, 2, 4-triazole -5 (1H) -on

1- [2,4-dichloro-5- (1-methylethoxy) phenyl] -3-difluoromethyl-4, 5-dihydro-1, 2, 4-triazole-5 (1H in 160 ml of acetone) A stirring mixture of 4.0 g (0.012 mol) of) -one and 4.1 g (0.03 mol) of calcium carbonate is heated at reflux for 0.5 h and then cooled to about 50 ° C. 8.4 g (0.06 mol) of methyl iodide are added and the mixture is stirred at 45 'for 1 hour and then refluxed for 1 hour. The mixture is cooled to room temperature and evaporated under reduced pressure to yield an oil.

This oil is partitioned between methylene chloride and water. The organic phase is washed with 10% aqueous sodium hydroxide solution and then dried over anhydrous magnesium sulfate. The mixture is filtered and the filtrate is evaporated under reduced pressure to give an oil. When the oil is stirred with petroleum ether, it solidifies and is filtered to give 1- [2,4-dichloro-5- (1-methylethoxy) phenyl] -3-difluoromethyl-4, 5-dihydro-4- 2.6 g of methyl-1, 2, 4-triazol-5- (1H) -one (melting point: 95 to 96 ° C) are obtained.

Step D: 1- (2, 4-Dichloro-5-hydroxyphenyl) -3-difluoromethyl-4, 5-dihydro-4-methyl-1, 2, 4-triazole-5 (1H) -On

1- [2,4-dichloro-5- (1-methylethoxy) phenyl] -3-difluoromethyl-4, 5-dihydro-4-methyl-1, 2, 4-tria in 5 ml of concentrated sulfuric acid 2.2 g (0.0063 mol) of sol-5 (1H) -one was hydrolyzed to yield 1- (2,4-dichloro-5-hydroxyphenyl) -3-difluoromethyl-4, 5-dihydro-4- Methyl-1, 2, 4-triazol-5 (1H) -one (melting point 176-179 ° C.) is obtained.

Step E: [2, 4-dichloro-5- (3-difluoromethyl-4, 5-dihydro-4-methyl-5-oxo-1H-1, 2, 4-triazol-1-yl) Phenoxy] acetamide

In a similar manner to Example 1, 1- (2,4-dichloro-5-hydroxyphenyl) -3-difluoromethyl-4, 5-dihydro-4-methyl-1, 2, 4- in 5 ml of acetone. 0.72 g (0.00023 mol) of triazole-5 (1H) -one, 0.32 g (0.00023 mol) of calcium carbonate and 0.47 g (0.00025 mol) of uridoacetamide were reacted to [2,4-dichloro-5- (3-di 0.69 g of fluoromethyl-4, 5-dihydro-4-methyl-5-oxo-1H-1, 2, 4-triazol-1-yl) phenoxy] -acetamide (melting point 190 to 193.5 ° C.) To obtain.

The nmr spectrum is consistent with the proposed structure.

The following compounds are prepared from Compound A2 and the following reagents according to the methods of S. Chandrasekaran et al., Synthetic Communications, 12 (9), 727-731 (1982).

Compound reagents

B 8 tetrahydrofurfuryl alcohol

B 9 methyl hydroxyacetate

B10 2-Methyl-3, 3, 4, 4-tetrafluoro-2-butanol

B12 furfuryl alcohol

B13 N, N-dimethylethanolamine

B14 3-hydroxytetrahydrofuran

B15 phenol

B17 ethanethiol

B18 ethyl 2-mercaptoacetate

B30 trifluoroethanol

B31 Acetone Cyanohydrin

B32 Benzyl Alcohol

B33 2-propanethiol

C11 O, N-dimethylhydroxyaminehydrochloride

C12 (2-propynyl) amine

C13 Aniline

C14 Dimethylamine

C15 diethylamine

C16 ethylamine hydrochloride

C17 glycine methyl ester hydrochloride

C22 2-amino-2-methylpropionitrile

C23 N-methylaniline

Compound B25 is described in the literature by Lonord et al., J. Org. Chem. 27, 282 to 284 (1962).

Compound A5 is prepared by hydrolyzing Compound 22 according to methods in the literature (Kurter et al., Synthesis (1975), 106-108).

The properties of some compounds of the invention are described in Table 6 below.

Example 14

N- (2,5-dimethoxyphenylsulfonyl) -2- [2-chloro-4-fluoro-5- (4-difluoromethyl-4, 5-dihydro-3-methyl-5-oxo -1H-1, 2, 4-triazol-1-yl) phenoxy] propionamide.

Step A: 2.5-dimethoxyphenylsulfonamide

To a stirred solution of 15.0 g (0.063 mol) of 2,5-dimethoxybenzenesulfonyl-chloride in 150 ml of tetrahydrofuran was added dropwise 80 ml of ammonia (28% aqueous solution). After the addition is complete the mixture is stirred at room temperature for 1.75 h. Allow the mixture to settle and separate into two phases. The organic phase is removed from the aqueous phase and evaporated under reduced pressure to give a solid residue. The residue is recrystallized from hot water (125 ml) and ethanol (40 ml) to give 13.1 g of 2,5-dimethoxyphenylsulfonamide (melting point; 146.5 to 148.5).

The nmr spectrum is consistent with the proposed structure.

Step B: N- (2, 5-dimethoxyphenylsulfonyl) -2-bromopropionamide

A stirred mixture of 7.0 g (0.032 mol) of 1, 5-dimethoxyphenylsulfonamide in 10 ml of 2-bromopropionyl chloride is heated at reflux for 40 minutes and then cooled to room temperature. The resulting solution is poured into petroleum ether. Crystals form after raking the sides of the flask and are collected by filtration. The filter cake was washed four times with fresh petroleum ether to give 10.3 g of N- (2, 5-dimethoxyphenylsulfonyl) -2-bromo propionamide (melting point 116-118 ° C.).

The nmr spectrum is consistent with the proposed structure.

Step C: N- (2, 5-dimethoxyphenylsulfonyl) -2- [2-chloro-4-fluoro-5- (4-difluoromethyl-4, 5-dihydro-3-methyl- 5-oxo-1H-1, 2, 4-triazol-1-yl) phenoxy] -propionamide.

1- (4-chloro-2-fluoro-5-hydroxyphenyl) -4-difluoromethyl-4, 5-dihydro-3-methyl-1, 2, 4-triazole-5 in 50 ml of acetone 1.04 g (0.0026 mol) of potassium carbonate in a stirred solution of 0.75 g (0.0026 mol) of (1H) -one and 0.89 g (0.0026 mol) of N- (2,5-dimethoxyphenylsulfonyl) -2-bromopropionamide Add. After addition is complete the mixture is heated at 45 ° C. for 2 days. The resulting mixture is cooled and the solvent is evaporated off under reduced pressure to give a residue.

This residue is dissolved in 100 ml of water. Acid hydrochloric acid is added dropwise to the aqueous solution to give a precipitate. The precipitate is collected by filtration. The filter cake was washed with water and then dried under reduced pressure to give N- (2, 5-dimethoxyphenylsulfonyl) -2- [2-chloro-4-fluoro-5- (4-difluoromethyl-4, 5- Dihydro-3-methyl-5-oxo-1H-1, 2, 4-triazol-1-yl) phenoxy] propionamide (melting point 168 to 172 ° C), 1.23 g of compound C90 are obtained.

The nmr spectrum is consistent with the proposed structure.

Example 15

1- (4-chloro-2-fluoro-5-methoxyphenyl) -4, 5-dihydro-3-methyl-1, 2, 4-triazol-5 (1H) -one as intermediate

Step A: N '-(4-chloro-2-fluoro-5-methoxyphenyl) acetamiderazon

1.9 g (0.01 mol) of 4-chloro-2-fluoro-5-methoxyphenylhydrazine and 3- (1-iminoethylmercapto) -1-propanesulfonic acid, salts in 50 ml of anhydrous ethanol (Reid et al. , Ann. Chem. 676, 114 (1964)) 1.97 g (0.01 mol) of a stirred mixture is heated under reflux for 1.25 h. Cool the mixture and evaporate under reduced pressure to afford 3.96 g of residue. 3.33 g of this residue fraction is dissolved in 50 ml of water. The resulting cloudy solution is filtered through a pad of celite and the filtrate is extracted with methylene chloride. The separated aqueous solution is basified to about 8 ml of a 10% sodium hydroxide aqueous solution. The oil precipitates out of the basic mixture and slowly solidifies.

This solid is collected by filtration. The filter cake was washed with water to obtain 1.31 g of N '-(4-chloro-2-fluoro-5-methoxyphenyl) acetamide razone (melting point 106 to 107 ° C).

nmr analysis is consistent with the proposed structure.

Elemental Analysis of C ₉ H ₁₁ ClFN ₃ O

Calc .: C, 46.66; H, 4.79; N, 18.14

Found: C, 46.10; H, 4.81; N, 17.70

Step B: 1- (4-Chloro-2-fluoro-5-methoxyphenyl) -4, 5-dihydro-3-methyl-1, 2, 4-triazol-5 (1H) -one

A solution of 1.71 g (0.0086 mol) of trichloromethyl chloroformate in 5 ml of toluene was added to 1.0 g (0.0043 mol) of N '-(4-chloro-2-fluoro-5-methoxyphenyl) acetamide razone in 50 ml of toluene. Add dropwise to the stirred solution. After the addition is complete the mixture is stirred for 5 hours at room temperature and then slowly heated until reflux. Continue reflux for about 15 minutes. Cool the mixture and evaporate under reduced pressure to afford 1.22 g of solid. About 1.0 g of solid is dissolved in 100 ml of methylene chloride. The resulting solution is filtered and the filtrate is extracted three times with 25 ml of 10% aqueous sodium hydroxide solution and three times with 25 ml of 1N sodium hydroxide. Each of the three extracts are combined and washed with methylene chloride. Both washed extracts are acidified with concentrated hydrochloric acid to give a precipitate. The solid was recovered by filtration to obtain 1- (4-chloro-2-fluoro-5-methoxyphenyl) -4, 5-dihydro-3-methyl-1, 2 from 10% base solution and 1N base solution, respectively. 0.3 g and 0.12 g of 4-triazol-5 (1H) -one (melting point 209 to 211 ° C.) are obtained.

The nmr spectrum is consistent with the proposed structure.

Example 16

1- (2, 4-dichloro-5-hydroxyphenyl) -3-chloro-difluoromethyl-4, 5-dihydro-4-methyl-1, 2, 4-triazole-5 (1H as intermediate )-On

Step A: N '-[2, 4-dichloro-5- (1-methylethoxy) phenyl] -chlorodifluoroacetamide razone

9.4 g (0.04 mol) of 2, 4-dichloro-5- (1-methylethoxy) phenylhydrazine in 350 ml of pure methanol is cooled to 0 deg. Gas phase chlorodifluoroacetonitrile (8.0 g, 0.07 mole) is added to the mixture. After the addition is complete the mixture is allowed to warm to room temperature and stirred for 3.5 h. Agitation is stopped and the mixture is stopped for 2 days at room temperature. The solvent is evaporated from the mixture under reduced pressure to afford 13.86 g of N '[2,4-dichloro-5- (1-methylethoxy) phenyl] chlorodifluoroacetamiderazone in oil form.

Step B: 1- [2, 4-dichloro-5- (1-methylethoxy) phenyl] -3-chlorodifluoromethyl-4, 5-dihydro-1, 2, 4-triazole-5 ( 1H) -on

13.86 g of the oily residue obtained in step A and 19.87 g (0.1 mol) of the same 2.7 g and trichloromethylchloroformate prepared in separate experiments were reacted in 600 ml of toluene in a similar manner to Step B of Example 15 [2,4-dichloro-5- (1-methylethoxy) phenyl] -3-chlorodifluoromethyl-4, 5-dihydro-1, 2, 4-triazol-5 (1H) -one ( Melting point 115 to 119 ° C.) to 5.4 g.

The nmr spectrum is consistent with the proposed structure.

Step C: 1- [2, 3-dichloro-5- (1-methylethoxy) phenyl] -3-chlorodifluoromethyl-4, 5-dihydro-4-methyl-1, 2, 4-tria Zol-5 (1H) -one

In a similar manner to Step C of Example 13, 1- [2, 4-dichloro-5- (1-methylethoxy) phenyl] -3-chlorodifluoromethyl-4, 5-dihydro-1, 2, 4.0 g (0.011 mol) of 4-triazol-5 (1H) -one, 4.26 g (0.03 mol) of methyl iodide and 2.07 g (0.015 mol) of potassium carbonate were reacted in 40 ml of acetone to give a solid 1- [2, 4-dichloro-5- (1-methylethoxy) phenyl] -3-chlorodifluoromethyl-4, 5-dihydro-4-methyl-1, 2, 4-triazol-5 (1H) -one 3.74 g is obtained. The small fraction of the solid is recrystallized from ethanol and water to give a pale yellow solid with a melting point of 69 to 72 ° C.

The nmr spectrum is consistent with the proposed structure.

Elemental Analysis of C ₁₃ H ₁₂ Cl ₃ F ₂ N ₃ O ₂

Calc .: C, 40.39; H, 3.13; N, 10.87

Found: C, 40.92; H, 3. 28; N, 10.96

Step D: 1- (2, 4-Dichloro-5-hydroxyphenyl) -3-chlorodi-fluoromethyl-4, 5-dihydro-4-methyl-1, 2, 4-triazole-5 ( 1H) -on

1- [2,4-dichloro-5- (1-methylethoxy) phenyl] -3-chlorodifluoromethyl-4, 5-dihydro-4-methyl-1, 2, 4- in 10 ml of concentrated sulfuric acid Triazole-5 (1H) -one 2.6 g (0.0067 mol) was hydrolyzed to give solid 1- (2,4-dichloro-5-hydroxyphenyl) -3-chlorodifluoromethyl-4, 5- Dihydro-4-methyl-1, 2, 4-triazol-5 (1H) -one (melting point 146-148 ° C.) is obtained.

The nmr spectrum is consistent with the proposed structure.

Elemental Analysis of C ₁₀ H ₆ Cl ₃ F ₂ N ₃ O ₂

Calc .: C, 34.85; H, 1.76; N, 12.20

Found: C, 35.30; H, 1.59; N, 12.25

Herbicide activity

Plant species used to demonstrate herbicidal activity of the compounds of the present invention include cotton (Gossypium hirsutum Var.Stoneville), soybean (Glycine max Var. Williams), corn (Zea mays Var. Agway 595S), wheat (Triticum aestivium Var. Prodax) ), Rice (Oryza sativa), Convolvulus arvensis, morning glory (Ipomea Iacunosa or Ipomea hederacea), velvet life (Abutilon theophrasti), Echinochloacrus galli, Setaria viridis, and Johnson Grass (Sorghum halepense) It contains a citrus (Cyperus esculentus).

Seeds or tubers of plant test species are furrowed in steam sterilized sandy loam in disposable fiber sowing boxes. The same fraction is evenly placed in the upper soil consisting of sand and sandy loam to the top of each sowing box approximately 0.5 cm deep.

Water the test seeding box before germination and wet it with an appropriate amount of the test compound solution in the form of a mixture of acetone and water containing a small amount (less than 0.5% V / V) of sorbitan monolaurate emulsifier / solubilizer. The concentration of test compound in solution varies, but is generally the equivalent of 8.0 kg / ha and its divisor. Put the seeding box in the greenhouse and water the soil surface regularly for 21 days and record the phytotoxicity data.

After germination, the test seeding box is placed in a greenhouse, watered for 8 to 10 days, and the leaf surface of the germinated test crop is sprayed with a solution of the test compound in acetone-water containing 0.5% or less sorbitan monolaurate. After spraying, the foliar is dried for 24 hours and then watered regularly for 21 hours and phytotoxic data is recorded.

Phytotoxicity data are expressed as percent death or percent control. Control putts are measured in a similar manner to the 0-100 rating system described in the literature, "Research Methods in Weed Science," 2nd ed., B. Truelove, Ed: Southern Weed Science Society; Auburn University, Auburn, Alabama, 1977]. These rating systems are as follows:

Herbicide evaluation

Herbicide data in selected uses are described for the various compounds of the present invention in the table below. The test compound is the same as the table in the herbicide data with the number corresponding to the compound used above

Herbicide data in the table are as follows.

"Kg / dl" is kilograms per hectare, "% K" is killing percent and "% C" is percent control.

The active compounds described above in the use of the preparations may be formulated into herbicide compositions by mixing herbicidally effective amounts with conventional adjuvants and carriers which facilitate the dispersion of the active ingredient for a particular use. In the above, the formulation and use of the toxic substance is thought to affect the activity of the substance. Accordingly, the herbicide compounds for agriculture can be formulated in relatively large particle sized water-soluble or water-dispersible granules, powders, wetting powders, emulsion concentrates, solutions, and many other known formulations.

For germination purposes, these herbicide compositions are generally used as sprays, powders or granules in areas where plant growth is desired. Sprays or powders are most commonly used for the purpose of suppressing post-germination of plant growth. These formulations may contain from 0.5% to 95% active ingredient.

Powder is a fluidized bed mixture with finely divided solids such as talc, natural clays, kieselguhr, powders such as hawkskins and cottonseeds, and other organic and inorganic solids that act as carriers and dispersants for toxic substances, and The average particle size of the finely divided solids is less than about 50 microns. Representative powders useful in the present invention are formulations containing 1.0 part of herbicide compound and 99.0 parts of talc.

Wet powders, useful as both herbicides before and after germination, are in the form of finely divided particles that are readily dispersed in water or other dispersants. Wetting acid is ultimately used in soil as a dry powder, or as an emulsion in water or other liquids. Representative carriers for humectants include tabletops, kaolin clays, silica and other superabsorbents, easily moisturizing inorganic lime. Wetting powders are prepared such that, depending on the absorbency of the carrier, they generally contain from about 5 to 80% of the active ingredient and generally contain small amounts of wetting agents, dispersants, or emulsifiers that facilitate dispersing.

For example, useful wetting powders contain 80.8 parts of herbicide compounds, 17.9 parts of Palmetto clay, 1.0 parts of sodium lignosulfonate as wetting agent and 0.3 parts of sulfonated aliphatic polyester. Frequently, it can be added to tank-mixtures for further post-germination use to facilitate foliar dispersion and absorption into plants.

Another agent useful for the use of herbicides is an emulsifier concentrate. Emulsifying thickeners are paste compositions that can be dispersed in a homogeneous liquid or in water or other dispersants and consist entirely of herbicide compounds and liquid or solid emulsifiers, or liquids such as xylenes, heavy aromatic naphtha, isophorone, or other nonvolatile organic solvents. It may also contain a carrier. These concentrates are dispersed in water or other liquid carriers for herbicide application and generally applied as a spray to the area to be treated. The weight percentage of the required active ingredient depends on the method of application of the composition, but generally contains from 0.5 to 95% by weight of the active ingredient of the herbicide composition.

Representative wetting agents, dispersants or emulsifiers used in agricultural preparations include, for example, alkyl and alkylaryl sulfonates and sulfates and salts thereof; Polyhydric alcohol; And other forms of surfactants, most of which are commercially available. If a surfactant is used, it generally contains 1 to 15% by weight of the herbicide composition.

Other agents useful for herbicide application include solutions of the active ingredient in dispersants (eg acetone, alkylated naphthalene, xylene or other organic solvents) that dissolve completely at the desired concentration. Granules containing toxic substances on relatively coarse particles are particularly useful for airborne distribution or percutaneous plant crop penetration. It is also possible to use conventional aerosols (eg Freons) in which the active ingredient is dispersed in finely divided form as a result of evaporating the pressurized spray and the low boiling point dispersion solvent carrier. Water-soluble or water-dispersible granules are also useful agents for herbicide application of the compounds. These granules are free-flowing, non-powdery and easily soluble in water or miscible with water. Soluble or dispersible granules are described in US Pat. No. 3,920,442, incorporated herein by reference, and are also useful as herbicide compounds.

The herbicide active compounds of the invention can be formulated and / or used with insecticides, fungicides, nematicides, plant growth regulators, fertilizers or other agrochemicals, and used as effective soil fungicides as well as selective herbicides in agriculture. Can be. In the application of the active compounds of the invention, effective amounts and effective concentrations of the active compounds, whether formulated alone or in combination with other agrochemicals, are used, for example the amount may be up to 7 g / dl.

The herbicide active compounds of the invention can be used in admixture with other herbicides, for example chloroacetanilide herbicides [eg. 2-Chloro-N- (2, 6-diethylphenyl) -N- (methoxymethyl) -acetamide (alachloro), 2-chloro-N- (2-methoxy-1-methylethyl) -acet Amide (methacrylchloro), and N-chloroacetyl-N- (2, 6-diethylphenyl) glycine (diethylethyl)]; Benzothiadiazinone herbicides [eg. 3- (1-methylethyl)-(1H) -2, 1, 3-benzothiadiazine-4- (3H) -one-2, 2-dioxide (bentazone)]; Triazine herbicides [eg. 6-chloro-N-ethyl-N- (1-methylethyl) -1, 3, 5-triazine-2, 4-diamine (atrazine), and 2- [4-chloro-6- (ethylamino)- 1, 3, 5-triazin-2-yl] -amino-2-methylpropanitrile (cyanazine)]; Dinitroaniline herbicides [eg. 2, 6-dinitro-N, N-dipropyl-4- (trifluoromethyl) benzeneamine (trifluralin)]; And aryl urea herbicides [eg. Such as N '-(3,4-dichlorophenyl) -N, N-dimethylurea (dialon) and N, N-dimethyl-N' [30trifluoromethyl) phenyl] -urea (fluoromethuron)] It can be mixed with an equivalent or excessive amount of known herbicides.

It is apparent that various modifications may be made in the formulation and application of the present invention without departing from the concept of the invention as described in the claims below.

TABLE 1

Control percent

TABLE 2

Other representative compounds are the same as compounds 1 to 54, 57 to 60, 62 and 64 to 65, respectively, provided that X is F and Y is Br. Other representative compounds are the same as compounds 1 to 61, and 63 to 65, respectively, provided that X is F and Y is CF ₃ .

TABLE 3

Other representative compounds are the same as compounds A1 to A21 and A24 to A29, respectively, provided that X is F and Y is Br. Another representative compound is the same as compounds A1 to A29, respectively, provided that X is F and Y is CF ₃ .

TABLE 4

Other representative compounds are the same as compounds B1 to B88, B90 and B92 to B96, respectively, provided that X is F and Y is Br. Another representative compound is the same as compounds B1 to B96, respectively, provided that X is F and Y is CF ₃ .

TABLE 5

Other representative compounds are compounds C1 to C95, C97 and C114, C116 to C122, C124 to C132 to C142, C142 to C143, C145 to C147, C149 to C150, C152 to C156, C161 to C165, C168, C170, C173 to C150, respectively Same as C184, C186, C189 to C192, and C196 to C203, with the proviso that X is F and Y is Br. Another representative compound is the same as compounds C1 to C203, respectively, provided that X is F and Y is CF ₃ .

TABLE 6

characteristic

TABLE 7

Herbicide activity before germination

TABLE 8

Herbicide activity after germination

Claims (19)

Carboxylic acid or a salt of this carboxylic acid of the following general formula.

Wherein R ¹ is halogen, alkyl, haloalkyl, cyanoalkyl, arylalkyl, alkoxyalkyl, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylthioalkyl, alkylsulfinylalkyl, or alkylsulfonylalkyl; R ² is CHF ₂ or CH ₂ F; X is Br, Cl, F or haloalkyl; Y is Br, Cl, F, methyl, haloalkyl, or a radical of the formula R ⁸ OCH _2- , R ⁸ SCH _2- , R ⁸ SOCH ₂ -or R ⁸ SO ₂ CH _2- [In these radicals, R ⁸ Is C ₁ -C ₃ alkyl, C ₂ -C ₅ alkenyl, C ₃ -C ₅ alkynyl, phenyl or substituted phenyl; R ³ is alkylene or haloalkylene. The herbicidal compound of the following general formula (II).

Wherein X is Br, Cl, F or haloalkyl; Y is Br, Cl, F, methyl, haloalkyl, or a radical of the formula R ⁸ OCH _2- , R ⁸ SCH _2- , R ⁸ SOCH ₂ -or R ⁸ SO ₂ CH _2- [In these radicals, R ⁸ Is C ₁ -C ₃ alkyl, C ₂ -C ₅ alkenyl, C ₃ -C ₅ alkynyl, phenyl or substituted phenyl; Z is oxygen or sulfur; R ³ is alkylene or haloalkylene; R ⁴ is a substituted alkyl, alkenyl, alkynyl or monovalent cyclic group of a 5 or 6 membered ring present on a carbon atom of a valent ring; R ¹ is halogen, alkyl, haloalkyl, cyanoalkyl, arylalkyl, alkoxyalkyl, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylthioalkyl, alkylsulfinylalkyl, or alkylsulfonylalkyl; R ² is alkyl, haloalkyl, alkenyl, alkynyl, cyanoalkyl, thiocyanoalkyl or a general formula -alkylene-Y'-R ⁵ group wherein the alkylene group has 1 to 5 carbon atoms, Y Is oxygen or S (O) _r wherein r is 0 to 2 and R ⁵ is alkyl, alkenyl or alkynyl; Substituents on the substituted alkyl of R ⁴ are nitro, halo, furyl or tetrahydrofuryl, acetyl, cyano,

(here,

Is a residue of ammonia or a primary or secondary amine), -COOR ^IV (where R ^IV is a residue of alcohol), phenyl or substituted phenyl, alkylamino, dialkylamino, or trialkylammonium salts, alkoxy, alkylthio , Alkylsulfinyl, or alkylsulfonyl, or phenoxy, phenylthio, phenylsulfinyl or phenylsulfonyl. The herbicidal compound of the following general formula (III).

Wherein X is Br, Cl, F or haloalkyl; Y is Br, Cl, F, methyl, haloalkyl, or a radical of the formula R ⁸ OCH _2- , R ⁸ SCH _2- , R ⁸ SOCH ₂ -or R ⁸ SO ₂ CH _2- [In these radicals, R ⁸ Is C ₁ -C ₃ alkyl, C ₂ -C ₅ alkenyl, C ₃ -C ₅ alkynyl, phenyl or substituted phenyl; R ³ is alkylene or haloalkylene; R ¹ is halogen, alkyl, haloalkyl, cyanoalkyl, arylalkyl, alkoxyalkyl, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylthioalkyl, alkylsulfinylalkyl, or alkylsulfonylalkyl; R ² is alkyl, haloalkyl, alkenyl, alkynyl, cyanoalkyl, thiocyanoalkyl or a general formula -alkylene-Y'-R ⁵ group wherein the alkylene group has 1 to 5 carbon atoms, Y Is oxygen or S (O) r wherein r is 0 to 2 and R ⁵ is alkyl, alkenyl or alkynyl]

Is NH ₂ , or a residue of a primary or secondary amine or a residue of sulfonamide. The method of claim 3, wherein

A compound which is a residue of this sulfonamide. The method of claim 4, wherein

A compound which is a residue of this alkylsulfonamide or haloalkylsulfonamide. The method of claim 4, wherein

The compound which is a residue of this aryl sulfonamide. The method of claim 4, wherein

A compound which is a residue of this amine. 7. Compounds according to claim 6, wherein the arylsulfonamide is halophenyl, alkoxyphenyl or alkylphenylsulfonamide. The herbicidal compound of the following general formula (IV).

Wherein X is Br, Cl, F or haloalkyl; Y is Br, Cl, F, methyl, haloalkyl, or a radical of the formula R ⁸ OCH _2- , R ⁸ SCH _2- , R ⁸ SOCH ₂ -or R ⁸ SO ₂ CH _2- [In these radicals, R ⁸ Is C ₁ -C ₃ alkyl, C ₂ -C ₅ alkenyl, C ₃ -C ₅ alkynyl, phenyl or substituted phenyl; R ³ is alkylene or haloalkylene; R ¹ is halogen, alkyl, haloalkyl, cyanoalkyl, arylalkyl, alkoxyalkyl, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylthioalkyl, alkylsulfinylalkyl, or alkylsulfonylalkyl; R ² is alkyl, haloalkyl, alkenyl, alkynyl, cyanoalkyl, thiocyanoalkyl or a general formula -alkylene-Y'-R ⁵ group wherein the alkylene group has 1 to 5 carbon atoms, Y Is oxygen or S (O) _r wherein r is 0 to 2 and R ⁵ is alkyl, alkenyl or alkynyl; OR ⁹ is a residue of oxime. Herbicide composition comprising a mixture of an herbicidally effective amount of a compound according to claim 1 with a suitable carrier. Herbicide composition comprising a mixture of an herbicidally effective amount of a compound according to claim 2 with a suitable carrier. Herbicide composition comprising a mixture of an herbicidally effective amount of a compound according to claim 3 with a suitable carrier. Herbicide composition comprising a mixture of an herbicidally effective amount of a compound according to claim 9 with a suitable carrier. A method for producing a compound of formula (III), characterized by reacting a compound of formula (A) with a compound of formula (B).

Wherein X is bromine, chlorine, fluorine or haloalkyl; Y is bromine, chlorine fluorine, methyl, haloalkyl, or a radical of the formula R ⁸ OCH _2- , R ⁸ SCH _2- , R ⁸ SOCH ₂ -or R ⁸ SO ₂ CH _2- [In these radicals, R ⁸ is C ₁ -C ₃ alkyl, C ₂ -C ₅ alkenyl, C ₃ -C ₅ alkynyl, phenyl or substituted phenyl; R ³ is alkylene or haloalkylene; R ¹ is halogen, alkyl, haloalkyl, cyanoalkyl, arylalkyl, alkoxyalkyl, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylthioalkyl, alkylsulfinylalkyl, or alkylsulfonylalkyl; R ² is alkyl, haloalkyl, alkenyl, alkynyl, cyanoalkyl, thiocyanoalkyl or a general formula -alkylene-Y'-R ⁵ group wherein the alkylene group has 1 to 5 carbon atoms, Y Is oxygen or S (O) _r wherein r is 0 to 2 and R ⁵ is alkyl, alkenyl or alkynyl; R ³ is an alkylene radical or a fluoroalkylene radical;

Is a residue of —NH ₂ , primary or secondary amine or a residue of sulfonamide; M is a reactive leaving substituent. The method of claim 14, wherein R ⁶ is arylsulfonyl and R ⁷ is hydrogen. A method of preparing a compound of formula (II), wherein the compound of formula (A) is formed and the compound is reacted with a compound of formula (D).

Wherein X is bromine, chlorine, fluorine or haloalkyl; Y is bromine, chlorine fluorine, methyl, haloalkyl, or a radical of the formula R ⁸ OCH _2- , R ⁸ SCH _2- , R ⁸ SOCH ₂ -or R ⁸ SO ₂ CH _2- [In these radicals, R ⁸ is C ₁ -C ₃ alkyl, C ₂ -C ₅ alkenyl, C ₃ -C ₅ alkynyl, phenyl or substituted phenyl; R ³ is alkylene or haloalkylene; R ¹ is halogen, alkyl, haloalkyl, cyanoalkyl, arylalkyl, alkoxyalkyl, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylthioalkyl, alkylsulfinylalkyl, or alkylsulfonylalkyl; R ² is alkyl, haloalkyl, alkenyl having 2 to 5 carbon atoms, alkynyl having 3 to 5 carbon atoms, cyanoalkyl, thiocyanoalkyl or a general formula -alkylene-Y'-R ⁵ group [where alkylene The group has 1 to 5 carbon atoms, Y 'is oxygen or S (O) _r (where r is 0 to 2), and R ⁵ is alkyl, alkenyl having 2 to 5 carbon atoms or alkoxy having 3 to 5 carbon atoms Neil]; R ³ is alkylene or fluoroalkylene; R ⁴ is a 5-membered or 6-membered monovalent cyclic group on a substituted alkyl group, alkenyl group, alkynyl group or a valence ring carbon atom; M is a reactive leaving substituent; Z is oxygen or sulfur. A compound of the following general formula (A) is formed, and the compound is reacted with a compound of the following general formula (E) to produce a compound of the following general formula (IV).

Wherein X is bromine, chlorine, fluorine or haloalkyl; Y is bromine, chlorine fluorine, methyl, haloalkyl, or a radical of the formula R ⁸ OCH _2- , R ⁸ SCH _2- , R ⁸ SOCH ₂ -or R ⁸ SO ₂ CH _2- [In these radicals, R ⁸ is C ₁ -C ₃ alkyl, C ₂ -C ₅ alkenyl, C ₃ -C ₅ alkynyl, phenyl or substituted phenyl; R ³ is alkylene or haloalkylene; R ¹ is halogen, alkyl, haloalkyl, cyanoalkyl, arylalkyl, alkoxyalkyl, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylthioalkyl, alkylsulfinylalkyl, or alkylsulfonylalkyl; R ² is alkyl, haloalkyl, alkenyl having 2 to 5 carbon atoms, alkynyl having 3 to 5 carbon atoms, cyanoalkyl, thiocyanoalkyl or a general formula -alkylene-Y'-R ⁵ group [where alkylene The group has 1 to 5 carbon atoms, Y 'is oxygen or S (O) _r (where r is 0 to 2), and R ⁵ is alkyl, alkenyl having 2 to 5 carbon atoms or alkoxy having 3 to 5 carbon atoms Neil]; R ³ is alkylene or fluoroalkylene; M is a reactive leaving substituent; -OR ⁹ is a residue of oxime. Reacting N-2-fluorophenyl triazolinone by reacting a 2-fluorophenylhydrazine unsubstituted in 4-position with a reagent or reagents for converting a hydrazine group, -NHNH ₂ , to a triazolinone ring having the structure And then halogenated with chlorine or bromine at the unsubstituted 4-position.

19. The process of claim 18, wherein the 2-fluorophenylhydrazine has nitro alkoxy groups at the 5-position of the benzene ring.