KR100529814B1 - 3- (substitutedphenyl) -5- (thienyl or furyl) -1,2,4-triazole insecticide - Google Patents

Abstract

The 3- (substituted phenyl) -5- (thienyl or furyl) -1,2,4-triazole compounds of the invention are useful as insect insecticides and tick repellents. Novel synthetic methods and intermediates for producing this compound, pesticide compositions containing the compound, and methods for controlling insects and ticks using the compound are also provided.

Description

3- (substituted phenyl) -5- (thienyl or furyl) -1,2,4-triazole pesticide

The present invention provides novel compounds useful as insecticides and tick repellents, novel synthetic methods and intermediates for preparing the compounds, insecticide compositions containing the compounds, and methods for controlling insects and ticks using the compounds.

There is an urgent need for new insecticides and tick repellents. Insects and ticks are becoming more resistant to pesticides and tick repellents in use today. More than 400 arthropods are resistant to one or more pesticides. Increased resistance to some of the older pesticides such as DDT, carbamate and organophosphate is well known. However, resistance to some of the new pyrethroid insecticides and tick repellents is already developing. Therefore, there is a need for new insecticides and tick repellents, especially compounds having a new or special way of action.

Many 3,5-diphenyl-1H-1,2,4-triazole derivatives have been described in the literature as having mite parasitic activity. See US Pat. No. 5,482,951, Japanese Patent No. 882224, European Patent No. 572142, Japanese Patent No. 08283261]. However, to the best of our knowledge, no products are commercially available among these compounds. Nitrofuranyl triazole is L.I. LE Benjamin and H. R. It is described by HR Snyder as an antimicrobial substance ( J. Heterocyclic Chem . 1976, 13, 1115) and in other documents as an antimicrobial substance ( J. Med. Chem. 1973, 16 (4) , 312-319; J. Med. Chem. 1974, 17 (7), 756-758 ). The present invention provides novel compounds having commercial levels of activity against insects and ticks.

Summary of the Invention

The present invention provides novel substituted thienyl and furanyl triazole derivatives that are particularly useful for controlling insects and ticks.

More particularly, the present invention provides novel pesticidal active compounds of formula (1) or botanically acceptable acid addition salts thereof.

[Formula 1]

In Formula 1 above,

Ar is substituted phenyl,

Y is O or S,

R ² is lower alkyl, haloalkyl, lower alkenyl, lower alkynyl or alkoxyalkyl,

R ³ is H, halo, lower alkyl, (C ₇ -C ₂₁ ) straight or branched alkyl, hydroxy, lower alkoxy, haloalkyl, haloalkoxy, alkoxyalkyl, alkoxyalkoxy, lower alkenyl, lower alkynyl, haloal Kenyl, CN, NO ₂ , COR ⁶ , CO ₂ R ⁶ , CON (R ⁶ ) ₂ , (C ₃ -C ₆ ) cycloalkyl, S (O) _m R ⁶ , -OSO ₂ R ⁶ , SCN,-( CH ₂ ) _n R ⁶ , -CH = CHR ⁶ , -C≡CR ⁶ ,-(CH ₂ ) _q OR ⁶ ,-(CH ₂ ) _q SR ⁶ ,-(CH ₂ ) _q NR ⁶ R ⁶ , -O (CH ₂ ) _q R ⁶ , -S (CH ₂ ) _q R ⁶ , -NR ⁶ (CH ₂ ) _q R ⁶ , , , , , , , , , -Si (R ⁷ ) ₃ , pyridyl, substituted pyridyl, isoxazolyl, substituted isooxazolyl, naphthyl, substituted naphthyl, phenyl, substituted phenyl, thienyl, substituted thienyl, pyri Midiyl, substituted pyrimidyl, pyrazolyl or substituted pyrazolyl,

R ⁴ and R ⁵ are independently H, halo, lower alkyl, lower alkoxy, haloalkyl, haloalkoxy, CN, CO ₂ R ⁶ , CON (R ⁶ ) ₂ or S (O) _m alkyl, or

When R ⁴ and R ⁵ are attached to adjacent carbon atoms, they together form a five or six membered saturated or unsaturated carbocyclic ring which may be substituted by one or two halo, lower alkyl, lower alkoxy or haloalkyl groups. You can,

R ⁶ is H, lower alkyl, haloalkyl, lower alkenyl, lower alkynyl, phenyl or substituted phenyl,

R ⁷ is lower alkyl,

m is 0, 1 or 2,

n is 1 or 2,

p is an integer from 2 to 6,

q is 0 or 1;

Preferred groups of compounds are the compounds of formula 1A or a botanically acceptable acid addition salt thereof.

[Formula 1A]

In Formula 1A above,

R ¹ and R ^{1 ′} are independently H, Cl, F, methyl, halomethyl, methoxy or halomethoxy,

Y is O or S,

R ² is lower alkyl, haloalkyl, lower alkenyl, lower alkynyl or alkoxyalkyl,

R ³ is H, halo, lower alkyl, (C ₇ -C ₂₁ ) straight chain alkyl, hydroxy, lower alkoxy, haloalkyl, haloalkoxy, alkoxyalkyl, alkoxyalkoxy, lower alkenyl, haloalkenyl, CN, NO ₂ , CO ₂ R ⁶ , CON (R ⁶ ) ₂ , (C ₃ -C ₆ ) cycloalkyl, S (O) _m R ⁶ , SCN, pyridyl, substituted pyridyl, isoxazolyl, substituted isoxazolyl , Naphthyl, substituted naphthyl, phenyl, substituted phenyl,-(CH ₂ ) _n R ⁶ , -CH = CHR ⁶ , -C≡CR ⁶ , -CH ₂ OR ⁶ , -CH ₂ SR ⁶ , -CH _{^{2 NR 6 R 6, -OCH 2}} R 6, -SCH 2 R 6, -NR 6 CH 2 R 6, , , , , , , , or Is selected from,

R ⁴ and R ⁵ are independently H, halo, lower alkyl, lower alkoxy, haloalkyl, haloalkoxy, CN, CO ₂ R ⁶ , CON (R ⁶ ) ₂ or S (O) _m alkyl, or

R ⁴ and R ^{5 form} a 5 or 6 membered saturated or unsaturated carbocyclic ring which may be substituted by one or two halo, lower alkyl, lower alkoxy or haloalkyl groups,

R ⁶ is H, lower alkyl, haloalkyl, lower alkenyl, lower alkynyl, phenyl or substituted phenyl,

m is 0, 1 or 2,

n is 1 or 2,

p is an integer of 2-6.

Preferred compounds of formula (I) are

a) a compound class of Formula 1A wherein R ^{1 '} is F;

b) a class of compounds of Formula 1A wherein Y is sulfur;

c) a compound of formula 1A wherein R ¹ and R ^{1 '} are independently Cl or F, in particular the compound class of a) and b) above;

d) a compound of formula 1A wherein R ¹ and R ^{1 '} are both F, in particular the compound class of a) to c) above;

e) a compound of formula 1A wherein R ¹ and R ^{1 '} are both Cl, in particular the compound class of a) to c) above;

f) a compound of formula 1A wherein R ¹ is Cl and R ^{1 '} is F, in particular the compound class of a) to c) above;

g) a compound of formula 1A wherein R ² is methyl, in particular the compound class of one of a) to f) above;

h) a compound of formula 1A wherein R ³ , R ⁴ and R ⁵ are independently selected from H, halo, methyl and methoxy, in particular the compound class of one of a) to g) above;

i) a compound of formula 1A wherein R ³ , R ⁴ and R ⁵ are independently H or halo, in particular the compound class of one of a) to g) above;

j) a compound of formula 1A wherein R ³ , R ⁴ and R ⁵ are independently H, Cl or Br, in particular the compound class of one of a) to g) above;

k) a compound of formula 1A wherein R ³ , R ⁴ and R ⁵ are each halo, in particular the compound class of one of a) to g) above; And

l) compounds of formula 1A wherein R ³ , R ⁴ and R ⁵ are each chloro, in particular the compound class of one of a) to g) above.

Particularly preferred classes of compounds include those of the formula

[Formula 1B]

In Formula 1B above,

R ¹ and R ^{1 ′} are independently F or Cl,

R ² is lower alkyl, most preferred is methyl,

R ³ , R ⁴ and R ⁵ are independently H, Cl or Br.

The present invention also provides novel methods and intermediates for the preparation of compounds of formula (I) and novel compositions and methods of use. These will be described in detail below.

Throughout this specification, unless stated otherwise, all temperatures are in degrees Celsius (° C.) and all percentages are in weight percent.

The term "lower alkyl" refers to a (C ₁ -C ₆ ) straight chain hydrocarbon or (C ₃ -C ₆ ) branched or cyclic hydrocarbon group.

The terms "lower alkenyl" and "lower alkynyl" refer to (C ₂ -C ₆ ) straight chain hydrocarbon or (C ₃ -C ₆ ) branched hydrocarbon groups each containing one or more double or triple bonds.

The term "lower alkoxy" means -O-lower alkyl.

The terms "halomethyl" and "haloalkyl" refer to methyl and lower alkyl groups substituted with one or more halogen atoms.

The terms "halomethoxy" and "haloalkoxy" refer to methoxy and lower alkoxy groups substituted with one or more halogen atoms.

The term "alkoxyalkyl" refers to a lower alkyl group substituted with a lower alkoxy group.

The terms "substituted naphthyl", "substituted thienyl", "substituted pyrimidyl", "substituted pyrazolyl", "substituted pyridyl" and "substituted isoxazolyl" are independently halo, halo ( C ₁ -C ₄ ) alkyl, CN, NO ₂ , (C ₁ -C ₄ ) alkyl, (C ₃ -C ₄ ) branched alkyl, phenyl, (C ₁ -C ₄ ) alkoxy or halo (C ₁ -C ₄ A ring system substituted with one or more groups selected from alkoxy.

The term “substituted phenyl” is independently halo, (C ₁ -C ₁₀ ) alkyl, branched (C ₃ -C ₆ ) alkyl, halo (C ₁ -C ₇ ) alkyl, hydroxy (C ₁ -C ₇ ) alkyl , (C ₁ -C ₇ ) alkoxy, halo (C ₁ -C ₇ ) alkoxy, phenoxy, phenyl, NO ₂ , OH, CN, (C ₁ -C ₄ ) alkanoyl, benzoyl, (C ₁ -C ₄ ) Alkanoyloxy, (C ₁ -C ₄ ) alkoxycarbonyl, phenoxycarbonyl or benzoyloxy means a phenyl group substituted with one or more groups selected from.

The term "substituted benzenesulfonyl" means p-chlorobenzenesulfonyl and p-toluenesulfonyl.

Unless otherwise indicated, where a group is mentioned to be substituted with one or more substituents selected from the identified class, such substituents may be independently selected from that class.

synthesis

Compounds of Formula 1 can be prepared by the methods described in US Pat. Nos. 5,380,944 and 5,284,860 (Manufacturing Methods 1, 2 and 3). Another method will be described below.

For example, a compound of Formula 1 wherein R ^{1 ′} is F can be prepared according to Scheme I below.

Scheme I

In Scheme I,

Ar, R ² , R ³ , R ⁴ , R ⁵ and Y are as defined in Formula 1,

W is a common amino protecting group.

Examples of common amino protecting groups include, but are not limited to, carbenzyloxy groups, tert-alkoxycarbonyl groups, amides, phosphinyl and phosphoryl groups, and sulfenyl and sulfonyl groups. As shown in Scheme I, N-protected amidrazone (2) is reacted with a compound of formula 3 in the presence of an acid or a base as a catalyst. Intermediates of formulas (2) and (3) can be obtained by applying well known procedures.

An example of an intermediate of formula 3 is 3,4,5-trichlorothiophene-2-carboxylic acid chloride. Such carboxylic acids can be obtained by treating tetrachlorothiophene with n-butyllithium and then quenching with carbon dioxide. J. Organometal . 1968, 13, 419-430. As described in Example 2 below, the carboxylic acid is converted to the acid chloride by conventional methods.

Scheme II illustrates the preparation of protected benzamiderazone starting material (2).

Scheme II

A benzimidate derivative (4) wherein Z is O or S and R ¹⁰ is lower alkyl is reacted with a hydrazine derivative (5) as Ar, W and R ² are defined in the case of Scheme I.

An example of an intermediate of formula 5 is N-methyl-Nt-butylcarboxyhydrazine. The use of this in making site specific 1-alkyl [1,2,4] triazoles is described in the literature . Chem. Ber . 1982, 115, 2807-2818]. Methods for preparing benzimide compounds are well known. An example is described in Synth. Commun . 1983, 13, 753.

Another aspect of the present invention is a novel process for preparing compounds of Formula 1A, wherein R ¹ and R ^{1 ′} are F, as shown in Scheme III.

Scheme III

In Scheme III above,

R ¹¹ is lower alkyl, preferably methyl,

R ¹² is lower alkyl, preferably methyl,

Het is a chemical formula Is a furyl or thiethyl group of 9, wherein Y, R ³ , R ⁴ and R ⁵ are as defined in formula (1).

The method shown in Scheme III may also be used to prepare compounds wherein Het is one of a variety of other heterocyclic groups, for example pyridyl or pyrazolyl.

In another aspect of the invention, the invention provides novel intermediates of formulas 6 and 7 as defined above.

As shown in step a of Scheme III, 2,6-difluorobenzonitrile is reacted with triethylamine, sodium sulfide hydrate and hydrochloric acid in pyridine at room temperature to give 2,6-difluorobenzenethioamide.

In step b of Scheme III, 2,6-difluorobenzenethioamide is reacted with a lower alkyl iodide such as iodomethane in acetone to give the S- (lower alkyl) thio-2,6- Obtain difluorobenzimidium iodide. Acetone is the preferred solvent, but other polar aprotic solvents such as DMF or THF can be used.

In step c of Scheme III, S- (lower alkyl) thio-2,6-difluorobenzimidinium iodide is reacted with Nt-butoxycarbonyl-N- (lower alkyl) hydrazine to give Gets a Dragon The reaction is carried out in methanol or ethanol, preferably in methanol, at a temperature of from 0 ° C. to the boiling point of the solvent used.

In step d of Scheme III, the amidrazone of formula (7) is dissolved in a non-reactive organic solvent such as benzene, toluene, xylene, chloroform, dichloromethane or 1,2-dichloroethane at a temperature between Reacts with offenne or furan acid chloride.

Since the process of Scheme III uses milder conditions than the processes already disclosed, it is possible to use heat-sensitive heterocycles. In addition, higher yields are obtained.

Details of steps a through c in Scheme III are described in Example 1. Details of step d are described in Examples 2-4.

Example 1

The next step illustrates the preparation of amidrazone of formula 2a.

[Formula 2a]

A. 2,6-difluorobenzenethioamide

In a 3-liter three-neck round bottom flask equipped with a mechanical stirrer, a dry ice condenser, a dropping funnel and a bleach-filled trap, 550 ml of pyridine, 2,6-difluorobenzonitrile (208 g, 1.50 mol), triethyl An amine (202 g, 279 mL, 2.0 moles) and sodium sulfide hydrate (521 g, 2.17 moles; ground to pieces small enough to fit the flask) were added. The temperature of the stirred mixture was lowered to about 5 ° C. and concentrated hydrochloric acid (143 g, 288 mL, 3.99 mol) was added dropwise to the slurry. Note the exotherm, the rate of addition of hydrochloric acid ensures that the temperature of the reaction mixture does not exceed 25 ° C. for a total of 75 minutes. The cooling bath was removed and the slurry was allowed to warm to room temperature and stirred overnight. The mixture was poured into water (2 L) and extracted with ether (3 x 500 mL). The ether layer was washed with dilute sulfuric acid, water, brine, dried over MgSO ₄ , and the solvent was removed in vacuo to yield 232 g of crude product. The starting material is removed from the product by kugelrohr distillation to give 197 g (76%) of 2,6-difluorobenzenethioamide. This material was used without further purification.

B. S-methylthio-2,6-difluorobenzimidinium iodide

To a 3-liter three-necked flask equipped with a mechanical stirrer and a dropping funnel, 1150 ml of acetone and 197 g (1.14 mol) of 2,6-difluorobenzenethioamide were added. The temperature of the stirred solution was lowered to about 5 ° C., and iodomethane (161 g, 70.6 mL, 1.14 mol) was added dropwise. The ice bath was removed and the slurry was stirred overnight. The resulting yellow solid was removed by filtration and washed with ether to give 223 g. Additional material was obtained from the filtrate by removing the solvent in vacuo. Ether was added to the residue and the resulting solid was removed by filtration to give 57 g of additional material. The combined solids were all 280 g (77.9% yield) of S-methylthio-2,6-difluoro-benzimidinium iodide. Melting point 168-169 ° C.

¹ H NMR (DMSO-d ₆ ) δ 7.7 (m, 1H), 7.4 (m, 2H), 2.7 (s, 3H).

C. N-tert-butoxycarbonyl-N-methylhydrazine

In a 1 L three-necked round bottom flask equipped with a mechanical stirrer and a dropping funnel, methyl hydrazine (42.2 g, 0.916 mol) and THF (100 mL) were added. The temperature of the mixture was lowered to 5 ° C. and a solution of di-tert-butyl dicarbonate (100 g, 0.458 mol) dissolved in THF (150 mL) was added dropwise. The cooling bath was removed and the mixture was stirred at rt overnight. The liquid was decanted from the rubbery precipitate and the solvent was removed in vacuo to yield about 70 g of clear liquid. The rubbery precipitate is partitioned between methylene chloride and water. Methylene chloride was washed with brine, dried over Na ₂ S0 ₄ and the solvent removed in vacuo. The resulting residue was combined with the one obtained by the previous evaporation and distilled at about 20 mmHg (boiling point 77-78 ° C.) to give N-tert-butoxycarbonyl-N-methylhydrazine (40.2 g, 60% yield). .

¹ H NMR (CDCl ₃ ) δ 4.1 (s, b, 2H), 3.05 (s, 3H), 1.5 (s, 9H).

D. Amidrazone of Formula 2a

S-methyl-2,6-difluorobenzimium iodide (63.8 g, 0.202 mol) and methanol (180 Ml) was added. N-tert-butoxycarbonyl-N-methylhydrazine (29.6 g, 0.202 mol) was added dropwise to the stirred solution. The solution was stirred overnight and the methanol was removed in vacuo. The residue was triturated with ether and the solids were removed by filtration to give amidrazon (66.3 g, 79.0% yield) of formula 2a. Melting point 172-173 ° C. (decomposition).

¹ H NMR (DMSO-d ₆ ) δ 12.3 (s, b, 1H), 10.4 (d, b, 2H), 7.9 (m, 1H), 7.4 (m, 2H), 3.1 (s, 3H), 1.5 (s, 9H).

Example 2

3- (2,6-difluorophenyl) -5- (3-n-hexylthien-2-yl) -1-methyl [1,2,4] triazole (Compound 35)

To a mixture of 3-n-hexyl-2-thiophene carboxylic acid (0.5 g, 2.4 mmol) in anhydrous 1,2-dichloroethane (25 mL), one drop of thionyl chloride (2.0 mL) and dimethylformamide were added. The mixture was refluxed for 4 hours. After cooling, the reaction mixture was evaporated in vacuo and the residue was mixed with anhydrous toluene (25 mL) and 1.24 g (3.0 mmol) of amidrazon of formula 2a (Example 1). The mixture was refluxed overnight, cooled and partitioned between brine and ether. The organic phase was dried over MgSO ₄ , the solvent was evaporated and the residue was chromatographed on silica gel using ethyl acetate / hexane (5:95 to 20:80) as eluent. The product fractions were combined and evaporated to afford the title compound (0.66 g, 76% yield) as an oil.

¹ H NMR δ 7.26-7.46 (m, 2H), 6.97-7.06 (m, 2H), 3.97 (s, 3H), 2.71 (m, 2H), 1.23 (m, 6H), 0.84 (m, 3H),

Elemental Analysis for C ₁₉ H ₂₁ F ₂ N ₃ S:

Calculated value; C 63.14, H 5.86, N 11.63, S 8.87;

Found; C 62.90, H 5.79, N 11.70, S 8.77.

Example 3

3- (2,6-difluorophenyl) -5- (4-p-chlorobenzenesulfonyl-3-methylthien-2-yl) -1-methyl [1,2,4] triazole (Compound 12 )

4- (p-chlorobenzenesulfonyl) -3-methylthiophene-2-carbonyl, which is amidrazone (Example 1) (0.9 g, 2.2 mmol) of compound 2a in 100 ml of toluene and thiophenic acid chloride To a solution of chloride (0.75 g, 2.2 mmol) was added one equivalent of p-toluenesulfonic acid monohydrate (0.4 g, 2.2 mmol) with stirring. The mixture was refluxed overnight using a Dean-Stark trap to remove water. The solution was cooled and the solvent removed in vacuo. The residue was dissolved in 100 mL of dichloromethane, washed with 2N NaOH and then with water. The organic phase was dried over MgSO ₄ and the solvent was evaporated. The residue was recrystallized from ethyl acetate / hexanes to give 0.6 g of product as off white crystals. Melting point: 183-185 ° C. Yield: 59.4%.

¹ H NMR δ 8.4 (s, 1H), 7.8 (d, 2H), 7.4 (d, 2H), 7.3 (m, 1H), 7.0 (m, 2H), 3.98 (s, 3H), 2.25 (s, 3H).

Elemental Analysis for C ₂₀ H ₁₄ F ₂ ClN ₃ O ₂ S ₂ :

Calculated value; C 51.55, H 3.01, N 9.02;

Found; C 51.76, H 3.26, N 8.92.

Example 4

3- (2,6-difluorophenyl) -5- (5-p-chlorophenyl) furan-2-yl) -1-methyl [1,2,4] triazole (Compound 13)

To a solution of amidrazon (Example 1) (1.0 g, 2.4 mmol) and 5- (p-chlorophenyl) -furan-2-carbonyl chloride (0.61 g, 2.4 mmol) of compound 2a in 100 ml of toluene, One equivalent of p-toluenesulfonic acid monohydrate (0.43 g, 2.4 mmol) was added while stirring. The mixture was refluxed overnight using a Dean-Stark trap to remove water. The solution was cooled and the solvent removed in vacuo. The residue was dissolved in 100 mL of dichloromethane, washed with 2N NaOH and then with water. The organic phase was dried over MgSO ₄ and the solvent was evaporated. The residue was recrystallized from ethyl acetate / hexanes to give 0.6 g of product as off white crystals. Melting point: 171-173 ° C. Yield 44.9%.

Elemental Analysis for C ₁₉ H ₁₂ F ₂ ClN ₃ O:

Calculated value; C 61.37, H 3.23, N 11.30;

Found; C 61.34, H 3.19, N 11.06.

The present invention also provided a novel method for preparing a compound of Formula 1A as shown in Scheme IV below.

Scheme IV

In Scheme IV above,

R ¹ , R ^{1 ′} , Y, R ³ , R ⁴ and R ⁵ are the same as defined in Formula 1,

R ¹⁴ is methanesulfonyl, benzenesulfonyl or substituted benzenesulfonyl.

In step a, 2,6-substituted benzoylchloride (10) is converted to triethylamine in THF and hydrazide of formula 11 wherein R ¹⁴ is methanesulfonyl, benzenesulfonyl or substituted benzenesulfonyl, ie p-Cl or p-CH ₃ benzenesulfonyl) to give a substituted benzhydrazone of formula (12).

In step b, the substituted benzhydrazone of formula 12 was first reacted with sodium hydride in N, N-dimethylformamide and then with iodomethane to produce the substituted hydrazine of formula 13.

In step c, the substituted hydrazine of formula 13 is chlorinated using, for example, PCl ₅ to produce substituted benzylhydrazonoyl chloride of formula 14. This reaction is carried out in an unreactive organic solvent such as dichloroethane.

In step d, substituted benzylhydrazonoyl chloride of formula 14 is reacted with a cyanothiophene of formula 15 or a mixture of cyanofuran and aluminum chloride in a solvent such as o-dichlorobenzene to give 3- (2, To 6-substituted phenyl) -5- (substituted thienyl) -1- (methyl [1,2,4] triazole.

The detailed description of steps a to c of Scheme IV is given in Example 5. Details of step d are given in Examples 6-9, 11, 13 and 15.

Example 5

The next step shows the preparation of benzhydrazonoyl chloride of formula 14a.

[Formula 14a]

A. 1-benzenesulfonyl-2- (2,6-dichloro) benzhydrazone

In a 1 liter three-necked round bottom flask equipped with a condenser, a mechanical stirrer and a thermometer, THF (500 mL), benzenesulfonyl hydrazide (41.1 g, 0.238 mol) and triethylamine (24.1 g, 33.2 mL) under nitrogen atmosphere , 0.238 mole). The resulting solution is cooled to −5 ° C. and 2,6-dichlorobenzoyl chloride (50.0 g, 34.2 mL, 0.238 mol) is added dropwise for 55 minutes, at which time the temperature does not rise above 0 ° C. The reaction mixture was stirred for 1 hour, then the cooling bath was removed and the reaction mixture was stirred for 21 hours at room temperature while monitored by TLC and HPLC. Most of the solvent was removed in vacuo and the residue was partitioned between methylene chloride (1000 mL) and water (2 × 200 mL). The organic layer was washed with saturated brine (250 mL), dried over Na ₂ SO ₄ , and the solvent was removed in vacuo to yield a white solid. The white solid was slurried in ether, removed by filtration and dried in vacuo overnight to yield 74.3 g (90.5% yield) of 1-benzenesulfonyl-2- (2,6-dichlorobenz) hydrazone. Melting point; 180-181 ° C.

TIC mass spectrometry 345/347/349.

¹ H NMR (CDCl ₃ ) δ 8.05 (m, 2H), 7.9 (m, 1H), 7.5-7.7 (m, 4H), 7.3 (m, 3H).

B. 1- (2,6-dichloro) benzoyl-2-methyl-2-benzenesulfonyl hydrazine

In a 1 liter three-necked round bottom flask equipped with a mechanical stirrer, thermometer and dropping funnel, under a nitrogen atmosphere, a suspension of sodium hydride (8.49 g of 60% dispersion, 0.212 moles) was washed with hexane (3 parts) and hexane from the final wash. Most of was removed by suction. N, N-dimethylformamide (200 mL) was added and the temperature of the slurry was reduced to -5 ° C. A solution of N-benzenesulfonyl-2,6-dichloro-benzhydrazone (73.3 g, 0.212 mol) in 300 ml of N, N-dimethylformamide was added dropwise over 120 minutes, at which time the temperature was at least 3 ° C. It does not rise and the hydrogen release rate is maintained at an easy rate to treat. As the addition proceeded, the mixture turned lemony and thickened, but when the addition was complete the mixture was clear and easily stirred. The resulting mixture was stirred at 0 ° C. for 1 hour, the cooling bath was removed, and further stirred for 1 hour (the temperature was raised to 15 ° C.). The mixture was then cooled to -5 ° C and iodomethane (30.0 g, 13.2 mL) was added dropwise at a rate such that the temperature did not rise above 0 ° C. The cooling bath was removed and the reaction mixture was allowed to warm to room temperature and stirred for 2 hours. The reaction mixture was diluted with brine (300 mL) and extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over Na ₂ SO ₄ , and the solvent was removed in vacuo to yield a crude product contaminated with N, N-dimethylformamide, which was removed via a vacuum pump. The crude mixture was crystallized in hexane / ethyl acetate and the solids removed by filtration and dried in vacuo to give 40.2 g. The solvent was removed from the filtrate to give an additional 21.4 g of 1- (2,6-dichlorobenzoyl) -2-methyl-2-benzenesulfonyl hydrazine total amount (80.9% yield). Melting point; 177-178 ° C.

¹ H NMR (CDCl ₃ ) δ 8.0 (m, 2H), 7.4-7.8 (m, 4H), 7.2 (m, 3H), 3.4 and 3.05 (two s combined for 3H).

C. N- (benzenesulfonyl) -N-methyl- (2,6-dichlorobenz) hydrazonoyl chloride

In a 1 L three-necked round bottom flask equipped with a magnetic stirrer and a condenser, under a nitrogen atmosphere, N-benzenesulfonyl-N-methyl-2,6-dichlorobenzoyl hydrazine (35.9 g, 0.10 mol), 1,2-dichloroethane (500 mL) and phosphorus pentachloride (31.2 g, 0.15 mol) were added. The temperature of the mixture was raised to reflux and stirred for 30 minutes. The solvent was removed in vacuo, the residue was dissolved in methylene chloride and carefully diluted with water. The organic phase is washed with water, washed with brine, dried over Na ₂ SO ₄ , the solvent is removed in vacuo to give an oil, which is solidified when polished with an ethyl acetate / hexane mixture to give N-benzene as a white crystalline solid. 36.1 g (95.7% yield) of sulfonyl-N-methyl-2,6-dichlorobenzhydrazonoyl chloride was obtained. Melting point; 103-104 ° C.

¹ H NMR (CDCl ₃ ) δ 7.9 (m, 2H), 7.4-7.7 (m, 3H), 7.2-7.4 (m, 3H), 3.1 (s, 3H).

The same procedure was used to obtain N-benzenesulfonyl-N-methyl-2-chloro-6-fluorobenzhydrazonoyl chloride.

Example 6

3- (2-chloro-6-fluorophenyl) -5- (3,4,5-trichlorothien-2-yl) -1-methyl [1,2,4] triazole (Compound 2)

N-methyl-N-benzenesulfonyl-2-chloro-6-fluorobenzhydrazonoyl chloride (47.5 g, 0.313 mol) and 2-cyano-3,4,5-trichloroti in 18 ml of o-dichlorobenzene Aluminum chloride (11.1 g, 0.083 mole) was added to a mixture of opene (26.5 g, 0.125 mole). The mixture was placed in a preheated oil bath maintained at 140-150 ° C. The mixture was kept in a hot oil bath for 40 minutes, then the bath was removed and stirred for 2 hours with slow cooling. The reaction mixture was poured into 2N sodium hydroxide (300 ml sufficient to dissolve the aluminum salt) and extracted with methylene chloride (3 × 250 ml each). The organic phases were combined, washed with brine, dried over MgSO ₄ and the solvent removed in vacuo to afford the crude product. The residue was placed on silica gel (150 g) and then chromatographed with ethyl acetate / hexanes as eluent to give 39.7 g (55.3% yield) of the title compound. Purity by GC analysis; 99.4%. Melting point 129-130 ° C.

¹ H NMR (CDCl ₃ ) δ 7.3 (m, 2H), 7.1 (m, 1H), 4.0 (s, 3H).

Elemental Analysis for C ₁₃ H ₆ Cl ₄ FN ₃ S:

Calculated value; C 39.32, H 1.52, N 10.58.

Found; C 39.08, H 1.30, N 10.34.

Example 7

3- (2,6-dichlorophenyl) -5- (3,4,5-trichlorothien-2-yl) -1-methyl [1,2,4] triazole (Compound 45)

In a 500 ml round bottom flask equipped with a mechanical stirrer and a condenser, under a nitrogen atmosphere, o-dichlorobenzene (150 ml), 2-cyano-3,4,5-trichlorothiophene (23.6 g, 111 mmol) and aluminum chloride ( 14.8 g, 111 mmol) was added. The stirred reaction mixture was placed in an oil bath at 145-150 ° C. When the internal temperature of the mixture reached 133 ° C., N- (benzenesulfonyl) -N-methyl- (2,6-dichlorobenz) hydrazonoyl chloride (35.0 g, 92.6 mmol) was added over 5 minutes in 40 minutes. Added. The temperature rises to 141 ° C. The reaction mixture was stirred from the beginning of the addition of N- (benzenesulfonyl) -N-methyl- (2,6-dichlorobenz) hydrazonoyl chloride for 1 hour 40 minutes while monitoring by HPLC and GC. The oil bath was removed from the reactor and the mixture was cooled to about 90 ° C. and added to stirred 2N silver nitrate (350 ml). The mixture was stirred for 5 minutes, the pH was made base and diluted with methylene chloride (800 ml). The methylene chloride layer is washed with water (250 ml), brine (250 ml), dried over Na ₂ S0 ₄ , solvent removed in vacuo, and o-dichlorobenzene and benzenesulfonyl chloride removed by Kugeleur distillation. It was. Recrystallization of the pale yellow solid from ethyl acetate gave 31.3 g (81.7% yield) of the title compound. Melting point 146-147 ° C.

¹ H NMR (CDCl ₃ ) δ 7.2-7.5 (m, 3H), 4.0 (s, 3H).

Example 8

3- (2,6-dichlorophenyl) -5- (thien-3-yl) -1-methyl [1,2,4] triazole (Compound 48)

N- (benzenesulfonyl) -N-methyl- (2,6-dichlorobenz) hydrazonoyl chloride (1.13 g, 3 mmol), 3-cyanothiophene (0.327 g, 6 mmol) and aluminum chloride (0.40 g , 3 mmol) was heated at 135-140 ° C. for about 14 hours and then stirred at room temperature for about 48 hours. The mixture was then diluted with dichloromethane, washed with water, brine and dried over magnesium sulfate. Chromatography yielded 290 mg of the title compound as a clear oil.

¹ H NMR (CDCl ₃ ) δ 7.27-7.85 (m, 5H), 4.15 (s, 3H).

Example 9

3- (2,6-dichlorophenyl) -5- (thien-2-yl) -1-methyl [1,2,4] triazole (Compound 50)

N- (benzenesulfonyl) -N-methyl-2,6-dichlorobenzhydrazonoyl chloride (0.42 g, 1.1 mmol), 3-cyanothiophene (0.24 g, 2.2 mmol) and aluminum chloride (0.147 g, 1.1 Mmol) was mixed and heated at 138 ° C. for about 8 hours. The mixture was then poured into an ice bath of 1M NaOH, stirred for 1 hour, extracted with dichloromethane, washed with brine, dried over magnesium sulfate and concentrated to 230 mg of oil. Chromatography (SiO ₂ , 10% EtOAc-Hex) gave the product (100 mg) as a white solid. Melting point; 161-163 ° C.

The present invention also provides a process for preparing the compound of formula 16 as shown in Scheme V:

Scheme V

In Scheme V above,

R ¹⁵ is methyl, phenyl, p-chlorophenyl or p-tolyl,

R ¹⁴ is methanesulfonyl, benzenesulfonyl or substituted benzenesulfonyl,

R ¹ , R ^{1 ′} , R ³ , R ⁴ and R ⁵ are as defined for Formula 1.

In step a of Scheme V, sulfonyl chloride of formula 17 is reacted with methyl hydrazine in an unreactive organic solvent such as THF in the presence of triethylamine. The reaction can be carried out at room temperature. It is usually completed for 4 hours.

In step b of Scheme V, sulfonyl hydrazine of formula 19 is reacted with 2,6-substituted benzoyl chloride of formula 10 to obtain an intermediate of formula 13.

Steps c and d in Scheme V are the same as steps c and d in Scheme IV.

Example 10

This example shows the preparation of benzhydrazonoyl chloride of formula 14b:

[Formula 14b]

A. 2-methyl-2- (4-methylphenyl) sulfonyl hydrazine

In a 100 ml three-neck round bottom flask equipped with a mechanical stirrer, thermometer and dropping funnel, under nitrogen atmosphere, THF (25 ml), methylhydrazine (2.53 g, 2.92 ml, 55 mmol) and triethylamine (4.35 g, 5.99 ml) , 55 mmol) was added. The temperature of the mixture was lowered to about 5 ° C. and 4-methylbenzenesulfonyl chloride (9.5 g, 50 mmol) dissolved in 25 ml of THF was added dropwise at a rate such that the temperature did not rise above 10 ° C. The cooling bath was removed and the mixture was stirred at rt overnight. Ether (100 ml) was added to the reaction mixture, the resulting slurry was washed with water (50 ml), washed with brine (50 ml), dried over Na ₂ SO ₄ and removed in vacuo to remove 9.5 g of the title compound ( Yield; 95%) was obtained.

¹ H NMR (CDCl ₃ ) δ 7.7 (d, 2H), 7.4 (d, 2H), 3.6 (s, b, 2H), 2.8 (s, 3H), 2.4 (s, 3H).

B. 1- (2-Fluoro-6-chlorobenzoyl) -2-methyl-2- (4-methylphenyl) sulfonyl hydrazine

In a 100 ml three-neck round bottom flask equipped with a mechanical stirrer, thermometer and condenser, under a nitrogen atmosphere, 2-methyl-2-[(4-methylphenyl) sulfonyl] hydrazine (9.5 g, 47.4 mmol), pyridine (3.75 g, 3.83 ml, 47.4 mmol), 4-dimethylaminopyridine (0.30 g, 2.4 mmol) and acetonitrile (50 ml) were added. The resulting mixture was cooled to 10 ° C. and 2-fluoro-6-chlorobenzoyl chloride (8.99 g, 45.2 mmol) was added dropwise at a rate such that the temperature did not rise above 10 ° C. The cooling bath was removed and the mixture was stirred at rt overnight. The solvent was removed from the reaction mixture in vacuo to afford an off white solid, which was diluted with methylene chloride, extracted with 1N HCl (20 ml), washed with saturated sodium chloride solution (20 ml), dried over Na ₂ SO ₄ , and The solvent was removed in vacuo to yield an off-white solid. This material was recrystallized from ethyl acetate to give 5.6 g of 1- (2-fluoro-6-chlorobenzoyl) -2-methyl-2- (4-methylphenyl) sulfonyl] hydrazine as a crystalline solid (yield; 34.7%). Obtained. Melting point: 135-136 ° C.

¹ H NMR (CDCl ₃ ) δ 7.6-7.8 (m, 3H), 7.0-7.4 (m, 5H), 3.4 and 3.0 (s combined for 3H), 2.4 and 2.45 (s combined for 3H).

¹³ C (CDCl ₃ ) 160.2, 144.7, 133.6, 132.7, 132.6, 132.1, 131.9, 130.2, 129.6, 129.0, 128.7, 125.7, 114.6, 114.3, 37.7, 21.7.

Elemental Analysis for C ₁₅ H ₁₄ ClFN ₂ O ₃ S:

Calculated: C 50.49, H 3.59, N 7.85.

Found: C 50.55, H 3.89, N 7.81.

C. N- (4-methylbenzenesulfonyl) -N-methyl- (2-fluoro-6-chlorobenz) hydrazonoyl chloride

In a 250 ml one-neck round bottom flask equipped with a magnetic stirrer and a condenser, under a nitrogen atmosphere, 1- (2-fluoro-6-chlorobenzoyl) -2-methyl-2-[(4-methylphenyl) sulfonyl] hydrazine ( 5.0 g, 14.0 mmol), ethylene dichloride (50 ml) and phosphorus pentachloride (3.2 g, 21.6 mmol) were added. The mixture was heated to reflux and held at that temperature for about 30 minutes. The progress of the reaction was monitored by TLC using 50/50 ethyl acetate / hexanes (starter Rf = 0.55; product Rf = 0.70). The solvent was removed in vacuo and the residue was dissolved in methylene chloride (100 ml) and carefully diluted with water. The organic phase was washed with water, brine, dried over Na ₂ S0 ₄ and the solvent removed in vacuo to give a yellow oil which was cooled and solidified. The solid was slurried in hexane / ethyl acetate (70/30) and removed by filtration to remove N- (4-methylbenzenesulfonyl) -N-methyl- (2-fluoro-6-chlorobenz) hydro 4.5 g (yield: 87%) of lazonoyl chloride were obtained. Melting point; 98-99 ° C.

¹ H NMR (CDCl ₃ ) δ 7.8 (d, 2H), 7.2-7.5 (m, 4H), 7.1 (m, H), 3.1 (s, 3H), 2.5 (s, 3H).

¹³ C (CDCl ₃ ) 161.6, 158.5, 144.6, 140.7, 133.6, 132.1, 131.9, 131.1, 129.5, 125.6, 125.5, 114.7, 114.4, 38.1, 21.6.

Elemental Analysis for C ₁₅ H ₁₃ Cl ₂ FN ₂ O ₃ S:

Calculated: C 48.01, H 3.49, N 7.47.

Found; C 48.10, H 3.49, N 7.47.

Example 11

3- (2-chloro-6-fluorophenyl) -5- (3,4,5-trichlorothien-2-yl) -1-methyl [1,2,4] triazole (Compound 2)

In a 50 ml necked flask equipped with a magnetic stirrer and thermometer, under a nitrogen atmosphere, N- (4-methylbenzenesulfonyl) -N-methyl- (2-fluoro-6-chlorobenz) hydrazonoyl chloride Example 10) (1.4 g, 3.73 mmol), 2-cyano-3,4,5-trichlorothiophene (0.83 g, 3.92 mmol), aluminum chloride (0.53 g, 4.0 mmol) and o-dichlorobenzene (10 ml) Was added. The flask containing the reaction mixture was immersed in a preheated oil bath maintained at 120 ° C. Within 8 minutes the temperature of the reaction mixture was raised to 109 ° C. and heating continued for another 30 minutes. The flask was removed from the oil bath and poured into a solution (10 g of sodium hydroxide with 10 ml of ice) with rapid stirring when the stirred reaction mixture reached about 80 ° C. and then added to methylene chloride (50 ml) for extraction. The organic phase was washed with water (25 ml), washed with brine, dried over Na ₂ SO ₄ and the solvent removed in vacuo. O-dichlorobenzene was removed from the residue by Kugeleur distillation to give a residue, dissolved in 20 ml of ether, stirred with activated charcoal at room temperature, filtered and the solvent removed from the filtrate in vacuo. The solid is recrystallized from ethyl acetate to give 3- (2-chloro-6-fluorophenyl) -5- (3,4,5-trichlorothien-2-yl) -1-methyl [as the crystalline solid. 1,2,4] 0.9 g of triazole was obtained (yield: 60.8%).

Purity by HPLC analysis; Greater than 97%.

¹ H NMR (CDCl ₃ ) δ 7.2-7.4 (m, 2H), 7.0-7.4 (m, 1H), 4.0 (s, 3H).

Example 12

This example shows the preparation of benzhydrazonoyl chloride of formula 14c:

[Formula 14c]

A. 2-methyl-2-[(4-chlorophenyl) sulfonyl] hydrazine

In a 100 ml three-neck round bottom flask equipped with a mechanical stirrer, thermometer and dropping funnel, under nitrogen atmosphere, THF (25 ml), methylhydrazine (2.53 g, 2.92 ml, 55 mmol) and triethylamine (4.35 g, 43 mmol) ) Was added. The temperature of the mixture was lowered to about 5 ° C., and the crude 4-chlorophenylsulfonyl chloride (10.5 g, 50 mmol, containing 4-chlorophenyl sulfonic acid) dissolved in 25 ml of THF was used to prevent the temperature from rising above 10 ° C. It was added dropwise. The cooling bath was removed and the mixture was warmed and stirred overnight at room temperature. Ether (100 ml) was added to the reaction mixture, the resulting slurry was washed with water (50 ml), brine (50 ml), dried over Na ₂ SO ₄ , and the solvent was removed in vacuo to 2-methyl-2 5.4 g (yield: 49%) of-[(4-chlorophenyl) sulfonyl] hydrazine were obtained.

¹ H NMR (CDCl ₃ ) δ 7.8 (d, 2H), 7.6 (d, 2H), 3.6 (s, b, 2H), 2.9 (s, 3H).

B. 1- (2-Fluoro-6-chlorobenzoyl) -2-methyl-2-[(4-chlorophenyl) sulfonyl] hydrazine

In a 100 ml three-neck round bottom flask equipped with a magnetic stirrer and a condenser, under a nitrogen atmosphere, 2-methyl-2-[(4-chlorophenyl) sulfonyl] hydrazine (5.4 g, 24.5 mmol), pyridine (1.93 g, 1.98) ml, 24.5 mmol), 4-dimethylaminopyridine (0.15 g, 1.2 mmol) and acetonitrile (50 ml) were added. The mixture was cooled to 10 ° C. and 2-fluoro-6-chlorobenzoyl chloride (4.65 g, 23.4 mmol) was added dropwise at a rate such that the temperature did not rise above 10 ° C. The mixture was stirred at rt overnight. The solvent was removed from the reaction mixture in vacuo to afford an off white solid, which was diluted with methylene chloride, extracted with 1N HCl (20 ml), extracted with saturated sodium bicarbonate solution (20 ml) and dried over Na ₂ SO ₄ . And the solvent was removed in vacuo to give 1- (2-fluoro-6-chlorobenzoyl) -2-methyl-2-[(4-chlorophenyl) sulfonyl] hydrazine as a yellow oil, which was further purified. Used without.

C. N- (4-chlorophenylsulfonyl) -N-methyl- (2-fluoro-6-chlorobenz) hydrazonoyl chloride

In a 250 ml one-neck round bottom flask equipped with a magnetic stirrer and a condenser, under a nitrogen atmosphere, 1- (2-fluoro-6-chlorobenzoyl) -2-methyl-2- (4-chlorophenylsulfonyl) hydrazine (7.3 g, 16.8 mmol, purity by HPLC; 87%), ethylene dichloride (50 ml) and phosphorus pentachloride (6.03 g, 28.9 mmol) were added. The mixture was heated to reflux and held at that temperature for about 30 minutes. The solvent was removed in vacuo and the residue was dissolved in methylene chloride (100 ml) and carefully diluted with water. The organic phase is washed with water, washed with brine, dried over Na ₂ S0 ₄ , the solvent is removed in vacuo to give a yellow oil, dissolved in hot ethyl acetate, added hexane to reach cloud point, cooled by scratching The solids formed. The solid was recrystallized from hexane / ethyl acetate (70/30) and seeded to give N- (4-chlorophenylsulfonyl) -N-methyl- (2-fluoro-6-chlorobenz) hydrazonoyl chloride ( 2.7 g, yield: 40.9%). Melting point; 100-101 ° C.

¹ H NMR (CDCl ₃ ) δ 7.8 (d, 2H), 7.2-7.5 (m, 4H), 7.1 (m, H), 3.1 (s, 3H), 2.5 (s, 3H).

Elemental Analysis for C ₁₄ H ₁₀ Cl ₃ FN ₂ O ₂ S:

Calculated value; C 42.50, H 2.55, N 7.08.

Found; C 42.56, H 2.47, N 6.99.

Example 13

3- (2-chloro-6-fluorophenyl) -5- (3,4,5-trichlorothien-2-yl) -1-methyl [1,2,4] triazole (Compound 2)

In a 50 ml necked flask equipped with a magnetic stirrer and thermometer, under a nitrogen atmosphere, N- (4-chlorophenylsulfonyl) -N-methyl- (2-fluoro-6-chlorobenz) hydrazonoyl chloride (prepared) Method 4) (2.7 g, 6.8 mmol), 2-cyano-3,4,5-trichlorothiophene (1.44 g, 6.8 mmol), aluminum chloride (1.18 g, 8.9 mmol) and o-dichlorobenzene (20 ml) Was added. The flask containing the reaction mixture was immersed in a preheated oil bath maintained at 120 ° C. Within 8 minutes the temperature of the reaction mixture was raised to 109 ° C. and heating continued for a further 50 minutes. The flask was removed from the oil bath and poured into a solution of 20 g of sodium hydroxide with 20 ml of ice with rapid stirring when the stirred reaction mixture reached about 80 ° C. and then added to methylene chloride (100 ml) for extraction. The organic phase was washed with water, brine, dried over Na ₂ S0 ₄ and the solvent removed in vacuo. O-dichlorobenzene was removed from the residue by Kugeleur distillation to give a residue, dissolved in 50 ml of ether, stirred with activated charcoal at room temperature, filtered and the solvent removed from the filtrate in vacuo. The resulting off-white solid is recrystallized to give 3- (2-chloro-6-fluorophenyl) -5- (3,4,5-trichlorothien-2-yl) -1-methyl [as a crystalline solid. 1,2,4] triazole 1.8 g (yield: 26.6%) was obtained.

Purity by HPLC analysis; Greater than 98%.

Example 14

This example shows the preparation of benzhydrazonoyl chloride of formula 14d:

[Formula 14d]

A. 2-methyl-2-methanesulfonyl hydrazine

In a 250 ml three-neck round bottom flask equipped with a mechanical stirrer, thermometer and dropping funnel, under nitrogen atmosphere, THF (100 ml), methylhydrazine (5.07 g, 5.85 ml, 110 mmol) and triethylamine (11.1 g, 15.3 ml) , 110 mmol) was added. The temperature of the mixture was lowered to about 5 ° C. and methanesulfonyl chloride (11.4 g, 7.73 ml, 100 mmol) was added dropwise at a rate such that the temperature did not rise above 10 ° C. The cooling bath was removed and the mixture was allowed to warm to room temperature and stirred overnight. Ether (100 ml) was added to the reaction mixture, washed with water (50 ml), washed with brine (50 ml), dried over Na ₂ SO ₄ , and the solvent was removed in vacuo to remove 2-methyl-2-methanesulfonyl 2.4 g (yield: 19.3%) of hydrazine was obtained.

¹ H NMR (CDCl ₃ ) δ 3.8 (s, b, 2H), 2.95 (s, 3H), 2.9 (s, 3H).

B. 1- (2-Fluoro-6-chlorobenzoyl) -2-methyl-2-methanesulfonyl hydrazine

To 50 ml, under a nitrogen atmosphere, 2-methyl-2-methanesulfonyl hydrazine (2.4 g, 19.3 mmol), pyridine (1.5 g, 1.55 ml, 19.3 mmol) and acetonitrile (50 ml) were added. The mixture was cooled to about 0 ° C. and 2-chloro-6-fluorobenzoyl chloride (3.77 g, 19.3 mmol) was added dropwise. The mixture was allowed to warm to room temperature and stirred for about 3 hours monitoring by TLC using 50/50 ethyl acetate / hexanes (Rf = 0.7 of 2-chloro-6-fluorobenzoyl chloride; Rf = 0.44 of product). . The solvent is removed from the reaction mixture in vacuo, the residue is dissolved in methylene chloride, extracted with 1N hydrochloric acid (10 ml), extracted with saturated sodium bicarbonate, dried over MgSO ₄ , and the solvent is removed in vacuo, 4.6 g of a semisolid was obtained. This material was recrystallized from ethyl acetate to give 1- (2-fluoro-6-chlorobenzoyl) -2-methyl-2-methanesulfonyl hydrazine (1.8 g, yield; 33.3%) as a crystalline solid. Melting point; 135-136 ° C.

¹ H NMR (CDCl ₃ ) δ 7.8 (s, b, 1H), 7.2-7.4 (m, 3H), 3.4 (s, 3H), 3.15 (s, 3H).

Elemental Analysis for C ₉ H ₁₀ ClFN ₂ O ₃ S:

Calculated value; C 38.51, H 3.59, N 9.98.

Found; C 38.28, H 3.41, N 9.48.

C. N-methanesulfonyl-N-methyl- (2-fluoro-6-chlorobenz) hydrazonoyl chloride

In a 250 ml one-neck round bottom flask equipped with a magnetic stirrer and a condenser, under a nitrogen atmosphere, 1- (2-fluoro-6-chlorobenzoyl) -2-methyl-2-methanesulfonyl hydrazine (1.6 g, 7.12 mmol, Ethylene dichloride (25 ml) and phosphorus pentachloride (2.2 g, 10.7 mmol) were added The mixture was heated to reflux and held at that temperature for about 30 minutes 50/50 ethyl acetate / hexane (Rf of starting material) The progress of the reaction was monitored by TLC using Rf = 0.60) of the product, the solvent was removed in vacuo, the residue was dissolved in methylene chloride (50 ml) and carefully diluted with water. Washed with water (2 times 50 ml), washed with brine (50 ml), dried over Na ₂ S0 ₄ , removed the solvent in vacuo to give a colorless oil, cooled and solidified. 70/30) to recrystallize N-methanesulfur Neil -N- methyl-2- (2-chloro-benz fluorophenyl) hydroxy rajo alkanoyl chloride (1.2g, yield: 56.6%) of the title compound Melting point; 83-85 ℃.

Purity by HPLC analysis: 93%.

¹ H NMR (CDCl ₃ ) δ 7.8 (d, 2H), 7.0-7.4 (m, 3H), 3.45 and 3.35 (s added to 3H), 3.15 and 3.05 (s added to 3H).

Example 15

3- (2-chloro-6-fluorophenyl) -5- (3,4,5-trichlorothien-2-yl) -1-methyl [1,2,4] triazole (Compound 2)

In a 50 ml necked flask equipped with a magnetic stirrer and thermometer, under a nitrogen atmosphere, N-methanesulfonyl-N-methyl- (2-fluoro-6-chlorobenz) hydrazonoyl chloride (Example 14) (1.0 g, 3.3 mmol), 2-cyano-3,4,5-trichlorothiophene (0.78 g, 3.7 mmol), aluminum chloride (0.49 g, 3.7 mmol) and o-dichlorobenzene (10 ml) were added. The flask containing the reaction mixture was immersed in a preheated oil bath maintained at 120 ° C. Within 10 minutes the temperature of the reaction mixture was raised to 111 ° C. and heating continued for a further 90 minutes. GC analysis showed a conversion of about 66%. The flask was removed from the oil bath. When the stirred reaction mixture reached about 90 ° C., it was poured into a solution of 10 g of sodium hydroxide with 10 ml of ice with rapid stirring and then added to methylene chloride (50 ml) for extraction. The organic phase was washed with water (25 ml), washed with brine, dried over Na ₂ SO ₄ and the solvent removed in vacuo. O-dichlorobenzene was removed from the residue by Cougeleur distillation to give a residue, dissolved in 20 ml of ether, stirred with activated carbon at room temperature, filtered and the solvent removed from the filtrate in vacuo, 3,4, 3- (2-chloro-6-fluorophenyl) -5- (3,4,5-trichlorothien-2-yl) -1-methyl [1 contaminated with 5-trichloro-2-cyanothiophene , 2,4] triazole (0.4 g) was obtained.

The compounds of the present invention can be changed using general methods to provide other compounds of the present invention, as described in Examples 16 and 17.

Example 16

3- (2,6-dichlorophenyl) -5- (5-bromo-3,4-dichlorothien-2-yl) -1-methyl [1,2,4] triazole (Compound 46)

Of 3- (2,6-dichlorophenyl) -5- (3,4,5-trichlorothien-2-yl) -1-methyl [1,2,4] triazole (325 mg, 1.0 mmol) in THF To the solution was slowly added n-butyllithium (2.5 mmol) at -78 ° C and the mixture was stirred for 1 hour. Bromine (3.0 mmol) was added and the reaction stirred for 2 hours, then diluted with water, extracted with ether, washed with brine and dried over magnesium sulfate. The product was concentrated to 620 mg of thick oil. This was chromatographed (SiO ₂ , 10% EtOAc-Hex) to give 79 mg of the title compound as a pink solid. Melting point: 197-199 ° C.

Example 17

3- (2,6-dichlorophenyl) -5- (5-bromothien-2-yl) -1-methyl [1,2,4] triazole (Compound 47)

3- (2,6-dichlorophenyl) -5- (thien-2-yl) -1-methyl [1,2,4] triazole (75 mg, 0.242 mmol) and bromine (39 mg, 0.242 mmol) were dissolved in glacial acetic acid ( 3 ml), and the mixture was stirred at rt overnight and then heated to 95 ° C. for 5 h. The reaction mixture is poured into saturated sodium bicarbonate solution, extracted with ether and dried over magnesium sulfate. This was chromatographed (SiO ₂ , 25% Hex-CH ₂ Cl ₂ ) to afford the title compound as a white waxy solid. Melting point: 130-132 ° C.

Botanically acceptable acid addition salts of compounds of formula 1 are also included within the scope of the present invention. For example, boron tetrafluoride, hydrogen chloride, hydrogen bromide, hydrogen iodide, hydrogen sulfate or an organic acid salt can be used.

The compounds identified in Table 1 below were prepared and tested.

TABLE 1a

TABLE 1b

TABLE 1c

TABLE 1d

TABLE 1e

TABLE 1f

Table 1g

Table 1h

TABLE 1i

TABLE 1j

Table 1k

TABLE 1L

[Table 1m]

TABLE 1n

Table 1o

Table 1p

TABLE 1q

CA ⁺ shows activity against cotton aphid at 50 ppm,

TSSM ^‡ shows activity against two-spotted spider mites at 100 ppm

WF ^* shows activity against white fly at 800 ppm. This test procedure is described below.

In each case the classes are classified as follows:

Use of insecticides and tick repellents

The compounds of the present invention are also useful for controlling insects, mites and aphids. Therefore, the present invention also relates to a method for inhibiting insects, mites or aphids, including applying an insect or mite inhibitory amount of the compound of formula 1 to the habitat of the insects or mites.

The compounds are useful for reducing the population of insects and ticks and inhibiting the insect or tick community by applying an amount of the compound of formula 1 to the habitat of the insects or ticks in an amount effective to inactivate the insects or ticks. It is useful in the way. The term "dwelling" of insects or ticks is used herein to mean the environment in which insects or ticks live or where their eggs exist, including the air around them, the food they eat or the objects they contact. For example, plant ingested insects or ticks can be controlled by applying the present active compounds to parts of the plant that the insects or ticks eat, especially leaves. It is contemplated that such active compounds may be applied to fabrics, paper, stored grain or seeds to be useful for protecting these materials. The term "inhibition of insects or ticks" means reducing the number of live insects or ticks, or reducing the number of viable eggs of insects or ticks. The extent of the reduction performed by the compound depends, of course, on the application of the compound, the particular compound used and the desired insect or tick species. At least the amount of inactivation should be used. The terms “amount to inactivate insects” and “amount to inactivate ticks” are used to describe an amount sufficient to reduce the amount of treated insects or tick populations to be measurable. Generally, active compounds in the range of about 1 to about 1000 ppm are used.

In a preferred embodiment, the present invention relates to a method for inhibiting aphids or aphids, comprising applying to a plant an amount of a compound of formula 1 effective to inactivate aphids or aphids.

Cotton aphid ( Aphis gossypii Insecticide test for)

A spray solution was prepared by dissolving 2 mg of each test compound in 2 ml of acetone: ethanol (90:10) solvent. 2 ml of this chemical solution was added to 38 ml of water containing 0.05% Tween 20 surfactant to make a 50 ppm spray solution.

Pumpkin cotyledon was infected with cotton aphids for 16-20 hours prior to application of the spray solution (all leaf stages). A total of 2 ml of spray solution was used to spray this solution with a sweeping action on both sides of each infected pumpkin cotyledon (2 × 0.5 ml each on each side). The plants were air dried and maintained for 3 days in a room controlled at 26 ° C. and 40% RH, after which the test was evaluated. Evaluation was performed by using an anatomical microscope to count actual numbers and compare what was tested on untreated.

Two-spotted spider mite Tetranychus urticae Insecticide test for)

Sallanche Method:

Ten adult female two-pointed spider mites were placed on eight 2.2 cm leaf discs of a cotton garden, spawned for 24 hours and then removed. The leaf discs are immersed in 100 ppm test solution for 3 seconds, then dried and 16 discs are left as untreated negative controls. The disc was placed on an agar substrate and left for 6 days at a temperature of 24 ° C. and 90% relative humidity. Control rates based on the number of larvae hatched on the treated disc and the number of larvae hatched on the untreated disc are listed in Table 1.

Evaluation of Test Compounds for Sweet Potato Powder ( Bemisia tabacia ) Under Laboratory Conditions

16 mg of each test compound was dissolved by adding 5 ml of acetone: ethanol (90:10) solvent mixture to a glass bottle containing the sample compound. This solution was added to 15 ml of water containing 0.05% Tween 20 surfactant, resulting in 20 ml of 800 ppm spray solution.

In a five-week-old cotton tree grown in a greenhouse, all leaves were removed, except for the top two real leaves that were more than 5 cm in diameter. This cottonwood is then placed in the laboratory flour for 3 days to spawn the female colonies. Then, pressurized air was used to remove all flour from the test plants. The spray solution was then applied to the test plant using a portable syringe with a hollow conical nozzle. A total of 4 ml per plant, ie 1 ml of spray solution, was applied before and after each leaf. Repeated four times for each test compound using a total of 16 ml of spray solution. The plants were air dried and then placed in a storage chamber (26 ° C. and 40% RH) for 21 days. Under dissecting microscope, compound pupae per leaf were counted to assess compound efficiency. An empty chrysalis means that the powder has not been controlled because it indicates that the eggs have grown to adulthood.

The control rates based on the reduction of the empty pupa collection of the test compound compared to the plants sprayed with only the solution containing no test compound are shown in Table 1 below.

Seed Treatment of Cotton Aphids from Pumpkin

Soil mixtures (70% sand / 30% soil grind) were sieved to fill 2/3 of the 4 inch jar. The compound was sprinkled as a suspension in the center of 4 ml volume. Pumpkin seeds placed in the chemical area sprayed with the compound were covered with a soil mixture 1 cm deep. If you water the jar and leave it in the greenhouse for 10 days, at some point each plant will have fully expanded leaves that can be infected. The plant is then infected with aphids. After 4 days, the aphids were counted. The results are summarized in the following table.

Number of Cotton Aphids on Pumpkin Cotyledon

Number of cotton aphids for amber-primary real leaves

In addition to being effective against mites, aphids and insects when applied to leaves, the compounds of formula 1 exhibit systemic activity. Thus, another aspect of the present invention is to use an effective amount of a compound of formula 1 to treat plant seeds before sowing, to treat the soil to be sown, or to treat the soil at the root of the plant after sowing. It is a method of protecting a plant from insects, including.

Composition

The compounds of the present invention are used in the form of compositions which are an important aspect of the present invention, including the compounds of the present invention and botanically acceptable inert carriers. The composition is a concentrated formulation to be used dispersed in water or a dust or granule formulation to be used without further treatment. The compositions are common in the field of agrochemicals, but are prepared according to novel and important procedures and modalities because the compounds of the invention are present therein. However, in order to confirm that an agrochemist can easily prepare any desired composition, some explanation is given to the formulation of the composition.

Dispersions in which the compounds are used are mostly aqueous suspensions or emulsions prepared from concentrated formulations of the compounds. Such water soluble, water suspension or emulsion formulations are solids generally known as wettable powders or liquids generally known as emulsifiable concentrates or aqueous suspensions. The wettable powder can be compacted to form water dispersible granules and comprises a homogeneous mixture of the active compound and an inert carrier and surfactant. The concentration of the active compound is usually about 10 to about 90% by weight. The inert carrier is usually selected from attapulgite clays, montmorillonite clays, diatomaceous earth or purified silicates. Effective surfactants include from about 0.5 to about 10% wettable powder and include sulfonated lignin, concentrated naphthalenesulfonates, naphthalenesulfonates, alkylbenzenesulfonates, alkyl sulfates and nonionic surfactants such as ethylene oxide of alkyl phenols. Adduct).

The emulsifiable concentrates of the compounds may be prepared in an inert carrier which is a water miscible solvent or a mixture of a water immiscible organic solvent and an emulsifier at a convenient concentration, for example from about 50 to about 500 g per liter of liquid, i.e. from about 10 to And dissolved at a concentration of about 50%. Organic solvents that can be used include aromatics, in particular xylenes, and petroleum fractions, in particular high boiling naphthalene and olefinic portions of petroleum such as heavy aromatic naphtha. As other organic solvents, for example, terpene solvents containing rosin derivatives, aliphatic ketones such as cyclohexanone, and complex alcohols such as 2-ethoxyethanol are used. Suitable emulsifiers for emulsifiable concentrates are selected from the conventional nonionic surfactants described above.

Aqueous suspensions included suspensions of the water insoluble compounds of the present invention dispersed in an aqueous vehicle at a concentration of about 5 to about 50 weight percent. Suspensions are prepared by finely grinding the compound and mixing it vigorously into a vehicle comprising water and a surfactant selected from the kind as described above. In order to increase the density and viscosity of the aqueous vehicle, it is also possible to add inorganic salts and inert components such as synthetic rubber or natural rubber. By preparing an aqueous mixture and homogenizing in a tool such as a sand mill, ball mill or piston type homogenizer, it is often the most effective to simultaneously grind and mix the compounds.

The mixture can also be used as a granulation composition, which is particularly useful for use on soil. The granular composition usually contains from about 0.5 to about 10 weight percent of the present compound, dispersed in an inert carrier consisting entirely or mostly of clay or similar inexpensive material. Such compositions are usually prepared by dissolving the compound in a suitable solvent and applying it to a granular carrier preformed to a suitable particle size of about 0.5 to 3 mm. Such compositions may also be formulated by preparing, crushing and drying the dough or paste of the carrier and the compound to the desired granular particle size.

Dusts containing this compound are prepared simply by mixing the powder form of the compound directly with suitable dusty agricultural carriers such as kaolin clay and ground volcanic rock. The dust may suitably contain about 1 to about 10% of the present compound.

If desired for some reason, it is also practical to use this compound in the form of a solution in a suitable organic solvent such as spray oil, which is widely used in the field of agrochemicals, usually less toxic petroleum.

Pesticides and tick repellents are generally used in the form of a dispersion of the active ingredient in a liquid carrier. It is common to regard the concentration of the active ingredient in the carrier as an applied amount. The most widely used carrier is water.

The compounds of the present invention can also be used in the form of aerosol compositions. In such compositions, the active ingredient is dissolved or dispersed in an inert carrier, which is a pressure generating propellant mixture. The aerosol composition is packaged in a container from which the mixture is dispersed through a spray valve. Propellant mixtures include low boiling halocarbons that can be mixed with organic solvents, or aqueous suspensions compressed with an inert gas or hydrocarbon gas.

The actual amount of compound to be applied to the habitat of insects, ticks and aphids is not critical and can be readily determined by those skilled in the art with reference to the examples above. Generally, when the concentration of the compound is 10 to 5000 ppm, it is expected that excellent control will be achieved. Even if a large amount of the compound is used, a concentration of 100 to 1500 pm will be sufficient. For field crops such as soybeans and cotton, suitable amounts of the present compounds are about 0.5 to 1.5 1b / A and are typically used at 5 to 20 gal / A in spray formulations containing 1200 to 3600 ppm of the compound. For citrus crops, a suitable dosage is a spray formulation of about 100 to 1500 gal / A, which is 100 to 1000 ppm.

The place where the compound is used can be used in any place where insects or ticks live, for example, vegetable crops, fruit trees and nuts, grape vines and ornamental plants. As long as many tick species are specific to a particular host, the tick species listed above provide examples of a wide range of settings in which the compounds may be used.

Because of the unique ability of tick eggs to resist toxic effects, it may be desirable to apply them repeatedly to control emerging larvae (as is true with other known tick repellents).

The following formulations of the compounds of the present invention are typical compositions useful in practice of the present invention.

A. 0.75 emulsifiable concentrate

B. 1.5 Emulsifiable Concentrates

C. 1.0 Emulsifiable Concentrates

D. 1.0 Aqueous Suspension

E. 1.0 Aqueous Suspension

F. 1.0 Aqueous Suspension

G. Wettable Powder

H. 1.0 Aqueous Suspension

I. 1.0 Emulsifiable Concentrates

J. Wettable Powder

K. 0.5 Emulsifiable Concentrate

L. Emulsifiable Concentrate

Related Applications

This application claims priority to US Patent Application No. 60 / 044,697, filed April 24, 1997, and US Patent Application No. 60 / 066,135, filed November 19, 1997.

Claims (22)

A compound of formula (1) or a botanically acceptable acid addition salt thereof. Formula 1 In Formula 1 above, Ar is substituted phenyl, Y is O or S, R ² is (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl; (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl substituted by halo atom; (C ₂ -C ₆ ) straight chain alkenyl or (C ₃ -C ₆ ) branched alkenyl; (C ₂ -C ₆ ) straight chain alkynyl or (C ₃ -C ₆ ) branched alkynyl; Or (C ₁ -C ₆₎ straight chain alkoxy, (C ₃ -C ₆₎ branched chain alkoxy, or (C ₃ -C ₆₎ substituted by a cyclic alkoxy (C ₁ -C ₆₎ straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl, R ³ is H; Halo; (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) side chain or (C ₃ -C ₆ ) cyclic alkyl; (C ₇ -C ₂₁ ) straight or branched alkyl; Hydroxy; (C ₁ -C ₆ ) straight alkoxy, (C ₃ -C ₆ ) branched alkoxy or (C ₃ -C ₆ ) cyclic alkoxy; (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl substituted by halo atom; (C ₁ -C ₆ ) straight chain alkoxy substituted by halo atoms, (C ₃ -C ₆ ) branched alkoxy or (C ₃ -C ₆ ) cyclic alkoxy; (C ₁ -C ₆₎ straight chain alkoxy, (C ₃ -C ₆₎ branched chain alkoxy, or (C ₃ -C ₆₎ substituted by a cyclic alkoxy (C ₁ -C ₆₎ straight chain alkyl, (C ₃ -C ₆ ) Branched alkyl or (C ₃ -C ₆ ) cyclic alkyl; (C ₁ -C ₆₎ straight chain alkoxy, (C ₃ -C ₆₎ branched chain alkoxy, or (C ₃ -C ₆₎ substituted by a cyclic alkoxy (C ₁ -C ₆₎ straight chain alkoxy, (C ₃ -C ₆ ) Branched alkoxy or (C ₃ -C ₆ ) cyclic alkoxy; (C ₂ -C ₆ ) straight chain alkenyl or (C ₃ -C ₆ ) branched alkenyl; (C ₂ -C ₆ ) straight chain alkynyl or (C ₃ -C ₆ ) branched alkynyl; (C ₂ -C ₆ ) straight chain alkenyl or (C ₃ -C ₆ ) branched alkenyl substituted by halo atom; CN, NO ₂ , COR ⁶ , CO ₂ R ⁶ , CON (R ⁶ ) ₂ , (C ₃ -C ₆ ) cycloalkyl, S (O) _m R ⁶ , -OSO ₂ R ⁶ , SCN,-(CH ₂ ) _n R ⁶ , -CH = CHR ⁶ , -C≡CR ⁶ ,-(CH ₂ ) _q OR ⁶ ,-(CH ₂ ) _q SR ⁶ ,-(CH ₂ ) _q NR ⁶ R ⁶ , -O (CH ₂ ) _q R ⁶ , -S (CH ₂ ) _q R ⁶ , -NR ⁶ (CH ₂ ) _q R ⁶ , , , , , , , , , -Si (R ⁷ ) ₃ , pyridyl, substituted pyridyl, isoxazolyl, substituted isooxazolyl, naphthyl, substituted naphthyl, phenyl, substituted phenyl, thienyl, substituted thienyl, pyri Midiyl, substituted pyrimidyl, pyrazolyl and substituted pyrazolyl, R ⁴ and R ⁵ are independently H; Halo; (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl; (C ₁ -C ₆ ) straight alkoxy, (C ₃ -C ₆ ) branched alkoxy or (C ₃ -C ₆ ) cyclic alkoxy; (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl substituted by halo atom; (C ₁ -C ₆ ) straight chain alkoxy substituted by halo atoms, (C ₃ -C ₆ ) branched alkoxy or (C ₃ -C ₆ ) cyclic alkoxy; CN; CO ₂ R ⁶ ; CON (R ⁶ ) ₂ ; Or S (0) _n- (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl, or When R ⁴ and R ⁵ are attached to adjacent carbon atoms, they are taken together with one or two halo; (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl; (C ₁ -C ₆ ) straight alkoxy, (C ₃ -C ₆ ) branched alkoxy or (C ₃ -C ₆ ) cyclic alkoxy; Or 5 or 6 membered saturation which may be substituted by (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl group substituted by halo atom or Can form unsaturated carbocyclic rings, R ⁶ is H; (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl; (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl substituted by halo atom; (C ₂ -C ₆ ) straight chain alkenyl or (C ₃ -C ₆ ) branched alkenyl; (C ₂ -C ₆ ) straight chain alkynyl or (C ₃ -C ₆ ) branched alkynyl; Phenyl; Or substituted phenyl, R ⁷ is (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl, m is 0, 1 or 2, n is 1 or 2, p is an integer from 2 to 6, q is 0 or 1; The compound of formula 1A or a botanically acceptable acid addition salt thereof. Formula 1A In Formula 1A above, R ¹ and R ^{1 ′} are independently H, Cl, F, methyl, halomethyl, methoxy or halomethoxy, Y is O or S, R ² is (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl; (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl substituted by halo atom; (C ₂ -C ₆ ) straight chain alkynyl or (C ₃ -C ₆ ) branched alkenyl; (C ₂ -C ₆ ) straight chain alkynyl or (C ₃ -C ₆ ) branched alkynyl; Or (C ₁ -C ₆₎ straight chain alkoxy, (C ₃ -C ₆₎ branched chain alkoxy, or (C ₃ -C ₆₎ substituted by a cyclic alkoxy (C ₁ -C ₆₎ straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl, R ³ is H; Halo; (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl; (C ₇ -C ₂₁ ) straight chain alkyl; Hydroxy; (C ₁ -C ₆ ) straight alkoxy, (C ₃ -C ₆ ) branched alkoxy or (C ₃ -C ₆ ) cyclic alkoxy; (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl substituted by halo atom; (C ₁ -C ₆ ) straight chain alkoxy substituted by halo atoms, (C ₃ -C ₆ ) branched alkoxy or (C ₃ -C ₆ ) cyclic alkoxy; (C ₁ -C ₆₎ straight chain alkoxy, (C ₃ -C ₆₎ branched chain alkoxy, or (C ₃ -C ₆₎ substituted by a cyclic alkoxy (C ₁ -C ₆₎ straight chain alkyl, (C ₃ -C ₆ ) Branched alkyl or (C ₃ -C ₆ ) cyclic alkyl; (C ₁ -C ₆₎ straight chain alkoxy, (C ₃ -C ₆₎ branched chain alkoxy, or (C ₃ -C ₆₎ substituted by a cyclic alkoxy (C ₁ -C ₆₎ straight chain alkoxy, (C ₃ -C ₆ ) Branched alkoxy or (C ₃ -C ₆ ) cyclic alkoxy; (C ₂ -C ₆ ) straight chain alkenyl or (C ₃ -C ₆ ) branched alkenyl; CN, NO ₂ , CO ₂ R ⁶ , CON (R ⁶ ) ₂ , (C ₃ -C ₆ ) cycloalkyl, S (O) _m R ⁶ , SCN, pyridyl, substituted pyridyl, isoxazolyl, substitution Isooxazolyl, naphthyl, substituted naphthyl, phenyl, substituted phenyl,-(CH ₂ ) _n R ⁶ , -CH = CHR ⁶ , -C≡CR ⁶ , -CH ₂ OR ⁶ , -CH ₂ SR _{^{6, -CH 2 NR 6 R 6}} , -OCH 2 R 6, -SCH 2 R 6, -NR 6 CH 2 R 6, , , , , , , , And Is selected from the group consisting of R ⁴ and R ⁵ are independently H; Halo; (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl; (C ₁ -C ₆ ) straight alkoxy, (C ₃ -C ₆ ) branched alkoxy or (C ₃ -C ₆ ) cyclic alkoxy; (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl substituted by halo atom; (C ₁ -C ₆ ) straight chain alkoxy substituted by halo atoms, (C ₃ -C ₆ ) branched alkoxy or (C ₃ -C ₆ ) cyclic alkoxy; CN; CO ₂ R ⁶ ; CON (R ⁶ ) ₂ ; Or S (O) _m- (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl, or R ⁴ and R ⁵ are 1 or 2 halo; (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl; (C ₁ -C ₆ ) straight alkoxy, (C ₃ -C ₆ ) branched alkoxy or (C ₃ -C ₆ ) cyclic alkoxy; Or 5 or 6 membered saturation which may be substituted by (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl group substituted by halo atom or To form an unsaturated carbocyclic ring, R ⁶ is H; (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl; (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl substituted by halo atom; (C ₂ -C ₆ ) straight chain alkenyl or (C ₃ -C ₆ ) branched alkenyl; (C ₂ -C ₆ ) straight chain alkynyl or (C ₃ -C ₆ ) branched alkynyl; Phenyl; Or substituted phenyl, m is 0, 1 or 2, n is 1 or 2, p is an integer of 2-6. The compound of claim 2, wherein Y is sulfur. The method of claim 2, wherein Formula A 2-thienyl group of. The compound of claim 2, wherein R ¹ is chloro and R ^{1 ′} is chloro or fluoro. The compound of claim 2, wherein R ² is methyl. The compound of claim 2, wherein R ³ , R ⁴ and R ⁵ are each halo. A compound of formula 1B Formula 1B In Formula 1B above, R ¹ and R ^{1 ′} are independently F or Cl, R ² is (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl, most preferably methyl, R ³ , R ⁴ and R ⁵ are independently H, Cl or Br. The compound of claim 8, wherein R ¹ is F or Cl and R ^{1 ′} is F. 10. The compound according to claim 9, which is 3- (2-chloro-6-fluorophenyl) -5- (3,4,5-trichlorothien-2-yl) -1-methyl [1,2,4] triazole compound. The compound of claim 8, wherein R ¹ and R ^{1 ′} are Cl. 12. The compound of claim 11, which is 3- (2,6-dichlorophenyl) -5- (3,4,5-trichlorothien-2-yl) -1-methyl [1,2,4] triazole. A compound for controlling insects or mites comprising the compound of claim 1 in combination with a botanically acceptable carrier. A method of controlling insects or ticks, comprising applying the compound of claim 1 to a habitat in need of control of the insects or ticks in an amount capable of inactivating the insects or ticks. A method for controlling powdery rice, comprising applying the compound of claim 1 in an amount to inactivate white fly to a habitat requiring control of the powdery powder. A method for controlling ticks, comprising applying the compound of claim 1 to an habitat in need of controlling the ticks in an amount capable of inactivating the ticks. A method of controlling aphids, comprising applying the compound of claim 1 to an habitat in need of controlling the aphids in an amount capable of inactivating the aphids. Protecting plants from aphids, mites or insects, including treating the plant seeds before sowing, treating the soil to be sown, or treating the soil at the root of the plant after sowing, using the compound of claim 1 How to. A process for preparing the compound of claim 1, wherein R ¹ and R ^{1 ′} are F comprising reacting a compound of Formula 2b with a compound of Formula 3. 3. Formula 2b [Formula 3] In Formulas 2b and 3 above, R ¹² is (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl, R ¹³ is an amino protecting group selected from the group consisting of carbobenzyloxy, tertiary alkoxycarbonyl, amide, phosphinyl, phosphoryl, sulfenyl and sulfonyl, R ³ , R ⁴ and R ⁵ are independently H; Halo; (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl and (C ₃ -C ₆ ) cyclic alkyl. (a) reacting a compound of formula 6 with a compound of formula a to prepare a compound of formula 2b; and (b) A process for preparing the compound of claim 1, wherein R ¹ and R ^{1 '} are F comprising reacting the compound of Formula 2b with the compound of Formula 3. Formula 6 [Formula a] Formula 2b Formula 3 In Formula 6, a, 2b and 3 above, R ¹¹ is (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl, R ¹² is (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl, R ¹³ is an amino protecting group selected from the group consisting of carbobenzyloxy, tertiary alkoxycarbonyl, amide, phosphinyl, phosphoryl, sulfenyl and sulfonyl, R ³ , R ⁴ and R ⁵ are independently selected from the group consisting of H, halo, (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl and (C ₃ -C ₆ ) cyclic alkyl do. The method of producing a compound of claim 1 formula (14) the compound is, R ^2, including the step of reacting a compound of formula 15 in CH _3. [Formula 14] [Formula 15] In Formulas 14 and 15 above, R ¹ and R ^{1 ′} are as defined in claim 1, R ¹⁴ is methanesulfonyl, benzenesulfonyl or substituted benzenesulfonyl, R ³ is H; Halo; (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl; (C ₇ -C ₂₁ ) straight chain alkyl; Hydroxy; (C ₁ -C ₆ ) straight alkoxy, (C ₃ -C ₆ ) branched alkoxy or (C ₃ -C ₆ ) cyclic alkoxy; (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl substituted by halo atom; (C ₁ -C ₆ ) straight chain alkoxy substituted by halo atoms, (C ₃ -C ₆ ) branched alkoxy or (C ₃ -C ₆ ) cyclic alkoxy; (C ₁ -C ₆₎ straight chain alkoxy, (C ₃ -C ₆₎ branched chain alkoxy, or (C ₃ -C ₆₎ substituted by a cyclic alkoxy (C ₁ -C ₆₎ straight chain alkyl, (C ₃ -C ₆ ) Branched alkyl or (C ₃ -C ₆ ) cyclic alkyl; (C ₁ -C ₆₎ straight chain alkoxy, (C ₃ -C ₆₎ branched chain alkoxy, or (C ₃ -C ₆₎ substituted by a cyclic alkoxy (C ₁ -C ₆₎ straight chain alkoxy, (C ₃ -C ₆ ) Branched alkoxy or (C ₃ -C ₆ ) cyclic alkoxy; (C ₂ -C ₆ ) straight chain alkenyl or (C ₃ -C ₆ ) branched alkenyl; (C ₂ -C ₆ ) straight chain alkenyl or (C ₃ -C ₆ ) branched alkenyl substituted by halo atom; CN, NO ₂ , CO ₂ R ⁶ , CON (R ⁶ ) ₂ , (C ₃ -C ₆ ) cycloalkyl, S (O) _m R ⁶ , SCN, pyridyl, substituted pyridyl, isoxazolyl, substitution Isooxazolyl, naphthyl, substituted naphthyl, phenyl, substituted phenyl,-(CH ₂ ) _n R ⁶ , -CH = CHR ⁶ , -C≡CR ⁶ , -CH ₂ OR ⁶ , -CH ₂ SR _{^{6, -CH 2 NR 6 R 6}} , -OCH 2 R 6, -SCH 2 R 6, -NR 6 CH 2 R 6, , , , , , , , And Is selected from the group consisting of R ⁴ and R ⁵ are independently H; Halo; (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl; (C ₁ -C ₆ ) straight alkoxy, (C ₃ -C ₆ ) branched alkoxy or (C ₃ -C ₆ ) cyclic alkoxy; (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl substituted by halo atom; (C ₁ -C ₆ ) straight chain alkoxy substituted by halo atoms, (C ₃ -C ₆ ) branched alkoxy or (C ₃ -C ₆ ) cyclic alkoxy; CN; CO ₂ R ⁶ ; CON (R ⁶ ) ₂ ; Or S (O) _m- (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl, or When R ⁴ and R ⁵ are attached to adjacent carbon atoms, they are one or two halo; (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl; (C ₁ -C ₆ ) straight alkoxy, (C ₃ -C ₆ ) branched alkoxy or (C ₃ -C ₆ ) cyclic alkoxy; Or 5 or 6 membered saturation which may be substituted by (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl group substituted by halo atom or Can form unsaturated carbocyclic rings, R ⁶ is H, (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl; (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl substituted by halo atom; (C ₂ -C ₆ ) straight chain alkenyl or (C ₃ -C ₆ ) branched alkenyl; (C ₂ -C ₆ ) straight chain alkynyl or (C ₃ -C ₆ ) branched alkynyl; Phenyl; Or substituted phenyl, m is 0, 1 or 2, n is 1 or 2, p is an integer of 2-6. a) reacting a compound of Formula 10 with a compound of Formula 11 to produce a compound of Formula 12, b) methylating the compound of formula 12 to produce the compound of formula 13, c) chlorinating the compound of Formula 13 to produce a compound of Formula 14; and d) The method of producing a compound of claim 1 is, R ² for a compound of formula 14 comprising the step of reacting a compound of formula 15 CH _3. [Formula 10] [Formula 11] [Formula 12] [Formula 13] [Formula 14] [Formula 15] In the above formula 10 to 15, R ¹ and R ^{1 ′} are independently H, Cl, F, methyl, halomethyl, methoxy or halomethoxy, R ¹⁴ is methanesulfonyl, benzenesulfonyl or substituted benzenesulfonyl, R ³ is H; Halo; (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl; (C ₇ -C ₂₁ ) straight chain alkyl; Hydroxy; (C ₁ -C ₆ ) straight alkoxy, (C ₃ -C ₆ ) branched alkoxy or (C ₃ -C ₆ ) cyclic alkoxy; (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl substituted by halo atom; (C ₁ -C ₆ ) straight chain alkoxy substituted by halo atoms, (C ₃ -C ₆ ) branched alkoxy or (C ₃ -C ₆ ) cyclic alkoxy; (C ₁ -C ₆₎ straight chain alkoxy, (C ₃ -C ₆₎ branched chain alkoxy, or (C ₃ -C ₆₎ substituted by a cyclic alkoxy (C ₁ -C ₆₎ straight chain alkyl, (C ₃ -C ₆ ) Branched alkyl or (C ₃ -C ₆ ) cyclic alkyl; (C ₁ -C ₆₎ straight chain alkoxy, (C ₃ -C ₆₎ branched chain alkoxy, or (C ₃ -C ₆₎ substituted by a cyclic alkoxy (C ₁ -C ₆₎ straight chain alkoxy, (C ₃ -C ₆ ) Branched alkoxy or (C ₃ -C ₆ ) cyclic alkoxy; (C ₂ -C ₆ ) straight chain alkenyl or (C ₃ -C ₆ ) branched alkenyl; (C ₂ -C ₆ ) straight chain alkenyl or (C ₃ -C ₆ ) branched alkenyl substituted by halo atom; CN, NO ₂ , CO ₂ R ⁶ , CONHR ⁶ , CON (R ⁶ ) ₂ , (C ₃ -C ₆ ) cycloalkyl, S (O) _m R ⁶ , SCN, pyridyl, substituted pyridyl, isoxa Zolyl, substituted isooxazolyl, naphthyl, substituted naphthyl, phenyl, substituted phenyl,-(CH ₂ ) _n R ⁶ , -CH = CHR ⁶ , -C≡CR ⁶ , -CH ₂ OR ⁶ ,- _{^{CH 2 SR 6, -CH 2 NR}} 6 R 6, -OCH 2 R 6, -SCH 2 R 6, -NR 6 CH 2 R 6, , , , , , , , , And Is selected from the group consisting of R ⁴ and R ⁵ are independently H; Halo; (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl; (C ₁ -C ₆ ) straight alkoxy, (C ₃ -C ₆ ) branched alkoxy or (C ₃ -C ₆ ) cyclic alkoxy; (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl substituted by halo atom; (C ₁ -C ₆ ) straight chain alkoxy substituted by halo atoms, (C ₃ -C ₆ ) branched alkoxy or (C ₃ -C ₆ ) cyclic alkoxy; CN; CO ₂ R ⁶ ; CONHR ⁶ ; CON (R ⁶ ) ₂ ; Or S (O) _m- (C ₃ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl, or R ⁴ and R ⁵ are one or two halo; (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl; (C ₁ -C ₆ ) straight alkoxy, (C ₃ -C ₆ ) branched alkoxy or (C ₃ -C ₆ ) cyclic alkoxy; Or 5 or 6 membered saturation which may be substituted by (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl group substituted by halo atom or To form an unsaturated carbocyclic ring, R ⁶ is H; (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl; (C ₁ -C ₆ ) straight chain alkyl, (C ₃ -C ₆ ) branched alkyl or (C ₃ -C ₆ ) cyclic alkyl substituted by a halo atom; (C ₂ -C ₆ ) straight alkenyl or (C ₃ -C ₆ ) branched alkenyl; (C ₂ -C ₆ ) straight chain alkynyl or (C ₃ -C ₆ ) branched alkynyl; Phenyl; Or substituted phenyl, m is 0, 1 or 2, n is 1 or 2, p is an integer of 2-6.