HU206596B - Insecticide compositions containing phenyl-pyrimidinone derivatives as active components and process for producing the active components - Google Patents

Abstract

The insecticidal compositions of the present invention comprise from 0.01% to 60% by weight of the compounds of formula I wherein R1 and R2 are independently halogen, halogenated C1-4alkyl, C1-4alkoxy or nitro, R3 and R4 independently selected from hydrogen or C 1-4 alkyl, R 5 is halogen, nitro, halogenated C 1-4 alkyl, halogenated C 1-4 alkoxy, or -S (O) n R 10 wherein n is 0, 1 or 2, and R10-C4 alkyl or halogenated C1-C4 alkyl, R6 is halogenated C1-C4 alkyl, or -S (O) nR1, wherein n and R10 are as defined above, R7 is hydrogen, halogen, nitro , C 1-4 alkyl, halogenated C 1-4 alkyl ot, hydroxy (1-4C) alkyl, C1-4alkoxy, formyl or -S (O) nR10 or -NRnR12 in which n and R10 are as defined above, and R11 and R12 are independently selected from each other. is hydrogen or C 1-4 alkyl, R 8 is hydrogen, C 1-4 alkyl or -S (O) n R 10 or -NRUR 12 wherein n is R 10, R 11, and R 12 is as defined above and R 9 is oxygen or sulfur. It means. The invention also relates to a process for the preparation of the active compounds of formula (I). EN 206 596 B Scope of the description: 28 pages (including 3 sheets)

Description

Description: 28 pages (including 3 pages)

HU 206 596 Β

FIELD OF THE INVENTION The present invention relates to novel insecticidal compositions containing phenylpyrimidinone derivatives. The invention further relates to a process for the preparation of the active compounds.

No. 338,686. European Patent Application Publication No. 6,198,198 discloses compounds of formula A wherein R ¹ and R ² are each independently halogen or nitro, R ³ and R ⁴ are each independently hydrogen or halogen, R ^{5 is} hydrogen, halogen or cyano, and R ^{6 is} halogen. or represents a halogenated alkyl group, provided that at least one of R ¹ , R ² , R ³ and R ⁴ is other than fluorine.

The formulations of the present invention contain the compounds of formula (I) as active ingredients

R ¹ and R ² are each independently halogen, halogenated C 1 -C 4 alkyl, C 1 -C 4 alkoxy, or nitro, provided that when R 1 and R ^{2 are} nitro, the other substituent is not nitro,

R ³ and R ⁴ are each independently hydrogen or C 1-4 alkyl,

R ^{5 is} halogen, nitro, halogenated C 1-4 alkyl, halogenated C 1-4 alkoxy, or -S (O) _n R 10 wherein n is 0, 1 or 2, and

R 10 represents C 1 -C 4 alkyl or halogenated C 1 -C 4 alkyl,

R ^{6 is} halogenated C 1 -C 4 alkyl or -S (O) _n R ¹⁰ wherein n is R ¹⁰ as defined above,

R ^{7 is} hydrogen, halogen, nitro, C 14 alkyl, halogenated C 1-4 alkyl, hydroxyC 1-4 alkyl, C 1-4 alkoxy, formyl or -S (O) R ¹⁰ or -NR ^h R ^{12 is} wherein n and R 10 are as defined above, and

R ¹¹ and R ¹² independently of one another are hydrogen or C 1 -C 4 alkyl,

R ^{8 is} hydrogen, (C 1 -C 4) -alkyl, or -S (O) _n R ¹⁰ or -NR 1 R ¹² where n, R ¹⁰ , R and R ¹² are as defined above, and

R ⁹ is oxygen or sulfur, with the proviso that when R ⁵ represents a trifluoromethyl group, (i) ^R? or R ^{2 is} halogenated C 1 -C 4 alkyl or C 1 -C 4 alkoxy, (ii) R ³ or R ^{4 is C} 1 -C ⁴ alkyl, (iii) R ^{6 is} -S (O) _n R 10 °. (iv) R ^{7 is} nitro, halogenated C 1-4 alkyl, hydroxy (C 1-4 alkyl), C 1-4 alkoxy, formyl or -S (O) _n R 10 or -NRR ¹² ; (v) R ⁸ is other than hydrogen and / or (vi) R ^{9 is} sulfur and provided that at least one of R ¹ , R ² , R ³ and R ⁴ is other than fluorine; when R ^{5 is} chlorine, R ¹ and R ² are both halogen.

In the compounds of formula I, R ¹ , R ² , R ⁵ and R ^{7 as} halogen may be, for example, fluorine, chlorine, bromine or iodine.

The term "alkyl" as used herein includes both straight and branched chain alkyl groups. The same applies to the alkyl chain in halogenated alkyl groups.

R ¹ , R ² , R ⁵ , R ⁶ , R ⁷ and R ^{10 are} halogenated alkyl groups having from 1 to 4 carbon atoms to which one or more halogen atoms, such as chlorine, fluorine, bromine or iodine, are attached. These include di- and trihalomethyl groups (especially trifluoromethyl groups) and pentahaloethyl groups (primarily pentafluoroethyl groups).

Preferably, R ¹ , R ² and R ^{7 are} alkoxy or ethoxy.

The halogenated alkoxy group at R ⁵ and R ^{6 may} be a C 1 -C 4 alkoxy group to which is attached one or more halogen atoms, such as chlorine, fluorine, bromine or iodine.

R ¹ and R ² are preferably a fluorine, chlorine or bromine, nitro, trifluoromethyl or methoxy.

Preferably R ³ and R ⁴ are hydrogen or methyl.

^R5 is preferably iodine, bromine or chlorine atom or a trifluoromethyl, pentafluoroethyl et.il-, trifluoromethyl, methylthio, trifluoromethoxy or methylthio group can represent.

^R6 preferably represent trifluoromethyl or pentafluoro-ethyl.

^R7 is preferably a hydrogen atom, a halogen atom, or can be trifluoromethyl, alkylthio, methylthio or methyl.

Preferably ^{R8 is} hydrogen, methyl, amino or methylthio.

Preferably R ^{9 is} oxygen.

Representative compounds of Formula I are listed in Table I below.

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Serial number of compound r ' R ^J R ³ R ⁴ R ⁵ R ⁶ R ⁷ R ⁸ R ⁹ First cl cl Η ch ₃ cf ₃ cf ₃ Η Η 0 Second cf ₃ from ₂ H II cf ₃ cf ₃ H H 0

HU 206 596 Β

Serial number of compound R ¹ R ² R ³ R ⁴ R ⁵ R ⁶ R ⁷ R ⁸ R ⁹ Third cl cl H H cl cf ₃ H H 0 4th cl cl H H I cf ₃ H H 0 5th cl cl H H from ₂ cf ₃ H H 0 6th cl cl H H Br cf ₃ H H 0 7th cl and ₃ H H cf ₃ cf ₃ H H 0 8 cf ₃ from ₂ H H cf ₃ cf ₃ Br H 0 9th cf ₃ cl H H cf ₃ cf ₃ H H 0 10th cf ₃ cl H H cf ₃ cf ₃ Br H 0 11th CF ₃ Br H H cf ₃ CF ₃ H H 0 12th cf ₃ Br H H cf ₃ cf ₃ Br H 0 13th cl from ₂ H H ocf ₃ cf ₃ H H 0 14th cl cl H H ocf ₃ cf ₃ H H 0 15th cl Br H H ocf ₃ cf ₃ H H 0 16th cl cl H H ocf ₃ cf ₃ Br H 0 17th cl from ₂ H H ocf ₃ C ₂ F ₅ H H 0 18th cl cl H H ocf ₃ C ₂ F ₅ H H 0 19th cl cl H H c ₂ f ₅ c ₂ f ₅ H H 0 20th cl cl H H c ₂ f ₅ c ₂ f ₅ H H 0 21st cl cl H H C ₂ F ₅ cf ₃ Br H 0 22nd cl cl H H C ₂ F _s C ₂ F ₅ Br H 0 23rd cl cl H H cf ₃ cf ₃ H sch ₃ 0 24th cl cl H H cf ₃ cf ₃ H soch ₃ 0 25th cl cl H H cf ₃ cf ₃ H so ₂ ch ₃ 0 26th cl cl H H cf ₃ cf ₃ H nh ₂ 0 27th cl cl H H cf ₃ cf ₃ H nhch ₃ 0 28th cl cl H H cf ₃ cf ₃ H N (CH ₃ ) ₂ 0 29th cl cl H H cf ₃ cf ₃ H ch ₃ 0 30th cl cl H H cf ₃ cf ₃ sch ₃ H 0 31st cl from ₂ H H cf ₃ cf ₃ sch ₃ H 0 32nd cl from ₂ H H cf ₃ cf ₃ soch ₃ H 33rd cl cl H H cf ₃ cf ₃ so ₂ ch ₃ H 0 34th cl from ₂ H H cf ₃ cf ₃ scf ₃ H 0 35th cl from ₂ H H CF ₃ cf ₃ CHO H 0 36th cl cl H H cf ₃ cf ₃ OC ₂ H ₅ H 0 37th cl from ₂ H H cf ₃ cf ₃ och ₂ ch ₃ H 0 38th cl from ₂ H H cf ₃ cf ₃ chf ₂ H 0 39th cl cl H H cf ₃ cf ₃ ch ₃ H 0 40th cl from ₂ H H cf ₃ cf ₃ ch ₃ H 0 41st cl cl H H cf ₃ cf ₃ nh ₂ H 0 42nd cl from ₂ H H cf ₃ cf ₃ from ₂ H 0 43rd cl cl H H scf ₃ cf ₃ H H 0 44th cl cl H H sch ₃ cf ₃ H H 0

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Serial number of compound R ¹ R ² R ³ R ⁴ R ³ R ⁶ R ⁷ R ⁸ R ⁹ 45th cl NO ₂ H H CF ₃ cf ₃ CH ₂ OH H 0 46th cl cl H H cf ₃ cf ₃ CH (CH ₃ ) OH H 0 47th cl cl H H cf ₃ cf ₃ H H s 48th cl NO ₂ H H CF3 cf ₃ CH (CH ₃ ) F H 0 49th cl Br H H OCF 3 c ₂ f ₅ H H 0

Table IA lists compounds of formula I wherein R ³ and R ^{4 are} hydrogen.

Table IA

Serial number of compound R ¹ R ² R ⁵ R ⁶ R ⁷ R ^s R ⁹ 50th from ₂ cf ₃ from ₂ cf ₃ H H 0 51st from ₂ H ocf ₃ CF ₃ H H 0 52nd cl from ₂ cf ₃ soch ₃ H H 0 53rd cl from ₂ cf ₃ so ₂ ch ₃ H H 0 55th cl from ₂ cf ₃ cf ₃ and ₃ H 0 56th cl cl from ₂ c ₂ f ₅ H H 0 57th cl cl SOCH ₃ cf ₃ H H 0 58th cl cl 1 c ₂ f ₅ H H 0 59th cl cl scf ₃ c ₂ f ₅ H H 0 60th cl from ₂ cf ₃ cf ₃ nh ₂ H 0 61st cl cl scf ₃ C ₂ F ₅ Br H 0 62nd cl cl scf ₃ cf ₃ scf ₃ H 0 63rd cl cl cf ₃ cf ₃ and ₃ H 0 64th cl from ₂ cf ₃ cf ₃ chci ₂ H 0 65th cl cl SOCF3 C ₂ F _s H H 0 66th cl cl ocf ₃ C ₂ F ₅ Br H 0 67th cl cl cf ₃ cf ₃ scf ₃ H 0 68 cl cl scf ₃ cf ₃ Br H 0 69th cl cl scf ₃ cf ₃ and ₃ H 0 70th cl cl scf ₃ cf ₃ sch ₃ H 0 71st cl cl scf ₃ cf ₃ scf ₃ H 0 72nd cl cl socf ₃ cf ₃ H H 0 73rd cl cl so ₂ cf ₃ c ₂ f ₅ H H 0 74th cl cl so ₂ cf ₃ cf ₃ H H 0 75th cl from ₂ I cf ₃ H H 0 76th cl cl socf ₃ cf ₃ Br H 0 77th cl from ₂ scf ₃ cf ₃ H H 0 78th cl cl cf ₃ c ₂ f ₅ H H s 79th Br cl scf ₃ cf ₃ H H 0

For the physical constants of the compounds listed in Table IA, the chemical shift values are given in Table IB. Nuclear Magnetic Resonance Spectrum (NMR) spectra at 60 ppm.

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HU 206 596 Β

Table IB

Serial number of compound Mp. (° C) NMR psrectum needles 50th 179 to 180.5 9.25 (1H, s), 9.0 (1H, d), 8.1 (1H, s), 6.95 (1H, s) 51st 145-148 8.25 (1H, s), 8.1 (1H, d), 8.13 (1H, s), 7.32 (1H, d) 52nd 178-180 8.43 (1H, s), 8.21 (1H, s), 7.32 (1H, d) 53rd 163-164.5 8.41 (1H, s), 8.20 (1H, s), 8.00 (1H, s), 2.94 (3H, s) 55th 114.1 to 115.2 8.45 (1H, s), 8.20 (1H, s), 7.85 (1H, s), 4.05 (3H, s) 56th 115 to 115.4 8.40 (2H, s), 8.00 (1H, s), 7.05 (1H, s) 57th 165 to 165.9 8.00 (1H, s), 7.9 (1H, s), 7.75 (1H, s), 7.0 (1H, s), 2.85 (3H, s) 58th 132.1 to 133 7.90 (2H, s), 8.00 (1H, s), 7.00 (1H, s) 59th 154.5 to 156.2 7.85 (2H, s), 8.00 (1H, s), 7.05 (1H, s) 60th 184.4 to 185.9 8.40 (1H, s), 5.0 (2H, broad s), 8.20 (1H, s), 7.50 (1H, s) 61st 100.4 to 102.4 7.85 (2H, s), 7.95 (1H, s) 62nd 88.6 to 90.0 7.85 (2H, s), 8.10 (1H, s) 63rd 116.4 to 118 7.83 (2H, s), 7.75 (1H, s), 4.10 (3H, s) 64th 172.6 to 174 8.50 (1H, d), 8.23 (1H, d), 8.17 (1H, s), 7.0 (1H, s) 65th 153.4 to 154.8 7.95 (2H, dd), 8.05 (1H, s), 7.05 (1H, s) 66th 129.2 to 129.7 7.9 (1H, s), 7.45 (2H, s) 67th 137.4 to 139 7.84 (2H, s), 8.12 (1H, s) 68th 135.8 to 136.6 7.84 (2H, s), 7.97 (1H, s) 69th 76 to 77.4 7.85 (2H, s), 7.75 (1H, s), 4.10 (3H, s) 70th 72.2 to 74.2 7.84 (2H, s), 7.93 (1H.s), 2.55 (3H, s) 71st 108.4 to 110.4 7.85 (2H, s), 8.13 (1H, s) 72nd 145.8 to 147.2 7.90 (1H, s), 8.00 (1H, s), 8.05 (1H, s), 7.00 (1H, s) 73rd 186 to 187.6 8.20 (2H, s), 8.00 (1H, s), 7.07 (1H, s) 74th 136.8 to 139.0 8.20 (2H, s), 8.00 (1H, s), 7.03 (1H, s) 75th 157-159 8.28 (1H, d), 8.09 (1H, s), 6.93 (1H, s) 76th 200.5 to 202.6 7.92 (2H, s), 7.85 (1H, s) 77th 120.2 to 121.8 8.41 (1H, s), 8.20 (1H, s), 8.12 (1H, s), 6.95 (1H, s) 78th 101.7 to 102.8 8.0 (1H, s), 7.8 (2H, s), 7.75 (1H.s) 79th 119 to 121.2 7.87 (1H, s), 7.99 (1H, s), 8.01 (1H, s), 7.00 (1H, s)

The compounds of formula (I) wherein R ⁸ is hydrogen are prepared according to the invention by reacting a compound of formula (II) wherein R ', R ² , R ³ , R ⁴ and R ⁵ are as defined above, R ¹³ is a leaving group - (III) with a compound of the formula: - wherein ^{R6, R7} and ^R9 are as defined above and ^R8 is H -, or (d) converting the resulting product of the ^R'-R7 substituents other converting R'to R ⁷ substituent and / or (ii) the compounds having oxygen in place ^R9

R ⁹ is converted to compounds containing sulfur.

The reaction is preferably carried out in the presence of a solvent and a base. The base used is, for example, an alkali metal hydride, an alkali metal alkoxide or an alkali metal carbonate, and the solvent used is a hydrocarbon solvent (such as petroleum ether or toluene), an ether (such as tetrahydrofuran) or a polar aprotic solvent (such as dimethylformamide or dimethylacetamide). Ether-bonded compounds such as diglyme may also be used as the solvent.

R @ ³ leaving group may be, for example, trifluoromethylsulfonyloxy or methylsulfonyloxy or halogen (such as fluorine, chlorine, bromine or iodine).

Depending on the nature of the R ¹³ group, a catalyst such as crown ether, copper or potassium fluoride may be added if necessary.

R'-R ⁸ substituent may be converted by known methods into other R 'substituents at ^R8 and ^R9 is composed is an oxygen atom may also be replaced with a sulfur atom by known methods. For example, compounds of formula (I), wherein ^{R1, R2, R5, R6} and / or ^R7 is nitro, can be converted to the corresponding R ^1, R ^2, R ^s, R ^6, and / or R ^{7 to} halogen to reduce nitro groups, and then the resulting compounds of formula IV wherein R ³ , R ⁴ , R ⁸ and R ⁹ are as defined above and R ¹ ', R ² ', R ⁵ ' , R ⁶ 'and R ⁷ ' or R *, R ² , R ⁵ , R ⁶ or R ⁷ as defined above, but at least one of them represents an amino group - the amino group or groups thereof are replaced by halogen.

Some of the compounds of formula IV are novel.

The nitro group of the compounds of formula I can be reduced, for example, with stannous chloride in the presence of an acid such as concentrated aqueous hydrochloric acid. Reducing iron powder may also be used as a reducing agent in the presence of a hydroxyl-containing solvent (such as isopropanol) and an acidic catalyst such as hydrochloric acid. The reaction is usually carried out at a moderate temperature (2 ° C to 90 ° C).

The amino group may be exchanged for a halogen by reacting the amino compound with a metal halide such as copper (I) iodide in the presence of a diazotizing agent such as tert-butyl nitrite. The reaction is usually carried out in the presence of an organic solvent (such as acetonitrile) at a low temperature (-20 ° C to + 20 ° C), preferably at about 0 ° C.

HU 206 596 Β

Compounds of formula (I) wherein R ¹ or R ^{2 represents a} nitro group and R ⁹ represents an oxygen atom and the other substituent has the meanings given above may be converted to the corresponding R ¹ or R ² substituents by polarization. in a solvent such as diglime with an alkali metal halide such as lithium chloride.

Compounds of formula (I) wherein R ⁷ is hydrogen may be converted to derivatives of R ⁷ where halogen is known. For example, compounds of formula I wherein R ⁷ is hydrogen may be brominated in an acetic acid medium, preferably in the presence of a base such as sodium acetate. Compounds of formula (I) wherein R ⁷ is hydrogen may be converted to the corresponding nitro compounds by reaction with nitrating agents such as nitronium tetrafluoroborate. The reaction is carried out in the presence of a polar solvent such as acetonitrile or sulfolane.

Compounds of formula (I), (II) or (III) wherein R ⁵ -R ⁸ substituent to any SR is ¹⁰ radical, an oxidizing agent such as m-chloroperbenzoic acid with the appropriate R ⁵ R ⁸ site Can be converted to derivatives containing the formula -SOR ¹⁰ or -SO ₂ R ¹⁰ .

Compounds of formula (I) or (III) wherein R ⁷ is formyl or 1-hydroxyalkyl are reacted with diethylamino-sulfur trifluoride to form the corresponding difluoromethyl or I-fluoroalkyl R ⁷ containing derivatives.

^R5 or ^R7 is appropriate compound of formula (I) containing trifluoromethyl-thio group can be prepared from the corresponding halides - preferably the derivatives containing iodo ^R5 or ^R7 place - with trifluoroacetic methylthio-copper .

The compounds of formula (I) ^R9 is oxygen XXXV by reaction with a reagent such as phosphorus pentasulfide or Lawesson's reagent can be converted to the corresponding derivatives containing sulfur, R ⁹ is appropriate.

The reaction is preferably carried out at the boiling point of the mixture.

R ¹ and R ^{2 are} halogen, R ³ and R ^{4 are} hydrogen or methyl, R ⁵ is halogen, halogenated alkyl, halogenated alkoxy or -S (O) _n R '°, R ⁶ is halogenated alkyl, R Compounds of formula (I) wherein R ⁷ is hydrogen or alkyl, R ⁸ is alkyl, and R ⁹ is oxygen may be prepared by a preferred method by preparing the corresponding compounds of formula I wherein R * -R ⁷ are as defined herein. and R ^{8 is} hydrogen, in the presence of a hydroxyl-containing solvent such as methanol or ethanol, conveniently at room temperature to 80 ° C, with lower dialkylamines, and the resulting compounds of formula VI, wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ and R ^{9 are} the groups listed in this paragraph means an acylating agent. Acylating agents are, for example, acid chlorides, acid anhydrides or reactive esters. The reaction is carried out in the presence of a base such as a tertiary alkylamine such as triethylamine in an inert solvent such as toluene, dimethylformamide or dichloromethane. Instead of R ⁸ , the acylating grains used are compounds of the formula I having an appropriate group. The acylation is usually carried out at a temperature of 0 ° C to 30 ° C. Otherwise, the acylated compound of formula (VI) may spontaneously ring in the reaction mixture; however, the ring closure may also be facilitated by the addition of a catalytic amount of an organic or inorganic acid such as p-toluenesulfonic acid or hydrochloric acid or sulfuric acid. In the products thus obtained, the hydrogen atom of R ⁷ may optionally be replaced by a halogen atom and / or the oxygen atom of R ⁹ may optionally be replaced by a sulfur atom.

Compounds of formula (I) wherein R ¹ and R ^{2 are} halogen, R ³ and R ^{4 are} hydrogen or methyl, R ^{5 is} halogen, halogenated alkyl, halogenated alkoxy or -S (O) _n R ¹⁰ are R ⁶ a halogenated alkyl group, R ^{7 is} hydrogen, R ^{8 is} alkylthio and R ^{9 is} oxygen, and in a preferred method, the compounds of formula (VII) wherein R ¹ , R ² , R ³ , R ⁴ and R ⁷ may be prepared ⁵ is reacted with compounds of formula VIII given in this paragraph wherein R ⁶ is as defined in this paragraph. The reaction is carried out in the presence of a base such as a metal hydride such as sodium or potassium hydride and a dipolar aprotic solvent such as dimethylformamide, dimethyl sulfoxide or N-methylpyrrolidone. The reaction is usually carried out at a temperature between 0 ° C and room temperature. The resulting product can be converted in a known manner into the corresponding R ⁷ derivatives containing halogen.

The starting materials of formulas VII and VIII may be prepared by known methods.

Compounds of formula I wherein R ¹ and R ^{2 are} halogen, R ³ and R ^{4 are} hydrogen or methyl, R ^{5 is} halogen, halogenated alkyl, halogenated alkoxy or -S (O) ₂ R ¹⁰ are R ⁶ a halogenated alkyl group, R ^{7 is} hydrogen or halogen, and R ^{8 is} alkylsulfonyl; it is also possible to prepare, by a preferred method, the corresponding compounds of formula I wherein R ^{8 is} alkylthio and the other substituents are in the presence of a halogenated solvent such as chloroform, carbon tetrachloride or dichloromethane as defined in this paragraph, with an oxidizing agent such as m-chloroperbenzoic acid. During the reaction of compounds of formula (I) wherein the corresponding R ^s site alkylsulfinyl groups are formed as intermediates, and in an appropriate amount of oxidizing agent is separated by known methods.

Compounds of formula I wherein R ⁸ is -NR ¹¹ R ¹²

It is also possible to prepare the corresponding compounds of formula (I) containing an alkylsulfonyl group in the presence of R ⁸ in the presence of a solvent containing a hydroxyl group, such as tert-butanol, usually at 0-80 ° C with the appropriate nucleophilic reagent. such as ammonia or primary or secondary alkylamine (such as dimethylamine or methylamine).

Some of the compounds of formula (Π) and (III) are known, but others are novel. These novel compounds can be prepared by conventional methods from known starting materials. These compounds, if desired, the R * -R ⁸ groups converted to other groups by R'-R ⁸ before Linking (Π) and (ΠΙ) compounds. Transformations may occasionally lead to new intermediates; for example, new amino compounds formed by the conversion of the nitro group to a halogen atom. ^R'-R8 substituents are preferably replaced with each other as described previously, the compounds of formula (I), conversion of other methods ^R'-R8 substituents.

The novel compounds of the formula II are as follows:

6-nitro-2,4-bis (trifluoromethyl) bromobenzene,

2-chloro-4- (trifluoromethoxy) -6-nitroaniline,

3.4-dichloro-5-nitro-trifluoromethoxy-benzene,

3-chloro-4-fluoro-5-nitro-trifluoromethoxy-benzene,

3.5-Dichloro-4-fluoro-pentafluoroethylbenzene.

The preparation of these compounds is described in the following sections.

New compounds of formula (III) are those wherein R ^{7 is} alkyl, -S (O) _n R ¹⁰ , alkoxy, formyl or hydroxyalkyl, R ^{8 is} hydrogen, R ^{9 is} oxygen, and R ^{6 is} halogenated alkyl. means.

The compounds of formula (III) may be prepared by known organic chemical methods. For example, we can

a) For the preparation of compounds of formula III wherein R ⁸ is hydrogen, compounds of formula IX wherein R ⁶ and R ⁷ are as defined above are reacted with thiourea or S-alkylisothiourea and the resulting compound of formula (X) is obtained. the sulfur atom of a compound of the formula wherein R ⁶ and R ⁷ are as defined above is cleaved with Raney nickel; obsession

b) condensing the compounds of formula IX with formamidine to form compounds of formula III wherein R ⁸ is hydrogen; obsession

c) halogenation of the corresponding 4 (R ⁶ ) -pyrimidin-6-ones, where R ⁶ is as defined above, to produce compounds of formula (III) wherein R ⁸ is hydrogen;

5-halo-4- (R ⁶ ) -pyrimidin-6-ones (i) for the preparation of compounds of formula III wherein R ⁷ is alkoxy in a pyridine solvent, the corresponding alcohol (such as methanol or ethanol) and copper (I) iodide. in the presence of a metal alkoxide such as sodium alkoxide; or (ii) for the preparation of compounds of formula III wherein R ⁷ is formyl or -SR ^{10 in the} presence of a solvent such as tetrahydrofuran, sodium hydride followed by an alkyl lithium compound (such as tertiary butyl lithium) and the corresponding electrophilic compound (such as dimethylformamide or dialkyl disulfide).

If desired, compounds of formula (III) wherein R ⁷ is formyl may be reacted with a reducing agent (e.g., sodium borohydride) or Grignard reagent to give the corresponding compound of formula (ΙΠ) wherein R ⁷ is 1-hydroxyalkyl.

Compounds of formula (III) wherein R ⁸ is hydrogen may also be prepared by reacting compounds of formula (XI) wherein R ⁶ and R ⁷ are as defined above, R ^{9 is} oxygen and R ^{14 is} hydrogen or C 1 -C 4 alkyl. ethyl acetate) is treated with Raney nickel in the presence of a suitable solvent such as aqueous ammonia.

Compounds of formula (XI) are known or may be prepared by known methods from known starting materials, such as those described in J. Am. Chem. Soc., 80, 5744 (1958).

The compounds of formula I are useful for controlling insect pests and other invertebrate pests such as mites. For example, insect and acaricides that can be controlled by compounds of the formula I are harmful in agriculture (including food crops, fiber crops, horticulture and animal husbandry), forestry, and storage of plant products (such as fruits, seeds and tubers). insects and mites, and pests that transmit diseases to humans and animals.

The compounds of formula (I) are applied in the form of compositions to the area to be treated. The compositions contain, in addition to the active ingredient (s) of the formula (I), suitable inert diluents or carriers and / or surfactants. Other pesticidal agents, such as other insecticidal or acaricidal agents, fungicidal agents or insecticidal agents (such as dodecylimidazole, safroxane or piperonyl butoxide) may also be incorporated into the compositions.

The compositions may be, for example, solid compositions which may be applied directly (undiluted) or after dilution.

The undiluted solid compositions may be, for example, dusts, which may contain, in addition to the active ingredient, a solid diluent or carrier, such as kaolin, bentonite, silica gel, silica or talc. Another class of solid compositions are granules, which contain the active ingredient in a state as impregnated on a non-porous particulate material (such as calcium carbonate) or impregnated on a porous particulate material (such as pumice or gypsum).

Solid formulations which may be applied after dilution may be wettable powder formulations which, apart from the active ingredient and solid carriers or diluents (e.g. kaolinone, silica gel or silica)

They also contain a surfactant. Formulations which can be applied after dilution include water-dispersible granules, which are prepared by mixing the active ingredient with a solid carrier or diluent (such as kaolin, silica gel or silica) and a surfactant, and granulating the mixture.

The compositions may also be in the form of liquid preparations which will normally need to be diluted prior to use. Liquid compositions may be, for example, brushes, sprays, aerosol dispersions or non-aqueous solutions of the active ingredient.

Aqueous dispersions of the active compounds, which are usually diluted prior to application, may be, for example, suspension concentrates which contain the active ingredient dispersed in an aqueous medium. These compositions contain dispersing or wetting agents and one or more stabilizers, such as bentonite clay and / or polysaccharide gels. Other excipients such as antifreeze agents (e.g. ethylene glycol, propylene glycol or salts) and biocides (such as Proxel GXL (1,2-benzisothiazolin-3-one)) may also be added to the suspension concentrates.

Aqueous dispersions of the active compounds may also be in the form of microcapsule suspensions. In preparing these, the active ingredient is encapsulated in a polymer in the form of a water-immiscible high-drug solution, and the resulting microcapsules are dispersed in an aqueous medium. Microencapsulation can be carried out according to the methods described in the patent literature. These compositions also contain dispersing and / or wetting agents and one or more stabilizers, such as bentonite clay and / or polysaccharide gels. Other excipients such as antifreeze and biocides may be added to the compositions.

Aqueous dispersions of the active compounds may also be in the form of oil-in-water emulsions. In preparing these, the active ingredient is dissolved in a suitable solvent, such as an aromatic hydrocarbon (such as trimethylbenzene) or a ketone solvent (such as dihydroisophorone), optionally in the presence of one or more emulsifiers, and the resulting solution is emulsified in water. Optionally, the water may also contain a surfactant. As the organic solvent, ethylene dichloride, toluene, kerosene, white oil, methylnaphthalene, xylenes, trichlorethylene, vegetable oils, N-methyl-2-pyrrolidone and isophorone may also be used.

Liquid compositions may also be non-aqueous solutions which are used, immediately or after dilution, as a spray or aerosol mist formulation.

Non-aqueous formulations which can be used undiluted may be in a small volume or a very small volume of concentrate containing the active ingredient dissolved in a suitable solvent or solvent mixture such as an aromatic hydrocarbon (e.g. trimethylbenzene) or an aliphatic hydrocarbon (e.g. kerosene). In addition to the above, organic solvents include isophorone, dihydroisophorone, toluene, xylenes, methylnaphthalenes, N-methylpyrrolidone, petroleum oils and vegetable oils. These compositions may optionally be diluted with paraffinic solvents such as diesel before use.

Non-aqueous formulations may also be emulsifiable concentrates containing the active ingredient dissolved in a suitable solvent, such as trimethylbenzene or methylcyclohexanone, together with one or more emulsifiers. Non-aqueous solvents listed above may also be used as solvents. These formulations are diluted with water before use and applied as an aqueous dispersion to the area to be treated.

For specific purposes, aerosols may be prepared which contain, in addition to the active ingredient (s), a propellant and an inert diluent, for example odorless kerosene or alkylbenzenes. The aerosol formulations preferably contain from 0.001 to 4% by weight of active ingredient. The remainder of the composition also contains an aqueous base (the aqueous component is dispersed in a solution of the active ingredient as described above), a propellant and one or more surfactants. Aerosol formulations may optionally contain other additives such as articulating agents, adjuvants, fragrances, and corrosion inhibitors.

The compositions may also be in the form of a directly applied spray liquid containing the active ingredient dissolved in a solvent such as odorless kerosene or alkylbenzene. The formulation is sprayed onto the area to be treated using a high-power pump, utilizing the residual effect. These formulations may optionally contain other additives such as disintegrating agents, adjuvants and perfumes.

Wetting agents, dispersing agents and emulsifying agents can be cationic, anionic or nonionic.

Examples of cationic surfactants include quaternary ammonium compounds such as cetyltrimethylammonium bromide. Examples of anionic surfactants include soaps, aliphatic sulfuric acid monoester salts (such as sodium lauryl sulfate), and salts of sulfonated aromatic compounds (such as sodium dodecylbenzene sulfonate, sodium, calcium, and ammonium lignin sulfonate, and sulfonate, and a mixture of sodium di- and triisopropylnaphthalene sulfonate). Nonionic surfactants include, for example, condensation products of ethylene oxide fatty alcohols (such as oleyl alcohol or cetyl alcohol) or alkyl phenols (such as octylphenol, nonylphenol and octylcresol), long chain fatty acids and hexite derivatized partial esters, condensation products of the latter partial esters with ethylene oxide, and lecithins.

Formulations for use in the form of aqueous dispersions or emulsions are usually marketed in the form of concentrates of high active ingredient which are diluted with water to the desired final concentration before use. Concrete tracts1

The most commonly required requirement for EN 206596 is that they can be stored unchanged for extended periods of time and, after prolonged storage, dilute with water to form an aqueous formulation that remains homogeneous for a period of time sufficient to be applied by conventional spraying equipment. by weight. The active ingredient content of ready-to-use dilute aqueous compositions may vary depending on the intended use. For agricultural or horticultural use, formulations containing from 0.01 to 0.1% by weight of active ingredient (corresponding to application rates of 500 to 2000 g of active ingredient / ha) are particularly preferred.

During the treatment, the compositions are applied to insects, to insects, or to insects, or to growth plants exposed to infection, by known means, such as dusting or spraying.

The compositions of the invention may optionally be combined with one or more active ingredients, such as an insecticide, insecticide, herbicide, fungicide or plant growth regulator. Preferably, further active ingredients are added to the compositions which increase the spectrum of activity of the active compounds of formula (I) or enhance the persistence of the active compounds in the treated area. The additional active ingredients may enhance the activity of the compounds of the formula I or may supplement their activity, for example, by accelerating the action, increasing the partitioning effect or suppressing the repellency of the pests. The use of multi-component mixtures can also prevent or reduce resistance to the individual components.

The additional insecticidal, herbicidal or fungicidal active ingredient to be added to the composition is selected according to the purpose of use and the additional effect desired.

For example, the following additional insecticidal agents may be incorporated into the compositions:

(a) pyrethroids such as permethrin, esfenvalerate, deltamethrin, cyhalothrin (primarily lambda-cyhalothrin), bifenthrin, fenpropathrin, cyfluthrin, tefluthrin, fish-safe pyrethroids (such as etofenprox), natural pyrethrin, bioethanol, tetramethrin, s ) (lR, 3S) -2,2-dimethyl-3- (oxo-oxothiolan-3-ylidene-methyl) -cyclopropane-carboxylic acid-5-benzyl-3-furylmethyl ester;

b) organic phosphates such as profenophos, sulprophos, methyl parathion, azinphos-methyl, demeton-s-methyl, heptenophos, thiomethone, fenamiphos, monocrotophos, profenophos, triazophos, methamidophos, dimethoate, phosphamidon, malathion, chlorpyrifos, phonophos, phorate, oxime, primiphos-methyl, phenitrothion and diazinon;

c) carbamates including aryl carbamates such as primicarb, cloethocarb, carbofuran, etiofencarb, aldicarb, thiofurox, carbosulfan, beniocarb, phenobucarb, propoxur and oxamyl;

d) benzoyl ureas such as triflumerone and chlorofluazuron;

(e) organotin compounds such as cihexatin, fenbutatin oxide and azocyclotin;

f) macrolides such as avermectins and milbemins (e.g. abamectin, avermectin and milbemycin);

g) hormones such as pheromones;

h) organic chlorine compounds such as benzene hexachloride, DDT, chlordane and dieldrin;

(i) amidines such as chlordimeform and amitraz.

In addition to the insecticidal active ingredients of the main chemical groups listed, other specific insecticidal active ingredients may be incorporated into the compositions, depending on the intended use. These include, for example, selective insecticidal agents for the treatment of particular crops, such as stalk beetles (such as cartap or buprofezin) for use in the treatment of rice. Other insecticidal agents that are specific to the insect species or to the developmental insects that are present in the compositions, such as ovolarvicidal agents (such as clofentezine, flubenzimine, hexithiazoxote and tetradifon), motilicide agents (such as dicofol or propargitol), regulatory agents (such as hydramethylone, cyromazine, methoprene, chlorofluazuron and diflubenzuron) may also be mixed.

Insecticidal additives such as piperonyl butoxide, sesamex and dodecylimidazole may be added to the compositions.

Depending on the purpose of the treatment and the effect desired, the compositions may be mixed with herbicidal, fungicidal and plant growth regulating agents. As a rice-selective herbicidal agent, for example, propanil, as a plant growth regulator for cotton, e.g., Pix, and as a rice fungicide, for example, blasticides (such as blasticidin-S) may be incorporated.

The ratio of the active ingredient of formula (I) to the other active ingredient in the compositions may vary depending on the purpose of the treatment, the effect desired and other factors. However, the additional active ingredient is usually included in the formulation in the same amount as if it were used as the sole active ingredient; In case of synergism ^- but somewhat smaller volume is sufficient.

The formulations containing the compounds of formula I are effective against a wide variety of insects and other invertebrate pests. The compositions are particularly useful for controlling insects, such as flies and cockroaches, which endanger public health. The compositions may also be effective against organic phosphate and pyrethroid resistant strains of pests, such as Musca domestica. The formulations may be effective against susceptible and resistant pests at any stage of development (adult, larval, and transient). In animal husbandry, the compositions may be administered orally or parenterally to the infected host animals or may be used for topical treatment.

HU 206 596 Β

The invention is further illustrated by the following non-limiting examples. The preparation of starting materials in the specifications and the preparation of the final products are described in the examples.

The NMR spectra were recorded at a frequency of 270 MHz on a Jeol GSX spectrophotometer CDC ₃ in one or in _DMSOd6. Chemical shift values are given on a delta scale, in ppm. Mass spectra were recorded on a VG TRIO 1 spectrometer.

PREPARATION 1 Preparation of 1- (4-Amino-2,6-dichlorophenyl) -4- (trifluoromethyl) pyrimidin-6-one

To a suspension of tin (II) chloride (4.46 g) in concentrated aqueous hydrochloric acid (50 ml) was stirred at room temperature in one portion 2.0 g of 1- (2,6-dichloro-4-nitrophenyl) -4- (trifluoromethyl) ) -pyrimidin-6-one is added. After 6.5 hours, the reaction mixture was poured into ice water, basified with aqueous sodium hydroxide solution and extracted with ethyl acetate. The organic extracts were combined, dried over magnesium sulfate, filtered and the solvent was evaporated under reduced pressure. 1.41 g of 1- (4-amino-2,6-dichlorophenyl) -4-trifluoromethyl-pyrimidin-6-one are obtained; the yellow oily material solidifies on standing. The product melts at 156-159 ° C.

NMR (CDC1 _3): 8.03 (IH, s), 6.96 (IH, s), 6.75 (lH, .s), 4.90 (2H, br s).

Order 2

Preparation of 3,4,5-trichlorobenzonitrile

A solution of 5 g of 4-amino-3,5-dichlorobenzonitrile in 30 ml of anhydrous acetonitrile is added dropwise to a suspension of 4.3 g of copper (H) chloride and 6.95 g of tert-butyl nitrite in 90 ml of anhydrous acetonitrile. The mixture was maintained at 0-5 ° C during the addition of the reagent.

After the addition of the reagent, the mixture was stirred for an additional hour at 5 ° C and then allowed to warm slowly to room temperature.

After a further 2 hours, the reaction mixture was poured into dilute aqueous hydrochloric acid and extracted with ethyl acetate. The extracts were combined, washed with water and brine, dried over anhydrous magnesium sulfate, filtered, and the solvent was evaporated under reduced pressure. The resulting orange-red solid was ethyl acetate and petroleum ether (b.p. 60-80 ° C) 1; It is recrystallized from a 1% v / v mixture. 3,4,5-trichlorobenzonitrile is obtained.

Delta H NMR (CDC1 _3): 7.68 (s).

Inscription 3

4-Fluoro-3,5-dichloro-benzonitrile. production

A mixture of 2.11 g of anhydrous potassium fluoride, a catalytic amount of 18-crown-6.9 ml of anhydrous dimethylformamide and 33 ml of anhydrous toluene was removed and 35 ml of distillate were removed. The residue was cooled and 3.76 g of 3,4,5-trichlorobenzonitrile was added. The resulting solution was stirred at 140 ° C for 4 days. The mixture was cooled to room temperature, filtered, and the filter cake was washed with ethyl acetate. A brown solid is obtained

2: 1 by weight mixture of 3,4,5-trichlorobenzonitrile and 4-fluoro-3,5-dichlorobenzonitrile. This material was used without further purification.

NMR (CDC1 _3): 7.69 (4.3 H, s), 7.67 (2/3 H, d).

Inscription 4

Preparation of 6-nitro-2,4-bis (trifluoromethyl) bromobenzene To a solution of 2,4-bis (trifluoromethyl) bromobenzene in 48 ml of concentrated sulfuric acid, carefully add 2.6 ml of concentrated nitric acid and the mixture was heated at 80 ° C for 6 hours. The mixture was cooled to room temperature, allowed to stand overnight, then poured carefully onto ice and extracted with ethyl acetate. The organic extracts were combined, washed with water and brine, dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. 6-Nitro-2,4-bis (trifluoromethyl) bromobenzene is obtained as a yellow liquid.

NMR (CDC1 _3): 8.12 (IH, s), 8.08 (IH, s).

The NMR spectrum indicated that the product contained a small amount of the starting 2,4-bis (trifluoromethyl) bromobenzene as impurity, which was removed in the next step.

Inscription 5

Preparation of 1- [2-Amino-4,6-bis (trifluoromethyl) phenyl] -4- (trifluoromethyl) pyrimidin-6-one

1.5 g of 1- [2-nitro-4,6-bis (trifluoromethyl) phenyl] -4-trifluoromethyl-pyrimidin-6-one (Compound 2 in Table 1) in 12 ml of isopropanol and 2 ml of water are added 0.21 g of reduced iron powder. To the mixture was added 1 drop of concentrated hydrochloric acid, allowed to stand for 16 hours and then held at 80 ° C for 1 hour. The mixture was cooled to room temperature, allowed to stand for 2 days, then filtered through celite and the filter cake washed with ethyl acetate. The filtrate was concentrated under reduced pressure. The resulting viscous brown oil was chromatographed on a silica gel column using 30% ethyl acetate in petroleum ether (b.p. 60-80 ° C) as eluent. The appropriate fractions were further chromatographed; 20 volumes' #? petroleum ether containing diethyl ether (b.p. 60-80 ° C) was eluted with ethyl acetate. 1- [2-Amino-4,6-bis (trifluoromethyl) phenyl] -4- (trifluoromethyl) pyrimidin-6-one is obtained.

NMR (CDC1 _3): 8.05 (IH, s), 7.45 (IH, s), 7.38 (IH, s), 7.00 (IH, s), 4.15 (2H, s).

Order 6

Preparation of 2-chloro-4- (trifluoromethoxy) -6-nitroaniline

Chlorine gas was passed through a solution of 14.5 g of 2-nitro-4- (trifluoromethoxy) aniline in 175 ml of carbon tetrachloride. The reaction mixture solidifies; another 50 ml of carbon tetrachloride was added to the stirred mixture. All the chlorine gas1

The mixture was passed through the mixture until thin layer chromatography (adsorbent: silica gel, eluent: petroleum ether, 30% v / v ethyl acetate (b.p. 60-80 ° C)) showed the starting material. The gas supply is then stopped and the solvent is evaporated under reduced pressure. The resulting dark orange solid was triturated with petroleum ether (b.p. 60-80 ° C). 2-Chloro-4- (trifluoromethoxy) -6-nitroaniline was obtained as an orange solid.

NMR (CDC1 ₃₎ 8.04 (IH, d), 7.49 (IH, d), 6.60 (2H, bs).

Inscription 7

Preparation of 3,4-dichloro-5-ni.tro-trifluoromethoxy-benzene

This compound was prepared from 2-chloro-4- (trifluoromethoxy) -6-nitroaniline as described in Preparation 2. The product was distilled under reduced pressure through a balloon (0.25 mm Hg, 80 ° C).

NMR (CDCl3 ₎ . 7.60 (fine

d).

Inscription 8

Preparation of 3-Chloro-4-fluoro-5-nitro-trifluoromethoxy-benzene

This compound was prepared from 3,4-dichloro-5-nitro-trifluoromethoxy-benzene according to the procedure described in Preparation 3. The crude product was distilled through a balloon under reduced pressure (15 mm Hg, 125 ° C). The resulting product, which contains little impurity starting material, is used without further purification.

Electron Collision m / e: 259/261 (M ⁺ )

PREPARATION 9 Preparation of 1- [2-Amino-6-chloro-4- (trifluoromethoxy) phenyl] -4- (trifluoromethyl) pyrimidin-6-one

This compound was prepared from 1- [2-chloro-6-nitro-4- (trifluoromethoxy) phenyl] -4-trifluoromethylpyrimidin-6-one according to the procedure described in Preparation 5 (Table I). (Compound 13)).

NMR (CDC1 _3): 8.04 (IH, s), 7.00 (IH, s), 6.85 (IH, fine d), 6.66 (IH, fine d), 4.00 ( 2H, broad s).

PREPARATION 10 Preparation of 1- [2-Amino-6-chloro-4- (trifluoromethoxy) phenyl] -4- (pentafluoroethyl) pyrimidin-6-one

This compound was prepared from 1- [2-chloro-6-nitro-4- (trifluoromethoxy) phenyl] 4- (pentafluoroethyl) pyrimidin-6-one according to the procedure described in Preparation 5 (Table I). 17).

NMR (CDC1 _3): 8.02 (IH, s), 7.02 (IH, s), 6.79 (IH, d), 6.69 (IH, d), 4.6 (2H, wide s).

Entry 11

Preparation of 3.5-dichloro-4-fluoronitrobenzene

A mixture of 30.0 g of 3,4,5-trichloronitrobenzene and 11.5 g of anhydrous potassium fluoride in 60 ml of anhydrous dimethylformamide was heated at 140 ° C for 20 hours. The reaction mixture was cooled to room temperature, poured into water and extracted with diethyl ether. The ethereal solutions were combined, washed with water and brine, dried and the solvent was evaporated under reduced pressure. The bama oily residue was chromatographed on a short silica gel column eluting with 15% ethyl acetate / hexane. In the form of an orange solid

2,4-dichloro-3-fluoronitrobenzene is obtained.

Delta H NMR (CDC1 _3): 8.26 (d).

Rule 72

Preparation of 3.5-dichloro-4-fluoroaniline

This compound was prepared from 3,5-dichloro-4-fluoronitrobenzene as described in formula 1.

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ): 6.59 (2H, d), 3.64 (2H, broad s).

73

Preparation of 3.5-dichloro-4-fluoro-iodobenzene

This compound was prepared from 3,5-dichloro-4-fluoroaniline as described in Preparation 2. The halide used is copper (I) iodide. For purification, the product was chromatographed on a short silica gel column eluting with hexane.

Delta H NMR (CDC1 _3): 7.63 (d).

Inscription 14

Preparation of 3.5-dichloro-4-fluoro-pentafluoroethylbenzene g-3,5-dichloro-4-fluoro-iodobenzene, 13.4 g of copper (I) iodide, 24.6 g of anhydrous sodium pentafluoride Propionate and 200 ml of anhydrous dimethylformamide were heated at 130 ° C for 21 hours. The reaction mixture was cooled to room temperature, diluted with diethyl ether and filtered through celite. The filtrate was washed with water, dried and the solvent was evaporated at atmospheric pressure. The bama oily residue is distilled under reduced pressure. Fractions with a boiling range of 72-76 ° C, 80-82 ° C, 90-96 ° C and 90 ° C (84 mm Hg) were obtained, each of which had 3,5-dichloro-4-fluoro-pentafluoroethyl as the main component. Contains benzene.

Delta H NMR (CDC1 _3): 7.56 (d).

¹⁹ F NMR (CDC1 _3): -85.04 (3F);

-109.4 (IF), -115 (2F).

Inscription 75

Preparation of N- [2,6-Dichloro-4- (trifluoromethyl) phenyl] thiourea A solution of sodium thiocyanate (g) and benzoyl chloride (24 g) in acetone (180 ml) was heated to reflux, and 20 g of 2,6-dichloro were heated to reflux. A solution of 4-trifluoromethylaniline in acetone (70 ml) was added dropwise. After the addition of the reagent, the mixture was refluxed for another 6 hours, then allowed to cool to room temperature and poured into water. The precipitate was filtered off, washed with water and dried. The filtrate was extracted with ethyl acetate and the solvent was evaporated under reduced pressure. The resulting solid was combined with the precipitate isolated above. The solid was added to 10% w / w aqueous sodium hydroxide and the mixture was heated at 60 ° C for 16 hours. THE

Carefully acidify the reaction mixture with hot concentrated aqueous hydrochloric acid solution, then basify with aqueous ammonium hydroxide solution. The precipitate was filtered off and recrystallized from a mixture of ethyl acetate and petroleum ether (b.p. 60-80 ° C). A fine white needle crystal product is obtained; mp 165-166.2 ° C.

NMR (CDC1 _3): 8.73 (IH, br s);

7.65 (2H, s), 6.50 (2H, broad s).

Provision 16

Preparation of S-Methyl-N- [2,6-dichloro-4- (trifluoromethyl) phenyl] isothiourea

To a solution of 6.45 g of N- [2,6-dichloro-4- (trifluoromethyl) phenyl] thiourea (product obtained in Preparation 15) in 45 ml of anhydrous dimethylformamide was added 0.98 g of sodium hydride (60% w / w oily dispersion) was added. After stirring for 30 minutes at room temperature, 6.33 g of methyl iodide was added in one portion and the mixture was stirred at room temperature for 16 hours. The reaction mixture was poured into water and extracted with ethyl acetate. The organic extracts were combined, washed with water, dried and the solvent evaporated under reduced pressure. The brown oily residue was chromatographed on a short silica gel column using 33% ethyl acetate in petroleum ether (b.p. 60-80 ° C). The product was obtained as a pale yellow oil.

NMR (CDC1 _3): 7.50 (2H, s), 4.62 (2H, br s), 2.46 (3H, s).

Inscription 17

Preparation of N- [2,6-Dichloro-4- (trifluoromethyl) phenyl] -3-amino-4,4,4-trifluorobut-2-en-1-amide

2.5 g of 1- [2,6-dichloro-4- (trifluoromethyl) phenyl] -4- (trifluoromethyl) pyrimidin-6-one (the compound disclosed in European Patent Application No. 338,686) and 40 ml. A solution of diethylamine in methanol (40 mL) was heated at reflux for 48 hours. The reaction mixture was cooled to room temperature and the solvent and excess diethylamine evaporated under reduced pressure. The yellow oily residue was chromatographed on silica gel eluting with dichloromethane. The title compound is obtained as a white solid; mp 147-150 ° C.

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ): 7.66 (2H, s), 6.88 (1H, broad s), 6.50 (2H, broad), 5.20 (1H, s).

18th regulation

Preparation of 5- (methylthio) -4- (trifluoromethyl) pyrimidin-6-one

The sodium hydride dispersion (0.99 g, 55% in oil) was washed with hexane and the sodium hydroxide was suspended in 100 ml of anhydrous tetrahydrofuran. 5.00 g of 5-bromo-4- (trifluoromethyl) pyrimidin-6-one (the compound of European Patent No. 338,686) are added to the suspension under stirring under a nitrogen atmosphere for 5 minutes. The resulting solution was stirred for 20 minutes then cooled to -78 ° C and 26.6 ml of a 1.7M solution of tentbutyl lithium in pentane was added dropwise over 1 hour. The mixture was stirred for an additional 10 minutes at -78 ° C and then in one portion

Dimethyl disulfide (9.3 mL) was added. After stirring for 5 hours at -78 ° C, the mixture was allowed to warm slowly to room temperature and allowed to stand for 2 days. Aqueous 2M hydrochloric acid was added and the mixture was extracted with ethyl acetate. The extracts were combined, dried over magnesium sulfate and the solvent was evaporated under reduced pressure. The resulting 4.6 g pale yellow solid was recrystallized from chloroform / hexane. An off-white solid is obtained; mp 182.3-184.5 ° C.

NMR _(DMSO-d6): 8.30 (IH, s), 2.35 (3H, s).

Inscription 19

Preparation of 5-Formyl-4- (trifluoromethyl) pyrimidin-6-one

The sodium hydride dispersion (0.99 g, 55% in oil) was washed with hexane and the sodium hydride suspended in anhydrous tetrahydrofuran under a nitrogen atmosphere. 5.0 g of 5-bromo-4- (trifluoromethyl) pyrimidin-6-one are added in portions over 5 minutes with stirring. The mixture was stirred for 30 minutes at room temperature and then cooled to -78 ° C. 26.6 ml of a 1.7 M solution of tentbutyl lithium in pentane are added dropwise at -78 ° C over a period of 30 minutes. After 2 hours at -78 ° C, anhydrous dimethylformamide (6.4 ml) was added over 1 minute. The mixture was allowed to warm to room temperature over 5 hours, quenched with 2M aqueous hydrochloric acid and extracted with ethyl acetate. The extracts were combined, dried over magnesium sulfate and the solvent was evaporated under reduced pressure. The residue was recrystallized from toluene. 2.0 g of a pale yellow solid are obtained, m.p. 141.1-143.5 ° C.

NMR _(DMSO-d6): 13.8 (IH, s), 10.1 (IH, s), 8.50 (IH, s).

Inscription 20

Preparation of 5-Ethoxy-4- (trifluoromethyl) pyrimidin-6-one

To a solution of 0.76 g of metal sodium in 20 ml of ethanol is added 30 ml of pyridine, followed by 2.0 g of 5-bromo-4- (trifluoromethyl) pyrimidin-6-one and 1.6 g of copper (I) iodide. The mixture was stirred at room temperature under nitrogen for half an hour and then heated at 100 ° C for 5.5 hours. The mixture was cooled, 2M aqueous hydrochloric acid was added and the mixture was extracted with ethyl acetate. The extracts were combined, washed with brine, dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The brown residue was dissolved in ethyl acetate, treated with charcoal, filtered and the filtrate was evaporated under reduced pressure. The residue was recrystallized from toluene. 883 mg of a tan solid are obtained. An additional 580 mg of a pale yellow solid was collected by evaporation of the mother liquors and sublimation of the residue at 150 ° C / 1 Hg. The product melts at 134.8137.0 ° C.

NMR _(DMSO-d6): 8.00 (IH, s), 4.20 (2H, q), 1.20 (3H, t), 13.2 (IH, br).

HU 206596 Β

Entry 27

Preparation of 5-methyl-4- (trifluoromethyl) pyrimidin-6-one

To a suspension of 2.0 g of 5-methyl-6- (trifluoromethyl) -2-thiouracil (product obtained according to Preparation 22) in 25 ml of water and 0.96 ml of 0.88 aqueous ammonia solution 3.45 g of a 50% (w / w) aqueous dispersion of Raney nickel are added and the mixture is refluxed for 4.5 hours. The mixture was filtered hot and the residue was washed with hot methanol. The filtrates were combined and the solvent was evaporated under reduced pressure. The pale green solid residue was sublimated at 0.07 mmHg at 130 ° C. 0.98 g of a very pale green solid are obtained; mp 174.9-176.4 ° C.

NMR (CDC1 _3): 8.15 (IH, s), 2.25 (3H, s).

Entry 22

Preparation of 5-Methyl-5- (trifluoromethyl) -2-thiouracil

3.34 g of metal sodium are dissolved in 61.5 ml of methanol and 14.36 g of thiourea and 25 g of 4,4,4-trifluoro-2-methylacetacetic acid ethyl ester are added. The mixture

After refluxing for 47.5 hours, the solvent was evaporated under reduced pressure. The bama solid residue was dissolved in water, acidified with aqueous hydrochloric acid and extracted with ether. The extracts were combined, dried over magnesium sulfate and the solvent was evaporated under reduced pressure. The residue was stirred with hexane / ether and filtered. 7.3 g of pale pale yellow solid are obtained; m.p. 233.0-234.6 ° C.

NMR NMR _(DMSO-d6): 1.9 (3H, s), 12.8 (2H, br s).

Entry 23

Preparation of 5- (hydroxymethyl) -4- (trifluoromethyl) pyrimidin-6-one

To a suspension of 0.1 g of sodium borohydride in 10 ml of ethanol is added 0.5 g of 5-formyl-4- (trifluoromethyl) pyrimidin-6-one (product of Preparation 19) under stirring over 10 minutes. After 2 hours, the solution was evaporated and to the residue was added 2M aqueous hydrochloric acid. The mixture was extracted with ethyl acetate. The extracts were combined, washed with brine, dried over magnesium sulfate and evaporated. 0.353 g of an off-white solid is obtained; mp 186-186.8 ° C.

Nuclear Magnetic Resonance Spectrum (DMSO-d6) 13.15 (1H, broad s), 8.25 (1H, s), 4.35 (2H, s).

Inscription 24

Preparation of 5- (1-Hydroxyethyl) -4- (trifluoromethyl) pyrimidin-6-one

To a solution of 0.5 g of 5-formyl-4- (trifluoromethyl) pyrimidin-6-one (product of Preparation 19) in 15 ml of anhydrous tetrahydrofuran at a temperature below 5 ° C for 20 minutes 1.82 3 ml of a 3 molar solution of methylmagnesium bromide in ether are added. The mixture was allowed to warm to room temperature and stirred for 3 hours. The mixture was quenched with 2M aqueous hydrochloric acid and extracted with ethyl acetate. The extracts were combined, washed with brine, dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The resulting tan solid was recrystallized from ethyl acetate-hexane. 0.423 g of solid product are obtained; mp 145-146.6 ° C.

NMR _(DMSO-d6): 13.2 (IH, br s), 8.25 (lH, s), 5.0 (IH, m), 4.8 (IH, d), 1.35 (3H,

d).

Example 1 1- [2,6-Dichloro-5-methyl-4- (trifluoromethyl) phenyl] -4-trifluoromethyl-pyrimidin-6-one (Compound No. 1 in Table 1) production

0.24 g of a 50% w / w dispersion of sodium hydride are weighed into a dry flask purged with nitrogen. The dispersion is washed with pentane and the sodium hydride is suspended in 10 ml of anhydrous dimethylformamide.

0.75 g of 4- (trifluoromethyl) pyrimidin-6-one is added in portions to the suspension. After the addition of the reagent, the mixture was stirred for 30 minutes and then 2,26 g of 3,5-dichloro-4-fluoro-2-methyl-trifluoromethylbenzene (a compound disclosed in European Patent Application 259,048) were added. and kept at 90 ° C for 16 hours. The mixture was allowed to cool, poured into water and extracted with ethyl acetate. The organic layer was washed with aqueous sodium chloride solution, dried over magnesium sulfate and evaporated under reduced pressure. The light brown solid residue was chromatographed on a short silica gel column eluting with petroleum ether (b.p. 6080 ° C) containing 20% v / v diethyl ether. The solvent was evaporated under reduced pressure. The resulting pale amber solid was triturated with gasoline and then recrystallized from petroleum ether (b.p. 60-80 ° C) with a small amount of ethyl acetate. 1- [2,6-Dichloro-5-methyl-4- (trifluoromethyl) phenyl] -4- (trifluoromethyl) -pyrimidin-6-one is obtained, m.p. 204-205.5 ° C. in the form of needle crystals.

NMR (CDC1 _3): 8.00 (IH, s), 7.83 (IH, s), 7.0 (IH, s), 2.58 (3H, s).

Example 2

By following the procedure described in Example 1, the following compounds were prepared:

a) 1- [2,4-Bis (trifluoromethyl) -6-nitrophenyl] -4- (trifluoromethyl) of 6-nitro-2,4-bis (trifluoromethyl) bromobenzene obtained according to Preparation 4. pyrimidine-6-one (Compound # 2 in Table I); mp 142-143 ° C.

NMR (CDC1 _3): 8.70 (IH, s), 8.45 (IH, s), 8.14 (IH, s), 6.95 (IH, s).

¹⁹ F NMR (CDC1 _3): -60.38 (3F, s);

-63.76 (3F, s), -72.11 (3F, s).

b) 1- (2,6-Dichloro-4-nitrophenyl) -4- (trifluoromethyl) pyrimidin-6-one (3,5-dichloro-4-fluoronitrobenzene) obtained according to Rule 11 (a) Compound No. 5 (Table I); mp 138-139.8 ° C.

NMR (CDC1 _3): 8.41 (2H, s), 8.00 (IH, s), 7.00 (lH, s).

c) From 6-nitro-2,4-bis (trifluoromethyl) bromobenzene and 5-bromo-4- (trifluoromethyl) pi

## STR3 ## Prepared from 1- [2,4-bis (trifluoromethyl) -6-nitrophenyl] -5-bromo-4- (trifluoromethyl) pyrimidin-6-one; 135.5-137 ° C.

NMR (CDC1 _3): 8.75 (IH, s), 8.45 (IH, s), 8.05 (IH, s).

d) 1- [2-Chloro-6-nitro (trifluoromethoxy) phenyl] -4- (trifluoromethyl) of 3,4-dichloro-5-nitro-trifluoromethoxy-benzene obtained according to Preparation 7 ) -pyrimidin-6-one (Compound 13 in Table I) was prepared. The reaction mixture was heated at 90 ° C for 16 hours. The product was purified by medium pressure liquid chromatography (Gilson kit) using silica gel as the adsorbent, eluting with 5% ethyl acetate in hexane. The product was then recrystallized from petroleum ether (b.p. 60-80 ° C) containing 16% ethyl acetate.

NMR (CDC1 ₃₎ 8.1 (IH, s), 8.05 (IH,

d), 7.80 (1H, d), 6.98 (1H, s).

e) 1- [2-Chloro-6-nitro-1- (2-chloro-5-nitro-trifluoromethoxy) -benzene and 4- (pentafluoro-ethyl) -pyrimidin-6-one obtained according to Preparation 7. 4- (Trifluoromethoxy) phenyl] -4- (pentafluoroethyl) pyrimidin-6-one (Compound 17 in Table I) was prepared. The reaction mixture was heated at 90 ° C for 16 hours. The product was purified by medium pressure liquid chromatography (Gilson apparatus); silica gel adsorbent and 5% ethyl acetate / hexane as eluent. Melting point 139-140.5 ° C. NMR (CDC1 _3): 8.10 (IH, s), 8.05 (IH, d), 7.80 (IH, d), 7.00 (IH, s).

Alternatively, 1- [2-chloro-6-nitro-4-trifluoromethoxy-phenyl] -4- (pentafluoroethyl) -pyrimidin-6-one may be obtained from 3-chloro-4-fluoro-4-fluoro Prepared from -5-nitro (trifluoromethoxy) -benzene. The reaction is carried out at room temperature with stirring.

f) 1- [2,6-Dichloro- (pentafluoroethyl) phenyl] -4- (trifluoromethyl) pyrimidine from 3,5-dichloro-4-fluoro (pentafluoroethyl) -benzene, obtained according to Preparation 14. 6-on; mp 122-125 ° C.

NMR (CDC1 _3): 8.01 (IH, s), 7.78 (2H, s), 7.01 (lH, s).

g) 1- [2,6-Dichloro-4- (pentafluoro-ethyl) -phenyl] -4- (pentafluoro-ethyl) -pyrimidin-6-one from 3,5-dichloro-4- (fluoro-pentafluoro-ethyl) -benzene (Compound 20 in Table I); mp 165-167 ° C.

NMR (CDC1 ₃₎ 8.0 (IH, s), 7.79 (2H, s), 7.05 (IH, s).

Example 3

- Preparation of (2,4,6-trichlorophenyl) -4-trifluoromethylpyrimidin-6-one (Compound 3 in Table 1)

To a suspension of 0.37 g of copper (II) chloride and 1.46 g of tert-butyl nitrite in 8 ml of anhydrous acetonitrile at 0-5 ° C was added 0.9 g of the 1- (4) obtained in A solution of amino-2,6-dichlorophenyl) -4- (trifluoromethyl) pyrimidin-6-one in 10 ml of acetonitrile is added dropwise. After the addition of the reagent, the mixture was stirred for an additional hour at 5 ° C and then allowed to warm slowly to room temperature. The reaction mixture was poured into 20% aqueous hydrochloric acid and extracted with diethyl ether. The organic extracts were combined, washed with 20% aqueous hydrochloric acid, dried over anhydrous magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure. The oily residue was chromatographed on a short silica gel column using petroleum ether (b.p. 6080 ° C, 25% v / v diethyl ether). The resulting white solid was recrystallized from petroleum ether (b.p. 60-80 ° C). 1- (2,4,6-Trichlorophenyl) -4- (trifluoromethyl) pyrimidin-6-one is obtained; mp 154.5-156.5 ° C.

NMR (CDC1 _3): 7.98 (IH, s), 7.57 (2H, s), 6.98 (IH, s).

Example 4

The following compounds were prepared according to the procedure described in Example 3:

a) 1- (2,6-Dichloro-4-iodophenyl) from 1- (4-amino-2,6-dichlorophenyl) -4-trifluoromethylpyrimidin-6-one obtained according to Preparation 1. 4- (Trifluoromethyl) pyrimidin-6-one (Compound 4 in Table I) was prepared. Copper (I) iodide was used as the halide and the organic extract was washed with aqueous sodium metabisulfite solution before further processing. Product 148—

149.3 ° C.

NMR (CDC1 _3): 7.99 (IH, s), 7.90 (2H, s), 6.98 (IH, s).

b) 1- (4-Bromo-2,6-dichlorophenyl) -4- (1- (4-amino-2,6-dichlorophenyl) -4- (trifluoromethyl) pyrimidin-6-one) - (trifluoromethyl) pyrimidin-6-one (az

Table 6 in Table I compound). The halide used is copper (II) bromide. The product melts at 150-155 ° C.

NMR (CDC1 _3): 7.98 (IH, s), 7.72 (2H, s), 6.9 (lH, s).

c) 1- [2-Chloro-4,6-bis] of 1- [2-amino-4,6bis (trifluoromethyl) phenyl] -4- (trifluoromethyl) pyrimidin6-one obtained according to Preparation 5. (trifluoromethyl) phenyl] -4-trifluoromethyl-pyrimidin-6-one (Compound 9 in Table I) was prepared. The halide used is copper (II) chloride. Melting point 133.5-135.5 ° C.

NMR (CDC1 _3): 8.15 (IH, s), 8.05 (IH, s), 8.00 (IH, s), 6.95 (IH, s).

d) 1- [2-Bromo-4,6-bis] of 1- [2-amino-4,6bis (trifluoromethyl) phenyl] -4- (trifluoromethyl) pyrimidin6-one obtained according to Preparation 5. (trifluoromethyl) phenyl] -4-trifluoromethyl-pyrimidin-6-one (Compound 11 in Table I) was prepared. The halide used is copper (II) bromide. The product melts at 134-138 ° C.

NMR (CDC1 _3): 8.30 (IH, s), 8.10 (IH, s), 7.98 (lH, s), 6.99 (IH, s).

e) 1- [2-amino-6-chloro-4-trifluoromethoxy-phenyl] -4-trifluoromethyl-pyrimidin-6-one obtained according to Preparation 9; 6-dichloro-4- (trifluoromethoxy) phenyl] -4- (trifluoromethyl) pyrimidin-6-one (shown in Table I)

No. 14 compound). The halide used is copper (II) chloride. The product melts at 130.5-132.5 ° C.

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NMR (CDC1 _3): 8.00 (IH, s), 7.44 (2H, s), 7.00 (IH, s).

f) 1- [2-Bromo-6-chloro-1- (2-amino-6-chloro-4-trifluoromethoxy-phenyl) -4-trifluoromethyl-pyrimidin-6-one -4-Trifluoromethoxy-phenyl] -4-trifluoromethyl-pyrimidin-6-one (Compound 15 in Table I) was prepared. The halide used is copper (II) bromide. The product melts at 128-131 ° C.

NMR (CDC1 _3): 8.00 (IH, s), 7.60 (IH, d), 7.49 (IH, d), 6.99 (IH, s).

g) 1- (2,6-Dichloro-4) from 1- [2-amino-6-chloro-4-trifluoromethoxy-phenyl] -4- (pentafluoro-ethyl) -pyrimidin-6-one obtained according to Preparation 10. - (trifluoromethoxy) phenyl] -4- (pentafluoroethyl) pyrimidin-6-one (Compound 18 in Table I) was prepared. The halide used is copper (H) chloride. The product melts at 168-169 ° C.

NMR (CDC1 _3): 8.00 (IH, s), 7.45 (2H, s), 7.03 (IH, s).

h) 1- [2,6-Dichloro-4- (methylthio) 1- (4-amino-2,6-dichlorophenyl) -4-trifluoromethylpyrimidin-6-one obtained according to Preparation 1. ) -phenyl] -4-trifluoromethyl-pyrimidin-6-one (Compound 44 in Table I). 1.2 equivalents of dimethyl disulfide is used as the reagent instead of the copper salt. The product melts at 108-111 ° C.

NMR (CDC1 _3): 8.00 (IH, s), 7.33 (2H, br s), 6.98 (IH, s), 2.55 (3H, s).

i) 1- [2-Bromo-6-chloro obtained from 1- [2-amino-6-chloro-4-trifluoromethoxy-phenyl] -4- (pentafluoro-ethyl) -pyrimidin-6-one obtained according to Preparation 10. 4- (Trifluoromethoxy) phenyl] -4-pentafluoroethylpyrimidin-6-one (Compound 49 in Table I) was prepared. The halide used is copper (II) bromide.

NMR (CDC1 _3): 8.00 (IH, s), 7.60 (IH, d), 7.50 (IH, d), 7.05 (IH, s).

Example 5

- Preparation of [2-Chloro-6-methoxy-4-trifluoromethyl-phenyl] -4-trifluoromethyl-pyrimidin-6-one (Compound 7 in Table)

Metal sodium (0.03 g) was reacted with anhydrous methanol (10 mL) and the resulting sodium methoxide solution was treated with 0.5 g (338,686). 1-t-2-chloro-6-fluoro-4- (trifluoromethyl) phenyl] -4-trifluoromethyl-pyrimidin-6-one, prepared according to European Patent Specification No. 4,684,198, is added. After stirring for 24 hours at room temperature, the solvent was evaporated under reduced pressure. The viscous oily residue crystallizes on standing. This material was chromatographed on a silica gel column using 30% ethyl acetate in petroleum ether (b.p. 60-80 ° C) as the eluent. The first eluate fractions were combined, the solvent evaporated under reduced pressure and the residue triturated with boiling petroleum ether (b.p. 60-80 ° C). The title compound is obtained as a white solid.

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ): 7.98 (1H, s), 7.49 (1H, s), 7.22 (1H, s), 6.98 (1H, s), 3.93 (3H, s).

Example 6 1- [2-Chloro-4,6-bis (trifluoromethyl) phenyl] -5-bromo-4-trifluoromethyl-pyrimidin-6-one (Compound 10 in Table 1) 0.2 g of 1- [2-chloro-4,6-bis (trifluoromethyl) phenyl] -4- (trifluoromethyl) pyrimidin-6-one (Table 9 in Table I). To a solution of 0.2 g of sodium acetate trihydrate in 3 ml of acetic acid is added 0.086 g of bromine with stirring. The flask was stoppered and the mixture was stirred at room temperature for 16 hours. The solvent was evaporated under reduced pressure and the yellow residue was dissolved in ethyl acetate. The solution was washed with water, aqueous sodium thiosulfate solution, and finally aqueous sodium chloride solution, dried, and the solvent was evaporated under reduced pressure. The yellow residue was chromatographed on a short silica gel column using petroleum ether (b.p. 6080C) as the eluent (20% v / v). The title compound is obtained as a pale yellow solid, m.p. 136-139 'C.

NMR (CDC1 ₃₎ 8.15 (IH, s), 8.05 (1H, s), 7.92 (1H, s).

Example 7

By following the procedure described in Example 6, the following compounds were prepared:

a) 1- [2-Bromo-4,6-bis (trifluoromethyl) phenyl] -4- (trifluoromethyl) pyrimidin-6-one (Compound 11 in Table I) [2-Bromo-4,6-bis (trifluoromethyl) phenyl] -5-bromo-4- (trifluoromethyl) pyrimidin-6-one (Compound 12 in Table I) was prepared.

NMR (CDC1 _3): 8.30 (IH, s), 8.10 (lH, s), 7.95 (lH, s).

b) 1- [2,6-Dichloro-4- (trifluoromethoxy) phenyl] -4- (trifluoromethyl) pyrimidin-6-one (Compound No. 15 in Table I) 2,6-Dichloro-4- (trifluoromethoxy) phenyl] -5-bromo-4- (trifluoromethyl) pyrimidin-6-one (Compound 16 in Table I) was prepared. M.p. 130-132 ° C.

NMR (CDC1 _3): 7.95 (IH, s), 7.45 (2H, s).

c) 1- [2,6-Dichloro-4- (pentafluoro-ethyl) -phenyl] -4- (trifluoromethyl) -pyrimidin-6-one (Compound 19 in Table I); 2,6-Dichloro-4- (pentafluoroethyl) phenyl] -5-bromo-4- (trifluoromethyl) pyrimidin-6-one (Compound 21 in Table I) was prepared. The product melts at 137-140 ° C with decomposition.

NMR (CDC1 _3): 7.97 (IH, s), 7.79 (2H, s).

d) 1- [2,6-Dichloro-4- (pentafluoroethyl) phenyl] -4- (pentafluoroethyl) pyrimidin-6-one (Compound No. 20 in Table I); 2,6-Dichloro-4- (pentafluoroethyl) phenyl] -5-bromo-4- (pentafluoroethyl) pyrimidin-6-one (Compound 22 in Table I) was prepared. The product melts at 130 ° C with decomposition.

NMR (CDC1 _3): 7.94 (IH, s), 7.80 (2H, s).

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Example 8 1- [2,6-Dichloro-4- (trifluoromethyl) phenyl] -2- (methylthio) 4- (trifluoromethyl) pyrimidin-6-one (shown in Table Ϊ) Preparation of Compound 23 A suspension of 0.16 g of sodium hydride in 7 ml of anhydrous tetrahydrofuran was stirred with 1.0 g of S-methyl-N- [2,6-dichloro-4-trifluoromethyl] obtained according to Preparation 16. ) -phenyl] -isothiourea in 4 ml of anhydrous tetrahydrofuran was added dropwise. The mixture evolves hydrogen for 1 hour. A solution of 0.75 g of methyl 4,4,4-trifluorobutylcarboxylic acid in 1 ml of tetrahydrofuran is then added dropwise. After stirring at room temperature for 16 hours, the reaction mixture was poured into water, acidified with dilute aqueous hydrochloric acid and extracted with ethyl acetate. The organic extracts were combined, dried over magnesium sulfate, filtered and the solvent was evaporated under reduced pressure. The resulting orange gum was chromatographed on a silica gel column eluting with 8% ethyl acetate in petroleum ether (b.p. 6080 ° C). The resulting material was triturated with petroleum ether (b.p. 60-80 ° C). The title compound is obtained in the form of fine white needles, m.p. 156-157.6 ° C.

NMR (CDC1 _3): 7.79 (2H, s), 6.69 (IH, s), 2.59 (3H, s).

Example 9 1- [2,6-Dichloro-4- (trifluoromethyl) phenyl] -2- (methylsulfinyl) -4- (trifluoromethyl) -plimidin-6-one (shown in Table I). Preparation of Compound 24) 0.20 g of 1- [2,6-dichloro-4- (trifluoromethyl) phenyl] -2- (methylthio) -4- (trifluoromethyl) -phenyl] prepared as in Example 8. To a solution of methyl) pyrimidin-6-one in 6 ml of chloroform was added 0.33 g of m-chloroperbenzoic acid with stirring. After stirring for 30 minutes, the mixture was diluted with chloroform and washed with aqueous sodium bicarbonate solution, aqueous sodium bisulfite solution, and finally aqueous sodium chloride solution. The mixture was dried over anhydrous magnesium sulfate and the solvent was evaporated under reduced pressure. The pale yellow residue was chromatographed on a silica gel column using 20% by volume petroleum ether (b.p. 60-80 ° C) as the eluent. The title compound is obtained as a white solid, m.p. 159.8-162 ° C.

NMR (CDC1 _3): 7.80 (2H, xs), 7.00 (IH, s), 3.05 (3H, s).

Example 70

1- [2,6-Dichloro-4- (trifluoromethyl) phenyl] -2- (methylsulfonyl) -4- (trifluoromethyl) pyrimidin-6-one (Table 25 in Table 1). 0.15 g of 1- [2,6-dichloro-4- (trifluoromethyl) phenyl] -2- (methylthio) -4- (trifluoromethyl) obtained in Example 8 are obtained. To a solution of pyrimidin-6-one in 4 ml of chloroform was added 0.24 g of m-chloroperbenzoic acid with stirring. The mixture was stirred for 16 hours and allowed to stand for one week. The mixture was diluted with chloroform, washed with aqueous sodium bicarbonate solution, aqueous sodium bisulfite solution, and finally aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The yellow solid residue was triturated with petroleum ether (b.p. 60-80 ° C) containing little ethyl acetate. The title compound is obtained as a white solid, m.p. 191.7-193.4 ° C.

NMR (CDC1 _3): 7.78 (2H, s), 7.11 (IH, s), 3.42 (3H, s).

Example 77

- Preparation of [2,6-dichloro-4- (trifluoromethyl) phenyl] -2-amino-4- (trifluoromethyl) pyrimidin-6-one (Compound 26 in Table 7) 0.130 g. , in a solution of 1- (2,6-dichloro-4- (trifluoromethyl) phenyl] -2- (methylsulfonyl) -4- (trifluoromethyl) pyrimidin-1-one obtained in Example 10 in 5 ml of butanol. After 1 hour, the solvent was evaporated under reduced pressure, and the yellow solid residue was chromatographed on silica gel, eluting with 20% ethyl acetate in petroleum ether (b.p. 60-80 ° C). as a solid.

NMR (CDC1 _3): 7.84 (2H, s), 6.43 (IH, s), 5.10 (2H, br s).

Example 72

All. The following compounds were prepared according to the procedure for Example 1- 1- [2,6-dichloro-4- (trifluoromethyl) phenyl] -2- (methylsulfonyl) -4- (trifluoromethyl). of pyrimidin-6-one and the corresponding amines:

a) Using methylamine, 1- [2,6-dichloro-4- (trifluoromethyl) phenyl] -2- (methylamino) -4- (trifluoromethyl) pyrimidin-6-one ( (Compound 27 in Table 1). M.p. 211-213.6 ° C. NMR (CDC1 _3): 7.83 (2H, s), 6.35 (IH, s), 4.25 (IH, br s), 3.00 (3H, d).

b) Using 1- [2,6-dichloro-4- (trifluoromethyl) phenyl] -2- (dimethylamino) -4- (trifluoromethyl) pyrimidin-6-one using dimethylamine (Table 1) 28). The product melts at 120-125 ° C. NMR (CDC1 _3): 7.75 (2H, s), 6.39 (IH, s), 2.80 (6H, s).

Example 13

- Preparation of [2,6-dichloro-4- (trifluoromethyl) phenyl] -2-methyl-4- (trifluoromethyl) pyrimidin-6-one (Compound 29 in Table 1) 0.66 g of N- [2,6-dichloro-4- (trifluoromethyl) phenyl] -3-amino-4,4,4-trifluorobut-2-ene, obtained according to Preparation 7, is obtained. To a solution of 1-amide in 8 ml of anhydrous toluene was added 0.71 g of acetyl chloride and 0.26 g of Hunig's base. The reaction mixture was heated at 90 ° C for 3 hours and then allowed to cool to room temperature. The mixture was poured into water and extracted with ethyl acetate. The extract was washed with water, dried over anhydrous magnesium sulfate and the solvent was evaporated under reduced pressure. The bama gum was chromatographed on a silica gel column eluting with 11% ethyl acetate in petroleum ether (b.p.

HU 206596 Β

60-80 ° C). The title compound is obtained as a waxy solid.

NMR (CDC1 _3): 7.83 (2Η, s), 6.87 (IH, s), 2.26 (3H, s).

Example 14 Preparation of 1- [2,6-Dichloro-4- (trifluoromethyl) phenyl] -4- (trifluoromethyl) pyrimidine-6-thione (Compound 47 in Table 1)

0.5 g of anhydrous 1- [2,6-dichloro-4- (trifluoromethyl) phenyl] -4-trifluoromethylpyrimidin-6-one described in European Patent Application 338,686, solution of distilled pyridine with stirring 1 g

2,4-Bis (4-methoxyphenyl) -1,3-dithia-2,4-diphosphetane-2,4-disulfide (Lawesson's reagent) was added and the mixture was heated at 150 ° C for 24 hours. The mixture was cooled to room temperature, diluted with ethyl acetate, washed with brine, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The brown oily residue was purified by medium pressure liquid chromatography on a Gilson apparatus using silica gel as a stationary phase, eluting with 2% ethyl acetate / hexane. From the appropriate fractions, the title compound was isolated: the yellow oily substance darkened on standing. NMR (CDC1 _3):?. 8.02 (1Η, s), 7.81 (2H, s), 7.70 (lH, s) '

Example 15 1- [2-Chloro-6-nitro-4- (trifluoromethyl) phenyl] -5- (methylthio) -4- (trifluoromethyl) pyrimidin-6-one (shown in Table I) Preparation of Compound 31) 0.46 g of a 55% sodium hydride dispersion in oil was washed with hexane. The sodium hydride was suspended in 25 ml of anhydrous dimethylformamide and, under stirring, under nitrogen, under stirring, under nitrogen, in portions for 10 minutes, 2.0 g of 5- (methylthio) -4- (trifluoro- methyl) -pyrimidin-6-one is added. The solution was stirred at room temperature for 20 minutes and then 3-chloro-5-nitro-4-fluorobenzotrifluoride (4.60 g) was added dropwise. After stirring for 2 hours, the mixture was quenched with 2M aqueous hydrochloric acid and extracted with ethyl acetate. The extracts were combined, washed with water and brine, dried over magnesium sulfate and the solvent was evaporated under reduced pressure. The residue was stirred with hexane and filtered. 3.78 g of the expected product are obtained in the form of a pale yellow solid, mp 138.3-141.2 ° C.

NMR (CDC1 _3): 8.45 (1Η, d), 8.20 (lH, d), 8.00 (lH, s), 2.50 (3H, s).

Example 16

- [2,6-Dichloro-4- (trifluoromethyl) phenyl] -5- (methylthio) 4- (trifluoromethyl) pyrimidin-6-one (Compound 30 in Table 1) production

This compound was prepared as described in Example 15, but the reaction was carried out at 90 ° C. The product melts at 93.8-96.2 ° C.

NMR (CDC1 _3): 7.90 (IH, s), 7.80 (2H, s), 2.55 (3H, s).

Example 17 1- [2,6-Dichloro-4- (trifluoromethyl) phenyl] -5- (methylsulfonyl) -4- (trifluoromethyl) pyrimidin-6-one (shown in Table I) Preparation of compound 33) 0.540 g of 1- [2,6-dichloro-4- (trifluoromethyl) phenyl] -5- (methylthio) -4- (trifluoromethyl) pyrimidin-6-one (Compound 30 of Table I) in 10 ml of anhydrous chloroform was cooled to -15 ° C and 1 g of 55% m-chloroperbenzoic acid was added portionwise over 5 minutes with stirring. The mixture was stirred at -15 ° C for 3.5 hours, then allowed to warm to room temperature and stirred for 16 hours.

The solution was diluted with chloroform, washed with a saturated aqueous sodium metabisulfite solution, a saturated aqueous sodium bicarbonate solution, and finally with an aqueous sodium chloride solution, dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. 562 mg of the title compound are obtained in the form of a white solid melting at 190.8-191.2 ° C.

NMR (CDC1 _3): 8.20 (IH, s), 7.85 (2H, s), 3.40 (3H, s)..

Example 18 1- [2-Chloro-6-nitro-4- (trifluoromethyl) phenyl] -5- (methylsulfinyl) -4- (trifluoromethyl) pyrimidin-6-one (Table 32). 0.50 g of 1- [2-chloro-6-nitro-4- (trifluoromethyl) phenyl] -5-methylthio-4- (trifluoromethyl) pyrimidine-6 (0.50 g). (Compound 31 of Table I) in a solution of 10 ml of anhydrous chloroform at -15 ° C was added 0.40 g of 55% m-chloroperbenzoic acid with stirring. After stirring for 3.5 hours at -15 ° C, the mixture was washed with a saturated aqueous solution of sodium metabisulfite, a saturated aqueous solution of sodium bicarbonate and finally with an aqueous solution of sodium chloride. The solution was dried over magnesium sulfate and the solvent was evaporated under reduced pressure. The residue was purified by high-performance liquid chromatography; silica gel adsorbent, 70% ethyl acetate / hexane and 50% ethyl acetate / hexane as eluent. 247 mg of a pale yellow solid are obtained; mp 180.0-180.8 ° C.

NMR (CDC1 _3): 8.50 (IH, s), 8.25 (2H, s), 3.10 (3H, d).

Example 19 1- [2-Chloro-6-nitro-4- (trifluoromethyl) phenyl] -5- (trifluoromethylthio) -6- (trifluoromethyl) pyrimidin-6-one (a) (Compound 34 in Table 1) was obtained in an amount of 0.50 g, m.p. A solution of 1- [2-chloro-6-nitro-4- (trifluoromethyl) phenyl] -5-bromo-4- (trifluoromethyl) pyrimidin-6-one in 5 ml of anhydrous dimethylformamide described in 35 g of trifluoromethylthio-threo are added. The solution was heated at 90 ° C for 2.5 hours under nitrogen. An additional 0.20 g of reagent was added and heating continued for 2 hours. The mixture was cooled, water and ethyl acetate were added, and the insoluble residue was removed. The phases are separated and the aqueous phase is extracted with ethyl acetate. Organic solutions

The reaction mixture was combined, dried with water and over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The brown oily residue was chromatographed on Merck 7729 silica gel eluting with 50-70% v / v dichloromethane. 0.119 g of an off-white solid are obtained; mp 150.4153.0 ° C.

NMR (CDC1 _3): 8.50 (IH, s), 8.25 (IH, s), 8.20 (IH, s).

Trifluoromethylthio resin was prepared by the method of Yagupolski et al., Synthesis 721 (1975).

Example 20 1- [2-Chloro-6-nitro-4- (trifluoromethyl) phenyl] -5-formyl-4-trifluoromethyl-pyrimidin-6-one (Table 35 in Table I). Preparation of Compound A (125 mg) A 55% sodium hydride dispersion in oil is washed with hexane and the sodium hydride is suspended in anhydrous dimethylformamide (10 ml). To the slurry was added, under stirring, under nitrogen, 5-formyl-4- (trifluoromethyl) pyrimidin-6-one (0.50 g) over 5 minutes. The mixture was stirred for 30 minutes and then 1.30 g

3-Chloro-4-fluoro-5-nitrobenzotrifluoride was added and stirring was continued at room temperature for 5 hours. The mixture was quenched with 2M aqueous hydrochloric acid and extracted with ethyl acetate. The extracts were combined, washed with brine, dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The oily residue was triturated with a mixture of ether and hexane and the crude product was purified by high performance liquid chromatography (silica gel, 30% ethyl acetate / hexane as adsorbent). The product was recrystallized from ethyl acetate-hexane to give 238 mg of an off-white solid; mp 151.3-152.8 ° C.

NMR (CDC1 _3): 10.30 (IH, s), 8.50 (IH, s), 8.20 (2H, s).

Example 21

- [2-Chloro-6-nitro-4- (trifluoromethyl) phenyl] -5- (difluoromethyl) -4- (trifluoromethyl) pyrimidin-6-one (Table 38 in Table I). Preparation of Compound 1) To a solution of 0.035 ml of diethylamino-sulfur trifluoride in 0.5 ml of anhydrous carbon tetrachloride under stirring under a nitrogen atmosphere is 100 mg of 1- [2-chloro-6-nitro-4-trifluoromethylphenyl] -5. Formyl 4- (trifluoromethyl) pyrimidin-6-one (Compound 35 in Table I) and 0.5 mL of additional solvent were added. The mixture

After stirring for 2.5 hours at room temperature, 1 ml of anhydrous dichloromethane was added. The resulting homogeneous solution was stirred for 2 hours and allowed to stand overnight. To the mixture was added 5 drops of diethylamino sulfur trifluoride, stirring was continued for 1 hour, the mixture was poured into water and extracted with dichloromethane. The extracts were combined, washed with brine, dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The yellow oily residue was purified by high performance liquid chromatography; silica gel adsorbent and 30% ethyl acetate / hexane as eluent. 48 mg of a white solid are obtained; Op .:

137.5-140 ° C.

NMR (CDC1 _3): 8.50 (IH, s), 8.25 (IH, s), 8.20 (lH, s), 6.95 (IH, t).

Example 22 1- [2,6-Dichloro-4- (trifluoromethoxy) phenyl] -5-eloxy-4- (trifluoromethyl) pyrimidin-6-one (Compound 36 in Table I) )

0.162 g of a 55% w / w dispersion of sodium hydride in oil is washed with hexane and the sodium hydride is suspended in 15 ml of anhydrous dimethylformamide. To the slurry was added, under stirring, under nitrogen, 5-ethoxy-4- (trifluoromethyl) pyrimidin-6-one (0.70 g) in portions over 5 minutes. The mixture was stirred for 20 minutes then 1.57 g

3.5-Dichloro-4-fluorobenzotrifluoride was added. The mixture was stirred at 70 ° C for 7 hours and allowed to stand for 2 days. An additional 1.57 g of 3,5-dichloro-4-fluorobezotrifluoride was added and the mixture was heated at 100 ° C for 24 hours. The mixture was cooled, poured into 2M aqueous hydrochloric acid and extracted with ethyl acetate. The extracts were combined, washed with water and brine, dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The brown oily residue was purified by high performance liquid chromatography; silica gel adsorbent and 20% ethyl acetate / hexane as eluent. 244 mg of an off-white solid are obtained; Op .:

70.5-73 ° C.

Nuclear Magnetic Resonance Spectrum (CDCl3 ₎ : 7.85 (2H, s), 7.75 (1H, s), 4.45 (2H, q), 1.40 (3H, t).

Example 23

J- [2-Chloro-6-nitro-4- (trifluoromethyl) phenyl] -5-ethoxy-4- (trifluoromethyl) pyrimidin-6-one (Compound 37 in Table I) Purification by high-performance liquid chromatography as described in Example 22 also isolates 65 mg of the above compound, which is formed from 3-chloro-5-nitro-4-fluorobenzotrifluoride as impurity in the reagent. The product melts at 97.5-100.5 ° C.

NMR (CDC1 _3): 8.45 (IH, s), 8.20 (IH, s), 7.80 (IH, s), 4.40 (2H, q), 1.40 (3H, t).

Example 24

J- [2-Chloro-6-nitro-4- (trifluoromethyl) phenyl] -5-methyl-4- (trifluoromethyl) pyrimidin-6-one (Compound 40 in Table I) Preparation 0.40 g of a 55% w / w dispersion of sodium hydride in oil are washed with hexane and the sodium hydride is suspended in 30 ml of anhydrous dimethylformamide. To the slurry was added, under stirring, under nitrogen, 5-methyl-4- (trifluoromethyl) pyrimidin-6-one (1.50 g) obtained in a similar manner. When a clear solution is formed, 4.10 g of 3-chloro-4-fluoro-5-nitrobenzotrifluoride are added dropwise and the solution is stirred for 6 hours at room temperature. The mixture was poured into water

HU 206596 Β, acidified and extracted with ethyl acetate. The extracts were combined, washed with water, dried over magnesium sulfate and the solvent evaporated under reduced pressure. The residue was stirred with petroleum ether (b.p. 30-40 ° C). 2.77 g of a tan crystalline solid are obtained; mp 156.2-157,7 ° C.

NMR (CDC1 _3): 8.40 (IH, s), 8.20 (IH, s), 7.95 (IH, s), 2.30 (3H, s).

Example 25 1- [2,6-Dichloro-4- (trifluoromethyl) phenyl] -5-methyl-4- (trifluoromethyl) pyrimidin-6-one (Compound 39 in Table 1) This compound was prepared as described in Example 24, but the reaction was carried out at 90 ° C. The product melts at 156.3-157.6 ° C.

NMR (CDC1 _3): 7.80 (2H, s), 7.78 (IH, s), 2.35 (3H, s).

Example 26 1- [2,6-Dichloro-4- (trifluoromethyl) phenyl] -5-amino-4- (trifluoromethyl) pyrimidin-6-one (Compound 41 in Table I) ), 0.142 g of a 55% w / w dispersion of oily sodium hydride are washed with hexane and then suspended in 20 ml of anhydrous dimethylformamide. To the slurry under stirring was added 5-amino-4- (trifluoromethyl) pyrimidin-6-one (0.53 g) under nitrogen. When a clear solution is formed, 1.38 g of 3,5-dichloro-4-fluorobenzotrifluoride is added dropwise. The mixture was stirred for 2 hours at room temperature and allowed to stand for 2 days. The mixture was poured into water and extracted with ethyl acetate. The extracts were combined, washed with water and brine, dried over magnesium sulfate and the solvent was evaporated under reduced pressure. The residue was dissolved in 35% ethyl acetate in hexane, the little insoluble material was filtered off and the filtrate was purified by high performance liquid chromatography. Silica gel was used as adsorbent and hexane containing 35% by volume ethyl acetate was used as eluent. The still contaminated product was washed with hexane and then purified by high pressure liquid chromatography (hexane, 20% ethyl acetate). Finally, the product was washed with hexane. M.p. 163.0-163.5 ° C.

NMR (CDC1 ₃₎ 7.8 (2H, s), 7.4 (lH, s), 5.05 (2H, br s).

The 5-amino-4- (trifluoromethyl) pyrimidin-6-one used as reagent was prepared as described in J. Am. Chem. Soc., 80, 5744 (1958).

Example 27 Preparation of 1- [2,6-Dichloro-4- (trifluoromethylthio) -phenyl] -4- (trifluoromethyl) -pyrimidin-6-one (Compound 43 in Table 1)

0.6 g of 1- (2,6-dichloro-4-iodophenyl) -4- (trifluoromethyl) pyrimidin-6-one (Compound 4 in Table I, which was obtained in Example 4). To a solution of 10 ml of anhydrous dimethylformamide was added 0.9 g of trifluoromethylthiourea. The mixture was stirred at 100 ° C for 8.5 hours under nitrogen. A further 0.4 g of trifluoromethylthio-thiourea was added and the mixture was heated at 100 ° C for a further 11.5 hours.

The mixture was cooled, diluted with water and ethyl acetate and filtered. The phases are separated and the aqueous phase is extracted with ethyl acetate. The extracts were combined, washed with water and brine, dried over magnesium sulfate and the solvent was evaporated under reduced pressure. The residue is mixed with food and the ethereal solution is separated by decantation from the insoluble bama gum. Evaporation of the ether gave 883 mg of a yellow solid which was purified by high performance liquid chromatography. Silica gel was used as adsorbent and hexane containing 20% by volume ethyl acetate was used as eluent. 170 mg of a white solid are obtained; mp 113-114.3 ° C.

NMR (CDC1 _3): 8.00 (IH, s), 7.0 (IH, s), 7.85 (2H, s).

Trifluoromethylthio resin was prepared by the method of Yagupolski et al., Synthesis 721 (1975).

Example 28 1- [2-Chloro-6-nitro-4- (trifluoromethyl) phenyl] -5- (hydroxymethyl) -4- (trifluoromethyl) pyrimidin-6-one (I. Preparation of Compound 45 (Table 45) (50 mg) A 55% sodium hydride dispersion in oil is washed with hexane and the sodium hydride is suspended in 5 ml of anhydrous dimethylformamide. Under stirring, under nitrogen, 200 mg of 5- (hydroxymethyl) -4- (trifluoromethyl) pyrimidin-6-one (200 mg) was added portionwise over 5 minutes. After stirring for 30 minutes, 500 mg of 3-chloro-4-fluoro-5-nitrobenzotrifluoride was added and stirring was continued for another hour. The mixture was quenched with 2M aqueous hydrochloric acid and extracted with ethyl acetate. The extracts were combined, washed with water and brine, then dried over magnesium sulfate and the solvent was evaporated under reduced pressure. The resulting pale yellow oil was chromatographed on Merck 7729 silica gel eluting with 20-40% ethyl acetate / hexane. 314 mg of an off-white solid are obtained; mp 117.4-119.6 ° C.

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ): 8.45 (1H, s), 8.25 (1H, s), 8.10 (1H, s), 4.75 (2H, d), 3.0 (1H, t).

Example 29] - [2,6-Dichloro-4- (trifluoromethyl) phenyl] -5- (1-hydroxyethyl) -4- (trifluoromethyl) pyrimidin-6-one (shown in Table 46). Preparation of Compound No. 3) 70 mg of a 55% w / w dispersion of oily sodium hydride are washed with hexane and the sodium hydride is suspended in anhydrous dimethylformamide. To the slurry under stirring, under nitrogen, was added in portions 5-l-hydroxyethyl-4- (trifluoromethyl) pyrimidin-6-one (300 mg) over 5 minutes. The mixture was stirred for an additional 30 minutes and then

HU 206 596 Β

672 mg of 3,5-dichloro-4-fluorobenzotrifluoride was added. The mixture was stirred for 1 hour at room temperature and then held at 80 ° C for 4 hours. The mixture was cooled, quenched with 2M aqueous hydrochloric acid and extracted with ethyl acetate. The extracts were combined, washed with brine, dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The resulting yellow solvent was chromatographed on Merck 7729 silica gel eluting with 20 volumes of ethyl acetate in hexane. The resulting yellow gum was triturated with hexane. 82 mg of a white solid are obtained. NMR (CDC1 _3): 7.85 (2H, s), 7.95 (IH, s), 1.6 (3H, d), 4. II (IH, d), 5.12 (IH, m).

Example 30

- Preparation of [2-Chloro-6-nitro-4- (trifluoromethyl) phenyl] -5-nitro-4- (trifluoromethyl) pyrimidin-6-one (Compound 42 in Table A) No. 338,686 1- [2-Chloro-6-nitro-4- (trifluoromethyl) phenyl] -4- (trifluoromethyl) pyrimidin-6-one in tetramethylene sulphonic solution at 150 ° C. with tetrafluoroborate. The product is identified by its mass spectrum.

Electron collision m / e: 431 (1xCl, M ⁺ ), 397 (base peak, M ⁺ -Cl), 386 (M ⁺ -NO ₂ ), 351, 340, 313, 223, 193.187, 160, 143.121.

Example 31 1- [3-Chloro-5-nitro-4- (trifluoromethyl) phenyl] -5- (1-fluoroethyl) -4- (trifluoromethyl) pyrimidin-6-one ( Preparation of Compound 48 (Table I): 1- [3-Chloro-5-nitro-4- (trifluoromethyl) phenyl] -5- (1-hydroxyethyl) -4- (trifluoromethyl) 128 mg. ) -Pyrimidin-6-one in 2 ml of chloroform was added a solution of 0.043 ml of diethylamino sulfur trifluoride in 2 ml of chloroform at -50 ° C under stirring under nitrogen for 10 minutes. The solution was allowed to warm to room temperature over 40 minutes and allowed to stand overnight. The solution was diluted with dichloromethane, washed with water and brine, dried over magnesium sulfate and the solvent was evaporated under reduced pressure. The resulting yellow oil was chromatographed on Merck 7729 silica gel eluting with 50-90% (v / v) hexane in dichloromethane. 53 mg of a white solid are obtained; m.p. 127.3-129.8 ° C.

NMR (CDC1 _3): 8.45 (IH, s), 8.20 (IH, s), 8.10 (IH, s), 5.90 (IH, m), 1.70 (3H, m).

1- [3-Chloro-5-nitro-4-trifluoromethylphenyl] -5- (1-hydroxyethyl) -4- (trifluoromethyl) pyrimidin-6-one used as starting material according to the procedure described in Example 28. we produce

NMR (CDC1 _3): 8.45 (IH, s), 8.25 (IH, s), 8.05 (IH s), 1.60 (3H, d), 5.10 (IH, m )

3.90 (1H, m).

Example 32

Investigation of insecticidal activity

The insecticidal activity of the compounds of formula (I) was investigated as follows:

The active ingredient was dissolved in acetone and diluted with water containing 0.01% by weight of Synperonic NX wetting agent (condensate of nonylphenol with ethylene oxide) to the desired active ingredient content. Unless otherwise stated, formulations containing 500 ppm of active ingredient were used for the assays.

The insect pest is applied to a carrier (usually the host plant or nutrient to be consumed by the insect pest) and the pests and / or vehicle are treated with a formulation containing the active ingredient to be tested. In the contact effect assay, the composition was applied to the pests and vehicle, while in the residual effect, only the vehicle was treated and the pests were placed on the treated vehicle. The pest mortality rate is usually determined after 1-3 days. The experimental conditions are shown in Table II. The results are shown in Table III. in Table. The insecticidal activity is designated 9, 5, 0, where 9 is 80-100% mortality, 5 is 50-79% mortality, and 0 is 0. Indicates less than 50% mortality. In III. The horizontal lines in the table (-) indicate that no experiment was performed.

//. spreadsheet

The pest Carrier- material / nutrient Lale Types of test The perception time, day sign name BG Blattella germanica (cockroach, puppets) plastic tó the rest 3 MD Musca domestica (domestic fly, adult specimens) cotton / Cu disease contact 1 HV Heliothis virescens (Tobacco Beetle, Larvae) gyapotle- with the rest 2 SP Spodoptera cxigus (small sercghcmyó, larvae) gyapotle- with the rest 2

NEW. spreadsheet

The compound number The active ingredient content of the preparation pPM Insecticidal activity MD BG HV SP First 500 9 5 0 5 Second 500 9 5 0 5 Third 500 5 0 0 5 4th 500 9 0 9 0 5th 500 9 0 0 0 6th 500 9 0 0 9 7th 500 9 0 - . - 8th 500 9 9 0 0 9th 500 9 9 9 5

HU 206 596 Β

Avegyület number The active ingredient content is ppm Insecticidal activity MD BG HV SP 10th 500 0 9 0 0 11th 500 9 0 0 0 12. ' 500 0 9 0 0 13th 100 5 9 - - 14th 500 9 9 9 9 15th 500 9 9 0 0 16th 500 9 9 0 0 17th 500 9 9 0 0 18th 500 9 9 5 0 19th 500 9 9 0 9 20th 500 9 9 0 0 21st 500 9 9 0 0 22nd 500 9 9 9 0 23rd 500 9 9 0 0 24th 500 9 0 0 0 25th 500 9 0 0 0 26th 500 9 9 9 0 28th 500 9 5 0 0 29th 500 9 9 9 0 30th 500 9 9 9 9 31st 500 9 0 0 0 32nd 500 9 0 0 0 33rd 500 9 0 0 0 34th 500 9 5 0 5 35th 500 9 0 0 0 36th 500 9 9 0 0 37th 100 5 0 0 0 39th 500 9 9 0 0 40th 500 9 9 0 0 43rd 500 9 9 0 9 47th 500 9 9 9 0

The following examples illustrate the preparation of insecticidal compositions. In the examples, the chemical names of the trade names or trademarks are as follows:

Condensates of Synperonic NP8, NP13 and ΟΡΙΟ: nonylphenol with ethylene oxide

Aromasol H: mixture of alkylbenzenes (solvent)

Solvesso 200: inert organic diluent

From the east: polysaccharide.

Example 33

Preparation of an emulsifiable concentrate

By mixing the components, an emulsifiable concentrate can be prepared which is easy to dilute with water and can be used as a spray when diluted with water:

Active ingredient 25.0% by weight

Synperonic NP13 2.5% by weight

Calcium dodecylbenzene sulfonate 2.5% by weight Methylcyclohexanone 70.0% by weight

Example 34

Preparation of Emulsifiable Concentrate By mixing the components, the following emulsifiable concentrate is prepared, which can be easily diluted with water and diluted with water as a spray:

Active ingredient 10.0% by weight

Synperonic NP13 4.0% w / w

Calcium dodecylbenzene sulfonate 6.0% by weight

Aromasol H 50.0% by weight

Methyl cyclohexanone 30.0% by weight

Example 35

Preparation of Wettable Powder Formulation 20 By mixing the components, a wettable powder formulation which is readily diluted with water and diluted with water can be used to form a wettable powder formulation:

agent

Silicon dioxide

Sodium lignosulfonate

Sodium laureth sulfate

kaolinite

10.0% by weight

5.0% by weight 5.0% by weight 4.0% by weight 76.0% by weight

Example 36

Preparation of Wettable Powder Formulation By mixing the components, a wettable powder formulation which is easy to dilute with water and which can be used as a spray for dilution with water is prepared:

agent

Sodium lignosulfonate

Sodium laureth sulfate

kaolinite

1.0% by weight 5.0% by weight 2.0% by weight 92.0% by weight

Example 37

Preparation of Thickening Powder Formulation By mixing the components, the following formulation is prepared, which is readily diluted with water and can be used as a spray for dilution with water:

agent

Silicon dioxide

Calcium ligninsulfonate

Sodium laureth sulfate

kaolinite

40.0% by weight 20.0% by weight 5.0% by weight 2.0% by weight 33.0% by weight

Example 38

Preparation of dusting agent

By mixing the components, the following composition is applied, which can be applied directly to plants or other surfaces:

agent l 0tömeg% Silicon dioxide 2.0% by weight talc 97.0% by weight

HU 206 596 Β

Example 39

Preparation of a Liquid Concentrate By mixing the components, a very small volume of a liquid concentrate can be prepared by mixing with the following paraffinic diluents:

Active ingredient 25.0% by weight

N-methyl-2-pyrrolidine 50.0% by weight

Solvesso 200 25.0% by weight

Solvesso 200 2.0% by weight

Of kelp or other polysaccharides 0.1% by weight

Water 83.4% by weight

Example 44

Production of granules

Directly applied granules are prepared in known manner:

Active ingredient 0.5% by weight

Solvesso 200 0.2% w / w

Synperonic NP8 0.1% by weight

Calcium carbonate granulate (0.3-0.7 mm) 99.2% by weight

Example 40

Preparation of Liquid Liquid Liquid By mixing the components, the following formulations are prepared by mixing them with paraffinic diluents in a very small volume of liquid concentrate.

concentrate: Preparation of suspension concentrate. agent 10.0% by weight It is adjusted by grinding the components homogenously N-methyl-2-pirroliclin 20.0% by weight to prepare an aqueous suspension of the following composition Solvesso 200 70.0% by weight concentrate: 20 agent 50.0 wt% Example 41 kaolinite 15.0% by weight Preparation of a liquid preparation Sodium lignosulfonate 3.0% by weight By mixing the components, Synperonic NP8 1.5% by weight directly in a very small volume Propylene glycol 10.0% by weight (undiluted) liquid formulation: 25 bentonite 2.0% by weight agent 10.0% by weight From the Celts or other polysaccharides 0.1% by weight Cotton seed oil 50.0% by weight Proxel or other bactericidal agent 0.1% by weight Butyl acetate dietoxol 40.0% by weight Water 18.3% by weight Example 42 30 Example 46 Microencapsulation suspension concentrate Preparation of powder concentrate Bending By grinding the components, By a known microencapsulation method, a hand powder concentrate: of the following composition, easy to dilute with water, and agent 10.0% by weight water-diluted microcap 35 Silicon dioxide 20.0% by weight bovine suspension concentrate: Magnesium carbonate 70.0% by weight agent 10.0% by weight 10% by weight of concentrate of the above composition in 90% by weight Toluene diisocyanate 3.0% by weight mixed with% talc directly Ethylenediamine 2.0% by weight powder containing 1% by weight of the active ingredient Poly (vinyl alcohol) 2.0% by weight 40 we get. bentonite 1.5% by weight Dihydro-isophorone 30.0% by weight Example 47 Solvesso 200 10.0% by weight Production of granules From the Celts or other polysaccharides 0-0.1% by weight We produce the following composition in known manner, Water 41.4% by weight 45 directly applied granules: agent 5% by weight Synperonic NP8 2% by weight Example 43 Pumice granulate (20/40 BS measure- Microencapsulation suspension concentrate needle) 93% by weight Bending 50 By a known microencapsulation method, a Example 48 of the following composition, easy to dilute with water, and Water-dispersible granules, preparation water-diluted microcap We produce the following composition in known manner, bovine suspension concentrate: water dispersible granules: agent 1.0% by weight 55 agent 50% by weight Toluene diisocyanate 3.0% by weight Silicon dioxide 5% by weight Ethylenediamine 2.0% by weight Sodium lignosulfonate 10% by weight Poly (vinyl alcohol) 2.0% by weight Sodium dioctyl sulfosuccinate 5% by weight bentonite 1.5% by weight Sodium acetate with 10% Dihydro-isophorone 5.0% by weight 60 Montmorillons por 20% by weight

HU 206 596 Β

Example 49

Preparation of the Emulsifiable Concentrate By mixing the components, an emulsifiable concentrate is prepared which is easy to dilute with water and can be used as a spray when diluted with water:

agent 50.0% by weight Span40 0.8% by weight Tween 40 8.0% by weight Dihydro-isophorone 30.0% by weight 10 Solvesso 100 25.0% by weight Water 31,2tömeg% Example 50 A concentrate suitable for aerosol preparation 15 Bending By mixing the components, of the following composition suitable for aerosol preparation concentrate: agent 1.0% w / w 20 Methyl isobutyl ketone 50.0% by weight Solvesso 100 49.0% by weight Example 57 Aerosol production 25 The following composition is prepared in known manner aerosols: It has the composition of Example 50 concentrate 5.0% by weight Odorless kerosene 25.0% by weight 30 Methylene chloride 10.0% by weight Hydrocarbon propellant 60.0% by weight

after all.

Claims (8)

PATENT CLAIMS CLAIMS 1. An insecticidal composition comprising 0.01 to 60% by weight of the compound of formula (I) as an active ingredient, wherein R ¹ and R ² are independently halogen, halogenated C 1-4 alkyl, C 4 alkoxy or nitro, provided that when one of R ¹ and R ² is nitro 45, the other substituent is different from nitro, R ³ and R ⁴ are each independently hydrogen or C 1-4 alkyl, R ^{5 is} halogen, nitro, halogenated C 1-4 -C 50 alkyl, halogenated C 1-4 -alkoxy, or -S (O) _n R ¹⁰ wherein n is 0, 1 or 2, and R ^{10 is C} 1-4 alkyl or halogenated 55 C 1-4 alkyl, ^R6 halogenated C 1-4 alkyl group represents a group of formula R ^l ° or S (O) _n, in which n and ^R10 are as defined above, 60 R ^{7 is} hydrogen, halogen, nitro, C 14 alkyl, halogenated C 1-4 alkyl, hydroxy (C 1-4 alkyl), C 1-4 alkoxy, formyl or -S (O) _n R ¹⁰ or -NR ⁿ is a group of the formula R ¹² wherein n and R ¹⁰ are as defined above and R ⁿ and R ¹² are each independently hydrogen or C 1 -C 4 alkyl, R ^{8 is} hydrogen, C 1 -C 4 alkyl, or -S (O) _n R ¹⁰ or -NR ⁿ R ¹² wherein n, R ¹⁰ , R ⁿ and R ¹² are as defined above, and R ^{9 is} oxygen or sulfur, provided that when R ^{5 is} trifluoromethyl, then (i) R * or R ^{2 is} halogenated C 1-4 alkyl or C 1-4 alkoxy, (ii) R ³ or R ^{4 is C} 1 -C ⁴ alkyl, (iii) R ⁶ -S (O) _n R ¹⁰ , (iv) R ^{7 is} nitro, halogenated C 1 -C 4 alkyl, hydroxy-C 1 -C 4 alkyl. ), C 1 -C 4 alkoxy, formyl or -S (O) _n R ¹⁰ or -NR ^U R ¹² , (v) R ⁸ is other than hydrogen, and / or (vi) R ^{9 is} sulfur. and provided that at least one of R ¹ , R ² , R ³ and R ⁴ is other than fluorine, and when R ^{5 is} chlorine, both R ¹ and R ² are halogen - a mineral and / or organic solid and / or a liquid diluent or carrier, preferably clay with talc, silica, water, liquid hydrocarbon and / or ketone and optionally with an ionic and / or nonionic surfactant, preferably an aliphatic sulfuric acid monoester salt, a sulfonated aromatic compound salt and / or an alkyl phenol ethylene oxide condensate. . Composition according to claim 1, characterized in that it contains as an active ingredient a compound of the formula I in which R ¹ and R ² are both chlorine or bromine, R ³ and R ⁴ are each hydrogen, R ⁵ and R ⁶ independently of one another. trifluoromethyl or pentafluoroethyl; R ^{7 is} hydrogen or bromine; and R ^{8 is} hydrogen, amino, or methyl. 3. The method of claim 2. A composition, characterized in that it comprises (I) compound as an active ingredient, wherein both R ¹ and R ² represents chlorine or bromine, R ³ and R ⁴ are both hydrogen, ^R5 pentafluoroethyl group R ^{6 is} trifluoromethyl or pentafluoroethyl and R ⁷ and R ^{8 are} hydrogen. Composition according to claim 1, characterized in that it contains as an active ingredient a compound of the formula I in which R ^{1 is} chlorine or bromine, R ^{2 is} nitro, R ³ , R ⁴ , R ⁷ and R ^{8 are} hydrogen, R ^{5 is} pentafluoro. is ethyl, R ⁶ is trifluoromethyl or pentafluoroethyl group. HU 206 596 Β Composition according to claim 1, characterized in that it contains as an active ingredient a compound of the formula I in which R ^{1 is a} chlorine or bromine atom, R ^{2 is a} chlorine atom, a bromine atom or a nitro group, R ³ , R ⁴ and R ^{8 are} hydrogen atoms, R ⁵ trifluoromethoxy, trifluoromethylthio, trifluoromethylsulfinyl or trifluoromethylsulfonyl, R ⁶ trifluoromethyl or pentafluoroethyl, R ⁷ is hydrogen or bromo. 6. A composition according to claim 1, wherein the active ingredient is a compound of formula I wherein R ¹ and R ² are both bromo or chloro, R ³ , R ⁴ and R ^{8 are} hydrogen, R ⁵ and R ⁶ are independently trifluoromethyl, trifluoromethoxy or pentafluoroethyl; R ^{7 is} hydrogen or halogen; and R ⁹ is sulfur. 7. A composition according to claim 1, wherein the active ingredient is a compound of formula I wherein R ¹ and R ² are both chlorine or bromine, R ³ , R ⁴ and R ^{8 are} hydrogen, R ^{5 is} trifluoromethylthio. R ^{6 is} trifluoromethyl or pentafluoroethyl, R ^{7 is} hydrogen or halogen, and R ⁹ is sulfur. 8. A process for the preparation of compounds of formula I in the formula R ¹ and R ² independently represents a halogen atom, halogenated C1-4 alkyl, C1-4 alkoxy or nitro, with the proviso that if R ¹ and R ² is nitro, then the other substituent nitro groups, R ³ and R ⁴ are each independently hydrogen or C 1-4 alkyl, R ^{5 is} halogen, nitro, halogenated C 1-4 alkyl, halogenated C 1-4 alkoxy, or -S (O) _n R ¹⁰ wherein n is 0, 1 or 2, and R ^{10 is} C 1 -C 4 alkyl or halogenated C 1 -C 4 alkyl, R ^{6 is} halogenated C 1-4 alkyl or -S (O) _n R ¹⁰ wherein n and R 10 are as defined above, R ^{7 is} hydrogen, halogen, nitro, C 14 alkyl, halogenated C 1-4 alkyl, hydroxy (C 1-4 alkyl), C 1-4 alkoxy, formyl or -S (O) _n R ¹⁰ or -NR ^1] R ¹² wherein n and R ¹⁰ are as defined above, and R ¹¹ and R ¹² independently of one another are hydrogen or C 1 -C 4 alkyl, R ^{8 is} hydrogen, (C 1 -C 4) -alkyl or -S (O) _n R ¹⁰ or -NR ^H R ^{12 in} which n, R ¹⁰ , R ¹¹ and R ¹² are as defined above, and R ^{9 is} oxygen or sulfur, provided that when R ^{5 is} trifluoromethyl, then (i) R ¹ or R ^{2 is} halogenated C 1-4 alkyl or C 1-4 alkoxy, (ii) R ³ or R ^{4 is C} 1-4 alkyl, (iii) R ^{6 is} -S (O) _n R 10, (iv) R ^{7 is} nitro, halogenated C 1-4 alkyl, hydroxy (1-4). (C 1 -C 4 alkyl), (C 1 -C 4) alkoxy, formyl or -S (O) _n R 10 or -NR ⁿ R ' ² , (v) R ⁸ is other than hydrogen, and / or (vi) R ^{9 is} sulfur and provided that at least one of R ¹ , R ² , R ³ and R ⁴ is other than fluorine, and when R ^{5 is} chlorine, both R ¹ and R ² are halogen, that a) for the preparation of compounds of formula I wherein R ⁸ is hydrogen, a compound of formula II wherein R ¹ , R ² , R ³ , R ⁴ and R ⁵ are in the scope and R ^{13 is} leaving group - with a compound of formula (III): - wherein ^{R6, R7} and ^R9 are as stated above and ^R8 is hydrogen jelent-; obsession b) R ⁸ is C 1 -C 4 alkyl, R ¹ and R ^{2 are} halogen, R ³ and R ^{4 are} hydrogen or methyl, R ⁵ is halogen, halogenated C 1 -C 4 alkyl, halogenated C 1 -C 4 alkoxy or -S (O) _n is a group of formula R ¹⁰ (wherein n and R ¹⁰ are as defined herein), R ⁶ is halogenated C 1 -C 4 alkyl, R ⁷ is hydrogen or C 1 -C 4 alkyl, and R ⁹ is oxygen (I); ) for the preparation of a compound of the formula (VI), wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ and R ⁹ are as defined in (b), in an inert solvent with an acylating agent of the formula wherein Alk represents a C 1 -C 4 alkyl group and X represents a leaving group in an acylating agent; obsession c) for the preparation of compounds of formula I wherein R ¹ and R ^{2 are} halogen, R ³ and R ^{4 are} hydrogen or methyl, R ^{5 is} halogen, halogenated C 1-4 alkyl, halogenated C 1-4 alkoxy or -S (O). ) _n is a group of formula R ¹⁰ (wherein n and R ¹⁰ are as defined herein), R ^{6 is} halogenated C 1 -C 4 alkyl, R ^{7 is} hydrogen, R ^{8 is C} 1 -C 4 alkylthio, and R ^{9 is} oxygen; a compound of formula (VII): - wherein R ^1, R ^2, R ^3, R ⁴ and R ⁵ c) above - a base and a dipolar aprotic solvent with a compound of formula (VIII) - wherein R ⁶ is in (c) and "alkyl" means C1-C4 alkyl; obsession d) in a compound of Formula IV, wherein R ³ , R ⁴ , R ⁸ and R ⁹ are as defined in the scope and R ¹ ', R ² ', R ⁵ ', R ⁶ ' and R ⁷ 'are amino; or R ¹ , R ² , R ⁵ , R ⁶ or R ^{7 as} defined herein, provided that at least one of EN 206596 ük represents an amino group - converting the amino group (s) into the corresponding R ¹ , R ² , R ⁵ , R ⁶ and / or R ⁷ k substituents in known manner; then optionally (i) oxidizing a compound of formula (I) wherein R ⁸ is C 1-4 alkylthio or halogenated C 1-4 alkylthio to the corresponding sulfinyl or sulfonyl derivative; ^{It contains 8} sulfonyl groups having from 1 to 4 carbon atoms. A compound of formula (I) Reacting HNR ⁿ R ¹² , wherein R ¹¹ and R ¹² are within the scope of the invention, (iii) in a compound of formula I, any of the substituents R ¹ , R ² , R ⁵ and R ^{7 in} the subject circle. 5 is converted to specified other R ^1, R ^2, R ⁵ and / or R ⁷ substituent and / or (iv) reacting a compound of formula (I) ^R9 is oxygen atom is reacted with a sulfurizing agent.