CZ238990A3 - Process for preparing novel derivatives of pyrimidine - Google Patents

Abstract

2-Anilinopyrimidine derivs. of formula (I) are new: R1 and R2 = H, halogen, 1-3C alkyl, 1-2C haloalkyl, 1-3C alkoxy or 1-3C haloalkoxy; R3 = H, 1-4C alkyl (opt. substd. by halogen, OH or CN) or cyclopropyl (opt.substd. by 1-3 of Me and halogen); R4 = 3-6C cycloalkyl opt. substd. by 1-3 of Me and halogen.

Description

(IA1 (XV)

(XIV) The invention relates to a process for the preparation of novel pyrimidine derivatives which are used as intermediates in the preparation of the insecticidally and fungicidally active 2-anilinopyrimidine derivatives of the general formula I

in which

R ^ and Rg are each independently hydrogen, halogen, alkyl of 1 to 3 carbon atoms, haloalkyl of 1 to 2 carbon atoms, alkoxy of 1 to 3 carbon atoms or haloalkoxy of 1 to 3 carbon atoms,

R1 represents a hydrogen atom, a C1-C4 alkyl group or a halogen atom or a hydroxy-substituted C1-C4 alkyl group, a cyclopropyl group or a methyl group up to three times a cyclopropyl group,

R ^ represents a cycloalkyl group having 3 to 6 carbon atoms or a methyl group and / or a halogen atom up to three times the same or differently substituted cycloalkyl group having 3 to 6 carbon atoms,

Jj) as well as their acid addition salts and their metal salt complexes.

The preparation of these compounds is described in U.S. Pat.

In these processes, inter alia, pyrimidine derivatives of formula IA are used as intermediates

wherein R @ 1 is C1 -C4 alkyl, C3 -C6 cycloalkyl or methyl substituted C3 -C6 cycloalkyl.

C1-C4alkyl means, for example, methyl, ethyl, propyl, butyl, as well as their isomers, such as isopropyl, isobutyl, tert-butyl or sec-butyl.

J

Examples of C 3 -C 6 cycloalkyl include, for example, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

According to the present invention the compounds of the pattern ---- CE-IA-Pr-i pravuj-d-t-t-m-to-be-isothiuroniová ^- ~ o'b'e salt "of undispersed formula XV (XV) in which

A is an acid anion, reacted with a diketone of formula III

0 Η H

R ₃ - CCHgC - R ₄ DLI) / wherein ^R 3 ^{and R} 4 CN & her above meanings, in a solvent at temperatures from 20 to 140 ° C, preferably at temperatures from 20 to 80 ° C, to give a pyrimidine derivative of the formula XIV

wherein R 1 is as defined in formula IA, whereupon the compound of formula XIV obtained is oxidized. with an oxidizing agent to form a pyrimidine derivative of formula XVI

in which

R ^ and R ^ have the meanings given under formula IA.

Suitable anions of the acid kyseliny 'are, for example, the following salt residues: halide, sulfate or hydrogen sulfate.

Halogen means fluoride, chloride, bromide or iodide, preferably bromide or chloride.

The solvents which may be used are, for example, the following solvents, taking into account the respective reaction conditions: halogenated hydrocarbons, in particular chlorinated hydrocarbons such as tetrachlorethylene, carbon tetrachloride, dichloropropane, methylene chloride, dichlorobutane, chloroform, chlornaphthalene, carbon tetrachloride, trichloroethane, trichlorethylene, penta; chloroethane, difluorobenzene, 1,2-dichloroethane, 1,1-dichloroethane, 1,2-bis-dichloroethylene, chlorobenzene, fluorobenzene, bromobenzene, dichlorobenzene, dibromobenzene, chlorotoluene, trichlortoluene; ethers, such as ethylpropyl ether, methyl tert-butyl ether, n-butyl ether, di-n-butyl ether, diisobutyl ether, diisoamyl ether, diisopropyl ether, anisole, cyclohexylmethyl ether, diethyl ether, ethylene glycol dimethyl ether, tetrahydrofuran, dioxane, thioanisole; nitrated hydrocarbons such as nitromethane, nitroethane, nitrobenzene, chloronitrobenzene, o-nitrotoluene; nitriles such as acetonitrile, butyronitrile, isobutyronitrile, benzonitrile, m-chlorobenzonitrile; aliphatic or cycloaliphatic hydrocarbons, such as heptane, hexane, octane, nonane, cymene, benzine fractions within a boiling point range from 70 ° C to 190 ° θ ^'C y ^ ^{cyclohexanol>} methylcyclohexane, decalin, petroleum ether, ligroin, trimethylpentane, such as 2,3 3-trimethylpentane; esters such as ethyl acetate, ethyl acetate, isobutyl acetate; amides such as formamide, methylformamide, dimethylformamide; ketones such as acetone, methyl ethyl ketone; alcohols, especially lower aliphatic alcohols such as methanol, ethanol, n-propanol, isopropyl alcohol, as well as isomers of butanols; optionally also water. Mixtures of the abovementioned solvents and diluents are also suitable.

The following examples illustrate the process according to the invention.

Preparation of 2-methylmer-4-apto-4-methyl-6-cyclopropylpyrimidine

To 69.5 g (0.25 mol) of 4-methylisothiourea sulfate and 41 g (0.5 mol) of anhydrous sodium acetate in 375 ml of glacial acetic acid was added dropwise 63 g of (0.5 M) dropwise over 10 minutes at room temperature. 5 mol) of 1-cyclopropyl-1,3-butanedione and then the mixture is heated under reflux for 14 hours. After cooling to room temperature, the reaction mixture was filtered and the filter residue was washed with 100 ml glacial acetic acid. The filtrate is concentrated on a rotary evaporator and the residual brown oil is poured into 600 ml of water with stirring. After extracting twice with 200 ml of methylene chloride each time, the extracts are concentrated on a rotary evaporator and the residual oil is distilled under high vacuum. Boiling point 81-83 ° C / 30 Pa. Yield 64.8 g (0.36 mol; 72% of theory).

WJJJJ 1.2

Preparation of 2-methylsulfonyl-4-methyl-6-cyclopropylpyrimidine

.18 g (0.1 mol) of 2-methylmercapto-4-methyl-6-cyclopropylpyrimidine are dissolved in 100 ml of acetic acid and 28 g of (0, 0 g) are added at 0 DEG C. with stirring over 1 hour. 25 mol) 30% hydrogen peroxide. One hour

(f) after the dropwise addition, the reaction solution is heated at 70 ° C for 2 hours, then cooled to room temperature and poured into 800 ml of ice-water with stirring. Precipitated white crystals were collected. they are filtered and, after drying, melting at 74-76 ° C.

The following compounds of formula IA can be prepared in an analogous manner:

Compound No.

Physics constants "s

4.1 -CH ₃

4.2

-CH.

slouCeRR.

nina C.

physical constants

4.16 -C _? H ₅

4.24 '' ^C 2 ^E 5

CH

with

m.p. 64 68 ° C, Dj'SinAirilil ί'ί-'Κ ^ ί / Λ ^. u. · J

115 04 PRAGUE 1 2iU4 2i £ 2fe »li-lB Ϊ-

Claims (1)

PATENT REQUIREMENTS A process for the preparation of novel pyrimidine derivatives (IA) in which:. R is C 1 -C 4 alkyl, r is C 3 -C 6 cycloalkyl, or C 3 -C 3 -cycloalkyl substituted by methyl. Wherein the isothiuronium salt of formula (XV) is reacted Θ C - SCH, X X ³ AND rv "O r ~ U> ° CD & CD 13 ' * - é> m> ‘n <<x x m  ΰ CT> ID O re; e re (XV) in which A Φ represents an anion of the acid, with a diketone of the general formula III 0 0 tt H 'Ry ^ “C ~ CHp ^“ C — R ₄ --- “- (- ΠΙ -) - in which R 1 and R 2 are as defined in formula IA, in a solvent, at temperatures from 20 to 140 ° C, preferably at temperatures from 20 to 80 ° C, to form a pyrimidine derivative of the general formula XIV in which: R 1 and R 2 are as defined in formula IA, and the compound of formula XIV obtained is oxidized by treatment with an oxidizing agent to give a pyrimidine derivative of formula IA.