HU200588B - Process for producing keto esters - Google Patents

Abstract

The invention relates as fungicides useful derivatives of acrylic acid and processes for their preparation. The invention provides fungicides which penetrate the plant tissue and may be so volatile that they are effective in the vapor phase against fungi found on the plants. They can be used both in agriculture and in industry. The object of the invention is to provide as fungicides useful compounds and their preparation processes available, which are versatile. The compounds of the invention have the general formula and stereoisomers thereof, wherein X, Y and Z, which may be the same or different, are hydrogen or halogen atoms, or optionally substituted alkyl, optionally substituted alkenyl, optionally substituted aryl, optionally substituted alkynyl , Haloalkyl, alkoxy, haloalkoxy, optionally substituted aryloxy, optionally substituted arylalkoxy, optionally substituted acyloxy, optionally substituted amino, optionally substituted arylazo, acylamino, nitro, nitrile, CO2R3, CONR4R5, COR6 -, CR7NR8 or NCR9R10 groups are; or the groups X and Y, when in adjacent positions on the phenyl ring, can combine to form a fused ring which is either aromatic or aliphatic and optionally contains one or more heteroatoms; and R1, R2, R3, R4, R5, R6, R7, R8, R9 and R10, which may be the same or different, are hydrogen or alkyl, cycloalkyl, alkenyl, alkynyl, optionally substituted aryl, optionally substituted aralkyl or cycloalkylalkyl groups; and metal complexes thereof. formula

Description

The present invention relates to a process for the preparation of novel ketoesters of formula (I). The novel compounds of the present invention are useful as starting materials or intermediates in the preparation of fungicidal active ingredients.

Derivatives structurally similar to compounds of formula (I) are described in Tetrahedron Letters (1981), 22, 1509 and 25, 3529 (1984); J. Med. Chem. 1981, 24.399-403; No. 2,708,189 Publication document in Federal Republic of Germany; 80-79,345 and 77-27,745. Published Japanese Patent Application.

The compounds of the formula I can be prepared according to the invention

R is C 1-4 alkyl

Y is hydrogen and at the same time

X is phenoxy, nitrophenoxy, phenyl (C 1-4 alkyl), phenyl (C 2-4 alkenyl), phenyl (C 2-4 alkynyl), furyl (C 2-4 alkenyl). ), benzoylamino, furoylamino, N- (thienylcarbonyl) -N- (C1-C4 alkyl) amino, (C1-C4 alkoxy) carbonyl, benzyloxycarbonyl, C 3-6 cycloalkyloxy; or

X and Y together slept the group of formula (a)

The compound of formula (I) according to the present invention can be prepared by reacting an organometallic compound of formula (Π), wherein M represents a lithium atom or a magnesium halide group, and X and Y represent the oxalates of formula (IH) above, wherein R ¹ is as defined above.

The reaction is carried out under the usual conditions of Grignard reactions in anhydrous ether-type solvent, usually at -15 ° C to room temperature. The starting materials of formula (II) can be prepared from known halides of formula (IV), wherein L is halogen and X and Y are as defined above, by reacting compounds of formula (IV) with organic lithium compounds or with Grignard. and reacting with metal magnesium under the conditions of formation of the reagents.

The invention is further illustrated by the following non-limiting Examples.

Example 1

Preparation of Z-2- (2'-Phenylethenyl) phenylglyoxalic acid methyl ester

To a suspension of 21.02 g of benzyl triphenylphosphonium chloride in 250 ml of anhydrous ether, 530 g of potassium tert-butoxide is added in one portion under vigorous stirring. After 25 minutes, a solution of 5.00 g of 2-thromobenzaldehyde in 50 ml of anhydrous ether was added to the orange-red mixture. The color of the mixture lightens. After an additional hour, the reaction mixture was poured into water and extracted with ether. The extracts were combined, washed with water, concentrated under reduced pressure and chromatographed. Elution with dichloromethane. 5.95 g (85%) of 1-phenyl-2- (2-bromophenyl) ethylene are obtained as an almost colorless oil. The product contains the Z and E isomers in a ratio of 6: 1 (by gas chromatography and mass spectrum).

Grignaid reagent was prepared from 558 g of the 1-phenyl-2- (2-bromophenyl) -ethylene isomer mixture and 0.63 g of magnesium obtained in 20 ml of anhydrous tetrahydrofuran and 40 ml of 5.06 g of dimethyl oxalate in 30 minutes. dropwise to a solution of -15 ° C in anhydrous tetrahydrofuran. Stir the solution while adding the reagent. The resulting mixture was stirred for 30 minutes at -15 ° C, then stirred at room temperature for 1 min, then poured into dilute aqueous hydrochloric acid and extracted with ether. 30% by volume of ether in petrol and 20% by volume of dichloromethane in hexane were used to give 1.76 g (31%) of a yellow oily methyl Z-215 (2'-phenylethenyl) phenylglyoxalic acid methyl ester.

NMR (CDCl3); δ = 3.87 (3H, s), 6.78 (two doublets of doublets, 1H, J = 12 Hz) ppm.

Example 2

Preparation of E-2- (2'-Phenyl-ethenyl) -phenylglyoxalic acid methyl ester

From a solution of 12.64 g of benzyl chloride and 2.68 g of magnesium, a solution of benzyl magnesium chloride in 120 ml of anhydrous ether is added dropwise to a solution of 1850 g of 2-bromobenzaldehyde in 20 ml of anhydrous ether. A thick precipitate forms upon addition of the solution. After stirring for 1 hour at room temperature, the reaction mixture was poured into water, acidified with 2N aqueous hydrochloric acid and extracted with ether. The extracts were combined, washed with water, dried, concentrated and the residue chromatographed. The eluent was dichloromethane / gasoline (1: 1 v / v).

10.95 g (40%) of 1- (2-bromophenyl) -2-femlethan-1-ol are obtained as a white solid; m.p. 84-85 'C.

A mixture of 1- (2-bromophenyl) -2-phenylethan-1-ol (1550 g) and orthophosphoric acid (150 ml) was stirred at 170 ° C for 1 hour, poured into ice water and extracted with ether. The extracts were combined, washed with water. dried and concentrated. 14.29 g of an orange-red oily crude product are obtained which is distilled at 140 [deg.] C. and 0.4 mbar. 1253 g (86%) of E1-phenyl-2- (2-bromophenyl) ethylene are obtained; the pale 45 yellow oily product was 97% pure by gas chromatography.

Grignard reagent was prepared from 856 gE-1-phenyl-2- (2-bromophenyl) ethylene and 0.96 g of magnesium in 20 ml of anhydrous tetrahydrofuran, and 7.76 g of dimethyl oxalate in 70 ml of anhydrous It is added dropwise to its solution C. While the reagent was added, the mixture was stirred, the reaction mixture was stirred for an additional 30 minutes at -15 ° C, then for 1 hour at room temperature, and then poured into dilute aqueous hydrochloric acid and extracted. The extracts were combined, washed with water, dried and evaporated. 1732 g of a yellow oily crude product are obtained, which is purified by column chromatography. The eluent was dichloromethane / gasoline (1: 1 v / v). The product obtained is distilled at a bath temperature of 170 ° C and a pressure of 0.09 mbar. 2.01 g (23%) of methyl E-2- (2'-phenylethenyl) -ephylglyoxalic acid are obtained, and the yellow oil is pure by gas chromatography.

Nuclear Magnetic Resonance Spectrum (CDCl3): δ = 3.78 (3H, s).

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6.88 (center of two doublets, 1-1H, J = 16 Hz) ppm. Scope of the description:

Example 3 4 pages, 1

Preparation of 2-phenoxybenzoyl formic acid methyl ester

To a solution of 123 gdigenyl ether in 150 ml of anhydrous ether is added 5 µg of potassium tert-butoxide under stirring at -70 ° C. The resulting mixture was stirred at -70 ° C for 15 min and then 303 mL of a 1.62 M solution of η-butyllithium in hexane was added. The resulting red suspension was allowed to warm to room temperature. The resulting mixture was added over 20 minutes to a suspension of dimethyl oxalate (113 g) in ether (250 ml) at -10 DEG C. The mixture was stirred during the addition. The mixture was allowed to warm to room temperature and after 30 minutes was poured into water and extracted with ether. The extracts were combined, washed with water, dried and evaporated to give 14.21 g of a red oily residue, which was chromatographed with 20% by volume of ether in petrol as 2.23 g of yellow oily 2-phenoxybenzoyl. formic acid methyl ester.

Infrared (Film): 1736, 1678. 1595,1471,1450,1259,1227,1200,1150,740cm ¹ .4. example

Preparation of 2- (2'-Phenylethyl) phenylglyoxalic acid methyl ester

To a mixture of 1631 g of 1- (2-bromophenyl) -2-phenylethan-1-ol prepared as described in Example 2 and 13.80 g of triethylsilane was added 46 ml of trifluoroacetic acid. The resulting mixture was stirred at room temperature for 22 hours, then excess trifluoroacetic acid was evaporated under reduced pressure. The residue is dissolved in ether and the solution is washed three times with water, aqueous sodium bicarbonate solution and twice with water. The mixture was dried, concentrated under reduced pressure and the residue chromatographed. Petrol containing 10% by volume of dichloroethane was used as eluent. 8.02 g (52%) of crude 1- (2-bromophenyl) -2-phenylethane are obtained as an oil.

The stolen 1- (2-bromophenyl) -2-phenylethane was converted to the Grignard reagent as described in Examples 1 and 2 and the resulting Grignard reagent was reacted with dimethyl oxalate. The title product is stolen.

IR (film): 1735, 1681, 1597, 1448, 1198, 1172, 994, 750, 695 cm- ¹ .

5-14. example

By following the procedure described in Example ¹ , the compounds of formula (I) listed in Table I, wherein R1 is methyl, are prepared from the appropriate starting materials.

Table I

Apélda number X Y Physical constants 5th benzyloxy kaibonil- H NMR (CDCl₃): 3.70 (3H, s); 5.28 (2H, s) ppm 6th benzoylamino H op.75'C 7th Alkylamino 2.furoil H op. 85-88'C 8 E-2- (fur-2-yl) -ete- alkynyl H IR (film) 1744,1690,1600, 1212,1183,1020,1004,743 ^cm-1 9th 2-phenylethynyl, H IR (film) 2211,1746,1737, 1690,1589,1490,1200,995, 755.690 ^cm-1 10th N- (2-thienyl-carbo- fluorophenyl) -N-methylamino H op. 122-123 11th 4-nitrophenoxy H IR (film): 1729,1675,1589, 1504,1471,1340,1259,1234 744 cm ^-1 12th ethoxycarbonyl H IR (film): 1755, 1710, 1590, 1574, 1433, 1365, 1280, 1248, 1199, 1080, 1008, 757, 704 cm ^-1 13th cyclohexyloxy H NMR (CDCl3): 0.8-2.1 (10H, m) 3.80 (3H, s) 4.25 (1H, m), 6.8-7.8 (4H, m) ppm 14th a group of formula (a) m.p. 73-74 'C

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Claims (5)

PATENT CLAIMS A process for the preparation of ketoesters of general formula (I): wherein: R ^{1 is C} 1 -C 4 alkyl, Y is hydrogen and at the same time X-phenyl, nitro-phenoxy, phenyl (C 1-4 alkyl), phenyl (C 2-4 alkenyl), phenyl (C 2-4 alkynyl), furyl (C 2-4) alkenyl), benzoylamino, furoylamino, N- (thienylcarbonyl) N- (C 1-4 alkyl) amino, (C 1-4 alkoxy) carbonyl, benzylxoxycarbonyl- or C 3-6 cycloalkyloxy; or X and Y together form a group of formula (A), characterized in that the organometallic compounds of formula (II) in which M represents a lithium atom or a magnesium halide group and X and Y represent the oxalates of formula (ΙΠ) reacting - ^R1 is as defined in the formula of the object circuit. (Priority: 28.10.1988) Process according to claim 1, characterized in that the reaction is carried out in an ether-type anhydrous solvent at a temperature between -15 'C and room temperature. (Priority: 28.10.1988) 3. A process for the preparation of ketoesters of the formula I in the formula R ^{1 is C} 1 -C 4 alkyl, Y is hydrogen and at the same time X is phenoxy, nitrophenoxy, phenyl (C 1-4 alkyl), phenyl (C 2 -C 4 alkenyl), phenyl (C 2 -C 4 alkynyl), furyl (C 2 -C 4 alkenyl). , benzoylamino, furoylamino, N- (thienylcarbonyl) N- (C 1-4 alkyl) amino, (C 1-4 alkoxy) carbonyl, benzyloxycarbonyl or cyclohexyl represents an oxy group, or X and Y together form a group of formula (a), characterized in that the organometallic compounds of formula (Π), wherein M is lithium atom 5 or magnesium halide, and X and Y are of formula (ΠΙ) reacting with oxalates - wherein R is as defined herein. (Priority: 16.10.1985) Process according to claim 3, characterized in that the reaction is carried out in an ethereal anhydrous solvent at a temperature between 15 ° C and room temperature. (Priority: 16.10.1985) A process for the preparation of ketoesters of the formula I in the formula 15 R * is C 1 -C 4 alkyl, Y is hydrogen and X is phenoxy, nitrophenoxy, phenyl (C 1-4 alkyl), phenyl (C 2-4 alkenyl), phenyl (C 2-4 alkynyl). furyl (C 2 -C 4 alkenyl) 20, benzoylamino, furoylamino, N- (thienylcarbonyl) N- (C 1 -C 4 alkyl) amino, (C 1 -C 4 alkoxy) carbonyl - or a benzyloxycarbonyl group, characterized in that the compound of the formula (fém) and metal compounds - in which M represents a lithium atom or a magnesium halide group and X and Y represent the general formula (ΙΠ) * with sat oxalates - wherein R ¹ is as defined in the invention. (Priority: 19.10.1984) 6. The process according to claim 5, wherein the reaction is carried out in an ether-type anhydrous solvent at a temperature between -15 ° C and room temperature. (Priority: 19.10.1984)