EP1362025A2

EP1362025A2 - Polyhalogen-substituted cinnamic acids and cinnamic acid derivatives and a method for producing the same

Info

Publication number: EP1362025A2
Application number: EP02712904A
Authority: EP
Inventors: Walter Lange; Joachim Komoschinski; Markus Eckert; Michael Dockner
Original assignee: Bayer AG
Current assignee: Saltigo GmbH
Priority date: 2001-02-16
Filing date: 2002-02-13
Publication date: 2003-11-19
Also published as: WO2002066411A2; CN1491201A; US20020115885A1; US20080200731A1; US6956129B2; WO2002066411A3; US7381832B2; US20050234264A1; CN1246280C

Abstract

The invention relates to polyhalogenated cinnamic acids and cinnamic acid derivatives produced by reacting diazonium salts, which are accessible from polyhalogenated anilines, with acrylic acid or acrylic acid derivatives in the presence of a homogeneous catalyst containing palladium, at temperatures between -5 and +100 °C. Part of the cinnamic acids and cinnamic acid derivatives produced in this way is novel. Cinnamic acids and cinnamic acid derivatives produced according to the invention can be used to produce indanones, said indanones constituting precursors for agrochemicals and pharmachemicals and for substances having liquid crystalline properties.

Description

Polyhalogen-substituted cinnamic acids and cinnamic acid derivatives and a process for the production of polyhalogen-substituted cinnamic acids and cinnamic acid derivatives

The present invention relates to new polyhalogen-substituted cinnamic acids and cinnamic acid derivatives and a process for the production of known and new polyhalogen-substituted cinnamic acids and cinnamic acid derivatives.

Known halogen-substituted cinnamic acids and cinnamic acid derivatives are intermediates for the production of agrochemicals and pharmaceuticals (see DE-A 22 44 761, WO 95/30645, WO 94/26692, WO 94/7893, WO 94/26693 and US-A 5 753 655).

2,4-difluorocinnamic acid and its esters of formula (II) can be prepared by

Reacts benzyl halides of formula (I) with acetic anhydride or benzaldehydes of formula (I) with malonic acid or malonic acid esters.

The following reaction equation illustrates this:

A = OH or O-alkyl.

The disadvantage here is the high reaction temperature required, the unsatisfactory yield and the difficult accessibility of the compounds of the formula (I). The monthly issues of Chemie 90, 680 (1959) describe the conversion of 2,4-difluorobenz Aldehyde described with acetic anhydride at 180 ° C, 2,4-difluorocinnamic acid is obtained in 77% yield.

Another way of producing a halogen-substituted cinnamic acid derivative is based on 2,4-difluorobromobenzene and this with acrylic acid

Addition of triphenylphosphine palladium dichloride and potassium carbonate in dimethylformamide at 145 to 150 ° C. in the course of 6 hours. The corresponding cinnamic acid derivative is obtained in a yield of only 54% (Russ. J. Org. Chem. 33 (4), 563-569 (1997)). Here the yield is even more unsatisfactory and high reaction temperatures and long reaction times are also required.

Finally, it is known from EP-A-584 043 that compounds of the type Ar-CHR _a -CHR _b R _c can be prepared if diazonium salts of the type AR-N ₂ ^{® are used} with compounds of the type CR _a = CR ^ R _c to form compounds of the type Ar-CHR _a = CR _b R _c and works in the presence of homogeneous palladium catalysts and with the addition of 1 to 10 equivalents of base. This process is particularly suitable for the preparation of compounds in which the Ar radical is substituted by a sulfonic acid group, that is to say a strongly polar group. In addition to this restriction, it is disadvantageous that large amounts of bases have to be added in this process, which means additional costs and necessitates an expensive workup of the reaction mixture.

EP-A-584264 describes a process similar to that of EP-A-584 043. However, the process is carried out in the additional presence of arylphosphines, which is associated with further costs and additional effort.

There is therefore still a need for a process for the preparation of polyhalogenated cinnamic acids and cinnamic acid derivatives in which the desired products are obtainable in a higher yield than previously in a simple manner, at moderate temperatures, with short reaction times, without addition of base and without the mandatory addition of arylphosphines are. A process has now been found for the preparation of polyhalogenated cinnamic acids and cinnamic acid derivatives of the formula (III)

in the

R ¹ , R ² , R ³ and R ^{4 are the} same or different and each represents hydrogen, fluorine, chlorine or bromine, at least two of these radicals being different from hydrogen and

X represents OR ⁵ or N (R ⁶ ) (R ⁷ ), where

R ^{5 represents} hydrogen, optionally substituted Ci-C _j o-alkyl, optionally substituted phenyl or benzyl and

R ⁶ and R ^{7 are the} same or different and each represents optionally substituted C _j -C _Q alkyl and

R ^{8 represents} hydrogen, chlorine, bromine or optionally substituted C 1 -C 4 -alkyl,

which is characterized in that a diazonium salt of the formula (IV)

in the

R ¹ , R ² , R ³ and R ^{4 have} the meaning given for formula (III) and

A ^{Θ stands} for one equivalent of halide, hydrogen sulfate, nitrate, acetate or tetrafluoroborate ions or for V% equivalent of sulfate ions or for ₃ equivalent of phosphate ions,

with acrylic acid or an acrylic acid derivative of the formula (V)

in the

X has the meaning given for formula (III) and

R ^{8 represents} hydrogen, chlorine, bromine or optionally substituted -CC-alkyl,

in the presence of a homogeneous, palladium-containing catalyst at -5 to + 100 ° C. The method according to the invention is very particularly preferably carried out without the addition of a base. In general, 0.5 mol or less, preferably 0.1 mol or less and particularly preferably 0.05 mol of base per mol of diazonium salt of the formula (IV) can be used.

The process according to the invention is advantageously and very particularly preferably carried out without the addition of arylphosphines. In general, 4 mol or less, preferably 1 mol or less and particularly preferably 0.1 mol or less arylphosphines can be used per mol of palladium.

As far as the radicals R ⁵ , R ⁶ , R ⁷ and R ⁸ are optionally substituted alkyl radicals, substituents such as halogen, hydroxyl or Cg-C ₂ aryl radicals can be used. Of these substituents, 1 to 2 can be present, for example, per radical from the group R ⁵ , R ⁶ , R ⁷ and R ⁸ .

R ^{1 is} preferably hydrogen or chlorine, R ^{2 is} hydrogen, fluorine, chlorine or bromine, R ^{3 is} hydrogen or chlorine and R ^{4 is} fluorine or chlorine, at least one of the radicals R ¹ , R ² and R ^{3 being} different from hydrogen is.

R ⁵ preferably represents hydrogen, methyl, ethyl, isopropyl or benzyl. R ⁶ and

R ⁷ preferably represents methyl or ethyl. R ⁸ preferably represents hydrogen or methyl. A® preferably represents one equivalent of chloride, hydrogen sulfate or acetate or 1/2 equivalent of sulfate.

Examples of homogeneous, palladium-containing catalysts include Palladium (II) - and

Palladium (O) compounds in question such as PdCl ₂ , PdBr ₂ , Pd (NO ₃ ) ₂ , H ₂ PdCl ₄ , Pd (CH ₃ COO) ₂ , Na ₂ PdCl ₄ , K ₂ PdCl ₄ , Pd (II) - acetylacetonate, tetra (triphenylphosphine) Pd and tris (dibenzylidene acetone) Pd ₂ in question. PdCl ₂ , Pd (CH ₃ COO) ₂ and Pd (II) acetylacetonate are preferred. The respective palladium-containing catalyst can be used, for example, in an amount of 0.001 to 10 mol%, preferably on the diazonium salt of the formula (IN).

Preferred reaction temperatures are those from +20 to + 80 ° C, especially those from +40 to + 65 ° C.

The process according to the invention can optionally be carried out with the addition of simple solvents. Suitable simple solvents are, for example, water, alcohols such as e.g. Ci-Cö-alkyl alcohols, carboxylic acids such as e.g. Formic acid, ethers such as e.g. Tetrahydrofuran and nitriles, e.g. Acetonitrile.

The diazonium salts of the formula (IV) can be prepared in a manner known per se (see, for example, Houben-Weyl, volume X / 3, pages 7 to 113) from the corresponding anilines by reaction with sodium nitrite in an acidic aqueous solution or by reaction of methyl nitrite in acidic methanol The diazonium salts can be in

Form of the reaction mixture obtained in their preparation can be used in the process according to the invention, preferably after the destruction of any nitrite which may still be present. Isolation of the diazonium salts is not necessary.

Preferred compounds of the formula (V) are acrylic acid, methacrylic acid, acrylamide and methacrylamide.

Based on 1 mol of diazonium salt of the formula (IV), e.g. Use 0.5 to 2 moles of acrylic or acrylic acid derivatives of formula (V). This is preferably located

Amount at 0.9 to 1.5 moles.

The process according to the invention can be carried out, for example, by first starting from an aniline of the formula in the

R ¹ , R ² , R ³ and R ^{4 have} the meaning given for formula (III),

with sodium nitrite in sulfuric acid aqueous solution or with an alkyl nitrite such as methyl, ethyl, butyl or amyl nitrite, preferably methyl nitrite in acid, e.g. converted sulfuric acid methanol into a diazonium salt of the formula (IV), any nitrite present in the reaction mixture obtained was destroyed by adding amidosulfonic acid, the reaction mixture thus treated to a mixture of acrylic acid or an acrylic acid derivative of the formula (V) with a homogeneous, palladium-containing catalyst and optionally a simple solvent such as water, methanol, ethanol or isopropanol is added dropwise at the reaction temperature and, if appropriate after a subsequent stirring time, the product of the formula (III) is removed, if appropriate after cooling and / or dilution with water, for example by filtration, distillation or phase separation.

The process according to the invention has the advantages that it is simple, at low temperatures, in short reaction times, without large amounts and preferably without base additions without large amounts and preferably without absolutely necessary

Additions of arylphosphanes polyhalogen-substituted cinnamic acids and cinnamic acid derivatives in high yields. In addition, no special solvents such as amidic solvents e.g. Dimethylformamide used.

The present invention further relates to new polyhalogenated cinnamic acids and

Cinnamic acid derivatives of the formula

in the

R ² 'for chlorine and R ⁴ ' for fluorine or R ² 'for fluorine and R ⁴ ' for chlorine.

One way of producing the new compounds of formula (IIP) has been described above. Their usability is explained below.

The polyhalogenated cinnamic acids and cinnamic acid derivatives of the formula (III) including those of the formula (IIP) can be obtained by hydrogenation of the double bond (step 1) and subsequent cyclization (step 2) in indanone derivatives of the formula

in the

R ¹ to R ^{4 have} the meaning given for formula (III) and

R ⁸ is hydrogen, bromine, chlorine or optionally substituted C ^ _Q Ci -alkyl, are converted. Compounds of the general formula (VIIa) in which R ^{8 represents} hydrogen can be converted in a manner known per se by halogenation into the corresponding compounds of the general formula (VIIa) in which R ^{8 represents} bromine or chlorine.

Furthermore, Ner compounds of the general formula (VIIa) in which R ^{8 is} bromine or chlorine can be converted in a manner known per se, for example by palladium-catalyzed carbonylation reactions with carbon monoxide and a suitable nucleophile, into indanone derivatives of the formula (VIIIb),

in the

R ¹ to R ^{4 have} the meaning given for formula (III) and

R ^{9 represents} COOH, COΝH ₂ or COOR ¹⁰ , where

R ^{10 is} C _r C ₄ alkyl.

One can carry out the first step, for example, by in the presence of

Platinum or palladium, optionally hydrogenated at elevated pressure with hydrogen, and carry out the second step, for example, by converting the arylpropionic acids obtained into the corresponding acid chlorides and cyclizing them with the aid of Friedel-Crafts catalysts to give the indanones of the general formula (VIIa). These indanones and those of the formula (VIIIb) are agro- and pharmaceutical active ingredients and liquid-crystalline materials analogously to known processes (see, for example, WO 95/29171, EP-A 538 134, EP-A 401 166 and JP-OS 06-263 663) accessible.

The new compounds of the formula (IIP) broaden the range of available indanones and thus potential active ingredients in the agricultural and pharmaceutical fields and in the field of liquid-crystalline substances.

Examples

Example 1 2,4-difluorocinnamic acid

62 ml of concentrated sulfuric acid were added to 236 ml of water, the mixture was cooled to 5 ° C. and 38.7 g of 2,4-difluoroaniline were added. A solution of 23.9 g of sodium nitrite in 45 ml of water was added dropwise at 0 to 2 ° C. in the course of 40 minutes and the mixture was subsequently stirred for 30 minutes. Then enough amidosulfonic acid was added to destroy excess nitrite. 0.34 g of tris (dibenzylidene acetone) dipalladium (O) was added to 25.8 g of acrylic acid, and the diazonium salt solution was added dropwise at 40 ° C. over 4 hours and the mixture was subsequently stirred for 2 hours. After cooling to room temperature, 47.5 g of difluorocinnamic acid were isolated by filtration (86% yield of theory; melting point: 203 ° C.).

Example 2 2,4-difluorocinnamic acid

77.5 g of difluoroaniline were added dropwise to a mixture of 124 ml of concentrated sulfuric acid and 472 ml of water at 0.degree. A solution of 48.3 g of sodium nitrite in 90 ml of water was then added dropwise at 0 ° C. in 30 minutes, so that the temperature could be maintained. The mixture was then stirred at 0 ° C for 30 minutes. Excess nitrite was destroyed by the addition of sulfamic acid.

0.1 g of palladium (II) acetylacetonate was added to 54.8 g of acrylic acid and heated to 50.degree. At this temperature, the diazonium salt solution was added dropwise in 4 hours and stirring was continued for a further 2 hours. After cooling to room temperature, the solid was isolated by filtration, washed with water and dried (99.6 g; 90% yield of theory; melting point: 203 to 205 ° C). Example 3 4-Bromo-2-fluorocinnamic acid

62 ml of sulfuric acid were added to 236 ml of water and cooled to 5 ° C. At this temperature, 57.0 g of 4-bromo-2-fluoroaniline were added and a solution of 24.2 g of sodium nitrite in 45 ml of water was added dropwise at 0 to 2 ° C. in the course of 30 minutes and the mixture was subsequently stirred for 20 minutes. Then 2.8 g of amidosulfonic acid were added.

5 ml of the diazonium salt solution were added dropwise to 27.5 g of acrylic acid at 40 ° C., 0.23 g of palladium (II) acetylacetonate was added, and the remaining diazonium salt solution was added dropwise over the course of 20 minutes. The mixture was stirred at 40 ° C for 4 hours. The mixture was allowed to cool to room temperature and the product was isolated by filtration. After drying, 54.4 g of 4-bromo-2-fluorocinnamic acid were present (74% of theory; melting point: 218 ° C.).

Example 4 2,4-dichlorocinnamic acid

Gaseous methyl nitrite was prepared from 35 g of sodium nitrite in a methanol (20 ml) / water (60 ml) mixture by adding 30 ml of 50% sulfuric acid (30 ml), which at 0 ° C. was mixed into a mixture of 250 ml of water, 60 ml conc. Sulfuric acid and 53.5 g of 2,4-dichloroaniline was introduced. The mixture was stirred for 1 hour. Excess methyl nitrite was removed by passing a stream of nitrogen and adding 3 g of amidosulfonic acid. This solution was added over 2 hours at 40 ° C to a solution of 0.25 g palladium (II) acetylacetonate and 30 g acrylic acid and stirred for 2 hours. After cooling to room temperature, the precipitate was filtered and dried. 58.1 g of 2,4-dichlorocinnamic acid were obtained (81% yield of theory; melting point: 230 ° C.). Example 5 2,4-difluorocinnamic acid

To a mixture of 124 ml conc. Sulfuric acid and 472 ml of water were added dropwise at 0 ° C 77.5 g of difluoroaniline. A solution of 48.3 g of sodium nitrite in 90 ml of water was then added dropwise at 0 ° C. in such a way that the temperature could be maintained. The mixture was then stirred at 0 ° C for 30 minutes. Excess nitrite was destroyed by the addition of sulfamic acid.

0.34 g of palladium (II) acetate was added to 54.8 g of acrylic acid and heated to 47.degree. At this temperature, the diazonium salt solution was added dropwise in the course of 2 hours so that the temperature did not exceed 49 ° C., and the mixture was then stirred for a further 2 hours. After cooling to room temperature, the solid was isolated by filtration, washed with water and dried. This gave 105.1 g of 2,4-difluorocinnamic acid (95% yield of theory; melting point 204-205 ° C.).

Example 6 3- (2,4-difluorophenyl) -2-methylacrylic acid

To a mixture of 124 ml conc. Sulfuric acid and 472 ml of water were added dropwise at 0 ° C 77.5 g of difluoroaniline. A solution of 48.3 g of sodium nitrite in 90 ml of water was then added dropwise at 0 ° C. in such a way that the temperature could be maintained, and the mixture was then stirred at 0 ° C. for 30 minutes. Excess nitrite was destroyed by the addition of sulfamic acid.

0.34 g of palladium (II) acetate was added to 60.1 g of methacrylic acid and heated to 45.degree. At this temperature, the diazonium salt solution was added dropwise in the course of 2 hours so that the temperature did not exceed 50 ° C., and the mixture was then stirred for a further 2 hours. After cooling to room temperature, the solid was isolated by filtration, washed with water and dried. 118.0 g of 3- (2,4-difluorophenyl) -2-methylacrylic acid were obtained (85% yield of theory; melting point 140-142 ° C.). Example 7 3- (2,4-difluorophenyl) propionic acid (not according to the invention)

105 g of 2,4-difluorocinnamic acid from Example 5 were dissolved in 450 ml of tetrahydrofuran and reacted with 5 g of palladium on active cooling with stirring at 100 ° C. and 50 bar hydrogen pressure. After constant pressure was reached, the mixture was cooled to room temperature, the pressure was released, the palladium catalyst was filtered off and the solvent was distilled off. After drying in vacuo, 104.1 g of 3- (2,4-difluorophenyl) propionic acid (98% of theory; melting point: 100-102 ° C.) were obtained.

Example 8 2,5-difluoro-4-chlorocinnamic acid

To a mixture of 124 ml conc. Sulfuric acid and 472 ml of water were added dropwise at 0 ° C to 98.2 g of 2,5-difluoro-4-chloroaniline. A solution of 48.3 g of sodium nitrite in 90 ml of water was then added dropwise at 0 ° C. in such a way that the temperature could be maintained. The mixture was then stirred at 0 ° C for 30 minutes.

Excess nitrite was destroyed by the addition of sulfamic acid.

0.34 g of palladium (II) acetate was added to 54.8 g of acrylic acid and heated to 47.degree. At this temperature, the diazonium salt solution was added dropwise in the course of 2 hours so that the temperature did not exceed 49 ° C., and the mixture was then stirred for a further 2 hours. After cooling to room temperature, the solid was isolated by filtration, washed with water and dried. This gave 116.7 g of 2,5-difluoro-4-chlorocinnamic acid (89% yield of theory).

Example 9 2,5-difluoro-3-chlorocinnamic acid

To a mixture of 124 ml conc. Sulfuric acid and 472 ml of water were added dropwise at 0 ° C to 98.2 g of 2,5-difluoro-3-chloroaniline. A solution of 48.3 g of sodium nitrite in 90 ml of water was then added dropwise at 0 ° C. in such a way that the temperature could be maintained. The mixture was then stirred at 0 ° C for 30 minutes.

Excess nitrite was destroyed by the addition of sulfamic acid. 0.34 g of palladium (II) acetate was added to 54.8 g of acrylic acid and heated to 47.degree. At this temperature, the diazonium salt solution was added dropwise in the course of 2 hours so that the temperature did not exceed 49 ° C., and the mixture was then stirred for a further 2 hours. After cooling to room temperature, the solid was isolated by filtration, washed with water and dried. This gave 108.9 g of 2,5-difluoro-3-chlorocinnamic acid (83% yield of theory).

Example 10 2,3,4,5-tetrachlorocinnamic acid

To a mixture of 124 ml conc. Sulfuric acid and 472 ml of water were added dropwise at 0 ° C to 98.2 g of 2,3,4,5-tetrachloroaniline. A solution of 48.3 g of sodium nitrite in 90 ml of water was then added dropwise at 0 ° C. in such a way that the temperature could be maintained. The mixture was then stirred at 0 ° C for 30 minutes. Excess nitrite was destroyed by the addition of sulfamic acid.

0.34 g of palladium (II) acetate was added to 54.8 g of acrylic acid and heated to 47.degree. At this temperature, the diazonium salt solution was added dropwise in the course of 2 hours so that the temperature did not exceed 49 ° C., and the mixture was then stirred for a further 2 hours. After cooling to room temperature, the solid was isolated by filtration, washed with water and dried. This gave 144.1 g of 2,3,4,5-tetrachlorocinnamic acid (84% yield of theory).

Example 11 3- (2,4-difluorophenyl) propionic acid (not according to the invention)

The procedure was as in Example 5, but the 2,4-difluorocinnamic acid obtained was not isolated. The resulting aqueous-acidic product suspension was mixed with further stirring at 50 ° C. with 2 g Pd / C (5%) and heated to 100 ° C. Hydrogen was then injected up to 5 bar. After reaching constant pressure, the mixture was cooled to room temperature, the pressure was released and the solid was filtered off. The filter cake was taken up in methylene chloride and the palladium catalyst was filtered off and the solvent is removed. After drying in vacuo, 100.5 g of 3- (2,4-difluorophenyl) ρropionic acid (90% of theory; melting point: 100 ° C.) were obtained.

Example 12 3- (2,4-difluorophenyl) propionic acid (not according to the invention)

The procedure was as in Example 11, but the addition of palladium on activated carbon was dispensed with. 98.3 g of 3- (2,4-difluorophenyl) propionic acid (88% of theory) were obtained.

Example 13 3- (2,4-difluorophenyl) propionic acid (not according to the invention)

The procedure was as in Example 5, but the 2,4-difluorocinnamic acid obtained was not isolated. The aqueous-acidic product suspension obtained was made alkaline with sodium hydroxide solution and, with further stirring at 50 ° C., 2 g of Pd / C (5% strength) were added and the mixture was heated to 100 ° C. Hydrogen was then injected up to 5 bar.

After reaching constant pressure, the mixture was cooled to room temperature, the pressure was released and the palladium catalyst was filtered off. The alkaline product solution was acidified with sulfuric acid and the product precipitate was isolated by filtration. After drying in vacuo, 95.0 g of 3- (2,4-difluorophenyl) propionic acid (85% of theory) were obtained.

Example 14 4,6-difluoroindan-l-one (not according to the invention)

To a solution of 3- (2,4-difluorophenyl) propionic acid (57 g) in methylene chloride (200 ml) was added dropwise at 40 ° C thionyl chloride (54.6 g). After the reaction, excess thionyl chloride and the solvent were distilled off. The oily residue was added dropwise at 40 ° C. to a suspension of aluminum chloride (88.5 g) in methylene chloride (200 ml). The reaction mixture was added to dilute hydrochloric acid after 18 hours at 40 ° C. The aqueous phase was separated and extracted once with methylene chloride (250 ml). The combined organic phases were freed from the solvent and then distilled in vacuo. 41 g of a colorless solid were obtained (mp: 103 ° C.).

Example 15 4,6-dichloroindan-l-one (not according to the invention)

Thionyl chloride (36.9 g) was added dropwise at 40 ° C. to a solution of 3- (2,4-dichlorophenyl) propionic acid (43.8 g) in methylene chloride (200 ml). After the reaction, excess thionyl chloride and the solvent were distilled off. The oily residue was added dropwise at 40 ° C. to a suspension of aluminum chloride (53.3 g) in methylene chloride (200 ml). The reaction mixture became after 18 hours

40 ° C added to dilute hydrochloric acid. The aqueous phase was separated and extracted once with methylene chloride (250 ml). The combined organic phases were freed from the solvent. The residue was recrystallized from cyclohexane. 30 g of a colorless solid were obtained (mp: 115-116 ° C.).

Example 16 5,7-dichloroindan-l-one (not according to the invention)

Thionyl chloride (45.2 g) was added dropwise at 40 ° C. to a solution of 3- (3,5-dichlorophenyl) propionic acid (54.8 g) in methylene chloride (200 ml). After the reaction, excess thionyl chloride and the solvent were distilled off. The oily

The residue was added dropwise at 40 ° C. to a suspension of aluminum chloride (66.7 g) in methylene chloride (200 ml). The reaction mixture was added to dilute hydrochloric acid after 18 hours at 40 ° C. The aqueous phase was separated and extracted once with methylene chloride (250 ml). The combined organic phases were freed from the solvent. The residue was recrystallized from cyclohexane. 36 g of a colorless solid were obtained (mp: 119-120 ° C.). Example 17

Analogously to Example 5, starting from 2-chloro-5-fluorine in a yield of 80% of theory 2-C_ιlor-5-f_uorzimtsäure prepared. The melting point of this cinnamic acid was 182 ° C, the -NMR spectrum showed characteristic absorptions

6.6 ppm (d), 7.25 ppm (m), 7.5 ppm (m) and 7.75 (m), recorded in DMSO.

Example 18

Analogously to Example 5, starting from 2-fluoro-5-chloro-aniline in a yield of 81% of theory 2-fluoro-5-chloro-cinnamic acid. The melting point of this cinnamic acid was 183 ° C, the NMR NMR spectrum showed characteristic absorptions at 6.6 ppm (d), 7.25 ppm (t), 7.45 ppm (m), 7.55 ppm (d) and 7.9 ppm (m) recorded in DMSO.

Claims

claims

1. Process for the preparation of polyhalogenated cinnamic acids and cinnamic acid derivatives of the formula (III)

in the

X represents OR ⁵ or N (R ⁶ ) (R ⁷ ), where

R ^{5 represents} hydrogen or optionally substituted Ci-Ci Q-alkyl, optionally substituted phenyl or benzyl and

R ⁶ and R ^{7 are the} same or different and each represents optionally substituted Ci-Ci _Q alkyl and

R ^{8 represents} hydrogen, chlorine or bromine or optionally substituted Ci-C Q-alkyl,

characterized in that a diazonium salt of the formula (IV)

in the

R ¹ , R ² , R ³ and R ^{4 have} the meaning given for formula (III) and

A ^{Θ stands} for one equivalent of halide, hydrogen sulfate, nitrate, acetate or tetrafluoroborate ions or for V equivalent of sulfate ions or for 3 equivalent phosphate ions,

with acrylic acid or an acrylic acid derivative of the formula (V)

in the

X has the meaning given for formula (III) and

R ^{8 represents} hydrogen, chlorine or bromine or optionally substituted Ci-Ci Q-alkyl,

in the presence of a homogeneous, palladium-containing catalyst at -5 to + 100 ° C.

2. The method according spoke 1, characterized in that in the formulas R ¹ for hydrogen or chlorine, R ² for hydrogen, fluorine, chlorine or bromine, R ³ for hydrogen or chlorine and R ⁴ for fluorine or chlorine, at least one the radicals R ¹ , R ² and R ^{3 are} different from hydrogen,

R ^{5 represents} hydrogen, methyl, ethyl, isopropyl or benzyl,

R ⁶ and R ^{7 represent} methyl or ethyl,

R ^{8 represents} hydrogen or methyl and

A ^Θ for one equivalent of chloride, hydrogen sulfate or acetate or for V ₂ equivalent of sulfate.

3. Process according to Claims 1 to 2, characterized in that the catalysts are PdCl ₂ , PdBr ₂ , Pd (NO ₃ ) ₂ , H ₂ PdCl ₄ , Pd (CH ₃ COO) ₂ , Na ₂ PdCl ₄ , K ₂ PdCl ₄ , Pd (II) acetylacetonate, tetra (trisphenylphosphine) Pd or tris (di-benzylidene acetone) Pd ₂ in amounts of 0.001 to 10 mol%, based on the

Diazonium salt of formula (IV) is used.

4. Process according to Claims 1 to 3, characterized in that the diazonium salts of the formula (IV) are prepared from the corresponding anilines by reaction with sodium nitrite in acidic, aqueous solution or by reaction with an alkyl nitrite in acidic methanol and they are in the form the reaction mixtures obtained in their manufacture.

5. Process according to Claims 1 to 4, characterized in that 0.5 to 2 moles of acrylic acid or acrylic acid derivatives of the formula (V) are used per mole of diazonium salt of the formula (IV).

6. The method according to claims 1 to 5, characterized in that it is carried out without a base.

Polyhalogenated cinnamic acids and cinnamic acid derivatives of the formula

in the

8. Use of polyhalogenated cinnamic acids and cinnamic acid derivatives of the formula (III) for the preparation of indanone derivatives of the formula

in the

R ^{y is} COOH, CONH ₂ or COOR ¹⁰ , where

R ^{10 is} C _r C ₄ alkyl.

Use of polyhalogenated cinnamic acids and cinnamic acid derivatives of the formula (III) for the preparation of indanone derivatives of the formula in the

R ^{8 represents} hydrogen, chlorine, bromine or optionally substituted Ci

Cio-alkyl is.