HU188301B - Process for preparing 3-bromo-4-fluoro-benzaldehyde acetals - Google Patents

Abstract

A yarn false twisting apparatus is disclosed which comprises a pair of co-operating friction discs (1,2) which define a twisting zone between opposed friction surfaces thereof. One of the discs (2) is composed of a thin flexible material, and a pressure applying member (10) is mounted adjacent the back side of the flexible disc (2) for basing the disc toward the other disc (1) locally at the twisting zone to firmly engage the yarn (14) passing therethrough. The discs are laterally movable with respect to each other, and the pressure applying member is movable in a direction perpendicular to the movement of the discs, such that the ratio of twist insertion to yarn speed may be varied. In one illustrated embodiment, the discs and pressure applying member are interconnected for effecting synchronized relative movement, and these components are mounted on a support bracket (73) which is pivotal through 180 degrees thereby to permit selective operation in a first position wherein S twist is imparted to the yarn and a second position wherein Z twist is imparted. <IMAGE>

Description

The present invention relates to a novel process for the preparation of 3-bromo-4-fluorobenzaldehyde acetals.

It is known that an intermediate of pesticidal pyrethroids, 4-fluoro-3-phenoxybenzaldehyde, can be prepared by reacting 4-fluoro-3-phenoxybenzyl bromide with hexamethylenetetramine and heating the product of the reaction with acid (see 27 09 264). German Federal Procurement Document).

However, the yield of this method of synthesis, similar to the preparation of 4-fluoro-3-phenoxytoluene and N-bromosuccinimide starting materials, is unsatisfactory.

Furthermore, 3-Bromo-4-fluorobenzaldehyde and its acetals and intermediates for the preparation of 4-fluoro-3-phenoxybenzaldehyde acetals as 4-fluoro-3-phenoxybenzaldehyde are the subject of an earlier, unpublished patent application. German Patent Application No. 29 33 979).

1. We have discovered that the 3-bromo-4-fluorobenzaldehyde acetals of the formula I in which

R is C 1 -C 4 alkyl, or the two R substituents together form a C 2 -C 5 alkanediyl group, may be prepared if

a) 3-bromo-4-fluorobenzaldimine of formula II, wherein:

R ¹ is C 5 -C 6 cycloalkyl or phenyl optionally substituted with halo, C 1 -C 4 alkyl and / or nitro, alcohols of formula (III) or alkanediols

R is as defined above and n is 1 or 2 in the presence of sulfuric acid at a temperature of 0 ° C to 100 ° C, or

b) reacting a 3-bromo-4-fluorophenylglyoxylic acid of formula IV with an amine of formula V wherein R ¹ is as defined above, optionally in the presence of a diluent, at a temperature of 0 to 200 ° C and the resulting crude product comprising the compounds of formula (II) is reacted with an alcohol of formula (III) in the presence of a catalytic amount of sulfuric acid at a temperature of from 0 to 100 ° C;

2. We have further discovered that the compound of formula II

3-Chromo-4-fluorobenzaldimine can be prepared if

a) reacting a 3-bromo-4-fluorobenzaldehyde of formula (V) with an amine of formula (V):

R ¹ is as defined above, optionally in the presence of a diluent, or

b) a 3-bromo-4-fluoro-phenyl-glyoxylic acid of formula (IV) (V) with an amine of formula wherein ^R! is as defined above, optionally in the presence of a diluent;

3. We have further discovered that the 3-bromo-4-fluorophenylglyoxylic acid of formula (IV) can be obtained by

Reacting 3-bromo-4-fluorobenzoyl cyanide with hydrochloric acid or sulfuric acid;

4. We have further discovered that the 3-bromo-4-fluorobenzoyl cyanide of formula (VII) can be prepared by reacting a 3-bromo-4-fluorobenzoyl cyanide of formula (VIII) wherein

X is a fluorine, chlorine or bromine atom, reacted with sodium cyanide or potassium cyanide.

Surprisingly, the 3-bromo-4-fluorobenzaldehyde acetals can be obtained more readily and in higher yields by the process of the present invention via the novel 3-bromo-4-fluorobenzaldehyde than by the methods mentioned above. The advantage of the process according to the invention is, first of all, the use of cheaper starting materials and reaction components, no reduction or oxidizing agents being required and the possible formation of acetal without additional auxiliaries such as orthoester.

The new process described in (1) ("Process 1"), using N-phenyl-3-bromo-4-fluorobenzaldimine and ethanol (a) or 3-bromo-4-fluorophenylglyoxylic acid and aniline, and finally ethanol (b) reaction scheme.

In Scheme A, process (1) (a) is carried out at a temperature of 0 to 100 ° C, preferably 10 to 50 ° C.

The alcohols or alkanediols used as starting materials in process (1) are represented by formula (III). Examples include methanol, ethanol, n- and isopropanol, π-, iso-, chair- and tert-butanol as well as ethane-1,2-diol, propane-1,3-diol and 2,2-dimethyl propane-1,3-diol. Particularly preferred starting materials are methanol, ethanol cut ethane-1,2-diol.

The alcohols (III) are used in excess to dilute the reaction mixture. Generally, from 1 mol to 80 mol, preferably from 1 mol to 40 mol, of the alcohol (III) is used per mole of aldimine (II). Further, 0.5 mol to 1.5 mol, preferably 0.5 mol to 1 mol of sulfuric acid are used for 1 mol of aldimine (II).

In a preferred embodiment of process a), the 3-bromo-4-fluorobenzene-1-dimer of formula II is dissolved in the alcohol of formula III and sulfuric acid is added slowly to this solution. The reaction mixture was stirred until completion of the conversion. The processing is carried out according to the usual methods. For example, the alcohol is distilled off under reduced pressure and the residue is diluted with a substantially water-immiscible grain solvent such as toluene. filter off the dissolved residue. The filtrate is washed (e.g. with aqueous potassium carbonate), dried, filtered and evaporated. Vacuum distillation of the residue then affords the product of formula (1).

Preferably, the first step of variant b) of process 1) is carried out using a diluent. Virtually all inert organic solvents are suitable as diluents. These include in particular aliphatic and aromatic, optionally halogenated hydrocarbons such as pentane, hexane, heptane, cyclohexane, petroleum ether, gasoline, ligroin, benzene, toluene, xylene, methylene chloride, ethylene chloride, chloroform, carbon tetrachloride, chlorine benzene and o-dichlorobenzene, ethers such as diethyl and dibutyl ether, glycol dinethyl ether and diglycol dimethyl ether, tetrahydrofuran and dioxane, and amides such as dimethylformamide and dimethylacetamide.

-2188 301

The reaction temperature may vary within a wide range. Generally, temperatures of from 0 to 200 ° C, preferably from 50 to 150 ° C, are employed.

Generally, 0.9 to 1.5 moles, preferably 0.95 to 1.2 moles, of amine V are used per mole of phenylglyoxylic acid of formula (IV).

In a preferred embodiment of the first step of process b), the 3-bromo-4-fluorophenylglyoxylic acid of formula (IV) is dissolved in one of the above diluents at a temperature of 50 to 100 ° C and the amine of formula (V) at temperature,

The reaction mixture is heated to the end of the decarboxylation and the solvent is carefully removed by distillation under reduced pressure. The resulting crude product of formula II is converted to the product of formula I as described in process a).

Used as starting material in process 1)

The 3-bromo-N-fluorobenzaldimines are represented by the formula (II) and the corresponding amines are represented by the formula (V). In these formulas, 20

Preferably R ¹ is C 5 -C 6 cycloalkyl or phenyl optionally substituted with methyl, ethyl, chlorine and / or nitro.

Examples of aldimines of formula (II) include Ν-cyclopentyl, N-cyclohexyl, Ν-phenyl, N- (4-methylphenyl), N- (3-methylphenyl), N- (2) methylphenyl), N- (4-chlorophenyl), N- (4-nitrophenyl), N- (3-nitrophenyl), and N- (2,6-diethylphenyl) -. 3-Bromo-4-fluoro-benzaldimine. 30

Examples of amines of formula (V) are cyclopentylamine, cyclohexylamine, amine, 2-methyl, 3-methyl, 4-methyl, 4-chloro, 4-nitro,

3-nitro, and 2,6-diethylaniline,

The process described in 2) for the preparation of the new 3-bromo-4-fluorobenzaldimines ("process 2") 3-bromo-4-fluorobenzaldehyde and aniline (a) and 3-bromo-4-fluorophenyl Scheme B illustrates the use of glyoxylic acid and aniline (b) starting materials.

Preferably, the solvents used in Process 2 are the solvents used in Process 1). The reaction temperature can vary within wide limits. Generally, temperatures of from 0 to 200 ° C, preferably from 50 to 150 ° C, are employed. Generally 0.9 to 45 per mole of 3-bromo-4-fluorobenzaldehyde and 3-bromo-4-fluorophenylglyoxylic acid

1.5 mol, preferably 0.95-1.2 mol, of the amine V are used.

In a preferred embodiment of process 2 (a), the 3-bromo-4-fluorobenzaldehyde is boiled with an amine of formula (V) in one of the above-mentioned diluents, preferably an azeotropic water-separating solvent such as toluene. until it is expedient to remove the water from the coupling product through a water separator. The product of formula II is isolated by careful distillation of the liquid components under reduced pressure 55.

Process 2 (b) is carried out in the same manner as described in the first step of process l (b).

The process for the preparation of 3-bromo-4-fluorobenzo-θθ aldehyde as a starting material is the subject of a previous application (see German Patent Application No. 29 33 979).

The 3-bromo-4-fluorophenyl-glyoxylic acid used as an alternative starting material can be prepared from 3-bromo-4-fluoro-benzoic cyanide with hydrochloric acid or sulfuric acid, preferably hydrochloric acid. The reaction temperature is generally maintained at 0-100 ° C, preferably at 20-80 ° C. One mole of 3-bromo-4-fluorobenzoyl cyanide is used in 1-2 liters of the above acid in a concentration of 30-60% by weight. The acid concentration is optionally raised during the reaction by the introduction of hydrogen chloride gas.

In carrying out the procedure described under (3) above, the reaction mixture mixture is stirred at 20-30 ° C for several hours and then heated at 70-80 ° C for several hours. Upon cooling to 20 ° C, the reaction mixture precipitated in crystalline form and was isolated by filtration.

The 3-bromo-4-fluorobenzoyl cyanide used as starting material in process 3) can be prepared from the 3-bromo-4-fluorobenzoyl halides of formula VIII with sodium cyanide or potassium cyanide. The reaction is carried out at a temperature of 0 to 150 ° C, preferably 20 to 120 ° C. 0.9 to 1.5 moles, preferably 1 to 1.2 moles, of alkali cyanide are used per mole of the halide of formula VIII.

In a preferred embodiment of the process described in step 4), the reaction components are stirred at 20 ° C and the mixture is heated to 50-120 ° C until the reaction is complete. After cooling, the mixture was filtered. The product of formula (VII) in the filtrate can be purified by vacuum distillation.

The process for the preparation of the 3-bromo-4-fluorobenzoic acid halides of formula VIII used as starting material is the subject of an application which is not disclosed in the prior art (see German Patent Application No. 2915738).

For example, a mixture of 3-bromo-4-fluorobenzoyl acid fluoride and bromide can be prepared by converting 4-chlorobenzoyl chloride with potassium fluoride to 4-fluorobenzoyl fluoride and brominating the latter.

The ^? -Chlorobenzoyl chloride is reacted with potassium fluoride, for example in tetramethylene sulfone, at a temperature of 200-220 ° C. This gives 4-fluorobenzoyl fluoride, boiling at 53 ° C / 20 mBar (refractive index Πρ = 1.4792). The 4-fluorobenzoyl fluoride is reacted with elemental bromine in the presence of 1% ferric chloride at 70-75 ° C. Using one mole, 40 g of unreacted starting material and 182 g of 3-bromo-4-fluorobenzoyl fluoride (boiling point 82-83 ° C) are recovered at 15 mBar; refractive index = 1.5315; 32-34 DEG C.) and a mixture of 3-bromo-4-fluorobenzoyl bromide (m.p. 123 DEG C. m.p. 35-37 DEG C.).

The 3-bromo-4-fluorobenzaldehyde acetals of formula (I) can be used to prepare the 3-phenoxy-4-fluorobenzaldehyde intermediate known as insecticides (see German Patent Publication No. 2,709,264), while the 3-phenoxy-4-fluorobenzaldehyde acetals may be isolated as an intermediate.

For example, 3-phenoxy-4-fluorobenzaldehyde can be prepared according to Scheme C in the first step using 3-bromo-4-fluorobenzaldehyde diethyl acetal and potassium phenolate starting materials and in the second step by acetal cleavage with an acid such as hydrochloric acid.

The phenolic alkali and / or alkaline earth metal compounds which may be used as starting materials are, for example, sodium, potassium or magnesium phenolate. As catalyst 3

188 301 copper or copper compounds are used. Examples include copper, copper (I) oxide, copper (II) oxide, copper (I) chloride or copper (I) bromide. Preferred diluents are aprotic polar organic solvents such as dimethylformamide, dimethylacetamide, N-methylpyrrolidone, dimethylsulfoxide, tetramethylene sulfone, hexamethylphosphoric triamide or bis (2-methoxyethyl) ether. The latter is particularly advantageous.

The reaction temperature is maintained at 100-200 ° C, preferably 130-170 ° C. The process is usually carried out at normal pressure. For one mole of 3-bromo-4-fluorobenzaldehyde acetal of formula I, 1 to 2 moles, preferably 1.2 to 1.8 moles, of phenolate, 0.01 to 0.5 moles, preferably 0.1 to 0, 5 mol of copper catalyst and 100-500 ml of diluent are used. In a preferred embodiment of the process described, the phenolate is mixed with a copper catalyst in one of the solvents indicated above and the mixture is heated to the reaction temperature. 3-Bromo-4-fluorobenzaldehyde acetal is then added dropwise and the reaction mixture is stirred for several hours. The reaction mixture is worked up in the usual manner, for example by distilling off the diluent under reduced pressure, dissolving the residue in toluene, filtering, washing the filtrate with dilute sodium hydroxide solution and distilling off under reduced pressure. This gives 3-phenoxy-4-fluorobenzaldehyde acetal as a colorless solution.

The acetal is saponified in the usual manner to give 3-phenoxy-4-fluorobenzaldehyde. Preferably, the acetal is mixed with a dilute mineral acid such as hydrochloric acid or sulfuric acid and stirred at 20-60 ° C for several hours. During the work-up, it is extracted with an organic solvent which is practically immiscible with water, such as toluene, the extract is washed with sodium bicarbonate solution and water, and the solvent is distilled off under reduced pressure. 3-Phenoxy-4-fluorobenzaldehyde was obtained as an oily residue.

Production examples

Example 1

Preparation of 4-fluoro-3-bromobenzoyl cyanide

177 g (3.6 mol) of sodium cyanide and 663 g (3 mol)

3-Bromo-4-fluorobenzoyl fluoride was stirred and heated. At about 80 ° C, an exothermic reaction occurs, which must be quenched with mild cooling. Meanwhile, the temperature may rise to 100 ° C and stir at this temperature for 1 hour. The exothermic reaction lasts for about 10 minutes and then slightly warmed. Finally, the reaction mixture is cooled, the salt is filtered off and destroyed in a saturated solution of ferrous sulfate and the filtrate is distilled over a column. This gives 507 g (74% of theory) of a colorless oil boiling at 126 ° C / 26.6 mBar.

Example 2

Preparation of 4-fluoro-3-bromophenylglyoxylic acid

a) A mixture of 228 g of 4-fluoro-3-bromobenzoyl cyanide and 1625 ml of concentrated hydrochloric acid is stirred for 20 hours at room temperature. Then slowly

Heat to 70-80 ° C and stir at this temperature for 8 hours. After stirring for 17 hours at room temperature, a crystalline precipitate formed which was filtered off, washed with 1000 ml of water and dried in vacuo at 35-40 ° C for 24 hours. 246 g (99.6% of theory) of 4-fluoro-3-bromophenylglyoxylic acid are obtained in the form of a colorless powder, m.p. 68-73 ° C.

b) 4-Fluoro-3-bromobenzoyl cyanide (45.6 g, 0.2 mol) was dissolved in concentrated hydrochloric acid (200 mL) and a gentle stream of hydrogen chloride was introduced for 5 hours. Meanwhile, the temperature rises to + 30 ° C. Finally, the mixture was stirred at 80 ° C for 6 hours. The mixture is cooled and the precipitated crystals are filtered off. 433 g (87% of theory) of 4-fluoro-3-bromophenyl-glyoxylic acid are obtained in the form of colorless crystals.

Example 3

Preparation of 4-fluoro-3-bromobenzaldehydanyl

(a) 1300 ml of a mixture of toluene or chlorobenzene and 247 g of 4-fluoro-3-bromophenylglyoxylic acid. At 70-80 ° C, 102.3 g (1.1 mol) of freshly distilled aniline are added dropwise. The reaction mixture was then heated to reflux and stirred at reflux for a further 4 hours until the decarboxylation was complete and the solvent was removed under vacuum. 270 g (97% of theory) of anil are obtained as a colorless powder, m.p. 45-47 ° C.

b) 101.5 g (0.5 mol) of 4-fluoro-3-bromobenzaldehyde and 46.5 g (0.5 mol) of aniline are dissolved in 250 ml of toluene and cooked on a water separator for 1 hour. The solvent was then evaporated in vacuo. 129 g (93% of theory) of 4-chloro-3-bromobenzene] dehydanyl are obtained in the form of colorless crystals, m.p. 47-49 ° C.

In a manner analogous to Example 3, the following compounds of formula II can be prepared:

R ¹ mp (° C) cyclohexyl partially crystalline cyclopentyl partially crystalline p-tolyl p-chlorophenyl

Example 4

Preparation of 4-fluoro-3-bromobenzaldehyde dimethyl acetal ("one pot" procedure from glyoxylic acid)

To a mixture of 1300 ml of toluene or chlorobenzene and 247 g of 4-fluoro-3-bromophenylglyoxylic acid, 102.3 g (1.1 mol) of freshly distilled aniline are added dropwise at 70-80 ° C. The reaction mixture was then heated to reflux for 4 hours under reflux until the decarboxylation reaction was complete.

After stirring under vacuum, the solvent was distilled off at a pressure of 0.5 to 0.01 Torr.

The residue was dissolved in 1000 ml of anhydrous methanol and 54 g of sulfuric acid monohydrate was added dropwise at 20-25 ° C. After stirring at room temperature for 4 hours, the methanol was distilled off under a water-jet vacuum, the residue was taken up in toluene, filtered and the filtrate was washed once with dilute potassium carbonate solution. After drying over sodium sulfate, the organic phase is reduced under a water-jet vacuum and distilled at 0.1 Torr. After pre-distillate at 35-40 ° C, acetal is obtained at 65-70 ° C. This gave 209 g (84% of theory) of the title compound as a colorless oil.

Example 5

Preparation of 4-fluoro-3-bromobenzaldehyde dimethyl acetal from anil

27.8 g (0.1 mol) of 4-fluoro-3-bromobenzaldehydanil are dissolved in 100 ml of absolute methanol and 5.4 (0.055 mol) of anhydrous sulfuric acid is added dropwise at 20-25 ° C and the mixture is stirred for 4 hours at room temperature. Stir at 25 ° C. The solvent is then removed in vacuo, the residue is taken up in toluene and the insoluble residue is filtered off. The filtrate was washed with 50 ml of 5% potassium carbonate solution, dried over sodium sulfate and evaporated. The residue was distilled in vacuo. This gave 22.9 g (92% of theory) of acetal as a colorless oil boiling at 79 ° C / 0.665 mBar.

The following compounds may be prepared analogously:

....... ....... ...... 35

Formula Number Boiling Point (1) 70-72 ^ / 0.266 mBar (2) 67-70 ° C / 0.133 mBar 40

Claims (2)

A patent claim A process for the preparation of 3-bromo-4-fluorobenzaldehyde acetals of formula I wherein R is a C 1-4 alkyl group or the two R substituents taken together form a C 2-5 alkanediyl group, wherein a) a 3-bromo-4-fluorobenzaldimine of formula II, wherein: R ¹² is C 5 -C 6 cycloalkyl or phenyl optionally substituted with halo, C 1 -C 4 alkyl and / or nitro, alcohol or alkanediol of formula (III) wherein: 2Q R is as defined in the disclosure, n is 1 or 2, in the presence of sulfuric acid, at a temperature of 0 to 100 ° C, or b) a 3-bromo-4-fluoro-phenyl-glyoxylic acid of formula (IV) (V) with an amine of formula wherein R ¹ is as defined above, taxes appropriate using a diluent in the presence of from 0 to 200 at a temperature between ° C and the crude product which Containing compounds of formula (II), is reacted with an alcohol of formula (III) in the presence of a catalytic amount of sulfuric acid at 0-100 ° C.