HU184076B - Process for producing bracket-halogeno-alkenyl-bracket closed-benzenes - Google Patents

Abstract

The present invention relates to a process for the preparation of (haloalkenyl) benzenes of the formula (I) wherein R is independently halogen or C1-4 alkyl, Y is haloalkyl, wherein alkyl is 2 or 3; C3 and n are 1,2, or 3 such that a (polyhaloalkyl) benzene of formula (II) wherein Y, R and n are as defined above and X is halogen at 25 to 80 ° C is catalytic dehydrohalogenated in the presence of an amount of Lewis acid, preferably aluminum (1H) chloride, antimony (V) chloride, antimony (1H) chloride, titanium (IV) chloride, iron (1H) chloride or tin (IV) chloride. ch2 = c —y G11) H, C = C — CH1 —Chh A — H2C = C — CH — CCl * Cl (V) Cl

Description

This invention relates to processes for the preparation of (haloalkenyl) benzenes, including (polyhaloalkenyl) benzenes.

The ος (1-haloalkyl) styrenes are known for their parasiticidal and insecticidal activity and are also useful in the preparation of other biologically active compounds. C 1- (1-haloalkyl) styrenes are conventionally prepared by reacting a halogenated organic compound (K-methylstyrene) in the presence of a free radical initiator, which is usually an organic amine and a copper-containing material. These known processes for the preparation of alkenyl) benzenes require long reaction times and undesirably high temperatures, and the yields are quite poor.

According to the invention, the (haloalkenyl) benzenes of the formula (I), wherein the R substituents independently represent a halogen atom or a C 1-4 alkyl group, Y is a haloalkyl group, wherein the alkyl group has 2 or 3 carbon atoms and n is 1, 2 or 3 by preparing a (polyhaloalkyl) benzene of formula (II) wherein Y, R and n are as defined above and X is halogen at a catalytic amount of Lewis at 25-80 ° C. dehydrohalogenated in the presence of an acid, preferably aluminum (III) chloride, antimony (V) chloride, antimony (III) chloride, titanium (IV) chloride, iron (III) chloride or tin (IV) chloride. Surprisingly, in the polyhaloalkyl group, the halogen attached to the benzyl group can be selectively removed to produce the desired (haloalkenyl) benzene while the aliphatic halogen (s) attached to the non-benzyl group remain intact. The haloalkenylbenzenes of the formula (I) prepared according to the invention are known as biologically active compounds and are also useful in the preparation of other biologically active compounds.

When R in the formula (I) is halogen, for example, chlorine, bromine or fluorine, or when it is a C 1-4 alkyl group, e.g. methyl, ethyl, propyl. Most preferably, each R is independently chloro, bromo, Y is preferably a haloalkyl group of formula (III) wherein X 'is chloro or bromo, each R' is independently hydrogen, halo such as chloro, bromo - represents a fluorine atom or a methyl group. Most preferably, Y is -CH ₂ CC _{1 2} R ', wherein R' is hydrogen, chlorine, bromine or methyl. For example, most preferably, Y is -CH ₂ CCl ₃ , -CH ₂ CCl ₂ Br, -CH ₂ CHCl _2, or -CH ₂ CH ₂ Cl.

Particularly preferred examples of (polyhaloalkyl) benzenes are 1,3- (1,3,3,3-tetrachloro-1-methylpropyl) benzene, 1,3-dichloro-5- (1,3, 3-trichloro-1-methylpropyl) benzene and the like 1,3-dihalo-5- (polyhalobutyl) benzenes, and 3-chloro-1- (1,3,3,3-tetrachloro) 1-methylpropyl) benzene and the like 3-halo-1- (polyhalobutyl) benzenes.

Polyhaloalkylbenzenes may be prepared by known methods, for example, o-methylstyrene or methylstyrene substituted with an aromatic compound, in the presence of an amine compound or copper (I) chloride with a polyhaloalkane such as carbon tetrachloride, methane, methylene chloride, or dichloro-nitromethane.

In the process of the invention, Lewis acids, whether in pure form or supported on a support, are used to catalyze the separation of benzyl halogens from (polyhaloalkyl) benzene in a dehydrohalogenation reaction while all non-benzylic acids attached to (polyhaloalkyl) benzene are used. the halogen remains essentially intact. These Lewis acids are considered suitable if the halogen elimination ratio is greater than 95 mol% for benzyl halide of (polyhaloalkyl) benzene and more than 10 mol% for non-benzyl halogens, less than%.

Suitably active, pure (undiluted) Lewis acids are titanium halides, preferably water-treated titanium (IV) chloride and antimony halides, preferably antimony (V) chloride. Of the pure Lewis acids, titanium tetrahalides which are treated with 0.1 to 2 moles of water per mole are preferred, with titanium (IV) chlorides treated with 0.25 to 1.75 moles of water per mole being most preferred.

While the most common Lewis acids, such as aluminum chloride, ferric chloride, tin (IV) chloride, and the like, do not exhibit sufficient activity in pure form when separated on a solid catalyst support or excipient, likewise, they obtain adequate activity. Such Lewis acids which exhibit appropriate activity upon application to a carrier include, for example, metal halides, in particular aluminum, iron, zinc, antimony, titanium, bismuth, arsenic, tantalum, vanadium. chlorides and bromides of magnesium, boron and tin. Most preferred of said Lewis acids are the halides, especially chlorides, of aluminum, antimony, iron and titanium, which are combined with solid particulate catalyst excipients.

Examples of solid catalyst excipients are: silica, silica gel, titanium dioxide, alumina, silica / alumina; magnesium oxide, asbestos, charcoal, pumice, diatomaceous earth, vanadium-magnesium silicate, bauxite, dausonite, gibbsite, florida earth, concrete, kaolin, clay, montmorillonite and diatomaceous earth. The catalyst excipient is preferably a solid particulate material having an average diameter of 100 to 100 micrometres and a specific surface area of 80 to 200 m ² / g. When a catalyst excipient is used, the amount of Lewis acid is 5-15% by weight of the catalyst excipient and the remainder is the solid excipient itself. The Lewis acid combined with the excipient is preferably prepared by suspending the excipient in a desired Lewis acid and an inert organic solvent such as a hydrocarbon or halogenated hydrocarbon solvent, e.g. carbon tetrachloride, dichloromethane, chloroform, methyl chloroform or tetrachlorethylene. Alternatively, both the Lewis acid and the excipient are suspended in an organic solvent that does not dissolve either the Lewis acid or the excipient. In each process, 1 to 30 parts by weight of solid excipient and 0.1 to 3 parts by weight of Lewis acid are added to 100 parts by weight of organic solvent. Preferably, the suspension is as shown in Figure 3

-2184 076 at the boiling point of organic liquid - e.g. 50 ° C to 80 ° C - for a period of time sufficient to separate the Lewis acid into the excipient, which usually takes 10 to 60 minutes.

In the process of the present invention, the catalytic amount is defined as any amount of suitably active Lewis acid which catalyzes the selective dehydrohalogenation of (polyhaloalkyl) benzene to eliminate substantially all benzyl halogen. Such a catalytic amount is a suitably active Lewis acid containing from 0.1% to 20%, more preferably from 0.1% to 10%, most preferably from 0.2% to 3% by weight of (polyhaloalkyl) benzene. These concentration values represent only the concentration of the Lewis acid itself, and do not refer to the amount of vehicle used as desired. When a Lewis acid is deposited on a support, the concentration of the support is from 1 to 100%, preferably from 1 to 30%, by weight of the (polyhaloalkyl) benzene.

In addition to the starting materials mentioned above, solvents such as carbon tetrachloride, dichloromethane or similar halogenated hydrocarbons may be used. In this case, 0.5 to 3 liters of solvent are used per mole of (polyhaloalkyl) benzene.

Although the temperature is not particularly critical when carrying out the dehydrohalogenation reaction, the reaction is carried out in a liquid phase at temperatures below 100 ° C, preferably 25-80 ° C, and most preferably 55-80 ° C. The Lewis acid is preferably added under stirring to a mixture of (polyhaloalkyl) benzene and any solvent. It is sometimes desirable to add the solvent-diluted (polyhaloalkyl) benzene to a mixed solution of the catalyst in the solvent, especially when using a Lewis acid which is particularly pure. Thus, the rate of evolution of the hydrogen halide can be controlled by slow addition of the reagent. When using a supported Lewis acid, the (polyhaloalkyl) benzene is preferably added to a stirred suspension of the supported Lewis acid in the organic solvent.

As evidenced by the evolution of the hydrogen halide gas, the reaction begins immediately upon contact of the (polyhaloalkyl) benzene with the catalyst. The reaction is conveniently carried out at atmospheric pressure.

The product of the dehydrohalogenation reaction is primarily a (polyhaloalkenyl) benzene, which is formed by the elimination of benzyl halogen and hydrogen on a neighboring carbon atom. In the most preferred embodiments of the invention, dehydrohalogenation is suitably selective and eliminates more than 95% but preferably more than 99% of the benzyl halogen and only less than 5% but preferably less than 2% of the non-benzyl halogen. - eliminates.

The following examples further illustrate the invention. The percentages in the examples are weight percentages.

Example 1

Preparation of 3,5-dichloro-o (. Methyl-styrene a

U.S. Patent No. 816,934

Under illumination, chlorine gas is bubbled through 129 g of 3,5-dichlorotoluene until adsorption is complete. The adsorption results in a weight gain of 83 g. To a product weighing 212 g is added dropwise 400 g of 8% fuming sulfuric acid. After stirring for 30 hours, the mixture is poured onto crushed ice. The precipitated 3,5-dichlorobenzoic acid is washed well with water and dried. It weighs 145 g and has a yield of 95% based on dichlorotoluene. The acid was converted to 3,5-dichlorobenzoyl chloride (95% yield) by treatment with 125 g of thionyl chloride. 151 g of chloride are reacted with 150 ml of methanol to give 3,5-dichlorobenzoate which is distilled at 120-125 ° C and 7 mm Hg to give 133 g, 90% of theory. . The ester is treated with 2 equivalents (125 grams) of methyl magnesium chloride, the Grignard complex is hydrolyzed and the product is dehydrated by refluxing with sodium bisulfate. The weight of the recovered 3,5-dichloro-α-methylstyrene was 88 g, which was 72% based on the ester used and had a boiling point of 12 mmHg at 109 ° C to 111 ° C. The product has a specific gravity of 1.196 at 25 ° C and a refractive index of 1.5660 at 25 ° C.

Addition of carbon tetrachloride according to U.S. Patent 3,454,665

The 3,5-dichloro-8-methyl-styrene is placed in a 250 ml vessel fitted with stirring and heating. In addition to 18.7 g (0.1 mol) of 3,5-dichloro-o-methylstyrene, 46.2 g (0.3 mol) of carbon tetrachloride and 0.4 g of copper (I) chloride were added. To the mixture was added 1.6 g (0.016 mol) of cyclohexylamine, which was warmed to the boiling point of carbon tetrachloride and maintained at this temperature for 30 minutes until the reaction was complete. The reaction mixture was cooled, filtered and the solvent evaporated in vacuo. 31.2 g (91.5% yield) of product are obtained, which is recrystallized from hexane to give substantially pure 1,3-dichloro-5- (1,3, m.p. 44.5-46.5 ° C). 3,3-Tetrachloro-1-methylpropyl) -benzene (DCTCB) is obtained.

Dehydrohalogenation with Antimony (V) chloride

A mixture of the above 1,3-dichloro-5- (1,3,3,3-tetrachloro-1-methylpropyl) benzene (DCTCB) containing 137 grams and 250 ml of carbon tetrachloride was heated to 500 with heating and stirring capacity. Place in a 1 ml flask. While stirring at room temperature, 7 g (0.023 mol) of antimony (V) chloride was added to the flask and the evolution of hydrochloric acid gas evidenced the dehydrohalogenation process. The mixture containing the crude product

Heat to reflux (82 ° C) at -3184,076 for 30 minutes and allow to cool to near room temperature. To the mixture containing the crude product was first added 50 ml of carbon tetrachloride, followed by 200 ml of 3N hydrochloric acid. An aqueous and an organic phase are formed. The two phases are separated and 200 ml of water are added with stirring to the organic phase. The organic phase is dried over sodium sulfate to remove residual water. Removal of the carbon tetrachloride in solution in vacuo left 115.8 g of crude product. After distillation of the crude product, 100.2 g (0.33 mol) of product are obtained in at least 95% of 3,5-dichloro-o - (2,2,2-trichloro-1-yl) ethylstyrene (DCTCS) and contains less than 5% of diene V.

Example 2

Dehydrohalogenation with water-treated titanium (IV) chloride

A 100 mL flask was charged with 5 g (0.0147 mL of DCTCB from Example 1), 50 mL of carbon tetrachloride and 0.020 mL of water. The mixture was heated to reflux (about 90 ° C) and 0.173 g Titanium (IV) chloride (0.000911 moles) was added and during the reflux for 2 hours, hydrogen chloride gas evolution was observed. The mixture was cooled to 45 ° C and 25 ml cc hydrochloric acid was added to form an organic and an aqueous phase. The organic phase was washed with water and the solvent removed in vacuo to give a residue (4.05 g, 0.0133 mole), 91% yield, which was identified as DCTCS prepared in Example 1. Analysis by gas-liquid chromatography (GLC) showed that the product contained 97.5% of the above styrene (DCTCS) and contained less than 2.5% diene.

Example 3

Dehydrohalogenation on silica gel with alurrdnium trichloride separated

An approx. 10% aluminum trichloride and ca. 2.5 g of a commercially available supported catalyst containing 90% silica gel (about 300 micrometre particles) was added to a mixture of 10.6 g (0.031 mol) of DCTCB and 30 ml of carbon tetrachloride. The resulting mixture was stirred at room temperature and then heated to 70 ° C for 5 hours. During the reaction, the mixture is stirred so as to ensure a uniform dispersion of the supported catalyst on the mixture. The mixture was filtered to remove the solid catalyst. The solvent was removed from the filtrate by rotary evaporation under vacuum. The residual oil was DCTCS, 9.3 g (0.03 mol), 97% yield. GLC analysis of the product showed 96% styrene and less than 4% diene.

Example 4

Dehydrohalogenation with alumina trichloride on alumina

A supported catalyst is prepared by suspending 0.4 g of aluminum trichloride and 4.5 g of aluminum oxide (about 150 micrometre particles) in 20 ml of carbon tetrachloride and stirring the suspension at 70 ° C for one hour. To this slurry is added a mixture of 250 g, 125-125 g of DCTCB and carbon tetrachloride at 70 ° C for less than 10 minutes. The resulting mixture was heated to 80 ° C and maintained at this temperature for 4 hours. During this time, the reaction mixture is stirred so as to keep the supported catalyst dispersed. The solvent was evaporated from the filtrate. The residual oil weighed 110 g (0.355 mol), representing 97% yield of DCTCS. CLC analysis indicated that the product was ca. It contains 97.6% DCTCS and 2.8% diene.

Example 5

Dehydrohalogenation with titanium (IV) chloride deposited on alumina

A supported catalyst is prepared by suspending 0.45 g of titanium (IV) chloride and 4.5 g of alumina in 20 ml of carbon tetrachloride and stirring at 70 ° C for one hour. To this suspension is added 150 g of a mixture of 75-75 g of DCTCB and carbon tetrachloride at 80 ° C and for less than 10 minutes. The mixture was heated at 80 ° C for 4 hours. During this time, the mixture is stirred to uniformly disperse the catalyst deposited on the support. The solid catalyst was removed by filtration and the solvent was evaporated from the filtrate. The residual oil weighed 65.5 g (0.211 mole), which was about 40% of DCTCS. 96.5% yield. GLC analysis showed 95.6% DCTCS and 3.8% diene.

Example 6

Dehydrohalogenation with tin (IV) chloride deposited on alumina

A supported catalyst is prepared by suspending 0.3 g of tin (IV) chloride and 3.0 g of alumina in 10 ml of carbon tetrachloride and stirring at 70 ° C for one hour. Following the procedure of Example 3, DCTCB is dehydrohalogenated using a supported catalyst. Analysis of the resulting dehydrohalogenated product showed 95.7% DCTCS and 3.4% diene.

-4.184,076

Example 7

Dehydrohalogenation with alumina-separated antimony (V) chloride

A supported catalyst is prepared by suspending 0.2 g of antimony (V) chloride and 2.0 g of alumina (about 150 micrometre particles) in 20 ml of carbon tetrachloride and stirring at 70 ° C for one hour. Then, following the procedure of Example 3, the DCTCB is dehydrohalogenated using a supported catalyst. Analysis of the dehydrohalogenated product shows 95.1% DCTCS and 2.7% diene.

then the solvent was removed in vacuo. The dark brown oil is distilled as follows:

faction Mp C pressure (mm) quantity (g) 1 110-100 0.6 to 0.4 1.7 2 100-94 0.4 to 0.06 28.0

Fraction 2 contains about 96% 2,2-dichloro-4- (3,5-dichloro-10-phenyl) 4-pentene. Refractive index at 25 ° C

1.5695.

Example 8

Dehydrohalogenation was carried out as in Example 1.

Analysis: Calculated

46.51 found * 46.5

H Cl

3.55 49.94

3.64 49.8

Materials: 127.45 g

4.78 g

500 ml

1,2,3-trichloro- (1,3,3,3-tetrachloro-1-methylpropyl) benzene (0.319 mol) antimony (V) chloride (0.016 mol) carbon tetrachloride

Example 10

Dehydrohalogenation was carried out as in Example 1.

Materials: 750 g

6.32 g

650 ml

1,1,1,3-Tetrachloro-3- (m-bromo-phenyl) butane (2.14 mol) copper (I) chloride (0.0319 mol) 0-dichlorobenzene

The reaction starts immediately with the simultaneous evolution of hydrochloric acid vapor. After about 15 minutes, the mixture was heated to reflux temperature and held for 10 minutes. The orange oil obtained after processing the mixture is distilled as follows:

faction Mp C pressure (mm) quantity (g) 1 25-130 0.45 to 0.1 10.7 2 130-142 0.1 -0.04 93.18 3 142-155 0.04 live smaller 0.70

After refluxing for 80 minutes, methylene chloride (1000 ml) was added and washed three times with 300 ml of 3N hydrochloric acid and four times with 750 ml of water. The reaction mixture was then dried over sodium sulfate and the solvent removed in vacuo. 619.4 g (92%) of a dark black oil are obtained which is distilled as follows:

Fraction 2.3 contains 98% 3,4,5-trichloro-x- (2,2,2-trichloroethyl) styrene.

Example 9

The dehydrohalogenation was carried out as in Example 1.

Materials: 62 g of 2,2,4-trichloro-4- (3,5-dichlorophenyl) pentane (0.1935 mol)

3.47 g of antimony (V) chloride (0.0116 mol)

200 ml of carbon tetrachloride

To the solution, heated to 45 ° C, is added dropwise the antimony (V) chloride and the mixture is heated to 70 ° C and maintained at this temperature for 30 minutes. After cooling, the solution was filtered through silica gel and the gel washed with carbon tetrachloride. The whole filtrate was washed with water and the organic phase was dried over sodium sulfate.

faction Mp C pressure (mm) quantity (g) 1 112 0.9 73.2 She f. 112-125 0.9 17.4 3 125-128 0.9-0.8 121.6 4 128-126 0.8 to 0.75 156.0 5 126-132 0.75 to 0.8 66.5 6 132-137 0.8-1.1 79.1 7 137-151 1.1-1.4 56.3 570.1

Fractions 3-7 (474 g) contained 90% (N - (2,2,2-trichloroethyl) -m-bromostyrene).

Example 11

Dehydrohalogenation was carried out as in Example J.

Materials: 230 g

4.87 g in 1000 mL

1,1,1,3-tetrachloro-3- (3,5-dichloro-4-methyl) phenylbutane (0.0492 mol) copper (I) chloride (0.0492 g) o-dichlorobenzene

The mixture was refluxed at 182 ° C for 20 minutes and then

-5184 076 is cooled, filtered and the filtrate is distilled. 127.57 g are obtained, which is distilled at a pressure of 0.1 mm at 125-145 ° C. About 95% of O (- (2,2,2-trichloroethyl) -3-dichloro-4-methylstyrene) is obtained.

Analysis: Calculated for C H 41.48 2.85 Found 41.3 2.82

Claims (5)

Patent claims A process for the preparation of (haloalkenyl) benzenes of the formula I in which the substituents R independently represent a halogen atom or a C 1-4 alkyl group, Y represents a haloalkyl group wherein the alkyl group is 2 or 3 and n is 1, 2 or 3, wherein a (polyhaloalkyl) benzene of formula II wherein Y, R and n are as defined above and X is halogen at a temperature of 25 to 80 ° C is catalytic. The Lewis acid is dehydrohalogenated in the presence of an acid, preferably aluminum (III) chloride, antimony (V) chloride, antimony (IH) chloride, titanium (IV) chloride, iron (III) chloride or tin (IV) chloride. 2. A process according to claim 1 wherein titanium (IV) chloride is present in a concentration of 0.25 to 1.75 moles of water per mole. 3. A process according to claim 1 wherein the process is of formula (II) 1,3-dichloro-5- (1,3,3,3-tetrachloro-1-methylpropyl) benzene is used as the 5-polyhaloalkylbenzene and the dehydrohalogenation reaction with respect to (polyhaloalkyl) benzene is 1. With 5 to 5% by weight of titanium (IV) chloride containing 0.25 to 1.75 mol of water per mole 10 finally. 4. A process according to any one of claims 1 to 4, wherein the Lewis precipitated on a neutral solid particulate carrier 15 acids are used. 5. The process of claim 4, wherein the solid support is aluminum oxide. 6 6. The process of FIGS. The process of claim 1, wherein the (polyhaloalkyl) benzene is 1,3-dichloro-5- (1,3,3,3-tetrachloro-1-methylpropyl) benzene and the dehydrohalogenation reaction is carried out. 1 to 100% by weight based on (polyhaloalkyl) benzene It is carried out in the presence of 0.1 to 10% by weight of alumina trichloride on 25 alumina with an average diameter of 100 to 400 micrometers of alumina.