GB2060605A - Process for Dehydrogenating (Polyhaloalkyl)Benzenes - Google Patents

Abstract

A process for the dehydrohalogenation of a (polyhaloalkyl)benzene containing a benzylic halogen such as 1,3-dichloro- 5-(1,3,3,3-tetrachloro-1-methylpropyl)benzene by contacting the (polyhaloalkyl)benzene with a suitably active Lewis acid catalyst such as SbCl5 or TiCl4, neat or supported, under conditions sufficient to catalyze the dehydrohalogenation to form a (polyhaloalkenyl)benzene such as 3,5- dichloro- alpha -(2,2,2- trichloroethyl)styrene.

Description

SPECIFICATION Process for Dehydrohalogenating (Polyhaloalkyl)benzenes This invention relates to processes for preparing (haloalkenyltbenzenes including (polyhaloalkenyl)benzenes.

a-(1-Haloalkyl)styrenes are useful as parasiticides and insecticides. They are also useful intermediates in the manufacture of other biologically active compounds. Such compounds are conventionally prepared by reacting a halogenated organic compound with an a- methylstyrene in the presence of a free-radical initiator which usually comprises an organic amine and a copper-containing material. These known methods for preparing (haloalkenyl)benzenes require long reaction times and undesirably high reaction temperatures and give somewhat low yields of product.

In accordance with the present invention, (haloalkenyl)benzenes and other (haloalkenyl)arenes are advantageously obtained by a dehydrohalogenation process, which comprises contacting a (polyhaloalkyl)arene in which polyhaloalkyl has a benzylic halogen and at least one non-benzylic aliphatic halogen with a catalytic amount of a suitably active Lewis acid, preferably deposited on an inert solid particulate support (hereinafter called supported Lewis acid) under dehydrohalogenation conditions.

Surprisingly, the benzylic halogen of the polyhaloalkyl group is selectively eliminated to form the desired (haloalkenyl)arene while the none-benzylic aliphatic halogen(s) are left undisturbed. The (haloalkenyl)benzenes produced in the practice of this invention are useful as biologically active compounds as described hereinbefore and as intermediates in the preparation of other biologically active compounds.

By a (polyhaloalkyl)arene is meant an aromatic compound in which an aromatic ring bears at least one polyhaloalkyl substituent. In the polyhaloalkyl substituent, one halogen is bonded to the alkyl carbon bonded to the aromatic ring (hereinafter called a benzylic halogen) and at least one halogen is bonded to one other alkyl carbon (hereinafter called a non-benzylic halogen). By "arene" is meant an aromatic compound having one or more aromatic rings such as benzene, naphthalene, anthracene as well as substituted arenes. The substituents include halo, nitro, alkyl, alkoxy, alkylthio, aryl, aryloxy, sulfo, carboxy, carboxylate ester, haloalkyl including polyhaloalkyl, haloaryl and other substituent groups that do not interfere with dehydrohalogenation reactions that are catalyzed by Lewis acids. Such substituents are inert in the dehydrohalogenation reactions.

Preferred (polyhaloalkyl)arenes are represented by Formula I:

wherein Ar is arene, preferably benzene, each R is individually halo, alkyl, haloalkyl including polyhaloalkyl such as -OX3 (e.g., -CF3) and

wherein X and Y are as defined herein, aryl, haloaryl, nitro, alkoxy, and other inert monovalent organic radicals, X is halo, Y is haloalkyl or substituted haloalkyl wherein alkyl has from 2 to 3 carbons and the non-halogen substituent or substituents may be, for example, nitro or alkoxy, and n is O to the maximum number of remaining available ring positions on Ar. Preferably n is from O to 2 when Ar is benzene.More preferably, each R is individually halo such as Cl, Br, or F; alkyl having 1 to 4 carbons such as -CH3; alkoxy such as -OCH3 and others having 1 to 4 carbons; and -NO2. Most preferably each R is individually Cl, Br or -NO2. X is more preferably Cl or Br, most preferably Cl. Y is more preferably haloalkyl represented by the formula:

wherein X' is Cl or Br, each R' is individually H, halo such as Cl, Br or F, lower alkyl or -NO2.

Most preferably Y is -CH2CCl2R' wherein R' is H, Cl, Br, -CH3 or-C2H5. For example, Y is most preferably-CH2CCl 3,-CH2CCl2Br, -CH2C HCl2 and -CH2CH2Cl.

Examples of especially preferred poly(haloalkyl)arenes include 1,3-dichloro-5 (1 ,3,3,3-tetrachloro- 1 -methylpropyl)benzene, 1 ,3-dichloro-5-( 1 ,3,3-trichloro-1 - methylpropyl)benzene and similar 1,3-dihalo-5 (polyhalobutyl)benzenes. Other preferred (polyhaioalkyl)arenes include 3-chloro-1 -(1,3,3,3- tetrachloro-1-methylpropyl)benzene and similar 3-halo-1 -(polyhalobutyl)benzenes.

(Polyhaloalkyl)arenes may be prepared by known methods. For example, a-methylstyrene or ar-substituted methylstyrene is reacted with a polyhaloalkane such as carbon tetrachloride, bromotrichloromethane, methylene chloride or dichloronitromethane in the presence of an amine and cuprous chloride to produce a desired (polyhaloalkyl)benzene.

Lewis acids which are suitably employed in the practice of this invention are the Lewis acids which either in neat form or when deposited on a support catalyze the elimination of the benzylic halogen from the (poiyhaloalkyl)arene via a dehydrohalogenation reaction while essentially all of the nonbenzylic halogen substituent(s) of the (polyhaloalkyl)arene remain bonded to the (polyhaloalkyl)arene. Such Lewis acids are stated herein to be suitably active if, during the preferential dehydrohalogenation of essentially all ( > 95 mole percent) of benzylic halogen of the (polyhaloalkyl)arene, less than 10, preferably less than 5, mole percent of non-benzylic halogen is eliminated.

Examples of Lewis acids which, in neat (undiluted) form, are suitably active include (1) the halides of titanium, preferably TiCI4, which have been treated with water and (2) the halides of antimony, preferably antimony pentachloride.

Of the neat forms, the titanium tetrahalides which have been treated with from 0.1 to 2 moles of water per mole of the titanium tetrahalide are more preferred, with TiCI4 being treated from 0.25 to 1.75 moles of water per mole of TiCI4 being most preferred.

While most other common Lewis acids such as AICI3, FeCI3 SnCI4 and the like are not suitably active in neat form, they, as well as most other Lewis acids, are suitably active when deposited on a solid catalyst carrier or support. Examples of such Lewis acids which in supported for are suitably active include the halides, particularly the chlorides and bromides, of such metals as aluminum, iron, zinc, copper, antimony, titanium, bismuth, arsenic, tantalum, vanadium, magnesium, boron and tin; as well as the oxyhalides, oxides, sulfates, phosphates, nitrates and oxylates of such metals. Of the foregoing Lewis acids, the halides, especially the chlorides, of aluminum, antimony, iron and titanium are most preferably employed in combination with a solid particulate catalyst support.

Exemplary solid catalyst supports include silica, silica gel, titania, alumina, silica/alumina, magnesia, asbestos, charcoal, Fuller's earth, diatomaceous earths, vanadia magnesium silicate, bauxite dausonite, gibbsite, Florida earth, bentonite, kaolin, pipe clay, montmorillonite, and kieselguhr. Advantageously, the catalyst support is in the form of a particulate solid, preferably one having an average particle diameter in the range from 100 to 400 micrometers and a surface area in the range from 80 to 200 square meters per gram. When using the catalyst support, the Lewis acid catalyst component preferably constitutes from 5 to 1 5 weight percent of the total support catalyst with the remainder being the solid support.The supported Lewis acid is advantageously prepared by slurrying the support in a solution of the desired Lewis acid in an inert organic solvent such as hydrocarbon or halogenated hydrocarbon solvents, e.g., carbon tetrachloride (CCI4), dichloromethane, chloroform, methylch loroform and tetrachloroethylene.

Alternatively, both Lewis acid and support can be slurried in an organic diluent which does not dissolve the Lewis acid or the support. In either case, from 0.1 to 3 weight parts of Lewis acid and from 1 to 30 weight parts of solid support are added to 100 weight parts of organic liquid.

Advantageously, the resulting slurry is heated at about the reflux temperature, e.g., from 50 to 800C, of the organic liquid for a time sufficient to cause deposition of the Lewis acid on the support, usually from 10 to 60 minutes. While the concentration of Lewis acid in the the total supported catalyst (i.e., the supported Lewis acid) is not particularly critical, the Lewis acid preferably constitutes from 5 to 1 5 weight percent of the total supported catalyst with the remainder being the solid support. The supported Lewis acid catalysts are preferred over the neat catalysts.

In the practice of this invention, the (polyhaloalkyl)arene is contacted with a catalytic amount of a suitably active Lewis acid under dehydrohalogenation conditions. A catalytic amount is any amount of suitably active Lewis acid which catalyzes the selective dehydrohalogenation of the (polyhaloalkyl)arene such that substantially all of the benzylic halogen thereof is eliminated. Advantageously, such catalytic amounts are within the range from 0.1 to 20 weight percent of suitably active Lewis acid based on the weight of (polyhaloalkyl)arene, preferably from 0.1 to 10 weight percent of the Lewis acid, most preferably from 0.2 to 3 weight percent of the Lewis acid. The foregoing concentrations of catalyst include only the concentration of Lewis acid and not support which is optionally employed.When a supported Lewis acid is employed, the concentration of the support is advantageously in the range from 1 to 100, preferably from 1 to 30, weight percent based on the weight of (polyhaloalkyl)arene.

In addition to the aforementioned starting ingredients, a solvent such as carbon tetrachloride, ethylene dichloride or similar halohydrocarbons is optionally employed. When used, the solvent is present in an amount between 0.5 and 3 liters of solvent per mole of the (polyhaloalkyl)arene.

While the temperature of the dehydrohalogenation reaction is not particularly critical, the reaction is advantageously conducted in the liquid phase at a temperature below 1 000C, preferably between 250C and 800C, and most preferably between 550C and 800C.

Preferably, the suitably active Lewis acid catalyst is added to a stirred mixture of the (polyhaloalkyl)arene and the optional solvent. It is sometimes desirable, particularly when a neat Lewis acid catalyst is employed, to add the (polyhaloalkyl)arene diluted with solvent to stirred solution of the catalyst in solvent. Thus, the rate of hydrogen halide evolution is controlled by the slow addition of reactant. When a supported Lewis acid is employed, diluted (polyhaloalkyl)arene is preferably added to a stirred slurry of the supported Lewis acid in organic solvent.

After the (polyhaloalkyl)arene is contacted with catalyst, the reaction begins immediately, as evidenced by evolution of hydrogen halide gas.

The reaction is allowed to proceed to completion while agitating the reaction mixture sufficiently to keep the catalyst in suspension. The reaction pressure is not critical and is conveniently atmospheric.

The product of the dehydrohalogenation reaction is primarily a (polyhaloalkenyl)arene wherein the benzylic halogen and hydrogen on an adjacent carbon are eliminated. In embodiments of particular interest, the (polyhaloalkenyl)arene is represented by formula II:

wherein R, Y and n are as defined hereinbefore. In preferred embodiments of this invention, the dehydrohalogenation is sufficiently selective such that more than 95 mole percent of benzylic halogen is eliminated, most preferably more than 99 mole percent, and less than 5 mole percent of non-benzylic halogen is eliminated most preferably less than 2 mole percent.

The following examples are given to further illustrate the invention. All percentages in the examples are by weight unless otherwise indicated.

Example 1 Preparation of 3,5-dichloro-a-methylstyrene According to U.S. Patent 2,816,934 Chlorine gas is bubbled through 1 29g of 3,5dichlorotoluene in the presence of light until no further adsorption occurs. An increase in weight of 839 results. To the product, weighing 2129, is added dropwise 400g of 8 percent fuming sulfuric acid. After being stirred for 30 hours the mixture is poured over cracked ice. The 3,5dichlorobenzoic acid which precipitated is washed well with water and dried. It weighs 1 45g, or 95 percent yield based on the dichlorotoluene. The acid is converted to 3,5-dichlorobenzoyl chloride in 95 percent yield by treating with 1259 thionyl chloride.The chloride, weighing 1 51 g, is then allowed to react with 150ml of methyl alcohol and the resulting methyl 3,5-di-chlorobenzoate, which when distilled at 1 200C--1 25 OC at 7mm weighs 133g, or 90 percent of theory. The ester is treated with 2 equivaients of methyl magnesium chloride (125g), the Grignard complex hydrolyzed, and the product then dehydrated by refluxing with NaHSO4. The 3,5-dichloro-a-methylstyrene obtained weighs 889, or 72 percent of theory based on the ester used, and boiled at 1 090C- 111 C at 12 mm. Its specific gravity is 1.196 and its refractive index is 1.5660, both measured at 250C.

Addition of CCI4 According to U.S. Patent 3,454,657 The 3,5-dichloro-a-methylstyrene is placed in a 250ml vessel equipped with stirring means and a heating means. A mixture including 18.7g (0.1 mole) of 3,5-dichloro-a-methylstyrene, as well as 46.2g (0.3 mole) of CCI4 and 0.4g of cuprous chloride is formed with stirring. To the mixture is added 1.6g (0.016 mole) of cyclohexylamine. The mixture is heated to the reflux temperature of CCI4 and maintained at reflux temperature until completion of the reaction in 30 minutes. The reaction mixture is cooled and filtered, and the solvent is removed under vacuum leaving 31 .2g (91.5 percent yield) of residual product.This residue is recrystallized from hexane to yield essentially pure 1 ,3-dichloro-5-(1 3,3,3- tetrachloro- 1 -methylpropyl)benzene exhibiting a melting point of 44.5 0--46.5 0 C.

Dehydrohalogenation with SbCI6 A mixture composed of a 137 g (0.40 mole) portion of the 1 ,3-dichloro-5-(1 ,3,3,3-tetrachloro- 1-methylpropyl)benzene (DCTCB) obtained above and 250ml of CCI4 is formed in a 500ml flask equipped with a stirring and a heating means.

With stirring, a 7g portion (0.023 mole) of SbCI5 is added to the flask and dehydrochlorination (as evidenced by HCI gas) to form a crude product mixture occurs at room temperature. The crude product mixture is heated to reflux (82 OC), is held at this temperature for 30 minutes, and is then allowed to cool to a temperature near ambient. To the crude product mixture a 150ml portion of CCI4 is added and then a 200-ml portion of 3N HCI is added with stirring. An aqueous and an organic layer are formed. The organic and aqueous layers are separated and 200ml of water is added to the organic layer with stirring. The organic layer is stirred over Na2SO4 to remove any water remaining. The carbon tetrachloride present in the organic layer is removed under a vacuum leaving 11 5.8g of a crude product.Distillation of the crude product yields 100.2g (0.33 mole) of product containing at least 95 percent of 3,5 dichloro--(2,2,2-trichloroethyl)styrene (DCTCS) represented by the structure:

and less than 5 percent of diene represented by the structure:

Example 2 Dehydrohalogenation with H20 Treated TiCI4 A mixture consisting of 5g (0.0147 mole) of the DCTCB produced according to Example 1, 50ml of CCI4 and 0.020ml of water is placed in a 100ml flask. The mixture is heated to reflux (about 900C) and 0.1739 (0.000911 mole) of TiCI4 is added to the mixture. Evolution of HCI is noted as the reflux continues for 2 hours. The mixture is cooled to 450C and 25ml of concentrated hydrochloric acid is added.An organic layer and an aqueous layer are formed and separated. The organic layer is washed with water. The solvent is then removed from the organic layer in vacuum. The remaining residue which weighs 4.059 (0.0133 mole) for a 91 percent yield is identified as DCTCS as prepared in Example 1. Analysis by gas-liquid chromatography (GLC) shows the residue to contain 97.5 percent of the aforementioned styrene (DCTCS) and less than 2.5 percent of the diene.

Example 3 Dehydrohalogenation with AlCI3/Silica Gel A commercially available supported catalyst comprising ~ 10 percent of AIR13 and 90 percent silica gel (~300 micrometers) is added in the amount of 2.5g to a mixture consisting of 1 0.6g (0.031 mole) of DCTCB and 30 ml of Cm14. The resulting mixture is stirred at room temperature and then heated to 700C for a period of 5 hours.

Throughout the reaction period, the mixture is stirred at a rate sufficient to maintain the supported catalyst uniformly dispersed throughout the mixture. The reaction mixture is then filtered to remove solid catalyst. The filtrate is placed in a rotary evaporator and evacuated to remove solvent. The residue is an oil which weighs 9.39 (0.03 mole) for a 97 percent yield is identified as DCTCS. Analysis of this residue by GLC shows that it contains 96 percent of the aforementioned styrene and less than 4 percent of the diene.

Example 4 Dehydrohalogenation with AlCI3/Alumina A supported catalyst is prepared by slurrying 0.49 of AlCl3 and 4.5g of alumina (-1 50 micrometers) in 20ml of CCI4 and then stirring the slurry at 700C for one hour. To this slurry at 700C is added 2509 of a mixture of 1259 of DCTCB and 1259 of CCl4 in less than 10 minutes.

The resulting mixture is heated to 800C and maintained there for 4 hours. During this time, the reaction mixture is stirred to maintain the supported catalyst dispersed therein. The reaction mixture is then filtered to remove solid catalyst.

The resulting filtrate is evaporated to remove solvent. The remaining oily residue weighs 11 Og (0.355 mole) indicating a yield of 97 percent of DCTCS. Analysis of this residue by GLC shows that it contains 97.6 percent of DCTCS and 2.8 percent of diene.

Example 5 Dehydrohalogenation with TiCI4/Alumina A supported catalyst is prepared by slurrying 0.45g of TiCI4 and 4.59 of the alumina used in Example 2 in 20ml of CCI4 and then stirring the slurry at 700C for one hour. To this slurry at 800C is added 150g of a mixture of 759 of DCTCB and 75g of CCI4 in less than 10 minutes. The resulting mixture is heated to 800C and maintained there for 4 hours. During this time, the reaction mixture is stirred to maintain the supported catalyst uniformly dispersed therein. The reaction mixture is then filtered to remove solid catalyst. The resulting filtrate is evaporated to remove solvent.

The remaining oily residue weighs 65.5g (0.211 mole) indicating a yield of 96.5 percent of DCTCS. Analysis of this residue by GLC shows that it contains 95.6 percent of DCTCS and 3.8 percent of the diene.

Example 6 Dehydrohalogenation with SnCI4/Alu mina A supported catalyst is prepared by slurrying 0.3g of SnCI4 and 3.09 of the alumina used in Example 2 in 1 Oml of CCI4 and then stirring the slurry at 700C for one hour. DCTCB is then dehydrohalogenated using this supported catalyst according to the procedure of Example 3. Analysis of the resulting dehydrohalogenated product shows that it contains 95.7 percent of DCTCS and 3.4 percent of the diene.

Example 7 Dehydrohalogenation with SbCI5/Alumina A supported catalyst is prepared by slurrying 0.2g of SbCI5 and 2.09 of alumina (N 50 micrometers) in 20ml of CCI4 and then stirring the slurry at 700C for one hour.

DCTCB is then dehydrohalogenated using this supported catalyst according to the procedure of Example 3. Analysis of the dehydrohalogenated product shows that it contains 95.1 percent of DCTCS and 2.7 percent of the diene.

Claims (9)

Claims

1. A process for the dehydrohalogenation of a (polyhaloalkyl)arene wherein in the polyhaloalkyl one halogen is a benzylic halogen and at least one halogen is a nonbenzylic halogen which process comprises contacting the (polyhaloalkyl)arene with a catalytic amount of a suitably active Lewis acid under dehydrohalogenation conditions to form a (haloalkenyl)arene.

2. A process as claimed in claim 1 wherein the (polyhaloalkyl)arene employed is represented by the formula:

wherein Ar is arene, each R is individually halo, nitro or an inert monovalent, organic radical, X is halo, Y is haloalkyl or substituted haloalkyl wherein alkyl has 2 or 3 carbons and the nonhalogen substituent or substituents are nitro or alkoxy; and n is O or a whole number from 1 to the maximum number of remaining available ring positions on Ar and the (haloalkenyl)arene is represented by the formula:

in which Y, Ar, R and n are as defined above.

3. A process as claimed in claim 2 wherein each R is individually halo, nitro, alkoxy, alkyl, haloalkyl, aryl or haloaryl, Y is polyhaloalkyl and n isO, 1 or2.

4. A process as claimed in claim 2 wherein the (polyhaloalkyl)arene is a (polyhaloalkyl)benzene represented by the structural formula:

wherein X is chloro or bromo; R is Cl, Br, F, -NO2, alkyl having 1 to 4 carbons, or alkoxy having 1 to 4 carbons; Y is haloalkyl represented by the formula:

wherein X' is Cl or Br, each R' is individually H, Cl or Br; and n is O, 1 or 2.

5. A process as claimed in any one of the preceding claims wherein the Lewis acid is SbCI5 orTiCI4 combined with from 0.25 to 1.75 moles of water per mole of TiCI4.

6. A process as claimed in claim 5 wherein the (polyhaloalkyl)benzene is 1,3-dichloro-5-(1,3,3,3- tetrachloro-1 -methylpropyl)benzene and the dehydrohalogenation is carried out in the presence of from 1.5 to 5 weight percent of TiCI4 based on the weight of the (polyhaloalkyl)benzene and from 0.25 to 1.75 moles of water per mole of TiCI4 at a reaction temperature in the range of from 250 to 800C.

7. A process as claimed in any one of claims 1 to 4 wherein the Lewis acid is deposited on an inert solid particulate support.

8. A process as claimed in claim 6 wherein the Lewis acid is AlCl3,SbCl5, SbCI3, TiCI4 or SnOl4 and the solid support in alumina.

9. A process as claimed in claim 8 wherein the (polyhaloalkyl)benzene is 1 ,3-dichloro-S-(1 3,3,3- tetrachloro- 1 -m ethylpropyl)benzene and the dehydrohalogenation is carried out in the presence of from 0.1 to 10 weight percent of AICI3 and from 1 to 100 weight percent of alumina, both percentages being based on the weight of (polyhaloalkyl) benzene, at a reaction temperature in the range of from 250 to 800C, the alumina having an average particle diameter in the range of from 100 to 400 micrometers.