DE3642329A1 - Process for acylating aromatics - Google Patents

Abstract

Process for acylating aromatics by the process of Friedel-Crafts by carrying out the acylation in the presence of metal alkyls or metal alkyl halides of metals or semi-metals of the second to the fifth main group and/or metals of the second or fourth sub-group of the Periodic Table, with the exception of aluminium.

Description

The invention relates to an improved process for the acylation of Aromatics according to Friedel-Crafts, especially for the production of alkyl substituted aromatic ketones by reaction of Carboxylic acid halides or carboxylic acid anhydrides with alkyl aromatics in Presence of a Friedel-Crafts catalyst.

Friedel-craft acylation of aromatics, i.e. H. the introduction of a Acyl group in aromatic compounds by the action of a Acylating agent on aromatics in the presence of certain metal halides such as aluminum chloride, is well known, e.g. B. from Houben-Weyl, Methods of the org. Chem. Vol. VII / 2a, 1973, pages 15-39 and 311-325. The disadvantage of this method is the occurrence of Side reactions, especially when alkyl-substituted aromatics are acylated will. This leads to the formation of resinous by-products, as well as Cleavage of the alkyl group and to isomerizations, especially if Aromatics are implemented with secondary or tertiary alkyl radicals. How emerges from various publications, these should Side reactions due to the interaction of AlCl₃ and hydrogen chloride which, if not present in the catalyst, during the Friedel-Crafts acylation occurs (see C. A. Olah, Friedel-Crafts and Related Reactions, Vol. I, page 207 and Vol. III, Part I, p. 550 ff, Intersience 1964). To the side reactions to suppress it is recommended to add freshly sublimed catalysts use and the resulting hydrogen halide by applying reduced pressure or passage of inert gases from the Remove the reaction mixture (see C. A. Olah, Friedel-Crafts and Related Reactions, Vol. III, p. 549 and literature cited there). Through this Measures can, as can be seen from DE-AS 27 20 294, the Isomerization to some extent be suppressed, however that is Result still unsatisfactory; the further separation of the accruing Product mixtures are complex and in many cases not economical possible so that the appropriate mixtures for subsequent reactions must be used. Another disadvantage is that considerable amounts the reactants are removed from the reaction mixture, causing poor Yields result.

The invention was therefore based on the object Friedel-Crafts acylation of aromatics so improve that Side reactions are largely avoided and the products in high Yields are incurred. In particular, when implementing Alkyl aromatics the cleavage and isomerization of the alkyl groups  be suppressed. According to the earlier application P 36 19 169.8 (O. Z. 0050/38479) from 06. 06. 86 this problem was solved by the Acylation in the presence of aluminum alkyl or alkyl aluminum halides carried out.

A method for acylating aromatics according to Friedel-Crafts has now been found found, which is characterized in that the acylation in Presence of metal alkyls or metal alkyl halides of metals or Semi-metals of the second to fifth main group and / or metals of the second or fourth subgroup of the periodic table, except for Aluminum.

Can be particularly advantageous according to the inventive method Carboxylic acid halides or anhydrides with alkyl aromatics alkyl-substituted ketones are implemented. When using a) acetyl chloride or b) phthalic anhydride and tert-butylbenzene as Starting materials and a mixture of metal alkyl or metal alkyl halide and aluminum chloride as a catalyst can be carried out by the reaction describe the following reaction equations:

R = alkyl radical X = halogen M = metal or semimetal n = 1 to 4 m = 0 to 4

where m + n = valence of the metal

According to the invention, Friedel-Crafts acylation is more effective in the presence Amounts of metal alkyls or metal alkyl halides of metals or Semi-metals of the second to fifth, especially the third main group of the periodic table and metals of the second and / or fourth Subgroup performed. You can use the general formula

R _n MX _m (I)

represent in which R is the same or different alkyl groups each having 1 to 12, preferably 1 to 6, in particular 1 to 4 carbon atoms z. B. methyl, ethyl, n-propyl, iso-propyl, n-butyl or iso-butyl groups means metals or semimetals of the groups mentioned, for. B. represents beryllium, magnesium, boron, gallium, indium, thallium, silicon, tin, lead, antimony, zinc, cadmium, mercury and titanium, X represents fluorine, chlorine, bromine or iodine, chlorine often being preferred for reasons of cost, n the numbers 1 to 4 and m the numbers 0 to 4, the sum n plus m giving the valence of the metal.

The preparation of the organometallic compounds I can in itself known manner, e.g. B. as in Brockhaus ABC Chemie, Vol. 2, pp. 867-869, 1971 described.

Are particularly advantageous for the method according to the invention organometallic compounds of magnesium such as dialkyl magnesium or Grignard compounds (RMgX), boron such as trialkylboron, dialkylborhalide or Alkyl boron dihalide, tin such as tetraalkyl tin or trialkyl tin halides, Titanium such as alkyltitanium trihalide or dialkyltitanium dihalide and organic zinc and cadmium compounds such as dialkyl zinc or Dialkyl cadmium. Organic zinc in particular can be particularly preferred Connections are used.

Mixtures of different compounds are also possible.

For example, the following connections are listed:
Methylmagnesium chloride, ethylmagnesium bromide, diethylmagnesium, trimethylbor, triethylboron, diethylborchloride, diethylborbromide, ethylboron dichloride, tetramethyltin, triethyltin chloride, methyltitanium trichloride, diethyltitanium dichloride, dimethylcadmium and in particular dimethylzinczinc, diethyl zinc diphenyl, zinczinc, diethyl zinc diphtyl

The compounds known per se can be used as Friedel-Crafts catalysts such as FeCl₃, BF₃, ZnCl₂ or TiCl₄ can be used. Are particularly suitable Aluminum halides, preferably aluminum bromide and in particular Aluminum chloride.

The aromatics that are usually used for Friedel-Crafts reactions used compounds such as isocyclic and heterocyclic aromatic Hydrocarbons into consideration. According to the method according to the invention can be particularly advantageous alkyl aromatics, for. B. alkyl substituted Benzenes, naphthalenes, anthracenes, furans, benzofurans, thiophenes etc. implement. Alkyl residues are e.g. B. those with 1 to 20, in particular 1 to 12, preferably 1 to 8 carbon atoms. The alkyl radical and the aromatic nucleus can also other substituents such as halogen, z. B. chlorine or carry bromine or C₁-C₄ alkyl radicals. Alkylbenzenes are preferred implemented with 1 or 2 branched or unbranched alkyl radicals. Examples include the following alkylbenzenes:

Toluene, ethylbenzene, n-propylbenzene, iso-propylbenzene, n-butylbenzene, sec-butylbenzene, tert-butylbenzene, n-pentylbenzene, (2-methylbutyl) benzene, (3-methylbutyl)) benzene, (1-methylbutyl) benzene, (1,1-dimethylpropyl) benzene, n-hexylbenzene, (1-ethyl-1-methylpropyl) benzene, (1,1-dimethylbutyl) benzene, (1-methylpentyl) benzene, (1-ethyl-1-methyl) benzene, (1-ethylhexyl) benzene, (4-octyl) benzene, 1,2-dimethylbenzene or 1,4-diethylbenzene.

The commonly used compounds serve as acylating agents, especially carboxylic acid halides and anhydrides.

With regard to the carboxylic acid halides or There are no restrictions on carboxylic anhydrides Implement acid fluorides, iodides and especially bromides and chlorides. As a rule, the acid chlorides become more aliphatic, cycloaliphatic, araliphatic, aromatic and heterocyclic Implement carboxylic acids. For example, acid chlorides of the formula R¹COCl listed in which R¹ is hydrogen or an aliphatic radical, e.g. B. an alkyl radical having 1 to 20, in particular 1 to 8 carbon atoms, an optionally substituted alkyl radical, preferably phenyl radical, which, if substituted, in particular 1 to 2 substituents such as C₁ to C₄ alkyl radicals, aryloxy such as phenoxy, halogen such as fluorine, chlorine or can carry bromine or nitro groups. In addition, R1 can be a Aralkyl radical such as benzyl radical or a heterocyclic radical, preferably an oxygen- or sulfur-containing heterocyclic radical with 5 or 6 ring members, e.g. B. a furanyl, pyranyl or thiophene residue mean.  

For example, the following acid chlorides are mentioned:

Formyl chloride, acetyl chloride, propionyl chloride, n-butyryl chloride, n-octadecanoic acid chloride, 3,3-dimethylacrylic acid chloride, benzoyl chloride, 3-phenoxybenzoyl chloride, o-chlorobenzoyl chloride, 3-chloro-5-methylbenzoyl chloride, 2,6-dichlorobenzoyl chloride, m-bromobenzoyl chloride, o-bromobenzoyl chloride, p-methylbenzoyl chloride, p-tert-butyl-benzoyl chloride, p-nitrobenzoyl chloride, Phenylacetic acid chloride, 4-chlorophenylacetic acid chloride, cinnamic acid chloride, 4-chlorocinnamic acid chloride, furan-2-carboxylic acid chloride, Thiophene-2-carboxylic acid chloride.

As acid anhydrides, anhydrides of aliphatic, cycloaliphatic, araliphatic, aromatic or heterocyclic mono- or Dicarboxylic acids are used. Anhydrides of monocarboxylic acids are for example those of alkyl carboxylic acids such as acetic anhydride, Propionic anhydride, n-butyric anhydride or benzoic anhydride, Anhydrides of dicarboxylic acids are, for example, those of the formula

in which R² has the meaning of R¹ and moreover R¹ and R² together ring-shaped to an optionally substituted aromatic system, e.g. B. can be connected to a benzene ring. For example Maleic anhydride, succinic anhydride, methyl maleic anhydride, Tetraethylsuccinic anhydride or phthalic anhydride called.

Conveniently, stoichiometric amounts of aromatic Compound and acylating agent can be used. It is also possible, one of the two components in excess of the other to use, you can for example 1 to 1.5 moles of aromatic per mole Use acylating agents.  

Those commonly used for Friedel-Crafts reactions Amounts of catalyst can also be used in the process according to the invention be, the total amount of catalyst from the sum of Lewis acid such as aluminum halide and the organometallic compound I results.

The addition of the organoaluminum compound causes that in Reaction mixture present or emerging hydrogen chloride bound becomes. The effective amount therefore depends on the number of those in the molecule existing alkyl residues. By the proportion of metal alkyl or Metal alkyl halide can be the ratio of the isomerization products (e.g. in the case of tert-amyl-substituted aromatics, the tert./sec.-alkyl ratio) and the amount of by-products can be influenced. Typically, 0.1 to about 1 per equivalent of carboxylic acid halide 1.5 mol Friedel-Crafts catalysts, e.g. B. added aluminum halide be, it being advantageous to 1 mol of Friedel-Crafts catalyst, e.g. B. aluminum halide, corresponding to a 10% excess, based on carboxylic acid halide, to be used. Higher Surpluses can be used, but have no advantage. At Carboxylic acid anhydrides or carboxylic acid halides, the substituents wear which with Friedel-Crafts catalysts, for. B. aluminum halides and organometallic compounds form stable complexes are pro Substitute one equivalent of catalyst additionally required.

The reaction can be carried out without or advantageously in the presence of a solvent be carried out, the conventional being the solvent Solvents for Friedel-Crafts reactions come into consideration, e.g. B. Chlorobenzene, dichlorobenzene, 1,2-dichloroethane, carbon disulfide, Nitromethane or nitrobenzene. The amount of solvent is not critical in general, 200 to 1000 g of solvent per mole of alkylbenzene be used.

The reaction can be carried out in a manner known per se, where the starting materials at temperatures from -20 to 100, preferably 0 to 60, in particular 10 to 40 ° C and at elevated or can implement reduced pressure, preferably at normal pressure.

The carboxylic acid halide or anhydride is expediently placed together with the solvent and gives the aluminum halide as well then the alkylaromatic in a mixture with the metal alkyl or Metal alkyl halide added.  

Working up the reaction mixture and isolating the products takes place in the usual way, e.g. B. by placing the reaction mixture on water and / or pouring ice and after separating the aqueous phase through the ketone Distillation or crystallization wins.

According to the inventive method, it is surprisingly possible to aromatic ketones, the valuable intermediate and end products for example for dyes, auxiliaries, pesticides and Pharmaceuticals are in higher yields compared to the prior art to manufacture. Furthermore, alkyl-substituted, in particular tert-alkyl-substituted aromatics are acylated without a strong Isomerization of the alkyl radical occurs, which is particularly the case with Synthesis of (tert-amybenzoyl) benzoic acid is of interest since this an important intermediate for the production of tert-amyanthraquinone represents that for the production of hydrogen peroxide (s. DE-OS 20 13 299) is required.

Example 1

74 g (0.5 mol) of phthalic anhydride were in 200 ml of o-dichlorobenzene submitted and 128 g (1.05 mol) of AlCl₃ in portions at 15 to 20 ° C. admitted. In the course of 5 hours a Mixture of 8.3 g (0.07 mol) of diethyl zinc and 74 g (0.5 mol) tert-amylbenzene added dropwise to the reaction solution. Then was Stirred for 2 hours at room temperature.

After the reaction had ended, the reaction mixture was poured onto a mixture of 1 l Poured water with 300 g of ice and 30 ml of H₂SO (conc.), The organic phase extracted with dilute sodium hydroxide solution and the amylbenzoyl-benzoic acids the aqueous phase precipitated with sulfuric acid and dried. You get 133 g (90%) of a mixture of 4-tert-amyl and 4-sec-iso-amyl benzoyl-benzoic acid (ratio tert./sec. = 79: 21).

Example 2

74 g (0.5 mol) of phthalic anhydride were analogous to Example 1 with 128 g (1.05 mol) AlCl₃ and 25 g (0.2 mol) diethyl zinc in 74 g tert-amylbenzene brought to reaction. After working up, 118 g (80%) of pure are obtained 4-tert-amylbenzoyl-benzoic acid.  

Example 3

74 g (0.5 mol) of phthalic anhydride and 134 g (1.10 mol) of AlCl₃ were as described in Example 1, with 20 g (0.2 mol) of triethylboron in 74 g tert-amylbenzoyl reacted in 8 hours. You get after the usual working up 127 g (86%) of a mixture of 4-tert-amyl and 4-sec-isoamylbenzoyl-benzoic acid (ratio tert./sec. = 60:40).

Comparative Example 1 4- (tert-amyl-benzoyl) benzoic acid

74 g (0.5 mol) of phthalic anhydride were in 150 ml of dichlorobenzene submitted and 145 g (1.1 mol) AlCl₃ added in portions. During 74 g were in this solution at 15 to 20 ° C for 5 hours tert-amylbenzene was added dropwise and then was 1 hour at 30 ° C. stirred. After working up, 120 g (81%) of a mixture are obtained from 4-tert.- and 4-sec.-isoamylbenzoyl-benzoic acid (ratio tert./sec. = 43: 57).

Claims (7)

1. A process for the acylation of aromatics according to Friedel-Crafts, characterized in that the acylation in the presence of metal alkyls or metal alkyl halides of metals or semimetals of the second to fifth main group and / or metals of the second or fourth subgroup of the periodic table, with the exception of aluminum, carries out. 2. The method according to claim 1, characterized in that one Carboxylic acid halides or carboxylic acid anhydrides with alkyl aromatics alkyl-substituted aromatic ketones. 3. Process according to claims 1 and 2, characterized in that Metal alkyls or metal alkyl halides of magnesium, boron, tin, zinc or titanium used. 4. Process according to claims 1 to 3, characterized in that used as metal alkyl halides or metal alkyl chlorides or bromides. 5. Process according to claims 1 to 4, characterized in that aluminum chloride or bromide as Friedel-Crafts catalyst used. 6. The method according to claims 1 to 5, characterized in that alkylbenzenes used as aromatics. 7. The method according to claims 2 to 6, characterized in that per equivalent of acid halide 1 to 1.5 mol or per equivalent Acid anhydride 2 to 3 mol of the Friedel-Crafts catalyst and 0.1 to 1.1 metal alkyl equivalents as metal alkyl or metal alkyl halide used.