阅读说明：本技术 一种新型Friedel-Crafts反应方法及其催化剂 (Novel Friedel-Crafts reaction method and catalyst thereof ) 是由 崔桅龙 杜宏军 吴文挺 于 2019-10-15 设计创作，主要内容包括：本发明涉及通过称为Friedel-Crafts的反应分别制备或合成酰化或烷基化芳基化合物,例如酰化或烷基化苯的新方法,以及用于该方法的新催化剂。本发明特别涉及用于合成所述酰化或烷基化化合物Friedel-Crafts反应的新的环保方法。(The present invention relates to a novel process for the preparation or synthesis of acylated or alkylated aryl compounds, such as acylated or alkylated benzenes, respectively, by a reaction known as Friedel-Crafts, and a novel catalyst for use in the process. The invention particularly relates to a novel, environmentally friendly process for the Friedel-Crafts reaction for the synthesis of said acylated or alkylated compounds.)

1. A process for the preparation of a compound by a Friedel-Crafts reaction, characterized in that the reaction is carried out in the presence of an antimony pentahalide catalyst (SbHal) ₅) In the presence of an activated antimony pentahalide catalyst (SbHal) ₅) In the presence of Hydrogen Fluoride (HF), optionally activating the antimony pentahalide catalyst.

2. Antimony pentahalide catalyst (SbHal) ₅) Preferably activated antimony pentahalide catalysts (SbHal) ₅) Use of an antimony pentahalide catalyst, optionally activated with Hydrogen Fluoride (HF), as a catalyst in a Friedel-Crafts reaction.

3. Antimony pentahalide catalyst (SbHal) ₅) Preferably activated antimony pentahalide catalysts (SbHal) ₅) Use of an antimony pentahalide catalyst, optionally activated with Hydrogen Fluoride (HF), as a catalyst in a process for the preparation of compounds by a Friedel-Crafts reaction.

4. The method of claim 1, or the use of claim 2 or claim 3, wherein the Friedel-Crafts reaction is combined with a fluorination reaction, which may be before the Friedel-Crafts reaction, or which may be after the Friedel-Crafts reaction.

5. Process for the preparation of compounds by Friedel-Crafts reaction according to claim 1 characterized in that the reaction is carried out in antimony pentahalide catalysts (SbHal) ₅) In the presence of an activated antimony pentahalide catalyst (SbHal) ₅) Optionally, the antimony pentahalide catalyst is activated with Hydrogen Fluoride (HF), and wherein the compound produced is a fluorinated compound.

6. Process for the preparation of compounds by Friedel-Crafts reaction according to any of claims 1 and 4 to 5, in particular compounds comprising one or more aromatic rings, characterized in that the aromatic ring of the starting material compound is in the presence of an antimony pentahalide catalyst (SbHal) ₅) With Friedel-Crafts reagents, preferably in the presence of activated antimony pentahalide catalysts (SbHal) ₅) Optionally, the antimony pentahalide catalyst is activated by Hydrogen Fluoride (HF) in the presence of Hydrogen Fluoride (HF), preferably wherein the compound produced is a fluorinated compound.

7. The method for preparing a compound according to any one of claims 1 and 4 to 6, wherein the starting material compound is selected from compounds having formula (I):

wherein: rn independently represents one or more selected from hydrogen (H), nitrogen dioxide (NO) ₂) And if present, preferably only one Rn group is nitrogen dioxide (NO2), halogen (preferably fluorine (F) or chlorine (Cl)), substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 alkoxy (preferably difluoroalkoxy or trifluoroalkoxy, more preferably difluoromethoxy or trifluoromethoxy), substituted or unsubstituted C1-C4 haloalkyl (wherein halogen is selected from fluorine (F), chlorine (Cl), bromine (Br) or iodine (I)), substituted or unsubstituted C1-C4 haloalkoxy (wherein halogen is selected from fluorine (F), chlorine (Cl), bromine (Br) or iodine (I));

hal represents a halogen selected from fluorine (F), chlorine (Cl), bromine (Br) or iodine (I); preferably fluorine (F) or chlorine (Cl); or Hal is absent, i.e. hydrogen (H) is present at the position of Hal.

8. The process for preparing a compound according to any one of claims 1 and 4 to 7, wherein the Friedel-Crafts reagent is selected from one of the compounds having formula (II), formula (III), or formula (IV):

wherein in formula (II): r 'n independently represents one or more substituents selected from the group consisting of hydrogen (H), nitrogen dioxide (NO2), and if present, preferably only one R' n group is nitrogen dioxide (NO2), halogen (preferably fluorine (F) or chlorine (Cl)), substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 alkoxy (preferably difluoroalkoxy or trifluoroalkoxy, more preferably difluoromethoxy or trifluoromethoxy), substituted or unsubstituted C1-C4 haloalkyl (wherein halogen is selected from fluorine (F), chlorine (Cl), bromine (Br) or iodine (I)), substituted or unsubstituted C1-C4 haloalkoxy (wherein halogen (Hal) is selected from fluorine (F), chlorine (Cl), bromine (Br) or iodine (I)); and

r1 and R2 independently of one another represent hydrogen, trihalomethyl (-CHal) ₃) Halocarbonyl (- (C ═ O) Hal) or halomethyl (— CH) ₂Hal), and at least one of R1 and R2 is trihalomethyl (-CHal) ₃) Halocarbonyl (- (C ═ O) Hal) or halomethyl (— CH) ₂Hal), and wherein each halogen (Hal) is selected from fluorine (F), chlorine (Cl), bromine (Br) or iodine (I), preferably wherein halogen (Hal) is selected from fluorine (F) and chlorine (Cl), more preferably wherein halogen (Hal) is chlorine (Cl); a boronic acid group;

wherein in formula (III): r3 independently represents substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 haloalkyl, wherein halogen is selected from fluorine (F) and/or chlorine, preferably wherein R3 is C1-C4-perfluoroalkyl or C1-C4-chlorofluoroalkyl, and X represents halogen selected from fluorine (F), chlorine (Cl), bromine (Br) or iodine (I), preferably wherein halogen is selected from fluorine (F) or chlorine (Cl), more preferably wherein halogen is chlorine (Cl); or X represents an anhydride group-O- (C ═ O) -R '3, wherein R '3 independently has the meaning as defined for R3, preferably wherein R '3 and R3 are the same;

wherein in formula (IV): r4 independently represents substituted or unsubstituted C1-C4 alkyl, substituted or unsubstituted C1-C4 haloalkyl, wherein halogen is selected from fluorine (F) and/or chlorine, preferably wherein R4 is C1-C4-perfluoroalkyl or C1-C4-chlorofluoroalkyl, and Y represents halogen, which may be at any position in R4, and wherein is selected from chlorine (Cl), bromine (Br) or iodine (I), preferably wherein halogen is chlorine (Cl).

9. A process for the preparation of a compound by a Friedel-Crafts reaction according to any of claims 1 and 4 to 8 characterized in that,

(a) the reaction is carried out in the presence of an antimony pentahalide catalyst (SbHal) ₅) In the presence of an activated antimony pentahalide catalyst (SbHal) ₅) In the presence of an antimony pentahalide catalyst, optionally activated with Hydrogen Fluoride (HF), and the process is a continuous process;

or (b) if the process comprises two or more steps, it comprises (b1) as one of the steps of a Friedel-Crafts reaction wherein the starting material compound is reacted with a Friedel-Crafts reagent in an antimony pentahalide catalyst (SbHal) ₅) In the presence of Hydrogen Fluoride (HF), optionally activating the antimony pentahalide catalyst, and (b2) in one step of the fluorination reaction, wherein the compound is in antimony pentahalide catalyst (SbHal) ₅) With Hydrogen Fluoride (HF) present in excess concentration, wherein at least one of the steps (b1) and (b2) is a continuous process,

preferably, wherein at least (b2) the step of fluorination is a continuous process,

more preferably, wherein in said step both (b1) Friedel-Crafts reaction and (b2) fluorination reaction are continuous processes.

10. The method for preparing a compound according to claim 9, wherein at least one of the step (b1) and step (b2) is a continuous process,

preferably, wherein at least (b2) the step of fluorination is a continuous process,

more preferably, wherein in said step both (b1) Friedel-Crafts reaction and (b2) fluorination reaction are continuous processes,

wherein the continuous process is carried out in at least one continuous flow reactor having an upper limit of lateral dimension of about ≦ 5mm, or about ≦ 4mm, preferably in at least one microreactor;

most preferably, wherein at least (b2) of said steps of fluorination is a continuous process in at least one microreactor under one or more of the following conditions:

-flow rate: from about 10ml/h to at most about 400 l/h;

-temperature: from about 30 ℃ to up to about 150 ℃;

-pressure: about 5bar to at most about 50 bar;

-residence time: from about 1 minute to up to about 60 minutes, preferably from about 1 minute to up to about 60 minutes.

Technical Field

The invention relates to the field of Friedel-Crafts reaction, in particular to a novel Friedel-Crafts reaction method and a catalyst thereof.

Background

For example, the Friedel-Crafts reaction is used for the industrial manufacture of PAEKs (polyaryletherketones), in particular PEEK (polyetheretherketone).

PEEK, for example, is made from hydroquinone condensed with 4,4' -difluorobenzophenone made from fluorobenzene as the key raw material, as described in Victrex WO2018/055384, and also in patent in CN107573500 patent application (2018). 4,4 '-Difluorobenzophenone is prepared from 4,4' -difluorodiphenylmethane by oxidation (ChemCatchem (2018),10(5),1096-1106), or alternatively from fluorobenzene and CCl ₄By Friedel-Crafts alkylation (Advances in chemical engineering (2015),34(4),1104-1108) or by Friedel-Crafts acylation of fluorobenzene with 4-fluorobenzoyl chloride (as described in U.S. Pat. No. 4,4814508 to Raychem). The most common synthesis of difluorodiphenylmethane is currently the synthesis of 4,4' -methylenebis [ aniline ] by the Balz-Schiemann reaction]Among others, dirty NaNO2/HBF4 chemistry described in CN106008182 patent application (2016) or other authors. The synthesis of difluorodiphenylmethane from fluorobenzene and formaldehyde has been described earlier in French bulletin (1951) at pages 318 and 323 or from 4-fluorobenzyl chloride, as described in journal of the chemical society, communications (1989) (18), 1353-4.

Another synthesis based on Friedel-Crafts acylation of 4,4' -difluorobenzophenone is derived from fluorobenzene or alternatively from 4-fluorophenylboronic acid, as described in the chemical communications (Cambridge, England) (2017),53(93),12584-12587, and the 4-fluorobenzoic acid derivative or 4-fluorotrichlorotoluene derivative described in the patent application CN106045828 (2016). All these processes involve a combination of a Balz-Schiemann reaction with a Friedel-Crafts reaction in at least one step. Both reaction types are quite old technologies and may have to be replaced by newer environmentally friendly chemistry and reaction technologies. The synthesis of 4,4 '-difluorobenzophenone from 4,4' -dichlorobenzophenone by the "dirty" Halex reaction is described in Mitsui, patent US 4453009. The Halex chemicals are generally considered "dirty" due to incomplete conversion, and product separation is challenging and often produces large amounts of toxic waste water. The "dirty" KCl obtained as the coupling product is typically used in landfills.

Generally, Friedel-Crafts reaction of benzoyl chloride with chlorobenzene in a prior art reactor (Lewis acid catalyzed in ionic liquid) is known, Friedel-Crafts reaction with α -Fe2O3 and CaCO3 nanoparticles in chemical engineering journal (Netherlands Amsterdam) (2018)331,443-449 in a microreactor with α -Fe2O3 and CaCO3 nanoparticles is described in Friedel-Crafts, 96% and 87-90% in New chemical materials (2012),40(2), perfluorooctanesulfonate with rare earth (III) in fluorine solvent in 86% in further Friedel-Crafts, and benzophenone prepared by using rare earth (III) in fluorine solvent in 99% in further Friedel-Crafts, PFA-BPA is prepared by using barium chloride in Federal chloride catalysis reaction with benzoic acid (150, 70-benzoylchloride), PFA-BPA is prepared by using barium chloride in chlorobenzene thermal chemistry journal of the general chemical technology (PAC), PFA-A is prepared by using a phenylformic acid chloride catalyzed by Friedel-Crafts, 150-benzoylchloride, 35, PFA-benzoylbenzophenone is also known in the prior art (CAS), and is prepared by Friedel-Crafts, 35, and is also known as a phenylformyl chloride catalyzed by the reaction with benzoic acid chloride in the other benzoic acid chloride catalyzed by the national chloride-carboxylation reaction with benzoic acid chloride in the national chloride-150, 35, the national chloride-150, 35, the national chloride-150, the same as a phenylformic acid chloride-benzoylchloride-150, the national chloride-150, the chloride-benzoylchloride-7-150, the chloride-90, the chloride-150, the chloride-95-150, the chloride-95-90, the chloride-95, the chloride-95-90, the chloride-95, the chloride-95, the same-95, the chloride-95.

With respect to the nature, diphenyldichloromethane is of the formula (C) ₆H ₅) ₂CCl ₂The organic compound of (1). It is a colorless solid and can be used as a precursor for other organic compounds. In the prior art, diphenyldichloromethane is prepared in the double Friedel-Crafts alkylation of benzene by using carbon tetrachloride and anhydrous aluminum chloride as catalysts. Or, treating benzophenone with phosphorus pentachloride:

(C ₆H ₅) ₂CO+PCl ₅→(C ₆H ₅) ₂CCl ₂+POCl ₃

hydrolysis of diphenyl dichloromethane to benzophenone:

(C6H5)2CCl2+H2O→(C6H5)2CO+2HCl

diphenyldichloromethane is used for the synthesis of tetraphenylethylene, diphenylmethanimine hydrochloride and benzoic anhydride. With respect to diphenylmethane, diphenylmethane is of the formula (C) ₆H ₅) ₂CH ₂The organic compound of (1). The compound consists of methane, in which two hydrogen atoms are substituted by two phenyl groups. Diphenylmethane forms a common backbone in organic chemistry; the benzhydryl group is also called benzhydryl (benzhydryl). It is prepared by Friedel-Crafts alkylation of benzyl chloride with benzene in the presence of a Lewis acid such as aluminum trichloride:

C ₆H ₅CH ₂Cl+C ₆H ₆→(C ₆H ₅) ₂CH ₂+HCl

all of the above reactions produce large amounts of waste and waste water, require expensive reagents or are impractical on an industrial scale.

It is an object of the present invention to overcome the disadvantages of the processes of the prior art, in particular to provide a more efficient and energy-saving process for preparing compounds by a Friedel-Crafts reaction, as well as a more environmentally friendly process, and to provide a useful catalyst for the process. It is another object of the present invention to provide a Friedel-Crafts reaction and to provide a useful catalyst for the process, which can be easily combined with a fluorination reaction, wherein the fluorination reaction can be performed before the Friedel-Crafts reaction or can be performed after the Friedel-Crafts reaction. It is another object of the present invention to provide a catalyst for Friedel-Crafts reaction, which can be used for Friedel-Crafts reaction and fluorination reaction.

Disclosure of Invention

The objects of the invention are achieved as defined in the claims and described in detail below. In particular, in one aspect, the present invention relates to a novel, environmentally friendly process for the preparation or synthesis of acylated or alkylated aryl compounds, such as acylated or alkylated benzenes, respectively, by the so-called Friedel-Crafts reaction, and novel catalysts useful in the process. Thus, in another aspect, the present invention relates to novel Friedel-Crafts catalysts or the novel use of catalysts, respectively, in Friedel-Crafts reactions.

In the context of organic molecules, aryl is any functional group or substituent derived from an aromatic ring, typically an aromatic hydrocarbon such as phenyl and naphthyl. The term "aryl" is used for abbreviation or generalization, and "Ar" is used as a placeholder for aryl groups in the chemical structure diagram. A simple aryl group is phenyl (formula C) ₆H ₅) A group derived from benzene. The most basic aryl group is phenyl, which consists of a phenyl ring and one hydrogen atom substituted by certain substituents and has the formula C ₆H ₅-. For the purposes of naming compounds containing phenyl groups, the phenyl group may be used as the parent hydrocarbon and is indicated with the suffix "-benzene". Alternatively, phenyl groups may be treated as substituents, described in the name as "phenyl". This is usually done when the group attached to the phenyl group consists of six or more carbon atoms. The so-called Friedel-Crafts reaction is well known to the person skilled in the art. For example, the Friedel-Crafts reaction is known as a series of reactions developed by Charles Friedel and James Crafts in 1877 for attaching substituents to aromatic rings. There are two main types of Friedel-Crafts reactions: alkylation and acylation reactions. Both by electrophilic aromatic substitution. Friedel-Crafts alkylation involves the alkylation of aromatic rings with alkyl halides using strong Lewis acid catalystsAnd (4) transforming. The alkyl group is attached at the front site of the chloride ion using anhydrous ferric chloride as a catalyst. The disadvantage of this reaction is that the product is more nucleophilic than the reactants. Therefore, over-alkylation must result. In addition, the reaction is very useful only with tertiary alkylating agents, some secondary alkylating agents, or those that produce stable carbocations (e.g., benzylated ones). In the case of primary alkyl halides, the initial carbocation (R) ⁽⁺⁾–X–Al ^(-)–Cl ₃) A carbocation rearrangement reaction will occur.

Friedel-Crafts acylation involves the acylation of aromatic rings. Typical acylating agents are acid chlorides. Typical lewis acid catalysts are acids and aluminum trichloride. Friedel-Crafts acylation can also be carried out using anhydrides. The reaction conditions are similar to Friedel-Crafts alkylation. This reaction has several advantages over alkylation reactions. Due to the electron withdrawing effect of the carbonyl group, the ketone product is always less reactive than the original molecule, and thus multiple acylation does not occur. Furthermore, there is no rearrangement of the carbocations, since the acyl ions are stabilized by a resonant structure, in which the positive charge is on the oxygen. The feasibility of Friedel-Crafts acylation depends on the stability of the acid chloride reagent. Related compounds in the context of the present invention are: terephthaloyl chloride (TCL, 1, 4-benzenedicarbonyl chloride), also known as terephthaloyl dichloride. The preferred IUPAC name is benzene-1, 4-dicarbonyldichloride. Other names are terephthaloyl chloride, 1, 4-benzenedicarbonyl chloride, benzene-1, 4-dicarbonyl chloride, terephthaloyl dichloride, terephthaloyl chloride; one common abbreviation is TCL.

As previously mentioned, all reactions known in the prior art produce large amounts of waste and wastewater, require expensive reagents or are not practical on an industrial scale. The present invention overcomes the disadvantages of the prior art. Therefore, the invention provides a method which has no waste water, reasonable reagent price and is suitable for industrial scale. More particularly, by using very inexpensive clean and easy-to-prepare starting materials and by using SbHal-based ₅To achieve this object. The present invention is highly advantageous even if fluorinated compounds are to be prepared, and furthermore, in one embodiment, the Friedel-Crafts reaction of the present invention is optionallyIn a microreactor system. In one aspect, the invention relates to a process for preparing compounds by a Friedel-Crafts reaction, characterized in that the reaction is carried out in the presence of an antimony pentahalide catalyst (SbHal) ₅) In the presence of an activated antimony pentahalide catalyst (SbHal) ₅) Optionally activated by Hydrogen Fluoride (HF). In another aspect, the invention relates to antimony pentafluoride catalysts (SbHal) ₅) Preferably activated antimony pentahalide catalysts (SbHal) ₅) (optionally activated by Hydrogen Fluoride (HF)) as a catalyst in Friedel-Crafts reactions. In another aspect, the invention relates to antimony pentahalide catalysts (SbHal) ₅) Preferably an activated antimony pentahalide catalyst (SbHal) ₅) (optionally activated by Hydrogen Fluoride (HF)) as a catalyst in a process for the preparation of compounds by a Friedel-Crafts reaction. In another aspect, the invention relates to a method or use as described before, wherein the Friedel-Crafts reaction is combined with a fluorination reaction, wherein the fluorination reaction can be performed before the Friedel-Crafts reaction, or wherein the fluorination reaction can be performed after the Friedel-Crafts reaction.

The invention therefore also relates, in one embodiment, to a process for preparing compounds by the Friedel-Crafts reaction, which is characterized in that the reaction is carried out in the presence of an antimony pentahalide catalyst (SbHal) ₅) In the presence of an activated antimony pentahalide catalyst (SbHal) ₅) (optionally activated by Hydrogen Fluoride (HF)) and wherein the compound produced is a fluorinated compound.

It has also been found that fluorination catalysts, which are commonly used with excess HF in industrially advantageous processes for the preparation of fluorobenzene to form hydrogen halide from a halobenzene precursor using HF, can additionally provide an advantageous simple use as a Friedel-Crafts catalyst (if HF is used at "low" concentrations, or if HF is not involved in the reaction), thereby providing new opportunities to provide acylated or alkylated compounds as industrially interesting starting materials for the preparation of compounds by Friedel-Crafts reactions, in ways not known in the prior art prior to the present invention. The term "low" concentration is defined more specifically in the detailed description of the invention below.

Halogenation catalysts and/or fluorination catalysts are well known to the skilled person and are preferably based on Sb, As, Bi, Al, Zn, Fe, Mg, Cr, Ru, Sn, Ti, Co, Ni, preferably Sb, in the context of the present invention. Fluorination catalysts are more preferred, especially the provision of the active species H2F + SbF ₆Sb fluorination catalyst of (A) if SbHal ₅Before or after the Friedel-Crafts reaction, it is kept in excess HF for the fluorination step, but where in the Friedel-Crafts reaction itself, HF is used only in "low" concentrations, for example in the ppm range. According to the invention, antimony (Sb) is the best and least expensive catalyst, but As and Bi can also be used As fluorination catalysts and, if desired, also for Friedel-Crafts reactions, in the oxidation stage III of the metals, in particular in the presence of SbHal ₅In the presence of SbHal-III, or with other metal compounds, e.g. MHal3 compounds (e.g. AsHal ₃And BiHal ₃) When coexisting. The Friedel-Crafts reaction can be carried out in reactors commonly used for Friedel-Crafts reactions, with preferred reactors being resistant to corrosion by hydrofluoric acid, at least trace amounts of hydrofluoric acid, in the PPM range. . The Friedel-Crafts reaction can be carried out batchwise or continuously. The continuous Friedel-Crafts reaction process is more optimized. In one embodiment of the Friedel-Crafts reaction in the present invention, the use of microreactors is particularly preferred.

Drawings

Figure 1 shows a representative reaction scheme for the conversion of trifluoroacetophenone and 3-chloro-trifluoroacetophenone by trifluoroacetylation.

FIG. 2 shows a representative reaction scheme through heptafluoroisopropyl-3-methylnitrobenzene.

Detailed Description

The deficiencies of the prior art are overcome as briefly described in the summary and defined in the claims and further elaborated by the following description and examples herein.

The present invention thus overcomes the disadvantages of the prior art. Therefore, the invention provides a method which has no waste water, reasonable reagent price and is suitable for industrial scale. More particularly, toBy using very inexpensive and clean, readily preparable starting materials and by using SbHal-based catalysts ₅The catalyst system of (1) to achieve this object. The present invention is applicable even if it is desired to prepare fluorinated compounds, and furthermore, in one embodiment, the Friedel-Crafts reaction of the present invention is optionally carried out in a microreactor system; for some options, chemistry is given as an example in the following schemes, but does not therefore limit the embodiments of the invention.

Scheme 1: Friedel-Crafts reaction with CCl4 (one-pot) batchwise or continuously (process of the invention). lowconcentration: low concentration of

Scheme 2: Friedel-Crafts reaction with 4-chlorobenzoyl chloride (one pot) batchwise or continuously (process of the invention). low concentration: low concentration of

As an alternative to the use of 4-chlorobenzoyl chloride, the use of p-chlorophenyl boronic acid can also be used as an alternative according to the invention. The reaction can be carried out batchwise in one or several batch reactors or continuously in a microreactor system. The organic material is separated from the catalyst and HF by phase separation. The separated organic material was further purified by crystallization (MP: 107 ℃). Boronic acids are compounds related to boronic acids (b (oh)3) in which one of the three hydroxyl groups is substituted with an alkyl or aryl group. The general structure of boronic acids is R '-B (OH)2, where R' is a substituent. As compounds containing carbon-boron bonds, members of this class therefore belong to a larger class of organoboranes. Boric acid is used as the lewis acid.

Scheme 3: Friedel-Crafts reaction with 4-chloro-1- (chloromethyl) benzene for the preparation of dichlorodiphenylmethane, batchwise or continuously (process according to the invention).

If fluorobenzene is used instead of chlorobenzene, only the Friedel-Crafts step is applied and, as the present invention implies, no additional fluorination step is required, since the difluoro compound is obtained directly.

All the reactions of the invention can be carried out in a batch reactor (autoclave) lined with HDPTFE or SiC equipment, or continuously in a microreactor or a plug flow reactor. A series of STRs ("stirred vessels") is also possible, but plug flow and microreactors are more advantageous.

Of course, in addition to the inventive processes disclosed herein, the Friedel-Crafts reaction of 4-chlorobenzoyl chloride, 4-chlorobenzyl chloride and terephthaloyl chloride can be carried out by known methods, but when using the inventive processes described herein, additional separation steps are avoided and the product yield is increased.

Scheme 5: acylation of chlorobenzene according to the invention. low concentration: low concentration of

Scheme 6: acylation of fluorobenzene according to the present invention.

low concentration: low concentration of

Scheme 7: 4,4' -difluorophenylmethane is prepared by acylation of chlorobenzene in accordance with the invention.

low concentration: low concentration of

In one aspect, the present invention relates to a novel, environmentally friendly process for the preparation or synthesis of acylated or alkylated aryl compounds (e.g., acylated or alkylated benzenes) by the so-called Friedel-Crafts reaction, and novel catalysts useful in the process. The present invention relates to a novel process for carrying out a Friedel-Crafts reaction, in particular wherein said Friedel-Crafts reaction as defined in the claims and further described herein relates to the environmentally friendly production of acylated or alkylated aryl compounds. In another aspect, the invention relates to new Friedel-Crafts catalysts or new uses of the catalysts in Friedel-Crafts reactions, respectively.

The present invention thus overcomes the disadvantages of the prior art processes and provides, in a simple and advantageous manner and in comparison with the prior art processes, a more efficient and energy-saving process and also a more environmentally friendly process for carrying out the Friedel-Crafts reaction.

The Friedel-Crafts reaction can be carried out in reactors commonly used for Friedel-Crafts reactions, but the preferred reactor is to have the ability to resist corrosion by Hydrogen Fluoride (HF), at least as a measure of HF corrosion, for example in the ppm range. The Friedel-Crafts reaction can be carried out batchwise or continuously. A continuous Friedel-Crafts reaction procedure may be preferred. In one embodiment of the Friedel-Crafts reaction in the present invention, the use of microreactors is particularly preferred.

Catalyst: it has been found experimentally that the fluorination catalyst, which is commonly used with excess HF in commercially beneficial processes for the preparation of fluorobenzene to form hydrogen halide from a halobenzene precursor using HF, can additionally provide a beneficial simple use as a Friedel-Crafts catalyst (if HF is used at "low" concentrations, or if HF is not involved in the reaction), thereby providing new opportunities to provide acylated or alkylated compounds as industrially interesting starting materials for the preparation of compounds by Friedel-Crafts reactions in ways not known in the prior art prior to the present invention. The process of the invention uses a halogenation catalyst, preferably a fluorination catalyst, which may also be, but not exclusively, a so-called lewis acid. Halogenation is a chemical reaction that involves the addition of one or more halogens to a compound or material. The route and stoichiometry of halogenation depends on the structural features and functional groups of the organic substrate, as well as the particular halogen. Inorganic compounds such as metals also undergo halogenation. Fluorination is halogenation, wherein F (fluorine) is a halogen introduced into a compound or material. Halogenation and/or fluorination, and halogenation catalysts and/or fluorination catalysts involved in such reactions, are well known to those skilled in the art. For example, halogens (e.g., chlorine and/or fluorine) are added to the olefin through an intermediate onium ion as an active species, where "halide" in organic chemistry means any onium compound (ion) containing a halogen atom, e.g., fluorine in the context of the present invention all carry a positive charge.

The person skilled in the art is familiar with halogenation catalysts and/or fluorination catalysts and is preferably, in the context of the present invention, based on Sb, As, Bi, Al, Zn, Fe, Mg, Cr, Ru, Sn, Ti, Co, Ni, preferably Sb. Fluorination catalysts are more preferred, especially the provision of the active species H2F + SbF ₆Sb fluorination catalyst of (e), if SbHal ₅Before or after the Friedel-Crafts reaction, it is kept in excess HF for the fluorination step, but where in the Friedel-Crafts reaction itself, HF is only used in "low" concentrations, for example in the ppm range. In the present invention antimony (Sb) is the best and least expensive catalyst, but As and Bi can also be used As fluorination catalysts and if desired also for Friedel-Crafts reactions, in the oxidation stage III of the metals, in particular in the presence of SbHal ₅In the presence of SbHal-III, or with other metal compounds, e.g. MHal3 compounds (e.g. AsHal ₃And BiHal ₃) When coexisting.

For example, in one aspect of the invention, which also relates to fluorination reactions, the use of antimony (Sb) catalysts for the manufacture of nuclear fluorinated aromatic systems ("fluorobenzene") is new and advantageous. For example, the catalyst is SbF in HF ₅From SbCl ₅Is prepared from natural materials. Of course, at the beginning of the reaction with fresh catalyst, one or two chlorine atoms on the antimony (Sb) of the catalyst can be exchanged and all chlorine atoms will be exchanged after a certain time of fluorination. To date, for example, fluorobenzene and derivatives have been prepared industrially using the Balz Schiemann or Sandmeyer reaction. Both types of reactions are very efficient in chemical application, but the disadvantages result in large amounts of waste and the waste water is also present in a very toxic form.For this reason, even entire chemical plants are currently shut down, e.g., in china, many companies around the world now have no reliable and environmentally acceptable fluorobenzene source. The same or similar problems described here by way of example for fluorobenzene can also be applied generally for the preparation of other fluorinated aromatic and heteroaromatic compounds, for example for use as building blocks in the pharmaceutical and agrochemical sector.