IMPROVEMENTS IN OR RELATING TO FRIEDEL-CRAFTS REACTIONS

Abstract: A Friedel-Crafts acylation reaction is carried out in the presence of an ionic liquid system as catalyst. The ionic liquid system preferably also functions as a reaction solvent.

Description: Improvements in or relating to Friedel-Crafts Reactions Field of the Invention This invention concerns Friedel-Crafts reactions, particularly Friedel-Crafts acylation reactions. Background to the Invention Friedel-Crafts acylation reactions are an important and well known class of reactions of substantial commercial significance that involve reaction of an acylating group with a benzene ring or other unsaturated compound e.g. an alkene, resulting in substitution of an acyl group for hydrogen in the unsaturated compound, e.g. on the aromatic nucleus. The acylating agent is usually an acid chloride or an anhydride. The reaction is generally performed using a Lewis acid catalyst, commonly aiuminium(lll) chloride. Common solvents for the reaction include nitrobenzene, methylene chloride and 1 ,2-dichloroethylene. A simple example is aluminium(lll) chloride-catalysed reaction of benzene with acetyl chloride to produce the ketone acetophenone, as illustrated in Figure 1 . Although the Lewis acid is commonly referred to as a catalyst, the reaction requires more than a stoicheiometric amount of the Lewis acid which is therefore not functioning as a true catalyst. This arises because the Lewis acid bonds strongly to the ketone product to form a complex. In order to recover the ketone product the complex is typically subjected to aqueous hydrolysis to remove the Lewis acid as a hydroxide, e.g. aluminium(lll) hydroxide, freeing up the ketone product. The Lewis acid is therefore not recoverable and reusable, and moreover the reaction usually results in large quantities of aqueous waste, commonly aluminium laden, that must be suitably disposed of. There are reports in the literature of the use of various alternative materials as catalysts, including zeolites, superacids, lithium perchlorate/lanthanum triflate etc, but these materials are generally only effective in restrictive circumstances, e.g. with activated aromatic reagents having activating substituents, high molecular weight acylating agents etc. The present invention is based on a novel approach to Friedel-Crafts acylations, using an ionic liquid system catalyst. Summary of the Invention According to the present invention, there is provided a method of performing a Friedel-Crafts acylation reaction, characterised by the use of an ionic liquid system as catalyst. An ionic liquid system is a liquid composed entirely of ions, i.e. no neutral molecules are present, as opposed to an ionic solution, which is a solution of ions in a solvent. To be of practical value, the ionic liquid system should be in the form of a liquid at normal room temperature (20°C). The system comprises a mixture of cations and anions, often formed by acid-base neutralisation. The acid is conveniently a Lewis acid, such as iron(lll) chloride. The base is conveniently a chloride ion, acting as a Lewis base. The base is conveniently [Q]CI, where Q is any of a wide range of organic cations (e.g. substituted imidazolium, pyridinium, ammonium or phosphonium cations) currently used in the formation of ionic liquid systems. One material commonly used as the basic fraction in ionic liquid systems is 1-ethyl-3-methylimidazolium chloride, which for brevity is represented as [emimJCI. ionic liquid systems are commercially available, and can also be made by those skilled in the art. Good results have been obtained with the invention by using as catalyst the ionic liquid system derived from [emim]CI and iron(lll) chloride (denoted [emim]CI-FeCI 3 ). For reasons that are not yet fully understood, the ionic liquid system catalyst does not form a strong complex with the ketone product of the acylation reactions, so the catalyst is reusable and functions as a true catalyst. The invention is generally applicable to Friedel-Crafts acylation reactions. The approach can thus be applied to reaction of any suitable unsaturated compound with a suitable source of acylating groups, typically an acid chloride or anhydride. Appropriate reaction conditions can be readily determined by experiment. Unlike certain prior art proposals mentioned above, the invention is of general application to Friedel-Crafts acylation reactions, and not just restricted reactions e.g. using activated aromatic reagents, high molecular weight acylating agents etc. in performing the reaction, an unsaturated compound, e.g. an aromatic compound, and acylating- agent are reacted together in the presence of the ionic liquid system, under suitable conditions to produce a ketone product. The ionic liquid system is preferably functioning both as a catalyst and a reaction solvent. The reaction is conveniently carried out in the presence of an organic solvent less polar than the ionic liquid system, such as cyclohexane or benzene, into which the ketone product can be extracted. The organic solvent is thus functioning as an extraction, and preferably not a reaction, solvent. The organic solvent is preferably also a starting material for the reaction. The ketone product is preferably removed and collected, e.g. by an evaporation process. Conveniently the ionic liquid system has no significant vapour pressure. Where the ketone is produced in solution in organic solvent, as discussed above, the ketone is preferably separated from the solvent by evaporating the solvent off to leave pure ketone. The organic solvent can then be recycled. The reaction may be performed continuously or batch-wise. The invention also includes within its scope ketone product produced by the method of the invention. The invention can provide a number of benefits and advantages over the prior art, including the following: 1) The ionic liquid system acts as a true catalyst, and the invention is generally applicable to Friedel-Crafts acylation reactions. 2) No aqueous treatment is required to free the ketone product, meaning there is no consequential salt-laden aqueous waste for disposal. 3) There is no need to use polar organic solvents such as nitrobenzene etc which would normally form part of the aqueous waste, requiring appropriate neutralising or extractive treatment of the waste. The invention will be further described, by way of illustration, in the following Example and with reference to the accompanying figures, in which: Figure 1 shows the Friedel-Crafts reaction of benzene with acetyl chloride; and Figure 2 is a schematic illustration of laboratory equipment used for performing a Friedel-Crafts reaction of benzene with acetyl chloride in accordance with the invention. Example 1 Figure 2 shows the arrangement of a preliminary laboratory apparatus for performing a Friedel-Crafts reaction of benzene with acetyl chloride, as shown in Figure 1 , in accordance with the invention that was constructed from readily available glassware to demonstrate functioning of the invention and that has not been optimised. The apparatus is to be modified in a number of ways to improve the efficiency of the process. For example, a centre-fed distillation column may be used for collecting the reaction product. The apparatus of Figure 2 nevertheless functions well and has been used to demonstrate that genuinely catalytic Friedel-Crafts acylation reaction in ionic liquid systems is feasible, and extraction of the ketone product from the ionic liquid (leaving both intact) is feasible. Moreover, the reaction is effective in a situation not using an activated aromatic material having activating substituents and not using a high molecular weight acylating agent, which can therefore be regarded as a difficult and testing example, leading to the expectation that the approach is generally applicable and will work in easy cases as well as difficult cases. Referring to Figure 2, the illustrated apparatus comprises a reaction flask 10 with associated oil bath 12 and thermometer 14 located on a stirrer hot plate 16. A pressure equalising dropping funnel 18 is fitted to the flask 10. A condenser 20 with associated water inlet 22 and outlet 24 is fitted to the funnel 18, and leads to a nitrogen stream venting arrangement 26. Side arms 28 from the neck of flask 10 lead to an electrically heated column 30 with associated power supply, the column being packed with glass helices. A thermometer 32 is located at the column inlet. The column outlet leads to a collection flask 34. The apparatus was used to perform a Friedel-Crafts reaction of benzene with acetyl chloride using an ionic liquid system as catalyst. The ionic liquid system used was [emim]CI-FeCI 3 (having a mole ratio of iron to [emimJCI of 53.47%), made from 2.93g [emimjCI and 3.66g of sublimed FeCI 3 . The operating procedure was as follows: Flask 10, containing the ionic liquid system 36, was charged with benzene until completely full. The dropping funnel 18 was charged with a mixture of benzene/acetyl chloride at a molar ratio of 10:1. The oil bath 12 was heated to the reaction temperature of 80°C. The electrically heated column 30 was heated to a temperature in the range 100-200°C, with good results being obtained in the present example at a temperature of 170°C. The benzene/acetyl chloride mixture was allowed to run dropwise into the reaction flask. The product acetophenone, in solution in benzene, drips slowly into the collection flask 34. It is thought that the reactions taking place are as follows: As benzene/acetyl chloride reacts with the ionic liquid, a Friedel-Crafts reaction takes place, to give acetophenone as the iron(lll) chloride complex. When this complex is extracted into benzene, which acts as a non-coordinating organic solvent, the complex dissociates into the insoluble iron(lll) chloride and a solution of the acetophenone. Because the acetophenone deactivates the catalyst, it must be removed from the reaction vessel to free up the catalyst. The acetophenone is removed by means of a continuous extractor, where benzene and acetyl chloride are used as both the solvent and the reagents. Benzene/acetyl chloride is continuously dripped into the reaction vessel and is continuously removed and recycled by means of an evaporator (electrically heated column 30). The acetophenone is separated from the benzene/acetyl chloride in the column and simply percolates to the collection flask at the base of the column. Hydrogen chloride produced in the reaction is carried away in a stream of nitrogen, and is vented into the air in the illustrated arrangement. Catalyst turnover was 5 - 10 based on "active" FeCI 3 . The ionic liquid system is a mixture of FeCI 3 and [emimjCI. [FeCIJ " is expected to be catalytically inactive. Hence "active" FeCI 3 is the excess that is not complexed as [FeCIJ " . The reaction was stopped prior to completion, so no meaningful yield figures can be given. However there were no detectable by-products, so conversion appears to be complete. Currently, some of the catalyst is deactivated in this process, due to the following problems: (i) Oxidative coupling reactions (not a major problem with benzene/acetyl chloride), (ii) Aldol reactions (specific to acetophenone and not a general problem), (iii) Catalyst solubility in benzene, resulting in the catalyst being transferred to the separating column. With the temperatures at which the column is currently operated, the catalyst is damaged. This is not an insoluble problem, and can be dealt with by redesigning the apparatus and solvent systems.

Claims: CLAIMS 1. A method of performing a Friedel-Crafts acylation reaction, characterised by the use of an ionic liquid system as catalyst. 2. A reaction according to claim 1 , wherein the ionic liquid system also functions as a reaction solvent. 3. A reaction according to either one of claims 1 and 2, wherein the ionic liquid system comprises [Q]CI-FeCI 3 , where Q is any of a wide range of organic cations (e.g. substituted imidazolium, pyridinium, ammonium or phosphonium cations) currently used in the formation of ionic liquid systems. 4. A reaction according to claim 3, wherein the ionic liquid system comprises [emimjCI-FeCl j . 5. A reaction according to any one of the preceding claims, carried out in the presence of an organic solvent less polar than the ionic liquid system catalyst, into which ketone product is extracted. 6. A reaction according to claim 5, wherein the organic solvent is also a starting material for the reaction. 7. A reaction according to either one of claims 5 and 6, wherein the solvent is cyclohexane or benzene. 8. A reaction according to any one of the preceding claims, wherein ketone product is separated and collected. 9. A reaction according to claim 8, wherein ketone product is separated and collected by an evaporation process. 10. Ketone produced by the method of any one of the preceding claims.

Inventors: DAVEY PAUL NICHOLAS, EARLE MARTYN JOHN, NEWMAN CHRISTOPHER PAUL, SEDDON KENNETH RICHARD, DAVEY, PAUL, NICHOLAS, EARLE, MARTYN, JOHN, NEWMAN, CHRISTOPHER, PAUL, SEDDON, KENNETH, RICHARD
Applicants: DAVEY PAUL NICHOLAS, EARLE MARTYN JOHN, NEWMAN CHRISTOPHER PAUL, QUEST INT, SEDDON KENNETH RICHARD, DAVEY, PAUL, NICHOLAS, EARLE, MARTYN, JOHN, NEWMAN, CHRISTOPHER, PAUL, QUEST INTERNATIONAL B.V., SEDDON, KENNETH, RICHARD
Application year: 1998
Main classification: C07C45
IPC codes: B01J31, C07B61, C07C45, C07C49