Process for the preparation of 4′-isobutylacetophenone

Details Process for the preparation of 4′-isobutylacetophenone Process for the preparation of 4′-isobutylacetophenone

2000-03-29

2002-05-07

Richter, Johann (Department: 1621)

Organic compounds -- part of the class 532-570 series

Organic compounds

Oxygen containing

Reexamination Certificate

active

06384285

ABSTRACT:

FIELD OF THE INVENTION
The present invention relates to a process for 4′-isobutylacetophenone (4-IBAP) by Friedel-Crafts acylation of isobutylbenzene. More particularly, this invention relates to a process for the preparation of 4′-isobutylacetophenone (4-IBAP) from isobutylbenzene using acetic anhydride as an acylating agent in the presence of nanocrystalline, microcrystalline and metal exchanged zeolite beta catalysts.
BACKGROUND OF THE INVENTION
4′-isobutylacetophenone (4-IBAP) is an important intermediate for 2-(4-isobutylphenyl)propionic acid (trade name, ibuprofen), a well-known nonsteroidal anti-inflammatory, antipyretic and analgesic drug and also other medical drugs.
This invention particularly relates to an ecofriendly process for 4′-isobutylacetophenone (4-IBAP) from isobutylbenzene using acetic anhydride as an acylating agent and zeolite beta as catalyst dispensing the use of stoichiometric amounts of corrosive, toxic aluminium chloride and hydrogen fluoride as Friedel-Crafts reagents.
PRIOR ART REFERENCES
Reference may be made to a publication by Baddley et al., Journal of Chemical Society, 1956, 4943, wherein 4′isobutylacetophenone is prepared by the Friedel-Crafts acetylation of isobutylbenzene with acetyl chloride using aluminium chloride as catalyst. Reference may be made to a U.S. Pat. No. 3,385,886 wherein the production of ibuprofen the first step of the process is preparation of 4′isobutylacetophenone by the Friedel-Crafts acetylation of isobutylbenzene with acetyl chloride in the presence of aluminium chloride. The draw-backs in the above processes are the use of stoichiometric amounts of anhydrous aluminium chloride, an hazardous material that leaves large amount of solid wastes after the reaction and tedious separation process from the alumina gel to obtain the product.
Reference may be made to a Japanese patent publication (Early disclosure) No. 60[1985]-188,343, wherein 4′isobutylacetophenone is prepared by the acetylation of isobutylbenzene using acetyl fluoride as an acetylating agent, prepared by reacting acetic anhydride with hydrogen fluoride as a catalyst a combination of hydrogen fluoride and boron trifluoride. Reference may be made to U.S. Pat. Nos. 4,981,995 and 5,068,448 wherein the production of ibuprofen, 4′isobutylacetophenone is prepared by the Friedel-Crafts acetylation of isobutylbenzene with acetic anhydride using hydrogen fluoride. The 4′isobutylacetophenone is an intermediate in a process for the production of ibuprofen. The draw-bracks in the above processes are hydrogen fluoride is extremely toxic, corrosive, generation of large amount of solid wastes after the reaction and need for industrially expensive equipment to work with hydrofluoric acid.
The inherent disadvantages in the use of conventional Lewis acid metal chlorides for Friedel-Crafts acylation are that they are non-regenerable and require more than stoichiometric amounts because of complexation with the carbonyl product formed. Work-up to decompose the resultant intermediate complex by hydrolysis forms a large amount of waste product and separation is lengthy and expensive.
Obviously, different approaches have been employed for the preparation of 4′-isobutylacetophenone. There was therefore a need for a process for the preparation of 4′-isobutylacetophenone which is simple to operate and can be carried out in a media which are not toxic and corrosive. Moreover the catalyst should be simple to separate and reusable
OBJECTS OF THE INVENTION
The main object of the present invention is a process for the preparation of 4′-isobutylacetophenone from isobutylbenzene which comprises reacting isobutyl benzene with acetic anhydride as an acylating agent in the presence of nanocrystalline, microcrystalline and metal exchanged zeolite beta catalysts at a temperature ranges between 60 to 165° C. for 2 to 24 hrs, separating the catalyst by filtration from the reaction mixture and recovering the product by a conventional method which obviates the drawbacks as detailed above.
Another object of the present invention is the use of the nano- and microcrystalline and metal exchanged nano- and microcrystalline zeolite beta as catalysts.
Still another object of the present invention is the metal ions selected for the exchange of nano- and microcrystalline zeolite beta are Fe
3+
, Zn
2+
, Ce
3+
and La
2+
.
Still another object of the present invention is the use of acetic anhydride as an acylating agent.
Still another object of the present invention is the use of isobutylbenzene as the reaction solvent.
Still another object of the present invention is the ratio of isobutylbenzene and acylating agent is 5:1 to 1:5.
Still another object of the present invention is the quantity of the catalyst is 10 to 50% by weight with respect to the acylating agent, acetic anhydride.
Yet another object of the present invention is the reaction is effected at a temperature in the range of 60 to 165° C. for 2-12 h.
SUMMARY OF THE INVENTION
The novelty of the present invention lies in the use of nanocrystalline and microcrystalline and metal exchanged nano- and microcrystalline zeolite beta for the acylation of isobutyl benzene for the first time. Decrease in particle size of zeolite beta, enhances the density of acidic sites and surface area of zeolites, which are essential factors to increase the activity of acylation reaction. In fact the activity of these nano-and microcrystalline forms increases manifold over normal zeolites. As a result of this, the acylation of isobutyl benzene is effected successfully in reasonable yields for the first time. 4′-isobutylacetophenone is obtained by a simple process involving filtration of the catalyst from the reaction mixture and recovering the product by conventional methods.
DETAILED DESCRIPTION OF THE INVENTION
Accordingly, the present invention provides a process for the preparation of 4′-isobutylacetophenone, an important intermediate for ibuprofen, a widely used non-steroidal anti-inflammatory drug wherein the said process comprises reacting isobutylbenzene with acetic anhydride as an acylating agent in the presence of nanocrystalline, microcrystalline and metal exchanged zeolite beta catalysts at a temperature ranges between 60 to 165° C. for 2-24 h separating the catalyst by filtration from the reaction mixture and recovering the product by a conventional method.
In an embodiment of the present invention metal exchanged, nanocrystalline and microcrystalline zeolite beta are used as the catalysts.
In an embodiment of the present invention the particle size of nanocrystalline and microcrystalline zeolite beta are 10 nm to 100 nm and 1 &mgr;m to 50 &mgr;m.
In another embodiment of the present invention the metal ions selected for the exchange of nano- and microcrystalline zeolite beta are Fe
3+
, Zn
2+
, Ce
3+
and La
2+
.
In yet another embodiment of the present invention acetic anhydride is used as an acylating agent.
In still another embodiment of the present invention the reaction is effected at a temperature in the range of 60 to 165° C. for 2-12 hrs.
In still another embodiment of the present invention the catalyst is separated by filtration from the reaction mixture.
SCIENTIFIC EXPLANATION
In the nano- and microcrystalline zeolite by the density of the acidic sites increases because of increased number of broken edges resulted from the broken aluminium silicate rings. The surface area of these particles is also increased due to reduction of the particle size of zeolites. The higher density of acidic sites eventually increases number of acyl cations generated in the reaction in the electrophilic substitution of the Freidel-Crafts acylation and thus enhances activity of the reaction. Thus the higher density of acid sites present in nano-, microcrystalline, metal exchanged zeolite beta are responsible for the Friedel-Crafts acylation of isobutyl benzene for the first time.
Nanocrystalline, microcrystalline and metal exchanged zeoli

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