Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2000-03-29
2001-08-14
Oswecki, Jane C. (Department: 1626)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
C549S070000, C549S483000, C549S489000
Reexamination Certificate
active
06274741
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to an improved process for the preparation of acyl heteroaromatic compounds from heteroaromatic compounds, important intermediates for drugs, pharmaceuticals and flavoring agents for foodstuffs. More particularly, this invention relates a process for the preparation of acyl heteroaromatic compounds of high purity from heteroaromatic compounds using C2-C5 acid anhydrides as acylating agents in the presence of metal exchanged clays.
BACKGROUND OF THE INVENTION
This invention particularly relates to an ecofriendly process for the preparation of acyl heteroaromatic compounds from heteroaromatic compounds using acid anhydrides as acylating agents and metal exchanged clays as catalysts dispensing the use of stoichiometric amounts of corrosive, toxic aluminium chloride and other Lewis and protic acids as Friedel-Crafts reagents. The acylated products are valuable intermediates for drugs, pharmaceuticals, flavours and fragrances.
2-acetylthiophene is normally prepared by Friedel-Crafts acetylation of thiophene with acetic acid, acetyl chloride or acetic anhydride in the presence of a Lewis acid or a proton acid. The product is purified by distillation and it regularly contains from 1-2% of 3-acetyl thiophene as an impurity. For most purposes 2 -acetylthiophene of 98-99% is adequate.
PRIOR ART REFERENCES
Reference may be made to publication by Finan et al, Journal Chemical Society, 2728, 1963 Wherein 2-acylfuran derivatives are prepared from furans using BF
3
.Et
2
O. The Drawbacks are BF
3
.Et
2
O is expensive and difficult to handle.
Reference may be made to a U.S. Pat. No. 4,266,066 wherein acylated compounds are prepared by reacting carboxylic acid halides, in particular carboxylic acid chlorides, with aluminium-alkyl compounds at a temperature between 20-100° C. The reaction mixture is worked up in usual manner, suitably by decomposition with water followed by distillation. The draw-backs in the above processes are the use of stoichiometric amounts of aluminium compounds, an hazardous material that leaves large amount of solid wastes after the reaction and tedious separation process from the alumina get to obtain the product.
Reference may be made to a German patent, Ger. Offen. DE3,618,964 and to a publication by Hoelderich et al., Studies in Surface Science and Catalysts, 49A,69, 1989, wherein a procedure for vapour phase acylation of heteroaromatics with acylating agents in the presence of zeolite catalysts is describes. The main drawbacks are the yields of the acyl heteroaromatics are poor, 23-41% and the vapor phase reaction requires more energies.
Reference may be made to Kirk-Othmer, Encyclopedia of Chemical Technology, Vol 24, IVth edition, p38,1997, wherein acylation of thiophene is carried out with acid anhydrides in presence of phosphoric acid or other catalysts like AlCl
2
, SnCl
4
ZnCl
2
with acid chlorides. The draw back is all the reactions give between 0.5% and 2.0% of 3-isomer. There has been much striving to find catalyst systems that minimize the 3-isomer content attempting to meet the customers specification.
Reference may be made to a U.S. Pat. No. 5,371,240 wherein 3-acetylthiophene contaminating 2-acetylthiophene, is removed by a selective electrophilic substitution process, bromination, followed by fractional distillation. The drawback is an additional step, bromination is required to get the pure product.
Reference may be made to a publication by Fripiat et al., Journal Catalysis, 182, 257, 1999 wherein the acylation of thiophene with butyryl chloride is been carried out in the presence of zeolites in quantitative yields in liquid phase. The draw back is synthetic zeolites are expensive.
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 acyl heteroaromatic compounds. There was therefore a need for a process for the preparation of acyl heteroaromatic compounds which is simple to operate and can be carried out in a media which are not toxic and/or corrosive. Moreover the catalyst should be simple to separate and reusable.
OBJECTS OF THE INVENTION
The main object of the present invention is to provide an improved process for the preparation of acylheteroaromatic compounds from heteroaromatic compounds selected from thiophene, furan and pyrrole using C2-C5 acid anhydrides as acylating agents in the presence of metal ion exchanged clays at a temperature in the range of 0 to 130° C. for 1-24 h and separating the acyl heteroaromatic compound by a conventional method to obtain a product of high purity, which obviates the drawbacks as detailed above.
Another object of the present invention is the use of the metal ion exchanged clays as catalysts, sourced from cheaper and natural clays.
Another object of the present invention is metal ions selected for exchange are Fe
3+
,Zn
2+
,Cu
2+
,Al,
3+
La
3+
Another object of the present invention is heteroaromtic compounds selected are thiophene, furan and pyrrole.
Still another object of the present invention is quantity of catalyst used is 1 to 30% by weight with respect to the acylating agent.
Still another object of the present invention is the use of C2-C5 acid anhydrides as acylating agents.
Still another object of the present invention is the ratio of heteroaromatic compound and acylating agent is 5:1 to 1:5.
Yet another object of the present invention is the reaction is effected at a temperature in the range of 0 to 130° C. for 1-24 h.
SUMMARY OF THE INVENTION
The novelty of the present invention lies in the use of metal ion exchanged clays obtained easily by ion exchange process from naturally available montmorillonite and acid treated montmorillonite for the acylation of heteroaromatic compounds such as furan, thiophene, and pyrrole to afford 2-acyl heteroaromatic compounds selectively >99% in excellent yields for the first time. The 2-acyl heteroaromatic compounds thus obtained are devoid of the regioisomer, 3-acyl heteroaromatic compound usual contaminant in the acylation process employing soluble Lewis acids. Thus this invention offers highly pure and desired isomer to be used as an intermediate for specialised drugs and pharmaceuticals. Unlike soluble Lewis acids, the solid catalysts employed here does not produce any effluents. Since the catalyst is cheap and reusable for several times under mild reaction conditions, the process invented here is not only ecofriendly but also economically viable.
REFERENCES:
Jackson et al., “Reactions on Solid Supports Part II: A Convenient Method for Synthesis of Pyrromethanes Using a Montmorillonite Clay As Catalyst,” Tetrahedron Letters, vol. 26, No. 6, pp. 793-796, 1985.
Choudary Boyapati Manoranjan
Kantam Mannepalli Lakshmi
Raghaven Kondapuram Vijaya
Sateesh Mutyala
Council of Scientific and Industrial Research
Oswecki Jane C.
Samuels Gauthier & Stevens
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