Envirocat EPZG and natural clay as efficient catalysts for transesterification of β-keto esters

Abstract

Ethyl/methyl β-keto esters react with various alcohols in the presence of a catalytic amount of Envirocat EPZG or natural clay and undergo transesterification effectively.

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Green Context

Transesterifications are important reactions in many sectors of the chemical industry. They are traditionally carried out using soluble strong acids which need to be washed from the product mixture and are lost as waste. The transesterification of β-ketoesters is especially problematic and while numerous methods have been reported, none are entirely satisfactory. Here, the use of a commercial clay-based catalyst is described. The new method is widely applicable giving good product yields but since the catalyst can be easily separated and reused, there is no acidic waste and catalyst lifetime can be maximised.

JHC

Introduction

Transesterification reactions, one of the most effective and useful methods of ester synthesis has wide applications in academic and industrial research.¹ It is accelerated by protic acids,² Lewis acids² and basic catalysts.² Various methods are reported for transesterification. However most of them are not general as far as β-keto esters are concerned. More recently various catalysts have been developed for transesterification.^2,3 Normal methods of transesterification of β-keto esters are equilibrium driven reactions where usage of excess of one of the reactants is mandatory to obtain good yields. Toxic and expensive 4-(dimethylamino)pyridine⁴ which catalyzes transesterification requires a large amount of catalyst whereas use of tert-butyl acetoacetate⁵ leads to restriction to tert-butyl esters, thus lacking generality. Distannoxanes⁶ gave good yields of β-keto esters but such catalysts are difficult to prepare while transesterification of β-keto esters with propargylic alcohols in general is not trivial. Conventional transesterification reactions with propargylic alcohols provided in most cases low yields of the propargylic β-keto esters; furthermore the Taber procedure,⁴ as well as a modified version,⁷ produce considerable tarring. As can be clearly seen, there is an obvious need to develop a satisfactory method for transesterification of β-ketoesters using eco-friendly catalysts.

In recent years, there has been considerable growth in interest in the catalysis of organic reactions by inorganic reagents supported on high surface area inorganic materials.⁸ Envirocats, a new family of solid supported reagents have led to a significant breakthrough in environmentally friendly chemistry.⁹ These solid supported catalysts are non toxic powders which can be filtered easily from the process and may be reused after activation. Envirocat EPZG^R is a solid supported catalyst which exhibits both Bronsted and Lewis acid characteristics.⁹ Envirocat EPZG^R represents a major step forward in the development of truly heterogeneous catalysis in acid catalyzed reactions,¹⁰ reducing gaseous emission and eliminating liquid effluent. There is a 10-fold reduction in the quantity of catalyst required when it is substituted for aluminium trichloride.⁹ This catalysis is also possible to use Envirocat EPZG^R in non-polar or solvent-free reaction systems. It is synthesized and supplied by Contract Chemicals, UK and is a free flowing yellow–green powder having a bulk density of 0.76 g cm⁻³. The pH of a 2% (w/v) aqueous suspension is 2.2 and the surface area is ca. 250 m² g⁻¹. Generally, it requires activation by azeotropic drying overnight or heating at 300–350 °C for 1 h (and cooling) in a flow of nitrogen (heating or cooling EPZG in air can denature the catalyst, rendering it inactive).

Clays have many advantages such as ease of handling, non-corrosiveness, low cost and regeneration. Owing their Brönsted and Lewis acidities, clays, both in their natural and ion-exchanged forms, function as efficient catalysts for various organic transformations.¹¹ We have recently reported the catalytic property of natural kaolinitic clay for selective deprotection of thioacetals¹² and aryl acetates.¹³ In this report we demonstrate that Envirocat EPZG and natural Kaolinitic clay are novel, efficient catalysts for transesterification of β-keto esters (Scheme 1).

Scheme 1

Results and discussion

Natural kaolinitic clay was procured from the Padappakara mine of Quilon district, Kerala, India and it was subsequently purified and characterized by FTIR, XRD, UV, EPR, SEM, EDX and chemical analysis (AAS). The composition of clay has been determined (i) by wet chemical analysis (%): SiO₂ = 67.45, Al₂O₃ = 22.2, Fe₂O₃ = 6.1, TiO₂ = 3.45, K = 0.8 and (ii) by electron dispersive X-ray (EDX) analysis (%) SiO₂ = 62.8, Al₂O₃ = 24.92, Fe₂O₃ = 7.5, TiO₂ = 3.79 and K = 0.4. Natural kaolinitic clay was supplied by Dr Lalithambika, RRL, Trivandrum, India and used as obtained without any pretreatment or activation.

Treatment of ethyl or methyl β-keto ester with alcohols along with a catalytic amount of EPZG or natural clay in refluxing toluene with a distillation condenser to remove methanol or ethanol afforded the β-keto ester in excellent to high yields. Various alcohols used (primary, secondary, tertiary, benzylic, allylic) underwent smooth transesterification to give the β-keto esters (Table 1). At the temperature used, only a very small amount of toluene was collected along with liberated ethanol or methanol and there was no need to add additional toluene. Transesterification with tertiary alcohols is often problematic in acid catalyzed reactions and indeed fail to undergo transesterification with Ti(OEt)_4.^3e However, with the present catalysts even the less reactive tert-butyl alcohol afforded the corresponding β-keto ester in low to moderate yield depending on the reaction time (entry 7) It should be pointed out that transesterification of β-keto esters with unsaturated alcohols is rather difficult as it is offset by facile decarboxylation rearrangment;¹⁴ however β-keto esters underwent smooth transesterification using this method even with unsaturated alcohols (entries 8,10,11,14). The superiority of this procedure can be clearly visualized in transesterifications leading to the synthesis of β-keto esters containing an aromatic moiety in good yields (entry 14). In this connection it should be mentioned that a recent literature report¹⁵ which describes the synthesis of alkyl β-keto esters employing a tin-based super-acid catalyst, (sulfated tin oxide) failed with aromatic substrates. The important feature of our method is that the conversion of the methyl ester to a higher homologue appears to be efficient (entry 1) and the reverse transformation could be achieved equally well in excellent yield (entry 2). It is important to note that the chiral integrity of the alcohol (−)-menthol is maintained under these reaction conditions (chiral alcohol is recovered by base hydrolysis of the ester and measuring its optical rotation) (entries 6, 13). Very little attention has been paid to transestrifications of β-keto esters required for the synthesis of lignans including podophylotoxin.^3a,d In this connection it should be mentioned that the present protocol is successfully used for transesterification of these types of β-keto esters (entry 14).

Table 1 EPZG and natural clay transesterification of β-ketoesters

The effectiveness of this protocol is manifested in its selectivity towards β-keto esters whereas normal esters are found to be unreactive. Selective transesterification of ß-keto esters suggests that the role of the carbonyl group in enhancing the reactivity by chelation with the catalyst is crucial for success of the reaction.

In conclusion, the present results demonstrate that natural kaolinitic clay and Envirocat EPZG serve as efficient, convenient and general catalysts to effect transesterification of β-keto esters. The superiority and flexibility of this method over the existing methods coupled with the ease of operation and the simplicity of work-up makes such catalysts potentially very useful. Both catalysts can be recovered and reused at least three times without appreciable loss of activity.

Experimental

IR spectra were recorded on a Bomem MB 104 FTIR spectrometer and ¹H NMR spectra were recorded on a Brucker AC 300F NMR spectrometer (300 MHz).

Typical procedure

Ethyl acetoacetate (5 mmol), n-butyl alcohol (5 mmol) and catalyst (100 mg) in toluene (20 ml) were heated to 110 °C in a round bottom flask equipped with distillation condenser to remove ethanol. After completion (TLC) the reaction mixture was cooled, filtered and the filtrate concentrated and chromatographed on silica [hexane–ethyl acetate (9∶1)] to afford the ester, butyl acetocetate, in excellent yield.

Acknowledgement

We thank Contract Chemicals, England and Dr Lalithambika, RRL, Trivandrum, India for generous gifts of Envirocat EPZG and natural Kaolinitic Clay respectively. V.S.S. thanks CSIR, New Delhi for a Junior Research Fellowship.

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