Envirocat EPZG and natural clay as efficient catalysts fortransesterification of b-keto esters

B. P. Bandgar,* L. S. Uppalla and V. S. Sadavarte

Organic Chemistry Research Laboratory, School of Chemical Sciences, Swami RamanandTeerth Marathwada University, Nanded-431 606, India. E-mail: upekam@hotmail.com

Received 25th August 2000First published as an Advance Article on the web 9th January 2001

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

Introduction

Transesterification reactions, one of the most effective anduseful methods of ester synthesis has wide applications inacademic and industrial research.1 It is accelerated by proticacids,2 Lewis acids2 and basic catalysts.2 Various methods arereported for transesterification. However most of them are notgeneral as far as b-keto esters are concerned. More recentlyvarious catalysts have been developed for transesterification.2,3

Normal methods of transesterification of b-keto esters areequilibrium driven reactions where usage of excess of one of thereactants is mandatory to obtain good yields. Toxic andexpensive 4-(dimethylamino)pyridine4 which catalyzes trans-esterification requires a large amount of catalyst whereas use oftert-butyl acetoacetate5 leads to restriction to tert-butyl esters,thus lacking generality. Distannoxanes6 gave good yields of b-keto esters but such catalysts are difficult to prepare whiletransesterification of b-keto esters with propargylic alcohols ingeneral is not trivial. Conventional transesterification reactionswith propargylic alcohols provided in most cases low yields ofthe propargylic b-keto esters; furthermore the Taber procedure,4as well as a modified version,7 produce considerable tarring. Ascan be clearly seen, there is an obvious need to develop asatisfactory method for transesterification of b-ketoesters usingeco-friendly catalysts.

In recent years, there has been considerable growth in interestin the catalysis of organic reactions by inorganic reagentssupported on high surface area inorganic materials.8 Envirocats,a new family of solid supported reagents have led to asignificant breakthrough in environmentally friendly chem-istry.9 These solid supported catalysts are non toxic powderswhich can be filtered easily from the process and may be reusedafter activation. Envirocat EPZGR is a solid supported catalystwhich exhibits both Bronsted and Lewis acid characteristics.9Envirocat EPZGR represents a major step forward in thedevelopment of truly heterogeneous catalysis in acid catalyzedreactions,10 reducing gaseous emission and eliminating liquideffluent. There is a 10-fold reduction in the quantity of catalystrequired when it is substituted for aluminium trichloride.9 Thiscatalysis is also possible to use Envirocat EPZGR in non-polaror solvent-free reaction systems. It is synthesized and suppliedby Contract Chemicals, UK and is a free flowing yellow–greenpowder having a bulk density of 0.76 g cm23. The pH of a 2%(w/v) aqueous suspension is 2.2 and the surface area is ca. 250m2 g21. Generally, it requires activation by azeotropic dryingovernight or heating at 300–350 °C for 1 h (and cooling) in aflow of nitrogen (heating or cooling EPZG in air can denaturethe catalyst, rendering it inactive).

Clays have many advantages such as ease of handling, non-corrosiveness, low cost and regeneration. Owing their Bronsted

and Lewis acidities, clays, both in their natural and ion-exchanged forms, function as efficient catalysts for variousorganic transformations.11 We have recently reported thecatalytic property of natural kaolinitic clay for selectivedeprotection of thioacetals12 and aryl acetates.13 In this reportwe demonstrate that Envirocat EPZG and natural Kaoliniticclay are novel, efficient catalysts for transesterification of b-keto esters (Scheme 1).

Results and discussion

Natural kaolinitic clay was procured from the Padappakaramine of Quilon district, Kerala, India and it was subsequentlypurified and characterized by FTIR, XRD, UV, EPR, SEM,EDX and chemical analysis (AAS). The composition of clay hasbeen 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 pretreat-ment or activation.

Treatment of ethyl or methyl b-keto ester with alcohols alongwith a catalytic amount of EPZG or natural clay in refluxingtoluene with a distillation condenser to remove methanol or

Scheme 1

Green ContextTransesterifications are important reactions in many sec-tors of the chemical industry. They are traditionally carriedout using soluble strong acids which need to be washed fromthe product mixture and are lost as waste. The transester-ification of b-ketoesters is especially problematic and whilenumerous methods have been reported, none are entirelysatisfactory. Here, the use of a commercial clay-basedcatalyst is described. The new method is widely applicablegiving good product yields but since the catalyst can beeasily separated and reused, there is no acidic waste andcatalyst lifetime can be maximised. JHC

This journal is © The Royal Society of Chemistry 2001

DOI: 10.1039/b006946i Green Chemistry, 2001, 3, 39–41 39

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ethanol afforded the b-keto ester in excellent to high yields.Various alcohols used (primary, secondary, tertiary, benzylic,allylic) underwent smooth transesterification to give the b-ketoesters (Table 1). At the temperature used, only a very smallamount of toluene was collected along with liberated ethanol ormethanol and there was no need to add additional toluene.Transesterification with tertiary alcohols is often problematic inacid catalyzed reactions and indeed fail to undergo transester-ification with Ti(OEt)4.

3e However, with the present catalystseven the less reactive tert-butyl alcohol afforded the corre-sponding b-keto ester in low to moderate yield depending on thereaction time (entry 7) It should be pointed out that transester-ification of b-keto esters with unsaturated alcohols is ratherdifficult as it is offset by facile decarboxylation rearrangment;14

however b-keto esters underwent smooth transesterification

using this method even with unsaturated alcohols (entries8,10,11,14). The superiority of this procedure can be clearlyvisualized in transesterifications leading to the synthesis of b-keto esters containing an aromatic moiety in good yields (entry14). In this connection it should be mentioned that a recentliterature report15 which describes the synthesis of alkyl b-ketoesters employing a tin-based super-acid catalyst, (sulfated tinoxide) failed with aromatic substrates. The important feature ofour method is that the conversion of the methyl ester to a higherhomologue appears to be efficient (entry 1) and the reversetransformation could be achieved equally well in excellent yield(entry 2). It is important to note that the chiral integrity of thealcohol (2)-menthol is maintained under these reaction condi-tions (chiral alcohol is recovered by base hydrolysis of the esterand measuring its optical rotation) (entries 6, 13). Very little

Table 1 EPZG and natural clay transesterification of b-ketoesters

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attention has been paid to transestrifications of b-keto estersrequired for the synthesis of lignans including podophylotox-in.3a,d In this connection it should be mentioned that the presentprotocol is successfully used for transesterification of thesetypes of b-keto esters (entry 14).

The effectiveness of this protocol is manifested in itsselectivity towards b-keto esters whereas normal esters arefound to be unreactive. Selective transesterification of ß-ketoesters suggests that the role of the carbonyl group in enhancingthe reactivity by chelation with the catalyst is crucial for successof the reaction.

In conclusion, the present results demonstrate that naturalkaolinitic clay and Envirocat EPZG serve as efficient, conven-ient and general catalysts to effect transesterification of b-ketoesters. The superiority and flexibility of this method over theexisting methods coupled with the ease of operation and thesimplicity of work-up makes such catalysts potentially veryuseful. Both catalysts can be recovered and reused at least threetimes without appreciable loss of activity.

Experimental

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

Typical procedure

Ethyl acetoacetate (5 mmol), n-butyl alcohol (5 mmol) andcatalyst (100 mg) in toluene (20 ml) were heated to 110 °C in around bottom flask equipped with distillation condenser toremove ethanol. After completion (TLC) the reaction mixturewas cooled, filtered and the filtrate concentrated and chromato-graphed on silica [hexane–ethyl acetate (9+1)] to afford theester, 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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