Journal of Molecular Catalysis A: Chemical 216 (2004) 115–119 Li–X-type zeolite mediated Michael addition of thiols to cyclic enones and its application in the synthesis of 13-thiaprostaglandins Popat D. Shinde, Vishal A. Mahajan, Hanumant B. Borate, Vasudha H. Tillu, Rajaram Bal, Asha Chandwadkar, Radhika D. Wakharkar ∗ National Chemical Laboratory, Pashan Road, Pune 411008, India Received 25 June 2003; received in revised form 15 October 2003; accepted 10 February 2004 Available online 16 March 2004 Abstract Michael addition of various thiols to cyclic enones in presence of Li–X-type zeolite has been described. 13-Thiaprostaglandins have been synthesized in good yields using substituted hydroxycyclopentenone as the Michael acceptor and arylthiols as Michael donors. © 2004 Elsevier B.V. All rights reserved. Keywords: Michael addition; Thiaprostaglandins; Zeolites; Thiols; Enones 1. Introduction There has been increasing emphasis on the development and use of environment-friendly solid base catalysts to re- place soluble bases like metal hydroxides and alkoxides which are widely used in the C–C bond forming reactions [1]. Although the Michael addition reaction is one of the effective methods for C–C bond formation and is widely em- ployed in organic synthesis, conjugate additions of mercap- tans and amines are relatively less explored. Traditionally the 1,4-addition of mercaptans is catalyzed by strong bases such as alkali metal alkoxides, hydroxides [2] and amines [3]. Use of these strong bases lead to the formation of undesirable side products due to competing reactions like polymeriza- tion, self-condensation and rearrangements [4]. On the con- trary, zeolites afford cleaner Michael addition products with good yields [5]. Several organic transformations including oxidations [6], protection of aldehydes and ketones [7], Heck reaction [8], deprotection of allyl and cinnamyl esters [9], transthioacetalization [10], etc. using heterogeneous catalysts have been reported from our laboratory. We have explored the utility of Li–X-type zeolite in the synthesis of 13-thiaprostaglandins by Michael addition of various thiols to substituted cyclopentenones as depicted in Scheme 1. To our knowledge there is no report available in the literature ∗ Corresponding author. Tel.: +91-20-5893614; fax: +91-20-5893614. E-mail address: rdw@dalton.ncl.res.in (R.D. Wakharkar). in which Li–X-type zeolite is employed to promote the Michael addition and therefore the potential of Li–X-type zeolite has been investigated here. Present method demon- strates the utility of Li–X-type zeolite for Michael addition and its application in the synthesis of 13-thiaprostaglandins which are biologically active compounds [11]. 2. Experimental section 2.1. Synthesis of catalyst [12] Zeolite-X was synthesized using the gel composition in terms of oxides 4.54 Na 2 O:3.44 SiO 2 :Al 2 O 3 :180 H 2 O. Sodium silicate (28.6% SiO2, 8.88% Na 2 O and 62.6% H 2 O) was used as the silicon (SiO 2 ) source and NaAlO 2 was used as the alumina (Al 2 O 3 ) source. In a typical syn- thesis 18.6 g of sodium silicate was taken in a beaker and a mixture of 5.9 g sodium aluminate, 3.9 g sodium hydroxide and 70 g water was added to it. The mixture was stirred for 1 h, transferred into an autoclave, aged for 24 h at room temperature and then heated at 373 K for 6 h. The prod- uct was filtered, washed with distilled water and dried at ambient temperature. Ion exchange of zeolite-X was carried out using the hy- droxide and chloride solutions (1 M) of cesium, potassium and lithium. Ion exchange was carried out at 353 K using 50 ml of solution per g of sample (6 h elution). The exchange 1381-1169/$ – see front matter © 2004 Elsevier B.V. All rights reserved. doi:10.1016/j.molcata.2004.02.008