EPOXIDATION OF SOME * , ^-UNSATURATED CARBONYL SYSTEMS

Abstract

During the past few decades the chemistry of organic compounds and their reactions has made such a tremendous impact on theoretical and synthetic organic chemistry that it has- become very difficult to keep pace with day to day developments and achievements described in the chemical literature. The oxides of olefins have immensely contributed to the progress of the scientific and commercial world in the past few years. Epoxidation processes have evinced considerable interest due to their varied applications in the field of synthetic, industrial and biological chemistry. The varied utility of epoxides in synthetic organic chemistry is practicable as these compounds can be exploited under various conditions in a multitude of predictable trans formations. They are widely used as reagents, intermediates and end-products. Due to the presence of a three membered strained ring, a -epoxides are very reactive. The opening of this ring has been extensively studied as it affords a very convenient route for forming C-C (or C-X, where X=N,0,S,Se or Te)a bonds. Epoxides have recently been employed as intermediates in the synthesis of a-tochopherol, prostaglandins, pederamides, dendrobatid toxin 251D, lepiochlorin, 24 (R-24,25-dihydroxy vitamin D 3) pheromones and maytansinoids etc. They play a very important role in industry and are widely used in textiles, pharmaceutical, cosmetics, food and feed, leather -11- and fur, metal, paint, varnish, plastics, mineral oil and a host of other industries. Besides their industrial applica tions, epoxides are also biologically significant, for example, Leukotriene(L.TA), the biogenetic precursor of the leukotrienes(LTC, LTD and LTF) which are important natural mediators of allergic asthma. The biological activities of aglatoxin B and precocenes are due to epoxides derived from them. Although a large amount of work has been done on the epoxidation of alkenes in presence of transition metal salts and complexes, very little work seems to have been carried out on the epoxidation of a , B-unsaturated carbonyl systems. It was, therefore, thought worthwhile to study the epoxidation of various a , B -unsaturated carbonyl systems with special reference to substituted chalcones, which are useful for their potential fungicidal, antimicrobial, germicidal and anticarcinogenic activities. They also find application as artificial sweetners, stabilizer against heat, polymerization catalysts and organic brightening additives. Various catalytic methods have been developed as they increase the yield, make reaction conditions milder and are economically more viable. Phase transfer catalysts which have recently been added to catalysts often used in synthetic organic chemistry, have been employed to facilitate the epoxidation of water insoluble chalcones. The present dissertation comprises seven chapters. The first chapter is an introductory one dealing with the -inhistorical developments and significance of the epoxidation processes, general methods for the syntheses of epoxides, different mechanistic aspects involved and their characteriza tion. The second chapter concerns with the synthesis of various substituted 1,3-diphenyl propen-1-ones afforded by condensing substituted acetophenones with appropriate substituted benzaldehydes. They have been characterized by elemental analysis, IR, HNMR, UV and mass spectra and colour reactions. The third chapter describes the epoxidation of different substituted 1,3-diphenyl propen-1-ones with a number of oxidizing systems i.e. t-butyl hydroperoxide/NaOH, t-butyl hydroperoxide/ K2C03,perchloric acid, t-butyl hydroperoxide/Triton-B, hydrogen peroxide/NaOH and m-chloroperoxybenzoic acid. The homogeneity and purity of the products were checked by thin layer chromato graphy. The fourth chapter deals with epoxides of substituted chalcones under phase transfer catalysis conditions to provide a homogeneous single phase system. Phase transfer catalysts such as tetrabutylammonium bromide, tetraethylammonium bromide and tetramethylammonium bromide have been used for transferring the oxidant from the aqueous to the non-aqueous phase in order to epoxidize water insoluble chalcones. Sodium hypochlorite which is a cheaper and versatile oxidant has also been employed. -IVThe fifth chapter incorporates methods of syntheses of various transition metal complexes namely, Bis(acetylacetonato) oxovanadium (IV), N, N1- ethylene bis(salicylaldimine- 5-sulphonato) cobalt(II), trans dichloro - 5,. 7, 7, 12, 14,14 - hexa'methyl - 1, 4, 8, 11-tetraaza cyclo tetradeca-4, 11-diene cobalt(lll) perchlorate, N, N'-[bis-(salicylalyl) ethylenediminato] copper(II)j ll,13-dimethyl-l,4,7,10-tetraazacyclotrideca-lO,12-dienato (1-) nickel(ll) perchlorate, 11,13-dimethyl-l,4,7,10-tetraazacy. clotrideca-10,12-dienato(l-) nickel(n) iodide, sym dichloro Bis [bis (salicylalyl) ethylenediminato] di iron(III) and N,N'-e thylene bis (salicylideniminato) iron(III)- ji-toxo-N, N' -ethylene bis(salicylideneiminato) iron(III). The sixth chapter reports about metal catalysed epoxidations of different substituted 1,3-diphenyl propen-1-ones in presence of metal complexes of V(IV), Co(II), Co(III),Cu(II),Ni(II) and Fe(lll) as catalysts. Suitable mechanisms have been proposed for the epoxidation processes. The seventh chapter deals with the kinetic studies of the epoxidation of a , B-unsaturated carbonyl systems. 12- Phosphotungstic acid, a heteropolyacid not so far employed in epoxidation processes, has been used as a catalyst in the epoxidation of different unsaturated acids with hydrogen peroxide. The kinetic studies on the epoxidation of different substituted chalcones with m-chloroperoxybenzoic acid have also been carried out. -VThe epoxides were characterized by physico-chemical methods such as IR, UV, HNMR and mass spectroscopy. ****** CHAPTER-1 GENERAL INTRODUCTION The oxides of olefins have hit the scientific and commercial world over the past two decades. The simplest amongst them, ethylene oxide(1), propylene oxide(2) and their adducts find use as detergents, polishes, emulsifiers, antioxidants, fertilizer additives, corrosion inhibitors, evaporation suppressors and automatic antifreeze agents. They are also used in textile, phar maceutical, cosmetic, food and feed, leather and fur, metal, paint, varnish, plastics and mineral oil industries. Epoxides, therefore, are considered exceptionally valuable chemicals which have prompted a number of research workers to further explore the area of epoxidation. The epoxidation of alkenes by peracids was first discovered by a Russian Chemist, Nikolaus Prileschajew(3) in Warsaw in 1909. After 30 to 40 years, the use of organic peracids became popular through the research efforts of Daniel Swern of Temple University, Philadelphia, who showed that the epoxidation was stereospecific. Weitz and Scheffer (1921) used alkaline peroxide solutions for the epoxidation of mesityl oxide and benzal ketones, the epoxides of which were prepared earlier by the action of potassium carbonate on their chlorohydrins(4) . The breakthrough involving a metal catalysed route to epoxidation using alkyl hydroperoxides such as t-butyl hydroperoxide (t-BuOOH) as an oxygen source, was achieved .in mid-1960s by Mingsheng and John Zajacek at ARCO and John Kollar at Halcon. Their discovery quickly led to the oxirane process for producing propylene oxide, one of the world's most -2- profitable commercial chemical process. From 1965 onwards, due to the pioneering work of Makosza, Starks and Bradstorm, a very powerful technique of phase transfer catalysis was developed which gave better yields of epoxides in comparison to conventional methods. Epoxidation has been extensively studied not only for their intrinsic interest but also because of their synthetic, biological and industrial applications. 1.1 SYNTHETIC APPLICATI0NS(5-10) Different epoxides have been employed for the synthesis of various types of useful compounds: a) Nucleophilic substitution reactions(intermolecular): Oxiranes undergo ring opening when reacted with nucelophilic reagents such as Grignard reagents. b) Nucleophilic substitution reactions(intramolecular): A number of epoxynitriles are cyclized to obtain interme diates for the synthesis of compounds like grandisol. c) Nucleophilic substitution reactions of vinyl oxiranes and benzyl oxiranes: The oxirane ring of leukotrieneA(LTA) methyl ester undergoes a Sir attack regioselectively at C-6 when reacted with sulphur nucleophiles to give Leukotrienes LTC,LTD and LTE. -3- d) Synthesis of allylic alcohols from oxiranes: Oxiranes when treated with a strong base such as lithium diethylamide furnish besides allylic alcohols,ketones,amino alcohols and transannular cyclization products in case of medium ring compounds. e) Synthetic applications of a, £-epoxy ketones: The reaction of a, B -epoxyketones with hydrazine, has been utilized extensively for the synthesis of allylic alcohols. f) Syntheses of Phenolic Metabolites: Different types of aromatic substrates are enzymatically transformed into arene oxides which rearrange to phenolic metabolites. g) Thermolysis of Oxiranes: Suitably substituted oxiranes due to ring strain furnish readily rearranged products via the cleavage of C-C or C=0 linkage on heating. 1.2 INDUSTRIAL APPLICATIONS The use of epoxides as adhesion improvers for silicon rubbers (11), as corrosion inhibitors(12) , for metal coatings(13) and as lubricants for PVC(14) has added new dimensions to their applications. Recently epoxides have been reported as effective -4- marble and semiconductor coatings(15). Epoxidized rubbers(l6) and resins find large applications as binders for polymers(17), concrete and as coupling agents for mineral fibres in PVC(18). They are used as cross-linking agents in polymer technology(19) and as copolymer emulsions. Recently epoxides have been employed in pollution abatement in South Africa. 1.3 BIOLOGICAL APPLICATIONS Several epoxides possess biological activities(20-25) . Tetrahydrodiol epoxides i.e. 7B,8a-dihydroxy-9B, 10 @ -epoxy-7,8,9 , 10-tetrahydrobenzo [ a] pyrene [I ] are carcinogenic metabolites of polycyclic aromatic hydrocarbons. C0£H3 OH [I] [II] LeukotrieneA(LTA) methyl ester(II) reacts with sulphur nucelophiles to give leukotrienes LTC,LTD and LTE which are impor tant natural mediators of allergic asthma. -5- 1.4 NATURALLY OCCURRING EPOXIDES Reissantioloxide, a novel epoxytriterpenoid has been obtained from Reissantia indica found in Sri Lanka(26). (+)-9,10-Epoxy-9, 10-secoabieta-8, 11,13-triene has been isolated from the nonsaponifiable portion of Western Pine Bark (27). Anthracycline antibiotic nogalamycin is the only example of a glycosidic natural product containing a perhydroxylated epoxyoxocin ring system (28). 1.5 MECHANISM OF EPOXIDATION REACTIONS Chemical kinetics still remains as the most useful weapon in the armoury of a chemist to get a deeper insight into the probable mechanism by which a particular reaction takes place. Different workers have proposed different mechanisms for the epoxidation process based on their kinetic studies. In the year 1947, Swern (29) gave the earliest mechanism for epoxidation. He suggested an electrophilic addition reaction as: A CH-, > CH = CHQ + per-acid *- 3 +o -S2 [CH3—»CH - CuJ > CH3 > CH —CH2 *C \ / r-i •• \ ' ^o: o: Scheme 1.1 -6- Bunton and Minkoff(30) in 1949 proposed a nucleophilic addition mechanism for the epoxidation of a, g-unsaturated ketones. Weisenborn and Taub(31) in 1952, suggested that the electrophilic part of the organic hydroperoxide seeks the electron rich unsatura ted double bond and thus peracids act by providing free hydroxyl cations. R C03H - n. c = c + OH' ^ RC02 + OH" OH Scheme 1.2 ->/C - Cs +H+ \/ 0 In the nucleophilic mechanism proposed by Bunton and Minkoff, there is an attack on the double bond by the nucleophile, HO ?#- Though kinetic evidence for the transition state was establish ed, no evidence for the attack of HCU could be given. The mechanism follows the general scheme: H202*OH' ,CH3 RSc-ch-c-CH3- R2 SCHEME 1.3 omdh © „CH3 >C-CH-C -7- Bartlett proposed another type of mechanism which has been a very useful guide for interpreting the course of many epoxidations reported in literature during the last decade. The mechanism proceeds through a cyclic transition state: .............