____________________________________________________________________________________________________ Subject Chemistry Paper No and Title Paper-9, Organic Chemistry-III (Reaction Mechanism-2) Module No and Title Module-7, Nucleophilic and Free Radical Addition Reactions of Alkenes Module Tag CHE_P9_M7 CHEMISTRY PAPER No. : Paper-9, Organic Chemistry-III (Reaction Mechanism-2) MODULE No. : Module-7, Nucleophilic and Free Radical Addition Reactions of Alkenes ____________________________________________________________________________________________________ TABLE OF CONTENTS 1. Learning Outcomes 2. Introduction 3. Nucleophilic Additions to Alkenes 3.1 Cyanoethylation 3.2 Hydro-cyano-addition 3.3 Michael Addition 3.4 Epoxidation of α,β-unsaturated Carbonyls 4. Free Radical Addition Reactions of Alkenes 4.1 Free radical addition of HBr 4.2 Free Radical Addition of Halomethanes 4.3 Other Free Radical Additions of Alkenes 6. Summary CHEMISTRY PAPER No. : Paper-9, Organic Chemistry-III (Reaction Mechanism-2) MODULE No. : Module-7, Nucleophilic and Free Radical Addition Reactions of Alkenes ____________________________________________________________________________________________________ 1. Learning Outcomes After studying this module, you shall be able to • Know about reactivity of alkene towards nucleophiles and free radicals • Learn about the alkene substrates that undergo nucleophilic additions • Familiarize with the mechanistic aspects of nucleophilic and free radical additions • Be acquainted with alkene’s nucleophilic and free radical additions of synthetic importance • Identify the stereochemistry and orientation of nucleophilic and free radical additions of alkenes 2. Introduction Besides the electrophilic addition reactions which constitute the major and most important of reactions of the carbon-cabon double bonds, alkenes also undergo few important nucleophilic additions and free radical addition reactions. Simple alkenes are not so much electrophilic that thay can undergo addition with nucleophiles. However, if the carbon-carbon double bond is activated by the presence of electron withdrawing groups (EWG), it leads to polarization of the double bond making it electrophilic and susceptible to a nucleophilic attack. Common electron-withdrawing groups and their order of effectiveness in making alkenes prone to nucleophilic addition are as shown below. Similar effects wre observed with -SOR, -SO2R and –F substituents and these groups act by reducing the π electron density at the alkene carbons either inductively (electronegative atoms), or mesomerically (by resonance) aiding the approach of the nucleophile. Most groups conjugate with the alkene and render the alkene more electrophilic. CHEMISTRY PAPER No. : Paper-9, Organic Chemistry-III (Reaction Mechanism-2) MODULE No. : Module-7, Nucleophilic and Free Radical Addition Reactions of Alkenes ____________________________________________________________________________________________________ Alkenes also undergo a variety of free radical addition reaction wherein free radicals (a highly reactive species with an unpaired electron) add up to the carbon-carbon double bond. A free radical addition of alkene also involves an initiation step, a propagation step and termination steps as in any other free radical reaction. The free radicals are formed via homolytic bond cleavage as shown below for HBr and which can be brought about through light (photo-initiation) or by adding other free radical initiators. The addition of a free radical to the alkene leads to a radical intermediate which unlike other intermediates such as carbocations in electrophilic additions, does not rearrange. A general reaction sequence for free radical addition to alkenes is shown below: 3. Nucleophilic Additions to Alkenes The steps of nucleophilic addition to alkenes are just the reverse of electrophilic addition. Thus, the nucleophile first attacks the alkene double bond and adds up to form a carbanion. In the second step, the carbanion combines with the electropositive species. This is illustrated in the following figure. CHEMISTRY PAPER No. : Paper-9, Organic Chemistry-III (Reaction Mechanism-2) MODULE No. : Module-7, Nucleophilic and Free Radical Addition Reactions of Alkenes ____________________________________________________________________________________________________ Because of the conjugation, the α,β-unsaturated carbonyls have two electrophilic sites: the carbonyl carbon and the β-carbon. Thus, the nucleophile may possibly attack both sites leading to either a 1,2-addition or a 1,4-addition respectively. The latter is also known as conjugate addition as addition occurs to the double bond conjugated with the carbonyl functionality. The conjugate addition results initially to an enol which tautomerizes to the keto form. The addition to the 3- position never occurs since the resulting carbanion would have no resonance stabilization. These scenarios are illustrated in the following figure. The regiochemistry of nucleophilic addtions is dependent upon the type of nucleophile employed. Stronger the nucleophile, the more chance is for 1,2-addition. Thus strong nucleophiles such as Grignard reagents (RMgX) or RLi or hydride ion favour 1,2-addition. Whereas weaker nucleophiles such as enolate ions favour 1,4-addition. Actually, a 1,2-addition occurs first (kinetically favoured) and it may be reversible or irreversible (again depending upon the nature of nucleophile; stronger nucleophiles are poor leaving groups and hence difficult to eliminate from a 1,2-addition product). If irreversible, then 1,2-addition predominates. If reversible and allowed to run for more time, then 1,4-addition product will predominate as it is more stable and thermodynamically favoured. Also if perfomed at lower temperatures, kinetic product i.e. 1,2-addition product predominates while at higher temperatures thermodynamic product i.e. 1,4-addirion product prevails. Important nucleophilic addition reactions of alkenes are discussed as follows: 3.1 Cyanoethylation With alkenes containing a -CN substituent, the most common being acrylonitrile, a variety of nucleophiles such as phenols, alcohols, amines or sulfides may easily add to the unsubstituted carbon of the double bond. Thus, on abstraction of a proton from the solvent, the original nucleophile now has an attached 2-cyanoethyl group and this process is termed as cyanoethylation. Thus, incorporation of a 3-carbon unit takes place in which the terminal cyano group can be transformed via reduction, hydrolysis etc. for further synthetic manipulations. The cyanoethylation procedure is performed in presence of a base which can convert the HNu to the ¯ more powerful nucleophile Nu . 3.2 Hydro-cyano-addition Alkenes having electron-withdrawing groups and also poly haloalkenes undergo base catalysed addition with HCN to give nitriles. CHEMISTRY PAPER No. : Paper-9, Organic Chemistry-III (Reaction Mechanism-2) MODULE No. : Module-7, Nucleophilic and Free Radical Addition Reactions of Alkenes ____________________________________________________________________________________________________ HCN in presence of base gives –CN which is a good nucleophile and adds to the activated alkene. Proton abstraction ten results in the formation of the nitrile product. When the reaction is performed with α,β-unstaurated carbonyls, then the 1,2-addition may be the competing reaction an sometimes is the major reaction. 3.3 Michael Addition With any substrate, when the nucleophile attacking the substituted alkene is a carbanion, the nucleophilic addition is termed as Michael addition. The carbanion id formed by abstraction of a proton drom the organic substrate of the form EWG–CHR2 (R may be alkyl, aryl, hydrogen, or another EWG) by a base such as NaOH. For example CH2(COOEt)2 or CH2(CN)2 etc. on proton abstraction by a base give a stable carbanion which can act as a nucleophile and undergo addition with an activated alkene. An example is illustrated in the following figure. Here also 1,2-addition can compete with the 1,4-addition. Besides this reaction, due to the popularity and synthetic importance of this reaction, all other similar conjugate additions have been termed Michael-type additions in the literature. CHEMISTRY PAPER No. : Paper-9, Organic Chemistry-III (Reaction Mechanism-2) MODULE No. : Module-7, Nucleophilic and Free Radical Addition Reactions of Alkenes ____________________________________________________________________________________________________ 3.4 Epoxidation of α,β-unsaturated Carbonyls The epoxidation of α,β-unsaturated ketones with hydrogen peroxide under basic conditions is essentially a nucleophilic addition reaction. These conjugated alkenes usually do not give epoxides when treated with peroxyacids. But this method is quite good for prepartaion of epoxides from α,β-unsaturated ketones, aldehydes and even sulfones. The reaction involves 1,4- – addition of the nucleophile HOO (generated by reaction of H2O2 and NaOH) to the conjugated alkene and subsequent internal attack of the carbanion to the O—O bond to form an epoxide ring via liberation of an OH– ion as depicted below 4. Free Radical Addition Reactions of Alkenes 4.1 Free radical addition of HBr It was observed that in presence of peroxide, the addition of HBr to alkenes takes place in an anti-Markovnikov manner. This was discovered by famous chemist Kharasch and this effect came to be known as peroxide effect or Kharasch effect. Thus, 1-butene gave 1-bromobutane (anti- Markovnikov product) with HBr/H2O2,