Addition Reactions and Their Mechanism Lecture Notes PDF

Lecture-5 Addition reactions and their mechanism College of Pharmacy Department of Pharmaceutical Chemistry Section -Addition reaction-Introduction -Types of addition reaction -Electrophilic addition -Nucleoph...

Lecture-5 Addition reactions and their mechanism College of Pharmacy Department of Pharmaceutical Chemistry Section -Addition reaction-Introduction -Types of addition reaction -Electrophilic addition -Nucleophilic addition -Nucleophilic addition at conjugated system -Free radical addition -Rearrangement reactions-Introduction -Rearrangement reactions-Classification -Rearrangement reactions-Specific examples -References Introduction Addition reaction is defined as that reaction in which all the reagent atoms are added to the reactant and thus the product contains all the atoms of the reactant as well as.that of the reagent Characteristic feature of unsaturated compounds (alkenes, alkynes) in which double or triple bonds acts as the electron pair donor for bond formation. Substrate Reagent Product ٣ Types of addition reaction Electrophilic addition Nucleophilic addition Nucleophilic addition to conjugated system Free radical addition ٤ Electrophilic addition - Page - 283 (1 It is the characteristic reaction of alkenes in which electrons in the 𝑝𝑖 bond react with.electrophiles Electrophiles can be proton donors-Bronsted-Lowry acids, neutral reagents-bromine,.Lewis acids-BH3, BF3, AlCl3 It is a bimolecular reaction in which formation of carbocation is a rate determining step. Rate = k[alkene][ENu] Step 1 Step 2 ٥  a) Addition of halogens (X2) - (Halogenation) Page 286 Halogens such as chlorine (Cl2) and bromine (Br2) react readily with alkenes to produce.1,2-dihalogen derivatives Reaction Mechanism ٦  Mechanism – Page - 287 During the course of the reaction, the reactants get closer, there is a flow of electrons from the π bond to the nearer halogen, followed by departure of the further halogen.as halide (nucleophile). This results in formation of a carbocation In the next step, there is formation of a cyclic halonium ion (bromonium ion). This is achieved by bonding of a lone pair of electrons from the large halogen atom to the.carbocation Finally the nucleophile (Br-) attack from the opposite side of the cyclic halonium ion, the net result is the formation of a 1,2-dihalo system, and, stereochemically, the halogen atoms have been inserted onto opposite faces of the double bond. This is.described as anti addition (Greek: anti = against) ٧ :Examples of electrophilic addition reactions Addition of bromine (Br2) to (z)-but-2-ene: Page-287.1 The stereochemical consequences of the electrophilic addition of Br2 to (Z)-.but-2-ene (cis 2-butene) can be precdict as follows but-2-ene (cis 2-butane) on reaction with Br2 gives 2,3-dibromo--(Z) butane as a pair of enantiomers, R,R and S,S, a result of the anti addition. A.racemic product will thus be formed ٨ ٩  Addition of bromine (Br2) to (E)-but-2-ene: Page-288.2 Addition of bromine to (E)-but-2-ene (trans 2-butene) gives meso R,S isomer of 2,3-dibromo-.butane ١٠  Addition of bromine (Br2) to cyclohexene: Page-288 (3 Cyclohexene on reaction with Br2 form 1,2 –dibromocyclohexane as a racemic product,.again R,R and S,S two isomers ١١  :Note.Addition of halogens (Halogenations) to alkene is always an anti addition process.1 Cis alkene on halogenation gives 2 isomers (R,R and S,S isomer in equal percentage.2.(therefore the product is known as a racemic mixture.Trans alkene on halogenation gives one isomer (meso isomer).3 ١٢ b) Addition of hydrogen halides (HX) (Hydrohalgenation) - page - 284 HI >HBr >HCl >HF.Alkenes reacts with hydrogen halides to form alkyl halides The order of reactivity of hydrogen halides is :General reaction equation ١٣ b) Addition of hydrogen halides (HX) (Hydrohalgenation) - page - 284 The addition of a hydrogen halide, e.g., HCl, to an alkene is a simple example of an electrophilic.addition.butene on reaction with HCl it gives 2-chlorobutane-2 ١٤ b) Addition of hydrogen halides (HX) (Hydrohalgenation) - page - 284 :Mechanism of the reaction During the course of the reaction 1st hydrogen will get adds as an electrophile which leads to the.formation of carbocation and in the 2nd step chloride will gets added as a nucleophile In the hydrogenation reactions if alkenes are symmetrical then only one product forms and.alkenes are unsymmetrical then two product (one major and one minor) forms ١٥  Examples of symmetrical alkenes are H3C C C CH3 H2C CH2 H H 2-Butene Ethylene Examples of unsymmetrical alkenes are H2C C CH3 H2C C C2H5 H H Propene 1-Butene ١٦.If alkene is symmetrical simple alkyl halide is formed If alkene is unsymmetrical, addition of HX is regioselective, follows Markovnikov’s rule and.gives two different alky halides in which one product usually predominates Markovnikov’s addition ١٧ Addition of hydrogen halides to unsymmetrical alkenes: -page -285 :Addition of HCl to 2-methyl but-2-ene During the course of the reaction two carbocation are formed. Tertiary carbocation and secondary carbocation. As tertiary carbocation is more stable so the major product is obtained from the tertiary carbocation and minor product is formed from secondary.carbocation ١٨ Addition of hydrogen halides to unsymmetrical alkenes: -page -285 :Addition of HCl to 2-methyl but-2-ene ١٩ - :Addition of hydrogen halides to unsymmetrical alkenes :Markovnikov’s rule page -286 Marknovinov’s rule had beed utilized to predict the regiochemistry for addition of HX to.unsymmetrical alkene Marknovinov’s rule states that in the addition of HX to an unsymmetrical alkene, the hydrogen atom adds to the carbon atom of the double bond that has the greater number.of hydrogen atoms ٢٠ - :Addition of hydrogen halides to unsymmetrical alkenes :Markovnikov’s rule Mechanism ٢١ Electrophilic addition to conjugated system: Page-296 The first step in the reaction of HX with alkene is protonation to yield the more stable cation. If we extend this principle to a conjugated diene, e.g., buta-1,3-diene, then we can see the preferred carbocation will be produced if protonation occurs on a terminal carbon atom, where as protonation of either C2 or C3 would produce an unfavorable.primary carbocation :The addition of HBr to buta-1,3-diene ٢٢ Electrophilic addition to conjugated system: Page-296 :The addition of HBr to buta-1,3-diene ٢٣ :Nucleophilic addition -2 In nucleophilic addition reactions, the nucleophile attacks first at the carbon to form.carbanion intermediate Reaction Mechanism ٢٤ :Nucleophilic addition to conjugated system – page- 393 (3 Conjugate addition, or 1,4 addition of a nucleophile only occur to C=C double bonds.next to C=O groups Alkenes when conjugated with a carbonyl becomes electrophilic and reacts with.nucleophiles Reaction ٢٥ Mechanism β α ٢٦ Free radical addition – page -328 (4 The bond which is present between two atoms undergoes either homolytic cleavage or.heterolytic cleavage Homolytic cleavage forms free radiclas and heterolytic cleavage forms positive and.negative ions ٢٧ Free radical addition – page -328 (4 :Addition of HBr to unsymmetrical alkene (1-propene) Addition of HBr to propene in the presence of peroxides yields predominantly anti- markovnikov product. That means during the course of the reaction the hydrogen atom attaches to the carbon atom with the fewer hydrogen atoms. It is also termed as.peroxide effect This anti-Markovnikov addition occurs only when HBr is used in the presence of peroxides and does not occur significantly with HF, HCl, and HI even when peroxides.are present ٢٨ Free radical addition – page -328 (4 :Addition of HBr to unsymmetrical alkene (1-propene) bromo-2-methylpropane-1 bromo-2-methylpropane-2 ٢٩ Free radical addition – page -328 (4 :Addition of HBr to unsymmetrical alkene (1-propene) ٣٠ Mechanism – Page -329 ٣١ Radical addition of HBr to conjugated dienes – page -330 ٣٢  Rearrangement Reactions-Introduction A rearrangement reaction is a broad class of organic reactions where the carbon skeleton of a molecule is rearranged to give a structural isomer of the original molecule. Often a substituent moves from one atom to.another atom in the same molecule Generally the migrating group never leaves the molecule ٣٣ Classification Rearrangement to Electron Deficient Carbon.1 Wagner-Meerwein Rearrangement Pinacol Rearrangement Benzilic Acid Rearrangement Arndt-Eistert Homologation Reaction Rearrangement to Electron Deficient Nitrogen.2 Hofmann Rearrangement Curtius Rearrangement Schmidt Rearrangement Lossen Rearrangement Beckmann Rearrangement ٣٤