Organic Chemistry Unit 4 PDF

UNIT 4 MAJOR ORGANIC REACTIONS Kind of organic reaction 1  Curved arrows indicate breaking and forming of bonds Arrowheads with a “half” head (“fish-hook”) indicate homolytic and homogenic steps Arro...

UNIT 4 MAJOR ORGANIC REACTIONS Kind of organic reaction 1  Curved arrows indicate breaking and forming of bonds Arrowheads with a “half” head (“fish-hook”) indicate homolytic and homogenic steps Arrowheads with a complete head indicate heterolytic and heterogenic steps Bond breaking Symmetrical Unsymmetrical Bond making Symmetrical Unsymmetrical 2 Nucleophile (Nu): - is a substance that is nucleus-loving. - has a negatively polarized, electron reach atom and can form a bond by donating electrons. Characteristics: Nucleophilic atoms have either lone pairs or pi bonds that can be used to form new bonds to electrophiles 3 Electrophile (E): - is a substance that is electron-loving. - has a positively charge, electron poor atom and can form a bond by accepting a pair of electrons from nucleophiles. Characteristics: Electrophilic atoms have Positive charge, a partial positive charge, or be very polarizable 4 Electrons move from a nucleophilic source (Nu) to an electrophilic sink (E) The octet rule must be followed during electron movement. 5  4.1 Substitution reactions Nucleophiles attack electrophilic centers There are two mechanisms of substitution: SN1 & SN2 6  SN2 Mechanism  substitution nucleophilic bimolecular second order overall  It is a single-step process (concerted reaction) in which both the alkyl halide and the nucleophile are involved at the transition state.  It is a concerted reaction 7  SN2 occurs with inversion of configuration with back side attack. transition state 8  SN1 Mechanism is Substitution nucleophilic unimolecular First order overall The rate depends on only the alkyl halide 9 10  Carbocations are formed in SN1 reaction. Thus, the rate depends on the stability of carbocations. Carbocation is a carbon cation The order of carbocation stability is: 3o > 2o > 1o > methyl Alkyl group stabilize carbocations by inductive effect. 11 The more stable the carbocation, the rapid the reaction by SN1 Reaction (a) takes place more rapidly than (b) since passes through more stable 3o carbocation. Carbocation stability 12  Stereochemistry of SN1 Reactions  SN1 is not stereospecific  Since carbocation has a trigonal planar structure, the Nucleophile can attack from front side or back side 13 A mixture of (R) and (S) products are possible= Racemization The Structure of Substrate  SN1 depends on the nature of carbocations. The more stable the carbocation, the faster the reaction.  In general, more highly substituted alkyl halides are more reactive toward SN1reaction than less substituted ones. SN1 reactivity rates follow the trend: 3 > 2 > 1 > methyl 14 E.g reaction of alkyl halides with acetic acid Ex. Rank the following substances in order of their expected SN1 reactivity: 15 SN2 is a single step reaction. Large groups prevent the approach of a nucleophile in SN2 reaction. The nucleophile must approach the alkyl halide from the side opposite the bond to the leaving group. Easy approach of the approach of the nucleophile is nucleophile. difficult 16 SN2 reactivity rates follow the trend: methyl > 1 > 2 > 3 17  Applications of Substitution Reactions 1. Alkyl halides  Williamson ether synthesis preparation of primary amine 18  Preparation of alkynes 19 2. Alcohols -OH is too basic to be displaced by a nucleophile Acid protonation change –OH to –OH2+ (good leaving group) 20  Preparation of alkyl halide from alcohol Thionyl chloride (SOCl2) and phosphorus halide (PX3) are also used for this purpose 21 3. Ether 22 4. Epoxides Acid catalysed cleavage of epoxides 23  4.2 ELIMINATION REACTIONS An elimination reaction is a type of organic reaction in which two substituents (two atoms or groups) are removed from a molecule base removes H+ as X- leaves base attacks H (nucleophile attacks C) There are two mechanisms of elimination: E1 and E2 24  E2 and E1 Mechanism E2 Elimination Mechanism  concerted (single step)  all bond-breaking and bond-forming steps are concerted  the H and X eliminated must be aligned anti to one another 25  E1 Elimination Mechanism  two-step mechanism Step 1: ionization of C-X gives a carbocation intermediate CH3 s low , rate CH3 determin ing – CH2 -C-CH3 CH3 -C-CH 3 + Br + Br (A carb ocation in termediate) Step 2: proton transfer from the carbocation intermediate to a base (in this case, the solvent) gives the alkene CH3 CH3 H fas t H + O + H-CH2 -C-CH3 O H + CH2 =C-CH3 H3 C + H3 C 26  Zaitsev’s Rule  Elimination reactions almost always give mixtures of alkene products.  Zaitsev's rule states that if more than one alkene can be formed by an elimination reaction, the more stable alkene is the major product. H H H H H R R H R R Stability of alkenes: C C < C C < C C < C C < C C H H R H R H R R R R Mono-substituted Di-substituted Tri-substituted Tetra-substituted more highly substituted C=C double bond is more stable due to the electron donating properties of the alkyl group 27 28  Elimination versus Substitution Nucleophilic substitution and elimination reactions often compete. Since bases are nucleophilic, they can undergo substitution to favor elimination: use a strong, hindered base e.g., KOtBu (Potassium tert-butoxide) to favor substitution: use a small, unhindered nucleophile 29  Reactivity Patterns With 1o halide substitution is highly favoured With 2o halide elimination favoured steric effect makes substitution difficult With 3o halide elimination highly favoured 30  Applications of Elimination Reactions 1. Dehydration of alcohol 2. Dehydrohalogination 3. Elimination of vicinal dihalides 31  4.3 ADDITION REACTIONS Rules for Addition Reactions Markovnikov's Rule: addition reaction pass through the formation of more stable carbocation as an intermediate. The reaction tends to pass through more stable carbocation. 32 Carbocation stability: 3° > 2° > 1° Examples 33  Anti-Markovnikov’s (Radical) addition Addition of HX on double bond in the presence of peroxides follow anti-Markovnikov’s rule The overall reaction Mechanism a) Initiation Step 1 : dissociation of a peroxide in to two radicals 34  Step 2: Hydrogen atom abstraction from hydrogen bromide by an alkoxy radical: (b) Chain propagation Step 3: Addition of a bromine atom to the alkene: 2o A secondary alkyl radical is more stable than a primary radical. Step 4: Abstraction of a hydrogen atom from hydrogen bromide by the free radical formed in step 3: 35  Application of Addition Reactions 1. Hydrogenation 36 Partial hydrogenation of an alkyne to produce alkene could be achieved using Lindlar catalyst. Lindlar catalyst = palladium on CaCO3combination to which lead acetate and quinoline have been added. Hydrogenation of alkynes with internal triple bonds gives cis alkenes 37 2. Addition of Halogens anti-stereochemistry-two new groups are added to opposite sides of the original pi bond 38 The reaction intermediate is not a carbocation but is instead a bromonium ion, R2Br+. Formed by addition of Br+ to the alkene. 39 3. Addition of Hydrogen Halide (HX) The major product is determined by Markovnikov's rule 4. Addition of water (Hydration) The reaction follows Markovnikov's rule. 40  The reaction follows Markovnikov's rule. 5. Hydroboration-Oxidation of Alkenes A two steps reaction borane-tetrahydrofuran complex (H3B-THF)-common hydroborating agent anti-Markovnikov's addition 41 6. Conversion of Alkenes to Vicinal Halohydrins 42 7. Ozonolysis of Alkenes Ozone is a powerful electrophile and undergoes a remarkable reaction with alkenes in which both the σ and π components of the carbon-carbon double bond are cleaved to give a product referred to as an ozonide. Ozonides undergo hydrolysis in water, giving carbonyl compounds. The two-stage reaction sequence is called ozonolysis 43 ozonolysis 44 8. Ozonolysis of Alkynes Ozonolysis of an internal alkyne produces two carboxylic acids Ozonolysis of a terminal alkyne yields a carboxylic acid and carbon dioxide. 45 8. Hydroxylation addition of two OH groups to each of the two double bonded carbon 46 9. Oxidative cleavage of an alkene using hot alkaline KMnO4 Acidic KMnO4 also causes double bond cleavage like ozone. 47