Reaction mechanisms

Ionic Reactions

Ionic Reactions

Ionic Reactions

Ionic Reactions

Bond Polarity Partial charges

Nucleophiles and Electrophiles

Leaving Groups

Radical Reactions

Type of Reactions

Nucleophilic reactions: nucleophilic substitution (SN) Nucleophilic substitution: -> reagent is nucleophil -> nucleophil replaces leaving group -> competing reaction (elimination + rearrangements) in the following general reaction, substitution takes place on an sp3 hybridized (tetrahedral) carbon

Nucleophilic Substitution Some nucleophilic substitution reactions

Mechanism Chemists propose two limiting mechanisms for nucleophilic displacement a fundamental difference between them is the timing of bond breaking and bond forming steps At one extreme, the two processes take place simultaneously; designated SN2 S = substitution N = nucleophilic 2 = bimolecular (two species are involved in the rate-determining step) rate = k[haloalkane][nucleophile] In the other limiting mechanism, bond breaking between carbon and the leaving group is entirely completed before bond forming with the nucleophile begins. This mechanism is designated SN1 where S = substitution N = nucleophilic 1 = unimolecular (only one species is involved in the rate-determining step) rate = k[haloalkane]

SN2 reaction: bimolecular nucleophilic substitution both reactants are involved in the transition state of the rate-determining step the nucleophile attacks the reactive center from the side opposite the leaving group

SN2 An energy diagram for an SN 2 reaction there is one transition state and no reactive intermediate

SN1 reaction: unimolecular nucleophilic substitution SN1 is illustrated by the solvolysis of tert-butyl bromide Step 1: ionization of the C-X bond gives a carbocation intermediate

SN1 Step 2: reaction of the carbocation (an electrophile) with methanol (a nucleophile) gives an oxonium ion Step 3: proton transfer completes the reaction

SN1 An energy diagram for an SN1 reaction

SN1 For an SN1 reaction at a stereocenter, the product is a racemic mixture the nucleophile attacks with equal probability from either face of the planar carbocation intermediate + A racemic mixture Cl C 6 H 5 OCH 3 CH O (R)-Enantiomer (S)-Enantiomer

Effect of variables on SN Reactions the nature of substituents bonded to the atom attacked by nucleophile the nature of the nucleophile the nature of the leaving group the solvent effect

Effect of substituents on SN2

Effect of substituents on SN1

Effect of substituents on SN reactions governed by electronic factors, namely the relative stabilities of carbocation intermediates relative rates: 3° > 2° > 1° > methyl SN2 reactions governed by steric factors, namely the relative ease of approach of the nucleophile to the site of reaction relative rates: methyl > 1° > 2° > 3°

Effect of substituents on SN reactions Effect of electronic and steric factors in competition between SN1 and SN2 reactions

Nucleophilicity Nucleophilicity: a kinetic property measured by the rate at which a Nu attacks a reference compound under a standard set of experimental conditions for example, the rate at which a set of nucleophiles displaces bromide ion from bromoethane Two important features: An anion is a better nucleophile than a uncharged conjugated acid strong bases are good nucleophiles

Nucleophilicity

Nucleophilicity

Leaving Group

Leaving Group

The Leaving Group the best leaving groups in this series are the halogens I-, Br-, and Cl- OH-, RO-, and NH2- are such poor leaving groups that they are rarely if ever displaced in nucleophilic substitution reactions

Solvent Effect Protic solvent: a solvent that contains an -OH group these solvents favor SN1 reactions; the greater the polarity of the solvent, the easier it is to form carbocations in it

Solvent Effect Aprotic solvent: does not contain an -OH group it is more difficult to form carbocations in aprotic solvents aprotic solvents favor SN2 reactions

Summary of SN1 and SN2

Competing Reaction: Elimination -Elimination: removal of atoms or groups of atoms from adjacent carbons to form a carbon-carbon double bond we study a type of b-elimination called dehydrohalogenation (the elimination of HX)

b-Elimination There are two limiting mechanisms for β-elimination reactions E1 mechanism: at one extreme, breaking of the C-X bond is complete before reaction with base breaks the C-H bond only R-X is involved in the rate-determining step E2 mechanism: at the other extreme, breaking of the C-X and C-H bonds is concerted both R-X and base are involved in the rate-determining step

E2 Mechanism A one-step mechanism; all bond-breaking and bond-forming steps are concerted

E1 Mechanism Step 1: ionization of C-X gives a carbocation intermediate Step 2: proton transfer from the carbocation intermediate to a base (in this case, the solvent) gives the alkene Nucleophile -> acting as a strong base

Elimination Saytzeff rule: the major product of a elimination is the more stable (the more highly substituted) alkene

Elimination Reactions Summary of E1 versus E2 Reactions for Haloalkanes

Substitution vs Elimination Many nucleophiles are also strong bases (OH- and RO-) and SN and E reactions often compete the ratio of SN/E products depends on the relative rates of the two reactions What favors Elimination reactions: attacking nucleophil is a strong and large base steric crowding in the substrate High temperatures and low polarity of solvent

SN1 versus E1 Reactions of 2° and 3° haloalkanes in polar protic solvents give mixtures of substitution and elimination products

SN2 versus E2 It is considerably easier to predict the ratio of SN2 to E2 products

Summary of S vs E for Haloalkanes for methyl and 1°haloalkanes

Summary of S vs E for Haloalkanes for 2° and 3° haloalkanes

Summary of S vs E for Haloalkanes Examples: predict the major product and the mechanism for each reaction Elimination, strong base, high temp. SN2, weak base, good nucleophil SN1 (+Elimination), strong base, good nucleophil, protic solvent No reaction, I is a weak base (SN2) I better leaving group than Cl

Carbocation rearrangements Also 1,3- and other shifts are possible The driving force of rearrangements is -> to form a more stable carbocation !!! Happens often with secondary carbocations -> more stable tertiary carbocation

Carbocation rearrangements in SN + E reactions

Carbocation rearrangements in SN + E reactions -> Wagner – Meerwein rearrangements Rearrangement of a secondary carbocations -> more stable tertiary carbocation Plays an important role in biosynthesis of molecules, i.e. Cholesterol -> (Biochemistry)

Carbocation rearrangements in Electrophilic addition reactions