Mechanisms of organic reactions

How Organic Reactions Occur Homolytic bond breaking (radical): A-B  A  + B  radicals are formed Heterolytic bond breaking (polar): A-B  A + + :B - ions are formed

Heterolytic Reactions Nucleophile has an electron-rich atom (e.g Cl -, CN -, NH 3 ) and can form a bond by donating a pair of electrons to electron-poor atom Electrophile has an electron-poor atom (e.g H +, CH 3 + ) and can form a bond by accepting a pair of electrons from a nucleophile A + + :B -  A:B

Kinds of Organic Reaction I. Addition reactions Addition reactions - two reactants add together to form a single new product with no atoms „left over“ Elimination reactions Elimination reactions - single reactant splits into two products

Kinds of Organic Reaction II. Substitution reactions Substitution reactions - two reactants exchange parts to give new products Rearrangement reactions Rearrangement reactions - single reactant undergoes a reorganization of bonds and atoms

Nuccleophilic Substitution reactions SN1 & SN2 SN1 & SN2

Uni-/Bi- molecular reactions S N 1 & S N 2 Unimolecular reaction SN1 Unimolecular reaction SN1 only one of the reactant molecules is present in the transition state R - X + Y -  R + + X - + Y - R + + Y -  R - Y Bimolecular reaction SN2 Bimolecular reaction SN2 both of reactants must be present together in transition state Y - + R - X  [Y…R…X]  R - Y + X -

Electrophilic Substitution  - an electrophile (E  ) reacts with an aromatic ring and substitutes for one of the hydrogens MECHANISM Resonance forms of  complex

Electrophiles Substance that is „electron-loving“ Has an electron-poor atom Lewis acids Lewis acids (AlCl 3, FeCl 3 ) catalyze formation of electrophilic molecules Lewis acid – accepts electron pair Lewis base – donates electron pair

Aromatic Electrophilic Substitutions I Halogenation MECHANISM X = Cl

Aromatic Electrophilic Substitutions II. Friedel-Crafts alkylation reactionFriedel-Crafts alkylation reaction Friedel-Crafts acylation reactionFriedel-Crafts acylation reaction AlCl 3 benzene + HCl tert- butylchloride tert- butylbenzene

Aromatic Electrophilic Substitutions III. Nitration

Substituent Effects in Substituted Aromatic Rings 1. Ortho- and para-directing substituents increase the electron density inside the ring Y = - NH 2, -OH, -F, -Cl, alkyl 2. Meta-directing substituents decrease the electron density inside the ring Y = - NO 2, -CN, -COOH, -SO 3 H

2. Nucleophilic Substitution Reactions of Alkyl Halides Reactions of Alkyl Halides Nu : - + CH 3 -Br  CH 3 -Nu + Br - Nucleophile = HS - > CN - > I - > HO - > Cl -

3. Radical Substitution Initiation Initiation Cl 2  2Cl  Propagation Propagation Cl  + H 3 C-CH 3  H 3 C -CH 2  + HCl CH 3 -CH 2  + Cl 2  H 3 C -CH 2 Cl + Cl  Termination TerminationH 3 C -CH 2  + Cl   H 3 C -CH 2 Cl UV

Electrophilic addition Markovnikov´s Rule: Markovnikov´s Rule: In the addition of HX to an alkene, the H attaches to the carbon with more H. cis addition – both groups attach to the same side of the double bond trans addition –groups attach to the opposite side of the double bond

Elimination Reactions Dehydration Dehydrohalogenation

Organic halide SN1 Remember the reactivity order Benzylic > allylic > 3° RX> 2° RX> 1° RX

SN2 Remember the reactivity order 1° RX > 2° RX > 3° RX > allylic >Benzylic

SN2 example

E1 Remember the reactivity order Benzylic > allylic > 3° RX> 2° RX> 1° RX

E1 & SN1

E2 Remember the reactivity order 1° RX > 2° RX > 3° RX > allylic >Benzylic

ALCOHOLS & Phenols Forming the phenoxide ion Remember that the negative charge here is localized, therefore this ion more stable than the alkoxide ion (from alcohol)

Mechanism of the Kolbe-Schmitt Reaction

Ethers

Williamson synthesis

Aldehydes & Ketones IDOFORM REACTION OF THE METHYL KETONE

Aldol condensation

Amines HOFMANN rearrangement