Organic Mechanisms

Basic Ideas Behind All Mechanisms Substances can be broken into 2 categories: Electrophile – electron loving – Acts as Lewis Acid – Accepts a pair of electrons – ex. Carbons in alkane chains, hydrogen Ions Nucleophile – nucleus loving – Acts as Lewis Base – Donates a pair of electrons – ex. Halogens, Double bonds

Strengths of Nucleophiles Related to K b value. More negative charge makes it stronger (same particle) ex. OH - stronger than H 2 O Decreases as you go to the right on the periodic table. Ex. Ammonia is stronger than water Solvation impedes nucleophilicity Ex. Iodine is a larger anion so the solvent doesn’t surround as easily making it easier for Iodine to react. – Causes an increase as you go down a column on the periodic table.

Nucleophilic Power continued Increasing polarizability increases power. – Larger atoms are more polarizable (dispersion forces) Overall strength H 3 C - >HS - >Br - >OH - >CN - >NH 3 >Cl - >F - >H 2 O>ROH

Organic Redox Oxidation is defined as any process that adds electronegative atoms or removes hydrogen. – Adding oxygen to carbon in combustion – Alcohol to aldehyde or ketone Reduction is any process that adds hydrogen and removes electronegative elements. – Adding hydrogens to a double bond – Aldehyde or ketone to alcohol

Biochemistry The body uses complex catalysts to help with these organic reactions, but the principles and products are the same. Ex. Alcohol in the body. NAD + is called a dehydrogenase (enzyme) because it removes two hydrogens each time. It is also the electron acceptor in the redox.

Oxidation of Alcohols, Aldehydes, Ketones and Carboxylic Acids 1˚ primary alchohol Aldehyde Carboxylic Acid 2˚ primary alchoholKetone

Homo and heterolytic cleavage When a bond is broken, each fragment gets one of the electrons from the bond and is left with an extra unpaired electron This is called homolysis or homolytic cleavage. The result is two free radicals Usually free radicals are intermediates and are high energy. A. + B. A-B → A. + B. If a bond is broken and both electrons go to one fragment, then they both become ions This is called heterolytic cleavage. A + + :B - A-B → A + + :B -

Organic Reactions Pyrolysis Substitution -halogenation – with a halogen -S N 2 – with a nucleophile -S N 1 or hydrolysis (solvolysis) – substitution by solvent E1 - Elimination – removes halogen and makes alkene E2 – Elimination – same as E1 but different mechanism Hydrogenation – double bond eliminated by hydrogen Hydration – double bond is eliminated and makes an alcohol. Dehydration – water is released. Electrophilic addition – double bond is broken by a strong acid. Polymerization – taking alkenes and linking them into (essentially) unending chains.

Pyrolysis When alkanes are exposed to high temperatures, C-H and C-C bonds begin to break leaving two radicals. The radicals can combine to form smaller chains. Process is called cracking. Heat can also cause hydrogen to be lost from the radical leaving an alkene Called hydrogen abstraction. CH 3 CH 2. + CH 3 CH 2 CH 2. → CH 3 CH 3 + CH 3 CH=CH 2 Zeolytes (catalysts like sodium aluminosilicates) help specialize what products will be made.

Hyperconjugation When the electron is removed from the molecule, an sp 3 orbital is left half empty. The electron in the orbital delocalizes into a p orbital leaving the other bonds in a planar formation. Resonance and hyperconjugation are forms of delocalization of electrons. Resonance is of a π bond overlap of p-orbitals Hyperconjugation is delocalization with σ bonds.

Substitution Reaction A general reaction type in which an atom or group of atoms in a molecule is replaced by another atom or group of atoms. Halogenation reactions are one type: 12

Halogenation Activity series determines which halogen is most likely to react and substitute Fluorine is exothermic, the rest are increasingly endothermic. UV light breaks the halogen bond enabling the reaction. Secondary carbons are more likely to substitute than primary. Tertiary are more likely than secondary.

S N 2 mechanism Reaction mechanisms provide a powerful way to organize the vast amount of information about organic reactions. S N 2 mechanism One very important reaction mechanism. The symbol (S N 2) stands for substitution nucleophilic bimolecular. Nucleophile “Nucleus loving.” A species that is attracted by a positive charge. OH -, I -, NH 3, CH 3 O -, NC -

S N 2 mechanism Example Example HO - + CH 3 Br (aq) CH 3 OH (aq) + Br - For this reaction: nucleophileHO - is the nucleophile. Increases with increasing negative charge, decreases to right on periodic table substrateCH 3 Br is the substrate - a species that undergoes reaction. leaving groupBr - is the leaving group. Because it is replaced by HO -. Weak bases are good leaving groups.

S N 2 mechanism The mechanism takes place in a single step. This is supported by the observed rate law. Rate = k [HO - ][CH 3 Br] S N 2 reactions also take place with inversion of configuration.

S N 2 mechanism ++ -- -- ++ To account for the inversion, the nucleophile must approach from the back of the carbon The nucleophile acts as a Lewis base and the substrate as a Lewis acid. To account for the inversion, the nucleophile must approach from the back of the carbon The nucleophile acts as a Lewis base and the substrate as a Lewis acid.

S N 2 mechanism Predicting whether an S N 2 reaction will occur is possible. The S N 2 reaction Nuc: - + RX RNuc + X - is similar to a Bronsted-Lowry acid base reaction B: - + HX HB + X -

S N 2 mechanism To predict whether a S N 2 reaction will occur, you must consider the relative base strength of the nucleophile and the leaving group. If the nucleophile is a stronger base, the reaction will occur. Relative base strength Relative base strength OH - > Cl - > Br - > I - Second order based on concentration of the base and the halide.

Hydrolysis (S N 1) Haloalkane reacts with water solvent. Halogen ionizes away from a carbon leaving a carbocation. Tertiary carbocations are the best while primary are the worst. Due to hyperconjugation the positive charge is stabilized in the tertiary formation. Polar water is attracted to carbocation. Extra hydrogen is attracted to next water molecule to create a hydronium ion. First order based on concentration of halide.

E1 Elimination Haloalkanes react with a base or nucleophile. Alternate S N 1 pathway. Instead of adding water, it kicks out another proton (H + ) and forms a double bond between carbons in its place. Leaves you with an alkene and a halogenated acid. Weak bases give substitutions S N 1and S N 2, strong bases give eliminations E1. First order reaction: only dependent on the concentration of the halide.

E2 - Elimination Second order reaction due to concentration of both the halide and the base. Base attacks a hydrogen on a carbon away from the halide. Hydrogen leaves donating its electron pair to the carbon giving it four pairs. Carbon makes double bond with the other carbon which causes the release of the halogen ion.

Hydrogenation A carbonyl group from an aldehyde or a ketone or a double bond in an alkene is attacked by hydrogen gas or some other hydride in the presence of a catalyst. Catalyst is usually heterogeneous (insoluble) like platinum, palladium, or nickel deposited on carbon. Results in an alcohol when an aldehyde or ketone is involved, and an alkane when an alkene is involved.

24 Hydration: The addition of water, in the presence of a strong acid catalyst, to a multiple bond to give an alcohol product.

Dehydration A strong acid is added to an alcohol making a halide and water. HBr + C 2 H 5 OH → C 2 H 5 Br + H 2 O A carboxylic acid and alcohol react in the presence of an acid to make an ester. Called esterfication. An alcohol in acid (sulfuric) make an ether and water. An alcohol with an acid and heat will make an alkene

Electrophilic Addition The acid attacks the pi bond breaking it an leaving a carbocation. The halogen attaches to the ion to make a halide. Also called hydrohalogenation. Product can be determined using Markalnikov’s rule.

Hydrohalogenation 27 Hydrochoric and hydrobromic acids are hydrohalides HCl, HBr

Markovnikov’s rule In the addition of HX to an alkene, the H attaches to the carbon that already has the most H’s, and the X attaches to the carbon that has fewer H’s. 28

Markonvnikov’s Rule 29 Only one product is produced because of the mechanism of hydrohalogenation

30 Reaction Mechanism

Use Markovnikov’s rule to predict the product for a hydration as well.

Alkynes It is important to note that all reactions that occur with alkenes will occur in alkynes. Each step in the mechanism just has to happen twice.