Mechanisms

One of the most practical aspects of organic chemistry is the study and application of chemical reactions.

Due to the large number of reactants that can be used, it is virtually impossible to memorize all possible reactions.

Organic reactions are often organized into groups based on their mechanisms and the intermediates that are involved.

Mechanisms

Mechanism: a step-by-step pathway from reactants

to products that shows which bonds break, which bonds form and the order in which they happen

includes structures of all reactants, intermediates and products and curved arrows showing the movement of electrons

Mechanisms

Your success in this class depends in large part on learning the mechanisms of key reactions and applying these mechanisms to predict the products formed from starting materials you have not used before.

Mechanisms

Halogenation of alkanes:

alkane + halogen alkyl halide(s) + HX

CH4 (g) + Cl2 (g) CH3Cl + CH2Cl2 + CHCl3 + CCl4 +

HCl

or h

or h

Mechanisms

The halogenation of alkanes is a substitution reaction that occurs via a chain reaction mechanism.

Substitution reaction: a reaction in which one atom

substitutes for or replaces another atom

In the chlorination of methane, a chlorine atom replaces a hydrogen atom.

Mechanisms

Three types of steps occur in all chain reactions: Initiation:

generates a reactive intermediate

Reactive intermediate: a short-lived species that reacts as quickly as it is formed

never present in high concentration

Mechanisms

Three types of steps occur in all chain reactions: propagation

reactive intermediate reacts with a stable molecule to form a new reactive intermediate and a new stable molecule

continues until reactants are exhausted or reactive intermediate is destroyed

termination side reaction that destroy the reactive intermediate

slows or stops reaction

Mechanisms

Chlorination of Methane (Mechanism) Initiation:

Chlorine absorbs h generating two free radicals.

Use half arrows to show movement of one electron.

Cl + Clh

ClCl

Mechanisms

Free radical a reactive intermediate with one or

more unpaired electrons also called a radical electron deficient (doesn’t have octet)

Mechanisms

Chlorination of Methane (Mechanism) cont. Propagation:

First propagation step: Chlorine radical collides with a methane molecule and abstracts a hydrogen atom

H C

H

H

H + Cl H C

H

H

+ H Cl

Mechanisms

Chlorination of Methane (Mechanism) cont. Second Propagation step:

methyl radical reacts with chlorine molecule, generating product and another reactive species

The new chlorine radical continues the chain by abstracting another hydrogen atom from methane, etc.

H C

H

H

ClH C

H

H

+ Cl Cl + Cl

Mechanisms Chlorination of Methane (Mechanism)

con’t. Termination:

Any reaction that produces fewer reactive intermediates than it uses will slow or stop the reaction:

Cl ClCl+Cl

CH3Cl+ ClH C

H

H

Mechanisms

More possible termination reactions:

H C

H

HH C

H

H

+ CH3CH3

H C

H

H

collides with wall H3C wall

Cl collides with wall Cl wall

Thermodynamics

Information about chemical reactions is obtained using thermodynamics and kinetics.

Thermodynamics: used to study the stability of reactants and products predicts which compounds are favored

by the equilibrium

Thermodynamics

For an equilibrium reaction:

a A + b B c C + d D

Go = -RTlnKc

Spontaneous reaction (favors products): Kc > 1 G = neg

Nonspontaneous reaction (favors reactants): Kc < 1 G = pos

Thermodynamics

Two thermodynamic quantities contribute to G:

G = H - TS

H = enthalpy change (amount of heat gained or lost) H = positive (endothermic: heat

gained) H = negative (exothermic: heat lost)

S = entropy change change in the randomness or disorder

Thermodynamics

For many organic reactions, TS is small relative to H G ~ H

Therefore, most exothermic organic reactions tend to favor the formation of products.

The Hrxn can be estimated using the bond dissociation energies of the bonds broken and formed during the reaction.

Thermodynamics

Bond dissociation energy: the amount of energy required to break

a bond homolytically equally each atom in the bond being broken gets one electron

forms free radicals

As BDE increases, more energy is needed to break the bond: stronger bond

Thermodynamics

Example: Which of the following bonds is the strongest? The weakest?

F - F, Cl - Cl, CH3 - F, CH3 - Cl, H - F, or H - Cl

F - FCl - ClCH3 - FCH3 - ClH - FH - Cl

38 kcal/mol5810984136103

Thermodynamics

Example: Rank the following C-H bonds in order from the easiest to the hardest to break homolytically.

Methyl H104 kcal/mol

1o H98 kcal/mol

2o H95 kcal/mol

3o H91 kcal/mol

H3C H CH3CH2C

H

H

H

CH3CHCH3

H CH3CCH3

CH3

H

Thermodynamics

As BDE increases, it is harder to break the bond: Ease of homolytic cleavage:

3o > 2o > 1o > methyl

The stability of methyl, 1o, 2o, and 3o free radicals follows the same trend:

3o > 2o > 1o > methyl

i.e. 3o free radicals are the most stable and methyl radicals are the least stable

(easiest) (hardest)

Kinetics Many reactions that have favorable energy

changes (G = neg or H = neg) occur so slowly that the reaction is imperceptible. Very slow reaction rate

For the general reaction:a A + b B c C + d D

Rate = k [A]m[B]n

where k = rate constantm = reaction order with respect to An = reaction order with respect to B

Kinetics

The reaction rate depends on: collision frequency a probability or orientation factor activation energy (Ea)

The reaction rate increases as the number of collisions between reacting species increase. Concentration temperature

Cl .

Kinetics

Collisions must occur in a particular orientation for reactions to occur.

For the reaction: Cl. + H - Br H - Cl + Br.

Br H No HCl formed

Cl . BrH HCl can form

Cl . Br

H

No HCl formed

Kinetics

Collisions must occur with a specific minimum amount of energy in order for a reaction to take place.

Activation energy (Ea) the minimum energy the reactants must have for a reaction to occur

the energy difference between the reactants and the transition state

Kinetics

Transition state: a particular arrangement of atoms of

the reacting species in which bonds are partially broken and partially formed

the state of highest energy between reactants and products

a relative maximum on the reaction-energy diagram

Reaction Energy Diagram

Reaction energy diagram: a plot of potential energy changes that

occur as reactants are converted to products

Hammond Postulate

What does the transition state look like? The appearance of the transition state

depends on whether the reaction is endothermic or exothermic.

governed by the Hammond Postulate

Hammond Postulate: Related species that are closer in energy

are also closer in structure. The structure of the transition state resembles the structure of the closest stable species.

Hammond Postulate

For an endothermic reaction, the transition state more closely resembles the products.

For an exothermic reaction, the transition state more closely resembles the reactants.

endothermicexothermic

Rate Determining Step

Chlorination of methane has two propagation steps. The first propagation step controls the

rate of the overall reaction and is called the rate-determining step.

Rate-determining step (rate-limiting step): the slowest step in a multi-step process the step with the highest energy

transition state

Rate Determining Step

intermediate

ClH C

H

H

HClH C

H

H

Cl