117  

5.9 Resolution of Enantiomers - a process of separating a racemate into pure enantiomers.

Crystallization

Chiral resolving agents. The enantiomers of the racemate must be temporarily converted into diastereomers.

N(S)(S)

(R)(R)

(R)(R)

(S)(S)N

H

H

H3C CO2HC(R)(R)

NH2H

H3C CO2HC(S)(S)

HH2N

+

H3C CO2C(R)(R)

NH2H

N(S)(S)

(R)(R)

(R)(R)

(S)(S)N

H

H

N(S)(S)

(R)(R)

(R)(R)

(S)(S)N

H

H

H

H

•

•

(-)-sparteine

H3O+

H3O+

H3C CO2C(S)(S)

HH2N

H3C CO2HCNH2H

H3C CO2HCHH2N

(S)-(+)

(R)-(–)

118  

Chapter 6 Chemical Reactivity and Mechanisms 6.1 Enthalpy (ΔH) - the heat (energy) exchange between the reaction and its environment at constant pressure

Bond breaking processes require heat from the environment. Homolytic: symmetrical bond breaking process

Heterolytic: unsymmetrical bond breaking processes Bond dissociation energy (ΔH°) – energy required for homolytic cleavage of a covalent bond. Table 6.1 (p. 238)

Heat of reaction (ΔH°) - total enthalpy change bond during a reaction. ΔH°products – ΔH°reactant = ΔH°reaction

59

Some bond dissociation energy values from Table 6.1 (p. 238)

119  

C=C 632 KJ/mol (σ + π bonds) H–Br 368 KJ/mol

C–C – 368 KJ/mol (σ bond) C–H – 410 KJ/mol C-Br – 285 KJ/mol

+ 1000 KJ/mol –1063 KJ/mol – 63 KJ/mol

Exothermic = product are favored Heat is released

Endothermic = reactant are favored Heat is absorbed for the reaction to proceed

C CH

HH

H+ C C

H H

HH

H

BrH Br

120  

60

Enthaphy (ΔH°): heat of reaction Change in total bond energies during a reaction

ΔH° < 0: bond energies of the products are stronger (more stable) than those of the reactants. The reaction is favored, heat is released, exothermic.

ΔH° > 0: bond energies of the products are weaker (less stable) than those of the reactants. The reaction is disfavored, heat is absorbed, endothermic.

6.2 Entropy (ΔS°): Entropy change: measure of molecular disorder

ΔS° < 0: disorder is decreased (more order), disfavored ΔS° > 0: disorder is increased (less order), favored

121  

6.3 Gibbs Free Energy ΔG° = ΔH° - TΔS°

ΔG° < 0: free energy change for the reaction is favorable - spontaneous – exergonic

ΔG° > 0: free energy change for the reaction is unfavorable. - not spontaneous – endergonic  

122  

61

6.4 Equilibria

ΔG° = ΔH° - TΔS° ΔG° = -RT ln Keq R= 8.314 x 10-3 KJ • mol-1• °K-1

C CH

HH

H+ C C

H H

HH

H

BrH Br

Keq = [CH3CH2Br]

[H2C=CH2] [HBr]

Keq tells us which side of the equilibrium arrows is energetically more favorable. if: Keq > 1, then [products] is greater than [reactants] and products

are favored Keq < 1, then [reactants] is greater than [products] and reactants

are favored

123  

ΔG° = -2.0 KJ/mol Cl

H

H

Cl

124  

62

6.5 Kinetics Thermodynamics (equilibria, Gibbs Free Energy) can only tell us the position of an equilibrium (Keq) or if a reaction is theoretically possible. It does not tell us how fast a reaction occur.

Rate = how fast (or slow) a reaction will occur

Rate Equations – the rate of a reaction can be expressed as the time-dependent disappearance of reactants or appearance of products.

Reactions require molecular collisions of sufficient energy (Ea) and the proper orientation.

Activation Energy (Ea, ΔG‡): Energy difference between reactants and the transition state. The rate of a reaction depends on the activation energy (Ea)  

Small Ea - fast reaction rate Large Ea- slow reaction rate

126  

ΔG° ΔG°

63

Temperature – Reaction rates increase as temperature increases. • increasing the temperature increases the kinetic energy of the reactants • increasing the temperature increases the frequency of molecular collisions

Sterics – effects of bulk. Steric congestion slows reactions.

Catalysts – substance that increases the reaction rate but is not consumed in the overall reaction. Catalysts increase rates by lowering the Ea. Catalysts do not affect the free energy change of the reaction (ΔG°).

127  

ΔG°

128  

6.6 Reading Energy Diagrams Kinetics vs Thermodynamic

Transition States vs Intermediates Transition state – structure corresponding to maxima on the

reaction coordinate. Intermediate – structure corresponding to a minima on the

reaction coordinate, between the reactants and products

64

129  

reactants  

products  

Transition states can not be isolated or “trapped.” Intermediates in principle, can be isolated or “trapped.”

What is the structure of a transition state? How do the structures of the reactants and products affect Ea?

ΔG°1

Ea1

Ea2

ΔG°2

Ea3

ΔG°3

ΔG°

130  

The Hammond Postulate – an intuitive relationship between rate (Ea) and product stability (ΔG°). The structure of the transition state more closely resembles the nearest stable species (i.e., the reactant, intermediate, or product).

For an endothermic reaction (ΔG° > 0), the TS is nearer to the product. The structure of the TS more closely resembles that of the product. Therefore, factors that stabilize the product will also stabilize the TS leading to that product.

For an exothermic reaction (ΔG° < 0), the TS is nearer to the reactant. The structure of the TS more closely resembles that of the reactants.

65

131  

6.7 Nucleophiles and Electrophiles Reactive species for polar (ionic) reactions

Electron rich (δ–) sites in a functional group of one molecule react with an electron-poor (δ+) sites of another functional group

Electrophile: electron poor (lover of electrons) Nucleophile: electron rich (lover of nuclei)

Note the similarity to Lewis acid-base definition Lewis acid: electron pair acceptor (electrophile) Lewis base: electron pair donor (nucleophile)

A + B+ (δ+) - (δ -)A-B

electrophile nucleophile

Some nucleophiles Some electrophiles

H3N H2O HO X– –

H+ H3C–X C

Oδ+

δ+

δ–

CC

C +

132  

6.8 Mechanisms and Arrow Pushing Nucleophilic Attack – nucleophilic center adding to (attacking) an electrophilic center. Loss of a Leaving Group – Nucleophilic addition often results in the loss of an atom or group (the leaving group) from the electrophile. The leaving group departs with an electron pair.

66

133  

Proton Transfer – it is common for protons to be shuffled (transferred) between atoms during reactions. This is often a crucial part of the reaction mechanism.

Rearrangements – a single reactant undergoes bond reorganization to give a product that is an isomer of the reactant

134  

6.9 Combining the Patterns of Arrow Pushing

67

6.10 Drawing Curved Arrows (adapted from slide 39, Chap. 2)

1.  Curved arrows show the movement (flow) of electrons during bond breaking and/or bond making processes (mechanism). The movement of an electron pair is denoted by a curved double headed arrow for polar reactions. The foot of the arrow indicates where the electron pair originates (nucleophile for polar mechanisms), the head of the arrow shows where the electron pair ends up (electrophile for polar mechanisms).

2. If an electron pair from a nucleophile moves in on (attacks) an electrophilic

atom, another electron pair must leave so that the electrophilic atom does not exceed a full valance of eight electrons. A common exceptions is when the electrophilic atom has an incomplete valance (R3C+).

3. The arrows completely dictate the Lewis structure of the product.

double-headed arrow (electron pair)

135  

136  

6.11 Carbocation Rearrangements – a –H (hydride) or –CH3 (methyl) from a carbon adjacent to a carbocation may migrate with its electron pair to the cationic carbon to generate an isomeric carbocation. The rearrangement will occur if the new carbocation is more stable than the original.

Carbocation stability: Increased substitution stabilizes carbocations through:

Inductive Effects: shifting of electrons in a σ-bond in response to the electronegativity of a nearby atom (or group). Carbon is a good electron donor. Substitution can stabilize carbocations by donating electron density through the σ -bond.

3°: three alkyl groups donating electrons

2°: two alkyl groups donating electrons

1°: one alkyl group donating electrons

H HC

H

+H H

C

R

+R H

C

R

+R R

C

R

+

methyl: no alkyl groups donating electrons

68

137  

Hyperconjugation: The C-H σ -bond on the neighboring carbon lines up with the vacant p-orbital and can donate electron density to the carbon cation. This is a “bonding” interaction and is stabilizing. More substituted carbocations have more possible hyperconjugation interactions.

C C

H

138  

6.12 Reversible and Irreversible Reaction Arrows All reactions are in principle reversible. The mechanism of the reverse reaction is identical to that of the forward reaction, only in reverse (Principle of Microscopic Reversibility).

Nucleophilic attack – is potentially reversible if the nucleophilic group is also capable of acting as a leaving group

Leaving groups – many of the properties of a good leaving group also makes them good nucleophiles.

Proton transfer – differences in pKa between the proton donor and acceptor gives an indication of reversibility; however, low concentrations of a protonate species (unfavorable equlibrium) can still be useful.

Carbocation rearrangements – the equilibrium between a carbocation and its rearrangement product is reflective of their relative stability.

69