CHEMISTRY 3331
Summary about isomers
Isomers
Constitutional (structural)
 Same formula
 Different
connectivity
Stereoisomer
 Same formula,
same connectivity
 Different spatial
arrangement
Configurational
Cannot be interconverted
unless bonds are broken
Enantiomers
Mirror images that are
not superimposable
Diastereomers
Config. isomers that
are NOT mirror images
(includes cis/trans
isomers)
Conformational
Rapidly interconverts
without breaking bonds,
usually cannot isolate
C—C single bond
rotation
conformers
CH 4: Study of Chemical Reactions –
We study reactions by investigating reaction mechanisms. Mechanisms is a complete step-by-step
description of the bond-making and bond-breaking steps in reactions; it depends on:
1) thermodynamics- which is the study of energy that accompanies a chemical reaction.
2) kinetics—which is the study of reaction rates.
Study of reactions can be organized in 2 ways:
1) what kinds of reactions occur
2) how reactions occur
etc.
1. Types of Reactions
o
Addition Reaction: A + B  C
o
Elimination Reaction (reverse of addition rxn) : A  B + C
o
Substitution Reaction: A + B  C + D
o
Rearrangement Reaction
2. How Reactions Occur - Mechanisms
Bond-breaking and bond-making can occur in 2 ways:
1) Homolytic bond cleavage (radical):
2) Heterolytic bond cleavage (polar):
Good example is chlorination reactions. Note that radical is species containing an unpaired electron.
What are the important characteristics? :
1) Needs energy to start
2) Most efficiently the reaction is initiated by light of wavelength that is absorbed by Cl2.
3) One photon introduced into reaction mixture produces many molecules of product.
The following is mechanism that is consistent with all these facts. It contains 3 steps
1) Initiation- generates reactive intermediate
2) Propagationreactive intermediate reacts with stable molecule to form another reactive intermediate,
allowing the chain to continue
Notice the arrows are
different than when 2
electrons move.
overall process is a chain reaction.
3) Termination- which is side reaction that destroy reactive intermediates and slows or stops
reaction. Several possible
The second possibility is to break bond in heterolytic way. This kind of bond breaking is characteristic of
polar reactions. The electrons in this case move in pairs.
Certain bonds are polar—
If break this bond, electrons tend to go with Cl
If break this bond, electrons tend to go with C
3. Equilibria and Rates
A) Equilibria
Equilibrium concentrations of reactants and products are governed by the equilibrium constant of the
reaction.
If K > 1 equilibrium lies to the right.
If K < 1, equilibrium lies to the left
In any reactions an energy change must occur since the overall energy required to break all necessary
bonds really equals the energy given off by forming new bonds. We call that change in energy Gibbs free
energy GO = Free energy change.
𝑐𝑎𝑙
It may be expressed as GO = - RTlnKeq (R = the gas constant, 1.987
, T = temp in Kelvin)
𝐾∙𝑚𝑜𝑙
If K = 1 ,  G = 0 then product and SM have same free energy and thus are in equal concentration.
K=1
K>1
K<1
G = 0, product and SM have same free energy and thus are in equal concentration.
G = negative, exothermic (favorable)
G = positive, endothermic (*show which direction it goes*)
G is dependent on 2 factors:
GO = HO - TSO
SO = entropy term,
HO = standard heat of reaction, usually larger than TSO
For S, positive values indicate that products have more freedom of motion than reactants and it makes
a favorable (negative) contribution to G.
H, the change in enthalpy is also called the heat of reaction—it is the amount of heat evolved or
consumed in the course of reaction.
It can be related to the energies required to break and form bonds.

HO = HO (bonds broken) — HO (bonds formed) Negative = exothermic (favored)
Positive = endothermic (unfavorable)
Table 4-2 gives some values of B.D.E
HO for reaction:
Bonds Broken
H3C—H 104 kcal/mol
Cl—Cl 58 kcal/mol

kcal/mol
HO =
–
= -
Bonds Formed
H3C—Cl 84 kcal/mol
H—Cl
103 kcal/mol
 kcal/mol
kcal/mol (very exothermic reaction)
propagation steps
First propagation step:
Break C—H bond
Form H—Cl bond
+ 104 kcal/mol
- 103 kcal/mol
+ 1 kcal mol
Second propagation step:
Break Cl—Cl bond
Form CH3—Cl bond
+ 58 kcal/mol
- 84 kcal/mol
- 26 kcal mol
Overall -25 kcal/mol
B) Kinetics (rates)
Kinetics is the study of rxn rates. Rate equation is the relationship between concentration of reactants
and observed reaction rate
The rate equation must be determined experimentally.
Consider energy distribution of molecules at some constant temp
Boltzmann- Gaussian Distribution
For the chemical reaction to occur, molecules need
to possess a certain amount of energy called Eact.
When Eact = E1 a greater fraction of molecules
possess needed energy than when Eact = E2.
From this we can get the rate constant of the reaction kr = Ae-Ea/RT
Ea = the minimal kinetic energy molecules need to react
e-Ea/RT relates to fraction of collisions where molecules have that energy
R= gas constant (1.987 cal/ K mol)
e = 2.718 (base of natural logarithm)
A = frequency factor; frequency of collisions and fraction of collisions
w/correct orientation
Temperature effects on rate are very large. Basically, raising temp by 10 o makes rxn faster 2-4x. How do
we explain that?
in 2nd case more molecules have E>Ea
C) Reaction Profiles
1) One-step reactions
Consider change in the structure of system as a reaction proceeds
Bond breaking- requires energy
Bond forming- releases energy
Overall energy- HO for the rxn
Reaction Coordinates – Potential Energy
These are 1 step reactions (no intermediates)
Activation energy – energetic difference between SM (reactants) and TS.
Heat of reaction—difference in energy between SM and TS
Large Ea = slower rxn
There is activation barrier even for very exothermic processes:
CH4 + 2 O2  CO2 + 2 H2O + energy
(not spontaneous)
The top of energy barrier called “TS”. Equal probability of going to products or SM. TS is a transient,
high energy state; we cannot easily deduce its exact structure. This structure is important because it tell
us how the reaction occurs.
2) Multiple-step reactions
Some reactions have more than one step. Between each step, an intermediate is represented by a
minimum on reaction coordinate. Stability of intermediate is a function of depth of this well
1. Chlorination of methane:
The lower the energy barrier (Ea), the larger the rate constant (k) thus k2 > k-1 > k1 > k-2
Slow forward step (containing highest energy TS) is called the rate determining step.
How can we prove that 1st step is RDS? – Use CD4, deuterated methane (H with 2 neutrons), instead of
CH4.
o C—D bond stronger than C—H bond so, reaction where C—D(H) bond breaking is RDS ; will go
slower for C—D
o
Chlorination of CH4 is ca 12x faster than chlorination of CD4  C—H(D) breaking is RDS.
2. Halogenation of higher alkanes
Problem with halogenation is that we obtain mixtures, even in the case of methane. Product also reacts:
What happens for higher alkanes? – In this case, situation is worse than in case of methane; most
alkanes give mixture of products.
Look at example of isomeric butane, how many different monosubstituted products can we obtain?
(monosubstitution means introductin one atom in molecule, in this case one chlorine)
We need to take into account both product rations and number of each type of H and we can calculate
relative reactivities of three types ( 1o, 2o, 3o hydrogens) towards chlorination
Hydrogens:
1o hydrogen:
H attached to primary C (CH3 groups)
2o hydrogen:
H attached to secondary C
3o hydrogen:
H attached to tertiary C
Relative reactivity of 1o vs 2o vs 3o H’s per H substituted
reactivity
𝐶𝐻3 30 4 20
1
=
× =
=
𝐶𝐻2 70 6 70 3.5
ratio
𝐶𝐻3 65 1
7
1
=
× =
=
𝐶𝐻
35 9 35 5
amt of H’s
Relative reactivity towards chlorination:
R3CH > R2CH2 > RCH3
5.0
3.5
1.0
Reflect the relative stability of intermediate radicals R3C∙ > R2CH∙ > RCH2∙
This is also reflected in bond-dissociation energies
Is there a way to correlate TS structure with reactant or product structure? – We can draw this using
example of chlorination of propane vs bromination of propane:
The step that determines the structure of product is the following—
How can we put these 2 facts- selectivity and energetics of reaction- together?
Look at reaction diagram for these processes:
Endothermic process: TS resembles products
Exothermic process: TS resembles SM
Hammond Postulate
Related species that are similar in energy are also similar in structure. The structure of a TS resembles
the structure of closest stable species.
o Endothermic rxn- TS close in structure to products
o Exothermic rxn- TS close in structure to reactants
According to the above postulate, why is bromination of propane more selective than chlorination? -Let’s draw the reaction energy diagram for each case
The larger energy difference in TS, the more selective the reaction will be.
1. Bromination selectivity determining step is endothermic – products higher in energy – similar in
structure to TS – 3 kcal/mol difference in product energy translates to nearly the same difference in TS
energy that leads to two products – selective reaction
2. Chlorination – exothermic – TS similar in energy to reactants – very small difference in TS energies –
non-selective reaction
DO NOT COVER 4-15 (RADICAL INHIBITORS)
4. Reactive intermediates –
Which are short-lived species that are never present in high concentrations because they react as
quickly as they are formed. We will cover:
A) Carbocation – trivalent C bearing a positive charge
Electrophile, sp2 hybridized
6 e- species
Electron donating groups stabilize positive charge, alkyl groups e- donate by hyperconjugation
(orbital overlap, Fig 4-14).
Stability
*Resonance also stabilizes carbocation*
B) Free radicals are also sp2 hybridized and planar
Since they are also electron deficient, they follow the same stability order as carbocations and
can also be stabilized by resonance.
C) Carbanion is a trivalent C with a negative charge—hybridization changes to sp3
Because alkyls are e- donating, they destabilize negative charge. However, resonance stabilizes.
Notice the stability order of carbanions is opposite from the cations and radicals:
D) Carbenes: uncharged divalent carbon. Sp2 hybridized
Example of carbene generation--
Carbenes are very reactive and dimerize—
React with double bonds to form cyclopropanes—