A. Introduction to Reaction Principles
1. Rate of Reaction-The rate at
whichEFFECTIVE collisions between react-
ing species occurs each second in each cc of space.
Rate= Z x P x f
a. Collision Frequency-Total number of collisions per second per cc.
b. Probability Factor-The probability
that a collision will have the proper ORIENTATION for reaction to occur.
c. Energy Factor-The fraction of collisions which have sufficient energy to cause a reaction.
2. Kinetics-The branch of chemistry which deals with the effects of changes in CONCENTRATION on rates of reactions.
For the Reaction:
A + B ----> C
Rate=k[A]x[B]y
a. k=Rate Constant-The NUMBER,
which multiplied by these concentrations, gives the number
of moles of product formed per second per volume.
b. Order-The order of reaction with
respect to a given reactant, A or B, is the POWER to which the concentration of that reactant must be raised to have direct proportionality between concention and the rate of reaction.
c. A Change in the concentration of
a reactant will alter the rate of
reaction ONLY when that reactant
is involved in the SLOW step (rate
limiting) of the reaction process.
d. The order of reaction gives one
information about the number
of molecules of each type which
are involved in the SLOW STEP of
a reaction process.
B. Nucleophilic Substitution Reactions
1. General Pattern
a. Nu:- + R-X ---> R-Nu + :X:-
Nucleophile Alkyl Halide Product Halide
b. Examples-See Next Slide
2. Nucleophiles-Lewis Bases-A species
with an unshared electron pair. They
seek a center of positive charge.
a. Examples- -OH , -:CN, :I:-, H-O-H
b. Nucleophiles react here:
3. Leaving Group-The group lost in the
reaction. Good leaving groups form
relatively stable, weakly basic ions or molecules.
The halides are relatively good
leaving groups. I > Br > Cl > F
4. The SN Reaction- SubstitutionNucleophilic Bimolecular
Backside attack by nucleophile
rate=k[Nu-][R-X]
a. Mechanism
b. Transition State=Activated Complex
c. The Energy Diagramfor an SN2 reaction-one step
d. Stereochemistry of an SN2 Reaction
The SN2 reaction always proceeds
with INVERSION OF CONFIRGURA-
TION at the reacting carbon.
(1) cis ---> trans in cyclic systems
(2) At a chiral carbon one observes INVERSION of Configuration. The product will
be optically active.
R-(-)-2-Bromooctane S-(+)-2-Octanol
[å]= -34.25o [å]= +9.9o
5. The SN1 Reaction- Substitution
Nucleophilic Unimolecular
(CH3)3C-Cl + NaOH--> (CH3)3C-OH + NaCl
rate=k[(CH3)3C-Cl]
a. Mechanism-This process occurs in
several steps, and is referred to
as a multistep reaction.
OR Water could be the nucleophile
c. Stereochemistry of the SN1 Reaction
The SN1 reaction proceeds with
racemization of configuration at
a reacting chiral carbon.
(R) (S)
The planar carbocation can be attacked
from either side.
d. Solvolysis in SN1 reactions-In these
reactions the solvent often serves
as the nucleophile.
(1) Water=hydrolysis
Ethanol=ethanolysis
(2) Examples
6. Factors Affecting the Rates of SN1
and SN2 Reactions
a. The Structure of the Substrate
The R (alkyl) group
(1) For SN2
CH3X > 1o RX > 2o RX >> 3o RX
Increased steric hindrance SLOWS the reaction in SN2. The Backside attack of the nucleophile is blocked by the group(s).
(2) For SN1
3o RX > 2o RX >> 1oRX
The stability of the Carbocation is the critical factor in an SN1 process.
(3) Hammond-Leffler Postulate-
The transition state of an endothermic step should bear a strong resemblance to the product of that step.
Any factor which would stabilize
the product would also stabilize
the transition state leading to it,
and its Ea would be lowered,
resulting in a FASTER reaction.
b. Effect of the Nucleophile-
Important ONLY in the SN2 process.
(1) Higher concentration of a
nucleophile=Faster reaction
(2) Stronger nucleophile=Faster
reaction
(a) A negatively charged nucleophile is always a stronger nucleophile than its conjugate acid.
-OH > H2O : -OCH3 > HOCH3
(b) In a group of nucleophiles
in which the nucleophilic atom is the same, the stronger base=the stronger nucleophile
-OR > -OH > RCO2- > ROH > H2O
c. Solvent Effects
(1) Protic Solvents=H is attached
to an electronegative atom,
usually O or N.
(2) Aprotic Solvents=No H attached to an electronegative atom
(3) Polar Aprotic Solvents promote
SN2 reactions.
These solvents stabilize
positive (+) ions, but do not
stabilize negative (-) ions.
(4) In these solvents the order
of nucleophilicity is F- > Cl-
> Br- > I-.
(5) Polar Protic solvents promote
SN1 reactions. These solvents stabilize positive ions, and solvate negative ions.
Alcohols or alcohol/water
mixtures.
d. The Leaving Group-the better the
leaving group the FASTER the reaction for either SN1 or SN2. For the halogens: I>Br>Cl>>F
Other good leaving groups are:
7. Nucleophilic Substitution In Synthesis
a. Many different types of organic
compounds can be prepared form
1o and 2o alkyl halides via an SN2
reaction.
b. Inversion of configuration will
occur at a chiral center.
C. b-ELIMINATION REACTIONS OF ALKYL HALIDES
ALKENE PREPARATION
1. Dehydrohalogenation-Loss of H-X
from an alkyl halide
2. Bases Used In Dehydrohalogenation- Requires a Strong Base:
KOH/Alcohol, Sodium Salts of Alcohols (Na+-OR), Potassium Salts of Alcohols (K+-OR)
3. The E2 Elimination Process
rate=k[Base][RX]-Like SN2
a. Mechanism-anti elimination of H and X in one step
4. The E1 Elimination Process-
rate=k[RX]-Like SN1
a. Mechanism-Formation of a carbocation
b. Observed for 3o Halides in the presence of weak nucleophiles
5. Orientation of the C=C-Zaitzev’s Rule-
Predicts the major alkene product in this type of reaction.
General Statement-Zaitzev’s Rule-
The major product in this type of
reaction is the MORE stable alkene.
(1) Trans > Cis
(2) More substituted double bond=
more stable.
6. The E2 process proceeds by ANTI elimination of H and L.
This shows that ANTI elimination is preferred
even though the LESS stable alkene is formed.
D. Substitution versus Elimination
1. SN2 and E2 Occur under similar conditions.
a. Substrate-1o Alkyl Halides favor substitution-as branching increases- elimination becomes more likely.
b. Higher temperature favors elimination
c. Using large bases such as the t- butoxide ion favors elimination
d. Strong nucleophiles favor E2- weaker nucleophiles favor SN2
-NH2 > -OR > -OH > X- > CH3COO-
2. SN1 versus E1-Tertiary Halides only
a. E1 favored if weak nucleophiles are used in polar solvent.
b. SN1 is usually not useful as a synthetic tool, and usually not the main process.
A lower temperature favors SN1.