Ch6,7,8,9 and 11 Revised SUMMARY

6.
6 Energy Diagrams –
Transition States vs. Intermediates
Copyright 2012 John Wiley & Sons, Inc.

6 -1 Klein, Organic Chemistry 1e
6.6 Energy Diagrams –
The Hammond Postulate
• Two points on an energy diagram that are close in
energy should be similar in structure.

6.6 Energy Diagrams –
The Hammond Postulate
• For each of the diagrams below, will the transition
state structure look more like the reactants or the
products?

6.7 Nucleophiles and Electrophiles
• A major focus in this course is on predicting reaction
products for IONIC reactions, and explaining HOW such
reactions work.
– Ionic or polar reactions result from the force of attraction
between opposite charges.
– Ionic reactions are also guided by the octet rule
• Consider how methyl chloride and methyl lithium
might react.

• NUCLEOPHILE
– an atom carries a formal or partial negative charge and an available pair of
electrons,
– It will love to attack a nucleus.
• ELECTROPHILE
– an atom carries a formal or partial positive charge and can accept a pair of
electrons.
– It will love available electrons.

• Label all of the nucleophilic and electrophilic sites on
the following molecule.
HO O
O NH2

6.8 Mechanisms and Arrow Pushing
• We use arrows to show how electrons move when
bonds break and form.
• It will be a HUGE benefit in this course to master the
skill of arrow pushing.
• There are four main ways that electrons move in ionic
reactions:
1. Nucleophilic attack
2. Loss of a leaving group
3. Proton transfers (acid/base)
4. Rearrangements
Patterns of Mechanism
Copyright 2012 John Wiley & Sons, Inc. 7 -8

6.8 Mechanisms and Arrow Pushing –
Nucleophilic Attack
• When you identify a nucleophilic site and an electrophilic
site, the arrow shows the nucleophile attacking.
• The tail of the arrow starts on the electrons (- charge).

• The head of the arrow ends on a nucleus (+ charge).
• The electrons end up being shared rather
than transferred.

Proton Transfers
• Multiple arrows may be necessary to show the
complete electron flow when a proton is exchanged.
– Such electron flow can also be thought of as a proton

transfer combined with resonance.

Carbocation Rearrangements
• Carbocations can be stabilized by neighboring groups
through slight orbital overlap called
HYPERCONJUGATION.

• HYPERCONJUGATION and INDUCTION can both be
invoked to explain the stability trend below. HOW?
• If a carbocation can INTRAMOLECULARLY rearrange to

become more stable, it will likely do so before
reacting with a nucleophile. WHY?
• Two types of carbocation rearrangement are common:
– Hydride shift:
– Methyl shift:
– Shifts can only occur from an adjacent carbon. WHY?

– Do the shifts above make the carbocation more stable?

• Classify each step in the following mechanism.

GENERAL ORGANIC REACTIONS
Substitution Reaction
Addition Reaction

Elimination Reaction
Rearrangement Reaction

REDOX Reaction

7.1 Introduction to Substitution Reactions
• One group of atoms is replaced with another.
– Generic example:
– Specific example:
• During the substitution, one group ATTACKS and one

group LEAVES.
• A leaving group always takes a pair of electrons with it

Some leaving groups encourage a substitution better than
others. A good leaving group must:
1. Create a positive charge to attract the nucleophile:
The electronegative leaving
group creates a partial charge on
Nuc: the site of attack to attract the
negative charge of the nucleophile.
2. Be able to stabilize the electrons it leaves with:

7.2 Alkyl Halides – Structure
• Greek letters are often used to label the carbons of the
alkyl group attached to the halide:
– Substitutions occur at the alpha carbon.
WHY?
• The amount of branching at the alpha carbon affects the

reaction mechanism. There are three types of alkyl
halides:
R≠H

7.3 Possible Mechanisms for
Substitution Reactions
• EVERY nucleophilic substitution reaction will involve
nucleophilic attack and the loss of a leaving group.
• The order in which these steps occur can vary.

• The inclusion of a proton transfer or rearrangement can
also vary.
SUBSTITUTION REACTION – Summary

7.4 SN2 – Mechanism
How might you write a rate law for this reaction?

RECALL: RATE LAW EXPRESSION

7.4 SN2 – Backside Attack
• The nucleophile attacks from the backside:
– The backside is less hindered with electron density.
– The nucleophile must approach the backside to allow proper
orbital overlap that is necessary for bonding.

7.4 SN2 – Kinetics (Structure of the Substrate)
• Less sterically hindered electrophiles react more readily under
SN2 conditions.
H H3C
Nuc: H3C Nuc:
X X
H Nuc:
X H3C
H H H
H

7.5 SN1 – A Stepwise Mechanism
• If kinetic experiments were performed to determine

the rate law, you would find that:

7.5 SN1 – Kinetics
• In a multistep mechanism, one step
will be the slowest.
• The slow step is the ratedetermining
step (RDS).
• Let’s consider a simple example.
Which step determines how
frequently the sand moves from the
top of the hourglass to the bottom?

7.5 SN1 – Reaction Coordinate

7.5 SN1 – Kinetics (Structure of the
Substrate)
• The structure–rate relationship for SN1 reactions is the
opposite of what it is for SN2 reactions.
• To explain this trend, we must examine the mechanism and

the reaction coordinate diagram.
7.5 SN1 – Stereochemistry
• For the pure SN1 reaction below, predict the product(s).
Pay close attention to stereochemistry.

7.5 SN – Summary

7.8 SN1 vs. SN2 – The Leaving Group
• The most commonly used leaving groups are halides
and sulfonate ions.

7.8 SN1 vs. SN2 – The Solvent
The solvent(δ-δ+ ) surrounds each species in the
mechanism, including the transition state:
δ-
δ+ δ- δ-
δ+ δ+ δ+
δ- H H
δ+ δ- δ- δ-
δ-δ+ LGδ-δ+ δ- δ+ Nuc LGδ-δ+
δ- δ+ δ+ R δ+
δ+ δ-
δ- δ-

• To promote an SN1 reaction, use
a polar, protic solvent:
• The protic solvent will hydrogen
bond with the nucleophile,
stabilizing it, while the leaving
group leaves first.

• To promote an SN2, use a
polar, aprotic solvent, such
as DMSO or acetonitrile.
• Polar aprotic solvents can Ready to

attack!
stabilize the counterion of
the nucleophile, leaving the
nucleophile mostly naked
and ready to attack the
electrophile.
Copyright 2012 John Wiley & Sons, Inc. 7 -36 Klein, Organic Chemistry 1e
7.9 Selecting Reagents to Accomplish
Functional Group Transformation
• Some options and choices:

SN – Summary

8.5 Alkene Stability
• Because of STERIC STRAIN, cis isomers are generally
less stable than trans.


• Consider the following stability trend:

Substitution vs. Elimination
• Consider –OH, which can act as a base or a nucleophile:
Attack at the α
carbon
ALKENE
β or 1,2
Attack at the β
hydrogen
8.6 Elimination Reactions in Detail
• All elimination reactions involve both LOSS OF A LEAVING GROUP AND
PROTON TRANSFER.
• The mechanism may be a concerted (one step) process or a step-wise
process.
• The mechanism of the STEP-WISE PROCESS

8.7 Elimination by E2 –
The Effect of Substrate
• The kinetics of E2 and SN2 are quite similar.
• 3° substrates are more reactive toward E2 than are 1° substrates

even though 1° substrates are less hindered.

E2 Elimination Reaction
• If there are MULTIPLE
REACTIVE SITES OR
REGIONS on a molecule,
MULTIPLE PRODUCTS
ARE POSSIBLE.
• In elimination reactions,
there are often different β
sites that could be
deprotonated to yield
different alkenes.
• REGIOSELECTIVITY
occurs when
one product is formed
predominantly over the
other.
Stereospecificity
• There are two coplanar options for the molecule.
• Evidence suggests that a strict
180° angle is not necessary for
E2 mechanisms.
• Similar angles (175-179°) are
sufficient.
• The term, ANTI-PERIPLANAR is
generally used instead of anti-
coplanar to account for slight
deviations from coplanarity.
• Although the E isomer is usually
more stable because it is less
sterically hindered, the
requirement for an anti-
periplanar transition state can
often lead to the less stable Z
isomer.
The Mechanism
• The E1 mechanism is a two-step process.
• Similar to SN1 (Chapter 7), the reaction rate for E1 is not affected by
the concentration of the base.
The Effect of Substrate
• Just like we did for SN1 in Chapter 7, to explain the
reactivity trend above, we must compare the
energy diagrams for each substrate.

Regioselectivity
• The final step of the E1 mechanism determines the
regioselectivity.
• E1 reactions generally produce the Zaitsev product
predominantly. WHY?

Substitution vs. Elimination – Basicity vs.
Nucleophilicity
• Consider each of the reagent categories.
• Reagents that act only as nucleophiles are highly
polarizable and/or they have very strong conjugate
acids.

SUBSTRATE (1o, 2o, 3o)
ADDITION REACTION
REGIOSELECTIVITY OF REACTIONS
MARKOVNIKOV ADDITION
ANTI-MARKOVNIKOV ADDITION
STEREOSELECTIVITY
• SYN Addition
• HOMOGENEOUS CATALYST
– Wilkinson’s catalyst - Knowles Catalyst

• ANTI Addition (cyclic intermediates)

Alkene Preparations and Reactions
Copyright 2012 John Wiley & Sons, Inc. 9 -58

10.1 Alkynes
• Given the presence of two pi bonds and their associated
electron density, alkynes are similar to alkenes in their
ability to act as a nucleophile.
• Converting pi bonds to sigma bonds generally makes a

molecule more stable.
10.3 Alkyne Acidity
• Recall that terminal alkynes have a lower pKa than other hydrocarbons.
• Acetylene is 19 pKa units more acidic than ethylene, which is 1019 times
stronger.
• Because acetylene (pKa=25) is still much weaker than water (pKa=15.7), a
strong base is needed to make it react.

Alkyne Preparations and Reactions
11.1 Free Radicals
• Free radicals form when bonds break HOMOLYTICALLY.

11.1 Free Radicals – Stability
• Free radicals do not have a formal charge but are
unstable because of an incomplete octet.
• Groups that can push (donate) electrons toward the
free radical will help to stabilize it.
• Consider hyperconjugation.

11.1 Free Radicals – Stability
11.2 Radical Electron Movement
• Free radical electron movement is quite different from
electron movement in ionic reactions.
– For example, free radicals don’t undergo rearrangement.
Radical Electron Movement
• Note the reversibility of radical processes:
11.3 Radical Reactions – Chlorination
of Methane
• Reactions that have self-sustaining propagation steps
are called CHAIN REACTIONS.
• In a chain reaction, the products from one step are
reactants for a different step in the mechanism.
• Polychlorination is difficult to prevent, especially when
an excess of Cl2 is present.
11.4 Halogenation Thermodynamics
11.5 Halogenation Regioselectivity
• Which process is least regioselective? WHY?
11.5 Halogenation Regioselectivity
• For the CHLORINATION process,

the actual product distribution
favors 2-chloropropane over 1-
chloropropane.
• For the BROMINATION

process, the product
distribution vastly favors 2-
bromopropane over 1-
bromopropane.
11.10 Addition – Anti-Markovnikov
Addition
• We learned in Chapter 9 that H–X will add across a C=C
double bond with anti-Markovnikov regioselectivity
when peroxides are present.
18.1 Introduction to Aromatic
Compounds
• 8 of the 10 best-selling drugs have aromatic moieties.

18-72 Klein, Organic Chemistry 1e
18.3 Structure of Benzene
• In 1866, August Kekulé proposed that benzene is a ring comprised of
alternating double and single bonds in equilibrium process.
• aromatic structures are resonance contributors rather than in equilibrium.

18.4 Stability of Benzene
The stability that results from a ring being aromatic is striking.
•Recall that in general, alkenes readily undergo addition reactions.
•Aromatic rings are stable enough that they do not undergo such reactions.
•Heats of hydrogenation can be used to quantify aromatic stability.

• Molecular orbital (MO)
theory can help us explain
aromatic stability.
• The six atomic p-orbitals
of benzene overlap to
make six MOs.
• The locations of nodes in
the MOs determines their
shapes based on high-level
mathematical calculations.
• The delocalization of the six
pi electrons in the three
bonding molecular orbitals
accounts for the stability of
benzene.

18.4 Stability of Benzene
• AROMATIC compounds fulfill two criteria:
1. A fully conjugated ring with overlapping p-orbitals
2. Meets HÜCKEL’S RULE: an ODD number of electron pairs or
4n+2 total π electrons where n = 0, 1, 2, 3, 4, etc.
• Show how the molecules below do NOT meet the
criteria.

Aromatic Reactions
Copyright © 2015 John Wiley & Sons,

Inc. All rights reserved. Klein, Organic Chemistry 2e
Aromatic Substitution Reactions

Inc. All rights reserved. Klein, Organic Chemistry 2e
Determining the Directing Effects
of a Substituent
• Let’s summarize the directing effects of more
substituents
1. STRONG activators. WHAT makes them strong?
2. Moderate activators. What makes them moderate?

Inc. All rights reserved.
Klein, Organic Chemistry 2e
of a Substituent
substituents
3. WEAK activators. WHAT makes them weak?
4. WEAK deactivators. WHAT makes them weak?

of a Substituent
substituents
5. Moderate deactivators. WHAT makes them moderate?
6. STRONG deactivators. WHAT makes them strong?


Ch6,7,8,9 and 11 Revised SUMMARY

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6.

Copyright 2012 John Wiley & Sons, Inc.

Copyright 2012 John Wiley & Sons, Inc.

Copyright 2012 John Wiley & Sons, Inc.

Copyright 2012 John Wiley & Sons, Inc.

Copyright 2012 John Wiley & Sons, Inc.

Copyright 2012 John Wiley & Sons, Inc.

Copyright 2012 John Wiley & Sons, Inc. 7 -8

• The tail of the arrow starts on the electrons (- charge).

Copyright 2012 John Wiley & Sons, Inc.

– Such electron flow can also be thought of as a proton

Copyright 2012 John Wiley & Sons, Inc.

Copyright 2012 John Wiley & Sons, Inc.

• If a carbocation can INTRAMOLECULARLY rearrange to

– Shifts can only occur from an adjacent carbon. WHY?

Copyright 2012 John Wiley & Sons, Inc.

Copyright 2012 John Wiley & Sons, Inc.

Copyright 2012 John Wiley & Sons, Inc.

Copyright 2012 John Wiley & Sons, Inc.

Copyright 2012 John Wiley & Sons, Inc.

• During the substitution, one group ATTACKS and one

Copyright 2012 John Wiley & Sons, Inc.

2. Be able to stabilize the electrons it leaves with:

Copyright 2012 John Wiley & Sons, Inc.

• The amount of branching at the alpha carbon affects the

Copyright 2012 John Wiley & Sons, Inc.

• The order in which these steps occur can vary.

Copyright 2012 John Wiley & Sons, Inc.

How might you write a rate law for this reaction?

Copyright 2012 John Wiley & Sons, Inc.

Copyright 2012 John Wiley & Sons, Inc.

Copyright 2012 John Wiley & Sons, Inc.

• If kinetic experiments were performed to determine

Copyright 2012 John Wiley & Sons, Inc.

Copyright 2012 John Wiley & Sons, Inc.

Copyright 2012 John Wiley & Sons, Inc.

• To explain this trend, we must examine the mechanism and

Copyright 2012 John Wiley & Sons, Inc.

Copyright 2012 John Wiley & Sons, Inc.

Copyright 2012 John Wiley & Sons, Inc.

Copyright 2012 John Wiley & Sons, Inc.

Copyright 2012 John Wiley & Sons, Inc.

• Polar aprotic solvents can Ready to

Copyright 2012 John Wiley & Sons, Inc.

Copyright 2012 John Wiley & Sons, Inc.

Copyright 2012 John Wiley & Sons, Inc.

Copyright 2012 John Wiley & Sons, Inc.

Copyright 2012 John Wiley & Sons, Inc.

• The mechanism of the STEP-WISE PROCESS

Copyright 2012 John Wiley & Sons, Inc.

• 3° substrates are more reactive toward E2 than are 1° substrates

Copyright 2012 John Wiley & Sons, Inc.

Copyright 2012 John Wiley & Sons, Inc.

Copyright 2012 John Wiley & Sons, Inc.

Copyright 2012 John Wiley & Sons, Inc.

Copyright 2012 John Wiley & Sons, Inc.

Copyright 2012 John Wiley & Sons, Inc.

Copyright 2012 John Wiley & Sons, Inc. 9 -58

• Converting pi bonds to sigma bonds generally makes a

Copyright 2012 John Wiley & Sons, Inc.

Copyright 2012 John Wiley & Sons, Inc.

Copyright 2012 John Wiley & Sons, Inc.

• For the CHLORINATION process,