6.
An Overview of
Organic Reactions
Why & How do the reactions occur?
6.1 Kinds of Organic Reactions
◼ In general, we look at what occurs and try to learn how it happens
◼ Common patterns describe the changes
◼ Addition reactions – two molecules combine
◼ Elimination reactions – one molecule splits into two
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◼ Substitution – parts from two molecules exchange
◼ Rearrangement reactions – a molecule undergoes changes
in the way its atoms are connected
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6.2 How Organic Reactions
Occur: Mechanisms
◼ In an organic reaction, we see the transformation that has occurred.
The mechanism describes the steps behind the changes that we
can observe
◼ Reactions occur in defined steps that lead from reactant to product
◼ We classify the types of steps in a sequence
◼ A step involves either the formation or breaking of a covalent
bond
◼ Steps can occur in individually or in combination with other steps
◼ When several steps occur at the same time they are said to be
concerted
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Types of Steps in Reaction
Mechanisms
◼ Bond formation or breakage can be symmetrical or unsymetrical
◼ Symmetrical- homolytic, homogenic
◼ Unsymmetrical- heterolytic, heterogenic
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Indicating Steps in Mechanisms
◼ Curved arrows indicate breaking and forming of bonds
◼ Arrowheads with a “half” head (“fish-hook”) indicate homolytic and
homogenic steps (called ‘radical processes’)
◼ Arrowheads with a complete head indicate heterolytic and
heterogenic steps (called ‘polar processes’)
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6.3 Radical Reactions
◼ Not as common as polar reactions
◼ Radicals react to complete electron octet of valence shell
◼ A radical can break a bond in another molecule and abstract a
partner with an electron, giving substitution in the original
molecule
◼ A radical can add to an alkene to give a new radical, causing an
addition reaction
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Steps in Radical Substitution
◼ Three types of steps
◼ Initiation – homolytic formation of two reactive species with
unpaired electrons
◼ Example – formation of Cl atoms form Cl2 and light
◼ Propagation – reaction with molecule to generate radical
◼ Example - reaction of chlorine atom with methane to give HCl
and CH3.
◼ Termination – combination of two radicals to form a stable
product: CH3. + CH3. → CH3CH3
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Steps in Radical Substitution
◼ Example: Prostaglandin biosynthesis
Problem 6.3. Mechanism?
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6.4 Polar Reactions
◼ Molecules can contain local unsymmetrical electron distributions
due to differences in electronegativities
◼ This causes a partial negative charge on an atom and a
compensating partial positive charge on an adjacent atom
◼ The more electronegative atom has the greater electron density
◼ Elements such as O, F, N, Cl more electronegative than carbon
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Polar bond induced by acid or
base
◼ Upon protonation, a full positive charge on oxygen attracts electrons
in the C-O bond much more strongly and makes the carbon much
more electron-poor
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Polarizability
◼ Polarization is a change in electron distribution as a response to
change in electronic nature of the surroundings
◼ Polarizability is the tendency to undergo polarization
◼ Larger atoms (more, loosely held electrons): more polarizable
◼ Small atoms (fewer, tightly held electrons): less polarizable
◼ S > O; I > Cl
◼ C-S, C-I: nonpolar (electronegativity) but reacts as if polar
◼ Polarity as well as Polarizability should be considered
◼ Polar reactions occur between regions of high electron density and
regions of low electron density
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Generalized Polar Reactions
◼ An electrophile (an electron-poor species) combines with a
nucleophile (an electron-rich species)
◼ An electrophile is a Lewis acid
◼ A nucleophile is a Lewis base
◼ The combination is indicate with a curved arrow from nucleophile to
electrophile
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Nucleophiles & Electrophiles
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Nucleophiles & Electrophiles
◼ Worked Ex.6.1
(a) NO2+ (b) CN- (c) CH3NH2 (d) (CH3)3S+
◼ Problem 6.4
(a) CH3Cl (b) CH3S- (c) (d) CH3CHO
◼ Problem 6.5. BF3?
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6.5 An Example of a Polar Reaction:
Addition of HBr to Ethylene
◼ HBr adds to the part of C-C double bond
◼ The bond is electron-rich, allowing it to function as a nucleophile
◼ H-Br is electron deficient at the H since Br is much more
electronegative, making HBr an electrophile (Electrophilic addition)
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Mechanism of Addition of HBr
to Ethylene
◼ HBr electrophile is attacked
by electrons of ethylene
(nucleophile) to form a
carbocation intermediate and
bromide ion
◼ Bromide adds to the positive
center of the carbocation,
which is an electrophile,
forming a C-Br bond
◼ The result is that ethylene
and HBr combine to form
bromoethane
◼ All polar reactions occur by
combination of an electron-
rich site of a nucleophile and
an electron-deficient site of
an electrophile
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6.6 Using Curved Arrows in
Polar Reaction Mechanisms
◼ Curved arrows are a way to keep track of changes in bonding in
polar reaction
◼ The arrows track “electron movement”
◼ Electrons always move in pairs (in polar reactions)
◼ Charges change during the reaction
◼ One curved arrow corresponds to one step in a reaction mechanism
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Rules for Using Curved Arrows
◼ Rule 1: Electrons move from a nucleophilic source (Nu: or Nu:-) to
an electrophilic sink (E or E+)
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Rules for Using Curved Arrows
◼ Rule 2: The nucleophile can be either negatively charged or neutral
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Rules for Using Curved Arrows
◼ Rule 3: The electrophile can be either positively charged or neutral
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Rules for Using Curved Arrows
◼ Rule 4: The octet rule must be followed
◼ No 2nd-row atom can be left with ten electrons (4 for H)
◼ If an electron pair moves to an atom that already has an octet (2
for H), another electron pair must simultaneously move from that
atom to maintain the octet
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Rules for Using Curved Arrows
◼ Worked Ex. 6.2
◼ Problem 6.9
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6.7 Describing a Reaction: Equilibria,
Rates, and Energy Changes
◼ Reactions can go either forward or backward to reach equilibrium
◼ Equilibrium constant, Keq
◼ Keq > 1
◼ At equilibrium, most of the material is present as products
◼ Keq = 10: [Product] = 10 x [Reactant]
◼ Keq < 1
◼ At equilibrium, most of the material is present as the reactant
◼ Keq = 0.10: [Reactant] = 10 x [Product]
aA + bB cC + dD
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Free Energy and Equilibrium
◼ For forward reaction, Eproduct < Ereactant (Release of energy)
◼ Gibbs free-energy change (ΔG): Energy change during a reaction
◼ Favorable reaction (Keq > 1), ΔG < 0 (exergonic)
◼ Unfavorable reaction (Keq < 1), ΔG > 0 (endergonic)
◼ The standard free energy change at 1 atm and 298 K is Gº
◼ The relationship between Gº and Keq is:
◼ Gº = - RT ln Keq [R = 8.314 J/(K∙mol), T = Kelvin temp.]
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Free Energy and Equilibrium
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Keq vs Rate
◼ Keq
◼ Position of equilibrium (how much product is possible)
◼ No relationship with rate !!!
◼ Thermodynamic property vs Kinetic property
◼ Rate: Is the reaction fast or slow?
◼ Equilibrium: In what direction does the reaction proceed?
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6.8 Describing a Reaction: Bond
Dissociation Energies
◼ Bond dissociation energy (D): amount of energy required to break a
given bond to produce two radical fragments when the molecule is in
the gas phase at 25˚ C (Bond strength)
◼ The energy is mostly determined by the type of bond, independent of
the molecule
◼ The C-H bond in methane requires a net heat input of 105
kcal/mol to be broken at 25 ºC.
◼ Changes in bonds can be used to calculate net changes in heat
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6.8 Describing a Reaction: Bond
Dissociation Energies
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6.9 Describing a Reaction: Energy
Diagrams and Transition States
◼ Energy diagram
◼ Energy changes during the reaction, graphically depicted
◼ Total Ereactant (y-axis) vs Reaction coordinates (x-axis)
◼ Transition state: Highest energy point in a reaction step
◼ Activation energy (G‡): Energy needed to go from reactant to
transition state (# of collisions with enough energy)
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6.9 Describing a Reaction: Energy
Diagrams and Transition States
◼ Transition-state structure for the first step
◼ The bond between carbons begins to break
◼ The C–H bond begins to form
◼ The H–Br bond begins to break
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6.9 Describing a Reaction: Energy
Diagrams and Transition States
◼ If a reaction occurs in more than one step, it must involve species
that are neither the reactant nor the final product (intermediates)
◼ Each step has its own free energy of activation
◼ Overall G: difference between initial reactants and final products
◼ Intermediates can’t normally be isolated but more stable than TS
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6.10 A Comparison between Biological
Reactions and Laboratory Reactions
◼ Laboratory reactions usually carried out in organic solvent
◼ Biological reactions in aqueous medium inside cells
◼ They are promoted by catalysts that lower the activation barrier
◼ The catalysts are usually proteins, called enzymes
◼ Enzymes provide an alternative mechanism that is compatible with
the conditions of life
◼ low temperature
◼ Series of small steps rather than one or two large steps
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