10/11/15 Chapter 6- An Overview of Organic
Reactions
Ashley Piekarski, Ph.D. Why am I learning this, Dr. P?
•  To understand organic and biochemistry, it is necessary to know: •  What occurs
•  Why and how chemical reactions take place
•  We will see how a reacAon can be described 1 10/11/15 Kinds of Organic Reactions
•  In general, we look at what occurs and try to learn how it happens •  Common paFerns describe the changes •  Addition reactions- two molecules combine
•  Elimination reactions- one molecule splits into two
Kinds of Organic Reactions
•  In general, we look at what occurs and try to learn how it happens •  Common paFerns describe the changes •  Substitution- parts from two molecules
exchange
2 10/11/15 Kinds of Organic Reactions
•  In general, we look at what occurs and try to learn how it happens •  Common paFerns describe the changes •  Rearrangement reactions- a molecule
undergoes changes in the way its atoms are
connected
How Organic Reactions Occur: Mechanisms
•  In an organic reacAon, we see the transformaAon that has occurred. The mechanism describes the steps behind the changes that we can observe •  ReacAons occur in defined steps that lead from reactant to product 3 10/11/15 Steps in Mechanisms
•  We classify the types of steps in a sequence •  A step involves either the formaAon or breaking of a covalent bond •  Steps can occur individually or in combinaAon with other steps •  When several steps occur at the same Ame they are said to be concerted Types of Steps in Reaction Mechanisms
•  Bond formaAon or breakage can be symmetrical or unsymmetrical •  Symmetrical- homolytic formation or breakage
•  Unsymmetrical- heterolytic formation or
breakage
4 10/11/15 Indicating Steps in Mechanisms
•  Curved arrow indicated breaking and forming bonds •  Arrowheads with a “half” head (“fish-­‐hook”) indicate homolyAc and homogenic steps (called ‘radical processes’) •  Arrowheads with a complete head indicate heterolyAc and heterogenic steps (called ‘polar processes’) Radical 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
5 10/11/15 Steps in Radical Substitution
•  Three types of steps •  Initiation- homolytic formation of two reactive
species with unpaired electrons
•  Example- formation of Cl radicals from 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
Radical Substitution
6 10/11/15 Polar reactions
•  Molecules can contain local unsymmetrical electron distribuAons due to differences in electronegaAviAes •  This causes a parAal negaAve charge on an atom and a compensaAng parAal posiAve charge on an adjacent atom •  The more electronegaAve atom has the greater electron density 7 10/11/15 Polarizability
•  Polariza0on is a change in electron distribuAon as a response to change in electronic nature of the surroundings •  Polar reacAons occur between regions of high electron density and regions of low electron density 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 combinaAon is indicated with a curved arrow 8 10/11/15 Learning check
•  Which of the following species is likely to be a nucleophile and which an electrophile? Generalized Polar Reactions
This is an extremely important slide J 9 10/11/15 Examples
An Example of a Polar Reaction
•  HBr adds to the pi part of C-­‐C double bond •  The pi bond is electron-­‐rich, allowing it to funcAon as a nucleophile •  H-­‐Br is electron deficient at the H since Br is more electronegaAve, making HBr and electrophile 10 10/11/15 Comparison
Mechanism!
•  HBr electrophile is aFacked by pi electrons of ethylene (nucleophile) to form a carbocaAon intermediate and bromide ion •  Bromide adds to the posiAve center of the carboca&on, which is an electrophile, forming a C-­‐Br bond •  The result is that ethylene and HBr combine to form bromoethane •  All polar reacAons occur by combinaAon of an electron-­‐rich site of a nucleophile and an electron-­‐deficient site of an electrophile 11 10/11/15 Mechanism
Using Curved Arrows in Polar Reaction
Mechanisms
•  Curved arrows are a way to keep track of changes in bonding in polar reacAon •  The arrows track “electron movement” •  Electrons always move in pairs •  Charges change during the reacAon •  One curved arrow corresponds to one step in a reacAon mechanism 12 10/11/15 Rules!
•  The arrow goes from the nucleophilic reacAon site to the electrophilic reacAon site Rules!
•  The nucleophilic site can be neutral or negaAvely charged 13 10/11/15 Rules!
•  The electrophilic site can be neutral or posiAvely charged Rules!
•  The octet rule must be followed This hydrogen already has two electrons. When another electron pair moves to the hydrogen from the double bond, the electron pair in the H-­‐O bond must leave 14 10/11/15 Learning check
•  Add curved arrows to the following polar reacAon to show the flow of electrons: Learning check
•  Add curved arrows to the following polar reacAon to show the flow of electrons: 15 10/11/15 Describing a Reaction: Equilibria, Rates,
and Energy Changes
•  ReacAons can go either forward or backward to reach equilibrium •  The multiplied concentrations of the products
divided by the multiplied concentrations of the
reactant is the equilibrium constant, Keq
•  Each concentration is raised to the power of
its coefficient in the balanced equation.
Magnitudes of Equilibrium Constants
•  If the value of Keq is greater than 1, this indicates that at equilibrium most of the material is present as products •  If Keq is 10, then the concentration of the
product is ten times that of the reactant
•  A value of Keq less than one indicates that at equilibrium most of the material is present as the reactant •  If Keq is 0.10, then the concentration of the
reactant is ten times that of the product
16 10/11/15 Free Energy and Equilibrium
•  The raAo of products to reactants is controlled by their relaAve Gibbs free energy •  This energy is released on the favored side of an equilibrium reacAon •  The change in Gibbs free energy between products and reacts is wriFen as “ΔG” •  If Keq > 1, energy is released to the surroundings (exergonic reacAon) •  If Keq < 1, energy is absorbed from the surroundings (endergonic reacAon) Numerical Relationship of Keq and Free
Energy Change
•  The standard free energy change at 1 atm pressure and 298 K is ΔG° •  The relaAonship between free energy change and an equilibrium constant is: •  ΔG° = - RT ln Keq where
•  R = 1.987 cal/(K x mol)
•  T = temperature in Kelvin
•  ln Keq = natural logarithm of Keq
17 10/11/15 Thermodynamics
Describing a Reaction: Bond Dissociation
Energies
•  Bond dissociaAon 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 •  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.
•  Table 5.3 lists energies for many bond types
•  Changes in bonds can be used to calculate net changes in heat 18 10/11/15 Describing a Reaction: Energy Diagrams
and Transition States
•  The highest energy point in a reacAon step is called the transi&on state •  The energy needed to go from reactant to transiAon state is the ac&va&on energy ΔG‡) 19 10/11/15 First Step in Addition
•  In the addiAon of HBr the (conceptual) transiAon-­‐state structure for the first step •  The pi bond between carbons begins to break •  The C–H bond begins to form
•  The H–Br bond begins to break
Describing a Reaction: Intermediates
•  If a reacAon occurs in more than one step, it must involve species that are neither the reactant nor the final product •  These are called reac&on intermediates or simply “intermediates” •  Each step has its own free energy of acAvaAon •  The complete diagram for the reacAon shows the free energy changes associated with an intermediate 20 10/11/15 Intermediates
Comparison between Biological reactions
and Laboratory reactions
•  Laboratory reacAons usually carried out in organic solvent •  Biological reacAons in aqueous medium inside cells •  They are promoted by catalysts that lower the acAvaAon barrier •  The catalysts are usually proteins, called enzymes •  Enzymes provide an alternaAve mechanism that is compaAble with the condiAons of life 21 10/11/15 Enzymes
hFp://en.wikipedia.org/wiki/
Adenosine_triphosphate hFp://www.youtube.com/
watch?v=mmACA_eVLTE Comparison
22