1 Understanding Organic Reactions Writing organic reaction equations and use of arrows. Types of reactions: substitution, elimination, addition. Bond breaking: homolytic and heterolytic Reactive species: radicals, carbocations and carbanions. Calculation of  H of reaction (enthalpy) from bond dissociation energies. Thermodynamics: free energy (  G), enthalpy (  H), entropy (  S) and the equilibrium constant K eq. Energy diagrams: single step concerted and multistep. Kinetics: 1st & 2nd order rates, activation energy, catalysis. Chapter 11 Topics:

2 Understanding Organic Reactions Equations for organic reactions are usually drawn with reagents to the left of a reaction arrow (  ) and products to the right. A reagent, the chemical substance with which an organic compound reacts, may be placed to the left of the arrow or on the arrow itself. The solvent and temperature are often omitted but at times is also placed above or below the arrow. The symbols “h ” and “  ” are placed above or below the arrow for reactions that require light and heat, respectively. Writing Equations for Organic Reactions:

3 Figure 6.1 Different ways of writing organic reactions Understanding Organic Reactions Writing Equations for Organic Reactions: Here, all are needed together.

4 When two sequential reactions are carried out without drawing any intermediate compound, the steps are numbered above or below the reaction arrow. This convention signifies that the first step occurs before the second step, and the reagents are added in sequence. Omitting the numbers means they are present together. Understanding Organic Reactions Writing Equations for Organic Reactions:

5 Substitution Reactions: A substitution is a reaction in which an atom or a group of atoms is replaced by another atom or group of atoms. Below, Y replaces Z on a carbon atom. Kinds of Organic Reactions

6 Substitution reactions involve breaking one  bond and forming another at the same carbon atom. In a nucleophilic attack, the group that departs needs to have some stability to exist by itself (a weak base). Kinds of Organic Reactions Substitution Reactions:

7 Elimination is a reaction in which elements of the starting material are “lost” and a  bond is formed. Water is frequently an eliminated component. Kinds of Organic Reactions Elimination Reactions:

8 In an elimination reaction, two groups X and Y are removed from a starting material. Two  bonds are broken, and a  bond is formed between adjacent atoms. The most common examples of elimination occur when X = H and Y is a heteroatom more electronegative than carbon. Kinds of Organic Reactions Elimination Reactions:

9 Addition is a reaction in which elements are added to the starting material. (Opposite of elimination.) Kinds of Organic Reactions Addition Reactions:

10 In an addition reaction, new groups X and Y are added to the starting material. A  bond is broken and two  bonds are formed. Kinds of Organic Reactions Addition Reactions:

11 Addition and elimination reactions are exactly opposite. A  bond is formed in elimination reactions, whereas a  bond is broken in addition reactions. Kinds of Organic Reactions Addition and Elimination Reactions:

12 Bond Making and Bond Breaking are the essence of chemical reactions: A reaction mechanism is a detailed description of how bonds are broken and formed as starting material is converted into product. A reaction can occur either in one step or a series of steps. Understanding Organic Reactions

13 Regardless of how many steps there are in a reaction, there are only two ways to break (cleave) a bond: the electrons in the bond can be divided equally or unequally between the two atoms of the bond. Understanding Organic Reactions Homolytic Bond Breaking:

14 Homolysis and heterolysis require energy. Homolysis generates uncharged reactive intermediates with unpaired electrons (radicals). Heterolysis generates charged intermediates. Understanding Organic Reactions Heterolytic Bond Breaking:

15 To illustrate the movement of a single electron, use a half- headed curved arrow, sometimes called a fishhook. A full headed curved arrow shows the movement of an electron pair. Understanding Organic Reactions Bond Making and Bond Breaking:

16 Homolysis: Homolysis generates two uncharged species with unpaired electrons. A reactive intermediate with a single unpaired electron is called a radical. Radicals are highly unstable because they contain an atom that does not have an octet of electrons. Heterolysis: Heterolysis generates a carbocation or a carbanion. Both carbocations and carbanions are unstable intermediates. A carbocation contains a carbon surrounded by only six electrons, and a carbanion has a negative charge on carbon, which is not a very electronegative atom. Understanding Organic Reactions

17 Figure 6.2 Three reactive intermediates resulting from homolysis and heterolysis of a C – Z bond Understanding Organic Reactions Radicals, Carbocations and Carbanions

18 Radicals and carbocations are electrophiles because they contain an electron deficient carbon (sp 2 carbon atoms). Carbanions are nucleophiles because they contain a carbon with a lone pair (sp 3 carbon atoms). Understanding Organic Reactions Radicals, Carbocations and Carbanions

19 Bond formation occurs in two different ways. Two radicals can each donate one electron to form a two- electron bond. Alternatively, two ions with unlike charges can come together, with the negatively charged ion donating both electrons to form the resulting two-electron bond. Bond formation always releases energy. Understanding Organic Reactions Bond Making:

20 A number of types of arrows are used in describing organic reactions. Understanding Organic Reactions Use of Arrows:

21 Bond Dissociation Energy: The energy absorbed or released in any reaction, symbolized by  H 0, is called the enthalpy change or heat of reaction. Bond dissociation energy is the  H 0 for a specific kind of reaction, the homolysis of a covalent bond to form two radicals. Understanding Organic Reactions

22 Because bond breaking requires energy, bond dissociation energies are always positive numbers, and homolysis is always endothermic. Conversely, bond formation always releases energy, and thus is always exothermic. For example, the H—H bond requires +104 kcal/mol to cleave and releases –104 kcal/mol when formed. Understanding Organic Reactions Bond Dissociation Energy:

23

24 Comparing bond dissociation energies is equivalent to comparing bond strength. The stronger the bond, the higher its bond dissociation energy. Bond dissociation energies decrease down a column of the periodic table. Generally, shorter bonds are stronger bonds. Understanding Organic Reactions Bond Dissociation Energy:

25 Bond dissociation energies are used to calculate the enthalpy change (  H 0 ) in a reaction in which several bonds are broken and formed. Understanding Organic Reactions Bond Dissociation Energy:

26 Understanding Organic Reactions Bond Dissociation Energy:

27 Bond dissociation energies have some important limitations. Bond dissociation energies present overall energy changes only. They reveal nothing about the reaction mechanism or how fast a reaction proceeds. Bond dissociation energies are determined for reactions in the gas phase, whereas most organic reactions occur in a liquid solvent where solvation energy contributes to the overall enthalpy of a reaction. Bond dissociation energies are imperfect indicators of energy changes in a reaction. However, using bond dissociation energies to calculate  H ° gives a useful approximation of the energy changes that occur when bonds are broken and formed in a reaction. Understanding Organic Reactions Bond Dissociation Energy:

28 Thermodynamics and Kinetics: For a reaction to be practical, the equilibrium must favor products and the reaction rate must be fast enough to form them in a reasonable time. These two conditions depend on thermodynamics and kinetics respectively. Thermodynamics describes how the energies of reactants and products compare, and what the relative amounts of reactants and products are at equilibrium. Kinetics describes reaction rates. The equilibrium constant, K eq, is a mathematical expression that relates the amount of starting material and product at equilibrium. Understanding Organic Reactions

29  G° is the term for standard state free energy and represents the overall energy difference between reactants (R) and products (P).  H° is the term for enthalpy in the standard state.  S° is the term for entropy in the standard state. Standard state conditions have reactants and products at 1 M concentrations or 1 atmosphere pressure. The overall free energy at any concentrations of R and P is:  G =  G° + RT ln [P]/[R] Where R is the constant joules /mol- o K and T = o K (R also = cal /mol- o K) Understanding Organic Reactions Thermodynamic Terms:

30 At equilibrium the overall free energy of reaction is zero.  G = 0 so the equation:  G =  G° + RT ln [P]/[R] Becomes:  G° = - RT ln K eq This provides a relationship between the standard state free energy and the equilibrium constant. For the reaction: R  P K eq = 1000 at 25 o C  G° = -(8.314)(298) ln 1000  G° = cal/mol Understanding Organic Reactions Thermodynamics:

31 The size of K eq expresses whether the starting materials or products predominate once equilibrium is reached. When K eq > 1, equilibrium favors the products (C and D) and the equilibrium lies to the right as the equation is written. This is a useful reaction. When K eq < 1, equilibrium favors the starting materials (A and B) and the equilibrium lies to the left as the equation is written. The position of the equilibrium is determined by the relative energies of the reactants and products. Understanding Organic Reactions Thermodynamics:

32 Figure 6.3 Summary of the relationship between ∆G° and K eq. Note the use of base a 10 log vs a natural log in these equations. Understanding Organic Reactions ∆G° = RT log Keq = - RT ln Keq Thermodynamics:

33 Compounds that are lower in energy have increased stability. The equilibrium favors the products when they are more stable (lower in energy) than the starting materials of a reaction. Because  G° depends on the logarithm of K eq, a small change in energy corresponds to a large difference in the relative amount of starting material and product at equilibrium. Understanding Organic Reactions Thermodynamics:

34 Understanding Organic Reactions Thermodynamics:

35 These equations can be used for any process with two states in equilibrium. E.g., monosubstituted cyclohexanes exist as two different chair conformations that rapidly interconvert at room temperature and equatorial position favored. Knowing the energy difference between two conformations permits the calculation of the amount of each at equilibrium. Understanding Organic Reactions Thermodynamics:

36 Enthalpy and Entropy:  G° depends both on  H° and  S°. Entropy change,  S°, is a measure of the change in the randomness of a system. The more disorder present, the higher the entropy. The value of  S° is (+) when the products are more disordered than the reactants and (-) when the products are less disordered than the reactants. Reactions resulting in increased entropy contribute to a negative  G°.  G° is related to  H° and  S° by the following equation: Understanding Organic Reactions

37 The previous equation indicates that the total free energy change is due to two factors: the change in bonding energy (  H°) and the change in disorder (  S°). The change in bonding energy can be calculated from bond dissociation energies. Entropy changes are important when The number of molecules of starting material differs from the number of molecules of product in the balanced chemical equation. An acyclic molecule is cyclized to a cyclic one, or a cyclic molecule is converted to an acyclic one. Understanding Organic Reactions Enthalpy (  H° ) and Entropy (  S°) :

38 In most other reactions that are not carried out at high temperature, the entropy term (T  S°) is small compared to the enthalpy term (  H 0 ), and therefore it is usually neglected. Understanding Organic Reactions Enthalpy and Entropy:

39 Energy Diagrams: An energy diagram is a schematic representation of the energy changes that take place as reactants are converted to products. An energy diagram plots the energy on the y axis versus the progress of reaction, often labeled as the reaction coordinate, on the x axis. The bond energy difference between reactants and products is  H°. If the products have lower bond energy than the reactants, the reaction is exothermic and energy is released. If the products have higher bond energy than the reactants, the reaction is endothermic and energy is consumed. Understanding Organic Reactions

40 Energy Diagrams: A diagram can also be made by plotting free energy. Then energy difference between reactants and products is  G°. If the products are lower in energy than the reactants, the reaction is exergonic and energy is released. If the products are higher in energy than the reactants, the reaction is endergonic and energy is required. The unstable energy maximum as a chemical reaction proceeds from reactants to products is called the transition state. The transition state species can never be isolated. The energy difference between the transition state and the starting material is called the energy of activation, E a. Understanding Organic Reactions

41 For the general reaction: The energy diagram would be shown as: Understanding Organic Reactions Energy Diagrams:

42 The energy of activation is the minimum amount of energy needed to break the bonds in the reactants. The larger the E a, the greater the amount of energy that is needed to break bonds, and the slower the reaction rate. The structure of the transition state is somewhere between the structures of the starting material and product. Any bond that is partially formed or broken is drawn with a dashed line. Any atom that gains or loses a charge contains a partial charge in the transition state. Transition states are drawn in brackets, with a superscript double dagger ( ‡ ). Understanding Organic Reactions Energy Diagrams:

43 Example 1 Figure 6.4 Some Representative energy diagrams Understanding Organic Reactions Energy Diagrams:

44 Example 2 Understanding Organic Reactions Figure 6.4 Some Representative energy diagrams Energy Diagrams:

45 Example 3 Understanding Organic Reactions Figure 6.4 Some Representative energy diagrams Energy Diagrams:

46 Example 4 Understanding Organic Reactions Figure 6.4 Some Representative energy diagrams Energy Diagrams:

47 Figure 6.5 Comparing ∆H° and E a in two energy diagrams Understanding Organic Reactions Energy Diagrams:

48 Consider the following two step reaction: An energy diagram must be drawn for each step. The two energy diagrams must then be combined to form an energy diagram for the overall two-step reaction. Each step has its own energy barrier, with a transition state at the energy maximum. Understanding Organic Reactions Energy Diagrams:

49 Understanding Organic Reactions Energy Diagrams:

50 Understanding Organic Reactions Energy Diagrams:

51 Figure 6.6 Complete energy diagram for the two-step conversion of Understanding Organic Reactions Energy Diagrams:

52 Kinetics: Kinetics is the study of reaction rates. Recall that E a is the energy barrier that must be exceeded for reactants to be converted to products. Understanding Organic Reactions

53 The higher the concentration, the faster the rate. The higher the temperature, the faster the rate.  G °,  H °, and K eq do not determine the rate of a reaction. These quantities indicate the direction of the equilibrium and the relative energy of reactants and products. A rate law or rate equation shows the relationship between the reaction rate and the concentration of the reactants. It is experimentally determined. Understanding Organic Reactions Kinetics:

54 Fast reactions have large rate constants. Slow reactions have small rate constants. The rate constant k and the energy of activation E a are inversely related. A high E a corresponds to a small k. A rate equation contains concentration terms for all reactants in a one-step mechanism but contains concentration terms for only the reactants involved in the rate-determining step in a multi-step reaction. The order of a rate equation equals the sum of the exponents of the concentration terms in the rate equation. Understanding Organic Reactions Kinetics:

55 A two-step reaction has a slow rate-determining step, and a fast step. The reaction can occur no faster than its slow step. Only the concentration of the reactants in the rate- determining step appears in the rate equation. Understanding Organic Reactions Kinetics:

56 Catalysts: Some reactions do not proceed at a reasonable rate unless a catalyst is added. A catalyst is a substance that speeds up the rate of a reaction. It is recovered unchanged in a reaction, and it does not appear in the product. Figure 6.7 The effect of a catalyst on a reaction Understanding Organic Reactions