1 Chapter 6 Understanding Organic Reactions

2 Writing Equations for Organic Reactions Equations for organic reactions are usually drawn with a single reaction arrow (  ) between the starting material and product. The reagent, the chemical substance with which an organic compound reacts, is sometimes drawn on the left side of the equation with the other reactants. At other times, the reagent is drawn above the arrow itself. Although the solvent is often omitted from the equation, most organic reactions take place in liquid solvent.

3 Understanding Organic Reactions Writing Equations for Organic Reactions The solvent and temperature of the reaction may be added above or below the arrow. The symbols “h ” and “  ” are used for reactions that require light and heat respectively.

4 Understanding Organic Reactions Writing Equations for Organic Reactions This convention signifies that the first step occurs before the second step, and the reagents are added in sequence, not at the same time.

5 Understanding Organic Reactions Kinds of Organic Reactions substitution reaction : an atom or a group of atoms is replaced by another atom or group of atoms. In a general substitution, Y replaces Z on a carbon atom. Acid-Base reaction, Oxidation-Reduction

6 Understanding Organic Reactions Kinds of Organic Reactions Substitution reactions involve  bonds: one  bond breaks and another forms at the same carbon atom. The most common examples of substitution occur when Z is an atom that is more electronegative than carbon.

7 Understanding Organic Reactions Kinds of Organic Reactions Elimination reaction : elements of the starting material are “lost” and a  bond is formed. 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.

8 Understanding Organic Reactions Kinds of Organic Reactions The most common examples of elimination occur when X = H and Y is a heteroatom more electronegative than carbon. dehydrohalogenation dehydration

9 Understanding Organic Reactions Kinds of Organic Reactions Addition reaction : elements are added to the starting material.

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

11 Understanding Organic Reactions Kinds of Organic Reactions Addition and elimination reactions are exactly opposite. A  bond is formed in elimination reactions, whereas a  bond is broken in addition reactions. Rearrangement (sigmatropic rearrangement) : change of carbon skeleton

12 Understanding Organic Reactions Bond Making and Bond Breaking reaction mechanism : 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.

13 Understanding Organic Reactions Bond Making and Bond Breaking Two ways to break a bond (two ways to deal with bonding electron pair.) : homolytic cleavage heterolytic cleavage Mostly depend on bond strength (bonding energy)

14 Understanding Organic Reactions Bond Making and Bond Breaking Polarity of the bond plays bigger role. Generally, more electronegative part takes the pair of electrons.

15 Understanding Organic Reactions Radicals, Carbocations, Carbanions A full headed curved arrow shows the movement of an electron pair. To illustrate the movement of a single electron, use a half- headed curved arrow, sometimes called a fishhook.

16 Understanding Organic Reactions Radical : reactive intermediate with a single unpaired electron. generated from homolysis Radicals are highly unstable because they contain an atom that does not have an octet of electrons. 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. Radicals, Carbocations, Carbanions

17 Understanding Organic Reactions Radicals, Carbocations, Carbanions

18 Understanding Organic Reactions Radicals, Carbocations, Carbanions

19 Understanding Organic Reactions 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.

20 Understanding Organic Reactions A number of types of arrows are used in describing organic reactions. Bond Making and Bond Breaking

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22 Understanding Organic Reactions 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.

23 Understanding Organic Reactions Bond Dissociation Energy bond dissociation energies are always positive numbers, and homolysis is always endothermic. 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.

24 Comparing bond dissociation energies is equivalent to comparing bond strength.

25 Understanding Organic Reactions Bond Dissociation Energy Bond dissociation energies decrease down a column of the periodic table. Generally, shorter bonds are stronger bonds.

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

27 Understanding Organic Reactions Bond Dissociation Energy

28 Understanding Organic Reactions oxidation of isooctane and glucose to yield CO 2 and H 2 O.  H ° is negative for both oxidations, so both reactions are exothermic. Both isooctane and glucose release energy on oxidation because the bonds in the products are stronger than the bonds in the reactants.

29 Understanding Organic Reactions Bond Dissociation Energy 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.

30 Understanding Organic Reactions Thermodynamics 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.

31 Understanding Organic Reactions The Equilibrium Constant At equilibrium,  G = 0 and Q = K If we replace Q eq by K, equilibrium constant

32 Understanding Organic Reactions Thermodynamics 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.

33 Understanding Organic Reactions Thermodynamics

34 Understanding Organic Reactions Energy Changes and Conformational Isomerism

35 Understanding Organic Reactions Enthalpy and Entropy  G ° depends on  H ° and the entropy change,  S °.  S ° (Entropy change) : a measure of the change in the randomness of a system. The more disorder present, the higher the entropy. Gas molecules move more freely than liquid molecules and are higher in entropy. Cyclic molecules have more restricted bond rotation than similar acyclic molecules and are lower in entropy.  S ° is (+) when the products are more disordered than the reactants.  S ° is (-) when the products are less disordered than the reactants. Reactions resulting in increased entropy are favored.  G ° is related to  H ° and  S ° by the following equation:

36 Understanding Organic Reactions 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.

37 Understanding Organic Reactions Enthalpy and Entropy 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.

38 Energy Diagrams For the general reaction of a single step reaction The energy diagram would be shown as: An energy diagram is a schematic representation of the energy changes that take place as reactants are converted to products.

39 Understanding Organic Reactions Activation energy and Transition state E a : the minimum amount of energy needed to break the bonds in the reactants. The transition state : 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 ( ‡ ).

40 Understanding Organic Reactions Energy Diagrams Example 1 Example 2

41 Understanding Organic Reactions Energy Diagrams Example 3 Example 4

42 Understanding Organic Reactions Comparison of two pathways

43 Understanding Organic Reactions Energy Diagrams for a two-step reaction mechanism Consider the following two step reaction: An energy diagram must be drawn for each step.

44 Understanding Organic Reactions Energy Diagrams

45 Understanding Organic Reactions Energy Diagrams

46 Understanding Organic Reactions Energy Diagrams for a two-step reaction mechanism 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.

47 Understanding Organic Reactions

48 Understanding Organic Reactions 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.

49 Understanding Organic Reactions Kinetics 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. A rate law or rate equation shows the relationship between the reaction rate and the concentration of the reactants. It is experimentally determined.

50 Understanding Organic Reactions Kinetics 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.

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

52 Understanding Organic Reactions Catalysts A catalyst is a substance that speeds up or slows down the rate of a reaction. It is recovered unchanged in a reaction, and it does not appear in the product.

53 Understanding Organic Reactions Common catalysts in organic chemistry acids metals Lowers activation energy by creating intermediates!

54 Understanding Organic Reactions Enzymes Enzymes are biochemical catalysts. An enzyme contains a region called its active site which binds an organic reactant, called a substrate. The resulting unit is called the enzyme-substrate complex. Once bound, the organic substrate undergoes a very specific reaction at an enhanced rate. The products are then released. Through stabilization of the transition state

6.2, 6.10, 6.18, 6.22, 6.23, 6.26, 6.27, 6.35, 6.38, 6.43, 6.46, 6.49, 6.50 Homework

Preview of Chapter 7 Alkyl Halides and Nucleophilic substitution 1.What is Hammond postulation? 2. What is the product and stereochemical outcome of the reaction of (S)-2-bromobutane with - OH a) through S N 1 mechanism? b) through S N 2 mechanism?