1. John E. McMurry http://www.cengage.com/chemistry/mcmurry Richard Morrison University of Georgia, Athens Chapter 6 An Overview of Organic Reactions

2. Organic chemical reactions broadly organized in two ways: 1. What kinds of reactions occur 2. How those reactions occur Organic Chemical Reactions

3. Addition reactions Occur when two reactants add together to form a single product with no atoms “left over” Reaction of fumarate with water to yield malate (a step in the citric acid cycle of food metabolism) 6.1 Kinds of Organic Reactions

4. Elimination reactions Occur when a single reactant splits into two products (usually with the formation of a small molecule such as water) Reaction of hydroxybutyryl ACP to yield trans-crotonyl ACP and water (a step in the biosynthesis of fat molecules) Kinds of Organic Reactions

5. Substitution reactions Occur when two reactants exchange parts to give two new products Reaction of an ester such as methyl acetate with water to yield a carboxylic acid and an alcohol In biological pathways this type of reaction occurs in the metabolism of dietary fats Kinds of Organic Reactions

6. Rearrangement reactions Occur when a single reactant undergoes a reorganization of bonds and atoms to yield an isomeric product Rearrangement of dihydroxyacetone phosphate into its constitutional isomer glyceraldehyde 3-phosphate (a step in the metabolism of carbohydrates) Kinds of Organic Reactions

7. Reaction Mechanism An overall description of how a reaction occurs at each stage of a chemical transformation Which bonds are broken and in what order Which bonds are formed and in what order What is the relative rate of each step A complete mechanism accounts for all reactants consumed and all products formed 6.2 How Organic Reactions Occur: Mechanisms

8. All chemical reactions involve bond breaking and bond making Two ways a covalent two-electron bond can break: 1. Symmetrical - HOMOLYTIC One electron remains with each product fragment 2. Unsymmetrical - HETEROLYTIC Both bonding electrons remain with one product fragment, leaving the other with a vacant orbital Half-headed arrow, “fishhook”, indicates movement of one electron Full-headed arrow indicates movement of two electrons How Organic Reactions Occur: Mechanisms

9. Two ways a covalent two-electron bond can form: 1. Symmetrical One electron is donated to the new bond by each reactant (radical) 2. Unsymmetrical Both bonding electrons are donated by one reactant (polar) How Organic Reactions Occur: Mechanisms

10. Radical reaction Process that involves symmetrical bond breaking and bond making Radical (free radical) A neutral chemical species that contains an odd number of electrons and has a single unpaired electron Polar reactions Process that involves unsymmetrical bond breaking and bond making Involve species that have an even number of electrons Common in both organic and biological chemistry How Organic Reactions Occur: Mechanisms

11. Radical Highly reactive because it contains an atom with an odd number of electrons Can achieve stability through: Radical substitution reaction Radical abstracts an atom and one bonding electron from another reactant Radical Reactions

12. Radical addition reaction A reactant radical adds to a double bond, taking one electron from double bond and leaving one behind to form a new radical Radical Reactions

13. Industrial radical reaction The chlorination of methane to yield chloromethane A substitution reaction First step in the preparation of the solvents dichloromethane (CH 2 Cl 2 ) and chloroform (CHCl 3 ) Radical Reactions

14. Radical chlorination of methane requires three kinds of steps: initiation, propagation, and termination 1. Initiation Ultraviolet light breaks Cl-Cl bond to generate chlorine radicals Radical Reactions

15. 2. Propagation Reaction with CH 4 to generate new radicals and propagate the chain reaction Radical Reactions

16. 3. Termination Two radicals combine to end the chain reaction No new radical species is formed Radical Reactions

17. Carbon radicals are categorized as primary (1°), secondary (2°) and tertiary (3°) based on the number of attached R groups. 1°1° 2°2°3°3° A carbon radical is sp 2 hybridized with a trigonal planar geometry with the unpaired electron in the unhybridized p orbital. Radical Reactions

18. Bond dissociation energy is used as a measure of radical stability. Radical Reactions

20. What type of radical are each of the following? Of these three radicals, which is the most stable? Radical Reactions

21. Which C-H bond in each compound is most reactive?

22. Predict the products from the monobromination of the following compound? Radical Reactions

23. Chlorination is faster and nonselective. This is due to it’s rate determining step being exothermic. Bromination is slower and chooses the most stable radical. This due to it’s rate determining step being endothermic. Bond Dissociation Energies BondBond Energy (kj/mol) H—F565 H—Cl427 H—Br363 H—I295 C—H413 C—F485 C—Cl339 C—Br276 C—I240.

24. Bond polarity Certain bonds within a molecule are polar Consequence of an unsymmetrical electron distribution in a bond One atoms preference over the electrons between the bonded atoms. Polar reactions electrical attraction between positive and negative centers on functional groups in molecules Two electron type reactions Double headed arrows used to show two electron flow in mechanisms Polar Reactions

25. Certain bonds within molecules with functional groups are polar Carbon is positively polarized (  ) when bonded to more electronegative elements Carbon is negatively polarized (  ) when bonded to metals Polar Reactions

28. Polar of bonds can be enhanced! Interactions of functional groups with acids or bases Methanol In neutral methanol the carbon atom is somewhat electron-poor Protonation of the methanol oxygen by an acid makes carbon much more electron-poor Polar Reactions

29. Polarizability of the atom The measure of change in electron distribution around the atom to an external electrical influence Larger atoms (more, loosely held electrons) – more polarizable Smaller atoms (fewer, tightly held electrons) – less polarizable Effects of polarizability on bonds Although carbon-sulfur and carbon-iodine bonds are nonpolar according to electronegativity values, they usually react as if they are polar because sulfur and iodine are highly polarizable Polar Reactions

30. Nucleophile – A Lewis Base Substance that is “nucleus-loving” Has a negatively polarized electron-rich atom Can form a bond by donating a pair of electrons to a positively polarized, electron-poor atom May be either neutral or negatively charged Electrophile – A Lewis Acid Substance that is “electron-loving” Has a positively polarized, electron-poor atom Can form a bond by accepting a pair of electrons from a nucleophile May be either neutral or positively charged Polar Reactions

31. Which of the following species is likely to behave as a nucleophile and which as an electrophile? (a) (CH 3 ) 3 S + (b)  CN (c) CH 3 NH 2 Worked Example 6.1 Identifying Electrophiles and Nucleophiles

32. Addition of water to ethylene Typical polar process Acid catalyzed addition reaction (Electophilic addition reaction) An Example of a Polar Reaction: Addition of H 2 O to Ethylene

33. Addition of water to ethylene 1) 2) 3) An Example of a Polar Reaction: Addition of H 2 O to Ethylene

34. Addition of HBr to ethylene 1) 2) 3) An Example of a Polar Reaction: Addition of HBr to Ethylene

35. Add curved arrows to the following polar reactions to show the flow of electrons Example 6.2 Using Curved Arrows in Reaction Mechanisms

36. Every chemical reaction can proceed in either the forward or reverse direction The position of the resulting chemical equilibrium is expressed by the equilibrium constant equation K eq K>1 K=1 K<1 ∆G = G products – G reactant Describing a Reaction: Equilibrium, Rates, and Energy Changes

37. The free-energy change ∆G made up of two terms: 1. Enthalpy ∆H 2. Entropy T∆S (temperature depended) ∆Gº = ∆Hº - T∆Sº (standard conditions) Reaction of ethylene with H 2 O at 298 K Describing a Reaction: Equilibria, Rates, and Energy Changes

38. K eq Tells position of equilibrium Tells how much product is theoretically possible Does not tell the rate of reaction Does not tell how fast equilibrium is established Rate → Is the reaction fast or slow? Equilibrium → In what direction does the reaction proceed? Describing a Reaction: Equilibria, Rates, and Energy Changes

39. Bond strength is a measure of the heat change that occurs on breaking a bond, formally defined as bond dissociation energy Each bond has its own characteristic strength Bond Dissociation Energy (D) The amount of energy required to break a given bond to produce two radical fragments when the molecule is in the gas phase at 25ºC Describing a Reaction: Bond Dissociation Energies

42. For a reaction to take place Reactant molecules must collide Reorganization of atoms and bonds must occur Describing a Reaction: Energy Diagrams and Transition States

43. Chemists use energy diagrams to graphically depict the energy changes that occur during a chemical reaction Vertical axis the total energy of all reactants Horizontal axis “reaction coordinate” the progress of the reaction from beginning to end Addition of water to ethylene Describing a Reaction: Energy Diagrams and Transition States

44. Activation Energy (∆G ‡ ) The energy difference between reactants and transition state Determines how rapidly the reaction occurs at a given temperature Large activation energy results in a slow reaction Small activation energy results in a rapid reaction Many organic reactions have activation energies in the range of 40 – 150 kJ/mol If ∆G ‡ less than 80 kJ/mol the reaction takes place at or below room temperature If ∆G ‡ more than 80 kJ/mol the reaction requires heating above room temperature Describing a Reaction: Energy Diagrams and Transition States

45. Activation energy leads to transition state The Transition State Represents the highest-energy structure involved in the reaction Unstable and cannot be isolated A hypothetical transition–state structure for the first step of the reaction of ethylene with H 3 O + the C=C bond about to break the C-H bond is beginning to form

46. Once transition-state is reached the reaction either: Continues on to give carbocation product New C-H bond forms fully Amount of energy corresponding to difference between transition-state (∆G ‡ ) and carbocation product is released Since carbocation is higher in energy than the starting alkene, the step is endergonic (+∆Gº, absorbs energy) Reverts back to reactants Transition-state structure comes apart Amount of free-energy (-∆G ‡ ) is released Describing a Reaction: Energy Diagrams and Transition States

47. Each reaction has its own profile (a)a fast exergonic reaction (small G ‡, negative G°); (b)a slow exergonic reaction (large G ‡, negative G°); (c)a fast endergonic reaction (small G ‡, small positive G°); (d)a slow endergonic reaction (large G ‡, positive G°).

48. Reaction Intermediate A species that is formed during the course of a multi-step reaction but is not final product More stable than transition states May or may not be stable enough to isolate The hydration of ethylene proceeds through two reaction intermediates, a carbocation intermediate and a protonated alcohol intermediate Describing a Reaction: Intermediates

49. Each step in a multi-step process can be considered separately (each step has ∆G ‡ and ∆Gº) Overall ∆Gº of reaction is the energy difference between initial reactants and final products Describing a Reaction: Intermediates Overall energy diagram for the reaction of ethylene with water

50. Biological reactions occur at physiological conditions Must have low activation energy Must release energy in relatively small amounts Enzyme catalyst changes the mechanism of reaction to an alternative pathway which proceeds through a series of smaller steps rather than one or two large steps Describing a Reaction: Intermediates

51. Sketch an energy diagram for a one-step reaction that is fast and highly exergonic Worked Example 6.3 Drawing Energy Diagram for Reactions