© 2011 Pearson Education, Inc. 1 Organic Chemistry 6 th Edition Paula Yurkanis Bruice Chapter 7 Delocalized Electrons and Their Effect on Stability, Reactivity, and pK a More About Molecular Orbital Theory

© 2011 Pearson Education, Inc. 2 Localized Versus Delocalized Electrons

© 2011 Pearson Education, Inc. 3 Benzene Has Delocalized Electrons A planar molecule Has six identical carbon–carbon bonds Each  electron is shared by all six carbons The  electrons are delocalized

© 2011 Pearson Education, Inc. 4 Resonance Contributors and the Resonance Hybrid Resonance contributors do not depict any real electron distribution

© 2011 Pearson Education, Inc. 5  electrons cannot delocalize in nonplanar molecules

© 2011 Pearson Education, Inc. 6 Rules for Drawing Resonance Contributors 1. Only electrons move. 2. Only  electrons and lone-pair electrons move. 3. The total number of electrons in the molecule does not change. 4. An sp 3 carbon cannot accept electrons; it already has an octet. 5. Do not break sp 3 (  ) bonds.

© 2011 Pearson Education, Inc. 7 Many Resonance Structures Consist of Two-Center and/or Three-Center Systems Two-Center Systems: Three-Center Systems: No  bonds broken! Only  or lone pair electrons move!

© 2011 Pearson Education, Inc. 8 Allylic Resonance Move  electrons toward an sp 2 carbon:

© 2011 Pearson Education, Inc. 9 Multi-Center Allylic Resonance Composed of allylic centers: Allylic Benzylic cation: Allylic

© 2011 Pearson Education, Inc. 10 Three-Center Bonding: Nitro Group Resonance

© 2011 Pearson Education, Inc. 11 Three-Center Bonding: Amide Resonance Amide resonance responsible for the strength of amide bonds found in hair, skin, muscle, Kevlar vests, etc. Electropositive nitrogen Electronegative oxygen Electronic push-pull Move lone-pair electrons toward the sp 2 oxygen:

© 2011 Pearson Education, Inc. 12 B is less stable than A, no electronic push- pull. Ester bonds not as robust as amide bonds. C and D are equally stable: carboxylate resonance responsible for the acidity of carboxylic acids. Three-Center Bonding: Carboxylic Acid Derivatives (R) derivative

© 2011 Pearson Education, Inc. 13 ,  -Unsaturated Carbonyl Compounds A four-center system composed of two and three center systems: Predicted reactivity: ,  -Unsaturated carbonyl compounds are toxic because they trap YOUR nucleophiles. Allyl cation Carbonyl center

© 2011 Pearson Education, Inc. 14 Summary of Electron Delocalization Examples 1. Move  electrons toward an sp 2 carbon 2. Move lone-pair electrons toward an sp 2 carbon

© 2011 Pearson Education, Inc Move lone-pair or  electrons towards an sp carbon: 4. Do not move electrons to an sp 3 carbon:

© 2011 Pearson Education, Inc Electrons always move toward the more electronegative atom: 6. Do not break sp 3 (  ) bonds : No + charge here, cross conjugated Alkene cross conjugated with carboxylate

© 2011 Pearson Education, Inc. 17 Resonance release of lone-pair electrons (competes with inductive withdrawal by the electronegative oxygen): Substituent Effects Isoelectronic with allyl anion The methoxy group makes the benzene ring electron-rich: Electron-releasing groups have a lone pair at the point of attachment.

© 2011 Pearson Education, Inc. 18 Substituent Effects The nitro group makes the benzene ring electron-deficient by resonance withdrawal: Electron-withdrawing groups possess an electron-deficient center at the point of attachment:

© 2011 Pearson Education, Inc. 19 Features that decrease the predicted stability of a contributing resonance structure: 1. An atom with an incomplete octet: 2. A negative charge that is not on the most electronegative atom: More stable

© 2011 Pearson Education, Inc A positive charge that is not on the most electropositive atom: 4. Charge separation: Not a valid structure More stable charge-separated structure More stable

© 2011 Pearson Education, Inc. 21 Delocalization Energy The extra stability a compound gains from having delocalized electrons is called the delocalization energy Electron delocalization is also called resonance Delocalization energy is also called resonance energy A resonance hybrid is more stable than any of its resonance contributors is predicted to be

© 2011 Pearson Education, Inc. 22 Summary The greater the predicted stability of a resonance contributor, the more it contributes to the resonance hybrid The greater the number of relatively stable resonance contributors, the greater is the resonance energy The more nearly equivalent the resonance contributors, the greater is the resonance energy

© 2011 Pearson Education, Inc. 23 Using Resonance to Predict Stability Carbonate is stable and ubiquitous in nature: Cement, shells, limestone… The guanidium ion is stabilized by resonance and deprotonated only in strong base: The amino acid arginine, guanidium pK a = 12.5, cationic at physiological pH= 7.4 Important physiologically:

© 2011 Pearson Education, Inc. 24 Relative Stabilities of Carbocations and Radicals Carbocations: hyperconjugation more important than resonance. Radicals: resonance more important than hyperconjugation.

© 2011 Pearson Education, Inc. 25 Cation Stabilization by Resonance and Hyperconjugation

© 2011 Pearson Education, Inc. 26 Example: Delocalized Electrons Can Affect the Product of a Reaction

© 2011 Pearson Education, Inc. 27 Delocalized Electrons Affect pK a Carboxylic acid is a stronger acid because… Electron withdrawal and electron delocalization stabilize the conjugate base:

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© 2011 Pearson Education, Inc. 29 Phenol is a stronger acid than cyclohexanol because of phenolate ion delocalization: pKa = 10 Delocalized Anion pKa = 16 Localized Anion

© 2011 Pearson Education, Inc. 30 Protonated aniline is a stronger acid than protonated cyclohexylamine because the aniline lone pair is delocalized: pK a = 4.62 Delocalized lone pair pK a = 11.2 Localized lone pair

© 2011 Pearson Education, Inc. 31 Connecting Delocalization, Substituent Effects, and pK a Values Important in understanding drug design and reaction mechanisms: Which phenol is the stronger acid? First, show the resonance delocalization of the phenolate anion:

© 2011 Pearson Education, Inc. 32 Second, pick the structure in which the anion interacts with the nitro group. This structure represents the more stable anion: Third, the conjugate acid of the more stable anion is the strongest acid: Anion adjacent to electron- withdrawing nitro group Anion delocalizes into the nitro group Stronger acid, pK a = 7.2 Weaker acid, pK a = 8.4. Nitro only exerts inductive withdrawal

© 2011 Pearson Education, Inc. 33 Stability of Dienes

© 2011 Pearson Education, Inc. 34 The most stable diene has the lower -  H o value : Why: The hybridization of the orbitals forming the carbon- carbon single bonds also causes a conjugated diene to be more stable than an isolated diene: Closer in energy to pentane

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© 2011 Pearson Education, Inc. 36 A Molecular Orbital Description of Stability Bonding MO: constructive (in-phase) overlap Antibonding MO: destructive (out-of-phase) overlap

© 2011 Pearson Education, Inc. 37 MOs for the Allyl System

© 2011 Pearson Education, Inc. 38 The Molecular Orbitals of 1,3-Butadiene

© 2011 Pearson Education, Inc. 39 Symmetry in Molecular Orbitals  1 and  3 in 1,3-butadiene are symmetrical molecular orbitals  2 and  4 in 1,3-butadiene are fully asymmetrical orbitals

© 2011 Pearson Education, Inc. 40 HOMO = the highest occupied molecular orbital LUMO = the lowest unoccupied molecular orbital The highest-energy molecular orbital of 1,3-butadiene that contains electrons is  2 (HOMO) The lowest-energy molecular orbital of 1,3-butadiene that does not contain electrons is  3 (LUMO)

© 2011 Pearson Education, Inc. 41 Consider the  molecular orbitals of 1,4-pentadiene: This compound has four  electrons that are completely separated from one another

© 2011 Pearson Education, Inc. 42 The Molecular Orbitals of 1,3,5-Hexatriene

© 2011 Pearson Education, Inc. 43 Benzene has six  molecular orbitals

© 2011 Pearson Education, Inc. 44 As the energy of the p orbitals increase, the net number of bonding interactions decreases

© 2011 Pearson Education, Inc. 45 Benzene is unusually stable because of large delocalization energies:

© 2011 Pearson Education, Inc. 46 Why isn’t cyclooctatetrene flat? Pattern of bonding orbitals of planar cyclic  systems (e.g., benzene): Pattern of bonding orbitals of non- planar or non-cyclic  systems (e.g., 1,3-butadiene): Needs 4N+2 (N = 0, 1, 2, 3…) electrons to fill orbitals Needs an even number of electrons to fill orbitals Answer: Cyclooctatetrene has 8  electrons, which cannot fill the degenerate orbitals of a planar  system. Therefore it has a tub shape to remove these degenerate orbitals.

© 2011 Pearson Education, Inc. 47 Reactions of Isolated Dienes In the presence of limiting electrophilic reagent, only the more reactive double bond reacts

© 2011 Pearson Education, Inc. 48 Reactions of Conjugated Dienes An isolated diene undergoes only 1,2-addition A conjugated diene undergoes both 1,2- and 1,4-addition

© 2011 Pearson Education, Inc. 49 Mechanism of HBr Addition to a Conjugated Diene More stable cation More stable alkene Thermodynamic product Kinetic product

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© 2011 Pearson Education, Inc. 51 If the conjugated diene is not symmetrical… Protonate to form the more stable carbocation: More stable carbocation

© 2011 Pearson Education, Inc. 52 The kinetic product is the product that is formed most rapidly The kinetic product predominates when the reaction is irreversible (kinetic control) The thermodynamic product is the most stable product The thermodynamic product predominates when the reaction is reversible (thermodynamic control) Thermodynamic Versus Kinetic Control Reactions

© 2011 Pearson Education, Inc. 53 The kinetic product predominates when the reaction is irreversible (temperature too low): The thermodynamic product predominates when the reaction is reversible (higher temperature):

© 2011 Pearson Education, Inc. 54 Consider the reaction coordinate diagram…

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© 2011 Pearson Education, Inc. 57 Do not assume that the 1,4-addition product is always the thermodynamic product…

© 2011 Pearson Education, Inc. 58 How to Identify the Kinetic and Thermodynamic Products First, protonate at the least-substituted carbon: Second, show both allylic resonance forms: Third, identify the more stable carbocation. Halide trapping affords the kinetic product: Fourth, identify the resonance form with the more stable alkene. Halide trapping affords the thermodynamic product:

© 2011 Pearson Education, Inc. 59 The Diels–Alder Reaction: A 1,4-Addition Reaction The Diels–Alder reaction is a pericyclic reaction; a [4+2] cycloaddition reaction

© 2011 Pearson Education, Inc. 60 The reactivity of the dienophile is increased if one or more electron-withdrawing groups are attached to its sp 2 carbons

© 2011 Pearson Education, Inc. 61 A Molecular Orbital Description of the Diels–Alder Reaction Let’s focus on the HOMO and the LUMO of the reactants

© 2011 Pearson Education, Inc. 62 Preparation of Cyclic Compounds Using the Diels–Alder Reaction

© 2011 Pearson Education, Inc. 63 Predicting the Product When Both Reagents Are Unsymmetrically Substituted

© 2011 Pearson Education, Inc. 64 The charge distribution in each of the reactants determines the yield of the products

© 2011 Pearson Education, Inc. 65 Major product

© 2011 Pearson Education, Inc. 66 Two Possible Configurations of Bridged Bicyclic Compounds

© 2011 Pearson Education, Inc. 67 A conjugated diene locked in an s-cis conformation is highly reactive in a Diels–Alder reaction: And affords the endo isomer as the major product (the endo rule).

© 2011 Pearson Education, Inc. 68 The Stereochemisty of the Diels–Alder Reaction If a Diels–Alder reaction creates a product with an asymmetric center, identical amounts of the R and S enantiomers will be formed

© 2011 Pearson Education, Inc. 69 Spanish Fly: Cantharidin A potent vesicant that the insect uses to protect its eggs. Originally used as an aphrodisiac; causes priapism, but is too toxic. Now used to remove warts.

© 2011 Pearson Education, Inc. 70 Failed Attempt Using a Diels– Alder Approach Problems: Reaction is reversible Major product is endo

© 2011 Pearson Education, Inc. 71 The Successful Dauben Synthesis