Chemical Reactivity and Mechanisms Organic Chemistry Second Edition David Klein Chapter 6 Chemical Reactivity and Mechanisms Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

6.7 Nucleophiles and Electrophiles A major focus in this course is on predicting reaction products for ionic reactions and explaining HOW such reactions work Ionic or polar reactions result from the force of attraction between opposite charges Ionic reactions are also guided by the octet rule Consider how methyl chloride and methyl lithium might react Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

6.7 Nucleophiles When an atom carries a formal or partial negative charge and an available pair of electrons, it is considered a nucleophile It will love to attack a nucleus. WHY? Explain how the molecules below are nucleophiles What is the difference between a nucleophile and a Lewis Base? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

6.7 Electrophiles When an atom carries a formal or partial positive charge and can accept a pair of electrons, it is considered a electrophile It will love available electrons. WHY? Explain how the molecules above are electrophiles What is the difference between an electrophile and a Lewis Acid? Practice with SkillBuilder 6.2 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

6.7 Electrophiles Label all of the nucleophilic and electrophilic sites on the following molecule Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

6.8 Mechanisms and Arrow Pushing We use arrows to show how electrons move when bonds break and form It will be a huge benefit in this course to master the skill of arrow pushing There are four main ways that electrons move in ionic reactions Nucleophilic Attack Loss of a Leaving Group Proton Transfers (Acid/Base) Rearrangements Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

6.8 Nucleophilic Attack When you identify a nucleophilic site and an electrophilic site, the arrow shows the nucleophile attacking The tail of the arrow starts on the electrons (- charge) The head of the arrow ends on a nucleus (+ charge) The electrons end up being sharing rather than transferred Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

6.8 Nucleophilic Attack Nucleophilic attack may appear to occur in two steps Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

6.8 Loss of a Leaving Group Loss of a leaving group occurs when a bond breaks and one atom from the bond takes BOTH electrons Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

6.8 Loss of a Leaving Group 1. Which arrow shows the loss of a leaving group? 2. What are the other arrows for? 3. Draw the product after the leaving group leaves Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

6.8 Proton Transfers Recall from Chapter 3 that a base is protonated when it uses a pair of electrons to take an H+ from the acid. A group can also be deprotonated (sometimes shown by writing –H+ over the reaction arrow) or Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

6.8 Proton Transfers Such electron flow can also be thought of as a proton transfer combined with resonance Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Klein, Organic Chemistry 2e Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

6.8 Carbocation Rearrangements Carbocations can be stabilized by neighboring groups through slight orbital overlapping called hyperconjugation Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

6.8 Carbocation Rearrangements Hyperconjugation and induction can both be invoked to explain the stability trend below. HOW? If a carbocation can INTRAmolecularly rearrange to become more stable, it will likely do so before reacting with a nucleophile. WHY? Allylic Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

6.8 Carbocation Rearrangements Two types of carbocation rearrangement are common Hydride shift Methyl shift Shifts can only occur from an adjacent carbon. WHY? Do the shifts above make the carbocation more stable? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

6.11 Carbocation Rearrangements When you encounter a carbocation, you must consider all possible rearrangements (Hydride and methyl shifts) Identify all adjacent carbons Identify all –H and –CH3 groups on the adjacent carbons that are capable of shifting Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

6.11 Carbocation Rearrangements When you encounter a carbocation, you must consider all possible rearrangements (Hydride and methyl shifts) Imagine each of the groups shifting to see which yields the most stable resulting carbocation In this case, a hydride shift will result in a more stable tertiary carbocation Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

6.11 Carbocation Rearrangements Complete the same analysis for the molecule below Identify all adjacent carbons Identify all –H and –CH3 groups capable of shifting Determine which shift yields the most stable carbocation Recall that allylic carbocations are especially stable Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Klein, Organic Chemistry 2e Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

6.9 Combining Arrow Pushing Patterns Classify each step in the following mechanism Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

6.9 Combining Arrow Pushing Patterns Many times a single step in a mechanism will include more than one arrow pushing pattern Identify the patterns below There are hundreds of mechanisms that involve these key patterns Practice with SkillBuilder 6.4 Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

6.10 Arrow Pushing Rules To draw reasonable mechanisms, a few key rules should be followed The arrow starts ON A PAIR OF ELECTRONS (a bonded pair or a lone pair) Don’t make the mistake of starting an arrow on a nucleus! Both arrows below are incorrect. WHY? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

6.10 Arrow Pushing Rules A few key rules should be followed The arrow ends ON A NUCLEUS (electrons become a lone pair) or between two NUCLEI (electrons move into position to become a bond) Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

6.10 Arrow Pushing Rules A few key rules should be followed Avoid breaking the octet rule. NEVER give C, N, O, or F more than 8 valence electrons Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

6.10 Arrow Pushing Rules A few key rules should be followed Draw arrows that follow the 4 key patterns we outlined Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

6.10 Arrow Pushing Rules Fill in necessary arrows for the reaction below Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

6.10 Arrow Pushing Rules For each mechanism below, identify the unreasonable arrows and redraw the mechanism with correct arrows Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

6.12 Reversible and Irreversible Reaction Arrows Why are some reactions drawn as equilibria and others are essentially irreversible? The question of reversibility a both kinetic and a thermodynamic question. HOW? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

6.12 Reversible and Irreversible Reaction Arrows Consider nucleophilic attack Draw a mechanism for the reverse reaction How do we judge whether it will be reversible? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

6.12 Reversible and Irreversible Reaction Arrows If the attacking nucleophile is also a good leaving group, it will be a reversible attack The reverse reaction will have a relatively low transition state energy (kinetically favored) The reactants and products of the reaction will be similar in energy allowing significant quantities of both to exist at equilibrium (thermodynamic equilibrium) Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

6.12 Reversible and Irreversible Reaction Arrows If the attacking nucleophile is a poor leaving group, it will essentially be an irreversible attack The reverse reaction will have a relatively HIGH transition state energy (kinetically disfavored) The products will be much lower in energy so an insignificant quantity of reactant will remain at equilibrium Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

6.12 Reversible and Irreversible Reaction Arrows Consider loss or a leaving group Draw a mechanism for the reverse reaction How do we judge whether it will be reversible? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

6.12 Reversible and Irreversible Reaction Arrows Consider proton transfer We analyzed this in detail in chapter 3 using pKa values How do we judge reversiblity? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

6.12 Reversible and Irreversible Reaction Arrows Consider proton transfer If the pKa difference is 10 units or more, it is generally considered irreversible Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

6.12 Reversible and Irreversible Reaction Arrows Carbocations are generally considered irreversible thermodynamically. WHY? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

6.12 Reversible and Irreversible Reaction Arrows When considering thermodynamic equilibrium, in addition to comparing relative energies, Le Châtelier’s principle must also be considered. WHY is the reaction below irreversible? Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Additional Practice Problems Label all of the nucleophilic and electrophilic sites on the following molecules Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Additional Practice Problems Draw a mechanism for a generic nucleophilic attack followed by a proton transfer. Draw a mechanism for a generic loss of leaving group followed by a carbocation rearrangement. Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e

Additional Practice Problems For each of the mechanistic steps below, identify what is incorrect about it. Copyright © 2015 John Wiley & Sons, Inc. All rights reserved. Klein, Organic Chemistry 2e