1 Introduction

Mechanisms of Reactions Since there are enormous numbers of possible reactions of organic molecules, understanding organic chemistry would be an enormous difficult task. However, the all varied reactions result from a relatively small number of basic processes. (Mysterious or even impossible) Consider three things in this book - meaning of the “mechanism’ of a reaction - “Proposing” or “writing” a mechanism means - a mechanism is “reasonable” Reaction mechanism - Description everything that happens as the starting materials for the reaction are converted into the products

Mechanisms of Reactions If reaction proceed by a sequence of several consecutive reactions, the proposal should include equations for every step in the overall mechanism. - Intermediate identification is a crucial part of any proposal for the reaction mechanism - Description of changes in the electronic structures of molecules (use of curved arrows which show the change in position of a pair of electrons)

Mechanisms of Reactions In free radical reaction Transition state (rate-limiting step) – no isolation - the point of highest energy in a reaction or in each step of a reaction involving more than one step

Mechanisms of Reactions Knowledge of the transition state(TS) for organic reaction is important to understand the mechanism, but description of transition state as part of proposed reaction mechanism is impossible. - TS always involve partially formed or partially broken bonds (representation of dotted lines)

Mechanisms of Reactions Microscopic reversibility The reverse of any reaction must proceed along exactly the same route as the forward reaction (the lowest energy route in one diraction in a reaction equilibrium must also be the lowest energy route in the other) - Application of this concept in the case of identical condition for both reactions Reasonable mechanism - Basic principle Each step in the reaction of any compound should be a well-known reaction of that type of compound under the conditions of the reaction. Nearly all chemical changes that appear extraordinary are simple the result of well- known routine reactions (combination of reactions you studied)

Mechanisms of Reactions Proposing reaction mechanisms Rejecting an unreasonable mechanism Nucleophilic substitution Reaction (SN2)? -OC2H5 is good leaving group?

Mechanisms of Reactions Proposing reaction mechanisms Rejecting an unreasonable mechanism Anions, all the conjugate bases of strong acids, can act as leaving group in SN2 reactions - Cl-, Br-, I-, RSO3- (benzenesulfonate anions) Neutral molecules (H2O, ROH, ROR’) can act as leaving groups in acid-catalyzed SN1 and E1 reactions

Mechanisms of Reactions Proposing reaction mechanisms Proposing a reasonable mechanism - Focus on the starting materials instead of the product, and select the reaction they are most likely to undergo under the reaction conditions - When there are several reasonable alternatives at each mechanism, check the product formation from the each alternative. If this not reasonable, go back to other alternative and check again. Above reaction has only one reasonable pathway

Mechanisms of Reactions Proposing reaction mechanisms Proposing a reasonable mechanism The mechanism is reasonable, because each step is very common, routine reaction

Mechanisms of Reactions Proposing reaction mechanisms Another example Reaction (8) can be accounted for by a retro-cyanohydrin reaction

Mechanisms of Reactions Proposing reaction mechanisms Another example Mechanism in (9b) is reasonable because each step is a common reaction, with many precedents.

Mechanisms of Reactions Proposing reaction mechanisms More about leaving groups Actually, CN- and C2H5O- are not good leaving groups. Why CN- and C2H5O- can be ejected from Eq (7b) and (9b)? The leaving group and a negatively charged atom are both bonded to the same atom, so that ejection of the leaving group resulted in the formation of a new p bond. - This type of reactions occur much more easily than do substitution by external nucleophiles or elimination by external bases. (Common anions : CN-, OH-, RO-, C=C-O-) - However, hydrocarbon anions and hydride anions can not act as leaving group.

Electron Delocalization and Resonance The Theory of resonance Hybrid structures Most primary halides and ethers are quite unreactive under the same conditions. However, above reaction is a rapid. How can you explain about this? The theory of resonance provides a simple explanation for the formation of the reaction products as well as for the rapid of the reaction.

Electron Delocalization and Resonance The Theory of resonance Hybrid structures Changing the positions of p electrons or unshared electrons The actual structure is ‘a hybrid’ of all the individual resonance forms. The lower in energy a particular resonance form would be, the more closely the actual structure will resemble that resonance form.

Electron Delocalization and Resonance The theory of resonance Hybrid structures Delocalized bonds are sometimes represented by dotted lines.

Electron Delocalization and Resonance The theory of resonance Significant and insignificant forms Resonance forms that would be a great deal higher in energy than other forms may be considered ‘insignificant’ How to figure out which form is ‘significant’ or which form is ‘insignificant’? Resonance forms that have the maximum number of bonds that may be drawn for a particular structure. Significant form

Electron Delocalization and Resonance The theory of resonance Significant and insignificant forms (2) Every resonance form that can be drawn without losing one or more bonds must be considered significant Nonpolar form More significant Dipolar form Less significant

Electron Delocalization and Resonance The theory of resonance Significant and insignificant forms (3) Hyperconjugation resonance forms, involving the delocalization of s bonds rather than p bonds, are not usually included among the significant forms. However, the appreciable stabilization of carbocations by alkyl groups is usually attributed to hyperconjuga- tion rather than to inductive effects. More important form is resonance with s bonds rather than p bonds (No-bond resonance)

Electron Delocalization and Resonance The theory of resonance Using resonance structure There are two basic rules to follow in using resonance structures to predict possible products of organic reactions and to propose reasonable mechanisms Draw all significant resonance structures for ions and molecules taking part in a reaction. (2) Imagine that each resonance form has an individual existence, with localized bonds and charges, and draw the reaction products arising from each form. Each product is a possible product of the actual ion or molecule.

Electron Delocalization and Resonance The theory of resonance Using resonance structure All resonance forms after dissociation of C-Cl bond (Rule 1)

Electron Delocalization and Resonance The theory of resonance Using resonance structure Possible reactions of the individual resonance forms (1) Resonance form 3a

Electron Delocalization and Resonance The theory of resonance Using resonance structure (2) Resonance form 3b Hemiacetal form (unstable)

Electron Delocalization and Resonance The theory of resonance Using resonance structure (2) Resonance form 3b Hemiacetal is rapidly converted to carbonyl compound in acid solution.

Electron Delocalization and Resonance The theory of resonance Which products are actually formed? There is no simple set of rules that will reliably predict which products will be obtained from the reactions of a molecule or ion with several significant resonance structures.

Electron Delocalization and Resonance The theory of resonance (less stable) Kinetic product Thermodynamic product (more stable) The relative amounts of each depend on the reaction time and reaction condition

Electron Delocalization and Resonance The theory of resonance Alkylation at a-carbon to the carbonyl group No alkylation at g carbon Acylation at oxygen atom of the carbonyl group Thereare no general rules that can reliably predict the relatively yields of products from reaction of molecules or ions with delocalized bonds.

Electron Delocalization and Resonance Resonance stabilization A molecule or ion with delocalized bonds is always more stable than its lowest energy resonance form. Resonance stabilization energy The difference in energy between the actual structure and the lowest energy form. Dependance of the number of possible resonance forms

Electron Delocalization and Resonance Resonance stabilization The value of the resonance stabilization energy also depends on the relative stabilities of the various resonance forms. “The closer in energy the different resonance forms are, the greater the degree of delocalization of the electrons and the higher the resonance energy” 8 is less effective than allyl radical (high resonance energy)

Electron Delocalization and Resonance Resonance stabilization Resonance is a general term applied to the phenomenon of bond delocalization. Aromaticity (or antiaromaticity) is special properties of rings composed entirely of conjugated p bonds, empty orbitals, or unshared pairs of electrons.

Electron Delocalization and Resonance Nonplanar p systems The orbitals should be lined up parallel to several p orbitals in order for electrons to be delocalization. However, if one or more orbitals are twisted away from the parallel arrangement, the energy of the system will be increased. - no possibility in open p systems - possibility in cyclic molecules - Steric inhibition of resonance

Electron Delocalization and Resonance Nonplanar p systems

Electron Delocalization and Resonance Nonplanar p systems Not undergo ionic dissociation even when heated with strong Lewis acids.

Electron Delocalization and Resonance Nonplanar p systems Compound (12) is more than 104 times less basic than Compound (13) even though alkyl substitution usually has only a slight effect on the basicity of anilines. - Unshared electrons on the amino group in 12 could interact effectively with p systems of the ring and the nitro group.