Orbitals and Mechanism 1 Dr Robert Paton robert.paton@chem.ox.ac.uk http://paton.chem.ox.ac.uk

Digital versions of handouts and supplementary material will be made available for download: http://paton.chem.ox.ac.uk/teaching

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Orbitals and Mechanism 1

http://paton.chem.ox.ac.uk 1

Course Outline:

These eight lectures focus on structure, to develop the ability to understand & predict reactivity before the

introduction of new functional group transformations and experimental detail. Overall the lectures will:

introduce curly arrow formalisms for organic reactions; provide an overview that unifies the classical

mechanisms through the primitive steps that are common to each; link this with simple MO concepts and

with stereochemical features of mechanism.

Lecture 1: Acids: equilibrium, pKa, resonance effects. Phenols, C-H bond acidity. Importance of solvent.

Lecture 2: Bases: pKaH, amines, amides, anilines – resonance and inductive effects.

Lecture 3: Basic thermodynamics, reaction diagrams, transition states and intermediates, kinetic vs.

thermodynamic control. Hammond postulate. Reactivity: polarity in molecules, nucleophilicity &

electrophilicity. Electrophiles (El) and nucleophiles (Nu). Relate to FMO interactions/relative energies and

electronegativity, ±I & ±M. Consequences of conjugation; vinylogy.

Lecture 4: Reactions: curly arrow rules illustrated with simple one-step processes. ‘Neutralisation reactions’

and non-charged counterparts. The concept of electron flow. Atoms bearing formal charges do not

necessarily react according to that charge (a-atom activation: eg R2C=OH+, BH4–). Where do the electrons

come from and go? Homing-in on reaction sites: filled and empty orbitals, HOMO & LUMO add a 3D aspect

to mechanism. Relate mechanism with structure as a natural consequence of FMO interactions.

Lecture 5: The importance of the reaction medium. Refer to earlier acid/base discussion. Solvent effects on

neutral and charged species, ability to promote ionisation, counterions. Reactive intermediates: C–, C•, C+.

A unified approach to mechanism. Real examples to illustrate [A+ + B–] (neutralisation) and its exact reverse

(ionisation) leads to SN1. Generalise [A+ + B:] & [A + B–] etc leads to 1,2-addition to C=O and b-elimination

(E1cB, E2). Extension of this leads to SN2. MO discussion as appropriate.

Lecture 6: The case of B: = an alkene. Electrophilic addition with H+ giving a cation leads to discussion of

cation structure, stabilisation & regiochemistry. Hyperconjugation. Exact reverse leads to E1 mechanism. El+

where El bears a lone pair (El = Cl, Br, I) leads to bridged ions and directionality in their opening,

stereospecificity.

Lecture 7: Special case where C=C + El+ is followed by loss of H+ leads to SEAr. Attack by neutral species I

(carbenes, dienes) = pericyclic (should follow naturally from Br2 attack). Attack by neutral species II

(radicals), orientation.

Lecture 8: Review of mechanism types setting the scene for the rest of the course. Redox concepts –

prelude to carbonyl course.

General Texts: Clayden, Greeves, Warren and Wothers, Organic Chemistry, OUP; Keeler and Wothers,

Why Chemical Reactions Happen, OUP

Primers: Hornby and Peach, Foundations of Organic Chemistry OCP #9; Meakins, Functional Groups:

Characteristics and Interconversions, OCP #35; Hornby and Peach, Foundations of Organic Chemistry:

Worked Examples, OCP #87; Robinson, Organic Stereochemistry, OCP #88.