Intermediate Organic Chemistry I

Learning Outcomes

Learning Outcomes

Having successfully completed this module you will be able to:

• Combine reactions to achieve simple synthesis of target molecules.
• Predict the reactivity and regiochemistry of electrohilic addition to alkenes and aromatic systems.
• Use spectroscopic information to distinguish between structures.
• Use curly arrow reaction mechanisms and a knowledge of the relative stability of intermediates to predict and / or account for the products of reactions.
• Predict outcomes and draw mechanisms for nucleophilic addition to alkenes and nucleophilic aromatic substitution reactions.
• Predict outcomes and draw mechanisms for reactions of carbonyl compounds (condensations, additions, cyclisations).
• Recognise neighboring group participation and rearrangement reactions.
• Appreciate the scope and limitations of nucleophilic additions to pi-systems.
• Design experiments to probe mechanisms, particularly using stereochemistry or isotopic labelling.

Mechanisms and reactive intermediates

• SN2 mechanism. Orbital picture. Transition state. Inversion of configuration. Leaving groups. Nucleophiles. Steric hindrance. Activation by adjacent pi-systems; Dipolar aprotic solvents.
• SN1 mechanism. Carbenium ions – relative stability of a wide range (delocalisation, stabilisation by lone pairs on adjacent heteroatoms; ‘hyperconjugation’, stabilisation of tertiary carbenium ions by release of steric strain). Importance of polar protic solvents. Loss of stereochemistry.
• Neighbouring Group participation. Rearrangements (Wagner Meerwein; Pinacol; Baeyer-Villiger; Beckmann; Benzylic acid and semi-benzylic) with particular emphasis on steric requirements.
• E1, E2, and E1CB elimination mechanisms. Kinetic isotope effect.
• Neutral reactive intermediates: Carbenes and Radicals (brief introduction)

Electrophilic Addition to π-Systems

• Electrophilic addition to alkenes, regioselectivity and stereoselectivity issues of typical reactions including hydrogen halide addition (Markovnikov), halogen addition, bromolactonisation and epoxidation. Hydrogen halide addition to 1,3-dienes, including kinetic vs thermodynamic control.
• Electrophilic aromatic substitution of benzene and substituted benzene derivatives; examples (including halogenation, sulfonation, nitration, Friedel-Crafts acylation and alkylation), mechanism, and substituent effects upon rate and regioselectivity.

Carbanions

• Structure, stability and methods of formation. Anion-driven rearrangements. Revision of acid-base equilibria and pKa, basicity and pKa(H).

Chemistry of Enols and Enolates

• Enolisation.
• Enols and enolate ions as reactive intermediates – enolate formation by deprotonation, regioselectivity of deprotonation. Aldol addition and condensation, including intramolecular and crossed versions. Claisen and Dieckmann condensation, Knoevenagel. Enolate alkylation.
• Silyl enol ethers – preparation and reactivity.

Nucleophilic Addition to π-Systems

• Conjugate addition of alcohols, thiols, amines, enolates, cyanide to alpha,beta-unsaturated carbonyl compounds. Discussion of factors affecting 1,2 vs 1,4-addition, including kinetic and thermodynamically controlled cyanide addition.
• Nucleophilic aromatic substitution. Addition-elimination and benzyne mechanisms.

Teaching and learning methods

Lectures, problem-solving tutorials with tutor support

Resources & Reading list

Textbooks

J. Clayden, N. Greeves, S. Warren (2012). Organic Chemistry. OUP.

Summative

This is how we’ll formally assess what you have learned in this module.

Referral

This is how we’ll assess you if you don’t meet the criteria to pass this module.