Pre-requisites: CHEM1031 AND CHEM1032
Aims and Objectives
Having successfully completed this module you will be able to:
- Appreciate the scope and limitations of nucleophilic additions to pi-systems.
- Use analytical information to assign or confirm structures.
- Predict outcomes and draw mechanisms for nucleophilic addition to alkenes and nucleophilic aromatic substitution reactions.
- Analyse the outcome of reactions via melting point, spectroscopic methods (1H-, 13C-NMR and DEPT experiments), IR (ATR) and mass spectrometry (ES and EI ionisation);
- Recognise neighboring group participation and rearrangement reactions.
- Use curly arrow reaction mechanisms and a knowledge of the relative stability of intermediates to predict and / or account for the products of reactions.
- Suggest mechanisms for the reactions performed and to draw these using curly arrows.
- Design experiments to probe mechanisms, particularly using stereochemistry or isotopic labelling.
- Separate by-products and to purify products by various methods (liquid-liquid extraction, inclusive of pH-manipulations during extractive work-up, column chromatography, recrystallisation, trituration)
- Evaluate green credentials of reactions;
- Monitor reactions by TLC;
- Perform multi-step syntheses under normal or inert conditions using standard or microwave heating, or cooling baths using cardice;
- Generate full COSHH assessments;
- Maintain a laboratory notebook and to write a formal report using appropriate text and chemistry artwork software;
- Combine reactions to achieve simple synthesis of target molecules.
- Present results formally and informally, individually or as a group;
- Predict the reactivity and regiochemistry of electrohilic addition to alkenes and aromatic systems.
- Safely handle flammable, corrosive, harmful, toxic and pyrophoric substances;
- Predict outcomes and draw mechanisms for reactions of carbonyl compounds (condensations, additions, cyclisations).
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 in multiple substitution reactions.
Chemistry of Enols and Enolates
- Enolisation: revision of general aspects of carbonyl chemistry, including acid-base equilibria and pKa.
- Enols and enolate ions as reactive intermediates – structure, stability and methods of formation, regioselectivity of deprotonation (kinetic vs thermodynamic control), general aspects of enolate ion reactivity.
- Using enolates as reactive substrates. Enolate alkylation. Aldol addition and condensation, including intramolecular and crossed versions. Claisen and Dieckmann condensation, Mannich.
- Silyl enol ethers – preparation and reactivity including substrate selectivity through control of reaction conditions.
- Dicarbonyl compounds: synthesis, reactivity and use as substrates in enolate chemistry; decarboxylation and Knoevenagel condensation.
Nucleophilic Addition to π-Systems
- Conjugate addition of carbanions (Grignard), alcohols, thiols, amines, enolates, cyanide to alpha,beta-unsaturated carbonyl compounds. Discussion of factors affecting 1,2 vs 1,4-addition
- Nucleophilic aromatic substitution. Addition-elimination and benzyne mechanisms.
Completion of three practical experiments and associated reports covering a range of topics and skills in organic chemistry including the application of a variety of fundamental techniques and methodologies (including spectroscopy) to the synthesis and analysis of molecules and materials; the ability to analyse experimental data to provide an explanation for the observed experimental outcomes; understanding the importance of experimental safety and time management. There is also a workshop on NMR assignment to reinforce 1st year work.
Learning and Teaching
Teaching and learning methods
Lectures, Seminars, tutorials, lab practical classes
Practical hours includes pre-laboratory e-learning.
Preparation for scheduled sessions hours includes other independent study.
|Completion of assessment task||24|
|Preparation for scheduled sessions||57|
|Practical classes and workshops||29|
|Total study time||150|
Resources & Reading list
J Clayden, N Greeves, S Warren (2012). Organic Chemistry. Oxford: OUP.
M. Hesse, H. Meier, B. Zeeh (2008). Spectroscopic Methods in Organic Chemistry. Stuttgart: Thieme.
D Williams, I. Flemming (2008). Spectroscopic Methods in Organic Chemistry. London: McGraw-Hill.
All absences from practical sessions must be validated and unexcused absences will result in failure of the module.
Repeat year externally: allowed if practical attendance criteria has been met. The practical marks are retained, the theory assessment is exam only.
Repeat year internally: note that practical may be reassessed by resubmission of reports or repeated.
This is how we’ll formally assess what you have learned in this module.
This is how we’ll assess you if you don’t meet the criteria to pass this module.
Repeat type: Internal & External