CHEM2001 Organic Reaction Mechanisms

Module Overview

Aims and Objectives

Module Aims

The aim of this course is to provide an understanding of Organic reaction mechanisms for future studies in chemistry and allied subjects, and enhanced practical skills including safe working practices (risk, hazard and control measures), laboratory report writing (written and verbal communication of results), error and accuracy. Lecture component: The aim of the theory component of the course is to provide students with the tools to describe and work out reaction mechanisms using the ‘curly arrow’ notation. Appreciation of the relative stabilities and reactivities of the reactive intermediates (Carbenium ions, Carbanions, Radicals and Carbenes) are important. The SN2, SN1, E1, E2 and E1CB mechanisms are reinforced including solvent effects, basicity and nucleophilicity, and steric and electronc effects of substrate structure on rates of reaction. Neighbouring group participation and rearrangements are introduced together woth basic radical and carbene chemisty. Stability of carbanions is particualry developed in the context of enolate chemistry including condensation and cyclisation reactions. Electrophilic addition to alkenes and aromatic sytems is developed, alongside nucleophilic addition to alkenes and aromatic substitution. Practical Component: The aim of the practical component of the course is to develop the skills that will be needed in students future practical work. Students will undertake three organic practicals.

Learning Outcomes

Having successfully completed this module you will be able to:

Use curly arrow reaction mechanisms and a knowledge of the relative stability of intermediates to predict and / or account for the products of reactions.
Perform multi-step syntheses under normal or inert conditions using standard or microwave heating, or cooling baths using cardice;
Monitor reactions by TLC;
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)
Safely handle flammable, corrosive, harmful, toxic and pyrophoric substances;
Evaluate green credentials of 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);
Maintain a laboratory notebook and to write a formal report using appropriate text and chemistry artwork software;
Present results formally and informally, individually or as a group;
Suggest mechanisms for the reactions performed and to draw these using curly arrows.
Generate full COSHH assessments;
Design experiments to probe mechanisms, particularly using stereochemistry or isotopic labelling.
Recognise neighboring group participation and rearrangement reactions.
Use analytical information to assign or confirm structures.
Combine reactions to achieve simple synthesis of target molecules.
Predict the reactivity and regiochemistry of electrohilic addition to alkenes and aromatic systems.
Predict outcomes and draw mechanisms for reactions of carbonyl compounds (condensations, additions, cyclisations).
Predict outcomes and draw mechanisms for nucleophilic addition to alkenes and nucleophilic aromatic substitution reactions.
Appreciate the scope and limitations of nucleophilic additions to pi-systems.

Syllabus

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 p-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 p-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. Practical 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.

Special Features

Core chemistry.

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.

Type	Hours
Lecture	24
Completion of assessment task	24
Practical classes and workshops	29
Preparation for scheduled sessions	57
Revision	10
Seminar
Tutorial	6
Total study time	150

Resources & Reading list

M. Hesse, H. Meier, B. Zeeh (2008). Spectroscopic Methods in Organic Chemistry.

D Williams, I. Flemming (2008). Spectroscopic Methods in Organic Chemistry.

Assessment

Assessment Strategy

The practical and theory (examination plus tutorial) components must be passed separately at the module pass mark for the student’s programme, i.e. 40% if core, 25% if compulsory or optional (if compensation is allowed). All absences from practical sessions must be validated and unexcused absences will result in failure of the module..

Summative

Method	Percentage contribution
Assessed Tutorials	10%
Examination (2 hours)	65%
Practical write-ups	25%

Referral

Method	Percentage contribution
Examination (2 hours)	75%
Practical write-ups	25%

Repeat Information

Repeat type: Internal & External

Linked modules

Pre-requisites

To study this module, you will need to have studied the following module(s):

Code	Module
CHEM1032	Fundamentals of Organic Chemistry II
CHEM1031	Fundamentals of Organic Chemistry I