Structure and reactivity of organic molecules

CHEM20412 Structure and reactivity of organic molecules 10 Semester 2 Undergraduate Level 2 Nathan Owston Unit coordinator Department of Chemistry 1 FHEQ level (Framework for Higher Education Qualifications) ' Middle part of Bachelors ' European Credit Transfer & Accumulation System Rating : 5.0 Weeks 1-4: Rings and Stereoelectronics (Dr Nathan Owston)Weeks 5-8: Introduction to Biomolecules (Dr Michael James)Weeks 9-12: Retrosynthetic Analysis (Dr Andrew Regan)  <div>This course unit detail provides the framework for delivery in 21/22 and may be subject to change due to any additional Covid-19 impact.  Please see Blackboard / course unit related emails for any further updates</div><div>Weeks 1-4: Rings and Stereoelectronics (Dr Nathan Owston)<ul> <li>Rates and barriers in organic reactions</li> <li>Rotation, interconversion, conformers and rotamers</li> <li>The Eyring Equatiion</li> <li>Stereoelectronic effects: 6 membered rings - substituted cyclohexanes and cyclohexane epoxides, ring closing reactions, stereo and regiochemical considerations.</li> <li>Electrophilic addition to cyclic alkenes</li> <li>Synthesis of small, medium and large rings – ring formation and ring stability, kinetic and thermodynamic considerations.</li> <li>The Thorpe-Ingold Effect, kinetic and thermodynamic considerations</li> <li>Ring-closing and ring-opening reactions: Baldwin’s rules.</li> <li>Neighbouring group participation – lone pairs and pi-bonds, stereo- and regio-chemical outcomes.</li> <li>Molecular rearrangements: Migration, Carbocation Rearrangements, Pinacol-type rearrangements, the Beckmann rearrangement and the applications of these in ring synthesis.</li> <li>Fragmentation reactions: ring expansion by fragmentation, applications in ring synthesis.</li></ul>Weeks 5-8 Introduction to Primary MetabolitesCarbohydrates – mono, di & oligosaccharides<ul> <li>The basics – functional groups, chain length, aldose & ketose</li> <li>Stereochemistry – Enantiomers, diastereomers & epimers</li> <li>Hemiacetal reaction mechanism – cyclic hemiacetals, lactols, equilibrium</li> <li>Cyclic structures – 2D, 3D, wedge & dash bonds, R/S centres, chair, axial, equatorial</li></ul>Anomeric centre<ul> <li>Anomeric centre – anomeric effect, steric effects & conformational analysis.</li> <li>Mutarotation – optical rotation, mole fractions</li> <li>Fischer glycosylation - Acetal reaction mechanism, “dry” acidic conditions, equilibrium & acetal hydrolysis</li></ul>Alcohol groups<ul> <li>Reactions of alcohols – Williamson ether synthesis, silyl ethers, tosyl groups, reduction, oxidation</li> <li>Problems with synthesis for monosaccharides</li> <li>Protecting groups</li></ul>Glycosylation – Glycosyl acceptor, glycosyl donor,<ul> <li>Position of glycosyl linkage</li> <li>Strategies for synthesis</li></ul>α-Amino acids & Peptides<ul> <li>Stereochemistry – Enantiomers, diastereomers</li> <li>Reactivity – zwitterions, amines, carboxylates, pKa, isoelectric point</li> <li>Side chains – solubility, acidic, basicity, steric effect, S-S bridges, lactam formation</li> <li>Peptide chains – primary structure, nomenclature, abbreviations, N & C termini, sequence & composition</li></ul>α -Amino acid synthesis<ul> <li>Synthesis of racemic mixtures e.g. ammonlysis of a-halo acids, modification of the Gabriel synthesis, Strecker synthesis.</li> <li>Resolution of racemic α-amino acids</li> <li>Stereoselective α-amino acid synthesis e.g. chiral hydrogenation</li></ul>Peptides & oligopeptide synthesis<ul> <li>Peptide synthesis – problems with solution phase synthesis, multi-step yields, solid phase synthesis, Merryfield, WANG, PAM & Kent</li> <li>Protecting groups – Fmoc, tBoc, tBu, Bn</li></ul>Analysis of Polypeptides<ul> <li>Secondary structure – sequence & secondary structure</li> <li>Composition analysis – hydrolysis, ninhydrin, chromatographs</li> <li>Sequence analysis – Terminal residue analysis, Edman degradation, enzymatic cleavage, Trypsin & Chymotrypsin</li></ul> Weeks 9-12: Retrosynthetic Analysis (Dr Andrew Regan)<ul> <li>Retrosynthetic analysis of compounds containing one functional group:</li></ul></div><div>Disconnections of alcohols and α-alkylated carbonyl compounds. Control of enolate reactions.<ul> <li>Retrosynthetic analysis of compounds containing two functional groups:</li></ul>Disconnections of 1,2- 1,3- 1,4- 1,5- and 1,6-difunctional compoundsDisconnections of difunctional compounds in rings: intramolecular cyclisation reactions.<ul> <li>Functional group interconversions</li></ul></div>  The unit aims to extend the concepts presented in previous courses to the structural, mechanistic, physical and biological properties of organic molecules.  On successful completion of the course students should be able to:   Predict whether organic reactions will occur through consideration of stereoelectronic effects, basic kinetics and thermodynamics.Evaluate and propose strategies for the synthesis of cyclic and acyclic molecules based on consideration of stereoelectronic effects, basic kinetics and thermodynamics.Describe, evaluate and propose strategies for the synthesis of amino acids, peptides and carbohydrates based on selective protecting group strategies.Apply the concepts of reactivity, stereochemistry, and stereoelectronics to evaluate the nature of amino acids, peptides and carbohydrates.Choose appropriate disconnections for difunctional target molecules, based on stabilities of the synthons generatedAnalyse the relationships between functional groups in difunctional compoundsChoose appropriate synthetic equivalents for synthons resulting from retrosynthetic analysisChoose appropriate reagents for the reactions involved in planned synthesesDecide whether any extra methods of control are required for a synthesis to proceed as planned  • Problem-solving skills • Analytical skills  Weeks 1-4: Rings and Stereoelectronics (Dr Nathan Owston)<ul><li>Rates and barriers in organic reactions</li><li>Rotation, interconversion, conformers and rotamers  </li><li>Stereoelectronic effects: 6 membered rings - substituted cyclohexanes and cyclohexane epoxides, ring closing reactions, stereo and regiochemical considerations. </li><li>    Electrophilic addition to cyclic alkenes  </li></ul>Synthesis of small, medium and large rings – ring formation and ring stability. <ul><li>  The Thorpe-Ingold Effect, kinetic and thermodynamic considerations</li><li>Ring-closing and ring-opening reactions: Baldwin’s rules. </li><li>Neighbouring group participation: stereo- and regio-chemical outcomes.</li><li>Molecular rearrangements: Migration, Carbocation Rearrangements, Pinacol-type rearrangements, the Beckmann rearrangement, applications of these in ring synthesis.</li><li>Fragmentation reactions: ring expansion, applications in ring synthesis. </li></ul>Weeks 5-8 Introduction to Primary Metabolites (Dr Michael James) <ul><li>Amino acids & Peptides</li><li>Basic structure and ionisation – zwitterions, isoelectric points</li><li>Side chains – acidity, basicity, electrostatic effects, hydrogen bonding</li><li>Stereochemistry – Enantiomers, diastereomers</li><li>Peptide chains – primary structure, nomenclature, abbreviations, N & C termini, sequence & composition</li><li>Synthesis of racemic mixtures – nucleophilic substitution, reductive amination, Strecker synthesis</li><li>Amino & Carboxy Protecting groups – e.g. Cbz, Fmoc, Boc</li><li>Peptide synthesis – DCC + HOBt or HBTU</li></ul>Carbohydrates<ul><li>Basic structure – functional groups, chain length, aldose & ketose</li><li>Stereochemistry – Enantiomers, diastereomers & epimers</li><li>Hemiacetal formation reaction mechanism – cyclic hemiacetals, lactols, equilibrium</li><li>Cyclic structures – 2D, 3D, wedge & dash bonds, R/S centres, chair, axial, equatorial</li><li>Anomeric centre – anomeric effect, mutarotation</li><li>Selective functionalisation and protection of alcohols – Fischer glycosidation, benzyl and trityl ethers, silyl ethers, tosyl groups, cyclic acetals, esterification</li><li>Selective synthesis of monosaccharides and disaccharides – glycosyl bromides, thiogylcosides, neighbouring group participation</li></ul> Weeks 9-12: Retrosynthetic Analysis (Dr Andrew Regan) •    Retrosynthetic analysis of compounds containing one functional group:Disconnections of alcohols and α-alkylated carbonyl compoundsControl of enolate reactions. •    Retrosynthetic analysis of compounds containing two functional groups:Disconnections of 1,2- 1,3- 1,4- 1,5- and 1,6-difunctional compoundsDisconnections of difunctional compounds in rings: intramolecular cyclisation reactions.  1 Written exam 100% <div>CHEM20412 is delivered in a way which allows students to regularly receive feedback on their work and progress in synchronous sessions. This is achieved through a significant amount of content being delivered as worked examples/content/problems during lectures. Such delivery allows provision of formative feedback through material, comments and suggestions which are designed to help guide students in their own conceptualization and approach to solving problems.   Worked content and problems offer opportunities for both facilitator and peer feedback by -    Providing opportunities for students to master concepts introduced in lectures, and apply these concepts to unseen material. -    Encouraging development of thinking skills (with a focus on critical thinking, analysis, evaluation and application, rather than simple reproduction of knowledge/process) -    Promoting teamwork and collaboration, and the development of skills associated with this, as well as individual responsibility for learning. -    Providing time for students to reflect upon their own learning, and to self-evaluate. In addition, facilitators share problem-solving approaches/common misconceptions through whole-class feedback. Tutorials In addition to the above, three tutorials provide opportunities for more personalised tutor feedback and for informal peer feedback on CHEM20412 material in a collaborative, small-group environment.   E-learning CHEM20412 is supported by a selection of supplementary E-learning materials which provide an opportunity for students to evaluate their own progress during the module.   Workshop sessions Provide an opportunity to deliver assessment-specific feedback relating to assessment criteria and understanding of question demand, as well as concerning problem solving in examinations (using past paper questions as exemplars). Staff Individual lecturers provide office hours or operate an open-door policy to provide individual, personalised feedback.</div>  CHEM10101 Introductory Chemistry Pre-Requisite Compulsory CHEM10212 Energy and Change Pre-Requisite Compulsory CHEM10312 Coordination Chemistry Pre-Requisite Compulsory CHEM10412 Structure and Reactivity Pre-Requisite Compulsory CHEM20411 Organic Synthesis Pre-Requisite Compulsory <span class="TextRun SCXW222653942 BCX8 NormalTextRun" style="-webkit-tap-highlight-color:transparent;-webkit-text-stroke-width:0px;-webkit-user-drag:none;font-family:"Microsoft Sans Serif", "Microsoft Sans Serif_EmbeddedFont", "Microsoft Sans Serif_MSFontService", sans-serif;font-size:11pt;font-style:normal;font-variant-caps:normal;font-variant-ligatures:none !important;font-weight:400;letter-spacing:normal;line-height:17.2667px;margin:0px;orphans:2;padding:0px;text-align:left;text-decoration-color:initial;text-decoration-style:initial;text-decoration-thickness:initial;text-indent:0px;text-transform:none;user-select:text;white-space:pre-wrap;widows:2;word-spacing:0px;" data-contrast="auto" xml:lang="EN-GB" lang="EN-GB">Pre-requisite units<span class="EOP SCXW222653942 BCX8" style="-webkit-tap-highlight-color:transparent;-webkit-text-stroke-width:0px;-webkit-user-drag:none;font-family:"Microsoft Sans Serif", "Microsoft Sans Serif_EmbeddedFont", "Microsoft Sans Serif_MSFontService", sans-serif;font-size:11pt;font-style:normal;font-variant-caps:normal;font-variant-ligatures:normal;font-weight:400;letter-spacing:normal;line-height:17.2667px;margin:0px;orphans:2;padding:0px;text-align:left;text-decoration-color:initial;text-decoration-style:initial;text-decoration-thickness:initial;text-indent:0px;text-transform:none;user-select:text;white-space:pre-wrap;widows:2;word-spacing:0px;" data-ccp-props="{"335559738":60,"335559739":60}"> <span class="TextRun SCXW52763273 BCX8 NormalTextRun" style="-webkit-tap-highlight-color:transparent;-webkit-text-stroke-width:0px;-webkit-user-drag:none;font-family:"Microsoft Sans Serif", "Microsoft Sans Serif_EmbeddedFont", "Microsoft Sans Serif_MSFontService", sans-serif;font-size:11pt;font-style:normal;font-variant-caps:normal;font-variant-ligatures:none !important;font-weight:400;letter-spacing:normal;line-height:17.2667px;margin:0px;orphans:2;padding:0px;text-align:left;text-decoration-color:initial;text-decoration-style:initial;text-decoration-thickness:initial;text-indent:0px;text-transform:none;user-select:text;white-space:pre-wrap;widows:2;word-spacing:0px;" data-contrast="auto" xml:lang="EN-GB" lang="EN-GB">All year 1 and year 2 semester 1 core CHEM modules.<span class="EOP SCXW52763273 BCX8" style="-webkit-tap-highlight-color:transparent;-webkit-text-stroke-width:0px;-webkit-user-drag:none;font-family:"Microsoft Sans Serif", "Microsoft Sans Serif_EmbeddedFont", "Microsoft Sans Serif_MSFontService", sans-serif;font-size:11pt;font-style:normal;font-variant-caps:normal;font-variant-ligatures:normal;font-weight:400;letter-spacing:normal;line-height:17.2667px;margin:0px;orphans:2;padding:0px;text-align:left;text-decoration-color:initial;text-decoration-style:initial;text-decoration-thickness:initial;text-indent:0px;text-transform:none;user-select:text;white-space:pre-wrap;widows:2;word-spacing:0px;" data-ccp-props="{}">  <span class="TextRun SCXW98546726 BCX8 NormalTextRun" style="-webkit-tap-highlight-color:transparent;-webkit-text-stroke-width:0px;-webkit-user-drag:none;font-family:"Microsoft Sans Serif", "Microsoft Sans Serif_EmbeddedFont", "Microsoft Sans Serif_MSFontService", sans-serif;font-size:11pt;font-style:normal;font-variant-caps:normal;font-variant-ligatures:none !important;font-weight:400;letter-spacing:normal;line-height:17.2667px;margin:0px;orphans:2;padding:0px;text-align:left;text-decoration-color:initial;text-decoration-style:initial;text-decoration-thickness:initial;text-indent:0px;text-transform:none;user-select:text;white-space:pre-wr N • J. Clayden, N. Greeves, and S. Warren, Organic Chemistry, 2nd edition (Oxford University Press, 2012), ISBN 978-0199270-29-3.• S. Doonan, Peptides and Proteins, RSC Tutorial Chemistry Texts (RSC, Cambridge, 2002), ISBN 0-85404-692-5• S. Warren, Organic Synthesis: the Disconnection Approach, Wiley, 2nd edition, 2008; also Workbook for 2nd edition (both available as online e-books). • The following Oxford University Press Chemistry Primers are recommended, and are freely available to students as e-books via the University Library catalogue and Bibliotech:•    A. J. Kirby, Stereoelectronic Effects, 1996.•    B. G. Davis & A. G. Fairbanks, Carbohydrate Chemistry, 2002.•    C. M. Dobson, J. A. Gerrard & A. J. Pratt, Foundations of Chemical Biology, 2001•    J. Jones, Amino Acid & Peptide Synthesis, 2002.•    C. L. Willis and M. Wills, Organic Synthesis, 1991.•    R. S. Ward, Bifunctional Compounds, 1994.•    J. Jones, Core Carbonyl Chemistry 1997. A set of molecular models is also highly recommended.  Assessment written exam 2 Lectures 24 Tutorials 3 0 71