CHEM20180 Intermediate Organic & Biological Chemistry

Unit catalogue DLM

Monofunctional Carbonyl Compounds and Carbanion Chemistry

Lecturer Professor Tim Gallagher
Format 6 lectures
Learning objectives
  • Understand the structure and reactivity of enols and enolates.
  • Understand strong vs. weak bases; relative acidity of C-H bonds; how to stabilize negative charge.
  • How enols/enolates react and how to recognize nucleophilic reactivity within different environments.
  • Appreciate the role of “neutral” nucleophiles – enols, silyl enol ethers and enamines – how these react as nucleophiles and when these must be employed.
  • How to link functionality in a target molecule with a reaction that could be used to make it.
  • A unified mechanistic understanding of all the key reactions described.
Synopsis As its central theme, this course covers the chemistry of enolates and enols, which represent one of the most important classes of nucleophile in organic chemistry. We will address the relationship between enols and enolates and how to generate and exploit carbanion character. This will focus on: C-H acidity, deprotonation and the structure and properties of important bases; understanding lone pair/π-bond interactions and the stabilization of charge; how nucleophilic character is expressed and issues of reactivity. Putting these principles into a broader context is important, and the ideas discussed will be developed to include other systems, both carbanion (use of other “stabilizing groups”) but also “neutral” nucleophiles (e.g. silyl enol ethers and enamines). Clearly as important nucleophiles, the reactivity of enolates (and enols) is critical and we will examine the scope of this chemistry in terms of different electrophiles based on alkylation (with alkyl halides), aldol (with aldehydes/ketones) and acylation (with carboxylic acid derivatives, such as esters).
This course will provide the background essential to the next topic - difunctional carbonyl compounds – in part by showing you how to make difunctional carbonyl compounds (the reactivity of which will be covered next), and by addressing new and very important aspects of carbonyl reactivity, this course also provides a foundation for a number of other areas that will be covered in Year 2 (and beyond).
Additional reading Organic Chemistry, 2nd Edition, J Clayden, N Greeves, and S Warren, Oxford, 2012

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Difunctional Carbonyl Compounds

Lecturer Professor Paul Wyatt
Format 6 lectures
Learning objectives
  • How to generate enolates or enol equivalents in different circumstances.
  • How to employ a control group.
  • How to recognise appropriate starting materials for a given target molecule.
  • A mechanistic understanding of all the principal reactions used.
Synopsis This course provides a background into the chemistry of difunctional compounds with a particular emphasis on dicarbonyl compounds. This course builds on the previous course concerning anions and monofunctional carbonyl compounds. The synthesis and reactivity of 1,n-dicarbonyl compounds are discussed with the reagents necessary to achieve the chemoselectivity and regioselectivity are addressed. Topics specifically discussed include, the use of the 1,3-dicarbonyl system in synthesis, the reactivity of enones (Michael addition reactions), the synthesis of 1,5-dicarbonyl compounds and reagents for the synthesis of 1,2- and 1,4-dicarbonyl compounds. The Examples of compounds made using this chemistry are given. The fundamental ideas of retrosynthesis and their application to the molecules discussed in the course are explored.
Additional reading
  • Organic Chemistry 2nd Edition, J Clayden, N Greeves and S Warren, Oxford, 2012.
  • Organic Synthesis – The Disconnection Approach, 2nd Edition, S Warren and P Wyatt, Wiley, 2008

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Physical Organic Chemistry and Amines

Lecturer Dr Laura Broad
Format 6 lectures
Learning objectives
  • Understand structure and reactivity of amines and be able to design their synthesis
  • Understand organic acidity and basicity and be able to estimate pKA values for common functional groups
  • Be able to interpret simple physical organic chemical data and relate to reaction mechanism
Synopsis The course will begin with the synthesis and properties of aliphatic and aromatic amines, expanding on the basic introduction given in Chemistry 1Y. This will lead into an introduction to some of the basic concepts in physical organic chemistry, expanding on topics that you will have already met in Chemistry 1X and Chemistry 1Z, that allow us to link structure and reactivity in a qualitative and quantitative sense, and to interpret reaction mechanism data.

Amines

  • Amine synthesis via alkylation, reduction and rearrangements;
  • Reactions with acids, alkylating agents, carbonyl compounds and strong bases
  • Structure, properties and occurrence in nature.

Physical Organic Chemistry

  • Acid / base equilibria
  • Scales for acidity and basicity including pKA and pKB
  • Resonance
  • Solvation and solvent effects
  • Interpretation of simple reaction kinetics
  • Hammett correlations and their interpretation
Additional reading
  • Organic Chemistry, 6th Edition, KPC Vollhardt and NE Schore, Freeman, 2011, Chapter 21
  • Organic Chemistry, 2nd Edition, J Clayden, N Greeves, and S Warren, Oxford, 2012, Chapter 8
For a more advanced treatment, see, for example: Modern Physical Organic Chemistry, EV Anslyn and DA Dougherty, University Science Books, 2006

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Carbocations and Aromatic Chemistry

Lecturer Professor Tom Simpson
Format 6 lectures
Learning objectives
  • Influence of structure on stability and reactivity.
  • Application of different chemistries to achieve similar final outcomes.
  • Role of reactive intermediates in chemical and biological reactions.
  • Seeing interrelationships of areas of organic chemistry.
Synopsis The course will start by revising the formation, relative stabilities and reactions of carbocations. Their importance as reactive intermediates in a number of reactions will be discussed: rearrangements (e.g. Wagner-Meerwein shifts, pinacol-pinacolone), ring expansions and contractions, and their role in terpenoid (e.g. cholesterol) biosynthesis. These will be covered in three lectures.
The remaining lectures will deal with further methods (following on from Year 1 introduction to electrophilic aromatic substitution) for the preparation of substituted aromatic compounds: nucleophilic aromatic substitution, ipso substitution, diazonium salts and “benzyne”. Other methods for the de novo synthesis of aromatic rings, e.g. Diels-Alder cycloadditions and use of carbonyl condensation chemistry will be described. Finally further chemistry of aromatic compounds and the influence of the aromatic ring on substituents, e.g. “benzylic” reactivity will be covered.
Additional reading Organic Chemistry, 2nd Edition, J Clayden, N Greeves, and S Warren, Oxford, 2012

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Heterocyclic Compounds

Lecturer Professor Kevin Booker-Milburn
Format 6 lectures
Learning objectives
  • Hückel's (4n+2) rule and heteroaromaticity
  • Electrophilic substitution of heterocycles
  • Metallation of hetero C-H bonds
  • Nucleophilic addition to pyridines
  • Use of carbonyl compounds in heterocyclic synthesis
Synopsis This course will introduce you to the concept of heteroaromaticity and some of the most common mono-heteroaromatic compounds and their roles in healthcare and society. In particular we will focus on the chemistry and synthesis of the 5-membered heterocycles pyrrole, furan and thiophene before moving onto the 6-membered benzene analogue pyridine. How these compounds differ from benzene in their reactivity will be explored in detail. Synthetic approaches to these heterocycles will highlight and reinforce the importance of carbonyl chemistry, particularly dicarbonyl compounds.
Additional reading
  • Aromatic Heterocyclic Chemistry, D T Davies, Oxford Chemistry Primer,1992
  • Useful references to larger textbooks, reference books and series are given at the end of chapter 1
  • Heterocyclic Chemistry, 4th Edition, J A Joule and K Mills, Chapman and Hall, 2000
  • Heterocyclic Chemistry, 3rd Edition, T L Gilchrist, Longman, 1997
  • Organic Chemistry, 6th Edition, K P C Vollhardt and N E Schore, Freeman, 2011, Chapter 25
  • Organic Chemistry, 2nd Edition, J Clayden, N Greeves, and S Warren, Oxford, 2012, Chapter 43 and 44

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Selective Reactions in Organic Synthesis

Lecturer Professor Chris Willis
Format 6 lectures
Learning objectives
  • How to use protecting groups in organic synthesis
  • A mechanistic understanding of oxidation of alcohols and reduction of carbonyl compounds.
  • How to use selective reactions in the synthesis of organic compounds
  • An understanding of radical reactions in organic synthesis.
Synopsis The synthesis of complex organic compounds requires the use of selective reactions and reagents. In this course mild and selective methods to achieve chemoselectivity, regioselectivity and functional group interconversions will be outlined as well as the use of protecting groups in synthesis. Methods for the selective oxidation of alcohols and reduction of carbonyl compounds will be considered in the context of their reaction mechanisms. Radical reactions will be introduced. Examples of the applications of this chemistry to the synthesis of biologically significant molecules will be highlighted.
Additional reading Organic Chemistry, 2nd Edition, J Clayden, N Greeves, and S Warren, Oxford, 2012

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Stereochemistry and Conformation

Lecturer Professor Tony Davis
Format 6 lectures
Learning objectives
  • An understanding of the shapes of organic molecules.
  • An understanding of the modes of flexibility of organic molecules, including especially cyclic molecules.
  • An appreciation of the way that the shape and flexibility of a molecule affects its reactivity.
Synopsis The three-dimensional shapes of molecules are critical for determining their properties, and also the way in which they react. This course will cover the shapes of organic molecules in detail, including aspects which are permanent for a given molecule (stereochemistry) as well as aspects which are temporary and dynamic (conformation). The first part will reinforce concepts introduced in the first year, e.g. stereoisomers, chirality, diastereomers, enantiomers, conformers, boat and chair forms of cyclohexanes. Additional topics will include the resolution of enantiomers, molecular symmetry elements, ring strain, and the stereochemistry of complex biomolecules (including carbohydrate anomers). The second part of the course will cover the relationship between stereochemistry/conformation and reactivity, including the concepts of stereoselectivity and stereospecificity, and the strategies used to achieve particular stereochemical outcomes in reactions. The latter will be illustrated using carbon-carbon bond forming reactions such as the Diels Alder reaction, and functional group interconversions such as the oxidation of alkenes.
Additional reading
  • Organic Chemistry, 2nd Edition, J Clayden, N Greeves, and S Warren, Oxford, 2012, Chapters 16 and 18
  • Stereochemistry of Organic Compounds, EL Eliel and SH Wilen, Wiley, 1994 (for reference only)

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Amino Acids, Peptides and Proteins

Lecturers Dr John Crosby and Prof Matt Crump
Format 6 lectures
Learning objective To achieve a basic grounding in peptide chemistry, structure and function, and to be able to apply this to address problems in relating protein sequence to protein structure and function.
Synopsis

Peptides and proteins are the workhorses of biology. Their functions include hormones and signalling molecules that convey messages within and between cells, molecular gateways and channels on cell surfaces, enzymes that catalyse any manner of chemical reaction, and structural components of cells and tissues. The vast majority of these functions rely on the polypeptide chains reproducibly forming well-defined three-dimensional structures. Protein chemists and engineers are now manipulating polypeptides and, consequently, their structures and functions for applications in industry, medicine and nanotechnology. This course will introduce the underlying principles of protein structure from the bottom up; i.e., from the amino acids, peptide bonds and peptide/protein sequences and how these relate to and determine the functional three-dimensional structures of peptides and proteins. We will introduce a range of enzyme catalyzed reactions and relate these to core chemistry that you have encountered in the first and second year chemistry course. Modern methods for protein structure determination and assay will be described and the final lecture will introduce protein and peptide synthesis.

Additional reading

Any of the basic “Biochemistry” texts that you are comfortable with (e.g. Horton (Prentice Hall), “Berg (previously known as Stryer)” (Freeman), or Voet and Voet (Wiley), or one of the following:

Introduction to Protein Structure, 2nd Edition, C Branden and J Tooze, Garland, 1999

How Proteins Work, M Williamson, Garland, 2012

Proteins: Structure and Function, D Whitford, Wiley, 2005

Structure and Mechanism in Protein Science, A Fersht, Freeman, 1999

For chemical and synthetic aspects of the course:

Foundations of Chemical Biology, CM Dobson, JA Gerrard and AJ Pratt, Oxford Chemistry Primer, 2001

Amino Acid and Peptide Synthesis, 2nd Edition, JH Jones, Oxford Chemistry Primer, 2002

Peptides: Chemistry and Biology, 2nd Edition, N Sewald and HD Jakubke, Wiley-VCH, 2009

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